Dual-targeting siRNAs

PubMed Central

Tiemann, Katrin; Höhn, Britta; Ehsani, Ali; Forman, Stephen J.; Rossi, John J.; Sætrom, Pål

2010-01-01

We have developed an algorithm for the prediction of dual-targeting short interfering RNAs (siRNAs) in which both strands are deliberately designed to separately target different mRNA transcripts with complete complementarity. An advantage of this approach versus the use of two separate duplexes is that only two strands, as opposed to four, are competing for entry into the RNA-induced silencing complex. We chose to design our dual-targeting siRNAs as Dicer substrate 25/27mer siRNAs, since design features resembling pre-microRNAs (miRNAs) can be introduced for Dicer processing. Seven different dual-targeting siRNAs targeting genes that are potential targets in cancer therapy have been developed including Bcl2, Stat3, CCND1, BIRC5, and MYC. The dual-targeting siRNAs have been characterized for dual target knockdown in three different cell lines (HEK293, HCT116, and PC3), where they were as effective as their corresponding single-targeting siRNAs in target knockdown. The algorithm developed in this study should prove to be useful for predicting dual-targeting siRNAs in a variety of different targets and is available from http://demo1.interagon.com/DualTargeting/. PMID:20410240

SuperTarget and Matador: resources for exploring drug-target relationships.

PubMed

Günther, Stefan; Kuhn, Michael; Dunkel, Mathias; Campillos, Monica; Senger, Christian; Petsalaki, Evangelia; Ahmed, Jessica; Urdiales, Eduardo Garcia; Gewiess, Andreas; Jensen, Lars Juhl; Schneider, Reinhard; Skoblo, Roman; Russell, Robert B; Bourne, Philip E; Bork, Peer; Preissner, Robert

2008-01-01

The molecular basis of drug action is often not well understood. This is partly because the very abundant and diverse information generated in the past decades on drugs is hidden in millions of medical articles or textbooks. Therefore, we developed a one-stop data warehouse, SuperTarget that integrates drug-related information about medical indication areas, adverse drug effects, drug metabolization, pathways and Gene Ontology terms of the target proteins. An easy-to-use query interface enables the user to pose complex queries, for example to find drugs that target a certain pathway, interacting drugs that are metabolized by the same cytochrome P450 or drugs that target the same protein but are metabolized by different enzymes. Furthermore, we provide tools for 2D drug screening and sequence comparison of the targets. The database contains more than 2500 target proteins, which are annotated with about 7300 relations to 1500 drugs; the vast majority of entries have pointers to the respective literature source. A subset of these drugs has been annotated with additional binding information and indirect interactions and is available as a separate resource called Matador. SuperTarget and Matador are available at http://insilico.charite.de/supertarget and http://matador.embl.de.

About miRNAs, miRNA seeds, target genes and target pathways.

PubMed

Kehl, Tim; Backes, Christina; Kern, Fabian; Fehlmann, Tobias; Ludwig, Nicole; Meese, Eckart; Lenhof, Hans-Peter; Keller, Andreas

2017-12-05

miRNAs are typically repressing gene expression by binding to the 3' UTR, leading to degradation of the mRNA. This process is dominated by the eight-base seed region of the miRNA. Further, miRNAs are known not only to target genes but also to target significant parts of pathways. A logical line of thoughts is: miRNAs with similar (seed) sequence target similar sets of genes and thus similar sets of pathways. By calculating similarity scores for all 3.25 million pairs of 2,550 human miRNAs, we found that this pattern frequently holds, while we also observed exceptions. Respective results were obtained for both, predicted target genes as well as experimentally validated targets. We note that miRNAs target gene set similarity follows a bimodal distribution, pointing at a set of 282 miRNAs that seems to target genes with very high specificity. Further, we discuss miRNAs with different (seed) sequences that nonetheless regulate similar gene sets or pathways. Most intriguingly, we found miRNA pairs that regulate different gene sets but similar pathways such as miR-6886-5p and miR-3529-5p. These are jointly targeting different parts of the MAPK signaling cascade. The main goal of this study is to provide a general overview on the results, to highlight a selection of relevant results on miRNAs, miRNA seeds, target genes and target pathways and to raise awareness for artifacts in respective comparisons. The full set of information that allows to infer detailed results on each miRNA has been included in miRPathDB, the miRNA target pathway database (https://mpd.bioinf.uni-sb.de).

The Human Kinome Targeted by FDA Approved Multi-Target Drugs and Combination Products: A Comparative Study from the Drug-Target Interaction Network Perspective.

PubMed

Li, Ying Hong; Wang, Pan Pan; Li, Xiao Xu; Yu, Chun Yan; Yang, Hong; Zhou, Jin; Xue, Wei Wei; Tan, Jun; Zhu, Feng

2016-01-01

The human kinome is one of the most productive classes of drug target, and there is emerging necessity for treating complex diseases by means of polypharmacology (multi-target drugs and combination products). However, the advantages of the multi-target drugs and the combination products are still under debate. A comparative analysis between FDA approved multi-target drugs and combination products, targeting the human kinome, was conducted by mapping targets onto the phylogenetic tree of the human kinome. The approach of network medicine illustrating the drug-target interactions was applied to identify popular targets of multi-target drugs and combination products. As identified, the multi-target drugs tended to inhibit target pairs in the human kinome, especially the receptor tyrosine kinase family, while the combination products were able to against targets of distant homology relationship. This finding asked for choosing the combination products as a better solution for designing drugs aiming at targets of distant homology relationship. Moreover, sub-networks of drug-target interactions in specific disease were generated, and mechanisms shared by multi-target drugs and combination products were identified. In conclusion, this study performed an analysis between approved multi-target drugs and combination products against the human kinome, which could assist the discovery of next generation polypharmacology.

Enantioselective Effects of Chiral Pesticides on their Primary Targets and Secondary Targets.

PubMed

Yang, Ye; Zhang, Jianyun; Yao, Yijun

2017-01-01

Enantioselectivity has been well recognized in the environmental fate and effects of chiral pesticides. Enantiospecific action of the optical enantiomers on the biological molecules establishes the mechanistic basis for the enantioselective toxicity of chiral pesticides to both target and non-target organisms. We undertook a structured search of bibliographic databases for research literature concerning the enantioselective effects of chiral pesticides, including insecticides, herbicides and fungicides, on biomolecules in various species by using some key words. The results of the relevant literatures were reviewed in the text and summarized in tables. Pesticides generally exert their activity on the target organisms via disrupting the primary target biomolecules. In non-target species, effects of pesticides on the secondary targets distinguished from the primary ones make great contribution to their toxicity. Recent investigations have provided convincing evidence of enantioselective toxicity of chiral pesticides to both target and non-target species which is recognized to result from their enantiospecific action on the primary or secondary targets in organisms. This review confirms that chiral pesticides have enantiospecific effects on both primary and secondary target biomolecules in organisms. Future studies regarding toxicological effects of chiral pesticides should focus on the relationship between the enantiomeric difference in the compound-biomolecules interaction and the enantioselectivity in their toxicity.

Eye tracking a self-moved target with complex hand-target dynamics

PubMed Central

Landelle, Caroline; Montagnini, Anna; Madelain, Laurent

2016-01-01

Previous work has shown that the ability to track with the eye a moving target is substantially improved when the target is self-moved by the subject's hand compared with when being externally moved. Here, we explored a situation in which the mapping between hand movement and target motion was perturbed by simulating an elastic relationship between the hand and target. Our objective was to determine whether the predictive mechanisms driving eye-hand coordination could be updated to accommodate this complex hand-target dynamics. To fully appreciate the behavioral effects of this perturbation, we compared eye tracking performance when self-moving a target with a rigid mapping (simple) and a spring mapping as well as when the subject tracked target trajectories that he/she had previously generated when using the rigid or spring mapping. Concerning the rigid mapping, our results confirmed that smooth pursuit was more accurate when the target was self-moved than externally moved. In contrast, with the spring mapping, eye tracking had initially similar low spatial accuracy (though shorter temporal lag) in the self versus externally moved conditions. However, within ∼5 min of practice, smooth pursuit improved in the self-moved spring condition, up to a level similar to the self-moved rigid condition. Subsequently, when the mapping unexpectedly switched from spring to rigid, the eye initially followed the expected target trajectory and not the real one, thereby suggesting that subjects used an internal representation of the new hand-target dynamics. Overall, these results emphasize the stunning adaptability of smooth pursuit when self-maneuvering objects with complex dynamics. PMID:27466129

Sputter target

DOEpatents

Gates, Willard G.; Hale, Gerald J.

1980-01-01

The disclosure relates to an improved sputter target for use in the deposition of hard coatings. An exemplary target is given wherein titanium diboride is brazed to a tantalum backing plate using a gold-palladium-nickel braze alloy.

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

PubMed

Robinson, Sandra M; Walker, David J

2012-02-01

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

Targeted Nanomaterials for Phototherapy

PubMed Central

Chitgupi, Upendra; Qin, Yiru; Lovell, Jonathan F.

2017-01-01

Phototherapies involve the irradiation of target tissues with light. To further enhance selectivity and potency, numerous molecularly targeted photosensitizers and photoactive nanoparticles have been developed. Active targeting typically involves harnessing the affinity between a ligand and a cell surface receptor for improved accumulation in the targeted tissue. Targeting ligands including peptides, proteins, aptamers and small molecules have been explored for phototherapy. In this review, recent examples of targeted nanomaterials used in phototherapy are summarized. PMID:29071178

Polarized Solid State Target

NASA Astrophysics Data System (ADS)

Dutz, Hartmut; Goertz, Stefan; Meyer, Werner

2017-01-01

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

Post-targeting strategy for ready-to-use targeted nanodelivery post cargo loading.

PubMed

Zhu, J Y; Hu, J J; Zhang, M K; Yu, W Y; Zheng, D W; Wang, X Q; Feng, J; Zhang, X Z

2017-12-14

Based on boronate formation, this study reports a post-targeting methodology capable of readily installing versatile targeting modules onto a cargo-loaded nanoplatform in aqueous mediums. This permits the targeted nanodelivery of broad-spectrum therapeutics (drug/gene) in a ready-to-use manner while overcoming the PEGylation-dilemma that frequently occurs in conventional targeting approaches.

Magnetically attached sputter targets

DOEpatents

Makowiecki, Daniel M.; McKernan, Mark A.

1994-01-01

An improved method and assembly for attaching sputtering targets to cathode assemblies of sputtering systems which includes a magnetically permeable material. The magnetically permeable material is imbedded in a target base that is brazed, welded, or soldered to the sputter target, or is mechanically retained in the target material. Target attachment to the cathode is achieved by virtue of the permanent magnets and/or the pole pieces in the cathode assembly that create magnetic flux lines adjacent to the backing plate, which strongly attract the magnetically permeable material in the target assembly.

Glioma targeting and blood-brain barrier penetration by dual-targeting doxorubincin liposomes.

PubMed

Gao, Jian-Qing; Lv, Qing; Li, Li-Ming; Tang, Xin-Jiang; Li, Fan-Zhu; Hu, Yu-Lan; Han, Min

2013-07-01

Effective chemotherapy for glioblastoma requires a carrier that can penetrate the blood-brain barrier (BBB) and subsequently target the glioma cells. Dual-targeting doxorubincin (Dox) liposomes were produced by conjugating liposomes with both folate (F) and transferrin (Tf), which were proven effective in penetrating the BBB and targeting tumors, respectively. The liposome was characterized by particle size, Dox entrapment efficiency, and in vitro release profile. Drug accumulation in cells, P-glycoprotein (P-gp) expression, and drug transport across the BBB in the dual-targeting liposome group were examined by using bEnd3 BBB models. In vivo studies demonstrated that the dual-targeting Dox liposomes could transport across the BBB and mainly distribute in the brain glioma. The anti-tumor effect of the dual-targeting liposome was also demonstrated by the increased survival time, decreased tumor volume, and results of both hematoxylin-eosin staining and terminal deoxynucleotidyl transferase dUTP nick end labeling analysis. The dual-targeting Dox liposome could improve the therapeutic efficacy of brain glioma and were less toxic than the Dox solution, showing a dual-targeting effect. These results indicate that this dual-targeting liposome can be used as a potential carrier for glioma chemotherapy. Copyright © 2013 Elsevier Ltd. All rights reserved.

Polarized internal target apparatus

DOEpatents

Holt, Roy J.

1986-01-01

A polarized internal target apparatus with a polarized gas target of improved polarization and density achieved by mixing target gas atoms with a small amount of alkali metal gas atoms, and passing a high intensity polarized light source into the mixture to cause the alkali metal gas atoms to become polarized which interact in spin exchange collisions with target gas atoms yielding polarized target gas atoms.

Targeting an efficient target-to-target interval for P300 speller brain–computer interfaces

PubMed Central

Sellers, Eric W.; Wang, Xingyu

2013-01-01

Longer target-to-target intervals (TTI) produce greater P300 event-related potential amplitude, which can increase brain–computer interface (BCI) classification accuracy and decrease the number of flashes needed for accurate character classification. However, longer TTIs requires more time for each trial, which will decrease the information transfer rate of BCI. In this paper, a P300 BCI using a 7 × 12 matrix explored new flash patterns (16-, 18- and 21-flash pattern) with different TTIs to assess the effects of TTI on P300 BCI performance. The new flash patterns were designed to minimize TTI, decrease repetition blindness, and examine the temporal relationship between each flash of a given stimulus by placing a minimum of one (16-flash pattern), two (18-flash pattern), or three (21-flash pattern) non-target flashes between each target flashes. Online results showed that the 16-flash pattern yielded the lowest classification accuracy among the three patterns. The results also showed that the 18-flash pattern provides a significantly higher information transfer rate (ITR) than the 21-flash pattern; both patterns provide high ITR and high accuracy for all subjects. PMID:22350331

Polarized internal target apparatus

DOEpatents

Holt, R.J.

1984-10-10

A polarized internal target apparatus with a polarized gas target of improved polarization and density (achieved by mixing target gas atoms with a small amount of alkali metal gas atoms, and passing a high intensity polarized light source into the mixture to cause the alkali metal gas atoms to become polarized which interact in spin exchange collisions with target gas atoms yielding polarized target gas atoms) is described.

Integrin Targeted MR Imaging

PubMed Central

Tan, Mingqian; Lu, Zheng-Rong

2011-01-01

Magnetic resonance imaging (MRI) is a powerful medical diagnostic imaging modality for integrin targeted imaging, which uses the magnetic resonance of tissue water protons to display tissue anatomic structures with high spatial resolution. Contrast agents are often used in MRI to highlight specific regions of the body and make them easier to visualize. There are four main classes of MRI contrast agents based on their different contrast mechanisms, including T1, T2, chemical exchange saturation transfer (CEST) agents, and heteronuclear contrast agents. Integrins are an important family of heterodimeric transmembrane glycoproteins that function as mediators of cell-cell and cell-extracellular matrix interactions. The overexpressed integrins can be used as the molecular targets for designing suitable integrin targeted contrast agents for MR molecular imaging. Integrin targeted contrast agent includes a targeting agent specific to a target integrin, a paramagnetic agent and a linker connecting the targeting agent with the paramagnetic agent. Proper selection of targeting agents is critical for targeted MRI contrast agents to effectively bind to integrins for in vivo imaging. An ideal integrin targeted MR contrast agent should be non-toxic, provide strong contrast enhancement at the target sites and can be completely excreted from the body after MR imaging. An overview of integrin targeted MR contrast agents based on small molecular and macromolecular Gd(III) complexes, lipid nanoparticles and superparamagnetic nanoparticles is provided for MR molecular imaging. By using proper delivery systems for loading sufficient Gd(III) chelates or superparamagnetic nanoparticles, effective molecular imaging of integrins with MRI has been demonstrated in animal models. PMID:21547154

Magnetically attached sputter targets

DOEpatents

Makowiecki, D.M.; McKernan, M.A.

1994-02-15

An improved method and assembly for attaching sputtering targets to cathode assemblies of sputtering systems which includes a magnetically permeable material is described. The magnetically permeable material is imbedded in a target base that is brazed, welded, or soldered to the sputter target, or is mechanically retained in the target material. Target attachment to the cathode is achieved by virtue of the permanent magnets and/or the pole pieces in the cathode assembly that create magnetic flux lines adjacent to the backing plate, which strongly attract the magnetically permeable material in the target assembly. 11 figures.

Genomic Target Database (GTD): A database of potential targets in human pathogenic bacteria

PubMed Central

Barh, Debmalya; Kumar, Anil; Misra, Amarendra Narayana

2009-01-01

A Genomic Target Database (GTD) has been developed having putative genomic drug targets for human bacterial pathogens. The selected pathogens are either drug resistant or vaccines are yet to be developed against them. The drug targets have been identified using subtractive genomics approaches and these are subsequently classified into Drug targets in pathogen specific unique metabolic pathways,Drug targets in host-pathogen common metabolic pathways, andMembrane localized drug targets. HTML code is used to link each target to its various properties and other available public resources. Essential resources and tools for subtractive genomic analysis, sub-cellular localization, vaccine and drug designing are also mentioned. To the best of authors knowledge, no such database (DB) is presently available that has listed metabolic pathways and membrane specific genomic drug targets based on subtractive genomics. Listed targets in GTD are readily available resource in developing drug and vaccine against the respective pathogen, its subtypes, and other family members. Currently GTD contains 58 drug targets for four pathogens. Shortly, drug targets for six more pathogens will be listed. Availability GTD is available at IIOAB website http://www.iioab.webs.com/GTD.htm. It can also be accessed at http://www.iioabdgd.webs.com.GTD is free for academic research and non-commercial use only. Commercial use is strictly prohibited without prior permission from IIOAB. PMID:20011153

Pilots' Attention Distributions Between Chasing a Moving Target and a Stationary Target.

PubMed

Li, Wen-Chin; Yu, Chung-San; Braithwaite, Graham; Greaves, Matthew

2016-12-01

Attention plays a central role in cognitive processing; ineffective attention may induce accidents in flight operations. The objective of the current research was to examine military pilots' attention distributions between chasing a moving target and a stationary target. In the current research, 37 mission-ready F-16 pilots participated. Subjects' eye movements were collected by a portable head-mounted eye-tracker during tactical training in a flight simulator. The scenarios of chasing a moving target (air-to-air) and a stationary target (air-to-surface) consist of three operational phases: searching, aiming, and lock-on to the targets. The findings demonstrated significant differences in pilots' percentage of fixation during the searching phase between air-to-air (M = 37.57, SD = 5.72) and air-to-surface (M = 33.54, SD = 4.68). Fixation duration can indicate pilots' sustained attention to the trajectory of a dynamic target during air combat maneuvers. Aiming at the stationary target resulted in larger pupil size (M = 27,105, SD = 6565), reflecting higher cognitive loading than aiming at the dynamic target (M = 23,864, SD = 8762). Pilots' visual behavior is not only closely related to attention distribution, but also significantly associated with task characteristics. Military pilots demonstrated various visual scan patterns for searching and aiming at different types of targets based on the research settings of a flight simulator. The findings will facilitate system designers' understanding of military pilots' cognitive processes during tactical operations. They will assist human-centered interface design to improve pilots' situational awareness. The application of an eye-tracking device integrated with a flight simulator is a feasible and cost-effective intervention to improve the efficiency and safety of tactical training.Li W-C, Yu C-S, Braithwaite G, Greaves M. Pilots' attention distributions between chasing a moving target and a stationary target. Aerosp Med

TargetSpy: a supervised machine learning approach for microRNA target prediction.

PubMed

Sturm, Martin; Hackenberg, Michael; Langenberger, David; Frishman, Dmitrij

2010-05-28

Virtually all currently available microRNA target site prediction algorithms require the presence of a (conserved) seed match to the 5' end of the microRNA. Recently however, it has been shown that this requirement might be too stringent, leading to a substantial number of missed target sites. We developed TargetSpy, a novel computational approach for predicting target sites regardless of the presence of a seed match. It is based on machine learning and automatic feature selection using a wide spectrum of compositional, structural, and base pairing features covering current biological knowledge. Our model does not rely on evolutionary conservation, which allows the detection of species-specific interactions and makes TargetSpy suitable for analyzing unconserved genomic sequences.In order to allow for an unbiased comparison of TargetSpy to other methods, we classified all algorithms into three groups: I) no seed match requirement, II) seed match requirement, and III) conserved seed match requirement. TargetSpy predictions for classes II and III are generated by appropriate postfiltering. On a human dataset revealing fold-change in protein production for five selected microRNAs our method shows superior performance in all classes. In Drosophila melanogaster not only our class II and III predictions are on par with other algorithms, but notably the class I (no-seed) predictions are just marginally less accurate. We estimate that TargetSpy predicts between 26 and 112 functional target sites without a seed match per microRNA that are missed by all other currently available algorithms. Only a few algorithms can predict target sites without demanding a seed match and TargetSpy demonstrates a substantial improvement in prediction accuracy in that class. Furthermore, when conservation and the presence of a seed match are required, the performance is comparable with state-of-the-art algorithms. TargetSpy was trained on mouse and performs well in human and drosophila

TargetSpy: a supervised machine learning approach for microRNA target prediction

PubMed Central

2010-01-01

Background Virtually all currently available microRNA target site prediction algorithms require the presence of a (conserved) seed match to the 5' end of the microRNA. Recently however, it has been shown that this requirement might be too stringent, leading to a substantial number of missed target sites. Results We developed TargetSpy, a novel computational approach for predicting target sites regardless of the presence of a seed match. It is based on machine learning and automatic feature selection using a wide spectrum of compositional, structural, and base pairing features covering current biological knowledge. Our model does not rely on evolutionary conservation, which allows the detection of species-specific interactions and makes TargetSpy suitable for analyzing unconserved genomic sequences. In order to allow for an unbiased comparison of TargetSpy to other methods, we classified all algorithms into three groups: I) no seed match requirement, II) seed match requirement, and III) conserved seed match requirement. TargetSpy predictions for classes II and III are generated by appropriate postfiltering. On a human dataset revealing fold-change in protein production for five selected microRNAs our method shows superior performance in all classes. In Drosophila melanogaster not only our class II and III predictions are on par with other algorithms, but notably the class I (no-seed) predictions are just marginally less accurate. We estimate that TargetSpy predicts between 26 and 112 functional target sites without a seed match per microRNA that are missed by all other currently available algorithms. Conclusion Only a few algorithms can predict target sites without demanding a seed match and TargetSpy demonstrates a substantial improvement in prediction accuracy in that class. Furthermore, when conservation and the presence of a seed match are required, the performance is comparable with state-of-the-art algorithms. TargetSpy was trained on mouse and performs well

Human target acquisition performance

NASA Astrophysics Data System (ADS)

Teaney, Brian P.; Du Bosq, Todd W.; Reynolds, Joseph P.; Thompson, Roger; Aghera, Sameer; Moyer, Steven K.; Flug, Eric; Espinola, Richard; Hixson, Jonathan

2012-06-01

The battlefield has shifted from armored vehicles to armed insurgents. Target acquisition (identification, recognition, and detection) range performance involving humans as targets is vital for modern warfare. The acquisition and neutralization of armed insurgents while at the same time minimizing fratricide and civilian casualties is a mounting concern. U.S. Army RDECOM CERDEC NVESD has conducted many experiments involving human targets for infrared and reflective band sensors. The target sets include human activities, hand-held objects, uniforms & armament, and other tactically relevant targets. This paper will define a set of standard task difficulty values for identification and recognition associated with human target acquisition performance.

Target-directed catalytic metallodrugs

PubMed Central

Joyner, J.C.; Cowan, J.A.

2013-01-01

Most drugs function by binding reversibly to specific biological targets, and therapeutic effects generally require saturation of these targets. One means of decreasing required drug concentrations is incorporation of reactive metal centers that elicit irreversible modification of targets. A common approach has been the design of artificial proteases/nucleases containing metal centers capable of hydrolyzing targeted proteins or nucleic acids. However, these hydrolytic catalysts typically provide relatively low rate constants for target inactivation. Recently, various catalysts were synthesized that use oxidative mechanisms to selectively cleave/inactivate therapeutic targets, including HIV RRE RNA or angiotensin converting enzyme (ACE). These oxidative mechanisms, which typically involve reactive oxygen species (ROS), provide access to comparatively high rate constants for target inactivation. Target-binding affinity, co-reactant selectivity, reduction potential, coordination unsaturation, ROS products (metal-associated vs metal-dissociated; hydroxyl vs superoxide), and multiple-turnover redox chemistry were studied for each catalyst, and these parameters were related to the efficiency, selectivity, and mechanism(s) of inactivation/cleavage of the corresponding target for each catalyst. Important factors for future oxidative catalyst development are 1) positioning of catalyst reduction potential and redox reactivity to match the physiological environment of use, 2) maintenance of catalyst stability by use of chelates with either high denticity or other means of stabilization, such as the square planar geometric stabilization of Ni- and Cu-ATCUN complexes, 3) optimal rate of inactivation of targets relative to the rate of generation of diffusible ROS, 4) targeting and linker domains that afford better control of catalyst orientation, and 5) general bio-availability and drug delivery requirements. PMID:23828584

Target attribute-based false alarm rejection in small infrared target detection

NASA Astrophysics Data System (ADS)

Kim, Sungho

2012-11-01

Infrared search and track is an important research area in military applications. Although there are a lot of works on small infrared target detection methods, we cannot apply them in real field due to high false alarm rate caused by clutters. This paper presents a novel target attribute extraction and machine learning-based target discrimination method. Eight kinds of target features are extracted and analyzed statistically. Learning-based classifiers such as SVM and Adaboost are developed and compared with conventional classifiers for real infrared images. In addition, the generalization capability is also inspected for various infrared clutters.

Nuclear Security: Target Analysis

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

Singh, Surinder Paul; Gibbs, Philip W.; Bultz, Garl A.

2014-03-01

This objectives of this session were to understand the basic steps of target identification; describe the SNRI targets in detail; characterize specific targets with more detail; prioritize targets based on guidance documents; understand the graded safeguards concept; identify roll up and understand why it is a concern; and recognize the category for different materials.

Unification of automatic target tracking and automatic target recognition

NASA Astrophysics Data System (ADS)

Schachter, Bruce J.

2014-06-01

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

26 CFR 1.338-1 - General principles; status of old target and new target.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 26 Internal Revenue 4 2013-04-01 2013-04-01 false General principles; status of old target and new... principles; status of old target and new target. (a) In general—(1) Deemed transaction. Elections are..., old target and new target, generally are considered to exist for purposes of subtitle A of the...

26 CFR 1.338-1 - General principles; status of old target and new target.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 26 Internal Revenue 4 2012-04-01 2012-04-01 false General principles; status of old target and new... principles; status of old target and new target. (a) In general—(1) Deemed transaction. Elections are..., old target and new target, generally are considered to exist for purposes of subtitle A of the...

26 CFR 1.338-1 - General principles; status of old target and new target.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 26 Internal Revenue 4 2014-04-01 2014-04-01 false General principles; status of old target and new... principles; status of old target and new target. (a) In general—(1) Deemed transaction. Elections are..., old target and new target, generally are considered to exist for purposes of subtitle A of the...

Bar coded retroreflective target

DOEpatents

Vann, Charles S.

2000-01-01

This small, inexpensive, non-contact laser sensor can detect the location of a retroreflective target in a relatively large volume and up to six degrees of position. The tracker's laser beam is formed into a plane of light which is swept across the space of interest. When the beam illuminates the retroreflector, some of the light returns to the tracker. The intensity, angle, and time of the return beam is measured to calculate the three dimensional location of the target. With three retroreflectors on the target, the locations of three points on the target are measured, enabling the calculation of all six degrees of target position. Until now, devices for three-dimensional tracking of objects in a large volume have been heavy, large, and very expensive. Because of the simplicity and unique characteristics of this tracker, it is capable of three-dimensional tracking of one to several objects in a large volume, yet it is compact, light-weight, and relatively inexpensive. Alternatively, a tracker produces a diverging laser beam which is directed towards a fixed position, and senses when a retroreflective target enters the fixed field of view. An optically bar coded target can be read by the tracker to provide information about the target. The target can be formed of a ball lens with a bar code on one end. As the target moves through the field, the ball lens causes the laser beam to scan across the bar code.

Using the Dual-Target Cost to Explore the Nature of Search Target Representations

ERIC Educational Resources Information Center

Stroud, Michael J.; Menneer, Tamaryn; Cave, Kyle R.; Donnelly, Nick

2012-01-01

Eye movements were monitored to examine search efficiency and infer how color is mentally represented to guide search for multiple targets. Observers located a single color target very efficiently by fixating colors similar to the target. However, simultaneous search for 2 colors produced a dual-target cost. In addition, as the similarity between…

Target size matters: target errors contribute to the generalization of implicit visuomotor learning.

PubMed

Reichenthal, Maayan; Avraham, Guy; Karniel, Amir; Shmuelof, Lior

2016-08-01

The process of sensorimotor adaptation is considered to be driven by errors. While sensory prediction errors, defined as the difference between the planned and the actual movement of the cursor, drive implicit learning processes, target errors (e.g., the distance of the cursor from the target) are thought to drive explicit learning mechanisms. This distinction was mainly studied in the context of arm reaching tasks where the position and the size of the target were constant. We hypothesize that in a dynamic reaching environment, where subjects have to hit moving targets and the targets' dynamic characteristics affect task success, implicit processes will benefit from target errors as well. We examine the effect of target errors on learning of an unnoticed perturbation during unconstrained reaching movements. Subjects played a Pong game, in which they had to hit a moving ball by moving a paddle controlled by their hand. During the game, the movement of the paddle was gradually rotated with respect to the hand, reaching a final rotation of 25°. Subjects were assigned to one of two groups: The high-target error group played the Pong with a small ball, and the low-target error group played with a big ball. Before and after the Pong game, subjects performed open-loop reaching movements toward static targets with no visual feedback. While both groups adapted to the rotation, the postrotation reaching movements were directionally biased only in the small-ball group. This result provides evidence that implicit adaptation is sensitive to target errors. Copyright © 2016 the American Physiological Society.

TargetCompare: A web interface to compare simultaneous miRNAs targets.

PubMed

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

2014-01-01

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

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

PubMed

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

2016-11-21

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

TargetCompare: A web interface to compare simultaneous miRNAs targets

PubMed Central

Moreira, Fabiano Cordeiro; Dustan, Bruno; Hamoy, Igor G; Ribeiro-dos-Santos, André M; dos Santos, Ândrea Ribeiro

2014-01-01

MicroRNAs (miRNAs) are small non-coding nucleotide sequences between 17 and 25 nucleotides in length that primarily function in the regulation of gene expression. A since miRNA has thousand of predict targets in a complex, regulatory cell signaling network. Therefore, it is of interest to study multiple target genes simultaneously. Hence, we describe a web tool (developed using Java programming language and MySQL database server) to analyse multiple targets of pre-selected miRNAs. We cross validated the tool in eight most highly expressed miRNAs in the antrum region of stomach. This helped to identify 43 potential genes that are target of at least six of the referred miRNAs. The developed tool aims to reduce the randomness and increase the chance of selecting strong candidate target genes and miRNAs responsible for playing important roles in the studied tissue. Availability http://lghm.ufpa.br/targetcompare PMID:25352731

Targeted Therapy for Cancer

Cancer.gov

Targeted therapy is a type of cancer treatment that targets the changes in cancer cells that help them grow, divide, and spread. Learn how targeted therapy works against cancer and about side effects that may occur.

HYDROGEN ISOTOPE TARGETS

DOEpatents

Ashley, R.W.

1958-08-12

The design of targets for use in the investigation of nuclear reactions of hydrogen isotopes by bombardment with accelerated particles is described. The target con struction eomprises a backing disc of a metal selected from the group consisting of molybdenunn and tungsten, a eoating of condensed titaniunn on the dise, and a hydrogen isotope selected from the group consisting of deuterium and tritium absorbed in the coatiag. The proeess for preparing these hydrogen isotope targets is described.

Targets and methods for target preparation for radionuclide production

DOEpatents

Zhuikov, Boris L; Konyakhin, Nicolai A; Kokhanyuk, Vladimir M; Srivastava, Suresh C

2012-10-16

The invention relates to nuclear technology, and to irradiation targets and their preparation. One embodiment of the present invention includes a method for preparation of a target containing intermetallic composition of antimony Ti--Sb, Al--Sb, Cu--Sb, or Ni--Sb in order to produce radionuclides (e.g., tin-117 m) with a beam of accelerated particles. The intermetallic compounds of antimony can be welded by means of diffusion welding to a copper backing cooled during irradiation on the beam of accelerated particles. Another target can be encapsulated into a shell made of metallic niobium, stainless steel, nickel or titanium cooled outside by water during irradiation. Titanium shell can be plated outside by nickel to avoid interaction with the cooling water.

Immunotherapy Targets in Pediatric Cancer

PubMed Central

Orentas, Rimas J.; Lee, Daniel W.; Mackall, Crystal

2011-01-01

Immunotherapy for cancer has shown increasing success and there is ample evidence to expect that progress gleaned in immune targeting of adult cancers can be translated to pediatric oncology. This manuscript reviews principles that guide selection of targets for immunotherapy of cancer, emphasizing the similarities and distinctions between oncogene-inhibition targets and immune targets. It follows with a detailed review of molecules expressed by pediatric tumors that are already under study as immune targets or are good candidates for future studies of immune targeting. Distinctions are made between cell surface antigens that can be targeted in an MHC independent manner using antibodies, antibody derivatives, or chimeric antigen receptors versus intracellular antigens which must be targeted with MHC restricted T cell therapies. Among the most advanced immune targets for childhood cancer are CD19 and CD22 on hematologic malignancies, GD2 on solid tumors, and NY-ESO-1 expressed by a majority of synovial sarcomas, but several other molecules reviewed here also have properties which suggest that they too could serve as effective targets for immunotherapy of childhood cancer. PMID:22645714

Chemical Structural Novelty: On-Targets and Off-Targets

PubMed Central

Yera, Emmanuel R.; Cleves, Ann. E.; Jain, Ajay N.

2011-01-01

Drug structures may be quantitatively compared based on 2D topological structural considerations and based on 3D characteristics directly related to binding. A framework for combining multiple similarity computations is presented along with its systematic application to 358 drugs with overlapping pharmacology. Given a new molecule along with a set of molecules sharing some biological effect, a single score based on comparison to the known set is produced, reflecting either 2D similarity, 3D similarity, or their combination. For prediction of primary targets, the benefit of 3D over 2D was relatively small, but for prediction of off-targets, the added benefit was large. In addition to assessing prediction, the relationship between chemical similarity and pharmacological novelty was studied. Drug pairs that shared high 3D similarity but low 2D similarity (i.e. a novel scaffold) were shown to be much more likely to exhibit pharmacologically relevant differences in terms of specific protein target modulation. PMID:21916467

26 CFR 1.430(d)-1 - Determination of target normal cost and funding target.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 26 Internal Revenue 5 2014-04-01 2014-04-01 false Determination of target normal cost and funding target. 1.430(d)-1 Section 1.430(d)-1 Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE... Determination of target normal cost and funding target. (a) In general—(1) Overview. This section sets forth...

26 CFR 1.430(d)-1 - Determination of target normal cost and funding target.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 26 Internal Revenue 5 2012-04-01 2011-04-01 true Determination of target normal cost and funding target. 1.430(d)-1 Section 1.430(d)-1 Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE... Determination of target normal cost and funding target. (a) In general—(1) Overview. This section sets forth...

Changing paradigm from one target one ligand towards multi target directed ligand design for key drug targets of Alzheimer disease: An important role of Insilco methods in multi target directed ligands design.

PubMed

Kumar, Akhil; Tiwari, Ashish; Sharma, Ashok

2018-03-15

Alzheimer disease (AD) is now considered as a multifactorial neurodegenerative disorder and rapidly increasing to an alarming situation and causing higher death rate. One target one ligand hypothesis is not able to provide complete solution of AD due to multifactorial nature of disease and one target one drug seems to fail to provide better treatment against AD. Moreover, current available treatments are limited and most of the upcoming treatments under clinical trials are based on modulating single target. So the current AD drug discovery research shifting towards new approach for better solution that simultaneously modulate more than one targets in the neurodegenerative cascade. This can be achieved by network pharmacology, multi-modal therapies, multifaceted, and/or the more recently proposed term "multi-targeted designed drugs. Drug discovery project is tedious, costly and long term project. Moreover, multi target AD drug discovery added extra challenges such as good binding affinity of ligands for multiple targets, optimal ADME/T properties, no/less off target side effect and crossing of the blood brain barrier. These hurdles may be addressed by insilico methods for efficient solution in less time and cost as computational methods successfully applied to single target drug discovery project. Here we are summarizing some of the most prominent and computationally explored single target against AD and further we discussed successful example of dual or multiple inhibitors for same targets. Moreover we focused on ligand and structure based computational approach to design MTDL against AD. However is not an easy task to balance dual activity in a single molecule but computational approach such as virtual screening docking, QSAR, simulation and free energy are useful in future MTDLs drug discovery alone or in combination with fragment based method. However, rational and logical implementations of computational drug designing methods are capable of assisting AD drug

TargetNet: a web service for predicting potential drug-target interaction profiling via multi-target SAR models.

PubMed

Yao, Zhi-Jiang; Dong, Jie; Che, Yu-Jing; Zhu, Min-Feng; Wen, Ming; Wang, Ning-Ning; Wang, Shan; Lu, Ai-Ping; Cao, Dong-Sheng

2016-05-01

Drug-target interactions (DTIs) are central to current drug discovery processes and public health fields. Analyzing the DTI profiling of the drugs helps to infer drug indications, adverse drug reactions, drug-drug interactions, and drug mode of actions. Therefore, it is of high importance to reliably and fast predict DTI profiling of the drugs on a genome-scale level. Here, we develop the TargetNet server, which can make real-time DTI predictions based only on molecular structures, following the spirit of multi-target SAR methodology. Naïve Bayes models together with various molecular fingerprints were employed to construct prediction models. Ensemble learning from these fingerprints was also provided to improve the prediction ability. When the user submits a molecule, the server will predict the activity of the user's molecule across 623 human proteins by the established high quality SAR model, thus generating a DTI profiling that can be used as a feature vector of chemicals for wide applications. The 623 SAR models related to 623 human proteins were strictly evaluated and validated by several model validation strategies, resulting in the AUC scores of 75-100 %. We applied the generated DTI profiling to successfully predict potential targets, toxicity classification, drug-drug interactions, and drug mode of action, which sufficiently demonstrated the wide application value of the potential DTI profiling. The TargetNet webserver is designed based on the Django framework in Python, and is freely accessible at http://targetnet.scbdd.com .

TargetNet: a web service for predicting potential drug-target interaction profiling via multi-target SAR models

NASA Astrophysics Data System (ADS)

Yao, Zhi-Jiang; Dong, Jie; Che, Yu-Jing; Zhu, Min-Feng; Wen, Ming; Wang, Ning-Ning; Wang, Shan; Lu, Ai-Ping; Cao, Dong-Sheng

2016-05-01

Drug-target interactions (DTIs) are central to current drug discovery processes and public health fields. Analyzing the DTI profiling of the drugs helps to infer drug indications, adverse drug reactions, drug-drug interactions, and drug mode of actions. Therefore, it is of high importance to reliably and fast predict DTI profiling of the drugs on a genome-scale level. Here, we develop the TargetNet server, which can make real-time DTI predictions based only on molecular structures, following the spirit of multi-target SAR methodology. Naïve Bayes models together with various molecular fingerprints were employed to construct prediction models. Ensemble learning from these fingerprints was also provided to improve the prediction ability. When the user submits a molecule, the server will predict the activity of the user's molecule across 623 human proteins by the established high quality SAR model, thus generating a DTI profiling that can be used as a feature vector of chemicals for wide applications. The 623 SAR models related to 623 human proteins were strictly evaluated and validated by several model validation strategies, resulting in the AUC scores of 75-100 %. We applied the generated DTI profiling to successfully predict potential targets, toxicity classification, drug-drug interactions, and drug mode of action, which sufficiently demonstrated the wide application value of the potential DTI profiling. The TargetNet webserver is designed based on the Django framework in Python, and is freely accessible at http://targetnet.scbdd.com.

Targeted therapies: a nursing perspective.

PubMed

Kay, Polly

2006-02-01

To review the development of targeted therapies and the biology of relevant therapeutic targets. To analyze the relevance of targeted agents as part of current clinical practice. Research articles. Several targeted agents are now available for clinical use. Their mechanisms of action are more specific against tumor cells than traditional cytotoxics. Monotherapy regimens based on targeted agents tend to be better tolerated than chemotherapy, and most combination regimens with targeted agents have proven feasible. Their availability has greatly expanded cancer treatment options, especially for chemorefractory patients. Nurses involved in the care of patients with cancer can benefit from an increased understanding of targeted therapies, including their mechanisms of action, their efficacy profile, as well as prophylaxis and management of adverse events and administration procedures.

A method for detecting small targets based on cumulative weighted value of target properties

NASA Astrophysics Data System (ADS)

Jin, Xing; Sun, Gang; Wang, Wei-hua; Liu, Fang; Chen, Zeng-ping

2015-03-01

Laser detection based on the "cat's eye effect" has become the hot research project for its initiative compared to the passivity of sound detection and infrared detection. And the target detection is one of the core technologies in this system. The paper puts forward a method for detecting small targets based on cumulative weighted value of target properties using given data. Firstly, we make a frame difference to the images, then make image processing based on Morphology Principles. Secondly, we segment images, and screen the targets; then find some interesting locations. Finally, comparing to a quantity of frames, we locate the target. We did an exam to 394 true frames, the experimental result shows that the mathod can detect small targets efficiently.

Burglar Target Selection

PubMed Central

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

2015-01-01

Objectives: This study builds on research undertaken by Bernasco and Nieuwbeerta and explores the generalizability of a theoretically derived offender target selection model in three cross-national study regions. Methods: Taking a discrete spatial choice approach, we estimate the impact of both environment- and offender-level factors on residential burglary placement in the Netherlands, the United Kingdom, and Australia. Combining cleared burglary data from all study regions in a single statistical model, we make statistical comparisons between environments. Results: In all three study regions, the likelihood an offender selects an area for burglary is positively influenced by proximity to their home, the proportion of easily accessible targets, and the total number of targets available. Furthermore, in two of the three study regions, juvenile offenders under the legal driving age are significantly more influenced by target proximity than adult offenders. Post hoc tests indicate the magnitudes of these impacts vary significantly between study regions. Conclusions: While burglary target selection strategies are consistent with opportunity-based explanations of offending, the impact of environmental context is significant. As such, the approach undertaken in combining observations from multiple study regions may aid criminology scholars in assessing the generalizability of observed findings across multiple environments. PMID:25866418

UniDrug-target: a computational tool to identify unique drug targets in pathogenic bacteria.

PubMed

Chanumolu, Sree Krishna; Rout, Chittaranjan; Chauhan, Rajinder S

2012-01-01

Targeting conserved proteins of bacteria through antibacterial medications has resulted in both the development of resistant strains and changes to human health by destroying beneficial microbes which eventually become breeding grounds for the evolution of resistances. Despite the availability of more than 800 genomes sequences, 430 pathways, 4743 enzymes, 9257 metabolic reactions and protein (three-dimensional) 3D structures in bacteria, no pathogen-specific computational drug target identification tool has been developed. A web server, UniDrug-Target, which combines bacterial biological information and computational methods to stringently identify pathogen-specific proteins as drug targets, has been designed. Besides predicting pathogen-specific proteins essentiality, chokepoint property, etc., three new algorithms were developed and implemented by using protein sequences, domains, structures, and metabolic reactions for construction of partial metabolic networks (PMNs), determination of conservation in critical residues, and variation analysis of residues forming similar cavities in proteins sequences. First, PMNs are constructed to determine the extent of disturbances in metabolite production by targeting a protein as drug target. Conservation of pathogen-specific protein's critical residues involved in cavity formation and biological function determined at domain-level with low-matching sequences. Last, variation analysis of residues forming similar cavities in proteins sequences from pathogenic versus non-pathogenic bacteria and humans is performed. The server is capable of predicting drug targets for any sequenced pathogenic bacteria having fasta sequences and annotated information. The utility of UniDrug-Target server was demonstrated for Mycobacterium tuberculosis (H37Rv). The UniDrug-Target identified 265 mycobacteria pathogen-specific proteins, including 17 essential proteins which can be potential drug targets. UniDrug-Target is expected to accelerate

Targeted Nanotechnology for Cancer Imaging

PubMed Central

Toy, Randall; Bauer, Lisa; Hoimes, Christopher; Ghaghada, Ketan B.; Karathanasis, Efstathios

2014-01-01

Targeted nanoparticle imaging agents provide many benefits and new opportunities to facilitate accurate diagnosis of cancer and significantly impact patient outcome. Due to the highly engineerable nature of nanotechnology, targeted nanoparticles exhibit significant advantages including increased contrast sensitivity, binding avidity and targeting specificity. Considering the various nanoparticle designs and their adjustable ability to target a specific site and generate detectable signals, nanoparticles can be optimally designed in terms of biophysical interactions (i.e., intravascular and interstitial transport) and biochemical interactions (i.e., targeting avidity towards cancer-related biomarkers) for site-specific detection of very distinct microenvironments. This review seeks to illustrate that the design of a nanoparticle dictates its in vivo journey and targeting of hard-to-reach cancer sites, facilitating early and accurate diagnosis and interrogation of the most aggressive forms of cancer. We will report various targeted nanoparticles for cancer imaging using X-ray computed tomography, ultrasound, magnetic resonance imaging, nuclear imaging and optical imaging. Finally, to realize the full potential of targeted nanotechnology for cancer imaging, we will describe the challenges and opportunities for the clinical translation and widespread adaptation of targeted nanoparticles imaging agents. PMID:25116445

High or Low Target Prevalence Increases the Dual-Target Cost in Visual Search

ERIC Educational Resources Information Center

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

2010-01-01

Previous studies have demonstrated a dual-target cost in visual search. In the current study, the relationship between search for one and search for two targets was investigated to examine the effects of target prevalence and practice. Color-shape conjunction stimuli were used with response time, accuracy and signal detection measures. Performance…

RNA-Targeted Therapeutics.

PubMed

Crooke, Stanley T; Witztum, Joseph L; Bennett, C Frank; Baker, Brenda F

2018-04-03

RNA-targeted therapies represent a platform for drug discovery involving chemically modified oligonucleotides, a wide range of cellular RNAs, and a novel target-binding motif, Watson-Crick base pairing. Numerous hurdles considered by many to be impassable have been overcome. Today, four RNA-targeted therapies are approved for commercial use for indications as diverse as Spinal Muscular Atrophy (SMA) and reduction of low-density lipoprotein cholesterol (LDL-C) and by routes of administration including subcutaneous, intravitreal, and intrathecal delivery. The technology is efficient and supports approaching "undruggable" targets. Three additional agents are progressing through registration, and more are in clinical development, representing several chemical and structural classes. Moreover, progress in understanding the molecular mechanisms by which these drugs work has led to steadily better clinical performance and a wide range of mechanisms that may be exploited for therapeutic purposes. Here we summarize the progress, future challenges, and opportunities for this drug discovery platform. Copyright © 2018 Elsevier Inc. All rights reserved.

Controversies in targeted therapy of adult T cell leukemia/lymphoma: ON target or OFF target effects?

PubMed

Nasr, Rihab; El Hajj, Hiba; Kfoury, Youmna; de Thé, Hugues; Hermine, Olivier; Bazarbachi, Ali

2011-06-01

Adult T cell leukemia/lymphoma (ATL) represents an ideal model for targeted therapy because of intrinsic chemo-resistance of ATL cells and the presence of two well identified targets: the HTLV-I retrovirus and the viral oncoprotein Tax. The combination of zidovudine (AZT) and interferon-alpha (IFN) has a dramatic impact on survival of ATL patients. Although the mechanism of action remains unclear, arguments in favor or against a direct antiviral effect will be discussed. Yet, most patients relapse and alternative therapies are mandatory. IFN and arsenic trioxide induce Tax proteolysis, synergize to induce apoptosis in ATL cells and cure Tax-driven ATL in mice through specific targeting of leukemia initiating cell activity. These results provide a biological basis for the clinical success of arsenic/IFN/AZT therapy in ATL patients and suggest that both extinction of viral replication (AZT) and Tax degradation (arsenic/IFN) are needed to cure ATL.

HomoTarget: a new algorithm for prediction of microRNA targets in Homo sapiens.

