Chemical structure determines target organ carcinogenesis in rats

PubMed Central

Carrasquer, C. A.; Malik, N.; States, G.; Qamar, S.; Cunningham, S.L.; Cunningham, A.R.

2012-01-01

SAR models were developed for 12 rat tumour sites using data derived from the Carcinogenic Potency Database. Essentially, the models fall into two categories: Target Site Carcinogen – Non-Carcinogen (TSC-NC) and Target Site Carcinogen – Non-Target Site Carcinogen (TSC-NTSC). The TSC-NC models were composed of active chemicals that were carcinogenic to a specific target site and inactive ones that were whole animal non-carcinogens. On the other hand, the TSC-NTSC models used an inactive category also composed of carcinogens but to any/all other sites but the target site. Leave one out validations produced an overall average concordance value for all 12 models of 0.77 for the TSC-NC models and 0.73 for the TSC-NTSC models. Overall, these findings suggest that while the TSC-NC models are able to distinguish between carcinogens and non-carcinogens, the TSC-NTSC models are identifying structural attributes that associate carcinogens to specific tumour sites. Since the TSC-NTSC models are composed of active and inactive compounds that are genotoxic and non-genotoxic carcinogens, the TSC-NTSC models may be capable of deciphering non-genotoxic mechanisms of carcinogenesis. Together, models of this type may also prove useful in anticancer drug development since they essentially contain chemicals moieties that target specific tumour site. PMID:23066888

The system integration and verification testing of an orbital maneuvering vehicle for an air bearing floor

NASA Technical Reports Server (NTRS)

Shields, N. L., Jr.; Martin, M. F.; Paulukaitis, K. R.; Haslam, J. W., Jr.; Henderson, D. E.

1986-01-01

The teleoperator and Robotics Evaluation Facility (TOREF) is composed of a 4,000 square foot precision air bearing floor, the Teleoperator Motion Base, the Target Motion and Support Simulator, the mock-ups of the Hubble Space Telescope, Multi-mission Modular Spacecraft, and the Orbital Maneuvering Vehicle (OMV). The TOREF and its general capabilities to support the OMV and other remote system simulations; the facility operating procedures and requirements; and the results of generic OMV investigations are summarized.

Polysaccharide-based Noncovalent Assembly for Targeted Delivery of Taxol

NASA Astrophysics Data System (ADS)

Yang, Yang; Zhang, Ying-Ming; Chen, Yong; Chen, Jia-Tong; Liu, Yu

2016-01-01

The construction of synthetic straightforward, biocompatible and biodegradable targeted drug delivery system with fluorescent tracking abilities, high anticancer activities and low side effects is still a challenge in the field of biochemistry and material chemistry. In this work, we constructed targeted paclitaxel (Taxol) delivery nanoparticles composed of permethyl-β-cyclodextrin modified hyaluronic acid (HApCD) and porphyrin modified paclitaxel prodrug (PorTaxol), through host-guest and amphiphilic interactions. The obtained nanoparticles (HATXP) were biocompatible and enzymatic biodegradable due to their hydrophilic hyaluronic acid (HA) shell and hydrophobic Taxol core, and exhibited specific targeting internalization into cancer cells via HA receptor mediated endocytosis effects. The cytotoxicity experiments showed that the HATXP exhibited similar anticancer activities to, but much lower side effects than commercial anticancer drug Taxol. The present work would provide a platform for targeted paclitaxel drug delivery and a general protocol for the design of advanced multifunctional nanoscale biomaterials for targeted drug/gene delivery.

Compiler writing system detail design specification. Volume 2: Component specification

NASA Technical Reports Server (NTRS)

Arthur, W. J.

1974-01-01

The logic modules and data structures composing the Meta-translator module are desribed. This module is responsible for the actual generation of the executable language compiler as a function of the input Meta-language. Machine definitions are also processed and are placed as encoded data on the compiler library data file. The transformation of intermediate language in target language object text is described.

The ribonucleoprotein Csr network.

PubMed

Seyll, Ethel; Van Melderen, Laurence

2013-11-08

Ribonucleoprotein complexes are essential regulatory components in bacteria. In this review, we focus on the carbon storage regulator (Csr) network, which is well conserved in the bacterial world. This regulatory network is composed of the CsrA master regulator, its targets and regulators. CsrA binds to mRNA targets and regulates translation either negatively or positively. Binding to small non-coding RNAs controls activity of this protein. Expression of these regulators is tightly regulated at the level of transcription and stability by various global regulators (RNAses, two-component systems, alarmone). We discuss the implications of these complex regulations in bacterial adaptation.

Automated campaign system

NASA Astrophysics Data System (ADS)

Vondran, Gary; Chao, Hui; Lin, Xiaofan; Beyer, Dirk; Joshi, Parag; Atkins, Brian; Obrador, Pere

2006-02-01

To run a targeted campaign involves coordination and management across numerous organizations and complex process flows. Everything from market analytics on customer databases, acquiring content and images, composing the materials, meeting the sponsoring enterprise brand standards, driving through production and fulfillment, and evaluating results; all processes are currently performed by experienced highly trained staff. Presented is a developed solution that not only brings together technologies that automate each process, but also automates the entire flow so that a novice user could easily run a successful campaign from their desktop. This paper presents the technologies, structure, and process flows used to bring this system together. Highlighted will be how the complexity of running a targeted campaign is hidden from the user through technologies, all while providing the benefits of a professionally managed campaign.

Development of CRISPR/Cas9 mediated virus resistance in agriculturally important crops.

PubMed

Khatodia, Surender; Bhatotia, Kirti; Tuteja, Narendra

2017-05-04

Clustered regulatory interspaced short palindromic repeats (CRISPR)/CRISPR associated nuclease 9 (Cas9) system of targeted genome editing has already revolutionized the plant science research. This is a RNA guided programmable endonuclease based system composed of 2 components, the Cas9 nuclease and an engineered guide RNA targeting any DNA sequence of the form N20-NGG for novel genome editing applications. The CRISPR/Cas9 technology of targeted genome editing has been recently applied for imparting virus resistance in plants. The robustness, wide adaptability, and easy engineering of this system has proved its potential as an antiviral tool for plants. Novel DNA free genome editing by using the preassembled Cas9/gRNA ribonucleoprotein complex for development of virus resistance in any plant species have been prospected for the future. Also, in this review we have discussed the reports of CRISPR/Cas9 mediated virus resistance strategy against geminiviruses by targeting the viral genome and transgene free strategy against RNA viruses by targeting the host plant factors. In conclusion, CRISPR/Cas9 technology will provide a more durable and broad spectrum viral resistance in agriculturally important crops which will eventually lead to public acceptance and commercialization in the near future.

Galactosylated magnetic nanovectors for regulation of lipid metabolism based on biomarker-specific RNAi and MR imaging.

PubMed

Heo, Dan; Lee, Chanjoo; Ku, Minhee; Haam, Seungjoo; Suh, Jin-Suck; Huh, Yong-Min; Park, Sahng Wook; Yang, Jaemoon

2015-08-21

The specific delivery of ribonucleic acid (RNA) interfering molecules to disease-related cells is still a critical blockade for in vivo systemic treatment. Here, this study suggests a robust delivery carrier for targeted delivery of RNA-interfering molecules using galactosylated magnetic nanovectors (gMNVs). gMNVs are an organic-inorganic polymeric nanomaterial composed of polycationics and magnetic nanocrystal for delivery of RNA-interfering molecules and tracking via magnetic resonance (MR) imaging. In particular, the surface of gMNVs was modified by galactosylgluconic groups for targeted delivering to asialoglycoprotein receptor (ASGPR) of hepatocytes. Moreover, the small interfering RNAs were used to regulate target proteins related with low-density lipoprotein level and in vivo MR imaging was conducted for tracking of nanovectors. The obtained results show that the prepared gMNVs demonstrate potential as a systemic theragnostic nanoplatform for RNA interference and MR imaging.

Feature Extraction and Selection Strategies for Automated Target Recognition

NASA Technical Reports Server (NTRS)

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

2010-01-01

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

Feature extraction and selection strategies for automated target recognition

NASA Astrophysics Data System (ADS)

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

2010-04-01

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

Quetiapine Nanoemulsion for Intranasal Drug Delivery: Evaluation of Brain-Targeting Efficiency.

PubMed

Boche, Mithila; Pokharkar, Varsha

2017-04-01

To evaluate the possibility of improved drug delivery of quetiapine fumarate (QTP), a nanoemulsion system was developed for intranasal delivery. Effects of different HLBs of Emalex LWIS 10, PEG 400 and Transcutol P, as co-surfactants, were studied on isotropic region of pseudoternary-phase diagrams of nanoemulsion system composed of capmul MCM (CPM) as oil phase, Tween 80 as surfactant and water. Phase behaviour, globule size, transmission electron microscope (TEM) photographs and brain-targeting efficiency of quetiapine nanoemulsion were investigated. In vitro dissolution study of optimised nanoemulsion formulation, with mean diameter 144 ± 0.5 nm, showed more than twofold increase in drug release as compared with pure drug. According to results of in vivo tissue distribution study in Wistar rats, intranasal administration of QTP-loaded nanoemulsion had shorter T max compared with that of intravenous administration. Higher drug transport efficiency (DTE%) and direct nose-to-brain drug transport (DTP%) was achieved by nanoemulsion. The nanoemulsion system may be a promising strategy for brain-targeted delivery of QTP.

Preparative separation of six rhynchophylla alkaloids from Uncaria macrophylla wall by pH-zone refining counter-current chromatography.

PubMed

Zhang, Qinghai; Lin, Changhu; Duan, Wenjuan; Wang, Xiao; Luo, Aiqin

2013-12-12

pH-Zone refining counter-current chromatography was successfully applied to the preparative isolation and purification of six alkaloids from the ethanol extracts of Uncaria macrophylla Wall. Because of the low content of alkaloids (about 0.2%, w/w) in U. macrophylla Wall, the target compounds were enriched by pH-zone refining counter-current chromatography using a two-phase solvent system composed of petroleum ether-ethyl acetate-isopropanol-water (2:6:3:9, v/v), adding 10 mM triethylamine in organic stationary phase and 5 mM hydrochloric acid in aqueous mobile phase. Then pH-zone refining counter-current chromatography using the other two-phase solvent system was used for final purification. Six target compounds were finally isolated and purified by following two-phase solvent system composed of methyl tert-butyl ether (MTBE)-acetonitrile-water (4:0.5:5, v/v), adding triethylamine (TEA) (10 mM) to the organic phase and HCl (5 mM) to aqueous mobile phase. The separation of 2.8 g enriched total alkaloids yielded 36 mg hirsutine, 48 mg hirsuteine, 82 mg uncarine C, 73 mg uncarine E, 163 mg rhynchophylline, and 149 mg corynoxeine, all with purities above 96% as verified by HPLC Their structures were identified by electrospray ionization-mass spectrometry (ESI-MS) and 1H-NMR spectroscopy.

An Investigation to Manufacturing Analytical Services Composition using the Analytical Target Cascading Method.

PubMed

Tien, Kai-Wen; Kulvatunyou, Boonserm; Jung, Kiwook; Prabhu, Vittaldas

2017-01-01

As cloud computing is increasingly adopted, the trend is to offer software functions as modular services and compose them into larger, more meaningful ones. The trend is attractive to analytical problems in the manufacturing system design and performance improvement domain because 1) finding a global optimization for the system is a complex problem; and 2) sub-problems are typically compartmentalized by the organizational structure. However, solving sub-problems by independent services can result in a sub-optimal solution at the system level. This paper investigates the technique called Analytical Target Cascading (ATC) to coordinate the optimization of loosely-coupled sub-problems, each may be modularly formulated by differing departments and be solved by modular analytical services. The result demonstrates that ATC is a promising method in that it offers system-level optimal solutions that can scale up by exploiting distributed and modular executions while allowing easier management of the problem formulation.

Integrated verification and testing system (IVTS) for HAL/S programs

NASA Technical Reports Server (NTRS)

Senn, E. H.; Ames, K. R.; Smith, K. A.

1983-01-01

The IVTS is a large software system designed to support user-controlled verification analysis and testing activities for programs written in the HAL/S language. The system is composed of a user interface and user command language, analysis tools and an organized data base of host system files. The analysis tools are of four major types: (1) static analysis, (2) symbolic execution, (3) dynamic analysis (testing), and (4) documentation enhancement. The IVTS requires a split HAL/S compiler, divided at the natural separation point between the parser/lexical analyzer phase and the target machine code generator phase. The IVTS uses the internal program form (HALMAT) between these two phases as primary input for the analysis tools. The dynamic analysis component requires some way to 'execute' the object HAL/S program. The execution medium may be an interpretive simulation or an actual host or target machine.

Real-time visual target tracking: two implementations of velocity-based smooth pursuit

NASA Astrophysics Data System (ADS)

Etienne-Cummings, Ralph; Longo, Paul; Van der Spiegel, Jan; Mueller, Paul

1995-06-01

Two systems for velocity-based visual target tracking are presented. The first two computational layers of both implementations are composed of VLSI photoreceptors (logarithmic compression) and edge detection (difference-of-Gaussians) arrays that mimic the outer-plexiform layer of mammalian retinas. The subsequent processing layers for measuring the target velocity and to realize smooth pursuit tracking are implemented in software and at the focal plane in the two versions, respectively. One implentation uses a hybrid of a PC and a silicon retina (39 X 38 pixels) operating at 333 frames/second. The software implementation of a real-time optical flow measurement algorithm is used to determine the target velocity, and a closed-loop control system zeroes the relative velocity of the target and retina. The second implementation is a single VLSI chip, which contains a linear array of photoreceptors, edge detectors and motion detectors at the focal plane. The closed-loop control system is also included on chip. This chip realizes all the computational properties of the hybrid system. The effects of background motion, target occlusion, and disappearance are studied as a function of retinal size and spatial distribution of the measured motion vectors (i.e. foveal/peripheral and diverging/converging measurement schemes). The hybrid system, which tested successfully, tracks targets moving as fast as 3 m/s at 1.3 meters from the camera and it can compensate for external arbitrary movements in its mounting platform. The single chip version, whose circuits tested successfully, can handle targets moving at 10 m/s.

Target-in-the-loop remote sensing of laser beam and atmospheric turbulence characteristics.

PubMed

Vorontsov, Mikhail A; Lachinova, Svetlana L; Majumdar, Arun K

2016-07-01

A new target-in-the-loop (TIL) atmospheric sensing concept for in situ remote measurements of major laser beam characteristics and atmospheric turbulence parameters is proposed and analyzed numerically. The technique is based on utilization of an integral relationship between complex amplitudes of the counterpropagating optical waves known as overlapping integral or interference metric, whose value is preserved along the propagation path. It is shown that the interference metric can be directly measured using the proposed TIL sensing system composed of a single-mode fiber-based optical transceiver and a remotely located retro-target. The measured signal allows retrieval of key beam and atmospheric turbulence characteristics including scintillation index and the path-integrated refractive index structure parameter.

The Structures of Coiled-Coil Domains from Type III Secretion System Translocators Reveal Homology to Pore-Forming Toxins

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

Barta, Michael L.; Dickenson, Nicholas E.; Patil, Mrinalini

2012-03-26

Many pathogenic Gram-negative bacteria utilize type III secretion systems (T3SSs) to alter the normal functions of target cells. Shigella flexneri uses its T3SS to invade human intestinal cells to cause bacillary dysentery (shigellosis) that is responsible for over one million deaths per year. The Shigella type III secretion apparatus is composed of a basal body spanning both bacterial membranes and an exposed oligomeric needle. Host altering effectors are secreted through this energized unidirectional conduit to promote bacterial invasion. The active needle tip complex of S. flexneri is composed of a tip protein, IpaD, and two pore-forming translocators, IpaB and IpaC.more » While the atomic structure of IpaD has been elucidated and studied, structural data on the hydrophobic translocators from the T3SS family remain elusive. We present here the crystal structures of a protease-stable fragment identified within the N-terminal regions of IpaB from S. flexneri and SipB from Salmonella enterica serovar Typhimurium determined at 2.1 {angstrom} and 2.8 {angstrom} limiting resolution, respectively. These newly identified domains are composed of extended-length (114 {angstrom} in IpaB and 71 {angstrom} in SipB) coiled-coil motifs that display a high degree of structural homology to one another despite the fact that they share only 21% sequence identity. Further structural comparisons also reveal substantial similarity to the coiled-coil regions of pore-forming proteins from other Gram-negative pathogens, notably, colicin Ia. This suggests that these mechanistically separate and functionally distinct membrane-targeting proteins may have diverged from a common ancestor during the course of pathogen-specific evolutionary events.« less

Mechanical intermixing of components in (CoMoNi)-based systems and the formation of (CoMoNi)/WC nanocomposite layers on Ti sheets under ball collisions

NASA Astrophysics Data System (ADS)

Romankov, S.; Park, Y. C.; Shchetinin, I. V.

2017-11-01

Cobalt (Co), molybdenum (Mo), and nickel (Ni) components were simultaneously introduced onto titanium (Ti) surfaces from a composed target using ball collisions. Tungsten carbide (WC) balls were selected for processing as the source of a cemented carbide reinforcement phase. During processing, ball collisions continuously introduced components from the target and the grinding media onto the Ti surface and induced mechanical intermixing of the elements, resulting in formation of a complex nanocomposite structure onto the Ti surface. The as-fabricated microstructure consisted of uniformly dispersed WC particles embedded within an integrated metallic matrix composed of an amorphous phase with nanocrystalline grains. The phase composition of the alloyed layers, atomic reactions, and the matrix grain sizes depended on the combination of components introduced onto the Ti surface during milling. The as-fabricated layer exhibited a very high hardness compared to industrial metallic alloys and tool steel materials. This approach could be used for the manufacture of both cemented carbides and amorphous matrix composite layers.

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.

Composing only by thought: Novel application of the P300 brain-computer interface.

PubMed

Pinegger, Andreas; Hiebel, Hannah; Wriessnegger, Selina C; Müller-Putz, Gernot R

2017-01-01

The P300 event-related potential is a well-known pattern in the electroencephalogram (EEG). This kind of brain signal is used for many different brain-computer interface (BCI) applications, e.g., spellers, environmental controllers, web browsers, or for painting. In recent times, BCI systems are mature enough to leave the laboratories to be used by the end-users, namely severely disabled people. Therefore, new challenges arise and the systems should be implemented and evaluated according to user-centered design (USD) guidelines. We developed and implemented a new system that utilizes the P300 pattern to compose music. Our Brain Composing system consists of three parts: the EEG acquisition device, the P300-based BCI, and the music composing software. Seventeen musical participants and one professional composer performed a copy-spelling, a copy-composing, and a free-composing task with the system. According to the USD guidelines, we investigated the efficiency, the effectiveness and subjective criteria in terms of satisfaction, enjoyment, frustration, and attractiveness. The musical participants group achieved high average accuracies: 88.24% (copy-spelling), 88.58% (copy-composing), and 76.51% (free-composing). The professional composer achieved also high accuracies: 100% (copy-spelling), 93.62% (copy-composing), and 98.20% (free-composing). General results regarding the subjective criteria evaluation were that the participants enjoyed the usage of the Brain Composing system and were highly satisfied with the system. Showing very positive results with healthy people in this study, this was the first step towards a music composing system for severely disabled people.

Composing only by thought: Novel application of the P300 brain-computer interface

PubMed Central

Hiebel, Hannah; Wriessnegger, Selina C.; Müller-Putz, Gernot R.

2017-01-01

The P300 event-related potential is a well-known pattern in the electroencephalogram (EEG). This kind of brain signal is used for many different brain-computer interface (BCI) applications, e.g., spellers, environmental controllers, web browsers, or for painting. In recent times, BCI systems are mature enough to leave the laboratories to be used by the end-users, namely severely disabled people. Therefore, new challenges arise and the systems should be implemented and evaluated according to user-centered design (USD) guidelines. We developed and implemented a new system that utilizes the P300 pattern to compose music. Our Brain Composing system consists of three parts: the EEG acquisition device, the P300-based BCI, and the music composing software. Seventeen musical participants and one professional composer performed a copy-spelling, a copy-composing, and a free-composing task with the system. According to the USD guidelines, we investigated the efficiency, the effectiveness and subjective criteria in terms of satisfaction, enjoyment, frustration, and attractiveness. The musical participants group achieved high average accuracies: 88.24% (copy-spelling), 88.58% (copy-composing), and 76.51% (free-composing). The professional composer achieved also high accuracies: 100% (copy-spelling), 93.62% (copy-composing), and 98.20% (free-composing). General results regarding the subjective criteria evaluation were that the participants enjoyed the usage of the Brain Composing system and were highly satisfied with the system. Showing very positive results with healthy people in this study, this was the first step towards a music composing system for severely disabled people. PMID:28877175

Ultrastable Nontoxic RNA Nanoparticles for Targeting Triple-Negative Breast Cancer Stem Cells

DTIC Science & Technology

2016-04-01

delivery system to meet the urgent need of efficient strategies for the treatment of breast cancer. 15. SUBJECT TERMS RNA nanotechnology ; three-way...construct a new generation of drugs composed purely of RNA (Nature Nanotechnology , 2011, 6: 658; Nano Today, 2012, 7: 245). Our goal is to apply our...anti-proliferative, anti-invasive and anti- metastasis properties. 2. KEYWORDS: RNA nanotechnology ; three-way junction; RNA aptamer; miRNA; triple

An integrative top-down and bottom-up qualitative model construction framework for exploration of biochemical systems.

PubMed

Wu, Zujian; Pang, Wei; Coghill, George M

Computational modelling of biochemical systems based on top-down and bottom-up approaches has been well studied over the last decade. In this research, after illustrating how to generate atomic components by a set of given reactants and two user pre-defined component patterns, we propose an integrative top-down and bottom-up modelling approach for stepwise qualitative exploration of interactions among reactants in biochemical systems. Evolution strategy is applied to the top-down modelling approach to compose models, and simulated annealing is employed in the bottom-up modelling approach to explore potential interactions based on models constructed from the top-down modelling process. Both the top-down and bottom-up approaches support stepwise modular addition or subtraction for the model evolution. Experimental results indicate that our modelling approach is feasible to learn the relationships among biochemical reactants qualitatively. In addition, hidden reactants of the target biochemical system can be obtained by generating complex reactants in corresponding composed models. Moreover, qualitatively learned models with inferred reactants and alternative topologies can be used for further web-lab experimental investigations by biologists of interest, which may result in a better understanding of the system.

An optical processor for object recognition and tracking

NASA Technical Reports Server (NTRS)

Sloan, J.; Udomkesmalee, S.

1987-01-01

The design and development of a miniaturized optical processor that performs real time image correlation are described. The optical correlator utilizes the Vander Lugt matched spatial filter technique. The correlation output, a focused beam of light, is imaged onto a CMOS photodetector array. In addition to performing target recognition, the device also tracks the target. The hardware, composed of optical and electro-optical components, occupies only 590 cu cm of volume. A complete correlator system would also include an input imaging lens. This optical processing system is compact, rugged, requires only 3.5 watts of operating power, and weighs less than 3 kg. It represents a major achievement in miniaturizing optical processors. When considered as a special-purpose processing unit, it is an attractive alternative to conventional digital image recognition processing. It is conceivable that the combined technology of both optical and ditital processing could result in a very advanced robot vision system.

Fluorogenic reaction-based prodrug conjugates as targeted cancer theranostics.

PubMed

Lee, Min Hee; Sharma, Amit; Chang, Min Jung; Lee, Jinju; Son, Subin; Sessler, Jonathan L; Kang, Chulhun; Kim, Jong Seung

2018-01-02

Theranostic systems are receiving ever-increasing attention due to their potential therapeutic utility, imaging enhancement capability, and promise for advancing the field of personalized medicine, particularly as it relates to the diagnosis, staging, and treatment of cancer. In this Tutorial Review, we provide an introduction to the concepts of theranostic drug delivery effected via use of conjugates that are able to target cancer cells selectively, provide cytotoxic chemotherapeutics, and produce readily monitored imaging signals in vitro and in vivo. The underlying design concepts, requiring the synthesis of conjugates composed of imaging reporters, masked chemotherapeutic drugs, cleavable linkers, and cancer targeting ligands, are discussed. Particular emphasis is placed on highlighting the potential benefits of fluorogenic reaction-based targeted systems that are activated for both imaging and therapy by cellular entities, e.g., thiols, reactive oxygen species and enzymes, which are present at relatively elevated levels in tumour environments, physiological characteristics of cancer, e.g., hypoxia and acidic pH. Also discussed are systems activated by an external stimulus, such as light. The work summarized in this Tutorial Review will help define the role fluorogenic reaction-based, cancer-targeting theranostics may have in advancing drug discovery efforts, as well as improving our understanding of cellular uptake and drug release mechanisms.

PHOTONICS AND NANOTECHNOLOGY Laser synthesis and modification of composite nanoparticles in liquids

NASA Astrophysics Data System (ADS)

Tarasenko, N. V.; Butsen, A. V.

2010-12-01

The works devoted to the formation and modification of nanoparticles using laser ablation of solid targets in liquids are reviewed. Several approaches to implement laser ablation in liquids, aimed at synthesising nanoparticles of complex composition, are considered: direct laser ablation of a target of corresponding composition, laser ablation of a combined target composed of two different metals, laser irradiation of a mixture of two or more colloidal solutions, and laser ablation in reactive liquids. The properties of two-component bimetallic systems (Ag — Cu, Ag — Au), semiconductor nanocrystals (ZnO, CdSe), chalcopyrite nanoparticles, and doped oxide nanoparticles (ZnO:Ag, Gd2O2:Tb3+) formed as a result of single- and double-pulse laser ablation in different liquids (water, ethanol, acetone, solutions of polysaccharides) are discussed.

A deceptive pollination system targeting drosophilids through olfactory mimicry of yeast.

PubMed

Stökl, Johannes; Strutz, Antonia; Dafni, Amots; Svatos, Ales; Doubsky, Jan; Knaden, Markus; Sachse, Silke; Hansson, Bill S; Stensmyr, Marcus C

2010-10-26

In deceptive pollination, insects are bamboozled into performing nonrewarded pollination. A prerequisite for the evolutionary stability in such systems is that the plants manage to generate a perfect sensory impression of a desirable object in the insect nervous system [1]. The study of these plants can provide important insights into sensory preference of their visiting insects. Here, we present the first description of a deceptive pollination system that specifically targets drosophilid flies. We show that the examined plant (Arum palaestinum) accomplishes its deception through olfactory mimicry of fermentation, a strategy that represents a novel pollination syndrome. The lily odor is composed of volatiles characteristic of yeast, and produces in Drosophila melanogaster an antennal detection pattern similar to that elicited by a range of fermentation products. By functional imaging, we show that the lily odors target a specific subset of odorant receptors (ORs), which include the most conserved OR genes in the drosophilid olfactome. Furthermore, seven of eight visiting drosophilid species show a congruent olfactory response pattern to the lily, in spite of comprising species pairs separated by ∼40 million years [2], showing that the lily targets a basal function of the fly nose, shared by species with similar ecological preference. Copyright © 2010 Elsevier Ltd. All rights reserved.

Antenna complexes protect Photosystem I from Photoinhibition

PubMed Central

Alboresi, Alessandro; Ballottari, Matteo; Hienerwadel, Rainer; Giacometti, Giorgio M; Morosinotto, Tomas

2009-01-01

Background Photosystems are composed of two moieties, a reaction center and a peripheral antenna system. In photosynthetic eukaryotes the latter system is composed of proteins belonging to Lhc family. An increasing set of evidences demonstrated how these polypeptides play a relevant physiological function in both light harvesting and photoprotection. Despite the sequence similarity between antenna proteins associated with the two Photosystems, present knowledge on their physiological role is mostly limited to complexes associated to Photosystem II. Results In this work we analyzed the physiological role of Photosystem I antenna system in Arabidopsis thaliana both in vivo and in vitro. Plants depleted in individual antenna polypeptides showed a reduced capacity for photoprotection and an increased production of reactive oxygen species upon high light exposure. In vitro experiments on isolated complexes confirmed that depletion of antenna proteins reduced the resistance of isolated Photosystem I particles to high light and that the antenna is effective in photoprotection only upon the interaction with the core complex. Conclusion We show that antenna proteins play a dual role in Arabidopsis thaliana Photosystem I photoprotection: first, a Photosystem I with an intact antenna system is more resistant to high light because of a reduced production of reactive oxygen species and, second, antenna chlorophyll-proteins are the first target of high light damages. When photoprotection mechanisms become insufficient, the antenna chlorophyll proteins act as fuses: LHCI chlorophylls are degraded while the reaction center photochemical activity is maintained. Differences with respect to photoprotection strategy in Photosystem II, where the reaction center is the first target of photoinhibition, are discussed. PMID:19508723

Selective intracellular vaporisation of antibody-conjugated phase-change nano-droplets in vitro

NASA Astrophysics Data System (ADS)

Ishijima, A.; Minamihata, K.; Yamaguchi, S.; Yamahira, S.; Ichikawa, R.; Kobayashi, E.; Iijima, M.; Shibasaki, Y.; Azuma, T.; Nagamune, T.; Sakuma, I.

2017-03-01

While chemotherapy is a major mode of cancer therapeutics, its efficacy is limited by systemic toxicities and drug resistance. Recent advances in nanomedicine provide the opportunity to reduce systemic toxicities. However, drug resistance remains a major challenge in cancer treatment research. Here we developed a nanomedicine composed of a phase-change nano-droplet (PCND) and an anti-cancer antibody (9E5), proposing the concept of ultrasound cancer therapy with intracellular vaporisation. PCND is a liquid perfluorocarbon nanoparticle with a liquid-gas phase that is transformable upon exposure to ultrasound. 9E5 is a monoclonal antibody targeting epiregulin (EREG). We found that 9E5-conjugated PCNDs are selectively internalised into targeted cancer cells and kill the cells dynamically by ultrasound-induced intracellular vaporisation. In vitro experiments show that 9E5-conjugated PCND targets 97.8% of high-EREG-expressing cancer cells and kills 57% of those targeted upon exposure to ultrasound. Furthermore, direct observation of the intracellular vaporisation process revealed the significant morphological alterations of cells and the release of intracellular contents.

Single-molecule fluorescence measurements reveal the reaction mechanisms of the core RISC, composed of human Argonaute 2 and a guide RNA.

PubMed

Jo, Myung Hyun; Song, Ji-Joon; Hohng, Sungchul

2015-12-01

In eukaryotes, small RNAs play important roles in both gene regulation and resistance to viral infection. Argonaute proteins have been identified as a key component of the effector complexes of various RNA-silencing pathways, but the mechanistic roles of Argonaute proteins in these pathways are not clearly understood. To address this question, we performed single-molecule fluorescence experiments using an RNA-induced silencing complex (core-RISC) composed of a small RNA and human Argonaute 2. We found that target binding of core-RISC starts at the seed region of the guide RNA. After target binding, four distinct reactions followed: target cleavage, transient binding, stable binding, and Argonaute unloading. Target cleavage required extensive sequence complementarity and accelerated core-RISC dissociation for recycling. In contrast, the stable binding of core-RISC to target RNAs required seed-match only, suggesting a potential explanation for the seed-match rule of microRNA (miRNA) target selection.

Secondary neutron-production cross sections from heavy-ioninteractions in composite targets.

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

Heilbronn, L.; Iwata, Y.; Iwase,H.

Secondary neutron-production cross-sections have been measured from interactions of 290 MeV/nucleon C and 600 MeV/nucleon Ne in a target composed of simulated Martian regolith and polyethylene, and from 400 MeV/nucleon Ne interactions in wall material from the International Space Station. The data were measured between 5 and 80 deg in the laboratory. We report the double-differential cross sections, angular distributions, and total neutron-production cross sections from all three systems. The spectra from all three systems exhibit behavior previously reported in other heavy-ion, neutron production experiments; namely, a peak at forward angles near the energy corresponding to the beam velocity, withmore » the remaining spectra generated by pre-equilibrium and equilibrium processes. The double differential cross sections are fitted with a moving-source parameterization. Also reported are the data without corrections for neutron flux attenuation in the target and other intervening materials, and for neutron production in non-target materials near the target position. These uncorrected spectra are compared with SHIELD-HIT and PHITS transport model calculations. The transport model calculations reproduce the spectral shapes well, but, on average, underestimate the magnitudes of the cross sections.« less

DNA/RNA hybrid substrates modulate the catalytic activity of purified AID.

PubMed

Abdouni, Hala S; King, Justin J; Ghorbani, Atefeh; Fifield, Heather; Berghuis, Lesley; Larijani, Mani

2018-01-01

Activation-induced cytidine deaminase (AID) converts cytidine to uridine at Immunoglobulin (Ig) loci, initiating somatic hypermutation and class switching of antibodies. In vitro, AID acts on single stranded DNA (ssDNA), but neither double-stranded DNA (dsDNA) oligonucleotides nor RNA, and it is believed that transcription is the in vivo generator of ssDNA targeted by AID. It is also known that the Ig loci, particularly the switch (S) regions targeted by AID are rich in transcription-generated DNA/RNA hybrids. Here, we examined the binding and catalytic behavior of purified AID on DNA/RNA hybrid substrates bearing either random sequences or GC-rich sequences simulating Ig S regions. If substrates were made up of a random sequence, AID preferred substrates composed entirely of DNA over DNA/RNA hybrids. In contrast, if substrates were composed of S region sequences, AID preferred to mutate DNA/RNA hybrids over substrates composed entirely of DNA. Accordingly, AID exhibited a significantly higher affinity for binding DNA/RNA hybrid substrates composed specifically of S region sequences, than any other substrates composed of DNA. Thus, in the absence of any other cellular processes or factors, AID itself favors binding and mutating DNA/RNA hybrids composed of S region sequences. AID:DNA/RNA complex formation and supporting mutational analyses suggest that recognition of DNA/RNA hybrids is an inherent structural property of AID. Copyright © 2017 Elsevier Ltd. All rights reserved.

High pulse rate high resolution optical radar system

NASA Technical Reports Server (NTRS)

Goss, W. C.; Burns, R. H.; Chi, K. (Inventor)

1973-01-01

The system is composed of an optical cavity with a laser and a mode locking means to build up an optical pulse. An optical switch is also provided within the cavity to convert the polarization of the optical pulse generated within the cavity. The optical switch comprises an electro-optical crystal driven by a time delayed driver circuit which is triggered by a coincident signal made from an optical pulse signal and a gating pulse signal. The converted optical pulse strikes a polarization sensitive prism and is deflected out of the cavity toward the pending target in the form of a pulse containing most of the optical energy generated by the laser in the pulse build-up period. After striking the target, the reflected energy is picked up by a transceiver with the total travel time of the pulse being recorded.

Speckle-metric-optimization-based adaptive optics for laser beam projection and coherent beam combining.

PubMed

Vorontsov, Mikhail; Weyrauch, Thomas; Lachinova, Svetlana; Gatz, Micah; Carhart, Gary

2012-07-15

Maximization of a projected laser beam's power density at a remotely located extended object (speckle target) can be achieved by using an adaptive optics (AO) technique based on sensing and optimization of the target-return speckle field's statistical characteristics, referred to here as speckle metrics (SM). SM AO was demonstrated in a target-in-the-loop coherent beam combining experiment using a bistatic laser beam projection system composed of a coherent fiber-array transmitter and a power-in-the-bucket receiver. SM sensing utilized a 50 MHz rate dithering of the projected beam that provided a stair-mode approximation of the outgoing combined beam's wavefront tip and tilt with subaperture piston phases. Fiber-integrated phase shifters were used for both the dithering and SM optimization with stochastic parallel gradient descent control.

High density laser-driven target

DOEpatents

Lindl, John D.

1981-01-01

A high density target for implosion by laser energy composed of a central quantity of fuel surrounded by a high-Z pusher shell with a low-Z ablator-pusher shell spaced therefrom forming a region filled with low-density material.

Continuous composition-spread thin films of transition metal oxides by pulsed-laser deposition

NASA Astrophysics Data System (ADS)

Ohkubo, I.; Christen, H. M.; Khalifah, P.; Sathyamurthy, S.; Zhai, H. Y.; Rouleau, C. M.; Mandrus, D. G.; Lowndes, D. H.

2004-02-01

We have designed an improved pulsed-laser deposition-continuous composition-spread (PLD-CCS) system that overcomes the difficulties associated with earlier related techniques. Our new PLD-CCS system is based on a precisely controlled synchronization between the laser firing, target exchange, and substrate translation/rotation, and offers more flexibility and control than earlier PLD-based approaches. Most importantly, the deposition energetics and the film thickness are kept constant across the entire composition range, and the resulting samples are sufficiently large to allow characterization by conventional techniques. We fabricated binary alloy composition-spread films composed of SrRuO 3 and CaRuO 3. Alternating ablation from two different ceramic targets leads to in situ alloy formation, and the value of x in Sr xCa x-1 RuO 3 can be changed linearly from 0 to 1 (or over any arbitrarily smaller range) along one direction of the substrate.

Toward a systems-level view of dynamic phosphorylation networks

PubMed Central

Newman, Robert H.; Zhang, Jin; Zhu, Heng

2014-01-01

To better understand how cells sense and respond to their environment, it is important to understand the organization and regulation of the phosphorylation networks that underlie most cellular signal transduction pathways. These networks, which are composed of protein kinases, protein phosphatases and their respective cellular targets, are highly dynamic. Importantly, to achieve signaling specificity, phosphorylation networks must be regulated at several levels, including at the level of protein expression, substrate recognition, and spatiotemporal modulation of enzymatic activity. Here, we briefly summarize some of the traditional methods used to study the phosphorylation status of cellular proteins before focusing our attention on several recent technological advances, such as protein microarrays, quantitative mass spectrometry, and genetically-targetable fluorescent biosensors, that are offering new insights into the organization and regulation of cellular phosphorylation networks. Together, these approaches promise to lead to a systems-level view of dynamic phosphorylation networks. PMID:25177341

Coherent detection of position errors in inter-satellite laser communications

NASA Astrophysics Data System (ADS)

Xu, Nan; Liu, Liren; Liu, De'an; Sun, Jianfeng; Luan, Zhu

2007-09-01

Due to the improved receiver sensitivity and wavelength selectivity, coherent detection became an attractive alternative to direct detection in inter-satellite laser communications. A novel method to coherent detection of position errors information is proposed. Coherent communication system generally consists of receive telescope, local oscillator, optical hybrid, photoelectric detector and optical phase lock loop (OPLL). Based on the system composing, this method adds CCD and computer as position error detector. CCD captures interference pattern while detection of transmission data from the transmitter laser. After processed and analyzed by computer, target position information is obtained from characteristic parameter of the interference pattern. The position errors as the control signal of PAT subsystem drive the receiver telescope to keep tracking to the target. Theoretical deviation and analysis is presented. The application extends to coherent laser rang finder, in which object distance and position information can be obtained simultaneously.

High-speed railway real-time localization auxiliary method based on deep neural network

NASA Astrophysics Data System (ADS)

Chen, Dongjie; Zhang, Wensheng; Yang, Yang

2017-11-01

High-speed railway intelligent monitoring and management system is composed of schedule integration, geographic information, location services, and data mining technology for integration of time and space data. Assistant localization is a significant submodule of the intelligent monitoring system. In practical application, the general access is to capture the image sequences of the components by using a high-definition camera, digital image processing technique and target detection, tracking and even behavior analysis method. In this paper, we present an end-to-end character recognition method based on a deep CNN network called YOLO-toc for high-speed railway pillar plate number. Different from other deep CNNs, YOLO-toc is an end-to-end multi-target detection framework, furthermore, it exhibits a state-of-art performance on real-time detection with a nearly 50fps achieved on GPU (GTX960). Finally, we realize a real-time but high-accuracy pillar plate number recognition system and integrate natural scene OCR into a dedicated classification YOLO-toc model.

Optical system design of solar-blind UV target simulator with long focal length

NASA Astrophysics Data System (ADS)

Chen, Yu; Huo, Furong; Zheng, Liqin

2014-11-01

Ultraviolet (UV) radiation of 200nm-300nm waveband from the sun is absorbed by atmosphere, which is often referred to the solar-blind region of the solar spectrum. Solar-blind characteristics of this waveband have important application value, especially in military fields. The application of solar-blind waveband has developed very rapidly, which is receiving more and more attention. Sometimes, to test the performance of a UV optical system, a standard solar-blind UV target simulator is needed as the UV light source. In this paper, an optical system of a solar-blind UV target simulator is designed with waveband 240nm-280nm. To simulate a far UV target, the focal length of this UV optical system needs to be long. Besides, different field of view (FOV) of the system should meet aplanatic condition. The optional materials are very few for UV optical systems, in which only CaF2 and JGS1 are commonly used. Various aberrations are difficult to be corrected. To save production cost and enhance the precision of fabrication and test, aspheric surfaces and binary elements are not adopted in the system. Moreover, doublet or triplet cannot be used in UV optical system considering possible cracking for different thermal expansion coefficients of different materials. After optimization, the system is composed of 4 lenses with focal length 500mm. MTF curves of different FOV coincide together. The maximum RMS radius of the optimized system has almost the same size as Airy disk, which proves the good image quality after system optimization. The aplanatic condition is met very well in this system. In the spot diagram, root mean square (RMS) radius changes from 3 microns to 3.6 microns, which has similar size with Airy disk and meets aplanatic condition very well. This optical system of solar-blind UV target simulator also has relatively loose tolerance data, which can prove the system is designed in an optimal state.

