Early and late selection processes have separable influences on the neural substrates of attention.

PubMed

Drisdelle, Brandi Lee; Jolicoeur, Pierre

2018-05-01

To improve our understanding of the mechanisms of target selection, we examined how the spatial separation of salient items and their similarity to a pre-defined target interact using lateralised electrophysiological correlates of visual spatial attention (N2pc component) and visual short-term memory (VSTM; SPCN component). Using these features of target selection, we sought to expand on previous work proposing a model of early and late selection, where the N2pc is suggested to reflect the selection probability of visual stimuli (Aubin and Jolicoeur, 2016). The authors suggested that early-selection processes could be enhanced when items are adjacent. In the present work, the stimuli were short oriented lines, all of which were grey except for two that were blue and hence salient. A decrease in N2pc amplitude with decreasing spatial separation between salient items was observed. The N2pc increased in amplitude with increasing similarity of salient distractors to the target template, but only in target-absent trials. There was no interaction between these two factors, suggesting that separable attentional mechanisms influenced the N2pc. The findings suggest that selection is initially based on easily-distinguished attributes (i.e., both blue items) followed by a later identification-based process (if necessary), which depends on feature similarity to a target template. For the SPCN component, the results were in line with previous work: for target-present trials, an increase in similarity of salient distractors was associated with an increase in SPCN amplitude, suggesting more information was maintained in VSTM. In sum, results suggest there is a need for further inspection of salient distractors when they are similar to the target, increasing the need for focal attention, demonstrated by an increase in N2pc amplitude, followed by a higher probability of transfer to VSTM, demonstrated by an increase in SPCN amplitude. Copyright © 2018 Elsevier B.V. All rights reserved.

Categorization difficulty modulates the mediated route for response selection in task switching.

PubMed

Schneider, Darryl W

2017-12-22

Conflict during response selection in task switching is indicated by the response congruency effect: worse performance for incongruent targets (requiring different responses across tasks) than for congruent targets (requiring the same response). The effect can be explained by dual-task processing in a mediated route for response selection, whereby targets are categorized with respect to both tasks. In the present study, the author tested predictions for the modulation of response congruency effects by categorization difficulty derived from a relative-speed-of-processing hypothesis. Categorization difficulty was manipulated for the relevant and irrelevant task dimensions in a novel spatial task-switching paradigm that involved judging the locations of target dots in a grid, without repetition of dot configurations. Response congruency effects were observed and they varied systematically with categorization difficulty (e.g., being larger when irrelevant categorization was easy than when it was hard). These results are consistent with the relative-speed-of-processing hypothesis and suggest that task-switching models that implement variations of the mediated route for response selection need to address the time course of categorization.

Event-related potentials during visual selective attention in children of alcoholics.

PubMed

van der Stelt, O; Gunning, W B; Snel, J; Kok, A

1998-12-01

Event-related potentials were recorded from 7- to 18-year-old children of alcoholics (COAs, n = 50) and age- and sex-matched control children (n = 50) while they performed a visual selective attention task. The task was to attend selectively to stimuli with a specified color (red or blue) in an attempt to detect the occurrence of target stimuli. COAs manifested a smaller P3b amplitude to attended-target stimuli over the parietal and occipital scalp than did the controls. A more specific analysis indicated that both the attentional relevance and the target properties of the eliciting stimulus determined the observed P3b amplitude differences between COAs and controls. In contrast, no significant group differences were observed in attention-related earlier occurring event-related potential components, referred to as frontal selection positivity, selection negativity, and N2b. These results represent neurophysiological evidence that COAs suffer from deficits at a late (semantic) level of visual selective information processing that are unlikely a consequence of deficits at earlier (sensory) levels of selective processing. The findings support the notion that a reduced visual P3b amplitude in COAs represents a high-level processing dysfunction indicating their increased vulnerability to alcoholism.

Selective Attention and Distraction in Context-Interactive Situations in Children and Adults.

ERIC Educational Resources Information Center

Ackerman, Brian P.

1987-01-01

Results from three experiments suggest that attention to context may benefit target recall in situations in which the context can be meaningfully related to the target. Adults seem to be more able to engage in context-interactive processing of stimulus information than are children, who base target selection on perceptual information. (PCB)

Relations between 18-month-olds' gaze pattern and target action performance: a deferred imitation study with eye tracking.

PubMed

Óturai, Gabriella; Kolling, Thorsten; Knopf, Monika

2013-12-01

Deferred imitation studies are used to assess infants' declarative memory performance. These studies have found that deferred imitation performance improves with age, which is usually attributed to advancing memory capabilities. Imitation studies, however, are also used to assess infants' action understanding. In this second research program it has been observed that infants around the age of one year imitate selectively, i.e., they imitate certain kinds of target actions and omit others. In contrast to this, two-year-olds usually imitate the model's exact actions. 18-month-olds imitate more exactly than one-year-olds, but more selectively than two-year-olds, a fact which makes this age group especially interesting, since the processes underlying selective vs. exact imitation are largely debated. The question, for example, if selective attention to certain kinds of target actions accounts for preferential imitation of these actions in young infants is still open. Additionally, relations between memory capabilities and selective imitation processes, as well as their role in shaping 18-month-olds' neither completely selective, nor completely exact imitation have not been thoroughly investigated yet. The present study, therefore, assessed 18-month-olds' gaze toward two types of actions (functional vs. arbitrary target actions) and the model's face during target action demonstration, as well as infants' deferred imitation performance. Although infants' fixation times to functional target actions were not longer than to arbitrary target actions, they imitated the functional target actions more frequently than the arbitrary ones. This suggests that selective imitation does not rely on selective gaze toward functional target actions during the demonstration phase. In addition, a post hoc analysis of interindividual differences suggested that infants' attention to the model's social-communicative cues might play an important role in exact imitation, meaning the imitation of both functional and arbitrary target actions. Copyright © 2013 Elsevier Inc. All rights reserved.

The effect of spatial organization of targets and distractors on the capacity to selectively memorize objects in visual short-term memory

PubMed Central

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. PMID:25339978

Structure-Based Design of Highly Selective Inhibitors of the CREB Binding Protein Bromodomain.

PubMed

Denny, R Aldrin; Flick, Andrew C; Coe, Jotham; Langille, Jonathan; Basak, Arindrajit; Liu, Shenping; Stock, Ingrid; Sahasrabudhe, Parag; Bonin, Paul; Hay, Duncan A; Brennan, Paul E; Pletcher, Mathew; Jones, Lyn H; Chekler, Eugene L Piatnitski

2017-07-13

Chemical probes are required for preclinical target validation to interrogate novel biological targets and pathways. Selective inhibitors of the CREB binding protein (CREBBP)/EP300 bromodomains are required to facilitate the elucidation of biology associated with these important epigenetic targets. Medicinal chemistry optimization that paid particular attention to physiochemical properties delivered chemical probes with desirable potency, selectivity, and permeability attributes. An important feature of the optimization process was the successful application of rational structure-based drug design to address bromodomain selectivity issues (particularly against the structurally related BRD4 protein).

A bilateral advantage in controlling access to visual short-term memory.

PubMed

Holt, Jessica L; Delvenne, Jean-François

2014-01-01

Recent research on visual short-term memory (VSTM) has revealed the existence of a bilateral field advantage (BFA--i.e., better memory when the items are distributed in the two visual fields than if they are presented in the same hemifield) for spatial location and bar orientation, but not for color (Delvenne, 2005; Umemoto, Drew, Ester, & Awh, 2010). Here, we investigated whether a BFA in VSTM is constrained by attentional selective processes. It has indeed been previously suggested that the BFA may be a general feature of selective attention (Alvarez & Cavanagh, 2005; Delvenne, 2005). Therefore, the present study examined whether VSTM for color benefits from bilateral presentation if attentional selective processes are particularly engaged. Participants completed a color change detection task whereby target stimuli were presented either across both hemifields or within one single hemifield. In order to engage attentional selective processes, some trials contained irrelevant stimuli that needed to be ignored. Targets were selected based on spatial locations (Experiment 1) or on a salient feature (Experiment 2). In both cases, the results revealed a BFA only when irrelevant stimuli were presented among the targets. Overall, the findings strongly suggest that attentional selective processes at encoding can constrain whether a BFA is observed in VSTM.

BODY SENSING SYSTEM

NASA Technical Reports Server (NTRS)

Mah, Robert W. (Inventor)

2005-01-01

System and method for performing one or more relevant measurements at a target site in an animal body, using a probe. One or more of a group of selected internal measurements is performed at the target site, is optionally combined with one or more selected external measurements, and is optionally combined with one or more selected heuristic information items, in order to reduce to a relatively small number the probable medical conditions associated with the target site. One or more of the internal measurements is optionally used to navigate the probe to the target site. Neural net information processing is performed to provide a reduced set of probable medical conditions associated with the target site.

High affinity ligands from in vitro selection: Complex targets

PubMed Central

Morris, Kevin N.; Jensen, Kirk B.; Julin, Carol M.; Weil, Michael; Gold, Larry

1998-01-01

Human red blood cell membranes were used as a model system to determine if the systematic evolution of ligands by exponential enrichment (SELEX) methodology, an in vitro protocol for isolating high-affinity oligonucleotides that bind specifically to virtually any single protein, could be used with a complex mixture of potential targets. Ligands to multiple targets were generated simultaneously during the selection process, and the binding affinities of these ligands for their targets are comparable to those found in similar experiments against pure targets. A secondary selection scheme, deconvolution-SELEX, facilitates rapid isolation of the ligands to targets of special interest within the mixture. SELEX provides high-affinity compounds for multiple targets in a mixture and might allow a means for dissecting complex biological systems. PMID:9501188

Cell-specific transmembrane injection of molecular cargo with gold nanoparticle-generated transient plasmonic nanobubbles

PubMed Central

Lukianova-Hleb, Ekaterina Y.; Wagner, Daniel S.; Brenner, Malcolm K.; Lapotko, Dmitri O.

2012-01-01

Optimal cell therapies require efficient, selective and rapid delivery of molecular cargo into target cells without compromising their viability. Achieving these goals ex vivo in bulk heterogeneous multi-cell systems such as human grafts is impeded by low selectivity and speed of cargo delivery and by significant damage to target and non-target cells. We have developed a cell level approach for selective and guided trans-membrane injection of extracellular cargo into specific target cells using transient plasmonic nanobubbles (PNB) as cell-specific nano-injectors. As a technical platform for this method we developed a laser flow cell processing system. The PNB injection method and flow system were tested in heterogeneous cell suspensions of target and non-target cells for delivery of Dextran-FITC dye into squamous cell carcinoma HN31 cells and transfection of human T-cells with a green fluorescent protein-encoding plasmid. In both models the method demonstrated single cell type selectivity, high efficacy of delivery (96% both for HN31 cells T-cells), speed of delivery (nanoseconds) and viability of treated target cells (96% for HN31 cells and 75% for T-cells). The PNB injection method may therefore be beneficial for real time processing of human grafts without removal of physiologically important cells. PMID:22521612

Cell-specific transmembrane injection of molecular cargo with gold nanoparticle-generated transient plasmonic nanobubbles.

PubMed

Lukianova-Hleb, Ekaterina Y; Wagner, Daniel S; Brenner, Malcolm K; Lapotko, Dmitri O

2012-07-01

Optimal cell therapies require efficient, selective and rapid delivery of molecular cargo into target cells without compromising their viability. Achieving these goals ex vivo in bulk heterogeneous multi-cell systems such as human grafts is impeded by low selectivity and speed of cargo delivery and by significant damage to target and non-target cells. We have developed a cell level approach for selective and guided transmembrane injection of extracellular cargo into specific target cells using transient plasmonic nanobubbles (PNB) as cell-specific nano-injectors. As a technical platform for this method we developed a laser flow cell processing system. The PNB injection method and flow system were tested in heterogeneous cell suspensions of target and non-target cells for delivery of Dextran-FITC dye into squamous cell carcinoma HN31 cells and transfection of human T-cells with a green fluorescent protein-encoding plasmid. In both models the method demonstrated single cell type selectivity, high efficacy of delivery (96% both for HN31 cells T-cells), speed of delivery (nanoseconds) and viability of treated target cells (96% for HN31 cells and 75% for T-cells). The PNB injection method may therefore be beneficial for real time processing of human grafts without removal of physiologically important cells. Copyright © 2012 Elsevier Ltd. All rights reserved.

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

PubMed

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.

Attention to Color Sharpens Neural Population Tuning via Feedback Processing in the Human Visual Cortex Hierarchy.

PubMed

Bartsch, Mandy V; Loewe, Kristian; Merkel, Christian; Heinze, Hans-Jochen; Schoenfeld, Mircea A; Tsotsos, John K; Hopf, Jens-Max

2017-10-25

Attention can facilitate the selection of elementary object features such as color, orientation, or motion. This is referred to as feature-based attention and it is commonly attributed to a modulation of the gain and tuning of feature-selective units in visual cortex. Although gain mechanisms are well characterized, little is known about the cortical processes underlying the sharpening of feature selectivity. Here, we show with high-resolution magnetoencephalography in human observers (men and women) that sharpened selectivity for a particular color arises from feedback processing in the human visual cortex hierarchy. To assess color selectivity, we analyze the response to a color probe that varies in color distance from an attended color target. We find that attention causes an initial gain enhancement in anterior ventral extrastriate cortex that is coarsely selective for the target color and transitions within ∼100 ms into a sharper tuned profile in more posterior ventral occipital cortex. We conclude that attention sharpens selectivity over time by attenuating the response at lower levels of the cortical hierarchy to color values neighboring the target in color space. These observations support computational models proposing that attention tunes feature selectivity in visual cortex through backward-propagating attenuation of units less tuned to the target. SIGNIFICANCE STATEMENT Whether searching for your car, a particular item of clothing, or just obeying traffic lights, in everyday life, we must select items based on color. But how does attention allow us to select a specific color? Here, we use high spatiotemporal resolution neuromagnetic recordings to examine how color selectivity emerges in the human brain. We find that color selectivity evolves as a coarse to fine process from higher to lower levels within the visual cortex hierarchy. Our observations support computational models proposing that feature selectivity increases over time by attenuating the responses of less-selective cells in lower-level brain areas. These data emphasize that color perception involves multiple areas across a hierarchy of regions, interacting with each other in a complex, recursive manner. Copyright © 2017 the authors 0270-6474/17/3710346-12$15.00/0.

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

PubMed

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.

Parallel perceptual enhancement and hierarchic relevance evaluation in an audio-visual conjunction task.

PubMed

Potts, Geoffrey F; Wood, Susan M; Kothmann, Delia; Martin, Laura E

2008-10-21

Attention directs limited-capacity information processing resources to a subset of available perceptual representations. The mechanisms by which attention selects task-relevant representations for preferential processing are not fully known. Triesman and Gelade's [Triesman, A., Gelade, G., 1980. A feature integration theory of attention. Cognit. Psychol. 12, 97-136.] influential attention model posits that simple features are processed preattentively, in parallel, but that attention is required to serially conjoin multiple features into an object representation. Event-related potentials have provided evidence for this model showing parallel processing of perceptual features in the posterior Selection Negativity (SN) and serial, hierarchic processing of feature conjunctions in the Frontal Selection Positivity (FSP). Most prior studies have been done on conjunctions within one sensory modality while many real-world objects have multimodal features. It is not known if the same neural systems of posterior parallel processing of simple features and frontal serial processing of feature conjunctions seen within a sensory modality also operate on conjunctions between modalities. The current study used ERPs and simultaneously presented auditory and visual stimuli in three task conditions: Attend Auditory (auditory feature determines the target, visual features are irrelevant), Attend Visual (visual features relevant, auditory irrelevant), and Attend Conjunction (target defined by the co-occurrence of an auditory and a visual feature). In the Attend Conjunction condition when the auditory but not the visual feature was a target there was an SN over auditory cortex, when the visual but not auditory stimulus was a target there was an SN over visual cortex, and when both auditory and visual stimuli were targets (i.e. conjunction target) there were SNs over both auditory and visual cortex, indicating parallel processing of the simple features within each modality. In contrast, an FSP was present when either the visual only or both auditory and visual features were targets, but not when only the auditory stimulus was a target, indicating that the conjunction target determination was evaluated serially and hierarchically with visual information taking precedence. This indicates that the detection of a target defined by audio-visual conjunction is achieved via the same mechanism as within a single perceptual modality, through separate, parallel processing of the auditory and visual features and serial processing of the feature conjunction elements, rather than by evaluation of a fused multimodal percept.

Capture-SELEX: Selection of DNA Aptamers for Aminoglycoside Antibiotics

PubMed Central

2012-01-01

Small organic molecules are challenging targets for an aptamer selection using the SELEX technology (SELEX—Systematic Evolution of Ligans by EXponential enrichment). Often they are not suitable for immobilization on solid surfaces, which is a common procedure in known aptamer selection methods. The Capture-SELEX procedure allows the selection of DNA aptamers for solute targets. A special SELEX library was constructed with the aim to immobilize this library on magnetic beads or other surfaces. For this purpose a docking sequence was incorporated into the random region of the library enabling hybridization to a complementary oligo fixed on magnetic beads. Oligonucleotides of the library which exhibit high affinity to the target and a secondary structure fitting to the target are released from the beads for binding to the target during the aptamer selection process. The oligonucleotides of these binding complexes were amplified, purified, and immobilized via the docking sequence to the magnetic beads as the starting point of the following selection round. Based on this Capture-SELEX procedure, the successful DNA aptamer selection for the aminoglycoside antibiotic kanamycin A as a small molecule target is described. PMID:23326761

Human centromedian-parafascicular complex signals sensory cues for goal-oriented behavior selection.

PubMed

Schepers, Inga M; Beck, Anne-Kathrin; Bräuer, Susann; Schwabe, Kerstin; Abdallat, Mahmoud; Sandmann, Pascale; Dengler, Reinhard; Rieger, Jochem W; Krauss, Joachim K

2017-05-15

Experimental research has shown that the centromedian-parafascicular complex (CM-Pf) of the intralaminar thalamus is activated in attentional orienting and processing of behaviorally relevant stimuli. These observations resulted in the hypothesis that the CM-Pf plays a pivotal role in goal-oriented behavior selection. We here set out to test this hypothesis with electrophysiological recordings from patients with electrodes implanted in CM-Pf for deep brain stimulation (DBS) treatment of chronic neuropathic pain. Six patients participated in (1) an auditory three-class oddball experiment, which required a button press to target tones, but not to standard and deviant tones and in (2) a multi-speaker experiment with a target word that required attention selection and a target image that required response selection. Subjects showed transient neural responses (8-15Hz) to the target tone and the target word. Two subjects additionally showed transient neural responses (15-25Hz) to the target image. All sensory target stimuli were related to an internal goal and required a behavior selection (attention selection, response selection). In group analyses, neural responses were greater to target tones than deviant and standard tones and to target words than other task-relevant words that did not require attention selection. The transient neural responses occurred after the target stimuli but prior to the overt behavioral response. Our results demonstrate that in human subjects the CM-Pf is involved in signaling sensory inputs related to goal-oriented selection of behavior. Copyright © 2017 Elsevier Inc. All rights reserved.

Multiple products monitoring as a robust approach for peptide quantification.

PubMed

Baek, Je-Hyun; Kim, Hokeun; Shin, Byunghee; Yu, Myeong-Hee

2009-07-01

Quantification of target peptides and proteins is crucial for biomarker discovery. Approaches such as selected reaction monitoring (SRM) and multiple reaction monitoring (MRM) rely on liquid chromatography and mass spectrometric analysis of defined peptide product ions. These methods are not very widespread because the determination of quantifiable product ion using either SRM or MRM is a very time-consuming process. We developed a novel approach for quantifying target peptides without such an arduous process of ion selection. This method is based on monitoring multiple product ions (multiple products monitoring: MpM) from full-range MS2 spectra of a target precursor. The MpM method uses a scoring system that considers both the absolute intensities of product ions and the similarities between the query MS2 spectrum and the reference MS2 spectrum of the target peptide. Compared with conventional approaches, MpM greatly improves sensitivity and selectivity of peptide quantification using an ion-trap mass spectrometer.

Current Challenges in Detecting Food Allergens by Shotgun and Targeted Proteomic Approaches: A Case Study on Traces of Peanut Allergens in Baked Cookies

PubMed Central

Pedreschi, Romina; Nørgaard, Jørgen; Maquet, Alain

2012-01-01

There is a need for selective and sensitive methods to detect the presence of food allergens at trace levels in highly processed food products. In this work, a combination of non-targeted and targeted proteomics approaches are used to illustrate the difficulties encountered in the detection of the major peanut allergens Ara h 1, Ara h 2 and Ara h 3 from a representative processed food matrix. Shotgun proteomics was employed for selection of the proteotypic peptides for targeted approaches via selective reaction monitoring. Peanut presence through detection of the proteotypic Ara h 3/4 peptides AHVQVVDSNGNR (m/z 432.5, 3+) and SPDIYNPQAGSLK (m/z 695.4, 2+) was confirmed and the developed method was able to detect peanut presence at trace levels (≥10 μg peanut g−1 matrix) in baked cookies. PMID:22413066

The influence of cueing on attentional focus in perceptual decision making.

PubMed

Yang, Cheng-Ta; Little, Daniel R; Hsu, Ching-Chun

2014-11-01

Selective attention has been known to play an important role in decision making. In the present study, we combined a cueing paradigm with a redundant-target detection task to examine how attention affects the decision process when detecting the redundant targets. Cue validity was manipulated in two experiments. The results showed that when the cue was 50 % valid in one experiment, the participants adopted a parallel self-terminating processing strategy, indicative of a diffuse attentional focus on both target locations. When the cue was 100 % valid in the second experiment, all of the participants switched to a serial self-terminating processing strategy, which in our study indicated focused attention to a single target location. This study demonstrates the flexibility of the decision mechanism and highlights the importance of top-down control in selecting a decision strategy.

How humans search for targets through time: A review of data and theory from the attentional blink

PubMed Central

Dux, Paul E.; Marois, Réne

2009-01-01

Under conditions of rapid serial visual presentation (RSVP), subjects display a reduced ability to report the second of two targets (Target 2; T2) in a stream of distractors if it appears within 200–500 ms of Target 1 (T1). This effect, known as the attentional blink (AB), has been central in characterizing the limits of humans’ ability to consciously perceive stimuli distributed across time. Here we review theoretical accounts of the AB and examine how they explain key findings in the literature. We conclude that the AB arises from attentional demands of T1 for selection, working memory encoding, episodic registration and response selection, which prevents this high-level central resource from being applied to T2 at short T1–T2 lags. T1 processing also transiently impairs the re-deployment of these attentional resources to subsequent targets, and the inhibition of distractors that appear in close temporal proximity to T2. While these findings are consistent with a multi-factorial account of the AB, they can also be largely explained by assuming that the activation of these multiple processes depend on a common capacity-limited attentional process to select behaviorally relevant events presented amongst temporally distributed distractors. Thus, at its core, the attentional blink may ultimately reveal the temporal limits of the deployment of selective attention. PMID:19933555

Addressing the selective role of distinct prefrontal areas in response suppression: A study with brain tumor patients.

PubMed

Arbula, Sandra; Pacella, Valentina; De Pellegrin, Serena; Rossetto, Marta; Denaro, Luca; D'Avella, Domenico; Della Puppa, Alessandro; Vallesi, Antonino

2017-06-01

The diverging evidence for functional localization of response inhibition within the prefrontal cortex might be justified by the still unclear involvement of other intrinsically related cognitive processes like response selection and sustained attention. In this study, the main aim was to understand whether inhibitory impairments, previously found in patients with both left and right frontal lesions, could be better accounted for by assessing these potentially related cognitive processes. We tested 37 brain tumor patients with left prefrontal, right prefrontal and non-prefrontal lesions and a healthy control group on Go/No-Go and Foreperiod tasks. In both types of tasks inhibitory impairments are likely to cause false alarms, although additionally the former task requires response selection and the latter target detection abilities. Irrespective of the task context, patients with right prefrontal damage showed frequent Go and target omissions, probably due to sustained attention lapses. Left prefrontal patients, on the other hand, showed both Go and target omissions and high false alarm rates to No-Go and warning stimuli, suggesting a decisional rather than an inhibitory impairment. An exploratory whole-brain voxel-based lesion-symptom mapping analysis confirmed the association of left ventrolateral and dorsolateral prefrontal lesions with target discrimination failure, and right ventrolateral and medial prefrontal lesions with target detection failure. Results from this study show how left and right prefrontal areas, which previous research has linked to response inhibition, underlie broader cognitive control processes, particularly involved in response selection and target detection. Based on these findings, we suggest that successful inhibitory control relies on more than one functionally distinct process which, if assessed appropriately, might help us to better understand inhibitory impairments across different pathologies. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

Software for Partly Automated Recognition of Targets

NASA Technical Reports Server (NTRS)

Opitz, David; Blundell, Stuart; Bain, William; Morris, Matthew; Carlson, Ian; Mangrich, Mark; Selinsky, T.

2002-01-01

The Feature Analyst is a computer program for assisted (partially automated) recognition of targets in images. This program was developed to accelerate the processing of high-resolution satellite image data for incorporation into geographic information systems (GIS). This program creates an advanced user interface that embeds proprietary machine-learning algorithms in commercial image-processing and GIS software. A human analyst provides samples of target features from multiple sets of data, then the software develops a data-fusion model that automatically extracts the remaining features from selected sets of data. The program thus leverages the natural ability of humans to recognize objects in complex scenes, without requiring the user to explain the human visual recognition process by means of lengthy software. Two major subprograms are the reactive agent and the thinking agent. The reactive agent strives to quickly learn the user's tendencies while the user is selecting targets and to increase the user's productivity by immediately suggesting the next set of pixels that the user may wish to select. The thinking agent utilizes all available resources, taking as much time as needed, to produce the most accurate autonomous feature-extraction model possible.

Selective attention and control of action: comparative psychology of an artificial, evolved agent and people.

PubMed

Ward, Robert; Ward, Ronnie

2008-10-01

This study examined the selective attention abilities of a simple, artificial, evolved agent and considered implications of the agent's performance for theories of selective attention and action. The agent processed two targets in continuous time, catching one and then the other. This task required many cognitive operations, including prioritizing the first target (T1) over the second (T2); selectively focusing responses on T1, while preventing T2 from interfering with responses; creating a memory for the unselected T2 item, so that it could be efficiently processed later; and reallocating processing towards T2 after catching T1. The evolved agent demonstrated all these abilities. Analysis shows that the agent used reactive inhibition to selectively focus behavior. That is, the more salient T2, the more strongly responses towards T2 were inhibited and the slower the agent was to subsequently reallocate processing towards T2. Reactive inhibition was also suggested in two experiments with people, performing a virtually identical catch task. The presence of reactive inhibition in the simple agent and in people suggests that it is an important mechanism for selective processing.

Selective attention in perceptual adjustments to voice.

PubMed

Mullennix, J W; Howe, J N

1999-10-01

The effects of perceptual adjustments to voice information on the perception of isolated spoken words were examined. In two experiments, spoken target words were preceded or followed within a trial by a neutral word spoken in the same voice or in a different voice as the target. Over-all, words were reproduced more accurately on trials on which the voice of the neutral word matched the voice of the spoken target word, suggesting that perceptual adjustments to voice interfere with word processing. This result, however, was mediated by selective attention to voice. The results provide further evidence of a close processing relationship between perceptual adjustments to voice and spoken word recognition.

Spatial attention does not require preattentive grouping.

PubMed

Vecera, S P; Behrmann, M

1997-01-01

Does spatial attention follow a full preattentive analysis of the visual field, or can attention select from ungrouped regions of the visual field? We addressed this question by testing an apperceptive agnosic patient, J. W., in tasks involving both spatial selection and preattentive grouping. Results suggest that J.W. had intact spatial attention: He was faster to detect targets appearing at cued location relative to targets appearing at uncued locations. However, his preattentive processes were severely disrupted. Gestalt grouping and symmetry perception, both thought to involve preattentive processes, were impaired in J. W. Also, he could not use gestalt grouping cues to guide spatial attention. These results suggest that spatial attention is not completely dependent on preattentive grouping processes. We argue that preattentive grouping processes and spatial attention may mutually constrain one another in guiding the attentional selection of visual stimuli but that these 2 processes are isolated from one another.

Mapping protein-protein interactions with phage-displayed combinatorial peptide libraries.

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

Kay, B. K.; Castagnoli, L.; Biosciences Division

This unit describes the process and analysis of affinity selecting bacteriophage M13 from libraries displaying combinatorial peptides fused to either a minor or major capsid protein. Direct affinity selection uses target protein bound to a microtiter plate followed by purification of selected phage by ELISA. Alternatively, there is a bead-based affinity selection method. These methods allow one to readily isolate peptide ligands that bind to a protein target of interest and use the consensus sequence to search proteomic databases for putative interacting proteins.

Action video games and improved attentional control: Disentangling selection- and response-based processes.

PubMed

Chisholm, Joseph D; Kingstone, Alan

2015-10-01

Research has demonstrated that experience with action video games is associated with improvements in a host of cognitive tasks. Evidence from paradigms that assess aspects of attention has suggested that action video game players (AVGPs) possess greater control over the allocation of attentional resources than do non-video-game players (NVGPs). Using a compound search task that teased apart selection- and response-based processes (Duncan, 1985), we required participants to perform an oculomotor capture task in which they made saccades to a uniquely colored target (selection-based process) and then produced a manual directional response based on information within the target (response-based process). We replicated the finding that AVGPs are less susceptible to attentional distraction and, critically, revealed that AVGPs outperform NVGPs on both selection-based and response-based processes. These results not only are consistent with the improved-attentional-control account of AVGP benefits, but they suggest that the benefit of action video game playing extends across the full breadth of attention-mediated stimulus-response processes that impact human performance.

Trajectory Optimization for Missions to Small Bodies with a Focus on Scientific Merit.

PubMed

Englander, Jacob A; Vavrina, Matthew A; Lim, Lucy F; McFadden, Lucy A; Rhoden, Alyssa R; Noll, Keith S

2017-01-01

Trajectory design for missions to small bodies is tightly coupled both with the selection of targets for a mission and with the choice of spacecraft power, propulsion, and other hardware. Traditional methods of trajectory optimization have focused on finding the optimal trajectory for an a priori selection of destinations and spacecraft parameters. Recent research has expanded the field of trajectory optimization to multidisciplinary systems optimization that includes spacecraft parameters. The logical next step is to extend the optimization process to include target selection based not only on engineering figures of merit but also scientific value. This paper presents a new technique to solve the multidisciplinary mission optimization problem for small-bodies missions, including classical trajectory design, the choice of spacecraft power and propulsion systems, and also the scientific value of the targets. This technique, when combined with modern parallel computers, enables a holistic view of the small body mission design process that previously required iteration among several different design processes.

Selective Attention and Sensory Modality in Aging: Curses and Blessings.

PubMed

Van Gerven, Pascal W M; Guerreiro, Maria J S

2016-01-01

The notion that selective attention is compromised in older adults as a result of impaired inhibitory control is well established. Yet it is primarily based on empirical findings covering the visual modality. Auditory and especially, cross-modal selective attention are remarkably underexposed in the literature on aging. In the past 5 years, we have attempted to fill these voids by investigating performance of younger and older adults on equivalent tasks covering all four combinations of visual or auditory target, and visual or auditory distractor information. In doing so, we have demonstrated that older adults are especially impaired in auditory selective attention with visual distraction. This pattern of results was not mirrored by the results from our psychophysiological studies, however, in which both enhancement of target processing and suppression of distractor processing appeared to be age equivalent. We currently conclude that: (1) age-related differences of selective attention are modality dependent; (2) age-related differences of selective attention are limited; and (3) it remains an open question whether modality-specific age differences in selective attention are due to impaired distractor inhibition, impaired target enhancement, or both. These conclusions put the longstanding inhibitory deficit hypothesis of aging in a new perspective.

Selective tuning of the right inferior frontal gyrus during target detection

PubMed Central

Hampshire, Adam; Thompson, Russell; Duncan, John; Owen, Adrian M.

2010-01-01

In the human brain, a network of frontal and parietal regions is commonly recruited during tasks that demand the deliberate, focused control of thought and action. Previously, using a simple target detection task, we reported striking differences in the selectivity of the BOLD response in anatomically distinct subregions of this network. In particular, it was observed that the right inferior frontal gyrus (IFG) followed a tightly tuned function, selectively responding only to the current target object. Here, we examine this functional specialization further, using adapted versions of our original task. Our results demonstrate that the response of the right IFG to targets is a strong and replicable phenomenon. It occurs under increased attentional load, when targets and distractors are equally frequent, and when controlling for inhibitory processes. These findings support the hypothesis that the right IFG responds selectively to those items that are of the most relevance to the currently intended task schema. PMID:19246331

Directional emittance surface measurement system and process

NASA Technical Reports Server (NTRS)

Puram, Chith K. (Inventor); Daryabeigi, Kamran (Inventor); Wright, Robert (Inventor); Alderfer, David W. (Inventor)

1994-01-01

Apparatus and process for measuring the variation of directional emittance of surfaces at various temperatures using a radiometric infrared imaging system. A surface test sample is coated onto a copper target plate provided with selective heating within the desired incremental temperature range to be tested and positioned onto a precision rotator to present selected inclination angles of the sample relative to the fixed positioned and optically aligned infrared imager. A thermal insulator holder maintains the target plate on the precision rotator. A screen display of the temperature obtained by the infrared imager, and inclination readings are provided with computer calculations of directional emittance being performed automatically according to equations provided to convert selected incremental target temperatures and inclination angles to relative target directional emittance values. The directional emittance of flat black lacquer and an epoxy resin measurements obtained are in agreement with the predictions of the electromagnetic theory and with directional emittance data inferred from directional reflectance measurements made on a spectrophotometer.

The stage of priming: are intertrial repetition effects attentional or decisional?

PubMed

Becker, Stefanie I

2008-02-01

In a visual search task, reaction times to a target are shorter when its features are repeated than when they switch. The present study investigated whether these priming effects affect the attentional stage of target selection, as proposed by the priming of pop-out account, or whether they modulate performance at a later, post-selectional stage, as claimed by the episodic retrieval view. Secondly, to test whether priming affects only the target-defining feature, or whether priming can apply to all target-features in a holistic fashion, two presentation conditions were invoked, that either promoted encoding of only the target-defining feature or holistic encoding of all target features. Results from four eye tracking experiments involving a size and colour singleton target showed that, first, priming modulates selectional processes concerned with guiding attention. Second, there were traces of holistic priming effects, which however were not modulated by the displays, but by expectation and task difficulty.

Attention and emotion: an ERP analysis of facilitated emotional stimulus processing.

PubMed

Schupp, Harald T; Junghöfer, Markus; Weike, Almut I; Hamm, Alfons O

2003-06-11

Recent event-related potential studies observed an early posterior negativity (EPN) reflecting facilitated processing of emotional images. The present study explored if the facilitated processing of emotional pictures is sustained while subjects perform an explicit non-emotional attention task. EEG was recorded from 129 channels while subjects viewed a rapid continuous stream of images containing emotional pictures as well as task-related checkerboard images. As expected, explicit selective attention to target images elicited large P3 waves. Interestingly, emotional stimuli guided stimulus-driven selective encoding as reflected by augmented EPN amplitudes to emotional stimuli, in particular to stimuli of evolutionary significance (erotic contents, mutilations, and threat). These data demonstrate the selective encoding of emotional stimuli while top-down attentional control was directed towards non-emotional target stimuli.

Vigilance problems in orbiter processing

NASA Technical Reports Server (NTRS)

Swart, William W.; Safford, Robert R.; Kennedy, David B.; Yadi, Bert A.; Barth, Timothy S.

1993-01-01

A pilot experiment was done to determine what factors influence potential performance errors related to vigilance in Orbiter processing activities. The selected activities include post flight inspection for burned gap filler material and pre-rollout inspection for tile processing shim material. It was determined that the primary factors related to performance decrement were the color of the target and the difficulty of the target presentation.

Software for Partly Automated Recognition of Targets

NASA Technical Reports Server (NTRS)

Opitz, David; Blundell, Stuart; Bain, William; Morris, Matthew; Carlson, Ian; Mangrich, Mark

2003-01-01

The Feature Analyst is a computer program for assisted (partially automated) recognition of targets in images. This program was developed to accelerate the processing of high-resolution satellite image data for incorporation into geographic information systems (GIS). This program creates an advanced user interface that embeds proprietary machine-learning algorithms in commercial image-processing and GIS software. A human analyst provides samples of target features from multiple sets of data, then the software develops a data-fusion model that automatically extracts the remaining features from selected sets of data. The program thus leverages the natural ability of humans to recognize objects in complex scenes, without requiring the user to explain the human visual recognition process by means of lengthy software. Two major subprograms are the reactive agent and the thinking agent. The reactive agent strives to quickly learn the user s tendencies while the user is selecting targets and to increase the user s productivity by immediately suggesting the next set of pixels that the user may wish to select. The thinking agent utilizes all available resources, taking as much time as needed, to produce the most accurate autonomous feature-extraction model possible.

Feature Transformation Detection Method with Best Spectral Band Selection Process for Hyper-spectral Imaging

NASA Astrophysics Data System (ADS)

Chen, Hai-Wen; McGurr, Mike; Brickhouse, Mark

2015-11-01

We present a newly developed feature transformation (FT) detection method for hyper-spectral imagery (HSI) sensors. In essence, the FT method, by transforming the original features (spectral bands) to a different feature domain, may considerably increase the statistical separation between the target and background probability density functions, and thus may significantly improve the target detection and identification performance, as evidenced by the test results in this paper. We show that by differentiating the original spectral, one can completely separate targets from the background using a single spectral band, leading to perfect detection results. In addition, we have proposed an automated best spectral band selection process with a double-threshold scheme that can rank the available spectral bands from the best to the worst for target detection. Finally, we have also proposed an automated cross-spectrum fusion process to further improve the detection performance in lower spectral range (<1000 nm) by selecting the best spectral band pair with multivariate analysis. Promising detection performance has been achieved using a small background material signature library for concept-proving, and has then been further evaluated and verified using a real background HSI scene collected by a HYDICE sensor.

A novel heterogeneous training sample selection method on space-time adaptive processing

NASA Astrophysics Data System (ADS)

Wang, Qiang; Zhang, Yongshun; Guo, Yiduo

2018-04-01

The performance of ground target detection about space-time adaptive processing (STAP) decreases when non-homogeneity of clutter power is caused because of training samples contaminated by target-like signals. In order to solve this problem, a novel nonhomogeneous training sample selection method based on sample similarity is proposed, which converts the training sample selection into a convex optimization problem. Firstly, the existing deficiencies on the sample selection using generalized inner product (GIP) are analyzed. Secondly, the similarities of different training samples are obtained by calculating mean-hausdorff distance so as to reject the contaminated training samples. Thirdly, cell under test (CUT) and the residual training samples are projected into the orthogonal subspace of the target in the CUT, and mean-hausdorff distances between the projected CUT and training samples are calculated. Fourthly, the distances are sorted in order of value and the training samples which have the bigger value are selective preference to realize the reduced-dimension. Finally, simulation results with Mountain-Top data verify the effectiveness of the proposed method.

Highly Multiplexed RNA Aptamer Selection using a Microplate-based Microcolumn Device.

PubMed

Reinholt, Sarah J; Ozer, Abdullah; Lis, John T; Craighead, Harold G

2016-07-19

We describe a multiplexed RNA aptamer selection to 19 different targets simultaneously using a microcolumn-based device, MEDUSA (Microplate-based Enrichment Device Used for the Selection of Aptamers), as well as a modified selection process, that significantly reduce the time and reagents needed for selections. We exploited MEDUSA's reconfigurable design between parallel and serially-connected microcolumns to enable the use of just 2 aliquots of starting library, and its 96-well microplate compatibility to enable the continued use of high-throughput techniques in downstream processes. Our modified selection protocol allowed us to perform the equivalent of a 10-cycle selection in the time it takes for 4 traditional selection cycles. Several aptamers were discovered with nanomolar dissociation constants. Furthermore, aptamers were identified that not only bound with high affinity, but also acted as inhibitors to significantly reduce the activity of their target protein, mouse decapping exoribonuclease (DXO). The aptamers resisted DXO's exoribonuclease activity, and in studies monitoring DXO's degradation of a 30-nucleotide substrate, less than 1 μM of aptamer demonstrated significant inhibition of DXO activity. This aptamer selection method using MEDUSA helps to overcome some of the major challenges with traditional aptamer selections, and provides a platform for high-throughput selections that lends itself to process automation.

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

PubMed Central

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

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

PubMed

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.

Visual analytics in cheminformatics: user-supervised descriptor selection for QSAR methods.

PubMed

Martínez, María Jimena; Ponzoni, Ignacio; Díaz, Mónica F; Vazquez, Gustavo E; Soto, Axel J

2015-01-01

The design of QSAR/QSPR models is a challenging problem, where the selection of the most relevant descriptors constitutes a key step of the process. Several feature selection methods that address this step are concentrated on statistical associations among descriptors and target properties, whereas the chemical knowledge is left out of the analysis. For this reason, the interpretability and generality of the QSAR/QSPR models obtained by these feature selection methods are drastically affected. Therefore, an approach for integrating domain expert's knowledge in the selection process is needed for increase the confidence in the final set of descriptors. In this paper a software tool, which we named Visual and Interactive DEscriptor ANalysis (VIDEAN), that combines statistical methods with interactive visualizations for choosing a set of descriptors for predicting a target property is proposed. Domain expertise can be added to the feature selection process by means of an interactive visual exploration of data, and aided by statistical tools and metrics based on information theory. Coordinated visual representations are presented for capturing different relationships and interactions among descriptors, target properties and candidate subsets of descriptors. The competencies of the proposed software were assessed through different scenarios. These scenarios reveal how an expert can use this tool to choose one subset of descriptors from a group of candidate subsets or how to modify existing descriptor subsets and even incorporate new descriptors according to his or her own knowledge of the target property. The reported experiences showed the suitability of our software for selecting sets of descriptors with low cardinality, high interpretability, low redundancy and high statistical performance in a visual exploratory way. Therefore, it is possible to conclude that the resulting tool allows the integration of a chemist's expertise in the descriptor selection process with a low cognitive effort in contrast with the alternative of using an ad-hoc manual analysis of the selected descriptors. Graphical abstractVIDEAN allows the visual analysis of candidate subsets of descriptors for QSAR/QSPR. In the two panels on the top, users can interactively explore numerical correlations as well as co-occurrences in the candidate subsets through two interactive graphs.

System-level multi-target drug discovery from natural products with applications to cardiovascular diseases.

PubMed

Zheng, Chunli; Wang, Jinan; Liu, Jianling; Pei, Mengjie; Huang, Chao; Wang, Yonghua

2014-08-01

The term systems pharmacology describes a field of study that uses computational and experimental approaches to broaden the view of drug actions rooted in molecular interactions and advance the process of drug discovery. The aim of this work is to stick out the role that the systems pharmacology plays across the multi-target drug discovery from natural products for cardiovascular diseases (CVDs). Firstly, based on network pharmacology methods, we reconstructed the drug-target and target-target networks to determine the putative protein target set of multi-target drugs for CVDs treatment. Secondly, we reintegrated a compound dataset of natural products and then obtained a multi-target compounds subset by virtual-screening process. Thirdly, a drug-likeness evaluation was applied to find the ADME-favorable compounds in this subset. Finally, we conducted in vitro experiments to evaluate the reliability of the selected chemicals and targets. We found that four of the five randomly selected natural molecules can effectively act on the target set for CVDs, indicating the reasonability of our systems-based method. This strategy may serve as a new model for multi-target drug discovery of complex diseases.

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

PubMed

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 Physiological Society.

Rhythmic Sampling within and between Objects despite Sustained Attention at a Cued Location

PubMed Central

Fiebelkorn, Ian C.; Saalmann, Yuri B.; Kastner, Sabine

2013-01-01

SUMMARY The brain directs its limited processing resources through various selection mechanisms, broadly referred to as attention. The present study investigated the temporal dynamics of two such selection mechanisms: space- and object-based selection. Previous evidence has demonstrated that preferential processing resulting from a spatial cue (i.e., space-based selection) spreads to uncued locations, if those locations are part of the same object (i.e., resulting in object-based selection). But little is known about the relationship between these fundamental selection mechanisms. Here, we used human behavioral data to determine how space- and object-based selection simultaneously evolve under conditions that promote sustained attention at a cued location, varying the cue-to-target interval from 300—1100 ms. We tracked visual-target detection at a cued location (i.e., space-based selection), at an uncued location that was part of the same object (i.e., object-based selection), and at an uncued location that was part of a different object (i.e., in the absence of space- and object-based selection). The data demonstrate that even under static conditions, there is a moment-to-moment reweighting of attentional priorities based on object properties. This reweighting is revealed through rhythmic patterns of visual-target detection both within (at 8 Hz) and between (at 4 Hz) objects. PMID:24316204

Lorazepam induces multiple disturbances in selective attention: attentional overload, decrement in target processing efficiency, and shifts in perceptual discrimination and response bias.

PubMed

Michael, George Andrew; Bacon, Elisabeth; Offerlin-Meyer, Isabelle

2007-09-01

There is a general consensus that benzodiazepines affect attentional processes, yet only few studies have tried to investigate these impairments in detail. The purpose of the present study was to investigate the effects of a single dose of Lorazepam on performance in a target cancellation task with important time constraints. We measured correct target detections and correct distractor rejections, misses and false positives. The results show that Lorazepam produces multiple kinds of shifts in performance, which suggests that it impairs multipLe processes: (a) the evolution of performance over time was not the same between the placebo and the Lorazepam groups, with the Lorazepam affecting performance quite early after the beginning of the test. This is suggestive of a depletion of attentional resources during sequential attentional processing; (b) Lorazepam affected differently target and distractor processing, with target detection being the most impaired; (c) misses were more frequent under Lorazepam than under placebo, but no such difference was observed as far as false positives were concerned. Signal detection analyses showed that Lorazepam (d) decreased perceptual discrimination, and (e) reliably increased response bias. Our results bring new insights on the multiple effects of Lorazepam on selective attention which, when combined, may have deleterious effects on human performance.

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

NASA Astrophysics Data System (ADS)

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.

A community-engaged approach to select geographic areas for interventions to reduce health disparities.

PubMed

Cromley, Ellen; Kleinman, Lawrence C; Ramos, Michelle A; Arniella, Guedy; Viswanathan, Nalini; Garel, Mischka; Horowitz, Carol R

2011-01-01

While neighborhood-based approaches to eliminate health disparities are on the rise, there is little guidance on how researchers may engage with community partners to select geographic areas for interventions to reduce health disparities. We aimed to identify a small geographic area to target interventions to improve diabetes-related outcomes. We describe lessons learned from a community-engaged approach to specify the geographic area of focus. A community-academic partnership of more than 20 organizations collaborated to develop and employ a 5-stage process to specify a target area for diabetes preventions and control activities. A coalition with local knowledge and ties to the community can develop criteria and direct a process leading to selection of a geographic area, increased research capacity, and strengthened relationships among partners. A participatory approach can be effective in defining a geographic area for targeting interventions to reduce health disparities.

Cortical neurons of bats respond best to echoes from nearest targets when listening to natural biosonar multi-echo streams.

PubMed

Beetz, M Jerome; Hechavarría, Julio C; Kössl, Manfred

2016-10-27

Bats orientate in darkness by listening to echoes from their biosonar calls, a behaviour known as echolocation. Recent studies showed that cortical neurons respond in a highly selective manner when stimulated with natural echolocation sequences that contain echoes from single targets. However, it remains unknown how cortical neurons process echolocation sequences containing echo information from multiple objects. In the present study, we used echolocation sequences containing echoes from three, two or one object separated in the space depth as stimuli to study neuronal activity in the bat auditory cortex. Neuronal activity was recorded with multi-electrode arrays placed in the dorsal auditory cortex, where neurons tuned to target-distance are found. Our results show that target-distance encoding neurons are mostly selective to echoes coming from the closest object, and that the representation of echo information from distant objects is selectively suppressed. This suppression extends over a large part of the dorsal auditory cortex and may override possible parallel processing of multiple objects. The presented data suggest that global cortical suppression might establish a cortical "default mode" that allows selectively focusing on close obstacle even without active attention from the animals.

Cortical neurons of bats respond best to echoes from nearest targets when listening to natural biosonar multi-echo streams

PubMed Central

Beetz, M. Jerome; Hechavarría, Julio C.; Kössl, Manfred

2016-01-01

Bats orientate in darkness by listening to echoes from their biosonar calls, a behaviour known as echolocation. Recent studies showed that cortical neurons respond in a highly selective manner when stimulated with natural echolocation sequences that contain echoes from single targets. However, it remains unknown how cortical neurons process echolocation sequences containing echo information from multiple objects. In the present study, we used echolocation sequences containing echoes from three, two or one object separated in the space depth as stimuli to study neuronal activity in the bat auditory cortex. Neuronal activity was recorded with multi-electrode arrays placed in the dorsal auditory cortex, where neurons tuned to target-distance are found. Our results show that target-distance encoding neurons are mostly selective to echoes coming from the closest object, and that the representation of echo information from distant objects is selectively suppressed. This suppression extends over a large part of the dorsal auditory cortex and may override possible parallel processing of multiple objects. The presented data suggest that global cortical suppression might establish a cortical “default mode” that allows selectively focusing on close obstacle even without active attention from the animals. PMID:27786252

Clustering analysis of moving target signatures

NASA Astrophysics Data System (ADS)

Martone, Anthony; Ranney, Kenneth; Innocenti, Roberto

2010-04-01

Previously, we developed a moving target indication (MTI) processing approach to detect and track slow-moving targets inside buildings, which successfully detected moving targets (MTs) from data collected by a low-frequency, ultra-wideband radar. Our MTI algorithms include change detection, automatic target detection (ATD), clustering, and tracking. The MTI algorithms can be implemented in a real-time or near-real-time system; however, a person-in-the-loop is needed to select input parameters for the clustering algorithm. Specifically, the number of clusters to input into the cluster algorithm is unknown and requires manual selection. A critical need exists to automate all aspects of the MTI processing formulation. In this paper, we investigate two techniques that automatically determine the number of clusters: the adaptive knee-point (KP) algorithm and the recursive pixel finding (RPF) algorithm. The KP algorithm is based on a well-known heuristic approach for determining the number of clusters. The RPF algorithm is analogous to the image processing, pixel labeling procedure. Both algorithms are used to analyze the false alarm and detection rates of three operational scenarios of personnel walking inside wood and cinderblock buildings.

Separation of sodium-22 from irradiated targets

DOEpatents

Taylor, Wayne A.; Jamriska, David

1996-01-01

A process for selective separation of sodium-22 from an irradiated target including dissolving an irradiated target to form a first solution, contacting the first solution with hydrated antimony pentoxide to selectively separate sodium-22 from the first solution, separating the hydrated antimony pentoxide including the separated sodium-22 from the first solution, dissolving the hydrated antimony pentoxide including the separated sodium-22 in a mineral acid to form a second solution, and, separating the antimony from the sodium-22 in the second solution.

The role of spatial attention in visual word processing

NASA Technical Reports Server (NTRS)

Mccann, Robert S.; Folk, Charles L.; Johnston, James C.

1992-01-01

Subjects made lexical decisions on a target letter string presented above or below fixation. In Experiments 1 and 2, target location was cued 100 ms in advance of target onset. Responses were faster on validly than on invalidly cued trials. In Experiment 3, the target was sometimes accompanied by irrelevant stimuli on the other side of fixation; in such cases, responses were slowed (a spatial filtering effect). Both cuing and filtering effects on response time were additive with effects of word frequency and lexical status (words vs. nonwords). These findings are difficult to reconcile with claims that spatial attention is less involved in processing familiar words than in unfamiliar words and nonwords. The results can be reconciled with a late-selection locus of spatial attention only with difficulty, but are easily explained by early-selection models.

Normal aging delays and compromises early multifocal visual attention during object tracking.

PubMed

Störmer, Viola S; Li, Shu-Chen; Heekeren, Hauke R; Lindenberger, Ulman

2013-02-01

Declines in selective attention are one of the sources contributing to age-related impairments in a broad range of cognitive functions. Most previous research on mechanisms underlying older adults' selection deficits has studied the deployment of visual attention to static objects and features. Here we investigate neural correlates of age-related differences in spatial attention to multiple objects as they move. We used a multiple object tracking task, in which younger and older adults were asked to keep track of moving target objects that moved randomly in the visual field among irrelevant distractor objects. By recording the brain's electrophysiological responses during the tracking period, we were able to delineate neural processing for targets and distractors at early stages of visual processing (~100-300 msec). Older adults showed less selective attentional modulation in the early phase of the visual P1 component (100-125 msec) than younger adults, indicating that early selection is compromised in old age. However, with a 25-msec delay relative to younger adults, older adults showed distinct processing of targets (125-150 msec), that is, a delayed yet intact attentional modulation. The magnitude of this delayed attentional modulation was related to tracking performance in older adults. The amplitude of the N1 component (175-210 msec) was smaller in older adults than in younger adults, and the target amplification effect of this component was also smaller in older relative to younger adults. Overall, these results indicate that normal aging affects the efficiency and timing of early visual processing during multiple object tracking.

Computational Modeling and Neuroimaging Techniques for Targeting during Deep Brain Stimulation

PubMed Central

Sweet, Jennifer A.; Pace, Jonathan; Girgis, Fady; Miller, Jonathan P.

2016-01-01

Accurate surgical localization of the varied targets for deep brain stimulation (DBS) is a process undergoing constant evolution, with increasingly sophisticated techniques to allow for highly precise targeting. However, despite the fastidious placement of electrodes into specific structures within the brain, there is increasing evidence to suggest that the clinical effects of DBS are likely due to the activation of widespread neuronal networks directly and indirectly influenced by the stimulation of a given target. Selective activation of these complex and inter-connected pathways may further improve the outcomes of currently treated diseases by targeting specific fiber tracts responsible for a particular symptom in a patient-specific manner. Moreover, the delivery of such focused stimulation may aid in the discovery of new targets for electrical stimulation to treat additional neurological, psychiatric, and even cognitive disorders. As such, advancements in surgical targeting, computational modeling, engineering designs, and neuroimaging techniques play a critical role in this process. This article reviews the progress of these applications, discussing the importance of target localization for DBS, and the role of computational modeling and novel neuroimaging in improving our understanding of the pathophysiology of diseases, and thus paving the way for improved selective target localization using DBS. PMID:27445709

Categorization and identification of simultaneous targets.

PubMed

Theeuwes, J

1991-02-01

Early and late selection theories of visual attention disagree about whether identification occurs before or after selection. Studies showing the category effect, i.e., the time to detect a letter is hardly affected by the number of digits present in the display, are taken as evidence for late selection theories since these studies suggest parallel identification of all items in the display. As an extension of previous studies, in the present study two categorically different targets were presented simultaneously among a variable number of nontargets. Subjects were shown brief displays of two target letters among either 2, 4 or 6 nontarget digits. Subjects responded 'same' when the two letters were identical and 'different' otherwise. Since the 'same-different' response reflects the combined outcome of the simultaneous targets, late-selection theory predicts that the time to match the target letters is independent of the number of nontarget digits. Alternatively, early-selection theory predicts a linear increase of reaction time with display size since the presence of more than one target disrupts parallel preattentive processing, leading to a serial search through all items in the display. The results provide evidence for the early-selection view since reaction time increased linearly with the number of categorically different nontargets. A control experiment revealed that none of the alternative explanations could account for the display size effect.

Cortical Spatio-Temporal Dynamics Underlying Phonological Target Detection in Humans

ERIC Educational Resources Information Center

Chang, Edward F.; Edwards, Erik; Nagarajan, Srikantan S.; Fogelson, Noa; Dalal, Sarang S.; Canolty, Ryan T.; Kirsch, Heidi E.; Barbaro, Nicholas M.; Knight, Robert T.

2011-01-01

Selective processing of task-relevant stimuli is critical for goal-directed behavior. We used electrocorticography to assess the spatio-temporal dynamics of cortical activation during a simple phonological target detection task, in which subjects press a button when a prespecified target syllable sound is heard. Simultaneous surface potential…

Evidence for distinct mechanisms underlying attentional priming and sensory memory for bistable perception.

PubMed

Brinkhuis, M A B; Kristjánsson, Á; Brascamp, J W

2015-08-01

Attentional selection in visual search paradigms and perceptual selection in bistable perception paradigms show functional similarities. For example, both are sensitive to trial history: They are biased toward previously selected targets or interpretations. We investigated whether priming by target selection in visual search and sensory memory for bistable perception are related. We did this by presenting two trial types to observers. We presented either ambiguous spheres that rotated over a central axis and could be perceived as rotating in one of two directions, or search displays in which the unambiguously rotating target and distractor spheres closely resembled the two possible interpretations of the ambiguous stimulus. We interleaved both trial types within experiments, to see whether priming by target selection during search trials would affect the perceptual outcome of bistable perception and, conversely, whether sensory memory during bistable perception would affect target selection times during search. Whereas we found intertrial repetition effects among consecutive search trials and among consecutive bistable trials, we did not find cross-paradigm effects. Thus, even though we could ascertain that our experiments robustly elicited processes of both search priming and sensory memory for bistable perception, these same experiments revealed no interaction between the two.

Development of Cell-SELEX Technology and Its Application in Cancer Diagnosis and Therapy.

PubMed

Chen, Man; Yu, Yuanyuan; Jiang, Feng; Zhou, Junwei; Li, Yongshu; Liang, Chao; Dang, Lei; Lu, Aiping; Zhang, Ge

2016-12-10

SELEX (systematic evolution of ligands by exponential enrichment) is a process involving the progressive isolation of high selective ssDNA/RNA from a combinatorial single-stranded oligonucleotide library through repeated rounds of binding, partitioning and amplification. SELEX-derived single-stranded DNA/RNA molecules, called aptamers, are selected against a wide range of targets, including purified proteins, live cells, tissues, microorganisms, small molecules and so on. With the development of SELEX technology over the last two decades, various modified SELEX processes have been arisen. A majority of aptamers are selected against purified proteins through traditional SELEX. Unfortunately, more and more evidence showed aptamers selected against purified membrane proteins failed to recognize their targets in live cells. Cell-SELEX could develop aptamers against a particular target cell line to discriminate this cell line from others. Therefore, cell-SELEX has been widely used to select aptamers for the application of both diagnosis and therapy of various diseases, especially for cancer. In this review, the advantages and limitations of cell-SELEX and SELEX against purified protein will be compared. Various modified cell-SELEX techniques will be summarized, and application of cell-SELEX in cancer diagnosis and therapy will be discussed.

Development of Cell-SELEX Technology and Its Application in Cancer Diagnosis and Therapy

PubMed Central

Chen, Man; Yu, Yuanyuan; Jiang, Feng; Zhou, Junwei; Li, Yongshu; Liang, Chao; Dang, Lei; Lu, Aiping; Zhang, Ge

2016-01-01

SELEX (systematic evolution of ligands by exponential enrichment) is a process involving the progressive isolation of high selective ssDNA/RNA from a combinatorial single-stranded oligonucleotide library through repeated rounds of binding, partitioning and amplification. SELEX-derived single-stranded DNA/RNA molecules, called aptamers, are selected against a wide range of targets, including purified proteins, live cells, tissues, microorganisms, small molecules and so on. With the development of SELEX technology over the last two decades, various modified SELEX processes have been arisen. A majority of aptamers are selected against purified proteins through traditional SELEX. Unfortunately, more and more evidence showed aptamers selected against purified membrane proteins failed to recognize their targets in live cells. Cell-SELEX could develop aptamers against a particular target cell line to discriminate this cell line from others. Therefore, cell-SELEX has been widely used to select aptamers for the application of both diagnosis and therapy of various diseases, especially for cancer. In this review, the advantages and limitations of cell-SELEX and SELEX against purified protein will be compared. Various modified cell-SELEX techniques will be summarized, and application of cell-SELEX in cancer diagnosis and therapy will be discussed. PMID:27973403

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

PubMed

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.

Feature-based attention to unconscious shapes and colors.

PubMed

Schmidt, Filipp; Schmidt, Thomas

2010-08-01

Two experiments employed feature-based attention to modulate the impact of completely masked primes on subsequent pointing responses. Participants processed a color cue to select a pair of possible pointing targets out of multiple targets on the basis of their color, and then pointed to the one of those two targets with a prespecified shape. All target pairs were preceded by prime pairs triggering either the correct or the opposite response. The time interval between cue and primes was varied to modulate the time course of feature-based attentional selection. In a second experiment, the roles of color and shape were switched. Pointing trajectories showed large priming effects that were amplified by feature-based attention, indicating that attention modulated the earliest phases of motor output. Priming effects as well as their attentional modulation occurred even though participants remained unable to identify the primes, indicating distinct processes underlying visual awareness, attention, and response control.

In vitro selection using a dual RNA library that allows primerless selection

PubMed Central

Jarosch, Florian; Buchner, Klaus; Klussmann, Sven

2006-01-01

High affinity target-binding aptamers are identified from random oligonucleotide libraries by an in vitro selection process called Systematic Evolution of Ligands by EXponential enrichment (SELEX). Since the SELEX process includes a PCR amplification step the randomized region of the oligonucleotide libraries need to be flanked by two fixed primer binding sequences. These primer binding sites are often difficult to truncate because they may be necessary to maintain the structure of the aptamer or may even be part of the target binding motif. We designed a novel type of RNA library that carries fixed sequences which constrain the oligonucleotides into a partly double-stranded structure, thereby minimizing the risk that the primer binding sequences become part of the target-binding motif. Moreover, the specific design of the library including the use of tandem RNA Polymerase promoters allows the selection of oligonucleotides without any primer binding sequences. The library was used to select aptamers to the mirror-image peptide of ghrelin. Ghrelin is a potent stimulator of growth-hormone release and food intake. After selection, the identified aptamer sequences were directly synthesized in their mirror-image configuration. The final 44 nt-Spiegelmer, named NOX-B11-3, blocks ghrelin action in a cell culture assay displaying an IC50 of 4.5 nM at 37°C. PMID:16855281

Targeting as the basis for pre-test market of lithium-ion battery

NASA Astrophysics Data System (ADS)

Yuniaristanto, Zakaria, R.; Saputri, V. H. L.; Sutopo, W.; Kadir, E. A.

2017-11-01

This article discusses about market segmentation and targeting as a first step in pre-test market of a new technology. The benefits of targeting towards pre-test market are pre-test market can be conducted to focus on selected target markets so there is no bias during the pre-test market. In determining the target market then do some surveys to identify the state of market in the future, so that the marketing process is not misplaced. Lithium ion battery which is commercialized through start-up companies is the case study. This start-up companies must be able to respond the changes and bring in customers as well as maintain them so that companies can survive and evolve to achieve its objectives. The research aims to determine market segments and target market effectively. Marketing strategy (segmentation and targeting) is used to make questionnaire and cluster analysis in data processing. Respondents were selected by purposive sampling and have obtained data as many as 80 samples. As the results study, there are three segments for lithium ion battery with their own distinguished characteristics and there are two segments that can be used as the target market for the company.

Qualitative differences in the guidance of attention during single-color and multiple-color visual search: behavioral and electrophysiological evidence.

PubMed

Grubert, Anna; Eimer, Martin

2013-10-01

To find out whether attentional target selection can be effectively guided by top-down task sets for multiple colors, we measured behavioral and ERP markers of attentional target selection in an experiment where participants had to identify color-defined target digits that were accompanied by a single gray distractor object in the opposite visual field. In the One Color task, target color was constant. In the Two Color task, targets could have one of two equally likely colors. Color-guided target selection was less efficient during multiple-color relative to single-color search, and this was reflected by slower response times and delayed N2pc components. Nontarget-color items that were presented in half of all trials captured attention and gained access to working memory when participants searched for two colors, but were excluded from attentional processing in the One Color task. Results demonstrate qualitative differences in the guidance of attentional target selection between single-color and multiple-color visual search. They suggest that top-down attentional control can be applied much more effectively when it is based on a single feature-specific attentional template. PsycINFO Database Record (c) 2013 APA, all rights reserved.

Discovery-2: an interactive resource for the rational selection and comparison of putative drug target proteins in malaria

PubMed Central

2013-01-01

Background Drug resistance to anti-malarial compounds remains a serious problem, with resistance to newer pharmaceuticals developing at an alarming rate. The development of new anti-malarials remains a priority, and the rational selection of putative targets is a key element of this process. Discovery-2 is an update of the original Discovery in silico resource for the rational selection of putative drug target proteins, enabling researchers to obtain information for a protein which may be useful for the selection of putative drug targets, and to perform advanced filtering of proteins encoded by the malaria genome based on a series of molecular properties. Methods An updated in silico resource has been developed where researchers are able to mine information on malaria proteins and predicted ligands, as well as perform comparisons to the human and mosquito host characteristics. Protein properties used include: domains, motifs, EC numbers, GO terms, orthologs, protein-protein interactions, protein-ligand interactions. Newly added features include drugability measures from ChEMBL, automated literature relations and links to clinical trial information. Searching by chemical structure is also available. Results The updated functionality of the Discovery-2 resource is presented, together with a detailed case study of the Plasmodium falciparum S-adenosyl-L-homocysteine hydrolase (PfSAHH) protein. A short example of a chemical search with pyrimethamine is also illustrated. Conclusion The updated Discovery-2 resource allows researchers to obtain detailed properties of proteins from the malaria genome, which may be of interest in the target selection process, and to perform advanced filtering and selection of proteins based on a relevant range of molecular characteristics. PMID:23537208

Using an in Silico Approach to Teach 3D Pharmacodynamics of the Drug-Target Interaction Process Focusing on Selective COX2 Inhibition by Celecoxib

ERIC Educational Resources Information Center

Tavares, Maurício T.; Primi, Marina C.; Silva, Nuno A. T. F.; Carvalho, Camila F.; Cunha, Micael R.; Parise-Filho, Roberto

2017-01-01

Teaching the molecular aspects of drug-target interactions and selectivity is not always an easy task. In this context, the use of alternative and engaging approaches could help pharmacy and chemistry students better understand this important topic of medicinal chemistry. Herein a 4 h practical exercise that uses freely available software as a…

Aptamer entrapment in microfluidic channel using one-step sol-gel process, in view of the integration of a new selective extraction phase for lab-on-a-chip.