PubMed

Ahmadi, Hamed; Ahmadi, Ali; Azimzadeh-Jamalkandi, Sadegh; Shoorehdeli, Mahdi Aliyari; Salehzadeh-Yazdi, Ali; Bidkhori, Gholamreza; Masoudi-Nejad, Ali

2013-02-01

MiRNAs play an essential role in the networks of gene regulation by inhibiting the translation of target mRNAs. Several computational approaches have been proposed for the prediction of miRNA target-genes. Reports reveal a large fraction of under-predicted or falsely predicted target genes. Thus, there is an imperative need to develop a computational method by which the target mRNAs of existing miRNAs can be correctly identified. In this study, combined pattern recognition neural network (PRNN) and principle component analysis (PCA) architecture has been proposed in order to model the complicated relationship between miRNAs and their target mRNAs in humans. The results of several types of intelligent classifiers and our proposed model were compared, showing that our algorithm outperformed them with higher sensitivity and specificity. Using the recent release of the mirBase database to find potential targets of miRNAs, this model incorporated twelve structural, thermodynamic and positional features of miRNA:mRNA binding sites to select target candidates. Copyright © 2012 Elsevier Inc. All rights reserved.

Search for Two Categories of Target Produces Fewer Fixations to Target-Color Items

ERIC Educational Resources Information Center

Menneer, Tamaryn; Stroud, Michael J.; Cave, Kyle R.; Li, Xingshan; Godwin, Hayward J.; Liversedge, Simon P.; Donnelly, Nick

2012-01-01

Searching simultaneously for metal threats (guns and knives) and improvised explosive devices (IEDs) in X-ray images is less effective than 2 independent single-target searches, 1 for metal threats and 1 for IEDs. The goals of this study were to (a) replicate this dual-target cost for categorical targets and to determine whether the cost remains…

Properties of Protein Drug Target Classes

PubMed Central

Bull, Simon C.; Doig, Andrew J.

2015-01-01

Accurate identification of drug targets is a crucial part of any drug development program. We mined the human proteome to discover properties of proteins that may be important in determining their suitability for pharmaceutical modulation. Data was gathered concerning each protein’s sequence, post-translational modifications, secondary structure, germline variants, expression profile and drug target status. The data was then analysed to determine features for which the target and non-target proteins had significantly different values. This analysis was repeated for subsets of the proteome consisting of all G-protein coupled receptors, ion channels, kinases and proteases, as well as proteins that are implicated in cancer. Machine learning was used to quantify the proteins in each dataset in terms of their potential to serve as a drug target. This was accomplished by first inducing a random forest that could distinguish between its targets and non-targets, and then using the random forest to quantify the drug target likeness of the non-targets. The properties that can best differentiate targets from non-targets were primarily those that are directly related to a protein’s sequence (e.g. secondary structure). Germline variants, expression levels and interactions between proteins had minimal discriminative power. Overall, the best indicators of drug target likeness were found to be the proteins’ hydrophobicities, in vivo half-lives, propensity for being membrane bound and the fraction of non-polar amino acids in their sequences. In terms of predicting potential targets, datasets of proteases, ion channels and cancer proteins were able to induce random forests that were highly capable of distinguishing between targets and non-targets. The non-target proteins predicted to be targets by these random forests comprise the set of the most suitable potential future drug targets, and should therefore be prioritised when building a drug development programme. PMID

TARGET Research Goals

Cancer.gov

TARGET researchers use various sequencing and array-based methods to examine the genomes, transcriptomes, and for some diseases epigenomes of select childhood cancers. This “multi-omic” approach generates a comprehensive profile of molecular alterations for each cancer type. Alterations are changes in DNA or RNA, such as rearrangements in chromosome structure or variations in gene expression, respectively. Through computational analyses and assays to validate biological function, TARGET researchers predict which alterations disrupt the function of a gene or pathway and promote cancer growth, progression, and/or survival. Researchers identify candidate therapeutic targets and/or prognostic markers from the cancer-associated alterations.

Nuclear reactor target assemblies, nuclear reactor configurations, and methods for producing isotopes, modifying materials within target material, and/or characterizing material within a target material

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

Toth, James J.; Wall, Donald; Wittman, Richard S.

Target assemblies are provided that can include a uranium-comprising annulus. The assemblies can include target material consisting essentially of non-uranium material within the volume of the annulus. Reactors are disclosed that can include one or more discrete zones configured to receive target material. At least one uranium-comprising annulus can be within one or more of the zones. Methods for producing isotopes within target material are also disclosed, with the methods including providing neutrons to target material within a uranium-comprising annulus. Methods for modifying materials within target material are disclosed as well as are methods for characterizing material within a targetmore » material.« less

Targeting dendritic cells--why bother?

PubMed

Kreutz, Martin; Tacken, Paul J; Figdor, Carl G

2013-04-11

Vaccination is among the most efficient forms of immunotherapy. Although sometimes inducing lifelong protective B-cell responses, T-cell-mediated immunity remains challenging. Targeting antigen to dendritic cells (DCs) is an extensively explored concept aimed at improving cellular immunity. The identification of various DC subsets with distinct functional characteristics now allows for the fine-tuning of targeting strategies. Although some of these DC subsets are regarded as superior for (cross-) priming of naive T cells, controversies still remain about which subset represents the best target for immunotherapy. Because targeting the antigen alone may not be sufficient to obtain effective T-cell responses, delivery systems have been developed to target multiple vaccine components to DCs. In this Perspective, we discuss the pros and cons of targeting DCs: if targeting is beneficial at all and which vaccine vehicles and immunization routes represent promising strategies to reach and activate DCs.

Eye Tracking of Occluded Self-Moved Targets: Role of Haptic Feedback and Hand-Target Dynamics.

PubMed

Danion, Frederic; Mathew, James; Flanagan, J Randall

2017-01-01

Previous studies on smooth pursuit eye movements have shown that humans can continue to track the position of their hand, or a target controlled by the hand, after it is occluded, thereby demonstrating that arm motor commands contribute to the prediction of target motion driving pursuit eye movements. Here, we investigated this predictive mechanism by manipulating both the complexity of the hand-target mapping and the provision of haptic feedback. Two hand-target mappings were used, either a rigid (simple) one in which hand and target motion matched perfectly or a nonrigid (complex) one in which the target behaved as a mass attached to the hand by means of a spring. Target animation was obtained by asking participants to oscillate a lightweight robotic device that provided (or not) haptic feedback consistent with the target dynamics. Results showed that as long as 7 s after target occlusion, smooth pursuit continued to be the main contributor to total eye displacement (∼60%). However, the accuracy of eye-tracking varied substantially across experimental conditions. In general, eye-tracking was less accurate under the nonrigid mapping, as reflected by higher positional and velocity errors. Interestingly, haptic feedback helped to reduce the detrimental effects of target occlusion when participants used the nonrigid mapping, but not when they used the rigid one. Overall, we conclude that the ability to maintain smooth pursuit in the absence of visual information can extend to complex hand-target mappings, but the provision of haptic feedback is critical for the maintenance of accurate eye-tracking performance.

Eye Tracking of Occluded Self-Moved Targets: Role of Haptic Feedback and Hand-Target Dynamics

PubMed Central

Mathew, James

2017-01-01

Abstract Previous studies on smooth pursuit eye movements have shown that humans can continue to track the position of their hand, or a target controlled by the hand, after it is occluded, thereby demonstrating that arm motor commands contribute to the prediction of target motion driving pursuit eye movements. Here, we investigated this predictive mechanism by manipulating both the complexity of the hand-target mapping and the provision of haptic feedback. Two hand-target mappings were used, either a rigid (simple) one in which hand and target motion matched perfectly or a nonrigid (complex) one in which the target behaved as a mass attached to the hand by means of a spring. Target animation was obtained by asking participants to oscillate a lightweight robotic device that provided (or not) haptic feedback consistent with the target dynamics. Results showed that as long as 7 s after target occlusion, smooth pursuit continued to be the main contributor to total eye displacement (∼60%). However, the accuracy of eye-tracking varied substantially across experimental conditions. In general, eye-tracking was less accurate under the nonrigid mapping, as reflected by higher positional and velocity errors. Interestingly, haptic feedback helped to reduce the detrimental effects of target occlusion when participants used the nonrigid mapping, but not when they used the rigid one. Overall, we conclude that the ability to maintain smooth pursuit in the absence of visual information can extend to complex hand-target mappings, but the provision of haptic feedback is critical for the maintenance of accurate eye-tracking performance. PMID:28680964

Controversies in Targeted Therapy of Adult T Cell Leukemia/Lymphoma: ON Target or OFF Target Effects?

PubMed Central

Nasr, Rihab; Hajj, Hiba El; Kfoury, Youmna; de Thé, Hugues; Hermine, Olivier; Bazarbachi, Ali

2011-01-01

Adult T cell leukemia/lymphoma (ATL) represents an ideal model for targeted therapy because of intrinsic chemo-resistance of ATL cells and the presence of two well identified targets: the HTLV-I retrovirus and the viral oncoprotein Tax. The combination of zidovudine (AZT) and interferon-alpha (IFN) has a dramatic impact on survival of ATL patients. Although the mechanism of action remains unclear, arguments in favor or against a direct antiviral effect will be discussed. Yet, most patients relapse and alternative therapies are mandatory. IFN and arsenic trioxide induce Tax proteolysis, synergize to induce apoptosis in ATL cells and cure Tax-driven ATL in mice through specific targeting of leukemia initiating cell activity. These results provide a biological basis for the clinical success of arsenic/IFN/AZT therapy in ATL patients and suggest that both extinction of viral replication (AZT) and Tax degradation (arsenic/IFN) are needed to cure ATL. PMID:21994752

Seedling root targets

Treesearch

Diane L. Haase

2011-01-01

Roots are critical to seedling performance after outplanting. Although root quality is not as quick and simple to measure as shoot quality, target root characteristics should be included in any seedling quality assessment program. This paper provides a brief review of root characteristics most commonly targeted for operational seedling production. These are: root mass...

Nuclear Security: Target Analysis-rev

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

Singh, Surinder Paul; Gibbs, Philip W.; Bultz, Garl A.

2014-03-01

The objectives of this presentation are to understand target identification, including roll-up and protracted theft; evaluate target identification in the SNRI; recognize the target characteristics and consequence levels; and understand graded safeguards.

Targeting the tumor microenvironment

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

Kenny, P.A.; Lee, G.Y.; Bissell, M.J.

2006-11-07

Despite some notable successes cancer remains, for the most part, a seemingly intractable problem. There is, however, a growing appreciation that targeting the tumor epithelium in isolation is not sufficient as there is an intricate mutually sustaining synergy between the tumor epithelial cells and their surrounding stroma. As the details of this dialogue emerge, new therapeutic targets have been proposed. The FDA has already approved drugs targeting microenvironmental components such as VEGF and aromatase and many more agents are in the pipeline. In this article, we describe some of the 'druggable' targets and processes within the tumor microenvironment and reviewmore » the approaches being taken to disrupt these interactions.« less

Liquid film target impingement scrubber

DOEpatents

McDowell, William J.; Coleman, Charles F.

1977-03-15

An improved liquid film impingement scrubber is provided wherein particulates suspended in a gas are removed by jetting the particle-containing gas onto a relatively small thin liquid layer impingement target surface. The impingement target is in the form of a porous material which allows a suitable contacting liquid from a pressurized chamber to exude therethrough to form a thin liquid film target surface. The gas-supported particles collected by impingement of the gas on the target are continuously removed and flushed from the system by the liquid flow through each of a number of pores in the target.

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

NASA Astrophysics Data System (ADS)

Nyarko, Kofi; Thomas, Clayton; Torres, Gilbert

2016-05-01

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

Adaptive optics to enhance target recognition

NASA Astrophysics Data System (ADS)

McAulay, Alastair D.

2012-06-01

Target recognition can be enhanced by reducing image degradation due to atmospheric turbulence. This is accomplished by an adaptive optic system. We discuss the forms of degradation when a target is viewed through the atmosphere1: scintillation from ground targets on a hot day in visible or infrared light; beam spreading and wavering around in time; atmospheric turbulence caused by motion of the target or by weather. In the case of targets we can use a beacon laser that reflects back from the target into a wavefront detector to measure the effects of turbulence on propagation to and from the target before imaging.1 A deformable mirror then corrects the wavefront shape of the transmitted, reflected or scattered data for enhanced imaging. Further, recognition of targets is enhanced by performing accurate distance measurements to localized parts of the target using lidar. Distance is obtained by sending a short pulse to the target and measuring the time for the pulse to return. There is inadequate time to scan the complete field of view so that the beam must be steered to regions of interest such as extremities of the image during image recognition. Distance is particularly valuable to recognize fine features in range along the target or when segmentation is required to separate a target from background or from other targets. We discuss the issues involved.

Enhancing emotional-based target prediction

NASA Astrophysics Data System (ADS)

Gosnell, Michael; Woodley, Robert

2008-04-01

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

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.

Impacts of transgenic poplar-cotton agro-ecosystems upon target pests and non-target insects under field conditions.

PubMed

Zhang, D J; Liu, J X; Lu, Z Y; Li, C L; Comada, E; Yang, M S

2015-07-27

Poplar-cotton agro-ecosystems are the main agricultural planting modes of cotton fields in China. With increasing acres devoted to transgenic insect-resistant poplar and transgenic insect-resistant cotton, studies examining the effects of transgenic plants on target and non-target insects become increasingly important. We systematically surveyed populations of both target pests and non-target insects for 4 different combinations of poplar-cotton eco-systems over 3 years. Transgenic Bt cotton strongly resisted the target insects Fall webworm moth [Hyphantria cunea (Drury)], Sylepta derogata Fabrieius, and American bollworm (Heliothis armigera), but no clear impact on non-target insect cotton aphids (Aphis gossypii). Importantly, intercrops containing transgenic Pb29 poplar significantly increased the inhibitory effects of Bt cotton on Fall webworm moth in ecosystem IV. Highly resistant Pb29 poplar reduced populations of the target pests Grnsonoma minutara Hubner and non-target insect poplar leaf aphid (Chaitophorus po-pulialbae), while Fall webworm moth populations were unaffected. We determined the effects of Bt toxin from transgenic poplar and cotton on target and non-target pests in different ecosystems of cotton-poplar intercrops and identified the synergistic effects of such combinations toward both target and non-target insects.

Target-Pathogen: a structural bioinformatic approach to prioritize drug targets in pathogens.

PubMed

Sosa, Ezequiel J; Burguener, Germán; Lanzarotti, Esteban; Defelipe, Lucas; Radusky, Leandro; Pardo, Agustín M; Marti, Marcelo; Turjanski, Adrián G; Fernández Do Porto, Darío

2018-01-04

Available genomic data for pathogens has created new opportunities for drug discovery and development to fight them, including new resistant and multiresistant strains. In particular structural data must be integrated with both, gene information and experimental results. In this sense, there is a lack of an online resource that allows genome wide-based data consolidation from diverse sources together with thorough bioinformatic analysis that allows easy filtering and scoring for fast target selection for drug discovery. Here, we present Target-Pathogen database (http://target.sbg.qb.fcen.uba.ar/patho), designed and developed as an online resource that allows the integration and weighting of protein information such as: function, metabolic role, off-targeting, structural properties including druggability, essentiality and omic experiments, to facilitate the identification and prioritization of candidate drug targets in pathogens. We include in the database 10 genomes of some of the most relevant microorganisms for human health (Mycobacterium tuberculosis, Mycobacterium leprae, Klebsiella pneumoniae, Plasmodium vivax, Toxoplasma gondii, Leishmania major, Wolbachia bancrofti, Trypanosoma brucei, Shigella dysenteriae and Schistosoma Smanosoni) and show its applicability. New genomes can be uploaded upon request. © The Author(s) 2017. Published by Oxford University Press on behalf of Nucleic Acids Research.

Target-Pathogen: a structural bioinformatic approach to prioritize drug targets in pathogens

PubMed Central

Sosa, Ezequiel J; Burguener, Germán; Lanzarotti, Esteban; Radusky, Leandro; Pardo, Agustín M; Marti, Marcelo

2018-01-01

Abstract Available genomic data for pathogens has created new opportunities for drug discovery and development to fight them, including new resistant and multiresistant strains. In particular structural data must be integrated with both, gene information and experimental results. In this sense, there is a lack of an online resource that allows genome wide-based data consolidation from diverse sources together with thorough bioinformatic analysis that allows easy filtering and scoring for fast target selection for drug discovery. Here, we present Target-Pathogen database (http://target.sbg.qb.fcen.uba.ar/patho), designed and developed as an online resource that allows the integration and weighting of protein information such as: function, metabolic role, off-targeting, structural properties including druggability, essentiality and omic experiments, to facilitate the identification and prioritization of candidate drug targets in pathogens. We include in the database 10 genomes of some of the most relevant microorganisms for human health (Mycobacterium tuberculosis, Mycobacterium leprae, Klebsiella pneumoniae, Plasmodium vivax, Toxoplasma gondii, Leishmania major, Wolbachia bancrofti, Trypanosoma brucei, Shigella dysenteriae and Schistosoma Smanosoni) and show its applicability. New genomes can be uploaded upon request. PMID:29106651

Development of Bone Targeting Drugs.

PubMed

Stapleton, Molly; Sawamoto, Kazuki; Alméciga-Díaz, Carlos J; Mackenzie, William G; Mason, Robert W; Orii, Tadao; Tomatsu, Shunji

2017-06-23

The skeletal system, comprising bones, ligaments, cartilage and their connective tissues, is critical for the structure and support of the body. Diseases that affect the skeletal system can be difficult to treat, mainly because of the avascular cartilage region. Targeting drugs to the site of action can not only increase efficacy but also reduce toxicity. Bone-targeting drugs are designed with either of two general targeting moieties, aimed at the entire skeletal system or a specific cell type. Most bone-targeting drugs utilize an affinity to hydroxyapatite, a major component of the bone matrix that includes a high concentration of positively-charged Ca 2+ . The strategies for designing such targeting moieties can involve synthetic and/or biological components including negatively-charged amino acid peptides or bisphosphonates. Efficient delivery of bone-specific drugs provides significant impact in the treatment of skeletal related disorders including infectious diseases (osteoarthritis, osteomyelitis, etc.), osteoporosis, and metabolic skeletal dysplasia. Despite recent advances, however, both delivering the drug to its target without losing activity and avoiding adverse local effects remain a challenge. In this review, we investigate the current development of bone-targeting moieties, their efficacy and limitations, and discuss future directions for the development of these specific targeted treatments.

Development of Bone Targeting Drugs

PubMed Central

Stapleton, Molly; Sawamoto, Kazuki; Alméciga-Díaz, Carlos J.; Mackenzie, William G.; Mason, Robert W.; Orii, Tadao; Tomatsu, Shunji

2017-01-01

The skeletal system, comprising bones, ligaments, cartilage and their connective tissues, is critical for the structure and support of the body. Diseases that affect the skeletal system can be difficult to treat, mainly because of the avascular cartilage region. Targeting drugs to the site of action can not only increase efficacy but also reduce toxicity. Bone-targeting drugs are designed with either of two general targeting moieties, aimed at the entire skeletal system or a specific cell type. Most bone-targeting drugs utilize an affinity to hydroxyapatite, a major component of the bone matrix that includes a high concentration of positively-charged Ca2+. The strategies for designing such targeting moieties can involve synthetic and/or biological components including negatively-charged amino acid peptides or bisphosphonates. Efficient delivery of bone-specific drugs provides significant impact in the treatment of skeletal related disorders including infectious diseases (osteoarthritis, osteomyelitis, etc.), osteoporosis, and metabolic skeletal dysplasia. Despite recent advances, however, both delivering the drug to its target without losing activity and avoiding adverse local effects remain a challenge. In this review, we investigate the current development of bone-targeting moieties, their efficacy and limitations, and discuss future directions for the development of these specific targeted treatments. PMID:28644392

Feature-based RNN target recognition

NASA Astrophysics Data System (ADS)

Bakircioglu, Hakan; Gelenbe, Erol

1998-09-01

Detection and recognition of target signatures in sensory data obtained by synthetic aperture radar (SAR), forward- looking infrared, or laser radar, have received considerable attention in the literature. In this paper, we propose a feature based target classification methodology to detect and classify targets in cluttered SAR images, that makes use of selective signature data from sensory data, together with a neural network technique which uses a set of trained networks based on the Random Neural Network (RNN) model (Gelenbe 89, 90, 91, 93) which is trained to act as a matched filter. We propose and investigate radial features of target shapes that are invariant to rotation, translation, and scale, to characterize target and clutter signatures. These features are then used to train a set of learning RNNs which can be used to detect targets within clutter with high accuracy, and to classify the targets or man-made objects from natural clutter. Experimental data from SAR imagery is used to illustrate and validate the proposed method, and to calculate Receiver Operating Characteristics which illustrate the performance of the proposed algorithm.

Eye-Target Synchrony and Attention

NASA Astrophysics Data System (ADS)

Contreras, R.; Kolster, R.; Basu, S.; Voss, H. U.; Ghajar, J.; Suh, M.; Bahar, S.

2007-03-01

Eye-target synchrony is critical during smooth pursuit. We apply stochastic phase synchronization to human pursuit of a moving target, in both normal and mild traumatic brain injured (TBI) subjects. Smooth pursuit utilizes the same neural networks used by attention. To test whether smooth pursuit is modulated by attention, subjects tracked a target while loaded with tasks involving working memory. Preliminary results suggest that additional cognitive load increases normal subjects' performance, while the effect is reversed in TBI patients. We correlate these results with eye-target synchrony. Additionally, we correlate eye-target synchrony with frequency of target motion, and discuss how the range of frequencies for optimal synchrony depends on the shift from attentional to automatic-response time scales. Synchrony deficits in TBI patients can be correlated with specific regions of brain damage imaged with diffusion tensor imaging (DTI).

26 CFR 1.430(d)-1 - Determination of target normal cost and funding target.

Code of Federal Regulations, 2010 CFR

2010-04-01

... funding target and target normal cost for the plan year if the plan amendment— (i) Takes effect by the... (disregarding the effect on the plan's funding shortfall resulting from changes in interest and mortality... 26 Internal Revenue 5 2010-04-01 2010-04-01 false Determination of target normal cost and funding...

26 CFR 1.430(d)-1 - Determination of target normal cost and funding target.

Code of Federal Regulations, 2013 CFR

2013-04-01

... funding target and target normal cost for the plan year if the plan amendment— (i) Takes effect by the... (disregarding the effect on the plan's funding shortfall resulting from changes in interest and mortality... 26 Internal Revenue 5 2013-04-01 2013-04-01 false Determination of target normal cost and funding...

The fading affect bias shows positive outcomes at the general but not the individual level of analysis in the context of social media.

PubMed

Gibbons, Jeffrey A; Horowitz, Kyle A; Dunlap, Spencer M

2017-08-01

Unpleasant affect fades faster than pleasant affect (e.g., Walker, Vogl, & Thompson, 1997); this effect is referred to as the Fading Affect Bias (FAB; Walker, Skowronski, Gibbons, Vogl, & Thompson, 2003a). Research shows that the FAB is consistently related to positive/healthy outcomes at a general but not at a specific level of analysis based on event types and individual differences (e.g., Gibbons et al., 2013). Based on the positive outcomes for FAB and negative outcomes for social media (Bolton et al., 2013; Huang, 2010), the current study examined FAB in the context of social media events along with related individual differences. General positive outcomes were shown in the form of robust FAB effects across social media and non-social media events, a larger FAB for non-social media events than for social media events, negative correlations of FAB with depression, anxiety, and stress as well as a positive correlation of FAB with self-esteem. However, the lack of a negative correlation between FAB and anxiety for social media events in a 3-way interaction did not show positive outcomes at a specific level of analysis. Rehearsal ratings mediated the 3-way interaction. Implications are discussed. Copyright © 2017 Elsevier Inc. All rights reserved.

Emotionally conditioning the target-speech voice enhances recognition of the target speech under "cocktail-party" listening conditions.

PubMed

Lu, Lingxi; Bao, Xiaohan; Chen, Jing; Qu, Tianshu; Wu, Xihong; Li, Liang

2018-05-01

Under a noisy "cocktail-party" listening condition with multiple people talking, listeners can use various perceptual/cognitive unmasking cues to improve recognition of the target speech against informational speech-on-speech masking. One potential unmasking cue is the emotion expressed in a speech voice, by means of certain acoustical features. However, it was unclear whether emotionally conditioning a target-speech voice that has none of the typical acoustical features of emotions (i.e., an emotionally neutral voice) can be used by listeners for enhancing target-speech recognition under speech-on-speech masking conditions. In this study we examined the recognition of target speech against a two-talker speech masker both before and after the emotionally neutral target voice was paired with a loud female screaming sound that has a marked negative emotional valence. The results showed that recognition of the target speech (especially the first keyword in a target sentence) was significantly improved by emotionally conditioning the target speaker's voice. Moreover, the emotional unmasking effect was independent of the unmasking effect of the perceived spatial separation between the target speech and the masker. Also, (skin conductance) electrodermal responses became stronger after emotional learning when the target speech and masker were perceptually co-located, suggesting an increase of listening efforts when the target speech was informationally masked. These results indicate that emotionally conditioning the target speaker's voice does not change the acoustical parameters of the target-speech stimuli, but the emotionally conditioned vocal features can be used as cues for unmasking target speech.

Influence of lateral target size on hot electron production and electromagnetic pulse emission from laser-irradiated metallic targets

NASA Astrophysics Data System (ADS)

Chen, Zi-Yu; Li, Jian-Feng; Yu, Yong; Wang, Jia-Xiang; Li, Xiao-Ya; Peng, Qi-Xian; Zhu, Wen-Jun

2012-11-01

The influences of lateral target size on hot electron production and electromagnetic pulse emission from laser interaction with metallic targets have been investigated. Particle-in-cell simulations at high laser intensities show that the yield of hot electrons tends to increase with lateral target size, because the larger surface area reduces the electrostatic field on the target, owing to its expansion along the target surface. At lower laser intensities and longer time scales, experimental data characterizing electromagnetic pulse emission as a function of lateral target size also show target-size effects. Charge separation and a larger target tending to have a lower target potential have both been observed. The increase in radiation strength and downshift in radiation frequency with increasing lateral target size can be interpreted using a simple model of the electrical capacity of the target.

Design of a Covert RFID Tag Network for Target Discovery and Target Information Routing

PubMed Central

Pan, Qihe; Narayanan, Ram M.

2011-01-01

Radio frequency identification (RFID) tags are small electronic devices working in the radio frequency range. They use wireless radio communications to automatically identify objects or people without the need for line-of-sight or contact, and are widely used in inventory tracking, object location, environmental monitoring. This paper presents a design of a covert RFID tag network for target discovery and target information routing. In the design, a static or very slowly moving target in the field of RFID tags transmits a distinct pseudo-noise signal, and the RFID tags in the network collect the target information and route it to the command center. A map of each RFID tag’s location is saved at command center, which can determine where a RFID tag is located based on each RFID tag’s ID. We propose the target information collection method with target association and clustering, and we also propose the information routing algorithm within the RFID tag network. The design and operation of the proposed algorithms are illustrated through examples. Simulation results demonstrate the effectiveness of the design. PMID:22163693

Design of a covert RFID tag network for target discovery and target information routing.

PubMed

Pan, Qihe; Narayanan, Ram M

2011-01-01

Radio frequency identification (RFID) tags are small electronic devices working in the radio frequency range. They use wireless radio communications to automatically identify objects or people without the need for line-of-sight or contact, and are widely used in inventory tracking, object location, environmental monitoring. This paper presents a design of a covert RFID tag network for target discovery and target information routing. In the design, a static or very slowly moving target in the field of RFID tags transmits a distinct pseudo-noise signal, and the RFID tags in the network collect the target information and route it to the command center. A map of each RFID tag's location is saved at command center, which can determine where a RFID tag is located based on each RFID tag's ID. We propose the target information collection method with target association and clustering, and we also propose the information routing algorithm within the RFID tag network. The design and operation of the proposed algorithms are illustrated through examples. Simulation results demonstrate the effectiveness of the design.

Quantitative targeting maps based on experimental investigations for a branched tube model in magnetic drug targeting

NASA Astrophysics Data System (ADS)

Gitter, K.; Odenbach, S.

2011-12-01

Magnetic drug targeting (MDT), because of its high targeting efficiency, is a promising approach for tumour treatment. Unwanted side effects are considerably reduced, since the nanoparticles are concentrated within the target region due to the influence of a magnetic field. Nevertheless, understanding the transport phenomena of nanoparticles in an artery system is still challenging. This work presents experimental results for a branched tube model. Quantitative results describe, for example, the net amount of nanoparticles that are targeted towards the chosen region due to the influence of a magnetic field. As a result of measurements, novel drug targeting maps, combining, e.g. the magnetic volume force, the position of the magnet and the net amount of targeted nanoparticles, are presented. The targeting maps are valuable for evaluation and comparison of setups and are also helpful for the design and the optimisation of a magnet system with an appropriate strength and distribution of the field gradient. The maps indicate the danger of accretion within the tube and also show the promising result of magnetic drug targeting that up to 97% of the nanoparticles were successfully targeted.

Target-present guessing as a function of target prevalence and accumulated information in visual search.

PubMed

Peltier, Chad; Becker, Mark W

2017-05-01

Target prevalence influences visual search behavior. At low target prevalence, miss rates are high and false alarms are low, while the opposite is true at high prevalence. Several models of search aim to describe search behavior, one of which has been specifically intended to model search at varying prevalence levels. The multiple decision model (Wolfe & Van Wert, Current Biology, 20(2), 121--124, 2010) posits that all searches that end before the observer detects a target result in a target-absent response. However, researchers have found very high false alarms in high-prevalence searches, suggesting that prevalence rates may be used as a source of information to make "educated guesses" after search termination. Here, we further examine the ability for prevalence level and knowledge gained during visual search to influence guessing rates. We manipulate target prevalence and the amount of information that an observer accumulates about a search display prior to making a response to test if these sources of evidence are used to inform target present guess rates. We find that observers use both information about target prevalence rates and information about the proportion of the array inspected prior to making a response allowing them to make an informed and statistically driven guess about the target's presence.

TAPIR, a web server for the prediction of plant microRNA targets, including target mimics.

PubMed

Bonnet, Eric; He, Ying; Billiau, Kenny; Van de Peer, Yves

2010-06-15

We present a new web server called TAPIR, designed for the prediction of plant microRNA targets. The server offers the possibility to search for plant miRNA targets using a fast and a precise algorithm. The precise option is much slower but guarantees to find less perfectly paired miRNA-target duplexes. Furthermore, the precise option allows the prediction of target mimics, which are characterized by a miRNA-target duplex having a large loop, making them undetectable by traditional tools. The TAPIR web server can be accessed at: http://bioinformatics.psb.ugent.be/webtools/tapir. Supplementary data are available at Bioinformatics online.

26 CFR 1.430(d)-1 - Determination of target normal cost and funding target.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 26 Internal Revenue 5 2011-04-01 2011-04-01 false Determination of target normal cost and funding target. 1.430(d)-1 Section 1.430(d)-1 Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE TREASURY (CONTINUED) INCOME TAX (CONTINUED) INCOME TAXES (CONTINUED) Certain Stock Options § 1.430(d)-1 Determination of target normal cost and fundin...

Hitting the Target: Target Setting and Information Systems for the Learning and Skills Sector.

ERIC Educational Resources Information Center

Owen, Jane; Alterman, Jeff

The use of target setting in conjunction with good information systems in colleges and work-based learning (WBL) providers can lead to improved service provisions across the sector in the United Kingdom. Target setting must be carried out in a systematic way in which providers must develop target- setting processes with a focus on learner success;…

Inertial Confinement fusion targets

NASA Technical Reports Server (NTRS)

Hendricks, C. D.

1982-01-01

Inertial confinement fusion (ICF) targets are made as simple flat discs, as hollow shells or as complicated multilayer structures. Many techniques were devised for producing the targets. Glass and metal shells are made by using drop and bubble techniques. Solid hydrogen shells are also produced by adapting old methods to the solution of modern problems. Some of these techniques, problems, and solutions are discussed. In addition, the applications of many of the techniques to fabrication of ICF targets is presented.

Air Force, Cyberpower, Targeting: Airpower Lessons for an Air Force Cyberpower Targeting Theory

DTIC Science & Technology

2013-06-01

apply in future war. Following World War I, Airmen at the Air Corps Tactical School (ACTS) developed an “Industrial Web Theory” for targeting to...throughout its use. The targeting theory was employed with mixed results from World War II through the Vietnam War. In the late 20th century, Colonel...A review of the Inter-War period, World War II, Korean War, and Desert Storm intends to evaluate airpower targeting theories in order to develop

Targets and processes for fabricating same

DOEpatents

Cowan, Thomas [Dresden, DE; Malekos, Steven [Reno, NV; Korgan, Grant [Reno, NV; Adams, Jesse [Reno, NV; Sentoku, Yasuhiko [Reno, NV; Le Galloudec, Nathalie [Reno, NV; Fuchs, Julien [Paris, FR

2012-07-24

In particular embodiments, the present disclosure provides targets including a metal layer and defining a hollow inner surface. The hollow inner surface has an internal apex. The distance between at least two opposing points of the internal apex is less than about 15 .mu.m. In particular examples, the distance is less than about 1 .mu.m. Particular implementations of the targets are free standing. The targets have a number of disclosed shaped, including cones, pyramids, hemispheres, and capped structures. The present disclosure also provides arrays of such targets. Also provided are methods of forming targets, such as the disclosed targets, using lithographic techniques, such as photolithographic techniques. In particular examples, a target mold is formed from a silicon wafer and then one or more sides of the mold are coated with a target material, such as one or more metals.

Targets and processes for fabricating same

DOEpatents

Adams, Jesse D; Malekos, Steven; Le Galloudec, Nathalie; Korgan, Grant; Cowan, Thomas; Sentoku, Yasuhiko

2016-05-17

In particular embodiments, the present disclosure provides targets including a metal layer and defining a hollow inner surface. The hollow inner surface has an internal apex. The distance between at least two opposing points of the internal apex is less than about 15 .mu.m. In particular examples, the distance is less than about 1 .mu.m. Particular implementations of the targets are free standing. The targets have a number of disclosed shaped, including cones, pyramids, hemispheres, and capped structures. The present disclosure also provides arrays of such targets. Also provided are methods of forming targets, such as the disclosed targets, using lithographic techniques, such as photolithographic techniques. In particular examples, a target mold is formed from a silicon wafer and then one or more sides of the mold are coated with a target material, such as one or more metals.

Targets and processes for fabricating same

DOEpatents

Cowna, Thomas; Malekos, Steven; Korgan, Grant; Adams, Jesse; Sentoku, Yasuhiko; LeGalloudec, Nathalie

2014-06-10

In particular embodiments, the present disclosure provides targets including a metal layer and defining a hollow inner surface. The hollow inner surface has an internal apex. The distance between at least two opposing points of the internal apex is less than about 15 .mu.m. In particular examples, the distance is less than about 1 .mu.m. Particular implementations of the targets are free standing. The targets have a number of disclosed shaped, including cones, pyramids, hemispheres, and capped structures. The present disclosure also provides arrays of such targets. Also provided are methods of forming targets, such as the disclosed targets, using lithographic techniques, such as photolithographic techniques. In particular examples, a target mold is formed from a silicon wafer and then one or more sides of the mold are coated with a target material, such as one or more metals.

Towards large scale multi-target tracking

NASA Astrophysics Data System (ADS)

Vo, Ba-Ngu; Vo, Ba-Tuong; Reuter, Stephan; Lam, Quang; Dietmayer, Klaus

2014-06-01

Multi-target tracking is intrinsically an NP-hard problem and the complexity of multi-target tracking solutions usually do not scale gracefully with problem size. Multi-target tracking for on-line applications involving a large number of targets is extremely challenging. This article demonstrates the capability of the random finite set approach to provide large scale multi-target tracking algorithms. In particular it is shown that an approximate filter known as the labeled multi-Bernoulli filter can simultaneously track one thousand five hundred targets in clutter on a standard laptop computer.

The siRNA Non-seed Region and Its Target Sequences Are Auxiliary Determinants of Off-Target Effects.

PubMed

Kamola, Piotr J; Nakano, Yuko; Takahashi, Tomoko; Wilson, Paul A; Ui-Tei, Kumiko

2015-12-01

RNA interference (RNAi) is a powerful tool for post-transcriptional gene silencing. However, the siRNA guide strand may bind unintended off-target transcripts via partial sequence complementarity by a mechanism closely mirroring micro RNA (miRNA) silencing. To better understand these off-target effects, we investigated the correlation between sequence features within various subsections of siRNA guide strands, and its corresponding target sequences, with off-target activities. Our results confirm previous reports that strength of base-pairing in the siRNA seed region is the primary factor determining the efficiency of off-target silencing. However, the degree of downregulation of off-target transcripts with shared seed sequence is not necessarily similar, suggesting that there are additional auxiliary factors that influence the silencing potential. Here, we demonstrate that both the melting temperature (Tm) in a subsection of siRNA non-seed region, and the GC contents of its corresponding target sequences, are negatively correlated with the efficiency of off-target effect. Analysis of experimentally validated miRNA targets demonstrated a similar trend, indicating a putative conserved mechanistic feature of seed region-dependent targeting mechanism. These observations may prove useful as parameters for off-target prediction algorithms and improve siRNA 'specificity' design rules.

Off-target model based OPC

NASA Astrophysics Data System (ADS)

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

2005-11-01

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

Facility target insert shielding assessment

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

Mocko, Michal

2015-10-06

Main objective of this report is to assess the basic shielding requirements for the vertical target insert and retrieval port. We used the baseline design for the vertical target insert in our calculations. The insert sits in the 12”-diameter cylindrical shaft extending from the service alley in the top floor of the facility all the way down to the target location. The target retrieval mechanism is a long rod with the target assembly attached and running the entire length of the vertical shaft. The insert also houses the helium cooling supply and return lines each with 2” diameter. In themore » present study we focused on calculating the neutron and photon dose rate fields on top of the target insert/retrieval mechanism in the service alley. Additionally, we studied a few prototypical configurations of the shielding layers in the vertical insert as well as on the top.« less

Bioengineering Strategies for Designing Targeted Cancer Therapies

PubMed Central

Wen, Xuejun

2014-01-01

The goals of bioengineering strategies for targeted cancer therapies are (1) to deliver a high dose of an anticancer drug directly to a cancer tumor, (2) to enhance drug uptake by malignant cells, and (3) to minimize drug uptake by nonmalignant cells. Effective cancer-targeting therapies will require both passive- and active targeting strategies and a thorough understanding of physiologic barriers to targeted drug delivery. Designing a targeted therapy includes the selection and optimization of a nanoparticle delivery vehicle for passive accumulation in tumors, a targeting moiety for active receptor-mediated uptake, and stimuli-responsive polymers for control of drug release. The future direction of cancer targeting is a combinatorial approach, in which targeting therapies are designed to use multiple targeting strategies. The combinatorial approach will enable combination therapy for delivery of multiple drugs and dual ligand targeting to improve targeting specificity. Targeted cancer treatments in development and the new combinatorial approaches show promise for improving targeted anticancer drug delivery and improving treatment outcomes. PMID:23768509

Structural basis for microRNA targeting

DOE PAGES

Schirle, Nicole T.; Sheu-Gruttadauria, Jessica; MacRae, Ian J.

2014-10-31

MicroRNAs (miRNAs) control expression of thousands of genes in plants and animals. miRNAs function by guiding Argonaute proteins to complementary sites in messenger RNAs (mRNAs) targeted for repression. In this paper, we determined crystal structures of human Argonaute-2 (Ago2) bound to a defined guide RNA with and without target RNAs representing miRNA recognition sites. These structures suggest a stepwise mechanism, in which Ago2 primarily exposes guide nucleotides (nt) 2 to 5 for initial target pairing. Pairing to nt 2 to 5 promotes conformational changes that expose nt 2 to 8 and 13 to 16 for further target recognition. Interactions withmore » the guide-target minor groove allow Ago2 to interrogate target RNAs in a sequence-independent manner, whereas an adenosine binding-pocket opposite guide nt 1 further facilitates target recognition. Spurious slicing of miRNA targets is avoided through an inhibitory coordination of one catalytic magnesium ion. Finally, these results explain the conserved nucleotide-pairing patterns in animal miRNA target sites first observed over two decades ago.« less

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.

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

[Event-related synchronization/desynhronization during processing of target, no target and unknown visually presented words].

PubMed

Rebreikina, A B; Larionova, E B; Varlamov, A A

2015-01-01

The aim of this investigation is to study neurophysiologic mechanisms of processing of relevant words and unknown words. Event-related synchronization/desynchronization during categorization of three types of stimuli (known targets, known no targets and unknown words) was examined. The main difference between known targets and unknown stimuli was revealed in the thetal and theta2 bands at the early stage after stimuli onset (150-300 ms) and in the delta band (400-700 ms). In the late time window at about 800-1500 ms thetal ERS in response to the target stimuli was smaller than to other stimuli, but theta2 and alpha ERD in response to the target stimuli was larger than to known nontarget words.

Cooperative tumour cell membrane targeted phototherapy

NASA Astrophysics Data System (ADS)

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

2017-06-01

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

Cryogenic target system for hydrogen layering

DOE PAGES

Parham, T.; Kozioziemski, B.; Atkinson, D.; ...

2015-11-24

Here, a cryogenic target positioning system was designed and installed on the National Ignition Facility (NIF) target chamber. This instrument incorporates the ability to fill, form, and characterize the NIF targets with hydrogen isotopes needed for ignition experiments inside the NIF target bay then transport and position them in the target chamber. This effort brought to fruition years of research in growing and metrologizing high-quality hydrogen fuel layers and landed it in an especially demanding operations environment in the NIF facility. D-T (deuterium-tritium) layers for NIF ignition experiments have extremely tight specifications and must be grown in a very highlymore » constrained environment: a NIF ignition target inside a cryogenic target positioner inside the NIF target bay. Exquisite control of temperature, pressure, contaminant level, and thermal uniformity are necessary throughout seed formation and layer growth to create an essentially-groove-free single crystal layer.« less

Artificial Chemical Reporter Targeting Strategy Using Bioorthogonal Click Reaction for Improving Active-Targeting Efficiency of Tumor.

PubMed

Yoon, Hong Yeol; Shin, Min Lee; Shim, Man Kyu; Lee, Sangmin; Na, Jin Hee; Koo, Heebeom; Lee, Hyukjin; Kim, Jong-Ho; Lee, Kuen Yong; Kim, Kwangmeyung; Kwon, Ick Chan

2017-05-01

Biological ligands such as aptamer, antibody, glucose, and peptide have been widely used to bind specific surface molecules or receptors in tumor cells or subcellular structures to improve tumor-targeting efficiency of nanoparticles. However, this active-targeting strategy has limitations for tumor targeting due to inter- and intraheterogeneity of tumors. In this study, we demonstrated an alternative active-targeting strategy using metabolic engineering and bioorthogonal click reaction to improve tumor-targeting efficiency of nanoparticles. We observed that azide-containing chemical reporters were successfully generated onto surface glycans of various tumor cells such as lung cancer (A549), brain cancer (U87), and breast cancer (BT-474, MDA-MB231, MCF-7) via metabolic engineering in vitro. In addition, we compared tumor targeting of artificial azide reporter with bicyclononyne (BCN)-conjugated glycol chitosan nanoparticles (BCN-CNPs) and integrin α v β 3 with cyclic RGD-conjugated CNPs (cRGD-CNPs) in vitro and in vivo. Fluorescence intensity of azide-reporter-targeted BCN-CNPs in tumor tissues was 1.6-fold higher and with a more uniform distribution compared to that of cRGD-CNPs. Moreover, even in the isolated heterogeneous U87 cells, BCN-CNPs could bind artificial azide reporters on tumor cells more uniformly (∼92.9%) compared to cRGD-CNPs. Therefore, the artificial azide-reporter-targeting strategy can be utilized for targeting heterogeneous tumor cells via bioorthogonal click reaction and may provide an alternative method of tumor targeting for further investigation in cancer therapy.

Liquid Hydrogen Target Experience at SLAC

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

Weisend, J.G.; Boyce, R.; Candia, A.

2005-08-29

Liquid hydrogen targets have played a vital role in the physics program at SLAC for the past 40 years. These targets have ranged from small ''beer can'' targets to the 1.5 m long E158 target that was capable of absorbing up to 800 W without any significant density changes. Successful use of these targets has required the development of thin wall designs, liquid hydrogen pumps, remote positioning and alignment systems, safety systems, control and data acquisition systems, cryogenic cooling circuits and heat exchangers. Detailed operating procedures have been created to ensure safety and operational reliability. This paper surveys the evolutionmore » of liquid hydrogen targets at SLAC and discusses advances in several of the enabling technologies that made these targets possible.« less

Plant targets for Pseudomonas syringae type III effectors: virulence targets or guarded decoys?

PubMed

Block, Anna; Alfano, James R

2011-02-01

The phytopathogenic bacterium Pseudomonas syringae can suppress both pathogen-associated molecular pattern (PAMP)-triggered immunity (PTI) and effector-triggered immunity (ETI) by the injection of type III effector (T3E) proteins into host cells. T3Es achieve immune suppression using a variety of strategies including interference with immune receptor signaling, blocking RNA pathways and vesicle trafficking, and altering organelle function. T3Es can be recognized indirectly by resistance proteins monitoring specific T3E targets resulting in ETI. It is presently unclear whether the monitored targets represent bona fide virulence targets or guarded decoys. Extensive overlap between PTI and ETI signaling suggests that T3Es may suppress both pathways through common targets and by possessing multiple activities. Copyright © 2010 Elsevier Ltd. All rights reserved.

Vision-Based Target Finding and Inspection of a Ground Target Using a Multirotor UAV System.

PubMed

Hinas, Ajmal; Roberts, Jonathan M; Gonzalez, Felipe

2017-12-17

In this paper, a system that uses an algorithm for target detection and navigation and a multirotor Unmanned Aerial Vehicle (UAV) for finding a ground target and inspecting it closely is presented. The system can also be used for accurate and safe delivery of payloads or spot spraying applications in site-specific crop management. A downward-looking camera attached to a multirotor is used to find the target on the ground. The UAV descends to the target and hovers above the target for a few seconds to inspect the target. A high-level decision algorithm based on an OODA (observe, orient, decide, and act) loop was developed as a solution to address the problem. Navigation of the UAV was achieved by continuously sending local position messages to the autopilot via Mavros. The proposed system performed hovering above the target in three different stages: locate, descend, and hover. The system was tested in multiple trials, in simulations and outdoor tests, from heights of 10 m to 40 m. Results show that the system is highly reliable and robust to sensor errors, drift, and external disturbance.

Effects of target typicality on categorical search.

PubMed

Maxfield, Justin T; Stalder, Westri D; Zelinsky, Gregory J

2014-10-01

The role of target typicality in a categorical visual search task was investigated by cueing observers with a target name, followed by a five-item target present/absent search array in which the target images were rated in a pretest to be high, medium, or low in typicality with respect to the basic-level target cue. Contrary to previous work, we found that search guidance was better for high-typicality targets compared to low-typicality targets, as measured by both the proportion of immediate target fixations and the time to fixate the target. Consistent with previous work, we also found an effect of typicality on target verification times, the time between target fixation and the search judgment; as target typicality decreased, verification times increased. To model these typicality effects, we trained Support Vector Machine (SVM) classifiers on the target categories, and tested these on the corresponding specific targets used in the search task. This analysis revealed significant differences in classifier confidence between the high-, medium-, and low-typicality groups, paralleling the behavioral results. Collectively, these findings suggest that target typicality broadly affects both search guidance and verification, and that differences in typicality can be predicted by distance from an SVM classification boundary. © 2014 ARVO.

Impact of Target Distance, Target Size, and Visual Acuity on the Video Head Impulse Test.

PubMed

Judge, Paul D; Rodriguez, Amanda I; Barin, Kamran; Janky, Kristen L

2018-05-01

The video head impulse test (vHIT) assesses the vestibulo-ocular reflex. Few have evaluated whether environmental factors or visual acuity influence the vHIT. The purpose of this study was to evaluate the influence of target distance, target size, and visual acuity on vHIT outcomes. Thirty-eight normal controls and 8 subjects with vestibular loss (VL) participated. vHIT was completed at 3 distances and with 3 target sizes. Normal controls were subdivided on the basis of visual acuity. Corrective saccade frequency, corrective saccade amplitude, and gain were tabulated. In the normal control group, there were no significant effects of target size or visual acuity for any vHIT outcome parameters; however, gain increased as target distance decreased. The VL group demonstrated higher corrective saccade frequency and amplitude and lower gain as compared with controls. In conclusion, decreasing target distance increases gain for normal controls but not subjects with VL. Preliminarily, visual acuity does not affect vHIT outcomes.