Secondary neutron-production cross sections from heavy-ion interactions in composite targets

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

Heilbronn, L.; Iwata, Y.; Murakami, T.

Secondary neutron-production cross sections have been measured from interactions of 290 MeV/nucleon C and 600 MeV/nucleon Ne in a target composed of simulated Martian regolith and polyethylene, and from 400 MeV/nucleon Ne interactions in wall material from the International Space Station. The data were measured between 5 deg. and 80 deg. in the laboratory. We report the double-differential cross sections, angular distributions, and total neutron-production cross sections from all three systems. The spectra from all three systems exhibit behavior previously reported in other heavy-ion neutron-production experiments, namely, a peak at forward angles near the energy corresponding to the beam velocity,more » with the remaining spectra generated by pre-equilibrium and equilibrium processes. The double-differential cross sections are fitted with a moving-source parametrization. Also reported are the data without corrections for neutron flux attenuation in the target and other intervening materials and for neutron production in nontarget materials near the target position. These uncorrected spectra are compared with SHIELD-HIT and PHITS transport model calculations. The transport model calculations reproduce the spectral shapes well but, on average, underestimate the magnitudes of the cross sections.« less

Performance calculation and simulation system of high energy laser weapon

NASA Astrophysics Data System (ADS)

Wang, Pei; Liu, Min; Su, Yu; Zhang, Ke

2014-12-01

High energy laser weapons are ready for some of today's most challenging military applications. Based on the analysis of the main tactical/technical index and combating process of high energy laser weapon, a performance calculation and simulation system of high energy laser weapon was established. Firstly, the index decomposition and workflow of high energy laser weapon was proposed. The entire system was composed of six parts, including classical target, platform of laser weapon, detect sensor, tracking and pointing control, laser atmosphere propagation and damage assessment module. Then, the index calculation modules were designed. Finally, anti-missile interception simulation was performed. The system can provide reference and basis for the analysis and evaluation of high energy laser weapon efficiency.

Post-annealing-free, room temperature processed nanocrystalline indium tin oxide thin films for plastic electronics

NASA Astrophysics Data System (ADS)

Nyoung Jang, Jin; Jong Lee, You; Jang, YunSung; Yun, JangWon; Yi, Seungjun; Hong, MunPyo

2016-06-01

In this study, we confirm that bombardment by high energy negative oxygen ions (NOIs) is the key origin of electro-optical property degradations in indium tin oxide (ITO) thin films formed by conventional plasma sputtering processes. To minimize the bombardment effect of NOIs, which are generated on the surface of the ITO targets and accelerated by the cathode sheath potential on the magnetron sputter gun (MSG), we introduce a magnetic field shielded sputtering (MFSS) system composed of a permanent magnetic array between the MSG and the substrate holder to block the arrival of energetic NOIs. The MFSS processed ITO thin films reveal a novel nanocrystal imbedded polymorphous structure, and present not only superior electro-optical characteristics but also higher gas diffusion barrier properties. To the best of our knowledge, no gas diffusion barrier composed of a single inorganic thin film formed by conventional plasma sputtering processes achieves such a low moisture permeability.

Transmutation of uranium and thorium in the particle field of the Quinta sub-critical assembly

NASA Astrophysics Data System (ADS)

Hashemi-Nezhad, S. R.; Asquith, N. L.; Voronko, V. A.; Sotnikov, V. V.; Zhadan, Alina; Zhuk, I. V.; Potapenko, A.; Husak, Krystsina; Chilap, V.; Adam, J.; Baldin, A.; Berlev, A.; Furman, W.; Kadykov, M.; Khushvaktov, J.; Kudashkin, I.; Mar'in, I.; Paraipan, M.; Pronskih, V.; Solnyshkin, A.; Tyutyunnikov, S.

2018-03-01

The fission rates of natural uranium and thorium were measured in the particle field of Quinta, a 512 kg natural uranium target-blanket sub-critical assembly. The Quinta assembly was irradiated with deuterons of energy 4 GeV from the Nuclotron accelerator of the Joint Institute for Nuclear Research (JINR), Dubna, Russia. Fission rates of uranium and thorium were measured using Gamma spectroscopy and fission track techniques. The production rate of 239Np was also measured. The obtained experimental results were compared with Monte Carlo predictions using the MCNPX 2.7 code employing the physics and fission-evaporation models of INCL4-ABLA, CEM03.03 and LAQGSM03.03. Some of the neutronic characteristics of the Quinta are compared with the "Energy plus Transmutation (EpT)" subcritical assembly, which is composed of a lead target and natU blanket. This comparison clearly demonstrates the importance of target material, neutron moderator and reflector types on the performance of a spallation neutron driven subcritical system. As the dimensions of the Quinta are very close to those of an optimal multi-rod-uranium target, the experimental and Monte Carlo calculation results presented in this paper provide insights on the particle field within a uranium target as well as in Accelerator Driven Systems in general.

Deep turbulence effects mitigation with coherent combining of 21 laser beams over 7 km.

PubMed

Weyrauch, Thomas; Vorontsov, Mikhail; Mangano, Joseph; Ovchinnikov, Vladimir; Bricker, David; Polnau, Ernst; Rostov, Andrey

2016-02-15

We demonstrate coherent beam combining and adaptive mitigation of atmospheric turbulence effects over 7 km under strong scintillation conditions using a coherent fiber array laser transmitter operating in a target-in-the-loop setting. The transmitter system is composed of a densely packed array of 21 fiber collimators with integrated capabilities for piston, tip, and tilt control of the outgoing beams wavefront phases. A small cat's-eye retro reflector was used for evaluation of beam combining and turbulence compensation performance at the target plane, and to provide the feedback signal for control of piston and tip/tilt phases of the transmitted beams using the stochastic parallel gradient descent maximization of the power-in-the-bucket metric.

MINERvA CCInclusive Analysis

NASA Astrophysics Data System (ADS)

Martinez, David

2013-04-01

MINERvA is a few-GeV neutrino scattering experiment that has been taking data in the NuMI beam line at Fermilab since November 2009. The experiment will provide important inputs, both in support of neutrino oscillation searches and as a pure weak probe of the nuclear medium. For this, MINERvA employs a fine-grained detector, with an eight ton active target region composed of plastic scintillator and a suite of nuclear targets composed of helium, carbon, iron, lead and water placed upstream of the active region. In this talk, we present the current status of the charged current inclusive analysis for neutrinos and antineutrinos in plastic scintillator.

Polymeric micelles as a new drug carrier system and their required considerations for clinical trials.

PubMed

Yokoyama, Masayuki

2010-02-01

A polymeric micelle is a macromolecular assembly composed of an inner core and an outer shell, and most typically is formed from block copolymers. In the last two decades, polymeric micelles have been actively studied as a new type of drug carrier system, in particular for drug targeting of anticancer drugs to solid tumors. In this review, polymeric micelle drug carrier systems are discussed with a focus on toxicities of the polymeric micelle carrier systems and on pharmacological activities of the block copolymers. In the first section, the importance of the above-mentioned evaluation of these properties is explained, as this importance does not seem to be well recognized compared with the importance of targeting and enhanced pharmacological activity of drugs, particularly in the basic studies. Then, designs, types and classifications of the polymeric micelle system are briefly summarized and explained, followed by a detailed discussion regarding several examples of polymeric micelle carrier systems. Readers will gain a strategy of drug delivery with polymeric carriers as well as recent progress of the polymeric micelle carrier systems in their basic studies and clinical trials. The purpose of this review is to achieve tight connections between the basic studies and clinical trials.

Comparative efficiency analysis of fiber-array and conventional beam director systems in volume turbulence.

PubMed

Vorontsov, Mikhail; Filimonov, Grigory; Ovchinnikov, Vladimir; Polnau, Ernst; Lachinova, Svetlana; Weyrauch, Thomas; Mangano, Joseph

2016-05-20

The performance of two prominent laser beam projection system types is analyzed through wave-optics numerical simulations for various atmospheric turbulence conditions, propagation distances, and adaptive optics (AO) mitigation techniques. Comparisons are made between different configurations of both a conventional beam director (BD) using a monolithic-optics-based Cassegrain telescope and a fiber-array BD that uses an array of densely packed fiber collimators. The BD systems considered have equal input power and aperture diameters. The projected laser beam power inside the Airy size disk at the target plane is used as the performance metric. For the fiber-array system, both incoherent and coherent beam combining regimes are considered. We also present preliminary results of side-by-side atmospheric beam projection experiments over a 7-km propagation path using both the AO-enhanced beam projection system with a Cassegrain telescope and the coherent fiber-array BD composed of 21 densely packed fiber collimators. Both wave-optics numerical simulation and experimental results demonstrate that, for similar system architectures and turbulence conditions, coherent fiber-array systems are more efficient in mitigation of atmospheric turbulence effects and generation of a hit spot of the smallest possible size on a remotely located target.

Regeneration of strong-base anion-exchange resins by sequential chemical displacement

DOEpatents

Brown, Gilbert M.; Gu, Baohua; Moyer, Bruce A.; Bonnesen, Peter V.

2002-01-01

A method for regenerating strong-base anion exchange resins utilizing a sequential chemical displacement technique with new regenerant formulation. The new first regenerant solution is composed of a mixture of ferric chloride, a water-miscible organic solvent, hydrochloric acid, and water in which tetrachloroferrate anion is formed and used to displace the target anions on the resin. The second regenerant is composed of a dilute hydrochloric acid and is used to decompose tetrachloroferrate and elute ferric ions, thereby regenerating the resin. Alternative chemical displacement methods include: (1) displacement of target anions with fluoroborate followed by nitrate or salicylate and (2) displacement of target anions with salicylate followed by dilute hydrochloric acid. The methodology offers an improved regeneration efficiency, recovery, and waste minimization over the conventional displacement technique using sodium chloride (or a brine) or alkali metal hydroxide.

Video-Camera-Based Position-Measuring System

NASA Technical Reports Server (NTRS)

Lane, John; Immer, Christopher; Brink, Jeffrey; Youngquist, Robert

2005-01-01

A prototype optoelectronic system measures the three-dimensional relative coordinates of objects of interest or of targets affixed to objects of interest in a workspace. The system includes a charge-coupled-device video camera mounted in a known position and orientation in the workspace, a frame grabber, and a personal computer running image-data-processing software. Relative to conventional optical surveying equipment, this system can be built and operated at much lower cost; however, it is less accurate. It is also much easier to operate than are conventional instrumentation systems. In addition, there is no need to establish a coordinate system through cooperative action by a team of surveyors. The system operates in real time at around 30 frames per second (limited mostly by the frame rate of the camera). It continuously tracks targets as long as they remain in the field of the camera. In this respect, it emulates more expensive, elaborate laser tracking equipment that costs of the order of 100 times as much. Unlike laser tracking equipment, this system does not pose a hazard of laser exposure. Images acquired by the camera are digitized and processed to extract all valid targets in the field of view. The three-dimensional coordinates (x, y, and z) of each target are computed from the pixel coordinates of the targets in the images to accuracy of the order of millimeters over distances of the orders of meters. The system was originally intended specifically for real-time position measurement of payload transfers from payload canisters into the payload bay of the Space Shuttle Orbiters (see Figure 1). The system may be easily adapted to other applications that involve similar coordinate-measuring requirements. Examples of such applications include manufacturing, construction, preliminary approximate land surveying, and aerial surveying. For some applications with rectangular symmetry, it is feasible and desirable to attach a target composed of black and white squares to an object of interest (see Figure 2). For other situations, where circular symmetry is more desirable, circular targets also can be created. Such a target can readily be generated and modified by use of commercially available software and printed by use of a standard office printer. All three relative coordinates (x, y, and z) of each target can be determined by processing the video image of the target. Because of the unique design of corresponding image-processing filters and targets, the vision-based position- measurement system is extremely robust and tolerant of widely varying fields of view, lighting conditions, and varying background imagery.

Electrostatically assembled dendrimer complex with a high-affinity protein binder for targeted gene delivery.

PubMed

Kim, Jong-Won; Lee, Joong-Jae; Choi, Joon Sig; Kim, Hak-Sung

2018-06-10

Although a variety of non-viral gene delivery systems have been developed, they still suffer from low efficiency and specificity. Herein, we present the assembly of a dendrimer complex comprising a DNA cargo and a targeting moiety as a new format for targeted gene delivery. A PAMAM dendrimer modified with histidine and arginine (HR-dendrimer) was used to enhance the endosomal escape and transfection efficiency. An EGFR-specific repebody, composed of leucine-rich repeat (LRR) modules, was employed as a targeting moiety. A polyanionic peptide was genetically fused to the repebody, followed by incubation with an HR-dendrimer and a DNA cargo to assemble the dendrimer complex through an electrostatic interaction. The resulting dendrimer complex was shown to deliver a DNA cargo with high efficiency in a receptor-specific manner. An analysis using a confocal microscope confirmed the internalization of the dendrimer complex and subsequent dissociation of a DNA cargo from the complex. The present approach can be broadly used in a targeted gene delivery in many areas. Copyright © 2018 Elsevier B.V. All rights reserved.

A computational framework for modeling targets as complex adaptive systems

NASA Astrophysics Data System (ADS)

Santos, Eugene; Santos, Eunice E.; Korah, John; Murugappan, Vairavan; Subramanian, Suresh

2017-05-01

Modeling large military targets is a challenge as they can be complex systems encompassing myriad combinations of human, technological, and social elements that interact, leading to complex behaviors. Moreover, such targets have multiple components and structures, extending across multiple spatial and temporal scales, and are in a state of change, either in response to events in the environment or changes within the system. Complex adaptive system (CAS) theory can help in capturing the dynamism, interactions, and more importantly various emergent behaviors, displayed by the targets. However, a key stumbling block is incorporating information from various intelligence, surveillance and reconnaissance (ISR) sources, while dealing with the inherent uncertainty, incompleteness and time criticality of real world information. To overcome these challenges, we present a probabilistic reasoning network based framework called complex adaptive Bayesian Knowledge Base (caBKB). caBKB is a rigorous, overarching and axiomatic framework that models two key processes, namely information aggregation and information composition. While information aggregation deals with the union, merger and concatenation of information and takes into account issues such as source reliability and information inconsistencies, information composition focuses on combining information components where such components may have well defined operations. Since caBKBs can explicitly model the relationships between information pieces at various scales, it provides unique capabilities such as the ability to de-aggregate and de-compose information for detailed analysis. Using a scenario from the Network Centric Operations (NCO) domain, we will describe how our framework can be used for modeling targets with a focus on methodologies for quantifying NCO performance metrics.

Drug accumulation by means of noninvasive magnetic drug delivery system

NASA Astrophysics Data System (ADS)

Chuzawa, M.; Mishima, F.; Akiyama, Y.; Nishijima, S.

2011-11-01

The medication is one of the most general treatment methods, but drugs diffuse in the normal tissues other than the target part by the blood circulation. Therefore, side effect in the medication, particularly for a drug with strong effect such as anti-cancer drug, are a serious issue. Drug Delivery System (DDS) which accumulates the drug locally in the human body is one of the techniques to solve the side-effects. Magnetic Drug Delivery System (MDDS) is one of the active DDSs, which uses the magnetic force. The objective of this study is to accumulate the ferromagnetic drugs noninvasively in the deep part of the body by using MDDS. It is necessary to generate high magnetic field and magnetic gradient at the target part to reduce the side-effects to the tissues with no diseases. The biomimetic model was composed, which consists of multiple model organs connected with diverged blood vessel model. The arrangement of magnetic field was examined to accumulate ferromagnetic drug particles in the target model organ by using a superconducting bulk magnet which can generate high magnetic fields. The arrangement of magnet was designed to generate high and stable magnetic field at the target model organ. The accumulation experiment of ferromagnetic particles has been conducted. In this study, rotating HTS bulk magnet around the axis of blood vessels by centering on the target part was suggested, and the model experiment for magnet rotation was conducted. As a result, the accumulation of the ferromagnetic particles to the target model organ in the deep part was confirmed.

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.

Two distinct redox cascades cooperatively regulate chloroplast functions and sustain plant viability.

PubMed

Yoshida, Keisuke; Hisabori, Toru

2016-07-05

The thiol-based redox regulation system is believed to adjust chloroplast functions in response to changes in light environments. A redox cascade via the ferredoxin-thioredoxin reductase (FTR)/thioredoxin (Trx) pathway has been traditionally considered to serve as a transmitter of light signals to target enzymes. However, emerging data indicate that chloroplasts have a complex redox network composed of diverse redox-mediator proteins and target enzymes. Despite extensive research addressing this system, two fundamental questions are still unresolved: How are redox pathways orchestrated within chloroplasts, and why are chloroplasts endowed with a complicated redox network? In this report, we show that NADPH-Trx reductase C (NTRC) is a key redox-mediator protein responsible for regulatory functions distinct from those of the classically known FTR/Trx system. Target screening and subsequent biochemical assays indicated that NTRC and the Trx family differentially recognize their target proteins. In addition, we found that NTRC is an electron donor to Trx-z, which is a key regulator of gene expression in chloroplasts. We further demonstrate that cooperative control of chloroplast functions via the FTR/Trx and NTRC pathways is essential for plant viability. Arabidopsis double mutants impaired in FTR and NTRC expression displayed lethal phenotypes under autotrophic growth conditions. This severe growth phenotype was related to a drastic loss of photosynthetic performance. These combined results provide an expanded map of the chloroplast redox network and its biological functions.

Two distinct redox cascades cooperatively regulate chloroplast functions and sustain plant viability

PubMed Central

Yoshida, Keisuke; Hisabori, Toru

2016-01-01

The thiol-based redox regulation system is believed to adjust chloroplast functions in response to changes in light environments. A redox cascade via the ferredoxin-thioredoxin reductase (FTR)/thioredoxin (Trx) pathway has been traditionally considered to serve as a transmitter of light signals to target enzymes. However, emerging data indicate that chloroplasts have a complex redox network composed of diverse redox-mediator proteins and target enzymes. Despite extensive research addressing this system, two fundamental questions are still unresolved: How are redox pathways orchestrated within chloroplasts, and why are chloroplasts endowed with a complicated redox network? In this report, we show that NADPH-Trx reductase C (NTRC) is a key redox-mediator protein responsible for regulatory functions distinct from those of the classically known FTR/Trx system. Target screening and subsequent biochemical assays indicated that NTRC and the Trx family differentially recognize their target proteins. In addition, we found that NTRC is an electron donor to Trx-z, which is a key regulator of gene expression in chloroplasts. We further demonstrate that cooperative control of chloroplast functions via the FTR/Trx and NTRC pathways is essential for plant viability. Arabidopsis double mutants impaired in FTR and NTRC expression displayed lethal phenotypes under autotrophic growth conditions. This severe growth phenotype was related to a drastic loss of photosynthetic performance. These combined results provide an expanded map of the chloroplast redox network and its biological functions. PMID:27335455

Momentum sharing in imbalanced Fermi systems

NASA Astrophysics Data System (ADS)

Hen, O.; Sargsian, M.; Weinstein, L. B.; Piasetzky, E.; Hakobyan, H.; Higinbotham, D. W.; Braverman, M.; Brooks, W. K.; Gilad, S.; Adhikari, K. P.; Arrington, J.; Asryan, G.; Avakian, H.; Ball, J.; Baltzell, N. A.; Battaglieri, M.; Beck, A.; Beck, S. May-Tal; Bedlinskiy, I.; Bertozzi, W.; Biselli, A.; Burkert, V. D.; Cao, T.; Carman, D. S.; Celentano, A.; Chandavar, S.; Colaneri, L.; Cole, P. L.; Crede, V.; D'Angelo, A.; De Vita, R.; Deur, A.; Djalali, C.; Doughty, D.; Dugger, M.; Dupre, R.; Egiyan, H.; El Alaoui, A.; El Fassi, L.; Elouadrhiri, L.; Fedotov, G.; Fegan, S.; Forest, T.; Garillon, B.; Garcon, M.; Gevorgyan, N.; Ghandilyan, Y.; Gilfoyle, G. P.; Girod, F. X.; Goetz, J. T.; Gothe, R. W.; Griffioen, K. A.; Guidal, M.; Guo, L.; Hafidi, K.; Hanretty, C.; Hattawy, M.; Hicks, K.; Holtrop, M.; Hyde, C. E.; Ilieva, Y.; Ireland, D. G.; Ishkanov, B. I.; Isupov, E. L.; Jiang, H.; Jo, H. S.; Joo, K.; Keller, D.; Khandaker, M.; Kim, A.; Kim, W.; Klein, F. J.; Koirala, S.; Korover, I.; Kuhn, S. E.; Kubarovsky, V.; Lenisa, P.; Levine, W. I.; Livingston, K.; Lowry, M.; Lu, H. Y.; MacGregor, I. J. D.; Markov, N.; Mayer, M.; McKinnon, B.; Mineeva, T.; Mokeev, V.; Movsisyan, A.; Camacho, C. Munoz; Mustapha, B.; Nadel-Turonski, P.; Niccolai, S.; Niculescu, G.; Niculescu, I.; Osipenko, M.; Pappalardo, L. L.; Paremuzyan, R.; Park, K.; Pasyuk, E.; Phelps, W.; Pisano, S.; Pogorelko, O.; Price, J. W.; Procureur, S.; Prok, Y.; Protopopescu, D.; Puckett, A. J. R.; Rimal, D.; Ripani, M.; Ritchie, B. G.; Rizzo, A.; Rosner, G.; Roy, P.; Rossi, P.; Sabatié, F.; Schott, D.; Schumacher, R. A.; Sharabian, Y. G.; Smith, G. D.; Shneor, R.; Sokhan, D.; Stepanyan, S. S.; Stepanyan, S.; Stoler, P.; Strauch, S.; Sytnik, V.; Taiuti, M.; Tkachenko, S.; Ungaro, M.; Vlassov, A. V.; Voutier, E.; Walford, N. K.; Wei, X.; Wood, M. H.; Wood, S. A.; Zachariou, N.; Zana, L.; Zhao, Z. W.; Zheng, X.; Zonta, I.; aff16

2014-10-01

The atomic nucleus is composed of two different kinds of fermions: protons and neutrons. If the protons and neutrons did not interact, the Pauli exclusion principle would force the majority of fermions (usually neutrons) to have a higher average momentum. Our high-energy electron-scattering measurements using 12C, 27Al, 56Fe, and 208Pb targets show that even in heavy, neutron-rich nuclei, short-range interactions between the fermions form correlated high-momentum neutron-proton pairs. Thus, in neutron-rich nuclei, protons have a greater probability than neutrons to have momentum greater than the Fermi momentum. This finding has implications ranging from nuclear few-body systems to neutron stars and may also be observable experimentally in two-spin-state, ultracold atomic gas systems.

Using Docker Compose for the Simple Deployment of an Integrated Drug Target Screening Platform.

PubMed

List, Markus

2017-06-10

Docker virtualization allows for software tools to be executed in an isolated and controlled environment referred to as a container. In Docker containers, dependencies are provided exactly as intended by the developer and, consequently, they simplify the distribution of scientific software and foster reproducible research. The Docker paradigm is that each container encapsulates one particular software tool. However, to analyze complex biomedical data sets, it is often necessary to combine several software tools into elaborate workflows. To address this challenge, several Docker containers need to be instantiated and properly integrated, which complicates the software deployment process unnecessarily. Here, we demonstrate how an extension to Docker, Docker compose, can be used to mitigate these problems by providing a unified setup routine that deploys several tools in an integrated fashion. We demonstrate the power of this approach by example of a Docker compose setup for a drug target screening platform consisting of five integrated web applications and shared infrastructure, deployable in just two lines of codes.

Genetically engineered and self-assembled oncolytic protein nanoparticles for targeted cancer therapy.

PubMed

Lee, Joong-Jae; Kang, Jung Ae; Ryu, Yiseul; Han, Sang-Soo; Nam, You Ree; Rho, Jong Kook; Choi, Dae Seong; Kang, Sun-Woong; Lee, Dong-Eun; Kim, Hak-Sung

2017-03-01

The integration of a targeted delivery with a tumour-selective agent has been considered an ideal platform for achieving high therapeutic efficacy and negligible side effects in cancer therapy. Here, we present engineered protein nanoparticles comprising a tumour-selective oncolytic protein and a targeting moiety as a new format for the targeted cancer therapy. Apoptin from chicken anaemia virus (CAV) was used as a tumour-selective apoptotic protein. An EGFR-specific repebody, which is composed of LRR (Leucine-rich repeat) modules, was employed to play a dual role as a tumour-targeting moiety and a fusion partner for producing apoptin nanoparticles in E. coli, respectively. The repebody was genetically fused to apoptin, and the resulting fusion protein was shown to self-assemble into supramolecular repebody-apoptin nanoparticles with high homogeneity and stability as a soluble form when expressed in E. coli. The repebody-apoptin nanoparticles showed a remarkable anti-tumour activity with negligible side effects in xenograft mice through a cooperative action of the two protein components with distinct functional roles. The repebody-apoptin nanoparticles can be developed as a systemic injectable and tumour-selective therapeutic protein for targeted cancer treatment. Copyright © 2016 Elsevier Ltd. All rights reserved.

Development of a Recombinant Multifunctional Biomacromolecule for Targeted Gene Transfer to Prostate Cancer Cells.

PubMed

Hatefi, Arash; Karjoo, Zahra; Nomani, Alireza

2017-09-11

The objective of this study was to genetically engineer a fully functional single chain fusion peptide composed of motifs from diverse biological and synthetic origins that can perform multiple tasks including DNA condensation, cell targeting, cell transfection, particle shielding from immune system and effective gene transfer to prostate tumors. To achieve the objective, a single chain biomacromolecule (vector) consisted of four repeatative units of histone H2A peptide, fusogenic peptide GALA, short elastin-like peptide, and PC-3 cell targeting peptide was designed. To examine the functionality of each motif in the vector sequence, it was characterized in terms of size and zeta potential by Zetasizer, PC-3 cell targeting and transfection by flowcytometry, IgG induction by immunogenicity assay, and PC-3 tumor transfection by quantitative live animal imaging. Overall, the results of this study showed the possibility of using genetic engineering techniques to program various functionalities into one single chain vector and create a multifunctional nonimmunogenic biomacromolecule for targeted gene transfer to prostate cancer cells. This proof-of-concept study is a significant step forward toward creating a library of vectors for targeted gene transfer to any cancer cell type at both in vitro and in vivo levels.

Universal, colorimetric microRNA detection strategy based on target-catalyzed toehold-mediated strand displacement reaction

NASA Astrophysics Data System (ADS)

Park, Yeonkyung; Lee, Chang Yeol; Kang, Shinyoung; Kim, Hansol; Park, Ki Soo; Park, Hyun Gyu

2018-02-01

In this work, we developed a novel, label-free, and enzyme-free strategy for the colorimetric detection of microRNA (miRNA), which relies on a target-catalyzed toehold-mediated strand displacement (TMSD) reaction. The system employs a detection probe that specifically binds to the target miRNA and sequentially releases a catalyst strand (CS) intended to trigger the subsequent TMSD reaction. Thus, the presence of target miRNA releases the CS that mediates the formation of an active G-quadruplex DNAzyme which is initially caged and inactivated by a blocker strand. In addition, a fuel strand that is supplemented for the recycling of the CS promotes another TMSD reaction, consequently generating a large number of active G-quadruplex DNAzymes. As a result, a distinct colorimetric signal is produced by the ABTS oxidation promoted by the peroxidase mimicking activity of the released G-quadruplex DNAzymes. Based on this novel strategy, we successfully detected miR-141, a promising biomarker for human prostate cancer, with high selectivity. The diagnostic capability of this system was also demonstrated by reliably determining target miR-141 in human serum, showing its great potential towards real clinical applications. Importantly, the proposed approach is composed of separate target recognition and signal transduction modules. Thus, it could be extended to analyze different target miRNAs by simply redesigning the detection probe while keeping the same signal transduction module as a universal signal amplification unit, which was successfully demonstrated by analyzing another target miRNA, let-7d.

Universal, colorimetric microRNA detection strategy based on target-catalyzed toehold-mediated strand displacement reaction.

PubMed

Park, Yeonkyung; Lee, Chang Yeol; Kang, Shinyoung; Kim, Hansol; Park, Ki Soo; Park, Hyun Gyu

2018-02-23

In this work, we developed a novel, label-free, and enzyme-free strategy for the colorimetric detection of microRNA (miRNA), which relies on a target-catalyzed toehold-mediated strand displacement (TMSD) reaction. The system employs a detection probe that specifically binds to the target miRNA and sequentially releases a catalyst strand (CS) intended to trigger the subsequent TMSD reaction. Thus, the presence of target miRNA releases the CS that mediates the formation of an active G-quadruplex DNAzyme which is initially caged and inactivated by a blocker strand. In addition, a fuel strand that is supplemented for the recycling of the CS promotes another TMSD reaction, consequently generating a large number of active G-quadruplex DNAzymes. As a result, a distinct colorimetric signal is produced by the ABTS oxidation promoted by the peroxidase mimicking activity of the released G-quadruplex DNAzymes. Based on this novel strategy, we successfully detected miR-141, a promising biomarker for human prostate cancer, with high selectivity. The diagnostic capability of this system was also demonstrated by reliably determining target miR-141 in human serum, showing its great potential towards real clinical applications. Importantly, the proposed approach is composed of separate target recognition and signal transduction modules. Thus, it could be extended to analyze different target miRNAs by simply redesigning the detection probe while keeping the same signal transduction module as a universal signal amplification unit, which was successfully demonstrated by analyzing another target miRNA, let-7d.

Microstructures and properties of superconducting Y-ErBaCuO thin films obtained from disordered Y-ErBaF2Cu films

NASA Technical Reports Server (NTRS)

Cikmach, P.; Diociaiuti, M.; Fontana, A.; Giovannella, C.; Iannuzzi, M.; Lucchini, C.; Merlo, V.; Messi, R.; Paoluzi, L.; Scopa, L.

1991-01-01

The preparation procedure used to obtain superconducting thin films by radio frequency magnetron sputtering of a single mosaic target is described in detail. The single mosaic target is composed of (Y-Er), BaF2, and Cu.

Design and fabrication of an autonomous rendezvous and docking sensor using off-the-shelf hardware

NASA Technical Reports Server (NTRS)

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

1991-01-01

NASA Marshall Space Flight Center (MSFC) has developed and tested an engineering model of an automated rendezvous and docking sensor system composed of a video camera ringed with laser diodes at two wavelengths and a standard remote manipulator system target that has been modified with retro-reflective tape and 830 and 780 mm optical filters. TRW has provided additional engineering analysis, design, and manufacturing support, resulting in a robust, low cost, automated rendezvous and docking sensor design. We have addressed the issue of space qualification using off-the-shelf hardware components. We have also addressed the performance problems of increased signal to noise ratio, increased range, increased frame rate, graceful degradation through component redundancy, and improved range calibration. Next year, we will build a breadboard of this sensor. The phenomenology of the background scene of a target vehicle as viewed against earth and space backgrounds under various lighting conditions will be simulated using the TRW Dynamic Scene Generator Facility (DSGF). Solar illumination angles of the target vehicle and candidate docking target ranging from eclipse to full sun will be explored. The sensor will be transportable for testing at the MSFC Flight Robotics Laboratory (EB24) using the Dynamic Overhead Telerobotic Simulator (DOTS).

Aptamers and their Applications in Nanomedicine

PubMed Central

Sun, Hongguang; Zu, Youli

2015-01-01

Aptamers are composed of short RNA or single-stranded DNA sequences that, when folded into their unique three-dimensional conformation, can specifically bind to their cognate targets with high specificity and affinity. Although functionally similar to protein antibodies, oligonucleotide aptamers offer several advantages over protein antibodies in biomedical and clinical applications. Additionally, through the enhanced permeability and retention (EPR) effect, nanomedicines can improve the therapeutic index of a treatment and reduce side effects by enhancing accumulation at the disease site. However, this EPR effect is “passive targeting” to tumors and thus, may not be an ideal approach for targeted cancer therapy. To construct ligand-directed “active targeting” nano-based delivery systems, aptamer technology has been widely studied. The aptamer-equipped nanomedicines have been tested for in vitro diagnosis, in vivo imaging, targeted cancer therapy, theranostic approaches, sub-cellular molecule detection, food safety, and environment monitoring. This review will focus on the development of aptamer-conjugated nanomedicines and their application for in vivo imaging, targeted therapy, and theranostics. In some applications, aptamers can also be used as drug carriers or ON/OFF switches. Herein, some outstanding therapeutic approaches are also discussed on a case-by-case basis, such as an “on-command” release system and a combinational therapy strategy. PMID:25677591

Performance of a superconducting magnet system operated in the Super Omega Muon beam line at J-PARC

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

Makida, Yasuhiro; Ikedo, Yutaka; Ogitsu, Toru

A superconducting magnet system, which is composed of an 8 m long solenoid for transportation and 12 short solenoids for focusing, has been developed for Muon Science Establishment facility of J-PARC. The transport solenoid is composed of a 6 m straight section connected to a 45 degree curved section at each end. Muons of various momenta and of both electric charges are transported through the solenoid inner bore with an effective diameter of 0.3 m, where 2 T magnetic field is induced. There are 12 focusing solenoids with an effective bore diameter of 0.6 m and a length of 0.35more » m arranged on a straight line at suitable intervals. The maximum central field of each focusing solenoid is 0.66 T. All solenoid coils are cooled by GM cryocoolers through their own conductions. The magnet system has been installed into the beam line in the summer of 2012, and its performance has been checked. Beam commissioning has been carried out since October 2012. During beam operation, temperature rise over 6 K in the transport solenoid due to a nuclear heating from the muon production target is observed at beam intensity of about 300 kW.« less

Microbial Growth in the Magnesium- Chloride - Sodium- Sulphate Ion System: Implications for Habitability in Terrestrial and Extraterrestrial Salts

NASA Astrophysics Data System (ADS)

Loudon, C. M.; Aka, S.; Cockell, C. S.

2017-12-01

Icy moons in the outer solar system are key targets in the search for extra-terrestrial life as there is evidence that they harbour subsurface oceans. Observational evidence of icy moons such as Europa suggest that these likely brine oceans should be composed of chloride and sulphate salts. The effects of the ions that compose these salts on biology and how the interactions between them can create geochemical and geophysical barriers to life are poorly understood. Here we present an in depth study of four microorganisms grown in solutions with varying combinations of the magnesium- chloride- sodium- sulphate ions. We find that the ion composition of the brine solution can have a large effect on growth. Whilst the water activity must be permissible for growth we found that this alone could not predict the effects of the ions on growth, chaotropic effects and ion specific effects influenced by the specific physiology of organisms are also evident. For this reason we conclude that simply knowing which salts are present on icy moons is not sufficient information to determine their potential habitibility. A full sample of any brine ocean would need to be studied to fully determine the potential for biology on these outer solar system satellites.

A Phoswich Detector System to Measure Sub-Second Half-Lives using ICF Reactions

NASA Astrophysics Data System (ADS)

Coats, Micah; Cook, Katelyn; Yuly, Mark; Padalino, Stephen; Sangster, Craig; Regan, Sean

2017-10-01

The 3H(t,γ)6He cross section has not been measured at any bombarding energy due to the difficulties of simultaneously producing both a tritium beam and target at accelerator labs. An alternative technique may be to use an ICF tt implosion at the OMEGA Laser Facility. The 3H(t,γ)6He cross section could be determined in situ by measuring the beta decay of 6He beginning a few milliseconds after the shot along with other ICF diagnostics. A dE-E phoswich system capable of surviving in the OMEGA target chamber was tested using the SUNY Geneseo pelletron to create neutrons via 2H(d,n)3He and subsequently 6He via 9Be(n,α)6He in a beryllium target. The phoswich dE-E detector system was used to select beta decay events and measure the 807 ms half-life of 6He. It is composed of a thin, 2 ns decay time dE scintillator optically coupled to a thick, 285 ns E scintillator, with a linear gate to separate the short dE pulse from the longer E tail. Funded in part by a Grant from the DOE through the Laboratory for Laser Energetics.

Improvements to an earth observing statistical performance model with applications to LWIR spectral variability

NASA Astrophysics Data System (ADS)

Zhao, Runchen; Ientilucci, Emmett J.

2017-05-01

Hyperspectral remote sensing systems provide spectral data composed of hundreds of narrow spectral bands. Spectral remote sensing systems can be used to identify targets, for example, without physical interaction. Often it is of interested to characterize the spectral variability of targets or objects. The purpose of this paper is to identify and characterize the LWIR spectral variability of targets based on an improved earth observing statistical performance model, known as the Forecasting and Analysis of Spectroradiometric System Performance (FASSP) model. FASSP contains three basic modules including a scene model, sensor model and a processing model. Instead of using mean surface reflectance only as input to the model, FASSP transfers user defined statistical characteristics of a scene through the image chain (i.e., from source to sensor). The radiative transfer model, MODTRAN, is used to simulate the radiative transfer based on user defined atmospheric parameters. To retrieve class emissivity and temperature statistics, or temperature / emissivity separation (TES), a LWIR atmospheric compensation method is necessary. The FASSP model has a method to transform statistics in the visible (ie., ELM) but currently does not have LWIR TES algorithm in place. This paper addresses the implementation of such a TES algorithm and its associated transformation of statistics.

The Design and Evaluation of a Large-Scale Real-Walking Locomotion Interface

PubMed Central

Peck, Tabitha C.; Fuchs, Henry; Whitton, Mary C.

2014-01-01

Redirected Free Exploration with Distractors (RFED) is a large-scale real-walking locomotion interface developed to enable people to walk freely in virtual environments that are larger than the tracked space in their facility. This paper describes the RFED system in detail and reports on a user study that evaluated RFED by comparing it to walking-in-place and joystick interfaces. The RFED system is composed of two major components, redirection and distractors. This paper discusses design challenges, implementation details, and lessons learned during the development of two working RFED systems. The evaluation study examined the effect of the locomotion interface on users’ cognitive performance on navigation and wayfinding measures. The results suggest that participants using RFED were significantly better at navigating and wayfinding through virtual mazes than participants using walking-in-place and joystick interfaces. Participants traveled shorter distances, made fewer wrong turns, pointed to hidden targets more accurately and more quickly, and were able to place and label targets on maps more accurately, and more accurately estimate the virtual environment size. PMID:22184262

Combined chemo- and photo-thermal therapy delivered by multifunctional theranostic gold nanorod-loaded microcapsules

NASA Astrophysics Data System (ADS)

Chen, Haiyan; di, Yingfeng; Chen, Dan; Madrid, Kyle; Zhang, Min; Tian, Caiping; Tang, Liping; Gu, Yueqing

2015-05-01

A polyelectrolyte microcapsule-based, cancer-targeting, and controlled drug delivery system has been developed as a multifunctional theranostic agent for synergistic cancer treatment. This new system, called FA-MC@GNR, is composed of folic acid (FA)-modified, multi-layered, hollow microcapsules loaded with gold nanorods (GNRs), and undergoes thermal degradation under near infrared (NIR) light. Either an NIR dye (MPA) or anti-cancer drug (doxorubicin, DOX) was loaded into the microcapsules via physical adsorption, yielding FA-MC@GNRs/MPA or FA-MC@GNRs/DOX, both of which exhibit no obvious toxicity, high stability, and remarkably improved tumor-targeting capabilities in vivo. Utilizing the strong NIR absorption of FA-MC@GNRs/DOX, we demonstrate the system's ability to simultaneously elicit photothermal therapy and controlled chemotherapy, achieving synergistic cancer treatment both in vitro cellular and in vivo animal experiments. Our study presents a new type of multifunctional micro-carrier for the delivery of chemotherapeutic drugs and photothermal agents, which has been shown to be an effective therapeutic approach for combined cancer treatment.

A knowledge-based system for prototypical reasoning

NASA Astrophysics Data System (ADS)

Lieto, Antonio; Minieri, Andrea; Piana, Alberto; Radicioni, Daniele P.

2015-04-01

In this work we present a knowledge-based system equipped with a hybrid, cognitively inspired architecture for the representation of conceptual information. The proposed system aims at extending the classical representational and reasoning capabilities of the ontology-based frameworks towards the realm of the prototype theory. It is based on a hybrid knowledge base, composed of a classical symbolic component (grounded on a formal ontology) with a typicality based one (grounded on the conceptual spaces framework). The resulting system attempts to reconcile the heterogeneous approach to the concepts in Cognitive Science with the dual process theories of reasoning and rationality. The system has been experimentally assessed in a conceptual categorisation task where common sense linguistic descriptions were given in input, and the corresponding target concepts had to be identified. The results show that the proposed solution substantially extends the representational and reasoning 'conceptual' capabilities of standard ontology-based systems.