PubMed

Perréard, Camille; d'Orlyé, Fanny; Griveau, Sophie; Liu, Baohong; Bedioui, Fethi; Varenne, Anne

2017-10-01

There is a great demand for integrating sample treatment into μTASs. In this context, we developed a new sol-gel phase for extraction of trace compounds in complex matrices. For this purpose, the incorporation of aptamers in silica-based gel within PDMS/glass microfluidic channels was performed for the first time by a one-step sol-gel process. The effective gel attachment onto microchannel walls and aptamer incorporation in the polymerized gel were evaluated using fluorescence microscopy. A good gel stability and aptamer incorporation inside the microchannel was demonstrated upon rinsing and over storage time. The ability of gel-encapsulated aptamers to interact with its specific target (either sulforhodamine B as model fluorescent target, or diclofenac, a pain killer drug) was assessed too. The binding capacity of entrapped aptamers was quantified (in the micromolar range) and the selectivity of the interaction was evidenced. Preservation of aptamers binding affinity to target molecules was therefore demonstrated. Dissociation constant of the aptamer-target complex and interaction selectivity were evaluated similar to those in bulk solution. This opens the way to new selective on-chip SPE techniques for sample pretreatment. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Dynamic interactions between visual working memory and saccade target selection

PubMed Central

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

Neurons with object-centered spatial selectivity in macaque SEF: do they represent locations or rules?

PubMed

Tremblay, Léon; Gettner, Sonya N; Olson, Carl R

2002-01-01

In macaque monkeys performing a task that requires eye movements to the leftmost or rightmost of two dots in a horizontal array, some neurons in the supplementary eye field (SEF) fire differentially according to which side of the array is the target regardless of the array's location on the screen. We refer to these neurons as exhibiting selectivity for object-centered location. This form of selectivity might arise from involvement of the neurons in either of two processes: representing the locations of targets or representing the rules by which targets are selected. To distinguish between these possibilities, we monitored neuronal activity in the SEF of two monkeys performing a task that required the selection of targets by either an object-centered spatial rule or a color rule. On each trial, a sample array consisting of two side-by-side dots appeared; then a cue flashed on one dot; then the display vanished and a delay ensued. Next a target array consisting of two side-by-side dots appeared at an unpredictable location and another delay ensued; finally the monkey had to make an eye movement to one of the target dots. On some trials, the monkey had to select the dot on the same side as the cue (right or left). On other trials, he had to select the target of the same color as the cue (red or green). Neuronal activity robustly encoded the object-centered locations first of the cue and then of the target regardless of the whether the monkey was following a rule based on object-centered location or color. Neuronal activity was at most weakly affected by the type of rule the monkey was following (object-centered-location or color) or by the color of the cue and target (red or green). On trials involving a color rule, neuronal activity was moderately enhanced when the cue and target appeared on opposite sides of their respective arrays. We conclude that the general function of SEF neurons selective for object-centered location is to represent where the cue and target are in their respective arrays rather than to represent the rule for target selection.

Combinatorially Screened Peptide as Targeted Covalent Binder: Alteration of Bait-Conjugated Peptide to Reactive Modifier.

PubMed

Uematsu, Shuta; Tabuchi, Yudai; Ito, Yuji; Taki, Masumi

2018-06-01

A peptide-type covalent binder for a target protein was obtained by combinatorial screening of fluoroprobe-conjugated peptide libraries on bacteriophage T7. The solvatochromic fluoroprobe works as a bait during the affinity selection process of phage display. To obtain the targeted covalent binder, the bait in the selected consensus peptide was altered into a reactive warhead possessing a sulfonyl fluoride. The reaction efficiency and site/position specificity of the covalent conjugation between the binder and the target protein were evaluated by liquid chromatography-tandem mass spectrometry (LC-MS/MS), and rationalized by a protein-ligand docking simulation.

Water-soluble polymers for recovery of metal ions from aqueous streams

DOEpatents

Smith, Barbara F.; Robison, Thomas W.

1998-01-01

A process of selectively separating a target metal contained in an aqueous solution by contacting the aqueous solution containing a target metal with an aqueous solution including a water-soluble polymer capable of binding with the target metal for sufficient time whereby a water-soluble polymer-target metal complex is formed, and, separating the solution including the water-soluble polymer-target metal complex from the solution is disclosed.

A scalable, fully automated process for construction of sequence-ready human exome targeted capture libraries

PubMed Central

2011-01-01

Genome targeting methods enable cost-effective capture of specific subsets of the genome for sequencing. We present here an automated, highly scalable method for carrying out the Solution Hybrid Selection capture approach that provides a dramatic increase in scale and throughput of sequence-ready libraries produced. Significant process improvements and a series of in-process quality control checkpoints are also added. These process improvements can also be used in a manual version of the protocol. PMID:21205303

Sequential sensory and decision processing in posterior parietal cortex

PubMed Central

Ibos, Guilhem; Freedman, David J

2017-01-01

Decisions about the behavioral significance of sensory stimuli often require comparing sensory inference of what we are looking at to internal models of what we are looking for. Here, we test how neuronal selectivity for visual features is transformed into decision-related signals in posterior parietal cortex (area LIP). Monkeys performed a visual matching task that required them to detect target stimuli composed of conjunctions of color and motion-direction. Neuronal recordings from area LIP revealed two main findings. First, the sequential processing of visual features and the selection of target-stimuli suggest that LIP is involved in transforming sensory information into decision-related signals. Second, the patterns of color and motion selectivity and their impact on decision-related encoding suggest that LIP plays a role in detecting target stimuli by comparing bottom-up sensory inputs (what the monkeys were looking at) and top-down cognitive encoding inputs (what the monkeys were looking for). DOI: http://dx.doi.org/10.7554/eLife.23743.001 PMID:28418332

Recovery of niobium from irradiated targets

DOEpatents

Phillips, Dennis R.; Jamriska, Sr., David J.; Hamilton, Virginia T.

1994-01-01

A process for selective separation of niobium from proton irradiated molybdenum targets is provided and includes dissolving the molybdenum target in a hydrogen peroxide solution to form a first ion-containing solution, contacting the first ion-containing solution with a cationic resin whereby ions selected form the group consisting of molybdenum, biobium, technetium, selenium, vanadium, arsenic, germanium, zirconium and rubidium remain in a second ion-containing solution while ions selected from the group consisting of rubidium, zinc, beryllium, cobalt, iron, manganese, chromium, strontium, yttrium and zirconium are selectively adsorbed by the cationic resin; adjusting the pH of the second ion-containing solution to within a range of from about 5.0 to about 6.0; contacting the pH adjusting second ion-containing solution with a dextran-based material for a time to selectively separate niobium from the solution and recovering the niobium from the dextran-based material.

Is selective attention the basis for selective imitation in infants? An eye-tracking study of deferred imitation with 12-month-olds.

PubMed

Kolling, Thorsten; Oturai, Gabriella; Knopf, Monika

2014-08-01

Infants and children do not blindly copy every action they observe during imitation tasks. Research demonstrated that infants are efficient selective imitators. The impact of selective perceptual processes (selective attention) for selective deferred imitation, however, is still poorly described. The current study, therefore, analyzed 12-month-old infants' looking behavior during demonstration of two types of target actions: arbitrary versus functional actions. A fully automated remote eye tracker was used to assess infants' looking behavior during action demonstration. After a 30-min delay, infants' deferred imitation performance was assessed. Next to replicating a memory effect, results demonstrate that infants do imitate significantly more functional actions than arbitrary actions (functionality effect). Eye-tracking data show that whereas infants do not fixate significantly longer on functional actions than on arbitrary actions, amount of fixations and amount of saccades differ between functional and arbitrary actions, indicating different encoding mechanisms. In addition, item-level findings differ from overall findings, indicating that perceptual and conceptual item features influence looking behavior. Looking behavior on both the overall and item levels, however, does not relate to deferred imitation performance. Taken together, the findings demonstrate that, on the one hand, selective imitation is not explainable merely by selective attention processes. On the other hand, notwithstanding this reasoning, attention processes on the item level are important for encoding processes during target action demonstration. Limitations and future studies are discussed. Copyright © 2014 Elsevier Inc. All rights reserved.

Biasing spatial attention with semantic information: an event coding approach.

PubMed

Amer, Tarek; Gozli, Davood G; Pratt, Jay

2017-04-21

We investigated the influence of conceptual processing on visual attention from the standpoint of Theory of Event Coding (TEC). The theory makes two predictions: first, an important factor in determining the influence of event 1 on processing event 2 is whether features of event 1 are bound into a unified representation (i.e., selection or retrieval of event 1). Second, whether processing the two events facilitates or interferes with each other should depend on the extent to which their constituent features overlap. In two experiments, participants performed a visual-attention cueing task, in which the visual target (event 2) was preceded by a relevant or irrelevant explicit (e.g., "UP") or implicit (e.g., "HAPPY") spatial-conceptual cue (event 1). Consistent with TEC, we found relevant explicit cues (which featurally overlap to a greater extent with the target) and implicit cues (which featurally overlap to a lesser extent), respectively, facilitated and interfered with target processing at compatible locations. Irrelevant explicit and implicit cues, on the other hand, both facilitated target processing, presumably because they were less likely selected or retrieved as an integrated and unified event file. We argue that such effects, often described as "attentional cueing", are better accounted for within the event coding framework.

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

PubMed

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.

Toward a magic or imaginary bullet? Ligands for drug targeting to cancer cells: principles, hopes, and challenges

PubMed Central

Toporkiewicz, Monika; Meissner, Justyna; Matusewicz, Lucyna; Czogalla, Aleksander; Sikorski, Aleksander F

2015-01-01

There are many problems directly correlated with the systemic administration of drugs and how they reach their target site. Targeting promises to be a hopeful strategy as an improved means of drug delivery, with reduced toxicity and minimal adverse side effects. Targeting exploits the high affinity of cell-surface-targeted ligands, either directly or as carriers for a drug, for specific retention and uptake by the targeted diseased cells. One of the most important parameters which should be taken into consideration in the selection of an appropriate ligand for targeting is the binding affinity (KD). In this review we focus on the importance of binding affinities of monoclonal antibodies, antibody derivatives, peptides, aptamers, DARPins, and small targeting molecules in the process of selection of the most suitable ligand for targeting of nanoparticles. In order to provide a critical comparison between these various options, we have also assessed each technology format across a range of parameters such as molecular size, immunogenicity, costs of production, clinical profiles, and examples of the level of selectivity and toxicity of each. Wherever possible, we have also assessed how incorporating such a targeted approach compares with, or is superior to, original treatments. PMID:25733832

Methods for Selecting Phage Display Antibody Libraries.

PubMed

Jara-Acevedo, Ricardo; Diez, Paula; Gonzalez-Gonzalez, Maria; Degano, Rosa Maria; Ibarrola, Nieves; Gongora, Rafael; Orfao, Alberto; Fuentes, Manuel

2016-01-01

The selection process aims sequential enrichment of phage antibody display library in clones that recognize the target of interest or antigen as the library undergoes successive rounds of selection. In this review, selection methods most commonly used for phage display antibody libraries have been comprehensively described. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

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

PubMed

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.

Auditory Attentional Control and Selection during Cocktail Party Listening

PubMed Central

Hill, Kevin T.

2010-01-01

In realistic auditory environments, people rely on both attentional control and attentional selection to extract intelligible signals from a cluttered background. We used functional magnetic resonance imaging to examine auditory attention to natural speech under such high processing-load conditions. Participants attended to a single talker in a group of 3, identified by the target talker's pitch or spatial location. A catch-trial design allowed us to distinguish activity due to top-down control of attention versus attentional selection of bottom-up information in both the spatial and spectral (pitch) feature domains. For attentional control, we found a left-dominant fronto-parietal network with a bias toward spatial processing in dorsal precentral sulcus and superior parietal lobule, and a bias toward pitch in inferior frontal gyrus. During selection of the talker, attention modulated activity in left intraparietal sulcus when using talker location and in bilateral but right-dominant superior temporal sulcus when using talker pitch. We argue that these networks represent the sources and targets of selective attention in rich auditory environments. PMID:19574393

[Selective attention and schizophrenia before the administration of neuroleptics].

PubMed

Lussier, I; Stip, E

1999-01-01

In recent years, the presence of attention deficits has been recognized as a key feature of schizophrenia. Past studies reveal that selective attention, or the ability to select relevant information while ignoring simultaneously irrelevant information, is disturbed in schizophrenic patients. According to Treisman feature-integration theory of selective attention, visual search for conjunctive targets (e.g., shape and color) requires controlled processes, that necessitate attention and operate in a serial manner. Reaction times (RTs) are therefore function of the number of stimuli in the display. When subjects are asked to detect the presence or absence of a target in an array of a variable number of stimuli, different performance patterns are expected for positive (present target) and negative trials (absent target). For positive trials, a self-terminating search is triggered, that is, the search is ended when the target is encountered. For negative trials, an exhaustive search strategy is displayed, where each stimulus is examined before the search can end; the RT slope pattern is thus double that of the positive trials. To assess the integrity of these processes, thirteen drug naive schizophrenic patients were compared to twenty normal control subjects. Neuroleptic naive patients were chosen as subjects to avoid the potential influence of medication and chronicity-related factors on performance. The subjects had to specify as fast as possible the presence or absence of the target in an array of a variable number of stimuli presented in a circular display, and comprising or not the target. Results showed that the patients can use self-terminating search strategies as well as normal control subjects. However, their ability to trigger exhaustive search strategies is impaired. Not only were patients slower than controls, but their pattern of RT results was different. These results argue in favor of an early impairment in selective attention capacities in schizophrenia, which appears before the introduction of neuroleptics. The attention performance was also shown to present some association to clinical symptoms.

Improved targeted immunization strategies based on two rounds of selection

NASA Astrophysics Data System (ADS)

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.

Active listening impairs visual perception and selectivity: an ERP study of auditory dual-task costs on visual attention.

PubMed

Gherri, Elena; Eimer, Martin

2011-04-01

The ability to drive safely is disrupted by cell phone conversations, and this has been attributed to a diversion of attention from the visual environment. We employed behavioral and ERP measures to study whether the attentive processing of spoken messages is, in itself, sufficient to produce visual-attentional deficits. Participants searched for visual targets defined by a unique feature (Experiment 1) or feature conjunction (Experiment 2), and simultaneously listened to narrated text passages that had to be recalled later (encoding condition), or heard backward-played speech sounds that could be ignored (control condition). Responses to targets were slower in the encoding condition, and ERPs revealed that the visual processing of search arrays and the attentional selection of target stimuli were less efficient in the encoding relative to the control condition. Results demonstrate that the attentional processing of visual information is impaired when concurrent spoken messages are encoded and maintained, in line with cross-modal links in selective attention, but inconsistent with the view that attentional resources are modality-specific. The distraction of visual attention by active listening could contribute to the adverse effects of cell phone use on driving performance.

Selective enhancement of orientation tuning before saccades.

PubMed

Ohl, Sven; Kuper, Clara; Rolfs, Martin

2017-11-01

Saccadic eye movements cause a rapid sweep of the visual image across the retina and bring the saccade's target into high-acuity foveal vision. Even before saccade onset, visual processing is selectively prioritized at the saccade target. To determine how this presaccadic attention shift exerts its influence on visual selection, we compare the dynamics of perceptual tuning curves before movement onset at the saccade target and in the opposite hemifield. Participants monitored a 30-Hz sequence of randomly oriented gratings for a target orientation. Combining a reverse correlation technique previously used to study orientation tuning in neurons and general additive mixed modeling, we found that perceptual reports were tuned to the target orientation. The gain of orientation tuning increased markedly within the last 100 ms before saccade onset. In addition, we observed finer orientation tuning right before saccade onset. This increase in gain and tuning occurred at the saccade target location and was not observed at the incongruent location in the opposite hemifield. The present findings suggest, therefore, that presaccadic attention exerts its influence on vision in a spatially and feature-selective manner, enhancing performance and sharpening feature tuning at the future gaze location before the eyes start moving.

CstF-64 and 3'-UTR cis-element determine Star-PAP specificity for target mRNA selection by excluding PAPα.

PubMed

Kandala, Divya T; Mohan, Nimmy; A, Vivekanand; A P, Sudheesh; G, Reshmi; Laishram, Rakesh S

2016-01-29

Almost all eukaryotic mRNAs have a poly (A) tail at the 3'-end. Canonical PAPs (PAPα/γ) polyadenylate nuclear pre-mRNAs. The recent identification of the non-canonical Star-PAP revealed specificity of nuclear PAPs for pre-mRNAs, yet the mechanism how Star-PAP selects mRNA targets is still elusive. Moreover, how Star-PAP target mRNAs having canonical AAUAAA signal are not regulated by PAPα is unclear. We investigate specificity mechanisms of Star-PAP that selects pre-mRNA targets for polyadenylation. Star-PAP assembles distinct 3'-end processing complex and controls pre-mRNAs independent of PAPα. We identified a Star-PAP recognition nucleotide motif and showed that suboptimal DSE on Star-PAP target pre-mRNA 3'-UTRs inhibit CstF-64 binding, thus preventing PAPα recruitment onto it. Altering 3'-UTR cis-elements on a Star-PAP target pre-mRNA can switch the regulatory PAP from Star-PAP to PAPα. Our results suggest a mechanism of poly (A) site selection that has potential implication on the regulation of alternative polyadenylation. © The Author(s) 2015. Published by Oxford University Press on behalf of Nucleic Acids Research.

CstF-64 and 3′-UTR cis-element determine Star-PAP specificity for target mRNA selection by excluding PAPα

PubMed Central

Kandala, Divya T.; Mohan, Nimmy; A, Vivekanand; AP, Sudheesh; G, Reshmi; Laishram, Rakesh S.

2016-01-01

Almost all eukaryotic mRNAs have a poly (A) tail at the 3′-end. Canonical PAPs (PAPα/γ) polyadenylate nuclear pre-mRNAs. The recent identification of the non-canonical Star-PAP revealed specificity of nuclear PAPs for pre-mRNAs, yet the mechanism how Star-PAP selects mRNA targets is still elusive. Moreover, how Star-PAP target mRNAs having canonical AAUAAA signal are not regulated by PAPα is unclear. We investigate specificity mechanisms of Star-PAP that selects pre-mRNA targets for polyadenylation. Star-PAP assembles distinct 3′-end processing complex and controls pre-mRNAs independent of PAPα. We identified a Star-PAP recognition nucleotide motif and showed that suboptimal DSE on Star-PAP target pre-mRNA 3′-UTRs inhibit CstF-64 binding, thus preventing PAPα recruitment onto it. Altering 3′-UTR cis-elements on a Star-PAP target pre-mRNA can switch the regulatory PAP from Star-PAP to PAPα. Our results suggest a mechanism of poly (A) site selection that has potential implication on the regulation of alternative polyadenylation. PMID:26496945

Selective pressure against horizontally acquired prokaryotic genes as a driving force of plastid evolution.

PubMed

Llorente, Briardo; de Souza, Flavio S J; Soto, Gabriela; Meyer, Cristian; Alonso, Guillermo D; Flawiá, Mirtha M; Bravo-Almonacid, Fernando; Ayub, Nicolás D; Rodríguez-Concepción, Manuel

2016-01-11

The plastid organelle comprises a high proportion of nucleus-encoded proteins that were acquired from different prokaryotic donors via independent horizontal gene transfers following its primary endosymbiotic origin. What forces drove the targeting of these alien proteins to the plastid remains an unresolved evolutionary question. To better understand this process we screened for suitable candidate proteins to recapitulate their prokaryote-to-eukaryote transition. Here we identify the ancient horizontal transfer of a bacterial polyphenol oxidase (PPO) gene to the nuclear genome of an early land plant ancestor and infer the possible mechanism behind the plastidial localization of the encoded enzyme. Arabidopsis plants expressing PPO versions either lacking or harbouring a plastid-targeting signal allowed examining fitness consequences associated with its subcellular localization. Markedly, a deleterious effect on plant growth was highly correlated with PPO activity only when producing the non-targeted enzyme, suggesting that selection favoured the fixation of plastid-targeted protein versions. Our results reveal a possible evolutionary mechanism of how selection against heterologous genes encoding cytosolic proteins contributed in incrementing plastid proteome complexity from non-endosymbiotic gene sources, a process that may also impact mitochondrial evolution.

Comparison of Whole-Cell SELEX Methods for the Identification of Staphylococcus Aureus-Specific DNA Aptamers

PubMed Central

Moon, Jihea; Kim, Giyoung; Park, Saet Byeol; Lim, Jongguk; Mo, Changyeun

2015-01-01

Whole-cell Systemic Evolution of Ligands by Exponential enrichment (SELEX) is the process by which aptamers specific to target cells are developed. Aptamers selected by whole-cell SELEX have high affinity and specificity for bacterial surface molecules and live bacterial targets. To identify DNA aptamers specific to Staphylococcus aureus, we applied our rapid whole-cell SELEX method to a single-stranded ssDNA library. To improve the specificity and selectivity of the aptamers, we designed, selected, and developed two categories of aptamers that were selected by two kinds of whole-cell SELEX, by mixing and combining FACS analysis and a counter-SELEX process. Using this approach, we have developed a biosensor system that employs a high affinity aptamer for detection of target bacteria. FAM-labeled aptamer sequences with high binding to S. aureus, as determined by fluorescence spectroscopic analysis, were identified, and aptamer A14, selected by the basic whole-cell SELEX using a once-off FACS analysis, and which had a high binding affinity and specificity, was chosen. The binding assay was evaluated using FACS analysis. Our study demonstrated the development of a set of whole-cell SELEX derived aptamers specific to S. aureus; this approach can be used in the identification of other bacteria. PMID:25884791

Comparison of whole-cell SELEX methods for the identification of Staphylococcus aureus-specific DNA aptamers.

PubMed

Moon, Jihea; Kim, Giyoung; Park, Saet Byeol; Lim, Jongguk; Mo, Changyeun

2015-04-15

Whole-cell Systemic Evolution of Ligands by Exponential enrichment (SELEX) is the process by which aptamers specific to target cells are developed. Aptamers selected by whole-cell SELEX have high affinity and specificity for bacterial surface molecules and live bacterial targets. To identify DNA aptamers specific to Staphylococcus aureus, we applied our rapid whole-cell SELEX method to a single-stranded ssDNA library. To improve the specificity and selectivity of the aptamers, we designed, selected, and developed two categories of aptamers that were selected by two kinds of whole-cell SELEX, by mixing and combining FACS analysis and a counter-SELEX process. Using this approach, we have developed a biosensor system that employs a high affinity aptamer for detection of target bacteria. FAM-labeled aptamer sequences with high binding to S. aureus, as determined by fluorescence spectroscopic analysis, were identified, and aptamer A14, selected by the basic whole-cell SELEX using a once-off FACS analysis, and which had a high binding affinity and specificity, was chosen. The binding assay was evaluated using FACS analysis. Our study demonstrated the development of a set of whole-cell SELEX derived aptamers specific to S. aureus; this approach can be used in the identification of other bacteria.

The effects of visual search efficiency on object-based attention

PubMed Central

Rosen, Maya; Cutrone, Elizabeth; Behrmann, Marlene

2017-01-01

The attentional prioritization hypothesis of object-based attention (Shomstein & Yantis in Perception & Psychophysics, 64, 41–51, 2002) suggests a two-stage selection process comprising an automatic spatial gradient and flexible strategic (prioritization) selection. The combined attentional priorities of these two stages of object-based selection determine the order in which participants will search the display for the presence of a target. The strategic process has often been likened to a prioritized visual search. By modifying the double-rectangle cueing paradigm (Egly, Driver, & Rafal in Journal of Experimental Psychology: General, 123, 161–177, 1994) and placing it in the context of a larger-scale visual search, we examined how the prioritization search is affected by search efficiency. By probing both targets located on the cued object and targets external to the cued object, we found that the attentional priority surrounding a selected object is strongly modulated by search mode. However, the ordering of the prioritization search is unaffected by search mode. The data also provide evidence that standard spatial visual search and object-based prioritization search may rely on distinct mechanisms. These results provide insight into the interactions between the mode of visual search and object-based selection, and help define the modulatory consequences of search efficiency for object-based attention. PMID:25832192

A dissociation between selective attention and conscious awareness in the representation of temporal order information.

PubMed

Eimer, Martin; Grubert, Anna

2015-09-01

Previous electrophysiological studies have shown that attentional selection processes are highly sensitive to the temporal order of task-relevant visual events. When two successively presented colour-defined target stimuli are separated by a stimulus onset asynchrony (SOA) of only 10 ms, the onset latencies of N2pc components to these stimuli (which reflect their attentional selection) precisely match their objective temporal separation. We tested whether such small onset differences are accessible to conscious awareness by instructing participants to report the category (letter or digit) of the first of two target-colour items that were separated by an SOA of 10, 20, or 30 ms. Performance was at chance level for the 10 ms SOA, demonstrating that temporal order information which is available to attentional control processes cannot be utilized for conscious temporal order judgments. These results provide new evidence that selective attention and conscious awareness are functionally separable, and support the hypothesis that attention and awareness operate at different stages of cognitive processing. Copyright © 2015 Elsevier Inc. All rights reserved.

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

PubMed

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.

Legal Consciousness and Responses to Sexual Harassment*

PubMed Central

Blackstone, Amy; Uggen, Christopher; McLaughlin, Heather

2009-01-01

Studies of legal mobilization often focus on people who have perceived some wrong, but rarely consider the process that selects them into the pool of potential “mobilizers.” Similarly, studies of victimization or targeting rarely go on to consider what people do about the wrong, or why some targets come forward and others remain silent. We here integrate sociolegal, feminist, and criminological theories in a conceptual model that treats experiencing sexual harassment and mobilizing in response to it as interrelated processes. We then link these two processes by modeling them as jointly determined outcomes and examine their connections using interviews with a subset of our survey respondents. Our results suggest that targets of harassment are selected, in part, because they are least likely to tell others about the experience. Strategies that workers employ to cope with and confront harassment are also discussed. We find that traditional formal/informal dichotomies of mobilization responses may not fully account for the range of ways individuals respond to harassment, and we propose a preliminary typology of responses. PMID:20300446

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

NASA Astrophysics Data System (ADS)

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

2016-10-01

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

Salience-Based Selection: Attentional Capture by Distractors Less Salient Than the Target

PubMed Central

Goschy, Harriet; Müller, Hermann Joseph

2013-01-01

Current accounts of attentional capture predict the most salient stimulus to be invariably selected first. However, existing salience and visual search models assume noise in the map computation or selection process. Consequently, they predict the first selection to be stochastically dependent on salience, implying that attention could even be captured first by the second most salient (instead of the most salient) stimulus in the field. Yet, capture by less salient distractors has not been reported and salience-based selection accounts claim that the distractor has to be more salient in order to capture attention. We tested this prediction using an empirical and modeling approach of the visual search distractor paradigm. For the empirical part, we manipulated salience of target and distractor parametrically and measured reaction time interference when a distractor was present compared to absent. Reaction time interference was strongly correlated with distractor salience relative to the target. Moreover, even distractors less salient than the target captured attention, as measured by reaction time interference and oculomotor capture. In the modeling part, we simulated first selection in the distractor paradigm using behavioral measures of salience and considering the time course of selection including noise. We were able to replicate the result pattern we obtained in the empirical part. We conclude that each salience value follows a specific selection time distribution and attentional capture occurs when the selection time distributions of target and distractor overlap. Hence, selection is stochastic in nature and attentional capture occurs with a certain probability depending on relative salience. PMID:23382820

Science objectives and observing strategy for the OMEGA imaging spectrometer on Mars-Express

NASA Astrophysics Data System (ADS)

Erard, S.; Bibring, J.-P.; Drossart, P.; Forget, F.; Schmitt, B.; OMEGA Team

2003-04-01

The science objectives of OMEGA, which were first defined at the time of instruments selection for Mars-Express, were recently updated to integrate new results from MGS and Odyssey concerning three main fields: Martian surface and atmosphere, and polar processes. Thematic categories of observations are derived from the scientific objectives whenever spectral observations from OMEGA are expected to provide insights to Mars present situation and evolution. Targets within these categories are selected on the basis of their expected usefulness, which is related to their intrinsic properties and to the instrument capabilities. The whole surface will be mapped at low resolution (~5 km/pixel) in the course of the nominal mission, and possibly routinely at very coarse resolution to monitor time-varying processes from apocenter. However, only 5% of the surface can be observed at high resolution (up to 350 m/pixel) owing to constraints on telemetry rate. HR targets are therefore selected on the basis of telemetry constraints, orbital parameters, observing opportunities (visibility under given conditions), and spacecraft functionalities (e.g., depointing capacity), then prioritized within each category according to the probability to perform significant observations with OMEGA (in many situations, according to the estimated dust coverage). Target selection is performed interactively between OMEGA co-Is, in close contact with teams from other MEx experiments (mostly HRSC, PFS and Spicam) and other missions (e.g., MER and MRO). Most HR surface targets are selected on the basis of deep examination of Viking, THEMIS, and MOC HR images. Other surface targets include areas presenting unusual spectral properties in previous observations, or suspected to exhibit signatures of hydrothermal activity. Proposed landing sites and suggested source areas for the SNC meteorites are also included. Atmospheric/polar objectives more often translate as particular observing modes, sometimes at HR (e.g., limb observations, EPF sequences). The constraints are related to local time and seasonal occurrence of particular processes, and to spacecraft pointing. About 1000 HR targets are currently identified in the Southern hemisphere (first six month in orbit). The targets are described in a database with geographic coordinates in IAU-2000 system, context and detailed images, optimum observing conditions, science rationale and references. This database is currently being interfaced with ESA's MAPSS planning software.

Structure Mapping in Autism Spectrum Disorder: Levels of Information Processing and Relations to Executive Functions.

PubMed

Hetzroni, Orit E; Shalahevich, Kiril

2018-03-01

Analogical reasoning was investigated among children with autism spectrum disorders (ASD) without intellectual disabilities and typical development (TD). Children were asked to select one of two targets in two conditions: (1) with and without spatial structure similarity; (2) with and without a perceptual distractor. Results demonstrate that children with ASD were able to select targets based on structural similarity, but this ability decreased to chance level when presented with a perceptual distractor. Everyday executive functions were positively correlated with structural selections among children with ASD. Results suggest that although children with ASD were able to select based on systematicity principle, perceptual distractor decreased their selection so that their cognitive system produced less structure similarities, that negatively affects spatial analogical reasoning.

Antibody Drug Conjugates: Application of Quantitative Pharmacology in Modality Design and Target Selection.

PubMed

Sadekar, S; Figueroa, I; Tabrizi, M

2015-07-01

Antibody drug conjugates (ADCs) are a multi-component modality comprising of an antibody targeting a cell-specific antigen, a potent drug/payload, and a linker that can be processed within cellular compartments to release payload upon internalization. Numerous ADCs are being evaluated in both research and clinical settings within the academic and pharmaceutical industry due to their ability to selectively deliver potent payloads. Hence, there is a clear need to incorporate quantitative approaches during early stages of drug development for effective modality design and target selection. In this review, we describe a quantitative approach and framework for evaluation of the interplay between drug- and systems-dependent properties (i.e., target expression, density, localization, turnover, and affinity) in order to deliver a sufficient amount of a potent payload into the relevant target cells. As discussed, theoretical approaches with particular considerations given to various key properties for the target and modality suggest that delivery of the payload into particular effect cells to be more sensitive to antigen concentrations for targets with slow turnover rates as compared to those with faster internalization rates. Further assessments also suggest that increasing doses beyond the threshold of the target capacity (a function of target internalization and expression) may not impact the maximum amount of payload delivered to the intended effect cells. This article will explore the important application of quantitative sciences in selection of the target and design of ADC modalities.

Temporally selective attention modulates early perceptual processing: event-related potential evidence.

PubMed

Sanders, Lisa D; Astheimer, Lori B

2008-05-01

Some of the most important information we encounter changes so rapidly that our perceptual systems cannot process all of it in detail. Spatially selective attention is critical for perception when more information than can be processed in detail is presented simultaneously at distinct locations. When presented with complex, rapidly changing information, listeners may need to selectively attend to specific times rather than to locations. We present evidence that listeners can direct selective attention to time points that differ by as little as 500 msec, and that doing so improves target detection, affects baseline neural activity preceding stimulus presentation, and modulates auditory evoked potentials at a perceptually early stage. These data demonstrate that attentional modulation of early perceptual processing is temporally precise and that listeners can flexibly allocate temporally selective attention over short intervals, making it a viable mechanism for preferentially processing the most relevant segments in rapidly changing streams.

The EUVE Proposal Database

NASA Astrophysics Data System (ADS)

Christian, C. A.; Olson, E. C.

1993-01-01

The proposal database and scheduling system for the Extreme Ultraviolet Explorer is described. The proposal database has been implemented to take input for approved observations selected by the EUVE Peer Review Panel and output target information suitable for the scheduling system to digest. The scheduling system is a hybrid of the SPIKE program and EUVE software which checks spacecraft constraints, produces a proposed schedule and selects spacecraft orientations with optimal configurations for acquiring star trackers, etc. This system is used to schedule the In Orbit Calibration activities that took place this summer, following the EUVE launch in early June 1992. The strategy we have implemented has implications for the selection of approved targets, which have impacted the Peer Review process. In addition, we will discuss how the proposal database, founded on Sybase, controls the processing of EUVE Guest Observer data.

Designing Multi-target Compound Libraries with Gaussian Process Models.

PubMed

Bieler, Michael; Reutlinger, Michael; Rodrigues, Tiago; Schneider, Petra; Kriegl, Jan M; Schneider, Gisbert

2016-05-01

We present the application of machine learning models to selecting G protein-coupled receptor (GPCR)-focused compound libraries. The library design process was realized by ant colony optimization. A proprietary Boehringer-Ingelheim reference set consisting of 3519 compounds tested in dose-response assays at 11 GPCR targets served as training data for machine learning and activity prediction. We compared the usability of the proprietary data with a public data set from ChEMBL. Gaussian process models were trained to prioritize compounds from a virtual combinatorial library. We obtained meaningful models for three of the targets (5-HT2c , MCH, A1), which were experimentally confirmed for 12 of 15 selected and synthesized or purchased compounds. Overall, the models trained on the public data predicted the observed assay results more accurately. The results of this study motivate the use of Gaussian process regression on public data for virtual screening and target-focused compound library design. © 2016 The Authors. Published by Wiley-VCH Verlag GmbH & Co. KGaA. This is an open access article under the terms of the Creative Commons Attribution Non-Commercial NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.

Cognitive processes facilitated by contextual cueing: evidence from event-related brain potentials.

PubMed

Schankin, Andrea; Schubö, Anna

2009-05-01

Finding a target in repeated search displays is faster than finding the same target in novel ones (contextual cueing). It is assumed that the visual context (the arrangement of the distracting objects) is used to guide attention efficiently to the target location. Alternatively, other factors, e.g., facilitation in early visual processing or in response selection, may play a role as well. In a contextual cueing experiment, participant's electrophysiological brain activity was recorded. Participants identified the target faster and more accurately in repeatedly presented displays. In this condition, the N2pc, a component reflecting the allocation of visual-spatial attention, was enhanced, indicating that attention was allocated more efficiently to those targets. However, also response-related processes, reflected by the LRP, were facilitated, indicating that guidance of attention cannot account for the entire contextual cueing benefit.

Planar optical waveguide based sandwich assay sensors and processes for the detection of biological targets including protein markers, pathogens and cellular debris

DOEpatents

Martinez, Jennifer S [Santa Fe, NM; Swanson, Basil I [Los Alamos, NM; Grace, Karen M [Los Alamos, NM; Grace, Wynne K [Los Alamos, NM; Shreve, Andrew P [Santa Fe, NM

2009-06-02

An assay element is described including recognition ligands bound to a film on a single mode planar optical waveguide, the film from the group of a membrane, a polymerized bilayer membrane, and a self-assembled monolayer containing polyethylene glycol or polypropylene glycol groups therein and an assay process for detecting the presence of a biological target is described including injecting a biological target-containing sample into a sensor cell including the assay element, with the recognition ligands adapted for binding to selected biological targets, maintaining the sample within the sensor cell for time sufficient for binding to occur between selected biological targets within the sample and the recognition ligands, injecting a solution including a reporter ligand into the sensor cell; and, interrogating the sample within the sensor cell with excitation light from the waveguide, the excitation light provided by an evanescent field of the single mode penetrating into the biological target-containing sample to a distance of less than about 200 nanometers from the waveguide thereby exciting the fluorescent-label in any bound reporter ligand within a distance of less than about 200 nanometers from the waveguide and resulting in a detectable signal.

Adapting an Evidence-Based Intervention Targeting HIV-Infected Prisoners in Malaysia

PubMed Central

Copenhaver, Michael M.; Tunku, Noor; Ezeabogu, Ifeoma; Potrepka, Jessica; Zahari, Muhammad Muhsin A.; Kamarulzaman, Adeeba; Altice, Frederick L.

2011-01-01

HIV-infected prisoners in Malaysia represent a critical target population for secondary HIV risk reduction interventions and care. We report on the process and outcome of our formative research aimed at systematically selecting and adapting an EBI designed to reduce secondary HIV risk and improve adherence to antiretroviral therapy among soon-to-be-released HIV-infected prisoners. Our formative work involved a critical examination of established EBIs and associated published reports complemented by data elicited through structured interviews and focus groups with key stakeholders, members of the target population, and their family members. Based on all information, we adapted the Holistic Health Recovery Program targeting people living with HIV (HHRP+), an EBI, to consist of eight 2-hour sessions that cover a range of specified topics so that participants may individually apply intervention content as needed to accommodate their particular substance abuse, HIV risk, and antiretroviral adherence issues. This study provides a complete example of the process of selecting and adapting an EBI—taking into account both empirical evidence and input from target organization stakeholders and target population members and their families—for use in real world prison settings where high-risk populations are concentrated. PMID:21860786

Yersinia pestis targets neutrophils via complement receptor 3

PubMed Central

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

Disentangling the effects of spatial inconsistency of targets and distractors when searching in realistic scenes.

PubMed

Spotorno, Sara; Malcolm, George L; Tatler, Benjamin W

2015-02-10

Previous research has suggested that correctly placed objects facilitate eye guidance, but also that objects violating spatial associations within scenes may be prioritized for selection and subsequent inspection. We analyzed the respective eye guidance of spatial expectations and target template (precise picture or verbal label) in visual search, while taking into account any impact of object spatial inconsistency on extrafoveal or foveal processing. Moreover, we isolated search disruption due to misleading spatial expectations about the target from the influence of spatial inconsistency within the scene upon search behavior. Reliable spatial expectations and precise target template improved oculomotor efficiency across all search phases. Spatial inconsistency resulted in preferential saccadic selection when guidance by template was insufficient to ensure effective search from the outset and the misplaced object was bigger than the objects consistently placed in the same scene region. This prioritization emerged principally during early inspection of the region, but the inconsistent object also tended to be preferentially fixated overall across region viewing. These results suggest that objects are first selected covertly on the basis of their relative size and that subsequent overt selection is made considering object-context associations processed in extrafoveal vision. Once the object was fixated, inconsistency resulted in longer first fixation duration and longer total dwell time. As a whole, our findings indicate that observed impairment of oculomotor behavior when searching for an implausibly placed target is the combined product of disruption due to unreliable spatial expectations and prioritization of inconsistent objects before and during object fixation. © 2015 ARVO.

Selective Attention and Control of Action: Comparative Psychology of an Artificial, Evolved Agent and People

ERIC Educational Resources Information Center

Ward, Robert; Ward, Ronnie

2008-01-01

This study examined the selective attention abilities of a simple, artificial, evolved agent and considered implications of the agent's performance for theories of selective attention and action. The agent processed two targets in continuous time, catching one and then the other. This task required many cognitive operations, including prioritizing…

Microfluidics for Drug Discovery and Development: From Target Selection to Product Lifecycle Management

PubMed Central

Kang, Lifeng; Chung, Bong Geun; Langer, Robert; Khademhosseini, Ali

2009-01-01

Microfluidic technologies’ ability to miniaturize assays and increase experimental throughput have generated significant interest in the drug discovery and development domain. These characteristics make microfluidic systems a potentially valuable tool for many drug discovery and development applications. Here, we review the recent advances of microfluidic devices for drug discovery and development and highlight their applications in different stages of the process, including target selection, lead identification, preclinical tests, clinical trials, chemical synthesis, formulations studies, and product management. PMID:18190858

Bioassay and biomolecular identification, sorting, and collection methods using magnetic microspheres

DOEpatents

Kraus, Jr., Robert H.; Zhou, Feng [Los Alamos, NM; Nolan, John P [Santa Fe, NM

2007-06-19

The present invention is directed to processes of separating, analyzing and/or collecting selected species within a target sample by use of magnetic microspheres including magnetic particles, the magnetic microspheres adapted for attachment to a receptor agent that can subsequently bind to selected species within the target sample. The magnetic microspheres can be sorted into a number of distinct populations, each population with a specific range of magnetic moments and different receptor agents can be attached to each distinct population of magnetic microsphere.

The development of control processes supporting source memory discrimination as revealed by event-related potentials.

PubMed

de Chastelaine, Marianne; Friedman, David; Cycowicz, Yael M

2007-08-01

Improvement in source memory performance throughout childhood is thought to be mediated by the development of executive control. As postretrieval control processes may be better time-locked to the recognition response rather than the retrieval cue, the development of processes underlying source memory was investigated with both stimulus- and response-locked event-related potentials (ERPs). These were recorded in children, adolescents, and adults during a recognition memory exclusion task. Green- and red-outlined pictures were studied, but were tested in black outline. The test requirement was to endorse old items shown in one study color ("targets") and to reject new items along with old items shown in the alternative study color ("nontargets"). Source memory improved with age. All age groups retrieved target and nontarget memories as reflected by reliable parietal episodic memory (EM) effects, a stimulus-locked ERP correlate of recollection. Response-locked ERPs to targets and nontargets diverged in all groups prior to the response, although this occurred at an increasingly earlier time point with age. We suggest these findings reflect the implementation of attentional control mechanisms to enhance target memories and facilitate response selection with the greatest and least success, respectively, in adults and children. In adults only, response-locked ERPs revealed an early-onsetting parietal negativity for nontargets, but not for targets. This was suggested to reflect adults' ability to consistently inhibit prepotent target responses for nontargets. The findings support the notion that the development of source memory relies on the maturation of control processes that serve to enhance accurate selection of task-relevant memories.

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

PubMed

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 with the notion that both kinds of SL adjust the priority of specific locations within attentional priority maps of space. Copyright © 2017 Elsevier Ltd. All rights reserved.

Automation of cellular therapy product manufacturing: results of a split validation comparing CD34 selection of peripheral blood stem cell apheresis product with a semi-manual vs. an automatic procedure.

PubMed

Hümmer, Christiane; Poppe, Carolin; Bunos, Milica; Stock, Belinda; Wingenfeld, Eva; Huppert, Volker; Stuth, Juliane; Reck, Kristina; Essl, Mike; Seifried, Erhard; Bonig, Halvard

2016-03-16

Automation of cell therapy manufacturing promises higher productivity of cell factories, more economical use of highly-trained (and costly) manufacturing staff, facilitation of processes requiring manufacturing steps at inconvenient hours, improved consistency of processing steps and other benefits. One of the most broadly disseminated engineered cell therapy products is immunomagnetically selected CD34+ hematopoietic "stem" cells (HSCs). As the clinical GMP-compliant automat CliniMACS Prodigy is being programmed to perform ever more complex sequential manufacturing steps, we developed a CD34+ selection module for comparison with the standard semi-automatic CD34 "normal scale" selection process on CliniMACS Plus, applicable for 600 × 10(6) target cells out of 60 × 10(9) total cells. Three split-validation processings with healthy donor G-CSF-mobilized apheresis products were performed; feasibility, time consumption and product quality were assessed. All processes proceeded uneventfully. Prodigy runs took about 1 h longer than CliniMACS Plus runs, albeit with markedly less hands-on operator time and therefore also suitable for less experienced operators. Recovery of target cells was the same for both technologies. Although impurities, specifically T- and B-cells, were 5 ± 1.6-fold and 4 ± 0.4-fold higher in the Prodigy products (p = ns and p = 0.013 for T and B cell depletion, respectively), T cell contents per kg of a virtual recipient receiving 4 × 10(6) CD34+ cells/kg was below 10 × 10(3)/kg even in the worst Prodigy product and thus more than fivefold below the specification of CD34+ selected mismatched-donor stem cell products. The products' theoretical clinical usability is thus confirmed. This split validation exercise of a relatively short and simple process exemplifies the potential of automatic cell manufacturing. Automation will further gain in attractiveness when applied to more complex processes, requiring frequent interventions or handling at unfavourable working hours, such as re-targeting of T-cells.

Production Of High Specific Activity Copper-67

DOEpatents

Jamriska, Sr., David J.; Taylor, Wayne A.; Ott, Martin A.; Fowler, Malcolm; Heaton, Richard C.

2002-12-03

A process for the selective production and isolation of high specific activity cu.sup.67 from proton-irradiated enriched Zn.sup.70 target comprises target fabrication, target irradiation with low energy (<25 MeV) protons, chemical separation of the Cu.sup.67 product from the target material and radioactive impurities of gallium, cobalt, iron, and stable aluminum via electrochemical methods or ion exchange using both anion and cation organic ion exchangers, chemical recovery of the enriched Zn.sup.70 target material, and fabrication of new targets for re-irradiation is disclosed.

Production Of High Specific Activity Copper-67

DOEpatents

Jamriska, Sr., David J.; Taylor, Wayne A.; Ott, Martin A.; Fowler, Malcolm; Heaton, Richard C.

2003-10-28

A process for the selective production and isolation of high specific activity Cu.sup.67 from proton-irradiated enriched Zn.sup.70 target comprises target fabrication, target irradiation with low energy (<25 MeV) protons, chemical separation of the Cu.sup.67 product from the target material and radioactive impurities of gallium, cobalt, iron, and stable aluminum via electrochemical methods or ion exchange using both anion and cation organic ion exchangers, chemical recovery of the enriched Zn.sup.70 target material, and fabrication of new targets for re-irradiation is disclosed.

Recycling 100Mo for direct production of 99mTc on medical cyclotrons

NASA Astrophysics Data System (ADS)

Kumlin, Joel O.; Zeisler, Stefan K.; Hanemaayer, Victoire; Schaffer, Paul

2018-05-01

A scalable recycling technique for the recovery of 100Mo from previously irradiated and chemically processed targets is described. A combined process for both Cu and Ta supported targets and the respective `waste' solutions has been developed. This process involves selectively dissolving Cu target backings from undissolved portions of 100Mo pellets; precipitating Cu(OH)2 at pH 9; electrochemical removal of Cu traces; precipitating (NH4)2MoO4 at pH 2.5-3; thermally decomposing (NH4)2MoO4; and H2 reduction of MoO3 to Mo metal. Radionuclidic decontamination by a factor of 100 is observed, while overall 100Mo recovery from initial target plating to recycled Mo metal of 96% is achieved.

Building Face Composites Can Harm Lineup Identification Performance

ERIC Educational Resources Information Center

Wells, Gary L.; Charman, Steve D.; Olson, Elizabeth A.

2005-01-01

Face composite programs permit eyewitnesses to build likenesses of target faces by selecting facial features and combining them into an intact face. Research has shown that these composites are generally poor likenesses of the target face. Two experiments tested the proposition that this composite-building process could harm the builder's memory…

Target Selection for the SDSS-III MARVELS Survey

NASA Astrophysics Data System (ADS)

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.

Perceptual load manipulation reveals sensitivity of the face-selective N170 to attention.

PubMed

Mohamed, Tarik N; Neumann, Markus F; Schweinberger, Stefan R

2009-05-27

It has been controversial whether the face-sensitive N170 is affected by selective attention. We manipulated attention sensu Lavie's perceptual load theory to short (200 ms) presentations of task-irrelevant unfamiliar faces or houses, while participants identified superimposed target letters 'X' versus 'N'. These targets were strings of either six identical (low load) or six different letters (high load). Under low load, we found a prominent face-selective N170 response. Under high load, however, we not only observed a dramatic reduction of the face N170 but also an unexpected enhancement of the house N170, such that face selectivity was almost completely lost. We conclude that the early stages of face processing indexed by the N170 strongly depend on selective attention.

Selective amyloid β oligomer assay based on abasic site-containing molecular beacon and enzyme-free amplification.

PubMed

Zhu, Linling; Zhang, Junying; Wang, Fengyang; Wang, Ya; Lu, Linlin; Feng, Chongchong; Xu, Zhiai; Zhang, Wen

2016-04-15

Amyloid-beta (Aβ) oligomers are highly toxic species in the process of Aβ aggregation and are regarded as potent therapeutic targets and diagnostic markers for Alzheimer's disease (AD). Herein, a label-free molecular beacon (MB) system integrated with enzyme-free amplification strategy was developed for simple and highly selective assay of Aβ oligomers. The MB system was constructed with abasic site (AP site)-containing stem-loop DNA and a fluorescent ligand 2-amino-5,6,7-trimethyl-1,8-naphyridine (ATMND), of which the fluorescence was quenched upon binding to the AP site in DNA stem. Enzyme-free amplification was realized by target-triggered continuous opening of two delicately designed MBs (MB1 and MB2). Target DNA hybridization with MB1 and then MB2 resulted in the release of two ATMND molecules in one binding event. Subsequent target recycling could greatly amplify the detection sensitivity due to the greatly enhanced turn-on emission of ATMND fluorescence. Combining with Aβ oligomers aptamers, the strategy was applied to analyze Aβ oligomers and the results showed that it could quantify Aβ oligomers with high selectivity and monitor the Aβ aggregation process. This novel method may be conducive to improve the diagnosis and pathogenic study of Alzheimer's disease. Copyright © 2015 Elsevier B.V. All rights reserved.

Irrelevant reward and selection histories have different influences on task-relevant attentional selection.

PubMed

MacLean, Mary H; Giesbrecht, Barry

2015-07-01

Task-relevant and physically salient features influence visual selective attention. In the present study, we investigated the influence of task-irrelevant and physically nonsalient reward-associated features on visual selective attention. Two hypotheses were tested: One predicts that the effects of target-defining task-relevant and task-irrelevant features interact to modulate visual selection; the other predicts that visual selection is determined by the independent combination of relevant and irrelevant feature effects. These alternatives were tested using a visual search task that contained multiple targets, placing a high demand on the need for selectivity, and that was data-limited and required unspeeded responses, emphasizing early perceptual selection processes. One week prior to the visual search task, participants completed a training task in which they learned to associate particular colors with a specific reward value. In the search task, the reward-associated colors were presented surrounding targets and distractors, but were neither physically salient nor task-relevant. In two experiments, the irrelevant reward-associated features influenced performance, but only when they were presented in a task-relevant location. The costs induced by the irrelevant reward-associated features were greater when they oriented attention to a target than to a distractor. In a third experiment, we examined the effects of selection history in the absence of reward history and found that the interaction between task relevance and selection history differed, relative to when the features had previously been associated with reward. The results indicate that under conditions that demand highly efficient perceptual selection, physically nonsalient task-irrelevant and task-relevant factors interact to influence visual selective attention.

Lateral position detection and control for friction stir systems

DOEpatents

Fleming, Paul; Lammlein, David H.; Cook, George E.; Wilkes, Don Mitchell; Strauss, Alvin M.; Delapp, David R.; Hartman, Daniel A.

2012-06-05

An apparatus and computer program are disclosed for processing at least one workpiece using a rotary tool with rotating member for contacting and processing the workpiece. The methods include oscillating the rotary tool laterally with respect to a selected propagation path for the rotating member with respect to the workpiece to define an oscillation path for the rotating member. The methods further include obtaining force signals or parameters related to the force experienced by the rotary tool at least while the rotating member is disposed at the extremes of the oscillation. The force signals or parameters associated with the extremes can then be analyzed to determine a lateral position of the selected path with respect to a target path and a lateral offset value can be determined based on the lateral position. The lateral distance between the selected path and the target path can be decreased based on the lateral offset value.

Lateral position detection and control for friction stir systems

DOEpatents

Fleming, Paul [Boulder, CO; Lammlein, David H [Houston, TX; Cook, George E [Brentwood, TN; Wilkes, Don Mitchell [Nashville, TN; Strauss, Alvin M [Nashville, TN; Delapp, David R [Ashland City, TN; Hartman, Daniel A [Fairhope, AL

2011-11-08

Friction stir methods are disclosed for processing at least one workpiece using a rotary tool with rotating member for contacting and processing the workpiece. The methods include oscillating the rotary tool laterally with respect to a selected propagation path for the rotating member with respect to the workpiece to define an oscillation path for the rotating member. The methods further include obtaining force signals or parameters related to the force experienced by the rotary tool at least while the rotating member is disposed at the extremes of the oscillation. The force signals or parameters associated with the extremes can then be analyzed to determine a lateral position of the selected path with respect to a target path and a lateral offset value can be determined based on the lateral position. The lateral distance between the selected path and the target path can be decreased based on the lateral offset value.

Survey of Munitions Response Technologies

DTIC Science & Technology

2006-06-01

3-34 3.3.4 Digital Data Processing .......................................................................... 3-36 4.0 SOURCE DATA AND METHODS...6-4 6.1.6 DGM versus Mag and Flag Processes ..................................................... 6-5 6.1.7 Translation to...signatures, surface clutter, variances in operator technique, target selection, and data processing all degrade from and affect optimum performance

Secondary Students' Accounts of Carbon-Transforming Processes before and after Instruction

ERIC Educational Resources Information Center

Onyancha, Kennedy M.; Anderson, Charles W.

2012-01-01

The purpose of this study is to examine the extent to which more targeted instruction is helpful in eliciting students' scientific explanations of six selected carbon-transforming processes of combustion, cross processes, decomposition, growth, photosynthesis and respiration. We also examined these students' accounts regarding the corresponding…

The guidance of visual search by shape features and shape configurations.

PubMed

McCants, Cody W; Berggren, Nick; Eimer, Martin

2018-03-01

Representations of target features (attentional templates) guide attentional object selection during visual search. In many search tasks, targets objects are defined not by a single feature but by the spatial configuration of their component shapes. We used electrophysiological markers of attentional selection processes to determine whether the guidance of shape configuration search is entirely part-based or sensitive to the spatial relationship between shape features. Participants searched for targets defined by the spatial arrangement of two shape components (e.g., hourglass above circle). N2pc components were triggered not only by targets but also by partially matching distractors with one target shape (e.g., hourglass above hexagon) and by distractors that contained both target shapes in the reverse arrangement (e.g., circle above hourglass), in line with part-based attentional control. Target N2pc components were delayed when a reverse distractor was present on the opposite side of the same display, suggesting that early shape-specific attentional guidance processes could not distinguish between targets and reverse distractors. The control of attention then became sensitive to spatial configuration, which resulted in a stronger attentional bias for target objects relative to reverse and partially matching distractors. Results demonstrate that search for target objects defined by the spatial arrangement of their component shapes is initially controlled in a feature-based fashion but can later be guided by templates for spatial configurations. (PsycINFO Database Record (c) 2018 APA, all rights reserved).

Selective attention and subjective confidence calibration.

PubMed

Schoenherr, Jordan R; Leth-Steensen, Craig; Petrusic, William M

2010-02-01

In the present experiments, failures of selective visual attention were invoked using the B. A. Eriksen and C. W. Eriksen (1974) flanker task. On each trial, a three-letter stimulus array was flashed briefly, followed by a mask. The identity of the two flanking letters was response congruent, neutral, or incongruent with the identity of the middle target letter. On half of the trials, confidence ratings were obtained after each response. In the first three experiments, participants were highly overconfident in the accuracy of their responding to incongruent flanker stimulus arrays. In a final experiment, presenting a prestimulus target location cue greatly reduced both selective attention failure and overconfidence. The findings demonstrate that participants are often unaware of such selective attention failures and provide support for the notion that, in these cases, decisional processing is driven largely by the identities of the incongruent flankers. In addition, responding was invariably slower and sometimes more accurate when confidence was required than when it was not required, demonstrating that the need to provide posttrial confidence reports can affect decisional processing. Moreover, there was some evidence that the presence of neutral contextual flanking information can slow responding, suggesting that such nondiagnostic information can, indeed, contribute to decisional processing.

Identifying Educational Practices Supported by Rigorous Evidence: A Guide to the Selection of Evidence-Based Practices

ERIC Educational Resources Information Center

Regional Resource Center Program, 2014

2014-01-01

One component of the recently required State Systemic Improvement Plan (SSIP) for State Departments of Education calls for the selection and implementation of evidence-based practices (EBPs). This report provides six steps to guide the process of selecting evidence based practices (EBP): (1) Begin with the End in Mind--Determine Targeted Outcomes;…

Auditory selective attention in adolescents with major depression: An event-related potential study.

PubMed

Greimel, E; Trinkl, M; Bartling, J; Bakos, S; Grossheinrich, N; Schulte-Körne, G

2015-02-01

Major depression (MD) is associated with deficits in selective attention. Previous studies in adults with MD using event-related potentials (ERPs) reported abnormalities in the neurophysiological correlates of auditory selective attention. However, it is yet unclear whether these findings can be generalized to MD in adolescence. Thus, the aim of the present ERP study was to explore the neural mechanisms of auditory selective attention in adolescents with MD. 24 male and female unmedicated adolescents with MD and 21 control subjects were included in the study. ERPs were collected during an auditory oddball paradigm. Depressive adolescents tended to show a longer N100 latency to target and non-target tones. Moreover, MD subjects showed a prolonged latency of the P200 component to targets. Across groups, longer P200 latency was associated with a decreased tendency of disinhibited behavior as assessed by a behavioral questionnaire. To be able to draw more precise conclusions about differences between the neural bases of selective attention in adolescents vs. adults with MD, future studies should include both age groups and apply the same experimental setting across all subjects. The study provides strong support for abnormalities in the neurophysiolgical bases of selective attention in adolecents with MD at early stages of auditory information processing. Absent group differences in later ERP components reflecting voluntary attentional processes stand in contrast to results reported in adults with MD and may suggest that adolescents with MD possess mechanisms to compensate for abnormalities in the early stages of selective attention. Copyright © 2014 Elsevier B.V. All rights reserved.

A study of swing-curve physics in diffraction-based overlay

NASA Astrophysics Data System (ADS)

Bhattacharyya, Kaustuve; den Boef, Arie; Storms, Greet; van Heijst, Joost; Noot, Marc; An, Kevin; Park, Noh-Kyoung; Jeon, Se-Ra; Oh, Nang-Lyeom; McNamara, Elliott; van de Mast, Frank; Oh, SeungHwa; Lee, Seung Yoon; Hwang, Chan; Lee, Kuntack

2016-03-01

With the increase of process complexity in advanced nodes, the requirements of process robustness in overlay metrology continues to tighten. Especially with the introduction of newer materials in the film-stack along with typical stack variations (thickness, optical properties, profile asymmetry etc.), the signal formation physics in diffraction-based overlay (DBO) becomes an important aspect to apply in overlay metrology target and recipe selection. In order to address the signal formation physics, an effort is made towards studying the swing-curve phenomena through wavelength and polarizations on production stacks using simulations as well as experimental technique using DBO. The results provide a wealth of information on target and recipe selection for robustness. Details from simulation and measurements will be reported in this technical publication.

Inside the Black Box of Audit and Feedback: a Laboratory Study to Explore Determinants of Improvement Target Selection by Healthcare Professionals in Cardiac Rehabilitation.

PubMed

Gude, Wouter T; van der Veer, Sabine N; van Engen-Verheul, Mariëtte M; de Keizer, Nicolette F; Peek, Niels

2015-01-01

Audit and feedback (A&F) is widely used to aid healthcare professionals in improving clinical performance, but there is little understanding of the underlying mechanism that determines its effectiveness. The aim of this paper is to investigate the process by which healthcare professionals select indicators as improvement targets based on A&F. We performed a laboratory study among 41 healthcare professionals in the context of a web-based A&F intervention designed to improve the quality of cardiac rehabilitation care in the Netherlands. Feedback was provided on eighteen quality indicators, including a score and a colour (representing a recommendation for selection (red and yellow) or non-selection (green)). Indicators with more room for improvement were more likely to be selected, although this varied substantially between participants. In more than a quarter of the cases, participants did not select indicators with obvious room for improvement (yellow or red colour), or selected indicators without apparent room for improvement (green colour). We conclude that personal preferences and beliefs concerning quality and performance targets may dilute the efficiency of A&F.

New Kid on the Block.

PubMed

Reinheckel, Thomas

2017-01-01

Cysteine cathepsins are a group of proteases involved in many physiological and pathological processes. Yet, the selective detection and inhibition of individual cathepsins is still challenging. This editorial is discussing the context of a recent work introducing a designed ankyrin repeat protein (DARPin) as novel approach for selective targeting of the protease cathepsin B.

Cortical Mechanisms of Prioritizing Selection for Rejection in Visual Search.

PubMed

Donohue, Sarah E; Bartsch, Mandy V; Heinze, Hans-Jochen; Schoenfeld, Mircea A; Hopf, Jens-Max

2018-05-16

In visual search, the more one knows about a target, the faster one can find it. Surprisingly, target identification is also faster with knowledge about distractor-features. The latter is paradoxical, as it implies that to avoid the selection of an item, the item must somehow be selected to some degree. This conundrum has been termed the "ignoring paradox", and, to date, little is known about how the brain resolves it. Here, in data from four experiments using neuromagnetic brain recordings in male and female humans, we provide evidence that this paradox is resolved by giving distracting information priority in cortical processing. This attentional priority to distractors manifests as an enhanced early neuromagnetic index, which occurs before target-related processing, and regardless of distractor predictability. It is most pronounced on trials for which a response rapidly occurred, and is followed by a suppression of the distracting information. These observations together suggest that in visual search items cannot be ignored without first being selected. SIGNIFICANCE STATEMENT How can we ignore distracting stimuli in our environment? To do this successfully, a logical hypothesis is that as few neural resources as possible should be devoted to distractor processing. Yet, to avoid devoting resources to a distractor, the brain must somehow mark what to avoid; this is a philosophical problem, which has been termed the "ignoring paradox" or "white bear phenomenon". Here, we use MEG recordings to determine how the human brain resolves this paradox. Our data show that distractors are not only processed, they are given temporal priority, with the brain building a robust representation of the to-be-ignored items. Thus, successful suppression of distractors can only be achieved if distractors are first strongly neurally represented. Copyright © 2018 the authors 0270-6474/18/384738-11$15.00/0.

Parietal cortex integrates contextual and saliency signals during the encoding of natural scenes in working memory.

PubMed

Santangelo, Valerio; Di Francesco, Simona Arianna; Mastroberardino, Serena; Macaluso, Emiliano

2015-12-01

The Brief presentation of a complex scene entails that only a few objects can be selected, processed indepth, and stored in memory. Both low-level sensory salience and high-level context-related factors (e.g., the conceptual match/mismatch between objects and scene context) contribute to this selection process, but how the interplay between these factors affects memory encoding is largely unexplored. Here, during fMRI we presented participants with pictures of everyday scenes. After a short retention interval, participants judged the position of a target object extracted from the initial scene. The target object could be either congruent or incongruent with the context of the scene, and could be located in a region of the image with maximal or minimal salience. Behaviourally, we found a reduced impact of saliency on visuospatial working memory performance when the target was out-of-context. Encoding-related fMRI results showed that context-congruent targets activated dorsoparietal regions, while context-incongruent targets de-activated the ventroparietal cortex. Saliency modulated activity both in dorsal and ventral regions, with larger context-related effects for salient targets. These findings demonstrate the joint contribution of knowledge-based and saliency-driven attention for memory encoding, highlighting a dissociation between dorsal and ventral parietal regions. © 2015 Wiley Periodicals, Inc.

Changes of Attention during Value-Based Reversal Learning Are Tracked by N2pc and Feedback-Related Negativity

PubMed Central

Oemisch, Mariann; Watson, Marcus R.; Womelsdorf, Thilo; Schubö, Anna

2017-01-01

Previously learned reward values can have a pronounced impact, behaviorally and neurophysiologically, on the allocation of selective attention. All else constant, stimuli previously associated with a high value gain stronger attentional prioritization than stimuli previously associated with a low value. The N2pc, an ERP component indicative of attentional target selection, has been shown to reflect aspects of this prioritization, by changes of mean amplitudes closely corresponding to selective enhancement of high value target processing and suppression of high value distractor processing. What has remained unclear so far is whether the N2pc also reflects the flexible and repeated behavioral adjustments needed in a volatile task environment, in which the values of stimuli are reversed often and unannounced. Using a value-based reversal learning task, we found evidence that the N2pc amplitude flexibly and reversibly tracks value-based choices during the learning of reward associated stimulus colors. Specifically, successful learning of current value-contingencies was associated with reduced N2pc amplitudes, and this effect was more apparent for distractor processing, compared with target processing. In addition, following a value reversal the feedback related negativity(FRN), an ERP component that reflects feedback processing, was amplified and co-occurred with increased N2pc amplitudes in trials following low-value feedback. Importantly, participants that showed the greatest adjustment in N2pc amplitudes based on feedback were also the most efficient learners. These results allow further insight into how changes in attentional prioritization in an uncertain and volatile environment support flexible adjustments of behavior. PMID:29163113

Changes of Attention during Value-Based Reversal Learning Are Tracked by N2pc and Feedback-Related Negativity.

PubMed

Oemisch, Mariann; Watson, Marcus R; Womelsdorf, Thilo; Schubö, Anna

2017-01-01

Previously learned reward values can have a pronounced impact, behaviorally and neurophysiologically, on the allocation of selective attention. All else constant, stimuli previously associated with a high value gain stronger attentional prioritization than stimuli previously associated with a low value. The N2pc, an ERP component indicative of attentional target selection, has been shown to reflect aspects of this prioritization, by changes of mean amplitudes closely corresponding to selective enhancement of high value target processing and suppression of high value distractor processing. What has remained unclear so far is whether the N2pc also reflects the flexible and repeated behavioral adjustments needed in a volatile task environment, in which the values of stimuli are reversed often and unannounced. Using a value-based reversal learning task, we found evidence that the N2pc amplitude flexibly and reversibly tracks value-based choices during the learning of reward associated stimulus colors. Specifically, successful learning of current value-contingencies was associated with reduced N2pc amplitudes, and this effect was more apparent for distractor processing, compared with target processing. In addition, following a value reversal the feedback related negativity(FRN), an ERP component that reflects feedback processing, was amplified and co-occurred with increased N2pc amplitudes in trials following low-value feedback. Importantly, participants that showed the greatest adjustment in N2pc amplitudes based on feedback were also the most efficient learners. These results allow further insight into how changes in attentional prioritization in an uncertain and volatile environment support flexible adjustments of behavior.

Reward-associated stimuli capture the eyes in spite of strategic attentional set.