Target for production of X-rays

NASA Astrophysics Data System (ADS)

Korenev, S. A.

2004-09-01

The patented new type of X-ray target is considered in this report. The main concept of the target consists in developing a sandwich structure depositing a coating of materials with high Z on the substrate with low Z, high thermal conductivity and high thermal stability. The target presents multiple layers system. The thermal conditions for X-ray target are discussed. The experimental results for Ta target on the Al and Cu substrates are presented.

Guidance system for laser targets

DOEpatents

Porter, Gary D.; Bogdanoff, Anatoly

1978-01-01

A system for guiding charged laser targets to a predetermined focal spot of a laser along generally arbitrary, and especially horizontal, directions which comprises a series of electrostatic sensors which provide inputs to a computer for real time calculation of position, velocity, and direction of the target along an initial injection trajectory, and a set of electrostatic deflection means, energized according to a calculated output of said computer, to change the target trajectory to intercept the focal spot of the laser which is triggered so as to illuminate the target of the focal spot.

Targeting targeted agents: open issues for clinical trial design.

PubMed

Bria, Emilio; Di Maio, Massimo; Carlini, Paolo; Cuppone, Federica; Giannarelli, Diana; Cognetti, Francesco; Milella, Michele

2009-05-22

Molecularly targeted agents for the treatment of solid tumors had entered the market in the last 5 years, with a great impact upon both the scientific community and the society. Many randomized phase III trials conducted in recent years with new targeted agents, despite previous data coming from preclinical research and from phase II trials were often promising, have produced disappointingly negative results. Some other trials have actually met their primary endpoint, demonstrating a statistically significant result favouring the experimental treatment. Unfortunately, with a few relevant exceptions, this advantage is often small, if not negligible, in absolute terms. The difference between statistical significance and clinical relevance should always be considered when translating clinical trials' results in the practice. The reason why this 'revolution' did not significantly impact on cancer treatment to displace chemotherapy from the patient' bedside is in part due to complicated, and in many cases, unknown, mechanisms of action of such drugs; indeed, the traditional way the clinical investigators were used to test the efficacy of 'older' chemotherapeutics, has become 'out of date' from the methodological perspective. As these drugs should be theoretically tailored upon featured bio-markers expressed by the patients, the clinical trial design should follow new rules based upon stronger hypotheses than those developed so far. Indeed, the early phases of basic and clinical drug development are crucial in the correct process which is able to correctly identify the target (when present). Targeted trial designs can result in easier studies, with less, better selected, and supported by stronger proofs of response evidences, patients, in order to not waste time and resources.

Targeted therapies for cancer

MedlinePlus

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

A small molecule nanodrug consisting of amphiphilic targeting ligand-chemotherapy drug conjugate for targeted cancer therapy.

PubMed

Mou, Quanbing; Ma, Yuan; Zhu, Xinyuan; Yan, Deyue

2016-05-28

Targeted drug delivery is a broadly applicable approach for cancer therapy. However, the nanocarrier-based targeted delivery system suffers from batch-to-batch variation, quality concerns and carrier-related toxicity issues. Thus, to develop a carrier-free targeted delivery system with nanoscale characteristics is very attractive. Here, a novel targeting small molecule nanodrug self-delivery system consisting of targeting ligand and chemotherapy drug was constructed, which combined the advantages of small molecules and nano-assemblies together and showed excellent targeting ability and long blood circulation time with well-defined structure, high drug loading ratio and on-demand drug release behavior. As a proof-of-concept, lactose (Lac) and doxorubicin (DOX) were chosen as the targeting ligand and chemotherapy drug, respectively. Lac and DOX were conjugated through a pH-responsive hydrazone group. For its intrinsic amphiphilic property, Lac-DOX conjugate could self-assemble into nanoparticles in water. Both in vitro and in vivo assays indicated that Lac-DOX nanoparticles exhibited enhanced anticancer activity and weak side effects. This novel active targeting nanodrug delivery system shows great potential in cancer therapy. Copyright © 2016 Elsevier B.V. All rights reserved.

Identification of tissue-specific targeting peptide

NASA Astrophysics Data System (ADS)

Jung, Eunkyoung; Lee, Nam Kyung; Kang, Sang-Kee; Choi, Seung-Hoon; Kim, Daejin; Park, Kisoo; Choi, Kihang; Choi, Yun-Jaie; Jung, Dong Hyun

2012-11-01

Using phage display technique, we identified tissue-targeting peptide sets that recognize specific tissues (bone-marrow dendritic cell, kidney, liver, lung, spleen and visceral adipose tissue). In order to rapidly evaluate tissue-specific targeting peptides, we performed machine learning studies for predicting the tissue-specific targeting activity of peptides on the basis of peptide sequence information using four machine learning models and isolated the groups of peptides capable of mediating selective targeting to specific tissues. As a representative liver-specific targeting sequence, the peptide "DKNLQLH" was selected by the sequence similarity analysis. This peptide has a high degree of homology with protein ligands which can interact with corresponding membrane counterparts. We anticipate that our models will be applicable to the prediction of tissue-specific targeting peptides which can recognize the endothelial markers of target tissues.

Utilizing random Forest QSAR models with optimized parameters for target identification and its application to target-fishing server.

PubMed

Lee, Kyoungyeul; Lee, Minho; Kim, Dongsup

2017-12-28

The identification of target molecules is important for understanding the mechanism of "target deconvolution" in phenotypic screening and "polypharmacology" of drugs. Because conventional methods of identifying targets require time and cost, in-silico target identification has been considered an alternative solution. One of the well-known in-silico methods of identifying targets involves structure activity relationships (SARs). SARs have advantages such as low computational cost and high feasibility; however, the data dependency in the SAR approach causes imbalance of active data and ambiguity of inactive data throughout targets. We developed a ligand-based virtual screening model comprising 1121 target SAR models built using a random forest algorithm. The performance of each target model was tested by employing the ROC curve and the mean score using an internal five-fold cross validation. Moreover, recall rates for top-k targets were calculated to assess the performance of target ranking. A benchmark model using an optimized sampling method and parameters was examined via external validation set. The result shows recall rates of 67.6% and 73.9% for top-11 (1% of the total targets) and top-33, respectively. We provide a website for users to search the top-k targets for query ligands available publicly at http://rfqsar.kaist.ac.kr . The target models that we built can be used for both predicting the activity of ligands toward each target and ranking candidate targets for a query ligand using a unified scoring scheme. The scores are additionally fitted to the probability so that users can estimate how likely a ligand-target interaction is active. The user interface of our web site is user friendly and intuitive, offering useful information and cross references.

Target Fishing for Chemical Compounds using Target-Ligand Activity data and Ranking based Methods

PubMed Central

Wale, Nikil; Karypis, George

2009-01-01

In recent years the development of computational techniques that identify all the likely targets for a given chemical compound, also termed as the problem of Target Fishing, has been an active area of research. Identification of likely targets of a chemical compound helps to understand problems such as toxicity, lack of efficacy in humans, and poor physical properties associated with that compound in the early stages of drug discovery. In this paper we present a set of techniques whose goal is to rank or prioritize targets in the context of a given chemical compound such that most targets that this compound may show activity against appear higher in the ranked list. These methods are based on our extensions to the SVM and Ranking Perceptron algorithms for this problem. Our extensive experimental study shows that the methods developed in this work outperform previous approaches by 2% to 60% under different evaluation criterions. PMID:19764745

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

PubMed

Sadjadi, Firooz A; Mahalanobis, Abhijit

2006-05-01

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

Multiple shell fusion targets

DOEpatents

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

1975-10-31

Multiple shell fusion targets for use with electron beam and ion beam implosion systems are described. The multiple shell targets are of the low-power type and use a separate relatively low Z, low density ablator at large radius for the outer shell, which reduces the focusing and power requirements of the implosion system while maintaining reasonable aspect ratios. The targets use a high Z, high density pusher shell placed at a much smaller radius in order to obtain an aspect ratio small enough to protect against fluid instability. Velocity multiplication between these shells further lowers the power requirements. Careful tuning of the power profile and intershell density results in a low entropy implosion which allows breakeven at low powers. For example, with ion beams as a power source, breakeven at 10-20 Terrawatts with 10 MeV alpha particles for imploding a multiple shell target can be accomplished.

Ignition of deuterium-trtium fuel targets

DOEpatents

Musinski, Donald L.; Mruzek, Michael T.

1991-01-01

A method of igniting a deuterium-tritium ICF fuel target to obtain fuel burn in which the fuel target initially includes a hollow spherical shell having a frozen layer of DT material at substantially uniform thickness and cryogenic temperature around the interior surface of the shell. The target is permitted to free-fall through a target chamber having walls heated by successive target ignitions, so that the target is uniformly heated during free-fall to at least partially melt the frozen fuel layer and form a liquid single-phase layer or a mixed liquid/solid bi-phase layer of substantially uniform thickness around the interior shell surface. The falling target is then illuminated from exteriorly of the chamber while the fuel layer is at substantially uniformly single or bi-phase so as to ignite the fuel layer and release energy therefrom.

A novel double-targeted nondrug delivery system for targeting cancer stem cells

PubMed Central

Qiao, Shupei; Zhao, Yufang; Geng, Shuai; Li, Yong; Hou, Xiaolu; Liu, Yi; Lin, Feng-Huei; Yao, Lifen; Tian, Weiming

2016-01-01

Instead of killing cancer stem cells (CSCs), the conventional chemotherapy used for cancer treatment promotes the enrichment of CSCs, which are responsible for tumor growth, metastasis, and recurrence. However, most therapeutic agents are only able to kill a small proportion of CSCs by targeting one or two cell surface markers or dysregulated CSC pathways, which are usually shared with normal stem cells (NSCs). In this study, we developed a novel nondrug delivery system for the dual targeting of CSCs by conjugating hyaluronic acid (HA) and grafting the doublecortin-like kinase 1 (DCLK1) monoclonal antibody to the surface of poly(ethylene glycol) (PEG)–poly(d,l-lactide-co-glycolide) (PLGA) nanoparticles (NPs), which can specifically target CD44 receptors and the DCLK1 surface marker – the latter was shown to possess the capacity to distinguish between CSCSs and NSCs. The size and morphology of these NPs were characterized by dynamic light scattering (DLS), transmission electron microscopy (TEM), and scanning electron microscopy (SEM). This was followed by studies of NP encapsulation efficiency and in vitro drug release properties. Then, the cytotoxicity of the NPs was tested via Cell Counting Kit-8 assay. Finally, the 4T1 CSCs were obtained from the alginate-based platform, which we developed as an in vitro tumor model. Tumor-bearing nude mice were used as in vivo models to systematically detect the ability of NPs to target CSCs. Our results showed that the DCLK1–HA–PEG–PLGA NPs exhibited a targeting effect toward CSCs both in vitro and in vivo. These findings have important implications for the rational design of drug delivery systems that target CSCs with high efficacy. PMID:27994463

Flyer Target Acceleration and Energy Transfer at its Collision with Massive Targets

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

Borodziuk, S.; Kasperczuk, A.; Pisarczyk, T.

2006-01-15

Numerical modelling was aimed at simulation of successive events resulting from interaction of laser beam-single and double targets. It was performed by means of the 2D Lagrangian hydrodynamics code ATLANT-HE. This code is based on one-fluid and two-temperature model of plasma with electron and ion heat conductivity considerations. The code has an advanced treatment of laser light propagation and absorption. This numerical modelling corresponds to the experiment, which was carried out with the use of the PALS facility. Two types of planar solid targets, i.e. single massive Al slabs and double targets consisting of 6 {mu}m thick Al foil andmore » Al slab were applied. The targets were irradiated by the iodine laser pulses of two wavelengths: 1.315 and 0.438 {mu}m. A pulse duration of 0.4 ns and a focal spot diameter of 250 {mu}m at a laser energy of 130 J were used. The numerical modelling allowed us to obtain a more detailed description of shock wave propagation and crater formation.« less

Target validation: linking target and chemical properties to desired product profile.

PubMed

Wyatt, Paul G; Gilbert, Ian H; Read, Kevin D; Fairlamb, Alan H

2011-01-01

The discovery of drugs is a lengthy, high-risk and expensive business taking at least 12 years and is estimated to cost upwards of US$800 million for each drug to be successfully approved for clinical use. Much of this cost is driven by the late phase clinical trials and therefore the ability to terminate early those projects destined to fail is paramount to prevent unwanted costs and wasted effort. Although neglected diseases drug discovery is driven more by unmet medical need rather than financial considerations, the need to minimise wasted money and resources is even more vital in this under-funded area. To ensure any drug discovery project is addressing the requirements of the patients and health care providers and delivering a benefit over existing therapies, the ideal attributes of a novel drug needs to be pre-defined by a set of criteria called a target product profile. Using a target product profile the drug discovery process, clinical study design, and compound characteristics can be defined all the way back through to the suitability or druggability of the intended biochemical target. Assessment and prioritisation of the most promising targets for entry into screening programmes is crucial for maximising chances of success.

Tritium target manufacturing for use in accelerators

NASA Astrophysics Data System (ADS)

Bach, P.; Monnin, C.; Van Rompay, M.; Ballanger, A.

2001-07-01

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 target on copper substrate, and going to more sophisticated devices. A wide range of possible uses is covered, including thin targets for neutron calibration, thick targets with controlled loading of deuterium and tritium, rotating targets for higher lifetimes, or large size rotating targets for accelerators used in boron neutron therapy. Activity of targets lies in the 1 to 1000 Curie, diameter of targets being up to 30 cm. Special targets are also considered, including surface layer targets for lowering tritium desorption under irradiation, or those made from different kinds of occluders such as titanium, zirconium, erbium, scandium, with different substrates. It is then possible to optimize either neutron output, or lifetime and stability, or thermal behavior.

ANITA (Advanced Network for Isotope and TArget laboratories) - The urgent need for a European target preparation network

NASA Astrophysics Data System (ADS)

Schumann, Dorothea; Sibbens, Goedele; Stolarz, Anna; Eberhardt, Klaus; Lommel, Bettina; Stodel, Christelle

2018-05-01

A wide number of research fields in the nuclear sector requires high-quality and well-characterized samples and targets. Currently, only a few laboratories own or have access to the equipment allowing fulfilling such demands. Coordination of activities and sharing resources is therefore mandatory to meet the increasing needs. This very urgent issue has now been addressed by six European target laboratories with an initiative called ANITA (Advanced Network for Isotope and TArget laboratories). The global aim of ANITA is to establish an overarching research infrastructure service for isotope and target production and develop a tight cooperation between the target laboratories in Europe in order to transfer the knowledge and improve the production techniques of well-characterized samples and targets. Moreover, the interaction of the target producers with the users shall be encouraged and intensified to deliver tailor-made targets best-suited to the envisaged experiments. For the realization of this ambitious goal, efforts within the European Commission and strong support by the target-using communities will be necessary. In particular, an appropriate funding instrument has to be found and applied, enabling ANITA to develop from an initiative employed by the interested parties to a real coordination platform.

Target-to-Target Repetition Cost and Location Negative Priming Are Dissociable: Evidence for Different Mechanisms

ERIC Educational Resources Information Center

Chao, Hsuan-Fu

2011-01-01

In a location-selection task, the repetition of a prior distractor location as the target location would slow down the response. This effect is termed the location negative priming (NP) effect. Recently, it has been demonstrated that repetition of a prior target location as the current target location would also slow down response. Because such…

Ignition of deuterium-tritium fuel targets

DOEpatents

Musinski, D.L.; Mruzek, M.T.

1991-08-27

Disclosed is a method of igniting a deuterium-tritium ICF fuel target to obtain fuel burn in which the fuel target initially includes a hollow spherical shell having a frozen layer of DT material at substantially uniform thickness and cryogenic temperature around the interior surface of the shell. The target is permitted to free-fall through a target chamber having walls heated by successive target ignitions, so that the target is uniformly heated during free-fall to at least partially melt the frozen fuel layer and form a liquid single-phase layer or a mixed liquid/solid bi-phase layer of substantially uniform thickness around the interior shell surface. The falling target is then illuminated from exteriorly of the chamber while the fuel layer is at substantially uniformly single or bi-phase so as to ignite the fuel layer and release energy therefrom. 5 figures.

Performing target specific band reduction using artificial neural networks and assessment of its efficacy using various target detection algorithms

NASA Astrophysics Data System (ADS)

Yadav, Deepti; Arora, M. K.; Tiwari, K. C.; Ghosh, J. K.

2016-04-01

Hyperspectral imaging is a powerful tool in the field of remote sensing and has been used for many applications like mineral detection, detection of landmines, target detection etc. Major issues in target detection using HSI are spectral variability, noise, small size of the target, huge data dimensions, high computation cost, complex backgrounds etc. Many of the popular detection algorithms do not work for difficult targets like small, camouflaged etc. and may result in high false alarms. Thus, target/background discrimination is a key issue and therefore analyzing target's behaviour in realistic environments is crucial for the accurate interpretation of hyperspectral imagery. Use of standard libraries for studying target's spectral behaviour has limitation that targets are measured in different environmental conditions than application. This study uses the spectral data of the same target which is used during collection of the HSI image. This paper analyze spectrums of targets in a way that each target can be spectrally distinguished from a mixture of spectral data. Artificial neural network (ANN) has been used to identify the spectral range for reducing data and further its efficacy for improving target detection is verified. The results of ANN proposes discriminating band range for targets; these ranges were further used to perform target detection using four popular spectral matching target detection algorithm. Further, the results of algorithms were analyzed using ROC curves to evaluate the effectiveness of the ranges suggested by ANN over full spectrum for detection of desired targets. In addition, comparative assessment of algorithms is also performed using ROC.

Targets of curcumin

PubMed Central

Zhou, Hongyu; Beevers, Christopher S.; Huang, Shile

2010-01-01

Curcumin (diferuloylmethane), an orange-yellow component of turmeric or curry powder, is a polyphenol natural product isolated from the rhizome of the plant Curcuma longa. For centuries, curcumin has been used in some medicinal preparation or used as a food-coloring agent. In recent years, extensive in vitro and in vivo studies suggested curcumin has anticancer, antiviral, antiarthritic, anti-amyloid, antioxidant, and anti-inflammatory properties. The underlying mechanisms of these effects are diverse and appear to involve the regulation of various molecular targets, including transcription factors (such as nuclear factor-κB), growth factors (such as vascular endothelial cell growth factor), inflammatory cytokines (such as tumor necrosis factor, interleukin 1 and interleukin 6), protein kinases (such as mammalian target of rapamycin, mitogen-activated protein kinases, and Akt) and other enzymes (such as cyclooxygenase 2 and 5 lipoxygenase). Thus, due to its efficacy and regulation of multiple targets, as well as its safety for human use, curcumin has received considerable interest as a potential therapeutic agent for the prevention and/or treatment of various malignant diseases, arthritis, allergies, Alzheimer’s disease, and other inflammatory illnesses. This review summarizes various in vitro and in vivo pharmacological aspects of curcumin as well as the underlying action mechanisms. The recently identified molecular targets and signaling pathways modulated by curcumin are also discussed here. PMID:20955148

TargetMiner: microRNA target prediction with systematic identification of tissue-specific negative examples.

PubMed

Bandyopadhyay, Sanghamitra; Mitra, Ramkrishna

2009-10-15

Prediction of microRNA (miRNA) target mRNAs using machine learning approaches is an important area of research. However, most of the methods suffer from either high false positive or false negative rates. One reason for this is the marked deficiency of negative examples or miRNA non-target pairs. Systematic identification of non-target mRNAs is still not addressed properly, and therefore, current machine learning approaches are compelled to rely on artificially generated negative examples for training. In this article, we have identified approximately 300 tissue-specific negative examples using a novel approach that involves expression profiling of both miRNAs and mRNAs, miRNA-mRNA structural interactions and seed-site conservation. The newly generated negative examples are validated with pSILAC dataset, which elucidate the fact that the identified non-targets are indeed non-targets.These high-throughput tissue-specific negative examples and a set of experimentally verified positive examples are then used to build a system called TargetMiner, a support vector machine (SVM)-based classifier. In addition to assessing the prediction accuracy on cross-validation experiments, TargetMiner has been validated with a completely independent experimental test dataset. Our method outperforms 10 existing target prediction algorithms and provides a good balance between sensitivity and specificity that is not reflected in the existing methods. We achieve a significantly higher sensitivity and specificity of 69% and 67.8% based on a pool of 90 feature set and 76.5% and 66.1% using a set of 30 selected feature set on the completely independent test dataset. In order to establish the effectiveness of the systematically generated negative examples, the SVM is trained using a different set of negative data generated using the method in Yousef et al. A significantly higher false positive rate (70.6%) is observed when tested on the independent set, while all other factors are kept the

Small molecules targeting viral RNA.

PubMed

Hermann, Thomas

2016-11-01

Highly conserved noncoding RNA (ncRNA) elements in viral genomes and transcripts offer new opportunities to expand the repertoire of drug targets for the development of antiinfective therapy. Ligands binding to ncRNA architectures are able to affect interactions, structural stability or conformational changes and thereby block processes essential for viral replication. Proof of concept for targeting functional RNA by small molecule inhibitors has been demonstrated for multiple viruses with RNA genomes. Strategies to identify antiviral compounds as inhibitors of ncRNA are increasingly emphasizing consideration of drug-like properties of candidate molecules emerging from screening and ligand design. Recent efforts of antiviral lead discovery for RNA targets have provided drug-like small molecules that inhibit viral replication and include inhibitors of human immunodeficiency virus (HIV), hepatitis C virus (HCV), severe respiratory syndrome coronavirus (SARS CoV), and influenza A virus. While target selectivity remains a challenge for the discovery of useful RNA-binding compounds, a better understanding is emerging of properties that define RNA targets amenable for inhibition by small molecule ligands. Insight from successful approaches of targeting viral ncRNA in HIV, HCV, SARS CoV, and influenza A will provide a basis for the future exploration of RNA targets for therapeutic intervention in other viral pathogens which create urgent, unmet medical needs. Viruses for which targeting ncRNA components in the genome or transcripts may be promising include insect-borne flaviviruses (Dengue, Zika, and West Nile) and filoviruses (Ebola and Marburg). WIREs RNA 2016, 7:726-743. doi: 10.1002/wrna.1373 For further resources related to this article, please visit the WIREs website. © 2016 Wiley Periodicals, Inc.

TARGETING POLYMER THERAPEUTICS TO BONE

PubMed Central

Low, Stewart; Kopeček, Jindřich

2012-01-01

An aging population in the developing world has led to an increase in musculoskeletal diseases such as osteoporosis and bone metastases. Left untreated many bone diseases cause debilitating pain and in the case of cancer, death. Many potential drugs are effective in treating diseases but result in side effects preventing their efficacy in the clinic. Bone, however, provides an unique environment of inorganic solids, which can be exploited in order to effectively target drugs to diseased tissue. By integration of bone targeting moieties to drug-carrying water-soluble polymers, the payload to diseased area can be increased while side effects decreased. The realization of clinically relevant bone targeted polymer therapeutics depends on (1) understanding bone targeting moiety interactions, (2) development of controlled drug delivery systems, as well as (3) understanding drug interactions. The latter makes it possible to develop bone targeted synergistic drug delivery systems. PMID:22316530

Targeted marketing and public health.

PubMed

Grier, Sonya A; Kumanyika, Shiriki

2010-01-01

Targeted marketing techniques, which identify consumers who share common needs or characteristics and position products or services to appeal to and reach these consumers, are now the core of all marketing and facilitate its effectiveness. However, targeted marketing, particularly of products with proven or potential adverse effects (e.g., tobacco, alcohol, entertainment violence, or unhealthful foods) to consumer segments defined as vulnerable raises complex concerns for public health. It is critical that practitioners, academics, and policy makers in marketing, public health, and other fields recognize and understand targeted marketing as a specific contextual influence on the health of children and adolescents and, for different reasons, ethnic minority populations and other populations who may benefit from public health protections. For beneficial products, such understanding can foster more socially productive targeting. For potentially harmful products, understanding the nature and scope of targeted marketing influences will support identification and implementation of corrective policies.

Polarized targets in high energy physics

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

Cates, G.D. Jr.

1994-12-01

Various approaches are discussed for producing polarized nuclear targets for high energy physics experiments. As a unifying theme, examples are drawn from experiments to measure spin dependent structure functions of nucleons in deep inelastic scattering. This single physics goal has, over roughly two decades, been a driving force in advances in target technology. Actual or planned approaches have included solid targets polarized by dynamic nuclear polarization (DNP), several types of internal targets for use in storage rings, and gaseous {sup 3}He targets polarized by spin-exchange optical pumping. This last approach is the type of target adopted for SLAC E-142, anmore » experiment to measure the spin structure function of the neutron, and is described in detail.« less

Atmospheric electromagnetic pulse propagation effects from thick targets in a terawatt laser target chamber.

PubMed

Remo, John L; Adams, Richard G; Jones, Michael C

2007-08-20

Generation and effects of atmospherically propagated electromagnetic pulses (EMPs) initiated by photoelectrons ejected by the high density and temperature target surface plasmas from multiterawatt laser pulses are analyzed. These laser radiation pulse interactions can significantly increase noise levels, thereby obscuring data (sometimes totally) and may even damage sensitive probe and detection instrumentation. Noise effects from high energy density (approximately multiterawatt) laser pulses (approximately 300-400 ps pulse widths) interacting with thick approximately 1 mm) metallic and dielectric solid targets and dielectric-metallic powder mixtures are interpreted as transient resonance radiation associated with surface charge fluctuations on the target chamber that functions as a radiating antenna. Effective solutions that minimize atmospheric EMP effects on internal and proximate electronic and electro-optical equipment external to the system based on systematic measurements using Moebius loop antennas, interpretations of signal periodicities, and dissipation indicators determining transient noise origin characteristics from target emissions are described. Analytic models for the effect of target chamber resonances and associated noise current and temperature in a probe diode laser are described.

Atmospheric electromagnetic pulse propagation effects from thick targets in a terawatt laser target chamber

NASA Astrophysics Data System (ADS)

Remo, John L.; Adams, Richard G.; Jones, Michael C.

2007-08-01

Generation and effects of atmospherically propagated electromagnetic pulses (EMPs) initiated by photoelectrons ejected by the high density and temperature target surface plasmas from multiterawatt laser pulses are analyzed. These laser radiation pulse interactions can significantly increase noise levels, thereby obscuring data (sometimes totally) and may even damage sensitive probe and detection instrumentation. Noise effects from high energy density (approximately multiterawatt) laser pulses (˜300-400 ps pulse widths) interacting with thick (˜1 mm) metallic and dielectric solid targets and dielectric-metallic powder mixtures are interpreted as transient resonance radiation associated with surface charge fluctuations on the target chamber that functions as a radiating antenna. Effective solutions that minimize atmospheric EMP effects on internal and proximate electronic and electro-optical equipment external to the system based on systematic measurements using Moebius loop antennas, interpretations of signal periodicities, and dissipation indicators determining transient noise origin characteristics from target emissions are described. Analytic models for the effect of target chamber resonances and associated noise current and temperature in a probe diode laser are described.

Target Acquired: Progress and Promise of Targeted Therapeutics in the Treatment of Prostate Cancer.

PubMed

Stuchbery, Ryan; Kurganovs, Natalie J; McCoy, Patrick J; Nelson, Colleen C; Hayes, Vanessa M; Corcoran, Niall M; Hovens, Christopher M

2015-01-01

Cancer is fundamentally a genomic disease caused by mutations or rearrangements in the DNA or epigenetic machinery of a patient. An emerging field in cancer treatment targets key aberrations arising from the mutational landscape of an individual patient's disease rather than employing a cancer-wide cytotoxic therapy approach. In prostate cancer in particular, where there is an observed variation in response to standard treatments between patients with disease of a similar pathological stage and grade, mutationdirected treatment may grow to be a viable tool for clinicians to tailor more effective treatments. This review will describe a number of mutations across multiple forms of cancer that have been successfully antagonised by targeted therapeutics including their identification, the development of targeted compounds to combat them and the development of resistance to these therapies. This review will continue to examine these same mutations in the treatment and management of prostate cancer; the prevalence of targetable mutations in prostate cancer, recent clinical trials of targeted-agents and the potential or limitations for their use.

Atmospheric electromagnetic pulse propagation effects from thick targets in a terawatt laser target chamber

DOE PAGES

Remo, John L.; Adams, Richard G.; Jones, Michael C.

2007-08-16

Generation and effects of atmospherically propagated electromagnetic pulses (EMPs) initiated by photoelectrons ejected by the high density and temperature target surface plasmas from multiterawatt laser pulses are analyzed. These laser radiation pulse interactions can significantly increase noise levels, thereby obscuring data (sometimes totally) and may even damage sensitive probe and detection instrumentation. Noise effects from high energy density (approximately multiterawatt) laser pulses (~300–400 ps pulse widths) interacting with thick (~1 mm) metallic and dielectric solid targets and dielectric–metallic powder mixtures are interpreted as transient resonance radiation associated with surface charge fluctuations on the target chamber that functions as a radiatingmore » antenna. Effective solutions that minimize atmospheric EMP effects on internal and proximate electronic and electro-optical equipment external to the system based on systematic measurements using Moebius loop antennas, interpretations of signal periodicities, and dissipation indicators determining transient noise origin characteristics from target emissions are described. Analytic models for the effect of target chamber resonances and associated noise current and temperature in a probe diode laser are described.« less

Counterforce Targeting Capabilities and Challenges

DTIC Science & Technology

2004-08-01

COUNTERFORCE TARGETING CAPABILITIES AND CHALLENGES by Barry R. Schneider The Counterproliferation Papers Future Warfare Series No. 22 USAF...TITLE AND SUBTITLE Counterforce Targeting Capabilities and Challenges 5a. CONTRACT NUMBER 5b. GRANT NUMBER 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) 5d...Rev. 8-98) Prescribed by ANSI Std Z39-18 Counterforce Targeting Capabilities and Challenges Barry R. Schneider August 2004 The Counterproliferation

HPPD: ligand- and target-based virtual screening on a herbicide target.

PubMed

López-Ramos, Miriam; Perruccio, Francesca

2010-05-24

Hydroxyphenylpyruvate dioxygenase (HPPD) has proven to be a very successful target for the development of herbicides with bleaching properties, and today HPPD inhibitors are well established in the agrochemical market. Syngenta has a long history of HPPD-inhibitor research, and HPPD was chosen as a case study for the validation of diverse ligand- and target-based virtual screening approaches to identify compounds with inhibitory properties. Two-dimensional extended connectivity fingerprints, three-dimensional shape-based tools (ROCS, EON, and Phase-shape) and a pharmacophore approach (Phase) were used as ligand-based methods; Glide and Gold were used as target-based. Both the virtual screening utility and the scaffold-hopping ability of the screening tools were assessed. Particular emphasis was put on the specific pitfalls to take into account for the design of a virtual screening campaign in an agrochemical context, as compared to a pharmaceutical environment.

Target discrimination strategies in optics detection

NASA Astrophysics Data System (ADS)

Sjöqvist, Lars; Allard, Lars; Henriksson, Markus; Jonsson, Per; Pettersson, Magnus

2013-10-01

Detection and localisation of optical assemblies used for weapon guidance or sniper rifle scopes has attracted interest for security and military applications. Typically a laser system is used to interrogate a scene of interest and the retro-reflected radiation is detected. Different system approaches for area coverage can be realised ranging from flood illumination to step-and-stare or continuous scanning schemes. Independently of the chosen approach target discrimination is a crucial issue, particularly if a complex scene such as in an urban environment and autonomous operation is considered. In this work target discrimination strategies in optics detection are discussed. Typical parameters affecting the reflected laser radiation from the target are the wavelength, polarisation properties, temporal effects and the range resolution. Knowledge about the target characteristics is important to predict the target discrimination capability. Two different systems were used to investigate polarisation properties and range resolution information from targets including e.g. road signs, optical reflexes, rifle sights and optical references. The experimental results and implications on target discrimination will be discussed. If autonomous operation is required target discrimination becomes critical in order to reduce the number of false alarms.

USGS aerial resolution targets.

USGS Publications Warehouse

Salamonowicz, P.H.

1982-01-01

It is necessary to measure the achievable resolution of any airborne sensor that is to be used for metric purposes. Laboratory calibration facilities may be inadequate or inappropriate for determining the resolution of non-photographic sensors such as optical-mechanical scanners, television imaging tubes, and linear arrays. However, large target arrays imaged in the field can be used in testing such systems. The USGS has constructed an array of resolution targets in order to permit field testing of a variety of airborne sensing systems. The target array permits any interested organization with an airborne sensing system to accurately determine the operational resolution of its system. -from Author

Dual Target Design for CLAS12

NASA Astrophysics Data System (ADS)

Alam, Omair; Gilfoyle, Gerard; Christo, Steve

2015-10-01

An experiment to measure the neutron magnetic form factor (GnM) is planned for the new CLAS12 detector in Hall B at Jefferson Lab. This form factor will be extracted from the ratio of the quasielastic electron-neutron to electron-proton scattering off a liquid deuterium (LD2) target. A collinear liquid hydrogen (LH2) target will be used to measure efficiencies at the same time as production data is collected from the LD2 target. To test target designs we have simulated CLAS12 and the target geometry. Electron-nucleon events are produced first with the QUasiElastic Event Generator (QUEEG) which models the internal motion of the nucleons in deuterium.1 The results are used as input to the CLAS12 Monte Caro code gemc; a Geant4-based program that simulates the particle's interactions with each component of CLAS12 including the target material. The dual target geometry has been added to gemc including support structures and cryogenic transport systems. A Perl script was written to define the target materials and geometries. The output of the script is a set of database entries read by gemc at runtime. An initial study of the impact of this dual-target structure revealed limited effects on the electron momentum and angular resolutions. Work supported by the University of Richmond and the US Department of Energy.

Drug-Target Kinetics in Drug Discovery.

PubMed

Tonge, Peter J

2018-01-17

The development of therapies for the treatment of neurological cancer faces a number of major challenges including the synthesis of small molecule agents that can penetrate the blood-brain barrier (BBB). Given the likelihood that in many cases drug exposure will be lower in the CNS than in systemic circulation, it follows that strategies should be employed that can sustain target engagement at low drug concentration. Time dependent target occupancy is a function of both the drug and target concentration as well as the thermodynamic and kinetic parameters that describe the binding reaction coordinate, and sustained target occupancy can be achieved through structural modifications that increase target (re)binding and/or that decrease the rate of drug dissociation. The discovery and deployment of compounds with optimized kinetic effects requires information on the structure-kinetic relationships that modulate the kinetics of binding, and the molecular factors that control the translation of drug-target kinetics to time-dependent drug activity in the disease state. This Review first introduces the potential benefits of drug-target kinetics, such as the ability to delineate both thermodynamic and kinetic selectivity, and then describes factors, such as target vulnerability, that impact the utility of kinetic selectivity. The Review concludes with a description of a mechanistic PK/PD model that integrates drug-target kinetics into predictions of drug activity.

Drug–Target Kinetics in Drug Discovery

PubMed Central

2017-01-01

The development of therapies for the treatment of neurological cancer faces a number of major challenges including the synthesis of small molecule agents that can penetrate the blood-brain barrier (BBB). Given the likelihood that in many cases drug exposure will be lower in the CNS than in systemic circulation, it follows that strategies should be employed that can sustain target engagement at low drug concentration. Time dependent target occupancy is a function of both the drug and target concentration as well as the thermodynamic and kinetic parameters that describe the binding reaction coordinate, and sustained target occupancy can be achieved through structural modifications that increase target (re)binding and/or that decrease the rate of drug dissociation. The discovery and deployment of compounds with optimized kinetic effects requires information on the structure–kinetic relationships that modulate the kinetics of binding, and the molecular factors that control the translation of drug–target kinetics to time-dependent drug activity in the disease state. This Review first introduces the potential benefits of drug-target kinetics, such as the ability to delineate both thermodynamic and kinetic selectivity, and then describes factors, such as target vulnerability, that impact the utility of kinetic selectivity. The Review concludes with a description of a mechanistic PK/PD model that integrates drug–target kinetics into predictions of drug activity. PMID:28640596

Targeted Therapy: Attacking Cancer with Molecular and Immunological Targeted Agents.

PubMed

Wilkes, Gail M

2018-01-01

Today, personalized cancer therapy with targeted agents has taken center stage, and offers individualized treatment to many. As the mysteries of the genes in a cell's DNA and their specific proteins are defined, advances in the understanding of cancer gene mutations and how cancer evades the immune system have been made. This article provides a basic and simplified understanding of the available (Food and Drug Administration- approved) molecularly and immunologically targeted agents in the USA. Other agents may be available in Asia, and throughout the USA and the world, many more agents are being studied. Nursing implications for drug classes are reviewed.

Space based lidar shot pattern targeting strategies for small targets such as streams

NASA Technical Reports Server (NTRS)

Spiers, Gary D.

2001-01-01

An analysis of the effectiveness of four different types of lidar shot distribution is conducted to determine which is best for concentrating shots in a given location. A simple preemptive targeting strategy is found to work as adequately as a more involved dynamic strategy for most target sizes considered.

Intercepting moving targets: does memory from practice in a specific condition of target displacement affect movement timing?

PubMed

de Azevedo Neto, Raymundo Machado; Teixeira, Luis Augusto

2011-05-01

This investigation aimed at assessing the extent to which memory from practice in a specific condition of target displacement modulates temporal errors and movement timing of interceptive movements. We compared two groups practicing with certainty of future target velocity either in unchanged target velocity or in target velocity decrease. Following practice, both experimental groups were probed in the situations of unchanged target velocity and target velocity decrease either under the context of certainty or uncertainty about target velocity. Results from practice showed similar improvement of temporal accuracy between groups, revealing that target velocity decrease did not disturb temporal movement organization when fully predictable. Analysis of temporal errors in the probing trials indicated that both groups had higher timing accuracy in velocity decrease in comparison with unchanged velocity. Effect of practice was detected by increased temporal accuracy of the velocity decrease group in situations of decreased velocity; a trend consistent with the expected effect of practice was observed for temporal errors in the unchanged velocity group and in movement initiation at a descriptive level. An additional point of theoretical interest was the fast adaptation in both groups to a target velocity pattern different from that practiced. These points are discussed under the perspective of integration of vision and motor control by means of an internal forward model of external motion.

Finding off-targets, biological pathways, and target diseases for chymase inhibitors via structure-based systems biology approach.

PubMed

Arooj, Mahreen; Sakkiah, Sugunadevi; Cao, Guang Ping; Kim, Songmi; Arulalapperumal, Venkatesh; Lee, Keun Woo

2015-07-01

Off-target binding connotes the binding of a small molecule of therapeutic significance to a protein target in addition to the primary target for which it was proposed. Progressively such off-targeting is emerging to be regular practice to reveal side effects. Chymase is an enzyme of hydrolase class that catalyzes hydrolysis of peptide bonds. A link between heart failure and chymase is ascribed, and a chymase inhibitor is in clinical phase II for treatment of heart failure. However, the underlying mechanisms of the off-target effects of human chymase inhibitors are still unclear. Here, we develop a robust computational strategy that is applicable to any enzyme system and that allows the prediction of drug effects on biological processes. Putative off-targets for chymase inhibitors were identified through various structural and functional similarity analyses along with molecular docking studies. Finally, literature survey was performed to incorporate these off-targets into biological pathways and to establish links between pathways and particular adverse effects. Off-targets of chymase inhibitors are linked to various biological pathways such as classical and lectin pathways of complement system, intrinsic and extrinsic pathways of coagulation cascade, and fibrinolytic system. Tissue kallikreins, granzyme M, neutrophil elastase, and mesotrypsin are also identified as off-targets. These off-targets and their associated pathways are elucidated for the effects of inflammation, cancer, hemorrhage, thrombosis, and central nervous system diseases (Alzheimer's disease). Prospectively, our approach is helpful not only to better understand the mechanisms of chymase inhibitors but also for drug repurposing exercises to find novel uses for these inhibitors. © 2014 Wiley Periodicals, Inc.

COS FUV Target Acquisition Monitor

NASA Astrophysics Data System (ADS)

Penton, Steven V.

2017-08-01

Starting in Cycle 25, the COS Target Acquisition (TA) monitor has been divided into two pieces, NUV (15389) and FUV (15386). This program is the FUV portion and is designed specifically for FUV LP4. FUV LP4 uses NUM_POS > 1 PEAKXDs for cross-dispersion TA. All previous LPs used NUM_POS=1 PEAKXDs. The NUM_POS=1 PEAKXDs required the routine monitoring of the grating-dependent WCA-to-PSA offsets. The NUM_POS >1 PEAKXDs do not use these flight software (FSW) patchable constants as they use the LTAPKD FSW macro used in ACQ/PEAKD, but re-purposed for use in the cross-dispersion (XD).This program uses the HST standard star WD1657+343. This target was used previously in the COS TA Monitor programs, 13124 (C20), 13526 (C21), 13972 (C22), 14440 (C23) & 14857 (C24). In these programs, this target was used to co-align the PSA/MIRRORB and BOA/MIRRORA ACQ/IMAGE modes. We re-use this target here as it is safe with PSA/MIRRORA and visible almost year-round.Note that when presented to the mission office, the target 206W3 was listed as the target for this program. This target was a backup target in previous TA monitor programs and was the faintest of the 3 targets in the program. Switching to the next brighter target (WD1657+343) allows all the goals of this program to be accomplished in just 2 orbits. Also, as this target has been used for every generation of this program, the FUV monitoring can be bootstrapped to previous programs, if needed. See the observing description for more details.The LTAIMAGE that started the second orbit of Visit 26 had the TDF down and the shutter closed. This caused the ACQ/IMAGE to miscenter the target by about 1.3". Visit 90 was added as a partial repeat from HOPR 89665. This visit is as close to a repeat of the 2nd orbit of Visi t 25 as possible. Due to time lost doing a full acq instead of a RE-ACQ, the following changes were made:1) Changed Visit number to 902) Schedulability set to 90%3) Before date set to Feb-19-2018, but the earlier the better

Forming Uniform Deuterium-Ice Layers in Cryogenic Targets: Experiences Using the OMEGA Cryogenic Target Handling System

NASA Astrophysics Data System (ADS)

Harding, D. R.; Wittman, M. D.; Elasky, L.; Iwan, L. S.; Lund, L.

2001-10-01

The OMEGA Cryogenic Target Handling System (OCTHS) allows variable-thickness ice layers (nominal 100-μm) to be formed inside OMEGA-size (1-mm-diam., 3-μm-wall) plastic shells. The OCTHS design provides the most straightforward thermal environment for layering targets: permeation filled spherical targets are in a spherical isothermal environment. The layered target can be rotated 360^o to acquire multiple views of the ice layer. However, the capability of providing cryogenic targets for implosion experiments imposes constraints that do not exist in test systems dedicated to ice-layering studies. Most affected is the ability to characterize the target: space constraints and the need for multiple sets of windows limit the viewing access to f/5 optics, which affects the image quality. With these features, the OCTS provides the most relevant test system, to date, for layering targets and quantifying the overall ice roughness. No single layering protocol provides repeatable ice smoothness. All techniques require extensive operator interaction, and the layering process is lengthy. Typical ice rms smoothness varied from 5 to 10 μm for all targets studied. Characterizing the ice layer from different views shows a ~30% variation in the ice rms smoothness and a greater difference in the power spectra, depending on the view axis. This work was supported by the U.S. DOE Office of Inertial Confinement Fusion under Cooperative Agreement No. DE-FC03-92SF19460.

Cooled particle accelerator target

DOEpatents

Degtiarenko, Pavel V.

2005-06-14

A novel particle beam target comprising: a rotating target disc mounted on a retainer and thermally coupled to a first array of spaced-apart parallel plate fins that extend radially inwardly from the retainer and mesh without physical contact with a second array of spaced-apart parallel plate fins that extend radially outwardly from and are thermally coupled to a cooling mechanism capable of removing heat from said second array of spaced-apart fins and located within the first array of spaced-apart parallel fins. Radiant thermal exchange between the two arrays of parallel plate fins provides removal of heat from the rotating disc. A method of cooling the rotating target is also described.

Automatic Target Recognition Based on Cross-Plot

PubMed Central

Wong, Kelvin Kian Loong; Abbott, Derek

2011-01-01

Automatic target recognition that relies on rapid feature extraction of real-time target from photo-realistic imaging will enable efficient identification of target patterns. To achieve this objective, Cross-plots of binary patterns are explored as potential signatures for the observed target by high-speed capture of the crucial spatial features using minimal computational resources. Target recognition was implemented based on the proposed pattern recognition concept and tested rigorously for its precision and recall performance. We conclude that Cross-plotting is able to produce a digital fingerprint of a target that correlates efficiently and effectively to signatures of patterns having its identity in a target repository. PMID:21980508

Targeted polypeptide degradation

DOEpatents

Church, George M [Brookline, MA; Janse, Daniel M [Brookline, MA

2008-05-13

This invention pertains to compositions, methods, cells and organisms useful for selectively localizing polypeptides to the proteasome for degradation. Therapeutic methods and pharmaceutical compositions for treating disorders associated with the expression and/or activity of a polypeptide by targeting these polypeptides for degradation, as well as methods for targeting therapeutic polypeptides for degradation and/or activating therapeutic polypeptides by degradation are provided. The invention provides methods for identifying compounds that mediate proteasome localization and/or polypeptide degradation. The invention also provides research tools for the study of protein function.

Amino acids in a targeted versus a non-targeted metabolomics LC-MS/MS assay. Are the results consistent?

PubMed

Klepacki, Jacek; Klawitter, Jost; Klawitter, Jelena; Karimpour-Fard, Anis; Thurman, Joshua; Ingle, Gordon; Patel, Dharmesh; Christians, Uwe

2016-09-01

The results of plasma amino acid patterns in samples from kidney transplant patients with good and impaired renal function using a targeted LC-MS/MS amino acid assay and a non-targeted metabolomics assay were compared. EDTA plasma samples were prospectively collected at baseline, 1, 2, 4 and 6months post-transplant (n=116 patients, n=398 samples). Each sample was analyzed using both a commercial amino acid LC-MS/MS assay and a non-targeted metabolomics assay also based on MS/MS ion transitions. The results of both assays were independently statistically analyzed to identify amino acids associated with estimated glomerular filtration rates using correlation and partial least squares-discriminant analysis. Although there was overlap between the results of the targeted and non-targeted metabolomics assays (tryptophan, 1-methyl histidine), there were also substantial inconsistencies, with the non-targeted assay resulting in more "hits" than the targeted assay. Without further verification of the hits detected by the non-targeted discovery assay, this would have led to different interpretation of the results. There were also false negative results when the non-targeted assay was used (hydroxy proline). Several of said discrepancies could be explained by loss of sensitivity during analytical runs for selected amino acids (serine and threonine), retention time shifts, signals above the range of linear detector response and integration of peaks not separated from background and interferences (aspartate) when the non-targeted metabolomics assay was used. Whenever assessment of a specific pathway such as amino acids is the focus of interest, a targeted seems preferable to a non-targeted metabolomics assay. Copyright © 2016. Published by Elsevier Inc.

Hyperspectral target detection using manifold learning and multiple target spectra

DOE PAGES

Ziemann, Amanda K.; Theiler, James; Messinger, David W.

2016-03-31

Imagery collected from satellites and airborne platforms provides an important tool for remotely analyzing the content of a scene. In particular, the ability to remotely detect a specific material within a scene is of critical importance in nonproliferation and other applications. The sensor systems that process hyperspectral images collect the high-dimensional spectral information necessary to perform these detection analyses. For a d-dimensional hyperspectral image, however, where d is the number of spectral bands, it is common for the data to inherently occupy an m-dimensional space with m << d. In the remote sensing community, this has led to recent interestmore » in the use of manifold learning, which seeks to characterize the embedded lower-dimensional, nonlinear manifold that the data discretely approximate. The research presented in this paper focuses on a graph theory and manifold learning approach to target detection, using an adaptive version of locally linear embedding that is biased to separate target pixels from background pixels. Finally, this approach incorporates multiple target signatures for a particular material, accounting for the spectral variability that is often present within a solid material of interest.« less

Targeting ubiquitination for cancer therapies.