Navigation system for a mobile robot with a visual sensor using a fish-eye lens

NASA Astrophysics Data System (ADS)

Kurata, Junichi; Grattan, Kenneth T. V.; Uchiyama, Hironobu

1998-02-01

Various position sensing and navigation systems have been proposed for the autonomous control of mobile robots. Some of these systems have been installed with an omnidirectional visual sensor system that proved very useful in obtaining information on the environment around the mobile robot for position reckoning. In this article, this type of navigation system is discussed. The sensor is composed of one TV camera with a fish-eye lens, using a reference target on a ceiling and hybrid image processing circuits. The position of the robot, with respect to the floor, is calculated by integrating the information obtained from a visual sensor and a gyroscope mounted in the mobile robot, and the use of a simple algorithm based on PTP control for guidance is discussed. An experimental trial showed that the proposed system was both valid and useful for the navigation of an indoor vehicle.

MRI segmentation using dialectical optimization.

PubMed

dos Santos, Wellington P; de Assis, Francisco M; de Souza, Ricardo E

2009-01-01

Biology, Psychology and Social Sciences are intrinsically connected to the very roots of the development of algorithms and methods in Computational Intelligence, as it is easily seen in approaches like genetic algorithms, evolutionary programming and particle swarm optimization. In this work we propose a new optimization method based on dialectics using fuzzy membership functions to model the influence of interactions between integrating poles in the status of each pole. Poles are the basic units composing dialectical systems. In order to validate our proposal we designed a segmentation method based on the optimization of k-means using dialectics for the segmentation of MR images. As a case study we used 181 MR synthetic multispectral images composed by proton density, T(1)- and T(2)-weighted synthetic brain images of 181 slices with 1 mm, resolution of 1 mm(3), for a normal brain and a noiseless MR tomographic system without field inhomogeneities, amounting a total of 543 images, generated by the simulator BrainWeb [2]. Our principal target here is comparing our proposal to k-means, fuzzy c-means, and Kohonen's self-organized maps, concerning the quantization error, we proved that our method can improved results obtained using k-means.

Discovery and Early Development of AVI-7537 and AVI-7288 for the Treatment of Ebola Virus and Marburg Virus Infections

PubMed Central

Iversen, Patrick L.; Warren, Travis K.; Wells, Jay B.; Garza, Nicole L.; Mourich, Dan V.; Welch, Lisa S.; Panchal, Rekha G.; Bavari, Sina

2012-01-01

There are no currently approved treatments for filovirus infections. In this study we report the discovery process which led to the development of antisense Phosphorodiamidate Morpholino Oligomers (PMOs) AVI-6002 (composed of AVI-7357 and AVI-7539) and AVI-6003 (composed of AVI-7287 and AVI-7288) targeting Ebola virus and Marburg virus respectively. The discovery process involved identification of optimal transcript binding sites for PMO based RNA-therapeutics followed by screening for effective viral gene target in mouse and guinea pig models utilizing adapted viral isolates. An evolution of chemical modifications were tested, beginning with simple Phosphorodiamidate Morpholino Oligomers (PMO) transitioning to cell penetrating peptide conjugated PMOs (PPMO) and ending with PMOplus containing a limited number of positively charged linkages in the PMO structure. The initial lead compounds were combinations of two agents targeting separate genes. In the final analysis, a single agent for treatment of each virus was selected, AVI-7537 targeting the VP24 gene of Ebola virus and AVI-7288 targeting NP of Marburg virus, and are now progressing into late stage clinical development as the optimal therapeutic candidates. PMID:23202506

Discovery and early development of AVI-7537 and AVI-7288 for the treatment of Ebola virus and Marburg virus infections.

PubMed

Iversen, Patrick L; Warren, Travis K; Wells, Jay B; Garza, Nicole L; Mourich, Dan V; Welch, Lisa S; Panchal, Rekha G; Bavari, Sina

2012-11-06

There are no currently approved treatments for filovirus infections. In this study we report the discovery process which led to the development of antisense Phosphorodiamidate Morpholino Oligomers (PMOs) AVI-6002 (composed of AVI-7357 and AVI-7539) and AVI-6003 (composed of AVI-7287 and AVI-7288) targeting Ebola virus and Marburg virus respectively. The discovery process involved identification of optimal transcript binding sites for PMO based RNA-therapeutics followed by screening for effective viral gene target in mouse and guinea pig models utilizing adapted viral isolates. An evolution of chemical modifications were tested, beginning with simple Phosphorodiamidate Morpholino Oligomers (PMO) transitioning to cell penetrating peptide conjugated PMOs (PPMO) and ending with PMOplus containing a limited number of positively charged linkages in the PMO structure. The initial lead compounds were combinations of two agents targeting separate genes. In the final analysis, a single agent for treatment of each virus was selected, AVI-7537 targeting the VP24 gene of Ebola virus and AVI-7288 targeting NP of Marburg virus, and are now progressing into late stage clinical development as the optimal therapeutic candidates.

VizieR Online Data Catalog: Five years of blazar observations with VERITAS (Archambault+, 2016)

NASA Astrophysics Data System (ADS)

Archambault, S.; Archer, A.; Benbow, W.; Bird, R.; Biteau, J.; Buchovecky, M.; Buckley, J. H.; Bugaev, V.; Byrum, K.; Cerruti, M.; Chen, X.; Ciupik, L.; Connolly, M. P.; Cui, W.; Eisch, J. D.; Errando, M.; Falcone, A.; Feng, Q.; Finley, J. P.; Fleischhack, H.; Fortin, P.; Fortson, L.; Furniss, A.; Gillanders, G. H.; Griffin, S.; Grube, J.; Gyuk, G.; Hutten, M.; Hakansson, N.; Hanna, D.; Holder, J.; Humensky, T. B.; Johnson, C. A.; Kaaret, P.; Kar, P.; Kelley-Hoskins, N.; Kertzman, M.; Kieda, D.; Krause, M.; Krennrich, F.; Kumar, S.; Lang, M. J.; Maier, G.; McArthur, S.; McCann, A.; Meagher, K.; Moriarty, P.; Mukherjee, R.; Nguyen, T.; Nieto, D.; O'Faolain de Bhroithe, A.; Ong, R. A.; Otte, A. N.; Park, N.; Perkins, J. S.; Pichel, A.; Pohl, M.; Popkow, A.; Pueschel, E.; Quinn, J.; Ragan, K.; Reynolds, P. T.; Richards, G. T.; Roache, E.; Rovero, A. C.; Santander, M.; Sembroski, G. H.; Shahinyan, K.; Smith, A. W.; Staszak, D.; Telezhinsky, I.; Tucci, J. V.; Tyler, J.; Vincent, S.; Wakely, S. P.; Weiner, O. M.; Weinstein, A.; Williams, D. A.; Zitzer, B.

2018-04-01

In this paper, we present the results of the analysis of most of the non-detected blazars observed by VERITAS from 2007 (the beginning of full-scale scientific operations) to 2012 August (before the upgrade of the VERITAS array, see Kieda 2013arXiv1308.4849D). The VERITAS (Very Energetic Radiation Imaging Telescope Array System) telescope array is composed of four IACTs of 12 m diameter each, located at the Fred Lawrence Whipple Observatory, on the slopes of Mount Hopkins, in southern Arizona (31°40'N, 110°57'W). Each telescope has a segmented mirror that focuses light onto a camera composed of 499 photomultipliers located at the focal plane. The instrument FOV is 3.5°. For further details on the VERITAS instrument, see Holder et al. (2006APh....25..391H) and Holder (2011ICRC...12..137H). The VERITAS observations here have an average length of 20 minutes (referred to as a run), before switching targets or wobble directions. (7 data files).

Core–Shell Structure and Aggregation Number of Micelles Composed of Amphiphilic Block Copolymers and Amphiphilic Heterografted Polymer Brushes Determined by Small-Angle X-ray Scattering

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

Szymusiak, Magdalena; Kalkowski, Joseph; Luo, Hanying

2017-08-31

A large group of functional nanomaterials employed in biomedical applications, including targeted drug delivery, relies on amphiphilic polymers to encapsulate therapeutic payloads via self-assembly processes. Knowledge of the micelle structures will provide critical insights into design of polymeric drug delivery systems. Core–shell micelles composed of linear diblock copolymers poly(ethylene glycol)-b-poly(caprolactone) (PEG-b-PCL), poly(ethylene oxide)-b-poly(lactic acid) (PEG-b-PLA), as well as a heterografted brush consisting of a poly(glycidyl methacrylate) backbone with PEG and PLA branches (PGMA-g-PEG/PLA) were characterized by dynamic light scattering (DLS) and small-angle X-ray scattering (SAXS) measurements to gain structural information regarding the particle morphology, core–shell size, and aggregation number. Themore » structural information at this quasi-equilibrium state can also be used as a reference when studying the kinetics of polymer micellization.« less

Core–Shell Structure and Aggregation Number of Micelles Composed of Amphiphilic Block Copolymers and Amphiphilic Heterografted Polymer Brushes Determined by Small-Angle X-ray Scattering

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

Szymusiak, Magdalena; Kalkowski, Joseph; Luo, Hanying

2017-08-16

A large group of functional nanomaterials employed in biomedical applications, including targeted drug delivery, relies on amphiphilic polymers to encapsulate therapeutic payloads via self-assembly processes. Knowledge of the micelle structures will provide critical insights into design of polymeric drug delivery systems. Core–shell micelles composed of linear diblock copolymers poly(ethylene glycol)-b-poly(caprolactone) (PEG-b-PCL), poly(ethylene oxide)-b-poly(lactic acid) (PEG-b-PLA), as well as a heterografted brush consisting of a poly(glycidyl methacrylate) backbone with PEG and PLA branches (PGMA-g-PEG/PLA) were characterized by dynamic light scattering (DLS) and small-angle X-ray scattering (SAXS) measurements to gain structural information regarding the particle morphology, core–shell size, and aggregation number. Themore » structural information at this quasi-equilibrium state can also be used as a reference when studying the kinetics of polymer micellization.« less

Indoor imagery with a 3D through-wall synthetic aperture radar

NASA Astrophysics Data System (ADS)

Sévigny, Pascale; DiFilippo, David J.; Laneve, Tony; Fournier, Jonathan

2012-06-01

Through-wall radar imaging is an emerging technology with great interest to military and police forces operating in an urban environment. A through-wall imaging radar can potentially provide interior room layouts as well as detection and localization of targets of interest within a building. In this paper, we present our through-wall radar system mounted on the side of a vehicle and driven along a path in front of a building of interest. The vehicle is equipped with a LIDAR (Light Detection and Ranging) and motion sensors that provide auxiliary information. The radar uses an ultra wideband frequency-modulated continuous wave (FMCW) waveform to obtain high range resolution. Our system is composed of a vertical linear receive array to discriminate targets in elevation, and two transmit elements operated in a slow multiple-input multiple output (MIMO) configuration to increase the achievable elevation resolution. High resolution in the along-track direction is obtained through synthetic aperture radar (SAR) techniques. We present experimental results that demonstrate the 3-D capability of the radar. We further demonstrate target detection behind challenging walls, and imagery of internal wall features. Finally, we discuss future work.

Bioconjugation of recombinant tissue plasminogen activator to magnetic nanocarriers for targeted thrombolysis

PubMed Central

Yang, Hung-Wei; Hua, Mu-Yi; Lin, Kun-Ju; Wey, Shiaw-Pyng; Tsai, Rung-Ywan; Wu, Siao-Yun; Lu, Yi-Ching; Liu, Hao-Li; Wu, Tony; Ma, Yunn-Hwa

2012-01-01

Low-toxicity magnetic nanocarriers (MNCs) composed of a shell of poly [aniline-co-N-(1-one-butyric acid) aniline] over a Fe3O4 magnetic nanoparticle core were developed to carry recombinant tissue plasminogen activator (rtPA) in MNC-rtPA for targeted thrombolysis. With an average diameter of 14.8 nm, the MNCs exerted superparamagnetic properties. Up to 276 μg of active rtPA was immobilized per mg of MNCs, and the stability of the immobilized rtPA was greatly improved during storage at 4°C and 25°C. In vitro thrombolysis testing with a tubing system demonstrated that magnet-guided MNC-rtPA showed significantly improved thrombolysis compared with free rtPA and reduced the clot lysis time from 39.2 ± 3.2 minutes to 10.8 ± 4.2 minutes. In addition, magnet-guided MNC-rtPA at 20% of the regular rtPA dose restored blood flow within 15–25 minutes of treatment in a rat embolism model without triggering hematological toxicity. In conclusion, this improved system is based on magnetic targeting accelerated thrombolysis and is potentially amenable to therapeutic applications in thromboembolic diseases. PMID:23055728

Comprehension Tools for Teachers: Reading for Understanding from Prekindergarten through Fourth Grade

PubMed Central

Connor, Carol McDonald; Phillips, Beth M.; Kaschak, Michael; Apel, Kenn; Kim, Young-Suk; Al Otaiba, Stephanie; Crowe, Elizabeth C.; Thomas-Tate, Shurita; Johnson, Lakeisha Cooper; Lonigan, Christopher J.

2015-01-01

This paper describes the theoretical framework, as well as the development and testing of the intervention, Comprehension Tools for Teachers (CTT), which is composed of eight component interventions targeting malleable language and reading comprehension skills that emerging research indicates contribute to proficient reading for understanding for prekindergarteners through fourth graders. Component interventions target processes considered largely automatic as well as more reflective processes, with interacting and reciprocal effects. Specifically, we present component interventions targeting cognitive, linguistic, and text-specific processes, including morphological awareness, syntax, mental-state verbs, comprehension monitoring, narrative and expository text structure, enacted comprehension, academic knowledge, and reading to learn from informational text. Our aim was to develop a tool set composed of intensive meaningful individualized small group interventions. We improved feasibility in regular classrooms through the use of design-based iterative research methods including careful lesson planning, targeted scripting, pre- and postintervention proximal assessments, and technology. In addition to the overall framework, we discuss seven of the component interventions and general results of design and efficacy studies. PMID:26500420

Momentum sharing in imbalanced Fermi systems

DOE PAGES

Hen, O.; Sargsian, M.; Weinstein, L. B.; ...

2014-10-16

The atomic nucleus is composed of two different kinds of fermions, protons and neutrons. If the protons and neutrons did not interact, the Pauli exclusion principle would force the majority fermions (usually neutrons) to have a higher average momentum. Our high-energy electron scattering measurements using 12C, 27Al, 56Fe and 208Pb targets show that, even in heavy neutron-rich nuclei, short-range interactions between the fermions form correlated high-momentum neutron-proton pairs. Thus, in neutron-rich nuclei, protons have a greater probability than neutrons to have momentum greater than the Fermi momentum. This finding has implications ranging from nuclear few body systems to neutron starsmore » and may also be observable experimentally in two-spin state, ultra-cold atomic gas systems.« less

Nuclear physics. Momentum sharing in imbalanced Fermi systems.

PubMed

Hen, O; Sargsian, M; Weinstein, L B; Piasetzky, E; Hakobyan, H; Higinbotham, D W; Braverman, M; Brooks, W K; Gilad, S; Adhikari, K P; Arrington, J; Asryan, G; Avakian, H; Ball, J; Baltzell, N A; Battaglieri, M; Beck, A; May-Tal Beck, S; Bedlinskiy, I; Bertozzi, W; Biselli, A; Burkert, V D; Cao, T; Carman, D S; Celentano, A; Chandavar, S; Colaneri, L; Cole, P L; Crede, V; D'Angelo, A; De Vita, R; Deur, A; Djalali, C; Doughty, D; Dugger, M; Dupre, R; Egiyan, H; El Alaoui, A; El Fassi, L; Elouadrhiri, L; Fedotov, G; Fegan, S; Forest, T; Garillon, B; Garcon, M; Gevorgyan, N; Ghandilyan, Y; Gilfoyle, G P; Girod, F X; Goetz, J T; Gothe, R W; Griffioen, K A; Guidal, M; Guo, L; Hafidi, K; Hanretty, C; Hattawy, M; Hicks, K; Holtrop, M; Hyde, C E; Ilieva, Y; Ireland, D G; Ishkanov, B I; Isupov, E L; Jiang, H; Jo, H S; Joo, K; Keller, D; Khandaker, M; Kim, A; Kim, W; Klein, F J; Koirala, S; Korover, I; Kuhn, S E; Kubarovsky, V; Lenisa, P; Levine, W I; Livingston, K; Lowry, M; Lu, H Y; MacGregor, I J D; Markov, N; Mayer, M; McKinnon, B; Mineeva, T; Mokeev, V; Movsisyan, A; Munoz Camacho, C; Mustapha, B; Nadel-Turonski, P; Niccolai, S; Niculescu, G; Niculescu, I; Osipenko, M; Pappalardo, L L; Paremuzyan, R; Park, K; Pasyuk, E; Phelps, W; Pisano, S; Pogorelko, O; Price, J W; Procureur, S; Prok, Y; Protopopescu, D; Puckett, A J R; Rimal, D; Ripani, M; Ritchie, B G; Rizzo, A; Rosner, G; Roy, P; Rossi, P; Sabatié, F; Schott, D; Schumacher, R A; Sharabian, Y G; Smith, G D; Shneor, R; Sokhan, D; Stepanyan, S S; Stepanyan, S; Stoler, P; Strauch, S; Sytnik, V; Taiuti, M; Tkachenko, S; Ungaro, M; Vlassov, A V; Voutier, E; Walford, N K; Wei, X; Wood, M H; Wood, S A; Zachariou, N; Zana, L; Zhao, Z W; Zheng, X; Zonta, I

2014-10-31

The atomic nucleus is composed of two different kinds of fermions: protons and neutrons. If the protons and neutrons did not interact, the Pauli exclusion principle would force the majority of fermions (usually neutrons) to have a higher average momentum. Our high-energy electron-scattering measurements using (12)C, (27)Al, (56)Fe, and (208)Pb targets show that even in heavy, neutron-rich nuclei, short-range interactions between the fermions form correlated high-momentum neutron-proton pairs. Thus, in neutron-rich nuclei, protons have a greater probability than neutrons to have momentum greater than the Fermi momentum. This finding has implications ranging from nuclear few-body systems to neutron stars and may also be observable experimentally in two-spin-state, ultracold atomic gas systems. Copyright © 2014, American Association for the Advancement of Science.

Generation of a Knockout Mouse Embryonic Stem Cell Line Using a Paired CRISPR/Cas9 Genome Engineering Tool.

PubMed

Wettstein, Rahel; Bodak, Maxime; Ciaudo, Constance

2016-01-01

CRISPR/Cas9, originally discovered as a bacterial immune system, has recently been engineered into the latest tool to successfully introduce site-specific mutations in a variety of different organisms. Composed only of the Cas9 protein as well as one engineered guide RNA for its functionality, this system is much less complex in its setup and easier to handle than other guided nucleases such as Zinc-finger nucleases or TALENs.Here, we describe the simultaneous transfection of two paired CRISPR sgRNAs-Cas9 plasmids, in mouse embryonic stem cells (mESCs), resulting in the knockout of the selected target gene. Together with a four primer-evaluation system, it poses an efficient way to generate new independent knockout mouse embryonic stem cell lines.

Biocomputing nanoplatforms as therapeutics and diagnostics.

PubMed

Evans, A C; Thadani, N N; Suh, J

2016-10-28

Biocomputing nanoplatforms are designed to detect and integrate single or multiple inputs under defined algorithms, such as Boolean logic gates, and generate functionally useful outputs, such as delivery of therapeutics or release of optically detectable signals. Using sensing modules composed of small molecules, polymers, nucleic acids, or proteins/peptides, nanoplatforms have been programmed to detect and process extrinsic stimuli, such as magnetic fields or light, or intrinsic stimuli, such as nucleic acids, enzymes, or pH. Stimulus detection can be transduced by the nanomaterial via three different mechanisms: system assembly, system disassembly, or system transformation. The increasingly sophisticated suite of biocomputing nanoplatforms may be invaluable for a multitude of applications, including medical diagnostics, biomedical imaging, environmental monitoring, and delivery of therapeutics to target cell populations. Copyright © 2016 Elsevier B.V. All rights reserved.

Optical cell separation from three-dimensional environment in photodegradable hydrogels for pure culture techniques.

PubMed

Tamura, Masato; Yanagawa, Fumiki; Sugiura, Shinji; Takagi, Toshiyuki; Sumaru, Kimio; Matsui, Hirofumi; Kanamori, Toshiyuki

2014-05-07

Cell sorting is an essential and efficient experimental tool for the isolation and characterization of target cells. A three-dimensional environment is crucial in determining cell behavior and cell fate in biological analysis. Herein, we have applied photodegradable hydrogels to optical cell separation from a 3D environment using a computer-controlled light irradiation system. The hydrogel is composed of photocleavable tetra-arm polyethylene glycol and gelatin, which optimized cytocompatibility to adjust a composition of crosslinker and gelatin. Local light irradiation could degrade the hydrogel corresponding to the micropattern image designed on a laptop; minimum resolution of photodegradation was estimated at 20 µm. Light irradiation separated an encapsulated fluorescent microbead without any contamination of neighbor beads, even at multiple targets. Upon selective separation of target cells in the hydrogels, the separated cells have grown on another dish, resulting in pure culture. Cell encapsulation, light irradiation and degradation products exhibited negligible cytotoxicity in overall process.

Fragmentation of relativistic nuclei in peripheral interactions in nuclear track emulsion

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

Artemenkov, D. A., E-mail: artemenkov@lhe.jinr.ru; Bradnova, V.; Chernyavsky, M. M.

2008-09-15

The technique of nuclear track emulsions is used to explore the fragmentation of light relativistic nuclei down to the most peripheral interactions: nuclear 'white' stars. A complete pattern of the relativistic dissociation of a 8B nucleus with target fragment accompaniment is presented. Relativistic dissociation {sup 9}Be {yields} 2{alpha} is explored using significant statistics, and a relative contribution of {sup 8}Be decays from 0+ and 2+ states is established. Target fragment accompaniments are shown for relativistic fragmentation {sup 14}N {yields} 3He +H and {sup 22}Ne {yields} 5He. The leading role of the electromagnetic dissociation on heavy nuclei with respect to breakupsmore » on target protons is demonstrated in all these cases. It is possible to conclude that the peripheral dissociation of relativistic nuclei in nuclear track emulsion is a unique tool to study many-body systems composed of the lightest nuclei and nucleons in the energy scale relevant for nuclear astrophysics.« less

Peptide-Drug Conjugate: A Novel Drug Design Approach.

PubMed

Ma, Liang; Wang, Chao; He, Zihao; Cheng, Biao; Zheng, Ling; Huang, Kun

2017-01-01

More than 100 years ago, German physician Paul Ehrlich first proposed the concept of selectively delivering "magic bullets" to tumors through targeting agents. The targeting therapy with antibody-drug conjugates (ADCs) and peptide-drug conjugate (PDCs), which are usually composed of monoclonal antibodies or peptides, toxic payloads and cleavage/ noncleavage linkers, has been extensively studied for decades. The conjugates enable selective delivery of cytotoxic payloads to target cells, which results in improved efficacy, reduced systemic toxicity and improved pharmacokinetics (PK)/pharmacodynamics (PD) compared with traditional chemotherapy. PDC and ADC share similar concept, but with vastly different structures and properties. Humanized antibodies introduce high specificity and prolonged half-life, while small molecule weight peptides exhibit higher drug loading and enhanced tissue penetration capacity, and the flexible linear or cyclic peptides are also modified more easily. In this review, the principles of design, synthesis approaches and the latest advances of PDCs are summarized. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Process optimization for the preparation of oligomycin-loaded folate-conjugated chitosan nanoparticles as a tumor-targeted drug delivery system using a two-level factorial design method.

PubMed

Zu, Yuangang; Zhao, Qi; Zhao, Xiuhua; Zu, Shuchong; Meng, Li

2011-01-01

Oligomycin-A (Oli-A), an anticancer drug, was loaded to the folate (FA)-conjugated chitosan as a tumor-targeted drug delivery system for the purpose of overcoming the nonspecific targeting characteristics and the hydrophobicity of the compound. The two-level factorial design (2-LFD) was applied to modeling the preparation process, which was composed of five independent variables, namely FA-conjugated chitosan (FA-CS) concentration, Oli-A concentration, sodium tripolyphosphate (TPP) concentration, the mass ratio of FA-CS to TPP, and crosslinking time. The mean particle size (MPS) and the drug loading rate (DLR) of the resulting Oli-loaded FA-CS nanoparticles (FA-Oli-CSNPs) were used as response variables. The interactive effects of the five independent variables on the response variables were studied. The characteristics of the nanoparticles, such as amount of FA conjugation, drug entrapment rate (DER), DLR, surface morphology, and release kinetics properties in vitro were investigated. The FA-Oli-CSNPs with MPS of 182.6 nm, DER of 17.3%, DLR of 58.5%, and zeta potential (ZP) of 24.6 mV were obtained under optimum conditions. The amount of FA conjugation was 45.9 mg/g chitosan. The FA-Oli-CSNPs showed sustained-release characteristics for 576 hours in vitro. The results indicated that FA-Oli-CSNPs obtained as a targeted drug delivery system could be effective in the therapy of leukemia in the future.

DNA detection on ultrahigh-density optical fiber-based nanoarrays.

PubMed

Tam, Jenny M; Song, Linan; Walt, David R

2009-04-15

Nanoarrays for DNA detection were fabricated on etched nanofiber bundles based on recently developed techniques for microscale arrays. Two different-sized nanoarrays were created: one with 700 nm feature sizes and a 1 microm center-to-center pitch (approximately 1x10(6) array elements/mm(2)) and one with 300 nm feature sizes and a 500 nm center-to-center pitch (4.6x10(6) array elements/mm(2)). A random, multiplexed array composed of oligonucleotide-functionalized nanospheres was constructed and used for parallel detection and analysis of fluorescently labeled DNA targets. We have used these arrays to detect a variety of target sequences including Bacillus thuringiensis kurstaki and vaccina virus sequences, two potential biowarfare agents, as well as interleukin-2 sequences, an immune system modulator that has been used for the diagnosis of HIV.

Recognition of isotropic plane target from RCS diagram

NASA Astrophysics Data System (ADS)

Saillard, J.; Chassay, G.

1981-06-01

The use of electromagnetic waves for the recognition of a structure represented by point scatterers is seen as posing a fundamental problem. It is noted that much research has been done on this subject and that the study of aircraft observed in the yaw plane gives interesting results. To apply these methods, however, it is necessary to use many sophisticated acquisition systems. A method is proposed which can be applied to plane structures composed of isotropic scatterers. The method is considered to be of interest because it uses only power measurements and requires only a classical tracking radar.

Data acquisition using the 168/E. [CERN ISR

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

Carroll, J.T.; Cittolin, S.; Demoulin, M.

1983-03-01

Event sizes and data rates at the CERN anti p p collider compose a formidable environment for a high level trigger. A system using three 168/E processors for experiment UA1 real-time event selection is described. With 168/E data memory expanded to 512K bytes, each processor holds a complete event allowing a FORTRAN trigger algorithm access to data from the entire detector. A smart CAMAC interface reads five Remus branches in parallel transferring one word to the target processor every 0.5 ..mu..s. The NORD host computer can simultaneously read an accepted event from another processor.

Development and calibration of an accurate 6-degree-of-freedom measurement system with total station

NASA Astrophysics Data System (ADS)

Gao, Yang; Lin, Jiarui; Yang, Linghui; Zhu, Jigui

2016-12-01

To meet the demand of high-accuracy, long-range and portable use in large-scale metrology for pose measurement, this paper develops a 6-degree-of-freedom (6-DOF) measurement system based on total station by utilizing its advantages of long range and relative high accuracy. The cooperative target sensor, which is mainly composed of a pinhole prism, an industrial lens, a camera and a biaxial inclinometer, is designed to be portable in use. Subsequently, a precise mathematical model is proposed from the input variables observed by total station, imaging system and inclinometer to the output six pose variables. The model must be calibrated in two levels: the intrinsic parameters of imaging system, and the rotation matrix between coordinate systems of the camera and the inclinometer. Then corresponding approaches are presented. For the first level, we introduce a precise two-axis rotary table as a calibration reference. And for the second level, we propose a calibration method by varying the pose of a rigid body with the target sensor and a reference prism on it. Finally, through simulations and various experiments, the feasibilities of the measurement model and calibration methods are validated, and the measurement accuracy of the system is evaluated.

a Light-Weight Laser Scanner for Uav Applications

NASA Astrophysics Data System (ADS)

Tommaselli, A. M. G.; Torres, F. M.

2016-06-01

Unmanned Aerial Vehicles (UAV) have been recognized as a tool for geospatial data acquisition due to their flexibility and favourable cost benefit ratio. The practical use of laser scanning devices on-board UAVs is also developing with new experimental and commercial systems. This paper describes a light-weight laser scanning system composed of an IbeoLux scanner, an Inertial Navigation System Span-IGM-S1, from Novatel, a Raspberry PI portable computer, which records data from both systems and an octopter UAV. The performance of this light-weight system was assessed both for accuracy and with respect to point density, using Ground Control Points (GCP) as reference. Two flights were performed with the UAV octopter carrying the equipment. In the first trial, the flight height was 100 m with six strips over a parking area. The second trial was carried out over an urban park with some buildings and artificial targets serving as reference Ground Control Points. In this experiment a flight height of 70 m was chosen to improve target response. Accuracy was assessed based on control points the coordinates of which were measured in the field. Results showed that vertical accuracy with this prototype is around 30 cm, which is acceptable for forest applications but this accuracy can be improved using further refinements in direct georeferencing and in the system calibration.

Gamma-ray generation in the interaction of two tightly focused laser pulses with a low-density target composed of electrons

NASA Astrophysics Data System (ADS)

Jirka, M.; Klimo, O.; Weber, S.; Bulanov, Sergei V.; Esirkepov, Timur Zh.; Korn, G.

2015-05-01

With the continuing development of laser systems, new important and so-far unexplored fields of research related to interaction of ultra-intense laser beams with matter are opening. At intensities of the order of 1022 W=cm2, electrons may be accelerated in the electromagnetic field of the laser wave and achieve such a high energy that they can enter the regime affected by the radiation reaction. Due to the non-linear Thomson and Compton scattering the accelerated electrons emit photons. The interaction of emitted photons with the laser field may result in effective generation of electron-positron pairs by means of the Breit-Wheeler process. In this work we study the influence of laser pulse polarization on gamma-ray generation during interaction of two colliding and tightly focused laser pulses with a low density target composed of electrons. This paper focuses on evolution of electron trajectories and key parameters χe (probability of photon emission) and χγ(probability of pair generation) in the laser field. These interactions are studied using 2D PIC simulations. It is shown that in the case of circularly polarized and tightly focused laser beams, electrons are not following circular trajectories at the magnetic node of the standing wave established in the focus, which leads to lowering the radiation emission efficiency.

Superparamagnetic Iron Oxide-Loaded Lipid Nanocarriers Incorporated in Thermosensitive In Situ Gel for Magnetic Brain Targeting of Clonazepam.

PubMed

Abbas, Haidy; Refai, Hanan; El Sayed, Nesrine

2018-04-14

The objective of the study was to target clonazepam to the brain through the intranasal olfactory mucosa using nanolipid carriers loaded with superparamagnetic iron oxide nanoparticles (SPIONs) to allow nanocarrier guidance and retention with an external magnetic field. For improved delivery, the nanolipid carriers were incorporated in a thermosensitive mucoadhesive in situ gel. Different nanolipid carriers including solid lipid nanoparticles and nanostructured lipid carriers (NLC) were prepared and characterized with respect to particle size, zeta potential, entrapment efficiency, and in vitro release. The NLC composed of 3 solid lipids (Compritol ® 888, stearic acid, and glyceryl monostearate) and 2 liquid oils (oleic acid and glyceryl monooleate) showed the most satisfactory characteristics and was loaded with SPION (NLC/SPION). Both formulae (NLC and NLC/SPION) were incorporated in an optimized thermosensitive mucoadhesive in situ system composed of 15% pluronic 127 and 0.75% sodium alginate and evaluated for the anticonvulsant action in chemically induced convulsive Swiss Albino mice. The treatment of animals with NLC/SPION significantly prolonged the onset times for convulsion and considerably protected the animals from death. One can thus hope for the emergence of a new intranasal treatment of epilepsy with consequent decrease in peripheral side effects of clonazepam. Copyright © 2018 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.

An interesting two-phase solvent system and its use in preparative isolation of aconitines from aconite roots by counter-current chromatography.

PubMed

Han, Quan-Bin; Tang, Wai-Lun; Dong, Cai-Xia; Xu, Hong-Xi; Jiang, Zhi-Hong

2013-04-01

Two-phase solvent system plays crucial role in successful separation of organic compounds using counter-current chromatography (CCC). An interesting two-phase solvent system, composed of chloroform/ethyl acetate/methanol/water, is reported here, in which both phases contain sufficient organic solvents to balance their dissolving capacities. Adjusting the solvent system to get satisfactory partition coefficients (K values) for target compounds becomes relatively simple. This solvent system succeeded in sample preparation of aconitine (8.07 mg, 93.69%), hypaconitine (7.74 mg, 93.17%), mesaconitine (1.95 mg, 94.52%) from raw aconite roots (102.24 mg, crude extract), benzoylmesaconine (34.79 mg, 98.67%) from processed aconite roots (400.01 mg, crude extract), and yunaconitine (253.59 mg, 98.65%) from a crude extract of Aconitum forrestii (326.69 mg, crude extract). © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Cramer-Rao Lower Bound Evaluation for Linear Frequency Modulation Based Active Radar Networks Operating in a Rice Fading Environment.

PubMed

Shi, Chenguang; Salous, Sana; Wang, Fei; Zhou, Jianjiang

2016-12-06

This paper investigates the joint target parameter (delay and Doppler) estimation performance of linear frequency modulation (LFM)-based radar networks in a Rice fading environment. The active radar networks are composed of multiple radar transmitters and multichannel receivers placed on moving platforms. First, the log-likelihood function of the received signal for a Rician target is derived, where the received signal scattered off the target comprises of dominant scatterer (DS) component and weak isotropic scatterers (WIS) components. Then, the analytically closed-form expressions of the Cramer-Rao lower bounds (CRLBs) on the Cartesian coordinates of target position and velocity are calculated, which can be adopted as a performance metric to access the target parameter estimation accuracy for LFM-based radar network systems in a Rice fading environment. It is found that the cumulative Fisher information matrix (FIM) is a linear combination of both DS component and WIS components, and it also demonstrates that the joint CRLB is a function of signal-to-noise ratio (SNR), target's radar cross section (RCS) and transmitted waveform parameters, as well as the relative geometry between the target and the radar network architectures. Finally, numerical results are provided to indicate that the joint target parameter estimation performance of active radar networks can be significantly improved with the exploitation of DS component.

Sticker-type ECG/PPG concurrent monitoring system hybrid integration of CMOS SoC and organic sensor device.

PubMed

Yongsu Lee; Hyeonwoo Lee; Seunghyup Yoo; Hoi-Jun Yoo

2016-08-01

The sticker-type sensor system is proposed targeting ECG/PPG concurrent monitoring for cardiovascular diseases. The stickers are composed of two types: Hub and Sensor-node (SN) sticker. Low-power CMOS SoC for measuring ECG and PPG signal is hybrid integrated with organic light emitting diodes (OLEDs) and organic photo detector (OPD). The sticker has only 2g weight and only consumes 141μW. The optical calibration loop is adopted for maintaining SNR of PPG signal higher than 30dB. The pulse arrival time (PAT) and SpO2 value can be extracted from various body parts and verified comparing with the reference device from 20 people in-vivo experiments.

Spanish language generation engine to enhance the syntactic quality of AAC systems

NASA Astrophysics Data System (ADS)

Narváez A., Cristian; Sastoque H., Sebastián.; Iregui G., Marcela

2015-12-01

People with Complex Communication Needs (CCN) face difficulties to communicate their ideas, feelings and needs. Augmentative and Alternative Communication (AAC) approaches aim to provide support to enhance socialization of these individuals. However, there are many limitations in current applications related with systems operation, target scenarios and language consistency. This work presents an AAC approach to enhance produced messages by applying elements of Natural Language Generation. Specifically, a Spanish language engine, composed of a grammar ontology and a set of linguistic rules, is proposed to improve the naturalness in the communication process, when persons with CCN tell stories about their daily activities to non-disabled receivers. The assessment of the proposed method confirms the validity of the model to improve messages quality.

Transorbital therapy delivery: phantom testing

NASA Astrophysics Data System (ADS)

Ingram, Martha-Conley; Atuegwu, Nkiruka; Mawn, Louise; Galloway, Robert L.

2011-03-01

We have developed a combined image-guided and minimally invasive system for the delivery of therapy to the back of the eye. It is composed of a short 4.5 mm diameter endoscope with a magnetic tracker embedded in the tip. In previous work we have defined an optimized fiducial placement for accurate guidance to the back of the eye and are now moving to system testing. The fundamental difficulty in testing performance is establishing a target in a manner which closely mimics the physiological task. We have to have a penetrable material which obscures line of sight, similar to the orbital fat. In addition we need to have some independent measure of knowing when a target has been reached to compare to the ideal performance. Lastly, the target cannot be rigidly attached to the skull phantom since the optic nerve lies buried in the orbital fat. We have developed a skull phantom with white cloth stellate balls supporting a correctly sized globe. Placed in the white balls are red, blue, orange and yellow balls. One of the colored balls has been soaked in barium to make it bright on CT. The user guides the tracked endoscope to the target as defined by the images and tells us its color. We record task accuracy and time to target. We have tested this with 28 residents, fellows and attending physicians. Each physician performs the task twice guided and twice unguided. Results will be presented.

Freeform lens generation for quasi-far-field successive illumination targets

NASA Astrophysics Data System (ADS)

Zhuang, Zhenfeng; Thibault, Simon

2018-07-01

A predefined mapping to tailor one or more freeform surfaces is employed to build a freeform illumination system. The emergent rays from the light source corresponding to the prescribed target mesh for a pre-determined lighting distance are mapped by a point-to-point algorithm with respect to the freeform optics, which involves limiting design flexibility. To tackle the problem of design limitation and find the optimum design results, a freeform lens is exploited to produce the desired rectangular illumination distribution at successive target planes at quasi-far-field lighting distances. It is generated using numerical solutions to find out an initial starting point, and an appropriate approach to obtain variables for parameterization of the freeform surface is introduced. The relative standard deviation, which is a useful figure of merit for the analysis, is set up as merit function with respect to illumination non-uniformity at the successive sampled target planes. Therefore, the irradiance distribution in terms of the specific lighting distance range can be ensured by the proposed scheme. A design example of a freeform illumination system, composed of a spherical surface and a freeform surface, is given to produce desired irradiance distribution within the lighting distance range. An optical performance with low non-uniformity and high efficiency is achieved. Compared with the conventional approach, the uniformity of the sampled targets is dramatically enhanced; meanwhile, a design result with a large tolerance of LED size is offered.

Self-assembled amphiphilic zein-lactoferrin micelles for tumor targeted co-delivery of rapamycin and wogonin to breast cancer.

PubMed

Sabra, Sally A; Elzoghby, Ahmed O; Sheweita, Salah A; Haroun, Medhat; Helmy, Maged W; Eldemellawy, Maha A; Xia, Ying; Goodale, David; Allan, Alison L; Rohani, Sohrab

2018-07-01

Protein-based micelles have shown significant potential for tumor-targeted delivery of anti-cancer drugs. In this light, self-assembled nanocarriers based on GRAS (Generally recognized as safe) amphiphilic protein co-polymers were synthesized via carbodiimide coupling reaction. The new nano-platform is composed of the following key components: (i) hydrophobic zein core to encapsulate the hydrophobic drugs rapamycin (RAP) and wogonin (WOG) with high encapsulation efficiency, (ii) hydrophilic lactoferrin (Lf) corona to enhance the tumor targeting, and prolong systemic circulation of the nanocarriers, and (iii) glutaraldehyde (GLA)-crosslinking to reduce the particle size and improve micellar stability. Zein-Lf micelles showed relatively rapid release of WOG followed by slower diffusion of RAP from zein core. This sequential release may aid in efflux pump inhibition by WOG thus sensitizing tumor cells to RAP action. Interestingly, these micelles showed good hemocompatibility as well as enhanced serum stability owing to the brush-like architecture of Lf shell. Moreover, this combined nano-delivery system maximized synergistic cytotoxicity of RAP and WOG in terms of tumor inhibition in MCF-7 breast cancer cells and Ehrlich ascites tumor animal model as a result of enhanced active targeting. Collectively, GLA-crosslinked zein-Lf micelles hold great promise for combined RAP/WOG delivery to breast cancer with reduced drug dose, minimized side effects and maximized anti-tumor efficacy. Copyright © 2018. Published by Elsevier B.V.

A smart polymeric platform for multistage nucleus-targeted anticancer drug delivery.