PubMed

Hickey, Clayton; van Zoest, Wieske

2013-11-01

Theories of reinforcement learning have proposed that the association of reward to visual stimuli may cause these objects to become fundamentally salient and thus attention-drawing. A number of recent studies have investigated the oculomotor correlates of this reward-priming effect, but there is some ambiguity in this literature regarding the involvement of top-down attentional set. Existing paradigms tend to create a situation where participants are actively looking for a reward-associated stimulus before subsequently showing that this selective bias sustains when it no longer has strategic purpose. This perseveration of attentional set is potentially different in nature than the direct impact of reward proposed by theory. Here we investigate the effect of reward on saccadic selection in a paradigm where strategic attentional set is decoupled from the effect of reward. We find that during search for a uniquely oriented target, the receipt of reward following selection of a target characterized by an irrelevant unique color causes subsequent stimuli characterized by this color to be preferentially selected. Importantly, this occurs regardless of whether the color characterizes the target or distractor. Other analyses demonstrate that only features associated with correct selection of the target prime the target representation, and that the magnitude of this effect can be predicted by variability in saccadic indices of feedback processing. These results add to a growing literature demonstrating that reward guides visual selection, often in spite of our strategic efforts otherwise. Copyright © 2013 Elsevier B.V. All rights reserved.

PeptidePicker: a scientific workflow with web interface for selecting appropriate peptides for targeted proteomics experiments.

PubMed

Mohammed, Yassene; Domański, Dominik; Jackson, Angela M; Smith, Derek S; Deelder, André M; Palmblad, Magnus; Borchers, Christoph H

2014-06-25

One challenge in Multiple Reaction Monitoring (MRM)-based proteomics is to select the most appropriate surrogate peptides to represent a target protein. We present here a software package to automatically generate these most appropriate surrogate peptides for an LC/MRM-MS analysis. Our method integrates information about the proteins, their tryptic peptides, and the suitability of these peptides for MRM which is available online in UniProtKB, NCBI's dbSNP, ExPASy, PeptideAtlas, PRIDE, and GPMDB. The scoring algorithm reflects our knowledge in choosing the best candidate peptides for MRM, based on the uniqueness of the peptide in the targeted proteome, its physiochemical properties, and whether it previously has been observed. The modularity of the workflow allows further extension and additional selection criteria to be incorporated. We have developed a simple Web interface where the researcher provides the protein accession number, the subject organism, and peptide-specific options. Currently, the software is designed for human and mouse proteomes, but additional species can be easily be added. Our software improved the peptide selection by eliminating human error, considering multiple data sources and all of the isoforms of the protein, and resulted in faster peptide selection - approximately 50 proteins per hour compared to 8 per day. Compiling a list of optimal surrogate peptides for target proteins to be analyzed by LC/MRM-MS has been a cumbersome process, in which expert researchers retrieved information from different online repositories and used their own reasoning to find the most appropriate peptides. Our scientific workflow automates this process by integrating information from different data sources including UniProt, Global Proteome Machine, NCBI's dbSNP, and PeptideAtlas, simulating the researchers' reasoning, and incorporating their knowledge of how to select the best proteotypic peptides for an MRM analysis. The developed software can help to standardize the selection of peptides, eliminate human error, and increase productivity. Copyright © 2014 Elsevier B.V. All rights reserved.

Can We Retrieve the Information Which Was Intentionally Forgotten? Electrophysiological Correlates of Strategic Retrieval in Directed Forgetting.

PubMed

Mao, Xinrui; Tian, Mengxi; Liu, Yi; Li, Bingcan; Jin, Yan; Wu, Yanhong; Guo, Chunyan

2017-01-01

Retrieval inhibition hypothesis of directed forgetting effects assumed TBF (to-be-forgotten) items were not retrieved intentionally, while selective rehearsal hypothesis assumed the memory representation of retrieved TBF (to-be-forgotten) items was weaker than TBR (to-be-remembered) items. Previous studies indicated that directed forgetting effects of item-cueing method resulted from selective rehearsal at encoding, but the mechanism of retrieval inhibition that affected directed forgetting of TBF (to-be-forgotten) items was not clear. Strategic retrieval is a control process allowing the selective retrieval of target information, which includes retrieval orientation and strategic recollection. Retrieval orientation via the comparison of tasks refers to the specific form of processing resulted by retrieval efforts. Strategic recollection is the type of strategies to recollect studied items for the retrieval success of targets. Using a "directed forgetting" paradigm combined with a memory exclusion task, our investigation of strategic retrieval in directed forgetting assisted to explore how retrieval inhibition played a role on directed forgetting effects. When TBF items were targeted, retrieval orientation showed more positive ERPs to new items, indicating that TBF items demanded more retrieval efforts. The results of strategic recollection indicated that: (a) when TBR items were retrieval targets, late parietal old/new effects were only evoked by TBR items but not TBF items, indicating the retrieval inhibition of TBF items; (b) when TBF items were retrieval targets, the late parietal old/new effect were evoked by both TBR items and TBF items, indicating that strategic retrieval could overcome retrieval inhibition of TBF items. These findings suggested the modulation of strategic retrieval on retrieval inhibition of directed forgetting, supporting that directed forgetting effects were not only caused by selective rehearsal, but also retrieval inhibition.

Can We Retrieve the Information Which Was Intentionally Forgotten? Electrophysiological Correlates of Strategic Retrieval in Directed Forgetting

PubMed Central

Mao, Xinrui; Tian, Mengxi; Liu, Yi; Li, Bingcan; Jin, Yan; Wu, Yanhong; Guo, Chunyan

2017-01-01

Retrieval inhibition hypothesis of directed forgetting effects assumed TBF (to-be-forgotten) items were not retrieved intentionally, while selective rehearsal hypothesis assumed the memory representation of retrieved TBF (to-be-forgotten) items was weaker than TBR (to-be-remembered) items. Previous studies indicated that directed forgetting effects of item-cueing method resulted from selective rehearsal at encoding, but the mechanism of retrieval inhibition that affected directed forgetting of TBF (to-be-forgotten) items was not clear. Strategic retrieval is a control process allowing the selective retrieval of target information, which includes retrieval orientation and strategic recollection. Retrieval orientation via the comparison of tasks refers to the specific form of processing resulted by retrieval efforts. Strategic recollection is the type of strategies to recollect studied items for the retrieval success of targets. Using a “directed forgetting” paradigm combined with a memory exclusion task, our investigation of strategic retrieval in directed forgetting assisted to explore how retrieval inhibition played a role on directed forgetting effects. When TBF items were targeted, retrieval orientation showed more positive ERPs to new items, indicating that TBF items demanded more retrieval efforts. The results of strategic recollection indicated that: (a) when TBR items were retrieval targets, late parietal old/new effects were only evoked by TBR items but not TBF items, indicating the retrieval inhibition of TBF items; (b) when TBF items were retrieval targets, the late parietal old/new effect were evoked by both TBR items and TBF items, indicating that strategic retrieval could overcome retrieval inhibition of TBF items. These findings suggested the modulation of strategic retrieval on retrieval inhibition of directed forgetting, supporting that directed forgetting effects were not only caused by selective rehearsal, but also retrieval inhibition. PMID:28900411

Beyond the standard plate count: genomic views into microbial food ecology

USDA-ARS?s Scientific Manuscript database

Food spoilage is a complex process that involves multiple species with specific niches and metabolic processes; bacterial culturing techniques are the traditional methods for identifying the microbes responsible. These culture-dependent methods may be considered selective, targeting the isolation of...

Holistic metrology qualification extension and its application to characterize overlay targets with asymmetric effects

NASA Astrophysics Data System (ADS)

Dos Santos Ferreira, Olavio; Sadat Gousheh, Reza; Visser, Bart; Lie, Kenrick; Teuwen, Rachel; Izikson, Pavel; Grzela, Grzegorz; Mokaberi, Babak; Zhou, Steve; Smith, Justin; Husain, Danish; Mandoy, Ram S.; Olvera, Raul

2018-03-01

Ever increasing need for tighter on-product overlay (OPO), as well as enhanced accuracy in overlay metrology and methodology, is driving semiconductor industry's technologists to innovate new approaches to OPO measurements. In case of High Volume Manufacturing (HVM) fabs, it is often critical to strive for both accuracy and robustness. Robustness, in particular, can be challenging in metrology since overlay targets can be impacted by proximity of other structures next to the overlay target (asymmetric effects), as well as symmetric stack changes such as photoresist height variations. Both symmetric and asymmetric contributors have impact on robustness. Furthermore, tweaking or optimizing wafer processing parameters for maximum yield may have an adverse effect on physical target integrity. As a result, measuring and monitoring physical changes or process abnormalities/artefacts in terms of new Key Performance Indicators (KPIs) is crucial for the end goal of minimizing true in-die overlay of the integrated circuits (ICs). IC manufacturing fabs often relied on CD-SEM in the past to capture true in-die overlay. Due to destructive and intrusive nature of CD-SEMs on certain materials, it's desirable to characterize asymmetry effects for overlay targets via inline KPIs utilizing YieldStar (YS) metrology tools. These KPIs can also be integrated as part of (μDBO) target evaluation and selection for final recipe flow. In this publication, the Holistic Metrology Qualification (HMQ) flow was extended to account for process induced (asymmetric) effects such as Grating Imbalance (GI) and Bottom Grating Asymmetry (BGA). Local GI typically contributes to the intrafield OPO whereas BGA typically impacts the interfield OPO, predominantly at the wafer edge. Stack height variations highly impact overlay metrology accuracy, in particular in case of multi-layer LithoEtch Litho-Etch (LELE) overlay control scheme. Introducing a GI impact on overlay (in nm) KPI check quantifies the grating imbalance impact on overlay, whereas optimizing for accuracy using self-reference captures the bottom grating asymmetry effect. Measuring BGA after each process step before exposure of the top grating helps to identify which specific step introduces the asymmetry in the bottom grating. By evaluating this set of KPI's to a BEOL LELE overlay scheme, we can enhance robustness of recipe selection and target selection. Furthermore, these KPIs can be utilized to highlight process and equipment abnormalities. In this work, we also quantified OPO results with a self-contained methodology called Triangle Method. This method can be utilized for LELE layers with a common target and reference. This allows validating general μDBO accuracy, hence reducing the need for CD-SEM verification.

Assay Development Process | Office of Cancer Clinical Proteomics Research

Cancer.gov

Typical steps involved in the development of a  mass spectrometry-based targeted assay include: (1) selection of surrogate or signature peptides corresponding to the targeted protein or modification of interest; (2) iterative optimization of instrument and method parameters for optimal detection of the selected peptide; (3) method development for protein extraction from biological matrices such as tissue, whole cell lysates, or blood plasma/serum and proteolytic digestion of proteins (usually with trypsin); (4) evaluation of the assay in the intended biological matrix to determine if e

A real-time optical tracking and measurement processing system for flying targets.

PubMed

Guo, Pengyu; Ding, Shaowen; Zhang, Hongliang; Zhang, Xiaohu

2014-01-01

Optical tracking and measurement for flying targets is unlike the close range photography under a controllable observation environment, which brings extreme conditions like diverse target changes as a result of high maneuver ability and long cruising range. This paper first designed and realized a distributed image interpretation and measurement processing system to achieve resource centralized management, multisite simultaneous interpretation and adaptive estimation algorithm selection; then proposed a real-time interpretation method which contains automatic foreground detection, online target tracking, multiple features location, and human guidance. An experiment is carried out at performance and efficiency evaluation of the method by semisynthetic video. The system can be used in the field of aerospace tests like target analysis including dynamic parameter, transient states, and optical physics characteristics, with security control.

A Real-Time Optical Tracking and Measurement Processing System for Flying Targets

PubMed Central

Guo, Pengyu; Ding, Shaowen; Zhang, Hongliang; Zhang, Xiaohu

2014-01-01

Optical tracking and measurement for flying targets is unlike the close range photography under a controllable observation environment, which brings extreme conditions like diverse target changes as a result of high maneuver ability and long cruising range. This paper first designed and realized a distributed image interpretation and measurement processing system to achieve resource centralized management, multisite simultaneous interpretation and adaptive estimation algorithm selection; then proposed a real-time interpretation method which contains automatic foreground detection, online target tracking, multiple features location, and human guidance. An experiment is carried out at performance and efficiency evaluation of the method by semisynthetic video. The system can be used in the field of aerospace tests like target analysis including dynamic parameter, transient states, and optical physics characteristics, with security control. PMID:24987748

Processing Distracting Non-face Emotional Images: No Evidence of an Age-Related Positivity Effect

PubMed Central

Madill, Mark; Murray, Janice E.

2017-01-01

Cognitive aging may be accompanied by increased prioritization of social and emotional goals that enhance positive experiences and emotional states. The socioemotional selectivity theory suggests this may be achieved by giving preference to positive information and avoiding or suppressing negative information. Although there is some evidence of a positivity bias in controlled attention tasks, it remains unclear whether a positivity bias extends to the processing of affective stimuli presented outside focused attention. In two experiments, we investigated age-related differences in the effects of to-be-ignored non-face affective images on target processing. In Experiment 1, 27 older (64–90 years) and 25 young adults (19–29 years) made speeded valence judgments about centrally presented positive or negative target images taken from the International Affective Picture System. To-be-ignored distractor images were presented above and below the target image and were either positive, negative, or neutral in valence. The distractors were considered task relevant because they shared emotional characteristics with the target stimuli. Both older and young adults responded slower to targets when distractor valence was incongruent with target valence relative to when distractors were neutral. Older adults responded faster to positive than to negative targets but did not show increased interference effects from positive distractors. In Experiment 2, affective distractors were task irrelevant as the target was a three-digit array and did not share emotional characteristics with the distractors. Twenty-six older (63–84 years) and 30 young adults (18–30 years) gave speeded responses on a digit disparity task while ignoring the affective distractors positioned in the periphery. Task performance in either age group was not influenced by the task-irrelevant affective images. In keeping with the socioemotional selectivity theory, these findings suggest that older adults preferentially process task-relevant positive non-face images but only when presented within the main focus of attention. PMID:28450848

Processing Distracting Non-face Emotional Images: No Evidence of an Age-Related Positivity Effect.

PubMed

Madill, Mark; Murray, Janice E

2017-01-01

Cognitive aging may be accompanied by increased prioritization of social and emotional goals that enhance positive experiences and emotional states. The socioemotional selectivity theory suggests this may be achieved by giving preference to positive information and avoiding or suppressing negative information. Although there is some evidence of a positivity bias in controlled attention tasks, it remains unclear whether a positivity bias extends to the processing of affective stimuli presented outside focused attention. In two experiments, we investigated age-related differences in the effects of to-be-ignored non-face affective images on target processing. In Experiment 1, 27 older (64-90 years) and 25 young adults (19-29 years) made speeded valence judgments about centrally presented positive or negative target images taken from the International Affective Picture System. To-be-ignored distractor images were presented above and below the target image and were either positive, negative, or neutral in valence. The distractors were considered task relevant because they shared emotional characteristics with the target stimuli. Both older and young adults responded slower to targets when distractor valence was incongruent with target valence relative to when distractors were neutral. Older adults responded faster to positive than to negative targets but did not show increased interference effects from positive distractors. In Experiment 2, affective distractors were task irrelevant as the target was a three-digit array and did not share emotional characteristics with the distractors. Twenty-six older (63-84 years) and 30 young adults (18-30 years) gave speeded responses on a digit disparity task while ignoring the affective distractors positioned in the periphery. Task performance in either age group was not influenced by the task-irrelevant affective images. In keeping with the socioemotional selectivity theory, these findings suggest that older adults preferentially process task-relevant positive non-face images but only when presented within the main focus of attention.

Occipital Alpha and Gamma Oscillations Support Complementary Mechanisms for Processing Stimulus Value Associations.

PubMed

Marshall, Tom R; den Boer, Sebastiaan; Cools, Roshan; Jensen, Ole; Fallon, Sean James; Zumer, Johanna M

2018-01-01

Selective attention is reflected neurally in changes in the power of posterior neural oscillations in the alpha (8-12 Hz) and gamma (40-100 Hz) bands. Although a neural mechanism that allows relevant information to be selectively processed has its advantages, it may lead to lucrative or dangerous information going unnoticed. Neural systems are also in place for processing rewarding and punishing information. Here, we examine the interaction between selective attention (left vs. right) and stimulus's learned value associations (neutral, punished, or rewarded) and how they compete for control of posterior neural oscillations. We found that both attention and stimulus-value associations influenced neural oscillations. Whereas selective attention had comparable effects on alpha and gamma oscillations, value associations had dissociable effects on these neural markers of attention. Salient targets (associated with positive and negative outcomes) hijacked changes in alpha power-increasing hemispheric alpha lateralization when salient targets were attended, decreasing it when they were being ignored. In contrast, hemispheric gamma-band lateralization was specifically abolished by negative distractors. Source analysis indicated occipital generators of both attentional and value effects. Thus, posterior cortical oscillations support both the ability to selectively attend while at the same time retaining the ability to remain sensitive to valuable features in the environment. Moreover, the versatility of our attentional system to respond separately to salient from merely positively valued stimuli appears to be carried out by separate neural processes reflected in different frequency bands.

Rewarded visual items capture attention only in heterogeneous contexts.

PubMed

Feldmann-Wüstefeld, Tobias; Brandhofer, Ruben; Schubö, Anna

2016-07-01

Reward is known to affect visual search performance. Rewarding targets can increase search performance, whereas rewarding distractors can decrease search performance. We used subcomponents of the N2pc in the event-related EEG, the NT (target negativity) and ND /PD (distractor negativity/positivity), in a visual search task to disentangle target and distractor processing related to reward. The visual search task comprised homogeneous and heterogeneous contexts in which a target and a colored distractor were embedded. After each correct trial, participants were given a monetary reward that depended on the color of the distractor. We found longer response times for displays with high-reward distractors compared to displays with low-reward distractors, indicating reward-induced interference, however, only for heterogeneous contexts. The NT component, indicative of attention deployment to the target, showed that target selection was impaired by high-reward distractors, regardless of the context homogeneity. Processing of distractors was not affected by reward in homogeneous contexts. In heterogeneous contexts, however, high-reward distractors were more likely to capture attention (ND ) and required more effort to be suppressed (PD ) than low-reward distractors. In sum the results showed that, despite the fact that target selection is impaired by high-reward distractors in both homogeneous and heterogeneous background contexts, high-reward distractors capture attention only in scenarios that foster attentional capture. © 2016 Society for Psychophysiological Research.

Application of target costing in machining

NASA Astrophysics Data System (ADS)

Gopalakrishnan, Bhaskaran; Kokatnur, Ameet; Gupta, Deepak P.

2004-11-01

In today's intensely competitive and highly volatile business environment, consistent development of low cost and high quality products meeting the functionality requirements is a key to a company's survival. Companies continuously strive to reduce the costs while still producing quality products to stay ahead in the competition. Many companies have turned to target costing to achieve this objective. Target costing is a structured approach to determine the cost at which a proposed product, meeting the quality and functionality requirements, must be produced in order to generate the desired profits. It subtracts the desired profit margin from the company's selling price to establish the manufacturing cost of the product. Extensive literature review revealed that companies in automotive, electronic and process industries have reaped the benefits of target costing. However target costing approach has not been applied in the machining industry, but other techniques based on Geometric Programming, Goal Programming, and Lagrange Multiplier have been proposed for application in this industry. These models follow a forward approach, by first selecting a set of machining parameters, and then determining the machining cost. Hence in this study we have developed an algorithm to apply the concepts of target costing, which is a backward approach that selects the machining parameters based on the required machining costs, and is therefore more suitable for practical applications in process improvement and cost reduction. A target costing model was developed for turning operation and was successfully validated using practical data.

Filopodia Conduct Target Selection in Cortical Neurons Using Differences in Signal Kinetics of a Single Kinase.

PubMed

Mao, Yu-Ting; Zhu, Julia X; Hanamura, Kenji; Iurilli, Giuliano; Datta, Sandeep Robert; Dalva, Matthew B

2018-05-16

Dendritic filopodia select synaptic partner axons by interviewing the cell surface of potential targets, but how filopodia decipher the complex pattern of adhesive and repulsive molecular cues to find appropriate contacts is unknown. Here, we demonstrate in cortical neurons that a single cue is sufficient for dendritic filopodia to reject or select specific axonal contacts for elaboration as synaptic sites. Super-resolution and live-cell imaging reveals that EphB2 is located in the tips of filopodia and at nascent synaptic sites. Surprisingly, a genetically encoded indicator of EphB kinase activity, unbiased classification, and a photoactivatable EphB2 reveal that simple differences in the kinetics of EphB kinase signaling at the tips of filopodia mediate the choice between retraction and synaptogenesis. This may enable individual filopodia to choose targets based on differences in the activation rate of a single tyrosine kinase, greatly simplifying the process of partner selection and suggesting a general principle. Copyright © 2018 Elsevier Inc. All rights reserved.

Radiology Reports With Hyperlinks Improve Target Lesion Selection and Measurement Concordance in Cancer Trials.

PubMed

Machado, Laura B; Apolo, Andrea B; Steinberg, Seth M; Folio, Les R

2017-02-01

Radiology reports often lack the measurements of target lesions that are needed for oncology clinical trials. When available, the measurements in the radiology reports often do not match those in the records used to calculate therapeutic response. This study assessed the clinical value of hyperlinked tumor measurements in multimedia-enhanced radiology reports in the PACS and the inclusion of a radiologist assistant in the process of assessing tumor burden. We assessed 489 target lesions in 232 CT examinations of 71 patients with metastatic genitourinary cancer enrolled in two therapeutic trials. We analyzed target lesion selection and measurement concordance between oncology records (used to calculate therapeutic response) and two types of radiology reports in the PACS: multimedia-enhanced radiology reports and text-only reports. For statistical tests, we used the Wilcoxon signed rank, Wilcoxon rank sum test, and Fisher method to combine p values from the paired and unpaired results. The Fisher exact test was used to compare overall measurement concordance. Concordance on target lesion selection was greater for multimedia-enhanced radiology reports (78%) than the text-only reports (52%) (p = 0.0050). There was also improved overall measurement concordance with the multimedia-enhanced radiology reports (68%) compared with the text-only reports (38%) (p < 0.0001). Compared with text-only reports, hyperlinked multimedia-enhanced radiology reports improved concordance of target lesion selection and measurement with the measurements used to calculate therapeutic response.

How visual cues for when to listen aid selective auditory attention.

PubMed

Varghese, Lenny A; Ozmeral, Erol J; Best, Virginia; Shinn-Cunningham, Barbara G

2012-06-01

Visual cues are known to aid auditory processing when they provide direct information about signal content, as in lip reading. However, some studies hint that visual cues also aid auditory perception by guiding attention to the target in a mixture of similar sounds. The current study directly tests this idea for complex, nonspeech auditory signals, using a visual cue providing only timing information about the target. Listeners were asked to identify a target zebra finch bird song played at a random time within a longer, competing masker. Two different maskers were used: noise and a chorus of competing bird songs. On half of all trials, a visual cue indicated the timing of the target within the masker. For the noise masker, the visual cue did not affect performance when target and masker were from the same location, but improved performance when target and masker were in different locations. In contrast, for the chorus masker, visual cues improved performance only when target and masker were perceived as coming from the same direction. These results suggest that simple visual cues for when to listen improve target identification by enhancing sounds near the threshold of audibility when the target is energetically masked and by enhancing segregation when it is difficult to direct selective attention to the target. Visual cues help little when target and masker already differ in attributes that enable listeners to engage selective auditory attention effectively, including differences in spectrotemporal structure and in perceived location.

Object-based target templates guide attention during visual search.

PubMed

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).

Search time critically depends on irrelevant subset size in visual search.

PubMed

Benjamins, Jeroen S; Hooge, Ignace T C; van Elst, Jacco C; Wertheim, Alexander H; Verstraten, Frans A J

2009-02-01

In order for our visual system to deal with the massive amount of sensory input, some of this input is discarded, while other parts are processed [Wolfe, J. M. (1994). Guided search 2.0: a revised model of visual search. Psychonomic Bulletin and Review, 1, 202-238]. From the visual search literature it is unclear how well one set of items can be selected that differs in only one feature from target (a 1F set), while another set of items can be ignored that differs in two features from target (a 2F set). We systematically varied the percentage of 2F non-targets to determine the contribution of these non-targets to search behaviour. Increasing the percentage 2F non-targets, that have to be ignored, was expected to result in increasingly faster search, since it decreases the size of 1F set that has to be searched. Observers searched large displays for a target in the 1F set with a variable percentage of 2F non-targets. Interestingly, when the search displays contained 5% 2F non-targets, the search time was longer compared to the search time in other conditions. This effect of 2F non-targets on performance was independent of set size. An inspection of the saccades revealed that saccade target selection did not contribute to the longer search times in displays with 5% 2F non-targets. Occurrence of longer search times in displays containing 5% 2F non-targets might be attributed to covert processes related to visual analysis of the fixated part of the display. Apparently, visual search performance critically depends on the percentage of irrelevant 2F non-targets.

Distractor inhibition: principles of operation during selective attention.

PubMed

Wyatt, Natalie; Machado, Liana

2013-02-01

Research suggests that although target amplification acts as the main determinant of the efficacy of selective attention, distractor inhibition contributes under some circumstances. Here we aimed to gain insight into the operating principles that regulate the use of distractor inhibition during selective attention. The results suggest that, in contrast to target amplification, distractor inhibition does not onset earlier or strengthen in response to advance location information. Instead, when the location of the impending distractor was predictable, evidence of inhibitory processing weakened. Furthermore, the results suggest that distractor inhibition does not operate as a compensatory mechanism for target amplification, as evidenced by the lack of an increase in inhibitory effects when reliance on target amplification was disrupted. Unexpected emergence of inhibitory effects for improbable targets provided evidence that distractor inhibition was at work even when no inhibitory effects manifested. Overall, the pattern of inhibitory effects is interpreted as indicating that, although distractor inhibition mounts primarily reactively rather than preemptively, advance information can help prevent overreaction to the distractor. Of course, less overreaction reduces the chances of behavioral inhibitory effects manifesting even when distractor inhibition has contributed to selective attention; thus, interpreting an absence of inhibitory effects should be done cautiously. PsycINFO Database Record (c) 2013 APA, all rights reserved.

Exogenous attention can be counter-selective: onset cues disrupt sensitivity to color changes.

PubMed

Müller-Plath, Gisela; Klöckner, Nils

2014-03-01

In peripheral spatial cueing paradigms, exogenous attentional capture is commonly observed after salient onset cues or with cues contingent on target characteristics. We proposed that exogenously captured attention disrupts the selectivity to target features. We tested this by experimentally emulating the everyday observation that in a viewing situation in which the observer is monitoring a stationary display fort change to occur, the onset of a salient stimulus (onset cue) or a change in a stationary stimulus similar to the expected one (contingent cue) has a distracting effect. As predicted, we found that both types of cues reduced the target detection sensitivity but enhanced the bias to respond in a go-nogo-paradigm. With the onset cue, the sensitivity loss was more pronounced at the side of the cue, whereas the contingent cue affected both sides likewise. Moreover, the effects of the onset cue interacted with the task difficulty: the more selectivity a task required the more immune it was against disruption, but the more likely was a response. We concluded that onset capture disrupts selective attention by adding noise to the processing of the target location. The effects of contingent capture could be explained with cue-target confounding. Finally, we suggest a new model of attentional capture in which exogenous and endogenous components interact in a dynamic way.

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

PubMed

Grimm, Hans Peter

2009-10-01

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

Saccadic eye movements as an index of perceptual decision-making.

PubMed

McSorley, Eugene; McCloy, Rachel

2009-10-01

One of the most common decisions we make is the one about where to move our eyes next. Here we examine the impact that processing the evidence supporting competing options has on saccade programming. Participants were asked to saccade to one of two possible visual targets indicated by a cloud of moving dots. We varied the evidence which supported saccade target choice by manipulating the proportion of dots moving towards one target or the other. The task was found to become easier as the evidence supporting target choice increased. This was reflected in an increase in percent correct and a decrease in saccade latency. The trajectory and landing position of saccades were found to deviate away from the non-selected target reflecting the choice of the target and the inhibition of the non-target. The extent of the deviation was found to increase with amount of sensory evidence supporting target choice. This shows that decision-making processes involved in saccade target choice have an impact on the spatial control of a saccade. This would seem to extend the notion of the processes involved in the control of saccade metrics beyond a competition between visual stimuli to one also reflecting a competition between options.

Effects of task-irrelevant grouping on visual selection in partial report.

PubMed

Lunau, Rasmus; Habekost, Thomas

2017-07-01

Perceptual grouping modulates performance in attention tasks such as partial report and change detection. Specifically, grouping of search items according to a task-relevant feature improves the efficiency of visual selection. However, the role of task-irrelevant feature grouping is not clearly understood. In the present study, we investigated whether grouping of targets by a task-irrelevant feature influences performance in a partial-report task. In this task, participants must report as many target letters as possible from a briefly presented circular display. The crucial manipulation concerned the color of the elements in these trials. In the sorted-color condition, the color of the display elements was arranged according to the selection criterion, and in the unsorted-color condition, colors were randomly assigned. The distractor cost was inferred by subtracting performance in partial-report trials from performance in a control condition that had no distractors in the display. Across five experiments, we manipulated trial order, selection criterion, and exposure duration, and found that attentional selectivity was improved in sorted-color trials when the exposure duration was 200 ms and the selection criterion was luminance. This effect was accompanied by impaired selectivity in unsorted-color trials. Overall, the results suggest that the benefit of task-irrelevant color grouping of targets is contingent on the processing locus of the selection criterion.

Phage display and kinetic selection of antibodies that specifically inhibit amyloid self-replication.

PubMed

Munke, Anna; Persson, Jonas; Weiffert, Tanja; De Genst, Erwin; Meisl, Georg; Arosio, Paolo; Carnerup, Anna; Dobson, Christopher M; Vendruscolo, Michele; Knowles, Tuomas P J; Linse, Sara

2017-06-20

The aggregation of the amyloid β peptide (Aβ) into amyloid fibrils is a defining characteristic of Alzheimer's disease. Because of the complexity of this aggregation process, effective therapeutic inhibitors will need to target the specific microscopic steps that lead to the production of neurotoxic species. We introduce a strategy for generating fibril-specific antibodies that selectively suppress fibril-dependent secondary nucleation of the 42-residue form of Aβ (Aβ42). We target this step because it has been shown to produce the majority of neurotoxic species during aggregation of Aβ42. Starting from large phage display libraries of single-chain antibody fragments (scFvs), the three-stage approach that we describe includes ( i ) selection of scFvs with high affinity for Aβ42 fibrils after removal of scFvs that bind Aβ42 in its monomeric form; ( ii ) ranking, by surface plasmon resonance affinity measurements, of the resulting candidate scFvs that bind to the Aβ42 fibrils; and ( iii ) kinetic screening and analysis to find the scFvs that inhibit selectively the fibril-catalyzed secondary nucleation process in Aβ42 aggregation. By applying this approach, we have identified four scFvs that inhibit specifically the fibril-dependent secondary nucleation process. Our method also makes it possible to discard antibodies that inhibit elongation, an important factor because the suppression of elongation does not target directly the production of toxic oligomers and may even lead to its increase. On the basis of our results, we suggest that the method described here could form the basis for rationally designed immunotherapy strategies to combat Alzheimer's and related neurodegenerative diseases.

Visuospatial selective attention in chickens.

PubMed

Sridharan, Devarajan; Ramamurthy, Deepa L; Schwarz, Jason S; Knudsen, Eric I

2014-05-13

Voluntary control of attention promotes intelligent, adaptive behaviors by enabling the selective processing of information that is most relevant for making decisions. Despite extensive research on attention in primates, the capacity for selective attention in nonprimate species has never been quantified. Here we demonstrate selective attention in chickens by applying protocols that have been used to characterize visual spatial attention in primates. Chickens were trained to localize and report the vertical position of a target in the presence of task-relevant distracters. A spatial cue, the location of which varied across individual trials, indicated the horizontal, but not vertical, position of the upcoming target. Spatial cueing improved localization performance: accuracy (d') increased and reaction times decreased in a space-specific manner. Distracters severely impaired perceptual performance, and this impairment was greatly reduced by spatial cueing. Signal detection analysis with an "indecision" model demonstrated that spatial cueing significantly increased choice certainty in localizing targets. By contrast, error-aversion certainty (certainty of not making an error) remained essentially constant across cueing protocols, target contrasts, and individuals. The results show that chickens shift spatial attention rapidly and dynamically, following principles of stimulus selection that closely parallel those documented in primates. The findings suggest that the mechanisms that control attention have been conserved through evolution, and establish chickens--a highly visual species that is easily trained and amenable to cutting-edge experimental technologies--as an attractive model for linking behavior to neural mechanisms of selective attention.

A technology selection framework for supporting delivery of patient-oriented health interventions in developing countries

PubMed Central

Chan, Connie V.; Kaufman, David R.

2009-01-01

Health information technologies (HIT) have great potential to advance health care globally. In particular, HIT can provide innovative approaches and methodologies to overcome the range of access and resource barriers specific to developing countries. However, there is a paucity of models and empirical evidence informing the technology selection process in these settings. We propose a framework for selecting patient-oriented technologies in developing countries. The selection guidance process is structured by a set of filters that impose particular constraints and serve to narrow the space of possible decisions. The framework consists of three levels of factors: 1) situational factors, 2) the technology and its relationship with health interventions and with target patients, and 3) empirical evidence. We demonstrate the utility of the framework in the context of mobile phones for behavioral health interventions to reduce risk factors for cardiovascular disease. This framework can be applied to health interventions across health domains to explore how and whether available technologies can support delivery of the associated types of interventions and with the target populations. PMID:19796709

When congruence breeds preference: the influence of selective attention processes on evaluative conditioning.

PubMed

Blask, Katarina; Walther, Eva; Frings, Christian

2017-09-01

We investigated in two experiments whether selective attention processes modulate evaluative conditioning (EC). Based on the fact that the typical stimuli in an EC paradigm involve an affect-laden unconditioned stimulus (US) and a neutral conditioned stimulus (CS), we started from the assumption that learning might depend in part upon selective attention to the US. Attention to the US was manipulated by including a variant of the Eriksen flanker task in the EC paradigm. Similarly to the original Flanker paradigm, we implemented a target-distracter logic by introducing the CS as the task-relevant stimulus (i.e. the target) to which the participants had to respond and the US as a task-irrelevant distracter. Experiment 1 showed that CS-US congruence modulated EC if the CS had to be selected against the US. Specifically, EC was more pronounced for congruent CS-US pairs as compared to incongruent CS-US pairs. Experiment 2 disentangled CS-US congruence and CS-US compatibility and suggested that it is indeed CS-US stimulus congruence rather than CS-US response compatibility that modulates EC.

A feature-weighting account of priming in conjunction search.

PubMed

Becker, Stefanie I; Horstmann, Gernot

2009-02-01

Previous research on the priming effect in conjunction search has shown that repeating the target and distractor features across displays speeds mean response times but does not improve search efficiency: Repetitions do not reduce the set size effect-that is, the effect of the number of distractor items-but only modulate the intercept of the search function. In the present study, we investigated whether priming modulates search efficiency when a conjunctively defined target randomly changes between red and green. The results from an eyetracking experiment show that repeating the target across trials reduced the set size effect and, thus, did enhance search efficiency. Moreover, the probability of selecting the target as the first item in the display was higher when the target-distractor displays were repeated across trials than when they changed. Finally, red distractors were selected more frequently than green distractors when the previous target had been red (and vice versa). Taken together, these results indicate that priming in conjunction search modulates processes concerned with guiding attention to the target, by assigning more attentional weight to features sharing the previous target's color.

Anatomical constraints on attention: Hemifield independence is a signature of multifocal spatial selection

PubMed Central

Alvarez, George A; Gill, Jonathan; Cavanagh, Patrick

2012-01-01

Previous studies have shown independent attentional selection of targets in the left and right visual hemifields during attentional tracking (Alvarez & Cavanagh, 2005) but not during a visual search (Luck, Hillyard, Mangun, & Gazzaniga, 1989). Here we tested whether multifocal spatial attention is the critical process that operates independently in the two hemifields. It is explicitly required in tracking (attend to a subset of object locations, suppress the others) but not in the standard visual search task (where all items are potential targets). We used a modified visual search task in which observers searched for a target within a subset of display items, where the subset was selected based on location (Experiments 1 and 3A) or based on a salient feature difference (Experiments 2 and 3B). The results show hemifield independence in this subset visual search task with location-based selection but not with feature-based selection; this effect cannot be explained by general difficulty (Experiment 4). Combined, these findings suggest that hemifield independence is a signature of multifocal spatial attention and highlight the need for cognitive and neural theories of attention to account for anatomical constraints on selection mechanisms. PMID:22637710

Ad-hoc and context-dependent adjustments of selective attention in conflict control: an ERP study with visual probes.

PubMed

Nigbur, R; Schneider, J; Sommer, W; Dimigen, O; Stürmer, B

2015-02-15

Cognitive conflict control in flanker tasks has often been described using the zoom-lens metaphor of selective attention. However, whether and how selective attention - in terms of suppression and enhancement - operates in this context has remained unclear. To examine the dynamic interplay of selective attention and cognitive control we used electrophysiological measures and presented task-irrelevant visual probe stimuli at foveal, parafoveal, and peripheral display positions. Target-flanker congruency varied either randomly from trial to trial (mixed-block) or block-wise (fixed-block) in order to induce reactive versus proactive control modes, respectively. Three EEG measures were used to capture ad-hoc adjustments within trials as well as effects of context-based predictions: the N1 component of the visual evoked potential (VEP) to probes, the VEP to targets, and the conflict-related midfrontal N2 component. Results from probe-VEPs indicate that enhanced processing of the foveal target rather than suppression of the peripheral flankers supports interference control. In incongruent mixed-block trials VEPs were larger to probes near the targets. In the fixed-blocks probe-VEPs were not modulated, but contrary to the mixed-block the preceding target-related VEP was affected by congruency. Results of the control-related N2 reveal largest amplitudes in the unpredictable context, which did not differentiate for stimulus and response incongruency. In contrast, in the predictable context, N2 amplitudes were reduced overall and differentiated between stimulus and response incongruency. Taken together these results imply that predictability alters interference control by a reconfiguration of stimulus processing. During unpredictable sequences participants adjust their attentional focus dynamically on a trial-by-trial basis as reflected in congruency-dependent probe-VEP-modulation. This reactive control mode also elicits larger N2 amplitudes. In contrast, when task demands are predictable, participants focus selective attention earlier as reflected in the target-related VEPs. This proactive control mode leads to smaller N2 amplitudes and absent probe effects. Copyright © 2014 Elsevier Inc. All rights reserved.

Flanking Magnitudes: Dissociation between Numerosity and Numerical Value in a Selective Attention Task

ERIC Educational Resources Information Center

Naparstek, Sharon; Safadi, Ziad; Lichtenstein-Vidne, Limor; Henik, Avishai

2015-01-01

The current research examined whether peripherally presented numerical information can affect the speed of number processing. In 2 experiments, participants were presented with a target matrix flanked by a distractor matrix and were asked to perform a comparative judgment (i.e., decide whether the target was larger or smaller than the reference…

Miklós Bodanszky Award Lecture: Advances in the selective targeting of protein phosphatase‐1 and phosphatase‐2A with peptides

PubMed Central

2017-01-01

Protein phosphatase‐1 and phosphatase‐2A are two ubiquitously expressed enzymes known to catalyze the majority of dephosphorylation reactions on serine and threonine inside cells. They play roles in most cellular processes and are tightly regulated by regulatory subunits in holoenzymes. Their misregulation and malfunction contribute to disease development and progression, such as in cancer, diabetes, viral infections, and neurological as well as heart diseases. Therefore, targeting these phosphatases for therapeutic use would be highly desirable; however, their complex regulation and high conservation of the active site have been major hurdles for selectively targeting them in the past. In the last decade, new approaches have been developed to overcome these hurdles and have strongly revived the field. I will focus here on peptide‐based approaches, which contributed to showing that these phosphatases can be targeted selectively and aided in rethinking the design of selective phosphatase modulators. Finally, I will give a perspective on www.depod.org, the human dephosphorylation database, and how it can aid phosphatase modulator design. © 2017 The Authors. Journal of Peptide Science published by European Peptide Society and John Wiley & Sons Ltd. PMID:28876538

Strategic Review Process for an Accountable Care Organization and Emerging Accountable Care Best Practices.

PubMed

Conway, Sarah J; Himmelrich, Sarah; Feeser, Scott A; Flynn, John A; Kravet, Steven J; Bailey, Jennifer; Hebert, Lindsay C; Donovan, Susan H; Kachur, Sarah G; Brown, Patricia M C; Baumgartner, William A; Berkowitz, Scott A

2018-02-02

Accountable Care Organizations (ACOs), like other care entities, must be strategic about which initiatives they support in the quest for higher value. This article reviews the current strategic planning process for the Johns Hopkins Medicine Alliance for Patients (JMAP), a Medicare Shared Savings Program Track 1 ACO. It reviews the 3 focus areas for the 2017 strategic review process - (1) optimizing care coordination for complex, at-risk patients, (2) post-acute care, and (3) specialty care integration - reviewing cost savings and quality improvement opportunities, associated best practices from the literature, and opportunities to leverage and advance existing ACO and health system efforts in each area. It then reviews the ultimate selection of priorities for the coming year and early thoughts on implementation. After the robust review process, key stakeholders voted to select interventions targeted at care coordination, post-acute care, and specialty integration including Part B drug and imaging costs. The interventions selected incorporate a mixture of enhancing current ACO initiatives, working collaboratively and synergistically on other health system initiatives, and taking on new projects deemed targeted, cost-effective, and manageable in scope. The annual strategic review has been an essential and iterative process based on performance data and informed by the collective experience of other organizations. The process allows for an evidence-based strategic plan for the ACO in pursuit of the best care for patients.

Attentional selection and suppression in children and adults.

PubMed

Sun, Meirong; Wang, Encong; Huang, Jing; Zhao, Chenguang; Guo, Jialiang; Li, Dongwei; Sun, Li; Du, Boqi; Ding, Yulong; Song, Yan

2018-05-15

The fundamental role of covert spatial attention is to enhance the processing of attended items while simultaneously ignoring irrelevant items. However, relatively little is known about how brain electrophysiological activities associated with target selection and distractor suppression are involved as they develop and become fully functional. The current study aimed to identify the neurophysiological bases of the development of covert spatial attention, focusing on electroencephalographic (EEG) markers of attentional selection (N2pc) and suppression (P D ). EEG data were collected from healthy young adults and typically developing children (9-15 years old) as they searched for a shape singleton target in either the absence or the presence of a salient-but-irrelevant color singleton distractor. The ERP results showed that a lateral shape target elicited a smaller N2pc in children compared with adults regardless of whether a distractor was present or not. Moreover, the target-elicited N2pc was always followed by a similar positivity in both age groups. Counterintuitively, a lateral salient-but-irrelevant distractor elicited a large P D in children with low behavioral accuracy, whereas high-accuracy children exhibited a small and "adult-like" P D . More importantly, we found no evidence for a correlation between the target-elicited N2pc and the distractor-elicited P D in either age group. Our results provide neurophysiological evidence for the developmental differences between target selection and distractor suppression. Compared with adults, 9-15-year-old children deploy insufficient attentional selection resources to targets but use "adult-like" or even more attentional suppression resources to resist irrelevant distractors. A video abstract of this article can be viewed at: https://www.youtube.com/watch?v=NhWapx0d75I. © 2018 John Wiley & Sons Ltd.

Pressure waves in liquid mercury target from pulsed heat loads and the possible way controlling their effects

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

Ni, L.; Skala, K.

1996-06-01

In ESS project liquid metals are selected as the main target for the pulsed spallation neutron source. Since the very high instantaneous energy is deposited on the heavy molten target in a very short period time, pressure waves are generated. They travel through the liquid and cause high stress in the container. Also, additional stress should be considered in the wall which is the result of direct heating of the target window. These dynamic processes were simulated with computational codes with the static response being analized first. The total resulting dynamic wall stress has been found to have exceeded themore » design stress for the selected container material. Adding a small amount of gas bubbles in the liquid could be a possible way to reduce the pressure waves.« less

Dangerous animals capture and maintain attention in humans.

PubMed

Yorzinski, Jessica L; Penkunas, Michael J; Platt, Michael L; Coss, Richard G

2014-05-28

Predation is a major source of natural selection on primates and may have shaped attentional processes that allow primates to rapidly detect dangerous animals. Because ancestral humans were subjected to predation, a process that continues at very low frequencies, we examined the visual processes by which men and women detect dangerous animals (snakes and lions). We recorded the eye movements of participants as they detected images of a dangerous animal (target) among arrays of nondangerous animals (distractors) as well as detected images of a nondangerous animal (target) among arrays of dangerous animals (distractors). We found that participants were quicker to locate targets when the targets were dangerous animals compared with nondangerous animals, even when spatial frequency and luminance were controlled. The participants were slower to locate nondangerous targets because they spent more time looking at dangerous distractors, a process known as delayed disengagement, and looked at a larger number of dangerous distractors. These results indicate that dangerous animals capture and maintain attention in humans, suggesting that historical predation has shaped some facets of visual orienting and its underlying neural architecture in modern humans.

Self-Study Guide for Florida VPK Provider Improvement Plan Development

ERIC Educational Resources Information Center

Phillips, Beth M.; Mazzeo, Debbie; Smith, Kevin

2016-01-01

This Self-Study Guide has been developed to support Florida Voluntary Prekindergarten Providers (VPK) who are required to complete an improvement plan process (i.e., low-performing providers). The guide has sections that can be used during both the process of selecting target areas for an improvement plan and the process of implementing new or…

Temporal allocation of attention toward threat in individuals with posttraumatic stress symptoms.

PubMed

Amir, Nader; Taylor, Charles T; Bomyea, Jessica A; Badour, Christal L

2009-12-01

Research suggests that individuals with posttraumatic stress disorder (PTSD) selectively attend to threat-relevant information. However, little is known about how initial detection of threat influences the processing of subsequently encountered stimuli. To address this issue, we used a rapid serial visual presentation paradigm (RSVP; Raymond, J. E., Shapiro, K. L., & Arnell, K. M. (1992). Temporary suppression of visual processing in an RSVP task: An attentional blink? Journal of Experimental Psychology: Human Perception and Performance, 18, 849-860) to examine temporal allocation of attention to threat-related and neutral stimuli in individuals with PTSD symptoms (PTS), traumatized individuals without PTSD symptoms (TC), and non-anxious controls (NAC). Participants were asked to identify one or two targets in an RSVP stream. Typically processing of the first target decreases accuracy of identifying the second target as a function of the temporal lag between targets. Results revealed that the PTS group was significantly more accurate in detecting a neutral target when it was presented 300 or 500ms after threat-related stimuli compared to when the target followed neutral stimuli. These results suggest that individuals with PTSD may process trauma-relevant information more rapidly and efficiently than benign information.

Study for identification of Beneficial Uses of Space (BUS). Volume 2: Technical report. Book 1: Sections 1 through 4. [with emphasis on space manufacturing and product development

NASA Technical Reports Server (NTRS)

1973-01-01

Consolidated information is presented for the study whose purpose was to identify products, processes, and services to be produced in future spacecraft environments for direct utilization on earth. Discussion of methodology for selecting from among potential space processing approaches, definition of requirements for experiments and tests needed to acquire sufficient knowledge for proof testing of selected processes, formulation of research and development schedules to achieve proof testing, and documentation of the decision processes involved in the programs are presented. Technology and programmatics are reported for the following select studies: (1) surface acoustic wave components; (2) transparent oxides; (3) high purity tungsten X-ray targets; and (4) high specificity isoenzymes.

Performance evaluation of structure based and ligand based virtual screening methods on ten selected anti-cancer targets.

PubMed

Ramasamy, Thilagavathi; Selvam, Chelliah

2015-10-15

Virtual screening has become an important tool in drug discovery process. Structure based and ligand based approaches are generally used in virtual screening process. To date, several benchmark sets for evaluating the performance of the virtual screening tool are available. In this study, our aim is to compare the performance of both structure based and ligand based virtual screening methods. Ten anti-cancer targets and their corresponding benchmark sets from 'Demanding Evaluation Kits for Objective In silico Screening' (DEKOIS) library were selected. X-ray crystal structures of protein-ligand complexes were selected based on their resolution. Openeye tools such as FRED, vROCS were used and the results were carefully analyzed. At EF1%, vROCS produced better results but at EF5% and EF10%, both FRED and ROCS produced almost similar results. It was noticed that the enrichment factor values were decreased while going from EF1% to EF5% and EF10% in many cases. Published by Elsevier Ltd.

Evaluation 101: How One Department Embraced the Process

ERIC Educational Resources Information Center

Gothard, Katina; Gorham, Jayne

2011-01-01

An evaluation system was designed and implemented by a faculty support department to measure the value, identify gaps, and improve the quality of their training at a midsize community college. The Targeted Evaluation Process (Combs & Falletta, 2000) was selected as the evaluation framework because of its applicability to training and nontraining…

The unique peptidome: Taxon-specific tryptic peptides as biomarkers for targeted metaproteomics.

PubMed

Mesuere, Bart; Van der Jeugt, Felix; Devreese, Bart; Vandamme, Peter; Dawyndt, Peter

2016-09-01

The Unique Peptide Finder (http://unipept.ugent.be/peptidefinder) is an interactive web application to quickly hunt for tryptic peptides that are unique to a particular species, genus, or any other taxon. Biodiversity within the target taxon is represented by a set of proteomes selected from a monthly updated list of complete and nonredundant UniProt proteomes, supplemented with proprietary proteomes loaded into persistent local browser storage. The software computes and visualizes pan and core peptidomes as unions and intersections of tryptic peptides occurring in the selected proteomes. In addition, it also computes and displays unique peptidomes as the set of all tryptic peptides that occur in all selected proteomes but not in any UniProt record not assigned to the target taxon. As a result, the unique peptides can serve as robust biomarkers for the target taxon, for example, in targeted metaproteomics studies. Computations are extremely fast since they are underpinned by the Unipept database, the lowest common ancestor algorithm implemented in Unipept and modern web technologies that facilitate in-browser data storage and parallel processing. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Domain-Specific Control of Selective Attention

PubMed Central

Lin, Szu-Hung; Yeh, Yei-Yu

2014-01-01

Previous research has shown that loading information on working memory affects selective attention. However, whether the load effect on selective attention is domain-general or domain-specific remains unresolved. The domain-general effect refers to the findings that load in one content (e.g. phonological) domain in working memory influences processing in another content (e.g., visuospatial) domain. Attentional control supervises selection regardless of information domain. The domain-specific effect refers to the constraint of influence only when maintenance and processing operate in the same domain. Selective attention operates in a specific content domain. This study is designed to resolve this controversy. Across three experiments, we manipulated the type of representation maintained in working memory and the type of representation upon which the participants must exert control to resolve conflict and select a target into the focus of attention. In Experiments 1a and 1b, participants maintained digits and nonverbalized objects, respectively, in working memory while selecting a target in a letter array. In Experiment 2, we presented auditory digits with a letter flanker task to exclude the involvement of resource competition within the same input modality. In Experiments 3a and 3b, we replaced the letter flanker task with an object flanker task while manipulating the memory load on object and digit representation, respectively. The results consistently showed that memory load modulated distractibility only when the stimuli of the two tasks were represented in the same domain. The magnitude of distractor interference was larger under high load than under low load, reflecting a lower efficacy of information prioritization. When the stimuli of the two tasks were represented in different domains, memory load did not modulate distractibility. Control of processing priority in selective attention demands domain-specific resources. PMID:24866977

Corruption of phage display libraries by target-unrelated clones: diagnosis and countermeasures.

PubMed

Thomas, William D; Golomb, Miriam; Smith, George P

2010-12-15

Phage display is used to discover peptides or proteins with a desired target property-most often, affinity for a target selector molecule. Libraries of phage clones displaying diverse surface peptides are subject to a selection process designed to enrich for the target behavior and subsequently propagated to restore phage numbers. A recurrent problem is enrichment of clones, called target-unrelated phages or peptides (TUPs), that lack the target behavior. Many TUPs are propagation related; they have mutations conferring a growth advantage and are enriched during the propagations accompanying selection. Unlike other filamentous phage libraries, fd-tet-based libraries are relatively resistant to propagation-related TUP corruption. Their minus-strand origin is disrupted by a large cassette that simultaneously confers resistance to tetracycline and imposes a rate-limiting growth defect that cannot be bypassed with simple mutations. Nonetheless, a new type of propagation-related TUP emerged in the output of in vivo selections from an fd-tet library. The founding clone had a complex rearrangement that restored the minus-strand origin while retaining tetracycline resistance. The rearrangement involved two recombination events, one with a contaminant having a wild-type minus-strand origin. The founder's infectivity advantage spread by simple recombination to clones displaying different peptides. We propose measures for minimizing TUP corruption. Copyright © 2010 Elsevier Inc. All rights reserved.

Corruption of phage-display libraries by target-unrelated clones: Diagnosis and countermeasures

PubMed Central

Thomas, William D.; Golomb, Miriam; Smith, George P.

2010-01-01

Phage display is used to discover peptides or proteins with a desired target property—most often, affinity for a target selector molecule. Libraries of phage clones displaying diverse surface peptides are subject to a selection process designed to enrich for the target behavior, and subsequently propagated to restore phage numbers. A recurrent problem is enrichment of clones, called target-unrelated phage (TUPs), that lack the target behavior. Many TUPs are propagation-related; they have mutations conferring a growth advantage, and are enriched during the propagations accompanying selection. Unlike other filamentous phage libraries, fd-tet-based libraries are relatively resistant to propagation-related TUP corruption. Their minus strand origin is disrupted by a large cassette that simultaneously confers resistance to tetracycline and imposes a rate-limiting growth defect that cannot be bypassed with simple mutations. Nonetheless, a new type of propagation-related TUP emerged in the output of in vivo selections from an fd-tet library. The founding clone had a complex rearrangement that restored the minus strand origin while retaining tetracycline resistance. The rearrangement involved two recombination events, one with a contaminant having a wild-type minus strand origin. The founder’s infectivity advantage spread by simple recombination to clones displaying different peptides. We propose measures for minimizing TUP corruption. PMID:20692225

Evaluation of Multiple Immunoassay Technology Platforms to Select the Anti-Drug Antibody Assay Exhibiting the Most Appropriate Drug and Target Tolerance

PubMed Central

Collet-Brose, Justine

2016-01-01

The aim of this study was, at the assay development stage and thus with an appropriate degree of rigor, to select the most appropriate technology platform and sample pretreatment procedure for a clinical ADA assay. Thus, ELISA, MSD, Gyrolab, and AlphaLISA immunoassay platforms were evaluated in association with target depletion and acid dissociation sample pretreatment steps. An acid dissociation step successfully improved the drug tolerance for all 4 technology platforms and the required drug tolerance was achieved with the Gyrolab and MSD platforms. The target tolerance was shown to be better for the ELISA format, where an acid dissociation treatment step alone was sufficient to achieve the desired target tolerance. However, inclusion of a target depletion step in conjunction with the acid treatment raised the target tolerance to the desired level for all of the technologies. A higher sensitivity was observed for the MSD and Gyrolab assays and the ELISA, MSD, and Gyrolab all displayed acceptable interdonor variability. This study highlights the usefulness of evaluating the performance of different assay platforms at an early stage in the assay development process to aid in the selection of the best fit-for-purpose technology platform and sample pretreatment steps. PMID:27243038

Early Probe and Drug Discovery in Academia: A Minireview.

PubMed

Roy, Anuradha

2018-02-09

Drug discovery encompasses processes ranging from target selection and validation to the selection of a development candidate. While comprehensive drug discovery work flows are implemented predominantly in the big pharma domain, early discovery focus in academia serves to identify probe molecules that can serve as tools to study targets or pathways. Despite differences in the ultimate goals of the private and academic sectors, the same basic principles define the best practices in early discovery research. A successful early discovery program is built on strong target definition and validation using a diverse set of biochemical and cell-based assays with functional relevance to the biological system being studied. The chemicals identified as hits undergo extensive scaffold optimization and are characterized for their target specificity and off-target effects in in vitro and in animal models. While the active compounds from screening campaigns pass through highly stringent chemical and Absorption, Distribution, Metabolism, and Excretion (ADME) filters for lead identification, the probe discovery involves limited medicinal chemistry optimization. The goal of probe discovery is identification of a compound with sub-µM activity and reasonable selectivity in the context of the target being studied. The compounds identified from probe discovery can also serve as starting scaffolds for lead optimization studies.

Process for strontium-82 separation

DOEpatents

Heaton, Richard C.; Jamriska, Sr., David J.; Taylor, Wayne A.

1992-01-01

A process for selective separation of strontium-82 and strontium-85 from proton irradiated molybdenum targets comprises dissolving the molybdenum target in a hydrogen peroxide solution to form a first solution containing ions selected from a group consisting of molybdenum, niobium, technetium, selenium, vanadium, arsenic, germanium, zirconium, rubidium, zinc, beryllium, cobalt, iron, manganese, chromium, strontium, and yttrium; passing the solution through a first cationic resin whereby ions selected from a group consisting of zinc, beryllium, cobalt, iron, manganese, chromium, strontium, yttrium a portion of zirconium and a portion of rubidium are selectively absorbed by the first resin; contacting the first resin with an acid solution to strip and remove the absorbed ions from the first cationic exchange resin to form a second solution; evaporating the second solution for a time sufficient to remove substantially all of the acid and water from the solution whereby a residue remains; dissolving the residue in a dilute acid to form a third solution; passing the third solution through a second cationic resin whereby the ions are absorbed by the second resin; contacting the second resin with a dilute sulfuric acid solution whereby the absorbed ions selected from the group consisting of rubidium, zinc, beryllium, cobalt, iron, manganese, chromium and zirconium are selectively removed from the second resin; and contacting the second resin with a dilute acid solution whereby the absorbed strontium ions are selectively removed.

Process for strontium-82 separation

DOEpatents

Heaton, R.C.; Jamriska, D.J. Sr.; Taylor, W.A.

1992-12-01

A process for selective separation of strontium-82 and strontium-85 from proton irradiated molybdenum targets comprises dissolving the molybdenum target in a hydrogen peroxide solution to form a first solution containing ions selected from a group consisting of molybdenum, niobium, technetium, selenium, vanadium, arsenic, germanium, zirconium, rubidium, zinc, beryllium, cobalt, iron, manganese, chromium, strontium, and yttrium; passing the solution through a first cationic resin whereby ions selected from a group consisting of zinc, beryllium, cobalt, iron, manganese, chromium, strontium, yttrium a portion of zirconium and a portion of rubidium are selectively absorbed by the first resin; contacting the first resin with an acid solution to strip and remove the absorbed ions from the first cationic exchange resin to form a second solution; evaporating the second solution for a time sufficient to remove substantially all of the acid and water from the solution whereby a residue remains; dissolving the residue in a dilute acid to form a third solution; passing the third solution through a second cationic resin whereby the ions are absorbed by the second resin; contacting the second resin with a dilute sulfuric acid solution whereby the absorbed ions selected from the group consisting of rubidium, zinc, beryllium, cobalt, iron, manganese, chromium and zirconium are selectively removed from the second resin; and contacting the second resin with a dilute acid solution whereby the absorbed strontium ions are selectively removed. 1 fig.

Visualization of the membrane engineering concept: evidence for the specific orientation of electroinserted antibodies and selective binding of target analytes.

PubMed

Kokla, Anna; Blouchos, Petros; Livaniou, Evangelia; Zikos, Christos; Kakabakos, Sotiris E; Petrou, Panagiota S; Kintzios, Spyridon

2013-12-01

Membrane engineering is a generic methodology for increasing the selectivity of a cell biosensor against a target molecule, by electroinserting target-specific receptor-like molecules on the cell surface. Previous studies have elucidated the biochemical aspects of the interaction between various analytes (including viruses) and their homologous membrane-engineered cells. In the present study, purified anti-biotin antibodies from a rabbit antiserum along with in-house prepared biotinylated bovine serum albumin (BSA) were used as a model antibody-antigen pair of molecules for facilitating membrane engineering experiments. It was proven, with the aid of fluorescence microscopy, that (i) membrane-engineered cells incorporated the specific antibodies in the correct orientation and that (ii) the inserted antibodies are selectively interacting with the homologous target molecules. This is the first time the actual working concept of membrane engineering has been visualized, thus providing a final proof of the concept behind this innovative process. In addition, the fluorescence microscopy measurements were highly correlated with bioelectric measurements done with the aid of a bioelectric recognition assay. Copyright © 2013 John Wiley & Sons, Ltd.

Primer-Free Aptamer Selection Using A Random DNA Library

PubMed Central

Pan, Weihua; Xin, Ping; Patrick, Susan; Dean, Stacey; Keating, Christine; Clawson, Gary

2010-01-01

Aptamers are highly structured oligonucleotides (DNA or RNA) that can bind to targets with affinities comparable to antibodies 1. They are identified through an in vitro selection process called Systematic Evolution of Ligands by EXponential enrichment (SELEX) to recognize a wide variety of targets, from small molecules to proteins and other macromolecules 2-4. Aptamers have properties that are well suited for in vivo diagnostic and/or therapeutic applications: Besides good specificity and affinity, they are easily synthesized, survive more rigorous processing conditions, they are poorly immunogenic, and their relatively small size can result in facile penetration of tissues. Aptamers that are identified through the standard SELEX process usually comprise ~80 nucleotides (nt), since they are typically selected from nucleic acid libraries with ~40 nt long randomized regions plus fixed primer sites of ~20 nt on each side. The fixed primer sequences thus can comprise nearly ~50% of the library sequences, and therefore may positively or negatively compromise identification of aptamers in the selection process 3, although bioinformatics approaches suggest that the fixed sequences do not contribute significantly to aptamer structure after selection 5. To address these potential problems, primer sequences have been blocked by complementary oligonucleotides or switched to different sequences midway during the rounds of SELEX 6, or they have been trimmed to 6-9 nt 7, 8. Wen and Gray 9 designed a primer-free genomic SELEX method, in which the primer sequences were completely removed from the library before selection and were then regenerated to allow amplification of the selected genomic fragments. However, to employ the technique, a unique genomic library has to be constructed, which possesses limited diversity, and regeneration after rounds of selection relies on a linear reamplification step. Alternatively, efforts to circumvent problems caused by fixed primer sequences using high efficiency partitioning are met with problems regarding PCR amplification 10. We have developed a primer-free (PF) selection method that significantly simplifies SELEX procedures and effectively eliminates primer-interference problems 11, 12. The protocols work in a straightforward manner. The central random region of the library is purified without extraneous flanking sequences and is bound to a suitable target (for example to a purified protein or complex mixtures such as cell lines). Then the bound sequences are obtained, reunited with flanking sequences, and re-amplified to generate selected sub-libraries. As an example, here we selected aptamers to S100B, a protein marker for melanoma. Binding assays showed Kd s in the 10-7 - 10-8 M range after a few rounds of selection, and we demonstrate that the aptamers function effectively in a sandwich binding format. PMID:20689511

Design Principles of Nanoparticles as Contrast Agents for Magnetic Resonance Imaging

NASA Astrophysics Data System (ADS)

Shan, Liang; Gu, Xinbin; Wang, Paul

2013-09-01

Molecular imaging is an emerging field that introduces molecular agents into traditional imaging techniques, enabling visualization, characterization and measurement of biological processes at the molecular and cellular levels in humans and other living systems. The promise of molecular imaging lies in its potential for selective potency by targeting biomarkers or molecular targets and the imaging agents serve as reporters for the selectivity of targeting. Development of an efficient molecular imaging agent depends on well-controlled high-quality experiment design involving target selection, agent synthesis, in vitro characterization, and in vivo animal characterization before it is applied in humans. According to the analysis from the Molecular Imaging and Contrast Agent Database (MICAD, ), more than 6000 molecular imaging agents with sufficient preclinical evaluation have been reported to date in the literature and this number increases by 250-300 novel agents each year. The majority of these agents are radionuclides, which are developed for positron emission tomography (PET) and single photon emission computed tomography (SPECT). Contrast agents for magnetic resonance imaging (MRI) account for only a small part. This is largely due to the fact that MRI is currently not a fully quantitative imaging technique and is less sensitive than PET and SPECT. However, because of the superior ability to simultaneously extract molecular and anatomic information, molecular MRI is attracting significant interest and various targeted nanoparticle contrast agents have been synthesized for MRI. The first and one of the most critical steps in developing a targeted nanoparticle contrast agent is target selection, which plays the central role and forms the basis for success of molecular imaging. This chapter discusses the design principles of targeted contrast agents in the emerging frontiers of molecular MRI.

Quantitative self-assembly prediction yields targeted nanomedicines

NASA Astrophysics Data System (ADS)

Shamay, Yosi; Shah, Janki; Işık, Mehtap; Mizrachi, Aviram; Leibold, Josef; Tschaharganeh, Darjus F.; Roxbury, Daniel; Budhathoki-Uprety, Januka; Nawaly, Karla; Sugarman, James L.; Baut, Emily; Neiman, Michelle R.; Dacek, Megan; Ganesh, Kripa S.; Johnson, Darren C.; Sridharan, Ramya; Chu, Karen L.; Rajasekhar, Vinagolu K.; Lowe, Scott W.; Chodera, John D.; Heller, Daniel A.

2018-02-01

Development of targeted nanoparticle drug carriers often requires complex synthetic schemes involving both supramolecular self-assembly and chemical modification. These processes are generally difficult to predict, execute, and control. We describe herein a targeted drug delivery system that is accurately and quantitatively predicted to self-assemble into nanoparticles based on the molecular structures of precursor molecules, which are the drugs themselves. The drugs assemble with the aid of sulfated indocyanines into particles with ultrahigh drug loadings of up to 90%. We devised quantitative structure-nanoparticle assembly prediction (QSNAP) models to identify and validate electrotopological molecular descriptors as highly predictive indicators of nano-assembly and nanoparticle size. The resulting nanoparticles selectively targeted kinase inhibitors to caveolin-1-expressing human colon cancer and autochthonous liver cancer models to yield striking therapeutic effects while avoiding pERK inhibition in healthy skin. This finding enables the computational design of nanomedicines based on quantitative models for drug payload selection.

Selective Fenton-like oxidation of methylene blue on modified Fe-zeolites prepared via molecular imprinting technique.

PubMed

Zhang, Yuanyuan; Shang, Jiaobo; Song, Yanqun; Rong, Chuan; Wang, Yinghui; Huang, Wenyu; Yu, Kefu

2017-02-01

A facile strategy to increase the selectivity of heterogeneous Fenton oxidation is investigated. The increase was reached by increasing selective adsorption of heterogeneous Fenton catalyst to a target pollutant. The heterogeneous Fenton catalyst was prepared by a two-step process. First, zeolite particles were imprinted by the target pollutant, methylene blue (MB), in their aggregations, and second, iron ions were loaded on the zeolite aggregations to form the molecule imprinted Fe-zeolites (MI-FZ) Fenton catalyst. Its adsorption amount for MB reached as high as 44.6 mg g -1 while the adsorption amount of un-imprinted Fe-zeolites (FZ) is only 15.6 mg g -1 . Fenton removal efficiency of MI-FZ for MB was 87.7%, being 33.9% higher than that of FZ. The selective Fenton oxidation of MI-FZ for MB was further confirmed by its removal performance for the mixed MB and bisphenol A (BPA) in solution. The removal efficiency of MB was 44.7% while that of BPA was only 14.9%. This fact shows that molecular imprinting is suitable to prepare the Fe-zeolites (FZ)-based Fenton catalyst with high selectivity for removal of target pollutants, at least MB.