PubMed

Morrow, John Kenneth; Lin, Hui-Kuan; Sun, Shao-Cong; Zhang, Shuxing

2015-01-01

Ubiquitination, the structured degradation and turnover of cellular proteins, is regulated by the ubiquitin-proteasome system (UPS). Most proteins that are critical for cellular regulations and functions are targets of the process. Ubiquitination is comprised of a sequence of three enzymatic steps, and aberrations in the pathway can lead to tumor development and progression as observed in many cancer types. Recent evidence indicates that targeting the UPS is effective for certain cancer treatment, but many more potential targets might have been previously overlooked. In this review, we will discuss the current state of small molecules that target various elements of ubiquitination. Special attention will be given to novel inhibitors of E3 ubiquitin ligases, especially those in the SCF family.

Targeted Therapy: Attacking Cancer with Molecular and Immunological Targeted Agents

PubMed Central

Wilkes, Gail M.

2018-01-01

Today, personalized cancer therapy with targeted agents has taken center stage, and offers individualized treatment to many. As the mysteries of the genes in a cell's DNA and their specific proteins are defined, advances in the understanding of cancer gene mutations and how cancer evades the immune system have been made. This article provides a basic and simplified understanding of the available (Food and Drug Administration- approved) molecularly and immunologically targeted agents in the USA. Other agents may be available in Asia, and throughout the USA and the world, many more agents are being studied. Nursing implications for drug classes are reviewed. PMID:29607374

Content and Language in Targets and Target Related Assessment (TTRA): Implications for Schools.

ERIC Educational Resources Information Center

Clark, John L.; Scarino, Angela

This paper explores the nature of content and language across the curriculum in relation to the Targets and Target-Related Assessment (TTRA) initiative. The TTRA is an assessment initiative designed to improve the quality of individual learning from Primary 1 to Secondary 5 in Chinese, English, and Mathematics in Hong Kong. A picture of content…

Tumor-targeting peptides from combinatorial libraries*

PubMed Central

Liu, Ruiwu; Li, Xiaocen; Xiao, Wenwu; Lam, Kit S.

2018-01-01

Cancer is one of the major and leading causes of death worldwide. Two of the greatest challenges infighting cancer are early detection and effective treatments with no or minimum side effects. Widespread use of targeted therapies and molecular imaging in clinics requires high affinity, tumor-specific agents as effective targeting vehicles to deliver therapeutics and imaging probes to the primary or metastatic tumor sites. Combinatorial libraries such as phage-display and one-bead one-compound (OBOC) peptide libraries are powerful approaches in discovering tumor-targeting peptides. This review gives an overview of different combinatorial library technologies that have been used for the discovery of tumor-targeting peptides. Examples of tumor-targeting peptides identified from each combinatorial library method will be discussed. Published tumor-targeting peptide ligands and their applications will also be summarized by the combinatorial library methods and their corresponding binding receptors. PMID:27210583

Cryogenic Target-Implosion Experiments on OMEGA

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

Harding, D.R.; Meyerhofer, D.D.; Sangster, T.C.

The University of Rochester’s Laboratory for Laser Energetics has been imploding thick cryogenic targets for six years. Improvements in the Cryogenic Target Handling System and the ability to accurately design laser pulse shapes that properly time shocks and minimize electron preheat, produced high fuel areal densities in deuterium cryogenic targets (202+/-7 mg/cm^2). The areal density was inferred from the energy loss of secondary protons in the fuel (D2) shell. Targets were driven on a low final adiabat (alpha = 2) employing techniques to radially grade the adiabat (the highest adiabat at the ablation surface). The ice layer meets the target-designmore » toughness specification for DT ice of 1-um rms (all modes), while D2 ice layers average 3.0-um-rms roughness. The implosion experiments and the improvements in the quality and understanding of cryogenic targets are presented.« less

National Ignition Facility Target Chamber

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

Wavrik, R W; Cox, J R; Fleming, P J

2000-10-05

On June 11, 1999 the Department of Energy dedicated the single largest piece of the National Ignition Facility (NIF) at Lawrence Livermore National Laboratory (LLNL) in Livermore, California. The ten (10) meter diameter aluminum target high vacuum chamber will serve as the working end of the largest laser in the world. The output of 192 laser beams will converge at the precise center of the chamber. The laser beams will enter the chamber in two by two arrays to illuminate 10 millimeter long gold cylinders called hohlraums enclosing 2 millimeter capsule containing deuterium, tritium and isotopes of hydrogen. The twomore » isotopes will fuse, thereby creating temperatures and pressures resembling those found only inside stars and in detonated nuclear weapons, but on a minute scale. The NIF Project will serve as an essential facility to insure safety and reliability of our nation's nuclear arsenal as well as demonstrating inertial fusion's contribution to creating electrical power. The paper will discuss the requirements that had to be addressed during the design, fabrication and testing of the target chamber. A team from Sandia National Laboratories (SNL) and LLNL with input from industry performed the configuration and basic design of the target chamber. The method of fabrication and construction of the aluminum target chamber was devised by Pitt-Des Moines, Inc. (PDM). PDM also participated in the design of the chamber in areas such as the Target Chamber Realignment and Adjustment System, which would allow realignment of the sphere laser beams in the event of earth settlement or movement from a seismic event. During the fabrication of the target chamber the sphericity tolerances had to be addressed for the individual plates. Procedures were developed for forming, edge preparation and welding of individual plates. Construction plans were developed to allow the field construction of the target chamber to occur parallel to other NIF construction activities. This was

UCx target preparations and characterizations

NASA Astrophysics Data System (ADS)

Andrighetto, Alberto; Corradetti, Stefano; Manzolaro, Mattia; Scarpa, Daniele; Monetti, Alberto; Rossignoli, Massimo; Borgna, Francesca; Ballan, Michele; Agostini, Mattia; D'Agostini, Fabio; Ferrari, Matteo; Zenoni, Aldo

2018-05-01

The Target-Ion Source unit is the core of an ISOL-RIB facility. Many international ISOL facilities have chosen different layouts of this unit. Many research groups are involved in research and development of targets capable of dissipating high power and, at the same time, be able to have a fast isotope release. This is mandatory in order to produce beams of short half-life isotopes. The research of new materials with advanced microstructural features is crucial in this field. The design of a proper target is indeed strictly related to the obtainment of porous refractory materials, which are capable to work under extreme conditions (temperatures up to 2000 °C in high vacuum) with a high release efficiency. For SPES, the second generation Italian ISOL-RIB Facility, the target will be made of uranium carbide (UCx) in which, by fission induced by a proton beam of 40 MeV of energy (8 kW of power), isotopes in the 60-160 amu mass region are produced. The current technological developments are also crucial in the study of third generation ISOL facilities.

Multi-Agent Cooperative Target Search

PubMed Central

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

2014-01-01

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

Phage protein-targeted cancer nanomedicines

PubMed Central

Petrenko, V.A.; Jayanna, P.K.

2015-01-01

Nanoencapsulation of anticancer drugs improves their therapeutic indices by virtue of the enhanced permeation and retention effect which achieves passive targeting of nanoparticles in tumors. This effect can be significantly enhanced by active targeting of nanovehicles to tumors. Numerous ligands have been proposed and used in various studies with peptides being considered attractive alternatives to antibodies. This is further reinforced by the availability of peptide phage display libraries which offer an unlimited reservoir of target-specific probes. In particular landscape phages with multivalent display of target-specific peptides which enable the phage particle itself to become a nanoplatform creates a paradigm for high throughput selection of nanoprobes setting the stage for personalized cancer management. Despite its promise, this conjugate of combinatorial chemistry and nanotechnology has not made a significant clinical impact in cancer management due to a lack of using robust processes that facilitate scale-up and manufacturing. To this end we proposed the use of phage fusion protein as the navigating modules of novel targeted nanomedicine platforms which are described in this review. PMID:24269681

Predicting drug-target interaction for new drugs using enhanced similarity measures and super-target clustering.

PubMed

Shi, Jian-Yu; Yiu, Siu-Ming; Li, Yiming; Leung, Henry C M; Chin, Francis Y L

2015-07-15

Predicting drug-target interaction using computational approaches is an important step in drug discovery and repositioning. To predict whether there will be an interaction between a drug and a target, most existing methods identify similar drugs and targets in the database. The prediction is then made based on the known interactions of these drugs and targets. This idea is promising. However, there are two shortcomings that have not yet been addressed appropriately. Firstly, most of the methods only use 2D chemical structures and protein sequences to measure the similarity of drugs and targets respectively. However, this information may not fully capture the characteristics determining whether a drug will interact with a target. Secondly, there are very few known interactions, i.e. many interactions are "missing" in the database. Existing approaches are biased towards known interactions and have no good solutions to handle possibly missing interactions which affect the accuracy of the prediction. In this paper, we enhance the similarity measures to include non-structural (and non-sequence-based) information and introduce the concept of a "super-target" to handle the problem of possibly missing interactions. Based on evaluations on real data, we show that our similarity measure is better than the existing measures and our approach is able to achieve higher accuracy than the two best existing algorithms, WNN-GIP and KBMF2K. Our approach is available at http://web.hku.hk/∼liym1018/projects/drug/drug.html or http://www.bmlnwpu.org/us/tools/PredictingDTI_S2/METHODS.html. Copyright © 2015 Elsevier Inc. All rights reserved.

TargetLink, a new method for identifying the endogenous target set of a specific microRNA in intact living cells.

PubMed

Xu, Yan; Chen, Yan; Li, Daliang; Liu, Qing; Xuan, Zhenyu; Li, Wen-Hong

2017-02-01

MicroRNAs are small non-coding RNAs acting as posttranscriptional repressors of gene expression. Identifying mRNA targets of a given miRNA remains an outstanding challenge in the field. We have developed a new experimental approach, TargetLink, that applied locked nucleic acid (LNA) as the affinity probe to enrich target genes of a specific microRNA in intact cells. TargetLink also consists a rigorous and systematic data analysis pipeline to identify target genes by comparing LNA-enriched sequences between experimental and control samples. Using miR-21 as a test microRNA, we identified 12 target genes of miR-21 in a human colorectal cancer cell by this approach. The majority of the identified targets interacted with miR-21 via imperfect seed pairing. Target validation confirmed that miR-21 repressed the expression of the identified targets. The cellular abundance of the identified miR-21 target transcripts varied over a wide range, with some targets expressed at a rather low level, confirming that both abundant and rare transcripts are susceptible to regulation by microRNAs, and that TargetLink is an efficient approach for identifying the target set of a specific microRNA in intact cells. C20orf111, one of the novel targets identified by TargetLink, was found to reside in the nuclear speckle and to be reliably repressed by miR-21 through the interaction at its coding sequence.

Fluid mechanics aspects of magnetic drug targeting.

PubMed

Odenbach, Stefan

2015-10-01

Experiments and numerical simulations using a flow phantom for magnetic drug targeting have been undertaken. The flow phantom is a half y-branched tube configuration where the main tube represents an artery from which a tumour-supplying artery, which is simulated by the side branch of the flow phantom, branches off. In the experiments a quantification of the amount of magnetic particles targeted towards the branch by a magnetic field applied via a permanent magnet is achieved by impedance measurement using sensor coils. Measuring the targeting efficiency, i.e. the relative amount of particles targeted to the side branch, for different field configurations one obtains targeting maps which combine the targeting efficiency with the magnetic force densities in characteristic points in the flow phantom. It could be shown that targeting efficiency depends strongly on the magnetic field configuration. A corresponding numerical model has been set up, which allows the simulation of targeting efficiency for variable field configuration. With this simulation good agreement of targeting efficiency with experimental data has been found. Thus, the basis has been laid for future calculations of optimal field configurations in clinical applications of magnetic drug targeting. Moreover, the numerical model allows the variation of additional parameters of the drug targeting process and thus an estimation of the influence, e.g. of the fluid properties on the targeting efficiency. Corresponding calculations have shown that the non-Newtonian behaviour of the fluid will significantly influence the targeting process, an aspect which has to be taken into account, especially recalling the fact that the viscosity of magnetic suspensions depends strongly on the magnetic field strength and the mechanical load.

Prediction of miRNA targets.

PubMed

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

2015-01-01

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

Targeting the proteasome pathway.

PubMed

Tsukamoto, Sachiko; Yokosawa, Hideyoshi

2009-05-01

The ubiquitin-proteasome pathway functions as a main pathway in intracellular protein degradation and plays a vital role in almost all cellular events. Various inhibitors of this pathway have been developed for research purposes. The recent approval of bortezomib (PS-341, Velcade, a proteasome inhibitor, for the treatment of multiple myeloma has opened the way to the discovery of drugs targeting the proteasome and other components of the ubiquitin-proteasome pathway. We review the current understanding of the ubiquitin-proteasome pathway and inhibitors targeting this pathway, including proteasome inhibitors, as candidate drugs for chemical therapy. Preclinical and clinical data for inhibitors of the proteasome and the ubiquitin-proteasome pathway are discussed. The proteasome and other members in the ubiquitin-proteasome pathway have emerged as novel therapeutic targets.

Multiple target laser ablation system

DOEpatents

Mashburn, D.N.

1996-01-09

A laser ablation apparatus and method are provided in which multiple targets consisting of material to be ablated are mounted on a movable support. The material transfer rate is determined for each target material, and these rates are stored in a controller. A position detector determines which target material is in a position to be ablated, and then the controller controls the beam trigger timing and energy level to achieve a desired proportion of each constituent material in the resulting film. 3 figs.

Multiple target laser ablation system

DOEpatents

Mashburn, Douglas N.

1996-01-01

A laser ablation apparatus and method are provided in which multiple targets consisting of material to be ablated are mounted on a movable support. The material transfer rate is determined for each target material, and these rates are stored in a controller. A position detector determines which target material is in a position to be ablated, and then the controller controls the beam trigger timing and energy level to achieve a desired proportion of each constituent material in the resulting film.

Ca-48 targets - Home and abroad!

NASA Astrophysics Data System (ADS)

Greene, John P.; Carpenter, Michael; Janssens, Robert V. F.

2018-05-01

Using the method of reduction/distillation, high-purity films of robust and ductile calcium metal were prepared for use as targets in nuclear physics experiments. These targets, however, are extremely air-sensitive and procedures must be developed for their handling and use without exposure to the air. In most instances, the thin 48Ca target is used on a carrier foil (backing) and a thin covering film of similar material is employed to further reduce re-oxidation. Un-backed metallic targets are rarely produced due to these concerns. In addition, the low natural abundance of the isotope 48Ca provided an increased incentive for the best efficiencies available in their preparation. Here, we describe the preparation of 48Ca targets employing a gold backing and thin gold cover for use at home, Argonne National Laboratory (ANL), as well as abroad, at Osaka University. For the overseas shipments, much care and preparation were necessary to ensure good targets and safe arrival to the experimental facilities.

Tumor-targeting peptides from combinatorial libraries.

PubMed

Liu, Ruiwu; Li, Xiaocen; Xiao, Wenwu; Lam, Kit S

2017-02-01

Cancer is one of the major and leading causes of death worldwide. Two of the greatest challenges in fighting cancer are early detection and effective treatments with no or minimum side effects. Widespread use of targeted therapies and molecular imaging in clinics requires high affinity, tumor-specific agents as effective targeting vehicles to deliver therapeutics and imaging probes to the primary or metastatic tumor sites. Combinatorial libraries such as phage-display and one-bead one-compound (OBOC) peptide libraries are powerful approaches in discovering tumor-targeting peptides. This review gives an overview of different combinatorial library technologies that have been used for the discovery of tumor-targeting peptides. Examples of tumor-targeting peptides identified from each combinatorial library method will be discussed. Published tumor-targeting peptide ligands and their applications will also be summarized by the combinatorial library methods and their corresponding binding receptors. Copyright © 2017. Published by Elsevier B.V.

Capture of shrinking targets with realistic shrink patterns.

PubMed

Hoffmann, Errol R; Chan, Alan H S; Dizmen, Coskun

2013-01-01

Previous research [Hoffmann, E. R. 2011. "Capture of Shrinking Targets." Ergonomics 54 (6): 519-530] reported experiments for capture of shrinking targets where the target decreased in size at a uniform rate. This work extended this research for targets having a shrink-size versus time pattern that of an aircraft receding from an observer. In Experiment 1, the time to capture the target in this case was well correlated in terms of Fitts' index of difficulty, measured at the time of capture of the target, a result that is in agreement with the 'balanced' model of Johnson and Hart [Johnson, W. W., and Hart, S. G. 1987. "Step Tracking Shrinking Targets." Proceedings of the human factors society 31st annual meeting, New York City, October 1987, 248-252]. Experiment 2 measured the probability of target capture for varying initial target sizes and target shrink rates constant, defined as the time for the target to shrink to half its initial size. Data of shrink time constant for 50% probability of capture were related to initial target size but did not greatly affect target capture as the rate of target shrinking decreased rapidly with time.

Foam encapsulated targets

DOEpatents

Nuckolls, John H.; Thiessen, Albert R.; Dahlbacka, Glen H.

1983-01-01

Foam encapsulated laser-fusion targets wherein a quantity of thermonuclear fuel is embedded in low density, microcellular foam which serves as an electron conduction channel for symmetrical implosion of the fuel by illumination of the target by one or more laser beams. The fuel, such as DT, is contained within a hollow shell constructed of glass, for example, with the foam having a cell size of preferably no greater than 2 .mu.m, a density of 0.065 to 0.6.times.10.sup.3 kg/m.sup.3, and external diameter of less than 200 .mu.m.

Method for forming electrically charged laser targets

DOEpatents

Goodman, Ronald K.; Hunt, Angus L.

1979-01-01

Electrically chargeable laser targets and method for forming such charged targets in order to improve their guidance along a predetermined desired trajectory. This is accomplished by the incorporation of a small amount of an additive to the target material which will increase the electrical conductivity thereof, and thereby enhance the charge placed upon the target material for guidance thereof by electrostatic or magnetic steering mechanisms, without adversely affecting the target when illuminated by laser energy.

Targeted delivery of drugs for liver fibrosis.

PubMed

Li, Feng; Wang, Ji-yao

2009-05-01

Liver fibrosis and its end stage disease cirrhosis are a major cause of mortality and morbidity around the world. There is no effective pharmaceutical intervention for liver fibrosis at present. Many drugs that show potent antifibrotic activities in vitro often show only minor effects in vivo because of insufficient concentrations of drugs accumulating around the target cell and their adverse effects as a result of affecting other non-target cells. Hepatic stellate cells (HSC) play a critical role in the fibrogenesis of liver, so they are the target cells of antifibrotic therapy. Several kinds of targeted delivery system that could target the receptors expressed on HSC have been designed, and have shown an attractive targeted potential in vivo. After being carried by these delivery systems, many agents showed a powerful antifibrotic effect in animal models of liver fibrosis. These targeted delivery systems provide a new pathway for the therapy of liver fibrosis. The characteristics of theses targeted carriers are reviewed in this paper.

Identifying Drug-Target Interactions with Decision Templates.

PubMed

Yan, Xiao-Ying; Zhang, Shao-Wu

2018-01-01

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

Dual responsive PNIPAM-chitosan targeted magnetic nanopolymers for targeted drug delivery

NASA Astrophysics Data System (ADS)

Yadavalli, Tejabhiram; Ramasamy, Shivaraman; Chandrasekaran, Gopalakrishnan; Michael, Isaac; Therese, Helen Annal; Chennakesavulu, Ramasamy

2015-04-01

A dual stimuli sensitive magnetic hyperthermia based drug delivery system has been developed for targeted cancer treatment. Thermosensitive amine terminated poly-N-isopropylacrylamide complexed with pH sensitive chitosan nanoparticles was prepared as the drug carrier. Folic acid and fluorescein were tagged to the nanopolymer complex via N-hydroxysuccinimide and ethyl-3-(3-dimethylaminopropyl)carbodiimide reaction to form a fluorescent and cancer targeting magnetic carrier system. The formation of the polymer complex was confirmed using infrared spectroscopy. Gadolinium doped nickel ferrite nanoparticles prepared by a hydrothermal method were encapsulated in the polymer complex to form a magnetic drug carrier system. The proton relaxation studies on the magnetic carrier system revealed a 200% increase in the T1 proton relaxation rate. These magnetic carriers were loaded with curcumin using solvent evaporation method with a drug loading efficiency of 86%. Drug loaded nanoparticles were tested for their targeting and anticancer properties on four cancer cell lines with the help of MTT assay. The results indicated apoptosis of cancer cell lines within 3 h of incubation.

PIE preparation of the MEGAPIE target

NASA Astrophysics Data System (ADS)

Wohlmuther, Michael; Wagner, Werner

2012-12-01

The MEGAPIE target, after successfully operating for 4 months at a beam power of 0.77 MW, is now being prepared for post irradiation examination PIE. The lead-bismuth eutectic (LBE) target was irradiated from August until December 2006, and in this period received a beam charge of 2.8 A h of 575 MeV protons. After that, the target was stored in the target storage facility of PSI, waiting for its post irradiation examination. In the meantime several campaigns of tests have been conducted by PSI and ZWILAG, the interim storage facility of Swiss nuclear power plants. In these tests the feasibility of the conditioning of the target and the extraction of sample material for the PIE has been proven. After transport to the hot cell facility at ZWILAG in June 2009, the dismantling of the MEGAPIE target started. It finally was cut into 21 pieces. Ten of these pieces will be shipped to the Hot Laboratory of PSI ('PSI hotlab') to extract samples from the structural materials as well as from the LBE. Currently it is foreseen that the sample extraction will start in the first half of 2011. The remaining parts of the MEGAPIE target were conditioned as radioactive waste. The present paper will mainly focus on the dismantling and first visual inspection of the MEGAPIE target. In addition an outlook on the PIE phase of MEGAPIE is given.

Drug-Target Interactions: Prediction Methods and Applications.

PubMed

Anusuya, Shanmugam; Kesherwani, Manish; Priya, K Vishnu; Vimala, Antonydhason; Shanmugam, Gnanendra; Velmurugan, Devadasan; Gromiha, M Michael

2018-01-01

Identifying the interactions between drugs and target proteins is a key step in drug discovery. This not only aids to understand the disease mechanism, but also helps to identify unexpected therapeutic activity or adverse side effects of drugs. Hence, drug-target interaction prediction becomes an essential tool in the field of drug repurposing. The availability of heterogeneous biological data on known drug-target interactions enabled many researchers to develop various computational methods to decipher unknown drug-target interactions. This review provides an overview on these computational methods for predicting drug-target interactions along with available webservers and databases for drug-target interactions. Further, the applicability of drug-target interactions in various diseases for identifying lead compounds has been outlined. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Megajoule Dense Plasma Focus Solid Target Experiments

NASA Astrophysics Data System (ADS)

Podpaly, Y. A.; Falabella, S.; Link, A.; Povilus, A.; Higginson, D. P.; Shaw, B. H.; Cooper, C. M.; Chapman, S.; Bennett, N.; Sipe, N.; Olson, R.; Schmidt, A. E.

2016-10-01

Dense plasma focus (DPF) devices are plasma sources that can produce significant neutron yields from beam into gas interactions. Yield increases, up to approximately a factor of five, have been observed previously on DPFs using solid targets, such as CD2 and D2O ice. In this work, we report on deuterium solid-target experiments at the Gemini DPF. A rotatable target holder and baffle arrangement were installed in the Gemini device which allowed four targets to be deployed sequentially without breaking vacuum. Solid targets of titanium deuteride were installed and systematically studied at a variety of fill pressures, bias voltages, and target positions. Target holder design, experimental results, and comparison to simulations will be presented. Prepared by LLNL under Contract DE-AC52-07NA27344.

Laser ``M'egajoule'' cryogenic target program: from target fabrication to conformation of the deuterium-tritium ice layer

NASA Astrophysics Data System (ADS)

Collier, Rémy; Durut, Frédéric; Reneaume, Benoît; Chicane, Cédric; Théobald, Marc; Breton, Olivier; Martin, Michel; Fleury, Emmanuel; Vincent-Viry, Olivier; Bachelet, Franck; Jeannot, Laurent; Geoffray, Isabelle; Botrel, Ronan; Dauteuil, Christophe; Hermerel, Cyril; Choux, Alexandre; Bednarczyk, Sophie; Legaie, Olivier

2008-11-01

For the French inertial confinement fusion (ICF) experiments, cryogenic target assemblies (CTAs) for the LMJ program are manufactured and filled at CEA Valduc (Dijon) in the cryogenic targets filling station (IRCC). They will be moved at about 20 K into a transport cryostat for cryogenic targets and will be driven from CEA/Valduc to CEA/CESTA (Bordeaux). Cryogenic targets will then be transferred by several cryogenic grippers on the cryogenic target positioner before shots. The CTA has to meet severe specifications and involves a lot of challenging tasks for its manufacture. To fill CTAs by permeation with deuterium-tritium (DT), the IRCC need to meet strict thermal, mechanical and dimensional specifications. To obtain a good combustion yield, a very homogenous DT ice layer and very smooth roughness at 1.5 K below the DT triple point are also required. This paper deals with the up to date main issues in the different fields of the LMJ cryogenic target program.

Infrared small target tracking based on SOPC

NASA Astrophysics Data System (ADS)

Hu, Taotao; Fan, Xiang; Zhang, Yu-Jin; Cheng, Zheng-dong; Zhu, Bin

2011-01-01

The paper presents a low cost FPGA based solution for a real-time infrared small target tracking system. A specialized architecture is presented based on a soft RISC processor capable of running kernel based mean shift tracking algorithm. Mean shift tracking algorithm is realized in NIOS II soft-core with SOPC (System on a Programmable Chip) technology. Though mean shift algorithm is widely used for target tracking, the original mean shift algorithm can not be directly used for infrared small target tracking. As infrared small target only has intensity information, so an improved mean shift algorithm is presented in this paper. How to describe target will determine whether target can be tracked by mean shift algorithm. Because color target can be tracked well by mean shift algorithm, imitating color image expression, spatial component and temporal component are advanced to describe target, which forms pseudo-color image. In order to improve the processing speed parallel technology and pipeline technology are taken. Two RAM are taken to stored images separately by ping-pong technology. A FLASH is used to store mass temp data. The experimental results show that infrared small target is tracked stably in complicated background.

Voyager 2 Uranus and Neptune targeting

NASA Technical Reports Server (NTRS)

Gray, D. L.; Cesarone, R. J.; Van Allen, R. E.

1982-01-01

Targeting strategies are developed for the Voyager 2 flybys of Uranus and Neptune/Triton. The need to maximize science return, conserve propellant, and maintain spacecraft safety presents a challenge, given the difficulty in estimating the spacecraft orbit relative to these outer planets. Expected propellant usage, science return, and targeting complexity are presented for each targeting strategy. For the dual encounter of Neptune and its satellite Triton, split targeting conditions are proposed to fix the most important conditions at each body, and thus minimize science losses resulting from Triton ephemeris uncertainties.

Exploiting target amplitude information to improve multi-target tracking

NASA Astrophysics Data System (ADS)

Ehrman, Lisa M.; Blair, W. Dale

2006-05-01

Closely-spaced (but resolved) targets pose a challenge for measurement-to-track data association algorithms. Since the Mahalanobis distances between measurements collected on closely-spaced targets and tracks are similar, several elements of the corresponding kinematic measurement-to-track cost matrix are also similar. Lacking any other information on which to base assignments, it is not surprising that data association algorithms make mistakes. One ad hoc approach for mitigating this problem is to multiply the kinematic measurement-to-track likelihoods by amplitude likelihoods. However, this can actually be detrimental to the measurement-to-track association process. With that in mind, this paper pursues a rigorous treatment of the hypothesis probabilities for kinematic measurements and features. Three simple scenarios are used to demonstrate the impact of basing data association decisions on these hypothesis probabilities for Rayleigh, fixed-amplitude, and Rician targets. The first scenario assumes that the tracker carries two tracks but only one measurement is collected. This provides insight into more complex scenarios in which there are fewer measurements than tracks. The second scenario includes two measurements and one track. This extends naturally to the case with more measurements than tracks. Two measurements and two tracks are present in the third scenario, which provides insight into the performance of this method when the number of measurements equals the number of tracks. In all cases, basing data association decisions on the hypothesis probabilities leads to good results.

Tools for in silico target fishing.

PubMed

Cereto-Massagué, Adrià; Ojeda, María José; Valls, Cristina; Mulero, Miquel; Pujadas, Gerard; Garcia-Vallve, Santiago

2015-01-01

Computational target fishing methods are designed to identify the most probable target of a query molecule. This process may allow the prediction of the bioactivity of a compound, the identification of the mode of action of known drugs, the detection of drug polypharmacology, drug repositioning or the prediction of the adverse effects of a compound. The large amount of information regarding the bioactivity of thousands of small molecules now allows the development of these types of methods. In recent years, we have witnessed the emergence of many methods for in silico target fishing. Most of these methods are based on the similarity principle, i.e., that similar molecules might bind to the same targets and have similar bioactivities. However, the difficult validation of target fishing methods hinders comparisons of the performance of each method. In this review, we describe the different methods developed for target prediction, the bioactivity databases most frequently used by these methods, and the publicly available programs and servers that enable non-specialist users to obtain these types of predictions. It is expected that target prediction will have a large impact on drug development and on the functional food industry. Copyright © 2014 Elsevier Inc. All rights reserved.

Camera calibration: active versus passive targets

NASA Astrophysics Data System (ADS)

Schmalz, Christoph; Forster, Frank; Angelopoulou, Elli

2011-11-01

Traditionally, most camera calibrations rely on a planar target with well-known marks. However, the localization error of the marks in the image is a source of inaccuracy. We propose the use of high-resolution digital displays as active calibration targets to obtain more accurate calibration results for all types of cameras. The display shows a series of coded patterns to generate correspondences between world points and image points. This has several advantages. No special calibration hardware is necessary because suitable displays are practically ubiquitious. The method is fully automatic, and no identification of marks is necessary. For a coding scheme based on phase shifting, the localization accuracy is approximately independent of the camera's focus settings. Most importantly, higher accuracy can be achieved compared to passive targets, such as printed checkerboards. A rigorous evaluation is performed to substantiate this claim. Our active target method is compared to standard calibrations using a checkerboard target. We perform camera, calibrations with different combinations of displays, cameras, and lenses, as well as with simulated images and find markedly lower reprojection errors when using active targets. For example, in a stereo reconstruction task, the accuracy of a system calibrated with an active target is five times better.

Drug Target Discovery Methods In Targeting Neurotropic Parasitic Amoebae.

PubMed

Baig, Abdul Mannan; Waliani, Nuzair; Karim, Saiqa

2018-02-21

Neurotropic parasitic amoebal infections have imposed an enormous challenge to chemotherapy in patients who fall victims to the infections caused by them. Conventional antibiotics that are given to treat these infections have a low patient compliance because of the serious adverse effects that are associated with their use. Additionally, the growing incidence of the development of drug resistance by the neurotropic parasites like Naegleria fowleri, Balamuthia mandrillaris, and Acanthamoeba spp has made the drug therapy more challenging. Recent studies have reported some cellular targets in the neurotropic parasitic Acanthamoeba that are used as receptors by human neurotransmitters like acetylcholine. This Viewpoint attempts to highlight the novel methodologies that use drug assays and structural modeling to uncover cellular targets of diverse groups of drugs and the safety issues of the drugs proposed for their use in brain infections caused by the neurotropic parasitic amoebae.

Calibration Method for IATS and Application in Multi-Target Monitoring Using Coded Targets

NASA Astrophysics Data System (ADS)

Zhou, Yueyin; Wagner, Andreas; Wunderlich, Thomas; Wasmeier, Peter

2017-06-01

The technique of Image Assisted Total Stations (IATS) has been studied for over ten years and is composed of two major parts: one is the calibration procedure which combines the relationship between the camera system and the theodolite system; the other is the automatic target detection on the image by various methods of photogrammetry or computer vision. Several calibration methods have been developed, mostly using prototypes with an add-on camera rigidly mounted on the total station. However, these prototypes are not commercially available. This paper proposes a calibration method based on Leica MS50 which has two built-in cameras each with a resolution of 2560 × 1920 px: an overview camera and a telescope (on-axis) camera. Our work in this paper is based on the on-axis camera which uses the 30-times magnification of the telescope. The calibration consists of 7 parameters to estimate. We use coded targets, which are common tools in photogrammetry for orientation, to detect different targets in IATS images instead of prisms and traditional ATR functions. We test and verify the efficiency and stability of this monitoring method with multi-target.

Target Abundance-Based Fitness Screening (TAFiS) Facilitates Rapid Identification of Target-Specific and Physiologically Active Chemical Probes

PubMed Central

Butts, Arielle; DeJarnette, Christian; Peters, Tracy L.; Parker, Josie E.; Kerns, Morgan E.; Eberle, Karen E.; Kelly, Steve L.

2017-01-01

ABSTRACT Traditional approaches to drug discovery are frustratingly inefficient and have several key limitations that severely constrain our capacity to rapidly identify and develop novel experimental therapeutics. To address this, we have devised a second-generation target-based whole-cell screening assay based on the principles of competitive fitness, which can rapidly identify target-specific and physiologically active compounds. Briefly, strains expressing high, intermediate, and low levels of a preselected target protein are constructed, tagged with spectrally distinct fluorescent proteins (FPs), and pooled. The pooled strains are then grown in the presence of various small molecules, and the relative growth of each strain within the mixed culture is compared by measuring the intensity of the corresponding FP tags. Chemical-induced population shifts indicate that the bioactivity of a small molecule is dependent upon the target protein’s abundance and thus establish a specific functional interaction. Here, we describe the molecular tools required to apply this technique in the prevalent human fungal pathogen Candida albicans and validate the approach using two well-characterized drug targets—lanosterol demethylase and dihydrofolate reductase. However, our approach, which we have termed target abundance-based fitness screening (TAFiS), should be applicable to a wide array of molecular targets and in essentially any genetically tractable microbe. IMPORTANCE Conventional drug screening typically employs either target-based or cell-based approaches. The first group relies on biochemical assays to detect modulators of a purified target. However, hits frequently lack drug-like characteristics such as membrane permeability and target specificity. Cell-based screens identify compounds that induce a desired phenotype, but the target is unknown, which severely restricts further development and optimization. To address these issues, we have developed a second

Large scale RNAi screen in Tribolium reveals novel target genes for pest control and the proteasome as prime target.

PubMed

Ulrich, Julia; Dao, Van Anh; Majumdar, Upalparna; Schmitt-Engel, Christian; Schwirz, Jonas; Schultheis, Dorothea; Ströhlein, Nadi; Troelenberg, Nicole; Grossmann, Daniela; Richter, Tobias; Dönitz, Jürgen; Gerischer, Lizzy; Leboulle, Gérard; Vilcinskas, Andreas; Stanke, Mario; Bucher, Gregor

2015-09-03

Insect pest control is challenged by insecticide resistance and negative impact on ecology and health. One promising pest specific alternative is the generation of transgenic plants, which express double stranded RNAs targeting essential genes of a pest species. Upon feeding, the dsRNA induces gene silencing in the pest resulting in its death. However, the identification of efficient RNAi target genes remains a major challenge as genomic tools and breeding capacity is limited in most pest insects impeding whole-animal-high-throughput-screening. We use the red flour beetle Tribolium castaneum as a screening platform in order to identify the most efficient RNAi target genes. From about 5,000 randomly screened genes of the iBeetle RNAi screen we identify 11 novel and highly efficient RNAi targets. Our data allowed us to determine GO term combinations that are predictive for efficient RNAi target genes with proteasomal genes being most predictive. Finally, we show that RNAi target genes do not appear to act synergistically and that protein sequence conservation does not correlate with the number of potential off target sites. Our results will aid the identification of RNAi target genes in many pest species by providing a manageable number of excellent candidate genes to be tested and the proteasome as prime target. Further, the identified GO term combinations will help to identify efficient target genes from organ specific transcriptomes. Our off target analysis is relevant for the sequence selection used in transgenic plants.

Retention of ferrofluid aggregates at the target site during magnetic drug targeting

NASA Astrophysics Data System (ADS)

Asfer, Mohammed; Saroj, Sunil Kumar; Panigrahi, Pradipta Kumar

2017-08-01

The present study reports the retention dynamics of a ferrofluid aggregate localized at the target site inside a glass capillary (500 × 500 μm2 square cross section) against a bulk flow of DI water (Re = 0.16 and 0.016) during the process of magnetic drug targeting (MDT). The dispersion dynamics of iron oxide nanoparticles (IONPs) into bulk flow for different initial size of aggregate at the target site is reported using the brightfield visualization technique. The flow field around the aggregate during the retention is evaluated using the μPIV technique. IONPs at the outer boundary experience a higher shear force as compared to the magnetic force, resulting in dispersion of IONPs into the bulk flow downstream to the aggregate. The blockage effect and the roughness of the outer boundary of the aggregate resulting from chain like clustering of IONPs contribute to the flow recirculation at the downstream region of the aggregate. The entrapment of seeding particles inside the chain like clusters of IONPs at the outer boundary of the aggregate reduces the degree of roughness resulting in a streamlined aggregate at the target site at later time. The effect of blockage, structure of the aggregate, and disturbed flow such as recirculation around the aggregate are the primary factors, which must be investigated for the effectiveness of the MDT process for in vivo applications.

Molecular Targets for Antiepileptic Drug Development

PubMed Central

Meldrum, Brian S.; Rogawski, Michael A.

2007-01-01

Summary This review considers how recent advances in the physiology of ion channels and other potential molecular targets, in conjunction with new information on the genetics of idiopathic epilepsies, can be applied to the search for improved antiepileptic drugs (AEDs). Marketed AEDs predominantly target voltage-gated cation channels (the α subunits of voltage-gated Na+ channels and also T-type voltage-gated Ca2+ channels) or influence GABA-mediated inhibition. Recently, α2–δ voltage-gated Ca2+ channel subunits and the SV2A synaptic vesicle protein have been recognized as likely targets. Genetic studies of familial idiopathic epilepsies have identified numerous genes associated with diverse epilepsy syndromes, including genes encoding Na+ channels and GABAA receptors, which are known AED targets. A strategy based on genes associated with epilepsy in animal models and humans suggests other potential AED targets, including various voltage-gated Ca2+ channel subunits and auxiliary proteins, A- or M-type voltage-gated K+ channels, and ionotropic glutamate receptors. Recent progress in ion channel research brought about by molecular cloning of the channel subunit proteins and studies in epilepsy models suggest additional targets, including G-protein-coupled receptors, such as GABAB and metabotropic glutamate receptors; hyperpolarization-activated cyclic nucleotide-gated cation (HCN) channel subunits, responsible for hyperpolarization-activated current Ih; connexins, which make up gap junctions; and neurotransmitter transporters, particularly plasma membrane and vesicular transporters for GABA and glutamate. New information from the structural characterization of ion channels, along with better understanding of ion channel function, may allow for more selective targeting. For example, Na+ channels underlying persistent Na+ currents or GABAA receptor isoforms responsible for tonic (extrasynaptic) currents represent attractive targets. The growing understanding of the

Fabrication of light water reactor tritium targets

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

Pilger, J.P.

1991-11-01

The mission of the Fabrication Development Task of the Tritium Target Development Project is: to produce a documented technology basis, including specifications and procedures for target rod fabrication; to demonstrate that light water tritium targets can be manufactured at a rate consistent with tritium production requirements; and to develop quality control methods to evaluate target rod components and assemblies, and establish correlations between evaluated characteristics and target rod performance. Many of the target rod components: cladding tubes, end caps, plenum springs, etc., have similar counterparts in LWR fuel rods. High production rate manufacture and inspection of these components has beenmore » adequately demonstrated by nuclear fuel rod manufacturers. This summary describes the more non-conventional manufacturing processes and inspection techniques developed to fabricate target rod components whose manufacturability at required production rates had not been previously demonstrated.« less

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.

Microfluidic droplet enrichment for targeted sequencing

PubMed Central

Eastburn, Dennis J.; Huang, Yong; Pellegrino, Maurizio; Sciambi, Adam; Ptáček, Louis J.; Abate, Adam R.

2015-01-01

Targeted sequence enrichment enables better identification of genetic variation by providing increased sequencing coverage for genomic regions of interest. Here, we report the development of a new target enrichment technology that is highly differentiated from other approaches currently in use. Our method, MESA (Microfluidic droplet Enrichment for Sequence Analysis), isolates genomic DNA fragments in microfluidic droplets and performs TaqMan PCR reactions to identify droplets containing a desired target sequence. The TaqMan positive droplets are subsequently recovered via dielectrophoretic sorting, and the TaqMan amplicons are removed enzymatically prior to sequencing. We demonstrated the utility of this approach by generating an average 31.6-fold sequence enrichment across 250 kb of targeted genomic DNA from five unique genomic loci. Significantly, this enrichment enabled a more comprehensive identification of genetic polymorphisms within the targeted loci. MESA requires low amounts of input DNA, minimal prior locus sequence information and enriches the target region without PCR bias or artifacts. These features make it well suited for the study of genetic variation in a number of research and diagnostic applications. PMID:25873629

A high yield neutron target

NASA Technical Reports Server (NTRS)

Alger, D. L.; Steinberg, R.; Weisenbach, P.

1974-01-01

Target, in cylinder form, rotates rapidly in front of beam. Titanium tritide film is much thicker than range of accelerated deutron. Sputtering electrode permits full use of thick film. Stream of high-velocity coolant provides efficient transfer of heat from target.

Multiple Target Laser Designator (MTLD)

DTIC Science & Technology

2007-03-01

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

Nanocrystal Targeting In Vivo

DTIC Science & Technology

2002-08-01

Shearwater Polymers , Huntsville, AL) was thiolated with iminothiolane. Thiolated PEG was directly added to a solution of mercaptoacetic acid- coated qdots...Nanocrystal targeting in vivo Maria E. Åkerman*†‡, Warren C. W. Chan†‡, Pirjo Laakkonen*, Sangeeta N. Bhatia†, and Erkki Ruoslahti*§ *Cancer Research...set out to explore the feasibility of in vivo targeting by using semiconductor quantum dots (qdots). Qdots are small (᝺ nm) inorganic nanocrystals

A review of the ligands and related targeting strategies for active targeting of paclitaxel to tumours.

PubMed

Li, Juan; Wang, Fengshan; Sun, Deqing; Wang, Rongmei

2016-08-01

It has been 30 years since the discovery of the anti-tumour property of paclitaxel (PTX), which has been successfully applied in clinic for the treatment of carcinomas of the lungs, breast and ovarian. However, PTX is poorly soluble in water and has no targeting and selectivity to tumour tissue. Recent advances in active tumour targeting of PTX delivery vehicles have addressed some of the issues related to lack of solubility in water and non-specific toxicities associated with PTX. These PTX delivery vehicles are designed for active targeting to specific cancer cells by the addition of ligands for recognition by specific receptors/antigens on cancer cells. This article will focus on various ligands and related targeting strategies serving as potential tools for active targeting of PTX to tumour tissues, illustrating their use in different tumour models. This review also highlights the need of further studies on the discovery of receptors in different cells of specific organ and ligands with binding efficiency to these specific receptors.

Targeting, Air Force Doctrine Document 2-1.9

DTIC Science & Technology

2006-06-08

Target system analysis ( TSA ), as its name implies, approaches targets and target sets as systems to determine vulnerabilities and exploitable...weaknesses. Targeteers review how a functional target system works as a whole and analyze the interactions between components. TSA takes a system-of...effectiveness of target development. TSA begins in peacetime, before the commencement of conflict, and is accomplished with federated support and

Deep-Learning-Based Drug-Target Interaction Prediction.

PubMed

Wen, Ming; Zhang, Zhimin; Niu, Shaoyu; Sha, Haozhi; Yang, Ruihan; Yun, Yonghuan; Lu, Hongmei

2017-04-07

Identifying interactions between known drugs and targets is a major challenge in drug repositioning. In silico prediction of drug-target interaction (DTI) can speed up the expensive and time-consuming experimental work by providing the most potent DTIs. In silico prediction of DTI can also provide insights about the potential drug-drug interaction and promote the exploration of drug side effects. Traditionally, the performance of DTI prediction depends heavily on the descriptors used to represent the drugs and the target proteins. In this paper, to accurately predict new DTIs between approved drugs and targets without separating the targets into different classes, we developed a deep-learning-based algorithmic framework named DeepDTIs. It first abstracts representations from raw input descriptors using unsupervised pretraining and then applies known label pairs of interaction to build a classification model. Compared with other methods, it is found that DeepDTIs reaches or outperforms other state-of-the-art methods. The DeepDTIs can be further used to predict whether a new drug targets to some existing targets or whether a new target interacts with some existing drugs.

Upper Limb Kinematics in Stroke and Healthy Controls Using Target-to-Target Task in Virtual Reality.

PubMed

Hussain, Netha; Alt Murphy, Margit; Sunnerhagen, Katharina S

2018-01-01

Kinematic analysis using virtual reality (VR) environment provides quantitative assessment of upper limb movements. This technique has rarely been used in evaluating motor function in stroke despite its availability in stroke rehabilitation. To determine the discriminative validity of VR-based kinematics during target-to-target pointing task in individuals with mild or moderate arm impairment following stroke and in healthy controls. Sixty-seven participants with moderate (32-57 points) or mild (58-65 points) stroke impairment as assessed with Fugl-Meyer Assessment for Upper Extremity were included from the Stroke Arm Longitudinal study at the University of Gothenburg-SALGOT cohort of non-selected individuals within the first year of stroke. The stroke groups and 43 healthy controls performed the target-to-target pointing task, where 32 circular targets appear one after the other and disappear when pointed at by the haptic handheld stylus in a three-dimensional VR environment. The kinematic parameters captured by the stylus included movement time, velocities, and smoothness of movement. The movement time, mean velocity, and peak velocity were discriminative between groups with moderate and mild stroke impairment and healthy controls. The movement time was longer and mean and peak velocity were lower for individuals with stroke. The number of velocity peaks, representing smoothness, was also discriminative and significantly higher in both stroke groups (mild, moderate) compared to controls. Movement trajectories in stroke more frequently showed clustering (spider's web) close to the target indicating deficits in movement precision. The target-to-target pointing task can provide valuable and specific information about sensorimotor impairment of the upper limb following stroke that might not be captured using traditional clinical scale. The trial was registered with register number NCT01115348 at clinicaltrials.gov, on May 4, 2010. URL: https://clinicaltrials.gov/ct2

Targeted Endoscopic Imaging

PubMed Central

Li, Meng; Wang, Thomas D

2011-01-01

Summary Endoscopy has undergone explosive technological growth in over recent years, and with the emergence of targeted imaging, its truly transformative power and impact in medicine lies just over the horizon. Today, our ability to see inside the digestive tract with medical endoscopy is headed toward exciting crossroads. The existing paradigm of making diagnostic decisions based on observing structural changes and identifying anatomical landmarks may soon be replaced by visualizing functional properties and imaging molecular expression. In this novel approach, the presence of intracellular and cell surface targets unique to disease are identified and used to predict the likelihood of mucosal transformation and response to therapy. This strategy can result in the development of new methods for early cancer detection, personalized therapy, and chemoprevention. This targeted approach will require further development of molecular probes and endoscopic instruments, and will need support from the FDA for streamlined regulatory oversight. Overall, this molecular imaging modality promises to significantly broaden the capabilities of the gastroenterologist by providing a new approach to visualize the mucosa of the digestive tract in a manner that has never been seen before. PMID:19423025

Asymmetries in visual search for conjunctive targets.

PubMed

Cohen, A

1993-08-01

Asymmetry is demonstrated between conjunctive targets in visual search with no detectable asymmetries between the individual features that compose these targets. Experiment 1 demonstrated this phenomenon for targets composed of color and shape. Experiment 2 and 4 demonstrate this asymmetry for targets composed of size and orientation and for targets composed of contrast level and orientation, respectively. Experiment 3 demonstrates that search rate of individual features cannot predict search rate for conjunctive targets. These results demonstrate the need for 2 levels of representations: one of features and one of conjunction of features. A model related to the modified feature integration theory is proposed to account for these results. The proposed model and other models of visual search are discussed.

Integrin Targeted Therapeutics

PubMed Central

Millard, Melissa; Odde, Srinivas; Neamati, Nouri

2011-01-01

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

Cancer metabolism: strategic diversion from targeting cancer drivers to targeting cancer suppliers.