PubMed

Zhong, Jiaju; Li, Lian; Zhu, Xi; Guan, Shan; Yang, Qingqing; Zhou, Zhou; Zhang, Zhirong; Huang, Yuan

2015-10-01

Tumor cell nucleus-targeted delivery of antitumor agents is of great interest in cancer therapy, since the nucleus is one of the most frequent targets of drug action. Here we report a smart polymeric conjugate platform, which utilizes stimulus-responsive strategies to achieve multistage nuclear drug delivery upon systemic administration. The conjugates composed of a backbone based on N-(2-hydroxypropyl) methacrylamide (HPMA) copolymer and detachable nucleus transport sub-units that sensitive to lysosomal enzyme. The sub-units possess a biforked structure with one end conjugated with the model drug, H1 peptide, and the other end conjugated with a novel pH-responsive targeting peptide (R8NLS) that combining the strength of cell penetrating peptide and nuclear localization sequence. The conjugates exhibited prolonged circulation time and excellent tumor homing ability. And the activation of R8NLS in acidic tumor microenvironment facilitated tissue penetration and cellular internalization. Once internalized into the cell, the sub-units were unleashed for nuclear transport through nuclear pore complex. The unique features resulted in 50-fold increase of nuclear drug accumulation relative to the original polymer-drug conjugates in vitro, and excellent in vivo nuclear drug delivery efficiency. Our report provides a strategy in systemic nuclear drug delivery by combining the microenvironment-responsive structure and detachable sub-units. Copyright © 2015 Elsevier Ltd. All rights reserved.

Targeting interferons in systemic lupus erythematosus: current and future prospects.

PubMed

Mathian, Alexis; Hie, Miguel; Cohen-Aubart, Fleur; Amoura, Zahir

2015-05-01

Systemic lupus erythematosus (SLE) is a chronic autoimmune disease of unknown aetiology that can be debilitating and life threatening. As new insights are gained into the underlying pathology of SLE, there have been an unprecedented number of new agents under development to treat the disease via a diverse range of targets. One such class of emerging agents target interferon (IFN) signalling. In this article, we review the preclinical evidence that the inhibition of the secretion and downstream effectors of both IFN-α and IFN-γ may be effective for the treatment of SLE. The primary agents that are currently in clinical development to treat SLE via the targeting of interferon pathways are monoclonal neutralising antibodies (Mab) that bind to and neutralise IFN-γ (AMG 811), IFN-α (sifalimumab, rontalizumab and AGS-009) or its receptor (anifrolumab), and IFN-α kinoid, which is a drug composed of inactivated IFN-α molecules coupled to the keyhole limpet haemocyanin protein. Phase I and II trials have demonstrated acceptable short-term safety with no increase in severe viral infections or reactivation, favourable pharmacokinetic profiles and an inhibition of IFN-associated gene overexpression; however, the impact of these drugs on disease activity must still be assessed in phase III clinical trials. This review concludes with a summary of the challenges that are inherent to this approach to managing SLE.

Dual FOV infrared lens design with the laser common aperture optics

NASA Astrophysics Data System (ADS)

Chang, Wei-jun; Zhang, Xuan-zhi; Luan, Ya-dong; Zhang, Bo

2015-02-01

With the demand of autonomous precision guidance of air defense missile, the system scheme of the IR imaging/Ladar dual-mode seeker with a common aperture was proposed, and the optical system used in was designed. The system had a common receiving aperture, and its structure was very compact, so it could meet the requirement for the miniaturization of the seeker. Besides, it also could meet the demands of a wide field of view for searching target, and the demands for accurately recognizing and tracking the target at the same time. In order to increase the narrow FOV tracking performance, the dual FOV infrared optical used the zooming mode which some components flip in or out the optical system to firm the target signal. The dual FOV optics are divided into the zooming part, with dual variable focal length, and the reimaging part which was chosen in such a way to minimize the objective lens while maintaining 100% cold shield efficiency. The final infrared optics including 4°×3°(NFOV) and 16°×12°(WFOV) was designed. The NFOV lens composed of two common IR/Ladar lens, three relay lens, a beam splitter and two reflective fold mirrors, while WFOV lens increased two lens such as Germanium and Silicon. The common IR/Ladar lens ZnS and ZnSe could refractive the IR optics and Laser optics. The beam splitter which refractived IR optics and reflected Laser optics was located in the middle of Germanium and Silicon. The designed optical system had good image quality, and fulfilled the performance requirement of seeker system.

Lymphatic drainage system of the brain: A novel target for intervention of neurological diseases.

PubMed

Sun, Bao-Liang; Wang, Li-Hua; Yang, Tuo; Sun, Jing-Yi; Mao, Lei-Lei; Yang, Ming-Feng; Yuan, Hui; Colvin, Robert A; Yang, Xiao-Yi

2017-09-10

The belief that the vertebrate brain functions normally without classical lymphatic drainage vessels has been held for many decades. On the contrary, new findings show that functional lymphatic drainage does exist in the brain. The brain lymphatic drainage system is composed of basement membrane-based perivascular pathway, a brain-wide glymphatic pathway, and cerebrospinal fluid (CSF) drainage routes including sinus-associated meningeal lymphatic vessels and olfactory/cervical lymphatic routes. The brain lymphatic systems function physiological as a route of drainage for interstitial fluid (ISF) from brain parenchyma to nearby lymph nodes. Brain lymphatic drainage helps maintain water and ion balance of the ISF, waste clearance, and reabsorption of macromolecular solutes. A second physiological function includes communication with the immune system modulating immune surveillance and responses of the brain. These physiological functions are influenced by aging, genetic phenotypes, sleep-wake cycle, and body posture. The impairment and dysfunction of the brain lymphatic system has crucial roles in age-related changes of brain function and the pathogenesis of neurovascular, neurodegenerative, and neuroinflammatory diseases, as well as brain injury and tumors. In this review, we summarize the key component elements (regions, cells, and water transporters) of the brain lymphatic system and their regulators as potential therapeutic targets in the treatment of neurologic diseases and their resulting complications. Finally, we highlight the clinical importance of ependymal route-based targeted gene therapy and intranasal drug administration in the brain by taking advantage of the unique role played by brain lymphatic pathways in the regulation of CSF flow and ISF/CSF exchange. Copyright © 2017. Published by Elsevier Ltd.

Estimating the decomposition of predictive information in multivariate systems

NASA Astrophysics Data System (ADS)

Faes, Luca; Kugiumtzis, Dimitris; Nollo, Giandomenico; Jurysta, Fabrice; Marinazzo, Daniele

2015-03-01

In the study of complex systems from observed multivariate time series, insight into the evolution of one system may be under investigation, which can be explained by the information storage of the system and the information transfer from other interacting systems. We present a framework for the model-free estimation of information storage and information transfer computed as the terms composing the predictive information about the target of a multivariate dynamical process. The approach tackles the curse of dimensionality employing a nonuniform embedding scheme that selects progressively, among the past components of the multivariate process, only those that contribute most, in terms of conditional mutual information, to the present target process. Moreover, it computes all information-theoretic quantities using a nearest-neighbor technique designed to compensate the bias due to the different dimensionality of individual entropy terms. The resulting estimators of prediction entropy, storage entropy, transfer entropy, and partial transfer entropy are tested on simulations of coupled linear stochastic and nonlinear deterministic dynamic processes, demonstrating the superiority of the proposed approach over the traditional estimators based on uniform embedding. The framework is then applied to multivariate physiologic time series, resulting in physiologically well-interpretable information decompositions of cardiovascular and cardiorespiratory interactions during head-up tilt and of joint brain-heart dynamics during sleep.

Plasma block acceleration based upon the interaction between double targets and an ultra-intense linearly polarized laser pulse

NASA Astrophysics Data System (ADS)

Xu, Yanxia; Wang, Jiaxiang; Hora, Heinrich; Qi, Xin; Xing, Yifan; Yang, Lei; Zhu, Wenjun

2018-04-01

A new scheme of plasma block acceleration based upon the interaction between double targets and an ultra-intense linearly polarized laser pulse with intensity I ˜ 1022 W/cm2 is investigated via two-dimensional particle-in-cell simulations. The targets are composed of a pre-target of low-density aluminium plasma and an overdense main-target of hydrogen plasma. Through intensive parameter optimization, we have observed highly efficient plasma block accelerations with a monochromatic proton beam peaked at GeVs. The underlying mechanism is attributed to the enhancement of the charge separation field due to the properly selected pre-target.

pH-responsive unimolecular micelles self-assembled from amphiphilic hyperbranched block copolymer for efficient intracellular release of poorly water-soluble anticancer drugs.

PubMed

Tabatabaei Rezaei, Seyed Jamal; Abandansari, Hamid Sadeghi; Nabid, Mohammad Reza; Niknejad, Hassan

2014-07-01

Novel unimolecular micelles from amphiphilic hyperbranched block copolymer H40-poly(ε-caprolactone)-b-poly(acrylic acid)-b'-methoxy poly(ethylene glycol)/poly(ethylene glycol)-folate (i.e., H40-PCL-b-PAA-b'-MPEG/PEG-FA (HCAE-FA)) as new multifunctional nanocarriers to pH-induced accelerated release and tumor-targeted delivery of poorly water-soluble anticancer drugs were developed. The hydrophobic core of the unimolecular micelle was hyperbranched polyester (H40-poly(ε-caprolactone) (H40-PCL)). The inner hydrophilic layer was composed of PAA segments, while the outer hydrophilic shell was composed of PEG segments. This copolymer formed unimolecular micelles in the aqueous solution with a mean particle size of 33 nm, as determined by dynamic light scattering (DLS) and transmission electron microscopy (TEM). To study the feasibility of micelles as a potential nanocarrier for targeted drug delivery, we encapsulated a hydrophobic anticancer drug, paclitaxel (PTX), in the hydrophobic core, and the loading content was determined by UV-vis analysis to be 10.35 wt.%. In vitro release studies demonstrated that the drug-loaded delivery system is relatively stable at physiologic conditions but susceptible to acidic environments which would trigger the release of encapsulated drugs. Flow cytometry and fluorescent microscope studies revealed that the cellular binding of the FA-conjugated micelles against HeLa cells was higher than that of the neat micelles (without FA). The in vitro cytotoxicity studies showed that the PTX transported by these micelles was higher than that by the commercial PTX formulation Tarvexol®. All of these results show that these unique unimolecular micelles may offer a very promising approach for targeted cancer therapy. Copyright © 2014 Elsevier Inc. All rights reserved.

Folate receptor 1 (FOLR1) targeted chimeric antigen receptor (CAR) T cells for the treatment of gastric cancer

PubMed Central

Pyo, Suhkneung; Kang, Chung Hyo; Lee, Chong Ock; Lee, Heung Kyoung; Choi, Sang Un; Park, Chi Hoon

2018-01-01

Gastric cancer is a malignancy that has a high mortality rate. Although progress has been made in the treatment of gastric cancer, many patients experience cancer recurrence and metastasis. Folate receptor 1 (FOLR1) is overexpressed on the cell surface in over one-third of gastric cancer patients, but rarely is expressed in normal tissue. This makes FOLR1 a potential target for chimeric antigen receptor (CAR) T cell immunotherapy, although the function of FOLR1 has not been elucidated. CAR are engineered fusion receptor composed of an antigen recognition region and signaling domains. T cells expressing CAR have specific activation and cytotoxic effects against cancer cells containing the target antigen. In this study, we generated a CAR that targets FOLR1 composed of a single-chain variable fragment (scFv) of FOLR1 antibody and signaling domains consisting of CD28 and CD3ζ. Both FOLR1-CAR KHYG-1, a natural killer cell line, and FOLR1-CAR T cells recognized FOLR1-positive gastric cancer cells in a MHC-independent manner and induced secretion of various cytokines and caused cell death. Conclusively, this is the first study to demonstrate that CAR KHYG-1/T cells targeting FOLR1 are effective against FOLR1-positive gastric cancer cells. PMID:29874279

Infrared telephoto lenses design for joint transform correlator

NASA Astrophysics Data System (ADS)

Chen, Yu; Huo, Furong; Zheng, Liqin

2014-11-01

Joint transform correlator (JTC) is quite useful for pattern recognition in many fields, which can realize automatic real-time recognition of target in cluttered background with high precision. For military application, JTC can also be applied for thermo target recognition especially at night. To make JTC recognize thermo targets, an infrared telephoto lens is designed in this paper. Long focal length and short tube length are required for this usage. So the structure of a positive lens group and a negative lens group are adopted. Besides, the effective focal length and relative aperture should be large enough to ensure the distant targets can be detected with adequate illumination. In this paper, the working waveband of adopted infrared CCD detector is 8-12μm. According to Nyquist law, the characteristic frequency of the system is 14lp/mm. The optional materials are very few for infrared optical systems, in which only several kinds of materials such as Germanium, ZnSe, ZnS are commonly used. Various aberrations are not easy to be corrected. So it is very difficult to design a good infrared optical system. Besides, doublet or triplet should be avoided to be used in infrared optical system considering possible cracking for different thermal expansion coefficients of different infrared materials. The original configuration is composed of three lenses. After optimization, the image quality can get limit diffraction. The root mean square (RMS) radii of three fields are 6.754μm, 7.301μm and 12.158μm respectively. They are all less than the Airy spot diameter 48.8μm. Wavefront aberration at 0.707 field of view (FOV) is only 0.1wavelength. After adjusting the radius to surface templates, setting tolerances and giving element drawings, this system has been fabricated successfully. Optical experimental results of infrared target recognition using JTC are given in this paper. The correlation peaks can be detected and located easily, which confirms the good image quality of the designed infrared telephoto lens.

Isolation and purification of series bioactive components from Hypericum perforatum L. by counter-current chromatography.

PubMed

Cao, Xueli; Wang, Qiaoe; Li, Yan; Bai, Ge; Ren, Hong; Xu, Chunming; Ito, Yoichiro

2011-03-01

Counter-current chromatography (CCC) combined with pre-separation by ultrasonic solvent extraction was successively used for the separation of series bioactive compounds from the crude extract of Hypericum perforatum L. The petroleum ether extract was separated by the solvent system of n-heptane-methanol-acetonitrile (1.5:0.5:0.5, v/v) and n-heptane-methanol (1.5:1, v/v) in gradient elution, yielding a phloroglucinol compound, hyperforin with HPLC purity over 98%. The ethyl acetate extract was separated by using the solvent system composed of hexane-ethyl acetate-methanol-water (1:1:1:1 and 1:3:1:3, v/v) in gradient through both reverse phase and normal phase elution mode, yielding a naphthodianthrone compound, hypericin with HPLC purity about 95%. The n-butanol extract was separated with the solvent system composed of n-butanol-ethyl acetate-water (1:4:5 and 1.5:3.5:5, v/v) in elution and back-extrusion mode, yielding two of flavones, rutin and hyperoside, with HPLC purity over 95%. HPLC-MS, reference sample and UV spectrum were selectively used in separation to search for target compounds from HPLC-DAD profiles of different sub-extracts. The structures of isolated compounds were further identified by ESI-MS, ¹HNMR and ¹³CNMR. Copyright © 2011 Elsevier B.V. All rights reserved.

Isolation and purification of series bioactive components from Hypericum Perforatum L. by high-speed counter-current chromatography

PubMed Central

Cao, Xueli; Wang, Qiaoe; Li, Yan; Bai, Ge; Ren, Hong; Ito, Yiochiro

2011-01-01

High-speed counter-current chromatography (HSCCC) combined with pre-separation by ultrasonic solvent extraction was successively used for the separation of series bioactive compounds from the crude extract of Hypericum perforatum L. The petroleum ether extract was separated by the solvent system of n-heptane-methanol-acetonitrile (1.5:0.5:0.5, v/v) and n-heptane-methanol (1.5:1, v/v) in gradient elution, yielding a phloroglucinol compound, hyperforin with HPLC purity over 98%. The ethyl acetate extract was separated by using the solvent system composed of hexane-ethyl acetate-methanol-water (1:1:1:1 and 1:3:1:3, v/v) in gradient through both reverse phase and normal phase elution mode, yielding a naphthodianthrone compound, hypericin with HPLC purity about 95%. The n-butanol extract was separated with the solvent system composed of n-butanol-ethyl acetate–water (1:4:5 and 1.5:3.5:5, v/v) in elution and back-extrusion mode, yielding two of flavones, rutin and hyperoside, with HPLC purity over 95%. HPLC-MS, reference sample and UV spectrum were selectively used in separation to search for target compounds from HPLC-DAD profiles of different sub-extracts. The structures of isolated compounds were further identified by ESI-MS, 1HNMR and 13CNMR. PMID:21306961

Air-condition Control System of Weaving Workshop Based on LabVIEW

NASA Astrophysics Data System (ADS)

Song, Jian

The project of air-condition measurement and control system based on LabVIEW is put forward for the sake of controlling effectively the environmental targets in the weaving workshop. In this project, which is based on the virtual instrument technology and in which LabVIEW development platform by NI is adopted, the system is constructed on the basis of the virtual instrument technology. It is composed of the upper PC, central control nodes based on CC2530, sensor nodes, sensor modules and executive device. Fuzzy control algorithm is employed to achieve the accuracy control of the temperature and humidity. A user-friendly man-machine interaction interface is designed with virtual instrument technology at the core of the software. It is shown by experiments that the measurement and control system can run stably and reliably and meet the functional requirements for controlling the weaving workshop.

Cramer-Rao Lower Bound Evaluation for Linear Frequency Modulation Based Active Radar Networks Operating in a Rice Fading Environment

PubMed Central

Shi, Chenguang; Salous, Sana; Wang, Fei; Zhou, Jianjiang

2016-01-01

This paper investigates the joint target parameter (delay and Doppler) estimation performance of linear frequency modulation (LFM)-based radar networks in a Rice fading environment. The active radar networks are composed of multiple radar transmitters and multichannel receivers placed on moving platforms. First, the log-likelihood function of the received signal for a Rician target is derived, where the received signal scattered off the target comprises of dominant scatterer (DS) component and weak isotropic scatterers (WIS) components. Then, the analytically closed-form expressions of the Cramer-Rao lower bounds (CRLBs) on the Cartesian coordinates of target position and velocity are calculated, which can be adopted as a performance metric to access the target parameter estimation accuracy for LFM-based radar network systems in a Rice fading environment. It is found that the cumulative Fisher information matrix (FIM) is a linear combination of both DS component and WIS components, and it also demonstrates that the joint CRLB is a function of signal-to-noise ratio (SNR), target’s radar cross section (RCS) and transmitted waveform parameters, as well as the relative geometry between the target and the radar network architectures. Finally, numerical results are provided to indicate that the joint target parameter estimation performance of active radar networks can be significantly improved with the exploitation of DS component. PMID:27929433

Research on the photoelectric measuring method of warhead fragment velocity

NASA Astrophysics Data System (ADS)

Liu, Ji; Yu, Lixia; Zhang, Bin; Liu, Xiaoyan

2016-09-01

The velocity of warhead fragment is the key criteria to determine its mutilation efficiency. But owing to the small size, larger quantity, irregular shape, high speed, arbitrary direction, large dispersion of warhead fragment and adverse environment, the test of fragment velocity parameter is very difficult. The paper designed an optoelectronic system to measure the average velocity of warhead fragments accurately. The apparatus included two parallel laser screens spaced apart at a known fixed distance for providing time measurement between start and stop signals. The large effective screen area was composed of laser source, retro-reflector and large area photo-diode. Whenever a moving fragment interrupted two optical screens, the system would generate a target signal. Due to partial obscuration of the incident energy and the poor test condition of the explosion, fragment target signal is easily disturbed. Therefore, fragments signal processing technology has become a key technology of the system. The noise of signal was reduced by employing wavelet decomposition and reconstruction. The time of fragment passing though the target was obtained by adopting peak detection algorithm. Based on the method of search peak in different width scale and waveform trend by using optima wavelet, the problem of rolling waveform was solved. Lots of fragments experiments of the different types of the warheads were conducted. Experimental results show that: warhead fragments capture rate of system is better than 98%, which can give velocity of each fragment in the density of less than 20 pieces per m2.

A multi-electrode biomimetic electrolocation sensor

NASA Astrophysics Data System (ADS)

Mayekar, K.; Damalla, D.; Gottwald, M.; Bousack, H.; von der Emde, G.

2012-04-01

We present the concept of an active multi-electrode catheter inspired by the electroreceptive system of the weakly electric fish, Gnathonemus petersii. The skin of this fish exhibits numerous electroreceptor organs which are capable of sensing a self induced electrical field. Our sensor is composed of a sending electrode and sixteen receiving electrodes. The electrical field produced by the sending electrode was measured by the receiving electrodes and objects were detected by the perturbation of the electrical field they induce. The intended application of such a sensor is in coronary diagnostics, in particular in distinguishing various types of plaques, which are major causes of heart attack. For calibration of the sensor system, finite element modeling (FEM) was performed. To validate the model, experimental measurements were carried out with two different systems. The physical system was glass tubing with metal and plastic wall insertions as targets. For the control of the experiment and for data acquisition, the software LabView designed for 17 electrodes was used. Different parameters of the electric images were analyzed for the prediction of the electrical properties and size of the inserted targets in the tube. Comparisons of the voltage modulations predicted from the FEM model and the experiments showed a good correspondence. It can be concluded that this novel biomimetic method can be further developed for detailed investigations of atherosclerotic lesions. Finally, we discuss various design strategies to optimize the output of the sensor using different simulated models to enhance target recognition.

Prototype volumetric ultrasound tomography image guidance system for prone stereotactic partial breast irradiation: proof-of-concept

NASA Astrophysics Data System (ADS)

Chiu, Tsuicheng D.; Parsons, David; Zhang, Yue; Hrycushko, Brian; Zhao, Bo; Chopra, Rajiv; Kim, Nathan; Spangler, Ann; Rahimi, Asal; Timmerman, Robert; Jiang, Steve B.; Lu, Weiguo; Gu, Xuejun

2018-03-01

Accurate dose delivery in stereotactic partial breast irradiation (S-PBI) is challenging because of the target position uncertainty caused by breast deformation, the target volume changes caused by lumpectomy cavity shrinkage, and the target delineation uncertainty on simulation computed tomography (CT) images caused by poor soft tissue contrast. We have developed a volumetric ultrasound tomography (UST) image guidance system for prone position S-PBI. The system is composed of a novel 3D printed rotation water tank, a patient-specific resin breast immobilization cup, and a 1D array ultrasound transducer. Coronal 2D US images were acquired in 5° increments over a 360° range, and planes were acquired every 2 mm in elevation. A super-compounding technique was used to reconstruct the image volume. The image quality of UST was evaluated with a BB-1 breast phantom and BioZorb surgical marker, and the results revealed that UST offered better soft tissue contrast than CT and similar image quality to MR. In the evaluated plane, the size and location of five embedded objects were measured and compared to MR, which is considered as the ground truth. Objects’ diameters and the distances between objects in UST differ by approximately 1 to 2 mm from those in MR, which showed that UST offers the image quality required for S-PBI. In future work we will develop a robotic system that will be ultimately implemented in the clinic.

Prototype volumetric ultrasound tomography image guidance system for prone stereotactic partial breast irradiation: proof-of-concept.

PubMed

Chiu, Tsuicheng D; Parsons, David; Zhang, Yue; Hrycushko, Brian; Zhao, Bo; Chopra, Rajiv; Kim, Nathan; Spangler, Ann; Rahimi, Asal; Timmerman, Robert; Jiang, Steve B; Lu, Weiguo; Gu, Xuejun

2018-03-01

Accurate dose delivery in stereotactic partial breast irradiation (S-PBI) is challenging because of the target position uncertainty caused by breast deformation, the target volume changes caused by lumpectomy cavity shrinkage, and the target delineation uncertainty on simulation computed tomography (CT) images caused by poor soft tissue contrast. We have developed a volumetric ultrasound tomography (UST) image guidance system for prone position S-PBI. The system is composed of a novel 3D printed rotation water tank, a patient-specific resin breast immobilization cup, and a 1D array ultrasound transducer. Coronal 2D US images were acquired in 5° increments over a 360° range, and planes were acquired every 2 mm in elevation. A super-compounding technique was used to reconstruct the image volume. The image quality of UST was evaluated with a BB-1 breast phantom and BioZorb surgical marker, and the results revealed that UST offered better soft tissue contrast than CT and similar image quality to MR. In the evaluated plane, the size and location of five embedded objects were measured and compared to MR, which is considered as the ground truth. Objects' diameters and the distances between objects in UST differ by approximately 1 to 2 mm from those in MR, which showed that UST offers the image quality required for S-PBI. In future work we will develop a robotic system that will be ultimately implemented in the clinic.

Toxin–antitoxin systems

PubMed Central

Unterholzner, Simon J; Poppenberger, Brigitte; Rozhon, Wilfried

2013-01-01

Toxin–antitoxin (TA) systems are small genetic elements composed of a toxin gene and its cognate antitoxin. The toxins of all known TA systems are proteins while the antitoxins are either proteins or non-coding RNAs. Based on the molecular nature of the antitoxin and its mode of interaction with the toxin the TA modules are currently grouped into five classes. In general, the toxin is more stable than the antitoxin but the latter is expressed to a higher level. If supply of the antitoxin stops, for instance under special growth conditions or by plasmid loss in case of plasmid encoded TA systems, the antitoxin is rapidly degraded and can no longer counteract the toxin. Consequently, the toxin becomes activated and can act on its cellular targets. Typically, TA toxins act on crucial cellular processes including translation, replication, cytoskeleton formation, membrane integrity, and cell wall biosynthesis. TA systems and their components are also versatile tools for a multitude of purposes in basic research and biotechnology. Currently, TA systems are frequently used for selection in cloning and for single protein expression in living bacterial cells. Since several TA toxins exhibit activity in yeast and mammalian cells they may be useful for applications in eukaryotic systems. TA modules are also considered as promising targets for the development of antibacterial drugs and their potential to combat viral infection may aid in controlling infectious diseases. PMID:24251069

Advancements of diffraction-based overlay metrology for double patterning

NASA Astrophysics Data System (ADS)

Li, Jie; Kritsun, Oleg; Liu, Yongdong; Dasari, Prasad; Weher, Ulrich; Volkman, Catherine; Mazur, Martin; Hu, Jiangtao

2011-03-01

As the dimensions of integrated circuit continue to shrink, diffraction based overlay (DBO) technologies have been developed to address the tighter overlay control challenges. Previously data of high accuracy and high precision were reported for litho-etch-litho-etch double patterning (DP) process using normal incidence spectroscopic reflectometry on specially designed targets composed of 1D gratings in x and y directions. Two measurement methods, empirical algorithm (eDBO) using four pads per direction (2x4 target) and modeling based algorithm (mDBO) using two pads per direction (2x2 target) were performed. In this work, we apply DBO techniques to measure overlay errors for a different DP process, litho-freeze-litho-etch process. We explore the possibility of further reducing number of pads in a DBO target using mDBO. For standard targets composed of 1D gratings, we reported results for eDBO 2x4 targets, mDBO 2x2 targets, and mDBO 2x1 target. The results of all three types of targets are comparable in terms of accuracy, dynamic precision, and TIS. TMU (not including tool matching) is less than 0.1nm. In addition, we investigated the possibility of measuring overlay with one single pad that contains 2D gratings. We achieved good correlation to blossom measurements. TMU (not including tool matching) is ~ 0.2nm. To our best knowledge, this is the first time that DBO results are reported on a single pad. eDBO allows quick recipe setup but takes more space and measurement time. Although mDBO needs details of optical properties and modeling, it offers smaller total target size and much faster throughput, which is important in high volume manufacturing environment.

Synthesizing cognition in neuromorphic electronic systems

PubMed Central

Neftci, Emre; Binas, Jonathan; Rutishauser, Ueli; Chicca, Elisabetta; Indiveri, Giacomo; Douglas, Rodney J.

2013-01-01

The quest to implement intelligent processing in electronic neuromorphic systems lacks methods for achieving reliable behavioral dynamics on substrates of inherently imprecise and noisy neurons. Here we report a solution to this problem that involves first mapping an unreliable hardware layer of spiking silicon neurons into an abstract computational layer composed of generic reliable subnetworks of model neurons and then composing the target behavioral dynamics as a “soft state machine” running on these reliable subnets. In the first step, the neural networks of the abstract layer are realized on the hardware substrate by mapping the neuron circuit bias voltages to the model parameters. This mapping is obtained by an automatic method in which the electronic circuit biases are calibrated against the model parameters by a series of population activity measurements. The abstract computational layer is formed by configuring neural networks as generic soft winner-take-all subnetworks that provide reliable processing by virtue of their active gain, signal restoration, and multistability. The necessary states and transitions of the desired high-level behavior are then easily embedded in the computational layer by introducing only sparse connections between some neurons of the various subnets. We demonstrate this synthesis method for a neuromorphic sensory agent that performs real-time context-dependent classification of motion patterns observed by a silicon retina. PMID:23878215

Crystallization and preliminary X-ray diffraction analysis of the CRISPR-Cas RNA-silencing Cmr complex.

PubMed

Osawa, Takuo; Inanaga, Hideko; Numata, Tomoyuki

2015-06-01

Clustered regularly interspaced short palindromic repeat (CRISPR)-derived RNA (crRNA) and CRISPR-associated (Cas) proteins constitute a prokaryotic adaptive immune system (CRISPR-Cas system) that targets and degrades invading genetic elements. The type III-B CRISPR-Cas Cmr complex, composed of the six Cas proteins (Cmr1-Cmr6) and a crRNA, captures and cleaves RNA complementary to the crRNA guide sequence. Here, a Cmr1-deficient functional Cmr (CmrΔ1) complex composed of Pyrococcus furiosus Cmr2-Cmr3, Archaeoglobus fulgidus Cmr4-Cmr5-Cmr6 and the 39-mer P. furiosus 7.01-crRNA was prepared. The CmrΔ1 complex was cocrystallized with single-stranded DNA (ssDNA) complementary to the crRNA guide by the vapour-diffusion method. The crystals diffracted to 2.1 Å resolution using synchrotron radiation at the Photon Factory. The crystals belonged to the triclinic space group P1, with unit-cell parameters a = 75.5, b = 76.2, c = 139.2 Å, α = 90.3, β = 104.8, γ = 118.6°. The asymmetric unit of the crystals is expected to contain one CmrΔ1-ssDNA complex, with a Matthews coefficient of 2.03 Å(3) Da(-1) and a solvent content of 39.5%.

A DNA Nanotube-Peptide biocomplex for mRNA Detection and Its Application in Cancer Diagnosis and Targeted Therapy.

PubMed

Ji, Xiaoting; Lv, Haoyuan; Guo, Jiayi; Ding, Caifeng; Luo, Xiliang

2018-04-25

A biocomplex of DNA nanotube-peptide, consisting of six concatenated DNA strands, three lock DNA strands and a cell-penetrating peptide was developed herein. The barrel structured DNA nanotube-peptide was successfully applied as a co-drug delivery system for targeting cancer therapy. The mucin 1 proteins (MUC-1) aptamer which is part of DNA nanotube can specially recognize MUC-1 protein on the surface of MCF-7 cells. Cyclo (Arg-Gly-Asp-D-phe-Lys) (cRGD), as a cell-penetrating peptide, facilitates recruitment and uptake of targeting drugs by binding to integrin receptors (αvβ3) of cytomembrane surface. Anti-cancer drug doxorubicin (DOX) and paclitaxel (PTX) were loaded into the capsulated DNA nanotube-peptide (CDNP), which was used as co-drug cargo models. The as-prepared biocomplex can be utilized not only to deliver drug but also to achieve the anticancer effect in vivo. The experimental results suggested that the treatment efficacy of co-drug delivery platform (CDNP/DOX/PTX) was better than single-drug delivery platform (CDNP/DOX or CDNP/PTX). This system that was composed by DNA strands and peptide has good biocompatibility and biodegradability. Furthermore, the system can readily achieve detection of target mRNA of MCF-7 cell in vitro. The detection limits of mRNA are 9.7×10-8 M and 1.8×10-8 M by using CDNP/DOX and CDNP/PTX-FITC as a probe, respectively. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

FIRESTORM: a collaborative network suite application for rapid sensor data processing and precise decisive responses

NASA Astrophysics Data System (ADS)

Kaniyantethu, Shaji

2011-06-01

This paper discusses the many features and composed technologies in Firestorm™ - a Distributed Collaborative Fires and Effects software. Modern response management systems capitalize on the capabilities of a plethora of sensors and its output for situational awareness. Firestorm utilizes a unique networked lethality approach by integrating unmanned air and ground vehicles to provide target handoff and sharing of data between humans and sensors. The system employs Bayesian networks for track management of sensor data, and distributed auction algorithms for allocating targets and delivering the right effect without information overload to the Warfighter. Firestorm Networked Effects Component provides joint weapon-target pairing, attack guidance, target selection standards, and other fires and effects components. Moreover, the open and modular architecture allows for easy integration with new data sources. Versatility and adaptability of the application enable it to devise and dispense a suitable response to a wide variety of scenarios. Recently, this application was used for detecting and countering a vehicle intruder with the help of radio frequency spotter sensor, command driven cameras, remote weapon system, portable vehicle arresting barrier, and an unmanned aerial vehicle - which confirmed the presence of the intruder, as well as provided lethal/non-lethal response and battle damage assessment. The completed demonstrations have proved Firestorm's™ validity and feasibility to predict, detect, neutralize, and protect key assets and/or area against a variety of possible threats. The sensors and responding assets can be deployed with numerous configurations to cover the various terrain and environmental conditions, and can be integrated to a number of platforms.

Expression of membrane targeted aequorin in Xenopus laevis oocytes.

PubMed

Daguzan, C; Nicolas, M T; Mazars, C; Leclerc, C; Moreau, M

1995-08-01

We described here a system for high level of expression of the calcium activated photoprotein aequorin. This protein has been targeted to the plasma membrane of Xenopus oocyte by nuclear microinjection of a plasmid containing a construction of a chimeric cDNA encoding a fusion protein composed of the photoprotein aequorin and the 5-HT1A receptor. The expression of this fusion protein is placed under the control of RSV promoter. Functional photoprotein was reconstituted in the oocyte by incubation with coelenterazine. The amount of photoprotein 24 h after nuclear microinjection of the plasmid was sufficient to trigger a detectable light emission following calcium entry. The efficiency of the expression is correlated with the dose of plasmid injected. Intracytoplasmic injection of the plasmid always failed in photoprotein expression. Targeting of the apoprotein was demonstrated by immunolocalization under confocal microscopy. In our experimental conditions, the apoprotein was always localized at the animal pole above the nucleus. We never observed expression and targeting to the plasma membrane of the vegetal pole. WE suggest that such expression might be of great interest for the study of numerous problems of developmental biology, in which calcium-dependent pathways are involved.

Structural Insights into the Molecular Design of Flutolanil Derivatives Targeted for Fumarate Respiration of Parasite Mitochondria.

PubMed

Inaoka, Daniel Ken; Shiba, Tomoo; Sato, Dan; Balogun, Emmanuel Oluwadare; Sasaki, Tsuyoshi; Nagahama, Madoka; Oda, Masatsugu; Matsuoka, Shigeru; Ohmori, Junko; Honma, Teruki; Inoue, Masayuki; Kita, Kiyoshi; Harada, Shigeharu

2015-07-07

Recent studies on the respiratory chain of Ascaris suum showed that the mitochondrial NADH-fumarate reductase system composed of complex I, rhodoquinone and complex II plays an important role in the anaerobic energy metabolism of adult A. suum. The system is the major pathway of energy metabolism for adaptation to a hypoxic environment not only in parasitic organisms, but also in some types of human cancer cells. Thus, enzymes of the pathway are potential targets for chemotherapy. We found that flutolanil is an excellent inhibitor for A. suum complex II (IC50 = 0.058 μM) but less effectively inhibits homologous porcine complex II (IC50 = 45.9 μM). In order to account for the specificity of flutolanil to A. suum complex II from the standpoint of structural biology, we determined the crystal structures of A. suum and porcine complex IIs binding flutolanil and its derivative compounds. The structures clearly demonstrated key interactions responsible for its high specificity to A. suum complex II and enabled us to find analogue compounds, which surpass flutolanil in both potency and specificity to A. suum complex II. Structures of complex IIs binding these compounds will be helpful to accelerate structure-based drug design targeted for complex IIs.

Purification of optical imaging ligand-Cybesin by high-speed counter-current chromatography

PubMed Central

Ma, Zhiyong; Ma, Ying; Sun, Xilin; Ye, Yunpeng; Shen, Baozhong; Chen, Xiaoyuan; Ito, Yoichiro

2010-01-01

Fluorescent Cybesin (Cypate-Bombesin Peptide Analogue Conjugate) was synthesized from Indocyanine Green (ICG) and the bombesin receptor ligand as a contrast agent for detecting pancreas tumors. However, the LC–MS analysis indicated that the target compound was only a minor component in the reaction mixture. Since preparative HPLC can hardly separate such a small amount of the target compound directly from the original crude reaction mixture without a considerable adsorptive loss onto the solid support, high-speed counter-current chromatography (HSCCC) was used for purification since the method uses no solid support and promises high sample recovery. A suitable two-phase solvent system composed of hexane/ethyl acetate/methanol/methyl t.-butyl ether/acetonitrile/water) at a volume ratio of 1:1:1:4:4:7 was selected based on the partition coefficient of Cybesin (K ≈ 0.9) determined by LC–MS. The separation was performed in two steps using the same solvent system with lower aqueous mobile phase. From 400 mg of the crude reaction mixture the first separation yielded 7.7 mg of fractions containing the target compound at 12.8% purity, and in the second run 1 mg of Cybesin was obtained at purity of 94.0% with a sample recovery rate of over 95% based on the LC–MS Analysis. PMID:20933483

Structural Insights into the Molecular Design of Flutolanil Derivatives Targeted for Fumarate Respiration of Parasite Mitochondria

PubMed Central

Inaoka, Daniel Ken; Shiba, Tomoo; Sato, Dan; Balogun, Emmanuel Oluwadare; Sasaki, Tsuyoshi; Nagahama, Madoka; Oda, Masatsugu; Matsuoka, Shigeru; Ohmori, Junko; Honma, Teruki; Inoue, Masayuki; Kita, Kiyoshi; Harada, Shigeharu

2015-01-01

Recent studies on the respiratory chain of Ascaris suum showed that the mitochondrial NADH-fumarate reductase system composed of complex I, rhodoquinone and complex II plays an important role in the anaerobic energy metabolism of adult A. suum. The system is the major pathway of energy metabolism for adaptation to a hypoxic environment not only in parasitic organisms, but also in some types of human cancer cells. Thus, enzymes of the pathway are potential targets for chemotherapy. We found that flutolanil is an excellent inhibitor for A. suum complex II (IC50 = 0.058 μM) but less effectively inhibits homologous porcine complex II (IC50 = 45.9 μM). In order to account for the specificity of flutolanil to A. suum complex II from the standpoint of structural biology, we determined the crystal structures of A. suum and porcine complex IIs binding flutolanil and its derivative compounds. The structures clearly demonstrated key interactions responsible for its high specificity to A. suum complex II and enabled us to find analogue compounds, which surpass flutolanil in both potency and specificity to A. suum complex II. Structures of complex IIs binding these compounds will be helpful to accelerate structure-based drug design targeted for complex IIs. PMID:26198225

Interdisciplinary Matchmaking: Choosing Collaborators by Skill, Acquaintance and Trust

NASA Astrophysics Data System (ADS)

Hupa, Albert; Rzadca, Krzysztof; Wierzbicki, Adam; Datta, Anwitaman

Social networks are commonly used to enhance recommender systems. Most of such systems recommend a single resource or a person. However, complex problems or projects usually require a team of experts that must work together on a solution. Team recommendation is much more challenging, mostly because of the complex interpersonal relations between members. This chapter presents fundamental concepts on how to score a team based on members' social context and their suitability for a particular project. We represent the social context of an individual as a three-dimensional social network (3DSN) composed of a knowledge dimension expressing skills, a trust dimension and an acquaintance dimension. Dimensions of a 3DSN are used to mathematically formalize the criteria for prediction of the team's performance. We use these criteria to formulate the team recommendation problem as a multi-criteria optimization problem. We demonstrate our approach on empirical data crawled from two web2.0 sites: onephoto.net and a social networking site. We construct 3DSNs and analyze properties of team's performance criteria.

Copper signaling in the brain and beyond.

PubMed

Ackerman, Cheri M; Chang, Christopher J

2018-03-30

Transition metals have been recognized and studied primarily in the context of their essential roles as structural and metabolic cofactors for biomolecules that compose living systems. More recently, an emerging paradigm of transition-metal signaling, where dynamic changes in transitional metal pools can modulate protein function, cell fate, and organism health and disease, has broadened our view of the potential contributions of these essential nutrients in biology. Using copper as a canonical example of transition-metal signaling, we highlight key experiments where direct measurement and/or visualization of dynamic copper pools, in combination with biochemical, physiological, and behavioral studies, have deciphered sources, targets, and physiological effects of copper signals.