Manufacturing of Proteins and Antibodies: Chapter Downstream Processing Technologies : Harvest Operations.

PubMed

Turner, Richard; Joseph, Adrian; Titchener-Hooker, Nigel; Bender, Jean

2017-08-04

Cell harvesting is the separation or retention of cells and cellular debris from the supernatant containing the target molecule Selection of harvest method strongly depends on the type of cells, mode of bioreactor operation, process scale, and characteristics of the product and cell culture fluid. Most traditional harvesting methods use some form of filtration, centrifugation, or a combination of both for cell separation and/or retention. Filtration methods include normal flow depth filtration and tangential flow microfiltration. The ability to scale down predictably the selected harvest method helps to ensure successful production and is critical for conducting small-scale characterization studies for confirming parameter targets and ranges. In this chapter we describe centrifugation and depth filtration harvesting methods, share strategies for harvest optimization, present recent developments in centrifugation scale-down models, and review alternative harvesting technologies.

Specific Contributions of Ventromedial, Anterior Cingulate, and Lateral Prefrontal Cortex for Attentional Selection and Stimulus Valuation

PubMed Central

Kaping, Daniel; Vinck, Martin; Hutchison, R. Matthew; Everling, Stefan; Womelsdorf, Thilo

2011-01-01

Attentional control ensures that neuronal processes prioritize the most relevant stimulus in a given environment. Controlling which stimulus is attended thus originates from neurons encoding the relevance of stimuli, i.e. their expected value, in hand with neurons encoding contextual information about stimulus locations, features, and rules that guide the conditional allocation of attention. Here, we examined how these distinct processes are encoded and integrated in macaque prefrontal cortex (PFC) by mapping their functional topographies at the time of attentional stimulus selection. We find confined clusters of neurons in ventromedial PFC (vmPFC) that predominantly convey stimulus valuation information during attention shifts. These valuation signals were topographically largely separated from neurons predicting the stimulus location to which attention covertly shifted, and which were evident across the complete medial-to-lateral extent of the PFC, encompassing anterior cingulate cortex (ACC), and lateral PFC (LPFC). LPFC responses showed particularly early-onset selectivity and primarily facilitated attention shifts to contralateral targets. Spatial selectivity within ACC was delayed and heterogeneous, with similar proportions of facilitated and suppressed responses during contralateral attention shifts. The integration of spatial and valuation signals about attentional target stimuli was observed in a confined cluster of neurons at the intersection of vmPFC, ACC, and LPFC. These results suggest that valuation processes reflecting stimulus-specific outcome predictions are recruited during covert attentional control. Value predictions and the spatial identification of attentional targets were conveyed by largely separate neuronal populations, but were integrated locally at the intersection of three major prefrontal areas, which may constitute a functional hub within the larger attentional control network. PMID:22215982

Hippocampal-targeted Theta-burst Stimulation Enhances Associative Memory Formation.

PubMed

Tambini, Arielle; Nee, Derek Evan; D'Esposito, Mark

2018-06-19

The hippocampus plays a critical role in episodic memory, among other cognitive functions. However, few tools exist to causally manipulate hippocampal function in healthy human participants. Recent work has targeted hippocampal-cortical networks by performing TMS to a region interconnected with the hippocampus, posterior inferior parietal cortex (pIPC). Such hippocampal-targeted TMS enhances associative memory and influences hippocampal functional connectivity. However, it is currently unknown which stages of mnemonic processing (encoding or retrieval) are affected by hippocampal-targeted TMS. Here, we examined whether hippocampal-targeted TMS influences the initial encoding of associations (vs. items) into memory. To selectively influence encoding and not retrieval, we performed continuous theta-burst TMS before participants encoded object-location associations and assessed memory after the direct effect of stimulation dissipated. Relative to control TMS and baseline memory, pIPC TMS enhanced associative memory success and confidence. Item memory was unaffected, demonstrating a selective influence on associative versus item memory. The strength of hippocampal-pIPC functional connectivity predicted TMS-related memory benefits, which was mediated by parahippocampal and retrosplenial cortices. Our findings indicate that hippocampal-targeted TMS can specifically modulate the encoding of new associations into memory without directly influencing retrieval processes and suggest that the ability to influence associative memory may be related to the fidelity of hippocampal TMS targeting. Our results support the notion that pIPC TMS may serve as a potential tool for manipulating hippocampal function in healthy participants. Nonetheless, future work combining hippocampal-targeted continuous theta-burst TMS with neuroimaging is needed to better understand the neural basis of TMS-induced memory changes.

Recovery of germanium-68 from irradiated targets

DOEpatents

Phillips, Dennis R.; Jamriska, Sr., David J.; Hamilton, Virginia T.

1993-01-01

A process for selective separation of germanium-68 from proton irradiated molybdenum targets is provided and includes dissolving the molybdenum target in a hydrogen peroxide solution to form a first ion-containing solution, contacting the first ion-containing solution with a cationic resin whereby ions selected from the group consisting of molybdenum, niobium, technetium, selenium, vanadium, arsenic, germanium, zirconium and rubidium remain in a second ion-containing solution while ions selected from the group consisting of rubidium, zinc, beryllium, cobalt, iron, manganese, chromium, strontium, yttrium and zirconium are selectively adsorbed by the first resin, adjusting the pH of the second ion-containing solution to within a range of from about 0.7 to about 3.0, adjusting the soluble metal halide concentration in the second ion-containing solution to a level adapted for subsequent separation of germanium, contacting the pH-adjusted, soluble metal halide-containing second ion-containing solution with a dextran-based material whereby germanium ions are separated by the dextran-based material, and recovering the germanium from the dextran-based material, preferably by distillation.

Temporal kinetics of prefrontal modulation of the extrastriate cortex during visual attention.

PubMed

Yago, Elena; Duarte, Audrey; Wong, Ting; Barceló, Francisco; Knight, Robert T

2004-12-01

Single-unit, event-related potential (ERP), and neuroimaging studies have implicated the prefrontal cortex (PFC) in top-down control of attention and working memory. We conducted an experiment in patients with unilateral PFC damage (n = 8) to assess the temporal kinetics of PFC-extrastriate interactions during visual attention. Subjects alternated attention between the left and the right hemifields in successive runs while they detected target stimuli embedded in streams of repetitive task-irrelevant stimuli (standards). The design enabled us to examine tonic (spatial selection) and phasic (feature selection) PFC-extrastriate interactions. PFC damage impaired performance in the visual field contralateral to lesions, as manifested by both larger reaction times and error rates. Assessment of the extrastriate P1 ERP revealed that the PFC exerts a tonic (spatial selection) excitatory input to the ipsilateral extrastriate cortex as early as 100 msec post stimulus delivery. The PFC exerts a second phasic (feature selection) excitatory extrastriate modulation from 180 to 300 msec, as evidenced by reductions in selection negativity after damage. Finally, reductions of the N2 ERP to target stimuli supports the notion that the PFC exerts a third phasic (target selection) signal necessary for successful template matching during postselection analysis of target features. The results provide electrophysiological evidence of three distinct tonic and phasic PFC inputs to the extrastriate cortex in the initial few hundred milliseconds of stimulus processing. Damage to this network appears to underlie the pervasive deficits in attention observed in patients with prefrontal lesions.

Efficient Modeling and Active Learning Discovery of Biological Responses

PubMed Central

Naik, Armaghan W.; Kangas, Joshua D.; Langmead, Christopher J.; Murphy, Robert F.

2013-01-01

High throughput and high content screening involve determination of the effect of many compounds on a given target. As currently practiced, screening for each new target typically makes little use of information from screens of prior targets. Further, choices of compounds to advance to drug development are made without significant screening against off-target effects. The overall drug development process could be made more effective, as well as less expensive and time consuming, if potential effects of all compounds on all possible targets could be considered, yet the cost of such full experimentation would be prohibitive. In this paper, we describe a potential solution: probabilistic models that can be used to predict results for unmeasured combinations, and active learning algorithms for efficiently selecting which experiments to perform in order to build those models and determining when to stop. Using simulated and experimental data, we show that our approaches can produce powerful predictive models without exhaustive experimentation and can learn them much faster than by selecting experiments at random. PMID:24358322

Small-Molecule Binding Aptamers: Selection Strategies, Characterization, and Applications

PubMed Central

Ruscito, Annamaria; DeRosa, Maria C.

2016-01-01

Aptamers are single-stranded, synthetic oligonucleotides that fold into 3-dimensional shapes capable of binding non-covalently with high affinity and specificity to a target molecule. They are generated via an in vitro process known as the Systematic Evolution of Ligands by EXponential enrichment, from which candidates are screened and characterized, and then used in various applications. These applications range from therapeutic uses to biosensors for target detection. Aptamers for small molecule targets such as toxins, antibiotics, molecular markers, drugs, and heavy metals will be the focus of this review. Their accurate detection is needed for the protection and wellbeing of humans and animals. However, the small molecular weights of these targets, including the drastic size difference between the target and the oligonucleotides, make it challenging to select, characterize, and apply aptamers for their detection. Thus, recent (since 2012) notable advances in small molecule aptamers, which have overcome some of these challenges, are presented here, while defining challenges that still exist are discussed. PMID:27242994

Contextual cueing effects despite spatially cued target locations.

PubMed

Schankin, Andrea; Schubö, Anna

2010-07-01

Reaction times (RT) to targets are faster in repeated displays relative to novel ones when the spatial arrangement of the distracting items predicts the target location (contextual cueing). It is assumed that visual-spatial attention is guided more efficiently to the target resulting in reduced RTs. In the present experiment, contextual cueing even occurred when the target location was previously peripherally cued. Electrophysiologically, repeated displays elicited an enhanced N2pc component in both conditions and resulted in an earlier onset of the stimulus-locked lateralized readiness potential (s-LRP) in the cued condition and in an enhanced P3 in the uncued condition relative to novel displays. These results indicate that attentional guidance is less important than previously assumed but that other cognitive processes, such as attentional selection (N2pc) and response-related processes (s-LRP, P3) are facilitated by context familiarity.

Benzimidazoles: an ideal privileged drug scaffold for the design of multitargeted anti-inflammatory ligands.

PubMed

Kaur, Gaganpreet; Kaur, Maninder; Silakari, Om

2014-01-01

The recent research area endeavors to discover ultimate multi-target ligands, an increasingly feasible and attractive alternative to existing mono-targeted drugs for treatment of complex, multi-factorial inflammation process which underlays plethora of debilitated health conditions. In order to improvise this option, exploration of relevant chemical core scaffold will be an utmost need. Privileged benzimidazole scaffold being historically versatile structural motif could offer a viable starting point in the search for novel multi-target ligands against multi-factorial inflammation process since, when appropriately substituted, it can selectively modulate diverse receptors, pathways and enzymes associated with the pathogenesis of inflammation. Despite this remarkable capability, the multi-target capacity of the benzimidazole scaffold remains largely unexploited. With this in focus, the present review article attempts to provide synopsis of published research to exemplify the valuable use of benzimidazole nucleus and focus on their suitability as starting scaffold to develop multi-targeted anti-inflammatory ligands.

Attentional selection within and across hemispheres: implications for the perceptual load theory.

PubMed

Wei, Ping; Kang, Guanlan; Zhou, Xiaolin

2013-03-01

The perceptual load of a given task affects attentional selection, with the selection occurring earlier when the load is high and later when the load is low. Recent evidence suggests that local competitive interaction may underlie the perceptual load effect and determine to what extent a task-irrelevant distractor is processed. Here, we asked participants to search for a target bar among homogeneously oriented bars (the low load conditions) or heterogeneously oriented bars (the high load conditions) in the central display, while ignoring a congruent or incongruent flanker bar presented to the left or right side of the central display, or a bar presented at one of the six positions outer to the central display. Importantly, we differentiated conditions in which the target in the central display and the peripheral flanker was presented within the same hemifield or across different hemifields. Results showed a significant flanker effect for the low load condition, but not for the high load condition, when the target and the flanker were across hemifields. However, when the target and the flanker were presented within the same hemifield, there was no flanker effect for either low or high load conditions. These findings demonstrate that the ability to ignore the task-irrelevant distractor is affected by local competition within hemisphere and that the perceptual load theory needs to be supplemented with detailed analysis of cognitive processes and mechanisms underlying the consumption of attentional resources.

New rules for visual selection: Isolating procedural attention.

PubMed

Ramamurthy, Mahalakshmi; Blaser, Erik

2017-02-01

High performance in well-practiced, everyday tasks-driving, sports, gaming-suggests a kind of procedural attention that can allocate processing resources to behaviorally relevant information in an unsupervised manner. Here we show that training can lead to a new, automatic attentional selection rule that operates in the absence of bottom-up, salience-driven triggers and willful top-down selection. Taking advantage of the fact that attention modulates motion aftereffects, observers were presented with a bivectorial display with overlapping, iso-salient red and green dot fields moving to the right and left, respectively, while distracted by a demanding auditory two-back memory task. Before training, since the motion vectors canceled each other out, no net motion aftereffect (MAE) was found. However, after 3 days (0.5 hr/day) of training, during which observers practiced selectively attending to the red, rightward field, a significant net MAE was observed-even when top-down selection was again distracted. Further experiments showed that these results were not due to perceptual learning, and that the new rule targeted the motion, and not the color of the target dot field, and global, not local, motion signals; thus, the new rule was: "select the rightward field." This study builds on recent work on selection history-driven and reward-driven biases, but uses a novel paradigm where the allocation of visual processing resources are measured passively, offline, and when the observer's ability to execute top-down selection is defeated.

Neural control of visual search by frontal eye field: effects of unexpected target displacement on visual selection and saccade preparation.

PubMed

Murthy, Aditya; Ray, Supriya; Shorter, Stephanie M; Schall, Jeffrey D; Thompson, Kirk G

2009-05-01

The dynamics of visual selection and saccade preparation by the frontal eye field was investigated in macaque monkeys performing a search-step task combining the classic double-step saccade task with visual search. Reward was earned for producing a saccade to a color singleton. On random trials the target and one distractor swapped locations before the saccade and monkeys were rewarded for shifting gaze to the new singleton location. A race model accounts for the probabilities and latencies of saccades to the initial and final singleton locations and provides a measure of the duration of a covert compensation process-target-step reaction time. When the target stepped out of a movement field, noncompensated saccades to the original location were produced when movement-related activity grew rapidly to a threshold. Compensated saccades to the final location were produced when the growth of the original movement-related activity was interrupted within target-step reaction time and was replaced by activation of other neurons producing the compensated saccade. When the target stepped into a receptive field, visual neurons selected the new target location regardless of the monkeys' response. When the target stepped out of a receptive field most visual neurons maintained the representation of the original target location, but a minority of visual neurons showed reduced activity. Chronometric analyses of the neural responses to the target step revealed that the modulation of visually responsive neurons and movement-related neurons occurred early enough to shift attention and saccade preparation from the old to the new target location. These findings indicate that visual activity in the frontal eye field signals the location of targets for orienting, whereas movement-related activity instantiates saccade preparation.

Object integration requires attention: Visual search for Kanizsa figures in parietal extinction.

PubMed

Gögler, Nadine; Finke, Kathrin; Keller, Ingo; Müller, Hermann J; Conci, Markus

2016-11-01

The contribution of selective attention to object integration is a topic of debate: integration of parts into coherent wholes, such as in Kanizsa figures, is thought to arise either from pre-attentive, automatic coding processes or from higher-order processes involving selective attention. Previous studies have attempted to examine the role of selective attention in object integration either by employing visual search paradigms or by studying patients with unilateral deficits in selective attention. Here, we combined these two approaches to investigate object integration in visual search in a group of five patients with left-sided parietal extinction. Our search paradigm was designed to assess the effect of left- and right-grouped nontargets on detecting a Kanizsa target square. The results revealed comparable reaction time (RT) performance in patients and controls when they were presented with displays consisting of a single to-be-grouped item that had to be classified as target vs. nontarget. However, when display size increased to two items, patients showed an extinction-specific pattern of enhanced RT costs for nontargets that induced a partial shape grouping on the right, i.e., in the attended hemifield (relative to the ungrouped baseline). Together, these findings demonstrate a competitive advantage for right-grouped objects, which in turn indicates that in parietal extinction, attentional competition between objects particularly limits integration processes in the contralesional, i.e., left hemifield. These findings imply a crucial contribution of selective attentional resources to visual object integration. Copyright © 2016 Elsevier Ltd. All rights reserved.

Long-Term Memories Bias Sensitivity and Target Selection in Complex Scenes

PubMed Central

Patai, Eva Zita; Doallo, Sonia; Nobre, Anna Christina

2014-01-01

In everyday situations we often rely on our memories to find what we are looking for in our cluttered environment. Recently, we developed a new experimental paradigm to investigate how long-term memory (LTM) can guide attention, and showed how the pre-exposure to a complex scene in which a target location had been learned facilitated the detection of the transient appearance of the target at the remembered location (Summerfield, Lepsien, Gitelman, Mesulam, & Nobre, 2006; Summerfield, Rao, Garside, & Nobre, 2011). The present study extends these findings by investigating whether and how LTM can enhance perceptual sensitivity to identify targets occurring within their complex scene context. Behavioral measures showed superior perceptual sensitivity (d′) for targets located in remembered spatial contexts. We used the N2pc event-related potential to test whether LTM modulated the process of selecting the target from its scene context. Surprisingly, in contrast to effects of visual spatial cues or implicit contextual cueing, LTM for target locations significantly attenuated the N2pc potential. We propose that the mechanism by which these explicitly available LTMs facilitate perceptual identification of targets may differ from mechanisms triggered by other types of top-down sources of information. PMID:23016670

Top-down attentional control in spatially coincident stimuli enhances activity in both task-relevant and task-irrelevant regions of cortex

PubMed Central

Erickson, Kirk I.; Prakash, Ruchika Shaurya; Kim, Jennifer S.; Sutton, Bradley P.; Colcombe, Stanley J.; Kramer, Arthur F.

2010-01-01

Models of selective attention predict that focused attention to spatially contiguous stimuli may result in enhanced activity in areas of cortex specialized for processing task-relevant and task-irrelevant information. We examined this hypothesis by localizing color-sensitive areas (CSA) and word and letter sensitive areas of cortex and then examining modulation of these regions during performance of a modified version of the Stroop task in which target and distractors are spatially coincident. We report that only the incongruent condition with the highest cognitive demand showed increased activity in CSA relative to other conditions, indicating an attentional enhancement in target processing areas. We also found an enhancement of activity in one region sensitive to word/letter processing during the most cognitively demanding incongruent condition indicating greater processing of the distractor dimension. Correlations with performance revealed that top-down modulation during the task was critical for effective filtering of irrelevant information in conflict conditions. These results support predictions made by models of selective attention and suggest an important mechanism of top-down attentional control in spatially contiguous stimuli. PMID:18804123

Miklós Bodanszky Award Lecture: Advances in the selective targeting of protein phosphatase-1 and phosphatase-2A with peptides.

PubMed

Köhn, Maja

2017-10-01

Protein phosphatase-1 and phosphatase-2A are two ubiquitously expressed enzymes known to catalyze the majority of dephosphorylation reactions on serine and threonine inside cells. They play roles in most cellular processes and are tightly regulated by regulatory subunits in holoenzymes. Their misregulation and malfunction contribute to disease development and progression, such as in cancer, diabetes, viral infections, and neurological as well as heart diseases. Therefore, targeting these phosphatases for therapeutic use would be highly desirable; however, their complex regulation and high conservation of the active site have been major hurdles for selectively targeting them in the past. In the last decade, new approaches have been developed to overcome these hurdles and have strongly revived the field. I will focus here on peptide-based approaches, which contributed to showing that these phosphatases can be targeted selectively and aided in rethinking the design of selective phosphatase modulators. Finally, I will give a perspective on www.depod.org, the human dephosphorylation database, and how it can aid phosphatase modulator design. © 2017 The Authors. Journal of Peptide Science published by European Peptide Society and John Wiley & Sons Ltd. © 2017 The Authors. Journal of Peptide Science published by European Peptide Society and John Wiley & Sons Ltd.

Selection and trajectory design to mission secondary targets

NASA Astrophysics Data System (ADS)

Victorino Sarli, Bruno; Kawakatsu, Yasuhiro

2017-02-01

Recently, with new trajectory design techniques and use of low-thrust propulsion systems, missions have become more efficient and cheaper with respect to propellant. As a way to increase the mission's value and scientific return, secondary targets close to the main trajectory are often added with a small change in the transfer trajectory. As a result of their large number, importance and facility to perform a flyby, asteroids are commonly used as such targets. This work uses the Primer Vector theory to define the direction and magnitude of the thrust for a minimum fuel consumption problem. The design of a low-thrust trajectory with a midcourse asteroid flyby is not only challenging for the low-thrust problem solution, but also with respect to the selection of a target and its flyby point. Currently more than 700,000 minor bodies have been identified, which generates a very large number of possible flyby points. This work uses a combination of reachability, reference orbit, and linear theory to select appropriate candidates, drastically reducing the simulation time, to be later included in the main trajectory and optimized. Two test cases are presented using the aforementioned selection process and optimization to add and design a secondary flyby to a mission with the primary objective of 3200 Phaethon flyby and 25143 Itokawa rendezvous.

Target dependence of orientation and direction selectivity of corticocortical projection neurons in the mouse V1

PubMed Central

Matsui, Teppei; Ohki, Kenichi

2013-01-01

Higher order visual areas that receive input from the primary visual cortex (V1) are specialized for the processing of distinct features of visual information. However, it is still incompletely understood how this functional specialization is acquired. Here we used in vivo two photon calcium imaging in the mouse visual cortex to investigate whether this functional distinction exists at as early as the level of projections from V1 to two higher order visual areas, AL and LM. Specifically, we examined whether sharpness of orientation and direction selectivity and optimal spatial and temporal frequency of projection neurons from V1 to higher order visual areas match with that of target areas. We found that the V1 input to higher order visual areas were indeed functionally distinct: AL preferentially received inputs from V1 that were more orientation and direction selective and tuned for lower spatial frequency compared to projection of V1 to LM, consistent with functional differences between AL and LM. The present findings suggest that selective projections from V1 to higher order visual areas initiates parallel processing of sensory information in the visual cortical network. PMID:24068987

Resistance of Grape Rootstocks to Plant-parasitic Nematodes.

PubMed

Ferris, H; Zheng, L; Walker, M A

2012-12-01

Candidate grape rootstocks were selected through a rigorous screening program initiated with important sources of resistance to Meloidogyne pathotypes and to Xiphinema index in Muscadinia rotundifolia and Vitis species native to North America. Based on their rooting capability and horticultural characteristics, 200 candidates were selected from 5,000 progeny of multiple crosses between commercial grape rootstocks and wild grape species that exhibited resistance to nematodes. After a 15-year screening process, 13 selections emerged with either almost complete or complete combined resistance to M. incognita Race 3, M. incognita pathotype Harmony C, M. arenaria pathotype Harmony A, and X. index, important nematode pests of grapevines. Durability of this broad resistance was tested by challenging the selections with the target nematodes in combination and with the target nematodes in combinations with species not included in the screening process. Durability of resistance of the candidate rootstocks was also tested by exposure to the nematode communities of infested field soils from different locations. Breadth of resistance was determined on the basis of their host status to non-target nematodes, including Mesocriconema xenoplax, Pratylenchus vulnus, Tylenchulus semipenetrans and Paratylenchus hamatus. After a total of 204 separate trials, the rootstocks were released to the grape industry as UCD GRN1, UCD GRN2, UCD GRN3, UCD GRN4, and UCD GRN5. We provide a compilation of current knowledge of the host status of these five newly released rootstocks and of 27 other rootstock cultivars to plant-parasitic nematodes.

Resistance of Grape Rootstocks to Plant-parasitic Nematodes

PubMed Central

Ferris, H.; Zheng, L.; Walker, M. A.

2012-01-01

Candidate grape rootstocks were selected through a rigorous screening program initiated with important sources of resistance to Meloidogyne pathotypes and to Xiphinema index in Muscadinia rotundifolia and Vitis species native to North America. Based on their rooting capability and horticultural characteristics, 200 candidates were selected from 5,000 progeny of multiple crosses between commercial grape rootstocks and wild grape species that exhibited resistance to nematodes. After a 15-year screening process, 13 selections emerged with either almost complete or complete combined resistance to M. incognita Race 3, M. incognita pathotype Harmony C, M. arenaria pathotype Harmony A, and X. index, important nematode pests of grapevines. Durability of this broad resistance was tested by challenging the selections with the target nematodes in combination and with the target nematodes in combinations with species not included in the screening process. Durability of resistance of the candidate rootstocks was also tested by exposure to the nematode communities of infested field soils from different locations. Breadth of resistance was determined on the basis of their host status to non-target nematodes, including Mesocriconema xenoplax, Pratylenchus vulnus, Tylenchulus semipenetrans and Paratylenchus hamatus. After a total of 204 separate trials, the rootstocks were released to the grape industry as UCD GRN1, UCD GRN2, UCD GRN3, UCD GRN4, and UCD GRN5. We provide a compilation of current knowledge of the host status of these five newly released rootstocks and of 27 other rootstock cultivars to plant-parasitic nematodes. PMID:23482972

Robust human detection, tracking, and recognition in crowded urban areas

NASA Astrophysics Data System (ADS)

Chen, Hai-Wen; McGurr, Mike

2014-06-01

In this paper, we present algorithms we recently developed to support an automated security surveillance system for very crowded urban areas. In our approach for human detection, the color features are obtained by taking the difference of R, G, B spectrum and converting R, G, B to HSV (Hue, Saturation, Value) space. Morphological patch filtering and regional minimum and maximum segmentation on the extracted features are applied for target detection. The human tracking process approach includes: 1) Color and intensity feature matching track candidate selection; 2) Separate three parallel trackers for color, bright (above mean intensity), and dim (below mean intensity) detections, respectively; 3) Adaptive track gate size selection for reducing false tracking probability; and 4) Forward position prediction based on previous moving speed and direction for continuing tracking even when detections are missed from frame to frame. The Human target recognition is improved with a Super-Resolution Image Enhancement (SRIE) process. This process can improve target resolution by 3-5 times and can simultaneously process many targets that are tracked. Our approach can project tracks from one camera to another camera with a different perspective viewing angle to obtain additional biometric features from different perspective angles, and to continue tracking the same person from the 2nd camera even though the person moved out of the Field of View (FOV) of the 1st camera with `Tracking Relay'. Finally, the multiple cameras at different view poses have been geo-rectified to nadir view plane and geo-registered with Google- Earth (or other GIS) to obtain accurate positions (latitude, longitude, and altitude) of the tracked human for pin-point targeting and for a large area total human motion activity top-view. Preliminary tests of our algorithms indicate than high probability of detection can be achieved for both moving and stationary humans. Our algorithms can simultaneously track more than 100 human targets with averaged tracking period (time length) longer than the performance of the current state-of-the-art.

Evidence accumulation as a model for lexical selection.

PubMed

Anders, R; Riès, S; van Maanen, L; Alario, F X

2015-11-01

We propose and demonstrate evidence accumulation as a plausible theoretical and/or empirical model for the lexical selection process of lexical retrieval. A number of current psycholinguistic theories consider lexical selection as a process related to selecting a lexical target from a number of alternatives, which each have varying activations (or signal supports), that are largely resultant of an initial stimulus recognition. We thoroughly present a case for how such a process may be theoretically explained by the evidence accumulation paradigm, and we demonstrate how this paradigm can be directly related or combined with conventional psycholinguistic theory and their simulatory instantiations (generally, neural network models). Then with a demonstrative application on a large new real data set, we establish how the empirical evidence accumulation approach is able to provide parameter results that are informative to leading psycholinguistic theory, and that motivate future theoretical development. Copyright © 2015 Elsevier Inc. All rights reserved.

Sequence-based design of bioactive small molecules that target precursor microRNAs.

PubMed

Velagapudi, Sai Pradeep; Gallo, Steven M; Disney, Matthew D

2014-04-01

Oligonucleotides are designed to target RNA using base pairing rules, but they can be hampered by poor cellular delivery and nonspecific stimulation of the immune system. Small molecules are preferred as lead drugs or probes but cannot be designed from sequence. Herein, we describe an approach termed Inforna that designs lead small molecules for RNA from solely sequence. Inforna was applied to all human microRNA hairpin precursors, and it identified bioactive small molecules that inhibit biogenesis by binding nuclease-processing sites (44% hit rate). Among 27 lead interactions, the most avid interaction is between a benzimidazole (1) and precursor microRNA-96. Compound 1 selectively inhibits biogenesis of microRNA-96, upregulating a protein target (FOXO1) and inducing apoptosis in cancer cells. Apoptosis is ablated when FOXO1 mRNA expression is knocked down by an siRNA, validating compound selectivity. Markedly, microRNA profiling shows that 1 only affects microRNA-96 biogenesis and is at least as selective as an oligonucleotide.

Sequence-based design of bioactive small molecules that target precursor microRNAs

PubMed Central

Velagapudi, Sai Pradeep; Gallo, Steven M.; Disney, Matthew D.

2014-01-01

Oligonucleotides are designed to target RNA using base pairing rules, however, they are hampered by poor cellular delivery and non-specific stimulation of the immune system. Small molecules are preferred as lead drugs or probes, but cannot be designed from sequence. Herein, we describe an approach termed Inforna that designs lead small molecules for RNA from solely sequence. Inforna was applied to all human microRNA precursors and identified bioactive small molecules that inhibit biogenesis by binding to nuclease processing sites (41% hit rate). Amongst 29 lead interactions, the most avid interaction is between a benzimidazole (1) and precursor microRNA-96. Compound 1 selectively inhibits biogenesis of microRNA-96, upregulating a protein target (FOXO1) and inducing apoptosis in cancer cells. Apoptosis is ablated when FOXO1 mRNA expression is knocked down by an siRNA, validating compound selectivity. Importantly, microRNA profiling shows that 1 only significantly effects microRNA-96 biogenesis and is more selective than an oligonucleotide. PMID:24509821

Use of mathematics to guide target selection in systems pharmacology; application to receptor tyrosine kinase (RTK) pathways.

PubMed

Benson, Neil; van der Graaf, Piet H; Peletier, Lambertus A

2017-11-15

A key element of the drug discovery process is target selection. Although the topic is subject to much discussion and experimental effort, there are no defined quantitative rules around optimal selection. Often 'rules of thumb', that have not been subject to rigorous exploration, are used. In this paper we explore the 'rule of thumb' notion that the molecule that initiates a pathway signal is the optimal target. Given the multi-factorial and complex nature of this question, we have simplified an example pathway to its logical minimum of two steps and used a mathematical model of this to explore the different options in the context of typical small and large molecule drugs. In this paper, we report the conclusions of our analysis and describe the analysis tool and methods used. These provide a platform to enable a more extensive enquiry into this important topic. Copyright © 2017 Elsevier B.V. All rights reserved.

Dorsal premotor cortex: neural correlates of reach target decisions based on a color-location matching rule and conflicting sensory evidence

PubMed Central

Coallier, Émilie; Michelet, Thomas

2015-01-01

We recorded single-neuron activity in dorsal premotor (PMd) and primary motor cortex (M1) of two monkeys in a reach-target selection task. The monkeys chose between two color-coded potential targets by determining which target's color matched the predominant color of a multicolored checkerboard-like Decision Cue (DC). Different DCs contained differing numbers of colored squares matching each target. The DCs provided evidence about the correct target ranging from unambiguous (one color only) to very ambiguous and conflicting (nearly equal number of squares of each color). Differences in choice behavior (reach response times and success rates as a function of DC ambiguity) of the monkeys suggested that each applied a different strategy for using the target-choice evidence in the DCs. Nevertheless, the appearance of the DCs evoked a transient coactivation of PMd neurons preferring both potential targets in both monkeys. Reach response time depended both on how long it took activity to increase in neurons that preferred the chosen target and on how long it took to suppress the activity of neurons that preferred the rejected target, in both correct-choice and error-choice trials. These results indicate that PMd neurons in this task are not activated exclusively by a signal proportional to the net color bias of the DCs. They are instead initially modulated by the conflicting evidence supporting both response choices; final target selection may result from a competition between representations of the alternative choices. The results also indicate a temporal overlap between action selection and action initiation processes in PMd and M1. PMID:25787952

Production of sodium-22 from proton irradiated aluminum

DOEpatents

Taylor, Wayne A.; Heaton, Richard C.; Jamriska, David J.

1996-01-01

A process for selective separation of sodium-22 from a proton irradiated minum target including dissolving a proton irradiated aluminum target in hydrochloric acid to form a first solution including aluminum ions and sodium ions, separating a portion of the aluminum ions from the first solution by crystallization of an aluminum salt, contacting the remaining first solution with an anion exchange resin whereby ions selected from the group consisting of iron and copper are selectively absorbed by the anion exchange resin while aluminum ions and sodium ions remain in solution, contacting the solution with an cation exchange resin whereby aluminum ions and sodium ions are adsorbed by the cation exchange resin, and, contacting the cation exchange resin with an acid solution capable of selectively separating the adsorbed sodium ions from the cation exchange resin while aluminum ions remain adsorbed on the cation exchange resin is disclosed.

The Construct of Attention in Schizophrenia

PubMed Central

Luck, Steven J.; Gold, James M.

2008-01-01

Schizophrenia is widely thought to involve deficits of attention. However, the term attention can be defined so broadly that impaired performance on virtually any task could be construed as evidence for a deficit in attention, and this has slowed cumulative progress in understanding attention deficits in schizophrenia. To address this problem, we divide the general concept of attention into two distinct constructs: input selection, the selection of task-relevant inputs for further processing; and rule selection, the selective activation of task-appropriate rules. These constructs are closely tied to working memory, because input selection mechanisms are used to control the transfer of information into working memory and because working memory stores the rules used by rule selection mechanisms. These constructs are also closely tied to executive function, because executive systems are used to guide input selection and because rule selection is itself at key aspect of executive function. Within the domain of input selection, it is important to distinguish between the control of selection—the processes that guide attention to task-relevant inputs—and the implementation of selection—the processes that enhance the processing of the relevant inputs and suppress the irrelevant inputs. Current evidence suggests that schizophrenia involves a significant impairment in the control of selection but little or no impairment in the implementation of selection. Consequently, the CNTRICS participants agreed by consensus that attentional control should be a priority target for measurement and treatment research in schizophrenia. PMID:18374901

Porous Silicon-Based Biosensors: Towards Real-Time Optical Detection of Target Bacteria in the Food Industry

PubMed Central

Massad-Ivanir, Naama; Shtenberg, Giorgi; Raz, Nitzan; Gazenbeek, Christel; Budding, Dries; Bos, Martine P.; Segal, Ester

2016-01-01

Rapid detection of target bacteria is crucial to provide a safe food supply and to prevent foodborne diseases. Herein, we present an optical biosensor for identification and quantification of Escherichia coli (E. coli, used as a model indicator bacteria species) in complex food industry process water. The biosensor is based on a nanostructured, oxidized porous silicon (PSi) thin film which is functionalized with specific antibodies against E. coli. The biosensors were exposed to water samples collected directly from process lines of fresh-cut produce and their reflectivity spectra were collected in real time. Process water were characterized by complex natural micro-flora (microbial load of >107 cell/mL), in addition to soil particles and plant cell debris. We show that process water spiked with culture-grown E. coli, induces robust and predictable changes in the thin-film optical interference spectrum of the biosensor. The latter is ascribed to highly specific capture of the target cells onto the biosensor surface, as confirmed by real-time polymerase chain reaction (PCR). The biosensors were capable of selectively identifying and quantifying the target cells, while the target cell concentration is orders of magnitude lower than that of other bacterial species, without any pre-enrichment or prior processing steps. PMID:27901131

Porous Silicon-Based Biosensors: Towards Real-Time Optical Detection of Target Bacteria in the Food Industry.

PubMed

Massad-Ivanir, Naama; Shtenberg, Giorgi; Raz, Nitzan; Gazenbeek, Christel; Budding, Dries; Bos, Martine P; Segal, Ester

2016-11-30

Rapid detection of target bacteria is crucial to provide a safe food supply and to prevent foodborne diseases. Herein, we present an optical biosensor for identification and quantification of Escherichia coli (E. coli, used as a model indicator bacteria species) in complex food industry process water. The biosensor is based on a nanostructured, oxidized porous silicon (PSi) thin film which is functionalized with specific antibodies against E. coli. The biosensors were exposed to water samples collected directly from process lines of fresh-cut produce and their reflectivity spectra were collected in real time. Process water were characterized by complex natural micro-flora (microbial load of >10 7  cell/mL), in addition to soil particles and plant cell debris. We show that process water spiked with culture-grown E. coli, induces robust and predictable changes in the thin-film optical interference spectrum of the biosensor. The latter is ascribed to highly specific capture of the target cells onto the biosensor surface, as confirmed by real-time polymerase chain reaction (PCR). The biosensors were capable of selectively identifying and quantifying the target cells, while the target cell concentration is orders of magnitude lower than that of other bacterial species, without any pre-enrichment or prior processing steps.

Porous Silicon-Based Biosensors: Towards Real-Time Optical Detection of Target Bacteria in the Food Industry

NASA Astrophysics Data System (ADS)

Massad-Ivanir, Naama; Shtenberg, Giorgi; Raz, Nitzan; Gazenbeek, Christel; Budding, Dries; Bos, Martine P.; Segal, Ester

2016-11-01

Rapid detection of target bacteria is crucial to provide a safe food supply and to prevent foodborne diseases. Herein, we present an optical biosensor for identification and quantification of Escherichia coli (E. coli, used as a model indicator bacteria species) in complex food industry process water. The biosensor is based on a nanostructured, oxidized porous silicon (PSi) thin film which is functionalized with specific antibodies against E. coli. The biosensors were exposed to water samples collected directly from process lines of fresh-cut produce and their reflectivity spectra were collected in real time. Process water were characterized by complex natural micro-flora (microbial load of >107 cell/mL), in addition to soil particles and plant cell debris. We show that process water spiked with culture-grown E. coli, induces robust and predictable changes in the thin-film optical interference spectrum of the biosensor. The latter is ascribed to highly specific capture of the target cells onto the biosensor surface, as confirmed by real-time polymerase chain reaction (PCR). The biosensors were capable of selectively identifying and quantifying the target cells, while the target cell concentration is orders of magnitude lower than that of other bacterial species, without any pre-enrichment or prior processing steps.

Perceptual load vs. dilution: the roles of attentional focus, stimulus category, and target predictability

PubMed Central

Chen, Zhe; Cave, Kyle R.

2013-01-01

Many studies have shown that increasing the number of neutral stimuli in a display decreases distractor interference. This result has been interpreted within two different frameworks; a perceptual load account, based on a reduction in spare resources, and a dilution account, based on a degradation in distractor representation and/or an increase in crosstalk between the distractor and the neutral stimuli that contain visually similar features. In four experiments, we systematically manipulated the extent of attentional focus, stimulus category, and preknowledge of the target to examine how these factors would interact with the display set size to influence the degree of distractor processing. Display set size did not affect the degree of distractor processing in all situations. Increasing the number of neutral items decreased distractor processing only when a task induced a broad attentional focus that included the neutral stimuli, when the neutral stimuli were in the same category as the target and distractor, and when the preknowledge of the target was insufficient to guide attention to the target efficiently. These results suggest that the effect of neutral stimuli on the degree of distractor processing is more complex than previously assumed. They provide new insight into the competitive interactions between bottom-up and top-down processes that govern the efficiency of visual selective attention. PMID:23761777

Perceptual load vs. dilution: the roles of attentional focus, stimulus category, and target predictability.

PubMed

Chen, Zhe; Cave, Kyle R

2013-01-01

Many studies have shown that increasing the number of neutral stimuli in a display decreases distractor interference. This result has been interpreted within two different frameworks; a perceptual load account, based on a reduction in spare resources, and a dilution account, based on a degradation in distractor representation and/or an increase in crosstalk between the distractor and the neutral stimuli that contain visually similar features. In four experiments, we systematically manipulated the extent of attentional focus, stimulus category, and preknowledge of the target to examine how these factors would interact with the display set size to influence the degree of distractor processing. Display set size did not affect the degree of distractor processing in all situations. Increasing the number of neutral items decreased distractor processing only when a task induced a broad attentional focus that included the neutral stimuli, when the neutral stimuli were in the same category as the target and distractor, and when the preknowledge of the target was insufficient to guide attention to the target efficiently. These results suggest that the effect of neutral stimuli on the degree of distractor processing is more complex than previously assumed. They provide new insight into the competitive interactions between bottom-up and top-down processes that govern the efficiency of visual selective attention.

Processes in the Resolution of Ambiguous Words: Towards a Model of Selective Inhibition. Cognitive Science Program, Technical Report No. 86-6.

ERIC Educational Resources Information Center

Yee, Penny L.

This study investigates the role of specific inhibitory processes in lexical ambiguity resolution. An attentional view of inhibition and a view based on specific automatic inhibition between nodes predict different results when a neutral item is processed between an ambiguous word and a related target. Subjects were 32 English speakers with normal…

Open PHACTS computational protocols for in silico target validation of cellular phenotypic screens: knowing the knowns† †The authors declare no competing interests. ‡ ‡Electronic supplementary information (ESI) available: Pipeline Pilot protocols, xls file with the output of the Pipeline Pilot protocols, KNIME workflows, and supplementary figures showing the Pipeline Pilot protocols. See DOI: 10.1039/c6md00065g Click here for additional data file.

PubMed Central

Zdrazil, B.; Neefs, J.-M.; Van Vlijmen, H.; Herhaus, C.; Caracoti, A.; Brea, J.; Roibás, B.; Loza, M. I.; Queralt-Rosinach, N.; Furlong, L. I.; Gaulton, A.; Bartek, L.; Senger, S.; Chichester, C.; Engkvist, O.; Evelo, C. T.; Franklin, N. I.; Marren, D.; Ecker, G. F.

2016-01-01

Phenotypic screening is in a renaissance phase and is expected by many academic and industry leaders to accelerate the discovery of new drugs for new biology. Given that phenotypic screening is per definition target agnostic, the emphasis of in silico and in vitro follow-up work is on the exploration of possible molecular mechanisms and efficacy targets underlying the biological processes interrogated by the phenotypic screening experiments. Herein, we present six exemplar computational protocols for the interpretation of cellular phenotypic screens based on the integration of compound, target, pathway, and disease data established by the IMI Open PHACTS project. The protocols annotate phenotypic hit lists and allow follow-up experiments and mechanistic conclusions. The annotations included are from ChEMBL, ChEBI, GO, WikiPathways and DisGeNET. Also provided are protocols which select from the IUPHAR/BPS Guide to PHARMACOLOGY interaction file selective compounds to probe potential targets and a correlation robot which systematically aims to identify an overlap of active compounds in both the phenotypic as well as any kinase assay. The protocols are applied to a phenotypic pre-lamin A/C splicing assay selected from the ChEMBL database to illustrate the process. The computational protocols make use of the Open PHACTS API and data and are built within the Pipeline Pilot and KNIME workflow tools. PMID:27774140

Method for materials deposition by ablation transfer processing

DOEpatents

Weiner, Kurt H.

1996-01-01

A method in which a thin layer of semiconducting, insulating, or metallic material is transferred by ablation from a source substrate, coated uniformly with a thin layer of said material, to a target substrate, where said material is desired, with a pulsed, high intensity, patternable beam of energy. The use of a patternable beam allows area-selective ablation from the source substrate resulting in additive deposition of the material onto the target substrate which may require a very low percentage of the area to be covered. Since material is placed only where it is required, material waste can be minimized by reusing the source substrate for depositions on multiple target substrates. Due to the use of a pulsed, high intensity energy source the target substrate remains at low temperature during the process, and thus low-temperature, low cost transparent glass or plastic can be used as the target substrate. The method can be carried out atmospheric pressures and at room temperatures, thus eliminating vacuum systems normally required in materials deposition processes. This invention has particular application in the flat panel display industry, as well as minimizing materials waste and associated costs.

In vitro evolution of chemically-modified nucleic acid aptamers: Pros and cons, and comprehensive selection strategies.

PubMed

Lipi, Farhana; Chen, Suxiang; Chakravarthy, Madhuri; Rakesh, Shilpa; Veedu, Rakesh N

2016-12-01

Nucleic acid aptamers are single-stranded DNA or RNA oligonucleotide sequences that bind to a specific target molecule with high affinity and specificity through their ability to adopt 3-dimensional structure in solution. Aptamers have huge potential as targeted therapeutics, diagnostics, delivery agents and as biosensors. However, aptamers composed of natural nucleotide monomers are quickly degraded in vivo and show poor pharmacodynamic properties. To overcome this, chemically-modified nucleic acid aptamers are developed by incorporating modified nucleotides after or during the selection process by Systematic Evolution of Ligands by EXponential enrichment (SELEX). This review will discuss the development of chemically-modified aptamers and provide the pros and cons, and new insights on in vitro aptamer selection strategies by using chemically-modified nucleic acid libraries.

In vitro evolution of chemically-modified nucleic acid aptamers: Pros and cons, and comprehensive selection strategies

PubMed Central

Chen, Suxiang; Chakravarthy, Madhuri; Rakesh, Shilpa; Veedu, Rakesh N.

2016-01-01

ABSTRACT Nucleic acid aptamers are single-stranded DNA or RNA oligonucleotide sequences that bind to a specific target molecule with high affinity and specificity through their ability to adopt 3-dimensional structure in solution. Aptamers have huge potential as targeted therapeutics, diagnostics, delivery agents and as biosensors. However, aptamers composed of natural nucleotide monomers are quickly degraded in vivo and show poor pharmacodynamic properties. To overcome this, chemically-modified nucleic acid aptamers are developed by incorporating modified nucleotides after or during the selection process by Systematic Evolution of Ligands by EXponential enrichment (SELEX). This review will discuss the development of chemically-modified aptamers and provide the pros and cons, and new insights on in vitro aptamer selection strategies by using chemically-modified nucleic acid libraries. PMID:27715478

The JCSG high-throughput structural biology pipeline.

PubMed

Elsliger, Marc André; Deacon, Ashley M; Godzik, Adam; Lesley, Scott A; Wooley, John; Wüthrich, Kurt; Wilson, Ian A

2010-10-01

The Joint Center for Structural Genomics high-throughput structural biology pipeline has delivered more than 1000 structures to the community over the past ten years. The JCSG has made a significant contribution to the overall goal of the NIH Protein Structure Initiative (PSI) of expanding structural coverage of the protein universe, as well as making substantial inroads into structural coverage of an entire organism. Targets are processed through an extensive combination of bioinformatics and biophysical analyses to efficiently characterize and optimize each target prior to selection for structure determination. The pipeline uses parallel processing methods at almost every step in the process and can adapt to a wide range of protein targets from bacterial to human. The construction, expansion and optimization of the JCSG gene-to-structure pipeline over the years have resulted in many technological and methodological advances and developments. The vast number of targets and the enormous amounts of associated data processed through the multiple stages of the experimental pipeline required the development of variety of valuable resources that, wherever feasible, have been converted to free-access web-based tools and applications.

Biasing the brain's attentional set: I. cue driven deployments of intersensory selective attention.

PubMed

Foxe, John J; Simpson, Gregory V; Ahlfors, Seppo P; Saron, Clifford D

2005-10-01

Brain activity associated with directing attention to one of two possible sensory modalities was examined using high-density mapping of human event-related potentials. The deployment of selective attention was based on visually presented symbolic cue-words instructing subjects on a trial-by-trial basis, which sensory modality to attend. We measured the spatio-temporal pattern of activation in the approximately 1 second period between the cue-instruction and a subsequent compound auditory-visual imperative stimulus. This allowed us to assess the flow of processing across brain regions involved in deploying and sustaining inter-sensory selective attention, prior to the actual selective processing of the compound audio-visual target stimulus. Activity over frontal and parietal areas showed sensory specific increases in activation during the early part of the anticipatory period (~230 ms), probably representing the activation of fronto-parietal attentional deployment systems for top-down control of attention. In the later period preceding the arrival of the "to-be-attended" stimulus, sustained differential activity was seen over fronto-central regions and parieto-occipital regions, suggesting the maintenance of sensory-specific biased attentional states that would allow for subsequent selective processing. Although there was clear sensory biasing in this late sustained period, it was also clear that both sensory systems were being prepared during the cue-target period. These late sensory-specific biasing effects were also accompanied by sustained activations over frontal cortices that also showed both common and sensory specific activation patterns, suggesting that maintenance of the biased state includes top-down inputs from generators in frontal cortices, some of which are sensory-specific regions. These data support extensive interactions between sensory, parietal and frontal regions during processing of cue information, deployment of attention, and maintenance of the focus of attention in anticipation of impending attentionally relevant input.

Priming and the guidance by visual and categorical templates in visual search.

PubMed

Wilschut, Anna; Theeuwes, Jan; Olivers, Christian N L

2014-01-01

Visual search is thought to be guided by top-down templates that are held in visual working memory. Previous studies have shown that a search-guiding template can be rapidly and strongly implemented from a visual cue, whereas templates are less effective when based on categorical cues. Direct visual priming from cue to target may underlie this difference. In two experiments we first asked observers to remember two possible target colors. A postcue then indicated which of the two would be the relevant color. The task was to locate a briefly presented and masked target of the cued color among irrelevant distractor items. Experiment 1 showed that overall search accuracy improved more rapidly on the basis of a direct visual postcue that carried the target color, compared to a neutral postcue that pointed to the memorized color. However, selectivity toward the target feature, i.e., the extent to which observers searched selectively among items of the cued vs. uncued color, was found to be relatively unaffected by the presence of the visual signal. In Experiment 2 we compared search that was based on either visual or categorical information, but now controlled for direct visual priming. This resulted in no differences in overall performance nor selectivity. Altogether the results suggest that perceptual processing of visual search targets is facilitated by priming from visual cues, whereas attentional selectivity is enhanced by a working memory template that can formed from both visual and categorical input. Furthermore, if the priming is controlled for, categorical- and visual-based templates similarly enhance search guidance.

Foveal analysis and peripheral selection during active visual sampling

PubMed Central

Ludwig, Casimir J. H.; Davies, J. Rhys; Eckstein, Miguel P.

2014-01-01

Human vision is an active process in which information is sampled during brief periods of stable fixation in between gaze shifts. Foveal analysis serves to identify the currently fixated object and has to be coordinated with a peripheral selection process of the next fixation location. Models of visual search and scene perception typically focus on the latter, without considering foveal processing requirements. We developed a dual-task noise classification technique that enables identification of the information uptake for foveal analysis and peripheral selection within a single fixation. Human observers had to use foveal vision to extract visual feature information (orientation) from different locations for a psychophysical comparison. The selection of to-be-fixated locations was guided by a different feature (luminance contrast). We inserted noise in both visual features and identified the uptake of information by looking at correlations between the noise at different points in time and behavior. Our data show that foveal analysis and peripheral selection proceeded completely in parallel. Peripheral processing stopped some time before the onset of an eye movement, but foveal analysis continued during this period. Variations in the difficulty of foveal processing did not influence the uptake of peripheral information and the efficacy of peripheral selection, suggesting that foveal analysis and peripheral selection operated independently. These results provide important theoretical constraints on how to model target selection in conjunction with foveal object identification: in parallel and independently. PMID:24385588

Toward Optimal Target Placement for Neural Prosthetic Devices

PubMed Central

Cunningham, John P.; Yu, Byron M.; Gilja, Vikash; Ryu, Stephen I.; Shenoy, Krishna V.

2008-01-01

Neural prosthetic systems have been designed to estimate continuous reach trajectories (motor prostheses) and to predict discrete reach targets (communication prostheses). In the latter case, reach targets are typically decoded from neural spiking activity during an instructed delay period before the reach begins. Such systems use targets placed in radially symmetric geometries independent of the tuning properties of the neurons available. Here we seek to automate the target placement process and increase decode accuracy in communication prostheses by selecting target locations based on the neural population at hand. Motor prostheses that incorporate intended target information could also benefit from this consideration. We present an optimal target placement algorithm that approximately maximizes decode accuracy with respect to target locations. In simulated neural spiking data fit from two monkeys, the optimal target placement algorithm yielded statistically significant improvements up to 8 and 9% for two and sixteen targets, respectively. For four and eight targets, gains were more modest, as the target layouts found by the algorithm closely resembled the canonical layouts. We trained a monkey in this paradigm and tested the algorithm with experimental neural data to confirm some of the results found in simulation. In all, the algorithm can serve not only to create new target layouts that outperform canonical layouts, but it can also confirm or help select among multiple canonical layouts. The optimal target placement algorithm developed here is the first algorithm of its kind, and it should both improve decode accuracy and help automate target placement for neural prostheses. PMID:18829845

Using Multi-Objective Genetic Programming to Synthesize Stochastic Processes

NASA Astrophysics Data System (ADS)

Ross, Brian; Imada, Janine

Genetic programming is used to automatically construct stochastic processes written in the stochastic π-calculus. Grammar-guided genetic programming constrains search to useful process algebra structures. The time-series behaviour of a target process is denoted with a suitable selection of statistical feature tests. Feature tests can permit complex process behaviours to be effectively evaluated. However, they must be selected with care, in order to accurately characterize the desired process behaviour. Multi-objective evaluation is shown to be appropriate for this application, since it permits heterogeneous statistical feature tests to reside as independent objectives. Multiple undominated solutions can be saved and evaluated after a run, for determination of those that are most appropriate. Since there can be a vast number of candidate solutions, however, strategies for filtering and analyzing this set are required.

Spatial attention can be biased towards an expected dimension.

PubMed

Burnett, Katherine E; Close, Alex C; d'Avossa, Giovanni; Sapir, Ayelet

2016-11-01

A commonly held view in both exogenous and endogenous orienting is that spatial attention is associated with enhanced processing of all stimuli at the attended location. However, we often search for a specific target at a particular location, so an observer should be able to jointly specify the target identity and expected location. Whether attention can bias dimension-specific processes at a particular location is not yet clear. We used a dual task to examine the effects of endogenous spatial cues on the accuracy of perceptual judgments of different dimensions. Participants responded to a motion target and a colour target, presented at the same or different locations. We manipulated a central cue to predict the location of the motion or colour target. While overall performance in the two tasks was comparable, cueing effects were larger for the target whose location was predicted by the cue, implying that when attending a particular location, processing of the likely dimension was preferentially enhanced. Additionally, an asymmetry between the motion and colour tasks was seen; motion was modulated by attention, and colour was not. We conclude that attention has some ability to select a dimension at a particular location, indicating integration of spatial and feature-based attention.

Combining targeted and nontargeted data analysis for liquid chromatography/high-resolution mass spectrometric analyses.

PubMed

Croley, Timothy R; White, Kevin D; Wong, Jon; Callahan, John H; Musser, Steven M; Antler, Margaret; Lashin, Vitaly; McGibbon, Graham A

2013-03-01

Increasing importation of food and the diversity of potential contaminants have necessitated more analytical testing of these foods. Historically, mass spectrometric methods for testing foods were confined to monitoring selected ions (SIM or MRM), achieving sensitivity by focusing on targeted ion signals. A limiting factor in this approach is that any contaminants not included on the target list are not typically identified and retrospective data mining is limited. A potential solution is to utilize high-resolution MS to acquire accurate mass full-scan data. Based on the instrumental resolution, these data can be correlated to the actual mass of a contaminant, which would allow for identification of both target compounds and compounds that are not on a target list (nontargets). The focus of this research was to develop software algorithms to provide rapid and accurate data processing of LC/MS data to identify both targeted and nontargeted analytes. Software from a commercial vendor was developed to process LC/MS data and the results were compared to an alternate, vendor-supplied solution. The commercial software performed well and demonstrated the potential for a fully automated processing solution. © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

More insight into the interplay of response selection and visual attention in dual-tasks: masked visual search and response selection are performed in parallel.

PubMed

Reimer, Christina B; Schubert, Torsten

2017-09-15

Both response selection and visual attention are limited in capacity. According to the central bottleneck model, the response selection processes of two tasks in a dual-task situation are performed sequentially. In conjunction search, visual attention is required to select the items and to bind their features (e.g., color and form), which results in a serial search process. Search time increases as items are added to the search display (i.e., set size effect). When the search display is masked, visual attention deployment is restricted to a brief period of time and target detection decreases as a function of set size. Here, we investigated whether response selection and visual attention (i.e., feature binding) rely on a common or on distinct capacity limitations. In four dual-task experiments, participants completed an auditory Task 1 and a conjunction search Task 2 that were presented with an experimentally modulated temporal interval between them (Stimulus Onset Asynchrony, SOA). In Experiment 1, Task 1 was a two-choice discrimination task and the conjunction search display was not masked. In Experiment 2, the response selection difficulty in Task 1 was increased to a four-choice discrimination and the search task was the same as in Experiment 1. We applied the locus-of-slack method in both experiments to analyze conjunction search time, that is, we compared the set size effects across SOAs. Similar set size effects across SOAs (i.e., additive effects of SOA and set size) would indicate sequential processing of response selection and visual attention. However, a significantly smaller set size effect at short SOA compared to long SOA (i.e., underadditive interaction of SOA and set size) would indicate parallel processing of response selection and visual attention. In both experiments, we found underadditive interactions of SOA and set size. In Experiments 3 and 4, the conjunction search display in Task 2 was masked. Task 1 was the same as in Experiments 1 and 2, respectively. In both experiments, the d' analysis revealed that response selection did not affect target detection. Overall, Experiments 1-4 indicated that neither the response selection difficulty in the auditory Task 1 (i.e., two-choice vs. four-choice) nor the type of presentation of the search display in Task 2 (i.e., not masked vs. masked) impaired parallel processing of response selection and conjunction search. We concluded that in general, response selection and visual attention (i.e., feature binding) rely on distinct capacity limitations.

tLyP-1-conjugated mesoporous silica nanoparticles for tumor targeting and penetrating hydrophobic drug delivery

NASA Astrophysics Data System (ADS)

Xu, Baiyao; Ju, Yang; Song, Guanbin; Cui, Yanbin

2013-12-01

Mesoporous silica nanoparticles (MSNs) are among the most appealing candidates for targeted drug delivery, a process for which it is essential that nanoparticles be internalized into targeted cells with high speed and efficiency. Therefore, it is necessary to conjugate a targeting ligand to the surface of a nanocarrier in order to trigger rapid receptor-mediated endocytosis and effective cellular uptake, which occurs following recognition and selective binding to a target cell's membrane receptor. Here, a tumor targeting and penetrating drug delivery system (DDS) based on MSNs ( 100 nm in size) is described. The MSNs were functionalized by engrafting with the tumor-homing and penetrating peptide tLyP-1. The fabricated MSN-tLyP-1 loaded with camptothecin (CPT) showed a robust targeting and penetrating efficiency to HeLa cells and MCF-7 cells and induced the death of these cells. Moreover, the adverse side effect of CPT on human mesenchymal stem cells (hMSCs) was minimized, because the nanoparticles were selectively targeted to the tumor cells, and little hydrophobic CPT was released into the culture medium or blood. The results indicate that the MSN-tLyP-1 DDS has great potential for the delivery of hydrophobic anticancer drugs to target tumors.

Low-Energy Collisions of Protonated Enantiopure Amino Acids with Chiral Target Gases

NASA Astrophysics Data System (ADS)

Kulyk, K.; Rebrov, O.; Ryding, M.; Thomas, R. D.; Uggerud, E.; Larsson, M.

2017-12-01

Here we report on the gas-phase interactions between protonated enantiopure amino acids ( l- and d-enantiomers of Met, Phe, and Trp) and chiral target gases [( R)- and ( S)-2-butanol, and ( S)-1-phenylethanol] in 0.1-10.0 eV low-energy collisions. Two major processes are seen to occur over this collision energy regime, collision-induced dissociation and ion-molecule complex formation. Both processes were found to be independent of the stereo-chemical composition of the interacting ions and targets. These data shed light on the currently debated mechanisms of gas-phase chiral selectivity by demonstrating the inapplicability of the three-point model to these interactions, at least under single collision conditions. [Figure not available: see fulltext.

Xenophagic pathways and their bacterial subversion in cellular self-defense - παντα ρει - everything is in flux.

PubMed

Radomski, Nadine; Rebbig, Annica; Leonhardt, Ralf M; Knittler, Michael R

2017-11-02

Autophagy is an evolutionarily ancient and highly conserved eukaryotic mechanism that targets cytoplasmic material for degradation. Autophagic flux involves the formation of autophagosomes and their degradation by lysosomes. The process plays a crucial role in maintaining cellular homeostasis and responds to various environmental conditions. While autophagy had previously been thought to be a non-selective process, it is now clear that it can also selectively target cellular organelles, such as mitochondria (referred to as mitophagy) and/or invading pathogens (referred to as xenophagy). Selective autophagy is characterized by specific substrate recognition and requires distinct cellular adaptor proteins. Here we review xenophagic mechanisms involved in the recognition and autolysosomal or autophagolysosomal degradation of different intracellular bacteria. In this context, we also discuss a recently discovered cellular self-defense pathway, termed mito-xenophagy, which occurs during bacterial infection of dendritic cells and depends on a TNF-α-mediated metabolic switch from oxidative phosphorylation to glycolysis. Copyright © 2017 Elsevier GmbH. All rights reserved.

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

NASA Astrophysics Data System (ADS)

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.

A trait stacking system via intra-genomic homologous recombination.

PubMed

Kumar, Sandeep; Worden, Andrew; Novak, Stephen; Lee, Ryan; Petolino, Joseph F

2016-11-01

A gene targeting method has been developed, which allows the conversion of 'breeding stacks', containing unlinked transgenes into a 'molecular stack' and thereby circumventing the breeding challenges associated with transgene segregation. A gene targeting method has been developed for converting two unlinked trait loci into a single locus transgene stack. The method utilizes intra-genomic homologous recombination (IGHR) between stably integrated target and donor loci which share sequence homology and nuclease cleavage sites whereby the donor contains a promoterless herbicide resistance transgene. Upon crossing with a zinc finger nuclease (ZFN)-expressing plant, double-strand breaks (DSB) are created in both the stably integrated target and donor loci. DSBs flanking the donor locus result in intra-genomic mobilization of a promoterless selectable marker-containing donor sequence, which can be utilized as a template for homology-directed repair of a concomitant DSB at the target locus resulting in a functional selectable marker via nuclease-mediated cassette exchange (NMCE). The method was successfully demonstrated in maize using a glyphosate tolerance gene as a donor whereby up to 3.3 % of the resulting progeny embryos cultured on selection medium regenerated plants with the donor sequence integrated into the target locus. The process could be extended to multiple cycles of trait stacking by virtue of a unique intron sequence homology for NMCE between the target and the donor loci. This is the first report that describes NMCE via IGHR, thereby enabling trait stacking using conventional crossing.

Effects of paired-object affordance in search tasks across the adult lifespan.

PubMed

Wulff, Melanie; Stainton, Alexandra; Rotshtein, Pia

2016-06-01

The study investigated the processes underlying the retrieval of action information about functional object pairs, focusing on the contribution of procedural and semantic knowledge. We further assessed whether the retrieval of action knowledge is affected by task demands and age. The contribution of procedural knowledge was examined by the way objects were selected, specifically whether active objects were selected before passive objects. The contribution of semantic knowledge was examined by manipulating the relation between targets and distracters. A touchscreen-based search task was used testing young, middle-aged, and elderly participants. Participants had to select by touching two targets among distracters using two search tasks. In an explicit action search task, participants had to select two objects which afforded a mutual action (e.g., functional pair: hammer-nail). Implicit affordance perception was tested using a visual color-matching search task; participants had to select two objects with the same colored frame. In both tasks, half of the colored targets also afforded an action. Overall, middle-aged participants performed better than young and elderly participants, specifically in the action task. Across participants in the action task, accuracy was increased when the distracters were semantically unrelated to the functional pair, while the opposite pattern was observed in the color task. This effect was enhanced with increased age. In the action task all participants utilized procedural knowledge, i.e., selected the active object before the passive object. This result supports the dual-route account from vision to action. Semantic knowledge contributed to both the action and the color task, but procedural knowledge associated with the direct route was primarily retrieved when the task was action-relevant. Across the adulthood lifespan, the data show inverted U-shaped effects of age on the retrieval of action knowledge. Age also linearly increased the involvement of the indirect (semantic) route and the integration of information of the direct and the indirect routes in selection processes. Copyright © 2016 Elsevier Inc. All rights reserved.

Reduced auditory processing capacity during vocalization in children with Selective Mutism.

PubMed

Arie, Miri; Henkin, Yael; Lamy, Dominique; Tetin-Schneider, Simona; Apter, Alan; Sadeh, Avi; Bar-Haim, Yair

2007-02-01

Because abnormal Auditory Efferent Activity (AEA) is associated with auditory distortions during vocalization, we tested whether auditory processing is impaired during vocalization in children with Selective Mutism (SM). Participants were children with SM and abnormal AEA, children with SM and normal AEA, and normally speaking controls, who had to detect aurally presented target words embedded within word lists under two conditions: silence (single task), and while vocalizing (dual task). To ascertain specificity of auditory-vocal deficit, effects of concurrent vocalizing were also examined during a visual task. Children with SM and abnormal AEA showed impaired auditory processing during vocalization relative to children with SM and normal AEA, and relative to control children. This impairment is specific to the auditory modality and does not reflect difficulties in dual task per se. The data extends previous findings suggesting that deficient auditory processing is involved in speech selectivity in SM.

Out of control little-used clinical assets are draining healthcare budgets.

PubMed

Horblyuk, Ruslan; Kaneta, Kristopher; McMillen, Gary L; Mullins, Christopher; O'Brien, Thomas M; Roy, Ankita

2012-07-01

To improve utilization and reduce the cost of maintaining mobile clinical equipment, healthcare organization leaders should do the following: Select an initial asset group to target. Conduct a physical inventory. Evaluate the organization's asset "ecosystem." Optimize workflow processes. Phase in new processes, and phase out inventory. Devote time to change management. Develop a replacement strategy.

Writing for publication Part II--The writing process.

PubMed

Clarke, L K

1999-01-01

You have selected a topic, gathered resources, and identified your target audience. The next step is to begin to write and organize your ideas. Initiating the actual writing process can be intimidating, especially for a novice author. This portion of the writing for publication series focuses on helping the writer to organize ideas and get started.

Selective mitochondrial autophagy, or mitophagy, as a targeted defense against oxidative stress, mitochondrial dysfunction, and aging.