PubMed

Kim, Soo-Youl

2015-03-01

Drug development groups are close to discovering another pot of gold-a therapeutic target-similar to the success of imatinib (Gleevec) in the field of cancer biology. Modern molecular biology has improved cancer therapy through the identification of more pharmaceutically viable targets, and yet major problems and risks associated with late-phase cancer therapy remain. Presently, a growing number of reports have initiated a discussion about the benefits of metabolic regulation in cancers. The Warburg effect, a great discovery approximately 70 years ago, addresses the "universality" of cancer characteristics. For instance, most cancer cells prefer aerobic glycolysis instead of mitochondrial respiration. Recently, cancer metabolism has been explained not only by metabolites but also through modern molecular and chemical biological techniques. Scientists are seeking context-dependent universality among cancer types according to metabolic and enzymatic pathway signatures. This review presents current cancer metabolism studies and discusses future directions in cancer therapy targeting bio-energetics, bio-anabolism, and autophagy, emphasizing the important contribution of cancer metabolism in cancer therapy.

Optimum viewing distance for target acquisition

NASA Astrophysics Data System (ADS)

Holst, Gerald C.

2015-05-01

Human visual system (HVS) "resolution" (a.k.a. visual acuity) varies with illumination level, target characteristics, and target contrast. For signage, computer displays, cell phones, and TVs a viewing distance and display size are selected. Then the number of display pixels is chosen such that each pixel subtends 1 min-1. Resolution of low contrast targets is quite different. It is best described by Barten's contrast sensitivity function. Target acquisition models predict maximum range when the display pixel subtends 3.3 min-1. The optimum viewing distance is nearly independent of magnification. Noise increases the optimum viewing distance.

Marine Targets Classification in PolInSAR Data

NASA Astrophysics Data System (ADS)

Chen, Peng; Yang, Jingsong; Ren, Lin

2014-11-01

In this paper, marine stationary targets and moving targets are studied by Pol-In-SAR data of Radarsat-2. A new method of stationary targets detection is proposed. The method get the correlation coefficient image of the In-SAR data, and using the histogram of correlation coefficient image. Then, A Constant False Alarm Rate (CFAR) algorithm and The Probabilistic Neural Network model are imported to detect stationary targets. To find the moving targets, Azimuth Ambiguity is show as an important feature. We use the length of azimuth ambiguity to get the target's moving direction and speed. Make further efforts, Targets classification is studied by rebuild the surface elevation of marine targets.

Marine Targets Classification in PolInSAR Data

NASA Astrophysics Data System (ADS)

Chen, Peng; Yang, Jingsong; Ren, Lin

2014-11-01

In this paper, marine stationary targets and moving targets are studied by Pol-In-SAR data of Radarsat-2. A new method of stationary targets detection is proposed. The method get the correlation coefficient image of the In-SAR data, and using the histogram of correlation coefficient image. Then , A Constant False Alarm Rate (CFAR) algorithm and The Probabilistic Neural Network model are imported to detect stationary targets. To find the moving targets, Azimuth Ambiguity is show as an important feature. We use the length of azimuth ambiguity to get the target's moving direction and speed. Make further efforts, Targets classification is studied by rebuild the surface elevation of marine targets.

Students Target

NASA Image and Video Library

2005-12-19

Using the JMars targeting software, eighth grade students from Charleston Middle School in Charleston, IL, selected the location of -8.37N and 276.66E for capture by the THEMIS visible camera during Mars Odyssey sixth orbit of Mars on Nov. 22, 2005

Targeting hardwoods

Treesearch

Douglass F. Jacobs

2011-01-01

Increasing demand for hardwood seedlings has prompted research to identify target seedling characteristics that promote hardwood plantation establishment. Operational establishment of hardwood plantations has typically emphasized seed collection from non-improved genetic sources, bareroot nursery seedling production, and spring planting using machine planters. The...

Simultaneous quantification of tumor uptake for targeted and non-targeted liposomes and their encapsulated contents by ICP-MS

PubMed Central

Cheng, Zhiliang; Zaki, Ajlan Al; Hui, James Z; Tsourkas, Andrew

2012-01-01

Liposomes are intensively being developed for biomedical applications including drug and gene delivery. However, targeted liposomal delivery in cancer treatment is a very complicated multi-step process. Unfavorable liposome biodistribution upon intravenous administration and membrane destabilization in blood circulation could result in only a very small fraction of cargo reaching the tumors. It would therefore be desirable to develop new quantitative strategies to track liposomal delivery systems to improve the therapeutic index and decrease systemic toxicity. Here, we developed a simple and non-radiative method to quantify the tumor uptake of targeted and non-targeted control liposomes as well as their encapsulated contents simultaneously. Specifically, four different chelated lanthanide metals were encapsulated or surface-conjugated onto tumor-targeted and non-targeted liposomes, respectively. The two liposome formulations were then injected into tumor-bearing mice simultaneously and their tumor delivery was determined quantitatively via inductively coupled plasma-mass spectroscopy (ICP-MS), allowing for direct comparisons. Tumor uptake of the liposomes themselves and their encapsulated contents were consistent with targeted and non-targeted liposome formulations that were injected individually. PMID:22882145

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

Targeted Therapy for Melanoma

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

Quinn, Thomas; Moore, Herbert

The research project, entitled ”Targeted Therapy for Melanoma,” was focused on investigating the use of kidney protection measures to lower the non-specific kidney uptake of the radiolabeled Pb-DOTA-ReCCMSH peptide. Previous published work demonstrated that the kidney exhibited the highest non-target tissue uptake of the 212Pb/203Pb radiolabeled melanoma targeting peptide DOTA-ReCCMSH. The radiolabeled alpha-melanocyte stimulating hormone (α-MSH) peptide analog DOTA-Re(Arg 11)CCMSH, which binds the melanocortin-1 receptor over-expressed on melanoma tumor cells, has shown promise as a PRRT agent in pre-clinical studies. High tumor uptake of 212Pb labeled DOTA-Re(Arg 11)CCMSH resulted in tumor reduction or eradication in melanoma therapy studies. Of particularmore » note was the 20-50% cure rate observed when melanoma mice were treated with alpha particle emitter 212Pb. However, as with most PRRT agents, high radiation doses to the kidneys where observed. To optimize tumor treatment efficacy and reduce nephrotoxicity, the tumor to kidney uptake ratio must be improved. Strategies to reduce kidney retention of the radiolabeled peptide, while not effecting tumor uptake and retention, can be broken into several categories including modification of the targeting peptide sequence and reducing proximal tubule reabsorption.« less

Target fragmentation in radiobiology

NASA Technical Reports Server (NTRS)

Wilson, John W.; Cucinotta, Francis A.; Shinn, Judy L.; Townsend, Lawrence W.

1993-01-01

Nuclear reactions in biological systems produce low-energy fragments of the target nuclei seen as local high events of linear energy transfer (LET). A nuclear-reaction formalism is used to evaluate the nuclear-induced fields within biosystems and their effects within several biological models. On the basis of direct ionization interaction, one anticipates high-energy protons to have a quality factor and relative biological effectiveness (RBE) of unity. Target fragmentation contributions raise the effective quality factor of 10 GeV protons to 3.3 in reasonable agreement with RBE values for induced micronuclei in bean sprouts. Application of the Katz model indicates that the relative increase in RBE with decreasing exposure observed in cell survival experiments with 160 MeV protons is related solely to target fragmentation events. Target fragment contributions to lens opacity given an RBE of 1.4 for 2 GeV protons in agreement with the work of Lett and Cox. Predictions are made for the effective RBE for Harderian gland tumors induced by high-energy protons. An exposure model for lifetime cancer risk is derived from NCRP 98 risk tables, and protraction effects are examined for proton and helium ion exposures. The implications of dose rate enhancement effects on space radiation protection are considered.

Ground target recognition using rectangle estimation.

PubMed

Grönwall, Christina; Gustafsson, Fredrik; Millnert, Mille

2006-11-01

We propose a ground target recognition method based on 3-D laser radar data. The method handles general 3-D scattered data. It is based on the fact that man-made objects of complex shape can be decomposed to a set of rectangles. The ground target recognition method consists of four steps; 3-D size and orientation estimation, target segmentation into parts of approximately rectangular shape, identification of segments that represent the target's functional/main parts, and target matching with CAD models. The core in this approach is rectangle estimation. The performance of the rectangle estimation method is evaluated statistically using Monte Carlo simulations. A case study on tank recognition is shown, where 3-D data from four fundamentally different types of laser radar systems are used. Although the approach is tested on rather few examples, we believe that the approach is promising.

Detecting targets hidden in random forests

NASA Astrophysics Data System (ADS)

Kouritzin, Michael A.; Luo, Dandan; Newton, Fraser; Wu, Biao

2009-05-01

Military tanks, cargo or troop carriers, missile carriers or rocket launchers often hide themselves from detection in the forests. This plagues the detection problem of locating these hidden targets. An electro-optic camera mounted on a surveillance aircraft or unmanned aerial vehicle is used to capture the images of the forests with possible hidden targets, e.g., rocket launchers. We consider random forests of longitudinal and latitudinal correlations. Specifically, foliage coverage is encoded with a binary representation (i.e., foliage or no foliage), and is correlated in adjacent regions. We address the detection problem of camouflaged targets hidden in random forests by building memory into the observations. In particular, we propose an efficient algorithm to generate random forests, ground, and camouflage of hidden targets with two dimensional correlations. The observations are a sequence of snapshots consisting of foliage-obscured ground or target. Theoretically, detection is possible because there are subtle differences in the correlations of the ground and camouflage of the rocket launcher. However, these differences are well beyond human perception. To detect the presence of hidden targets automatically, we develop a Markov representation for these sequences and modify the classical filtering equations to allow the Markov chain observation. Particle filters are used to estimate the position of the targets in combination with a novel random weighting technique. Furthermore, we give positive proof-of-concept simulations.

The Holistic Targeting (HOT) Methodology as the Means to Improve Information Operations (IO) Target Development and Prioritization

DTIC Science & Technology

2008-09-01

software facilitate targeting problem understanding and the network analysis tool, Palantir , as an efficient and tailored semi-automated means to...the use of compendium software facilitate targeting problem understanding and the network analysis tool, Palantir , as an efficient and tailored semi...OBJECTIVES USING COMPENDIUM SOFTWARE .....63 E. HOT TARGET PRIORITIZATION AND DEVELOPMENT USING PALANTIR SOFTWARE .................................69 1

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

PubMed

Liang, Zhibing; Liu, Fuxian; Gao, Jiale

2018-01-01

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

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

PubMed Central

Liu, Fuxian; Gao, Jiale

2018-01-01

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

New Targets for New Accelerators

NASA Astrophysics Data System (ADS)

Frentz, Bryce; Manukyan, Khachatur; Aprahamian, Ani

2013-10-01

New accelerators, such as the 5 MV Sta Ana accelerator at the University of Notre Dame, will produce more powerful beams up to 100's of μAmps. These accelerators require a complete rethinking of target preparation since the high intensity of such beams would melt conventional targets. Traditionally, accelerator targets are made with a tantalum backing because of its high atomic mass. However, tantalum is brittle, a poor conductor, and, if produced commercially, often contains impurities (e.g. fluorine) that produce undesirable background and reaction products. Tungsten, despite its brittle structure and poor conductivity, has a high atomic mass and lacks impurities, making it a more desirable backing. In conjunction with tungsten's properties, copper is robust and a far superior thermal conductor. We describe a new method of reactive joining that we developed for creating targets that use the advantageous properties of both tungsten and copper. This process involved placing a reactive mixture between tungsten and copper and applying a load force. The mixture is then ignited, and while under pressure, the system produces conditions to join the materials. We present our investigation to optimize the process of reactive joining, as well as some of the final target's properties. This work was supported by the National Science Foundation under Grant PHY-1068192.

Pharmacophore based design of some multi-targeted compounds targeted against pathways of diabetic complications.

PubMed

Chadha, Navriti; Silakari, Om

2017-09-01

Diabetic complications is a complex metabolic disorder developed primarily due to prolonged hyperglycemia in the body. The complexity of the disease state as well as the unifying pathophysiology discussed in the literature reports exhibited that the use of multi-targeted agents with multiple complementary biological activities may offer promising therapy for the intervention of the disease over the single-target drugs. In the present study, novel thiazolidine-2,4-dione analogues were designed as multi-targeted agents implicated against the molecular pathways involved in diabetic complications using knowledge based as well as in-silico approaches such as pharmacophore mapping, molecular docking etc. The hit molecules were duly synthesized and biochemical estimation of these molecules against aldose reductase (ALR2), protein kinase Cβ (PKCβ) and poly (ADP-ribose) polymerase 1 (PARP-1) led to identification of compound 2 that showed good potency against PARP-1 and ALR2 enzymes. These positive results support the progress of a low cost multi-targeted agent with putative roles in diabetic complications. Copyright © 2017 Elsevier Inc. All rights reserved.

High-frequency ultrasound-guided disruption of glycoprotein VI-targeted microbubbles targets atheroprogressison in mice.

PubMed

Metzger, Katja; Vogel, Sebastian; Chatterjee, Madhumita; Borst, Oliver; Seizer, Peter; Schönberger, Tanja; Geisler, Tobias; Lang, Florian; Langer, Harald; Rheinlaender, Johannes; Schäffer, Tilman E; Gawaz, Meinrad

2015-01-01

Targeted contrast-enhanced ultrasound (CEU) using microbubble agents is a promising non-invasive imaging technique to evaluate atherosclerotic lesions. In this study, we decipher the diagnostic and therapeutic potential of targeted-CEU with soluble glycoprotein (GP)-VI in vivo. Microbubbles were conjugated with the recombinant fusion protein GPVI-Fc (MBGPVI) that binds with high affinity to atherosclerotic lesions. MBGPVI or control microbubbles (MBC) were intravenously administered into ApoE(-/-) or wild type mice and binding of the microbubbles to the vessel wall was visualized by high-resolution CEU. CEU molecular imaging signals of MBGPVI were substantially enhanced in the aortic arch and in the truncus brachiocephalicus in ApoE(-/-) as compared to wild type mice. High-frequency ultrasound (HFU)-guided disruption of MBGPVI enhanced accumulation of GPVI in the atherosclerotic lesions, which may interfere with atheroprogression. Thus, we establish targeted-CEU with soluble GPVI as a novel non-invasive molecular imaging method for atherosclerosis. Further, HFU-guided disruption of GPVI-targeted microbubbles is an innovate therapeutic approach that potentially prevents progression of atherosclerotic disease. Copyright © 2014 Elsevier Ltd. All rights reserved.

Target: Lifestyle.

ERIC Educational Resources Information Center

Poehlman, Eric T.

1985-01-01

"Target: Lifestyle" is a physical education curriculum adopted by Detroit Country Day School which incorporates instruction in nutrition, physical fitness, first aid, and lifetime sports. This curriculum aims to influence student attitudes and lifestyles in health and physical fitness. Four levels of instruction are described. (DF)

Evaluation of a dietary targets monitor.

PubMed

Lean, M E J; Anderson, A S; Morrison, C; Currall, J

2003-05-01

To evaluate a two-page food frequency list for use as a Dietary Targets Monitor in large scale surveys to quantify consumptions of the key foods groups targeted in health promotion. Intakes of fruit and vegetables, starchy foods and fish estimated from a validated food frequency questionnaire (FFQ) were compared with a short food frequency list (the Dietary Targets Monitor) specifically designed to assess habitual frequency of consumption of foods in relation to dietary targets which form the basis of a National (Scottish) Food and Health Policy. A total of 1085 adults aged 25-64 y from the Glasgow MONICA Study. : The two questionnaires both collected data on frequencies of food consumption for fruit and vegetables, starchy foods and fish. Comparing the two questionnaires, there were consistent biases, best expressed as ratios (FFQ:Dietary Targets Monitor) between the methods for fruit and vegetables (1.33, 95% CI 1.29, 1.38) and 'starchy foods' (1.08, 95% CI 1.05, 1.12), the DTM showing systematic under-reporting by men. For fish consumption, there was essentially no bias between the methods (0.99, 95% CI 0.94, 1.03). Using calibration factors to adjust for biases, the Dietary Targets Monitor indicated that 16% of the subjects were achieving the Scottish Diet food target (400 g/day) for fruit and vegetable consumption. Nearly one-third (32%) of the subjects were eating the recommended intakes of fish (three portions per week). The Dietary Targets Monitor measure of starchy foods consumption was calibrated using FFQ data to be able to make quantitative estimates: 20% of subjects were eating six or more portions of starchy food daily. A similar estimation of total fat intake and saturated fat intake (g/day) allowed the categorization of subjects as low, moderate or high fat consumers, with broad agreement between the methods. The levels of agreement demonstrated by Bland-Altman analysis, were insufficient to permit use of the adjusted DTM to estimate quantitative

Target assembly

DOEpatents

Lewis, Richard A.

1980-01-01

A target for a proton beam which is capable of generating neutrons for absorption in a breeding blanket includes a plurality of solid pins formed of a neutron emissive target material disposed parallel to the path of the beam and which are arranged axially in a plurality of layers so that pins in each layer are offset with respect to pins in all other layers, enough layers being used so that each proton in the beam will strike at least one pin with means being provided to cool the pins. For a 300 mA, 1 GeV beam (300 MW), stainless steel pins, 12 inches long and 0.23 inches in diameter are arranged in triangular array in six layers with one sixth of the pins in each layer, the number of pins being such that the entire cross sectional area of the beam is covered by the pins with minimum overlap of pins.

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

Federal Register 2010, 2011, 2012, 2013, 2014

2011-06-15

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

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

PubMed

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

2017-01-01

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

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

PubMed Central

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

2017-01-01

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

Development of Water Target for Radioisotope Production

NASA Astrophysics Data System (ADS)

Tripp, Nathan

2011-10-01

Ongoing studies of plant physiology at TUNL require a supply of nitrogen-13 for use as a radiotracer. Production of nitrogen-13 using a water target and a proton beam follows the nuclear reaction 16-O(p,a)13-N. Unfortunately the irradiation of trace amounts of oxygen-18 within a natural water target produces fluorine-18 by the reaction 18-O(p, n)18-F. The presence of this second radioisotope reduces the efficacy of nitrogen-13 as a radiotracer. Designing a natural water target for nitrogen-13 production at TUNL required the design of several new systems to address the problems inherent in nitrogen-13 production. A heat exchanger cools the target water after irradiation within the target cell. The resulting improved thermal regulation of the target water prevents the system from overheating and minimizes the effect of the cavitations occurring within the target. Alumina pellets within a scrubbing unit remove the fluorine-18 contamination from the irradiated water. The modular design of the water target apparatus makes the system highly adaptable, allowing for easy reuse and adaptation of the different components into future projects. The newly designed and constructed water target should meet the current and future needs of TUNL researchers in the production of nitrogen-13. This TUNL REU project was funded in part by a grant from the National Science Foundation (NSF) NSF-PHY-08-51813.

[Functional targets of Chinese herbal medicine].

PubMed

Xiao, Bin; Wang, Yun

2010-12-01

In order to elucidate the mechanisms of Chinese herbal medicine, much work has been done based on chemical constituent-target in the molecular system. It cannot comply with the holistic efficacy of Chinese herbal medicine. Thus, the authors of this paper proposed to study the functional target adopted from Western medicine. The data of Chinese herbal function were collected from 2005 edition of The People's Republic of China Pharmacopoeia. A total of 135 functional targets were found, and a network about functional target and mode of action was built. The authors also explored the applications of functional target and the network combined with Sijunzi Decoction and Mahuang Decoction. The results, reflecting the feature of Chinese herbal medicine, will not only be helpful to elucidate the holistic mechanisms of Chinese herbal medicine, but also beneficial to studying the theory of Chinese formulas and developing new formulas.

Novel targets for ATM-deficient malignancies

PubMed Central

Winkler, Johannes; Hofmann, Kay; Chen, Shuhua

2014-01-01

Conventional chemo- and radiotherapies for the treatment of cancer target rapidly dividing cells in both tumor and non-tumor tissues and can exhibit severe cytotoxicity in normal tissue and impair the patient's immune system. Novel targeted strategies aim for higher efficacy and tumor specificity. The role of ATM protein in the DNA damage response is well known and ATM deficiency frequently plays a role in tumorigenesis and development of malignancy. In addition to contributing to disease development, ATM deficiency also renders malignant cells heavily dependent on other pathways that cooperate with the ATM-mediated DNA damage response to ensure tumor cell survival. Disturbing those cooperative pathways by inhibiting critical protein components allows specific targeting of tumors while sparing healthy cells with normal ATM status. We review druggable candidate targets for the treatment of ATM-deficient malignancies and the mechanisms underlying such targeted therapies. PMID:27308314

Manpower Targets and Educational Investments

ERIC Educational Resources Information Center

Ritzen, Jo M.

1976-01-01

Discusses the use of quadratic programming to calculate the optimal distribution of educational investments required to closely approach manpower targets when financial resources are insufficient to meet manpower targets completely. Demonstrates use of the quadratic programming approach by applying it to the training of supervisory technicians in…

Targeted Training: An Integrated Initiative.

ERIC Educational Resources Information Center

Valvasori, Joe

The Learning Enrichment Foundation (LEF) in Toronto, Ontario (Canada) offers 12 targeted training programs that have successfully helped "hard-to-serve" clients return to the workforce. Compared with traditional training, targeted training has a much narrower focus and adapts quickly to industry trends to meet employers' changing…

Drug-targeting methodologies with applications: A review

PubMed Central

Kleinstreuer, Clement; Feng, Yu; Childress, Emily

2014-01-01

Targeted drug delivery to solid tumors is a very active research area, focusing mainly on improved drug formulation and associated best delivery methods/devices. Drug-targeting has the potential to greatly improve drug-delivery efficacy, reduce side effects, and lower the treatment costs. However, the vast majority of drug-targeting studies assume that the drug-particles are already at the target site or at least in its direct vicinity. In this review, drug-delivery methodologies, drug types and drug-delivery devices are discussed with examples in two major application areas: (1) inhaled drug-aerosol delivery into human lung-airways; and (2) intravascular drug-delivery for solid tumor targeting. The major problem addressed is how to deliver efficiently the drug-particles from the entry/infusion point to the target site. So far, most experimental results are based on animal studies. Concerning pulmonary drug delivery, the focus is on the pros and cons of three inhaler types, i.e., pressurized metered dose inhaler, dry powder inhaler and nebulizer, in addition to drug-aerosol formulations. Computational fluid-particle dynamics techniques and the underlying methodology for a smart inhaler system are discussed as well. Concerning intravascular drug-delivery for solid tumor targeting, passive and active targeting are reviewed as well as direct drug-targeting, using optimal delivery of radioactive microspheres to liver tumors as an example. The review concludes with suggestions for future work, considereing both pulmonary drug targeting and direct drug delivery to solid tumors in the vascular system. PMID:25516850

Choosing a therapy electron accelerator target.

PubMed

Hutcheon, R M; Schriber, S O; Funk, L W; Sherman, N K

1979-01-01

Angular distributions of photon depth dose produced by 25-MeV electrons incident on several fully stopping single-element targets (C, Al, Cu, Mo, Ta, Pb) and two composite layered targets (Ni-Al, W-Al) were studied. Depth-dose curves measured using TLD-700 (thermoluminescent dosimeter) chips embedded in lucite phantoms. Several useful therapy electron accelerator design curves were determined, including relative flattener thickness as a function of target atomic number, "effective" bremsstrahlung endpoint energy or beam "hardness" as a function of target atomic number and photon emission angle, and estimates of shielding thickness as a function of angle required to reduce the radiation outside the treatment cone to required levels.

Camouflage target reconnaissance based on hyperspectral imaging technology

NASA Astrophysics Data System (ADS)

Hua, Wenshen; Guo, Tong; Liu, Xun

2015-08-01

Efficient camouflaged target reconnaissance technology makes great influence on modern warfare. Hyperspectral images can provide large spectral range and high spectral resolution, which are invaluable in discriminating between camouflaged targets and backgrounds. Hyperspectral target detection and classification technology are utilized to achieve single class and multi-class camouflaged targets reconnaissance respectively. Constrained energy minimization (CEM), a widely used algorithm in hyperspectral target detection, is employed to achieve one class camouflage target reconnaissance. Then, support vector machine (SVM), a classification method, is proposed to achieve multi-class camouflage target reconnaissance. Experiments have been conducted to demonstrate the efficiency of the proposed method.

SETI target selection.

PubMed

Latham, D W; Soderblom, D R

1995-01-01

The NASA High Resolution Microwave Survey consists of two complementary elements: a Sky Survey of the entire sky to a moderate level of sensitivity; and a Targeted Search of nearby stars, one at a time, to a much deeper level of sensitivity. In this paper we propose strategies for target selection. We have two goals: to improve the chances of successful detection of signals from technical civilizations that inhabit planets around solar-type stars, and to minimize the chances of missing signals from unexpected sites. For the main Targeted Search survey of approximately 1000 nearby solar-type stars, we argue that the selection criteria should be heavily biased by what we know about the origin and evolution of life here on Earth. We propose that observations of stars with stellar companions orbiting near the habitable zone should be de-emphasized, because such companions would prevent the formation of habitable planets. We also propose that observations of stars younger than about three billion years should be de-emphasized in favor of older stars, because our own technical civilization took longer than three billion years to evolve here on Earth. To provide the information needed for the preparation of specific target lists, we have undertaken an inventory of a large sample of solar-type stars out to a distance of 60 pc, with the goal of characterizing the relevant astrophysical properties of these stars, especially their ages and companionship. To complement the main survey, we propose that a modest sample of the nearest stars should be observed without any selection biases whatsoever. Finally, we argue that efforts to identify stars with planetary systems should be expanded. If found, such systems should receive intensive scrutiny.

Setting conservation targets for sandy beach ecosystems

NASA Astrophysics Data System (ADS)

Harris, Linda; Nel, Ronel; Holness, Stephen; Sink, Kerry; Schoeman, David

2014-10-01

Representative and adequate reserve networks are key to conserving biodiversity. This begs the question, how much of which features need to be placed in protected areas? Setting specifically-derived conservation targets for most ecosystems is common practice; however, this has never been done for sandy beaches. The aims of this paper, therefore, are to propose a methodology for setting conservation targets for sandy beach ecosystems; and to pilot the proposed method using data describing biodiversity patterns and processes from microtidal beaches in South Africa. First, a classification scheme of valued features of beaches is constructed, including: biodiversity features; unique features; and important processes. Second, methodologies for setting targets for each feature under different data-availability scenarios are described. From this framework, targets are set for features characteristic of microtidal beaches in South Africa, as follows. 1) Targets for dune vegetation types were adopted from a previous assessment, and ranged 19-100%. 2) Targets for beach morphodynamic types (habitats) were set using species-area relationships (SARs). These SARs were derived from species richness data from 142 sampling events around the South African coast (extrapolated to total theoretical species richness estimates using previously-established species-accumulation curve relationships), plotted against the area of the beach (calculated from Google Earth imagery). The species-accumulation factor (z) was 0.22, suggesting a baseline habitat target of 27% is required to protect 75% of the species. This baseline target was modified by heuristic principles, based on habitat rarity and threat status, with final values ranging 27-40%. 3) Species targets were fixed at 20%, modified using heuristic principles based on endemism, threat status, and whether or not beaches play an important role in the species' life history, with targets ranging 20-100%. 4) Targets for processes and 5

Targeted alpha therapy using short-lived alpha-particles and the promise of nanobodies as targeting vehicle

PubMed Central

Dekempeneer, Yana; Keyaerts, Marleen; Krasniqi, Ahmet; Puttemans, Janik; Muyldermans, Serge; Lahoutte, Tony; D’huyvetter, Matthias; Devoogdt, Nick

2016-01-01

ABSTRACT Introduction: The combination of a targeted biomolecule that specifically defines the target and a radionuclide that delivers a cytotoxic payload offers a specific way to destroy cancer cells. Targeted radionuclide therapy (TRNT) aims to deliver cytotoxic radiation to cancer cells and causes minimal toxicity to surrounding healthy tissues. Recent advances using α-particle radiation emphasizes their potential to generate radiation in a highly localized and toxic manner because of their high level of ionization and short range in tissue. Areas covered: We review the importance of targeted alpha therapy (TAT) and focus on nanobodies as potential beneficial vehicles. In recent years, nanobodies have been evaluated intensively as unique antigen-specific vehicles for molecular imaging and TRNT. Expert opinion: We expect that the efficient targeting capacity and fast clearance of nanobodies offer a high potential for TAT. More particularly, we argue that the nanobodies’ pharmacokinetic properties match perfectly with the interesting decay properties of the short-lived α-particle emitting radionuclides Astatine-211 and Bismuth-213 and offer an interesting treatment option particularly for micrometastatic cancer and residual disease. PMID:27145158

Molecular Targets of Cannabidiol in Neurological Disorders.

PubMed

Ibeas Bih, Clementino; Chen, Tong; Nunn, Alistair V W; Bazelot, Michaël; Dallas, Mark; Whalley, Benjamin J

2015-10-01

Cannabis has a long history of anecdotal medicinal use and limited licensed medicinal use. Until recently, alleged clinical effects from anecdotal reports and the use of licensed cannabinoid medicines are most likely mediated by tetrahydrocannabinol by virtue of: 1) this cannabinoid being present in the most significant quantities in these preparations; and b) the proportion:potency relationship between tetrahydrocannabinol and other plant cannabinoids derived from cannabis. However, there has recently been considerable interest in the therapeutic potential for the plant cannabinoid, cannabidiol (CBD), in neurological disorders but the current evidence suggests that CBD does not directly interact with the endocannabinoid system except in vitro at supraphysiological concentrations. Thus, as further evidence for CBD's beneficial effects in neurological disease emerges, there remains an urgent need to establish the molecular targets through which it exerts its therapeutic effects. Here, we conducted a systematic search of the extant literature for original articles describing the molecular pharmacology of CBD. We critically appraised the results for the validity of the molecular targets proposed. Thereafter, we considered whether the molecular targets of CBD identified hold therapeutic potential in relevant neurological diseases. The molecular targets identified include numerous classical ion channels, receptors, transporters, and enzymes. Some CBD effects at these targets in in vitro assays only manifest at high concentrations, which may be difficult to achieve in vivo, particularly given CBD's relatively poor bioavailability. Moreover, several targets were asserted through experimental designs that demonstrate only correlation with a given target rather than a causal proof. When the molecular targets of CBD that were physiologically plausible were considered for their potential for exploitation in neurological therapeutics, the results were variable. In some cases

A mathematical analysis of multiple-target SELEX.

PubMed

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

2010-10-01

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

Interventions That Target Criminogenic Needs for Justice-Involved Persons With Serious Mental Illnesses: A Targeted Service Delivery Approach.

PubMed

Wilson, Amy Blank; Farkas, Kathleen; Bonfine, Natalie; Duda-Banwar, Janelle

2018-05-01

This research describes the development of a targeted service delivery approach that tailors the delivery of interventions that target criminogenic needs to the specific learning and treatment needs of justice-involved people with serious mental illnesses (SMIs). This targeted service delivery approach includes five service delivery strategies: repetition and summarizing, amplification, active coaching, low-demand practice, and maximizing participation. Examples of how to apply each strategy in session are provided, as well as recommendations on when to use each strategy during the delivery of interventions that target criminogenic needs. This targeted service delivery approach makes an important contribution to the development of interventions for justice-involved people with SMI by increasing the chances that people with SMI can participate fully in and benefit from these interventions that target criminogenic needs. These developments come at a critical time in the field as the next generation of services for justice-involved people with SMI are being developed.

Purity of targets prepared on Cu substrates

NASA Astrophysics Data System (ADS)

Méens, A.; Rossini, I.; Sens, J. C.

1993-09-01

The purity of several elemental self-supporting targets usually prepared by evaporation onto soluble Cu substrates has been studied. The targets were analysed by Rutherford backscattering and instrumental neutron activation analysis. Because of the high percentage of Cu observed in some Si targets, further measurements, including transmission electron microscopy, have been performed on Si targets deposited by e-gun bombardment onto Cu and ion-beam sputtering onto betaine.

Systems genetics for drug target discovery

PubMed Central

Penrod, Nadia M.; Cowper-Sal_lari, Richard; Moore, Jason H.

2011-01-01

The collection and analysis of genomic data has the potential to reveal novel druggable targets by providing insight into the genetic basis of disease. However, the number of drugs, targeting new molecular entities, approved by the US Food and Drug Administration (FDA) has not increased in the years since the collection of genomic data has become commonplace. The paucity of translatable results can be partly attributed to conventional analysis methods that test one gene at a time in an effort to identify disease-associated factors as candidate drug targets. By disengaging genetic factors from their position within the genetic regulatory system, much of the information stored within the genomic data set is lost. Here we discuss how genomic data is used to identify disease-associated genes or genomic regions, how disease-associated regions are validated as functional targets, and the role network analysis can play in bridging the gap between data generation and effective drug target identification. PMID:21862141

Treat-to-target trials in diabetes.

PubMed

Wangnoo, Subhash K; Sethi, Bipin; Sahay, Rakesh K; John, Mathew; Ghosal, Samit; Sharma, Surendra K

2014-03-01

Treat-to-target is a therapeutic concept that considers well defined and specific physiologic targets as aims in controlling the pathophysiology of the disease. It has been widely used in diseases that pathophysiology includes, chronic metabolic and physiological disturbances, namely rheumatic conditions, vascular medicine and diabetes. In diabetes, the availability of "gold-standard" quantitative measures like fasting plasma glucose and glycated hemoglobin make the application of treat-to-target trials especially pertinent. Treatment modalities which have used single therapeutic agents or combinations or in combination with a variety of titration algorithms and implementation protocols have broadened our understanding of diabetes management with specific reference to insulin initiation and maintenance. Treat-to-target trials have been used to investigate a wide variety of questions including efficacy, safety, effect of treatment on comorbidities and patient satisfaction, ideal mechanisms to implement insulin initiation etc. A more generalized acceptance and implementation of treat-to-target trials may finally revolutionize diabetes management by combining aspects of individual care with standard treatment protocols.

Progress on LMJ targets for ignition

NASA Astrophysics Data System (ADS)

Cherfils-Clérouin, C.; Boniface, C.; Bonnefille, M.; Dattolo, E.; Galmiche, D.; Gauthier, P.; Giorla, J.; Laffite, S.; Liberatore, S.; Loiseau, P.; Malinie, G.; Masse, L.; Masson-Laborde, P. E.; Monteil, M. C.; Poggi, F.; Seytor, P.; Wagon, F.; Willien, J. L.

2009-12-01

Targets designed to produce ignition on the Laser Megajoule (LMJ) are being simulated in order to set specifications for target fabrication. The LMJ experimental plans include the attempt of ignition and burn of an ICF capsule with 160 laser beams, delivering up to 1.4 MJ and 380 TW. New targets needing reduced laser energy with only a small decrease in robustness have then been designed for this purpose. Working specifically on the coupling efficiency parameter, i.e. the ratio of the energy absorbed by the capsule to the laser energy, has led to the design of a rugby-ball shaped cocktail hohlraum; with these improvements, a target based on the 240-beam A1040 capsule can be included in the 160-beam laser energy-power space. Robustness evaluations of these different targets shed light on critical points for ignition, which can trade off by tightening some specifications or by preliminary experimental and numerical tuning experiments.

Targeting the RAS oncogene

PubMed Central

Takashima, Asami

2013-01-01

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

Targeted enzyme prodrug therapies.

PubMed

Schellmann, N; Deckert, P M; Bachran, D; Fuchs, H; Bachran, C

2010-09-01

The cure of cancer is still a formidable challenge in medical science. Long-known modalities including surgery, chemotherapy and radiotherapy are successful in a number of cases; however, invasive, metastasized and inaccessible tumors still pose an unresolved and ongoing problem. Targeted therapies designed to locate, detect and specifically kill tumor cells have been developed in the past three decades as an alternative to treat troublesome cancers. Most of these therapies are either based on antibody-dependent cellular cytotoxicity, targeted delivery of cytotoxic drugs or tumor site-specific activation of prodrugs. The latter is a two-step procedure. In the first step, a selected enzyme is accumulated in the tumor by guiding the enzyme or its gene to the neoplastic cells. In the second step, a harmless prodrug is applied and specifically converted by this enzyme into a cytotoxic drug only at the tumor site. A number of targeting systems, enzymes and prodrugs were investigated and improved since the concept was first envisioned in 1974. This review presents a concise overview on the history and latest developments in targeted therapies for cancer treatment. We cover the relevant technologies such as antibody-directed enzyme prodrug therapy (ADEPT), gene-directed enzyme prodrug therapy (GDEPT) as well as related therapies such as clostridial- (CDEPT) and polymer-directed enzyme prodrug therapy (PDEPT) with emphasis on prodrug-converting enzymes, prodrugs and drugs.

The targets of curcumin.

PubMed

Zhou, Hongyu; Beevers, Christopher S; Huang, Shile

2011-03-01

Curcumin (diferuloylmethane), an orange-yellow component of turmeric or curry powder, is a polyphenol natural product isolated from the rhizome of the plant Curcuma longa. For centuries, curcumin has been used in some medicinal preparation or used as a food-coloring agent. In recent years, extensive in vitro and in vivo studies suggested curcumin has anticancer, antiviral, antiarthritic, anti-amyloid, antioxidant, and anti-inflammatory properties. The underlying mechanisms of these effects are diverse and appear to involve the regulation of various molecular targets, including transcription factors (such as nuclear factor-kB), growth factors (such as vascular endothelial cell growth factor), inflammatory cytokines (such as tumor necrosis factor, interleukin 1 and interleukin 6), protein kinases (such as mammalian target of rapamycin, mitogen-activated protein kinases, and Akt) and other enzymes (such as cyclooxygenase 2 and 5 lipoxygenase). Thus, due to its efficacy and regulation of multiple targets, as well as its safety for human use, curcumin has received considerable interest as a potential therapeutic agent for the prevention and/or treatment of various malignant diseases, arthritis, allergies, Alzheimer's disease, and other inflammatory illnesses. This review summarizes various in vitro and in vivo pharmacological aspects of curcumin as well as the underlying action mechanisms. The recently identified molecular targets and signaling pathways modulated by curcumin are also discussed here.

Targeted nanosystems: Advances in targeted dendrimers for cancer therapy.

PubMed

Yang, Hu

2016-02-01

Dendrimers possess discrete highly compact nanostructures constituted of successive branched layers. Soon after the inception of dendrimers, recognition of their tunable structures and biologically favorable properties provoked a great enthusiasm in delving deeply into the utility of dendrimers for biomedical and pharmaceutical applications. One of the most important nanotechnology applications is the development of nanomedicines for targeted cancer therapies. Tremendous success in targeted therapies has been achieved with the use of dendrimer-based nanomedicines. This article provides a concise review on latest advances in the utility of dendrimers in immunotherapies and hormone therapies. Much basic and clinical research has been done since the invention of dendrimers, which are highly branched nano-sized molecules with the ability to act as carriers in nanomedicine. In this concise review article, the authors highlighted the current use of dendrimers in immunotherapies and hormone therapies in the fight against cancers. Copyright © 2015 Elsevier Inc. All rights reserved.

Maximizing in vivo target clearance by design of pH-dependent target binding antibodies with altered affinity to FcRn.

PubMed

Yang, Danlin; Giragossian, Craig; Castellano, Steven; Lasaro, Marcio; Xiao, Haiguang; Saraf, Himanshu; Hess Kenny, Cynthia; Rybina, Irina; Huang, Zhong-Fu; Ahlberg, Jennifer; Bigwarfe, Tammy; Myzithras, Maria; Waltz, Erica; Roberts, Simon; Kroe-Barrett, Rachel; Singh, Sanjaya

2017-10-01

Antibodies with pH-dependent binding to both target antigens and neonatal Fc receptor (FcRn) provide an alternative tool to conventional neutralizing antibodies, particularly for therapies where reduction in antigen level is challenging due to high target burden. However, the requirements for optimal binding kinetic framework and extent of pH dependence for these antibodies to maximize target clearance from circulation are not well understood. We have identified a series of naturally-occurring high affinity antibodies with pH-dependent target binding properties. By in vivo studies in cynomolgus monkeys, we show that pH-dependent binding to the target alone is not sufficient for effective target removal from circulation, but requires Fc mutations that increase antibody binding to FcRn. Affinity-enhanced pH-dependent FcRn binding that is double-digit nM at pH 7.4 and single-digit nM at pH 6 achieved maximal target reduction when combined with similar target binding affinities in reverse pH directions. Sustained target clearance below the baseline level was achieved 3 weeks after single-dose administration at 1.5 mg/kg. Using the experimentally derived mechanistic model, we demonstrate the essential kinetic interplay between target turnover and antibody pH-dependent binding during the FcRn recycling, and identify the key components for achieving maximal target clearance. These results bridge the demand for improved patient dosing convenience with the "know-how" of therapeutic modality by design.

Incoherent imaging of radar targets

NASA Astrophysics Data System (ADS)

van Ommen, A.; van der Spek, G. A.

1986-05-01

Theory suggests that, if a target can be modeled as a rigid constellation of point scatterers, the RCS pattern over a certain aspect change can be used to produce a one-dimensional image. The results for actual measured RCS patterns, however, are not promising. This is illustrated by processing on 4 s of echo data obtained from a Boeing 737 in straight flight, during which its aspect change is 2 deg. The conclusion might be that, for the application considered, aircraft cannot be modeled as a rigid constellation of point scatterers; this is partly due to the treatment of a three-dimensional target as a line target.

Targeted therapy in esophageal cancer.

PubMed

Zhang, Lei; Ma, Jiaojiao; Han, Yu; Liu, Jinqiang; Zhou, Wei; Hong, Liu; Fan, Daiming

2016-01-01

An increasing number of patients are diagnosed with esophageal cancer at an advanced stages, and only a small group of them can benefit from the traditional chemotherapy and radiotherapy. So far, multiple monoclonal antibodies and tyrosine kinase inhibitors have been developed, alone or in combination with traditional therapy, to improve the prognosis of patients with advanced esophageal cancer. This review summarizes the recent advances of targeted therapies against EGFR, HER2, VEGFR and c-MET in esophageal cancer. More clinical trials should be performed to evaluate the efficacy and safety of various targeted therapy regimens. Future basic research should focus on investigating the molecular mechanisms of therapeutic targets in esophageal cancer.

Microtubule-Targeting Therapy for Prostate Cancer

DTIC Science & Technology

2007-02-01

that were done to achieve the above specific goals. 1. Biological effects of ribozyme -carrying adenoviruses that target stathmin mRNA in human...prostate cancer cells: A ribozyme is a small RNA molecule that acts stoichiometrically to cleave multiple target RNA molecules [1]. This unique ability...of a ribozyme to degrade multiple target RNA molecules is a more efficient approach for down regulating genes that are expressed at very high levels

TARGET: Rapid Capture of Process Knowledge

NASA Technical Reports Server (NTRS)

Ortiz, C. J.; Ly, H. V.; Saito, T.; Loftin, R. B.

1993-01-01

TARGET (Task Analysis/Rule Generation Tool) represents a new breed of tool that blends graphical process flow modeling capabilities with the function of a top-down reporting facility. Since NASA personnel frequently perform tasks that are primarily procedural in nature, TARGET models mission or task procedures and generates hierarchical reports as part of the process capture and analysis effort. Historically, capturing knowledge has proven to be one of the greatest barriers to the development of intelligent systems. Current practice generally requires lengthy interactions between the expert whose knowledge is to be captured and the knowledge engineer whose responsibility is to acquire and represent the expert's knowledge in a useful form. Although much research has been devoted to the development of methodologies and computer software to aid in the capture and representation of some types of knowledge, procedural knowledge has received relatively little attention. In essence, TARGET is one of the first tools of its kind, commercial or institutional, that is designed to support this type of knowledge capture undertaking. This paper will describe the design and development of TARGET for the acquisition and representation of procedural knowledge. The strategies employed by TARGET to support use by knowledge engineers, subject matter experts, programmers and managers will be discussed. This discussion includes the method by which the tool employs its graphical user interface to generate a task hierarchy report. Next, the approach to generate production rules for incorporation in and development of a CLIPS based expert system will be elaborated. TARGET also permits experts to visually describe procedural tasks as a common medium for knowledge refinement by the expert community and knowledge engineer making knowledge consensus possible. The paper briefly touches on the verification and validation issues facing the CLIPS rule generation aspects of TARGET. A description of

Collaborative filtering on a family of biological targets.

PubMed

Erhan, Dumitru; L'heureux, Pierre-Jean; Yue, Shi Yi; Bengio, Yoshua

2006-01-01

Building a QSAR model of a new biological target for which few screening data are available is a statistical challenge. However, the new target may be part of a bigger family, for which we have more screening data. Collaborative filtering or, more generally, multi-task learning, is a machine learning approach that improves the generalization performance of an algorithm by using information from related tasks as an inductive bias. We use collaborative filtering techniques for building predictive models that link multiple targets to multiple examples. The more commonalities between the targets, the better the multi-target model that can be built. We show an example of a multi-target neural network that can use family information to produce a predictive model of an undersampled target. We evaluate JRank, a kernel-based method designed for collaborative filtering. We show their performance on compound prioritization for an HTS campaign and the underlying shared representation between targets. JRank outperformed the neural network both in the single- and multi-target models.

Tackling Targets.

ERIC Educational Resources Information Center

Further Education Unit, London (England).

This document is designed to help British training and enterprise councils (TECs) and further education (FE) colleges develop and implement strategies for achieving the National Targets for Education and Training (NTET), which were developed by the Confederation of British Industry in 1992 and endorsed by the British government. The findings from…

Detection of Moving Targets Using Soliton Resonance Effect

NASA Technical Reports Server (NTRS)

Kulikov, Igor K.; Zak, Michail

2013-01-01

The objective of this research was to develop a fundamentally new method for detecting hidden moving targets within noisy and cluttered data-streams using a novel "soliton resonance" effect in nonlinear dynamical systems. The technique uses an inhomogeneous Korteweg de Vries (KdV) equation containing moving-target information. Solution of the KdV equation will describe a soliton propagating with the same kinematic characteristics as the target. The approach uses the time-dependent data stream obtained with a sensor in form of the "forcing function," which is incorporated in an inhomogeneous KdV equation. When a hidden moving target (which in many ways resembles a soliton) encounters the natural "probe" soliton solution of the KdV equation, a strong resonance phenomenon results that makes the location and motion of the target apparent. Soliton resonance method will amplify the moving target signal, suppressing the noise. The method will be a very effective tool for locating and identifying diverse, highly dynamic targets with ill-defined characteristics in a noisy environment. The soliton resonance method for the detection of moving targets was developed in one and two dimensions. Computer simulations proved that the method could be used for detection of singe point-like targets moving with constant velocities and accelerations in 1D and along straight lines or curved trajectories in 2D. The method also allows estimation of the kinematic characteristics of moving targets, and reconstruction of target trajectories in 2D. The method could be very effective for target detection in the presence of clutter and for the case of target obscurations.

Handling target obscuration through Markov chain observations

NASA Astrophysics Data System (ADS)

Kouritzin, Michael A.; Wu, Biao

2008-04-01

Target Obscuration, including foliage or building obscuration of ground targets and landscape or horizon obscuration of airborne targets, plagues many real world filtering problems. In particular, ground moving target identification Doppler radar, mounted on a surveillance aircraft or unattended airborne vehicle, is used to detect motion consistent with targets of interest. However, these targets try to obscure themselves (at least partially) by, for example, traveling along the edge of a forest or around buildings. This has the effect of creating random blockages in the Doppler radar image that move dynamically and somewhat randomly through this image. Herein, we address tracking problems with target obscuration by building memory into the observations, eschewing the usual corrupted, distorted partial measurement assumptions of filtering in favor of dynamic Markov chain assumptions. In particular, we assume the observations are a Markov chain whose transition probabilities depend upon the signal. The state of the observation Markov chain attempts to depict the current obscuration and the Markov chain dynamics are used to handle the evolution of the partially obscured radar image. Modifications of the classical filtering equations that allow observation memory (in the form of a Markov chain) are given. We use particle filters to estimate the position of the moving targets. Moreover, positive proof-of-concept simulations are included.

Multispectral infrared target detection: phenomenology and modeling

NASA Astrophysics Data System (ADS)

Cederquist, Jack N.; Rogne, Timothy J.; Schwartz, Craig R.