Experimental demonstration of three-dimensional broadband underwater acoustic carpet cloak

NASA Astrophysics Data System (ADS)

Bi, Yafeng; Jia, Han; Sun, Zhaoyong; Yang, Yuzhen; Zhao, Han; Yang, Jun

2018-05-01

We present the design, architecture, and detailed performance of a three-dimensional (3D) underwater acoustic carpet cloak (UACC). The proposed system of the 3D UACC is an octahedral pyramid, which is composed of periodical steel strips. This underwater acoustic device, placed over the target to hide, is able to manipulate the scattered wavefront to mimic a reflecting plane. The effectiveness of the prototype is experimentally demonstrated in an anechoic tank. The measured acoustic pressure distributions show that the 3D UACC can work in all directions in a wide frequency range. This experimental verification of 3D device paves the way for guidelines on future practical applications.

A system view and analysis of essential hypertension.

PubMed

Botzer, Alon; Grossman, Ehud; Moult, John; Unger, Ron

2018-05-01

The goal of this study was to investigate genes associated with essential hypertension from a system perspective, making use of bioinformatic tools to gain insights that are not evident when focusing at a detail-based resolution. Using various databases (pathways, Genome Wide Association Studies, knockouts etc.), we compiled a set of about 200 genes that play a major role in hypertension and identified the interactions between them. This enabled us to create a protein-protein interaction network graph, from which we identified key elements, based on graph centrality analysis. Enriched gene regulatory elements (transcription factors and microRNAs) were extracted by motif finding techniques and knowledge-based tools. We found that the network is composed of modules associated with functions such as water retention, endothelial vasoconstriction, sympathetic activity and others. We identified the transcription factor SP1 and the two microRNAs miR27 (a and b) and miR548c-3p that seem to play a major role in regulating the network as they exert their control over several modules and are not restricted to specific functions. We also noticed that genes involved in metabolic diseases (e.g. insulin) are central to the network. We view the blood-pressure regulation mechanism as a system-of-systems, composed of several contributing subsystems and pathways rather than a single module. The system is regulated by distributed elements. Understanding this mode of action can lead to a more precise treatment and drug target discovery. Our analysis suggests that insulin plays a primary role in hypertension, highlighting the tight link between essential hypertension and diseases associated with the metabolic syndrome.

IRLooK: an advanced mobile infrared signature measurement, data reduction, and analysis system

NASA Astrophysics Data System (ADS)

Cukur, Tamer; Altug, Yelda; Uzunoglu, Cihan; Kilic, Kayhan; Emir, Erdem

2007-04-01

Infrared signature measurement capability has a key role in the electronic warfare (EW) self protection systems' development activities. In this article, the IRLooK System and its capabilities will be introduced. IRLooK is a truly innovative mobile infrared signature measurement system with all its design, manufacturing and integration accomplished by an engineering philosophy peculiar to ASELSAN. IRLooK measures the infrared signatures of military and civil platforms such as fixed/rotary wing aircrafts, tracked/wheeled vehicles and navy vessels. IRLooK has the capabilities of data acquisition, pre-processing, post-processing, analysis, storing and archiving over shortwave, mid-wave and long wave infrared spectrum by means of its high resolution radiometric sensors and highly sophisticated software analysis tools. The sensor suite of IRLooK System includes imaging and non-imaging radiometers and a spectroradiometer. Single or simultaneous multiple in-band measurements as well as high radiant intensity measurements can be performed. The system provides detailed information on the spectral, spatial and temporal infrared signature characteristics of the targets. It also determines IR Decoy characteristics. The system is equipped with a high quality field proven two-axes tracking mount to facilitate target tracking. Manual or automatic tracking is achieved by using a passive imaging tracker. The system also includes a high quality weather station and field-calibration equipment including cavity and extended area blackbodies. The units composing the system are mounted on flat-bed trailers and the complete system is designed to be transportable by large body aircraft.

KSC-2009-1445

NASA Image and Video Library

2009-01-31

CAPE CANAVERAL, Fla. – The Ares I-X roll control system module is revealed after removal of the plastic wrap. The module is in the Vehicle Assembly Building at NASA's Kennedy Space Center in Florida. The system is designed to perform a 90-degree roll after the rocket clears the launch tower, preventing a roll during flight and maintaining the orientation of the rocket until separation of the upper and first stages. Part of the upper stage simulator, the system module is composed to two modules and four thrusters. The system module will return to earth and splash down; it will not be recovered. Ares I-X is the test vehicle for the Ares I, which is part of the Constellation Program to return men to the moon and beyond. Ares I is the essential core of a safe, reliable, cost-effective space transportation system that eventually will carry crewed missions back to the moon, on to Mars and out into the solar system. Ares I-X is targeted for launch in July 2009. Photo credit: NASA/Jack Pfaller

KSC-2009-1442

NASA Image and Video Library

2009-01-31

CAPE CANAVERAL, Fla. – The Ares I-X roll control system module has been placed on the floor of the Vehicle Assembly Building at NASA's Kennedy Space Center in Florida after its arrival. The system is designed to perform a 90-degree roll after the rocket clears the launch tower, preventing a roll during flight and maintaining the orientation of the rocket until separation of the upper and first stages. Part of the upper stage simulator, the system module is composed to two modules and four thrusters. The system module will return to earth and splash down; it will not be recovered. Ares I-X is the test vehicle for the Ares I, which is part of the Constellation Program to return men to the moon and beyond. Ares I is the essential core of a safe, reliable, cost-effective space transportation system that eventually will carry crewed missions back to the moon, on to Mars and out into the solar system. Ares I-X is targeted for launch in July 2009. Photo credit: NASA/Jack Pfaller

KSC-2009-1444

NASA Image and Video Library

2009-01-31

CAPE CANAVERAL, Fla. – On the floor of the Vehicle Assembly Building at NASA's Kennedy Space Center in Florida, workers start removing the plastic wrap from the Ares I-X roll control system module. The system is designed to perform a 90-degree roll after the rocket clears the launch tower, preventing a roll during flight and maintaining the orientation of the rocket until separation of the upper and first stages. Part of the upper stage simulator, the system module is composed to two modules and four thrusters. The system module will return to earth and splash down; it will not be recovered. Ares I-X is the test vehicle for the Ares I, which is part of the Constellation Program to return men to the moon and beyond. Ares I is the essential core of a safe, reliable, cost-effective space transportation system that eventually will carry crewed missions back to the moon, on to Mars and out into the solar system. Ares I-X is targeted for launch in July 2009. Photo credit: NASA/Jack Pfaller

KSC-2009-1443

NASA Image and Video Library

2009-01-31

CAPE CANAVERAL, Fla. – In the Vehicle Assembly Building at NASA's Kennedy Space Center in Florida, workers look at the Ares I-X roll control system module before removing the plastic wrap. The system is designed to perform a 90-degree roll after the rocket clears the launch tower, preventing a roll during flight and maintaining the orientation of the rocket until separation of the upper and first stages. Part of the upper stage simulator, the system module is composed to two modules and four thrusters. The system module will return to earth and splash down; it will not be recovered. Ares I-X is the test vehicle for the Ares I, which is part of the Constellation Program to return men to the moon and beyond. Ares I is the essential core of a safe, reliable, cost-effective space transportation system that eventually will carry crewed missions back to the moon, on to Mars and out into the solar system. Ares I-X is targeted for launch in July 2009. Photo credit: NASA/Jack Pfaller

KSC-2009-1441

NASA Image and Video Library

2009-01-31

CAPE CANAVERAL, Fla. – The Ares I-X roll control system module arrives in the Vehicle Assembly Building at NASA's Kennedy Space Center in Florida. The system is designed to perform a 90-degree roll after the rocket clears the launch tower, preventing a roll during flight and maintaining the orientation of the rocket until separation of the upper and first stages. Part of the upper stage simulator, the system module is composed to two modules and four thrusters. The system module will return to earth and splash down; it will not be recovered. Ares I-X is the test vehicle for the Ares I, which is part of the Constellation Program to return men to the moon and beyond. Ares I is the essential core of a safe, reliable, cost-effective space transportation system that eventually will carry crewed missions back to the moon, on to Mars and out into the solar system. Ares I-X is targeted for launch in July 2009. Photo credit: NASA/Jack Pfaller

Use of the CRISPR/Cas9 system as an intracellular defense against HIV-1 infection in human cells.

PubMed

Liao, Hsin-Kai; Gu, Ying; Diaz, Arturo; Marlett, John; Takahashi, Yuta; Li, Mo; Suzuki, Keiichiro; Xu, Ruo; Hishida, Tomoaki; Chang, Chan-Jung; Esteban, Concepcion Rodriguez; Young, John; Izpisua Belmonte, Juan Carlos

2015-03-10

To combat hostile viruses, bacteria and archaea have evolved a unique antiviral defense system composed of clustered regularly interspaced short palindromic repeats (CRISPRs), together with CRISPR-associated genes (Cas). The CRISPR/Cas9 system develops an adaptive immune resistance to foreign plasmids and viruses by creating site-specific DNA double-stranded breaks (DSBs). Here we adapt the CRISPR/Cas9 system to human cells for intracellular defense against foreign DNA and viruses. Using HIV-1 infection as a model, our results demonstrate that the CRISPR/Cas9 system disrupts latently integrated viral genome and provides long-term adaptive defense against new viral infection, expression and replication in human cells. We show that engineered human-induced pluripotent stem cells stably expressing HIV-targeted CRISPR/Cas9 can be efficiently differentiated into HIV reservoir cell types and maintain their resistance to HIV-1 challenge. These results unveil the potential of the CRISPR/Cas9 system as a new therapeutic strategy against viral infections.

An artificial arm/hand system with a haptic sensory function using electric stimulation of peripheral sensory nerve fibers.

PubMed

Mabuchi, Kunihiko

2013-01-01

We are currently developing an artificial arm/hand system which is capable of sensing stimuli and then transferring these stimuli to users as somatic sensations. Presently, we are evoking the virtual somatic sensations by electrically stimulating a sensory nerve fiber which innervates a single mechanoreceptor unit at the target area; this is done using a tungsten microelectrode that was percutaneously inserted into the use's peripheral nerve (a microstimulation method). The artificial arm/hand system is composed of a robot hand equipped with a pressure sensor system on its fingers. The sensor system detects mechanical stimuli, which are transferred to the user by means of the microstimulation method so that the user experiences the stimuli as the corresponding somatic sensations. In trials, the system worked satisfactorily and there was a good correlation between the pressure applied to the pressure sensors on the robot fingers and the subjective intensities of the evoked pressure sensations.

Live Imaging of HIV-1 Transfer across T Cell Virological Synapse to Epithelial Cells that Promotes Stromal Macrophage Infection.

PubMed

Real, Fernando; Sennepin, Alexis; Ganor, Yonatan; Schmitt, Alain; Bomsel, Morgane

2018-05-08

During sexual intercourse, HIV-1 crosses epithelial barriers composing the genital mucosa, a poorly understood feature that requires an HIV-1-infected cell vectoring efficient mucosal HIV-1 entry. Therefore, urethral mucosa comprising a polarized epithelium and a stroma composed of fibroblasts and macrophages were reconstructed in vitro. Using this system, we demonstrate by live imaging that efficient HIV-1 transmission to stromal macrophages depends on cell-mediated transfer of the virus through virological synapses formed between HIV-1-infected CD4 + T cells and the epithelial cell mucosal surface. We visualized HIV-1 translocation through mucosal epithelial cells via transcytosis in regions where virological synapses occurred. In turn, interleukin-13 is secreted and HIV-1 targets macrophages, which develop a latent state of infection reversed by lipopolysaccharide (LPS) activation. The live observation of virological synapse formation reported herein is key in the design of vaccines and antiretroviral therapies aimed at blocking HIV-1 access to cellular reservoirs in genital mucosa. Copyright © 2018. Published by Elsevier Inc.

The Mu2e Solenoid Cold Mass Position Monitor System

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

Strauss, Thomas; Feher, Sandor; Friedsam, Horst W.

The Mu2e experiment at Fermilab is designed to search for charged-lepton flavor violation by looking for muon to electron conversions in the field of the nucleus. The concept of the experiment is to generate a low momentum muon beam, stopping the muons in a target and measuring the momentum of the outgoing electrons. The implementation of this approach utilizes a complex magnetic field composed of graded solenoidal and toroidal fields. The location of the solenoid cold mass relative to external fiducials is needed for alignment as well as monitoring coil movements during cool down and magnet excitation. This study describesmore » a novel design of a Cold Mass Position Monitor System (CMPS) that will be implemented for the Mu2e experiment.« less

The Mu2e Solenoid Cold Mass Position Monitor System

DOE PAGES

Strauss, Thomas; Feher, Sandor; Friedsam, Horst W.; ...

2018-01-23

The Mu2e experiment at Fermilab is designed to search for charged-lepton flavor violation by looking for muon to electron conversions in the field of the nucleus. The concept of the experiment is to generate a low momentum muon beam, stopping the muons in a target and measuring the momentum of the outgoing electrons. The implementation of this approach utilizes a complex magnetic field composed of graded solenoidal and toroidal fields. The location of the solenoid cold mass relative to external fiducials is needed for alignment as well as monitoring coil movements during cool down and magnet excitation. This study describesmore » a novel design of a Cold Mass Position Monitor System (CMPS) that will be implemented for the Mu2e experiment.« less

Proteolysis targeting peptide (PROTAP) strategy for protein ubiquitination and degradation.

PubMed

Zheng, Jing; Tan, Chunyan; Xue, Pengcheng; Cao, Jiakun; Liu, Feng; Tan, Ying; Jiang, Yuyang

2016-02-19

Ubiquitination proteasome pathway (UPP) is the most important and selective way to degrade proteins in vivo. Here, a novel proteolysis targeting peptide (PROTAP) strategy, composed of a target protein binding peptide, a linker and a ubiquitin E3 ligase recognition peptide, was designed to recruit both target protein and E3 ligase and then induce polyubiquitination and degradation of the target protein through UPP. In our study, the PROTAP strategy was proved to be a general method with high specificity using Bcl-xL protein as model target in vitro and in cells, which indicates that the strategy has great potential for in vivo application. Copyright © 2016 Elsevier Inc. All rights reserved.

A green approach to dual-drug nanoformulations with targeting and synergistic effects for cancer therapy.

PubMed

Wu, Shichao; Yang, Xiangrui; Lu, Yue; Fan, Zhongxiong; Li, Yang; Jiang, Yuan; Hou, Zhenqing

2017-11-01

Exploration of efficient dual-drug nanohybrids, particularly those with high drug loading, specific targeting property, and long-termed stability, is of highly importance in cancer therapy. A pH-driven coprecipitation was performed in the aqueous phase to obtain a dual-drug nanoformulation, composed of 10-hydroxycamptothecine (HCPT) nanoneedles integrated with an exterior thin layer of the methotrexate (MTX)-chitosan conjugate. The high stability of nanohybrids in water and the targeting property provided by the MTX ingredient function synergistically to the prolonged and sustained drug release property in tumor tissues and the increased cellular uptake. The cytotoxicity test illustrates that dual-drug nanoneedles possess the remarkable killing ability to HeLa cells with the combination index at 0.33 ± 0.07. After cellular internalization, the release of both drug ingredients results in an excellent anticancer activity in vivo with the minimized adverse side effects. Design of a green approach to the carrier-free, dual-drug nanoformulations enables to develop emerging drug delivery systems for cancer diagnosis and treatment.

MASCOT2, a Lander to Characterize the Target of an Asteroid Kinetic Impactor Deflection Test (AIM) Mission

NASA Astrophysics Data System (ADS)

Biele, J.; Ulamec, S.; Krause, C.; Cozzoni, B.; Lange, C.; Grundmann, J. T.; Grimm, C.; Ho, T.-M.; Herique, A.; Plettemeier, D.; Grott, M.; Auster, H.-U.; Hercik, D.; Carnelli, I.; Galvez, A.; Philippe, C.; Küppers, M.; Grieger, B.; Gil Fernandez, J.; Grygorczuk, J.

2017-09-01

In the course of the AIDA/AIM mission studies [1,2] a lander, MASCOT2, has been studied to be deployed on the moon of the binary Near-Earth Asteroid system, (65803) Didymos. The AIDA technology demonstration mission, composed of a kinetic impactor, DART, and an observing spacecraft, AIM, has been designed to deliver vital data to determine the momentum transfer efficiency of the kinetic impact and key physical properties of the target asteroid. This will enable derivation of the impact response of the object as a function of its physical properties, a crucial quantitative point besides the qualitative proof that the asteroid has been deflected at all. A landed asset on the target asteroid greatly supports analyzing its dynamical state, mass, geophysical properties, surface and subsurface structure. The lander's main instrument is a bistatic, low frequency radar (LFR) [3a,b] to sound the interior structure of the asteroid. It is supported by a camera (MasCAM) [4], a radiometer (MARA)[5], an accelerometer (DACC [9]), and, optionally regarding the science case, also a magnetometer (MasMAG)[6].

Visiting Vehicle Ground Trajectory Tool

NASA Technical Reports Server (NTRS)

Hamm, Dustin

2013-01-01

The International Space Station (ISS) Visiting Vehicle Group needed a targeting tool for vehicles that rendezvous with the ISS. The Visiting Vehicle Ground Trajectory targeting tool provides the ability to perform both realtime and planning operations for the Visiting Vehicle Group. This tool provides a highly reconfigurable base, which allows the Visiting Vehicle Group to perform their work. The application is composed of a telemetry processing function, a relative motion function, a targeting function, a vector view, and 2D/3D world map type graphics. The software tool provides the ability to plan a rendezvous trajectory for vehicles that visit the ISS. It models these relative trajectories using planned and realtime data from the vehicle. The tool monitors ongoing rendezvous trajectory relative motion, and ensures visiting vehicles stay within agreed corridors. The software provides the ability to update or re-plan a rendezvous to support contingency operations. Adding new parameters and incorporating them into the system was previously not available on-the-fly. If an unanticipated capability wasn't discovered until the vehicle was flying, there was no way to update things.

Titanium-Dioxide Nano-Fiber-Cotton Targets for Efficient Multi-keV X-Ray Generation

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

Tanabe, M; Nishimura, H; Fujioka, S

Multi-keV x-ray generation from low-density (27 {+-} 7 mg/cc) nano-fiber-cotton targets composed of titanium-dioxide has been investigated. The cotton targets were heated volumetrically and supersonically to a peak electron temperature of 2.3 keV, which is optimal to yield Ti K-shell x rays. Considerable enhancement of conversion efficiency (3.7 {+-} 0.5%) from incident laser energy into Ti K-shell x rays (4-6 keV band) was attained in comparison with that (1.4 {+-} 0.9%) for a planar Ti-foil target.

Titanium dioxide nanofiber-cotton targets for efficient multi-keV x-ray generation

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

Tanabe, Minoru; Nishimura, Hiroaki; Fujioka, Shinsuke

Multi-keV x-ray generation from low-density (27{+-}7 mg/cm{sup 3}) nanofiber-cotton targets composed of titanium dioxide has been investigated. The cotton targets were heated volumetrically and supersonically to a peak electron temperature of 2.3 keV, which is optimal to yield Ti K-shell x rays. Considerable enhancement of conversion efficiency [(3.7{+-}0.5)%] from incident laser energy into Ti K-shell x rays (4-6 keV band) was attained in comparison with that [(1.4{+-}0.9)%] for a planar Ti-foil target.

Raman imaging of pharmaceutical materials: refractive index effects on contrast at buried interfaces.

PubMed

Mecker-Pogue, Laura C; Kauffman, John F

2015-02-01

Resolution targets composed of bilayer polydimethylsiloxane (PDMS) devices with buried polyethylene glycol (PEG) channels have been fabricated using traditional photolithographic and micromolding techniques to develop resolution targets that mimic pharmaceutical materials. Raman chemical images of the resulting PEG-in-PDMS devices composed of varying parallel line widths were investigated by imaging the PEG lines through a thin overlayer of PDMS. Additionally, a scattering agent, Al2O3, was introduced at varying concentrations to each layer of the device to explore the effects of scattering materials on Raman images. Features in the resulting chemical images of the PEG lines suggest that reflection at the PEG/PDMS interface contributes to the Raman signal. A model based on geometric optics was developed to simulate the observed image functions of the targets. The results emphasize the influence of refractive index discontinuities at the PEG/PDMS interface on the apparent size and shape of the PEG features. Such findings have an impact on interpretation of Raman images of nonabsorbing, opaque pharmaceutical samples. Published by Elsevier B.V.

Health conditions and residential concentration of poverty: a study in Rio de Janeiro, Brazil

PubMed Central

Szwarcwald, C.; Bastos, F. I.; Barcellos, C.; Pina, M. d.; Esteves, M. A.

2000-01-01

STUDY OBJECTIVES—To establish the geographical relation of health conditions to socioeconomic status in the city of Rio de Janeiro, Brazil.
DESIGN—All reported deaths in the municipality of Rio de Janeiro, from 1987 to 1995, obtained from the Mortality Information System, were considered in the study. The 24 "administrative regions" that compose the city were used as the geographical units. A geographical information system (GIS) was used to link mortality data and population census data, and allowed the authors to establish the geographical pattern of the health indicators considered in this study: "infant mortality rate"; "standardised mortality rate"; "life expectancy" and "homicide rate". Information on location of low income communities (slums) was also provided by the GIS. A varimax rotation principal component analysis combined information on socioeconomic conditions and provided a two dimension basis to assess contextual variation.
MAIN RESULTS—The 24 administrative regions were aggregated into three different clusters, identified as relevant to reflect the socioeconomic variation. Almost all health indicator thematic maps showed the same socioeconomic stratification pattern. The worst health situation was found in the cluster composed of the harbour area and northern vicinity, precisely in the sector where the highest concentration of slum residents are present. This sector of the city exhibited an extremely high homicide rate and a seven year lower life expectancy than the remainder of the city. The sector that concentrates affluence, composed of the geographical units located along the coast, showed the best health situation. Intermediate health conditions were found in the west area, which also has poor living standards but low concentration of slums.
CONCLUSIONS—The findings suggest that social and organisation characteristics of low income communities may have a relevant role in understanding health variations. Local health and other social programmes specifically targeting these communities are recommended.


Keywords: geographical information system; health conditions; low income communities PMID:10846196

Looking for Biosignatures in Carbonate Microbialites from the Laguna Negra, Argentinian Andes

NASA Astrophysics Data System (ADS)

Boidi, F. J.; Gomez, F. J.; Fike, D. A.; Bradley, A. S.; Farías, M. E.; Beeler, S.

2015-12-01

The distinction between biotic and abiotic control on microbialites formation and its signatures is relevant since stromatolites are considered the oldest evidence for life on Earth and a target for astrobiological research. The Laguna Negra is a shallow hypersaline lake placed at the Andes, Northwest Argentina, where carbonate microbialites and microbial mats develop. It is a unique system where microbial influence on carbonate precipitation and potential preserved biosignatures in the microbialites can be studied. Here we compare three distinct microbialites systems: carbonate laminar crusts with no visible microbial mats, stromatolites and dm-size oncoids, both related with different microbial mats. Our goal is to unravel the biotic controls on their formation, and the biosignatures there recorded. Laminar crusts are composed of stacked regular and isopachous carbonate lamina. Oncoids laminae are typically characterized by irregular hybrid micro-textures, composed of alternating micritic and botryoidal laminae, and the stromatolites are mostly composed by irregular micritic laminae. Sulfur isotopes of carbonate associated sulphate show similar values but they show differences in the pyrite sulfur isotopes suggesting differences in the fractionation degree, possibly related to sulphate reducing bacteria and variable sulphate reservoirs in the case of stromatolites and oncoids. δ13C fractionation between organic carbon and carbonates suggests photosynthesis, but other metabolisms cannot yet be discarded. 16S rDNA data of the microbial communities associated with the carbonate structures indicate the presence of these taxonomic groups and those that are known to influence carbonate precipitation, particularly in the stromatolites associated microbial community. Our data indicate significant differences between the three systems in terms of stable isotopes, textures and associated microbial diversity, suggesting a microbial control on stromatolites and oncoids formation in the Laguna Negra. Further studies may provide a valuable contribution on biosignatures preservation and recognition that can shed light on understanding the early biosphere record.

Updated optical read/write memory system components

NASA Technical Reports Server (NTRS)

1973-01-01

The fabrication of an updated block data composer and holographic storage array for a breadboard holographic read/write memory system is described. System considerations such as transform optics and controlled aberration lens design are described along with the block data composer, photoplastic recording materials, and material development.

Random intermittent search and the tug-of-war model of motor-driven transport

NASA Astrophysics Data System (ADS)

Newby, Jay; Bressloff, Paul C.

2010-04-01

We formulate the 'tug-of-war' model of microtubule cargo transport by multiple molecular motors as an intermittent random search for a hidden target. A motor complex consisting of multiple molecular motors with opposing directional preference is modeled using a discrete Markov process. The motors randomly pull each other off of the microtubule so that the state of the motor complex is determined by the number of bound motors. The tug-of-war model prescribes the state transition rates and corresponding cargo velocities in terms of experimentally measured physical parameters. We add space to the resulting Chapman-Kolmogorov (CK) equation so that we can consider delivery of the cargo to a hidden target at an unknown location along the microtubule track. The target represents some subcellular compartment such as a synapse in a neuron's dendrites, and target delivery is modeled as a simple absorption process. Using a quasi-steady-state (QSS) reduction technique we calculate analytical approximations of the mean first passage time (MFPT) to find the target. We show that there exists an optimal adenosine triphosphate (ATP) concentration that minimizes the MFPT for two different cases: (i) the motor complex is composed of equal numbers of kinesin motors bound to two different microtubules (symmetric tug-of-war model) and (ii) the motor complex is composed of different numbers of kinesin and dynein motors bound to a single microtubule (asymmetric tug-of-war model).

Reward and aversion in a heterogeneous midbrain dopamine system.

PubMed

Lammel, Stephan; Lim, Byung Kook; Malenka, Robert C

2014-01-01

The ventral tegmental area (VTA) is a heterogeneous brain structure that serves a central role in motivation and reward processing. Abnormalities in the function of VTA dopamine (DA) neurons and the targets they influence are implicated in several prominent neuropsychiatric disorders including addiction and depression. Recent studies suggest that the midbrain DA system is composed of anatomically and functionally heterogeneous DA subpopulations with different axonal projections. These findings may explain a number of previously confusing observations that suggested a role for DA in processing both rewarding as well as aversive events. Here we will focus on recent advances in understanding the neural circuits mediating reward and aversion in the VTA and how stress as well as drugs of abuse, in particular cocaine, alter circuit function within a heterogeneous midbrain DA system. This article is part of a Special Issue entitled 'NIDA 40th Anniversary Issue'. Copyright © 2013 Elsevier Ltd. All rights reserved.

Design and analysis of reflector for uniform light-emitting diode illuminance.

PubMed

Tsai, Chung-Yu

2013-05-01

A light-emitting diode (LED) projection system is proposed, composed of an LED chip and a variable-focus-parabolic (VFP) reflector, in which the focal length varies as a function of the vertical displacement of the incidence point relative to the horizontal centerline of the LED chip. The light-ray paths within the projection system are analyzed using an exact analytical model and a skew-ray tracing approach. The profile of the proposed VFP reflector and the position of the LED chip are then optimized in such a way as to enhance the uniformity of the illuminance distribution on the target region of the image plane. The validity of the optimized design is demonstrated by means of ZEMAX simulations. It is shown that the optimized VFP projector system yields a significant improvement in illuminance uniformity compared to conventional spherical and parabolic projectors and therefore minimizes the glare effect.

An image understanding system using attributed symbolic representation and inexact graph-matching

NASA Astrophysics Data System (ADS)

Eshera, M. A.; Fu, K.-S.

1986-09-01

A powerful image understanding system using a semantic-syntactic representation scheme consisting of attributed relational graphs (ARGs) is proposed for the analysis of the global information content of images. A multilayer graph transducer scheme performs the extraction of ARG representations from images, with ARG nodes representing the global image features, and the relations between features represented by the attributed branches between corresponding nodes. An efficient dynamic programming technique is employed to derive the distance between two ARGs and the inexact matching of their respective components. Noise, distortion and ambiguity in real-world images are handled through modeling in the transducer mapping rules and through the appropriate cost of error-transformation for the inexact matching of the representation. The system is demonstrated for the case of locating objects in a scene composed of complex overlapped objects, and the case of target detection in noisy and distorted synthetic aperture radar image.

PepComposer: computational design of peptides binding to a given protein surface

PubMed Central

Obarska-Kosinska, Agnieszka; Iacoangeli, Alfredo; Lepore, Rosalba; Tramontano, Anna

2016-01-01

There is a wide interest in designing peptides able to bind to a specific region of a protein with the aim of interfering with a known interaction or as starting point for the design of inhibitors. Here we describe PepComposer, a new pipeline for the computational design of peptides binding to a given protein surface. PepComposer only requires the target protein structure and an approximate definition of the binding site as input. We first retrieve a set of peptide backbone scaffolds from monomeric proteins that harbor the same backbone arrangement as the binding site of the protein of interest. Next, we design optimal sequences for the identified peptide scaffolds. The method is fully automatic and available as a web server at http://biocomputing.it/pepcomposer/webserver. PMID:27131789

A sensory complex consisting of an ATP-binding cassette transporter and a two-component regulatory system controls bacitracin resistance in Bacillus subtilis.

PubMed

Dintner, Sebastian; Heermann, Ralf; Fang, Chong; Jung, Kirsten; Gebhard, Susanne

2014-10-03

Resistance against antimicrobial peptides in many Firmicutes bacteria is mediated by detoxification systems that are composed of a two-component regulatory system (TCS) and an ATP-binding cassette (ABC) transporter. The histidine kinases of these systems depend entirely on the transporter for sensing of antimicrobial peptides, suggesting a novel mode of signal transduction where the transporter constitutes the actual sensor. The aim of this study was to investigate the molecular mechanisms of this unusual signaling pathway in more detail, using the bacitracin resistance system BceRS-BceAB of Bacillus subtilis as an example. To analyze the proposed communication between TCS and the ABC transporter, we characterized their interactions by bacterial two-hybrid analyses and could show that the permease BceB and the histidine kinase BceS interact directly. In vitro pulldown assays confirmed this interaction, which was found to be independent of bacitracin. Because it was unknown whether BceAB-type transporters could detect their substrate peptides directly or instead recognized the peptide-target complex in the cell envelope, we next analyzed substrate binding by the transport permease, BceB. Direct and specific binding of bacitracin by BceB was demonstrated by surface plasmon resonance spectroscopy. Finally, in vitro signal transduction assays indicated that complex formation with the transporter influenced the autophosphorylation activity of the histidine kinase. Taken together, our findings clearly show the existence of a sensory complex composed of TCS and ABC transporters and provide the first functional insights into the mechanisms of stimulus perception, signal transduction, and antimicrobial resistance employed by Bce-like detoxification systems. © 2014 by The American Society for Biochemistry and Molecular Biology, Inc.

A Sensory Complex Consisting of an ATP-binding Cassette Transporter and a Two-component Regulatory System Controls Bacitracin Resistance in Bacillus subtilis*

PubMed Central

Dintner, Sebastian; Heermann, Ralf; Fang, Chong; Jung, Kirsten; Gebhard, Susanne

2014-01-01

Resistance against antimicrobial peptides in many Firmicutes bacteria is mediated by detoxification systems that are composed of a two-component regulatory system (TCS) and an ATP-binding cassette (ABC) transporter. The histidine kinases of these systems depend entirely on the transporter for sensing of antimicrobial peptides, suggesting a novel mode of signal transduction where the transporter constitutes the actual sensor. The aim of this study was to investigate the molecular mechanisms of this unusual signaling pathway in more detail, using the bacitracin resistance system BceRS-BceAB of Bacillus subtilis as an example. To analyze the proposed communication between TCS and the ABC transporter, we characterized their interactions by bacterial two-hybrid analyses and could show that the permease BceB and the histidine kinase BceS interact directly. In vitro pulldown assays confirmed this interaction, which was found to be independent of bacitracin. Because it was unknown whether BceAB-type transporters could detect their substrate peptides directly or instead recognized the peptide-target complex in the cell envelope, we next analyzed substrate binding by the transport permease, BceB. Direct and specific binding of bacitracin by BceB was demonstrated by surface plasmon resonance spectroscopy. Finally, in vitro signal transduction assays indicated that complex formation with the transporter influenced the autophosphorylation activity of the histidine kinase. Taken together, our findings clearly show the existence of a sensory complex composed of TCS and ABC transporters and provide the first functional insights into the mechanisms of stimulus perception, signal transduction, and antimicrobial resistance employed by Bce-like detoxification systems. PMID:25118291

Lethal violence and psychosis: a clinical profile.

PubMed

Nestor, P G; Haycock, J; Doiron, S; Kelly, J; Kelly, D

1995-01-01

To investigate the relationship between lethal violence and psychosis, the authors examined symptomatology, neuropsychological functioning, and the nature of perpetrator-victim relationships of patients with psychotic disorders who were committed to a forensic psychiatric hospital following violent, primarily criminal behavior. A severely violent group, composed primarily of psychotic patients charged with murder, was compared with a less severely violent group that was composed primarily of psychotic patients involved with property crimes. As compared with the less violent group, the severely violent group was more likely to have delusional beliefs about specific personal targets and to have delusions about significant others being replaced by impostors. These beliefs were accompanied by higher scores on neuropsychological tests of intellectual and academic abilities. A high number of their blood relatives were victims of psychotic murder. These results indicated that a higher incidence of lethal or near lethal acts of violence may characterize intellectually intact but psychotic individuals with organize delusions involving personal, accessible targets.

Romantic partners in a market perspective: expectations about what ensures a highly desirable partner.

PubMed

Castro, Felipe N; Hattori, Wallisen T; Yamamoto, Maria Emília; Lopes, Fívia A

2013-10-01

This study used the biological market perspective and influential statistical models from the marketing field to investigate males' and females' expectations regarding which combination of characteristics are most relevant in ensuring desirable partnerships for same-sex individuals. Thus, 358 Brazilian undergraduates assessed eight descriptions of same-gender stimulus targets (formulated with different levels of physical attractiveness, social skills, and current or prospective social status) and evaluated the overall desirability of the targets' expected or probable partners. From the possible combinations, three groups emerged: for one group, mainly composed of men, status characteristics were the most important attributes; for the others, mostly composed of women, social skills or physical characteristics were identified as most important in appealing to a desirable partner. This work expands the understanding of variability in male and female romantic expectations, and its implications are discussed from an evolutionary perspective.

High-throughput screening identifies microRNAs that target Nox2 and improve function after acute myocardial infarction.

PubMed

Yang, Junyu; Brown, Milton E; Zhang, Hanshuo; Martinez, Mario; Zhao, Zhihua; Bhutani, Srishti; Yin, Shenyi; Trac, David; Xi, Jianzhong Jeff; Davis, Michael E

2017-05-01

Myocardial infarction (MI) is the most common cause of heart failure. Excessive production of ROS plays a key role in the pathogenesis of cardiac remodeling after MI. NADPH with NADPH oxidase (Nox)2 as the catalytic subunit is a major source of superoxide production, and expression is significantly increased in the infarcted myocardium, especially by infiltrating macrophages. While microRNAs (miRNAs) are potent regulators of gene expression and play an important role in heart disease, there still lacks efficient ways to identify miRNAs that target important pathological genes for treating MI. Thus, the overall objective was to establish a miRNA screening and delivery system for improving heart function after MI using Nox2 as a critical target. With the use of the miRNA-target screening system composed of a self-assembled cell microarray (SAMcell), three miRNAs, miR-106b, miR-148b, and miR-204, were identified that could regulate Nox2 expression and its downstream products in both human and mouse macrophages. Each of these miRNAs were encapsulated into polyketal (PK3) nanoparticles that could effectively deliver miRNAs into macrophages. Both in vitro and in vivo studies in mice confirmed that PK3-miRNAs particles could inhibit Nox2 expression and activity and significantly improve infarct size and acute cardiac function after MI. In conclusion, our results show that miR-106b, miR-148b, and miR-204 were able to improve heart function after myocardial infarction in mice by targeting Nox2 and possibly altering inflammatory cytokine production. This screening system and delivery method could have broader implications for miRNA-mediated therapeutics for cardiovascular and other diseases. NEW & NOTEWORTHY NADPH oxidase (Nox)2 is a promising target for treating cardiovascular disease, but there are no specific inhibitors. Finding endogenous signals that can target Nox2 and other inflammatory molecules is of great interest. In this study, we used high-throughput screening to identify microRNAs that target Nox2 and improve cardiac function after infarction. Copyright © 2017 the American Physiological Society.

Structure, Evolution, and Functions of Bacterial Type III Toxin-Antitoxin Systems.

PubMed

Goeders, Nathalie; Chai, Ray; Chen, Bihe; Day, Andrew; Salmond, George P C

2016-09-28

Toxin-antitoxin (TA) systems are small genetic modules that encode a toxin (that targets an essential cellular process) and an antitoxin that neutralises or suppresses the deleterious effect of the toxin. Based on the molecular nature of the toxin and antitoxin components, TA systems are categorised into different types. Type III TA systems, the focus of this review, are composed of a toxic endoribonuclease neutralised by a non-coding RNA antitoxin in a pseudoknotted configuration. Bioinformatic analysis shows that the Type III systems can be classified into subtypes. These TA systems were originally discovered through a phage resistance phenotype arising due to a process akin to an altruistic suicide; the phenomenon of abortive infection. Some Type III TA systems are bifunctional and can stabilise plasmids during vegetative growth and sporulation. Features particular to Type III systems are explored here, emphasising some of the characteristics of the RNA antitoxin and how these may affect the co-evolutionary relationship between toxins and cognate antitoxins in their quaternary structures. Finally, an updated analysis of the distribution and diversity of these systems are presented and discussed.

Toxin-Antitoxin Systems as Multilevel Interaction Systems

PubMed Central

Goeders, Nathalie; Van Melderen, Laurence

2014-01-01

Toxin-antitoxin (TA) systems are small genetic modules usually composed of a toxin and an antitoxin counteracting the activity of the toxic protein. These systems are widely spread in bacterial and archaeal genomes. TA systems have been assigned many functions, ranging from persistence to DNA stabilization or protection against mobile genetic elements. They are classified in five types, depending on the nature and mode of action of the antitoxin. In type I and III, antitoxins are RNAs that either inhibit the synthesis of the toxin or sequester it. In type II, IV and V, antitoxins are proteins that either sequester, counterbalance toxin activity or inhibit toxin synthesis. In addition to these interactions between the antitoxin and toxin components (RNA-RNA, protein-protein, RNA-protein), TA systems interact with a variety of cellular factors, e.g., toxins target essential cellular components, antitoxins are degraded by RNAses or ATP-dependent proteases. Hence, TA systems have the capacity to interact with each other at different levels. In this review, we will discuss the different interactions in which TA systems are involved and their implications in TA system functions and evolution. PMID:24434905

Structure, Evolution, and Functions of Bacterial Type III Toxin-Antitoxin Systems

PubMed Central

Goeders, Nathalie; Chai, Ray; Chen, Bihe; Day, Andrew; Salmond, George P. C.

2016-01-01

Toxin-antitoxin (TA) systems are small genetic modules that encode a toxin (that targets an essential cellular process) and an antitoxin that neutralises or suppresses the deleterious effect of the toxin. Based on the molecular nature of the toxin and antitoxin components, TA systems are categorised into different types. Type III TA systems, the focus of this review, are composed of a toxic endoribonuclease neutralised by a non-coding RNA antitoxin in a pseudoknotted configuration. Bioinformatic analysis shows that the Type III systems can be classified into subtypes. These TA systems were originally discovered through a phage resistance phenotype arising due to a process akin to an altruistic suicide; the phenomenon of abortive infection. Some Type III TA systems are bifunctional and can stabilise plasmids during vegetative growth and sporulation. Features particular to Type III systems are explored here, emphasising some of the characteristics of the RNA antitoxin and how these may affect the co-evolutionary relationship between toxins and cognate antitoxins in their quaternary structures. Finally, an updated analysis of the distribution and diversity of these systems are presented and discussed. PMID:27690100

Exploring the Hydrothermal System in the Chicxulub Crater and Implications for the Early Evolution of Life on Earth

NASA Astrophysics Data System (ADS)

Kring, D. A.; Schmieder, M.; Tikoo, S.; Riller, U. P.; Simpson, S. L.; Osinski, G.; Cockell, C. S.; Coolen, M.; Gulick, S. P. S.; Morgan, J. V.