PubMed

Lemasters, John J

2005-01-01

In autophagy, portions of cytoplasm are sequestered into autophagosomes and delivered to lysosomes for degradation. Long assumed to be a random process, increasing evidence suggests that autophagy of mitochondria, peroxisomes, and possibly other organelles is selective. A recent paper (Kissova et al., J. Biol. Chem. 2004;279:39068-39074) shows in yeast that a specific outer membrane protein, Uth1p, is required for efficient mitochondrial autophagy. For this selective autophagy of mitochondria, we propose the term "mitophagy" to emphasize the non-random nature of the process. Mitophagy may play a key role in retarding accumulation of somatic mutations of mtDNA with aging.

Mechanistic systems modeling to guide drug discovery and development

PubMed Central

Schmidt, Brian J.; Papin, Jason A.; Musante, Cynthia J.

2013-01-01

A crucial question that must be addressed in the drug development process is whether the proposed therapeutic target will yield the desired effect in the clinical population. Pharmaceutical and biotechnology companies place a large investment on research and development, long before confirmatory data are available from human trials. Basic science has greatly expanded the computable knowledge of disease processes, both through the generation of large omics data sets and a compendium of studies assessing cellular and systemic responses to physiologic and pathophysiologic stimuli. Given inherent uncertainties in drug development, mechanistic systems models can better inform target selection and the decision process for advancing compounds through preclinical and clinical research. PMID:22999913

Mechanistic systems modeling to guide drug discovery and development.

PubMed

Schmidt, Brian J; Papin, Jason A; Musante, Cynthia J

2013-02-01

A crucial question that must be addressed in the drug development process is whether the proposed therapeutic target will yield the desired effect in the clinical population. Pharmaceutical and biotechnology companies place a large investment on research and development, long before confirmatory data are available from human trials. Basic science has greatly expanded the computable knowledge of disease processes, both through the generation of large omics data sets and a compendium of studies assessing cellular and systemic responses to physiologic and pathophysiologic stimuli. Given inherent uncertainties in drug development, mechanistic systems models can better inform target selection and the decision process for advancing compounds through preclinical and clinical research. Copyright © 2012 Elsevier Ltd. All rights reserved.

Mariner-Venus-Mercury optical navigation demonstration - Results and implications for future missions

NASA Technical Reports Server (NTRS)

Acton, C. H., Jr.; Ohtakay, H.

1975-01-01

Optical navigation uses spacecraft television pictures of a target body against a known star background in a process which relates the spacecraft trajectory to the target body. This technology was used in the Mariner-Venus-Mercury mission, with the optical data processed in near-real-time, simulating a mission critical environment. Optical data error sources were identified, and a star location error analysis was carried out. Several methods for selecting limb crossing coordinates were used, and a limb smear compensation was introduced. Omission of planetary aberration corrections was the source of large optical residuals.

Rapid top-down control over template-guided attention shifts to multiple objects.

PubMed

Grubert, Anna; Fahrenfort, Johannes; Olivers, Christian N L; Eimer, Martin

2017-02-01

Previous research has shown that when observers search for targets defined by a particular colour, attention can be directed rapidly and independently to two target objects that appear in close temporal proximity. We investigated how such rapid attention shifts are modulated by task instructions to selectively attend versus ignore one of these objects. Two search displays that both contained a colour-defined target and a distractor in a different colour were presented in rapid succession, with a stimulus onset asynchrony (SOA) of 100ms. In different blocks, participants were instructed to attend and respond to target-colour objects in the first display and to ignore these objects in the second display, or vice versa. N2pc components were measured to track the allocation of spatial attention to target-colour objects in these two displays. When participants responded to the second display, irrelevant target-colour objects in the first display still triggered N2pc components, demonstrating task-set contingent attentional capture while a feature-specific target template is active. Critically, when participants responded to the first display instead, no N2pc was elicited by target-colour items in the second display, indicating that they no longer rapidly captured attention. However, these items still elicited a longer-latency contralateral negativity (SPCN component), suggesting that attention was oriented towards template-matching objects in working memory. This dissociation between N2pc and SPCN components shows that rapid attentional capture and subsequent attentional selection processes within working memory can be independent. We suggest that early attentional orienting mechanisms can be inhibited when task-set matching objects are no longer task-relevant, and that this type of inhibitory control is a rapid but transient process. Copyright © 2016 Elsevier Inc. All rights reserved.

Influence of aging on human sound localization

PubMed Central

Dobreva, Marina S.; O'Neill, William E.

2011-01-01

Errors in sound localization, associated with age-related changes in peripheral and central auditory function, can pose threats to self and others in a commonly encountered environment such as a busy traffic intersection. This study aimed to quantify the accuracy and precision (repeatability) of free-field human sound localization as a function of advancing age. Head-fixed young, middle-aged, and elderly listeners localized band-passed targets using visually guided manual laser pointing in a darkened room. Targets were presented in the frontal field by a robotically controlled loudspeaker assembly hidden behind a screen. Broadband targets (0.1–20 kHz) activated all auditory spatial channels, whereas low-pass and high-pass targets selectively isolated interaural time and intensity difference cues (ITDs and IIDs) for azimuth and high-frequency spectral cues for elevation. In addition, to assess the upper frequency limit of ITD utilization across age groups more thoroughly, narrowband targets were presented at 250-Hz intervals from 250 Hz up to ∼2 kHz. Young subjects generally showed horizontal overestimation (overshoot) and vertical underestimation (undershoot) of auditory target location, and this effect varied with frequency band. Accuracy and/or precision worsened in older individuals for broadband, high-pass, and low-pass targets, reflective of peripheral but also central auditory aging. In addition, compared with young adults, middle-aged, and elderly listeners showed pronounced horizontal localization deficiencies (imprecision) for narrowband targets within 1,250–1,575 Hz, congruent with age-related central decline in auditory temporal processing. Findings underscore the distinct neural processing of the auditory spatial cues in sound localization and their selective deterioration with advancing age. PMID:21368004

How Teacher Selection Practices in a High-Resource, Low-Need Suburban School District Compare with Best Practice Research: A Case Study

ERIC Educational Resources Information Center

Pease, Adam Steven

2012-01-01

The purpose of this study was to develop best practice standards for hiring public school teachers. This standard was developed from the available literature on recruiting, screening, selecting, and hiring high-quality teachers. The targeted and actual hiring processes of a case study district were compared to this teacher hiring standard.…

Perseveration in Tool Use: A Window for Understanding the Dynamics of the Action-Selection Process

ERIC Educational Resources Information Center

Smitsman, Ad W.; Cox, Ralf F. A.

2008-01-01

Two experiments investigated how 3-year-old children select a tool to perform a manual task, with a focus on their perseverative parameter choices for the various relationships involved in handling a tool: the actor-to-tool relation and the tool-to-target relation (topology). The first study concerned the parameter value for the tool-to-target…

Quasi Real Time Data Analysis for Air Quality Monitoring with an Electronic Nose

NASA Technical Reports Server (NTRS)

Zhou, Hanying; Shevade, Abhijit V.; Pelletier, Christine C.; Homer, Margie L.; Ryan, M. Amy

2006-01-01

Cabin Air Quality Monitoring: A) Functions; 1) Incident monitor for targeted contaminants exceeding targeted concentrations. Identify and quantify. 2) Monitor for presence of compounds associated with fires or overheating electronics. 3) Monitor clean-up process. B) Characteristics; 1) Low mass, low power device. 2) Requires little crew time for maintenance and calibration. 3) Detects, identifies and quantifies selected chemical species at or below 24 hour SMAC.

The effects of anterior arcuate and dorsomedial frontal cortex lesions on visually guided eye movements: 2. Paired and multiple targets.

PubMed

Schiller, P H; Chou, I

2000-01-01

This study examined the effects of anterior arcuate and dorsomedial frontal cortex lesions on the execution of saccadic eye movements made to paired and multiple targets in rhesus monkeys. Identical paired targets were presented with various temporal asynchronies to determine the temporal offset required to yield equal probability choices to either target. In the intact animal equal probability choices were typically obtained when the targets appeared simultaneously. After unilateral anterior arcuate lesions a major shift arose in the temporal offset required to obtain equal probability choices for paired targets that necessitated presenting the target in the hemifield contralateral to the lesion more than 100 ms prior to the target in the ipsilateral hemifield. This deficit was still pronounced 1 year after the lesion. Dorsomedial frontal cortex lesions produced much smaller but significant shifts in target selection that recovered more rapidly. Paired lesions produced deficits similar to those observed with anterior arcuate lesions alone. Major deficits were also observed on a multiple target temporal discrimination task after anterior arcuate but not after dorsomedial frontal cortex lesions. These results suggest that the frontal eye fields that reside in anterior bank of the arcuate sulcus play an important role in temporal processing and in target selection. Dorsomedial frontal cortex, that contains the medial eye fields, plays a much less important role in the execution of these tasks.

Idiosyncratic representation of peripersonal space depends on the success of one's own motor actions, but also the successful actions of others!

PubMed Central

Quesque, François; Gigliotti, Maria-Francesca; Ott, Laurent; Bruyelle, Jean-Luc

2018-01-01

Peripersonal space is a multisensory representation of the environment around the body in relation to the motor system, underlying the interactions with the physical and social world. Although changing body properties and social context have been shown to alter the functional processing of space, little is known about how changing the value of objects influences the representation of peripersonal space. In two experiments, we tested the effect of modifying the spatial distribution of reward-yielding targets on manual reaching actions and peripersonal space representation. Before and after performing a target-selection task consisting of manually selecting a set of targets on a touch-screen table, participants performed a two-alternative forced-choice reachability-judgment task. In the target-selection task, half of the targets were associated with a reward (change of colour from grey to green, providing 1 point), the other half being associated with no reward (change of colour from grey to red, providing no point). In Experiment 1, the target-selection task was performed individually with the aim of maximizing the point count, and the distribution of the reward-yielding targets was either 50%, 25% or 75% in the proximal and distal spaces. In Experiment 2, the target-selection task was performed in a social context involving cooperation between two participants to maximize the point count, and the distribution of the reward-yielding targets was 50% in the proximal and distal spaces. Results showed that changing the distribution of the reward-yielding targets or introducing the social context modified concurrently the amplitude of self-generated manual reaching actions and the representation of peripersonal space. Moreover, a decrease of the amplitude of manual reaching actions caused a reduction of peripersonal space when resulting from the distribution of reward-yielding targets, while this effect was not observed in a social interaction context. In that case, the decreased amplitude of manual reaching actions was accompanied by an increase of peripersonal space representation, which was not due to the mere presence of a confederate (control experiment). We conclude that reward-dependent modulation of objects values in the environment modifies the representation of peripersonal space, when resulting from either self-generated motor actions or observation of motor actions performed by a confederate. PMID:29771982

Idiosyncratic representation of peripersonal space depends on the success of one's own motor actions, but also the successful actions of others!

PubMed

Coello, Yann; Quesque, François; Gigliotti, Maria-Francesca; Ott, Laurent; Bruyelle, Jean-Luc

2018-01-01

Peripersonal space is a multisensory representation of the environment around the body in relation to the motor system, underlying the interactions with the physical and social world. Although changing body properties and social context have been shown to alter the functional processing of space, little is known about how changing the value of objects influences the representation of peripersonal space. In two experiments, we tested the effect of modifying the spatial distribution of reward-yielding targets on manual reaching actions and peripersonal space representation. Before and after performing a target-selection task consisting of manually selecting a set of targets on a touch-screen table, participants performed a two-alternative forced-choice reachability-judgment task. In the target-selection task, half of the targets were associated with a reward (change of colour from grey to green, providing 1 point), the other half being associated with no reward (change of colour from grey to red, providing no point). In Experiment 1, the target-selection task was performed individually with the aim of maximizing the point count, and the distribution of the reward-yielding targets was either 50%, 25% or 75% in the proximal and distal spaces. In Experiment 2, the target-selection task was performed in a social context involving cooperation between two participants to maximize the point count, and the distribution of the reward-yielding targets was 50% in the proximal and distal spaces. Results showed that changing the distribution of the reward-yielding targets or introducing the social context modified concurrently the amplitude of self-generated manual reaching actions and the representation of peripersonal space. Moreover, a decrease of the amplitude of manual reaching actions caused a reduction of peripersonal space when resulting from the distribution of reward-yielding targets, while this effect was not observed in a social interaction context. In that case, the decreased amplitude of manual reaching actions was accompanied by an increase of peripersonal space representation, which was not due to the mere presence of a confederate (control experiment). We conclude that reward-dependent modulation of objects values in the environment modifies the representation of peripersonal space, when resulting from either self-generated motor actions or observation of motor actions performed by a confederate.

The Impact of a Targeted Training Program on E-Mail System Processing Capabilities and Self-Perception of E-Mail Overload

ERIC Educational Resources Information Center

Einstein, Michael M.

2014-01-01

As business e-mail volumes continue to grow and employees spend increasingly larger portions of their day processing e-mail, there is strong evidence of the negative impacts of e-mail processing, especially with respect to e-mail overload. This study sought to determine whether a training program focused on select e-mail features and processing…

New Transgenic Mouse Lines for Selectively Targeting Astrocytes and Studying Calcium Signals in Astrocyte Processes In Situ and In Vivo.

PubMed

Srinivasan, Rahul; Lu, Tsai-Yi; Chai, Hua; Xu, Ji; Huang, Ben S; Golshani, Peyman; Coppola, Giovanni; Khakh, Baljit S

2016-12-21

Astrocytes exist throughout the nervous system and are proposed to affect neural circuits and behavior. However, studying astrocytes has proven difficult because of the lack of tools permitting astrocyte-selective genetic manipulations. Here, we report the generation of Aldh1l1-Cre/ERT2 transgenic mice to selectively target astrocytes in vivo. We characterized Aldh1l1-Cre/ERT2 mice using imaging, immunohistochemistry, AAV-FLEX-GFP microinjections, and crosses to RiboTag, Ai95, and new Cre-dependent membrane-tethered Lck-GCaMP6f knockin mice that we also generated. Two to three weeks after tamoxifen induction, Aldh1l1-Cre/ERT2 selectively targeted essentially all adult (P80) brain astrocytes with no detectable neuronal contamination, resulting in expression of cytosolic and Lck-GCaMP6f, and permitting subcellular astrocyte calcium imaging during startle responses in vivo. Crosses with RiboTag mice allowed sequencing of actively translated mRNAs and determination of the adult cortical astrocyte transcriptome. Thus, we provide well-characterized, easy-to-use resources with which to selectively study astrocytes in situ and in vivo in multiple experimental scenarios. Copyright © 2016 Elsevier Inc. All rights reserved.

Sentence processing selectivity in Broca's area: evident for structure but not syntactic movement.

PubMed

Rogalsky, Corianne; Almeida, Diogo; Sprouse, Jon; Hickok, Gregory

The role of Broca's area in sentence processing is hotly debated. Prominent hypotheses include that Broca's area supports sentence comprehension via syntax-specific processes ("syntactic movement" in particular), hierarchical structure building or working memory. In the present fMRI study we adopt a within subject, across task approach using targeted sentence-level contrasts and non-sentential comparison tasks to address these hypotheses regarding the role of Broca's area in sentence processing. For clarity, we have presented findings as three experiments: (i) Experiment 1 examines selectivity for a particular type of sentence construction, namely those containing syntactic movement. Standard syntactic movement distance effects in Broca's area were replicated but no difference was found between movement and non-movement sentences in Broca's area at the group level or consistently in individual subjects. (ii) Experiment 2 examines selectivity for sentences versus non-sentences, to assess claims regarding the role of Broca's area in hierarchical structure building. Group and individual results differ, but both identify subregions of Broca's area that are selective for sentence structure. (iii) Experiment 3 assesses whether activations in Broca's area are selective for sentences when contrasted with simple subvocal articulation. Group results suggest shared resources for sentence processing and articulation in Broca's area, but individual subject analyses contradict this finding. We conclude that Broca's area is not selectively involved in processing syntactic movement, but that subregions are selectively responsive to sentence structure. Our findings also reinforce Fedorenko & Kanwishser's call for the use of more individual subject analyses in functional imaging studies of sentence processing in Broca's area, as group findings can obscure selective response patterns.

Distinct Escape Pathway by Hepatitis C Virus Genotype 1a from a Dominant CD8+ T Cell Response by Selection of Altered Epitope Processing.

PubMed

Walker, Andreas; Skibbe, Kathrin; Steinmann, Eike; Pfaender, Stephanie; Kuntzen, Thomas; Megger, Dominik A; Groten, Svenja; Sitek, Barbara; Lauer, Georg M; Kim, Arthur Y; Pietschmann, Thomas; Allen, Todd M; Timm, Joerg

2016-01-01

Antiviral CD8(+) T cells are a key component of the adaptive immune response against HCV, but their impact on viral control is influenced by preexisting viral variants in important target epitopes and the development of viral escape mutations. Immunodominant epitopes highly conserved across genotypes therefore are attractive for T cell based prophylactic vaccines. Here, we characterized the CD8(+) T cell response against the highly conserved HLA-B*51-restricted epitope IPFYGKAI1373-1380 located in the helicase domain of NS3 in people who inject drugs (PWID) exposed predominantly to HCV genotypes 1a and 3a. Despite this epitope being conserved in both genotypes, the corresponding CD8(+) T cell response was detected only in PWID infected with genotype 3a and HCV-RNA negative PWID, but not in PWID infected with genotype 1a. In genotype 3a, the detection of strong CD8(+) T cell responses was associated with epitope variants in the autologous virus consistent with immune escape. Analysis of viral sequences from multiple cohorts confirmed HLA-B*51-associated escape mutations inside the epitope in genotype 3a, but not in genotype 1a. Here, a distinct substitution in the N-terminal flanking region located 5 residues upstream of the epitope (S1368P; P = 0.00002) was selected in HLA-B*51-positive individuals. Functional assays revealed that the S1368P substitution impaired recognition of target cells presenting the endogenously processed epitope. The results highlight that, despite an epitope being highly conserved between two genotypes, there are major differences in the selected viral escape pathways and the corresponding T cell responses. HCV is able to evolutionary adapt to CD8(+) T cell immune pressure in multiple ways. Beyond selection of mutations inside targeted epitopes, this study demonstrates that HCV inhibits epitope processing by modification of the epitope flanking region under T cell immune pressure. Selection of a substitution five amino acids upstream of the epitope underlines that efficient antigen presentation strongly depends on its larger sequence context and that blocking of the multistep process of antigen processing by mutation is exploited also by HCV. The pathways to mutational escape of HCV are to some extent predictable but are distinct in different genotypes. Importantly, the selected escape pathway of HCV may have consequences for the destiny of antigen-specific CD8(+) T cells. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

Deep Search for Satellites Around the Lucy Mission Targets

NASA Astrophysics Data System (ADS)

Noll, Keith

2017-08-01

By performing the first deep search for Trojan satellites with HST we will obtain unique constraints on satellite-forming processes in this population. We have selected the targets from NASA's Lucy mission because they represent a taxonomically and physically diverse set of targets that allow intercomparisons from a small survey. Also, by searching now to identify any orbiting material around the Lucy targets, it will be possible impact hardware decisions and plan for maximum scientific return from the mission. This search also is a necessary step to assure mission safety as the Lucy spacecraft will fly within 1000 km of the targets, well within the region where stable orbits can exist.

Clear & Simple

MedlinePlus

... page factsheet, a 10-page booklet, or a series of short factsheets delivered at different points in the learning process. Budget and target audience information help shape decisions about the length and scope of the product. Design questions include photo and graphics selection, layout and ...

Four Finalist Landing Site Candidates for Mars Science Laboratory

NASA Image and Video Library

2008-11-19

Out of more than 30 sites considered as possible landing targets for NASA Mars Science Laboratory mission, by November 2008 four of the most intriguing places on Mars rose to the final round of the site-selection process.

Top-down dimensional weight set determines the capture of visual attention: evidence from the PCN component.

PubMed

Töllner, Thomas; Müller, Hermann J; Zehetleitner, Michael

2012-07-01

Visual search for feature singletons is slowed when a task-irrelevant, but more salient distracter singleton is concurrently presented. While there is a consensus that this distracter interference effect can be influenced by internal system settings, it remains controversial at what stage of processing this influence starts to affect visual coding. Advocates of the "stimulus-driven" view maintain that the initial sweep of visual processing is entirely driven by physical stimulus attributes and that top-down settings can bias visual processing only after selection of the most salient item. By contrast, opponents argue that top-down expectancies can alter the initial selection priority, so that focal attention is "not automatically" shifted to the location exhibiting the highest feature contrast. To precisely trace the allocation of focal attention, we analyzed the Posterior-Contralateral-Negativity (PCN) in a task in which the likelihood (expectancy) with which a distracter occurred was systematically varied. Our results show that both high (vs. low) distracter expectancy and experiencing a distracter on the previous trial speed up the timing of the target-elicited PCN. Importantly, there was no distracter-elicited PCN, indicating that participants did not shift attention to the distracter before selecting the target. This pattern unambiguously demonstrates that preattentive vision is top-down modifiable.

Photostick: a method for selective isolation of target cells from culture† †Electronic supplementary information (ESI) available. See DOI: 10.1039/c4sc03676j Click here for additional data file.

PubMed Central

Chien, Miao-Ping; Werley, Christopher A.; Farhi, Samouil L.

2015-01-01

Sorting of target cells from a heterogeneous pool is technically difficult when the selection criterion is complex, e.g. a dynamic response, a morphological feature, or a combination of multiple parameters. At present, mammalian cell selections are typically performed either via static fluorescence (e.g. fluorescence activated cell sorter), via survival (e.g. antibiotic resistance), or via serial operations (flow cytometry, laser capture microdissection). Here we present a simple protocol for selecting cells based on any static or dynamic property that can be identified by video microscopy and image processing. The “photostick” technique uses a cell-impermeant photochemical crosslinker and digital micromirror array-based patterned illumination to immobilize selected cells on the culture dish. Other cells are washed away with mild protease treatment. The crosslinker also labels the selected cells with a fluorescent dye and a biotin for later identification. The photostick protocol preserves cell viability, permits genetic profiling of selected cells, and can be performed with complex functional selection criteria such as neuronal firing patterns. PMID:25705368

Selective elimination of long INterspersed element-1 expressing tumour cells by targeted expression of the HSV-TK suicide gene

PubMed Central

Chendeb, Mariam; Schneider, Robert; Davidson, Irwin; Fadloun, Anas

2017-01-01

In gene therapy, effective and selective suicide gene expression is crucial. We exploited the endogenous Long INterspersed Element-1 (L1) machinery often reactivated in human cancers to integrate the Herpes Simplex Virus Thymidine Kinase (HSV-TK) suicide gene selectively into the genome of cancer cells. We developed a plasmid-based system directing HSV-TK expression only when reverse transcribed and integrated in the host genome via the endogenous L1 ORF1/2 proteins and an Alu element. Delivery of these new constructs into cells followed by Ganciclovir (GCV) treatment selectively induced mortality of L1 ORF1/2 protein expressing cancer cells, but had no effect on primary cells that do not express L1 ORF1/2. This novel strategy for selective targeting of tumour cells provides high tolerability as the HSV-TK gene cannot be expressed without reverse transcription and integration, and high selectivity as these processes take place only in cancer cells expressing high levels of functional L1 ORF1/2. PMID:28415677

Surrogate species selection for assessing potential adverse environmental impacts of genetically engineered insect-resistant plants on non-target organisms.

PubMed

Carstens, Keri; Cayabyab, Bonifacio; De Schrijver, Adinda; Gadaleta, Patricia G; Hellmich, Richard L; Romeis, Jörg; Storer, Nicholas; Valicente, Fernando H; Wach, Michael

2014-01-01

Most regulatory authorities require that developers of genetically engineered insect-resistant (GEIR) crops evaluate the potential for these crops to have adverse impacts on valued non-target organisms (NTOs), i.e., organisms not intended to be controlled by the trait. In many cases, impacts to NTOs are assessed using surrogate species, and it is critical that the data derived from surrogates accurately predict any adverse impacts likely to be observed from the use of the crop in the agricultural context. The key is to select surrogate species that best represent the valued NTOs in the location where the crop is going to be introduced, but this selection process poses numerous challenges for the developers of GE crops who will perform the tests, as well as for the ecologists and regulators who will interpret the test results. These issues were the subject of a conference "Surrogate Species Selection for Assessing Potential Adverse Environmental Impacts of Genetically Engineered Plants on Non-Target Organisms" convened by the Center for Environmental Risk Assessment, ILSI Research Foundation. This report summarizes the proceedings of the conference, including the presentations, discussions and the points of consensus agreed to by the participants.

3D Visual Tracking of an Articulated Robot in Precision Automated Tasks

PubMed Central

Alzarok, Hamza; Fletcher, Simon; Longstaff, Andrew P.

2017-01-01

The most compelling requirements for visual tracking systems are a high detection accuracy and an adequate processing speed. However, the combination between the two requirements in real world applications is very challenging due to the fact that more accurate tracking tasks often require longer processing times, while quicker responses for the tracking system are more prone to errors, therefore a trade-off between accuracy and speed, and vice versa is required. This paper aims to achieve the two requirements together by implementing an accurate and time efficient tracking system. In this paper, an eye-to-hand visual system that has the ability to automatically track a moving target is introduced. An enhanced Circular Hough Transform (CHT) is employed for estimating the trajectory of a spherical target in three dimensions, the colour feature of the target was carefully selected by using a new colour selection process, the process relies on the use of a colour segmentation method (Delta E) with the CHT algorithm for finding the proper colour of the tracked target, the target was attached to the six degree of freedom (DOF) robot end-effector that performs a pick-and-place task. A cooperation of two Eye-to Hand cameras with their image Averaging filters are used for obtaining clear and steady images. This paper also examines a new technique for generating and controlling the observation search window in order to increase the computational speed of the tracking system, the techniques is named Controllable Region of interest based on Circular Hough Transform (CRCHT). Moreover, a new mathematical formula is introduced for updating the depth information of the vision system during the object tracking process. For more reliable and accurate tracking, a simplex optimization technique was employed for the calculation of the parameters for camera to robotic transformation matrix. The results obtained show the applicability of the proposed approach to track the moving robot with an overall tracking error of 0.25 mm. Also, the effectiveness of CRCHT technique in saving up to 60% of the overall time required for image processing. PMID:28067860

Structure-Based Virtual Screening for Drug Discovery: Principles, Applications and Recent Advances

PubMed Central

Lionta, Evanthia; Spyrou, George; Vassilatis, Demetrios K.; Cournia, Zoe

2014-01-01

Structure-based drug discovery (SBDD) is becoming an essential tool in assisting fast and cost-efficient lead discovery and optimization. The application of rational, structure-based drug design is proven to be more efficient than the traditional way of drug discovery since it aims to understand the molecular basis of a disease and utilizes the knowledge of the three-dimensional structure of the biological target in the process. In this review, we focus on the principles and applications of Virtual Screening (VS) within the context of SBDD and examine different procedures ranging from the initial stages of the process that include receptor and library pre-processing, to docking, scoring and post-processing of topscoring hits. Recent improvements in structure-based virtual screening (SBVS) efficiency through ensemble docking, induced fit and consensus docking are also discussed. The review highlights advances in the field within the framework of several success studies that have led to nM inhibition directly from VS and provides recent trends in library design as well as discusses limitations of the method. Applications of SBVS in the design of substrates for engineered proteins that enable the discovery of new metabolic and signal transduction pathways and the design of inhibitors of multifunctional proteins are also reviewed. Finally, we contribute two promising VS protocols recently developed by us that aim to increase inhibitor selectivity. In the first protocol, we describe the discovery of micromolar inhibitors through SBVS designed to inhibit the mutant H1047R PI3Kα kinase. Second, we discuss a strategy for the identification of selective binders for the RXRα nuclear receptor. In this protocol, a set of target structures is constructed for ensemble docking based on binding site shape characterization and clustering, aiming to enhance the hit rate of selective inhibitors for the desired protein target through the SBVS process. PMID:25262799

Differential Brain Activation to Angry Faces by Elite Warfighters: Neural Processing Evidence for Enhanced Threat Detection

PubMed Central

Paulus, Martin P.; Simmons, Alan N.; Fitzpatrick, Summer N.; Potterat, Eric G.; Van Orden, Karl F.; Bauman, James; Swain, Judith L.

2010-01-01

Background Little is known about the neural basis of elite performers and their optimal performance in extreme environments. The purpose of this study was to examine brain processing differences between elite warfighters and comparison subjects in brain structures that are important for emotion processing and interoception. Methodology/Principal Findings Navy Sea, Air, and Land Forces (SEALs) while off duty (n = 11) were compared with n = 23 healthy male volunteers while performing a simple emotion face-processing task during functional magnetic resonance imaging. Irrespective of the target emotion, elite warfighters relative to comparison subjects showed relatively greater right-sided insula, but attenuated left-sided insula, activation. Navy SEALs showed selectively greater activation to angry target faces relative to fearful or happy target faces bilaterally in the insula. This was not accounted for by contrasting positive versus negative emotions. Finally, these individuals also showed slower response latencies to fearful and happy target faces than did comparison subjects. Conclusions/Significance These findings support the hypothesis that elite warfighters deploy greater processing resources toward potential threat-related facial expressions and reduced processing resources to non-threat-related facial expressions. Moreover, rather than expending more effort in general, elite warfighters show more focused neural and performance tuning. In other words, greater neural processing resources are directed toward threat stimuli and processing resources are conserved when facing a nonthreat stimulus situation. PMID:20418943

Inaugural Maximum Values for Sodium in Processed Food Products in the Americas.

PubMed

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

2015-08-01

Reducing dietary salt/sodium is one of the most cost-effective interventions to improve population health. There are five initiatives in the Americas that independently developed targets for reformulating foods to reduce salt/sodium content. Applying selection criteria, recommended by the Pan American Health Organization (PAHO)/World Health Organization (WHO) Technical Advisory Group on Dietary Salt/Sodium Reduction, a consortium of governments, civil society, and food companies (the Salt Smart Consortium) agreed to an inaugural set of regional maximum targets (upper limits) for salt/sodium levels for 11 food categories, to be achieved by December 2016. Ultimately, to substantively reduce dietary salt across whole populations, targets will be needed for the majority of processed and pre-prepared foods. Cardiovascular and hypertension organizations are encouraged to utilize the regional targets in advocacy and in monitoring and evaluation of progress by the food industry. © 2015 Wiley Periodicals, Inc.

Transient Distraction and Attentional Control during a Sustained Selective Attention Task.

PubMed

Demeter, Elise; Woldorff, Marty G

2016-07-01

Distracting stimuli in the environment can pull our attention away from our goal-directed tasks. fMRI studies have implicated regions in right frontal cortex as being particularly important for processing distractors [e.g., de Fockert, J. W., & Theeuwes, J. Role of frontal cortex in attentional capture by singleton distractors. Brain and Cognition, 80, 367-373, 2012; Demeter, E., Hernandez-Garcia, L., Sarter, M., & Lustig, C. Challenges to attention: A continuous arterial spin labeling (ASL) study of the effects of distraction on sustained attention. Neuroimage, 54, 1518-1529, 2011]. Less is known, however, about the timing and sequence of how right frontal or other brain regions respond selectively to distractors and how distractors impinge upon the cascade of processes related to detecting and processing behaviorally relevant target stimuli. Here we used EEG and ERPs to investigate the neural consequences of a perceptually salient but task-irrelevant distractor on the detection of rare target stimuli embedded in a rapid, serial visual presentation (RSVP) stream. We found that distractors that occur during the presentation of a target interfere behaviorally with detection of those targets, reflected by reduced detection rates, and that these missed targets show a reduced amplitude of the long-latency, detection-related P3 component. We also found that distractors elicited a right-lateralized frontal negativity beginning at 100 msec, whose amplitude negatively correlated across participants with their distraction-related behavioral impairment. Finally, we also quantified the instantaneous amplitude of the steady-state visual evoked potentials elicited by the RSVP stream and found that the occurrence of a distractor resulted in a transient amplitude decrement of the steady-state visual evoked potential, presumably reflecting the pull of attention away from the RSVP stream when distracting stimuli occur in the environment.

Feature-based attentional modulation increases with stimulus separation in divided-attention tasks.

PubMed

Sally, Sharon L; Vidnyánsky, Zoltán; Papathomas, Thomas V

2009-01-01

Attention modifies our visual experience by selecting certain aspects of a scene for further processing. It is therefore important to understand factors that govern the deployment of selective attention over the visual field. Both location and feature-specific mechanisms of attention have been identified and their modulatory effects can interact at a neural level (Treue and Martinez-Trujillo, 1999). The effects of spatial parameters on feature-based attentional modulation were examined for the feature dimensions of orientation, motion and color using three divided-attention tasks. Subjects performed concurrent discriminations of two briefly presented targets (Gabor patches) to the left and right of a central fixation point at eccentricities of +/-2.5 degrees , 5 degrees , 10 degrees and 15 degrees in the horizontal plane. Gabors were size-scaled to maintain consistent single-task performance across eccentricities. For all feature dimensions, the data show a linear increase in the attentional effects with target separation. In a control experiment, Gabors were presented on an isoeccentric viewing arc at 10 degrees and 15 degrees at the closest spatial separation (+/-2.5 degrees ) of the main experiment. Under these conditions, the effects of feature-based attentional effects were largely eliminated. Our results are consistent with the hypothesis that feature-based attention prioritizes the processing of attended features. Feature-based attentional mechanisms may have helped direct the attentional focus to the appropriate target locations at greater separations, whereas similar assistance may not have been necessary at closer target spacings. The results of the present study specify conditions under which dual-task performance benefits from sharing similar target features and may therefore help elucidate the processes by which feature-based attention operates.

Targeted quantitative analysis of Streptococcus pyogenes virulence factors by multiple reaction monitoring.

PubMed

Lange, Vinzenz; Malmström, Johan A; Didion, John; King, Nichole L; Johansson, Björn P; Schäfer, Juliane; Rameseder, Jonathan; Wong, Chee-Hong; Deutsch, Eric W; Brusniak, Mi-Youn; Bühlmann, Peter; Björck, Lars; Domon, Bruno; Aebersold, Ruedi

2008-08-01

In many studies, particularly in the field of systems biology, it is essential that identical protein sets are precisely quantified in multiple samples such as those representing differentially perturbed cell states. The high degree of reproducibility required for such experiments has not been achieved by classical mass spectrometry-based proteomics methods. In this study we describe the implementation of a targeted quantitative approach by which predetermined protein sets are first identified and subsequently quantified at high sensitivity reliably in multiple samples. This approach consists of three steps. First, the proteome is extensively mapped out by multidimensional fractionation and tandem mass spectrometry, and the data generated are assembled in the PeptideAtlas database. Second, based on this proteome map, peptides uniquely identifying the proteins of interest, proteotypic peptides, are selected, and multiple reaction monitoring (MRM) transitions are established and validated by MS2 spectrum acquisition. This process of peptide selection, transition selection, and validation is supported by a suite of software tools, TIQAM (Targeted Identification for Quantitative Analysis by MRM), described in this study. Third, the selected target protein set is quantified in multiple samples by MRM. Applying this approach we were able to reliably quantify low abundance virulence factors from cultures of the human pathogen Streptococcus pyogenes exposed to increasing amounts of plasma. The resulting quantitative protein patterns enabled us to clearly define the subset of virulence proteins that is regulated upon plasma exposure.

Reinforcement learning and decision making in monkeys during a competitive game.

PubMed

Lee, Daeyeol; Conroy, Michelle L; McGreevy, Benjamin P; Barraclough, Dominic J

2004-12-01

Animals living in a dynamic environment must adjust their decision-making strategies through experience. To gain insights into the neural basis of such adaptive decision-making processes, we trained monkeys to play a competitive game against a computer in an oculomotor free-choice task. The animal selected one of two visual targets in each trial and was rewarded only when it selected the same target as the computer opponent. To determine how the animal's decision-making strategy can be affected by the opponent's strategy, the computer opponent was programmed with three different algorithms that exploited different aspects of the animal's choice and reward history. When the computer selected its targets randomly with equal probabilities, animals selected one of the targets more often, violating the prediction of probability matching, and their choices were systematically influenced by the choice history of the two players. When the computer exploited only the animal's choice history but not its reward history, animal's choice became more independent of its own choice history but was still related to the choice history of the opponent. This bias was substantially reduced, but not completely eliminated, when the computer used the choice history of both players in making its predictions. These biases were consistent with the predictions of reinforcement learning, suggesting that the animals sought optimal decision-making strategies using reinforcement learning algorithms.

Masking interrupts figure-ground signals in V1.

PubMed

Lamme, Victor A F; Zipser, Karl; Spekreijse, Henk

2002-10-01

In a backward masking paradigm, a target stimulus is rapidly (<100 msec) followed by a second stimulus. This typically results in a dramatic decrease in the visibility of the target stimulus. It has been shown that masking reduces responses in V1. It is not known, however, which process in V1 is affected by the mask. In the past, we have shown that in V1, modulations of neural activity that are specifically related to figure-ground segregation can be recorded. Here, we recorded from awake macaque monkeys, engaged in a task where they had to detect figures from background in a pattern backward masking paradigm. We show that the V1 figure-ground signals are selectively and fully suppressed at target-mask intervals that psychophysically result in the target being invisible. Initial response transients, signalling the features that make up the scene, are not affected. As figure-ground modulations depend on feedback from extrastriate areas, these results suggest that masking selectively interrupts the recurrent interactions between V1 and higher visual areas.

Fitts's law in a selective reaching task: the proximity-to-hand effect of action-centered attention revisited.

PubMed

Welsh, Timothy N; Zbinden, Michele

2009-01-01

The "proximity-to-hand" effect refers to the finding that distractors between the home position and the target cause more interference in a selective reaching movement than distractors farther from the home position. Based largely on the proximity-to-hand effect, Tipper, Lortie, and Baylis (1992) proposed that attention is distributed in an action-centered framework such that the interference caused by a specific stimulus depends on the action. The current experiments sought to determine if there is an attentional preference for stimuli closer to home or for stimuli that activate more efficiently executed actions regardless of the location. Results supported the latter hypothesis in that the greatest interference was observed when the distractor activated an action with a lower index of difficulty than the target, even though that distractor was farther from home than the target. These findings indicate that the action context mediates the influence that nontarget stimuli have on the processing of target responses.

Photo-ionization of aluminum in a hot cavity for the selective production of exotic species project

NASA Astrophysics Data System (ADS)

Scarpa, D.; Makhathini, L.; Tomaselli, A.; Grassi, D.; Corradetti, S.; Manzolaro, M.; Vasquez, J.; Calderolla, M.; Rossignoli, M.; Monetti, A.; Andrighetto, A.; Prete, G.

2014-02-01

SPES (Selective Production of Exotic Species) is an Isotope Separation On-Line (ISOL) based accelerator facility that will be built in the Legnaro-Istituto Nazionale di Fisica Nucleare (INFN) Laboratory (Italy), intended to provide intense neutron-rich radioactive ion beams obtained by proton-induced fission of a uranium carbide (UCx) target. Besides this main target material, silicon carbide (SiC) will be the first to be used to deliver p-rich beams. This target will also validate the functionality of the SPES facility with aluminum beam as result of impinging SiC target with proton beam. In the past, off line studies on laser photoionization of aluminum have been performed in Pavia Spectroscopy Laboratory and in Laboratori Nazionali di Legnaro; a XeCl excimer laser was installed in order to test the laser ionization in the SPES hot cavity. With the new Wien filter installed a better characterization of the ionization process in terms of efficiency was performed and results are discussed.

Discovery and process development of a novel TACE inhibitor for the topical treatment of psoriasis.

PubMed

Boiteau, Jean-Guy; Ouvry, Gilles; Arlabosse, Jean-Marie; Astri, Stéphanie; Beillard, Audrey; Bhurruth-Alcor, Yushma; Bonnary, Laetitia; Bouix-Peter, Claire; Bouquet, Karine; Bourotte, Marilyne; Cardinaud, Isabelle; Comino, Catherine; Deprez, Benoît; Duvert, Denis; Féret, Angélique; Hacini-Rachinel, Feriel; Harris, Craig S; Luzy, Anne-Pascale; Mathieu, Arnaud; Millois, Corinne; Orsini, Nicolas; Pascau, Jonathan; Pinto, Artur; Piwnica, David; Polge, Gaëlle; Reitz, Arnaud; Reversé, Kevin; Rodeville, Nicolas; Rossio, Patricia; Spiesse, Delphine; Tabet, Samuel; Taquet, Nathalie; Tomas, Loïc; Vial, Emmanuel; Hennequin, Laurent F

2018-02-15

Targeting the TNFα pathway is a validated approach to the treatment of psoriasis. In this pathway, TACE stands out as a druggable target and has been the focus of in-house research programs. In this article, we present the discovery of clinical candidate 26a. Starting from hits plagued with poor solubility or genotoxicity, 26a was identified through thorough multiparameter optimisation. Showing robust in vivo activity in an oxazolone-mediated inflammation model, the compound was selected for development. Following a polymorph screen, the hydrochloride salt was selected and the synthesis was efficiently developed to yield the API in 47% overall yield. Copyright © 2017. Published by Elsevier Ltd.

An electrophysiological insight into visual attention mechanisms underlying schizotypy.

PubMed

Fuggetta, Giorgio; Bennett, Matthew A; Duke, Philip A

2015-07-01

A theoretical framework has been put forward to understand attention deficits in schizophrenia (Luck SJ & Gold JM. Biological Psychiatry. 2008; 64:34-39). We adopted this framework to evaluate any deficits in attentional processes in schizotypy. Sixteen low schizotypal (LoS) and 16 high schizotypal (HiS) individuals performed a novel paradigm combining a match-to-sample task, with inhibition of return (using spatially uninformative cues) and memory-guided efficient visual-search within one trial sequence. Behavioural measures and event-related potentials (ERPs) were recorded. Behaviourally, HiS individuals exhibited a spatial cueing effect while LoS individuals showed the more typical inhibition of return effect. These results suggest HiS individuals have a relative deficit in rule selection - the endogenous control process involved in disengaging attention from the uninformative location cue. ERP results showed that the late-phase of N2pc evoked by the target stimulus had greater peak latency and amplitude in HiS individuals. This suggests a relative deficit in the implementation of selection - the process of focusing attention onto target features that enhances relevant/suppresses irrelevant inputs. This is a different conclusion than when the same theoretical framework has been applied to schizophrenia, which argues little or no deficit in implementation of selection amongst patients. Also, HiS individuals exhibited earlier onset and greater amplitude of the mismatch-triggered negativity component. In summary, our results indicate deficits of both control and implementation of selection in HiS individuals. Copyright © 2015 Elsevier B.V. All rights reserved.

Neuroplasticity of selective attention: Research foundations and preliminary evidence for a gene by intervention interaction

PubMed Central

Stevens, Courtney; Pakulak, Eric; Hampton Wray, Amanda; Bell, Theodore A.; Neville, Helen J.

2017-01-01

This article reviews the trajectory of our research program on selective attention, which has moved from basic research on the neural processes underlying selective attention to translational studies using selective attention as a neurobiological target for evidence-based interventions. We use this background to present a promising preliminary investigation of how genetic and experiential factors interact during development (i.e., gene × intervention interactions). Our findings provide evidence on how exposure to a family-based training can modify the associations between genotype (5-HTTLPR) and the neural mechanisms of selective attention in preschool children from lower socioeconomic status backgrounds. PMID:28819066

Neuroplasticity of selective attention: Research foundations and preliminary evidence for a gene by intervention interaction.

PubMed

Isbell, Elif; Stevens, Courtney; Pakulak, Eric; Hampton Wray, Amanda; Bell, Theodore A; Neville, Helen J

2017-08-29

This article reviews the trajectory of our research program on selective attention, which has moved from basic research on the neural processes underlying selective attention to translational studies using selective attention as a neurobiological target for evidence-based interventions. We use this background to present a promising preliminary investigation of how genetic and experiential factors interact during development (i.e., gene × intervention interactions). Our findings provide evidence on how exposure to a family-based training can modify the associations between genotype (5-HTTLPR) and the neural mechanisms of selective attention in preschool children from lower socioeconomic status backgrounds.

Multistate and phase change selection in constitutional multivalent systems.

PubMed

Barboiu, Mihail

2012-01-01

Molecular architectures and materials can be constitutionally self-sorted in the presence of different biomolecular targets or external physical stimuli or chemical effectors, thus responding to an external selection pressure. The high selectivity and specificity of different bioreceptors or self-correlated internal interactions may be used to describe the complex constitutional behaviors through multistate component selection from a dynamic library. The self-selection may result in the dynamic amplification of self-optimized architectures during the phase change process. The sol-gel resolution of dynamic molecular/supramolecular libraries leads to higher self-organized constitutional hybrid materials, in which organic (supramolecular)/inorganic domains are reversibily connected.

The guidance of spatial attention during visual search for color combinations and color configurations.

PubMed

Berggren, Nick; Eimer, Martin

2016-09-01

Representations of target-defining features (attentional templates) guide the selection of target objects in visual search. We used behavioral and electrophysiological measures to investigate how such search templates control the allocation of attention in search tasks where targets are defined by the combination of 2 colors or by a specific spatial configuration of these colors. Target displays were preceded by spatially uninformative cue displays that contained items in 1 or both target-defining colors. Experiments 1 and 2 demonstrated that, during search for color combinations, attention is initially allocated independently and in parallel to all objects with target-matching colors, but is then rapidly withdrawn from objects that only have 1 of the 2 target colors. In Experiment 3, targets were defined by a particular spatial configuration of 2 colors, and could be accompanied by nontarget objects with a different configuration of the same colors. Attentional guidance processes were unable to distinguish between these 2 types of objects. Both attracted attention equally when they appeared in a cue display, and both received parallel focal-attentional processing and were encoded into working memory when they were presented in the same target display. Results demonstrate that attention can be guided simultaneously by multiple features from the same dimension, but that these guidance processes have no access to the spatial-configural properties of target objects. They suggest that attentional templates do not represent target objects in an integrated pictorial fashion, but contain separate representations of target-defining features. (PsycINFO Database Record (c) 2016 APA, all rights reserved).

Object Selection Costs in Visual Working Memory: A Diffusion Model Analysis of the Focus of Attention

ERIC Educational Resources Information Center

Sewell, David K.; Lilburn, Simon D.; Smith, Philip L.

2016-01-01

A central question in working memory research concerns the degree to which information in working memory is accessible to other cognitive processes (e.g., decision-making). Theories assuming that the focus of attention can only store a single object at a time require the focus to orient to a target representation before further processing can…

Language Non-Selective Activation of Orthography during Spoken Word Processing in Hindi-English Sequential Bilinguals: An Eye Tracking Visual World Study

ERIC Educational Resources Information Center

Mishra, Ramesh Kumar; Singh, Niharika

2014-01-01

Previous psycholinguistic studies have shown that bilinguals activate lexical items of both the languages during auditory and visual word processing. In this study we examined if Hindi-English bilinguals activate the orthographic forms of phonological neighbors of translation equivalents of the non target language while listening to words either…

A Multi-Area Stochastic Model for a Covert Visual Search Task.

PubMed

Schwemmer, Michael A; Feng, Samuel F; Holmes, Philip J; Gottlieb, Jacqueline; Cohen, Jonathan D

2015-01-01

Decisions typically comprise several elements. For example, attention must be directed towards specific objects, their identities recognized, and a choice made among alternatives. Pairs of competing accumulators and drift-diffusion processes provide good models of evidence integration in two-alternative perceptual choices, but more complex tasks requiring the coordination of attention and decision making involve multistage processing and multiple brain areas. Here we consider a task in which a target is located among distractors and its identity reported by lever release. The data comprise reaction times, accuracies, and single unit recordings from two monkeys' lateral interparietal area (LIP) neurons. LIP firing rates distinguish between targets and distractors, exhibit stimulus set size effects, and show response-hemifield congruence effects. These data motivate our model, which uses coupled sets of leaky competing accumulators to represent processes hypothesized to occur in feature-selective areas and limb motor and pre-motor areas, together with the visual selection process occurring in LIP. Model simulations capture the electrophysiological and behavioral data, and fitted parameters suggest that different connection weights between LIP and the other cortical areas may account for the observed behavioral differences between the animals.

The effects of solar incidence angle over digital processing of LANDSAT data

NASA Technical Reports Server (NTRS)

Parada, N. D. J. (Principal Investigator); Novo, E. M. L. M.

1983-01-01

A technique to extract the topography modulation component from digital data is described. The enhancement process is based on the fact that the pixel contains two types of information: (1) reflectance variation due to the target; (2) reflectance variation due to the topography. In order to enhance the signal variation due to topography, the technique recommends the extraction from original LANDSAT data of the component resulting from target reflectance. Considering that the role of topographic modulation over the pixel information will vary with solar incidence angle, the results of this technique of digital processing will differ from one season to another, mainly in highly dissected topography. In this context, the effects of solar incidence angle over the topographic modulation technique were evaluated. Two sets of MSS/LANDSAT data, with solar elevation angles varying from 22 to 41 deg were selected to implement the digital processing at the Image-100 System. A secondary watershed (Rio Bocaina) draining into Rio Paraiba do Sul (Sao Paulo State) was selected as a test site. The results showed that the technique used was more appropriate to MSS data acquired under higher Sun elevation angles. Topographic modulation components applied to low Sun elevation angles lessens rather than enhances topography.

A Pressing Need for Gender Balance in AGU Honors Nominations

NASA Astrophysics Data System (ADS)

Ball, Jessica

2014-03-01

AGU thrives on the volunteer efforts of its scientists, which is how I found myself agreeing to be a member of AGU's Science for Solutions Award committee last year. The award is targeted specifically at students and postdoctoral scientists who use Earth and space science to solve societal problems, and it was an intriguing experience to go through the process of evaluating the nominees and selecting a winner. All across the Union, members of other honors committees were going through a similar process, and at the 2013 Fall Meeting, those award recipients selected by the committees were honored.

Optical-Correlator Neural Network Based On Neocognitron

NASA Technical Reports Server (NTRS)

Chao, Tien-Hsin; Stoner, William W.

1994-01-01

Multichannel optical correlator implements shift-invariant, high-discrimination pattern-recognizing neural network based on paradigm of neocognitron. Selected as basic building block of this neural network because invariance under shifts is inherent advantage of Fourier optics included in optical correlators in general. Neocognitron is conceptual electronic neural-network model for recognition of visual patterns. Multilayer processing achieved by iteratively feeding back output of feature correlator to input spatial light modulator and updating Fourier filters. Neural network trained by use of characteristic features extracted from target images. Multichannel implementation enables parallel processing of large number of selected features.

swga: a primer design toolkit for selective whole genome amplification.

PubMed

Clarke, Erik L; Sundararaman, Sesh A; Seifert, Stephanie N; Bushman, Frederic D; Hahn, Beatrice H; Brisson, Dustin

2017-07-15

Population genomic analyses are often hindered by difficulties in obtaining sufficient numbers of genomes for analysis by DNA sequencing. Selective whole-genome amplification (SWGA) provides an efficient approach to amplify microbial genomes from complex backgrounds for sequence acquisition. However, the process of designing sets of primers for this method has many degrees of freedom and would benefit from an automated process to evaluate the vast number of potential primer sets. Here, we present swga , a program that identifies primer sets for SWGA and evaluates them for efficiency and selectivity. We used swga to design and test primer sets for the selective amplification of Wolbachia pipientis genomic DNA from infected Drosophila melanogaster and Mycobacterium tuberculosis from human blood. We identify primer sets that successfully amplify each against their backgrounds and describe a general method for using swga for arbitrary targets. In addition, we describe characteristics of primer sets that correlate with successful amplification, and present guidelines for implementation of SWGA to detect new targets. Source code and documentation are freely available on https://www.github.com/eclarke/swga . The program is implemented in Python and C and licensed under the GNU Public License. ecl@mail.med.upenn.edu. Supplementary data are available at Bioinformatics online. © The Author(s) 2017. Published by Oxford University Press.

Selection of Surrogate Bacteria for Use in Food Safety Challenge Studies: A Review.

PubMed

Hu, Mengyi; Gurtler, Joshua B

2017-09-01

Nonpathogenic surrogate bacteria are prevalently used in a variety of food challenge studies in place of foodborne pathogens such as Listeria monocytogenes, Salmonella, Escherichia coli O157:H7, and Clostridium botulinum because of safety and sanitary concerns. Surrogate bacteria should have growth characteristics and/or inactivation kinetics similar to those of target pathogens under given conditions in challenge studies. It is of great importance to carefully select and validate potential surrogate bacteria when verifying microbial inactivation processes. A validated surrogate responds similar to the targeted pathogen when tested for inactivation kinetics, growth parameters, or survivability under given conditions in agreement with appropriate statistical analyses. However, a considerable number of food studies involving putative surrogate bacteria lack convincing validation sources or adequate validation processes. Most of the validation information for surrogates in these studies is anecdotal and has been collected from previous publications but may not be sufficient for given conditions in the study at hand. This review is limited to an overview of select studies and discussion of the general criteria and approaches for selecting potential surrogate bacteria under given conditions. The review also includes a list of documented bacterial pathogen surrogates and their corresponding food products and treatments to provide guidance for future studies.

Early Selection versus Late Correction: Age-Related Differences in Controlling Working Memory Contents

PubMed Central

Schwarzkopp, Tina; Mayr, Ulrich; Jost, Kerstin

2016-01-01

We examined whether a reduced ability to ignore irrelevant information is responsible for the age-related decline of working-memory (WM) functions. By means of event-related brain potentials we will show that filtering is not out of service in older adults but shifted to a later processing stage. Participants performed a visual short-term memory task (change-detection task) in which targets were presented along with distractors. To allow early selection, a cue was presented in advance of each display, indicating where the targets were to appear. Despite this relatively easy selection criterion, older adults’ filtering was delayed as indicated by the amplitude pattern of the contralateral delay activity. Importantly, WM-equated younger adults did not show a delay indicating that the delay is specific to older adults and not a general phenomenon that comes with low WM capacity. Moreover, the analysis of early visual potentials revealed qualitatively different perceptual/attentional processing between the age groups. Young adults exhibited stronger distractor sensitivity that in turn facilitated filtering. Older adults, in contrast, seemed to initially store distractors and to suppress them after the fact. These early-selection versus late-correction modes suggest an age-related shift in the strategy to control the contents of WM. PMID:27253867

Strategy Developed for Selecting Optimal Sensors for Monitoring Engine Health

NASA Technical Reports Server (NTRS)

2004-01-01

Sensor indications during rocket engine operation are the primary means of assessing engine performance and health. Effective selection and location of sensors in the operating engine environment enables accurate real-time condition monitoring and rapid engine controller response to mitigate critical fault conditions. These capabilities are crucial to ensure crew safety and mission success. Effective sensor selection also facilitates postflight condition assessment, which contributes to efficient engine maintenance and reduced operating costs. Under the Next Generation Launch Technology program, the NASA Glenn Research Center, in partnership with Rocketdyne Propulsion and Power, has developed a model-based procedure for systematically selecting an optimal sensor suite for assessing rocket engine system health. This optimization process is termed the systematic sensor selection strategy. Engine health management (EHM) systems generally employ multiple diagnostic procedures including data validation, anomaly detection, fault-isolation, and information fusion. The effectiveness of each diagnostic component is affected by the quality, availability, and compatibility of sensor data. Therefore systematic sensor selection is an enabling technology for EHM. Information in three categories is required by the systematic sensor selection strategy. The first category consists of targeted engine fault information; including the description and estimated risk-reduction factor for each identified fault. Risk-reduction factors are used to define and rank the potential merit of timely fault diagnoses. The second category is composed of candidate sensor information; including type, location, and estimated variance in normal operation. The final category includes the definition of fault scenarios characteristic of each targeted engine fault. These scenarios are defined in terms of engine model hardware parameters. Values of these parameters define engine simulations that generate expected sensor values for targeted fault scenarios. Taken together, this information provides an efficient condensation of the engineering experience and engine flow physics needed for sensor selection. The systematic sensor selection strategy is composed of three primary algorithms. The core of the selection process is a genetic algorithm that iteratively improves a defined quality measure of selected sensor suites. A merit algorithm is employed to compute the quality measure for each test sensor suite presented by the selection process. The quality measure is based on the fidelity of fault detection and the level of fault source discrimination provided by the test sensor suite. An inverse engine model, whose function is to derive hardware performance parameters from sensor data, is an integral part of the merit algorithm. The final component is a statistical evaluation algorithm that characterizes the impact of interference effects, such as control-induced sensor variation and sensor noise, on the probability of fault detection and isolation for optimal and near-optimal sensor suites.

Display technologies: application for the discovery of drug and gene delivery agents

PubMed Central

Sergeeva, Anna; Kolonin, Mikhail G.; Molldrem, Jeffrey J.; Pasqualini, Renata; Arap, Wadih

2007-01-01

Recognition of molecular diversity of cell surface proteomes in disease is essential for the development of targeted therapies. Progress in targeted therapeutics requires establishing effective approaches for high-throughput identification of agents specific for clinically relevant cell surface markers. Over the past decade, a number of platform strategies have been developed to screen polypeptide libraries for ligands targeting receptors selectively expressed in the context of various cell surface proteomes. Streamlined procedures for identification of ligand-receptor pairs that could serve as targets in disease diagnosis, profiling, imaging and therapy have relied on the display technologies, in which polypeptides with desired binding profiles can be serially selected, in a process called biopanning, based on their physical linkage with the encoding nucleic acid. These technologies include virus/phage display, cell display, ribosomal display, mRNA display and covalent DNA display (CDT), with phage display being by far the most utilized. The scope of this review is the recent advancements in the display technologies with a particular emphasis on molecular mapping of cell surface proteomes with peptide phage display. Prospective applications of targeted compounds derived from display libraries in the discovery of targeted drugs and gene therapy vectors are discussed. PMID:17123658

Is Attention Shared Between the Ears?1

PubMed Central

Shiffrin, Richard M.; Pisoni, David B.; Castaneda-Mendez, Kicab

2012-01-01

This study tests the locus of attention during selective listening for speech-like stimuli. Can processing be differentially allocated to the two ears? Two conditions were used. The simultaneous condition involved one of four randomly chosen stop-consonants being presented to one of the ears chosen at random. The sequential condition involved two intervals; in the first S listened to the right ear; in the second S listened to the left ear. One of the four consonants was presented to an attended ear during one of these intervals. Experiment I used no distracting stimuli. Experiment II utilized a distracting consonant not confusable with any of the four target consonants. This distractor was always presented to any ear not containing a target. In both experiments, simultaneous and sequential performance were essentially identical, despite the need for attention sharing between the two ears during the simultaneous condition. We conclude that selective attention does not occur during perceptual processing of speech sounds presented to the two ears. We suggest that attentive effects arise in short-term memory following processing. PMID:23226838

Unmanned aircraft systems image collection and computer vision image processing for surveying and mapping that meets professional needs

NASA Astrophysics Data System (ADS)

Peterson, James Preston, II

Unmanned Aerial Systems (UAS) are rapidly blurring the lines between traditional and close range photogrammetry, and between surveying and photogrammetry. UAS are providing an economic platform for performing aerial surveying on small projects. The focus of this research was to describe traditional photogrammetric imagery and Light Detection and Ranging (LiDAR) geospatial products, describe close range photogrammetry (CRP), introduce UAS and computer vision (CV), and investigate whether industry mapping standards for accuracy can be met using UAS collection and CV processing. A 120-acre site was selected and 97 aerial targets were surveyed for evaluation purposes. Four UAS flights of varying heights above ground level (AGL) were executed, and three different target patterns of varying distances between targets were analyzed for compliance with American Society for Photogrammetry and Remote Sensing (ASPRS) and National Standard for Spatial Data Accuracy (NSSDA) mapping standards. This analysis resulted in twelve datasets. Error patterns were evaluated and reasons for these errors were determined. The relationship between the AGL, ground sample distance, target spacing and the root mean square error of the targets is exploited by this research to develop guidelines that use the ASPRS and NSSDA map standard as the template. These guidelines allow the user to select the desired mapping accuracy and determine what target spacing and AGL is required to produce the desired accuracy. These guidelines also address how UAS/CV phenomena affect map accuracy. General guidelines and recommendations are presented that give the user helpful information for planning a UAS flight using CV technology.

Mechanistic studies on a sequential PDT protocol

NASA Astrophysics Data System (ADS)

Kessel, David

2016-03-01

A low (~LD15) PDT dose resulting in selective lysosomal photodamage can markedly promote photokilling by subsequent photodamage targeted to mitochondria. Experimental data are consistent with the proposal that cleavage of the autophagyassociated protein ATG5 to a pro-apoptotic fragment is responsible for this effect. This process is known to be dependent on the proteolytic activity of calpain. We have proposed that Ca2+ released from photodamaged lysosomes is the trigger for ATG5 cleavage. We can now document the conversion of ATG5 to the truncated form after lysosomal photodamage. Photofrin, a photosensitizer that targets both mitochondria and lysosomes, can be used for either phase of the sequential PDT process. The ability of Photofrin to target both loci may explain the well-documented efficacy of this agent.

Electrical Microstimulation of the Pulvinar Biases Saccade Choices and Reaction Times in a Time-Dependent Manner

PubMed Central

2017-01-01

The pulvinar complex is interconnected extensively with brain regions involved in spatial processing and eye movement control. Recent inactivation studies have shown that the dorsal pulvinar (dPul) plays a role in saccade target selection; however, it remains unknown whether it exerts effects on visual processing or at planning/execution stages. We used electrical microstimulation of the dPul while monkeys performed saccade tasks toward instructed and freely chosen targets. Timing of stimulation was varied, starting before, at, or after onset of target(s). Stimulation affected saccade properties and target selection in a time-dependent manner. Stimulation starting before but overlapping with target onset shortened saccadic reaction times (RTs) for ipsiversive (to the stimulation site) target locations, whereas stimulation starting at and after target onset caused systematic delays for both ipsiversive and contraversive locations. Similarly, stimulation starting before the onset of bilateral targets increased ipsiversive target choices, whereas stimulation after target onset increased contraversive choices. Properties of dPul neurons and stimulation effects were consistent with an overall contraversive drive, with varying outcomes contingent upon behavioral demands. RT and choice effects were largely congruent in the visually-guided task, but stimulation during memory-guided saccades, while influencing RTs and errors, did not affect choice behavior. Together, these results show that the dPul plays a primary role in action planning as opposed to visual processing, that it exerts its strongest influence on spatial choices when decision and action are temporally close, and that this choice effect can be dissociated from motor effects on saccade initiation and execution. SIGNIFICANCE STATEMENT Despite a recent surge of interest, the core function of the pulvinar, the largest thalamic complex in primates, remains elusive. This understanding is crucial given the central role of the pulvinar in current theories of integrative brain functions supporting cognition and goal-directed behaviors, but electrophysiological and causal interference studies of dorsal pulvinar (dPul) are rare. Building on our previous studies that pharmacologically suppressed dPul activity for several hours, here we used transient electrical microstimulation at different periods while monkeys performed instructed and choice eye movement tasks, to determine time-specific contributions of pulvinar to saccade generation and decision making. We show that stimulation effects depend on timing and behavioral state and that effects on choices can be dissociated from motor effects. PMID:28119401

How do infants and adults process communicative events in real time?

PubMed

Yamashiro, Amy; Vouloumanos, Athena

2018-09-01

Speech allows humans to communicate and to navigate the social world. By 12 months, infants recognize that speech elicits appropriate responses from others. However, it is unclear how infants process dynamic communicative scenes and how their processing abilities compare with those of adults. Do infants, like adults, process communicative events while the event is occurring or only after being presented with the outcome? We examined 12-month-olds' and adults' eye movements as they watched a Communicator grasp one (target) of two objects. During the test event, the Communicator could no longer reach the objects, so she spoke or coughed to a Listener, who selected either object. Infants' and adults' patterns of looking to the actors and objects revealed that both groups immediately evaluated the Communicator's speech, but not her cough, as communicative and recognized that the Listener should select the target object only when the Communicator spoke. Furthermore, infants and adults shifted their attention between the actors and the objects in very similar ways. This suggests that 12-month-olds can quickly process communicative events as they occur with adult-like accuracy. However, differences in looking reveal that 12-month-olds process slower than adults. This early developing processing ability may allow infants to learn language and acquire knowledge from communicative interactions. Copyright © 2018 Elsevier Inc. All rights reserved.

Multi atlas based segmentation: Should we prefer the best atlas group over the group of best atlases?

PubMed

Zaffino, Paolo; Ciardo, Delia; Raudaschl, Patrik; Fritscher, Karl; Ricotti, Rosalinda; Alterio, Daniela; Marvaso, Giulia; Fodor, Cristiana; Baroni, Guido; Amato, Francesco; Orecchia, Roberto; Jereczek-Fossa, Barbara Alicja; Sharp, Gregory C; Spadea, Maria Francesca

2018-05-22

Multi Atlas Based Segmentation (MABS) uses a database of atlas images, and an atlas selection process is used to choose an atlas subset for registration and voting. In the current state of the art, atlases are chosen according to a similarity criterion between the target subject and each atlas in the database. In this paper, we propose a new concept for atlas selection that relies on selecting the best performing group of atlases rather than the group of highest scoring individual atlases. Experiments were performed using CT images of 50 patients, with contours of brainstem and parotid glands. The dataset was randomly split in 2 groups: 20 volumes were used as an atlas database and 30 served as target subjects for testing. Classic oracle group selection, where atlases are chosen by the highest Dice Similarity Coefficient (DSC) with the target, was performed. This was compared to oracle Group selection, where all the combinations of atlas subgroups were considered and scored by computing DSC with the target subject. Subsequently, Convolutional Neural Networks (CNNs) were designed to predict the best group of atlases. The results were compared also with the selection strategy based on Normalized Mutual Information (NMI). Oracle group was proved to be significantly better that classic oracle selection (p<10-5). Atlas group selection led to a median±interquartile DSC of 0.740±0.084, 0.718±0.086 and 0.670±0.097 for brainstem and left/right parotid glands respectively, outperforming NMI selection 0.676±0.113, 0.632±0.104 and 0.606±0.118 (p<0.001) as well as classic oracle selection. The implemented methodology is a proof of principle that selecting the atlases by considering the performance of the entire group of atlases instead of each single atlas leads to higher segmentation accuracy, being even better then current oracle strategy. This finding opens a new discussion about the most appropriate atlas selection criterion for MABS. © 2018 Institute of Physics and Engineering in Medicine.

Methylphenidate alters selective attention by amplifying salience.