1993-10-01

Many targets of interest provide only very small signature differences from the clutter background. The ability to detect these small difference targets should be improved by using data which is diverse in space, time, wavelength or some other observable. Target materials often differ from background materials in the variation of their reflectance or emittance with wavelength. A multispectral sensor is therefore considered as a means to improve detection of small signal targets. If this sensor operates in the thermal infrared, it will not need solar illumination and will be useful at night as well as during the day. An understanding of the phenomenology of the spectral properties of materials and an ability to model and simulate target and clutter signatures is needed to understand potential target detection performance from multispectral infrared sensor data. Spectral variations in material emittance are due to vibrational energy transitions in molecular bonds. The spectral emittances of many materials of interest have been measured. Examples are vegetation, soil, construction and road materials, and paints. A multispectral infrared signature model has been developed which includes target and background temperature and emissivity, sky, sun, cloud and background irradiance, multiple reflection effects, path radiance, and atmospheric attenuation. This model can be used to predict multispectral infrared signatures for small signal targets.

Targeted left ventricular lead placement to guide cardiac resynchronization therapy: the TARGET study: a randomized, controlled trial.

PubMed

Khan, Fakhar Z; Virdee, Mumohan S; Palmer, Christopher R; Pugh, Peter J; O'Halloran, Denis; Elsik, Maros; Read, Philip A; Begley, David; Fynn, Simon P; Dutka, David P

2012-04-24

This study sought to assess the impact of targeted left ventricular (LV) lead placement on outcomes of cardiac resynchronization therapy (CRT). Placement of the LV lead to the latest sites of contraction and away from the scar confers the best response to CRT. We conducted a randomized, controlled trial to compare a targeted approach to LV lead placement with usual care. A total of 220 patients scheduled for CRT underwent baseline echocardiographic speckle-tracking 2-dimensional radial strain imaging and were then randomized 1:1 into 2 groups. In group 1 (TARGET [Targeted Left Ventricular Lead Placement to Guide Cardiac Resynchronization Therapy]), the LV lead was positioned at the latest site of peak contraction with an amplitude of >10% to signify freedom from scar. In group 2 (control) patients underwent standard unguided CRT. Patients were classified by the relationship of the LV lead to the optimal site as concordant (at optimal site), adjacent (within 1 segment), or remote (≥2 segments away). The primary endpoint was a ≥15% reduction in LV end-systolic volume at 6 months. Secondary endpoints were clinical response (≥1 improvement in New York Heart Association functional class), all-cause mortality, and combined all-cause mortality and heart failure-related hospitalization. The groups were balanced at randomization. In the TARGET group, there was a greater proportion of responders at 6 months (70% vs. 55%, p = 0.031), giving an absolute difference in the primary endpoint of 15% (95% confidence interval: 2% to 28%). Compared with controls, TARGET patients had a higher clinical response (83% vs. 65%, p = 0.003) and lower rates of the combined endpoint (log-rank test, p = 0.031). Compared with standard CRT treatment, the use of speckle-tracking echocardiography to the target LV lead placement yields significantly improved response and clinical status and lower rates of combined death and heart failure-related hospitalization. (Targeted Left Ventricular Lead

Emerging therapeutic targets for treatment of leishmaniasis.

PubMed

Sundar, Shyam; Singh, Bhawana

2018-06-01

Parasitic diseases that pose a threat to human life include leishmaniasis - caused by protozoan parasite Leishmania species. Existing drugs have limitations due to deleterious side effects like teratogenicity, high cost and drug resistance. This calls for the need to have an insight into therapeutic aspects of disease. Areas covered: We have identified different drug targets via. molecular, imuunological, metabolic as well as by system biology approaches. We bring these promising drug targets into light so that they can be explored to their maximum. In an effort to bridge the gaps between existing knowledge and prospects of drug discovery, we have compiled interesting studies on drug targets, thereby paving the way for establishment of better therapeutic aspects. Expert opinion: Advancements in technology shed light on many unexplored pathways. Further probing of well established pathways led to the discovery of new drug targets. This review is a comprehensive report on current and emerging drug targets, with emphasis on several metabolic targets, organellar biochemistry, salvage pathways, epigenetics, kinome and more. Identification of new targets can contribute significantly towards strengthening the pipeline for disease elimination.

Hybrid-drive implosion system for ICF targets

DOEpatents

Mark, J.W.K.

1987-10-14

Hybrid-drive implosion systems for ICF targets are described which permit a significant increase in target gain at fixed total driver energy. The ICF target is compressed in two phases, an initial compression phase and a final peak power phase, with each phase driven by a separate, optimized driver. The targets comprise a hollow spherical ablator surroundingly disposed around fusion fuel. The ablator is first compressed to higher density by a laser system, or by an ion beam system, that in each case is optimized for this initial phase of compression of the target. Then, following compression of the ablator, energy is directly delivered into the compressed ablator by an ion beam driver system that is optimized for this second phase of operation of the target. The fusion fuel is driven, at high gain, to conditions wherein fusion reactions occur. This phase separation allows hydrodynamic efficiency and energy deposition uniformity to be individually optimized, thereby securing significant advantages in energy gain. In additional embodiments, the same or separate drivers supply energy for ICF target implosion. 3 figs.

a Plutonium Ceramic Target for Masha

NASA Astrophysics Data System (ADS)

Wilk, P. A.; Shaughnessy, D. A.; Moody, K. J.; Kenneally, J. M.; Wild, J. F.; Stoyer, M. A.; Patin, J. B.; Lougheed, R. W.; Ebbinghaus, B. B.; Landingham, R. L.; Oganessian, Yu. Ts.; Yeremin, A. V.; Dmitriev, S. N.

2005-09-01

We are currently developing a plutonium ceramic target for the MASHA mass separator. The MASHA separator will use a thick plutonium ceramic target capable of tolerating temperatures up to 2000 °C. Promising candidates for the target include oxides and carbides, although more research into their thermodynamic properties will be required. Reaction products will diffuse out of the target into an ion source, where they will then be transported through the separator to a position-sensitive focal-plane detector array. Experiments on MASHA will allow us to make measurements that will cement our identification of element 114 and provide for future experiments where the chemical properties of the heaviest elements are studied.

A Plutonium Ceramic Target for MASHA

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

Wilk, P A; Shaughnessy, D A; Moody, K J

2004-07-06

We are currently developing a plutonium ceramic target for the MASHA mass separator. The MASHA separator will use a thick plutonium ceramic target capable of tolerating temperatures up to 2000 C. Promising candidates for the target include oxides and carbides, although more research into their thermodynamic properties will be required. Reaction products will diffuse out of the target into an ion source, where they will then be transported through the separator to a position-sensitive focal-plane detector array. Experiments on MASHA will allow us to make measurements that will cement our identification of element 114 and provide for future experiments wheremore » the chemical properties of the heaviest elements are studied.« less

Unified approach for two-target game analysis

NASA Technical Reports Server (NTRS)

Shinar, J.; Davidovitz, A.

1988-01-01

A two-target differential game is defined from the outset by a qualitative (game-of-kind) formulation. The solution of such a game is the decomposition of the space of admissible initial conditions into zones of different outcomes: two winning zones, one for each player, the zone of nowinning (draw) and (if the intersection of the two target sets is not empty) a zone of eventual mutual winning (mutual kill). In this paper it is shown that the solution of any two-target game can be constructed, based on solving first two single-target pursuit-evasion games of kind (one for each target set) in a systematic way.

Achieving target refraction after cataract surgery.

PubMed

Simon, Shira S; Chee, Yewlin E; Haddadin, Ramez I; Veldman, Peter B; Borboli-Gerogiannis, Sheila; Brauner, Stacey C; Chang, Kenneth K; Chen, Sherleen H; Gardiner, Matthew F; Greenstein, Scott H; Kloek, Carolyn E; Chen, Teresa C

2014-02-01

To evaluate the difference between target and actual refraction after phacoemulsification and intraocular lens implantation at an academic teaching institution's Comprehensive Ophthalmology Service. Retrospective study. We examined 1275 eye surgeries for this study. All consecutive cataract surgeries were included if they were performed by an attending or resident surgeon from January through December 2010. Postoperative refractions were compared with preoperative target refractions. Patients were excluded if they did not have a preoperative target refraction documented or if they did not have a recorded postoperative manifest refraction within 90 days. The main outcome measure was percentage of cases achieving a postoperative spherical equivalent ± 1.0 diopter (D) of target spherical equivalent. We performed 1368 cataract surgeries from January through December of 2010. Of these, 1275 (93%) had sufficient information for analysis. Of the included cases, 94% (1196 of 1275) achieved ± 1.0 D of target refraction by 90 days after cataract surgery. This paper establishes a new benchmark for a teaching hospital, where 94% of patients achieved within 1.0 D of target refraction after cataract surgery. The refractive outcomes after cataract surgery at this academic teaching institution were higher than average international benchmarks. Copyright © 2014 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.

Drug target identification in protozoan parasites.

PubMed

Müller, Joachim; Hemphill, Andrew

2016-08-01

Despite the fact that diseases caused by protozoan parasites represent serious challenges for public health, animal production and welfare, only a limited panel of drugs has been marketed for clinical applications. Herein, the authors investigate two strategies, namely whole organism screening and target-based drug design. The present pharmacopoeia has resulted from whole organism screening, and the mode of action and targets of selected drugs are discussed. However, the more recent extensive genome sequencing efforts and the development of dry and wet lab genomics and proteomics that allow high-throughput screening of interactions between micromolecules and recombinant proteins has resulted in target-based drug design as the predominant focus in anti-parasitic drug development. Selected examples of target-based drug design studies are presented, and calcium-dependent protein kinases, important drug targets in apicomplexan parasites, are discussed in more detail. Despite the enormous efforts in target-based drug development, this approach has not yet generated market-ready antiprotozoal drugs. However, whole-organism screening approaches, comprising of both in vitro and in vivo investigations, should not be disregarded. The repurposing of already approved and marketed drugs could be a suitable strategy to avoid fastidious approval procedures, especially in the case of neglected or veterinary parasitoses.

Drug target identification in protozoan parasites

PubMed Central

Müller, Joachim; Hemphill, Andrew

2016-01-01

Introduction Despite the fact that diseases caused by protozoan parasites represent serious challenges for public health, animal production and welfare, only a limited panel of drugs has been marketed for clinical applications. Areas covered Herein, the authors investigate two strategies, namely whole organism screening and target-based drug design. The present pharmacopoeia has resulted from whole organism screening, and the mode of action and targets of selected drugs are discussed. However, the more recent extensive genome sequencing efforts and the development of dry and wet lab genomics and proteomics that allow high-throughput screening of interactions between micromolecules and recombinant proteins has resulted in target-based drug design as the predominant focus in anti-parasitic drug development. Selected examples of target-based drug design studies are presented, and calcium-dependent protein kinases, important drug targets in apicomplexan parasites, are discussed in more detail. Expert opinion Despite the enormous efforts in target-based drug development, this approach has not yet generated market-ready antiprotozoal drugs. However, whole-organism screening approaches, comprising of both in vitro and in vivo investigations, should not be disregarded. The repurposing of already approved and marketed drugs could be a suitable strategy to avoid fastidious approval procedures, especially in the case of neglected or veterinary parasitoses. PMID:27238605

NDCX-II target experiments and simulations

DOE PAGES

Barnard, J. J.; More, R. M.; Terry, M.; ...

2013-06-13

The ion accelerator NDCX-II is undergoing commissioning at Lawrence Berkeley National Laboratory (LBNL). Its principal mission is to explore ion-driven High Energy Density Physics (HEDP) relevant to Inertial Fusion Energy (IFE) especially in the Warm Dense Matter (WDM) regime. We have carried out hydrodynamic simulations of beam-heated targets for parameters expected for the initial configuration of NDCX-II. For metal foils of order one micron thick (thin targets), the beam is predicted to heat the target in a timescale comparable to the hydrodynamic expansion time for experiments that infer material properties from measurements of the resulting rarefaction wave. We have alsomore » carried out hydrodynamic simulations of beam heating of metallic foam targets several tens of microns thick (thick targets) in which the ion range is shorter than the areal density of the material. In this case shock waves will form and we derive simple scaling laws for the efficiency of conversion of ion energy into kinetic energy of fluid flow. Geometries with a tamping layer may also be used to study the merging of a tamper shock with the end-of-range shock. As a result, this process can occur in tamped, direct drive IFE targets.« less

Optoelectronic System Measures Distances to Multiple Targets

NASA Technical Reports Server (NTRS)

Liebe, Carl Christian; Abramovici, Alexander; Bartman, Randall; Chapsky, Jacob; Schmalz, John; Coste, Keith; Litty, Edward; Lam, Raymond; Jerebets, Sergei

2007-01-01

An optoelectronic metrology apparatus now at the laboratory-prototype stage of development is intended to repeatedly determine distances of as much as several hundred meters, at submillimeter accuracy, to multiple targets in rapid succession. The underlying concept of optoelectronic apparatuses that can measure distances to targets is not new; such apparatuses are commonly used in general surveying and machining. However, until now such apparatuses have been, variously, constrained to (1) a single target or (2) multiple targets with a low update rate and a requirement for some a priori knowledge of target geometry. When fully developed, the present apparatus would enable measurement of distances to more than 50 targets at an update rate greater than 10 Hz, without a requirement for a priori knowledge of target geometry. The apparatus (see figure) includes a laser ranging unit (LRU) that includes an electronic camera (photo receiver), the field of view of which contains all relevant targets. Each target, mounted at a fiducial position on an object of interest, consists of a small lens at the output end of an optical fiber that extends from the object of interest back to the LRU. For each target and its optical fiber, there is a dedicated laser that is used to illuminate the target via the optical fiber. The targets are illuminated, one at a time, with laser light that is modulated at a frequency of 10.01 MHz. The modulated laser light is emitted by the target, from where it returns to the camera (photodetector), where it is detected. Both the outgoing and incoming 10.01-MHz laser signals are mixed with a 10-MHz local-oscillator to obtain beat notes at 10 kHz, and the difference between the phases of the beat notes is measured by a phase meter. This phase difference serves as a measure of the total length of the path traveled by light going out through the optical fiber and returning to the camera (photodetector) through free space. Because the portion of the path

One target, different effects: a comparison of distinct therapeutic antibodies against the same targets.

PubMed

Shim, Hyunbo

2011-10-31

To date, more than 30 antibodies have been approved worldwide for therapeutic use. While the monoclonal antibody market is rapidly growing, the clinical use of therapeutic antibodies is mostly limited to treatment of cancers and immunological disorders. Moreover, antibodies against only five targets (TNF-α, HER2, CD20, EGFR, and VEGF) account for more than 80 percent of the worldwide market of therapeutic antibodies. The shortage of novel, clinically proven targets has resulted in the development of many distinct therapeutic antibodies against a small number of proven targets, based on the premise that different antibody molecules against the same target antigen have distinct biological and clinical effects from one another. For example, four antibodies against TNF-α have been approved by the FDA -- infliximab, adalimumab, golimumab, and certolizumab pegol -- with many more in clinical and preclinical development. The situation is similar for HER2, CD20, EGFR, and VEGF, each having one or more approved antibodies and many more under development. This review discusses the different binding characteristics, mechanisms of action, and biological and clinical activities of multiple monoclonal antibodies against TNF-α, HER-2, CD20, and EGFR and provides insights into the development of therapeutic antibodies.

Video Guidance Sensors Using Remotely Activated Targets

NASA Technical Reports Server (NTRS)

Bryan, Thomas C.; Howard, Richard T.; Book, Michael L.

2004-01-01

Four updated video guidance sensor (VGS) systems have been proposed. As described in a previous NASA Tech Briefs article, a VGS system is an optoelectronic system that provides guidance for automated docking of two vehicles. The VGS provides relative position and attitude (6-DOF) information between the VGS and its target. In the original intended application, the two vehicles would be spacecraft, but the basic principles of design and operation of the system are applicable to aircraft, robots, objects maneuvered by cranes, or other objects that may be required to be aligned and brought together automatically or under remote control. In the first two of the four VGS systems as now proposed, the tracked vehicle would include active targets that would light up on command from the tracking vehicle, and a video camera on the tracking vehicle would be synchronized with, and would acquire images of, the active targets. The video camera would also acquire background images during the periods between target illuminations. The images would be digitized and the background images would be subtracted from the illuminated-target images. Then the position and orientation of the tracked vehicle relative to the tracking vehicle would be computed from the known geometric relationships among the positions of the targets in the image, the positions of the targets relative to each other and to the rest of the tracked vehicle, and the position and orientation of the video camera relative to the rest of the tracking vehicle. The major difference between the first two proposed systems and prior active-target VGS systems lies in the techniques for synchronizing the flashing of the active targets with the digitization and processing of image data. In the prior active-target VGS systems, synchronization was effected, variously, by use of either a wire connection or the Global Positioning System (GPS). In three of the proposed VGS systems, the synchronizing signal would be generated on, and

Ion acceleration enhanced by target ablation

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

Zhao, S.; State Key Laboratory of Nuclear Physics and Technology, and Key Lab of HEDPS, CAPT, Peking University, Beijing 100871; Institute of Radiation, Helmholtz-Zentrum Dresden-Rossendorf, 01314 Dresden

2015-07-15

Laser proton acceleration can be enhanced by using target ablation, due to the energetic electrons generated in the ablation preplasma. When the ablation pulse matches main pulse, the enhancement gets optimized because the electrons' energy density is highest. A scaling law between the ablation pulse and main pulse is confirmed by the simulation, showing that for given CPA pulse and target, proton energy improvement can be achieved several times by adjusting the target ablation.

Molecular-Targeted Immunotherapeutic Strategy for Melanoma via Dual-Targeting Nanoparticles Delivering Small Interfering RNA to Tumor-Associated Macrophages.

PubMed

Qian, Yuan; Qiao, Sha; Dai, Yanfeng; Xu, Guoqiang; Dai, Bolei; Lu, Lisen; Yu, Xiang; Luo, Qingming; Zhang, Zhihong

2017-09-26

Tumor-associated macrophages (TAMs) are a promising therapeutic target for cancer immunotherapy. Targeted delivery of therapeutic drugs to the tumor-promoting M2-like TAMs is challenging. Here, we developed M2-like TAM dual-targeting nanoparticles (M2NPs), whose structure and function were controlled by α-peptide (a scavenger receptor B type 1 (SR-B1) targeting peptide) linked with M2pep (an M2 macrophage binding peptide). By loading anti-colony stimulating factor-1 receptor (anti-CSF-1R) small interfering RNA (siRNA) on the M2NPs, we developed a molecular-targeted immunotherapeutic approach to specifically block the survival signal of M2-like TAMs and deplete them from melanoma tumors. We confirmed the validity of SR-B1 for M2-like TAM targeting and demonstrated the synergistic effect of the two targeting units (α-peptide and M2pep) in the fusion peptide (α-M2pep). After being administered to tumor-bearing mice, M2NPs had higher affinity to M2-like TAMs than to tissue-resident macrophages in liver, spleen, and lung. Compared with control treatment groups, M2NP-based siRNA delivery resulted in a dramatic elimination of M2-like TAMs (52%), decreased tumor size (87%), and prolonged survival. Additionally, this molecular-targeted strategy inhibited immunosuppressive IL-10 and TGF-β production and increased immunostimulatory cytokines (IL-12 and IFN-γ) expression and CD8 + T cell infiltration (2.9-fold) in the tumor microenvironment. Moreover, the siRNA-carrying M2NPs down-regulated expression of the exhaustion markers (PD-1 and Tim-3) on the infiltrating CD8 + T cells and stimulated their IFN-γ secretion (6.2-fold), indicating the restoration of T cell immune function. Thus, the dual-targeting property of M2NPs combined with RNA interference provides a potential strategy of molecular-targeted cancer immunotherapy for clinical application.

Resource implications of a national health target: The New Zealand experience of a Shorter Stays in Emergency Departments target.

PubMed

Jones, Peter; Sopina, Elizaveta; Ashton, Toni

2014-12-01

The Shorter Stays in Emergency Departments health target was introduced in New Zealand in 2009. District Health Boards (DHBs) are expected to meet the target with no additional funding or incentives. The costs of implementing such targets have not previously been studied. A survey of clinical/service managers in ED throughout New Zealand determined the type and cost of resources used for the target. Responses to the target were classified according to their impact in ED, the hospital and the community. Quantifiable resource changes were assigned a financial value and grouped into categories: structure (facilities/beds), staff and processes. Simple statistics were used to describe the data, and the correlation between expenditure and target performance was determined. There was 100% response to the survey. Most DHBs reported some expenditure specifically on the target, with estimated total expenditure of over NZ$52 m. The majority of expenditure occurred in ED (60.8%) and hospital (38.7%) with little spent in the community. New staff accounted for 76.5% of expenditure. Per capita expenditure in the ED was associated with improved target performance (r = 0.48, P = 0.03), whereas expenditure in the hospital was not (r = 0.08, P = 0.75). The fact that estimated expenditure on the target was over $50 million without additional funding suggests that DHBs were able to make savings through improved efficiencies and/or that funds were reallocated from other services. The majority of expenditure occurred in the ED. Most of the funds were spent on staff, and this was associated with improved target performance. © 2014 Australasian College for Emergency Medicine and Australasian Society for Emergency Medicine.

Digital-Electronic/Optical Apparatus Would Recognize Targets

NASA Technical Reports Server (NTRS)

Scholl, Marija S.

1994-01-01

Proposed automatic target-recognition apparatus consists mostly of digital-electronic/optical cross-correlator that processes infrared images of targets. Infrared images of unknown targets correlated quickly with images of known targets. Apparatus incorporates some features of correlator described in "Prototype Optical Correlator for Robotic Vision System" (NPO-18451), and some of correlator described in "Compact Optical Correlator" (NPO-18473). Useful in robotic system; to recognize and track infrared-emitting, moving objects as variously shaped hot workpieces on conveyor belt.

Probing microbubble targeting with atomic force microscopy.

PubMed

Sboros, V; Glynos, E; Ross, J A; Moran, C M; Pye, S D; Butler, M; McDicken, W N; Brown, S B; Koutsos, V

2010-10-01

Microbubble science is expanding beyond ultrasound imaging applications to biological targeting and drug/gene delivery. The characteristics of molecular targeting should be tested by a measurement system that can assess targeting efficacy and strength. Atomic force microscopy (AFM) is capable of piconewton force resolution, and is reported to measure the strength of single hydrogen bonds. An in-house targeted microbubble modified using the biotin-avidin chemistry and the CD31 antibody was used to probe cultures of Sk-Hep1 hepatic endothelial cells. We report that the targeted microbubbles provide a single distribution of adhesion forces with a median of 93pN. This interaction is assigned to the CD31 antibody-antigen unbinding event. Information on the distances between the interaction forces was obtained and could be important for future microbubble fabrication. In conclusion, the capability of single microbubbles to target cell lines was shown to be feasible with AFM.

Drug Target Protein-Protein Interaction Networks: A Systematic Perspective

PubMed Central

2017-01-01

The identification and validation of drug targets are crucial in biomedical research and many studies have been conducted on analyzing drug target features for getting a better understanding on principles of their mechanisms. But most of them are based on either strong biological hypotheses or the chemical and physical properties of those targets separately. In this paper, we investigated three main ways to understand the functional biomolecules based on the topological features of drug targets. There are no significant differences between targets and common proteins in the protein-protein interactions network, indicating the drug targets are neither hub proteins which are dominant nor the bridge proteins. According to some special topological structures of the drug targets, there are significant differences between known targets and other proteins. Furthermore, the drug targets mainly belong to three typical communities based on their modularity. These topological features are helpful to understand how the drug targets work in the PPI network. Particularly, it is an alternative way to predict potential targets or extract nontargets to test a new drug target efficiently and economically. By this way, a drug target's homologue set containing 102 potential target proteins is predicted in the paper. PMID:28691014

Targeted Therapies in NSCLC: Emerging oncogene targets following the success of EGFR

PubMed Central

Berge, Eamon M; Doebele, Robert C

2014-01-01

The diagnostic testing, treatment and prognosis of non-small cell lung cancer (NSCLC) has undergone a paradigm shift since the discovery of sensitizing mutations in the epidermal growth factor receptor (EGFR) gene in a subset of NSCLC patients. Several additional oncogenic mutations, including gene fusions and amplifications have since been discovered, with a number of drugs that target each specific oncogene. This review focuses on oncogenes in NSCLC other than EGFR and their companion ‘targeted therapies’. Particular emphasis is placed on the role of ALK, ROS1, RET, MET, BRAF, and HER2 in NSCLC. PMID:24565585

Targeting legume loci: A comparison of three methods for target enrichment bait design in Leguminosae phylogenomics.

PubMed

Vatanparast, Mohammad; Powell, Adrian; Doyle, Jeff J; Egan, Ashley N

2018-03-01

The development of pipelines for locus discovery has spurred the use of target enrichment for plant phylogenomics. However, few studies have compared pipelines from locus discovery and bait design, through validation, to tree inference. We compared three methods within Leguminosae (Fabaceae) and present a workflow for future efforts. Using 30 transcriptomes, we compared Hyb-Seq, MarkerMiner, and the Yang and Smith (Y&S) pipelines for locus discovery, validated 7501 baits targeting 507 loci across 25 genera via Illumina sequencing, and inferred gene and species trees via concatenation- and coalescent-based methods. Hyb-Seq discovered loci with the longest mean length. MarkerMiner discovered the most conserved loci with the least flagged as paralogous. Y&S offered the most parsimony-informative sites and putative orthologs. Target recovery averaged 93% across taxa. We optimized our targeted locus set based on a workflow designed to minimize paralog/ortholog conflation and thus present 423 loci for legume phylogenomics. Methods differed across criteria important for phylogenetic marker development. We recommend Hyb-Seq as a method that may be useful for most phylogenomic projects. Our targeted locus set is a resource for future, community-driven efforts to reconstruct the legume tree of life.

Targeted adenoviral vectors

NASA Astrophysics Data System (ADS)

Douglas, Joanne T.

The practical implementation of gene therapy in the clinical setting mandates gene delivery vehicles, or vectors, capable of efficient gene delivery selectively to the target disease cells. The utility of adenoviral vectors for gene therapy is restricted by their dependence on the native adenoviral primary cellular receptor for cell entry. Therefore, a number of strategies have been developed to allow CAR-independent infection of specific cell types, including the use of bispecific conjugates and genetic modifications to the adenoviral capsid proteins, in particular the fibre protein. These targeted adenoviral vectors have demonstrated efficient gene transfer in vitro , correlating with a therapeutic benefit in preclinical animal models. Such vectors are predicted to possess enhanced efficacy in human clinical studies, although anatomical barriers to their use must be circumvented.

Enhanced target normal sheath acceleration of protons from intense laser interaction with a cone-tube target

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

Xiao, K. D.; Huang, T. W.; Zhou, C. T., E-mail: zcangtao@iapcm.ac.cn

2016-01-15

Laser driven proton acceleration is proposed to be greatly enhanced by using a cone-tube target, which can be easily manufactured by current 3D-print technology. It is observed that energetic electron bunches are generated along the tube and accelerated to a much higher temperature by the combination of ponderomotive force and longitudinal electric field which is induced by the optical confinement of the laser field. As a result, a localized and enhanced sheath field is produced at the rear of the target and the maximum proton energy is about three-fold increased based on the two-dimentional particle-in-cell simulation results. It is demonstratedmore » that by employing this advanced target scheme, the scaling of the proton energy versus the laser intensity is much beyond the normal target normal sheath acceleration (TNSA) case.« less

Manifold structure preservative for hyperspectral target detection

NASA Astrophysics Data System (ADS)

Imani, Maryam

2018-05-01

A nonparametric method termed as manifold structure preservative (MSP) is proposed in this paper for hyperspectral target detection. MSP transforms the feature space of data to maximize the separation between target and background signals. Moreover, it minimizes the reconstruction error of targets and preserves the topological structure of data in the projected feature space. MSP does not need to consider any distribution for target and background data. So, it can achieve accurate results in real scenarios due to avoiding unreliable assumptions. The proposed MSP detector is compared to several popular detectors and the experiments on a synthetic data and two real hyperspectral images indicate the superior ability of it in target detection.

Striatal activity is modulated by target probability.

PubMed

Hon, Nicholas

2017-06-14

Target probability has well-known neural effects. In the brain, target probability is known to affect frontal activity, with lower probability targets producing more prefrontal activation than those that occur with higher probability. Although the effect of target probability on cortical activity is well specified, its effect on subcortical structures such as the striatum is less well understood. Here, I examined this issue and found that the striatum was highly responsive to target probability. This is consistent with its hypothesized role in the gating of salient information into higher-order task representations. The current data are interpreted in light of that fact that different components of the striatum are sensitive to different types of task-relevant information.

Shock effects in particle beam fusion targets

NASA Astrophysics Data System (ADS)

Sweeney, M. A.; Perry, F. C.; Asay, J. R.; Widner, M. M.

1982-04-01

At Sandia National Laboratorics we are assessing the response of fusion target materials to shock loading with the particle beam accelerators HYDRA and PROTO I and the gas gun facility. Nonlinear shock-accelerated unstable growth of fabriction irregularities has been demonstrated, and jetting is found to occur in imploding targets because of asymmetric beam deposition. Cylindrical ion targets display an instability due either to beam or target nonuniformity. However, the data suggest targets with aspect ratios of 30 may implode stably. The first time- and space-resolved measurements of shock-induced vaporization have been made. A homogeneous mixed phase EOS model cannot adequately explain the results because of the kinetic effects of vapor formation and expansion.

A dual-targeting liposome conjugated with transferrin and arginine-glycine-aspartic acid peptide for glioma-targeting therapy.

PubMed

Qin, Li; Wang, Cheng-Zheng; Fan, Hui-Jie; Zhang, Chong-Jian; Zhang, Heng-Wei; Lv, Min-Hao; Cui, Shu-DE

2014-11-01

The treatment of a brain glioma remains one of the most difficult challenges in oncology. In the present study a delivery system was developed for targeted drug delivery across the blood-brain barrier (BBB) to the brain cancer cells. A cyclic arginine-glycine-aspartic acid (RGD) peptide and transferrin (TF) were utilized as targeting ligands. Cyclic RGD peptides are specific targeting ligands of cancer cells and TFs are ligands that specifically target the BBB and cancer cells. Liposome (LP) was used to conjugate the cyclic RGD and TFs to establish the brain glioma cascade delivery system (RGD/TF-LP). The LPs were prepared by the thin film hydration method and physicochemical characterization was conducted. In vitro cell uptake and three-dimensional tumor spheroid penetration studies demonstrated that the system could target endothelial and tumor cells, as well as penetrate the tumor cells to reach the core of the tumor spheroids. The results of the in vivo imaging further demonstrated that the RGD/TF-LP provided the highest brain distribution. As a result, the paclitaxel-loaded RGD/TF-LP presents the best antiproliferative activity against C6 cells and tumor spheroids. In conclusion, the RGD/TF-LP may precisely target brain glioma, which may be valuable for glioma imaging and therapy.

Similar clinical benefits from below-target and target dose enalapril in patients with heart failure in the SOLVD Treatment trial.

PubMed

Lam, Phillip H; Dooley, Daniel J; Fonarow, Gregg C; Butler, Javed; Bhatt, Deepak L; Filippatos, Gerasimos S; Deedwania, Prakash; Forman, Daniel E; White, Michel; Fletcher, Ross D; Arundel, Cherinne; Blackman, Marc R; Adamopoulos, Chris; Kanonidis, Ioannis E; Aban, Inmaculada B; Patel, Kanan; Aronow, Wilbert S; Allman, Richard M; Anker, Stefan D; Pitt, Bertram; Ahmed, Ali

2018-02-01

To examine associations of below-target and target dose of enalapril, an angiotensin-converting enzyme (ACE) inhibitor, with outcomes in patients with heart failure and reduced ejection fraction (HFrEF) in the Studies of Left Ventricular Dysfunction (SOLVD) Treatment trial. Two thousand five hundred and sixty-nine patients with HFrEF (ejection fraction ≤35%) were randomized to below-target (5-10 mg/day) dose placebo (n = 1284) or enalapril (n = 1285). One month post-randomization, blind up-titration to target (20 mg/day) dose was attempted for both study drugs in 2458 patients. Among the 1444 patients who achieved dose up-titration (placebo, n = 748; enalapril, n = 696; mean dose for both groups, 20.0 mg/day), target dose enalapril (vs. target dose placebo) was associated with a 9% absolute lower risk of the combined endpoint of heart failure hospitalization or all-cause mortality [adjusted hazard ratio (HR) 0.70; 95% confidence interval (CI) 0.60-0.81; P < 0.001] during 4 years of follow-up. Among the 1014 patients who could not achieve target dose (placebo, n = 486; enalapril, n = 528; mean dose for both groups, 8.8 mg/day), below-target dose enalapril (vs. below-target dose placebo) was associated with a 12% absolute lower risk of the combined endpoint of heart failure hospitalization or all-cause mortality (adjusted HR 0.68; 95% CI 0.57-0.81; P < 0.001). Among the 1224 patients receiving enalapril, target (vs. below-target) dose had no association with the combined endpoint of heart failure hospitalization or all-cause mortality (adjusted HR 1.04; 95% CI 0.87-1.23; P = 0.695). In patients with HFrEF, the clinical benefits of ACE inhibitors appear to be similar at both below-target and target doses. © 2017 The Authors. European Journal of Heart Failure © 2017 European Society of Cardiology.

Thermal targets for satellite calibration

NASA Astrophysics Data System (ADS)

Villa-Aleman, Eliel; Garrett, Alfred J.; Kurzeja, Robert J.; O'Steen, Byron L.; Pendergast, Malcolm M.

2001-03-01

The Savannah River Technology Center (SRTC) is currently calibrating the Multispectral Thermal Imager (MTI) satellite sponsored by the Department of Energy. The MTI imager is a research and development project with 15 wavebands in the visible, near-infrared, short-wave infrared, mid-wave infrared and long-wave infrared spectral regions. A plethora of targets with known temperatures such as power plant heated lakes, volcano lava vents, desert playas and aluminized Mylar tarps are being used in the validation of the five thermal bands of the MTI satellite. SRTC efforts in the production of cold targets with aluminized Mylar tarps will be described. Visible and thermal imagery and wavelength dependent radiance measurements of the calibration targets will be presented.

Automatic measurement of target crossing speed

NASA Astrophysics Data System (ADS)

Wardell, Mark; Lougheed, James H.

1992-11-01

The motion of ground vehicle targets after a ballistic round is launched can be a major source of inaccuracy for small (handheld) anti-armour weapon systems. A method of automatically measuring the crossing component to compensate the fire control solution has been devised and tested against various targets in a range of environments. A photodetector array aligned with the sight's horizontal reticle obtains scene features, which are digitized and processed to separate target from sight motion. Relative motion of the target against the background is briefly monitored to deduce angular crossing rate and a compensating lead angle is introduced into the aim point. Research to gather quantitative data and optimize algorithm performance is described, and some results from field testing are presented.

Frnakenstein: multiple target inverse RNA folding.

PubMed

Lyngsø, Rune B; Anderson, James W J; Sizikova, Elena; Badugu, Amarendra; Hyland, Tomas; Hein, Jotun

2012-10-09

RNA secondary structure prediction, or folding, is a classic problem in bioinformatics: given a sequence of nucleotides, the aim is to predict the base pairs formed in its three dimensional conformation. The inverse problem of designing a sequence folding into a particular target structure has only more recently received notable interest. With a growing appreciation and understanding of the functional and structural properties of RNA motifs, and a growing interest in utilising biomolecules in nano-scale designs, the interest in the inverse RNA folding problem is bound to increase. However, whereas the RNA folding problem from an algorithmic viewpoint has an elegant and efficient solution, the inverse RNA folding problem appears to be hard. In this paper we present a genetic algorithm approach to solve the inverse folding problem. The main aims of the development was to address the hitherto mostly ignored extension of solving the inverse folding problem, the multi-target inverse folding problem, while simultaneously designing a method with superior performance when measured on the quality of designed sequences. The genetic algorithm has been implemented as a Python program called Frnakenstein. It was benchmarked against four existing methods and several data sets totalling 769 real and predicted single structure targets, and on 292 two structure targets. It performed as well as or better at finding sequences which folded in silico into the target structure than all existing methods, without the heavy bias towards CG base pairs that was observed for all other top performing methods. On the two structure targets it also performed well, generating a perfect design for about 80% of the targets. Our method illustrates that successful designs for the inverse RNA folding problem does not necessarily have to rely on heavy biases in base pair and unpaired base distributions. The design problem seems to become more difficult on larger structures when the target structures are

Frnakenstein: multiple target inverse RNA folding

PubMed Central

2012-01-01

Background RNA secondary structure prediction, or folding, is a classic problem in bioinformatics: given a sequence of nucleotides, the aim is to predict the base pairs formed in its three dimensional conformation. The inverse problem of designing a sequence folding into a particular target structure has only more recently received notable interest. With a growing appreciation and understanding of the functional and structural properties of RNA motifs, and a growing interest in utilising biomolecules in nano-scale designs, the interest in the inverse RNA folding problem is bound to increase. However, whereas the RNA folding problem from an algorithmic viewpoint has an elegant and efficient solution, the inverse RNA folding problem appears to be hard. Results In this paper we present a genetic algorithm approach to solve the inverse folding problem. The main aims of the development was to address the hitherto mostly ignored extension of solving the inverse folding problem, the multi-target inverse folding problem, while simultaneously designing a method with superior performance when measured on the quality of designed sequences. The genetic algorithm has been implemented as a Python program called Frnakenstein. It was benchmarked against four existing methods and several data sets totalling 769 real and predicted single structure targets, and on 292 two structure targets. It performed as well as or better at finding sequences which folded in silico into the target structure than all existing methods, without the heavy bias towards CG base pairs that was observed for all other top performing methods. On the two structure targets it also performed well, generating a perfect design for about 80% of the targets. Conclusions Our method illustrates that successful designs for the inverse RNA folding problem does not necessarily have to rely on heavy biases in base pair and unpaired base distributions. The design problem seems to become more difficult on larger structures

40 CFR 156.85 - Non-target organisms.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 40 Protection of Environment 23 2010-07-01 2010-07-01 false Non-target organisms. 156.85 Section 156.85 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) PESTICIDE PROGRAMS... Non-target organisms. (a) Requirement. Where a hazard exists to non-target organisms, EPA may require...

40 CFR 156.85 - Non-target organisms.

Code of Federal Regulations, 2011 CFR

2011-07-01

... 40 Protection of Environment 24 2011-07-01 2011-07-01 false Non-target organisms. 156.85 Section 156.85 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) PESTICIDE PROGRAMS... Non-target organisms. (a) Requirement. Where a hazard exists to non-target organisms, EPA may require...

Hybrid-drive implosion system for ICF targets

DOEpatents

Mark, James W.

1988-08-02

Hybrid-drive implosion systems (20,40) for ICF targets (10,22,42) are described which permit a significant increase in target gain at fixed total driver energy. The ICF target is compressed in two phases, an initial compression phase and a final peak power phase, with each phase driven by a separate, optimized driver. The targets comprise a hollow spherical ablator (12) surroundingly disposed around fusion fuel (14). The ablator is first compressed to higher density by a laser system (24), or by an ion beam system (44), that in each case is optimized for this initial phase of compression of the target. Then, following compression of the ablator, energy is directly delivered into the compressed ablator by an ion beam driver system (30,48) that is optimized for this second phase of operation of the target. The fusion fuel (14) is driven, at high gain, to conditions wherein fusion reactions occur. This phase separation allows hydrodynamic efficiency and energy deposition uniformity to be individually optimized, thereby securing significant advantages in energy gain. In additional embodiments, the same or separate drivers supply energy for ICF target implosion.

Hybrid-drive implosion system for ICF targets

DOEpatents

Mark, James W.

1988-01-01

Hybrid-drive implosion systems (20,40) for ICF targets (10,22,42) are described which permit a significant increase in target gain at fixed total driver energy. The ICF target is compressed in two phases, an initial compression phase and a final peak power phase, with each phase driven by a separate, optimized driver. The targets comprise a hollow spherical ablator (12) surroundingly disposed around fusion fuel (14). The ablator is first compressed to higher density by a laser system (24), or by an ion beam system (44), that in each case is optimized for this initial phase of compression of the target. Then, following compression of the ablator, energy is directly delivered into the compressed ablator by an ion beam driver system (30,48) that is optimized for this second phase of operation of the target. The fusion fuel (14) is driven, at high gain, to conditions wherein fusion reactions occur. This phase separation allows hydrodynamic efficiency and energy deposition uniformity to be individually optimized, thereby securing significant advantages in energy gain. In additional embodiments, the same or separate drivers supply energy for ICF target implosion.

Design of the LBNF Beamline Target Station

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

Tariq, S.; Ammigan, K.; Anderson, K.

2016-10-01

The Long Baseline Neutrino Facility (LBNF) project will build a beamline located at Fermilab to create and aim an intense neutrino beam of appropriate energy range toward the DUNE detectors at the SURF facility in Lead, South Dakota. Neutrino production starts in the Target Station, which consists of a solid target, magnetic focusing horns, and the associated sub-systems and shielding infrastructure. Protons hit the target producing mesons which are then focused by the horns into a helium-filled decay pipe where they decay into muons and neutrinos. The target and horns are encased in actively cooled steel and concrete shielding inmore » a chamber called the target chase. The reference design chase is filled with air, but nitrogen and helium are being evaluated as alternatives. A replaceable beam window separates the decay pipe from the target chase. The facility is designed for initial operation at 1.2 MW, with the ability to upgrade to 2.4 MW, and is taking advantage of the experience gained by operating Fermilab’s NuMI facility. We discuss here the design status, associated challenges, and ongoing R&D and physics-driven component optimization of the Target Station.« less

Novel GABA receptor pesticide targets.

PubMed

Casida, John E; Durkin, Kathleen A

2015-06-01

The γ-aminobutyric acid (GABA) receptor has four distinct but overlapping and coupled targets of pesticide action importantly associated with little or no cross-resistance. The target sites are differentiated by binding assays with specific radioligands, resistant strains, site-directed mutagenesis and molecular modeling. Three of the targets are for non-competitive antagonists (NCAs) or channel blockers of widely varied chemotypes. The target of the first generation (20th century) NCAs differs between the larger or elongated compounds (NCA-IA) including many important insecticides of the past (cyclodienes and polychlorocycloalkanes) or present (fiproles) and the smaller or compact compounds (NCA-IB) highly toxic to mammals and known as cage convulsants, rodenticides or chemical threat agents. The target of greatest current interest is designated NCA-II for the second generation (21st century) of NCAs consisting for now of isoxazolines and meta-diamides. This new and uniquely different NCA-II site apparently differs enough between insects and mammals to confer selective toxicity. The fourth target is the avermectin site (AVE) for allosteric modulators of the chloride channel. NCA pesticides vary in molecular surface area and solvent accessible volume relative to avermectin with NCA-IBs at 20-22%, NCA-IAs at 40-45% and NCA-IIs at 57-60%. The same type of relationship relative to ligand-docked length is 27-43% for NCA-IBs, 63-71% for NCA-IAs and 85-105% for NCA-IIs. The four targets are compared by molecular modeling for the Drosophila melanogaster GABA-R. The principal sites of interaction are proposed to be: pore V1' and A2' for NCA-IB compounds; pore A2', L6' and T9' for NCA-IA compounds; pore T9' to S15' in proximity to M1/M3 subunit interface (or alternatively an interstitial site) for NCA-II compounds; and M1/M3, M2 interfaces for AVE. Understanding the relationships of these four binding sites is important in resistance management and in the discovery and use

Divertor target for magnetic containment device

DOEpatents

Luzzi, Jr., Theodore E.

1982-01-01

In a plasma containment device of a type having superconducting field coils for magnetically shaping the plasma into approximately the form of a torus, an improved divertor target for removing impurities from a "scrape off" region of the plasma comprises an array of water cooled swirl tubes onto which the scrape off flux is impinged. Impurities reflected from the divertor target are removed from the target region by a conventional vacuum getter system. The swirl tubes are oriented and spaced apart within the divertor region relative to the incident angle of the scrape off flux to cause only one side of each tube to be exposed to the flux to increase the burnout rating of the target. The divertor target plane is oriented relative to the plane of the path of the scrape off flux such that the maximum heat flux onto a swirl tube is less than the tube design flux. The containment device is used to contain the plasma of a tokamak fusion reactor and is applicable to other long pulse plasma containment systems.

The SPES High Power ISOL production target

NASA Astrophysics Data System (ADS)

Andrighetto, A.; Corradetti, S.; Ballan, M.; Borgna, F.; Manzolaro, M.; Scarpa, D.; Monetti, A.; Rossignoli, M.; Silingardi, R.; Mozzi, A.; Vivian, G.; Boratto, E.; De Ruvo, L.; Sattin, N.; Meneghetti, G.; Oboe, R.; Guerzoni, M.; Margotti, A.; Ferrari, M.; Zenoni, A.; Prete, G.

2016-11-01

SPES (Selective Production of Exotic Species) is a facility under construction at INFN-LNL (Istituto Nazionale di Fisica Nucleare - Laboratori Nazionali di Legnaro), aimed to produce intense neutron-rich radioactive ion beams (RIBs). These will be obtained using the ISOL (Isotope Separation On-Line) method, bombarding a uranium carbide target with a proton beam of 40MeV energy and currents up to 200μA. The target configuration was designed to obtain a high number of fissions, up to 1013 per second, low power deposition and fast release of the produced isotopes. The exotic isotopes generated in the target are ionized, mass separated and re-accelerated by the ALPI superconducting LINAC at energies of 10AMeV and higher, for masses in the region of A = 130 amu , with an expected rate on the secondary target up to 109 particles per second. In this work, recent results on the R&D activities regarding the SPES RIB production target-ion source system are reported.

Game theoretic sensor management for target tracking

NASA Astrophysics Data System (ADS)

Shen, Dan; Chen, Genshe; Blasch, Erik; Pham, Khanh; Douville, Philip; Yang, Chun; Kadar, Ivan

2010-04-01

This paper develops and evaluates a game-theoretic approach to distributed sensor-network management for target tracking via sensor-based negotiation. We present a distributed sensor-based negotiation game model for sensor management for multi-sensor multi-target tacking situations. In our negotiation framework, each negotiation agent represents a sensor and each sensor maximizes their utility using a game approach. The greediness of each sensor is limited by the fact that the sensor-to-target assignment efficiency will decrease if too many sensor resources are assigned to a same target. It is similar to the market concept in real world, such as agreements between buyers and sellers in an auction market. Sensors are willing to switch targets so that they can obtain their highest utility and the most efficient way of applying their resources. Our sub-game perfect equilibrium-based negotiation strategies dynamically and distributedly assign sensors to targets. Numerical simulations are performed to demonstrate our sensor-based negotiation approach for distributed sensor management.

An Improved Compressive Sensing and Received Signal Strength-Based Target Localization Algorithm with Unknown Target Population for Wireless Local Area Networks.

PubMed

Yan, Jun; Yu, Kegen; Chen, Ruizhi; Chen, Liang

2017-05-30

In this paper a two-phase compressive sensing (CS) and received signal strength (RSS)-based target localization approach is proposed to improve position accuracy by dealing with the unknown target population and the effect of grid dimensions on position error. In the coarse localization phase, by formulating target localization as a sparse signal recovery problem, grids with recovery vector components greater than a threshold are chosen as the candidate target grids. In the fine localization phase, by partitioning each candidate grid, the target position in a grid is iteratively refined by using the minimum residual error rule and the least-squares technique. When all the candidate target grids are iteratively partitioned and the measurement matrix is updated, the recovery vector is re-estimated. Threshold-based detection is employed again to determine the target grids and hence the target population. As a consequence, both the target population and the position estimation accuracy can be significantly improved. Simulation results demonstrate that the proposed approach achieves the best accuracy among all the algorithms compared.

Lifting wavelet method of target detection

NASA Astrophysics Data System (ADS)

Han, Jun; Zhang, Chi; Jiang, Xu; Wang, Fang; Zhang, Jin

2009-11-01

Image target recognition plays a very important role in the areas of scientific exploration, aeronautics and space-to-ground observation, photography and topographic mapping. Complex environment of the image noise, fuzzy, all kinds of interference has always been to affect the stability of recognition algorithm. In this paper, the existence of target detection in real-time, accuracy problems, as well as anti-interference ability, using lifting wavelet image target detection methods. First of all, the use of histogram equalization, the goal difference method to obtain the region, on the basis of adaptive threshold and mathematical morphology operations to deal with the elimination of the background error. Secondly, the use of multi-channel wavelet filter wavelet transform of the original image de-noising and enhancement, to overcome the general algorithm of the noise caused by the sensitive issue of reducing the rate of miscarriage of justice will be the multi-resolution characteristics of wavelet and promotion of the framework can be designed directly in the benefits of space-time region used in target detection, feature extraction of targets. The experimental results show that the design of lifting wavelet has solved the movement of the target due to the complexity of the context of the difficulties caused by testing, which can effectively suppress noise, and improve the efficiency and speed of detection.