2017-12-01

Impact cratering, particularly large basin-size craters with diameters >100 km, have the potential to generate vast subsurface hydrothermal systems. There were dozens of such impacts during the Hadean and early Archean, some of which vaporized seas for brief periods of time, during which the safest niches for early life may have been in those subsurface hydrothermal systems. The Chicxulub crater can serve as a proxy for those events. New IODP-ICDP core recovered by Expedition 364 reveals a high-temperature (>300 degree C) system that may have persisted for more than 100,000 years. Of order 105 to 106 km3 of crust was structurally deformed, melted, and vaporized within about 10 minutes of the impact. The crust had to endure immense strain rates of 104/s to 106/s, up to 12 orders of magnitude greater than those associated with igneous and metamorphic processes. The outcome is a porous, permeable region that is a perfect host for hydrothermal circulation across the entire diameter of the crater to depths up to 5 or 6 km. The target rocks at Chicxulub are composed of an 3 km-thick carbonate platform sequence over a crystalline basement composed of igneous granite, granodiorite, and a few other intrusive components, such as dolerite, and metamorphic assemblages composed, in part, of gneiss and mica schist. Post-impact hydrothermal alteration includes Ca-Na- and K-metasomatism, pervasive hydration to produce layered silicates, and lower-temperature vug-filling zeolites as the system cycled from high temperatures to low temperatures. While the extent of granitic crust on early Earth is still debated and, thus, the direct application of those mineral reactions to the Hadean and early Archean can be debated, the thermal evolution of the system should be applicable to diverse crustal compositions. It is important to point out that pre-impact thermal conditions of Hadean and early Archean crust can affect the size of an impact basin and, in turn, the proportion of that basin that may experience hydrothermal conditions. The Chicxulub crater - as sampled by Expedition 364 - will provide the baseline needed to assess the spatial and temporal extent of Hadean and early Archean hydrothermal systems and their potential as crucibles for pre-biotic chemistry and the early evolution of microbial life.

Determining Methane Leak Locations and Rates with a Wireless Network Composed of Low-Cost, Printed Sensors

NASA Astrophysics Data System (ADS)

Smith, C. J.; Kim, B.; Zhang, Y.; Ng, T. N.; Beck, V.; Ganguli, A.; Saha, B.; Daniel, G.; Lee, J.; Whiting, G.; Meyyappan, M.; Schwartz, D. E.

2015-12-01

We will present our progress on the development of a wireless sensor network that will determine the source and rate of detected methane leaks. The targeted leak detection threshold is 2 g/min with a rate estimation error of 20% and localization error of 1 m within an outdoor area of 100 m2. The network itself is composed of low-cost, high-performance sensor nodes based on printed nanomaterials with expected sensitivity below 1 ppmv methane. High sensitivity to methane is achieved by modifying high surface-area-to-volume-ratio single-walled carbon nanotubes (SWNTs) with materials that adsorb methane molecules. Because the modified SWNTs are not perfectly selective to methane, the sensor nodes contain arrays of variously-modified SWNTs to build diversity of response towards gases with adsorption affinity. Methane selectivity is achieved through advanced pattern-matching algorithms of the array's ensemble response. The system is low power and designed to operate for a year on a single small battery. The SWNT sensing elements consume only microwatts. The largest power consumer is the wireless communication, which provides robust, real-time measurement data. Methane leak localization and rate estimation will be performed by machine-learning algorithms built with the aid of computational fluid dynamics simulations of gas plume formation. This sensor system can be broadly applied at gas wells, distribution systems, refineries, and other downstream facilities. It also can be utilized for industrial and residential safety applications, and adapted to other gases and gas combinations.

R&D of A MW-class solid-target for a spallation neutron source

NASA Astrophysics Data System (ADS)

Kawai, Masayoshi; Furusaka, Michihiro; Kikuchi, Kenji; Kurishita, Hiroaki; Watanabe, Ryuzo; Li, Jing-Feng; Sugimoto, Katsuhisa; Yamamura, Tsutomu; Hiraoka, Yutaka; Abe, Katsunori; Hasegawa, Akira; Yoshiie, Masatoshi; Takenaka, Hiroyuki; Mishima, Katsuichiro; Kiyanagi, Yoshiaki; Tanabe, Tetsuo; Yoshida, Naoaki; Igarashi, Tadashi

2003-05-01

R&D for a MW-class solid target composed of tungsten was undertaken to produce a pulsed intense neutron source for a future neutron scattering-facility. In order to solve the corrosion of tungsten, tungsten target blocks were clad with tantalum by means of HIP'ing, brazing and electrolytic coating in a molten salt bath. The applicability of the HIP'ing method was tested through fabricating target blocks for KENS (spallation neutron source at KEK). A further investigation to certify the optimum HIP conditions was made with the small punch test method. The results showed that the optimum temperature was 1500 °C at which the W/Ta interface gave the strongest fracture strength. In the case of the block with a hole for thermocouple, it was found that the fabrication preciseness of a straight hole and a tantalum sheath influenced the results. The development of a tungsten stainless-steel alloy was tried to produce a bare tungsten target, using techniques in powder metallurgy. Corrosion tests for various tungsten alloys were made while varying the water temperature and velocity. The mass loss of tungsten in very slow water at 180 °C was as low as 0.022 mg/y, but increased remarkably with water velocity. Simulation experiments for radiation damage to supplement the STIP-III experiments were made to investigate material hardening by hydrogen and helium, and microstructures irradiated by electrons. Both experiments showed consistent results on the order of the dislocation numbers and irradiation hardness among the different tungsten materials. Thermal-hydraulic designs were made for two types of solid target system of tungsten: slab and rod geometry as a function of the proton beam power. The neutronic performance of a solid target system was compared with that of mercury target based on Monte Carlo calculations by using the MCNP code.

An Efficient Strategy Based on Liquid-Liquid Extraction with Three-Phase Solvent System and High Speed Counter-Current Chromatography for Rapid Enrichment and Separation of Epimers of Minor Bufadienolide from Toad Meat.

PubMed

Zou, Denglang; Zhu, Xuelin; Zhang, Fan; Du, Yurong; Ma, Jianbin; Jiang, Renwang

2018-01-31

This study presents an efficient strategy based on liquid-liquid extraction with three-phase solvent system and high speed counter-current chromatography for rapid enrichment and separation of epimers of minor bufadienolide from toad meat. The reflux extraction conditions were optimized by response surface methodology first, and a novel three-phase solvent system composed of n-hexane/methyl acetate/acetonitrile/water (3:6:5:5, v/v) was developed for liquid-liquid extraction of the crude extract. This integrative extraction process could enrich minor bufadienolide from complex matrix efficiently and minimize the loss of minor targets induced by repeated extraction with different kinds of organic solvents occurring in the classical liquid two-phase extraction. As a result, four epimers of minor bufadienolide were greatly enriched in the middle phase and total content of these epimers of minor bufadienolide was increased from 3.25% to 46.23%. Then, the enriched four epimers were separated by HSCCC with a two-phase solvent system composed of chloroform/methanol/water (4:2:2, v/v) successfully. Furthermore, we tested Na + ,K + -ATPase (NKA) inhibitory effect of the four epimers. 3β-Isomers of bufadienolide showed stronger (>8-fold) inhibitory activity than 3α-isomers. The characterization of minor bufadienolide in toad meat and their significant difference of inhibitory effect on NKA would promote the further quantitative analysis and safety evaluation of toad meat as a food source.

Solute carrier transporters: potential targets for digestive system neoplasms.

PubMed

Xie, Jing; Zhu, Xiao Yan; Liu, Lu Ming; Meng, Zhi Qiang

2018-01-01

Digestive system neoplasms are the leading causes of cancer-related death all over the world. Solute carrier (SLC) superfamily is composed of a series of transporters that are ubiquitously expressed in organs and tissues of digestive systems and mediate specific uptake of small molecule substrates in facilitative manner. Given the important role of SLC proteins in maintaining normal functions of digestive system, dysregulation of these protein in digestive system neoplasms may deliver biological and clinical significance that deserves systemic studies. In this review, we critically summarized the recent advances in understanding the role of SLC proteins in digestive system neoplasms. We highlighted that several SLC subfamilies, including metal ion transporters, transporters of glucose and other sugars, transporters of urea, neurotransmitters and biogenic amines, ammonium and choline, inorganic cation/anion transporters, transporters of nucleotide, amino acid and oligopeptide organic anion transporters, transporters of vitamins and cofactors and mitochondrial carrier, may play important roles in mediating the initiation, progression, metastasis, and chemoresistance of digestive system neoplasms. Proteins in these SLC subfamilies may also have diagnostic and prognostic values to particular cancer types. Differential expression of SLC proteins in tumors of digestive system was analyzed by extracting data from human cancer database, which revealed that the roles of SLC proteins may either be dependent on the substrates they transport or be tissue specific. In addition, small molecule modulators that pharmacologically regulate the functions of SLC proteins were discussed for their possible application in the treatment of digestive system neoplasms. This review highlighted the potential of SLC family proteins as drug target for the treatment of digestive system neoplasms.

Solute carrier transporters: potential targets for digestive system neoplasms

PubMed Central

Xie, Jing; Zhu, Xiao Yan; Liu, Lu Ming; Meng, Zhi Qiang

2018-01-01

Digestive system neoplasms are the leading causes of cancer-related death all over the world. Solute carrier (SLC) superfamily is composed of a series of transporters that are ubiquitously expressed in organs and tissues of digestive systems and mediate specific uptake of small molecule substrates in facilitative manner. Given the important role of SLC proteins in maintaining normal functions of digestive system, dysregulation of these protein in digestive system neoplasms may deliver biological and clinical significance that deserves systemic studies. In this review, we critically summarized the recent advances in understanding the role of SLC proteins in digestive system neoplasms. We highlighted that several SLC subfamilies, including metal ion transporters, transporters of glucose and other sugars, transporters of urea, neurotransmitters and biogenic amines, ammonium and choline, inorganic cation/anion transporters, transporters of nucleotide, amino acid and oligopeptide organic anion transporters, transporters of vitamins and cofactors and mitochondrial carrier, may play important roles in mediating the initiation, progression, metastasis, and chemoresistance of digestive system neoplasms. Proteins in these SLC subfamilies may also have diagnostic and prognostic values to particular cancer types. Differential expression of SLC proteins in tumors of digestive system was analyzed by extracting data from human cancer database, which revealed that the roles of SLC proteins may either be dependent on the substrates they transport or be tissue specific. In addition, small molecule modulators that pharmacologically regulate the functions of SLC proteins were discussed for their possible application in the treatment of digestive system neoplasms. This review highlighted the potential of SLC family proteins as drug target for the treatment of digestive system neoplasms. PMID:29416375

HORN-6 special-purpose clustered computing system for electroholography.

PubMed

Ichihashi, Yasuyuki; Nakayama, Hirotaka; Ito, Tomoyoshi; Masuda, Nobuyuki; Shimobaba, Tomoyoshi; Shiraki, Atsushi; Sugie, Takashige

2009-08-03

We developed the HORN-6 special-purpose computer for holography. We designed and constructed the HORN-6 board to handle an object image composed of one million points and constructed a cluster system composed of 16 HORN-6 boards. Using this HORN-6 cluster system, we succeeded in creating a computer-generated hologram of a three-dimensional image composed of 1,000,000 points at a rate of 1 frame per second, and a computer-generated hologram of an image composed of 100,000 points at a rate of 10 frames per second, which is near video rate, when the size of a computer-generated hologram is 1,920 x 1,080. The calculation speed is approximately 4,600 times faster than that of a personal computer with an Intel 3.4-GHz Pentium 4 CPU.

Forecasting Tidal Disruption Events for Binary Black Holes with an Outer Tertiary.

PubMed

Seto, Naoki; Kyutoku, Koutarou

2017-04-14

We discuss the gravitational wave (GW) emission and the orbital evolution of a hierarchical triple system composed of an inner binary black hole (BBH) and an outer tertiary. Depending on the kick velocity at the merger, the merged BBH could tidally disrupt the tertiary. Even though the fraction of BBH mergers accompanied by such disruptions is expected to be much smaller than unity, the existence of a tertiary and its basic parameters (e.g., semimajor axis, projected mass) can be examined for more than 10^{3} BBHs with the follow-on missions to the space GW detector LISA. This allows us to efficiently prescreen the targets for the follow-up searches for the tidal disruption events (TDEs). The TDE probability would be significantly higher for triple systems with aligned orbital- and spin-angular momenta, compared with random configurations.

S-layer fusion proteins — construction principles and applications

PubMed Central

Ilk, Nicola; Egelseer, Eva M; Sleytr, Uwe B

2011-01-01

Crystalline bacterial cell surface layers (S-layers) are the outermost cell envelope component of many bacteria and archaea. S-layers are monomolecular arrays composed of a single protein or glycoprotein species and represent the simplest biological membrane developed during evolution. The wealth of information available on the structure, chemistry, genetics and assembly of S-layers revealed a broad spectrum of applications in nanobiotechnology and biomimetics. By genetic engineering techniques, specific functional domains can be incorporated in S-layer proteins while maintaining the self-assembly capability. These techniques have led to new types of affinity structures, microcarriers, enzyme membranes, diagnostic devices, biosensors, vaccines, as well as targeting, delivery and encapsulation systems. PMID:21696943

Tricomponent Immunopotentiating System as a Novel Molecular Design Strategy for Malaria Vaccine Development ▿

PubMed Central

Miyata, Takeshi; Harakuni, Tetsuya; Tsuboi, Takafumi; Sattabongkot, Jetsumon; Ikehara, Ayumu; Tachibana, Mayumi; Torii, Motomi; Matsuzaki, Goro; Arakawa, Takeshi

2011-01-01

The creation of subunit vaccines to prevent malaria infection has been hampered by the intrinsically weak immunogenicity of the recombinant antigens. We have developed a novel strategy to increase immune responses by creating genetic fusion proteins to target specific antigen-presenting cells (APCs). The fusion complex was composed of three physically linked molecular entities: (i) a vaccine antigen, (ii) a multimeric α-helical coiled-coil core, and (iii) an APC-targeting ligand linked to the core via a flexible linker. The vaccine efficacy of the tricomponent complex was evaluated using an ookinete surface protein of Plasmodium vivax, Pvs25, and merozoite surface protein-1 of Plasmodium yoelii. Immunization of mice with the tricomponent complex induced a robust antibody response and conferred substantial levels of P. vivax transmission blockade as evaluated by a membrane feed assay, as well as protection from lethal P. yoelii infection. The observed effect was strongly dependent on the presence of all three components physically integrated as a fusion complex. This system, designated the tricomponent immunopotentiating system (TIPS), onto which any recombinant protein antigens or nonproteinaceous substances could be loaded, may be a promising strategy for devising subunit vaccines or adjuvants against various infectious diseases, including malaria. PMID:21807905

A versatile microsatellite instability reporter system in human cells.

PubMed

Koole, Wouter; Schäfer, Henning S; Agami, Reuven; van Haaften, Gijs; Tijsterman, Marcel

2013-09-01

Here, we report the investigation of microsatellite instability (MSI) in human cells with a newly developed reporter system based on fluorescence. We composed a vector into which microsatellites of different lengths and nucleotide composition can be introduced between a functional copy of the fluorescent protein mCherry and an out-of-frame copy of EGFP; in vivo frameshifting will lead to EGFP expression, which can be quantified by fluorescence activated cell sorting (FACS). Via targeted recombineering, single copy reporters were introduced in HEK293 and MCF-7 cells. We found predominantly -1 and +1 base pair frameshifts, the levels of which are kept in tune by mismatch repair. We show that tract length and composition greatly influences MSI. In contrast, a tracts' potential to form a G-quadruplex structure, its strand orientation or its transcriptional status is not affecting MSI. We further validated the functionality of the reporter system for screening microsatellite mutagenicity of compounds and for identifying modifiers of MSI: using a retroviral miRNA expression library, we identified miR-21, which targets MSH2, as a miRNA that induces MSI when overexpressed. Our data also provide proof of principle for the strategy of combining fluorescent reporters with next-generation sequencing technology to identify genetic factors in specific pathways.

Design of a new type synchronous focusing mechanism

NASA Astrophysics Data System (ADS)

Zhang, Jintao; Tan, Ruijun; Chen, Zhou; Zhang, Yongqi; Fu, Panlong; Qu, Yachen

2018-05-01

Aiming at the dual channel telescopic imaging system composed of infrared imaging system, low-light-level imaging system and image fusion module, In the fusion of low-light-level images and infrared images, it is obvious that using clear source images is easier to obtain high definition fused images. When the target is imaged at 15m to infinity, focusing is needed to ensure the imaging quality of the dual channel imaging system; therefore, a new type of synchronous focusing mechanism is designed. The synchronous focusing mechanism realizes the focusing function through the synchronous translational imaging devices, mainly including the structure of the screw rod nut, the shaft hole coordination structure and the spring steel ball eliminating clearance structure, etc. Starting from the synchronous focusing function of two imaging devices, the structure characteristics of the synchronous focusing mechanism are introduced in detail, and the focusing range is analyzed. The experimental results show that the synchronous focusing mechanism has the advantages of ingenious design, high focusing accuracy and stable and reliable operation.

Design and development of hyaluronan-functionalized polybenzofulvene nanoparticles as CD44 receptor mediated drug delivery system

NASA Astrophysics Data System (ADS)

Licciardi, Mariano; Scialabba, Cinzia; Giammona, Gaetano; Paolino, Marco; Razzano, Vincenzo; Grisci, Giorgio; Giuliani, Germano; Makovec, Francesco; Cappelli, Andrea

2017-06-01

A tri-component polymer brush (TCPB ), composed of a polybenzofulvene copolymer bearing low molecular weight hyaluronic acid (HA) on the surface of its cylindrical brush-like backbone and oligo-PEG fractions, was employed in the preparation of 350 nm nanostructured drug delivery systems capable of delivering the anticancer drug doxorubicin. The obtained drug delivery systems were characterized on the basis of drug loading and release, dimensions and zeta potential, morphology and in vitro cell activity, and uptake on three different human cell lines, namely the bronchial epithelial 16HBE, the breast adenocarcinoma MCF-7, and the colon cancer HCT116 cells. Finally, the ability of doxorubicin-loaded TCPB nanoparticles (DOXO-TCPB) to be internalized into cancer cells by CD44 receptor mediated uptake was assessed by means of uptake studies in HCT cells. These data were supported by anti-CD44-FITC staining assay. The proposed TCPB nanostructured drug delivery systems have many potential applications in nanomedicine, including cancer targeted drug delivery.

Delivery Systems for Biopharmaceuticals. Part I: Nanoparticles and Microparticles.

PubMed

Silva, Ana C; Lopes, Carla M; Lobo, José M S; Amaral, Maria H

2015-01-01

Pharmaceutical biotechnology has been showing therapeutic success never achieved with conventional drug molecules. Therefore, biopharmaceutical products are currently well-established in clinic and the development of new ones is expected. These products comprise mainly therapeutic proteins, although nucleic acids and cells are also included. However, according to their sensitive molecular structures, the efficient delivery of biopharmaceuticals is challenging. Several delivery systems (e.g. microparticles and nanoparticles) composed of different materials (e.g. polymers and lipids) have been explored and demonstrated excellent outcomes, such as: high cellular transfection efficiency for nucleic acids, cell targeting, increased proteins and peptides bioavailability, improved immune response in vaccination, and viability maintenance of microencapsulated cells. Nonetheless, important issues need to be addressed before they reach clinics. For example, more in vivo studies in animals, accessing the toxicity potential and predicting in vivo failure of these delivery systems are required. This is the Part I of two review articles, which presents the state of the art of delivery systems for biopharmaceuticals. Part I deals with microparticles and polymeric and lipid nanoparticles.

Development of hydrolysis probe-based real-time PCR for identification of virulent gene targets of Burkholderia pseudomallei and B. mallei--a retrospective study on archival cases of service members with melioidosis and glanders.

PubMed

Zhang, Binxue; Wear, Douglas J; Kim, H S; Weina, Peter; Stojadinovic, Alexander; Izadjoo, Mina

2012-02-01

Burkholderia pseudomallei and B. mallei are two highly pathogenic bacteria responsible for melioidosis and glanders, respectively. Our laboratory developed hydrolysis probe-based real-time polymerase chain reaction assays targeting type three secretion system (TTS) and transposase family protein (TFP) of B. pseudomallei and B. malli, respectively. The assays were validated for target specificity, amplification sensitivity, and reproducibility. A bacterial DNA panel, composed of B. pseudomallei (13 strains), B. mallei (11 strains), Burkholderia species close neighbors (5 strains), and other bacterial species (17 strains), was prepared for specificity testing. Reference DNAs from B. pseudomallei and B. mallei bacterial cultures were used as controls for amplification, limit of detection, and reproducibility testing. The two TaqMan assays, Bp-TTS 1 and Bm-TFP, were optimized and applied in a retrospective study of archived cases from the Armed Forces Institute of Pathology. We tested 10 formalin-fixed paraffin-embedded blocks originally from autopsy specimens of patients who died of melioidosis or glanders during or after overseas tours in 1960s. Polymerase chain reaction results confirmed that DNA samples from formalin-fixed paraffin-embedded blocks of eight patients with melioidosis were positive for Bp-TTS 1 target and two patients with glanders were positive for Bm-TFP target.

Targeting Microvascular Pericytes in Angiogenic Vessels of Prostate Cancer

DTIC Science & Technology

2005-04-01

endothelial cells (BEC) were identified using a cocktail of rat antibodies against mouse endoglin ( CD 105), PECAM-1 (CD3 1), and VEGF receptor-2 (flk...immunohistochemistry, and imaging angiogenic tufts composed of endothelial cells positive for endoglin ( CD 105), PECAM- I (CD3 1), and VEGF receptor...TYPE AND DATES COVERED (Leave blank) - April 2005 Annual (1 Apr 2004 - 31 Mar 2005) 4. TITLE AND SUBTITLE 5. FUNDING NUMBERS Targeting Microvascular

Development of voice navigation system for the visually impaired by using IC tags.

PubMed

Takatori, Norihiko; Nojima, Kengo; Matsumoto, Masashi; Yanashima, Kenji; Magatani, Kazushige

2006-01-01

There are about 300,000 visually impaired persons in Japan. Most of them are old persons and, cannot become skillful in using a white cane, even if they make effort to learn how to use a white cane. Therefore, some guiding system that supports the independent activities of the visually impaired are required. In this paper, we will describe about a developed white cane system that supports the independent walking of the visually impaired in the indoor space. This system is composed of colored navigation lines that include IC tags and an intelligent white cane that has a navigation computer. In our system colored navigation lines that are put on the floor of the target space from the start point to the destination and IC tags that are set at the landmark point are used for indication of the route to the destination. The white cane has a color sensor, an IC tag transceiver and a computer system that includes a voice processor. This white cane senses the navigation line that has target color by a color sensor. When a color sensor finds the target color, the white cane informs a white cane user that he/she is on the navigation line by vibration. So, only following this vibration, the user can reach the destination. However, at some landmark points, guidance is necessary. At these points, an IC tag is set under the navigation line. The cane makes communication with the tag and informs the user about the land mark pint by pre recorded voice. Ten normal subjects who were blindfolded were tested with our developed system. All of them could walk along navigation line. And the IC tag information system worked well. Therefore, we have concluded that our system will be a very valuable one to support activities of the visually impaired.

Optoacoustic imaging of gold nanoparticles targeted to breast cancer cells

NASA Astrophysics Data System (ADS)

Eghtedari, Mohammad; Motamedi, Massoud; Popov, Vsevolod L.; Kotov, Nicholas A.; Oraevsky, Alexander A.

2004-07-01

Optoacoustic Tomography (OAT) is a rapidly growing technology that enables noninvasive deep imaging of biological tissues based on their light absorption. In OAT, the interaction of a pulsed laser with tissue increases the temperature of the absorbing components in a confined volume of tissue. Rapid perturbation of the temperature (<1°C) deep within tissue produces weak acoustic waves that easily travel to the surface of the tissue with minor attenuation. Abnormal angiogenesis in a malignant tumor, that increases its blood content, makes a native contrast for optoacoustic imaging; however, the application of OAT for early detection of malignant tumors requires the enhancement of optoacoustic signals originated from tumor by using an exogenous contrast agent. Due to their strong absorption, we have used gold nanoparticles (NP) as a contrast agent. 40nm spherical gold nanoparticles were attached to monoclonal antibody to target cell surface of breast cancer cells. The targeted cancer cells were implanted at depth of 5-6cm within a gelatinous object that optically resembles human breast. Experimental sensitivity measurements along with theoretical analysis showed that our optoacoustic imaging system is capable of detecting a phantom breast tumor with the volume of 0.15ml, which is composed of 25 million NP-targeted cancer cells, at a depth of 5 centimeters in vitro.

Multi-talker background and semantic priming effect

PubMed Central

Dekerle, Marie; Boulenger, Véronique; Hoen, Michel; Meunier, Fanny

2014-01-01

The reported studies have aimed to investigate whether informational masking in a multi-talker background relies on semantic interference between the background and target using an adapted semantic priming paradigm. In 3 experiments, participants were required to perform a lexical decision task on a target item embedded in backgrounds composed of 1–4 voices. These voices were Semantically Consistent (SC) voices (i.e., pronouncing words sharing semantic features with the target) or Semantically Inconsistent (SI) voices (i.e., pronouncing words semantically unrelated to each other and to the target). In the first experiment, backgrounds consisted of 1 or 2 SC voices. One and 2 SI voices were added in Experiments 2 and 3, respectively. The results showed a semantic priming effect only in the conditions where the number of SC voices was greater than the number of SI voices, suggesting that semantic priming depended on prime intelligibility and strategic processes. However, even if backgrounds were composed of 3 or 4 voices, reducing intelligibility, participants were able to recognize words from these backgrounds, although no semantic priming effect on the targets was observed. Overall this finding suggests that informational masking can occur at a semantic level if intelligibility is sufficient. Based on the Effortfulness Hypothesis, we also suggest that when there is an increased difficulty in extracting target signals (caused by a relatively high number of voices in the background), more cognitive resources were allocated to formal processes (i.e., acoustic and phonological), leading to a decrease in available resources for deeper semantic processing of background words, therefore preventing semantic priming from occurring. PMID:25400572

Effectiveness of Two-Talker Maskers That Differ in Talker Congruity and Perceptual Similarity to the Target Speech

PubMed Central

Buss, Emily; Bowdrie, Kristina

2017-01-01

Previous work has shown that masked-sentence recognition is particularly poor when the masker is composed of two competing talkers, a finding that is attributed to informational masking. Informational masking tends to be largest when the target and masker talkers are perceptually similar. Reductions in masking have been observed for a wide range of target and masker differences, including language: Performance is better when the target and masker talkers speak in different languages, compared with the same language. The present study evaluated normal-hearing adults’ sentence recognition in a two-talker masker as a function of the perceptual similarity between the target and each of the two masker streams. The target was English, and the maskers were composed of English, time-reversed English, or Dutch. These three masker types are known to vary in the informational masking they exert. The two talkers within the two-talker maskers were either congruent (e.g., both English) or incongruent (e.g., one English, one Dutch). As predicted, mean performance was worse for the congruent English masker than the congruent time-reversed English or congruent Dutch maskers. Incongruent two-talker maskers, with just one English masker stream, were only modestly less effective than the congruent English masker. This result indicates that two-talker masker effectiveness was determined predominantly by the one masker stream that was most perceptually similar to the target. Speech recognition in a single-talker masker differed only marginally between the English, Dutch, and time-reversed English masker types, suggesting that perceptual similarity may be more critical in a two-talker than a one-talker masker. PMID:29169315

Improvement of side-effects and treatment on the experimental colitis in mice of a resin microcapsule-loading hydrocortisone sodium succinate.

PubMed

Dong, Kai; Zhang, Hefeng; Yan, Yan; Sun, Jinyao; Dong, Yalin; Wang, Ke; Zhang, Lu; Shi, Xianpeng; Xing, Jianfeng

2017-03-01

Extensive or long-time use of corticosteroids often causes many toxic side-effects. The ion exchange resins and the coating material, Eudragit, can be used in combination to form a new oral delivery system to deliver corticosteroids. The resin microcapsule (DRM) composed by Amberlite 717 and Eudragit S100 was used to target hydrocortisone (HC) to the colon in order to improve its treatment effect on ulcerative colitis (UC) and reduce its toxic side-effects. Hydrocortisone sodium succinate (HSS) was sequentially encapsulated in Amberlite 717 and Eudragit S100 to prepare the HSS-loaded resin microcapsule (HSS-DRM). The scanning electron microscopy (SEM) was employed to investigate the morphology and structure of HSS-DRM. The in vitro release and in vivo studies of pharmacokinetics and intestinal drug residues in rat were used to study the colon-targeting of HSS-DRM. The mouse induced by 2,4,6-trinitrobenzenesulfonic acid was used to study the treatment of HSS-DRM on experimental colitis. SEM study showed good morphology and structure of HSS-DRM. In the in vitro release study, > 80% of HSS was released in the colon environment (pH 7.4). The in vivo studies showed good colon-targeting of HSS-DRM (T max  = 0.97 h, C max  = 118.28 µg/mL of HSS; T max  = 2.16 h, C max  = 64.47 µg/mL of HSS-DRM). Moreover, the HSS-DRM could reduce adverse reactions induced by HSS and had good therapeutic effects on the experimental colitis. The resin microcapsule system has good colon-targeting and can be used in the development of colon-targeting preparations.

Design of a novel Hyper-spectral riflescope system

NASA Astrophysics Data System (ADS)

Huang, YunHan; Fu, YueGang

2016-10-01

Hyper-spectral imaging involves many research areas, such as optics, spectroscopy, mechanical, microelectronics, and computers, etc. Hyper-spectral imaging system has an irreplaceable role in the detection field. At present, due to the improvement of camouflage technology, characteristic of target in battlefield becomes more complex and the targets became more and more difficult to be detected, According to this phenomenon the author designed a novel hyper-spectral riflescope optical system. In general, the riflescope optical system is composed of two parts front object lens and zoom relay system. Firstly, dispersion characteristics of the typical optical glasses varies during band 400nm 1 000nm, the author derived apochromatic theory that suitable to the front system and relay system without using special glass, and make a example to testify its correctness. In general, the zoom mode of relay system lens is different from the objective lens system, so we should take consideration of them separately. Secondly, based on the above theory, the articles designed a hyper-spectral riflescope system, which has a continuous zoom curve, zoom ratio is 4 times and the F number of the system is 4.8;Full field of view varies during 1.8° 7.2°.Structure of the system is relatively compact, and has not used special glass, eventually the article give the schematic of system MTF and zoom curves of relay movable parts. the curve is smooth and can be applied to practical engineering. The author adopt ZEMAX design software to analyses the results .Design result shows that, in the visible and near-infrared wavelengths, the MTF of imaging system at 60lp / mm during all bands are greater than 0.3, which prove the correctness of the design theory and good performance of system.

A microscale human liver platform that supports the hepatic stages of Plasmodium falciparum and vivax

PubMed Central

March, Sandra; Ng, Shengyong; Velmurugan, Soundarapandian; Galstian, Ani; Shan, Jing; Logan, David; Carpenter, Anne; Thomas, David; Lee Sim, B. Kim; Mota, Maria M.; Hoffman, Stephen L.; Bhatia, Sangeeta N.

2013-01-01

SUMMARY The Plasmodium liver stage is an attractive target for the development of anti-malarial drugs and vaccines, as it provides an opportunity to interrupt the life cycle of the parasite at a critical early stage. However, targeting the liver stage has been difficult. Undoubtedly, a major barrier has been the lack of robust, reliable and reproducible in vitro liver stage cultures. Here, we establish the liver stages for both Plasmodium falciparum and Plasmodium vivax in a microscale human liver platform composed of cryopreserved, micropatterned human primary hepatocytes surrounded by supportive stromal cells. Using this system, we have successfully recapitulated the full liver stage of P. falciparum including the release of infected merozoites and infection of overlaid erythrocytes, and also the establishment of small forms in late liver stages of P. vivax. Finally, we validate the potential of this platform as a tool for medium-throughput anti-malarial drug screening and vaccine development. PMID:23870318

On architecting and composing engineering information services to enable smart manufacturing

PubMed Central

Ivezic, Nenad; Srinivasan, Vijay

2016-01-01

Engineering information systems play an important role in the current era of digitization of manufacturing, which is a key component to enable smart manufacturing. Traditionally, these engineering information systems spanned the lifecycle of a product by providing interoperability of software subsystems through a combination of open and proprietary exchange of data. But research and development efforts are underway to replace this paradigm with engineering information services that can be composed dynamically to meet changing needs in the operation of smart manufacturing systems. This paper describes the opportunities and challenges in architecting such engineering information services and composing them to enable smarter manufacturing. PMID:27840595

The Mycobacterium tuberculosis cell-surface glycoprotein apa as a potential adhesin to colonize target cells via the innate immune system pulmonary C-type lectin surfactant protein A.

PubMed

Ragas, Aude; Roussel, Lucie; Puzo, Germain; Rivière, Michel

2007-02-23

Tuberculosis is still a major health problem, and understanding the mechanism by which Mycobacterium tuberculosis (Mtb) invades and colonizes its host target cells remains an important issue for the control of infection. The innate immune system C-type lectins (C-TLs), including the human pulmonary surfactant protein A (PSP-A), have been recently identified as determinant players in the early recognition of the invading pathogen and in mounting the host defense response. Although the antigenic lipoglycan mannosylated lipoarabinomannan is currently considered to be the major C-TL target on the mycobacterial surface, the recognition by some C-TLs of the only mycobacterial species composing the "Mtb complex" indicates that mannosylated lipoarabinomannan cannot account alone for this specificity. Thus, we searched for the mycobacterial molecules targeted by human PSP-A, focusing our attention on the Mtb surface glycoproteins. We developed an original functional proteomic approach based on a lectin blot assay using crude human bronchoalveolar lavage fluid as a source of physiological PSP-A. Combined with selective cell-surface protein extraction and mass spectrometry peptide mapping, this strategy allowed us to identify the Apa (alanine- and proline-rich antigenic) glycoprotein as new potential target for PSP-A. This result was supported by direct binding of PSP-A to purified Apa. Moreover, EDTA addition or deglycosylation of purified Apa samples completely abolished the interaction, demonstrating that the interaction is calcium- and mannose-dependent, as expected. Finally, we provide convincing evidence that Apa, formerly considered as mainly secreted, is associated with the cell wall for a sufficiently long time to aid in the attachment of PSP-A. Because, to date, Apa seems to be restricted to the Mtb complex strains, we propose that it may account for the selective recognition of those strains by PSP-A and other immune system C-TLs containing homologous functional domains.

The Tin Bider Impact Structure, Algeria: New Map with Field Inputs on Structural Aspect

NASA Astrophysics Data System (ADS)

Kassab, F.; Belhai, D.

2017-07-01

The Tin Bider impact structure is a complex type composed by sedimentary target rocks. We realized a geological map including new inputs on impact characters of a recent field investigation where we identify shatter cone and folds.

DockScreen: A database of in silico biomolecular interactions to support computational toxicology

EPA Science Inventory

We have developed DockScreen, a database of in silico biomolecular interactions designed to enable rational molecular toxicological insight within a computational toxicology framework. This database is composed of chemical/target (receptor and enzyme) binding scores calculated by...

Design of microcamera for field curvature and distortion correction in monocentric multiscale foveated imaging system

NASA Astrophysics Data System (ADS)

Wu, Xiongxiong; Wang, Xiaorui; Zhang, Jianlei; Yuan, Ying; Chen, Xiaoxiang

2017-04-01

To realize large field of view (FOV) and high-resolution dynamic gaze of the moving target, this paper proposes the monocentric multiscale foveated (MMF) imaging system based on monocentric multiscale design and foveated imaging. First we present the MMF imaging system concept. Then we analyze large field curvature and distortion of the secondary image when the spherical intermediate image produced by the primary monocentric objective lens is relayed by the microcameras. Further a type of zoom endoscope objective lens is selected as the initial structure and optimized to minimize the field curvature and distortion with ZEMAX optical design software. The simulation results show that the maximum field curvature in full field of view is below 0.25 mm and the maximum distortion in full field of view is below 0.6%, which can meet the requirements of the microcamera in the proposed MMF imaging system. In addition, a simple doublet is used to design the foveated imaging system. Results of the microcamera together with the foveated imager compose the results of the whole MMF imaging system.

Performance of a visuomotor walking task in an augmented reality training setting.

PubMed

Haarman, Juliet A M; Choi, Julia T; Buurke, Jaap H; Rietman, Johan S; Reenalda, Jasper

2017-12-01

Visual cues can be used to train walking patterns. Here, we studied the performance and learning capacities of healthy subjects executing a high-precision visuomotor walking task, in an augmented reality training set-up. A beamer was used to project visual stepping targets on the walking surface of an instrumented treadmill. Two speeds were used to manipulate task difficulty. All participants (n = 20) had to change their step length to hit visual stepping targets with a specific part of their foot, while walking on a treadmill over seven consecutive training blocks, each block composed of 100 stepping targets. Distance between stepping targets was varied between short, medium and long steps. Training blocks could either be composed of random stepping targets (no fixed sequence was present in the distance between the stepping targets) or sequenced stepping targets (repeating fixed sequence was present). Random training blocks were used to measure non-specific learning and sequenced training blocks were used to measure sequence-specific learning. Primary outcome measures were performance (% of correct hits), and learning effects (increase in performance over the training blocks: both sequence-specific and non-specific). Secondary outcome measures were the performance and stepping-error in relation to the step length (distance between stepping target). Subjects were able to score 76% and 54% at first try for lower speed (2.3 km/h) and higher speed (3.3 km/h) trials, respectively. Performance scores did not increase over the course of the trials, nor did the subjects show the ability to learn a sequenced walking task. Subjects were better able to hit targets while increasing their step length, compared to shortening it. In conclusion, augmented reality training by use of the current set-up was intuitive for the user. Suboptimal feedback presentation might have limited the learning effects of the subjects. Copyright © 2017 Elsevier B.V. All rights reserved.

A Benchmark Dataset for SSVEP-Based Brain-Computer Interfaces.

PubMed

Wang, Yijun; Chen, Xiaogang; Gao, Xiaorong; Gao, Shangkai

2017-10-01

This paper presents a benchmark steady-state visual evoked potential (SSVEP) dataset acquired with a 40-target brain- computer interface (BCI) speller. The dataset consists of 64-channel Electroencephalogram (EEG) data from 35 healthy subjects (8 experienced and 27 naïve) while they performed a cue-guided target selecting task. The virtual keyboard of the speller was composed of 40 visual flickers, which were coded using a joint frequency and phase modulation (JFPM) approach. The stimulation frequencies ranged from 8 Hz to 15.8 Hz with an interval of 0.2 Hz. The phase difference between two adjacent frequencies was . For each subject, the data included six blocks of 40 trials corresponding to all 40 flickers indicated by a visual cue in a random order. The stimulation duration in each trial was five seconds. The dataset can be used as a benchmark dataset to compare the methods for stimulus coding and target identification in SSVEP-based BCIs. Through offline simulation, the dataset can be used to design new system diagrams and evaluate their BCI performance without collecting any new data. The dataset also provides high-quality data for computational modeling of SSVEPs. The dataset is freely available fromhttp://bci.med.tsinghua.edu.cn/download.html.

Computational multiscale modeling in protein--ligand docking.

PubMed

Taufer, Michela; Armen, Roger; Chen, Jianhan; Teller, Patricia; Brooks, Charles

2009-01-01

In biological systems, the binding of small molecule ligands to proteins is a crucial process for almost every aspect of biochemistry and molecular biology. Enzymes are proteins that function by catalyzing specific biochemical reactions that convert reactants into products. Complex organisms are typically composed of cells in which thousands of enzymes participate in complex and interconnected biochemical pathways. Some enzymes serve as sequential steps in specific pathways (such as energy metabolism), while others function to regulate entire pathways and cellular functions [1]. Small molecule ligands can be designed to bind to a specific enzyme and inhibit the biochemical reaction. Inhibiting the activity of key enzymes may result in the entire biochemical pathways being turned on or off [2], [3]. Many small molecule drugs marketed today function in this generic way as enzyme inhibitors. If research identifies a specific enzyme as being crucial to the progress of disease, then this enzyme may be targeted with an inhibitor, which may slow down or reverse the progress of disease. In this way, enzymes are targeted from specific pathogens (e.g., virus, bacteria, fungi) for infectious diseases [4], [5], and human enzymes are targeted for noninfectious diseases such as cardiovascular disease, cancer, diabetes, and neurodegenerative diseases [6].

EMMA: a new paradigm in configurable software

DOE PAGES

Nogiec, J. M.; Trombly-Freytag, K.

2017-11-23

EMMA is a framework designed to create a family of configurable software systems, with emphasis on extensibility and flexibility. It is based on a loosely coupled, event driven architecture. The EMMA framework has been built upon the premise of composing software systems from independent components. It opens up opportunities for reuse of components and their functionality and composing them together in many different ways. As a result, it provides the developer of test and measurement applications with a lightweight alternative to microservices, while sharing their various advantages, including composability, loose coupling, encapsulation, and reuse.

EMMA: A New Paradigm in Configurable Software

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

Nogiec, J. M.; Trombly-Freytag, K.

EMMA is a framework designed to create a family of configurable software systems, with emphasis on extensibility and flexibility. It is based on a loosely coupled, event driven architecture. The EMMA framework has been built upon the premise of composing software systems from independent components. It opens up opportunities for reuse of components and their functionality and composing them together in many different ways. It provides the developer of test and measurement applications with a lightweight alternative to microservices, while sharing their various advantages, including composability, loose coupling, encapsulation, and reuse.

EMMA: a new paradigm in configurable software

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

Nogiec, J. M.; Trombly-Freytag, K.