PubMed

ter Huurne, Niels; Fallon, Sean James; van Schouwenburg, Martine; van der Schaaf, Marieke; Buitelaar, Jan; Jensen, Ole; Cools, Roshan

2015-12-01

Methylphenidate, the most common treatment of attention deficit hyperactivity disorder (ADHD), is increasingly used by healthy individuals as a "smart drug" to enhance cognitive abilities like attention. A key feature of (selective) attention is the ability to ignore irrelevant but salient information in the environment (distractors). Although crucial for cognitive performance, until now, it is not known how the use of methylphenidate affects resistance to attentional capture by distractors. The present study aims to clarify how methylphenidate affects distractor suppression in healthy individuals. The effect of methylphenidate (20 mg) on distractor suppression was assessed in healthy subjects (N = 20), in a within-subject double-blind placebo-controlled crossover design. We used a visuospatial attention task with target faces flanked by strong (faces) or weak distractors (scrambled faces). Methylphenidate increased accuracy on trials that required gender identification of target face stimuli (methylphenidate 88.9 ± 1.4 [mean ± SEM], placebo 86.0 ± 1.2 %; p = .003), suggesting increased processing of the faces. At the same time, however, methylphenidate increased reaction time when the target face was flanked by a face distractor relative to a scrambled face distractor (methylphenidate 34.9 ± 3.73, placebo 26.7 ± 2.84 ms; p = .027), suggesting enhanced attentional capture by distractors with task-relevant features. We conclude that methylphenidate amplifies salience of task-relevant information at the level of the stimulus category. This leads to enhanced processing of the target (faces) but also increased attentional capture by distractors drawn from the same category as the target.

Cascading activation from lexical processing to letter-level processing in written word production.

PubMed

Buchwald, Adam; Falconer, Carolyn

2014-01-01

Descriptions of language production have identified processes involved in producing language and the presence and type of interaction among those processes. In the case of spoken language production, consensus has emerged that there is interaction among lexical selection processes and phoneme-level processing. This issue has received less attention in written language production. In this paper, we present a novel analysis of the writing-to-dictation performance of an individual with acquired dysgraphia revealing cascading activation from lexical processing to letter-level processing. The individual produced frequent lexical-semantic errors (e.g., chipmunk → SQUIRREL) as well as letter errors (e.g., inhibit → INBHITI) and had a profile consistent with impairment affecting both lexical processing and letter-level processing. The presence of cascading activation is suggested by lower letter accuracy on words that are more weakly activated during lexical selection than on those that are more strongly activated. We operationalize weakly activated lexemes as those lexemes that are produced as lexical-semantic errors (e.g., lethal in deadly → LETAHL) compared to strongly activated lexemes where the intended target word (e.g., lethal) is the lexeme selected for production.

Method for materials deposition by ablation transfer processing

DOEpatents

Weiner, K.H.

1996-04-16

A method in which a thin layer of semiconducting, insulating, or metallic material is transferred by ablation from a source substrate, coated uniformly with a thin layer of said material, to a target substrate, where said material is desired, with a pulsed, high intensity, patternable beam of energy. The use of a patternable beam allows area-selective ablation from the source substrate resulting in additive deposition of the material onto the target substrate which may require a very low percentage of the area to be covered. Since material is placed only where it is required, material waste can be minimized by reusing the source substrate for depositions on multiple target substrates. Due to the use of a pulsed, high intensity energy source the target substrate remains at low temperature during the process, and thus low-temperature, low cost transparent glass or plastic can be used as the target substrate. The method can be carried out atmospheric pressures and at room temperatures, thus eliminating vacuum systems normally required in materials deposition processes. This invention has particular application in the flat panel display industry, as well as minimizing materials waste and associated costs. 1 fig.

Adaptive Spatial Filter Based on Similarity Indices to Preserve the Neural Information on EEG Signals during On-Line Processing

PubMed Central

Villa-Parra, Ana Cecilia; Bastos-Filho, Teodiano; López-Delis, Alberto; Frizera-Neto, Anselmo; Krishnan, Sridhar

2017-01-01

This work presents a new on-line adaptive filter, which is based on a similarity analysis between standard electrode locations, in order to reduce artifacts and common interferences throughout electroencephalography (EEG) signals, but preserving the useful information. Standard deviation and Concordance Correlation Coefficient (CCC) between target electrodes and its correspondent neighbor electrodes are analyzed on sliding windows to select those neighbors that are highly correlated. Afterwards, a model based on CCC is applied to provide higher values of weight to those correlated electrodes with lower similarity to the target electrode. The approach was applied to brain computer-interfaces (BCIs) based on Canonical Correlation Analysis (CCA) to recognize 40 targets of steady-state visual evoked potential (SSVEP), providing an accuracy (ACC) of 86.44 ± 2.81%. In addition, also using this approach, features of low frequency were selected in the pre-processing stage of another BCI to recognize gait planning. In this case, the recognition was significantly (p<0.01) improved for most of the subjects (ACC≥74.79%), when compared with other BCIs based on Common Spatial Pattern, Filter Bank-Common Spatial Pattern, and Riemannian Geometry. PMID:29186848

RoboTAP: Target priorities for robotic microlensing observations

NASA Astrophysics Data System (ADS)

Hundertmark, M.; Street, R. A.; Tsapras, Y.; Bachelet, E.; Dominik, M.; Horne, K.; Bozza, V.; Bramich, D. M.; Cassan, A.; D'Ago, G.; Figuera Jaimes, R.; Kains, N.; Ranc, C.; Schmidt, R. W.; Snodgrass, C.; Wambsganss, J.; Steele, I. A.; Mao, S.; Ment, K.; Menzies, J.; Li, Z.; Cross, S.; Maoz, D.; Shvartzvald, Y.

2018-01-01

Context. The ability to automatically select scientifically-important transient events from an alert stream of many such events, and to conduct follow-up observations in response, will become increasingly important in astronomy. With wide-angle time domain surveys pushing to fainter limiting magnitudes, the capability to follow-up on transient alerts far exceeds our follow-up telescope resources, and effective target prioritization becomes essential. The RoboNet-II microlensing program is a pathfinder project, which has developed an automated target selection process (RoboTAP) for gravitational microlensing events, which are observed in real time using the Las Cumbres Observatory telescope network. Aims: Follow-up telescopes typically have a much smaller field of view compared to surveys, therefore the most promising microlensing events must be automatically selected at any given time from an annual sample exceeding 2000 events. The main challenge is to select between events with a high planet detection sensitivity, with the aim of detecting many planets and characterizing planetary anomalies. Methods: Our target selection algorithm is a hybrid system based on estimates of the planet detection zones around a microlens. It follows automatic anomaly alerts and respects the expected survey coverage of specific events. Results: We introduce the RoboTAP algorithm, whose purpose is to select and prioritize microlensing events with high sensitivity to planetary companions. In this work, we determine the planet sensitivity of the RoboNet follow-up program and provide a working example of how a broker can be designed for a real-life transient science program conducting follow-up observations in response to alerts; we explore the issues that will confront similar programs being developed for the Large Synoptic Survey Telescope (LSST) and other time domain surveys.

Impact of auditory selective attention on verbal short-term memory and vocabulary development.

PubMed

Majerus, Steve; Heiligenstein, Lucie; Gautherot, Nathalie; Poncelet, Martine; Van der Linden, Martial

2009-05-01

This study investigated the role of auditory selective attention capacities as a possible mediator of the well-established association between verbal short-term memory (STM) and vocabulary development. A total of 47 6- and 7-year-olds were administered verbal immediate serial recall and auditory attention tasks. Both task types probed processing of item and serial order information because recent studies have shown this distinction to be critical when exploring relations between STM and lexical development. Multiple regression and variance partitioning analyses highlighted two variables as determinants of vocabulary development: (a) a serial order processing variable shared by STM order recall and a selective attention task for sequence information and (b) an attentional variable shared by selective attention measures targeting item or sequence information. The current study highlights the need for integrative STM models, accounting for conjoined influences of attentional capacities and serial order processing capacities on STM performance and the establishment of the lexical language network.

Drug-target residence time--a case for G protein-coupled receptors.

PubMed

Guo, Dong; Hillger, Julia M; IJzerman, Adriaan P; Heitman, Laura H

2014-07-01

A vast number of marketed drugs act on G protein-coupled receptors (GPCRs), the most successful category of drug targets to date. These drugs usually possess high target affinity and selectivity, and such combined features have been the driving force in the early phases of drug discovery. However, attrition has also been high. Many investigational new drugs eventually fail in clinical trials due to a demonstrated lack of efficacy. A retrospective assessment of successfully launched drugs revealed that their beneficial effects in patients may be attributed to their long drug-target residence times (RTs). Likewise, for some other GPCR drugs short RT could be beneficial to reduce the potential for on-target side effects. Hence, the compounds' kinetics behavior might in fact be the guiding principle to obtain a desired and durable effect in vivo. We therefore propose that drug-target RT should be taken into account as an additional parameter in the lead selection and optimization process. This should ultimately lead to an increased number of candidate drugs moving to the preclinical development phase and on to the market. This review contains examples of the kinetics behavior of GPCR ligands with improved in vivo efficacy and summarizes methods for assessing drug-target RT. © 2014 Wiley Periodicals, Inc.

Picky Eaters

ERIC Educational Resources Information Center

Hendrix, Marie

2008-01-01

Each day quality child care programs strive to provide for the nutritional well being of their children. Staff thoughtfully prepare menus that target balanced diets and address caloric needs. Careful consideration to nutritional value and safety guides the process of selecting and preparing food. The outcome is appealing, developmentally…

Tracking and recognition of multiple human targets moving in a wireless pyroelectric infrared sensor network.

PubMed

Xiong, Ji; Li, Fangmin; Zhao, Ning; Jiang, Na

2014-04-22

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%.

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

PubMed

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 <6.7-fold amplification of the background. SWGA-treated 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.

Visual encoding and fixation target selection in free viewing: presaccadic brain potentials

PubMed Central

Nikolaev, Andrey R.; Jurica, Peter; Nakatani, Chie; Plomp, Gijs; van Leeuwen, Cees

2013-01-01

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. PMID:23818877

Altered spatial profile of distraction in people with schizophrenia.

PubMed

Leonard, Carly J; Robinson, Benjamin M; Hahn, Britta; Luck, Steven J; Gold, James M

2017-11-01

Attention is critical for effective processing of incoming information and has long been identified as a potential area of dysfunction in people with schizophrenia (PSZ). In the realm of visual processing, both spatial attention and feature-based attention are involved in biasing selection toward task-relevant stimuli and avoiding distraction. Evidence from multiple paradigms has suggested that PSZ may hyperfocus and have a narrower "spotlight" of spatial attention. In contrast, feature-based attention seems largely preserved, with some suggestion of increased processing of stimuli sharing the target-defining feature. In the current study, we examined the spatial profile of feature-based distraction using a task in which participants searched for a particular color target and attempted to ignore distractors that varied in distance from the target location and either matched or mismatched the target color. PSZ differed from healthy controls in terms of interference from peripheral distractors that shared the target-color presented 200 ms before a central target. Specifically, PSZ showed an amplified gradient of spatial attention, with increased distraction to near distractors and less interference to far distractors. Moreover, consistent with hyperfocusing, individual differences in this spatial profile were correlated with positive symptoms, such that those with greater positive symptoms showed less distraction by target-colored distractors near the task-relevant location. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

On The Relationship between Suspended Solids of Different Size, the Observed Boundary Flux and Rejection Values for Membranes Treating a Civil Wastewater Stream.

PubMed

Stoller, Marco; Pulido, Javier Miguel Ochando; Palma, Luca Di

2014-08-04

Membrane fouling is one of the main issues in membrane processes, leading to a progressive decrease of permeability. High fouling rates strongly reduce the productivity of the membrane plant, and negatively affect the surviving rate of the membrane modules, especially when real wastewater is treated. On the other hand, since selectivity must meet certain target requirements, fouling may lead to unexpected selectivity improvements due to the formation of an additional superficial layer formed of foulants and that act like a selective secondary membrane layer. In this case, a certain amount of fouling may be profitable to the point where selectivity targets were reached and productivity is not significantly affected. In this work, the secondary clarifier of a step sludge recirculation bioreactor treating municipal wastewater was replaced by a membrane unit, aiming at recovering return sludge and producing purified water. Fouling issues of such a system were checked by boundary flux measurements. A simple model for the description of the observed productivity and selectivity values as a function of membrane fouling is proposed.

On The Relationship between Suspended Solids of Different Size, the Observed Boundary Flux and Rejection Values for Membranes Treating a Civil Wastewater Stream

PubMed Central

Stoller, Marco; Pulido, Javier Miguel Ochando; Di Palma, Luca

2014-01-01

Membrane fouling is one of the main issues in membrane processes, leading to a progressive decrease of permeability. High fouling rates strongly reduce the productivity of the membrane plant, and negatively affect the surviving rate of the membrane modules, especially when real wastewater is treated. On the other hand, since selectivity must meet certain target requirements, fouling may lead to unexpected selectivity improvements due to the formation of an additional superficial layer formed of foulants and that act like a selective secondary membrane layer. In this case, a certain amount of fouling may be profitable to the point where selectivity targets were reached and productivity is not significantly affected. In this work, the secondary clarifier of a step sludge recirculation bioreactor treating municipal wastewater was replaced by a membrane unit, aiming at recovering return sludge and producing purified water. Fouling issues of such a system were checked by boundary flux measurements. A simple model for the description of the observed productivity and selectivity values as a function of membrane fouling is proposed. PMID:25093867

A competitive interaction theory of attentional selection and decision making in brief, multielement displays.

PubMed

Smith, Philip L; Sewell, David K

2013-07-01

We generalize the integrated system model of Smith and Ratcliff (2009) to obtain a new theory of attentional selection in brief, multielement visual displays. The theory proposes that attentional selection occurs via competitive interactions among detectors that signal the presence of task-relevant features at particular display locations. The outcome of the competition, together with attention, determines which stimuli are selected into visual short-term memory (VSTM). Decisions about the contents of VSTM are made by a diffusion-process decision stage. The selection process is modeled by coupled systems of shunting equations, which perform gated where-on-what pathway VSTM selection. The theory provides a computational account of key findings from attention tasks with near-threshold stimuli. These are (a) the success of the MAX model of visual search and spatial cuing, (b) the distractor homogeneity effect, (c) the double-target detection deficit, (d) redundancy costs in the post-stimulus probe task, (e) the joint item and information capacity limits of VSTM, and (f) the object-based nature of attentional selection. We argue that these phenomena are all manifestations of an underlying competitive VSTM selection process, which arise as a natural consequence of our theory. PsycINFO Database Record (c) 2013 APA, all rights reserved.

Attention and implicit memory.

PubMed

Spataro, Pietro; Mulligan, Neil W; Rossi-Arnaud, Clelia

2011-01-01

The distinction between identification and production priming assumes that tasks based on production processes involve two distinct stages: the activation of multiple solutions and the following selection of a final response. Previous research demonstrated that divided attention reduced production but not identification priming. However, an unresolved issue concerns whether the activation of candidate solutions is sufficient to account for the enhanced request of attentional resources, independently from the contribution of selection processes. The present paper investigated this question by using a version of the lexical decision task (LDT) in which the target words had either many or few orthographic neighbors. Two experiments showed that the effects of divided and selective attention were equivalent in both conditions, suggesting that the inclusion of a process of generation of multiple solutions in the LDT is not sufficient to increase the amount of cognitive resources needed to achieve full priming to the levels of production tasks.

Phenotypic Screening Approaches to Develop Aurora Kinase Inhibitors: Drug Discovery Perspectives.

PubMed

Marugán, Carlos; Torres, Raquel; Lallena, María José

2015-01-01

Targeting mitotic regulators as a strategy to fight cancer implies the development of drugs against key proteins, such as Aurora-A and -B. Current drugs, which target mitosis through a general mechanism of action (stabilization/destabilization of microtubules), have several side effects (neutropenia, alopecia, and emesis). Pharmaceutical companies aim at avoiding these unwanted effects by generating improved and selective drugs that increase the quality of life of the patients. However, the development of these drugs is an ambitious task that involves testing thousands of compounds through biochemical and cell-based assays. In addition, molecules usually target complex biological processes, involving several proteins and different molecular pathways, further emphasizing the need for high-throughput screening techniques and multiplexing technologies in order to identify drugs with the desired phenotype. We will briefly describe two multiplexing technologies [high-content imaging (HCI) and flow cytometry] and two key processes for drug discovery research (assay development and validation) following our own published industry quality standards. We will further focus on HCI as a useful tool for phenotypic screening and will provide a concrete example of HCI assay to detect Aurora-A or -B selective inhibitors discriminating the off-target effects related to the inhibition of other cell cycle or non-cell cycle key regulators. Finally, we will describe other assays that can help to characterize the in vitro pharmacology of the inhibitors.

The study of infrared target recognition at sea background based on visual attention computational model

NASA Astrophysics Data System (ADS)

Wang, Deng-wei; Zhang, Tian-xu; Shi, Wen-jun; Wei, Long-sheng; Wang, Xiao-ping; Ao, Guo-qing

2009-07-01

Infrared images at sea background are notorious for the low signal-to-noise ratio, therefore, the target recognition of infrared image through traditional methods is very difficult. In this paper, we present a novel target recognition method based on the integration of visual attention computational model and conventional approach (selective filtering and segmentation). The two distinct techniques for image processing are combined in a manner to utilize the strengths of both. The visual attention algorithm searches the salient regions automatically, and represented them by a set of winner points, at the same time, demonstrated the salient regions in terms of circles centered at these winner points. This provides a priori knowledge for the filtering and segmentation process. Based on the winner point, we construct a rectangular region to facilitate the filtering and segmentation, then the labeling operation will be added selectively by requirement. Making use of the labeled information, from the final segmentation result we obtain the positional information of the interested region, label the centroid on the corresponding original image, and finish the localization for the target. The cost time does not depend on the size of the image but the salient regions, therefore the consumed time is greatly reduced. The method is used in the recognition of several kinds of real infrared images, and the experimental results reveal the effectiveness of the algorithm presented in this paper.

Selection of a turbine cooling system applying multi-disciplinary design considerations.

PubMed

Glezer, B

2001-05-01

The presented paper describes a multi-disciplinary cooling selection approach applied to major gas turbine engine hot section components, including turbine nozzles, blades, discs, combustors and support structures, which maintain blade tip clearances. The paper demonstrates benefits of close interaction between participating disciplines starting from early phases of the hot section development. The approach targets advancements in engine performance and cost by optimizing the design process, often requiring compromises within individual disciplines.

Hit to lead account of the discovery of bisbenzamide and related ureidobenzamide inhibitors of Rho kinase.

PubMed

Morwick, Tina; Büttner, Frank H; Cywin, Charles L; Dahmann, Georg; Hickey, Eugene; Jakes, Scott; Kaplita, Paul; Kashem, Mohammed A; Kerr, Steven; Kugler, Stanley; Mao, Wang; Marshall, Daniel; Paw, Zofia; Shih, Cheng-Kon; Wu, Frank; Young, Erick

2010-01-28

A highly selective series of bisbenzamide inhibitors of Rho-associated coiled-coil forming protein kinase (ROCK) and a related ureidobenzamide series, both identified by high throughput screening (HTS), are described. Details of the hit validation and lead generation process, including structure-activity relationship (SAR) studies, a selectivity assessment, target-independent profiling (TIP) results, and an analysis of functional activity using a rat aortic ring assay are discussed.

The waiting time problem in a model hominin population.

PubMed

Sanford, John; Brewer, Wesley; Smith, Franzine; Baumgardner, John

2015-09-17

Functional information is normally communicated using specific, context-dependent strings of symbolic characters. This is true within the human realm (texts and computer programs), and also within the biological realm (nucleic acids and proteins). In biology, strings of nucleotides encode much of the information within living cells. How do such information-bearing nucleotide strings arise and become established? This paper uses comprehensive numerical simulation to understand what types of nucleotide strings can realistically be established via the mutation/selection process, given a reasonable timeframe. The program Mendel's Accountant realistically simulates the mutation/selection process, and was modified so that a starting string of nucleotides could be specified, and a corresponding target string of nucleotides could be specified. We simulated a classic pre-human hominin population of at least 10,000 individuals, with a generation time of 20 years, and with very strong selection (50% selective elimination). Random point mutations were generated within the starting string. Whenever an instance of the target string arose, all individuals carrying the target string were assigned a specified reproductive advantage. When natural selection had successfully amplified an instance of the target string to the point of fixation, the experiment was halted, and the waiting time statistics were tabulated. Using this methodology we tested the effect of mutation rate, string length, fitness benefit, and population size on waiting time to fixation. Biologically realistic numerical simulations revealed that a population of this type required inordinately long waiting times to establish even the shortest nucleotide strings. To establish a string of two nucleotides required on average 84 million years. To establish a string of five nucleotides required on average 2 billion years. We found that waiting times were reduced by higher mutation rates, stronger fitness benefits, and larger population sizes. However, even using the most generous feasible parameters settings, the waiting time required to establish any specific nucleotide string within this type of population was consistently prohibitive. We show that the waiting time problem is a significant constraint on the macroevolution of the classic hominin population. Routine establishment of specific beneficial strings of two or more nucleotides becomes very problematic.

Ultrasensitive and selective signal-on electrochemical DNA detection via exonuclease III catalysis and hybridization chain reaction amplification.

PubMed

Ren, Wang; Gao, Zhong Feng; Li, Nian Bing; Luo, Hong Qun

2015-01-15

This work reported a novel, ultrasensitive, and selective platform for electrochemical detection of DNA, employing an integration of exonuclease III (Exo-III) assisted target recycling and hybridization chain reaction (HCR) for the dual signal amplification strategy. The hairpin capture probe DNA (C-DNA) with an Exo-III 3' overhang end was self-assembled on a gold electrode. In the presence of target DNA (T-DNA), C-DNA hybridized with the T-DNA to form a duplex region, exposing its 5' complementary sequence (initiator). Exo-III was applied to selectively digest duplex region from its 3-hydroxyl termini until the duplex was fully consumed, leaving the remnant initiator. The intact T-DNA spontaneously dissociated from the structure and then initiated the next hybridization process as a result of catalysis of the Exo-III. HCR event was triggered by the initiator and two hairpin helper signal probes labeled with methylene blue, facilitating the polymerization of oligonucleotides into a long nicked dsDNA molecule. The numerous exposed remnant initiators can trigger more HCR events. Because of integration of dual signal amplification and the specific HCR process reaction, the resultant sensor showed a high sensitivity for the detection of the target DNA in a linear range from 1.0 fM to 1.0 nM, and a detection limit as low as 0.2 fM. The proposed dual signal amplification strategy provides a powerful tool for detecting different sequences of target DNA by changing the sequence of capture probe and signal probes, holding a great potential for early diagnosis in gene-related diseases. Copyright © 2014 Elsevier B.V. All rights reserved.

The Effects of Visual Complexity for Japanese Kanji Processing with High and Low Frequencies

ERIC Educational Resources Information Center

Tamaoka, Katsuo; Kiyama, Sachiko

2013-01-01

The present study investigated the effects of visual complexity for kanji processing by selecting target kanji from different stroke ranges of visually simple (2-6 strokes), medium (8-12 strokes), and complex (14-20 strokes) kanji with high and low frequencies. A kanji lexical decision task in Experiment 1 and a kanji naming task in Experiment 2…

Environmentally Responsible Microbiological Production of Energetic Ingredients

DTIC Science & Technology

2007-11-01

effort was to develop an environmentally benign and economical microbial process for nitro-energetics production . The specific targets of this method...microbial production of nitro-based EM. As the processes and compounds of choice, RDX/HMX (nitramine) generation was selected. Microorganisms capable of...Current synthetic methods for the production of RDX and HMX utilize hexamine as the precursor. Hexamine is an industrial chemical available on a large

Highly Selective Photothermal Therapy by a Phenoxylated-Dextran-Functionalized Smart Carbon Nanotube Platform.

PubMed

Han, Seungmin; Kwon, Taeyun; Um, Jo-Eun; Haam, Seungjoo; Kim, Woo-Jae

2016-05-01

Near-infrared (NIR) photothermal therapy using biocompatible single-walled carbon nanotubes (SWNTs) is advantageous because as-produced SWNTs, without additional size control, both efficiently absorb NIR light and demonstrate high photothermal conversion efficiency. In addition, covalent attachment of receptor molecules to SWNTs can be used to specifically target infected cells. However, this technique interrupts SWNT optical properties and inevitably lowers photothermal conversion efficiency and thus remains major hurdle for SWNT applications. This paper presents a smart-targeting photothermal therapy platform for inflammatory disease using newly developed phenoxylated-dextran-functionalized SWNTs. Phenoxylated dextran is biocompatible and efficiently suspends SWNTs by noncovalent π-π stacking, thereby minimizing SWNT bundle formations and maintaining original SWNT optical properties. Furthermore, it selectively targets inflammatory macrophages by scavenger-receptor binding without any additional receptor molecules; therefore, its preparation is a simple one-step process. Herein, it is experimentally demonstrated that phenoxylated dextran-SWNTs (pD-SWNTs) are also biocompatible, selectively penetrate inflammatory macrophages over normal cells, and exhibit high photothermal conversion efficiency. Consequently, NIR laser-triggered macrophage treatment can be achieved with high accuracy by pD-SWNT without damaging receptor-free cells. These smart targeting materials can be a novel photothermal agent candidate for inflammatory disease. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Dry-plasma-free chemical etch technique for variability reduction in multi-patterning (Conference Presentation)

NASA Astrophysics Data System (ADS)

Kal, Subhadeep; Mohanty, Nihar; Farrell, Richard A.; Franke, Elliott; Raley, Angelique; Thibaut, Sophie; Pereira, Cheryl; Pillai, Karthik; Ko, Akiteru; Mosden, Aelan; Biolsi, Peter

2017-04-01

Scaling beyond the 7nm technology node demands significant control over the variability down to a few angstroms, in order to achieve reasonable yield. For example, to meet the current scaling targets it is highly desirable to achieve sub 30nm pitch line/space features at back-end of the line (BEOL) or front end of line (FEOL); uniform and precise contact/hole patterning at middle of line (MOL). One of the quintessential requirements for such precise and possibly self-aligned patterning strategies is superior etch selectivity between the target films while other masks/films are exposed. The need to achieve high etch selectivity becomes more evident for unit process development at MOL and BEOL, as a result of low density films choices (compared to FEOL film choices) due to lower temperature budget. Low etch selectivity with conventional plasma and wet chemical etch techniques, causes significant gouging (un-intended etching of etch stop layer, as shown in Fig 1), high line edge roughness (LER)/line width roughness (LWR), non-uniformity, etc. In certain circumstances this may lead to added downstream process stochastics. Furthermore, conventional plasma etches may also have the added disadvantage of plasma VUV damage and corner rounding (Fig. 1). Finally, the above mentioned factors can potentially compromise edge placement error (EPE) and/or yield. Therefore a process flow enabled with extremely high selective etches inherent to film properties and/or etch chemistries is a significant advantage. To improve this etch selectivity for certain etch steps during a process flow, we have to implement alternate highly selective, plasma free techniques in conjunction with conventional plasma etches (Fig 2.). In this article, we will present our plasma free, chemical gas phase etch technique using chemistries that have high selectivity towards a spectrum of films owing to the reaction mechanism ( as shown Fig 1). Gas phase etches also help eliminate plasma damage to the features during the etch process. Herein we will also demonstrate a test case on how a combination or plasma assisted and plasma free etch techniques has the potential to improve process performance of a 193nm immersion based self aligned quandruple patterning (SAQP) for BEOL compliant films (an example shown in Fig 2). In addition, we will also present on the application of gas etches for (1) profile improvement, (2) selective mandrel pull (3) critical dimension trim of mandrels, with an analysis of advantages over conventional techniques in terms of LER and EPE.

Category search speeds up face-selective fMRI responses in a non-hierarchical cortical face network.

PubMed

Jiang, Fang; Badler, Jeremy B; Righi, Giulia; Rossion, Bruno

2015-05-01

The human brain is extremely efficient at detecting faces in complex visual scenes, but the spatio-temporal dynamics of this remarkable ability, and how it is influenced by category-search, remain largely unknown. In the present study, human subjects were shown gradually-emerging images of faces or cars in visual scenes, while neural activity was recorded using functional magnetic resonance imaging (fMRI). Category search was manipulated by the instruction to indicate the presence of either a face or a car, in different blocks, as soon as an exemplar of the target category was detected in the visual scene. The category selectivity of most face-selective areas was enhanced when participants were instructed to report the presence of faces in gradually decreasing noise stimuli. Conversely, the same regions showed much less selectivity when participants were instructed instead to detect cars. When "face" was the target category, the fusiform face area (FFA) showed consistently earlier differentiation of face versus car stimuli than did the "occipital face area" (OFA). When "car" was the target category, only the FFA showed differentiation of face versus car stimuli. These observations provide further challenges for hierarchical models of cortical face processing and show that during gradual revealing of information, selective category-search may decrease the required amount of information, enhancing and speeding up category-selective responses in the human brain. Copyright © 2015 Elsevier Ltd. All rights reserved.

Characteristics of W-26% Re Target Material(LCC-0103)

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

Sunwoo, A.

2003-10-07

The W-26 wt-% Re alloy was selected as a Stanford Linear Collider (SLC) target material for its exceptional physics properties and for the high strength and good ductility at the anticipated target operating temperatures, above the DBTT. After several years of operation, the target failed catastrophically. A detailed microstructural and mechanical characterization of the non-irradiated disk indicates that the material has been PM processed, nonuniformly mechanically worked and stress relieved. As a result, the ductility of the material varies through the thickness of the disk, making it difficult to determine the DBTT. The results of tensile and fatigue properties aremore » reported with the corresponding fractography of the fracture surfaces.« less

Age-related decline in bottom-up processing and selective attention in the very old.

PubMed

Zhuravleva, Tatyana Y; Alperin, Brittany R; Haring, Anna E; Rentz, Dorene M; Holcomb, Philip J; Daffner, Kirk R

2014-06-01

Previous research demonstrating age-related deficits in selective attention have not included old-old adults, an increasingly important group to study. The current investigation compared event-related potentials in 15 young-old (65-79 years old) and 23 old-old (80-99 years old) subjects during a color-selective attention task. Subjects responded to target letters in a specified color (Attend) while ignoring letters in a different color (Ignore) under both low and high loads. There were no group differences in visual acuity, accuracy, reaction time, or latency of early event-related potential components. The old-old group showed a disruption in bottom-up processing, indexed by a substantially diminished posterior N1 (smaller amplitude). They also demonstrated markedly decreased modulation of bottom-up processing based on selected visual features, indexed by the posterior selection negativity (SN), with similar attenuation under both loads. In contrast, there were no group differences in frontally mediated attentional selection, measured by the anterior selection positivity (SP). There was a robust inverse relationship between the size of the SN and SP (the smaller the SN, the larger the SP), which may represent an anteriorly supported compensatory mechanism. In the absence of a decline in top-down modulation indexed by the SP, the diminished SN may reflect age-related degradation of early bottom-up visual processing in old-old adults.

MultiMiTar: a novel multi objective optimization based miRNA-target prediction method.

PubMed

Mitra, Ramkrishna; Bandyopadhyay, Sanghamitra

2011-01-01

Machine learning based miRNA-target prediction algorithms often fail to obtain a balanced prediction accuracy in terms of both sensitivity and specificity due to lack of the gold standard of negative examples, miRNA-targeting site context specific relevant features and efficient feature selection process. Moreover, all the sequence, structure and machine learning based algorithms are unable to distribute the true positive predictions preferentially at the top of the ranked list; hence the algorithms become unreliable to the biologists. In addition, these algorithms fail to obtain considerable combination of precision and recall for the target transcripts that are translationally repressed at protein level. In the proposed article, we introduce an efficient miRNA-target prediction system MultiMiTar, a Support Vector Machine (SVM) based classifier integrated with a multiobjective metaheuristic based feature selection technique. The robust performance of the proposed method is mainly the result of using high quality negative examples and selection of biologically relevant miRNA-targeting site context specific features. The features are selected by using a novel feature selection technique AMOSA-SVM, that integrates the multi objective optimization technique Archived Multi-Objective Simulated Annealing (AMOSA) and SVM. MultiMiTar is found to achieve much higher Matthew's correlation coefficient (MCC) of 0.583 and average class-wise accuracy (ACA) of 0.8 compared to the others target prediction methods for a completely independent test data set. The obtained MCC and ACA values of these algorithms range from -0.269 to 0.155 and 0.321 to 0.582, respectively. Moreover, it shows a more balanced result in terms of precision and sensitivity (recall) for the translationally repressed data set as compared to all the other existing methods. An important aspect is that the true positive predictions are distributed preferentially at the top of the ranked list that makes MultiMiTar reliable for the biologists. MultiMiTar is now available as an online tool at www.isical.ac.in/~bioinfo_miu/multimitar.htm. MultiMiTar software can be downloaded from www.isical.ac.in/~bioinfo_miu/multimitar-download.htm.

Aptamer Selection Express: A Novel Method for Rapid Single-Step Selection and Sensing of Aptamers

PubMed Central

Fan, Maomian; McBurnett, Shelly Roper; Andrews, Carrie J.; Allman, Amity M.; Bruno, John G.; Kiel, Johnathan L.

2008-01-01

Here we describe a new DNA capture element (DCE) sensing system, based on the quenching and dequenching of a double-stranded aptamer. This system shows very good sensitivity and thermal stability. While quenching, dequenching, and separating the DCE systems made from different aptamers (all selected by SELEX), an alternative method to rapidly select aptamers was developed—the Aptamer Selection Express (ASExp). This process has been used to select aptamers against different types of targets (Bacillus anthracis spores, Bacillus thuringiensis spores, MS-2 bacteriophage, ovalbumin, and botulinum neurotoxin). The DCE systems made from botulinum neurotoxin aptamers selected by ASExp have been investigated. The results of this investigation indicate that ASExp can be used to rapidly select aptamers for the DCE sensing system. PMID:19183794

Targeting Lysine Deacetylases (KDACs) in Parasites

PubMed Central

Wang, Qi; Rosa, Bruce A.; Nare, Bakela; Powell, Kerrie; Valente, Sergio; Rotili, Dante; Mai, Antonello; Marshall, Garland R.; Mitreva, Makedonka

2015-01-01

Due to an increasing problem of drug resistance among almost all parasites species ranging from protists to worms, there is an urgent need to explore new drug targets and their inhibitors to provide new and effective parasitic therapeutics. In this regard, there is growing interest in exploring known drug leads of human epigenetic enzymes as potential starting points to develop novel treatments for parasitic diseases. This approach of repurposing (starting with validated targets and inhibitors) is quite attractive since it has the potential to reduce the expense of drug development and accelerate the process of developing novel drug candidates for parasite control. Lysine deacetylases (KDACs) are among the most studied epigenetic drug targets of humans, and a broad range of small-molecule inhibitors for these enzymes have been reported. In this work, we identify the KDAC protein families in representative species across important classes of parasites, screen a compound library of 23 hydroxamate- or benzamide-based small molecules KDAC inhibitors, and report their activities against a range of parasitic species, including the pathogen of malaria (Plasmodium falciparum), kinetoplastids (Trypanosoma brucei and Leishmania donovani), and nematodes (Brugia malayi, Dirofilaria immitis and Haemonchus contortus). Compound activity against parasites is compared to that observed against the mammalian cell line (L929 mouse fibroblast) in order to determine potential parasite-versus-host selectivity). The compounds showed nanomolar to sub-nanomolar potency against various parasites, and some selectivity was observed within the small panel of compounds tested. The possible binding modes of the active compounds at the different protein target sites within different species were explored by docking to homology models to help guide the discovery of more selective, parasite-specific inhibitors. This current work supports previous studies that explored the use of KDAC inhibitors in targeting Plasmodium to develop new anti-malarial treatments, and also pioneers experiments with these KDAC inhibitors as potential new anthelminthics. The selectivity observed begins to address the challenges of targeting specific parasitic diseases while limiting host toxicity. PMID:26402733

Strategic Planning and the Marketing Process: Library Applications.

ERIC Educational Resources Information Center

Wood, Elizabeth J.

1983-01-01

Illustrates how basic principles of marketing and strategic market planning can be applied to libraries and discusses some concepts of strategic planning (organization mission, objectives and goals, growth strategy, program portfolio plan) and marketing (opportunity analysis, target market selection, marketing mix strategy, marketing systems…

Frameshifting in the p6 cDNA phage display system.

PubMed

Govarts, Cindy; Somers, Klaartje; Stinissen, Piet; Somers, Veerle

2010-12-20

Phage display is a powerful technique that enables easy identification of targets for any type of ligand. Targets are displayed at the phage surface as a fusion protein to one of the phage coat proteins. By means of a repeated process of affinity selection on a ligand, specific enrichment of displayed targets will occur. In our studies using C-terminal display of cDNA fragments to phage coat protein p6, we noticed the occasional enrichment of targets that do not contain an open reading frame. This event has previously been described in other phage display studies using N-terminal display of targets to phage coat proteins and was due to uncommon translational events like frameshifting. The aim of this study was to examine if C-terminal display of targets to p6 is also subjected to frameshifting. To this end, an enriched target not containing an open reading frame was selected and an E-tag was coupled at the C-terminus in order to measure target display at the surface of the phage. The tagged construct was subsequently expressed in 3 different reading frames and display of both target and E-tag measured to detect the occurrence of frameshifting. As a result, we were able to demonstrate display of the target both in the 0 and in the +1 reading frame indicating that frameshifting can also take place when C-terminal fusion to minor coat protein p6 is applied.

p62 Targeting to the autophagosome formation site requires self-oligomerization but not LC3 binding.

PubMed

Itakura, Eisuke; Mizushima, Noboru

2011-01-10

Autophagy is an intracellular degradation process by which cytoplasmic contents are degraded in the lysosome. In addition to nonselective engulfment of cytoplasmic materials, the autophagosomal membrane can selectively recognize specific proteins and organelles. It is generally believed that the major selective substrate (or cargo receptor) p62 is recruited to the autophagosomal membrane through interaction with LC3. In this study, we analyzed loading of p62 and its related protein NBR1 and found that they localize to the endoplasmic reticulum (ER)-associated autophagosome formation site independently of LC3 localization to membranes. p62 colocalizes with upstream autophagy factors such as ULK1 and VMP1 even when autophagosome formation is blocked by wortmannin or FIP200 knockout. Self-oligomerization of p62 is essential for its localization to the autophagosome formation site. These results suggest that p62 localizes to the autophagosome formation site on the ER, where autophagosomes are nucleated. This process is similar to the yeast cytoplasm to vacuole targeting pathway.

New learning following reactivation in the human brain: targeting emotional memories through rapid serial visual presentation.

PubMed

Wirkner, Janine; Löw, Andreas; Hamm, Alfons O; Weymar, Mathias

2015-03-01

Once reactivated, previously consolidated memories destabilize and have to be reconsolidated to persist, a process that might be altered non-invasively by interfering learning immediately after reactivation. Here, we investigated the influence of interference on brain correlates of reactivated episodic memories for emotional and neutral scenes using event-related potentials (ERPs). To selectively target emotional memories we applied a new reactivation method: rapid serial visual presentation (RSVP). RSVP leads to enhanced implicit processing (pop out) of the most salient memories making them vulnerable to disruption. In line, interference after reactivation of previously encoded pictures disrupted recollection particularly for emotional events. Furthermore, memory impairments were reflected in a reduced centro-parietal ERP old/new difference during retrieval of emotional pictures. These results provide neural evidence that emotional episodic memories in humans can be selectively altered through behavioral interference after reactivation, a finding with further clinical implications for the treatment of anxiety disorders. Copyright © 2015 Elsevier Inc. All rights reserved.

Process evaluation and in vitro selectivity analysis of aptamer-drug polymeric formulation for targeted pharmaceutical delivery.

PubMed

Tan, Kei X; Lau, Sie Yon; Danquah, Michael K

2018-05-01

Targeted drug delivery is a promising strategy to promote effective delivery of conventional and emerging pharmaceuticals. The emergence of aptamers as superior targeting ligands to direct active drug molecules specifically to desired malignant cells has created new opportunities to enhance disease therapies. The application of biodegradable polymers as delivery carriers to develop aptamer-navigated drug delivery system is a promising approach to effectively deliver desired drug dosages to target cells. This study reports the development of a layer-by-layer aptamer-mediated drug delivery system (DPAP) via a w/o/w double emulsion technique homogenized by ultrasonication or magnetic stirring. Experimental results showed no significant differences in the biophysical characteristics of DPAP nanoparticles generated using the two homogenization techniques. The DPAP formulation demonstrated a strong targeting performance and selectivity towards its target receptor molecules in the presence of non-targets. The DPAP formulation demonstrated a controlled and sustained drug release profile under the conditions of pH 7 and temperature 37 °C. Also, the drug release rate of DPAP formulation was successfully accelerated under an endosomal acidic condition of ∼pH 5.5, indicating the potential to enhance drug delivery within the endosomal micro-environment. The findings from this work are useful to understanding polymer-aptamer-drug relationship and their impact on developing effective targeted delivery systems. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

Histone deacetylases in monocyte/macrophage development, activation and metabolism: refining HDAC targets for inflammatory and infectious diseases.

PubMed

Das Gupta, Kaustav; Shakespear, Melanie R; Iyer, Abishek; Fairlie, David P; Sweet, Matthew J

2016-01-01

Macrophages have central roles in danger detection, inflammation and host defense, and consequently, these cells are intimately linked to most disease processes. Major advances in our understanding of the development and function of macrophages have recently come to light. For example, it is now clear that tissue-resident macrophages can be derived from either blood monocytes or through local proliferation of phagocytes that are originally seeded during embryonic development. Metabolic state has also emerged as a major control point for macrophage activation phenotypes. Herein, we review recent literature linking the histone deacetylase (HDAC) family of enzymes to macrophage development and activation, particularly in relation to these recent developments. There has been considerable interest in potential therapeutic applications for small molecule inhibitors of HDACs (HDACi), not only for cancer, but also for inflammatory and infectious diseases. However, the enormous range of molecular and cellular processes that are controlled by different HDAC enzymes presents a potential stumbling block to clinical development. We therefore present examples of how classical HDACs control macrophage functions, roles of specific HDACs in these processes and approaches for selective targeting of drugs, such as HDACi, to macrophages. Development of selective inhibitors of macrophage-expressed HDACs and/or selective delivery of pan HDACi to macrophages may provide avenues for enhancing efficacy of HDACi in therapeutic applications, while limiting unwanted side effects.

Histone deacetylases in monocyte/macrophage development, activation and metabolism: refining HDAC targets for inflammatory and infectious diseases

PubMed Central

Das Gupta, Kaustav; Shakespear, Melanie R; Iyer, Abishek; Fairlie, David P; Sweet, Matthew J

2016-01-01

Macrophages have central roles in danger detection, inflammation and host defense, and consequently, these cells are intimately linked to most disease processes. Major advances in our understanding of the development and function of macrophages have recently come to light. For example, it is now clear that tissue-resident macrophages can be derived from either blood monocytes or through local proliferation of phagocytes that are originally seeded during embryonic development. Metabolic state has also emerged as a major control point for macrophage activation phenotypes. Herein, we review recent literature linking the histone deacetylase (HDAC) family of enzymes to macrophage development and activation, particularly in relation to these recent developments. There has been considerable interest in potential therapeutic applications for small molecule inhibitors of HDACs (HDACi), not only for cancer, but also for inflammatory and infectious diseases. However, the enormous range of molecular and cellular processes that are controlled by different HDAC enzymes presents a potential stumbling block to clinical development. We therefore present examples of how classical HDACs control macrophage functions, roles of specific HDACs in these processes and approaches for selective targeting of drugs, such as HDACi, to macrophages. Development of selective inhibitors of macrophage-expressed HDACs and/or selective delivery of pan HDACi to macrophages may provide avenues for enhancing efficacy of HDACi in therapeutic applications, while limiting unwanted side effects. PMID:26900475

Monitoring Processes in Visual Search Enhanced by Professional Experience: The Case of Orange Quality-Control Workers

PubMed Central

Visalli, Antonino; Vallesi, Antonino

2018-01-01

Visual search tasks have often been used to investigate how cognitive processes change with expertise. Several studies have shown visual experts' advantages in detecting objects related to their expertise. Here, we tried to extend these findings by investigating whether professional search experience could boost top-down monitoring processes involved in visual search, independently of advantages specific to objects of expertise. To this aim, we recruited a group of quality-control workers employed in citrus farms. Given the specific features of this type of job, we expected that the extensive employment of monitoring mechanisms during orange selection could enhance these mechanisms even in search situations in which orange-related expertise is not suitable. To test this hypothesis, we compared performance of our experimental group and of a well-matched control group on a computerized visual search task. In one block the target was an orange (expertise target) while in the other block the target was a Smurfette doll (neutral target). The a priori hypothesis was to find an advantage for quality-controllers in those situations in which monitoring was especially involved, that is, when deciding the presence/absence of the target required a more extensive inspection of the search array. Results were consistent with our hypothesis. Quality-controllers were faster in those conditions that extensively required monitoring processes, specifically, the Smurfette-present and both target-absent conditions. No differences emerged in the orange-present condition, which resulted to mainly rely on bottom-up processes. These results suggest that top-down processes in visual search can be enhanced through immersive real-life experience beyond visual expertise advantages. PMID:29497392

Surrogate species selection for assessing potential adverse environmental impacts of genetically engineered insect-resistant plants on non-target organisms

PubMed Central

Carstens, Keri; Cayabyab, Bonifacio; De Schrijver, Adinda; Gadaleta, Patricia G; Hellmich, Richard L; Romeis, Jörg; Storer, Nicholas; Valicente, Fernando H; Wach, Michael

2014-01-01

Most regulatory authorities require that developers of genetically engineered insect-resistant (GEIR) crops evaluate the potential for these crops to have adverse impacts on valued non-target organisms (NTOs), i.e., organisms not intended to be controlled by the trait. In many cases, impacts to NTOs are assessed using surrogate species, and it is critical that the data derived from surrogates accurately predict any adverse impacts likely to be observed from the use of the crop in the agricultural context. The key is to select surrogate species that best represent the valued NTOs in the location where the crop is going to be introduced, but this selection process poses numerous challenges for the developers of GE crops who will perform the tests, as well as for the ecologists and regulators who will interpret the test results. These issues were the subject of a conference “Surrogate Species Selection for Assessing Potential Adverse Environmental Impacts of Genetically Engineered Plants on Non-Target Organisms” convened by the Center for Environmental Risk Assessment, ILSI Research Foundation. This report summarizes the proceedings of the conference, including the presentations, discussions and the points of consensus agreed to by the participants. PMID:24637519

Using Data Independent Acquisition (DIA) to Model High-responding Peptides for Targeted Proteomics Experiments*

PubMed Central

Searle, Brian C.; Egertson, Jarrett D.; Bollinger, James G.; Stergachis, Andrew B.; MacCoss, Michael J.

2015-01-01

Targeted mass spectrometry is an essential tool for detecting quantitative changes in low abundant proteins throughout the proteome. Although selected reaction monitoring (SRM) is the preferred method for quantifying peptides in complex samples, the process of designing SRM assays is laborious. Peptides have widely varying signal responses dictated by sequence-specific physiochemical properties; one major challenge is in selecting representative peptides to target as a proxy for protein abundance. Here we present PREGO, a software tool that predicts high-responding peptides for SRM experiments. PREGO predicts peptide responses with an artificial neural network trained using 11 minimally redundant, maximally relevant properties. Crucial to its success, PREGO is trained using fragment ion intensities of equimolar synthetic peptides extracted from data independent acquisition experiments. Because of similarities in instrumentation and the nature of data collection, relative peptide responses from data independent acquisition experiments are a suitable substitute for SRM experiments because they both make quantitative measurements from integrated fragment ion chromatograms. Using an SRM experiment containing 12,973 peptides from 724 synthetic proteins, PREGO exhibits a 40–85% improvement over previously published approaches at selecting high-responding peptides. These results also represent a dramatic improvement over the rules-based peptide selection approaches commonly used in the literature. PMID:26100116

Perceptual load corresponds with factors known to influence visual search

PubMed Central

Roper, Zachary J. J.; Cosman, Joshua D.; Vecera, Shaun P.

2014-01-01

One account of the early versus late selection debate in attention proposes that perceptual load determines the locus of selection. Attention selects stimuli at a late processing level under low-load conditions but selects stimuli at an early level under high-load conditions. Despite the successes of perceptual load theory, a non-circular definition of perceptual load remains elusive. We investigated the factors that influence perceptual load by using manipulations that have been studied extensively in visual search, namely target-distractor similarity and distractor-distractor similarity. Consistent with previous work, search was most efficient when targets and distractors were dissimilar and the displays contained homogeneous distractors; search became less efficient when target-distractor similarity increased irrespective of display heterogeneity. Importantly, we used these same stimuli in a typical perceptual load task that measured attentional spill-over to a task-irrelevant flanker. We found a strong correspondence between search efficiency and perceptual load; stimuli that generated efficient searches produced flanker interference effects, suggesting that such displays involved low perceptual load. Flanker interference effects were reduced in displays that produced less efficient searches. Furthermore, our results demonstrate that search difficulty, as measured by search intercept, has little bearing on perceptual load. These results suggest that perceptual load might be defined in part by well-characterized, continuous factors that influence visual search. PMID:23398258

Improved design of hammerhead ribozyme for selective digestion of target RNA through recognition of site-specific adenosine-to-inosine RNA editing

PubMed Central

Fukuda, Masatora; Kurihara, Kei; Yamaguchi, Shota; Oyama, Yui; Deshimaru, Masanobu

2014-01-01

Adenosine-to-inosine (A-to-I) RNA editing is an endogenous regulatory mechanism involved in various biological processes. Site-specific, editing-state–dependent degradation of target RNA may be a powerful tool both for analyzing the mechanism of RNA editing and for regulating biological processes. Previously, we designed an artificial hammerhead ribozyme (HHR) for selective, site-specific RNA cleavage dependent on the A-to-I RNA editing state. In the present work, we developed an improved strategy for constructing a trans-acting HHR that specifically cleaves target editing sites in the adenosine but not the inosine state. Specificity for unedited sites was achieved by utilizing a sequence encoding the intrinsic cleavage specificity of a natural HHR. We used in vitro selection methods in an HHR library to select for an extended HHR containing a tertiary stabilization motif that facilitates HHR folding into an active conformation. By using this method, we successfully constructed highly active HHRs with unedited-specific cleavage. Moreover, using HHR cleavage followed by direct sequencing, we demonstrated that this ribozyme could cleave serotonin 2C receptor (HTR2C) mRNA extracted from mouse brain, depending on the site-specific editing state. This unedited-specific cleavage also enabled us to analyze the effect of editing state at the E and C sites on editing at other sites by using direct sequencing for the simultaneous quantification of the editing ratio at multiple sites. Our approach has the potential to elucidate the mechanism underlying the interdependencies of different editing states in substrate RNA with multiple editing sites. PMID:24448449

Phenotype-information-phenotype cycle for deconvolution of combinatorial antibody libraries selected against complex systems.

PubMed

Zhang, Hongkai; Torkamani, Ali; Jones, Teresa M; Ruiz, Diana I; Pons, Jaume; Lerner, Richard A

2011-08-16

Use of large combinatorial antibody libraries and next-generation sequencing of nucleic acids are two of the most powerful methods in modern molecular biology. The libraries are screened using the principles of evolutionary selection, albeit in real time, to enrich for members with a particular phenotype. This selective process necessarily results in the loss of information about less-fit molecules. On the other hand, sequencing of the library, by itself, gives information that is mostly unrelated to phenotype. If the two methods could be combined, the full potential of very large molecular libraries could be realized. Here we report the implementation of a phenotype-information-phenotype cycle that integrates information and gene recovery. After selection for phage-encoded antibodies that bind to targets expressed on the surface of Escherichia coli, the information content of the selected pool is obtained by pyrosequencing. Sequences that encode specific antibodies are identified by a bioinformatic analysis and recovered by a stringent affinity method that is uniquely suited for gene isolation from a highly degenerate collection of nucleic acids. This approach can be generalized for selection of antibodies against targets that are present as minor components of complex systems.

Lung microenvironment promotes the metastasis of human hepatocellular carcinoma cells to the lungs.

PubMed

Jin, Yun; Ai, Junhua; Shi, Jun

2015-01-01

Cancer metastasis is a highly tissue-specific and organ-selective process. It has been shown that the affected tissues and/or organs play a major role in this complex process. The lung is the most common target organ of extrahepatic hepatocellular carcinoma (HCC) metastasis, but the precise molecular mechanism underlying this organ-specific metastasis remains unclear. We hypothesized that lung microenvironment was able to promote the metastasis of HCC cells to the lungs leading to distant metastases. In support of our hypothesis, we provided evidence from targeted metastasis in various types of cancer and contributing factors in the microenvironment of targeted tissues/organs. A better understanding of the steps involved in the interplay between HCC cells and lung microenvironment may offer new perspectives for the medical management of lung metastases of HCC.

Evaluation of advanced wastewater treatment systems for water reuse in the era of advanced wastewater treatment

NASA Astrophysics Data System (ADS)

Kon, Hisao; Watanabe, Masahiro

This study focuses on effluent COD concentration from wastewater treatment in regards to the reduction of pathogenic bacteria and trace substances in public waters. The main types of secondary wastewater treatment were conventional activated sludge processes. Recently, however, advance wastewater treatment processes have been developed aimed at the removal of nitrogen and phosphorus, and the effluent quality of these processes was analyzed in this study. Treatment processes for water reclamation that make effluent to meet the target water quality for reuse purposes were selected and also optimum design parameters for these processes were proposed. It was found that the treatment cost to water reclamation was greatly affected by the effluent COD of the secondary treatment. It is important to maintain low COD concentration in the secondary treated effluent. Therefore, it is considered that adequate cost benefits would be obtained by achieving target COD quality through shifting from a conventional activated sludge process to an advanced treatment process.

Selecting Great Lakes streams for lampricide treatment based on larval sea lamprey surveys

USGS Publications Warehouse

Christie, Gavin C.; Adams, Jean V.; Steeves, Todd B.; Slade, Jeffrey W.; Cuddy, Douglas W.; Fodale, Michael F.; Young, Robert J.; Kuc, Miroslaw; Jones, Michael L.

2003-01-01

The Empiric Stream Treatment Ranking (ESTR) system is a data-driven, model-based, decision tool for selecting Great Lakes streams for treatment with lampricide, based on estimates from larval sea lamprey (Petromyzon marinus) surveys conducted throughout the basin. The 2000 ESTR system was described and applied to larval assessment surveys conducted from 1996 to 1999. A comparative analysis of stream survey and selection data was conducted and improvements to the stream selection process were recommended. Streams were selected for treatment based on treatment cost, predicted treatment effectiveness, and the projected number of juvenile sea lampreys produced. On average, lampricide treatments were applied annually to 49 streams with 1,075 ha of larval habitat, killing 15 million larval and 514,000 juvenile sea lampreys at a total cost of $5.3 million, and marginal and mean costs of $85 and $10 per juvenile killed. The numbers of juvenile sea lampreys killed for given treatment costs showed a pattern of diminishing returns with increasing investment. Of the streams selected for treatment, those with > 14 ha of larval habitat targeted 73% of the juvenile sea lampreys for 60% of the treatment cost. Suggested improvements to the ESTR system were to improve accuracy and precision of model estimates, account for uncertainty in estimates, include all potentially productive streams in the process (not just those surveyed in the current year), consider the value of all larvae killed during treatment (not just those predicted to metamorphose the following year), use lake-specific estimates of damage, and establish formal suppression targets.

Atypical category processing and hemispheric asymmetries in high-functioning children with autism: revealed through high-density EEG mapping.

PubMed

Fiebelkorn, Ian C; Foxe, John J; McCourt, Mark E; Dumas, Kristina N; Molholm, Sophie

2013-05-01

Behavioral evidence for an impaired ability to group objects based on similar physical or semantic properties in autism spectrum disorders (ASD) has been mixed. Here, we recorded brain activity from high-functioning children with ASD as they completed a visual-target detection task. We then assessed the extent to which object-based selective attention automatically generalized from targets to non-target exemplars from the same well-known object class (e.g., dogs). Our results provide clear electrophysiological evidence that children with ASD (N=17, aged 8-13 years) process the similarity between targets (e.g., a specific dog) and same-category non-targets (SCNT) (e.g., another dog) to a lesser extent than do their typically developing (TD) peers (N=21). A closer examination of the data revealed striking hemispheric asymmetries that were specific to the ASD group. These findings align with mounting evidence in the autism literature of anatomic underconnectivity between the cerebral hemispheres. Years of research in individuals with TD have demonstrated that the left hemisphere (LH) is specialized toward processing local (or featural) stimulus properties and the right hemisphere (RH) toward processing global (or configural) stimulus properties. We therefore propose a model where a lack of communication between the hemispheres in ASD, combined with typical hemispheric specialization, is a root cause for impaired categorization and the oft-observed bias to process local over global stimulus properties. Copyright © 2012 Elsevier Ltd. All rights reserved.

Programming Native CRISPR Arrays for the Generation of Targeted Immunity.

PubMed

Hynes, Alexander P; Labrie, Simon J; Moineau, Sylvain

2016-05-03

The adaptive immune system of prokaryotes, called CRISPR-Cas (clustered regularly interspaced short palindromic repeats and CRISPR-associated genes), results in specific cleavage of invading nucleic acid sequences recognized by the cell's "memory" of past encounters. Here, we exploited the properties of native CRISPR-Cas systems to program the natural "memorization" process, efficiently generating immunity not only to a bacteriophage or plasmid but to any specifically chosen DNA sequence. CRISPR-Cas systems have entered the public consciousness as genome editing tools due to their readily programmable nature. In industrial settings, natural CRISPR-Cas immunity is already exploited to generate strains resistant to potentially disruptive viruses. However, the natural process by which bacteria acquire new target specificities (adaptation) is difficult to study and manipulate. The target against which immunity is conferred is selected stochastically. By biasing the immunization process, we offer a means to generate customized immunity, as well as provide a new tool to study adaptation. Copyright © 2016 Hynes et al.

Effects of aging and involuntary capture of attention on event-related potentials associated with the processing of and the response to a target stimulus

PubMed Central

Cid-Fernández, Susana; Lindín, Mónica; Díaz, Fernando

2014-01-01

The main aim of the present study was to assess whether aging modulates the effects of involuntary capture of attention by novel stimuli on performance, and on event-related potentials (ERPs) associated with target processing (N2b and P3b) and subsequent response processes (stimulus-locked Lateralized Readiness Potential -sLRP- and response-locked Lateralized Readiness Potential -rLRP-). An auditory-visual distraction-attention task was performed by 77 healthy participants, divided into three age groups (Young: 21–29, Middle-aged: 51–64, Old: 65–84 years old). Participants were asked to attend to visual stimuli and to ignore auditory stimuli. Aging was associated with slowed reaction times, target stimulus processing in working memory (WM, longer N2b and P3b latencies) and selection and preparation of the motor response (longer sLRP and earlier rLRP onset latencies). In the novel relative to the standard condition we observed, in the three age groups: (1) a distraction effect, reflected in a slowing of reaction times, of stimuli categorization in WM (longer P3b latency), and of motor response selection (longer sLRP onset latency); (2) a facilitation effect on response preparation (later rLRP onset latency), and (3) an increase in arousal (larger amplitudes of all ERPs evaluated, except for N2b amplitude in the Old group). A distraction effect on the stimulus evaluation processes (longer N2b latency) were also observed, but only in middle-aged and old participants, indicating that the attentional capture slows the stimulus evaluation in WM from early ages (from 50 years onwards, without differences between middle-age and older adults), but not in young adults. PMID:25294999

Target Capture during Mos1 Transposition*

PubMed Central

Pflieger, Aude; Jaillet, Jerôme; Petit, Agnès; Augé-Gouillou, Corinne; Renault, Sylvaine

2014-01-01

DNA transposition contributes to genomic plasticity. Target capture is a key step in the transposition process, because it contributes to the selection of new insertion sites. Nothing or little is known about how eukaryotic mariner DNA transposons trigger this step. In the case of Mos1, biochemistry and crystallography have deciphered several inverted terminal repeat-transposase complexes that are intermediates during transposition. However, the target capture complex is still unknown. Here, we show that the preintegration complex (i.e., the excised transposon) is the only complex able to capture a target DNA. Mos1 transposase does not support target commitment, which has been proposed to explain Mos1 random genomic integrations within host genomes. We demonstrate that the TA dinucleotide used as the target is crucial both to target recognition and in the chemistry of the strand transfer reaction. Bent DNA molecules are better targets for the capture when the target DNA is nicked two nucleotides apart from the TA. They improve strand transfer when the target DNA contains a mismatch near the TA dinucleotide. PMID:24269942

Target capture during Mos1 transposition.

PubMed

Pflieger, Aude; Jaillet, Jerôme; Petit, Agnès; Augé-Gouillou, Corinne; Renault, Sylvaine

2014-01-03

DNA transposition contributes to genomic plasticity. Target capture is a key step in the transposition process, because it contributes to the selection of new insertion sites. Nothing or little is known about how eukaryotic mariner DNA transposons trigger this step. In the case of Mos1, biochemistry and crystallography have deciphered several inverted terminal repeat-transposase complexes that are intermediates during transposition. However, the target capture complex is still unknown. Here, we show that the preintegration complex (i.e., the excised transposon) is the only complex able to capture a target DNA. Mos1 transposase does not support target commitment, which has been proposed to explain Mos1 random genomic integrations within host genomes. We demonstrate that the TA dinucleotide used as the target is crucial both to target recognition and in the chemistry of the strand transfer reaction. Bent DNA molecules are better targets for the capture when the target DNA is nicked two nucleotides apart from the TA. They improve strand transfer when the target DNA contains a mismatch near the TA dinucleotide.

Process for separation of zirconium-88, rubidium-83 and yttrium-88

DOEpatents

Heaton, Richard C.; Jamriska, Sr., David J.; Taylor, Wayne A.

1994-01-01

A process for selective separation of strontium-82 and strontium-85 from proton irradiated molybdenum targets is provided and includes dissolving the molybdenum target in a hydrogen peroxide solution to form a first ion-containing solution, passing the first ion-containing solution through a first cationic resin whereby ions selected from the group consisting of molybdenum, niobium, technetium, selenium, vanadium, arsenic, germanium, zirconium and rubidium remain in the first ion-containing solution while ions selected from the group consisting of rubidium, zinc, beryllium, cobalt, iron, manganese, chromium, strontium, yttrium and zirconium are selectively adsorbed by the first resin, contacting the first resin with an acid solution capable of stripping adsorbed ions from the first cationic exchange resin whereby the adsorbed ions are removed from the first resin to form a second ion-containing solution, evaporating the second ion-containing solution for time sufficient to remove substantially all of the acid and water from the second ion-containing solution whereby a residue remains, dissolving the residue from the evaporated second-ion containing solution in a dilute acid to form a third ion-containing solution, said third ion-containing solution having an acid molarity adapted to permit said ions to be adsorbed by a cationic exchange resin, passing the third ion-containing solution through a second cationic resin whereby the ions are adsorbed by the second resin, contacting the second resin with a dilute sulfuric acid solution whereby the adsorbed ions selected from the group consisting of rubidium, zinc, beryllium, cobalt, iron, manganese, chromium, and zirconium are selectively removed from the second resin, and contacting the second resin with a dilute acid solution whereby the adsorbed strontium ions are selectively removed. Zirconium, rubidium, and yttrium radioisotopes can also be recovered with additional steps.

Discovery of highly selective inhibitors of p38alpha.

PubMed

Popa-Burke, Ioana; Birkos, Steve; Blackwell, Leonard; Cheatham, Lynn; Clark, Jennifer; Dickson, John K; Galasinski, Scott; Janzen, William P; Mendoza, Jose; Miller, Jennifer L; Mohney, Robert P; Steed, Paul M; Hodge, C Nicholas

2005-01-01

The p38 MAP kinases are a family of serine/threonine protein kinases that play a key role in cellular pathways leading to pro-inflammatory responses. We have developed and implemented a method for rapidly identifying and optimizing potent and selective p38alpha inhibitors, which is amenable to other targets and target classes. A diverse library of druggable, purified and quantitated molecules was assembled and standardized enzymatic assays were performed in a microfluidic format that provided very accurate and precise inhibition data allowing for development of SAR directly from the primary HTS. All compounds were screened against a collection of more than 60 enzymes (kinases, proteases and phosphatases), allowing for removal of promiscuous and non-selective inhibitors very early in the discovery process. Follow-up enzymological studies included measurement of concentration of compound in buffer, yielding accurate determination of K(i) and IC50 values, as well as mechanism of action. In addition, active compounds were screened against less desirable properties such as inhibition of the enzyme activity by aggregation, irreversible binding, and time-dependence. Screening of an 88,634-compound library through the above-described process led to the rapid identification of multiple scaffolds (>5 active compounds per scaffold) of potential drug leads for p38alpha that are highly selective against all other enzymes tested, including the three other p38 isoforms. Potency and selectivity data allowed prioritization of the identified scaffolds for optimization. Herein we present results around our 3-thio-1,2,4-triazole lead series of p38- selective inhibitors, including identification, SAR, synthesis, selectivity profile, enzymatic and cellular data in their progression towards drug candidates.

Advancing Treatment of Pituitary Adenomas through Targeted Molecular Therapies: The Acromegaly and Cushing Disease Paradigms.

PubMed

Mooney, Michael A; Simon, Elias D; Little, Andrew S

2016-01-01

The current treatment of pituitary adenomas requires a balance of conservative management, surgical resection, and in select tumor types, molecular therapy. Acromegaly treatment is an evolving field where our understanding of molecular targets and drug therapies has improved treatment options for patients with excess growth hormone levels. We highlight the use of molecular therapies in this disease process and advances in this field, which may represent a paradigm shift for the future of pituitary adenoma treatment.

Tomographic diffractive microscopy with agile illuminations for imaging targets in a noisy background.

PubMed

Zhang, T; Godavarthi, C; Chaumet, P C; Maire, G; Giovannini, H; Talneau, A; Prada, C; Sentenac, A; Belkebir, K

2015-02-15

Tomographic diffractive microscopy is a marker-free optical digital imaging technique in which three-dimensional samples are reconstructed from a set of holograms recorded under different angles of incidence. We show experimentally that, by processing the holograms with singular value decomposition, it is possible to image objects in a noisy background that are invisible with classical wide-field microscopy and conventional tomographic reconstruction procedure. The targets can be further characterized with a selective quantitative inversion.

Targeted delivery of antigen processing inhibitors to antigen presenting cells via mannose receptors.