Cancer-linked targets modulated by curcumin

PubMed Central

Hasima, Noor; Aggarwal, Bharat B

2012-01-01

In spite of major advances in oncology, the World Health Organization predicts that cancer incidence will double within the next two decades. Although it is well understood that cancer is a hyperproliferative disorder mediated through dysregulation of multiple cell signaling pathways, most cancer drug development remains focused on modulation of specific targets, mostly one at a time, with agents referred to as “targeted therapies,” “smart drugs,” or “magic bullets.” How many cancer targets there are is not known, and how many targets must be attacked to control cancer growth is not well understood. Although more than 90% of cancer-linked deaths are due to metastasis of the tumor to vital organs, most drug targeting is focused on killing the primary tumor. Besides lacking specificity, the targeted drugs induce toxicity and side effects that sometimes are greater problems than the disease itself. Furthermore, the cost of some of these drugs is so high that most people cannot afford them. The present report describes the potential anticancer properties of curcumin, a component of the Indian spice turmeric (Curcuma longa), known for its safety and low cost. Curcumin can selectively modulate multiple cell signaling pathways linked to inflammation and to survival, growth, invasion, angiogenesis, and metastasis of cancer cells. More clinical trials of curcumin are needed to prove its usefulness in the cancer setting. PMID:23301199

Robust infrared targets tracking with covariance matrix representation

NASA Astrophysics Data System (ADS)

Cheng, Jian

2009-07-01

Robust infrared target tracking is an important and challenging research topic in many military and security applications, such as infrared imaging guidance, infrared reconnaissance, scene surveillance, etc. To effectively tackle the nonlinear and non-Gaussian state estimation problems, particle filtering is introduced to construct the theory framework of infrared target tracking. Under this framework, the observation probabilistic model is one of main factors for infrared targets tracking performance. In order to improve the tracking performance, covariance matrices are introduced to represent infrared targets with the multi-features. The observation probabilistic model can be constructed by computing the distance between the reference target's and the target samples' covariance matrix. Because the covariance matrix provides a natural tool for integrating multiple features, and is scale and illumination independent, target representation with covariance matrices can hold strong discriminating ability and robustness. Two experimental results demonstrate the proposed method is effective and robust for different infrared target tracking, such as the sensor ego-motion scene, and the sea-clutter scene.

Targeting the right journal.

PubMed

Piterman, L; McCall, L

1999-07-01

While research is scientific, publication is a mixture of science and political pragmatism. Targeting the right journal is influenced by the following factors: the discipline that best represents the subject; the purpose of the message; the audience who are to be recipients of the message; the realities of geographic parochialism; the desire of authors to maximise personal and professional opportunities. If the originally targeted journal rejects the article, authors should have alternative publication strategies that give them professional recognition without requiring them to compromise the message or their ethics.

Bypassing Protein Corona Issue on Active Targeting: Zwitterionic Coatings Dictate Specific Interactions of Targeting Moieties and Cell Receptors.

PubMed

Safavi-Sohi, Reihaneh; Maghari, Shokoofeh; Raoufi, Mohammad; Jalali, Seyed Amir; Hajipour, Mohammad J; Ghassempour, Alireza; Mahmoudi, Morteza

2016-09-07

Surface functionalization strategies for targeting nanoparticles (NP) to specific organs, cells, or organelles, is the foundation for new applications of nanomedicine to drug delivery and biomedical imaging. Interaction of NPs with biological media leads to the formation of a biomolecular layer at the surface of NPs so-called as "protein corona". This corona layer can shield active molecules at the surface of NPs and cause mistargeting or unintended scavenging by the liver, kidney, or spleen. To overcome this corona issue, we have designed biotin-cysteine conjugated silica NPs (biotin was employed as a targeting molecule and cysteine was used as a zwitterionic ligand) to inhibit corona-induced mistargeting and thus significantly enhance the active targeting capability of NPs in complex biological media. To probe the targeting yield of our engineered NPs, we employed both modified silicon wafer substrates with streptavidin (i.e., biotin receptor) to simulate a target and a cell-based model platform using tumor cell lines that overexpress biotin receptors. In both cases, after incubation with human plasma (thus forming a protein corona), cellular uptake/substrate attachment of the targeted NPs with zwitterionic coatings were significantly higher than the same NPs without zwitterionic coating. Our results demonstrated that NPs with a zwitterionic surface can considerably facilitate targeting yield of NPs and provide a promising new type of nanocarriers in biological applications.

Gene silencing in Tribolium castaneum as a tool for the targeted identification of candidate RNAi targets in crop pests.

PubMed

Knorr, Eileen; Fishilevich, Elane; Tenbusch, Linda; Frey, Meghan L F; Rangasamy, Murugesan; Billion, Andre; Worden, Sarah E; Gandra, Premchand; Arora, Kanika; Lo, Wendy; Schulenberg, Greg; Valverde-Garcia, Pablo; Vilcinskas, Andreas; Narva, Kenneth E

2018-02-01

RNAi shows potential as an agricultural technology for insect control, yet, a relatively low number of robust lethal RNAi targets have been demonstrated to control insects of agricultural interest. In the current study, a selection of lethal RNAi target genes from the iBeetle (Tribolium castaneum) screen were used to demonstrate efficacy of orthologous targets in the economically important coleopteran pests Diabrotica virgifera virgifera and Meligethes aeneus. Transcript orthologs of 50 selected genes were analyzed in D. v. virgifera diet-based RNAi bioassays; 21 of these RNAi targets showed mortality and 36 showed growth inhibition. Low dose injection- and diet-based dsRNA assays in T. castaneum and D. v. virgifera, respectively, enabled the identification of the four highly potent RNAi target genes: Rop, dre4, ncm, and RpII140. Maize was genetically engineered to express dsRNA directed against these prioritized candidate target genes. T 0 plants expressing Rop, dre4, or RpII140 RNA hairpins showed protection from D. v. virgifera larval feeding damage. dsRNA targeting Rop, dre4, ncm, and RpII140 in M. aeneus also caused high levels of mortality both by injection and feeding. In summary, high throughput systems for model organisms can be successfully used to identify potent RNA targets for difficult-to-work with agricultural insect pests.

ACCELERATOR TARGET POSITIONER AND CONTROL CIRCUIT THEREFOR

DOEpatents

Stone, K.F.; Force, R.J.; Olson, W.W.; Cagle, D.S.

1959-12-15

An apparatus is described for inserting and retracting a target material with respect to the internal beam of a charged particle accelerator and to circuitry for controlling the timing and motion of the target placement. Two drive coils are mounted on the shaft of a target holder arm and disposed within the accelerator magnetic field with one coil at right angles to the other. Control circuitry alternately connects each coil to a current source and to a varying shorting resistance whereby the coils interchangeably produce driving and braking forces which swing the target arm within a ninety degree arc. The target is thus moved into the beam and away from it at high speeds and is brought to rest after each movement without whiplash or vibration.

Tumor-targeted nanomedicines for cancer theranostics

PubMed Central

Lammers, Twan; Shi, Yang

2017-01-01

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

A Theory of Eye Movements during Target Acquisition

ERIC Educational Resources Information Center

Zelinsky, Gregory J.

2008-01-01

The gaze movements accompanying target localization were examined via human observers and a computational model (target acquisition model [TAM]). Search contexts ranged from fully realistic scenes to toys in a crib to Os and Qs, and manipulations included set size, target eccentricity, and target-distractor similarity. Observers and the model…

Tracking moving radar targets with parallel, velocity-tuned filters

DOEpatents

Bickel, Douglas L.; Harmony, David W.; Bielek, Timothy P.; Hollowell, Jeff A.; Murray, Margaret S.; Martinez, Ana

2013-04-30

Radar data associated with radar illumination of a movable target is processed to monitor motion of the target. A plurality of filter operations are performed in parallel on the radar data so that each filter operation produces target image information. The filter operations are defined to have respectively corresponding velocity ranges that differ from one another. The target image information produced by one of the filter operations represents the target more accurately than the target image information produced by the remainder of the filter operations when a current velocity of the target is within the velocity range associated with the one filter operation. In response to the current velocity of the target being within the velocity range associated with the one filter operation, motion of the target is tracked based on the target image information produced by the one filter operation.

Theranostics Targeting Metastatic Breast Cancer

DTIC Science & Technology

2017-10-01

AWARD NUMBER: W81XWH-15-1-0389 TITLE: Theranostics Targeting Metastatic Breast Cancer PRINCIPAL INVESTIGATOR: Kevin Burgess CONTRACTING...ADDRESS. 1. REPORT DATE October 2017 2. REPORT TYPE Annual 3. DATES COVERED 4. TITLE AND SUBTITLE Theranostics Targeting Metastatic Breast Cancer 5a...safe and effective interventions; (ii) elimination of mortality associated with metastatic breast cancer ; and, (iii) distinguishing aggressive breast

Synthetic aperture radar target simulator

NASA Technical Reports Server (NTRS)

Zebker, H. A.; Held, D. N.; Goldstein, R. M.; Bickler, T. C.

1984-01-01

A simulator for simulating the radar return, or echo, from a target seen by a SAR antenna mounted on a platform moving with respect to the target is described. It includes a first-in first-out memory which has digital information clocked in at a rate related to the frequency of a transmitted radar signal and digital information clocked out with a fixed delay defining range between the SAR and the simulated target, and at a rate related to the frequency of the return signal. An RF input signal having a frequency similar to that utilized by a synthetic aperture array radar is mixed with a local oscillator signal to provide a first baseband signal having a frequency considerably lower than that of the RF input signal.

N-terminal domain of the dual-targeted pea glutathione reductase signal peptide controls organellar targeting efficiency.

PubMed

Rudhe, Charlotta; Clifton, Rachel; Whelan, James; Glaser, Elzbieta

2002-12-06

Import of nuclear-encoded proteins into mitochondria and chloroplasts is generally organelle specific and its specificity depends on the N-terminal signal peptide. Yet, a group of proteins known as dual-targeted proteins have a targeting peptide capable of leading the mature protein to both organelles. We have investigated the domain structure of the dual-targeted pea glutathione reductase (GR) signal peptide by using N-terminal truncations. A mutant of the GR precursor (pGR) starting with the second methionine residue of the targeting peptide, pGRdelta2-4, directed import into both organelles, negating the possibility that dual import was controlled by the nature of the N terminus. The deletion of the 30 N-terminal residues (pGRdelta2-30) inhibited import efficiency into chloroplasts substantially and almost completely into mitochondria, whereas the removal of only 16 N-terminal amino acid residues (pGRdelta2-16) resulted in the strongly stimulated mitochondrial import without significantly affecting chloroplast import. Furthermore, N-terminal truncations of the signal peptide (pGRdelta2-16 and pGRdelta2-30) greatly stimulated the mitochondrial processing activity measured with the isolated processing peptidase. These results suggest a domain structure for the dual-targeting peptide of pGR and the existence of domains controlling organellar import efficiency therein.

Magnetic confinement system using charged ammonia targets

DOEpatents

Porter, Gary D.; Bogdanoff, Anatoly

1979-01-01

A system for guiding charged laser targets to a predetermined focal spot of a laser along generally arbitrary, and especially horizontal, directions which comprises a series of electrostatic sensors which provide inputs to a computer for real time calculation of position, velocity, and direction of the target along an initial injection trajectory, and a set of electrostatic deflection means, energized according to a calculated output of said computer, to change the target trajectory to intercept the focal spot of the laser which is triggered so as to illuminate the target of the focal spot.

Targeting tumor highly-expressed LAT1 transporter with amino acid-modified nanoparticles: Toward a novel active targeting strategy in breast cancer therapy.

PubMed

Li, Lin; Di, Xingsheng; Wu, Mingrui; Sun, Zhisu; Zhong, Lu; Wang, Yongjun; Fu, Qiang; Kan, Qiming; Sun, Jin; He, Zhonggui

2017-04-01

Designing active targeting nanocarriers with increased cellular accumulation of chemotherapeutic agents is a promising strategy in cancer therapy. Herein, we report a novel active targeting strategy based on the large amino acid transporter 1 (LAT1) overexpressed in a variety of cancers. Glutamate was conjugated to polyoxyethylene stearate as a targeting ligand to achieve LAT1-targeting PLGA nanoparticles. The targeting efficiency of nanoparticles was investigated in HeLa and MCF-7 cells. Significant increase in cellular uptake and cytotoxicity was observed in LAT1-targeting nanoparticles compared to the unmodified ones. More interestingly, the internalized LAT1 together with targeting nanoparticles could recycle back to the cell membrane within 3 h, guaranteeing sufficient transporters on cell membrane for continuous cellular uptake. The LAT1 targeting nanoparticles exhibited better tumor accumulation and antitumor effects. These results suggested that the overexpressed LAT1 on cancer cells holds a great potential to be a high-efficiency target for the rational design of active-targeting nanosystems. Copyright © 2016 Elsevier Inc. All rights reserved.

Tumor target amplification: Implications for nano drug delivery systems.

PubMed

Seidi, Khaled; Neubauer, Heidi A; Moriggl, Richard; Jahanban-Esfahlan, Rana; Javaheri, Tahereh

2018-04-10

Tumor cells overexpress surface markers which are absent from normal cells. These tumor-restricted antigenic signatures are a fundamental basis for distinguishing on-target from off-target cells for ligand-directed targeting of cancer cells. Unfortunately, tumor heterogeneity impedes the establishment of a solid expression pattern for a given target marker, leading to drastic changes in quality (availability) and quantity (number) of the target. Consequently, a subset of cancer cells remains untargeted during the course of treatment, which subsequently promotes drug-resistance and cancer relapse. Since target inefficiency is only problematic for cancer treatment and not for treatment of other pathological conditions such as viral/bacterial infections, target amplification or the generation of novel targets is key to providing eligible antigenic markers for effective targeted therapy. This review summarizes the limitations of current ligand-directed targeting strategies and provides a comprehensive overview of tumor target amplification strategies, including self-amplifying systems, dual targeting, artificial markers and peptide modification. We also discuss the therapeutic and diagnostic potential of these approaches, the underlying mechanism(s) and established methodologies, mostly in the context of different nanodelivery systems, to facilitate more effective ligand-directed cancer cell monitoring and targeting. Copyright © 2018 Elsevier B.V. All rights reserved.

Space moving target detection using time domain feature

NASA Astrophysics Data System (ADS)

Wang, Min; Chen, Jin-yong; Gao, Feng; Zhao, Jin-yu

2018-01-01

The traditional space target detection methods mainly use the spatial characteristics of the star map to detect the targets, which can not make full use of the time domain information. This paper presents a new space moving target detection method based on time domain features. We firstly construct the time spectral data of star map, then analyze the time domain features of the main objects (target, stars and the background) in star maps, finally detect the moving targets using single pulse feature of the time domain signal. The real star map target detection experimental results show that the proposed method can effectively detect the trajectory of moving targets in the star map sequence, and the detection probability achieves 99% when the false alarm rate is about 8×10-5, which outperforms those of compared algorithms.

Categorically Defined Targets Trigger Spatiotemporal Visual Attention

ERIC Educational Resources Information Center

Wyble, Brad; Bowman, Howard; Potter, Mary C.

2009-01-01

Transient attention to a visually salient cue enhances processing of a subsequent target in the same spatial location between 50 to 150 ms after cue onset (K. Nakayama & M. Mackeben, 1989). Do stimuli from a categorically defined target set, such as letters or digits, also generate transient attention? Participants reported digit targets among…

CDTI target selection criteria

NASA Technical Reports Server (NTRS)

Britt, C. L.; Davis, C. M.; Jackson, C. B.; Mcclellan, V. A.

1984-01-01

A Cockpit Display of Traffic Information (CDTI) is a cockpit instrument which provides information to the aircrew on the relative location of aircraft traffic in the vicinity of their aircraft (township). In addition, the CDTI may provide information to assist in navigation and in aircraft control. It is usually anticipated that the CDTI will be integrated with a horizontal situation indicator used for navigational purposes and/or with a weather radar display. In this study, several sets of aircraft traffic data are analyzed to determine statistics on the number of targets that will be displayed on a CDTI using various target selection criteria. Traffic data were obtained from an Atlanta Terminal Area Simulation and from radar tapes recorded at the Atlanta and Miami terminal areas. Results are given in the form of plots showing the average percentage of time (or probability) that an aircraft equipped with a CDTI would observe from 0 to 10 other aircraft on the display for range settings on the CDTI up to 30 n. mi. and using various target discrimination techniques.

Study Identifies New Lymphoma Treatment Target

Cancer.gov

NCI researchers have identified new therapeutic targets for diffuse large B-cell lymphoma. Drugs that hit these targets are under clinical development and the researchers hope to begin testing them in clinical trials of patients with DLBCL.

Radioligand Recognition of Insecticide Targets.

PubMed

Casida, John E

2018-04-04

Insecticide radioligands allow the direct recognition and analysis of the targets and mechanisms of toxic action critical to effective and safe pest control. These radioligands are either the insecticides themselves or analogs that bind at the same or coupled sites. Preferred radioligands and their targets, often in both insects and mammals, are trioxabicyclooctanes for the γ-aminobutyric acid (GABA) receptor, avermectin for the glutamate receptor, imidacloprid for the nicotinic receptor, ryanodine and chlorantraniliprole for the ryanodine receptor, and rotenone or pyridaben for NADH + ubiquinone oxidoreductase. Pyrethroids and other Na + channel modulator insecticides are generally poor radioligands due to lipophilicity and high nonspecific binding. For target site validation, the structure-activity relationships competing with the radioligand in the binding assays should be the same as that for insecticidal activity or toxicity except for rapidly detoxified or proinsecticide analogs. Once the radioligand assay is validated for relevance, it will often help define target site modifications on selection of resistant pest strains, selectivity between insects and mammals, and interaction with antidotes and other chemicals at modulator sites. Binding assays also serve for receptor isolation and photoaffinity labeling to characterize the interactions involved.

Improving scanner wafer alignment performance by target optimization

NASA Astrophysics Data System (ADS)

Leray, Philippe; Jehoul, Christiane; Socha, Robert; Menchtchikov, Boris; Raghunathan, Sudhar; Kent, Eric; Schoonewelle, Hielke; Tinnemans, Patrick; Tuffy, Paul; Belen, Jun; Wise, Rich

2016-03-01

In the process nodes of 10nm and below, the patterning complexity along with the processing and materials required has resulted in a need to optimize alignment targets in order to achieve the required precision, accuracy and throughput performance. Recent industry publications on the metrology target optimization process have shown a move from the expensive and time consuming empirical methodologies, towards a faster computational approach. ASML's Design for Control (D4C) application, which is currently used to optimize YieldStar diffraction based overlay (DBO) metrology targets, has been extended to support the optimization of scanner wafer alignment targets. This allows the necessary process information and design methodology, used for DBO target designs, to be leveraged for the optimization of alignment targets. In this paper, we show how we applied this computational approach to wafer alignment target design. We verify the correlation between predictions and measurements for the key alignment performance metrics and finally show the potential alignment and overlay performance improvements that an optimized alignment target could achieve.

A Targeting Microbubble for Ultrasound Molecular Imaging

PubMed Central

Yeh, James Shue-Min; Sennoga, Charles A.; McConnell, Ellen; Eckersley, Robert; Tang, Meng-Xing; Nourshargh, Sussan; Seddon, John M.; Haskard, Dorian O.; Nihoyannopoulos, Petros

2015-01-01

Rationale Microbubbles conjugated with targeting ligands are used as contrast agents for ultrasound molecular imaging. However, they often contain immunogenic (strept)avidin, which impedes application in humans. Although targeting bubbles not employing the biotin-(strept)avidin conjugation chemistry have been explored, only a few reached the stage of ultrasound imaging in vivo, none were reported/evaluated to show all three of the following properties desired for clinical applications: (i) low degree of non-specific bubble retention in more than one non-reticuloendothelial tissue; (ii) effective for real-time imaging; and (iii) effective for acoustic quantification of molecular targets to a high degree of quantification. Furthermore, disclosures of the compositions and methodologies enabling reproduction of the bubbles are often withheld. Objective To develop and evaluate a targeting microbubble based on maleimide-thiol conjugation chemistry for ultrasound molecular imaging. Methods and Results Microbubbles with a previously unreported generic (non-targeting components) composition were grafted with anti-E-selectin F(ab’)2 using maleimide-thiol conjugation, to produce E-selectin targeting microbubbles. The resulting targeting bubbles showed high specificity to E-selectin in vitro and in vivo. Non-specific bubble retention was minimal in at least three non-reticuloendothelial tissues with inflammation (mouse heart, kidneys, cremaster). The bubbles were effective for real-time ultrasound imaging of E-selectin expression in the inflamed mouse heart and kidneys, using a clinical ultrasound scanner. The acoustic signal intensity of the targeted bubbles retained in the heart correlated strongly with the level of E-selectin expression (|r|≥0.8), demonstrating a high degree of non-invasive molecular quantification. Conclusions Targeting microbubbles for ultrasound molecular imaging, based on maleimide-thiol conjugation chemistry and the generic composition described

Laser range profiling for small target recognition

NASA Astrophysics Data System (ADS)

Steinvall, Ove; Tulldahl, Michael

2016-05-01

The detection and classification of small surface and airborne targets at long ranges is a growing need for naval security. Long range ID or ID at closer range of small targets has its limitations in imaging due to the demand on very high transverse sensor resolution. It is therefore motivated to look for 1D laser techniques for target ID. These include vibrometry, and laser range profiling. Vibrometry can give good results but is also sensitive to certain vibrating parts on the target being in the field of view. Laser range profiling is attractive because the maximum range can be substantial, especially for a small laser beam width. A range profiler can also be used in a scanning mode to detect targets within a certain sector. The same laser can also be used for active imaging when the target comes closer and is angular resolved. The present paper will show both experimental and simulated results for laser range profiling of small boats out to 6-7 km range and a UAV mockup at close range (1.3 km). We obtained good results with the profiling system both for target detection and recognition. Comparison of experimental and simulated range waveforms based on CAD models of the target support the idea of having a profiling system as a first recognition sensor and thus narrowing the search space for the automatic target recognition based on imaging at close ranges. The naval experiments took place in the Baltic Sea with many other active and passive EO sensors beside the profiling system. Discussion of data fusion between laser profiling and imaging systems will be given. The UAV experiments were made from the rooftop laboratory at FOI.

32 CFR 644.526 - Reporting target ranges.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 32 National Defense 4 2010-07-01 2010-07-01 true Reporting target ranges. 644.526 Section 644.526... and Improvements § 644.526 Reporting target ranges. All Reports of Excess to GSA covering lands which have been used as target ranges of any kind will contain an affirmative or negative statement in regard...

32 CFR 644.526 - Reporting target ranges.

Code of Federal Regulations, 2011 CFR

2011-07-01

... 32 National Defense 4 2011-07-01 2011-07-01 false Reporting target ranges. 644.526 Section 644.526... and Improvements § 644.526 Reporting target ranges. All Reports of Excess to GSA covering lands which have been used as target ranges of any kind will contain an affirmative or negative statement in regard...

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.

Targeted nanoparticle delivery overcomes off-target immunostimulatory effects of oligonucleotides and improves therapeutic efficacy in chronic lymphocytic leukemia

PubMed Central

Yu, Bo; Mao, Yicheng; Bai, Li-Yuan; Herman, Sarah E. M.; Wang, Xinmei; Ramanunni, Asha; Jin, Yan; Mo, Xiaokui; Cheney, Carolyn; Chan, Kenneth K.; Jarjoura, David; Marcucci, Guido; Lee, Robert J.; Byrd, John C.

2013-01-01

Several RNA-targeted therapeutics, including antisense oligonucleotides (ONs), small interfering RNAs, and miRNAs, constitute immunostimulatory CpG motifs as an integral part of their design. The limited success with free antisense ONs in hematologic malignancies in recent clinical trials has been attributed to the CpG motif–mediated, TLR-induced prosurvival effects and inefficient target modulation in desired cells. In an attempt to diminish their off-target prosurvival and proinflammatory effects and specific delivery, as a proof of principle, in the present study, we developed an Ab-targeted liposomal delivery strategy using a clinically relevant CD20 Ab (rituximab)–conjugated lipopolyplex nanoparticle (RIT-INP)– and Bcl-2–targeted antisense G3139 as archetypical antisense therapeutics. The adverse immunostimulatory responses were abrogated by selective B cell–targeted delivery and early endosomal compartmentalization of G3139-encapsulated RIT-INPs, resulting in reduced NF-κB activation, robust Bcl-2 down-regulation, and enhanced sensitivity to fludarabine-induced cytotoxicity. Furthermore, significant in vivo therapeutic efficacy was noted after RIT-INP–G3139 administration in a disseminated xenograft leukemia model. The results of the present study demonstrate that CD20-targeted delivery overcomes the immunostimulatory properties of CpG-containing ON therapeutics and improves efficient gene silencing and in vivo therapeutic efficacy for B-cell malignancies. The broader implications of similar approaches in overcoming immunostimulatory properties of RNA-directed therapeutics in hematologic malignancies are also discussed. PMID:23165478

Computer-based prediction of mitochondria-targeting peptides.

PubMed

Martelli, Pier Luigi; Savojardo, Castrense; Fariselli, Piero; Tasco, Gianluca; Casadio, Rita

2015-01-01

Computational methods are invaluable when protein sequences, directly derived from genomic data, need functional and structural annotation. Subcellular localization is a feature necessary for understanding the protein role and the compartment where the mature protein is active and very difficult to characterize experimentally. Mitochondrial proteins encoded on the cytosolic ribosomes carry specific patterns in the precursor sequence from where it is possible to recognize a peptide targeting the protein to its final destination. Here we discuss to which extent it is feasible to develop computational methods for detecting mitochondrial targeting peptides in the precursor sequences and benchmark our and other methods on the human mitochondrial proteins endowed with experimentally characterized targeting peptides. Furthermore, we illustrate our newly implemented web server and its usage on the whole human proteome in order to infer mitochondrial targeting peptides, their cleavage sites, and whether the targeting peptide regions contain or not arginine-rich recurrent motifs. By this, we add some other 2,800 human proteins to the 124 ones already experimentally annotated with a mitochondrial targeting peptide.

Targeting Virus-host Interactions of HIV Replication.

PubMed

Weydert, Caroline; De Rijck, Jan; Christ, Frauke; Debyser, Zeger

2016-01-01

Cellular proteins that are hijacked by HIV in order to complete its replication cycle, form attractive new targets for antiretroviral therapy. In particular, the protein-protein interactions between these cellular proteins (cofactors) and viral proteins are of great interest to develop new therapies. Research efforts have led to the validation of different cofactors and some successes in therapeutic applications. Maraviroc, the first cofactor inhibitor approved for human medicinal use, provided a proof of concept. Furthermore, compounds developed as Integrase-LEDGF/p75 interaction inhibitors (LEDGINs) have advanced to early clinical trials. Other compounds targeting cofactors and cofactor-viral protein interactions are currently under development. Likewise, interactions between cellular restriction factors and their counteracting HIV protein might serve as interesting targets in order to impair HIV replication. In this respect, compounds targeting the Vif-APOBEC3G interaction have been described. In this review, we focus on compounds targeting the Integrase- LEDGF/p75 interaction, the Tat-P-TEFb interaction and the Vif-APOBEC3G interaction. Additionally we give an overview of currently discovered compounds presumably targeting cellular cofactor-HIV protein interactions.

Targeting therapeutics to the glomerulus with nanoparticles.

PubMed

Zuckerman, Jonathan E; Davis, Mark E

2013-11-01

Nanoparticles are an enabling technology for the creation of tissue-/cell-specific therapeutics that have been investigated extensively as targeted therapeutics for cancer. The kidney, specifically the glomerulus, is another accessible site for nanoparticle delivery that has been relatively overlooked as a target organ. Given the medical need for the development of more potent, kidney-targeted therapies, the use of nanoparticle-based therapeutics may be one such solution to this problem. Here, we review the literature on nanoparticle targeting of the glomerulus. Specifically, we provide a broad overview of nanoparticle-based therapeutics and how the unique structural characteristics of the glomerulus allow for selective, nanoparticle targeting of this area of the kidney. We then summarize literature examples of nanoparticle delivery to the glomerulus and elaborate on the appropriate nanoparticle design criteria for glomerular targeting. Finally, we discuss the behavior of nanoparticles in animal models of diseased glomeruli and review examples of nanoparticle therapeutic approaches that have shown promise in animal models of glomerulonephritic disease. Copyright © 2013 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.

Real-time target tracking and locating system for UAV

NASA Astrophysics Data System (ADS)

Zhang, Chao; Tang, Linbo; Fu, Huiquan; Li, Maowen

2017-07-01

In order to achieve real-time target tracking and locating for UAV, a reliable processing system is built on the embedded platform. Firstly, the video image is acquired in real time by the photovoltaic system on the UAV. When the target information is known, KCF tracking algorithm is adopted to track the target. Then, the servo is controlled to rotate with the target, when the target is in the center of the image, the laser ranging module is opened to obtain the distance between the UAV and the target. Finally, to combine with UAV flight parameters obtained by BeiDou navigation system, through the target location algorithm to calculate the geodetic coordinates of the target. The results show that the system is stable for real-time tracking of targets and positioning.

Staufen2 regulates neuronal target RNAs.

PubMed

Heraud-Farlow, Jacki E; Sharangdhar, Tejaswini; Li, Xiao; Pfeifer, Philipp; Tauber, Stefanie; Orozco, Denise; Hörmann, Alexandra; Thomas, Sabine; Bakosova, Anetta; Farlow, Ashley R; Edbauer, Dieter; Lipshitz, Howard D; Morris, Quaid D; Bilban, Martin; Doyle, Michael; Kiebler, Michael A

2013-12-26

RNA-binding proteins play crucial roles in directing RNA translation to neuronal synapses. Staufen2 (Stau2) has been implicated in both dendritic RNA localization and synaptic plasticity in mammalian neurons. Here, we report the identification of functionally relevant Stau2 target mRNAs in neurons. The majority of Stau2-copurifying mRNAs expressed in the hippocampus are present in neuronal processes, further implicating Stau2 in dendritic mRNA regulation. Stau2 targets are enriched for secondary structures similar to those identified in the 3' UTRs of Drosophila Staufen targets. Next, we show that Stau2 regulates steady-state levels of many neuronal RNAs and that its targets are predominantly downregulated in Stau2-deficient neurons. Detailed analysis confirms that Stau2 stabilizes the expression of one synaptic signaling component, the regulator of G protein signaling 4 (Rgs4) mRNA, via its 3' UTR. This study defines the global impact of Stau2 on mRNAs in neurons, revealing a role in stabilization of the levels of synaptic targets. Copyright © 2013 The Authors. Published by Elsevier Inc. All rights reserved.

Targeted protein degradation by PROTACs.

PubMed

Neklesa, Taavi K; Winkler, James D; Crews, Craig M

2017-06-01

Targeted protein degradation using the PROTAC technology is emerging as a novel therapeutic method to address diseases driven by the aberrant expression of a disease-causing protein. PROTAC molecules are bifunctional small molecules that simultaneously bind a target protein and an E3-ubiquitin ligase, thus causing ubiquitination and degradation of the target protein by the proteasome. Like small molecules, PROTAC molecules possess good tissue distribution and the ability to target intracellular proteins. Herein, we highlight the advantages of protein degradation using PROTACs, and provide specific examples where degradation offers therapeutic benefit over classical enzyme inhibition. Foremost, PROTACs can degrade proteins regardless of their function. This includes the currently "undruggable" proteome, which comprises approximately 85% of all human proteins. Other beneficial aspects of protein degradation include the ability to target overexpressed and mutated proteins, as well as the potential to demonstrate prolonged pharmacodynamics effect beyond drug exposure. Lastly, due to their catalytic nature and the pre-requisite ubiquitination step, an exquisitely potent molecules with a high degree of degradation selectivity can be designed. Impressive preclinical in vitro and in vivo PROTAC data have been published, and these data have propelled the development of clinically viable PROTACs. With the molecular weight falling in the 700-1000Da range, the delivery and bioavailability of PROTACs remain the largest hurdles on the way to the clinic. Solving these issues and demonstrating proof of concept clinical data will be the focus of many labs over the next few years. Copyright © 2017 Elsevier Inc. All rights reserved.

Research with Radioactive Targets

NASA Astrophysics Data System (ADS)

Ahle, Larry

2004-10-01

Obtaining precise information about neutron capture cross-sections for s-process branch points is a key goal of nuclear astrophysics. Since these nuclei are unstable and neutron targets do not exist, performing these measurements require a facility that can produce the nuclei of interest at a sufficient rate to allow formation of a meaningful target (at least 1015 atoms). The Rare Isotope Accelerator (RIA) promises such rates, often enabling collection of greater than 1016 atoms after only of few days of production running. By properly designing both the ISOL and fragmentation lines, these collections will often be possible to obtained parasitically to other radioactive ion beam production. But given a target, performing the neutron capture cross-section measurement also presents its own challenges. In many cases, activation measurements are feasible, providing one obtains a target of sufficient purity. But for many branch point nuclei, the capture product is stable or long enough lived that no radiation signature is available for detection. Measurements for these nuclei will require a BaF2 array like DANCE at Los Alamos National Laboratory, which uses gamma calorimetry to detect neutron capture events. Plans and issues associated with isotope harvesting will be discussed, as well as challenges associated with performing theses measurements. Current plans for doing DANCE type measurements at RIA will also be discussed. This work was performed under the auspices of the U.S. Department of Energy by the University of California, Lawrence Livermore National Laboratory under contract No. W-7405-Eng-48.

Electrophysiological correlates of target eccentricity in texture segmentation.

PubMed

Schaffer, Susann; Schubö, Anna; Meinecke, Cristina

2011-06-01

Event-related potentials and behavioural performance as a function of target eccentricity were measured while subjects performed a texture segmentation task. Fit-of-structures, i.e. easiness of target detection was varied: in Experiment 1, a texture with peripheral fit (easier detection of peripheral presented targets) and in Experiment 2, a texture with foveal fit (easier detection of foveal presented targets) was used. In the two experiments, the N2p was sensitive to target eccentricity showing larger amplitudes for foveal targets compared to peripheral targets, and at the foveal position, a reversal of the N2p differential amplitude effect was found. The anterior P2 seemed sensitive to the easiness of target detection. In both experiments the N2pc varied as a function of eccentricity. However, the P3 was neither sensitive to target eccentricity nor to the fit-of-structures. Results show the existence of a P2/N2 complex (Potts and Tucker, 2001) indicating executive functions located in the anterior cortex and perceptual processes located in the posterior cortex. Furthermore, the N2p might indicate the existence of a foveal vs. peripheral subsystem in visual processing. 2011 Elsevier B.V. All rights reserved.

Radar Imaging for Moving Targets

DTIC Science & Technology

2009-06-01

MOVING TARGETS by Teo Beng Koon William June 2009 Thesis Advisor: Brett H. Borden Second Reader: Donald L. Walters THIS PAGE...Reports, 1215 Jefferson Davis Highway, Suite 1204, Arlington, VA 22202-4302, and to the Office of Management and Budget, Paperwork Reduction Project...TITLE AND SUBTITLE Radar Imaging for Moving Targets 6. AUTHOR(S) Teo Beng Koon William 5. FUNDING NUMBERS 7. PERFORMING ORGANIZATION NAME(S

Ion beam inertial confinement target

DOEpatents

Bangerter, Roger O.; Meeker, Donald J.

1985-01-01

A target for implosion by ion beams composed of a spherical shell of frozen DT surrounded by a low-density, low-Z pusher shell seeded with high-Z material, and a high-density tamper shell. The target has various applications in the inertial confinement technology. For certain applications, if desired, a low-density absorber shell may be positioned intermediate the pusher and tamper shells.

Contingent attentional capture occurs by activated target congruence.

PubMed

Ariga, Atsunori; Yokosawa, Kazuhiko

2008-05-01

Contingent attentional capture occurs when a stimulus property captures an observer's attention, usually related to the observer's top-down attentional set for target-defining properties. In this study, we examined whether contingent attentional capture occurs for a distractor that does not share the target-defining property at a physical level, but does share that property at an abstract level of representation. In a rapid serial visual presentation stream, we defined the target by color (e.g., a green-colored Japanese kanji character). Before the target onset, we presented a distractor that referred to the target-defining color (e.g., a white-colored character meaning "green"). We observed contingent attentional capture by the distractor, which was reflected by a deficit in identifying the subsequent target. This result suggests that because of the attentional set, stimuli were scanned on the basis of the target-defining property at an abstract semantic level of representation.

29 mm Diameter Target Test Report

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

Woloshun, Keith Albert; Olivas, Eric Richard; Dale, Gregory E.

After numerous delays, the test of the 29 mm diameter target was conducted on 8/18/2017. The complete target design report, dated 8/15/2016, is reproduced below for completeness. This describes in detail the 10 disk target with varying thickness disks. The report presents and discusses the test results. In brief summary, there appears to have been multiple instrumentation errors. Measured temperatures, pressures and IR camera window temperature measurement are all suspect. All tests were done at 35 MeV, with 171 μA current, or 6 kW of beam power.

Quantitative and Systems Pharmacology. 1. In Silico Prediction of Drug-Target Interactions of Natural Products Enables New Targeted Cancer Therapy.

PubMed

Fang, Jiansong; Wu, Zengrui; Cai, Chuipu; Wang, Qi; Tang, Yun; Cheng, Feixiong

2017-11-27

Natural products with diverse chemical scaffolds have been recognized as an invaluable source of compounds in drug discovery and development. However, systematic identification of drug targets for natural products at the human proteome level via various experimental assays is highly expensive and time-consuming. In this study, we proposed a systems pharmacology infrastructure to predict new drug targets and anticancer indications of natural products. Specifically, we reconstructed a global drug-target network with 7,314 interactions connecting 751 targets and 2,388 natural products and built predictive network models via a balanced substructure-drug-target network-based inference approach. A high area under receiver operating characteristic curve of 0.96 was yielded for predicting new targets of natural products during cross-validation. The newly predicted targets of natural products (e.g., resveratrol, genistein, and kaempferol) with high scores were validated by various literature studies. We further built the statistical network models for identification of new anticancer indications of natural products through integration of both experimentally validated and computationally predicted drug-target interactions of natural products with known cancer proteins. We showed that the significantly predicted anticancer indications of multiple natural products (e.g., naringenin, disulfiram, and metformin) with new mechanism-of-action were validated by various published experimental evidence. In summary, this study offers powerful computational systems pharmacology approaches and tools for the development of novel targeted cancer therapies by exploiting the polypharmacology of natural products.

Exploring Polypharmacology Using a ROCS-Based Target Fishing Approach

DTIC Science & Technology

2012-01-01

target representatives. Target profiles were then generated for a given query molecule by computing maximal shape/ chemistry overlap between the query...molecule and the drug sets assigned to each protein target. The overlap was computed using the program ROCS (Rapid Overlay of Chemical Structures ). We...approaches in off-target prediction has been reviewed.9,10 Many structure -based target fishing (SBTF) approaches, such as INVDOCK11 and Target Fishing Dock

Comparative Effectiveness of Targeted Prostate Biopsy Using Magnetic Resonance Imaging Ultrasound Fusion Software and Visual Targeting: a Prospective Study.

PubMed

Lee, Daniel J; Recabal, Pedro; Sjoberg, Daniel D; Thong, Alan; Lee, Justin K; Eastham, James A; Scardino, Peter T; Vargas, Hebert Alberto; Coleman, Jonathan; Ehdaie, Behfar

2016-09-01

We compared the diagnostic outcomes of magnetic resonance-ultrasound fusion and visually targeted biopsy for targeting regions of interest on prostate multiparametric magnetic resonance imaging. Patients presenting for prostate biopsy with regions of interest on multiparametric magnetic resonance imaging underwent magnetic resonance imaging targeted biopsy. For each region of interest 2 visually targeted cores were obtained, followed by 2 cores using a magnetic resonance-ultrasound fusion device. Our primary end point was the difference in the detection of high grade (Gleason 7 or greater) and any grade cancer between visually targeted and magnetic resonance-ultrasound fusion, investigated using McNemar's method. Secondary end points were the difference in detection rate by biopsy location using a logistic regression model and the difference in median cancer length using the Wilcoxon signed rank test. We identified 396 regions of interest in 286 men. The difference in the detection of high grade cancer between magnetic resonance-ultrasound fusion biopsy and visually targeted biopsy was -1.4% (95% CI -6.4 to 3.6, p=0.6) and for any grade cancer the difference was 3.5% (95% CI -1.9 to 8.9, p=0.2). Median cancer length detected by magnetic resonance-ultrasound fusion and visually targeted biopsy was 5.5 vs 5.8 mm, respectively (p=0.8). Magnetic resonance-ultrasound fusion biopsy detected 15% more cancers in the transition zone (p=0.046) and visually targeted biopsy detected 11% more high grade cancer at the prostate base (p=0.005). Only 52% of all high grade cancers were detected by both techniques. We found no evidence of a significant difference in the detection of high grade or any grade cancer between visually targeted and magnetic resonance-ultrasound fusion biopsy. However, the performance of each technique varied in specific biopsy locations and the outcomes of both techniques were complementary. Combining visually targeted biopsy and magnetic resonance

Biased normalized cuts for target detection in hyperspectral imagery

NASA Astrophysics Data System (ADS)

Zhang, Xuewen; Dorado-Munoz, Leidy P.; Messinger, David W.; Cahill, Nathan D.

2016-05-01

The Biased Normalized Cuts (BNC) algorithm is a useful technique for detecting targets or objects in RGB imagery. In this paper, we propose modifying BNC for the purpose of target detection in hyperspectral imagery. As opposed to other target detection algorithms that typically encode target information prior to dimensionality reduction, our proposed algorithm encodes target information after dimensionality reduction, enabling a user to detect different targets in interactive mode. To assess the proposed BNC algorithm, we utilize hyperspectral imagery (HSI) from the SHARE 2012 data campaign, and we explore the relationship between the number and the position of expert-provided target labels and the precision/recall of the remaining targets in the scene.

Motion prediction of a non-cooperative space target

NASA Astrophysics Data System (ADS)

Zhou, Bang-Zhao; Cai, Guo-Ping; Liu, Yun-Meng; Liu, Pan

2018-01-01

Capturing a non-cooperative space target is a tremendously challenging research topic. Effective acquisition of motion information of the space target is the premise to realize target capture. In this paper, motion prediction of a free-floating non-cooperative target in space is studied and a motion prediction algorithm is proposed. In order to predict the motion of the free-floating non-cooperative target, dynamic parameters of the target must be firstly identified (estimated), such as inertia, angular momentum and kinetic energy and so on; then the predicted motion of the target can be acquired by substituting these identified parameters into the Euler's equations of the target. Accurate prediction needs precise identification. This paper presents an effective method to identify these dynamic parameters of a free-floating non-cooperative target. This method is based on two steps, (1) the rough estimation of the parameters is computed using the motion observation data to the target, and (2) the best estimation of the parameters is found by an optimization method. In the optimization problem, the objective function is based on the difference between the observed and the predicted motion, and the interior-point method (IPM) is chosen as the optimization algorithm, which starts at the rough estimate obtained in the first step and finds a global minimum to the objective function with the guidance of objective function's gradient. So the speed of IPM searching for the global minimum is fast, and an accurate identification can be obtained in time. The numerical results show that the proposed motion prediction algorithm is able to predict the motion of the target.

Common features of microRNA target prediction tools

PubMed Central

Peterson, Sarah M.; Thompson, Jeffrey A.; Ufkin, Melanie L.; Sathyanarayana, Pradeep; Liaw, Lucy; Congdon, Clare Bates

2014-01-01

The human genome encodes for over 1800 microRNAs (miRNAs), which are short non-coding RNA molecules that function to regulate gene expression post-transcriptionally. Due to the potential for one miRNA to target multiple gene transcripts, miRNAs are recognized as a major mechanism to regulate gene expression and mRNA translation. Computational prediction of miRNA targets is a critical initial step in identifying miRNA:mRNA target interactions for experimental validation. The available tools for miRNA target prediction encompass a range of different computational approaches, from the modeling of physical interactions to the incorporation of machine learning. This review provides an overview of the major computational approaches to miRNA target prediction. Our discussion highlights three tools for their ease of use, reliance on relatively updated versions of miRBase, and range of capabilities, and these are DIANA-microT-CDS, miRanda-mirSVR, and TargetScan. In comparison across all miRNA target prediction tools, four main aspects of the miRNA:mRNA target interaction emerge as common features on which most target prediction is based: seed match, conservation, free energy, and site accessibility. This review explains these features and identifies how they are incorporated into currently available target prediction tools. MiRNA target prediction is a dynamic field with increasing attention on development of new analysis tools. This review attempts to provide a comprehensive assessment of these tools in a manner that is accessible across disciplines. Understanding the basis of these prediction methodologies will aid in user selection of the appropriate tools and interpretation of the tool output. PMID:24600468

Common features of microRNA target prediction tools.

PubMed

Peterson, Sarah M; Thompson, Jeffrey A; Ufkin, Melanie L; Sathyanarayana, Pradeep; Liaw, Lucy; Congdon, Clare Bates

2014-01-01

The human genome encodes for over 1800 microRNAs (miRNAs), which are short non-coding RNA molecules that function to regulate gene expression post-transcriptionally. Due to the potential for one miRNA to target multiple gene transcripts, miRNAs are recognized as a major mechanism to regulate gene expression and mRNA translation. Computational prediction of miRNA targets is a critical initial step in identifying miRNA:mRNA target interactions for experimental validation. The available tools for miRNA target prediction encompass a range of different computational approaches, from the modeling of physical interactions to the incorporation of machine learning. This review provides an overview of the major computational approaches to miRNA target prediction. Our discussion highlights three tools for their ease of use, reliance on relatively updated versions of miRBase, and range of capabilities, and these are DIANA-microT-CDS, miRanda-mirSVR, and TargetScan. In comparison across all miRNA target prediction tools, four main aspects of the miRNA:mRNA target interaction emerge as common features on which most target prediction is based: seed match, conservation, free energy, and site accessibility. This review explains these features and identifies how they are incorporated into currently available target prediction tools. MiRNA target prediction is a dynamic field with increasing attention on development of new analysis tools. This review attempts to provide a comprehensive assessment of these tools in a manner that is accessible across disciplines. Understanding the basis of these prediction methodologies will aid in user selection of the appropriate tools and interpretation of the tool output.

Targeting cancer with kinase inhibitors

PubMed Central

Gross, Stefan; Rahal, Rami; Stransky, Nicolas; Lengauer, Christoph; Hoeflich, Klaus P.

2015-01-01

Kinase inhibitors have played an increasingly prominent role in the treatment of cancer and other diseases. Currently, more than 25 oncology drugs that target kinases have been approved, and numerous additional therapeutics are in various stages of clinical evaluation. In this Review, we provide an in-depth analysis of activation mechanisms for kinases in cancer, highlight recent successes in drug discovery, and demonstrate the clinical impact of selective kinase inhibitors. We also describe the substantial progress that has been made in designing next-generation inhibitors to circumvent on-target resistance mechanisms, as well as ongoing strategies for combining kinase inhibitors in the clinic. Last, there are numerous prospects for the discovery of novel kinase targets, and we explore cancer immunotherapy as a new and promising research area for studying kinase biology. PMID:25932675

Targeting human breast cancer cells by an oncolytic adenovirus using microRNA-targeting strategy.

PubMed

Shayestehpour, Mohammad; Moghim, Sharareh; Salimi, Vahid; Jalilvand, Somayeh; Yavarian, Jila; Romani, Bizhan; Mokhtari-Azad, Talat

2017-08-15

MicroRNA-targeting strategy is a promising approach that enables oncolytic viruses to replicate in tumor cells but not in normal cells. In this study, we targeted adenoviral replication toward breast cancer cells by inserting ten complementary binding sites for miR-145-5p downstream of E1A gene. In addition, we evaluated the effect of increasing miR-145 binding sites on inhibition of virus replication. Ad5-control and adenoviruses carrying five or ten copies of miR145-5p target sites (Ad5-5miR145T, Ad5-10miR145T) were generated and inoculated into MDA-MB-453, BT-20, MCF-7 breast cancer cell lines and human mammary epithelial cells (HMEpC). Titer of Ad5-10miR145T in HMEpC was significantly lower than Ad5-control titer. Difference between the titer of these two viruses at 12, 24, 36, and 48h after infection was 1.25, 2.96, 3.06, and 3.77 log TCID 50 . No significant difference was observed between the titer of both adenoviruses in MDA-MB-453, BT-20 and MCF-7 cells. The infectious titer of adenovirus containing 10 miR-145 binding sites in HMEpC cells at 24, 36, and 48h post-infection was 1.7, 2.08, and 4-fold, respectively, lower than the titer of adenovirus carrying 5 miR-145 targets. Our results suggest that miR-145-targeting strategy provides selectivity for adenovirus replication in breast cancer cells. Increasing the number of miRNA binding sites within the adenoviral genome confers more selectivity for viral replication in cancer cells. Copyright © 2017. Published by Elsevier B.V.