EMMA is a framework designed to create a family of configurable software systems, with emphasis on extensibility and flexibility. It is based on a loosely coupled, event driven architecture. The EMMA framework has been built upon the premise of composing software systems from independent components. It opens up opportunities for reuse of components and their functionality and composing them together in many different ways. As a result, it provides the developer of test and measurement applications with a lightweight alternative to microservices, while sharing their various advantages, including composability, loose coupling, encapsulation, and reuse.

EMMA: a new paradigm in configurable software

NASA Astrophysics Data System (ADS)

Nogiec, J. M.; Trombly-Freytag, K.

2017-10-01

EMMA is a framework designed to create a family of configurable software systems, with emphasis on extensibility and flexibility. It is based on a loosely coupled, event driven architecture. The EMMA framework has been built upon the premise of composing software systems from independent components. It opens up opportunities for reuse of components and their functionality and composing them together in many different ways. It provides the developer of test and measurement applications with a lightweight alternative to microservices, while sharing their various advantages, including composability, loose coupling, encapsulation, and reuse.

Curcumin targeting the thioredoxin system elevates oxidative stress in HeLa cells

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

Cai, Wenqing; Zhang, Baoxin; Duan, Dongzhu

2012-08-01

The thioredoxin system, composed of thioredoxin reductase (TrxR), thioredoxin (Trx), and NADPH, is ubiquitous in all cells and involved in many redox-dependent signaling pathways. Curcumin, a naturally occurring pigment that gives a specific yellow color in curry food, is consumed in normal diet up to 100 mg per day. This molecule has also been used in traditional medicine for the treatment of a variety of diseases. Curcumin has numerous biological functions, and many of these functions are related to induction of oxidative stress. However, how curcumin elicits oxidative stress in cells is unclear. Our previous work has demonstrated the waymore » by which curcumin interacts with recombinant TrxR1 and alters the antioxidant enzyme into a reactive oxygen species (ROS) generator in vitro. Herein we reported that curcumin can target the cytosolic/nuclear thioredoxin system to eventually elevate oxidative stress in HeLa cells. Curcumin-modified TrxR1 dose-dependently and quantitatively transfers electrons from NADPH to oxygen with the production of ROS. Also, curcumin can drastically down-regulate Trx1 protein level as well as its enzyme activity in HeLa cells, which in turn remarkably decreases intracellular free thiols, shifting the intracellular redox balance to a more oxidative state, and subsequently induces DNA oxidative damage. Furthermore, curcumin-pretreated HeLa cells are more sensitive to oxidative stress. Knockdown of TrxR1 sensitizes HeLa cells to curcumin cytotoxicity, highlighting the physiological significance of targeting TrxR1 by curcumin. Taken together, our data disclose a previously unrecognized prooxidant mechanism of curcumin in cells, and provide a deep insight in understanding how curcumin works in vivo. -- Highlights: ► Curcumin induces oxidative stress by targeting the thioredoxin system. ► Curcumin-modified TrxR quantitatively oxidizes NADPH to generate ROS. ► Knockdown of TrxR1 augments curcumin's cytotoxicity in HeLa cells. ► Curcumin sensitizes HeLa cells to oxidative stress.« less

Neutron-rich isotope production using the uranium carbide multi-foil SPES target prototype

NASA Astrophysics Data System (ADS)

Scarpa, D.; Biasetto, L.; Corradetti, S.; Manzolaro, M.; Andrighetto, A.; Carturan, S.; Prete, G.; Zanonato, P.; Stracener, D. W.

2011-03-01

In the framework of the R&D program for the SPES (Selective Production of Exotic Species) project of the Istituto Nazionale di Fisica Nucleare (INFN), production yields of neutron-rich isotopes have been measured at the Holifield Radioactive Ion Beam Facility (HRIBF, Oak Ridge National Laboratory, USA). This experiment makes use of the multi-foil SPES target prototype composed of 7 uranium carbide discs, with excess of graphite (ratio C/ U = 4 . 77 isotopes of medium mass (between 72 and 141amu), produced via proton-induced fission of uranium using a 40MeV proton beam, have been collected and analyzed for the target heated at 2000 ° C target temperature.

Etude theorique des fluctuations structurales dans les composes organiques a dimensionnalite reduite

NASA Astrophysics Data System (ADS)

Dumoulin, Benoit

Les systemes a dimensionnalite reduite constituent maintenant une branche entiere de la physique de la matiere condensee. Cette derniere s'est developpee rapidement au cours des dernieres annees, avec la decouverte des materiaux organiques qui presentent, justement, des proprietes physiques fortement anisotropes. Cette these presente une etude en trois parties de plusieurs composes organiques qui, bien que tres differents du point de vue de leurs compositions chimiques et de leurs proprietes physiques a haute temperature, subissent tous une instabilite structurale a tres basse temperature. De plus, dans chacun des cas, l'instabilite structurale est precedee d'un important regime fluctuatif a partir duquel les proprietes physiques changent de maniere significative. Notre etude suit un ordre chronologique inverse puisque nous nous attardons en premier lieu au cas de composes recemment decouverts: les composes de la famille des (BCPTTF)2X (X = PF6 , AsF6). Ces derniers sont des isolants magnetiques a la temperature ambiante et subissent une instabilite structurale de type spin-Peierls a une temperature appelee TSP. En particulier, nous nous interessons a l'etude des proprietes physiques de ces systemes dans le regime fluctuatif, qui precede cette instabilite. Notre etude theorique nous permet de comprendre en detail comment ces systemes s'approchent de l'instabilite struturale. Dans la seconde partie de cette these, nous etudions le regime fluctuatif (pre-transitionnel) observe experimentalement dans le compose de (TMTTF)2PF6. Ce compose organique, dont la structure s'apparente aux sels de Bechgaard, subit une instabilite de type spin-Peierls a une temperature T SP = 19K. Bien que ce compose possede la particularite d'etre un bon conducteur a la temperature ambiante, il subit une transition de type Mott-Hubbard a une temperature Trho ≈ 220K et devient alors un isolant magnetique, analogue aux composes de la famille des (BCPTTF)2X. Le regime fluctuatif precedant l'instabilite spin-Peierls apparait ensuite vers 60K. Notre etude theorique montre qu'un modele d'electrons en interaction de type "g-ologie" avec possibilite de processus umklapp permet de bien rendre compte des proprietes physiques de ce systeme. Finalement, la troisieme partie de cette these porte sur l'etude des premiers composes organiques quasi-unidimensionnels a avoir ete synthetises: les composes de la famille du TTF-TCNQ. Notre etude theorique des instabilites structurales que presentent ces composes n'est evidemment pas la premiere. L'originalite de cette derniere est qu'elle tient compte des fortes interactions entre les electrons, presentent dans ces composes. Pour tenir compte de telles interactions, nous avons choisi la formulation "liquide de Luttinger" qui nous permet de mieux traiter ce regimne dit de couplage fort.

Millimeter wave radar system on a rotating platform for combined search and track functionality with SAR imaging

NASA Astrophysics Data System (ADS)

Aulenbacher, Uwe; Rech, Klaus; Sedlmeier, Johannes; Pratisto, Hans; Wellig, Peter

2014-10-01

Ground based millimeter wave radar sensors offer the potential for a weather-independent automatic ground surveillance at day and night, e.g. for camp protection applications. The basic principle and the experimental verification of a radar system concept is described, which by means of an extreme off-axis positioning of the antenna(s) combines azimuthal mechanical beam steering with the formation of a circular-arc shaped synthetic aperture (SA). In automatic ground surveillance the function of search and detection of moving ground targets is performed by means of the conventional mechanical scan mode. The rotated antenna structure designed as a small array with two or more RX antenna elements with simultaneous receiver chains allows to instantaneous track multiple moving targets (monopulse principle). The simultaneously operated SAR mode yields areal images of the distribution of stationary scatterers. For ground surveillance application this SAR mode is best suited for identifying possible threats by means of change detection. The feasibility of this concept was tested by means of an experimental radar system comprising of a 94 GHz (W band) FM-CW module with 1 GHz bandwidth and two RX antennas with parallel receiver channels, placed off-axis at a rotating platform. SAR mode and search/track mode were tested during an outdoor measurement campaign. The scenery of two persons walking along a road and partially through forest served as test for the capability to track multiple moving targets. For SAR mode verification an image of the area composed of roads, grassland, woodland and several man-made objects was reconstructed from the measured data.

Optimal Power Allocation Strategy in a Joint Bistatic Radar and Communication System Based on Low Probability of Intercept

PubMed Central

Wang, Fei; Salous, Sana; Zhou, Jianjiang

2017-01-01

In this paper, we investigate a low probability of intercept (LPI)-based optimal power allocation strategy for a joint bistatic radar and communication system, which is composed of a dedicated transmitter, a radar receiver, and a communication receiver. The joint system is capable of fulfilling the requirements of both radar and communications simultaneously. First, assuming that the signal-to-noise ratio (SNR) corresponding to the target surveillance path is much weaker than that corresponding to the line of sight path at radar receiver, the analytically closed-form expression for the probability of false alarm is calculated, whereas the closed-form expression for the probability of detection is not analytically tractable and is approximated due to the fact that the received signals are not zero-mean Gaussian under target presence hypothesis. Then, an LPI-based optimal power allocation strategy is presented to minimize the total transmission power for information signal and radar waveform, which is constrained by a specified information rate for the communication receiver and the desired probabilities of detection and false alarm for the radar receiver. The well-known bisection search method is employed to solve the resulting constrained optimization problem. Finally, numerical simulations are provided to reveal the effects of several system parameters on the power allocation results. It is also demonstrated that the LPI performance of the joint bistatic radar and communication system can be markedly improved by utilizing the proposed scheme. PMID:29186850

Optimal Power Allocation Strategy in a Joint Bistatic Radar and Communication System Based on Low Probability of Intercept.

PubMed

Shi, Chenguang; Wang, Fei; Salous, Sana; Zhou, Jianjiang

2017-11-25

In this paper, we investigate a low probability of intercept (LPI)-based optimal power allocation strategy for a joint bistatic radar and communication system, which is composed of a dedicated transmitter, a radar receiver, and a communication receiver. The joint system is capable of fulfilling the requirements of both radar and communications simultaneously. First, assuming that the signal-to-noise ratio (SNR) corresponding to the target surveillance path is much weaker than that corresponding to the line of sight path at radar receiver, the analytically closed-form expression for the probability of false alarm is calculated, whereas the closed-form expression for the probability of detection is not analytically tractable and is approximated due to the fact that the received signals are not zero-mean Gaussian under target presence hypothesis. Then, an LPI-based optimal power allocation strategy is presented to minimize the total transmission power for information signal and radar waveform, which is constrained by a specified information rate for the communication receiver and the desired probabilities of detection and false alarm for the radar receiver. The well-known bisection search method is employed to solve the resulting constrained optimization problem. Finally, numerical simulations are provided to reveal the effects of several system parameters on the power allocation results. It is also demonstrated that the LPI performance of the joint bistatic radar and communication system can be markedly improved by utilizing the proposed scheme.

The cell wall: a carbohydrate armour for the fungal cell.

PubMed

Latgé, Jean-Paul

2007-10-01

The cell wall is composed of a polysaccharide-based three-dimensional network. Considered for a long time as an inert exoskeleton, the cell wall is now seen as a dynamic structure that is continuously changing as a result of the modification of culture conditions and environmental stresses. Although the cell wall composition varies among fungal species, chemogenomic comparative analysis have led to a better understanding of the genes and mechanisms involved in the construction of the common central core composed of branched beta1,3 glucan-chitin. Because of its essential biological role, unique biochemistry and structural organization and the absence in mammalian cells of most of its constitutive components, the cell wall is an attractive target for the development of new antifungal agents. Genomic as well as drug studies have shown that the death of the fungus can result from inhibition of cell wall polysaccharide synthases. To date, only beta1,3 glucan synthase inhibitors have been launched clinically and many more targets remain to be explored.

First-Passage Times in d -Dimensional Heterogeneous Media

NASA Astrophysics Data System (ADS)

Vaccario, G.; Antoine, C.; Talbot, J.

2015-12-01

Although there are many theoretical studies of the mean first-passage time (MFPT), most neglect the diffusive heterogeneity of real systems. We present exact analytical expressions for the MFPT and residence times of a pointlike particle diffusing in a spherically symmetric d -dimensional heterogeneous system composed of two concentric media with different diffusion coefficients with an absorbing inner boundary (target) and a reflecting outer boundary. By varying the convention, e.g., Itō, Stratonovich, or isothermal, chosen to interpret the overdamped Langevin equation with multiplicative noise describing the diffusion process, we find different predictions and counterintuitive results for the residence time in the outer region and hence for the MFPT, while the residence time in the inner region is independent of the convention. This convention dependence of residence times and the MFPT could provide insights about the heterogeneous diffusion in a cell or in a tumor, or for animal and insect searches inside their home range.

An Assembled Nanocomplex for Improving both Therapeutic Efficiency and Treatment Depth in Photodynamic Therapy.

PubMed

Cao, Hongqian; Wang, Lei; Yang, Yang; Li, Juan; Qi, Yanfei; Li, Yue; Li, Ying; Wang, Hao; Li, Junbai

2018-06-25

Photodynamic therapy (PDT) shows unique selectivity and irreversible destruction toward treated tissues or cells, but still has several problems in clinical practice. One is limited therapeutic efficiency, which is attributed to hypoxia in tumor sites. Another is the limited treatment depth because traditional photosensitizes are excited by short wavelength light (<700 nm). An assembled nano-complex system composed of oxygen donor, two-photon absorption (TPA) species, and photosensitizer (PS) was synthesized to address both problems. The photosensitizer is excited indirectly by two-photon laser through intraparticle FRET mechanism for improving treatment depth. The oxygen donor, hemoglobin, can supply extra oxygen into tumor location through targeting effect for enhanced PDT efficiency. The mechanism and PDT effect were verified through both in vitro and in vivo experiments. The simple system is promising to promote two-photon PDT for clinical applications. © 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Hyaluronic acid functional amphipathic and redox-responsive polymer particles for the co-delivery of doxorubicin and cyclopamine to eradicate breast cancer cells and cancer stem cells

NASA Astrophysics Data System (ADS)

Hu, Kelei; Zhou, Huige; Liu, Ying; Liu, Zhu; Liu, Jing; Tang, Jinglong; Li, Jiayang; Zhang, Jiakun; Sheng, Wang; Zhao, Yuliang; Wu, Yan; Chen, Chunying

2015-04-01

Cancer stem cells (CSCs) have the ability to transform into bulk cancer cells, to promote tumor growth and establish tumor metastasis. To effectively inhibit tumor growth and prevent metastasis, treatments with conventional chemotherapy drugs should be combined with CSC targeted drugs. In this study, we describe the synthesis and characterization of a new amphiphilic polymer, hyaluronic acid-cystamine-polylactic-co-glycolic acid (HA-SS-PLGA), composed of a hydrophobic PLGA head and a hydrophilic HA segment linked by a bioreducible disulfide bond. With a double emulsion method, a nano delivery system was constructed to deliver doxorubicin (DOX) and cyclopamine (CYC, a primary inhibitor of the hedgehog signaling pathway of CSCs) to both a CD44-overexpressing breast CSC subpopulation and bulk breast cancer cells and allow an on-demand release. The resulting drug-loaded NPs exhibited a redox-responsive drug release profile. Dual drug-loaded particles potently diminished the number and size of tumorspheres and HA showed a targeting effect towards breast CSCs. In vivo combination therapy further demonstrated a remarkable synergistic anti-tumor effect and prolonged survival compared to mono-therapy using the orthotopic mammary fat pad tumor growth model. The co-delivery of drug and the CSC specific inhibitor towards targeted cancer chemotherapeutics provides an insight into anticancer strategy with facile control and high efficacy.Cancer stem cells (CSCs) have the ability to transform into bulk cancer cells, to promote tumor growth and establish tumor metastasis. To effectively inhibit tumor growth and prevent metastasis, treatments with conventional chemotherapy drugs should be combined with CSC targeted drugs. In this study, we describe the synthesis and characterization of a new amphiphilic polymer, hyaluronic acid-cystamine-polylactic-co-glycolic acid (HA-SS-PLGA), composed of a hydrophobic PLGA head and a hydrophilic HA segment linked by a bioreducible disulfide bond. With a double emulsion method, a nano delivery system was constructed to deliver doxorubicin (DOX) and cyclopamine (CYC, a primary inhibitor of the hedgehog signaling pathway of CSCs) to both a CD44-overexpressing breast CSC subpopulation and bulk breast cancer cells and allow an on-demand release. The resulting drug-loaded NPs exhibited a redox-responsive drug release profile. Dual drug-loaded particles potently diminished the number and size of tumorspheres and HA showed a targeting effect towards breast CSCs. In vivo combination therapy further demonstrated a remarkable synergistic anti-tumor effect and prolonged survival compared to mono-therapy using the orthotopic mammary fat pad tumor growth model. The co-delivery of drug and the CSC specific inhibitor towards targeted cancer chemotherapeutics provides an insight into anticancer strategy with facile control and high efficacy. Electronic supplementary information (ESI) available. See DOI: 10.1039/c5nr01084e

Novel maximum likelihood approach for passive detection and localisation of multiple emitters

NASA Astrophysics Data System (ADS)

Hernandez, Marcel

2017-12-01

In this paper, a novel target acquisition and localisation algorithm (TALA) is introduced that offers a capability for detecting and localising multiple targets using the intermittent "signals-of-opportunity" (e.g. acoustic impulses or radio frequency transmissions) they generate. The TALA is a batch estimator that addresses the complex multi-sensor/multi-target data association problem in order to estimate the locations of an unknown number of targets. The TALA is unique in that it does not require measurements to be of a specific type, and can be implemented for systems composed of either homogeneous or heterogeneous sensors. The performance of the TALA is demonstrated in simulated scenarios with a network of 20 sensors and up to 10 targets. The sensors generate angle-of-arrival (AOA), time-of-arrival (TOA), or hybrid AOA/TOA measurements. It is shown that the TALA is able to successfully detect 83-99% of the targets, with a negligible number of false targets declared. Furthermore, the localisation errors of the TALA are typically within 10% of the errors generated by a "genie" algorithm that is given the correct measurement-to-target associations. The TALA also performs well in comparison with an optimistic Cramér-Rao lower bound, with typical differences in performance of 10-20%, and differences in performance of 40-50% in the most difficult scenarios considered. The computational expense of the TALA is also controllable, which allows the TALA to maintain computational feasibility even in the most challenging scenarios considered. This allows the approach to be implemented in time-critical scenarios, such as in the localisation of artillery firing events. It is concluded that the TALA provides a powerful situational awareness aid for passive surveillance operations.

Design and real-time control of a robotic system for fracture manipulation.

PubMed

Dagnino, G; Georgilas, I; Tarassoli, P; Atkins, R; Dogramadzi, S

2015-08-01

This paper presents the design, development and control of a new robotic system for fracture manipulation. The objective is to improve the precision, ergonomics and safety of the traditional surgical procedure to treat joint fractures. The achievements toward this direction are here reported and include the design, the real-time control architecture and the evaluation of a new robotic manipulator system. The robotic manipulator is a 6-DOF parallel robot with the struts developed as linear actuators. The control architecture is also described here. The high-level controller implements a host-target structure composed by a host computer (PC), a real-time controller, and an FPGA. A graphical user interface was designed allowing the surgeon to comfortably automate and monitor the robotic system. The real-time controller guarantees the determinism of the control algorithms adding an extra level of safety for the robotic automation. The system's positioning accuracy and repeatability have been demonstrated showing a maximum positioning RMSE of 1.18 ± 1.14mm (translations) and 1.85 ± 1.54° (rotations).

Erythrocyte membrane based cationic polymer-mcDNA complexes as an efficient gene delivery system.

PubMed

Huang, Ping; Zhao, Jing; Wei, Chiju; Hou, Xiaohu; Chen, Pingzhang; Tan, Yan; He, Cheng-Yi; Wang, Zhiyong; Chen, Zhi-Ying

2016-12-20

Gene therapy has great promise for the treatment of obtained and inherited serious diseases. However, the lack of safe and efficient gene delivery systems remains a barrier for their clinical application. Here, we reported a potential gene delivery vehicle composed of the erythrocyte membrane and cationic polymers, for example the XtremeGENE from Roche and the ε-caprolactone modified polyethylenimine. In addition to high efficiency, this system showed negligible cytotoxicity compared to the two cationic polymers alone in various cell lines, including human embryonic kidney cells (293T), human liver cancer cells (Huh7 and HepG2), murine dendritic cells (DC2.4) and human umbilical cord mesenchymal stem cells (Hu-MSCs). Moreover, the results of confocal laser scanning microscopy and flow cytometry suggested that the cell uptake of this gene vector was improved and might be introduced by the fusion interaction between the erythrocyte membrane and targeted cells.Thus, all the results revealed that the erythrocyte membrane based gene delivery system might be able to serve as an excellent gene delivery system.

Adapting forest health assessments to changing perspectives on threats--a case example from Sweden.

PubMed

Wulff, Sören; Lindelöw, Åke; Lundin, Lars; Hansson, Per; Axelsson, Anna-Lena; Barklund, Pia; Wijk, Sture; Ståhl, Göran

2012-04-01

A revised Swedish forest health assessment system is presented. The assessment system is composed of several interacting components which target information needs for strategic and operational decision making and accommodate a continuously expanding knowledge base. The main motivation for separating information for strategic and operational decision making is that major damage outbreaks are often scattered throughout the landscape. Generally, large-scale inventories (such as national forest inventories) cannot provide adequate information for mitigation measures. In addition to broad monitoring programs that provide time-series information on known damaging agents and their effects, there is also a need for local and regional inventories adapted to specific damage events. While information for decision making is the major focus of the health assessment system, the system also contributes to expanding the knowledge base of forest conditions. For example, the integrated monitoring programs provide a better understanding of ecological processes linked to forest health. The new health assessment system should be able to respond to the need for quick and reliable information and thus will be an important part of the future monitoring of Swedish forests.

DUSTER: demonstration of an integrated LWIR-VNIR-SAR imaging system

NASA Astrophysics Data System (ADS)

Wilson, Michael L.; Linne von Berg, Dale; Kruer, Melvin; Holt, Niel; Anderson, Scott A.; Long, David G.; Margulis, Yuly

2008-04-01

The Naval Research Laboratory (NRL) and Space Dynamics Laboratory (SDL) are executing a joint effort, DUSTER (Deployable Unmanned System for Targeting, Exploitation, and Reconnaissance), to develop and test a new tactical sensor system specifically designed for Tier II UAVs. The system is composed of two coupled near-real-time sensors: EyePod (VNIR/LWIR ball gimbal) and NuSAR (L-band synthetic aperture radar). EyePod consists of a jitter-stabilized LWIR sensor coupled with a dual focal-length optical system and a bore-sighted high-resolution VNIR sensor. The dual focal-length design coupled with precision pointing an step-stare capabilities enable EyePod to conduct wide-area survey and high resolution inspection missions from a single flight pass. NuSAR is being developed with partners Brigham Young University (BYU) and Artemis, Inc and consists of a wideband L-band SAR capable of large area survey and embedded real-time image formation. Both sensors employ standard Ethernet interfaces and provide geo-registered NITFS output imagery. In the fall of 2007, field tests were conducted with both sensors, results of which will be presented.

Dynamics of the Triple-Star System Alpha Centauri and its Impact on Habitable Planets

NASA Astrophysics Data System (ADS)

Jayla Jones, Ayanna; Fabrycky, Daniel

2018-01-01

The Alpha Centauri system, our solar system's closest neighbor, has become a target in the search for habitable planets. The system is composed of three stars: Alpha Centauri A and Alpha Centauri B, stars forming an inner binary, and Proxima Centauri, an outer star that orbits around the inner binary. We computed 3-body models to follow the dynamics for the main-sequence lifetimes of the stars that are based on 100 realizations of the observed orbits. In the majority of cases, Proxima only modestly torques the A-B binary orbit, and so previous studies of planet formation and dynamics, which find the habitable zones to be stable, are somewhat justified in ignoring this effect. On the other hand, in ~16% of the observationally allowed orbits, fluctuations in the orbital eccentricity of the A-B orbit destabilize the middle of the habitable zone of both stars. This result calls for further theoretical work to quantify the effect of galactic tides, passing stars, and massive planets in the triple-system dynamics.

Combined measurement system for double shield tunnel boring machine guidance based on optical and visual methods.

PubMed

Lin, Jiarui; Gao, Kai; Gao, Yang; Wang, Zheng

2017-10-01

In order to detect the position of the cutting shield at the head of a double shield tunnel boring machine (TBM) during the excavation, this paper develops a combined measurement system which is mainly composed of several optical feature points, a monocular vision sensor, a laser target sensor, and a total station. The different elements of the combined system are mounted on the TBM in suitable sequence, and the position of the cutting shield in the reference total station frame is determined by coordinate transformations. Subsequently, the structure of the feature points and matching technique for them are expounded, the position measurement method based on monocular vision is presented, and the calibration methods for the unknown relationships among different parts of the system are proposed. Finally, a set of experimental platforms to simulate the double shield TBM is established, and accuracy verification experiments are conducted. Experimental results show that the mean deviation of the system is 6.8 mm, which satisfies the requirements of double shield TBM guidance.

The mammalian respiratory system and critical windows of exposure for children's health.

PubMed Central

Pinkerton, K E; Joad, J P

2000-01-01

The respiratory system is a complex organ system composed of multiple cell types involved in a variety of functions. The development of the respiratory system occurs from embryogenesis to adult life, passing through several distinct stages of maturation and growth. We review embryonic, fetal, and postnatal phases of lung development. We also discuss branching morphogenesis and cellular differentiation of the respiratory system, as well as the postnatal development of xenobiotic metabolizing systems within the lungs. Exposure of the respiratory system to a wide range of chemicals and environmental toxicants during perinatal life has the potential to significantly affect the maturation, growth, and function of this organ system. Although the potential targets for exposure to toxic factors are currently not known, they are likely to affect critical molecular signals expressed during distinct stages of lung development. The effects of exposure to environmental tobacco smoke during critical windows of perinatal growth are provided as an example leading to altered cellular and physiological function of the lungs. An understanding of critical windows of exposure of the respiratory system on children's health requires consideration that lung development is a multistep process and cannot be based on studies in adults. Images Figure 1 Figure 4 PMID:10852845

Implosion of multilayered cylindrical targets driven by intense heavy ion beams.

PubMed

Piriz, A R; Portugues, R F; Tahir, N A; Hoffmann, D H H

2002-11-01

An analytical model for the implosion of a multilayered cylindrical target driven by an intense heavy ion beam has been developed. The target is composed of a cylinder of frozen hydrogen or deuterium, which is enclosed in a thick shell of solid lead. This target has been designed for future high-energy-density matter experiments to be carried out at the Gesellschaft für Schwerionenforschung, Darmstadt. The model describes the implosion dynamics including the motion of the incident shock and the first reflected shock and allows for calculation of the physical conditions of the hydrogen at stagnation. The model predicts that the conditions of the compressed hydrogen are not sensitive to significant variations in target and beam parameters. These predictions are confirmed by one-dimensional numerical simulations and thus allow for a robust target design.

Developing a Collection of Composable Data Translation Software Units to Improve Efficiency and Reproducibility in Ecohydrologic Modeling Workflows

NASA Astrophysics Data System (ADS)

Olschanowsky, C.; Flores, A. N.; FitzGerald, K.; Masarik, M. T.; Rudisill, W. J.; Aguayo, M.

2017-12-01

Dynamic models of the spatiotemporal evolution of water, energy, and nutrient cycling are important tools to assess impacts of climate and other environmental changes on ecohydrologic systems. These models require spatiotemporally varying environmental forcings like precipitation, temperature, humidity, windspeed, and solar radiation. These input data originate from a variety of sources, including global and regional weather and climate models, global and regional reanalysis products, and geostatistically interpolated surface observations. Data translation measures, often subsetting in space and/or time and transforming and converting variable units, represent a seemingly mundane, but critical step in the application workflows. Translation steps can introduce errors, misrepresentations of data, slow execution time, and interrupt data provenance. We leverage a workflow that subsets a large regional dataset derived from the Weather Research and Forecasting (WRF) model and prepares inputs to the Parflow integrated hydrologic model to demonstrate the impact translation tool software quality on scientific workflow results and performance. We propose that such workflows will benefit from a community approved collection of data transformation components. The components should be self-contained composable units of code. This design pattern enables automated parallelization and software verification, improving performance and reliability. Ensuring that individual translation components are self-contained and target minute tasks increases reliability. The small code size of each component enables effective unit and regression testing. The components can be automatically composed for efficient execution. An efficient data translation framework should be written to minimize data movement. Composing components within a single streaming process reduces data movement. Each component will typically have a low arithmetic intensity, meaning that it requires about the same number of bytes to be read as the number of computations it performs. When several components' executions are coordinated the overall arithmetic intensity increases, leading to increased efficiency.

Pretargeting immunotherapy: a novel treatment approach for systemic amyloidosis.

PubMed

Wall, Jonathan S; Foster, James S; Martin, Emily B; Kennel, Stephen J

2017-09-01

The amyloidoses are a complex group of disorders characterized by the deposition of proteinaceous amyloid fibrils in vital organs. The deposits are nonimmunogenic and may be composed of one of more than 35 proteins. We have developed a two-stage immunotherapeutic approach using peptides that recognize most, if not all, amyloid deposits to facilitate amyloid clearance. In the first embodiment, we have developed a bifunctional peptope to enhance and expand the utility of currently available antibodies. In the second, we have generated peptide-reactive antibodies that can be targeted to the amyloid deposits by peptides thereby providing alternative reagents for immunotherapy of amyloidosis. These technologies provide tools for treating the many forms of amyloid disease, restoring organ function and enhancing patient survival.

Depletion of Plasmodium berghei plasmoredoxin reveals a non-essential role for life cycle progression of the malaria parasite.

PubMed

Buchholz, Kathrin; Rahlfs, Stefan; Schirmer, R Heiner; Becker, Katja; Matuschewski, Kai

2008-06-25

Proliferation of the pathogenic Plasmodium asexual blood stages in host erythrocytes requires an exquisite capacity to protect the malaria parasite against oxidative stress. This function is achieved by a complex antioxidant defence system composed of redox-active proteins and low MW antioxidants. Here, we disrupted the P. berghei plasmoredoxin gene that encodes a parasite-specific 22 kDa member of the thioredoxin superfamily. The successful generation of plasmoredoxin knockout mutants in the rodent model malaria parasite and phenotypic analysis during life cycle progression revealed a non-vital role in vivo. Our findings suggest that plasmoredoxin fulfils a specialized and dispensable role for Plasmodium and highlights the need for target validation to inform drug development strategies.

Recreating the synthesis of starch granules in yeast

PubMed Central

Pfister, Barbara; Sánchez-Ferrer, Antoni; Diaz, Ana; Lu, Kuanjen; Otto, Caroline; Holler, Mirko; Shaik, Farooque Razvi; Meier, Florence; Mezzenga, Raffaele; Zeeman, Samuel C

2016-01-01

Starch, as the major nutritional component of our staple crops and a feedstock for industry, is a vital plant product. It is composed of glucose polymers that form massive semi-crystalline granules. Its precise structure and composition determine its functionality and thus applications; however, there is no versatile model system allowing the relationships between the biosynthetic apparatus, glucan structure and properties to be explored. Here, we expressed the core Arabidopsis starch-biosynthesis pathway in Saccharomyces cerevisiae purged of its endogenous glycogen-metabolic enzymes. Systematic variation of the set of biosynthetic enzymes illustrated how each affects glucan structure and solubility. Expression of the complete set resulted in dense, insoluble granules with a starch-like semi-crystalline organization, demonstrating that this system indeed simulates starch biosynthesis. Thus, the yeast system has the potential to accelerate starch research and help create a holistic understanding of starch granule biosynthesis, providing a basis for the targeted biotechnological improvement of crops. DOI: http://dx.doi.org/10.7554/eLife.15552.001 PMID:27871361

Daily Management System of the Henry Ford Production System: QTIPS to Focus Continuous Improvements at the Level of the Work.

PubMed

Zarbo, Richard J; Varney, Ruan C; Copeland, Jacqueline R; D'Angelo, Rita; Sharma, Gaurav

2015-07-01

To support our Lean culture of continuous improvement, we implemented a daily management system designed so critical metrics of operational success were the focus of local teams to drive improvements. We innovated a standardized visual daily management board composed of metric categories of Quality, Time, Inventory, Productivity, and Safety (QTIPS); frequency trending; root cause analysis; corrective/preventive actions; and resulting process improvements. In 1 year (June 2013 to July 2014), eight laboratory sections at Henry Ford Hospital employed 64 unique daily metrics. Most assessed long-term (>6 months), monitored process stability, while short-term metrics (1-6 months) were retired after successful targeted problem resolution. Daily monitoring resulted in 42 process improvements. Daily management is the key business accountability subsystem that enabled our culture of continuous improvement to function more efficiently at the managerial level in a visible manner by reviewing and acting based on data and root cause analysis. Copyright© by the American Society for Clinical Pathology.

Combinatorial Screening for Transgenic Yeasts with High Cellulase Activities in Combination with a Tunable Expression System

PubMed Central

Ito, Yoichiro; Yamanishi, Mamoru; Ikeuchi, Akinori; Imamura, Chie; Matsuyama, Takashi

2015-01-01

Combinatorial screening used together with a broad library of gene expression cassettes is expected to produce a powerful tool for the optimization of the simultaneous expression of multiple enzymes. Recently, we proposed a highly tunable protein expression system that utilized multiple genome-integrated target genes to fine-tune enzyme expression in yeast cells. This tunable system included a library of expression cassettes each composed of three gene-expression control elements that in different combinations produced a wide range of protein expression levels. In this study, four gene expression cassettes with graded protein expression levels were applied to the expression of three cellulases: cellobiohydrolase 1, cellobiohydrolase 2, and endoglucanase 2. After combinatorial screening for transgenic yeasts simultaneously secreting these three cellulases, we obtained strains with higher cellulase expressions than a strain harboring three cellulase-expression constructs within one high-performance gene expression cassette. These results show that our method will be of broad use throughout the field of metabolic engineering. PMID:26692026

Inkjet Printing Based Droplet Generation for Integrated Online Digital Polymerase Chain Reaction.

PubMed

Zhang, Weifei; Li, Nan; Koga, Daisuke; Zhang, Yong; Zeng, Hulie; Nakajima, Hizuru; Lin, Jin-Ming; Uchiyama, Katsumi

2018-04-17

We report on the development of a novel and flexible online digital polymerase chain reaction (dPCR) system. The system was composed of three parts: an inkjet for generating the droplets, a coiled fused-silica capillary for thermal cycling, and a laser-induced fluorescence detector (LIFD) for positive droplet counting. Upon inkjet printing, monodisperse droplets were continuously generated in the oil phase and then introduced into the capillary in the form of a stable dispersion. The droplets containing one or zero molecules of target DNA passed through the helical capillary that was attached to a cylindrical thermal cycler for PCR amplification, resulting in the generation of fluorescence for the DNA-positive droplet. After 36 PCR cycles, the fluorescence signal intensity was detected by laser-induced fluorescence located at the downstream of the capillary, followed by a positive/negative counting. The present system was successfully applied to the absolute quantification of the HPV sequence in Caski cells with dynamic ranges spanning 4 orders of magnitude.

A Contingency Management Intervention for Adolescent Marijuana Abuse and Conduct Problems.

ERIC Educational Resources Information Center

Kamon, Jody; Budney, Alan; Stanger, Catherine

2005-01-01

Objective: To describe an innovative treatment for adolescent marijuana abuse and provide initial information about its feasibility, acceptability, and potential efficacy. Method: Provided an intervention composed of (1) a clinic-administered, abstinence-based incentive program; (2) parent-directed contingency management targeting substance use…

The beneficial influence of inattention on visual interference in schizophrenia.

PubMed

Brodeur, Mathieu B; Kiang, Michael; Christensen, Bruce K

2016-09-01

Schizophrenia is associated with poor spatial attention. However, although this deficit undermines the perception of target information, it may be helpful for ignoring irrelevant inputs. The present study examined whether event-related brain potential (ERP) indices of visual spatial attention predicted the magnitude of the brain response to interference in schizophrenia. ERPs were recorded in 16 schizophrenia patients and 20 healthy control participants who had to indicate whether the target E was global or local in compound letter stimuli. The nontarget could be either highly similar to the target (i.e., a global E composed of local Ss and vice versa) and thus produce more interference, or it could be dissimilar (i.e., a global E composed of local Hs and vice versa) and generate less interference. Both groups' responses were slowed by interference. Voltage amplitudes of the P1, and of ERP interference effects from 300-500 ms after stimulus onset, were significantly smaller in schizophrenia patients than in healthy participants when the target was global. In patients, larger P1 amplitudes were correlated with larger interference effects and with more severe symptoms of attentional deficits and conceptual disorganization. Schizophrenia participants thus exhibited abnormal ERPs to interference despite normal behavioral performance. Schizophrenia patients likely pay less attention to stimuli in general; however, the impact of this impairment on target detection is compensated by relatively greater inattention to irrelevant components of the stimuli, and this explains why they are not more influenced by interference than healthy participants at the behavioral level. (PsycINFO Database Record (c) 2016 APA, all rights reserved).

Low-energy ion beamline scattering apparatus for surface science investigations

NASA Astrophysics Data System (ADS)

Gordon, M. J.; Giapis, K. P.

2005-08-01

We report on the design, construction, and performance of a high current (monolayers/s), mass-filtered ion beamline system for surface scattering studies using inert and reactive species at collision energies below 1500 eV. The system combines a high-density inductively coupled plasma ion source, high-voltage floating beam transport line with magnet mass-filter and neutral stripping, decelerator, and broad based detection capabilities (ions and neutrals in both mass and energy) for products leaving the target surface. The entire system was designed from the ground up to be a robust platform to study ion-surface interactions from a more global perspective, i.e., high fluxes (>100μA/cm2) of a single ion species at low, tunable energy (50-1400±5eV full width half maximum) can be delivered to a grounded target under ultrahigh vacuum conditions. The high current at low energy problem is solved using an accel-decel transport scheme where ions are created at the desired collision energy in the plasma source, extracted and accelerated to high transport energy (20 keV to fight space charge repulsion), and then decelerated back down to their original creation potential right before impacting the grounded target. Scattered species and those originating from the surface are directly analyzed in energy and mass using a triply pumped, hybrid detector composed of an electron impact ionizer, hemispherical electrostatic sector, and rf/dc quadrupole in series. With such a system, the collision kinematics, charge exchange, and chemistry occurring on the target surface can be separated by fully analyzing the scattered product flux. Key design aspects of the plasma source, beamline, and detection system are emphasized here to highlight how to work around physical limitations associated with high beam flux at low energy, pumping requirements, beam focusing, and scattered product analysis. Operational details of the beamline are discussed from the perspective of available beam current, mass resolution, projectile energy spread, and energy tunability. As well, performance of the overall system is demonstrated through three proof-of-concept examples: (1) elastic binary collisions at low energy, (2) core-level charge exchange reactions involving Ne+20 with Mg /Al/Si/P targets, and (3) reactive scattering of CF2+/CF3+ off Si. These studies clearly demonstrate why low, tunable incident energy, as well as mass and energy filtering of products leaving the target surface is advantageous and often essential for studies of inelastic energy losses, hard-collision charge exchange, and chemical reactions that occur during ion-surface scattering.

Highly abundant defense proteins in human sweat as revealed by targeted proteomics and label-free quantification mass spectrometry.

PubMed

Csősz, É; Emri, G; Kalló, G; Tsaprailis, G; Tőzsér, J

2015-10-01

The healthy human skin with its effective antimicrobial defense system forms an efficient barrier against invading pathogens. There is evidence suggesting that the composition of this chemical barrier varies between diseases, making the easily collected sweat an ideal candidate for biomarker discoveries. Our aim was to provide information about the normal composition of the sweat, and to study the chemical barrier found at the surface of skin. Sweat samples from healthy individuals were collected during sauna bathing, and the global protein panel was analysed by label-free mass spectrometry. SRM-based targeted proteomic methods were designed and stable isotope labelled reference peptides were used for method validation. Ninety-five sweat proteins were identified, 20 of them were novel proteins. It was shown that dermcidin is the most abundant sweat protein, and along with apolipoprotein D, clusterin, prolactin-inducible protein and serum albumin, they make up 91% of secreted sweat proteins. The roles of these highly abundant proteins were reviewed; all of which have protective functions, highlighting the importance of sweat glands in composing the first line of innate immune defense system, and maintaining the epidermal barrier integrity. Our findings with regard to the proteins forming the chemical barrier of the skin as determined by label-free quantification and targeted proteomics methods are in accordance with previous studies, and can be further used as a starting point for non-invasive sweat biomarker research. © 2015 European Academy of Dermatology and Venereology.