PubMed

Raiber, Eun-Ang; Tulone, Calogero; Zhang, Yanjing; Martinez-Pomares, Luisa; Steed, Emily; Sponaas, Anna M; Langhorne, Jean; Noursadeghi, Mahdad; Chain, Benjamin M; Tabor, Alethea B

2010-05-21

Improved chemical inhibitors are required to dissect the role of specific antigen processing enzymes and to complement genetic models. In this study we explore the in vitro and in vivo properties of a novel class of targeted inhibitor of aspartic proteinases, in which pepstatin is coupled to mannosylated albumin (MPC6), creating an inhibitor with improved solubility and the potential for selective cell tropism. Using these compounds, we have demonstrated that MPC6 is taken up via mannose receptor facilitated endocytosis, leading to a slow but continuous accumulation of inhibitor within large endocytic vesicles within dendritic cells and a parallel inhibition of intracellular aspartic proteinase activity. Inhibition of intracellular proteinase activity is associated with reduction in antigen processing activity, but this is epitope-specific, preferentially inhibiting processing of T cell epitopes buried within compact proteinase-resistant protein domains. Unexpectedly, we have also demonstrated, using quenched fluorescent substrates, that little or no cleavage of the disulfide linker takes place within dendritic cells. This does not appear to affect the activity of MPC6 as an inhibitor of cathepsins D and E in vitro and in vivo. Finally, we have shown that MPC6 selectively targets dendritic cells and macrophages in spleen in vivo. Preliminary results suggest that access to nonlymphoid tissues is very limited in the steady state but is strongly enhanced at local sites of inflammation. The strategy adopted for MPC6 synthesis may therefore represent a more general way to deliver chemical inhibitors to cells of the innate immune system, especially at sites of inflammation.

Processing and Properties of a Phenolic Composite System

NASA Technical Reports Server (NTRS)

Hou, Tan-Hung; Bai, J. M.; Baughman, James M.

2006-01-01

Phenolic resin systems generate water as a reaction by-product via condensation reactions during curing at elevated temperatures. In the fabrication of fiber reinforced phenolic resin matrix composites, volatile management is crucial in producing void-free quality laminates. A commercial vacuum-bag moldable phenolic prepreg system was selected for this study. The traditional single-vacuum-bag (SVB) process was unable to manage the volatiles effectively, resulting in inferior voidy laminates. However, a double vacuum bag (DVB) process was shown to afford superior volatile management and consistently yielded void-free quality parts. The DVB process cure cycle (temperature /pressure profiles) for the selected composite system was designed, with the vacuum pressure application point carefully selected, to avoid excessive resin squeeze-outs and achieve the net shape and target resin content in the final consolidated laminate parts. Laminate consolidation quality was characterized by optical photomicrography for the cross sections and measurements of mechanical properties. A 40% increase in short beam shear strength, 30% greater flexural strength, 10% higher tensile and 18% higher compression strengths were obtained in composite laminates fabricated by the DVB process.

Selective intracellular vaporisation of antibody-conjugated phase-change nano-droplets in vitro

NASA Astrophysics Data System (ADS)

Ishijima, A.; Minamihata, K.; Yamaguchi, S.; Yamahira, S.; Ichikawa, R.; Kobayashi, E.; Iijima, M.; Shibasaki, Y.; Azuma, T.; Nagamune, T.; Sakuma, I.

2017-03-01

While chemotherapy is a major mode of cancer therapeutics, its efficacy is limited by systemic toxicities and drug resistance. Recent advances in nanomedicine provide the opportunity to reduce systemic toxicities. However, drug resistance remains a major challenge in cancer treatment research. Here we developed a nanomedicine composed of a phase-change nano-droplet (PCND) and an anti-cancer antibody (9E5), proposing the concept of ultrasound cancer therapy with intracellular vaporisation. PCND is a liquid perfluorocarbon nanoparticle with a liquid-gas phase that is transformable upon exposure to ultrasound. 9E5 is a monoclonal antibody targeting epiregulin (EREG). We found that 9E5-conjugated PCNDs are selectively internalised into targeted cancer cells and kill the cells dynamically by ultrasound-induced intracellular vaporisation. In vitro experiments show that 9E5-conjugated PCND targets 97.8% of high-EREG-expressing cancer cells and kills 57% of those targeted upon exposure to ultrasound. Furthermore, direct observation of the intracellular vaporisation process revealed the significant morphological alterations of cells and the release of intracellular contents.

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

PubMed Central

Xiong, Ji; Li, Fangmin; Zhao, Ning; Jiang, Na

2014-01-01

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%. PMID:24759117

Time course of spatial and feature selective attention for partly-occluded objects.

PubMed

Kasai, Tetsuko; Takeya, Ryuji

2012-07-01

Attention selects objects/groups as the most fundamental units, and this may be achieved by an attention-spreading mechanism. Previous event-related potential (ERP) studies have found that attention-spreading is reflected by a decrease in the N1 spatial attention effect. The present study tested whether the electrophysiological attention effect is associated with the perception of object unity or amodal completion through the use of partly-occluded objects. ERPs were recorded in 14 participants who were required to pay attention to their left or right visual field and to press a button for a target shape in the attended field. Bilateral stimuli were presented rapidly, and were separated, connected, or connected behind an occluder. Behavioral performance in the connected and occluded conditions was worse than that in the separated condition, indicating that attention spread over perceptual object representations after amodal completion. Consistently, the late N1 spatial attention effect (180-220 ms post-stimulus) and the early phase (230-280 ms) of feature selection effects (target N2) at contralateral sites decreased, equally for the occluded and connected conditions, while the attention effect in the early N1 latency (140-180 ms) shifted most positively for the occluded condition. These results suggest that perceptual organization processes for object recognition transiently modulate spatial and feature selection processes in the visual cortex. Copyright © 2012 Elsevier Ltd. All rights reserved.

Mediators of effects of a selective family-focused violence prevention approach for middle school students.

PubMed

2012-02-01

This study examined how parenting and family characteristics targeted in a selective prevention program mediated effects on key youth proximal outcomes related to violence perpetration. The selective intervention was evaluated within the context of a multi-site trial involving random assignment of 37 schools to four conditions: a universal intervention composed of a student social-cognitive curriculum and teacher training, a selective family-focused intervention with a subset of high-risk students, a condition combining these two interventions, and a no-intervention control condition. Two cohorts of sixth-grade students (total N = 1,062) exhibiting high levels of aggression and social influence were the sample for this study. Analyses of pre-post change compared to controls using intent-to-treat analyses found no significant effects. However, estimates incorporating participation of those assigned to the intervention and predicted participation among those not assigned revealed significant positive effects on student aggression, use of aggressive strategies for conflict management, and parental estimation of student's valuing of achievement. Findings also indicated intervention effects on two targeted family processes: discipline practices and family cohesion. Mediation analyses found evidence that change in these processes mediated effects on some outcomes, notably aggressive behavior and valuing of school achievement. Results support the notion that changing parenting practices and the quality of family relationships can prevent the escalation in aggression and maintain positive school engagement for high-risk youth.

Targeted gene flow for conservation.

PubMed

Kelly, Ella; Phillips, Ben L

2016-04-01

Anthropogenic threats often impose strong selection on affected populations, causing rapid evolutionary responses. Unfortunately, these adaptive responses are rarely harnessed for conservation. We suggest that conservation managers pay close attention to adaptive processes and geographic variation, with an eye to using them for conservation goals. Translocating pre-adapted individuals into recipient populations is currently considered a potentially important management tool in the face of climate change. Targeted gene flow, which involves moving individuals with favorable traits to areas where these traits would have a conservation benefit, could have a much broader application in conservation. Across a species' range there may be long-standing geographic variation in traits or variation may have rapidly developed in response to a threatening process. Targeted gene flow could be used to promote natural resistance to threats to increase species resilience. We suggest that targeted gene flow is a currently underappreciated strategy in conservation that has applications ranging from the management of invasive species and their impacts to controlling the impact and virulence of pathogens. © 2015 Society for Conservation Biology.

Guidelines for Effective Selective Listening

DTIC Science & Technology

1979-05-01

N., & Lockhart , R. S. Levels -of processing : A framework for qor research. Journa of Verbal Learnina and Verbal Behavior, Doeknimgo D. 0,9...e.g., Craik & Lockhart , 1972), interfering activities (e.g., Postman, 1961), and manner in which retention is measured (e.g., Postman & Rau, 1957...TO ENHANCE THE PROCESSING OF TARGET I NFORMATIONT 8 WHEN OPERATING IN HEAVY BACKGROUND NOISE, IT MAY BE BENEFICIAL TO MAINTAIN SOME VISUAL CONTACT WITH

Design of freeze-drying processes for pharmaceuticals: practical advice.

PubMed

Tang, Xiaolin; Pikal, Michael J

2004-02-01

Design of freeze-drying processes is often approached with a "trial and error" experimental plan or, worse yet, the protocol used in the first laboratory run is adopted without further attempts at optimization. Consequently, commercial freeze-drying processes are often neither robust nor efficient. It is our thesis that design of an "optimized" freeze-drying process is not particularly difficult for most products, as long as some simple rules based on well-accepted scientific principles are followed. It is the purpose of this review to discuss the scientific foundations of the freeze-drying process design and then to consolidate these principles into a set of guidelines for rational process design and optimization. General advice is given concerning common stability issues with proteins, but unusual and difficult stability issues are beyond the scope of this review. Control of ice nucleation and crystallization during the freezing step is discussed, and the impact of freezing on the rest of the process and final product quality is reviewed. Representative freezing protocols are presented. The significance of the collapse temperature and the thermal transition, denoted Tg', are discussed, and procedures for the selection of the "target product temperature" for primary drying are presented. Furthermore, guidelines are given for selection of the optimal shelf temperature and chamber pressure settings required to achieve the target product temperature without thermal and/or mass transfer overload of the freeze dryer. Finally, guidelines and "rules" for optimization of secondary drying and representative secondary drying protocols are presented.

Radar Methods in Urban Environments

DTIC Science & Technology

2016-10-26

to appear in IEEE Journal of Selected Topics in Signal Processing. J8. M. Wang and A. Nehorai, “Coarrays, MUSIC , and the Cramér Rao bound,” to...Journal Papers: 1. P. Chavali and A. Nehorai, "Scheduling and resource allocation in a cognitive radar network for multiple- target tracking,’’ IEEE...Processing. 33. M. Wang and A. Nehorai, "Coarrays, MUSIC , and the Cramér Rao bound," to appear in IEEE Trans. on Signal Processing. 34. J. Li and A. Nehorai

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

PubMed

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.

Working memory load can both improve and impair selective attention: evidence from the Navon paradigm.

PubMed

Ahmed, Lubna; de Fockert, Jan W

2012-10-01

Selective attention to relevant targets has been shown to depend on the availability of working memory (WM). Under conditions of high WM load, processing of irrelevant distractors is enhanced. Here we showed that this detrimental effect of WM load on selective attention efficiency is reversed when the task requires global- rather than local-level processing. Participants were asked to attend to either the local or the global level of a hierarchical Navon stimulus while keeping either a low or a high load in WM. In line with previous findings, during attention to the local level, distractors at the global level produced more interference under high than under low WM load. By contrast, loading WM had the opposite effect of improving selective attention during attention to the global level. The findings demonstrate that the impact of WM load on selective attention is not invariant, but rather is dependent on the level of the to-be-attended information.

Evolutionary learning processes as the foundation for behaviour change.

PubMed

Crutzen, Rik; Peters, Gjalt-Jorn Ygram

2018-03-01

We argue that the active ingredients of behaviour change interventions, often called behaviour change methods (BCMs) or techniques (BCTs), can usefully be placed on a dimension of psychological aggregation. We introduce evolutionary learning processes (ELPs) as fundamental building blocks that are on a lower level of psychological aggregation than BCMs/BCTs. A better understanding of ELPs is useful to select the appropriate BCMs/BCTs to target determinants of behaviour, or vice versa, to identify potential determinants targeted by a given BCM/BCT, and to optimally translate them into practical applications. Using these insights during intervention development may increase the likelihood of developing effective interventions - both in terms of behaviour change as well as maintenance of behaviour change.

Category-based guidance of spatial attention during visual search for feature conjunctions.

PubMed

Nako, Rebecca; Grubert, Anna; Eimer, Martin

2016-10-01

The question whether alphanumerical category is involved in the control of attentional target selection during visual search remains a contentious issue. We tested whether category-based attentional mechanisms would guide the allocation of attention under conditions where targets were defined by a combination of alphanumerical category and a basic visual feature, and search displays could contain both targets and partially matching distractor objects. The N2pc component was used as an electrophysiological marker of attentional object selection in tasks where target objects were defined by a conjunction of color and category (Experiment 1) or shape and category (Experiment 2). Some search displays contained the target or a nontarget object that matched either the target color/shape or its category among 3 nonmatching distractors. In other displays, the target and a partially matching nontarget object appeared together. N2pc components were elicited not only by targets and by color- or shape-matching nontargets, but also by category-matching nontarget objects, even on trials where a target was present in the same display. On these trials, the summed N2pc components to the 2 types of partially matching nontargets were initially equal in size to the target N2pc, suggesting that attention was allocated simultaneously and independently to all objects with target-matching features during the early phase of attentional processing. Results demonstrate that alphanumerical category is a genuine guiding feature that can operate in parallel with color or shape information to control the deployment of attention during visual search. (PsycINFO Database Record (c) 2016 APA, all rights reserved).

The design and application of a multi-band IR imager

NASA Astrophysics Data System (ADS)

Li, Lijuan

2018-02-01

Multi-band IR imaging system has many applications in security, national defense, petroleum and gas industry, etc. So the relevant technologies are getting more and more attention in rent years. As we know, when used in missile warning and missile seeker systems, multi-band IR imaging technology has the advantage of high target recognition capability and low false alarm rate if suitable spectral bands are selected. Compared with traditional single band IR imager, multi-band IR imager can make use of spectral features in addition to space and time domain features to discriminate target from background clutters and decoys. So, one of the key work is to select the right spectral bands in which the feature difference between target and false target is evident and is well utilized. Multi-band IR imager is a useful instrument to collect multi-band IR images of target, backgrounds and decoys for spectral band selection study at low cost and with adjustable parameters and property compared with commercial imaging spectrometer. In this paper, a multi-band IR imaging system is developed which is suitable to collect 4 spectral band images of various scenes at every turn and can be expanded to other short-wave and mid-wave IR spectral bands combination by changing filter groups. The multi-band IR imaging system consists of a broad band optical system, a cryogenic InSb large array detector, a spinning filter wheel and electronic processing system. The multi-band IR imaging system's performance is tested in real data collection experiments.

Identification and Expression Analyses of miRNAs from Two Contrasting Flower Color Cultivars of Canna by Deep Sequencing.

PubMed

Roy, Sribash; Tripathi, Abhinandan Mani; Yadav, Amrita; Mishra, Parneeta; Nautiyal, Chandra Shekhar

2016-01-01

miRNAs are endogenous small RNA (sRNA) that play critical roles in plant development processes. Canna is an ornamental plant belonging to family Cannaceae. Here, we report for the first time the identification and differential expression of miRNAs in two contrasting flower color cultivars of Canna, Tropical sunrise and Red president. A total of 313 known miRNAs belonging to 78 miRNA families were identified from both the cultivars. Thirty one miRNAs (17 miRNA families) were specific to Tropical sunrise and 43 miRNAs (10 miRNA families) were specific to Red president. Thirty two and 18 putative new miRNAs were identified from Tropical sunrise and Red president, respectively. One hundred and nine miRNAs were differentially expressed in the two cultivars targeting 1343 genes. Among these, 16 miRNAs families targeting 60 genes were involved in flower development related traits and five miRNA families targeting five genes were involved in phenyl propanoid and pigment metabolic processes. We further validated the expression analysis of a few miRNA and their target genes by qRT-PCR. Transcription factors were the major miRNA targets identified. Target validation of a few randomly selected miRNAs by RLM-RACE was performed but was successful with only miR162. These findings will help in understanding flower development processes, particularly the color development in Canna.

The effects of interstimulus interval on event-related indices of attention: an auditory selective attention test of perceptual load theory.

PubMed

Gomes, Hilary; Barrett, Sophia; Duff, Martin; Barnhardt, Jack; Ritter, Walter

2008-03-01

We examined the impact of perceptual load by manipulating interstimulus interval (ISI) in two auditory selective attention studies that varied in the difficulty of the target discrimination. In the paradigm, channels were separated by frequency and target/deviant tones were softer in intensity. Three ISI conditions were presented: fast (300ms), medium (600ms) and slow (900ms). Behavioral (accuracy and RT) and electrophysiological measures (Nd, P3b) were observed. In both studies, participants evidenced poorer accuracy during the fast ISI condition than the slow suggesting that ISI impacted task difficulty. However, none of the three measures of processing examined, Nd amplitude, P3b amplitude elicited by unattended deviant stimuli, or false alarms to unattended deviants, were impacted by ISI in the manner predicted by perceptual load theory. The prediction based on perceptual load theory, that there would be more processing of irrelevant stimuli under conditions of low as compared to high perceptual load, was not supported in these auditory studies. Task difficulty/perceptual load impacts the processing of irrelevant stimuli in the auditory modality differently than predicted by perceptual load theory, and perhaps differently than in the visual modality.

Genetic landscape and deregulated pathways in B-cell lymphoid malignancies.

PubMed

Rosenquist, R; Beà, S; Du, M-Q; Nadel, B; Pan-Hammarström, Q

2017-11-01

With the introduction of next-generation sequencing, the genetic landscape of the complex group of B-cell lymphoid malignancies has rapidly been unravelled in recent years. This has provided important information about recurrent genetic events and identified key pathways deregulated in each lymphoma subtype. In parallel, there has been intense search and development of novel types of targeted therapy that 'hit' central mechanisms in lymphoma pathobiology, such as BTK, PI3K or BCL2 inhibitors. In this review, we will outline the current view of the genetic landscape of selected entities: follicular lymphoma, diffuse large B-cell lymphoma, mantle cell lymphoma, chronic lymphocytic leukaemia and marginal zone lymphoma. We will detail recurrent alterations affecting important signalling pathways, that is the B-cell receptor/NF-κB pathway, NOTCH signalling, JAK-STAT signalling, p53/DNA damage response, apoptosis and cell cycle regulation, as well as other perhaps unexpected cellular processes, such as immune regulation, cell migration, epigenetic regulation and RNA processing. Whilst many of these pathways/processes are commonly altered in different lymphoid tumors, albeit at varying frequencies, others are preferentially targeted in selected B-cell malignancies. Some of these genetic lesions are either involved in disease ontogeny or linked to the evolution of each disease and/or specific clinicobiological features, and some of them have been demonstrated to have prognostic and even predictive impact. Future work is especially needed to understand the therapy-resistant disease, particularly in patients treated with targeted therapy, and to identify novel targets and therapeutic strategies in order to realize true precision medicine in this clinically heterogeneous patient group. © 2017 The Association for the Publication of the Journal of Internal Medicine.

MESSI: metabolic engineering target selection and best strain identification tool.

PubMed

Kang, Kang; Li, Jun; Lim, Boon Leong; Panagiotou, Gianni

2015-01-01

Metabolic engineering and synthetic biology are synergistically related fields for manipulating target pathways and designing microorganisms that can act as chemical factories. Saccharomyces cerevisiae's ideal bioprocessing traits make yeast a very attractive chemical factory for production of fuels, pharmaceuticals, nutraceuticals as well as a wide range of chemicals. However, future attempts of engineering S. cerevisiae's metabolism using synthetic biology need to move towards more integrative models that incorporate the high connectivity of metabolic pathways and regulatory processes and the interactions in genetic elements across those pathways and processes. To contribute in this direction, we have developed Metabolic Engineering target Selection and best Strain Identification tool (MESSI), a web server for predicting efficient chassis and regulatory components for yeast bio-based production. The server provides an integrative platform for users to analyse ready-to-use public high-throughput metabolomic data, which are transformed to metabolic pathway activities for identifying the most efficient S. cerevisiae strain for the production of a compound of interest. As input MESSI accepts metabolite KEGG IDs or pathway names. MESSI outputs a ranked list of S. cerevisiae strains based on aggregation algorithms. Furthermore, through a genome-wide association study of the metabolic pathway activities with the strains' natural variation, MESSI prioritizes genes and small variants as potential regulatory points and promising metabolic engineering targets. Users can choose various parameters in the whole process such as (i) weight and expectation of each metabolic pathway activity in the final ranking of the strains, (ii) Weighted AddScore Fuse or Weighted Borda Fuse aggregation algorithm, (iii) type of variants to be included, (iv) variant sets in different biological levels.Database URL: http://sbb.hku.hk/MESSI/. © The Author(s) 2015. Published by Oxford University Press.

Optimisation of the manufacturing process of tritide and deuteride targets used for neutron production

NASA Astrophysics Data System (ADS)

Monnin, Carole; Bach, Pierre; Tulle, Pierre Alain; van Rompay, Marc; Ballanger, Anne

2002-03-01

As a neutron tube manufacturer, SODERN is now in charge of manufacturing tritium targets for accelerators, in cooperation with CEA/DAM/DTMN in Valduc. Specific deuterium and tritium targets are manufactured on request, according to the requirements of the users, starting from titanium targets on copper substrates, and going to more sophisticated devices. The range of possible uses is wide, including thin targets for neutron calibration, thick targets with controlled loading of deuterium and tritium, rotating targets or large size rotating targets for higher lifetimes. The activity of the targets ranges from 3.7×10 10 to 3.7×10 13 Bq (1-1000 Ci), the diameter being up to 30 cm. Sodern and the CEA/Valduc centre have developed different technologies for tritium target manufacture, allowing the selection of the best configuration for each kind of use. In order to optimize the production of high energy neutrons, the performance of tritide and deuteride titanium targets made by different processes has been studied experimentally by bombardment with 120 and 350 kV deuterons provided by electrostatic accelerators. It is then possible to optimize either neutron output or lifetime and stability or thermal behaviour. The importance of the deposit evaporation conditions on the efficiency of neutron emission is clearly demonstrated, as well as the thermomechanical stability of the Ti thin film under deuteron bombardment. The main parameters involved in the target performance are discussed from a thermodynamical approach.

Evaluation of target efficiencies for solid-liquid separation steps in biofuels production.

PubMed

Kochergin, Vadim; Miller, Keith

2011-01-01

Development of liquid biofuels has entered a new phase of large scale pilot demonstration. A number of plants that are in operation or under construction face the task of addressing the engineering challenges of creating a viable plant design, scaling up and optimizing various unit operations. It is well-known that separation technologies account for 50-70% of both capital and operating cost. Additionally, reduction of environmental impact creates technological challenges that increase project cost without adding to the bottom line. Different technologies vary in terms of selection of unit operations; however, solid-liquid separations are likely to be a major contributor to the overall project cost. Despite the differences in pretreatment approaches, similar challenges arise for solid-liquid separation unit operations. A typical process for ethanol production from biomass includes several solid-liquid separation steps, depending on which particular stream is targeted for downstream processing. The nature of biomass-derived materials makes it either difficult or uneconomical to accomplish complete separation in a single step. Therefore, setting realistic efficiency targets for solid-liquid separations is an important task that influences overall process recovery and economics. Experimental data will be presented showing typical characteristics for pretreated cane bagasse at various stages of processing into cellulosic ethanol. Results of generic material balance calculations will be presented to illustrate the influence of separation target efficiencies on overall process recoveries and characteristics of waste streams.

Cassini Maneuver Experience for the Fourth Year of the Solstice Mission

NASA Technical Reports Server (NTRS)

Vaquero, Mar; Hahn, Yungsun; Stumpf, Paul; Valerino, Powtawche; Wagner, Sean; Wong, Mau

2014-01-01

After sixteen years of successful mission operations and invaluable scientific discoveries, the Cassini orbiter continues to tour Saturn on the most complex gravity-assist trajectory ever flown. To ensure that the end-of-mission target of September 2017 is achieved, propellant preservation is highly prioritized over maneuver cycle minimization. Thus, the maneuver decision process, which includes determining whether a maneuver is performed or canceled, designing a targeting strategy and selecting the engine for execution, is being continuously re-evaluated. This paper summarizes the maneuver experience throughout the fourth year of the Solstice Mission highlighting 27 maneuvers targeted to nine Titan flybys.

Cereal phytochromes: targets of selection, targets for manipulation?

PubMed

Sawers, Ruairidh J H; Sheehan, Moira J; Brutnell, Thomas P

2005-03-01

Plants respond to shading through an adaptive syndrome termed shade avoidance. In high-density crop plantings, shade avoidance generally increases extension growth at the expense of yield and can be at odds with the agronomic performance of the crop as a whole. Studies in Arabidopsis are beginning to reveal the essential role phytochromes play in regulating this process and to identify genes underlying the response. In this article, we focus on how phytochrome signaling networks have been targeted in cereal breeding programs in the past and discuss the potential to alter these pathways through breeding and transgenic manipulation to develop crops that perform better under typical high density conditions.

Retrieval from Episodic Memory: Neural Mechanisms of Interference Resolution

ERIC Educational Resources Information Center

Wimber, Maria; Rutschmann, Roland Marcus; Greenlee, Mark W.; Bauml, Karl-Heinz

2009-01-01

Selectively retrieving a target memory among related memories requires some degree of inhibitory control over interfering and competing memories, a process assumed to be supported by inhibitory mechanisms. Evidence from behavioral studies suggests that such inhibitory control can lead to subsequent forgetting of the interfering information, a…

Design Course for Micropower Generation Devices

ERIC Educational Resources Information Center

Mitsos, Alexander

2009-01-01

A project-based design course is developed for man-portable power generation via microfabricated fuel cell systems. Targeted audience are undergraduate chemical/process engineering students in their final year. The course covers 6 weeks, with three hours of lectures per week. Two alternative projects are developed, one focusing on selection of…

Inflence of air shear and adjuvants on spray atomization

USDA-ARS?s Scientific Manuscript database

Droplet size is critical to maximizing pesticide efficacy and mitigating off-target movement and correct selection and adjustment of nozzles and application equipment, as well as the use of adjuvants can aid in this process. However, in aerial applications air shear tends to be the dominate factor ...

Grammatical Category Ambiguity in Aphasia

ERIC Educational Resources Information Center

Goldberg, Elmera; Goldfarb, Robert

2005-01-01

This study asked whether aphasic adults show different noun/verb retrieval patterns based upon their clinical categorization as fluent or nonfluent. Participants selected either the noun or the verb meaning of target words, as presented in three contexts. The framework was that nouns (associated with temporal lobe function) are processed, stored,…

A Blueprint for Student Recruitment

ERIC Educational Resources Information Center

Chamberlain, Frank M.

1977-01-01

A marketing plan from the Young Presidents' Organization Task Force is offered: define the market; identify the target student; clarify the college selection process; assess the competition; define the college in terms of market needs; develop a recruiting strategy; develop objectives for the year; spell out the tactics; and manage for results.…

A Flexible Workflow for Automated Bioluminescent Kinase Selectivity Profiling.

PubMed

Worzella, Tracy; Butzler, Matt; Hennek, Jacquelyn; Hanson, Seth; Simdon, Laura; Goueli, Said; Cowan, Cris; Zegzouti, Hicham

2017-04-01

Kinase profiling during drug discovery is a necessary process to confirm inhibitor selectivity and assess off-target activities. However, cost and logistical limitations prevent profiling activities from being performed in-house. We describe the development of an automated and flexible kinase profiling workflow that combines ready-to-use kinase enzymes and substrates in convenient eight-tube strips, a bench-top liquid handling device, ADP-Glo Kinase Assay (Promega, Madison, WI) technology to quantify enzyme activity, and a multimode detection instrument. Automated methods were developed for kinase reactions and quantification reactions to be assembled on a Gilson (Middleton, WI) PIPETMAX, following standardized plate layouts for single- and multidose compound profiling. Pipetting protocols were customized at runtime based on user-provided information, including compound number, increment for compound titrations, and number of kinase families to use. After the automated liquid handling procedures, a GloMax Discover (Promega) microplate reader preloaded with SMART protocols was used for luminescence detection and automatic data analysis. The functionality of the automated workflow was evaluated with several compound-kinase combinations in single-dose or dose-response profiling formats. Known target-specific inhibitions were confirmed. Novel small molecule-kinase interactions, including off-target inhibitions, were identified and confirmed in secondary studies. By adopting this streamlined profiling process, researchers can quickly and efficiently profile compounds of interest on site.

Prolonged Interruption of Cognitive Control of Conflict Processing Over Human Faces by Task-Irrelevant Emotion Expression

PubMed Central

Kim, Jinyoung; Kang, Min-Suk; Cho, Yang Seok; Lee, Sang-Hun

2017-01-01

As documented by Darwin 150 years ago, emotion expressed in human faces readily draws our attention and promotes sympathetic emotional reactions. How do such reactions to the expression of emotion affect our goal-directed actions? Despite the substantial advance made in the neural mechanisms of both cognitive control and emotional processing, it is not yet known well how these two systems interact. Here, we studied how emotion expressed in human faces influences cognitive control of conflict processing, spatial selective attention and inhibitory control in particular, using the Eriksen flanker paradigm. In this task, participants viewed displays of a central target face flanked by peripheral faces and were asked to judge the gender of the target face; task-irrelevant emotion expressions were embedded in the target face, the flanking faces, or both. We also monitored how emotion expression affects gender judgment performance while varying the relative timing between the target and flanker faces. As previously reported, we found robust gender congruency effects, namely slower responses to the target faces whose gender was incongruent with that of the flanker faces, when the flankers preceded the target by 0.1 s. When the flankers further advanced the target by 0.3 s, however, the congruency effect vanished in most of the viewing conditions, except for when emotion was expressed only in the flanking faces or when congruent emotion was expressed in the target and flanking faces. These results suggest that emotional saliency can prolong a substantial degree of conflict by diverting bottom-up attention away from the target, and that inhibitory control on task-irrelevant information from flanking stimuli is deterred by the emotional congruency between target and flanking stimuli. PMID:28676780

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

PubMed Central

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

Switching auditory attention using spatial and non-spatial features recruits different cortical networks.

PubMed

Larson, Eric; Lee, Adrian K C

2014-01-01

Switching attention between different stimuli of interest based on particular task demands is important in many everyday settings. In audition in particular, switching attention between different speakers of interest that are talking concurrently is often necessary for effective communication. Recently, it has been shown by multiple studies that auditory selective attention suppresses the representation of unwanted streams in auditory cortical areas in favor of the target stream of interest. However, the neural processing that guides this selective attention process is not well understood. Here we investigated the cortical mechanisms involved in switching attention based on two different types of auditory features. By combining magneto- and electro-encephalography (M-EEG) with an anatomical MRI constraint, we examined the cortical dynamics involved in switching auditory attention based on either spatial or pitch features. We designed a paradigm where listeners were cued in the beginning of each trial to switch or maintain attention halfway through the presentation of concurrent target and masker streams. By allowing listeners time to switch during a gap in the continuous target and masker stimuli, we were able to isolate the mechanisms involved in endogenous, top-down attention switching. Our results show a double dissociation between the involvement of right temporoparietal junction (RTPJ) and the left inferior parietal supramarginal part (LIPSP) in tasks requiring listeners to switch attention based on space and pitch features, respectively, suggesting that switching attention based on these features involves at least partially separate processes or behavioral strategies. © 2013 Elsevier Inc. All rights reserved.

Using geometric morphometric visualizations of directional selection gradients to investigate morphological differentiation.

PubMed

Weaver, Timothy D; Gunz, Philipp

2018-04-01

Researchers studying extant and extinct taxa are often interested in identifying the evolutionary processes that have lead to the morphological differences among the taxa. Ideally, one could distinguish the influences of neutral evolutionary processes (genetic drift, mutation) from natural selection, and in situations for which selection is implicated, identify the targets of selection. The directional selection gradient is an effective tool for investigating evolutionary process, because it can relate form (size and shape) differences between taxa to the variation and covariation found within taxa. However, although most modern morphometric analyses use the tools of geometric morphometrics (GM) to analyze landmark data, to date, selection gradients have mainly been calculated from linear measurements. To address this methodological gap, here we present a GM approach for visualizing and comparing between-taxon selection gradients with each other, associated difference vectors, and "selection" gradients from neutral simulations. To exemplify our approach, we use a dataset of 347 three-dimensional landmarks and semilandmarks recorded on the crania of 260 primate specimens (112 humans, 67 common chimpanzees, 36 bonobos, 45 gorillas). Results on this example dataset show how incorporating geometric information can provide important insights into the evolution of the human braincase, and serve to demonstrate the utility of our approach for understanding morphological evolution. © 2018 The Author(s). Evolution © 2018 The Society for the Study of Evolution.

Hybrid overlay metrology for high order correction by using CDSEM

NASA Astrophysics Data System (ADS)

Leray, Philippe; Halder, Sandip; Lorusso, Gian; Baudemprez, Bart; Inoue, Osamu; Okagawa, Yutaka

2016-03-01

Overlay control has become one of the most critical issues for semiconductor manufacturing. Advanced lithographic scanners use high-order corrections or correction per exposure to reduce the residual overlay. It is not enough in traditional feedback of overlay measurement by using ADI wafer because overlay error depends on other process (etching process and film stress, etc.). It needs high accuracy overlay measurement by using AEI wafer. WIS (Wafer Induced Shift) is the main issue for optical overlay, IBO (Image Based Overlay) and DBO (Diffraction Based Overlay). We design dedicated SEM overlay targets for dual damascene process of N10 by i-ArF multi-patterning. The pattern is same as device-pattern locally. Optical overlay tools select segmented pattern to reduce the WIS. However segmentation has limit, especially the via-pattern, for keeping the sensitivity and accuracy. We evaluate difference between the viapattern and relaxed pitch gratings which are similar to optical overlay target at AEI. CDSEM can estimate asymmetry property of target from image of pattern edge. CDSEM can estimate asymmetry property of target from image of pattern edge. We will compare full map of SEM overlay to full map of optical overlay for high order correction ( correctables and residual fingerprints).

Reducing the overlay metrology sensitivity to perturbations of the measurement stack

NASA Astrophysics Data System (ADS)

Zhou, Yue; Park, DeNeil; Gutjahr, Karsten; Gottipati, Abhishek; Vuong, Tam; Bae, Sung Yong; Stokes, Nicholas; Jiang, Aiqin; Hsu, Po Ya; O'Mahony, Mark; Donini, Andrea; Visser, Bart; de Ruiter, Chris; Grzela, Grzegorz; van der Laan, Hans; Jak, Martin; Izikson, Pavel; Morgan, Stephen

2017-03-01

Overlay metrology setup today faces a continuously changing landscape of process steps. During Diffraction Based Overlay (DBO) metrology setup, many different metrology target designs are evaluated in order to cover the full process window. The standard method for overlay metrology setup consists of single-wafer optimization in which the performance of all available metrology targets is evaluated. Without the availability of external reference data or multiwafer measurements it is hard to predict the metrology accuracy and robustness against process variations which naturally occur from wafer-to-wafer and lot-to-lot. In this paper, the capabilities of the Holistic Metrology Qualification (HMQ) setup flow are outlined, in particular with respect to overlay metrology accuracy and process robustness. The significance of robustness and its impact on overlay measurements is discussed using multiple examples. Measurement differences caused by slight stack variations across the target area, called grating imbalance, are shown to cause significant errors in the overlay calculation in case the recipe and target have not been selected properly. To this point, an overlay sensitivity check on perturbations of the measurement stack is presented for improvement of the overlay metrology setup flow. An extensive analysis on Key Performance Indicators (KPIs) from HMQ recipe optimization is performed on µDBO measurements of product wafers. The key parameters describing the sensitivity to perturbations of the measurement stack are based on an intra-target analysis. Using advanced image analysis, which is only possible for image plane detection of μDBO instead of pupil plane detection of DBO, the process robustness performance of a recipe can be determined. Intra-target analysis can be applied for a wide range of applications, independent of layers and devices.

Selective inhibitors of trypanosomal uridylyl transferase RET1 establish druggability of RNA post-transcriptional modifications

PubMed Central

Cording, Amy; Gormally, Michael; Bond, Peter J.; Carrington, Mark; Balasubramanian, Shankar; Miska, Eric A.; Thomas, Beth

2017-01-01

ABSTRACT Non-coding RNAs are crucial regulators for a vast array of cellular processes and have been implicated in human disease. These biological processes represent a hitherto untapped resource in our fight against disease. In this work we identify small molecule inhibitors of a non-coding RNA uridylylation pathway. The TUTase family of enzymes is important for modulating non-coding RNA pathways in both human cancer and pathogen systems. We demonstrate that this new class of drug target can be accessed with traditional drug discovery techniques. Using the Trypanosoma brucei TUTase, RET1, we identify TUTase inhibitors and lay the groundwork for the use of this new target class as a therapeutic opportunity for the under-served disease area of African Trypanosomiasis. In a broader sense this work demonstrates the therapeutic potential for targeting RNA post-transcriptional modifications with small molecules in human disease. PMID:26786754

Selective inhibitors of trypanosomal uridylyl transferase RET1 establish druggability of RNA post-transcriptional modifications.

PubMed

Cording, Amy; Gormally, Michael; Bond, Peter J; Carrington, Mark; Balasubramanian, Shankar; Miska, Eric A; Thomas, Beth

2017-05-04

Non-coding RNAs are crucial regulators for a vast array of cellular processes and have been implicated in human disease. These biological processes represent a hitherto untapped resource in our fight against disease. In this work we identify small molecule inhibitors of a non-coding RNA uridylylation pathway. The TUTase family of enzymes is important for modulating non-coding RNA pathways in both human cancer and pathogen systems. We demonstrate that this new class of drug target can be accessed with traditional drug discovery techniques. Using the Trypanosoma brucei TUTase, RET1, we identify TUTase inhibitors and lay the groundwork for the use of this new target class as a therapeutic opportunity for the under-served disease area of African Trypanosomiasis. In a broader sense this work demonstrates the therapeutic potential for targeting RNA post-transcriptional modifications with small molecules in human disease.

Label-free fluorescence strategy for sensitive microRNA detection based on isothermal exponential amplification and graphene oxide.

PubMed

Li, Wei; Hou, Ting; Wu, Min; Li, Feng

2016-01-01

MicroRNAs (miRNAs) play an important role in many biological processes, and have been regarded as potential targets and biomarkers in cancer diagnosis and therapy. Also, to meet the big challenge imposed by the characteristics of miRNAs, such as small size and vulnerability to enzymatic digestion, it is of great importance to develop accurate, sensitive and simple miRNA assays. Herein, we developed a label-free fluorescence strategy for sensitive miRNA detection by combining isothermal exponential amplification and the unique features of SYBR Green I (SG) and graphene oxide (GO), in which SG gives significantly enhanced fluorescence upon intercalation into double-stranded DNAs (dsDNAs), and GO selectively adsorbs miRNA, single-stranded DNA and SG, to protect miRNA from enzymatic digestion, and to quench the fluorescence of the adsorbed SG. In the presence of the target miRNA, the ingeniously designed hairpin probe (HP) is unfolded and the subsequent polymerization and strand displacement reaction takes place to initiate the target recycling process. The newly formed dsDNAs are then recognized and cleaved by the nicking enzyme, generating new DNA triggers with the same sequence as the target miRNA, which hybridize with intact HPs to initiate new extension reactions. As a result, the circular exponential amplification for target miRNA is achieved and large amount of dsDNAs are formed to generate significantly enhanced fluorescence upon the intercalation of SG. Thus sensitive and selective fluorescence miRNA detection is realized, and the detection limit of 3 fM is obtained. Besides, this method exhibits additional advantages of simplicity and low cost, since expensive and tedious labeling process is avoided. Therefore, the as-proposed label-free fluorescence strategy has great potential in the applications in miRNA-related clinical practices and biochemical researches. Copyright © 2015 Elsevier B.V. All rights reserved.

Age-related slowing of response selection and production in a visual choice reaction time task

PubMed Central

Woods, David L.; Wyma, John M.; Yund, E. William; Herron, Timothy J.; Reed, Bruce

2015-01-01

Aging is associated with delayed processing in choice reaction time (CRT) tasks, but the processing stages most impacted by aging have not been clearly identified. Here, we analyzed CRT latencies in a computerized serial visual feature-conjunction task. Participants responded to a target letter (probability 40%) by pressing one mouse button, and responded to distractor letters differing either in color, shape, or both features from the target (probabilities 20% each) by pressing the other mouse button. Stimuli were presented randomly to the left and right visual fields and stimulus onset asynchronies (SOAs) were adaptively reduced following correct responses using a staircase procedure. In Experiment 1, we tested 1466 participants who ranged in age from 18 to 65 years. CRT latencies increased significantly with age (r = 0.47, 2.80 ms/year). Central processing time (CPT), isolated by subtracting simple reaction times (SRT) (obtained in a companion experiment performed on the same day) from CRT latencies, accounted for more than 80% of age-related CRT slowing, with most of the remaining increase in latency due to slowed motor responses. Participants were faster and more accurate when the stimulus location was spatially compatible with the mouse button used for responding, and this effect increased slightly with age. Participants took longer to respond to distractors with target color or shape than to distractors with no target features. However, the additional time needed to discriminate the more target-like distractors did not increase with age. In Experiment 2, we replicated the findings of Experiment 1 in a second population of 178 participants (ages 18–82 years). CRT latencies did not differ significantly in the two experiments, and similar effects of age, distractor similarity, and stimulus-response spatial compatibility were found. The results suggest that the age-related slowing in visual CRT latencies is largely due to delays in response selection and production. PMID:25954175

Antibody-mediated targeting of replication-competent retroviral vectors.

PubMed

Tai, Chien-Kuo; Logg, Christopher R; Park, Jinha M; Anderson, W French; Press, Michael F; Kasahara, Noriyuki

2003-05-20

Replication-competent murine leukemia virus (MLV) vectors can be engineered to achieve high efficiency gene transfer to solid tumors in vivo and tumor-restricted replication, however their safety can be further enhanced by redirecting tropism of the virus envelope. We have therefore tested the targeting capability and replicative stability of ecotropic and amphotropic replication-competent retrovirus (RCR) vectors containing two tandem repeats from the immunoglobulin G-binding domain of Staphylococcal protein A inserted into the proline-rich "hinge" region of the envelope, which enables modular use of antibodies of various specificities for vector targeting. The modified envelopes were efficiently expressed and incorporated into virions, were capable of capturing monoclonal anti-HER2 antibodies, and mediated efficient binding of the virus-antibody complex to HER2-positive target cells. While infectivity was markedly reduced by pseudotyping with targeted envelopes alone, coexpression of wild-type envelope rescued efficient cellular entry. Both ecotropic and amphotropic RCR vector/anti-HER2 antibody complexes achieved significant enhancement of transduction on murine target cells overexpressing HER2, which could be competed by preincubation with excess free antibodies. Interestingly, HER2-expressing human breast cancer cells did not show enhancement of transduction despite efficient antibody-mediated cell surface binding, suggesting that target cell-specific parameters markedly affect the efficiency of post-binding entry processes. Serial replication of targeted vectors resulted in selection of Z domain deletion variants, but reduction of the overall size of the vector genome enhanced its stability. Application of antibody-mediated targeting to the initial localization of replication-competent virus vectors to tumor sites will thus require optimized target selection and vector design.

Development, evaluation, and application of sediment quality targets for assessing and managing contaminated sediments in Tampa Bay, Florida

USGS Publications Warehouse

MacDonald, D.D.; Carr, R.S.; Eckenrod, D.; Greening, H.; Grabe, S.; Ingersoll, C.G.; Janicki, S.; Janicki, T.; Lindskoog, R.A.; Long, E.R.; Pribble, R.; Sloane, G.; Smorong, D.E.

2004-01-01

Tampa Bay is a large, urban estuary that is located in west central Florida. Although water quality conditions represent an important concern in this estuary, information from numerous sources indicates that sediment contamination also has the potential to adversely affect aquatic organisms, aquatic-dependent wildlife, and human health. As such, protecting relatively uncontaminated areas of the bay from contamination and reducing the amount of toxic chemicals in contaminated sediments have been identified as high-priority sediment management objectives for Tampa Bay. To address concerns related to sediment contamination in the bay, an ecosystem-based framework for assessing and managing sediment quality conditions was developed that included identification of sediment quality issues and concerns, development of ecosystem goals and objectives, selection of ecosystem health indicators, establishment of metrics and targets for key indicators, and incorporation of key indicators, metrics, and targets into watershed management plans and decision-making processes. This paper describes the process that was used to select and evaluate numerical sediment quality targets (SQTs) for assessing and managing contaminated sediments. These SQTs included measures of sediment chemistry, whole-sediment and pore-water toxicity, and benthic invertebrate community structure. In addition, the paper describes how the SQTs were used to develop site-specific concentration-response models that describe how the frequency of adverse biological effects changes with increasing concentrations of chemicals of potential concern. Finally, a key application of the SQTs for defining sediment management areas is discussed.

The cognitive loci of the display and task-relevant set size effects on distractor interference: Evidence from a dual-task paradigm.

PubMed

Park, Bo Youn; Kim, Sujin; Cho, Yang Seok

2018-02-01

The congruency effect of a task-irrelevant distractor has been found to be modulated by task-relevant set size and display set size. The present study used a psychological refractory period (PRP) paradigm to examine the cognitive loci of the display set size effect (dilution effect) and the task-relevant set size effect (perceptual load effect) on distractor interference. A tone discrimination task (Task 1), in which a response was made to the pitch of the target tone, was followed by a letter discrimination task (Task 2) in which different types of visual target display were used. In Experiment 1, in which display set size was manipulated to examine the nature of the display set size effect on distractor interference in Task 2, the modulation of the congruency effect by display set size was observed at both short and long stimulus-onset asynchronies (SOAs), indicating that the display set size effect occurred after the target was selected for processing in the focused attention stage. In Experiment 2, in which task-relevant set size was manipulated to examine the nature of the task-relevant set size effect on distractor interference in Task 2, the effects of task-relevant set size increased with SOA, suggesting that the target selection efficiency in the preattentive stage was impaired with increasing task-relevant set size. These results suggest that display set size and task-relevant set size modulate distractor processing in different ways.

Retroviral integration: Site matters

PubMed Central

Demeulemeester, Jonas; De Rijck, Jan

2015-01-01

Here, we review genomic target site selection during retroviral integration as a multistep process in which specific biases are introduced at each level. The first asymmetries are introduced when the virus takes a specific route into the nucleus. Next, by co‐opting distinct host cofactors, the integration machinery is guided to particular chromatin contexts. As the viral integrase captures a local target nucleosome, specific contacts introduce fine‐grained biases in the integration site distribution. In vivo, the established population of proviruses is subject to both positive and negative selection, thereby continuously reshaping the integration site distribution. By affecting stochastic proviral expression as well as the mutagenic potential of the virus, integration site choice may be an inherent part of the evolutionary strategies used by different retroviruses to maximise reproductive success. PMID:26293289

Decision Support System for Determining Scholarship Selection using an Analytical Hierarchy Process

NASA Astrophysics Data System (ADS)

Puspitasari, T. D.; Sari, E. O.; Destarianto, P.; Riskiawan, H. Y.

2018-01-01

Decision Support System is a computer program application that analyzes data and presents it so that users can make decision more easily. Determining Scholarship Selection study case in Senior High School in east Java wasn’t easy. It needed application to solve the problem, to improve the accuracy of targets for prospective beneficiaries of poor students and to speed up the screening process. This research will build system uses the method of Analytical Hierarchy Process (AHP) is a method that solves a complex and unstructured problem into its group, organizes the groups into a hierarchical order, inputs numerical values instead of human perception in comparing relative and ultimately with a synthesis determined elements that have the highest priority. The accuracy system for this research is 90%.

A novel 9 × 9 map-based solvent selection strategy for targeted counter-current chromatography isolation of natural products.

PubMed

Liang, Junling; Meng, Jie; Wu, Dingfang; Guo, Mengzhe; Wu, Shihua

2015-06-26

Counter-current chromatography (CCC) is an efficient liquid-liquid chromatography technique for separation and purification of complex mixtures like natural products extracts and synthetic chemicals. However, CCC is still a challenging process requiring some special technical knowledge especially in the selection of appropriated solvent systems. In this work, we introduced a new 9 × 9 map-based solvent selection strategy for CCC isolation of targets, which permit more than 60 hexane-ethyl acetate-methanol-water (HEMWat) solvent systems as the start candidates for the selection of solvent systems. Among these solvent systems, there are clear linear correlations between partition coefficient (K) and the system numbers. Thus, an appropriate CCC solvent system (i.e., sweet spot for K = 1) may be hit by measurement of k values of the target only in two random solvent systems. Besides this, surprisingly, we found that through two sweet spots, we could get a line ("Sweet line") where there are infinite sweet solvent systems being suitable for CCC separation. In these sweet solvent systems, the target has the same partition coefficient (K) but different solubilities. Thus, the better sweet solvent system with higher sample solubility can be obtained for high capacity CCC preparation. Furthermore, we found that there is a zone ("Sweet zone") where all solvent systems have their own sweet partition coefficients values for the target in range of 0.4 < K< 2.5 or extended range of 0.25 < K < 16. All results were validated by using 14 pure GUESSmix mimic natural products as standards and further confirmed by isolation of several targets including honokiol and magnolol from the extracts of Magnolia officinalis Rehd. Et Wils and tanshinone IIA from Salvia miltiorrhiza Bunge. In practice, it is much easier to get a suitable solvent system only by making a simple screening two to four HEMWat two-phase solvent systems to obtain the sweet line or sweet zone without special knowledge or comprehensive standards as references. This is an important advancement for solvent system selection and also will be very useful for isolation of current natural products including Traditional Chinese Medicines. Copyright © 2015 Elsevier B.V. All rights reserved.

Selective autophagy mediated by autophagic adapter proteins

PubMed Central

Lamark, Trond

2011-01-01

Mounting evidence suggests that autophagy is a more selective process than originally anticipated. The discovery and characterization of autophagic adapters, like p62 and NBR1, has provided mechanistic insight into this process. p62 and NBR1 are both selectively degraded by autophagy and able to act as cargo receptors for degradation of ubiquitinated substrates. A direct interaction between these autophagic adapters and the autophagosomal marker protein LC3, mediated by a so-called LIR (LC3-interacting region) motif, their inherent ability to polymerize or aggregate as well as their ability to specifically recognize substrates are required for efficient selective autophagy. These three required features of autophagic cargo receptors are evolutionarily conserved and also employed in the yeast cytoplasm-to-vacuole targeting (Cvt) pathway and in the degradation of P granules in C. elegans. Here, we review the mechanistic basis of selective autophagy in mammalian cells discussing the degradation of misfolded proteins, p62 bodies, aggresomes, mitochondria and invading bacteria. The emerging picture of selective autophagy affecting the regulation of cell signaling with consequences for oxidative stress responses, tumorigenesis and innate immunity is also addressed. PMID:21189453

A bottom-up model of spatial attention predicts human error patterns in rapid scene recognition.

PubMed

Einhäuser, Wolfgang; Mundhenk, T Nathan; Baldi, Pierre; Koch, Christof; Itti, Laurent

2007-07-20

Humans demonstrate a peculiar ability to detect complex targets in rapidly presented natural scenes. Recent studies suggest that (nearly) no focal attention is required for overall performance in such tasks. Little is known, however, of how detection performance varies from trial to trial and which stages in the processing hierarchy limit performance: bottom-up visual processing (attentional selection and/or recognition) or top-down factors (e.g., decision-making, memory, or alertness fluctuations)? To investigate the relative contribution of these factors, eight human observers performed an animal detection task in natural scenes presented at 20 Hz. Trial-by-trial performance was highly consistent across observers, far exceeding the prediction of independent errors. This consistency demonstrates that performance is not primarily limited by idiosyncratic factors but by visual processing. Two statistical stimulus properties, contrast variation in the target image and the information-theoretical measure of "surprise" in adjacent images, predict performance on a trial-by-trial basis. These measures are tightly related to spatial attention, demonstrating that spatial attention and rapid target detection share common mechanisms. To isolate the causal contribution of the surprise measure, eight additional observers performed the animal detection task in sequences that were reordered versions of those all subjects had correctly recognized in the first experiment. Reordering increased surprise before and/or after the target while keeping the target and distractors themselves unchanged. Surprise enhancement impaired target detection in all observers. Consequently, and contrary to several previously published findings, our results demonstrate that attentional limitations, rather than target recognition alone, affect the detection of targets in rapidly presented visual sequences.

Influence of Temporal Expectations on Response Priming by Subliminal Faces

PubMed Central

Guex, Raphael; Vuilleumier, Patrik

2016-01-01

Unconscious processes are often assumed immune from attention influence. Recent behavioral studies suggest however that the processing of subliminal information can be influenced by temporal attention. To examine the neural mechanisms underlying these effects, we used a stringent masking paradigm together with fMRI to investigate how temporal attention modulates the processing of unseen (masked) faces. Participants performed a gender decision task on a visible neutral target face, preceded by a masked prime face that could vary in gender (same or different than target) and emotion expression (neutral or fearful). We manipulated temporal attention by instructing participants to expect targets to appear either early or late during the stimulus sequence. Orienting temporal attention to subliminal primes influenced response priming by masked faces, even when gender was incongruent. In addition, gender-congruent primes facilitated responses regardless of attention while gender-incongruent primes reduced accuracy when attended. Emotion produced no differential effects. At the neural level, incongruent and temporally unexpected primes increased brain response in regions of the fronto-parietal attention network, reflecting greater recruitment of executive control and reorienting processes. Congruent and expected primes produced higher activations in fusiform cortex, presumably reflecting facilitation of perceptual processing. These results indicate that temporal attention can influence subliminal processing of face features, and thus facilitate information integration according to task-relevance regardless of conscious awareness. They also suggest that task-congruent information between prime and target may facilitate response priming even when temporal attention is not selectively oriented to the prime onset time. PMID:27764124

Influence of Temporal Expectations on Response Priming by Subliminal Faces.

PubMed

Pichon, Swann; Guex, Raphael; Vuilleumier, Patrik

2016-01-01

Unconscious processes are often assumed immune from attention influence. Recent behavioral studies suggest however that the processing of subliminal information can be influenced by temporal attention. To examine the neural mechanisms underlying these effects, we used a stringent masking paradigm together with fMRI to investigate how temporal attention modulates the processing of unseen (masked) faces. Participants performed a gender decision task on a visible neutral target face, preceded by a masked prime face that could vary in gender (same or different than target) and emotion expression (neutral or fearful). We manipulated temporal attention by instructing participants to expect targets to appear either early or late during the stimulus sequence. Orienting temporal attention to subliminal primes influenced response priming by masked faces, even when gender was incongruent. In addition, gender-congruent primes facilitated responses regardless of attention while gender-incongruent primes reduced accuracy when attended. Emotion produced no differential effects. At the neural level, incongruent and temporally unexpected primes increased brain response in regions of the fronto-parietal attention network, reflecting greater recruitment of executive control and reorienting processes. Congruent and expected primes produced higher activations in fusiform cortex, presumably reflecting facilitation of perceptual processing. These results indicate that temporal attention can influence subliminal processing of face features, and thus facilitate information integration according to task-relevance regardless of conscious awareness. They also suggest that task-congruent information between prime and target may facilitate response priming even when temporal attention is not selectively oriented to the prime onset time.

Identification of regulators of polyploidization presents therapeutic targets for treatment of AMKL.

PubMed

Wen, Qiang; Goldenson, Benjamin; Silver, Serena J; Schenone, Monica; Dancik, Vlado; Huang, Zan; Wang, Ling-Zhi; Lewis, Timothy A; An, W Frank; Li, Xiaoyu; Bray, Mark-Anthony; Thiollier, Clarisse; Diebold, Lauren; Gilles, Laure; Vokes, Martha S; Moore, Christopher B; Bliss-Moreau, Meghan; Verplank, Lynn; Tolliday, Nicola J; Mishra, Rama; Vemula, Sasidhar; Shi, Jianjian; Wei, Lei; Kapur, Reuben; Lopez, Cécile K; Gerby, Bastien; Ballerini, Paola; Pflumio, Francoise; Gilliland, D Gary; Goldberg, Liat; Birger, Yehudit; Izraeli, Shai; Gamis, Alan S; Smith, Franklin O; Woods, William G; Taub, Jeffrey; Scherer, Christina A; Bradner, James E; Goh, Boon-Cher; Mercher, Thomas; Carpenter, Anne E; Gould, Robert J; Clemons, Paul A; Carr, Steven A; Root, David E; Schreiber, Stuart L; Stern, Andrew M; Crispino, John D

2012-08-03

The mechanism by which cells decide to skip mitosis to become polyploid is largely undefined. Here we used a high-content image-based screen to identify small-molecule probes that induce polyploidization of megakaryocytic leukemia cells and serve as perturbagens to help understand this process. Our study implicates five networks of kinases that regulate the switch to polyploidy. Moreover, we find that dimethylfasudil (diMF, H-1152P) selectively increased polyploidization, mature cell-surface marker expression, and apoptosis of malignant megakaryocytes. An integrated target identification approach employing proteomic and shRNA screening revealed that a major target of diMF is Aurora kinase A (AURKA). We further find that MLN8237 (Alisertib), a selective inhibitor of AURKA, induced polyploidization and expression of mature megakaryocyte markers in acute megakaryocytic leukemia (AMKL) blasts and displayed potent anti-AMKL activity in vivo. Our findings provide a rationale to support clinical trials of MLN8237 and other inducers of polyploidization and differentiation in AMKL. Copyright © 2012 Elsevier Inc. All rights reserved.

The insecticide target in the PSST subunit of complex I.

PubMed

Schuler, F; Casida, J E

2001-10-01

Current insecticides have been selected by sifting and winnowing hundreds of thousands of synthetic chemicals and natural products to obtain commercial preparations of optimal effectiveness and safety. This process has often ended up with compounds of high potency as inhibitors of the electron transport chain and more specifically of complex I (NADH:ubiquinone oxidoreductase). Many classes of chemicals are involved and the enzyme is one of the most complicated known, with 43 subunits catalyzing electron transfer from NADH to ubiquinone through flavin mononucleotide and up to eight iron-sulfur clusters. We used a potent photoaffinity ligand, (trifluoromethyl)diazirinyl[3H]pyridaben, to localize the insecticide target to a single high-affinity site in the PSST subunit that couples electron transfer from iron-sulfur cluster N2 to ubiquinone. Most importantly, all of the potent complex I-inhibiting pesticides, despite their great structural diversity, compete for this same specific binding domain in PSST. Finding their common mode of action and target provides insight into shared toxicological features and potential selection for resistant pests.

Functional imaging correlates of impaired distractor suppression following sleep deprivation.

PubMed

Kong, Danyang; Soon, Chun Siong; Chee, Michael W L

2012-05-15

Sleep deprivation (SD) has been shown to affect selective attention but it is not known how two of its component processes: target enhancement and distractor suppression, are affected. To investigate, young volunteers either attended to houses or were obliged to ignore them (when attending to faces) while viewing superimposed face-house pictures. MR signal enhancement and suppression in the parahippocampal place area (PPA) were determined relative to a passive viewing control condition. Sleep deprivation was associated with lower PPA activation across conditions. Critically SD specifically impaired distractor suppression in selective attention, leaving target enhancement relatively preserved. These findings parallel some observations in cognitive aging. Additionally, following SD, attended houses were not significantly better recognized than ignored houses in a post-experiment test of recognition memory contrasting with the finding of superior recognition of attended houses in the well-rested state. These results provide evidence for co-encoding of distracting information with targets into memory when one is sleep deprived. Copyright © 2012 Elsevier Inc. All rights reserved.

Biomarkers and patient selection for PI3K/Akt/mTOR targeted therapies: current status and future directions.

PubMed

Bartlett, John M S

2010-11-01

The phosphatidylinositol 3-kinase (PI3K)/Akt/ mammalian target of rapamycin (mTOR) pathway regulates a broad spectrum of physiologic and pathologic processes. In breast cancer mutation, amplification, deletion, methylation, and posttranslational modifications lead to significant dysregulation of this pathway leading to more aggressive and potentially drug-resistant disease. Multiple novel agents, targeting different nodes within the pathway are currently under development by both commercial and academic partners. The key to the successful validation of these markers is selection of the appropriate patient groups using biomarkers. This article reviews current progress in this area, highlighting the key molecular alterations described in genes within the PI3K/Akt/mTOR pathway that may have an effect on response to current and future therapeutic interventions. Herein, gaps in current knowledge are highlighted and suggestions for future research directions given that may facilitate biomarker development in partnership with current drug development.

Integrative screening approach identifies regulators of polyploidization and targets for acute megakaryocytic leukemia

PubMed Central

Wen, Qiang; Goldenson, Benjamin; Silver, Serena J.; Schenone, Monica; Dancik, Vladimir; Huang, Zan; Wang, Ling-Zhi; Lewis, Timothy; An, W. Frank; Li, Xiaoyu; Bray, Mark-Anthony; Thiollier, Clarisse; Diebold, Lauren; Gilles, Laure; Vokes, Martha S.; Moore, Christopher B.; Bliss-Moreau, Meghan; VerPlank, Lynn; Tolliday, Nicola J.; Mishra, Rama; Vemula, Sasidhar; Shi, Jianjian; Wei, Lei; Kapur, Reuben; Lopez, Cécile K.; Gerby, Bastien; Ballerini, Paola; Pflumio, Francoise; Gilliland, D. Gary; Goldberg, Liat; Birger, Yehudit; Izraeli, Shai; Gamis, Alan S.; Smith, Franklin O.; Woods, William G.; Taub, Jeffrey; Scherer, Christina A.; Bradner, James; Goh, Boon-Cher; Mercher, Thomas; Carpenter, Anne E.; Gould, Robert J.; Clemons, Paul A.; Carr, Steven A.; Root, David E.; Schreiber, Stuart L.; Stern, Andrew M.; Crispino, John D.

2012-01-01

Summary The mechanism by which cells decide to skip mitosis to become polyploid is largely undefined. Here we used a high-content image-based screen to identify small-molecule probes that induce polyploidization of megakaryocytic leukemia cells and serve as perturbagens to help understand this process. We found that dimethylfasudil (diMF, H-1152P) selectively increased polyploidization, mature cell-surface marker expression, and apoptosis of malignant megakaryocytes. A broadly applicable, highly integrated target identification approach employing proteomic and shRNA screening revealed that a major target of diMF is Aurora A kinase (AURKA), which has not been studied extensively in megakaryocytes. Moreover, we discovered that MLN8237 (Alisertib), a selective inhibitor of AURKA, induced polyploidization and expression of mature megakaryocyte markers in AMKL blasts and displayed potent anti-AMKL activity in vivo. This research provides the rationale to support clinical trials of MLN8237 and other inducers of polyploidization in AMKL. Finally, we have identified five networks of kinases that regulate the switch to polyploidy. PMID:22863010

Attentional adjustment to conflict strength: evidence from the effects of manipulating flanker-target SOA on response times and prestimulus pupil size.

PubMed

Wendt, Mike; Kiesel, Andrea; Geringswald, Franziska; Purmann, Sascha; Fischer, Rico

2014-01-01

Current models of cognitive control assume gradual adjustment of processing selectivity to the strength of conflict evoked by distractor stimuli. Using a flanker task, we varied conflict strength by manipulating target and distractor onset. Replicating previous findings, flanker interference effects were larger on trials associated with advance presentation of the flankers compared to simultaneous presentation. Controlling for stimulus and response sequence effects by excluding trials with feature repetitions from stimulus administration (Experiment 1) or from the statistical analyses (Experiment 2), we found a reduction of the flanker interference effect after high-conflict predecessor trials (i.e., trials associated with advance presentation of the flankers) but not after low-conflict predecessor trials (i.e., trials associated with simultaneous presentation of target and flankers). This result supports the assumption of conflict-strength-dependent adjustment of visual attention. The selective adaptation effect after high-conflict trials was associated with an increase in prestimulus pupil diameter, possibly reflecting increased cognitive effort of focusing attention.

Can Small Chemical Modifications of Natural Pan-inhibitors Modulate the Biological Selectivity? The Case of Curcumin Prenylated Derivatives Acting as HDAC or mPGES-1 Inhibitors.

PubMed

Iranshahi, Mehrdad; Chini, Maria Giovanna; Masullo, Milena; Sahebkar, Amirhossein; Javidnia, Azita; Chitsazian Yazdi, Mahsa; Pergola, Carlo; Koeberle, Andreas; Werz, Oliver; Pizza, Cosimo; Terracciano, Stefania; Piacente, Sonia; Bifulco, Giuseppe

2015-12-24

Curcumin, or diferuloylmethane, a polyphenolic molecule isolated from the rhizome of Curcuma longa, is reported to modulate multiple molecular targets involved in cancer and inflammatory processes. On the basis of its pan-inhibitory characteristics, here we show that simple chemical modifications of the curcumin scaffold can regulate its biological selectivity. In particular, the curcumin scaffold was modified with three types of substituents at positions C-1, C-8, and/or C-8' [C5 (isopentenyl, 5-8), C10 (geranyl, 9-12), and C15 (farnesyl, 13, 14)] in order to make these molecules more selective than the parent compound toward two specific targets: histone deacetylase (HDAC) and microsomal prostaglandin E2 synthase-1 (mPGES-1). From combined in silico and in vitro analyses, three selective inhibitors by proper substitution at position 8 were revealed. Compound 13 has improved HDAC inhibitory activity and selectivity with respect to the parent compound, while 5 and 9 block the mPGES-1 enzyme. We hypothesize about the covalent interaction of curcumin, 5, and 9 with the mPGES-1 binding site.

Nanomedicine Strategies to Target Tumor-Associated Macrophages

PubMed Central

Binnemars-Postma, Karin; Storm, Gert; Prakash, Jai

2017-01-01

In recent years, the influence of the tumor microenvironment (TME) on cancer progression has been better understood. Macrophages, one of the most important cell types in the TME, exist in different subtypes, each of which has a different function. While classically activated M1 macrophages are involved in inflammatory and malignant processes, activated M2 macrophages are more involved in the wound-healing processes occurring in tumors. Tumor-associated macrophages (TAM) display M2 macrophage characteristics and support tumor growth and metastasis by matrix remodeling, neo-angiogenesis, and suppressing local immunity. Due to their detrimental role in tumor growth and metastasis, selective targeting of TAM for the treatment of cancer may prove to be beneficial in the treatment of cancer. Due to the plastic nature of macrophages, their activities may be altered to inhibit tumor growth. In this review, we will discuss the therapeutic options for the modulation and targeting of TAM. Different therapeutic strategies to deplete, inhibit recruitment of, or re-educate TAM will be discussed. Current strategies for the targeting of TAM using nanomedicine are reviewed. Passive targeting using different nanoparticle systems is described. Since TAM display a number of upregulated surface proteins compared to non-TAM, specific targeting using targeting ligands coupled to nanoparticles is discussed in detail. PMID:28471401

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

ERIC Educational Resources Information Center

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…

Neural Dynamics Underlying Target Detection in the Human Brain

PubMed Central

Bansal, Arjun K.; Madhavan, Radhika; Agam, Yigal; Golby, Alexandra; Madsen, Joseph R.