Diversity, expression and mRNA targeting abilities of Argonaute-targeting miRNAs among selected vascular plants.

PubMed

Jagtap, Soham; Shivaprasad, Padubidri V

2014-12-02

Micro (mi)RNAs are important regulators of plant development. Across plant lineages, Dicer-like 1 (DCL1) proteins process long ds-like structures to produce micro (mi) RNA duplexes in a stepwise manner. These miRNAs are incorporated into Argonaute (AGO) proteins and influence expression of RNAs that have sequence complementarity with miRNAs. Expression levels of AGOs are greatly regulated by plants in order to minimize unwarranted perturbations using miRNAs to target mRNAs coding for AGOs. AGOs may also have high promoter specificity-sometimes expression of AGO can be limited to just a few cells in a plant. Viral pathogens utilize various means to counter antiviral roles of AGOs including hijacking the host encoded miRNAs to target AGOs. Two host encoded miRNAs namely miR168 and miR403 that target AGOs have been described in the model plant Arabidopsis and such a mechanism is thought to be well conserved across plants because AGO sequences are well conserved. We show that the interaction between AGO mRNAs and miRNAs is species-specific due to the diversity in sequences of two miRNAs that target AGOs, sequence diversity among corresponding target regions in AGO mRNAs and variable expression levels of these miRNAs among vascular plants. We used miRNA sequences from 68 plant species representing 31 plant families for this analysis. Sequences of miR168 and miR403 are not conserved among plant lineages, but surprisingly they differ drastically in their sequence diversity and expression levels even among closely related plants. Variation in miR168 expression among plants correlates well with secondary structures/length of loop sequences of their precursors. Our data indicates a complex AGO targeting interaction among plant lineages due to miRNA sequence diversity and sequences of miRNA targeting regions among AGO mRNAs, thus leading to the assumption that the perturbations by viruses that use host miRNAs to target antiviral AGOs can only be species-specific. We also show

Effect of Patient Set-up and Respiration motion on Defining Biological Targets for Image-Guided Targeted Radiotherapy

NASA Astrophysics Data System (ADS)

McCall, Keisha C.

Identification and monitoring of sub-tumor targets will be a critical step for optimal design and evaluation of cancer therapies in general and biologically targeted radiotherapy (dose-painting) in particular. Quantitative PET imaging may be an important tool for these applications. Currently radiotherapy planning accounts for tumor motion by applying geometric margins. These margins create a motion envelope to encompass the most probable positions of the tumor, while also maintaining the appropriate tumor control and normal tissue complication probabilities. This motion envelope is effective for uniform dose prescriptions where the therapeutic dose is conformed to the external margins of the tumor. However, much research is needed to establish the equivalent margins for non-uniform fields, where multiple biological targets are present and each target is prescribed its own dose level. Additionally, the size of the biological targets and close proximity make it impractical to apply planning margins on the sub-tumor level. Also, the extent of high dose regions must be limited to avoid excessive dose to the surrounding tissue. As such, this research project is an investigation of the uncertainty within quantitative PET images of moving and displaced dose-painting targets, and an investigation of the residual errors that remain after motion management. This included characterization of the changes in PET voxel-values as objects are moved relative to the discrete sampling interval of PET imaging systems (SPECIFIC AIM 1). Additionally, the repeatability of PET distributions and the delineating dose-painting targets were measured (SPECIFIC AIM 2). The effect of imaging uncertainty on the dose distributions designed using these images (SPECIFIC AIM 3) has also been investigated. This project also included analysis of methods to minimize motion during PET imaging and reduce the dosimetric impact of motion/position-induced imaging uncertainty (SPECIFIC AIM 4).

Flash trajectory imaging of target 3D motion

NASA Astrophysics Data System (ADS)

Wang, Xinwei; Zhou, Yan; Fan, Songtao; He, Jun; Liu, Yuliang

2011-03-01

We present a flash trajectory imaging technique which can directly obtain target trajectory and realize non-contact measurement of motion parameters by range-gated imaging and time delay integration. Range-gated imaging gives the range of targets and realizes silhouette detection which can directly extract targets from complex background and decrease the complexity of moving target image processing. Time delay integration increases information of one single frame of image so that one can directly gain the moving trajectory. In this paper, we have studied the algorithm about flash trajectory imaging and performed initial experiments which successfully obtained the trajectory of a falling badminton. Our research demonstrates that flash trajectory imaging is an effective approach to imaging target trajectory and can give motion parameters of moving targets.

Action-perception dissociation in response to target acceleration.

PubMed

Dubrowski, Adam; Carnahan, Heather

2002-05-01

The purpose of this study was to investigate whether information about the acceleration characteristics of a moving target can be used for both action and perception. Also of interest was whether prior movement experience altered perceptual judgements. Participants manually intercepted targets moving with various acceleration, velocity and movement time characteristics. They also made perceptual judgements about the acceleration characteristics of these targets either with or without prior manual interception experience. Results showed that while aiming kinematics were sensitive to the acceleration characteristics of the target, participants were only able to perceptually discriminate the velocity characteristics of target motion, even after performing interceptive actions to the same targets. These results are discussed in terms of a two channel (action-perception) model of visuomotor control.

Folate targeted polymeric 'green' nanotherapy for cancer

NASA Astrophysics Data System (ADS)

Narayanan, Sreeja; Binulal, N. S.; Mony, Ullas; Manzoor, Koyakutty; Nair, Shantikumar; Menon, Deepthy

2010-07-01

The concept of 'green' chemotherapy by employing targeted nanoparticle mediated delivery to enhance the efficacy of phytomedicines is reported. Poly (lactide-co-glycolide) (PLGA) nanoparticles encapsulating a well known nutraceutical namely, grape seed extract (GSE)—'NanoGSE'—was prepared by a nanoprecipitation technique. The drug-loaded nanoparticles of size ~ 100 nm exhibited high colloidal stability at physiological pH. Molecular receptor targeting of this nanophytomedicine against folate receptor over-expressing cancers was demonstrated in vitro by conjugation with a potential cancer targeting ligand, folic acid (FA). Fluorescence microscopy and flow cytometry data showed highly specific cellular uptake of FA conjugated NanoGSE on folate receptor positive cancer cells. Studies were also conducted to investigate the efficiency of targeted (FA conjugated) versus non-targeted (non-FA conjugated) nanoformulations in causing cancer cell death. The IC50 values were lowered by a factor of ~ 3 for FA-NanoGSE compared to the free drug, indicating substantially enhanced bioavailability to the tumor cells, sparing the normal ones. Receptor targeting of FA-NanoGSE resulted in a significant increase in apoptotic index, which was also quantified by flow cytometry and fluorescence microscopy. This in vitro study provides a basis for the use of nanoparticle mediated delivery of anticancer nutraceuticals to enhance bioavailability and effectively target cancer by a 'green' approach.

Gene Therapy and Targeted Toxins for Glioma

PubMed Central

Castro, Maria G.; Candolfi, Marianela; Kroeger, Kurt; King, Gwendalyn D.; Curtin, James F.; Yagiz, Kader; Mineharu, Yohei; Assi, Hikmat; Wibowo, Mia; Muhammad, AKM Ghulam; Foulad, David; Puntel, Mariana; Lowenstein, Pedro R.

2011-01-01

The most common primary brain tumor in adults is glioblastoma. These tumors are highly invasive and aggressive with a mean survival time of nine to twelve months from diagnosis to death. Current treatment modalities are unable to significantly prolong survival in patients diagnosed with glioblastoma. As such, glioma is an attractive target for developing novel therapeutic approaches utilizing gene therapy. This review will examine the available preclinical models for glioma including xenographs, syngeneic and genetic models. Several promising therapeutic targets are currently being pursued in pre-clinical investigations. These targets will be reviewed by mechanism of action, i.e., conditional cytotoxic, targeted toxins, oncolytic viruses, tumor suppressors/oncogenes, and immune stimulatory approaches. Preclinical gene therapy paradigms aim to determine which strategies will provide rapid tumor regression and long-term protection from recurrence. While a wide range of potential targets are being investigated preclinically, only the most efficacious are further transitioned into clinical trial paradigms. Clinical trials reported to date are summarized including results from conditionally cytotoxic, targeted toxins, oncolytic viruses and oncogene targeting approaches. Clinical trial results have not been as robust as preclinical models predicted; this could be due to the limitations of the GBM models employed. Once this is addressed, and we develop effective gene therapies in models that better replicate the clinical scenario, gene therapy will provide a powerful approach to treat and manage brain tumors. PMID:21453286

Reflectance differences between Target and Torch rape cultivars

NASA Technical Reports Server (NTRS)

Gausman, H. W.; Leamer, R. W. (Principal Investigator)

1982-01-01

Spectroradiometric reflectance measurements were made on Target and Torch plants (four and five leaves, respectively) that were growing in 0.09 m2 soil-containing flats. Torch's spectrophotometric single leaf reflectance was consistently lower than Target's at the 650-nm chlorophyll absorption band because Torch's chlorophyll concentration was larger than Target's, which caused more red light absorption. Spectroradiometric measurements indicate that: wet soil strongly absorbs visible light (500 to 700 nm) so that Target's soil-containing flat with 60% plant cover has less reflectance than Torch's soil-containing flat with 75% plant cover; Torch (most foiliage) has higher near-infrared (750 to 1,350 nm) reflectance than Target (least foliage); and the 2,200-nm wavelength is a candidate band to distinguish Target from Torch. The difference in chlorophyll concentrations between Target and Torch, compared with leaf structural differences, is apparently the most important factor that would affect the infrared color film's tonal response to vegetation in the photographic sensitive region (500 to 900 nm).

Human immune cell targeting of protein nanoparticles - caveospheres

NASA Astrophysics Data System (ADS)

Glass, Joshua J.; Yuen, Daniel; Rae, James; Johnston, Angus P. R.; Parton, Robert G.; Kent, Stephen J.; de Rose, Robert

2016-04-01

Nanotechnology has the power to transform vaccine and drug delivery through protection of payloads from both metabolism and off-target effects, while facilitating specific delivery of cargo to immune cells. However, evaluation of immune cell nanoparticle targeting is conventionally restricted to monocultured cell line models. We generated human caveolin-1 nanoparticles, termed caveospheres, which were efficiently functionalized with monoclonal antibodies. Using this platform, we investigated CD4+ T cell and CD20+ B cell targeting within physiological mixtures of primary human blood immune cells using flow cytometry, imaging flow cytometry and confocal microscopy. Antibody-functionalization enhanced caveosphere binding to targeted immune cells (6.6 to 43.9-fold) within mixed populations and in the presence of protein-containing fluids. Moreover, targeting caveospheres to CCR5 enabled caveosphere internalization by non-phagocytic CD4+ T cells--an important therapeutic target for HIV treatment. This efficient and flexible system of immune cell-targeted caveosphere nanoparticles holds promise for the development of advanced immunotherapeutics and vaccines.

Optimal random search for a single hidden target.

PubMed

Snider, Joseph

2011-01-01

A single target is hidden at a location chosen from a predetermined probability distribution. Then, a searcher must find a second probability distribution from which random search points are sampled such that the target is found in the minimum number of trials. Here it will be shown that if the searcher must get very close to the target to find it, then the best search distribution is proportional to the square root of the target distribution regardless of dimension. For a Gaussian target distribution, the optimum search distribution is approximately a Gaussian with a standard deviation that varies inversely with how close the searcher must be to the target to find it. For a network where the searcher randomly samples nodes and looks for the fixed target along edges, the optimum is either to sample a node with probability proportional to the square root of the out-degree plus 1 or not to do so at all.

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

DTIC Science & Technology

1992-07-01

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

A novel algorithm for finding optimal driver nodes to target control complex networks and its applications for drug targets identification.

PubMed

Guo, Wei-Feng; Zhang, Shao-Wu; Shi, Qian-Qian; Zhang, Cheng-Ming; Zeng, Tao; Chen, Luonan

2018-01-19

The advances in target control of complex networks not only can offer new insights into the general control dynamics of complex systems, but also be useful for the practical application in systems biology, such as discovering new therapeutic targets for disease intervention. In many cases, e.g. drug target identification in biological networks, we usually require a target control on a subset of nodes (i.e., disease-associated genes) with minimum cost, and we further expect that more driver nodes consistent with a certain well-selected network nodes (i.e., prior-known drug-target genes). Therefore, motivated by this fact, we pose and address a new and practical problem called as target control problem with objectives-guided optimization (TCO): how could we control the interested variables (or targets) of a system with the optional driver nodes by minimizing the total quantity of drivers and meantime maximizing the quantity of constrained nodes among those drivers. Here, we design an efficient algorithm (TCOA) to find the optional driver nodes for controlling targets in complex networks. We apply our TCOA to several real-world networks, and the results support that our TCOA can identify more precise driver nodes than the existing control-fucus approaches. Furthermore, we have applied TCOA to two bimolecular expert-curate networks. Source code for our TCOA is freely available from http://sysbio.sibcb.ac.cn/cb/chenlab/software.htm or https://github.com/WilfongGuo/guoweifeng . In the previous theoretical research for the full control, there exists an observation and conclusion that the driver nodes tend to be low-degree nodes. However, for target control the biological networks, we find interestingly that the driver nodes tend to be high-degree nodes, which is more consistent with the biological experimental observations. Furthermore, our results supply the novel insights into how we can efficiently target control a complex system, and especially many evidences on the

47 CFR 10.450 - Geographic targeting.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 47 Telecommunication 1 2010-10-01 2010-10-01 false Geographic targeting. 10.450 Section 10.450 Telecommunication FEDERAL COMMUNICATIONS COMMISSION GENERAL COMMERCIAL MOBILE ALERT SYSTEM Alert Message Requirements § 10.450 Geographic targeting. This section establishes minimum requirements for the geographic...

Target identification using Zernike moments and neural networks

NASA Astrophysics Data System (ADS)

Azimi-Sadjadi, Mahmood R.; Jamshidi, Arta A.; Nevis, Andrew J.

2001-10-01

The development of an underwater target identification algorithm capable of identifying various types of underwater targets, such as mines, under different environmental conditions pose many technical problems. Some of the contributing factors are: targets have diverse sizes, shapes and reflectivity properties. Target emplacement environment is variable; targets may be proud or partially buried. Environmental properties vary significantly from one location to another. Bottom features such as sand, rocks, corals, and vegetation can conceal a target whether it is partially buried or proud. Competing clutter with responses that closely resemble those of the targets may lead to false positives. All the problems mentioned above contribute to overly difficult and challenging conditions that could lead to unreliable algorithm performance with existing methods. In this paper, we developed and tested a shape-dependent feature extraction scheme that provides features invariant to rotation, size scaling and translation; properties that are extremely useful for any target classification problem. The developed schemes were tested on an electro-optical imagery data set collected under different environmental conditions with variable background, range and target types. The electro-optic data set was collected using a Laser Line Scan (LLS) sensor by the Coastal Systems Station (CSS), located in Panama City, Florida. The performance of the developed scheme and its robustness to distortion, rotation, scaling and translation was also studied.

Limitations of contrast enhancement for infrared target identification

NASA Astrophysics Data System (ADS)

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

2009-05-01

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

Observations of Spacecraft Targets, Unusual Asteroids, and Targets of Opportunity

NASA Technical Reports Server (NTRS)

Tholen, David J.

1998-01-01

Obtain physical and astrometric observations of: (1) spacecraft targets to support mission operations; (2) known asteroids with unusual orbits to help determine their origin; and (3) newly discovered minor planets (including both asteroids and comets) that represent a particular opportunity to add significant new knowledge of the Solar System.

Using Targeting Outcomes of Programs as a Framework to Target Photographic Events in Nonformal Educational Programs

ERIC Educational Resources Information Center

Rockwell, S. Kay; Albrecht, Julie A.; Nugent, Gwen C.; Kunz, Gina M.

2012-01-01

Targeting Outcomes of Programs (TOP) is a seven-step hierarchical programming model in which the program development and performance sides are mirror images of each other. It served as a framework to identify a simple method for targeting photographic events in nonformal education programs, indicating why, when, and how photographs would be useful…

Low-enriched uranium high-density target project. Compendium report

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

Vandegrift, George; Brown, M. Alex; Jerden, James L.

2016-09-01

At present, most 99Mo is produced in research, test, or isotope production reactors by irradiation of highly enriched uranium targets. To achieve the denser form of uranium needed for switching from high to low enriched uranium (LEU), targets in the form of a metal foil (~125-150 µm thick) are being developed. The LEU High Density Target Project successfully demonstrated several iterations of an LEU-fission-based Mo-99 technology that has the potential to provide the world’s supply of Mo-99, should major producers choose to utilize the technology. Over 50 annular high density targets have been successfully tested, and the assembly and disassemblymore » of targets have been improved and optimized. Two target front-end processes (acidic and electrochemical) have been scaled up and demonstrated to allow for the high-density target technology to mate up to the existing producer technology for target processing. In the event that a new target processing line is started, the chemical processing of the targets is greatly simplified. Extensive modeling and safety analysis has been conducted, and the target has been qualified to be inserted into the High Flux Isotope Reactor, which is considered above and beyond the requirements for the typical use of this target due to high fluence and irradiation duration.« less

How many genomics targets can a portfolio afford?

PubMed

Betz, Ulrich A K

2005-08-01

The pharmaceutical industry can look back at a history of successful innovations. Although genomics technologies have provided drug discovery pipelines with a plethora of new potential drug targets, solid target validation is crucial to avoiding high attrition rates. Biomarkers for patient stratification and approaches for personalized medicine will further help to reduce the risk associated with new targets. To achieve an overall risk balance, portfolios have to be supplemented with precedented targets, me-too approaches and line extensions of existing drugs. However, capitalizing on genomics investments and working on unprecedented targets is essential for a continuous stream of innovative drugs.

A generalized target theory and its applications.

PubMed

Zhao, Lei; Mi, Dong; Hu, Bei; Sun, Yeqing

2015-09-28

Different radiobiological models have been proposed to estimate the cell-killing effects, which are very important in radiotherapy and radiation risk assessment. However, most applied models have their own scopes of application. In this work, by generalizing the relationship between "hit" and "survival" in traditional target theory with Yager negation operator in Fuzzy mathematics, we propose a generalized target model of radiation-induced cell inactivation that takes into account both cellular repair effects and indirect effects of radiation. The simulation results of the model and the rethinking of "the number of targets in a cell" and "the number of hits per target" suggest that it is only necessary to investigate the generalized single-hit single-target (GSHST) in the present theoretical frame. Analysis shows that the GSHST model can be reduced to the linear quadratic model and multitarget model in the low-dose and high-dose regions, respectively. The fitting results show that the GSHST model agrees well with the usual experimental observations. In addition, the present model can be used to effectively predict cellular repair capacity, radiosensitivity, target size, especially the biologically effective dose for the treatment planning in clinical applications.

Allegany Ballistics Lab: sensor test target system

NASA Astrophysics Data System (ADS)

Eaton, Deran S.

2011-06-01

Leveraging the Naval Surface Warfare Center, Indian Head Division's historical experience in weapon simulation, Naval Sea Systems Command commissioned development of a remote-controlled, digitally programmable Sensor Test Target as part of a modern, outdoor hardware-in-the-loop test system for ordnance-related guidance, navigation and control systems. The overall Target system design invokes a sciences-based, "design of automated experiments" approach meant to close the logistical distance between sensor engineering and developmental T&E in outdoor conditions over useful real world distances. This enables operating modes that employ broad spectrum electromagnetic energy in many a desired combination, variably generated using a Jet Engine Simulator, a multispectral infrared emitter array, optically enhanced incandescent Flare Simulators, Emitter/Detector mounts, and an RF corner reflector kit. As assembled, the recently tested Sensor Test Target prototype being presented can capably provide a full array of useful RF and infrared target source simulations for RDT&E use with developmental and existing sensors. Certain Target technologies are patent pending, with potential spinoffs in aviation, metallurgy and biofuels processing, while others are variations on well-established technology. The Sensor Test Target System is planned for extended installation at Allegany Ballistics Laboratory (Rocket Center, WV).

Global preamplification simplifies targeted mRNA quantification

PubMed Central

Kroneis, Thomas; Jonasson, Emma; Andersson, Daniel; Dolatabadi, Soheila; Ståhlberg, Anders

2017-01-01

The need to perform gene expression profiling using next generation sequencing and quantitative real-time PCR (qPCR) on small sample sizes and single cells is rapidly expanding. However, to analyse few molecules, preamplification is required. Here, we studied global and target-specific preamplification using 96 optimised qPCR assays. To evaluate the preamplification strategies, we monitored the reactions in real-time using SYBR Green I detection chemistry followed by melting curve analysis. Next, we compared yield and reproducibility of global preamplification to that of target-specific preamplification by qPCR using the same amount of total RNA. Global preamplification generated 9.3-fold lower yield and 1.6-fold lower reproducibility than target-specific preamplification. However, the performance of global preamplification is sufficient for most downstream applications and offers several advantages over target-specific preamplification. To demonstrate the potential of global preamplification we analysed the expression of 15 genes in 60 single cells. In conclusion, we show that global preamplification simplifies targeted gene expression profiling of small sample sizes by a flexible workflow. We outline the pros and cons for global preamplification compared to target-specific preamplification. PMID:28332609

Collisional disruptions of rotating targets

NASA Astrophysics Data System (ADS)

Ševeček, Pavel; Broz, Miroslav

2017-10-01

Collisions are key processes in the evolution of the Main Asteroid Belt and impact events - i.e. target fragmentation and gravitational reaccumulation - are commonly studied by numerical simulations, namely by SPH and N-body methods. In our work, we extend the previous studies by assuming rotating targets and we study the dependence of resulting size-distributions on the pre-impact rotation of the target. To obtain stable initial conditions, it is also necessary to include the self-gravity already in the fragmentation phase which was previously neglected.To tackle this problem, we developed an SPH code, accelerated by SSE/AVX instruction sets and parallelized. The code solves the standard set of hydrodynamic equations, using the Tillotson equation of state, von Mises criterion for plastic yielding and scalar Grady-Kipp model for fragmentation. We further modified the velocity gradient by a correction tensor (Schäfer et al. 2007) to ensure a first-order conservation of the total angular momentum. As the intact target is a spherical body, its gravity can be approximated by a potential of a homogeneous sphere, making it easy to set up initial conditions. This is however infeasible for later stages of the disruption; to this point, we included the Barnes-Hut algorithm to compute the gravitational accelerations, using a multipole expansion of distant particles up to hexadecapole order.We tested the code carefully, comparing the results to our previous computations obtained with the SPH5 code (Benz and Asphaug 1994). Finally, we ran a set of simulations and we discuss the difference between the synthetic families created by rotating and static targets.

Targeted polymeric nanoparticles for cancer gene therapy

PubMed Central

Kim, Jayoung; Wilson, David R.; Zamboni, Camila G.; Green, Jordan J.

2015-01-01

In this article, advances in designing polymeric nanoparticles for targeted cancer gene therapy are reviewed. Characterization and evaluation of biomaterials, targeting ligands, and transcriptional elements are each discussed. Advances in biomaterials have driven improvements to nanoparticle stability and tissue targeting, conjugation of ligands to the surface of polymeric nanoparticles enable binding to specific cancer cells, and the design of transcriptional elements has enabled selective DNA expression specific to the cancer cells. Together, these features have improved the performance of polymeric nanoparticles as targeted non-viral gene delivery vectors to treat cancer. As polymeric nanoparticles can be designed to be biodegradable, non-toxic, and to have reduced immunogenicity and tumorigenicity compared to viral platforms, they have significant potential for clinical use. Results of polymeric gene therapy in clinical trials and future directions for the engineering of nanoparticle systems for targeted cancer gene therapy are also presented. PMID:26061296

Methods and limitations in radar target imagery

NASA Astrophysics Data System (ADS)

Bertrand, P.

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

GEM-loaded magnetic albumin nanospheres modified with cetuximab for simultaneous targeting, magnetic resonance imaging, and double-targeted thermochemotherapy of pancreatic cancer cells.

PubMed

Wang, Ling; An, Yanli; Yuan, Chenyan; Zhang, Hao; Liang, Chen; Ding, Fengan; Gao, Qi; Zhang, Dongsheng

2015-01-01

Targeted delivery is a promising strategy to improve the diagnostic imaging and therapeutic effect of cancers. In this paper, novel cetuximab (C225)-conjugated, gemcitabine (GEM)-containing magnetic albumin nanospheres (C225-GEM/MANs) were fabricated and applied as a theranostic nanocarrier to conduct simultaneous targeting, magnetic resonance imaging (MRI), and double-targeted thermochemotherapy against pancreatic cancer cells. Fe3O4 nanoparticles (NPs) and GEM co-loaded albumin nanospheres (GEM/MANs) were prepared, and then C225 was further conjugated to synthesize C225-GEM/MANs. Their morphology, mean particle size, GEM encapsulation ratio, specific cell-binding ability, and thermal dynamic profiles were characterized. The effects of discriminating different EGFR-expressing pancreatic cancer cells (AsPC-1 and MIA PaCa-2) and monitoring cellular targeting effects were assessed by targeted MRI. Lastly, the antitumor efficiency of double/C225/magnetic-targeted and nontargeted thermochemotherapy was compared with chemotherapy alone using 3-(4, 5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) and flow cytometry (FCM) assay. When treated with targeted nanospheres, AsPC-1 cells showed a significantly less intense MRI T2 signal than MIA PaCa-2 cells, while both cells had similar signal strength when incubated with nontargeted nanospheres. T2 signal intensity was significantly lower when magnetic and C225 targeting were combined, rather than used alone. The inhibitory and apoptotic rates of each thermochemotherapy group were significantly higher than those of the chemotherapy-alone groups. Additionally, both MTT and FCM analysis verified that double-targeted thermochemotherapy had the highest targeted killing efficiency among all groups. The C225-GEM/MANs can distinguish various EGFR-expressing live pancreatic cancer cells, monitor diverse cellular targeting effects using targeted MRI imaging, and efficiently mediate double-targeted thermochemotherapy

Margin selection to compensate for loss of target dose coverage due to target motion during external‐beam radiation therapy of the lung

PubMed Central

Osei, Ernest; Barnett, Rob

2015-01-01

The aim of this study is to provide guidelines for the selection of external‐beam radiation therapy target margins to compensate for target motion in the lung during treatment planning. A convolution model was employed to predict the effect of target motion on the delivered dose distribution. The accuracy of the model was confirmed with radiochromic film measurements in both static and dynamic phantom modes. 502 unique patient breathing traces were recorded and used to simulate the effect of target motion on a dose distribution. A 1D probability density function (PDF) representing the position of the target throughout the breathing cycle was generated from each breathing trace obtained during 4D CT. Changes in the target D95 (the minimum dose received by 95% of the treatment target) due to target motion were analyzed and shown to correlate with the standard deviation of the PDF. Furthermore, the amount of target D95 recovered per millimeter of increased field width was also shown to correlate with the standard deviation of the PDF. The sensitivity of changes in dose coverage with respect to target size was also determined. Margin selection recommendations that can be used to compensate for loss of target D95 were generated based on the simulation results. These results are discussed in the context of clinical plans. We conclude that, for PDF standard deviations less than 0.4 cm with target sizes greater than 5 cm, little or no additional margins are required. Targets which are smaller than 5 cm with PDF standard deviations larger than 0.4 cm are most susceptible to loss of coverage. The largest additional required margin in this study was determined to be 8 mm. PACS numbers: 87.53.Bn, 87.53.Kn, 87.55.D‐, 87.55.Gh

Self-assessing target with automatic feedback

DOEpatents

Larkin, Stephen W.; Kramer, Robert L.

2004-03-02

A self assessing target with four quadrants and a method of use thereof. Each quadrant containing possible causes for why shots are going into that particular quadrant rather than the center mass of the target. Each possible cause is followed by a solution intended to help the marksman correct the problem causing the marksman to shoot in that particular area. In addition, the self assessing target contains possible causes for general shooting errors and solutions to the causes of the general shooting error. The automatic feedback with instant suggestions and corrections enables the shooter to improve their marksmanship.

Targeting EGFRvIII for glioblastoma multiforme.

PubMed

Yang, Ju; Yan, Jing; Liu, Baorui

2017-09-10

Glioblastoma multiforme (GBM) is the most progressive primary brain tumor. Targeting a novel and highly specific tumor antigen is one of the strategies to overcome tumors. EGFR variant III (EGFRvIII) is present in 25%-33% of all patients with GBM and is exclusively expressed on tumor tissue cells. Currently, there are various approaches to target EGFRvIII, including CAR T-cell therapy, therapeutic vaccines, antibodies, and Bi-specific T Cell Engager. In this review, we focus on the preclinical and clinical findings of targeting EGFRvIII for GBM. Copyright © 2017 Elsevier B.V. All rights reserved.

Targets of drugs are generally, and targets of drugs having side effects are specifically good spreaders of human interactome perturbations.

PubMed

Perez-Lopez, Áron R; Szalay, Kristóf Z; Türei, Dénes; Módos, Dezső; Lenti, Katalin; Korcsmáros, Tamás; Csermely, Peter

2015-05-11

Network-based methods are playing an increasingly important role in drug design. Our main question in this paper was whether the efficiency of drug target proteins to spread perturbations in the human interactome is larger if the binding drugs have side effects, as compared to those which have no reported side effects. Our results showed that in general, drug targets were better spreaders of perturbations than non-target proteins, and in particular, targets of drugs with side effects were also better spreaders of perturbations than targets of drugs having no reported side effects in human protein-protein interaction networks. Colorectal cancer-related proteins were good spreaders and had a high centrality, while type 2 diabetes-related proteins showed an average spreading efficiency and had an average centrality in the human interactome. Moreover, the interactome-distance between drug targets and disease-related proteins was higher in diabetes than in colorectal cancer. Our results may help a better understanding of the network position and dynamics of drug targets and disease-related proteins, and may contribute to develop additional, network-based tests to increase the potential safety of drug candidates.

Targets of drugs are generally, and targets of drugs having side effects are specifically good spreaders of human interactome perturbations

NASA Astrophysics Data System (ADS)

Perez-Lopez, Áron R.; Szalay, Kristóf Z.; Türei, Dénes; Módos, Dezső; Lenti, Katalin; Korcsmáros, Tamás; Csermely, Peter

2015-05-01

Network-based methods are playing an increasingly important role in drug design. Our main question in this paper was whether the efficiency of drug target proteins to spread perturbations in the human interactome is larger if the binding drugs have side effects, as compared to those which have no reported side effects. Our results showed that in general, drug targets were better spreaders of perturbations than non-target proteins, and in particular, targets of drugs with side effects were also better spreaders of perturbations than targets of drugs having no reported side effects in human protein-protein interaction networks. Colorectal cancer-related proteins were good spreaders and had a high centrality, while type 2 diabetes-related proteins showed an average spreading efficiency and had an average centrality in the human interactome. Moreover, the interactome-distance between drug targets and disease-related proteins was higher in diabetes than in colorectal cancer. Our results may help a better understanding of the network position and dynamics of drug targets and disease-related proteins, and may contribute to develop additional, network-based tests to increase the potential safety of drug candidates.

Targets of drugs are generally, and targets of drugs having side effects are specifically good spreaders of human interactome perturbations

PubMed Central

Perez-Lopez, Áron R.; Szalay, Kristóf Z.; Türei, Dénes; Módos, Dezső; Lenti, Katalin; Korcsmáros, Tamás; Csermely, Peter

2015-01-01

Network-based methods are playing an increasingly important role in drug design. Our main question in this paper was whether the efficiency of drug target proteins to spread perturbations in the human interactome is larger if the binding drugs have side effects, as compared to those which have no reported side effects. Our results showed that in general, drug targets were better spreaders of perturbations than non-target proteins, and in particular, targets of drugs with side effects were also better spreaders of perturbations than targets of drugs having no reported side effects in human protein-protein interaction networks. Colorectal cancer-related proteins were good spreaders and had a high centrality, while type 2 diabetes-related proteins showed an average spreading efficiency and had an average centrality in the human interactome. Moreover, the interactome-distance between drug targets and disease-related proteins was higher in diabetes than in colorectal cancer. Our results may help a better understanding of the network position and dynamics of drug targets and disease-related proteins, and may contribute to develop additional, network-based tests to increase the potential safety of drug candidates. PMID:25960144

New targeted therapies in pancreatic cancer.

PubMed

Seicean, Andrada; Petrusel, Livia; Seicean, Radu

2015-05-28

Patients with pancreatic cancer have a poor prognosis with a median survival of 4-6 mo and a 5-year survival of less than 5%. Despite therapy with gemcitabine, patient survival does not exceed 6 mo, likely due to natural resistance to gemcitabine. Therefore, it is hoped that more favorable results can be obtained by using guided immunotherapy against molecular targets. This review summarizes the new leading targeted therapies in pancreatic cancers, focusing on passive and specific immunotherapies. Passive immunotherapy may have a role for treatment in combination with radiochemotherapy, which otherwise destroys the immune system along with tumor cells. It includes mainly therapies targeting against kinases, including epidermal growth factor receptor, Ras/Raf/mitogen-activated protein kinase cascade, human epidermal growth factor receptor 2, insulin growth factor-1 receptor, phosphoinositide 3-kinase/Akt/mTOR and hepatocyte growth factor receptor. Therapies against DNA repair genes, histone deacetylases, microRNA, and pancreatic tumor tissue stromal elements (stromal extracellular matric and stromal pathways) are also discussed. Specific immunotherapies, such as vaccines (whole cell recombinant, peptide, and dendritic cell vaccines), adoptive cell therapy and immunotherapy targeting tumor stem cells, have the role of activating antitumor immune responses. In the future, treatments will likely include personalized medicine, tailored for numerous molecular therapeutic targets of multiple pathogenetic pathways.

Voyager 2 Neptune targeting strategy

NASA Technical Reports Server (NTRS)

Potts, C. L.; Francis, K.; Matousek, S. E.; Cesarone, R. J.; Gray, D. L.

1989-01-01

The success of the Voyager 2 flybys of Neptune and Triton depends upon the ability to correct the spacecraft's trajectory. Accurate spacecraft delivery to the desired encounter conditions will promote the maximum science return. However, Neptune's great distance causes large a priori uncertainties in Neptune and Triton ephemerides and planetary system parameters. Consequently, the 'ideal' trajectory is unknown beforehand. The targeting challenge is to utilize the gradually improving knowledge as the spacecraft approaches Neptune to meet the science objectives, but with an overriding concern for spacecraft safety and a desire to limit propellant expenditure. A unique targeting strategy has been developed in response to this challenge. Through the use of a Monte Carlo simulation, candidate strategies are evaluated by the degree to which they meet these objectives and are compared against each other in determining the targeting strategy to be adopted.

Dispersion of Projectile and Target Debris Upon Penetration of Thin Targets

NASA Astrophysics Data System (ADS)

Gwynn, D.; Bernhard, R. P.; See, T. H.; Horz, F.

1996-03-01

We continue to conduct penetration experiments of thin foils to support the development of cosmic-dust flight instruments that utilize thin films for the measurement of particle trajectories, or for the potential soft capture of hypervelocity impactors for subsequent compositional analysis upon retrieval to Earth. Each experiment is equipped with a witness plate, mounted to the rear of the target and fabricated from soft Aluminum-1100, ~30 x 30 cm in size and ranging from 2 to 5 mm thick; these witness plates essentially simulate the rear wall of a capture cell onto which the projectile material will plate out, including material that is being dislodged from the penetrated foil itself. Using compositionally contrasting projectile and foil materials in the laboratory, such as soda-lime glass impactors and aluminum targets, one produces two distinct populations of craters on the witness plates.

Realism and Effectiveness of Robotic Moving Targets

DTIC Science & Technology

2017-04-01

scenario or be manually controlled . The targets can communicate with other nearby targets, which means they can move independently, as a group , or...present a realistic three- dimensional human-sized target that can freely move with semi-autonomous control . The U.S. Army Research Institute for...Procedure: Performance and survey data were collected during multiple training exercises from Soldiers who engaged the RHTTs. Different groups

Visualizing Energy on Target: Molecular Dynamics Simulations

DTIC Science & Technology

2017-12-01

ARL-TR-8234 ● DEC 2017 US Army Research Laboratory Visualizing Energy on Target: Molecular Dynamics Simulations by DeCarlos E...return it to the originator. ARL-TR-8234● DEC 2017 US Army Research Laboratory Visualizing Energy on Target: Molecular Dynamics...REPORT TYPE Technical Report 3. DATES COVERED (From - To) 1 October 2015–30 September 2016 4. TITLE AND SUBTITLE Visualizing Energy on Target

A comparison of directed search target detection versus in-scene target detection in Worldview-2 datasets

NASA Astrophysics Data System (ADS)

Grossman, S.

2015-05-01

Since the events of September 11, 2001, the intelligence focus has moved from large order-of-battle targets to small targets of opportunity. Additionally, the business community has discovered the use of remotely sensed data to anticipate demand and derive data on their competition. This requires the finer spectral and spatial fidelity now available to recognize those targets. This work hypothesizes that directed searches using calibrated data perform at least as well as inscene manually intensive target detection searches. It uses calibrated Worldview-2 multispectral images with NEF generated signatures and standard detection algorithms to compare bespoke directed search capabilities against ENVI™ in-scene search capabilities. Multiple execution runs are performed at increasing thresholds to generate detection rates. These rates are plotted and statistically analyzed. While individual head-to-head comparison results vary, 88% of the directed searches performed at least as well as in-scene searches with 50% clearly outperforming in-scene methods. The results strongly support the premise that directed searches perform at least as well as comparable in-scene searches.

Automatic target alignment of the Helios laser system

NASA Astrophysics Data System (ADS)

Liberman, I.; Viswanathan, V. K.; Klein, M.; Seery, B. D.

1980-05-01

An automatic target-alignment technique for the Helios laser facility is reported and verified experimentally. The desired alignment condition is completely described by an autocollimation test. A computer program examines the autocollimated return pattern from the surrogate target and correctly describes any changes required in mirror orientation to yield optimum target alignment with either aberrated or misaligned beams. Automated on-line target alignment is thus shown to be feasible.

Theory of Radar Target Discrimination

DTIC Science & Technology

1991-02-01

which a capability for target or system identification could be put to good use: air traffic control , border patrol, security and surveillance...different targets from each other, there would be big advantages in air safety. Airport traffic controllers have made serious errors from their...in a way that we can neither predict nor control . Of course, any data function d(t) which can be recorded for computer processing will be digitized and

Nonlinear Acoustic Characterization of Targets

DTIC Science & Technology

2008-01-01

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

Mars Target Encyclopedia: Information Extraction for Planetary Science

NASA Astrophysics Data System (ADS)

Wagstaff, K. L.; Francis, R.; Gowda, T.; Lu, Y.; Riloff, E.; Singh, K.

2017-06-01

Mars surface targets / and published compositions / Seek and ye will find. We used text mining methods to extract information from LPSC abstracts about the composition of Mars surface targets. Users can search by element, mineral, or target.

Setting Achievement Targets for School Children.

ERIC Educational Resources Information Center

Thanassoulis, Emmanuel

1999-01-01

Develops an approach for setting performance targets for schoolchildren, using data-envelopment analysis to identify benchmark pupils who achieve the best observed performance (allowing for contextual factors). These pupils' achievement forms the basis of targets estimated. The procedure also identifies appropriate role models for weaker students'…

Association Between Hospital Penalty Status Under the Hospital Readmission Reduction Program and Readmission Rates for Target and Non-Target Conditions

PubMed Central

Desai, Nihar R.; Ross, Joseph S.; Kwon, Ji Young; Herrin, Jeph; Dharmarajan, Kumar; Bernheim, Susannah M.; Krumholz, Harlan M.; Horwitz, Leora I.

2017-01-01

Importance Readmission rates declined after announcement of the Hospital Readmission Reduction Program (HRRP), which penalizes hospitals for excess readmissions for acute myocardial infarction (AMI), heart failure (HF), and pneumonia. Objective To compare trends in readmission rates for target and non-target conditions, stratified by hospital penalty status. Design, Setting, Participants Retrospective cohort study of 48,137,102 hospitalizations of 20,351,161 Medicare fee-for-service beneficiaries over 64 years discharged between January 1, 2008 and June 30, 2015 from 3,497 hospitals. Difference interrupted time series models were used to compare trends in readmission rates by condition and penalty status. Exposure Hospital penalty status or target condition under the HRRP. Outcome 30-day risk adjusted, all-cause unplanned readmission rates for target and non-target conditions. Results In January 2008, the mean readmission rates for AMI, HF, pneumonia and non-target conditions were 21.9%, 27.5%, 20.1%, and 18.4% respectively at hospitals later subject to financial penalties (n=2,189) and 18.7%, 24.2%, 17.4%, and 15.7% at hospitals not subject to penalties (n=1,283). Between January 2008 and March 2010, prior to HRRP announcement, readmission rates were stable across hospitals (except AMI at non-penalty hospitals). Following announcement of HRRP (March 2010), readmission rates for both target and non-target conditions declined significantly faster for patients at hospitals later subject to financial penalties compared with those at non-penalized hospitals (AMI, additional decrease of −1.24 (95% CI, −1.84, −0.65) percentage points per year relative to non-penalty discharges; HF, −1.25 (−1.64, −0.65); pneumonia, −1.37 (−0.95, −1.80); non-target, −0.27 (−0.38, −0.17); p<0.001 for all). For penalty hospitals, readmission rates for target conditions declined significantly faster compared with non-target conditions (AMI: additional decline of −0

Laser-driven proton acceleration with nanostructured targets

NASA Astrophysics Data System (ADS)

Vallières, Simon; Morabito, Antonia; Veltri, Simona; Scisciò, Massimiliano; Barberio, Marianna; Antici, Patrizio

2017-05-01

Laser-driven particle acceleration has become a growing field of research, in particular for its numerous interesting applications. One of the most common proton acceleration mechanism that is obtained on typically available multi-hundred TW laser systems is based on the irradiation of thin solid metal foils by the intense laser, generating the proton acceleration on its rear target surface. The efficiency of this acceleration scheme strongly depends on the type of target used. Improving the acceleration mechanism, i.e. enhancing parameters such as maximum proton energy, laminarity, efficiency, monocromaticy, and number of accelerated particles, is heavily depending on the laser-to-target absorption, where obviously cheap and easy to implement targets are best candidates. In this work, we present nanostructured targets that are able to increase the absorption of light compared to what can be achieved with a classical solid (non-nanostructured) target and are produced with a method that is much simpler and cheaper than conventional lithographic processes. Several layers of gold nanoparticles were deposited on solid targets (aluminum, Mylar and multiwalled carbon nanotube buckypaper) and allow for an increased photon absorption. This ultimately permits to increase the laser-to-particle energy transfer, and thus to enhance the yield in proton production. Experimental characterization results on the nanostructured films are presented (UV-Vis spectroscopy and AFM), along with preliminary experimental proton spectra obtained at the JLF-TITAN laser facility at LLNL.

Mathematical description of drug-target interactions: application to biologics that bind to targets with two binding sites.

PubMed

Gibiansky, Leonid; Gibiansky, Ekaterina

2018-02-01

The emerging discipline of mathematical pharmacology occupies the space between advanced pharmacometrics and systems biology. A characteristic feature of the approach is application of advance mathematical methods to study the behavior of biological systems as described by mathematical (most often differential) equations. One of the early application of mathematical pharmacology (that was not called this name at the time) was formulation and investigation of the target-mediated drug disposition (TMDD) model and its approximations. The model was shown to be remarkably successful, not only in describing the observed data for drug-target interactions, but also in advancing the qualitative and quantitative understanding of those interactions and their role in pharmacokinetic and pharmacodynamic properties of biologics. The TMDD model in its original formulation describes the interaction of the drug that has one binding site with the target that also has only one binding site. Following the framework developed earlier for drugs with one-to-one binding, this work aims to describe a rigorous approach for working with similar systems and to apply it to drugs that bind to targets with two binding sites. The quasi-steady-state, quasi-equilibrium, irreversible binding, and Michaelis-Menten approximations of the model are also derived. These equations can be used, in particular, to predict concentrations of the partially bound target (RC). This could be clinically important if RC remains active and has slow internalization rate. In this case, introduction of the drug aimed to suppress target activity may lead to the opposite effect due to RC accumulation.

A framework for small infrared target real-time visual enhancement

NASA Astrophysics Data System (ADS)

Sun, Xiaoliang; Long, Gucan; Shang, Yang; Liu, Xiaolin

2015-03-01

This paper proposes a framework for small infrared target real-time visual enhancement. The framework is consisted of three parts: energy accumulation for small infrared target enhancement, noise suppression and weighted fusion. Dynamic programming based track-before-detection algorithm is adopted in the energy accumulation to detect the target accurately and enhance the target's intensity notably. In the noise suppression, the target region is weighted by a Gaussian mask according to the target's Gaussian shape. In order to fuse the processed target region and unprocessed background smoothly, the intensity in the target region is treated as weight in the fusion. Experiments on real small infrared target images indicate that the framework proposed in this paper can enhances the small infrared target markedly and improves the image's visual quality notably. The proposed framework outperforms tradition algorithms in enhancing the small infrared target, especially for image in which the target is hardly visible.

Targeting the Notch signaling pathway in autoimmune diseases.

PubMed

Ma, Daoxin; Zhu, Yuanchao; Ji, Chunyan; Hou, Ming

2010-05-01

The Notch signaling pathway regulates a variety of processes and has been linked to diverse effects. Aberrant Notch function is important in several disorders. Pre-clinical studies have suggested that inhibition of Notch is an attractive approach to treat hematologic and solid malignancies. Many patients with refractory autoimmune diseases respond poorly to therapy and have significant morbidity and the treatment is highly toxic, so more effective therapies for autoimmune diseases are being examined. The role of the Notch pathway and therapeutic strategies targeting it in many illnesses, especially autoimmune diseases. The Notch pathway has unique and attractive advantages for targeting. Targeting it has already been trialed in many experiments, which may show better efficacy and fewer side effects compared with classical drugs for the treatment. Targeting Notch might provide etiological rather than symptomatic treatment. Various methods targeting the Notch pathway have been under investigation. Rational targeting of the Notch signaling pathway in cancer and some autoimmune diseases has proven to be successful. Classical drugs for the treatment of autoimmune diseases are inefficient and toxic to some extent, and targeting the Notch pathway is a promising therapeutic concept. However, there are still many questions about targeting Notch in autoimmune diseases, and further investigation will be needed.

Mitochondrial Targets for Pharmacological Intervention in Human Disease

PubMed Central

2015-01-01

Over the past several years, mitochondrial dysfunction has been linked to an increasing number of human illnesses, making mitochondrial proteins (MPs) an ever more appealing target for therapeutic intervention. With 20% of the mitochondrial proteome (312 of an estimated 1500 MPs) having known interactions with small molecules, MPs appear to be highly targetable. Yet, despite these targeted proteins functioning in a range of biological processes (including induction of apoptosis, calcium homeostasis, and metabolism), very few of the compounds targeting MPs find clinical use. Recent work has greatly expanded the number of proteins known to localize to the mitochondria and has generated a considerable increase in MP 3D structures available in public databases, allowing experimental screening and in silico prediction of mitochondrial drug targets on an unprecedented scale. Here, we summarize the current literature on clinically active drugs that target MPs, with a focus on how existing drug targets are distributed across biochemical pathways and organelle substructures. Also, we examine current strategies for mitochondrial drug discovery, focusing on genetic, proteomic, and chemogenomic assays, and relevant model systems. As cell models and screening techniques improve, MPs appear poised to emerge as relevant targets for a wide range of complex human diseases, an eventuality that can be expedited through systematic analysis of MP function. PMID:25367773

Evolving phage vectors for cell targeted gene delivery.

PubMed

Larocca, David; Burg, Michael A; Jensen-Pergakes, Kristen; Ravey, Edward Prenn; Gonzalez, Ana Maria; Baird, Andrew