2014-01-01

Sensory signals must be interpreted in the context of goals and tasks. To detect a target in an image, the brain compares input signals and goals to elicit the correct behavior. We examined how target detection modulates visual recognition signals by recording intracranial field potential responses from 776 electrodes in 10 epileptic human subjects. We observed reliable differences in the physiological responses to stimuli when a cued target was present versus absent. Goal-related modulation was particularly strong in the inferior temporal and fusiform gyri, two areas important for object recognition. Target modulation started after 250 ms post stimulus, considerably after the onset of visual recognition signals. While broadband signals exhibited increased or decreased power, gamma frequency power showed predominantly increases during target presence. These observations support models where task goals interact with sensory inputs via top-down signals that influence the highest echelons of visual processing after the onset of selective responses. PMID:24553944

Is that a belt or a snake? object attentional selection affects the early stages of visual sensory processing

PubMed Central

2012-01-01

Background There is at present crescent empirical evidence deriving from different lines of ERPs research that, unlike previously observed, the earliest sensory visual response, known as C1 component or P/N80, generated within the striate cortex, might be modulated by selective attention to visual stimulus features. Up to now, evidence of this modulation has been related to space location, and simple features such as spatial frequency, luminance, and texture. Additionally, neurophysiological conditions, such as emotion, vigilance, the reflexive or voluntary nature of input attentional selection, and workload have also been related to C1 modulations, although at least the workload status has received controversial indications. No information is instead available, at present, for objects attentional selection. Methods In this study object- and space-based attention mechanisms were conjointly investigated by presenting complex, familiar shapes of artefacts and animals, intermixed with distracters, in different tasks requiring the selection of a relevant target-category within a relevant spatial location, while ignoring the other shape categories within this location, and, overall, all the categories at an irrelevant location. EEG was recorded from 30 scalp electrode sites in 21 right-handed participants. Results and Conclusions ERP findings showed that visual processing was modulated by both shape- and location-relevance per se, beginning separately at the latency of the early phase of a precocious negativity (60-80 ms) at mesial scalp sites consistent with the C1 component, and a positivity at more lateral sites. The data also showed that the attentional modulation progressed conjointly at the latency of the subsequent P1 (100-120 ms) and N1 (120-180 ms), as well as later-latency components. These findings support the views that (1) V1 may be precociously modulated by direct top-down influences, and participates to object, besides simple features, attentional selection; (2) object spatial and non-spatial features selection might begin with an early, parallel detection of a target object in the visual field, followed by the progressive focusing of spatial attention onto the location of an actual target for its identification, somehow in line with neural mechanisms reported in the literature as "object-based space selection", or with those proposed for visual search. PMID:22300540

Evaluation of Treatment Technologies for Wastewater from Insensitive Munitions Production. Phase 1: Technology Down-Selection

DTIC Science & Technology

2013-11-01

the AOP reactor according to the target process formulation. Gases were vented to a GAC vessel. ERDC/EL TR-13-20 94 10.2.2 Results and Discussion...destructive and filtration methods such as biological treatment (destructive), chemical reduction (destructive), reverse osmosis (RO)/nano- filtration ... filtration ), and advanced oxidation processes (destructive). A comprehensive evaluation of alternatives relies on a detailed list of criteria, allowing for

How They Decide: A Case Study Examining the Decision Making Process for Keeping or Cutting Music Education in a K-12 Public School District

ERIC Educational Resources Information Center

Major, Marci L.

2010-01-01

The purpose of this study was to examine and understand the decision making process for keeping or cutting music programs in one selected public school district. Berkley School District, in the Detroit suburb of Berkley, Michigan, has not made extreme cuts to the music program in over ten years, nor have they specifically targeted their music…

How They Decide: A Case Study Examining the Decision-Making Process for Keeping or Cutting Music in a K-12 Public School District

ERIC Educational Resources Information Center

Major, Marci L.

2013-01-01

This study was designed to examine the decision-making process for keeping or cutting the music program in one selected public school district. Lekbery School District, in the Detroit suburb of Lekbery, Michigan, had not made extreme cuts to the music program in over 10 years, nor had it specifically targeted the music program when budgets cuts…

Sequential Adaptive Multi-Modality Target Detection and Classification Using Physics Based Models

DTIC Science & Technology

2006-09-01

estimation," R. Raghuram, R. Raich and A.O. Hero, IEEE Intl. Conf. on Acoustics, Speech , and Signal Processing, Toulouse France, June 2006, <http...can then be solved using off-the-shelf classifiers such as radial basis functions, SVM, or kNN classifier structures. When applied to mine detection we...stage waveform selection for adaptive resource constrained state estimation," 2006 IEEE Intl. Conf. on Acoustics, Speech , and Signal Processing

Multiple source/multiple target fluid transfer apparatus

DOEpatents

Turner, Terry D.

1997-01-01

A fluid transfer apparatus includes: a) a plurality of orifices for connection with fluid sources; b) a plurality of orifices for connection with fluid targets; c) a set of fluid source conduits and fluid target conduits associated with the orifices; d) a pump fluidically interposed between the source and target conduits to transfer fluid therebetween; e) a purge gas conduit in fluid communication with the fluid source conduits, fluid target conduits and pump to receive and pass a purge gas under pressure; f) a solvent conduit in fluid communication with the fluid source conduits, fluid target conduits and pump to receive and pass solvent, the solvent conduit including a solvent valve; g) pump control means for controlling operation of the pump; h) purge gas valve control means for controlling operation of the purge gas valve to selectively impart flow of purge gas to the fluid source conduits, fluid target conduits and pump; i) solvent valve control means for controlling operation of the solvent valve to selectively impart flow of solvent to the fluid source conduits, fluid target conduits and pump; and j) source and target valve control means for controlling operation of the fluid source conduit valves and the fluid target conduit valves to selectively impart passage of fluid between a selected one of the fluid source conduits and a selected one of the fluid target conduits through the pump and to enable passage of solvent or purge gas through selected fluid source conduits and selected fluid target conduits.

Multiple source/multiple target fluid transfer apparatus

DOEpatents

Turner, T.D.

1997-08-26

A fluid transfer apparatus includes: (a) a plurality of orifices for connection with fluid sources; (b) a plurality of orifices for connection with fluid targets; (c) a set of fluid source conduits and fluid target conduits associated with the orifices; (d) a pump fluidically interposed between the source and target conduits to transfer fluid there between; (e) a purge gas conduit in fluid communication with the fluid source conduits, fluid target conduits and pump to receive and pass a purge gas under pressure; (f) a solvent conduit in fluid communication with the fluid source conduits, fluid target conduits and pump to receive and pass solvent, the solvent conduit including a solvent valve; (g) pump control means for controlling operation of the pump; (h) purge gas valve control means for controlling operation of the purge gas valve to selectively impart flow of purge gas to the fluid source conduits, fluid target conduits and pump; (i) solvent valve control means for controlling operation of the solvent valve to selectively impart flow of solvent to the fluid source conduits, fluid target conduits and pump; and (j) source and target valve control means for controlling operation of the fluid source conduit valves and the fluid target conduit valves to selectively impart passage of fluid between a selected one of the fluid source conduits and a selected one of the fluid target conduits through the pump and to enable passage of solvent or purge gas through selected fluid source conduits and selected fluid target conduits. 6 figs.

How do we select multiple features? Transient costs for selecting two colors rather than one, persistent costs for color-location conjunctions.

PubMed

Lo, Shih-Yu; Holcombe, Alex O

2014-02-01

In a previous study Lo, Howard, & Holcombe (Vision Research 63:20-33, 2012), selecting two colors did not induce a performance cost, relative to selecting one color. For example, requiring possible report of both a green and a red target did not yield a worse performance than when both targets were green. Yet a cost of selecting multiple colors was observed when selection needed be contingent on both color and location. When selecting a red target to the left and a green target to the right, superimposing a green distractor to the left and a red distractor to the right impeded performance. Possibly, participants cannot confine attention to a color at a particular location. As a result, distractors that share the target colors disrupt attentional selection of the targets. The attempt to select the targets must then be repeated, which increases the likelihood that the trial terminates when selection is not effective, even for long trials. Consistent with this, here we find a persistent cost of selecting two colors when the conjunction of color and location is needed, but the cost is confined to short exposure durations when the observer just has to monitor red and green stimuli without the need to use the location information. These results suggest that selecting two colors is time-consuming but effective, whereas selection of simultaneous conjunctions is never entirely successful.

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

PubMed

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.

Selection of peptides interfering with protein-protein interaction.

PubMed

Gaida, Annette; Hagemann, Urs B; Mattay, Dinah; Räuber, Christina; Müller, Kristian M; Arndt, Katja M

2009-01-01

Cell physiology depends on a fine-tuned network of protein-protein interactions, and misguided interactions are often associated with various diseases. Consequently, peptides, which are able to specifically interfere with such adventitious interactions, are of high interest for analytical as well as medical purposes. One of the most abundant protein interaction domains is the coiled-coil motif, and thus provides a premier target. Coiled coils, which consist of two or more alpha-helices wrapped around each other, have one of the simplest interaction interfaces, yet they are able to confer highly specific homo- and heterotypic interactions involved in virtually any cellular process. While there are several ways to generate interfering peptides, the combination of library design with a powerful selection system seems to be one of the most effective and promising approaches. This chapter guides through all steps of such a process, starting with library options and cloning, detailing suitable selection techniques and ending with purification for further down-stream characterization. Such generated peptides will function as versatile tools to interfere with the natural function of their targets thereby illuminating their down-stream signaling and, in general, promoting understanding of factors leading to specificity and stability in protein-protein interactions. Furthermore, peptides interfering with medically relevant proteins might become important diagnostics and therapeutics.

Clinical-scale laser-based scanning and processing of live cells: selective photothermal killing of fluorescent tumor targets for autologous stem cell transplantation

NASA Astrophysics Data System (ADS)

Koller, Manfred R.; Hanania, Elie G.; Eisfeld, Timothy; O'Neal, Robert A.; Khovananth, Kevin M.; Palsson, Bernhard O.

2001-04-01

High-dose chemotherapy, followed by autologous hematopoietic stem cell (HSC) transplantation, is widely used for the treatment of cancer. However, contaminating tumor cells within HSC harvests continue to be of major concern since re-infused tumor cells have proven to contribute to disease relapse. Many tumor purging methods have been evaluated, but all leave detectable tumor cells in the transplant and result in significant loss of HSCs. These shortcomings cause engraftment delays and compromise the therapeutic value of purging. A novel approach integrating automated scanning cytometry, image analysis, and selective laser-induced killing of labeled cells within a cell mixture is described here. Non-Hodgkin's lymphoma (NHL) cells were spiked into cell mixtures, and fluorochrome-conjugated antibodies were used to label tumor cells within the mixture. Cells were then allowed to settle on a surface, and as the surface was scanned with a fluorescence excitation source, a laser pulse was fired at every detected tumor cell using high-speed beam steering mirrors. Tumor cells were selectively killed with little effect on adjacent non-target cells, demonstrating the feasibility of this automated cell processing approach. This technology has many potential research and clinical applications, one example of which is tumor cell purging for autologous HSC transplantation.

Flight control system design factors for applying automated testing techniques

NASA Technical Reports Server (NTRS)

Sitz, Joel R.; Vernon, Todd H.

1990-01-01

The principal design features and operational experiences of the X-29 forward-swept-wing aircraft and F-18 high alpha research vehicle (HARV) automated test systems are discussed. It is noted that operational experiences in developing and using these automated testing techniques have highlighted the need for incorporating target system features to improve testability. Improved target system testability can be accomplished with the addition of nonreal-time and real-time features. Online access to target system implementation details, unobtrusive real-time access to internal user-selectable variables, and proper software instrumentation are all desirable features of the target system. Also, test system and target system design issues must be addressed during the early stages of the target system development. Processing speeds of up to 20 million instructions/s and the development of high-bandwidth reflective memory systems have improved the ability to integrate the target system and test system for the application of automated testing techniques. It is concluded that new methods of designing testability into the target systems are required.

Searching for the bull's eye: agents and targets of selection vary among geographically disparate cyanogenesis clines in white clover (Trifolium repens L.)

PubMed Central

Kooyers, N J; Olsen, K M

2013-01-01

The recurrent evolution of adaptive clines within a species can be used to elucidate the selective factors and genetic responses that underlie adaptation. White clover is polymorphic for cyanogenesis (HCN release with tissue damage), and climate-associated cyanogenesis clines have evolved throughout the native and introduced species range. This polymorphism arises through two independently segregating Mendelian polymorphisms for the presence/absence of two required components: cyanogenic glucosides and their hydrolyzing enzyme linamarase. Cyanogenesis is commonly thought to function in herbivore defense; however, the individual cyanogenic components may also serve other physiological functions. To test whether cyanogenesis clines have evolved in response to the same selective pressures acting on the same genetic targets, we examined cyanogenesis cline shape and its environmental correlates in three world regions: southern New Zealand, the central United States and the US Pacific Northwest. For some regional comparisons, cline shapes are remarkably similar despite large differences in the spatial scales over which clines occur (40–1600 km). However, we also find evidence for major differences in both the agents and targets of selection among the sampled clines. Variation in cyanogenesis frequency is best predicted using a combination of minimum winter temperature and aridity variables. Together, our results provide evidence that recurrent adaptive clines do not necessarily reflect shared adaptive processes. PMID:23900395

Perceptual load corresponds with factors known to influence visual search.

PubMed

Roper, Zachary J J; Cosman, Joshua D; Vecera, Shaun P

2013-10-01

One account of the early versus late selection debate in attention proposes that perceptual load determines the locus of selection. Attention selects stimuli at a late processing level under low-load conditions but selects stimuli at an early level under high-load conditions. Despite the successes of perceptual load theory, a noncircular definition of perceptual load remains elusive. We investigated the factors that influence perceptual load by using manipulations that have been studied extensively in visual search, namely target-distractor similarity and distractor-distractor similarity. Consistent with previous work, search was most efficient when targets and distractors were dissimilar and the displays contained homogeneous distractors; search became less efficient when target-distractor similarity increased irrespective of display heterogeneity. Importantly, we used these same stimuli in a typical perceptual load task that measured attentional spillover to a task-irrelevant flanker. We found a strong correspondence between search efficiency and perceptual load; stimuli that generated efficient searches produced flanker interference effects, suggesting that such displays involved low perceptual load. Flanker interference effects were reduced in displays that produced less efficient searches. Furthermore, our results demonstrate that search difficulty, as measured by search intercept, has little bearing on perceptual load. We conclude that rather than be arbitrarily defined, perceptual load might be defined by well-characterized, continuous factors that influence visual search. PsycINFO Database Record (c) 2013 APA, all rights reserved.

A visual salience map in the primate frontal eye field.

PubMed

Thompson, Kirk G; Bichot, Narcisse P

2005-01-01

Models of attention and saccade target selection propose that within the brain there is a topographic map of visual salience that combines bottom-up and top-down influences to identify locations for further processing. The results of a series of experiments with monkeys performing visual search tasks have identified a population of frontal eye field (FEF) visually responsive neurons that exhibit all of the characteristics of a visual salience map. The activity of these FEF neurons is not sensitive to specific features of visual stimuli; but instead, their activity evolves over time to select the target of the search array. This selective activation reflects both the bottom-up intrinsic conspicuousness of the stimuli and the top-down knowledge and goals of the viewer. The peak response within FEF specifies the target for the overt gaze shift. However, the selective activity in FEF is not in itself a motor command because the magnitude of activation reflects the relative behavioral significance of the different stimuli in the visual scene and occurs even when no saccade is made. Identifying a visual salience map in FEF validates the theoretical concept of a salience map in many models of attention. In addition, it strengthens the emerging view that FEF is not only involved in producing overt gaze shifts, but is also important for directing covert spatial attention.

Process Pharmacology: A Pharmacological Data Science Approach to Drug Development and Therapy.

PubMed

Lötsch, Jörn; Ultsch, Alfred

2016-04-01

A novel functional-genomics based concept of pharmacology that uses artificial intelligence techniques for mining and knowledge discovery in "big data" providing comprehensive information about the drugs' targets and their functional genomics is proposed. In "process pharmacology", drugs are associated with biological processes. This puts the disease, regarded as alterations in the activity in one or several cellular processes, in the focus of drug therapy. In this setting, the molecular drug targets are merely intermediates. The identification of drugs for therapeutic or repurposing is based on similarities in the high-dimensional space of the biological processes that a drug influences. Applying this principle to data associated with lymphoblastic leukemia identified a short list of candidate drugs, including one that was recently proposed as novel rescue medication for lymphocytic leukemia. The pharmacological data science approach provides successful selections of drug candidates within development and repurposing tasks. © 2016 The Authors CPT: Pharmacometrics & Systems Pharmacology published by Wiley Periodicals, Inc. on behalf of American Society for Clinical Pharmacology and Therapeutics.

Sensor selection and chemo-sensory optimization: toward an adaptable chemo-sensory system.

PubMed

Vergara, Alexander; Llobet, Eduard

2011-01-01

Over the past two decades, despite the tremendous research on chemical sensors and machine olfaction to develop micro-sensory systems that will accomplish the growing existent needs in personal health (implantable sensors), environment monitoring (widely distributed sensor networks), and security/threat detection (chemo/bio warfare agents), simple, low-cost molecular sensing platforms capable of long-term autonomous operation remain beyond the current state-of-the-art of chemical sensing. A fundamental issue within this context is that most of the chemical sensors depend on interactions between the targeted species and the surfaces functionalized with receptors that bind the target species selectively, and that these binding events are coupled with transduction processes that begin to change when they are exposed to the messy world of real samples. With the advent of fundamental breakthroughs at the intersection of materials science, micro- and nano-technology, and signal processing, hybrid chemo-sensory systems have incorporated tunable, optimizable operating parameters, through which changes in the response characteristics can be modeled and compensated as the environmental conditions or application needs change. The objective of this article, in this context, is to bring together the key advances at the device, data processing, and system levels that enable chemo-sensory systems to "adapt" in response to their environments. Accordingly, in this review we will feature the research effort made by selected experts on chemical sensing and information theory, whose work has been devoted to develop strategies that provide tunability and adaptability to single sensor devices or sensory array systems. Particularly, we consider sensor-array selection, modulation of internal sensing parameters, and active sensing. The article ends with some conclusions drawn from the results presented and a visionary look toward the future in terms of how the field may evolve.

Sensor Selection and Chemo-Sensory Optimization: Toward an Adaptable Chemo-Sensory System

PubMed Central

Vergara, Alexander; Llobet, Eduard

2011-01-01

Over the past two decades, despite the tremendous research on chemical sensors and machine olfaction to develop micro-sensory systems that will accomplish the growing existent needs in personal health (implantable sensors), environment monitoring (widely distributed sensor networks), and security/threat detection (chemo/bio warfare agents), simple, low-cost molecular sensing platforms capable of long-term autonomous operation remain beyond the current state-of-the-art of chemical sensing. A fundamental issue within this context is that most of the chemical sensors depend on interactions between the targeted species and the surfaces functionalized with receptors that bind the target species selectively, and that these binding events are coupled with transduction processes that begin to change when they are exposed to the messy world of real samples. With the advent of fundamental breakthroughs at the intersection of materials science, micro- and nano-technology, and signal processing, hybrid chemo-sensory systems have incorporated tunable, optimizable operating parameters, through which changes in the response characteristics can be modeled and compensated as the environmental conditions or application needs change. The objective of this article, in this context, is to bring together the key advances at the device, data processing, and system levels that enable chemo-sensory systems to “adapt” in response to their environments. Accordingly, in this review we will feature the research effort made by selected experts on chemical sensing and information theory, whose work has been devoted to develop strategies that provide tunability and adaptability to single sensor devices or sensory array systems. Particularly, we consider sensor-array selection, modulation of internal sensing parameters, and active sensing. The article ends with some conclusions drawn from the results presented and a visionary look toward the future in terms of how the field may evolve. PMID:22319492

A SPR strategy for high-throughput ligand screenings based on synthetic peptides mimicking a selected subdomain of the target protein: a proof of concept on HER2 receptor.

PubMed

Monfregola, Luca; Vitale, Rosa Maria; Amodeo, Pietro; De Luca, Stefania

2009-10-01

The discovery of pharmaceutical agents is a complex, lengthy and costly process, critically depending on the availability of rapid and efficient screening methods. In particular, when targets are large, multidomain proteins, their complexity may affect unfavorably technical feasibility, costs and unambiguity of binding test interpretation. A possible strategy to overcome these problems relies on molecular design of receptor fragments that are: sensible targets for ligand screenings, conformationally stable also as standalone domains, easily synthesized and immobilized on chip for Biacore experiments. An additional desirable feature for new ligands is the ability of selectively targeting alternative conformational states typical of many proteins. To test the feasibility of such approach on a case with potential applicative interest, we developed a surface plasmon resonance (SPR)-based screening method for drug candidates toward HER2, a Tyr-kinase receptor targeted in anticancer therapies. HER2 was mimicked by HER2-DIVMP, a modified fragment of it immobilized onto the sensor surface specifically modeling HER2 domain IV in its bounded form, designed by structural comparison of HER2 alone and in complex with Herceptin, a monoclonal therapeutic anti-HER2 antibody. This design and its implementation in SPR devices was validated by investigating Herceptin- HER2-DIVMP affinity, measuring its dissociation constant (K(D)=19.2 nM). An efficient synthetic procedure to prepare the HER2-DIVMP peptide was also developed. The HER2-DIVMP conformational stability suggested by experimental and computational results, makes it also a valuable candidate as a mold to design new molecules selectively targeting domain IV of HER2.

Potential Alternatives Report for Validation of Alternative Low-Emission Surface PreparationlDepainting Technologies for Structural Steel

NASA Technical Reports Server (NTRS)

Lewis, Pattie

2006-01-01

For this project, particulates and solvents used during the depainting process of steel structures were the identified hazardous material (HazMat) targeted for elimination or reduction. This Potential Alternatives Report (PAR) provides technical analyses of identified alternatives to the current coating removal processes, criteria used to select alternatives for further analysis, and a list of those alternatives recommended for testing. The initial coating removal alternatives list was compiled using literature searches and center participant recommendations. The involved project participants initially considered fifteen (15) alternatives. In late 2004, stakeholders down-selected the list and identified specific processes as potential alternatives to the current depainting methods. The selected alternatives were: 1. Plastic Blast Media 2. Hard Abrasive Media 3. Sponge Blast Media 4. Mechanical Removal with Vacuum Attachment 5. Liquid Nitrogen 6. Laser Coating Removal Available information about these processes was used to analyze the technical merits and the potential environmental, safety, and occupational health (ESOH) impacts of these methods. A preliminary cost benefit analysis will be performed to determine if implementation of alternative technologies is economically justified. NASA AP2

Affimer proteins are versatile and renewable affinity reagents

PubMed Central

Tiede, Christian; Bedford, Robert; Heseltine, Sophie J; Smith, Gina; Wijetunga, Imeshi; Ross, Rebecca; AlQallaf, Danah; Roberts, Ashley PE; Balls, Alexander; Curd, Alistair; Hughes, Ruth E; Martin, Heather; Needham, Sarah R; Zanetti-Domingues, Laura C; Sadigh, Yashar; Peacock, Thomas P; Tang, Anna A; Gibson, Naomi; Kyle, Hannah; Platt, Geoffrey W; Ingram, Nicola; Taylor, Thomas; Coletta, Louise P; Manfield, Iain; Knowles, Margaret; Bell, Sandra; Esteves, Filomena; Maqbool, Azhar; Prasad, Raj K; Drinkhill, Mark; Bon, Robin S; Patel, Vikesh; Goodchild, Sarah A; Martin-Fernandez, Marisa; Owens, Ray J; Nettleship, Joanne E; Webb, Michael E; Harrison, Michael; Lippiat, Jonathan D; Ponnambalam, Sreenivasan; Peckham, Michelle; Smith, Alastair; Ferrigno, Paul Ko; Johnson, Matt; McPherson, Michael J; Tomlinson, Darren Charles

2017-01-01

Molecular recognition reagents are key tools for understanding biological processes and are used universally by scientists to study protein expression, localisation and interactions. Antibodies remain the most widely used of such reagents and many show excellent performance, although some are poorly characterised or have stability or batch variability issues, supporting the use of alternative binding proteins as complementary reagents for many applications. Here we report on the use of Affimer proteins as research reagents. We selected 12 diverse molecular targets for Affimer selection to exemplify their use in common molecular and cellular applications including the (a) selection against various target molecules; (b) modulation of protein function in vitro and in vivo; (c) labelling of tumour antigens in mouse models; and (d) use in affinity fluorescence and super-resolution microscopy. This work shows that Affimer proteins, as is the case for other alternative binding scaffolds, represent complementary affinity reagents to antibodies for various molecular and cell biology applications. DOI: http://dx.doi.org/10.7554/eLife.24903.001 PMID:28654419

It takes a team: reflections on insecticide discoveries, toxicological problems and enjoying the unexpected.

PubMed

Wing, Keith D

2017-04-01

Absorption/distribution/metabolism/excretion (ADME)-related studies are mandatory in agrochemical development/registration, but can also play a valuable role in the discovery process. In combination with target-site potency, bioavailability/ADME characteristics determine agrochemical bioactivity and selectivity, and these concerns can dictate the fate of a discovery lead area. Bioavailability/ADME research was critical to the eventual commercialization of three different insecticide chemistries examined in this paper. In one situation, improved systemicity in anthranilic diamides was required to expand pest spectrum. In another, ADME tools were needed to improve the selective toxicity and non-target safety of sodium channel blocker insecticides. Finally, differential ADME characteristics of two classes of hormone agonists dictated differential insecticidal activity, and were useful in optimizing the dibenzoylhydrazine ecdysone agonists. ADME discovery research will help companies to advance novel, efficacious and selective agrochemicals, but organizational patience and a desire to understand lead areas in depth are required. © 2016 Society of Chemical Industry. © 2016 Society of Chemical Industry.

The significance of transferrin receptors in oncology: the development of functional nano-based drug delivery systems.

PubMed

Tortorella, Stephanie; Karagiannis, Tom C

2014-01-01

Anticancer therapeutic research aims to improve clinical management of the disease through the development of strategies that involve currently-relevant treatment options and targeted delivery. Tumour-specific and -targeted delivery of compounds to the site of malignancy allows for enhanced cellular uptake, increased therapeutic benefit with high intratumoural drug concentrations, and decreased systemic exposure. Due to the upregulation of transferrin receptor expression in a wide variety of cancers, its function and its highly efficient recycling pathway, strategies involving the selective targeting of the receptor are well documented. Direct conjugation and immunotoxin studies using the transferrin peptide or anti-transferrin receptor antibodies as the targeting moiety have established the capacity to enhance cellular uptake, cross the blood brain barrier, limit systemic toxicity and reverse multi-drug resistance. Limitations in direct conjugation, including the difficulty in linking an adequate amount of therapeutic compound to the ligand or antibody have identified the requirement to develop novel delivery methods. The application of nanoparticulate theory in the development of functional drug delivery systems has proven to be most promising, with the ability to selectively modify size-dependent properties and surface chemistry. The transferrin modification on a range of nanoparticle formulations enhances selective cellular uptake through transferrin-mediated processes, and increases therapeutic benefit through the ability to encapsulate high concentrations of relevant drug to the tumour site. Although ineffective in crossing the blood brain barrier in its free form, chemotherapeutic compounds including doxorubicin, may be loaded into transferrin-conjugated nanocarriers and impart cytotoxic effects in glioma cells in vitro and in vivo. Additionally, transferrin-targeted nanoparticles may be used in selective diagnostic applications with enhanced selectivity and sensitivity. Four transferrin-modified nano-based drug delivery systems are currently in early phases of human clinical trials. Despite the collective promise, inconsistencies in some studies have exposed some limitations in current formulations and the difficulty in translating preliminary studies into clinically-relevant therapeutic options. The main objective of this review is to investigate the development of transferrin targeted nano-based drug delivery systems in order to establish the use of transferrin as a cancer-targeted moiety, and to ultimately evaluate the progression of cancer therapeutic strategies for future research.

A category-specific top-down attentional set can affect the neural responses outside the current focus of attention.

PubMed

Jiang, Yunpeng; Wu, Xia; Gao, Xiaorong

2017-10-17

A top-down set can guide attention to enhance the processing of task-relevant objects. Many studies have found that the top-down set can be tuned to a category level. However, it is unclear whether the category-specific top-down set involving a central search task can exist outside the current area of attentional focus. To directly probe the neural responses inside and outside the current focus of attention, we recorded continuous EEG to measure the contralateral ERP components for central targets and the steady-state visual evoked potential (SSVEP) oscillations associated with a flickering checkerboard placed on the visual periphery. The relationship of color categories between targets and non-targets was manipulated to investigate the effect of category-specific top-down set. Results showed that when the color categories of targets and non-targets in the central search arrays were the same, larger SSVEP oscillations were evoked by target color peripheral checkerboards relative to the non-target color ones outside the current attentional focus. However, when the color categories of targets and non-targets were different, the peripheral checkerboards in two different colors of the same category evoked similar SSVEP oscillations, indicating the effects of category-specific top-down set. These results firstly demonstrate that the category-specific top-down set can affect the neural responses of peripheral distractors. The results could support the idea of a global selection account and challenge the attentional window account in selective attention. Copyright © 2017. Published by Elsevier B.V.

Process Evaluation of the Type 2 Diabetes Mellitus PULSE Program Randomized Controlled Trial: Recruitment, Engagement, and Overall Satisfaction.

PubMed

Aguiar, Elroy J; Morgan, Philip J; Collins, Clare E; Plotnikoff, Ronald C; Young, Myles D; Callister, Robin

2017-07-01

Men are underrepresented in weight loss and type 2 diabetes mellitus (T2DM) prevention studies. To determine the effectiveness of recruitment, and acceptability of the T2DM Prevention Using LifeStyle Education (PULSE) Program-a gender-targeted, self-administered intervention for men. Men (18-65 years, high risk for T2DM) were randomized to intervention ( n = 53) or wait-list control groups ( n = 48). The 6-month PULSE Program intervention focused on weight loss, diet, and exercise for T2DM prevention. A process evaluation questionnaire was administered at 6 months to examine recruitment and selection processes, and acceptability of the intervention's delivery and content. Associations between self-monitoring and selected outcomes were assessed using Spearman's rank correlation. A pragmatic recruitment and online screening process was effective in identifying men at high risk of T2DM (prediabetes prevalence 70%). Men reported the trial was appealing because it targeted weight loss, T2DM prevention, and getting fit, and because it was perceived as "doable" and tailored for men. The intervention was considered acceptable, with men reporting high overall satisfaction (83%) and engagement with the various components. Adherence to self-monitoring was poor, with only 13% meeting requisite criteria. However, significant associations were observed between weekly self-monitoring of weight and change in weight ( r s = -.47, p = .004) and waist circumference ( r s = -.38, p = .026). Men reported they would have preferred more intervention contact, for example, by phone or email. Gender-targeted, self-administered lifestyle interventions are feasible, appealing, and satisfying for men. Future studies should explore the effects of additional non-face-to-face contact on motivation, accountability, self-monitoring adherence, and program efficacy.

Selecting a Targeting Method to Identify BPL Households in India

ERIC Educational Resources Information Center

Alkire, Sabina; Seth, Suman

2013-01-01

This paper proposes how to select a methodology to target multidimensionally poor households, and how to update that targeting exercise periodically. We present this methodology in the context of discussions regarding the selection of a targeting methodology in India. In 1992, 1997, and 2002 the Indian government identified households that are…

77 FR 49819 - Agency Information Collection Activities; Proposed Collection; Comment Request; Pretesting of...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-08-17

.... Knowledge of these decisionmaking processes will be applied by FDA to help design effective communication... effectively design messages and select formats that have the greatest potential to influence the target... each new pretest will vary, depending on the nature of the material or message being tested and the...

Trainers for Operators of Guided Missiles

DTIC Science & Technology

1945-09-28

APPENDIX I SELECTION AND TRAINING IN THE PROCESS UF. REMOTE CUNTRÜL " . Treater: Henschke. One of the most difficult tasks in new hrms is...perimeter to the center. The carriage of arm No, 2 has a magnet upon which a target (a small iron automobile ) may be placed. Since the arms can be set

Inhibition of human TDP2 by deazaflavins | Center for Cancer Research

Cancer.gov

Tyrosyl-DNA phosphodiesterase 2 repairs irreversible topoisomerase II-mediated cleavage complexes generated by anticancer topoisomerase-targeted drugs and processes replication intermediates for picornaviruses (VPg unlinkase) and hepatitis B virus. There is currently no TDP2 inhibitor in clinical development. Here, we report a series of deazaflavin derivatives that selectively

Organizing Self-Employment Programs: A Guide for Development Organizations.

ERIC Educational Resources Information Center

Rinehart, Eric L., Ed.; Lamb, Melissa, Ed.

This resource guide is intended to help communities that want to implement an entrepreneurship training program. Chapters I and II contain general advice for the planning process, such as how to assess need and community support, assess current services for entrepreneurs, select target clientele, develop a community support network, and identify…

Structure Mapping in Autism Spectrum Disorder: Levels of Information Processing and Relations to Executive Functions

ERIC Educational Resources Information Center

Hetzroni, Orit E.; Shalahevich, Kiril

2018-01-01

Analogical reasoning was investigated among children with autism spectrum disorders (ASD) without intellectual disabilities and typical development (TD). Children were asked to select one of two targets in two conditions: (1) with and without spatial structure similarity; (2) with and without a perceptual distractor. Results demonstrate that…

Wild capuchin monkeys adjust stone tools according to changing nut properties.

PubMed

Luncz, Lydia V; Falótico, Tiago; Pascual-Garrido, Alejandra; Corat, Clara; Mosley, Hannah; Haslam, Michael

2016-09-14

Animals foraging in their natural environments need to be proficient at recognizing and responding to changes in food targets that affect accessibility or pose a risk. Wild bearded capuchin monkeys (Sapajus libidinosus) use stone tools to access a variety of nut species, including otherwise inaccessible foods. This study tests whether wild capuchins from Serra da Capivara National Park in Brazil adjust their tool selection when processing cashew (Anacardium spp.) nuts. During the ripening process of cashew nuts, the amount of caustic defensive substance in the nut mesocarp decreases. We conducted field experiments to test whether capuchins adapt their stone hammer selection to changing properties of the target nut, using stones of different weights and two maturation stages of cashew nuts. The results show that although fresh nuts are easier to crack, capuchin monkeys used larger stone tools to open them, which may help the monkeys avoid contact with the caustic hazard in fresh nuts. We demonstrate that capuchin monkeys are actively able to distinguish between the maturation stages within one nut species, and to adapt their foraging behaviour accordingly.

Wild capuchin monkeys adjust stone tools according to changing nut properties

PubMed Central

Luncz, Lydia V.; Falótico, Tiago; Pascual-Garrido, Alejandra; Corat, Clara; Mosley, Hannah; Haslam, Michael

2016-01-01

Animals foraging in their natural environments need to be proficient at recognizing and responding to changes in food targets that affect accessibility or pose a risk. Wild bearded capuchin monkeys (Sapajus libidinosus) use stone tools to access a variety of nut species, including otherwise inaccessible foods. This study tests whether wild capuchins from Serra da Capivara National Park in Brazil adjust their tool selection when processing cashew (Anacardium spp.) nuts. During the ripening process of cashew nuts, the amount of caustic defensive substance in the nut mesocarp decreases. We conducted field experiments to test whether capuchins adapt their stone hammer selection to changing properties of the target nut, using stones of different weights and two maturation stages of cashew nuts. The results show that although fresh nuts are easier to crack, capuchin monkeys used larger stone tools to open them, which may help the monkeys avoid contact with the caustic hazard in fresh nuts. We demonstrate that capuchin monkeys are actively able to distinguish between the maturation stages within one nut species, and to adapt their foraging behaviour accordingly. PMID:27624672

p62 targeting to the autophagosome formation site requires self-oligomerization but not LC3 binding

PubMed Central

Itakura, Eisuke

2011-01-01

Autophagy is an intracellular degradation process by which cytoplasmic contents are degraded in the lysosome. In addition to nonselective engulfment of cytoplasmic materials, the autophagosomal membrane can selectively recognize specific proteins and organelles. It is generally believed that the major selective substrate (or cargo receptor) p62 is recruited to the autophagosomal membrane through interaction with LC3. In this study, we analyzed loading of p62 and its related protein NBR1 and found that they localize to the endoplasmic reticulum (ER)–associated autophagosome formation site independently of LC3 localization to membranes. p62 colocalizes with upstream autophagy factors such as ULK1 and VMP1 even when autophagosome formation is blocked by wortmannin or FIP200 knockout. Self-oligomerization of p62 is essential for its localization to the autophagosome formation site. These results suggest that p62 localizes to the autophagosome formation site on the ER, where autophagosomes are nucleated. This process is similar to the yeast cytoplasm to vacuole targeting pathway. PMID:21220506

Imaging of Homeostatic, Neoplastic, and Injured Tissues by HA-Based Probes

PubMed Central

Veiseh, Mandana; Breadner, Daniel; Ma, Jenny; Akentieva, Natalia; Savani, Rashmin C; Harrison, Rene; Mikilus, David; Collis, Lisa; Gustafson, Stefan; Lee, Ting-Yim; Koropatnick, James; Luyt, Leonard G.; Bissell, Mina J.; Turley, Eva A.

2013-01-01

An increase in hyaluronan (HA) synthesis, cellular uptake, and metabolism occurs during the remodeling of tissue microenvironments following injury and during disease processes such as cancer. We hypothesized that multimodality HA-based probes selectively target and detectably accumulate at sites of high HA metabolism, thus providing a flexible imaging strategy for monitoring disease and repair processes. Kinetic analyses confirmed favorable available serum levels of the probe following intravenous (i.v.) or subcutaneous (s.c.) injection. Nuclear (technetium-HA, 99mTc-HA, and iodine-HA, 125I-HA), optical (fluorescent Texas Red-HA, TR-HA), and magnetic resonance (gadolinium-HA, Gd-HA) probes imaged liver (99mTc-HA), breast cancer cells/xenografts (TR-HA, Gd-HA), and vascular injury (125I-HA, TR-HA). Targeting of HA probes to these sites appeared to result from selective HA receptor-dependent localization. Our results suggest that HA-based probes, which do not require polysaccharide backbone modification to achieve favorable half-life and distribution, can detect elevated HA metabolism in homeostatic, injured, and diseased tissues. PMID:22066590

Stress-Driven Selection of Novel Phenotypes

NASA Technical Reports Server (NTRS)

Fox, George E.; Stepaov, Victor G.; Liu, Yamei

2011-01-01

A process has been developed that can confer novel properties, such as metal resistance, to a host bacterium. This same process can also be used to produce RNAs and peptides that have novel properties, such as the ability to bind particular compounds. It is inherent in the method that the peptide or RNA will behave as expected in the target organism. Plasmid-born mini-gene libraries coding for either a population of combinatorial peptides or stable, artificial RNAs carrying random inserts are produced. These libraries, which have no bias towards any biological function, are used to transform the organism of interest and to serve as an initial source of genetic variation for stress-driven evolution. The transformed bacteria are propagated under selective pressure in order to obtain variants with the desired properties. The process is highly distinct from in vitro methods because the variants are selected in the context of the cell while it is experiencing stress. Hence, the selected peptide or RNA will, by definition, work as expected in the target cell as the cell adapts to its presence during the selection process. Once the novel gene, which produces the sought phenotype, is obtained, it can be transferred to the main genome to increase the genetic stability in the organism. Alternatively, the cell line can be used to produce novel RNAs or peptides with selectable properties in large quantity for separate purposes. The system allows for easy, large-scale purification of the RNAs or peptide products. The process has been reduced to practice by imposing sub-inhibitory concentrations of NiCl2 on cells of the bacterium Escherichia coli that were transformed separately with the peptide library and RNA library. The evolved resistant clones were isolated, and sequences of the selected mini-gene variants were established. Clones resistant to NiCl2 were found to carry identical plasmid variants with a functional mini-gene that specifically conferred significant nickel tolerance on the host cells. Sequencing of the selected mini-gene revealed a propensity of the encoded peptide to bind transient metal ions. Expression of the mini-gene markedly improved growth parameters of the evolved clones at sub-inhibitory concentrations of NiCl2 while being slightly detrimental in the absence of stress. Similar results have been obtained with the RNA libraries. Overall, the results demonstrate a very natural outcome of the selection experiments in which the mini-genes were expected to be either successfully integrated into bacterial genetic networks, or rejected depending upon their effect on host fitness. This described approach can be useful as a laboratory model to study the dynamics of bacterial adaptive evolution on the molecular level. It can also provide a strategy for screening expressed DNA libraries in search of novel genes with desirable properties.

Targeting Neural Endophenotypes of Eating Disorders with Non-invasive Brain Stimulation

PubMed Central

Dunlop, Katharine A.; Woodside, Blake; Downar, Jonathan

2016-01-01

The term “eating disorders” (ED) encompasses a wide variety of disordered eating and compensatory behaviors, and so the term is associated with considerable clinical and phenotypic heterogeneity. This heterogeneity makes optimizing treatment techniques difficult. One class of treatments is non-invasive brain stimulation (NIBS). NIBS, including repetitive transcranial magnetic stimulation (rTMS) and transcranial direct current stimulation (tDCS), are accessible forms of neuromodulation that alter the cortical excitability of a target brain region. It is crucial for NIBS to be successful that the target is well selected for the patient population in question. Targets may best be selected by stepping back from conventional DSM-5 diagnostic criteria to identify neural substrates of more basic phenotypes, including behavior related to rewards and punishment, cognitive control, and social processes. These phenotypic dimensions have been recently laid out by the Research Domain Criteria (RDoC) initiative. Consequently, this review is intended to identify potential dimensions as outlined by the RDoC and the underlying behavioral and neurobiological targets associated with ED. This review will also identify candidate targets for NIBS based on these dimensions and review the available literature on rTMS and tDCS in ED. This review systematically reviews abnormal neural circuitry in ED within the RDoC framework, and also systematically reviews the available literature investigating NIBS as a treatment for ED. PMID:26909013

Nonviral siRNA delivery for gene silencing in neurodegenerative diseases.

PubMed

Prakash, Satya; Malhotra, Meenakshi; Rengaswamy, Venkatesh

2010-01-01

Linking genes with the underlying mechanisms of diseases is one of the biggest challenges of genomics-driven drug discovery research. Designing an inhibitor for any neurodegenerative disease that effectively halts the pathogenicity of the disease is yet to be achieved. The challenge lies in crossing the blood-brain barrier (BBB)/blood-cerebrospinal fluid barrier (BCSFB) to reach the catalytic pockets of the enzyme/protein involved in the molecular mechanism of the disease process. Designing siRNA with exquisite specificity may result in selective suppression of the disease-linked gene. Although siRNA is the most promising method, it loses its potency in downregulating the gene due to its inherent instability, off-target effects, and lack of on-target effective delivery systems. Viral as well as nonviral delivery methods have been effectively tested in vivo for silencing of molecular targets and have resulted in significant efficacy in animal models of Alzheimer's disease, amyotrophic lateral sclerosis (ALS), anxiety, depression, encephalitis, glioblastoma, Huntington's disease, neuropathic pain, and spinocerebellar ataxia. To realize the full therapeutic potential of siRNA for neurodegenerative diseases, we need to overcome many hurdles and challenges such as selecting suitable tissue-specific delivery vectors, minimizing the off-target effects, and achieving distribution in sufficient concentrations at the target tissue without any side effects. Cationic nanoparticle-mediated targeted siRNA delivery for therapeutic purposes has gained considerable clinical importance as a result of its promising efficacy.

Computational design of nanoparticle drug delivery systems for selective targeting

NASA Astrophysics Data System (ADS)

Duncan, Gregg A.; Bevan, Michael A.

2015-09-01

Ligand-functionalized nanoparticles capable of selectively binding to diseased versus healthy cell populations are attractive for improved efficacy of nanoparticle-based drug and gene therapies. However, nanoparticles functionalized with high affinity targeting ligands may lead to undesired off-target binding to healthy cells. In this work, Monte Carlo simulations were used to quantitatively determine net surface interactions, binding valency, and selectivity between targeted nanoparticles and cell surfaces. Dissociation constant, KD, and target membrane protein density, ρR, are explored over a range representative of healthy and cancerous cell surfaces. Our findings show highly selective binding to diseased cell surfaces can be achieved with multiple, weaker affinity targeting ligands that can be further optimized by varying the targeting ligand density, ρL. Using the approach developed in this work, nanomedicines can be optimally designed for exclusively targeting diseased cells and tissues.Ligand-functionalized nanoparticles capable of selectively binding to diseased versus healthy cell populations are attractive for improved efficacy of nanoparticle-based drug and gene therapies. However, nanoparticles functionalized with high affinity targeting ligands may lead to undesired off-target binding to healthy cells. In this work, Monte Carlo simulations were used to quantitatively determine net surface interactions, binding valency, and selectivity between targeted nanoparticles and cell surfaces. Dissociation constant, KD, and target membrane protein density, ρR, are explored over a range representative of healthy and cancerous cell surfaces. Our findings show highly selective binding to diseased cell surfaces can be achieved with multiple, weaker affinity targeting ligands that can be further optimized by varying the targeting ligand density, ρL. Using the approach developed in this work, nanomedicines can be optimally designed for exclusively targeting diseased cells and tissues. Electronic supplementary information (ESI) available: Movie showing simulation renderings of targeted (ρL = 1820/μm2, KD = 120 μM) nanoparticle selective binding to cancer (ρR = 256/μm2) vs. healthy (ρR = 64/μm2) cell surfaces. Target membrane proteins have linear color scale depending on binding energy ranging from white when unbound (URL = 0) to red when tightly bound (URL = UM). See DOI: 10.1039/c5nr03691g

Multi-surface topography targeted plateau honing for the processing of cylinder liner surfaces of automotive engines

NASA Astrophysics Data System (ADS)

Lawrence, K. Deepak; Ramamoorthy, B.

2016-03-01

Cylinder bores of automotive engines are 'engineered' surfaces that are processed using multi-stage honing process to generate multiple layers of micro geometry for meeting the different functional requirements of the piston assembly system. The final processed surfaces should comply with several surface topographic specifications that are relevant for the good tribological performance of the engine. Selection of the process parameters in three stages of honing to obtain multiple surface topographic characteristics simultaneously within the specification tolerance is an important module of the process planning and is often posed as a challenging task for the process engineers. This paper presents a strategy by combining the robust process design and gray-relational analysis to evolve the operating levels of honing process parameters in rough, finish and plateau honing stages targeting to meet multiple surface topographic specifications on the final running surface of the cylinder bores. Honing experiments were conducted in three stages namely rough, finish and plateau honing on cast iron cylinder liners by varying four honing process parameters such as rotational speed, oscillatory speed, pressure and honing time. Abbott-Firestone curve based functional parameters (Rk, Rpk, Rvk, Mr1 and Mr2) coupled with mean roughness depth (Rz, DIN/ISO) and honing angle were measured and identified as the surface quality performance targets to be achieved. The experimental results have shown that the proposed approach is effective to generate cylinder liner surface that would simultaneously meet the explicit surface topographic specifications currently practiced by the industry.

Large-scale production of diesel-like biofuels - process design as an inherent part of microorganism development.

PubMed

Cuellar, Maria C; Heijnen, Joseph J; van der Wielen, Luuk A M

2013-06-01

Industrial biotechnology is playing an important role in the transition to a bio-based economy. Currently, however, industrial implementation is still modest, despite the advances made in microorganism development. Given that the fuels and commodity chemicals sectors are characterized by tight economic margins, we propose to address overall process design and efficiency at the start of bioprocess development. While current microorganism development is targeted at product formation and product yield, addressing process design at the start of bioprocess development means that microorganism selection can also be extended to other critical targets for process technology and process scale implementation, such as enhancing cell separation or increasing cell robustness at operating conditions that favor the overall process. In this paper we follow this approach for the microbial production of diesel-like biofuels. We review current microbial routes with both oleaginous and engineered microorganisms. For the routes leading to extracellular production, we identify the process conditions for large scale operation. The process conditions identified are finally translated to microorganism development targets. We show that microorganism development should be directed at anaerobic production, increasing robustness at extreme process conditions and tailoring cell surface properties. All the same time, novel process configurations integrating fermentation and product recovery, cell reuse and low-cost technologies for product separation are mandatory. This review provides a state-of-the-art summary of the latest challenges in large-scale production of diesel-like biofuels. Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Oligonucleotide Sensor Based on Selective Capture of Upconversion Nanoparticles Triggered by Target-Induced DNA Interstrand Ligand Reaction

PubMed Central

2017-01-01

We present a sensor that exploits the phenomenon of upconversion luminescence to detect the presence of specific sequences of small oligonucleotides such as miRNAs among others. The sensor is based on NaYF4:Yb,Er@SiO2 nanoparticles functionalized with ssDNA that contain azide groups on the 3′ ends. In the presence of a target sequence, interstrand ligation is possible via the click-reaction between one azide of the upconversion probe and a DBCO-ssDNA-biotin probe present in the solution. As a result of this specific and selective process, biotin is covalently attached to the surface of the upconversion nanoparticles. The presence of biotin on the surface of the nanoparticles allows their selective capture on a streptavidin-coated support, giving a luminescent signal proportional to the amount of target strands present in the test samples. With the aim of studying the analytical properties of the sensor, total RNA samples were extracted from healthy mosquitoes and were spiked-in with a specific target sequence at different concentrations. The result of these experiments revealed that the sensor was able to detect 10–17 moles per well (100 fM) of the target sequence in mixtures containing 100 ng of total RNA per well. A similar limit of detection was found for spiked human serum samples, demonstrating the suitability of the sensor for detecting specific sequences of small oligonucleotides under real conditions. In contrast, in the presence of noncomplementary sequences or sequences having mismatches, the luminescent signal was negligible or conspicuously reduced. PMID:28332400

The costs and benefits of temporal predictability: impaired inhibition of prepotent responses accompanies increased activation of task-relevant responses.

PubMed

Korolczuk, Inga; Burle, Boris; Coull, Jennifer T

2018-06-20

While the benefit of temporal predictability on sensorimotor processing is well established, it is still unknown whether this is due to efficient execution of an appropriate response and/or inhibition of an inappropriate one. To answer this question, we examined the effects of temporal predictability in tasks that required selective (Simon task) or global (Stop-signal task) inhibitory control of prepotent responses. We manipulated temporal expectation by presenting cues that either predicted (temporal cues) or not (neutral cues) when the target would appear. In the Simon task, performance was better when target location (left/right) was compatible with the hand of response and performance was improved further still if targets were temporally cued. However, Conditional Accuracy Functions revealed that temporal predictability selectively increased the number of fast, impulsive errors. Temporal cueing had no effect on selective response inhibition, as measured by the dynamics of the interference effect (delta plots) in the Simon task. By contrast, in the Stop-signal task, Stop-signal reaction time, a covert measure of a more global form of response inhibition, was significantly longer in temporally predictive trials. Therefore, when the time of target onset could be predicted in advance, it was harder to stop the impulse to respond to the target. Collectively, our results indicate that temporal cueing compounded the interfering effects of a prepotent response on task performance. We suggest that although temporal predictability enhances activation of task-relevant responses, it impairs inhibition of prepotent responses. Copyright © 2018 Elsevier B.V. All rights reserved.

Mediators of Effects of a Selective Family-Focused Violence Prevention Approach for Middle School Students

PubMed Central

2013-01-01

This study examined how parenting and family characteristics targeted in a selective prevention program mediated effects on key youth proximal outcomes related to violence perpetration. The selective intervention was evaluated within the context of a multi-site trial involving random assignment of 37 schools to four conditions: a universal intervention composed of a student social-cognitive curriculum and teacher training, a selective family-focused intervention with a subset of high-risk students, a condition combining these two interventions, and a no-intervention control condition. Two cohorts of sixth-grade students (total N=1,062) exhibiting high levels of aggression and social influence were the sample for this study. Analyses of pre-post change compared to controls using intent-to-treat analyses found no significant effects. However, estimates incorporating participation of those assigned to the intervention and predicted participation among those not assigned revealed significant positive effects on student aggression, use of aggressive strategies for conflict management, and parental estimation of student’s valuing of achievement. Findings also indicated intervention effects on two targeted family processes: discipline practices and family cohesion. Mediation analyses found evidence that change in these processes mediated effects on some outcomes, notably aggressive behavior and valuing of school achievement. Results support the notion that changing parenting practices and the quality of family relationships can prevent the escalation in aggression and maintain positive school engagement for high-risk youth. PMID:21932067

Detection of hydroxyapatite in calcified cardiovascular tissues.

PubMed

Lee, Jae Sam; Morrisett, Joel D; Tung, Ching-Hsuan

2012-10-01

The objective of this study is to develop a method for selective detection of the calcific (hydroxyapatite) component in human aortic smooth muscle cells in vitro and in calcified cardiovascular tissues ex vivo. This method uses a novel optical molecular imaging contrast dye, Cy-HABP-19, to target calcified cells and tissues. A peptide that mimics the binding affinity of osteocalcin was used to label hydroxyapatite in vitro and ex vivo. Morphological changes in vascular smooth muscle cells were evaluated at an early stage of the mineralization process induced by extrinsic stimuli, osteogenic factors and a magnetic suspension cell culture. Hydroxyapatite components were detected in monolayers of these cells in the presence of osteogenic factors and a magnetic suspension environment. Atherosclerotic plaque contains multiple components including lipidic, fibrotic, thrombotic, and calcific materials. Using optical imaging and the Cy-HABP-19 molecular imaging probe, we demonstrated that hydroxyapatite components could be selectively distinguished from various calcium salts in human aortic smooth muscle cells in vitro and in calcified cardiovascular tissues, carotid endarterectomy samples and aortic valves, ex vivo. Hydroxyapatite deposits in cardiovascular tissues were selectively detected in the early stage of the calcification process using our Cy-HABP-19 probe. This new probe makes it possible to study the earliest events associated with vascular hydroxyapatite deposition at the cellular and molecular levels. This target-selective molecular imaging probe approach holds high potential for revealing early pathophysiological changes, leading to progression, regression, or stabilization of cardiovascular diseases. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

Detection of Hydroxyapatite in Calcified Cardiovascular Tissues

PubMed Central

Lee, Jae Sam; Morrisett, Joel D.; Tung, Ching-Hsuan

2012-01-01

Objective The objective of this study is to develop a method for selective detection of the calcific (hydroxyapatite) component in human aortic smooth muscle cells in vitro and in calcified cardiovascular tissues ex vivo. This method uses a novel optical molecular imaging contrast dye, Cy-HABP-19, to target calcified cells and tissues. Methods A peptide that mimics the binding affinity of osteocalcin was used to label hydroxyapatite in vitro and ex vivo. Morphological changes in vascular smooth muscle cells were evaluated at an early stage of the mineralization process induced by extrinsic stimuli, osteogenic factors and a magnetic suspension cell culture. Hydroxyapatite components were detected in monolayers of these cells in the presence of osteogenic factors and a magnetic suspension environment. Results Atherosclerotic plaque contains multiple components including lipidic, fibrotic, thrombotic, and calcific materials. Using optical imaging and the Cy-HABP-19 molecular imaging probe, we demonstrated that hydroxyapatite components could be selectively distinguished from various calcium salts in human aortic smooth muscle cells in vitro and in calcified cardiovascular tissues, carotid endarterectomy samples and aortic valves, ex vivo. Conclusion Hydroxyapatite deposits in cardiovascular tissues were selectively detected in the early stage of the calcification process using our Cy-HABP-19 probe. This new probe makes it possible to study the earliest events associated with vascular hydroxyapatite deposition at the cellular and molecular levels. This target-selective molecular imaging probe approach holds high potential for revealing early pathophysiological changes, leading to progression, regression, or stabilization of cardiovascular diseases. PMID:22877867

Utility-based early modulation of processing distracting stimulus information.

PubMed

Wendt, Mike; Luna-Rodriguez, Aquiles; Jacobsen, Thomas

2014-12-10

Humans are selective information processors who efficiently prevent goal-inappropriate stimulus information to gain control over their actions. Nonetheless, stimuli, which are both unnecessary for solving a current task and liable to cue an incorrect response (i.e., "distractors"), frequently modulate task performance, even when consistently paired with a physical feature that makes them easily discernible from target stimuli. Current models of cognitive control assume adjustment of the processing of distractor information based on the overall distractor utility (e.g., predictive value regarding the appropriate response, likelihood to elicit conflict with target processing). Although studies on distractor interference have supported the notion of utility-based processing adjustment, previous evidence is inconclusive regarding the specificity of this adjustment for distractor information and the stage(s) of processing affected. To assess the processing of distractors during sensory-perceptual phases we applied EEG recording in a stimulus identification task, involving successive distractor-target presentation, and manipulated the overall distractor utility. Behavioral measures replicated previously found utility modulations of distractor interference. Crucially, distractor-evoked visual potentials (i.e., posterior N1) were more pronounced in high-utility than low-utility conditions. This effect generalized to distractors unrelated to the utility manipulation, providing evidence for item-unspecific adjustment of early distractor processing to the experienced utility of distractor information. Copyright © 2014 the authors 0270-6474/14/3416720-06$15.00/0.

Where have we gone wrong? Perceptual load does not affect selective attention.

PubMed

Benoni, Hanna; Tsal, Yehoshua

2010-06-18

The theory of perceptual load (Lavie & Tsal, 1994) proposes that with low load in relevant processing left over resources spill over to process irrelevant distractors. Interference could only be prevented under High-Load Conditions where relevant processing exhausts attentional resources. The theory is based primarily on the finding that distractor interference obtained in low load displays, when the target appears alone, is eliminated in high load displays when it is embedded among neutral letters. However, a possible alternative interpretation of this effect is that the distractor is similarly processed in both displays, yet its interference in the large displays is diluted by the presence of the neutral letters. We separated the possible effects of load and dilution by adding dilution displays that were high in dilution and low in perceptual load. In the first experiment these displays contained as many letters as the high load displays, but their neutral letters were clearly distinguished from the target, thereby allowing for a low load processing mode. In the second experiment we presented identical multicolor displays in the Dilution and High-Load Conditions. However, in the former the target color was known in advance (thereby preserving a low load processing mode) whereas in the latter it was not. In both experiments distractor interference was completely eliminated under the Dilution Condition. Thus, it is dilution not perceptual load affecting distractor processing. 2010 Elsevier Ltd. All rights reserved.

Particle Filtering with Region-based Matching for Tracking of Partially Occluded and Scaled Targets*

PubMed Central

Nakhmani, Arie; Tannenbaum, Allen

2012-01-01

Visual tracking of arbitrary targets in clutter is important for a wide range of military and civilian applications. We propose a general framework for the tracking of scaled and partially occluded targets, which do not necessarily have prominent features. The algorithm proposed in the present paper utilizes a modified normalized cross-correlation as the likelihood for a particle filter. The algorithm divides the template, selected by the user in the first video frame, into numerous patches. The matching process of these patches by particle filtering allows one to handle the target’s occlusions and scaling. Experimental results with fixed rectangular templates show that the method is reliable for videos with nonstationary, noisy, and cluttered background, and provides accurate trajectories in cases of target translation, scaling, and occlusion. PMID:22506088

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

PubMed

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.

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

PubMed

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 suggests that unrecognized function(s) might exist for this PPR protein. PPR gene sequences that encode helix A are under strong selection, and could be involved in RNA substrate recognition.

Decentralized cooperative TOA/AOA target tracking for hierarchical wireless sensor networks.

PubMed

Chen, Ying-Chih; Wen, Chih-Yu

2012-11-08

This paper proposes a distributed method for cooperative target tracking in hierarchical wireless sensor networks. The concept of leader-based information processing is conducted to achieve object positioning, considering a cluster-based network topology. Random timers and local information are applied to adaptively select a sub-cluster for the localization task. The proposed energy-efficient tracking algorithm allows each sub-cluster member to locally estimate the target position with a Bayesian filtering framework and a neural networking model, and further performs estimation fusion in the leader node with the covariance intersection algorithm. This paper evaluates the merits and trade-offs of the protocol design towards developing more efficient and practical algorithms for object position estimation.

Selective binding and transcytosis of Ulex europaeus 1 lectin by mouse Peyer's patch M-cells in vivo.

PubMed

Clark, M A; Jepson, M A; Simmons, N L; Hirst, B H

1995-12-01

The in vivo interaction of the lectin Ulex europaeus agglutinin 1 with mouse Peyer's patch follicle-associated epithelial cells was studied in the mouse Peyer's patch gut loop model by immunofluorescence and electron microscopy. The lectin targets to mouse Peyer's patch M-cells and is rapidly endocytosed and transcytosed. These processes are accompanied by morphological changes in the M-cell microvilli and by redistribution of polymerised actin. The demonstration of selective binding and uptake of a lectin by intestinal M-cells in vivo suggests that M-cell-specific surface glycoconjugates might act as receptors for the selective adhesion/uptake of microorganisms.

Joint Waveform Optimization and Adaptive Processing for Random-Phase Radar Signals

DTIC Science & Technology

2014-01-01

extended targets,” IEEE Journal of Selected Topics in Signal Processing, vol. 1, no. 1, pp. 42– 55, June 2007. [2] S. Sen and A. Nehorai, “ OFDM mimo ...radar compared to traditional waveforms. I. INTRODUCTION There has been much recent interest in waveform design for multiple-input, multiple-output ( MIMO ...amplitude. When the resolution capability of the MIMO radar system is of interest, the transmit waveform can be designed to sharpen the radar ambiguity

Food sensing: selection and characterization of DNA aptamers to Alicyclobacillus spores for trapping and detection from orange juice.

PubMed

Hünniger, Tim; Fischer, Christin; Wessels, Hauke; Hoffmann, Antonia; Paschke-Kratzin, Angelika; Haase, Ilka; Fischer, Markus

2015-03-04

The quality of the beverage industry's products has to be constantly monitored to fulfill consumers' high expectations. The thermo-acidophilic Gram-positive Alicyclobacillus spp. are not pathogenic, but their heat-resistant endospores can survive juice-processing conditions and have become a major economic concern for the fruit juice industry. Current detection methods rely on cultivation, isolation, and organism identification, which can take up to a week, resulting in economic loss. This work presents the selection and identification of DNA aptamers targeting Alicyclobacillus spores by spore-SELEX (systematic evolution of ligands by exponential enrichment) in orange-juice-simulating buffer. The selection process was verified by various techniques, including flow cytometric binding assays, radioactive binding assays, and agarose gel electrophoresis. The subsequent aptamer characterization included the determination of dissociations constants and selectivity by different techniques, such as surface plasmon resonance spectroscopy and fluorescence microscopy. In summary, 10 different aptamers with an affinity to Alicyclobacillus spp. have been developed, analyzed, and characterized in terms of affinity and specificity.

Selective visual scaling of time-scale processes facilitates broadband learning of isometric force frequency tracking.

PubMed

King, Adam C; Newell, Karl M

2015-10-01

The experiment investigated the effect of selectively augmenting faster time scales of visual feedback information on the learning and transfer of continuous isometric force tracking tasks to test the generality of the self-organization of 1/f properties of force output. Three experimental groups tracked an irregular target pattern either under a standard fixed gain condition or with selectively enhancement in the visual feedback display of intermediate (4-8 Hz) or high (8-12 Hz) frequency components of the force output. All groups reduced tracking error over practice, with the error lowest in the intermediate scaling condition followed by the high scaling and fixed gain conditions, respectively. Selective visual scaling induced persistent changes across the frequency spectrum, with the strongest effect in the intermediate scaling condition and positive transfer to novel feedback displays. The findings reveal an interdependence of the timescales in the learning and transfer of isometric force output frequency structures consistent with 1/f process models of the time scales of motor output variability.

Mitochondria and Mitochondrial ROS in Cancer: Novel Targets for Anticancer Therapy.

PubMed

Yang, Yuhui; Karakhanova, Svetlana; Hartwig, Werner; D'Haese, Jan G; Philippov, Pavel P; Werner, Jens; Bazhin, Alexandr V

2016-12-01

Mitochondria are indispensable for energy metabolism, apoptosis regulation, and cell signaling. Mitochondria in malignant cells differ structurally and functionally from those in normal cells and participate actively in metabolic reprogramming. Mitochondria in cancer cells are characterized by reactive oxygen species (ROS) overproduction, which promotes cancer development by inducing genomic instability, modifying gene expression, and participating in signaling pathways. Mitochondrial and nuclear DNA mutations caused by oxidative damage that impair the oxidative phosphorylation process will result in further mitochondrial ROS production, completing the "vicious cycle" between mitochondria, ROS, genomic instability, and cancer development. The multiple essential roles of mitochondria have been utilized for designing novel mitochondria-targeted anticancer agents. Selective drug delivery to mitochondria helps to increase specificity and reduce toxicity of these agents. In order to reduce mitochondrial ROS production, mitochondria-targeted antioxidants can specifically accumulate in mitochondria by affiliating to a lipophilic penetrating cation and prevent mitochondria from oxidative damage. In consistence with the oncogenic role of ROS, mitochondria-targeted antioxidants are found to be effective in cancer prevention and anticancer therapy. A better understanding of the role played by mitochondria in cancer development will help to reveal more therapeutic targets, and will help to increase the activity and selectivity of mitochondria-targeted anticancer drugs. In this review we summarized the impact of mitochondria on cancer and gave summary about the possibilities to target mitochondria for anticancer therapies. J. Cell. Physiol. 231: 2570-2581, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Candidiasis drug discovery and development: new approaches targeting virulence for discovering and identifying new drugs

PubMed Central

Pierce, Christopher G.; Lopez-Ribot, Jose L.

2014-01-01

Introduction Targeting pathogenetic mechanisms rather than essential processes represents a very attractive alternative for the development of new antibiotics. This may be particularly important in the case of antimycotics, due to the urgent need for novel antifungal drugs and the paucity of selective fungal targets. The opportunistic pathogenic fungus Candida albicans is the main etiological agent of candidiasis, the most common human fungal infection. These infections carry unacceptably high mortality rates, a clear reflection of the many shortcomings of current antifungal therapy, including the limited armamentarium of antifungal agents, their toxicity, and the emergence of resistance. Moreover the antifungal pipeline is mostly dry. Areas covered This review covers some of the most recent progress towards understanding C. albicans pathogenetic processes and how to harness this information for the development of anti-virulence agents. The two principal areas covered are filamentation and biofilm formation, as C. albicans pathogenicity is intimately linked to its ability to undergo morphogenetic conversions between yeast and filamentous morphologies and to its ability to form biofilms. Expert opinion We argue that filamentation and biofilm formation represent high value targets, yet clinically unexploited, for the development of novel anti-virulence approaches against candidiasis. Although this has proved a difficult task despite increasing understanding at the molecular level of C. albicans virulence, we highlight new opportunities and prospects for antifungal drug development targeting these two important biological processes. PMID:23738751