Using the PORS Problems to Examine Evolutionary Optimization of Multiscale Systems

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

Reinhart, Zachary; Molian, Vaelan; Bryden, Kenneth

2013-01-01

Nearly all systems of practical interest are composed of parts assembled across multiple scales. For example, an agrodynamic system is composed of flora and fauna on one scale; soil types, slope, and water runoff on another scale; and management practice and yield on another scale. Or consider an advanced coal-fired power plant: combustion and pollutant formation occurs on one scale, the plant components on another scale, and the overall performance of the power system is measured on another. In spite of this, there are few practical tools for the optimization of multiscale systems. This paper examines multiscale optimization of systemsmore » composed of discrete elements using the plus-one-recall-store (PORS) problem as a test case or study problem for multiscale systems. From this study, it is found that by recognizing the constraints and patterns present in discrete multiscale systems, the solution time can be significantly reduced and much more complex problems can be optimized.« less

Robustness of network of networks under targeted attack.

PubMed

Dong, Gaogao; Gao, Jianxi; Du, Ruijin; Tian, Lixin; Stanley, H Eugene; Havlin, Shlomo

2013-05-01

The robustness of a network of networks (NON) under random attack has been studied recently [Gao et al., Phys. Rev. Lett. 107, 195701 (2011)]. Understanding how robust a NON is to targeted attacks is a major challenge when designing resilient infrastructures. We address here the question how the robustness of a NON is affected by targeted attack on high- or low-degree nodes. We introduce a targeted attack probability function that is dependent upon node degree and study the robustness of two types of NON under targeted attack: (i) a tree of n fully interdependent Erdős-Rényi or scale-free networks and (ii) a starlike network of n partially interdependent Erdős-Rényi networks. For any tree of n fully interdependent Erdős-Rényi networks and scale-free networks under targeted attack, we find that the network becomes significantly more vulnerable when nodes of higher degree have higher probability to fail. When the probability that a node will fail is proportional to its degree, for a NON composed of Erdős-Rényi networks we find analytical solutions for the mutual giant component P(∞) as a function of p, where 1-p is the initial fraction of failed nodes in each network. We also find analytical solutions for the critical fraction p(c), which causes the fragmentation of the n interdependent networks, and for the minimum average degree k[over ¯](min) below which the NON will collapse even if only a single node fails. For a starlike NON of n partially interdependent Erdős-Rényi networks under targeted attack, we find the critical coupling strength q(c) for different n. When q>q(c), the attacked system undergoes an abrupt first order type transition. When q≤q(c), the system displays a smooth second order percolation transition. We also evaluate how the central network becomes more vulnerable as the number of networks with the same coupling strength q increases. The limit of q=0 represents no dependency, and the results are consistent with the classical percolation theory of a single network under targeted attack.

The merged basins of signal transduction pathways in spatiotemporal cell biology.

PubMed

Hou, Yingchun; Hou, Yang; He, Siyu; Ma, Caixia; Sun, Mengyao; He, Huimin; Gao, Ning

2014-03-01

Numerous evidences have indicated that a signal system is composed by signal pathways, each pathway is composed by sub-pathways, and the sub-pathway is composed by the original signal terminals initiated with a protein/gene. We infer the terminal signals merged signal transduction system as "signal basin". In this article, we discussed the composition and regulation of signal basins, and the relationship between the signal basin control and triple W of spatiotemporal cell biology. Finally, we evaluated the importance of the systemic regulation to gene expression by signal basins under triple W. We hope our discussion will be the beginning to cause the attention for this area from the scientists of life science. © 2013 Wiley Periodicals, Inc.

A miniature mimic of host defense peptides with systemic antibacterial efficacy

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

Sarig, Hadar; Livne, Liran; Held-Kuznetsov, Victoria

Oligomers of acylated lysines (OAKs) are synthetic mimics of host defense peptides (HDPs) with promising antimicrobial properties. Here we challenged the OAK concept for its ability to generate both systemically efficient and economically viable lead compounds for fighting multidrug-resistant bacteria. We describe the design and characterization of a miniature OAK composed of only 3 lysyls and 2 acyls (designated C{sub 12({omega}7)}K-{beta}{sub 12}) that preferentially targets gram-positive species by a bacteriostatic mode of action. To gain insight into the mechanism of action, we examined the interaction of OAK with various potential targets, including phospholipid bilayers, using surface plasmon resonance, and Langmuirmore » monolayers, using insertion assays, epifluorescence microscopy, and grazing incidence X-ray diffraction, in a complementary manner. Collectively, the data support the notion that C{sub 12({omega}7)}K-{beta}{sub 12} damages the plasma-membrane architecture similarly to HDPs, that is, following a near-classic 2-step interaction including high-affinity electrostatic adhesion and a subsequent shallow insertion that was limited to the phospholipid head group region. Notably, preliminary acute toxicity and efficacy studies performed with mouse models of infection have consolidated the potential of OAK for treating bacterial infections, including systemic treatments of methicillin-resistant Staphylococcus aureus. Such simple yet robust chemicals might be useful for various antibacterial applications while circumventing potential adverse effects associated with cytolytic compounds.« less

A wave-mechanical model of incoherent quasielastic scattering in complex systems.

PubMed

Frauenfelder, Hans; Fenimore, Paul W; Young, Robert D

2014-09-02

Quasielastic incoherent neutron scattering (QENS) is an important tool for the exploration of the dynamics of complex systems such as biomolecules, liquids, and glasses. The dynamics is reflected in the energy spectra of the scattered neutrons. Conventionally these spectra are decomposed into a narrow elastic line and a broad quasielastic band. The band is interpreted as being caused by Doppler broadening due to spatial motion of the target molecules. We propose a quantum-mechanical model in which there is no separate elastic line. The quasielastic band is composed of sharp lines with twice the natural line width, shifted from the center by a random walk of the protein in the free-energy landscape of the target molecule. The walk is driven by vibrations and by external fluctuations. We first explore the model with the Mössbauer effect. In the subsequent application to QENS we treat the incoming neutron as a de Broglie wave packet. While the wave packet passes the protons in the protein and the hydration shell it exchanges energy with the protein during the passage time of about 100 ns. The energy exchange broadens the ensemble spectrum. Because the exchange involves the free-energy landscape of the protein, the QENS not only provides insight into the protein dynamics, but it may also illuminate the free-energy landscape of the protein-solvent system.

Ciliary targeting of olfactory CNG channels requires the CNGB1b subunit and the kinesin-2 motor protein, KIF17.

PubMed

Jenkins, Paul M; Hurd, Toby W; Zhang, Lian; McEwen, Dyke P; Brown, R Lane; Margolis, Ben; Verhey, Kristen J; Martens, Jeffrey R

2006-06-20

Nonmotile cilia on olfactory sensory neurons (OSNs) compartmentalize signaling molecules, including odorant receptors and cyclic nucleotide-gated (CNG) channels, allowing for efficient, spatially confined responses to sensory stimuli . Little is known about the mechanisms of the ciliary targeting of olfactory CNG channels, composed of three subunits: CNGA2, CNGA4, and CNGB1b . Recent reports suggest that subunit composition of the retinal CNG channel influences localization, leading to disease . However, the mechanistic role of subunits in properly targeting native olfactory CNG channels remains unclear. Here, we show that heteromeric assembly with CNGB1b, containing a critical carboxy-terminal motif (RVxP), is required for ciliary trafficking of olfactory CNG channels. Movement of proteins within the cilia is governed by intraflagellar transport (IFT), a process that facilitates bidirectional movement of cargo along microtubules. Work in C. elegans has established that heterotrimeric and homodimeric kinesin-2 family members play a critical role in anterograde transport . In mammalian systems, the heterotrimeric KIF3a/KIF3b/KAP-3 complex plays a clear role in IFT; however, no role has been established for KIF17, the mammalian homolog of OSM-3 . Here, we demonstrate that KIF17 is required for olfactory CNG channel targeting, providing novel insights into mechanisms of mammalian ciliary transport.

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

PubMed

Raghavan, Ramanujan T; Joshua, Mati

2017-10-01

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

Candidate Socioemotional Remediation Program for Individuals with Intellectual Disability

ERIC Educational Resources Information Center

Glaser, Bronwyn; Lothe, Amelie; Chabloz, Melanie; Dukes, Daniel; Pasca, Catherine; Redoute, Jerome; Eliez, Stephan

2012-01-01

The authors developed a computerized program, Vis-a-Vis (VAV), to improve socioemotional functioning and working memory in children with developmental disabilities. The authors subsequently tested whether participants showed signs of improving the targeted skills. VAV is composed of three modules: Focus on the Eyes, Emotion Recognition and…

Targets of Opportunity: Strategies for Managing a Staff Development Consortium.

ERIC Educational Resources Information Center

Parsons, Michael H.

The Appalachian Staff Development Consortium, comprised of three community colleges and the state college located in Appalachian Maryland, attempts to integrate staff development activities into the operational framework of the sponsoring agencies. The consortium, which is managed by a steering committee composed of one teaching faculty member and…

Overexpression of SbMyb60 impacts phenylpropanoid biosynthesis and alters secondary cell wall composition in sorghum bicolor

USDA-ARS?s Scientific Manuscript database

The phenylpropanoid biosynthesis pathway that generates lignin subunits represents a significant target to alter the abundance and composition of lignin. The major regulators of phenylpropanoid metabolism are myb transcription factors, which have been shown to modulate secondary cell wall compositi...

Comprehension Tools for Teachers: Reading for Understanding from Prekindergarten through Fourth Grade

ERIC Educational Resources Information Center

Connor, Carol McDonald; Phillips, Beth M.; Kaschak, Michael; Apel, Kenn; Kim, Young-Suk; Al Otaiba, Stephanie; Crowe, Elizabeth C.; Thomas-Tate, Shurita; Johnson, Lakeisha Cooper; Lonigan, Christopher J.

2014-01-01

This paper describes the theoretical framework, as well as the development and testing of the intervention, "Comprehension Tools for Teachers" (CTT), which is composed of eight component interventions targeting malleable language and reading comprehension skills that emerging research indicates contribute to proficient reading for…

Active magnetic compensation composed of shielding panels.

PubMed

Kato, K; Yamazaki, K; Sato, T; Haga, A; Okitsu, T; Muramatsu, K; Ueda, T; Kobayashi, K; Yoshizawa, M

2004-11-30

Magnetically shielded rooms (MSRs) with materials of high permeability and active shield systems have been used to shield magnetic noise for biomagnetic measurements up to now. However, these techniques have various disadvantages. Therefore, we have developed a new shielding system composed of shielding panels using an active compensation technique. In this study, we evaluated the shielding performance of several unit panels attached together. Numerical and experimental approaches indicated that the shielding factor of a cubic model composed of 24 panels was 17 for uniform fields, and 7 for disturbances due to car movement. Furthermore, the compensation space is larger than that of an ordinary active system using large coils rather than panels. Moreover, the new active compensation system has the important advantage that panels of any shape can be assembled for occasional use because the unit panels are small and light.

A new chemotherapy agent-free theranostic system composed of graphene oxide nano-complex and aptamers for treatment of cancer cells.

PubMed

Bahreyni, Amirhossein; Yazdian-Robati, Rezvan; Hashemitabar, Shirin; Ramezani, Mohammad; Ramezani, Pouria; Abnous, Khalil; Taghdisi, Seyed Mohammad

2017-06-30

The common cancer treatment strategies like chemotherapy and radiotherapy are nonspecific and can trigger severe side effects by damaging normal cells. So, targeted cancer therapies, such as apoptosis induction, have attracted great attention in recent years. In this project, two nano-complexes, MUC1 aptamer-NAS-24 aptamer-Graphene oxide (GO) and MUC1 aptamer-Cytochrome C aptamer-GO, were designed to induce cell programmed death in MDA-MB-231 and MCF-7 cells (breast cancer cell lines) and to verify the level of apoptosis in both cell lines. MUC1 aptamer was a molecular recognition probe that led the internalization of two nano-complexes into MDA-MB-231 and MCF-7 cells (MUC1 positive cells) but not into HepG2 cell (liver cancer cell line, MUC1 negative cells). The apoptosis induction relied on binding of NAS-24 aptamer to its target, vimentin, in MDA-MB-231 and MCF-7 (target cells) with different levels of vimentin content. The function of first nano-complex was confirmed by binding of FAM-labeled cytochrome C aptamer to its target (cytochrome C) which was released from mitochondria, based on the function of the first nano-complex. Fluorometric analysis and gel retardation assay proved the formation of nano-complexes. The results of flow cytometry and fluorescence microscopy indicated efficient apoptosis induction just in target cells (MDA-MB-231 and MCF-7 cells) but not in non-target cells (HepG2 cell). The results of MTT assay also confirmed cell death process. Overall, our results proved excellent targeted apoptosis in breast cancer cells by designed nano-complexes which can be applied as an efficient cancer therapy method. Copyright © 2017 Elsevier B.V. All rights reserved.

Formal groups and Z-entropies

PubMed Central

2016-01-01

We shall prove that the celebrated Rényi entropy is the first example of a new family of infinitely many multi-parametric entropies. We shall call them the Z-entropies. Each of them, under suitable hypotheses, generalizes the celebrated entropies of Boltzmann and Rényi. A crucial aspect is that every Z-entropy is composable (Tempesta 2016 Ann. Phys. 365, 180–197. (doi:10.1016/j.aop.2015.08.013)). This property means that the entropy of a system which is composed of two or more independent systems depends, in all the associated probability space, on the choice of the two systems only. Further properties are also required to describe the composition process in terms of a group law. The composability axiom, introduced as a generalization of the fourth Shannon–Khinchin axiom (postulating additivity), is a highly non-trivial requirement. Indeed, in the trace-form class, the Boltzmann entropy and Tsallis entropy are the only known composable cases. However, in the non-trace form class, the Z-entropies arise as new entropic functions possessing the mathematical properties necessary for information-theoretical applications, in both classical and quantum contexts. From a mathematical point of view, composability is intimately related to formal group theory of algebraic topology. The underlying group-theoretical structure determines crucially the statistical properties of the corresponding entropies. PMID:27956871

Development of a High Precision Displacement Measurement System by Fusing a Low Cost RTK-GPS Sensor and a Force Feedback Accelerometer for Infrastructure Monitoring.

PubMed

Koo, Gunhee; Kim, Kiyoung; Chung, Jun Yeon; Choi, Jaemook; Kwon, Nam-Yeol; Kang, Doo-Young; Sohn, Hoon

2017-11-28

A displacement measurement system fusing a low cost real-time kinematic global positioning system (RTK-GPS) receiver and a force feedback accelerometer is proposed for infrastructure monitoring. The proposed system is composed of a sensor module, a base module and a computation module. The sensor module consists of a RTK-GPS rover and a force feedback accelerometer, and is installed on a target structure like conventional RTK-GPS sensors. The base module is placed on a rigid ground away from the target structure similar to conventional RTK-GPS bases, and transmits observation messages to the sensor module. Then, the initial acceleration, velocity and displacement responses measured by the sensor module are transmitted to the computation module located at a central monitoring facility. Finally, high precision and high sampling rate displacement, velocity, and acceleration are estimated by fusing the acceleration from the accelerometer, the velocity from the GPS rover, and the displacement from RTK-GPS. Note that the proposed displacement measurement system can measure 3-axis acceleration, velocity as well as displacement in real time. In terms of displacement, the proposed measurement system can estimate dynamic and pseudo-static displacement with a root-mean-square error of 2 mm and a sampling rate of up to 100 Hz. The performance of the proposed system is validated under sinusoidal, random and steady-state vibrations. Field tests were performed on the Yeongjong Grand Bridge and Yi Sun-sin Bridge in Korea, and the Xihoumen Bridge in China to compare the performance of the proposed system with a commercial RTK-GPS sensor and other data fusion techniques.

Data communications in a parallel active messaging interface of a parallel computer

DOEpatents

Archer, Charles J; Blocksome, Michael A; Ratterman, Joseph D; Smith, Brian E

2015-02-03

Data communications in a parallel active messaging interface (`PAMI`) of a parallel computer, the PAMI composed of data communications endpoints, each endpoint including a specification of data communications parameters for a thread of execution on a compute node, including specifications of a client, a context, and a task, endpoints coupled for data communications through the PAMI and through data communications resources, including receiving in an origin endpoint of the PAMI a SEND instruction, the SEND instruction specifying a transmission of transfer data from the origin endpoint to a first target endpoint; transmitting from the origin endpoint to the first target endpoint a Request-To-Send (`RTS`) message advising the first target endpoint of the location and size of the transfer data; assigning by the first target endpoint to each of a plurality of target endpoints separate portions of the transfer data; and receiving by the plurality of target endpoints the transfer data.

Data communications in a parallel active messaging interface of a parallel computer

DOEpatents

Archer, Charles J; Blocksome, Michael A; Ratterman, Joseph D; Smith, Brian E

2014-11-18

Data communications in a parallel active messaging interface (`PAMI`) of a parallel computer, the PAMI composed of data communications endpoints, each endpoint including a specification of data communications parameters for a thread of execution on a compute node, including specifications of a client, a context, and a task, endpoints coupled for data communications through the PAMI and through data communications resources, including receiving in an origin endpoint of the PAMI a SEND instruction, the SEND instruction specifying a transmission of transfer data from the origin endpoint to a first target endpoint; transmitting from the origin endpoint to the first target endpoint a Request-To-Send (`RTS`) message advising the first target endpoint of the location and size of the transfer data; assigning by the first target endpoint to each of a plurality of target endpoints separate portions of the transfer data; and receiving by the plurality of target endpoints the transfer data.

Addressing the Immunogenicity of the Cargo and of the Targeting Antibodies with a Focus on Deimmunized Bacterial Toxins and on Antibody-Targeted Human Effector Proteins

PubMed Central

Grinberg, Yehudit; Benhar, Itai

2017-01-01

Third-generation immunotoxins are composed of a human, or humanized, targeting moiety, usually a monoclonal antibody or an antibody fragment, and a non-human effector molecule. Due to the non-human origin of the cytotoxic domain, these molecules stimulate potent anti-drug immune responses, which limit treatment options. Efforts are made to deimmunize such immunotoxins or to combine treatment with immunosuppression. An alternative approach is using the so-called “human cytotoxic fusion proteins”, in which antibodies are used to target human effector proteins. Here, we present three relevant approaches for reducing the immunogenicity of antibody-targeted protein therapeutics: (1) reducing the immunogenicity of the bacterial toxin, (2) fusing human cytokines to antibodies to generate immunocytokines and (3) addressing the immunogenicity of the targeting antibodies. PMID:28574434

Protease-sensitive, polymer-caged liposomes: a method for making highly targeted liposomes using triggered release.

PubMed

Basel, Matthew T; Shrestha, Tej B; Troyer, Deryl L; Bossmann, Stefan H

2011-03-22

Liposomes have become useful and well-known drug delivery vehicles because of their ability to entrap drugs without chemically modifying them and to deliver them somewhat selectively to tumorous tissue via the enhanced permeation and retention (EPR) effect. Although useful, liposome preparations are still less than ideal because of imperfect specificity, slow release kinetics in the tumor, and leakiness prior to reaching the tumor site. Cancer-associated proteases (CAPs), which are differentially expressed in tumors, have also gained traction recently as a method for tumor targeting and drug delivery. By combining the EPR effect with CAPs sensitivity, a much more specific liposome can be produced. The method described here creates an improved liposome system that can target more specifically, with faster release kinetics and lower general leaking, by deliberately producing a very unstable liposome (loaded with hyperosmotic vehicle) that is subsequently stabilized by a cross-linked polymer shell containing consensus sequences for cancer-associated proteases (protease-triggered, caged liposomes). A cholesterol-anchored, graft copolymer, composed of a short peptide sequence for urokinase plasminogen activator (uPA) and poly(acrylic acid), was synthesized and incorporated into liposomes prepared at high osmolarities. Upon cross-linking of the polymers, the protease-triggered, caged liposomes showed significant resistance to osmotic swelling and leaking of contents. Protease-triggered, caged liposomes also showed significant and substantial differential release of contents in the presence of uPA, while bare liposomes showed no differential effect in the presence of uPA. Thus a protease-sensitive liposome system with fast release kinetics was developed that could be used for more specific targeting to tumors.

Robust Target Tracking with Multi-Static Sensors under Insufficient TDOA Information.

PubMed

Shin, Hyunhak; Ku, Bonhwa; Nelson, Jill K; Ko, Hanseok

2018-05-08

This paper focuses on underwater target tracking based on a multi-static sonar network composed of passive sonobuoys and an active ping. In the multi-static sonar network, the location of the target can be estimated using TDOA (Time Difference of Arrival) measurements. However, since the sensor network may obtain insufficient and inaccurate TDOA measurements due to ambient noise and other harsh underwater conditions, target tracking performance can be significantly degraded. We propose a robust target tracking algorithm designed to operate in such a scenario. First, track management with track splitting is applied to reduce performance degradation caused by insufficient measurements. Second, a target location is estimated by a fusion of multiple TDOA measurements using a Gaussian Mixture Model (GMM). In addition, the target trajectory is refined by conducting a stack-based data association method based on multiple-frames measurements in order to more accurately estimate target trajectory. The effectiveness of the proposed method is verified through simulations.

Oligonucleotide Aptamers: New Tools for Targeted Cancer Therapy

PubMed Central

Sun, Hongguang; Zhu, Xun; Lu, Patrick Y; Rosato, Roberto R; Tan, Wen; Zu, Youli

2014-01-01

Aptamers are a class of small nucleic acid ligands that are composed of RNA or single-stranded DNA oligonucleotides and have high specificity and affinity for their targets. Similar to antibodies, aptamers interact with their targets by recognizing a specific three-dimensional structure and are thus termed “chemical antibodies.” In contrast to protein antibodies, aptamers offer unique chemical and biological characteristics based on their oligonucleotide properties. Hence, they are more suitable for the development of novel clinical applications. Aptamer technology has been widely investigated in various biomedical fields for biomarker discovery, in vitro diagnosis, in vivo imaging, and targeted therapy. This review will discuss the potential applications of aptamer technology as a new tool for targeted cancer therapy with emphasis on the development of aptamers that are able to specifically target cell surface biomarkers. Additionally, we will describe several approaches for the use of aptamers in targeted therapeutics, including aptamer-drug conjugation, aptamer-nanoparticle conjugation, aptamer-mediated targeted gene therapy, aptamer-mediated immunotherapy, and aptamer-mediated biotherapy. PMID:25093706

Investigating a multi-purpose target for electron linac based photoneutron sources for BNCT of deep-seated tumors

NASA Astrophysics Data System (ADS)

Masoudi, S. Farhad; Rasouli, Fatemeh S.

2015-08-01

Recent studies in BNCT have focused on investigating appropriate neutron sources as alternatives for nuclear reactors. As the most prominent facilities, the electron linac based photoneutron sources benefit from two consecutive reactions, (e, γ) and (γ, n). The photoneutron sources designed so far are composed of bipartite targets which involve practical problems and are far from the objective of achieving an optimized neutron source. This simulation study deals with designing a compact, optimized, and geometrically simple target for a photoneutron source based on an electron linac. Based on a set of MCNPX simulations, tungsten is found to have the potential of utilizing as both photon converter and photoneutron target. Besides, it is shown that an optimized dimension for such a target slows-down the produced neutrons toward the desired energy range while keeping them economy, which makes achieving the recommended criteria for BNCT of deep-tumors more available. This multi-purpose target does not involve complicated designing, and can be considered as a significant step toward finding application of photoneutron sources for in-hospital treatments. In order to shape the neutron beam emitted from such a target, the beam is planned to pass through an optimized arrangement of materials composed of moderators, filters, reflector, and collimator. By assessment with the recommended in-air parameters, it is shown that the designed beam provides high intensity of desired neutrons, as well as low background contamination. The last section of this study is devoted to investigate the performance of the resultant beam in deep tissue. A typical simulated liver tumor, located within a phantom of human body, was subjected to the irradiation of the designed spectrum. The dosimetric results, including evaluated depth-dose curves and carried out in-phantom parameters show that the proposed configuration establishes acceptable agreement between the appropriate neutron intensity, and penetrating deep in tissue in a reasonable treatment time.

Targeting histone deacetylases: perspectives for epigenetic-based therapy in cardio-cerebrovascular disease

PubMed Central

Wang, Zi-Ying; Qin, Wen; Yi, Fan

2015-01-01

Although the pathogenesis of cardio-cerebrovascular disease (CCVD) is multifactorial, an increasing number of experimental and clinical studies have highlighted the importance of histone deacetylase (HDAC)-mediated epigenetic processes in the development of cardio-cerebrovascular injury. HDACs are a family of enzymes to balance the acetylation activities of histone acetyltransferases on chromatin remodeling and play essential roles in regulating gene transcription. To date, 18 mammalian HDACs are identified and grouped into four classes based on similarity to yeast orthologs. The zinc-dependent HDAC family currently consists of 11 members divided into three classes (class I, II, and IV) on the basis of structure, sequence homology, and domain organization. In comparison, class III HDACs (also known as the sirtuins) are composed of a family of NAD+-dependent protein-modifying enzymes related to the Sir2 gene. HDAC inhibitors are a group of compounds that block HDAC activities typically by binding to the zinc-containing catalytic domain of HDACs and have displayed anti-inflammatory and antifibrotic effects in the cardio-cerebrovascular system. In this review, we summarize the current knowledge about classifications, functions of HDACs and their roles and regulatory mechanisms in the cardio-cerebrovascular system. Pharmacological targeting of HDAC-mediated epigenetic processes may open new therapeutic avenues for the treatment of CCVD. PMID:25870619

Fast fission neutron detection using the Cherenkov effect

NASA Astrophysics Data System (ADS)

Millard, Matthew James

The Cherenkov effect in optically clear media of varying indices of refraction and composition was investigated for quantification of fast neutrons. The ultimate application of the proposed detection system is criticality monitoring. The optically clear medium, composed of select target nuclei, was coupled to a photomultiplier tube. Neutron reaction products of the target nuclei contained within the optical medium emit beta particles and gamma rays that produce Cherenkov photons within the medium which can be detected. Assessed media include quartz (SiO2), sapphire (Al2O3), spinel (MgAl2O4), and zinc sulfide (ZnS), which were irradiated with un-moderated 252Cf. Monte Carlo N-Particle (MCNP) code simulations were conducted to quantify the neutron flux incident on the media. High resolution gamma-ray spectroscopic measurements of the samples were conducted to verify the MCNP estimate. The threshold reactions of interest were 28Si (n, p) 28Al, 27 Al (n, p) 27Mg, 24Mg(n, p)24 Na, and 64Zn(n, p)64Cu which have neutron reaction cross sections in the 1 to 10 MeV range on the order of 0.1 barn. The detection system offers a unique way to measure a criticality event; it can count in place, making retrieval by emergency personnel unnecessary.

Cell source determines the immunological impact of biomimetic nanoparticles.

PubMed

Evangelopoulos, Michael; Parodi, Alessandro; Martinez, Jonathan O; Yazdi, Iman K; Cevenini, Armando; van de Ven, Anne L; Quattrocchi, Nicoletta; Boada, Christian; Taghipour, Nima; Corbo, Claudia; Brown, Brandon S; Scaria, Shilpa; Liu, Xuewu; Ferrari, Mauro; Tasciotti, Ennio

2016-03-01

Recently, engineering the surface of nanotherapeutics with biologics to provide them with superior biocompatibility and targeting towards pathological tissues has gained significant popularity. Although the functionalization of drug delivery vectors with cellular materials has been shown to provide synthetic particles with unique biological properties, these approaches may have undesirable immunological repercussions upon systemic administration. Herein, we comparatively analyzed unmodified multistage nanovectors and particles functionalized with murine and human leukocyte cellular membrane, dubbed Leukolike Vectors (LLV), and the immunological effects that may arise in vitro and in vivo. Previously, LLV demonstrated an avoidance of opsonization and phagocytosis, in addition to superior targeting of inflammation and prolonged circulation. In this work, we performed a comprehensive evaluation of the importance of the source of cellular membrane in increasing their systemic tolerance and minimizing an inflammatory response. Time-lapse microscopy revealed LLV developed using a cellular coating derived from a murine (i.e., syngeneic) source resulted in an active avoidance of uptake by macrophage cells. Additionally, LLV composed of a murine membrane were found to have decreased uptake in the liver with no significant effect on hepatic function. As biomimicry continues to develop, this work demonstrates the necessity to consider the source of biological material in the development of future drug delivery carriers. Copyright © 2015. Published by Elsevier Ltd.

Pleiotropic and Epistatic Network-Based Discovery: Integrated Networks for Target Gene Discovery

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

Weighill, Deborah; Jones, Piet; Shah, Manesh

Biological organisms are complex systems that are composed of functional networks of interacting molecules and macro-molecules. Complex phenotypes are the result of orchestrated, hierarchical, heterogeneous collections of expressed genomic variants. However, the effects of these variants are the result of historic selective pressure and current environmental and epigenetic signals, and, as such, their co-occurrence can be seen as genome-wide correlations in a number of different manners. Biomass recalcitrance (i.e., the resistance of plants to degradation or deconstruction, which ultimately enables access to a plant's sugars) is a complex polygenic phenotype of high importance to biofuels initiatives. This study makes usemore » of data derived from the re-sequenced genomes from over 800 different Populus trichocarpa genotypes in combination with metabolomic and pyMBMS data across this population, as well as co-expression and co-methylation networks in order to better understand the molecular interactions involved in recalcitrance, and identify target genes involved in lignin biosynthesis/degradation. A Lines Of Evidence (LOE) scoring system is developed to integrate the information in the different layers and quantify the number of lines of evidence linking genes to target functions. This new scoring system was applied to quantify the lines of evidence linking genes to lignin-related genes and phenotypes across the network layers, and allowed for the generation of new hypotheses surrounding potential new candidate genes involved in lignin biosynthesis in P. trichocarpa, including various AGAMOUS-LIKE genes. Lastly, the resulting Genome Wide Association Study networks, integrated with Single Nucleotide Polymorphism (SNP) correlation, co-methylation, and co-expression networks through the LOE scores are proving to be a powerful approach to determine the pleiotropic and epistatic relationships underlying cellular functions and, as such, the molecular basis for complex phenotypes, such as recalcitrance.« less

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

Shiltsev, V.

The idea of exploring collisions in the center-of-mass system to fully exploit the energy of the accelerated particles had been given serious consideration by the Norwegian engineer and inventor Rolf Wideröe, who had applied for a patent on the idea in 1943 (and got the patent in 1953 [1]) after considering the kinematic advantage of keeping the center of mass at rest to produce larger momentum transfers. Describing this advantage G.K.O’Neill, one of the collider pioneers, wrote in 1956 [2]: “…as accelerators of higher and higher energy are built, their usefulness is limited by the fact that the energy availablemore » for creating new particles is measured in the center-of-mass system of the target nucleon and the bombarding particle. In the relativistic limit, this energy rises only as the square root of the accelerator energy. However, if two particles of equal energy traveling in opposite directions could be made to collide, the available energy would be twice the whole energy of one particle...” Therefore, no kinetic energy is wasted by the motion of the center of mass of the system, and the available reaction energy E R = 2E beam (while a particle with the same energy E beam colliding with another particle of the mass m at rest produces only E R = (2E beam m)½ in the extreme relativistic case.) One can also add that the colliders are “cleaner” machines with respect to the fixed target ones since the colliding beams do not interact with the target materials. The other advantage is that it is much easier to organize collisions of beams composed of matter-antimatter particles, like in electron-positron and proton-antiproton colliders.« less

The first colliders: AdA, VEP-1 and Princeton-Stanford

NASA Astrophysics Data System (ADS)

Shiltsev, Vladimir

The idea of exploring collisions in the center-of-mass system to fully exploit the energy of the accelerated particles had been given serious consideration by the Norwegian engineer and inventor Rolf Wideröe, who applied for a patent on the idea in 1943 (and got the patent in 1953 [1]) after considering the kinematic advantage of keeping the center of mass at rest to produce larger momentum transfers. Describing this advantage, G. K. O'Neill, one of the collider pioneers, wrote in 1956 [2]: "... as accelerators of higher and higher energy are built, their usefulness is limited by the fact that the energy available for creating new particles is measured in the center-of-mass system of the target nucleon and the bombarding particle. In the relativistic limit, this energy rises only as the square root of the accelerator energy. However, if two particles of equal energy traveling in opposite directions could be made to collide, the available energy would be twice the whole energy of one particle ... " Therefore, no kinetic energy is wasted by the motion of the center of mass of the system, and the available reaction energy ER = 2Ebeam (while a particle with the same energy Ebeam colliding with another particle of the mass m at rest produces only ER = (2Ebeamm)1/2 in the extreme relativistic case). One can also add that the colliders are "cleaner" machines with respect to the fixed-target ones since the colliding beams do not interact with the target materials. The other advantage is that it is much easier to organize collisions of beams composed of matter-antimatter particles, like in electron-positron and proton-antiproton colliders...

Pleiotropic and Epistatic Network-Based Discovery: Integrated Networks for Target Gene Discovery

DOE PAGES

Weighill, Deborah; Jones, Piet; Shah, Manesh; ...

2018-05-11

Biological organisms are complex systems that are composed of functional networks of interacting molecules and macro-molecules. Complex phenotypes are the result of orchestrated, hierarchical, heterogeneous collections of expressed genomic variants. However, the effects of these variants are the result of historic selective pressure and current environmental and epigenetic signals, and, as such, their co-occurrence can be seen as genome-wide correlations in a number of different manners. Biomass recalcitrance (i.e., the resistance of plants to degradation or deconstruction, which ultimately enables access to a plant's sugars) is a complex polygenic phenotype of high importance to biofuels initiatives. This study makes usemore » of data derived from the re-sequenced genomes from over 800 different Populus trichocarpa genotypes in combination with metabolomic and pyMBMS data across this population, as well as co-expression and co-methylation networks in order to better understand the molecular interactions involved in recalcitrance, and identify target genes involved in lignin biosynthesis/degradation. A Lines Of Evidence (LOE) scoring system is developed to integrate the information in the different layers and quantify the number of lines of evidence linking genes to target functions. This new scoring system was applied to quantify the lines of evidence linking genes to lignin-related genes and phenotypes across the network layers, and allowed for the generation of new hypotheses surrounding potential new candidate genes involved in lignin biosynthesis in P. trichocarpa, including various AGAMOUS-LIKE genes. Lastly, the resulting Genome Wide Association Study networks, integrated with Single Nucleotide Polymorphism (SNP) correlation, co-methylation, and co-expression networks through the LOE scores are proving to be a powerful approach to determine the pleiotropic and epistatic relationships underlying cellular functions and, as such, the molecular basis for complex phenotypes, such as recalcitrance.« less

Ubiquitous-health (U-Health) monitoring systems for elders and caregivers

NASA Astrophysics Data System (ADS)

Moon, Gyu; Lim, Kyung-won; Yoo, Young-min; An, Hye-min; Lee, Ki Seop; Szu, Harold

2011-06-01

This paper presents two aordable low-tack system for household biomedical wellness monitoring. The rst system, JIKIMI (pronounced caregiver in Korean), is a remote monitoring system that analyzes the behavior patterns of elders that live alone. JIKIMI is composed of an in-house sensing system, a set of wireless sensor nodes containing a pyroelectric infrared sensor to detect the motion of elders, an emergency button and a magnetic sensor that detects the opening and closing of doors. The system is also equipped with a server system, which is comprised of a database and web server. The server provides the mechanism for web-based monitoring to caregivers. The second system, Reader of Bottle Information (ROBI), is an assistant system which advises the contents of bottles for elders. ROBI is composed of bottles that have connected RFID tags and an advice system, which is composed of a wireless RFID reader, a gateway and a remote database server. The RFID tags are connected to the caps of the bottles are used in conjunction with the advice system These systems have been in use for three years and have proven to be useful for caregivers to provide more ecient and eective care services.

A Novel Bioreactor System for the Assessment of Endothelialization on Deformable Surfaces

PubMed Central

Bachmann, Björn J.; Bernardi, Laura; Loosli, Christian; Marschewski, Julian; Perrini, Michela; Ehrbar, Martin; Ermanni, Paolo; Poulikakos, Dimos; Ferrari, Aldo; Mazza, Edoardo

2016-01-01

The generation of a living protective layer at the luminal surface of cardiovascular devices, composed of an autologous functional endothelium, represents the ideal solution to life-threatening, implant-related complications in cardiovascular patients. The initial evaluation of engineering strategies fostering endothelial cell adhesion and proliferation as well as the long-term tissue homeostasis requires in vitro testing in environmental model systems able to recapitulate the hemodynamic conditions experienced at the blood-to-device interface of implants as well as the substrate deformation. Here, we introduce the design and validation of a novel bioreactor system which enables the long-term conditioning of human endothelial cells interacting with artificial materials under dynamic combinations of flow-generated wall shear stress and wall deformation. The wall shear stress and wall deformation values obtained encompass both the physiological and supraphysiological range. They are determined through separate actuation systems which are controlled based on validated computational models. In addition, we demonstrate the good optical conductivity of the system permitting online monitoring of cell activities through live-cell imaging as well as standard biochemical post-processing. Altogether, the bioreactor system defines an unprecedented testing hub for potential strategies toward the endothelialization or re-endothelialization of target substrates. PMID:27941901

Multifunctional Surface-Enhanced Raman Spectroscopy-Detectable Silver Nanoparticles Combined Photodynamic Therapy and pH-Triggered Chemotherapy.

PubMed

Srinivasan, Supriya; Bhardwaj, Vinay; Nagasetti, Abhignyan; Fernandez-Fernandez, Alicia; McGoron, Anthony J

2016-12-01

This research paper reports the development of a multifunctional anti-cancer prodrug system based on silver nanoparticles. This prodrug system is composed of 70-nm sized nanoparticles and features photodynamic therapeutic properties and active, pH-triggered drug release. The silver nanoparticles are decorated with a folic acid (FA) targeting ligand via an amide bond, and also conjugated to the chemotherapeutic drug doxorubicin (DOX) via an acid-cleavable hydrazone bond. Both FA and DOX are attached to the silver nanoparticles through a polyethylene glycol (PEG) spacer. This prodrug system can preferentially enter cells that over-express folic acid receptors, with subsequent intracellular drug release triggered by reduced intracellular pH. Moreover, the silver nanoparticle carrier system exhibits photodynamic therapeutic (PDT) activity, so that the cell viability of cancer cells that overexpress folate receptors can be further reduced upon light irradiation. The dual effects of pH-triggered drug release and PDT increase the therapeutic efficacy of this system. The multifunctional nanoparticles can be probed intracellularly through Surface-Enhanced Raman Spectroscopy (SERS) and fluorescence spectroscopy. The current report explores the applicability of this multifunctional silver nanoparticle-based system for cancer theranostics.

Miniature photometric stereo system for textile surface structure reconstruction

NASA Astrophysics Data System (ADS)

Gorpas, Dimitris; Kampouris, Christos; Malassiotis, Sotiris

2013-04-01

In this work a miniature photometric stereo system is presented, targeting the three-dimensional structural reconstruction of various fabric types. This is a supportive module to a robot system, attempting to solve the well known "laundry problem". The miniature device has been designed for mounting onto the robot gripper. It is composed of a low-cost off-the-shelf camera, operating in macro mode, and eight light emitting diodes. The synchronization between image acquisition and lighting direction is controlled by an Arduino Nano board and software triggering. The ambient light has been addressed by a cylindrical enclosure. The direction of illumination is recovered by locating the reflection or the brightest point on a mirror sphere, while a flatfielding process compensates for the non-uniform illumination. For the evaluation of this prototype, the classical photometric stereo methodology has been used. The preliminary results on a large number of textiles are very promising for the successful integration of the miniature module to the robot system. The required interaction with the robot is implemented through the estimation of the Brenner's focus measure. This metric successfully assesses the focus quality with reduced time requirements in comparison to other well accepted focus metrics. Besides the targeting application, the small size of the developed system makes it a very promising candidate for applications with space restrictions, like the quality control in industrial production lines or object recognition based on structural information and in applications where easiness in operation and light-weight are required, like those in the Biomedical field, and especially in dermatology.

Optimal Signal Processing of Frequency-Stepped CW Radar Data

NASA Technical Reports Server (NTRS)

Ybarra, Gary A.; Wu, Shawkang M.; Bilbro, Griff L.; Ardalan, Sasan H.; Hearn, Chase P.; Neece, Robert T.

1995-01-01

An optimal signal processing algorithm is derived for estimating the time delay and amplitude of each scatterer reflection using a frequency-stepped CW system. The channel is assumed to be composed of abrupt changes in the reflection coefficient profile. The optimization technique is intended to maximize the target range resolution achievable from any set of frequency-stepped CW radar measurements made in such an environment. The algorithm is composed of an iterative two-step procedure. First, the amplitudes of the echoes are optimized by solving an overdetermined least squares set of equations. Then, a nonlinear objective function is scanned in an organized fashion to find its global minimum. The result is a set of echo strengths and time delay estimates. Although this paper addresses the specific problem of resolving the time delay between the first two echoes, the derivation is general in the number of echoes. Performance of the optimization approach is illustrated using measured data obtained from an HP-X510 network analyzer. It is demonstrated that the optimization approach offers a significant resolution enhancement over the standard processing approach that employs an IFFT. Degradation in the performance of the algorithm due to suboptimal model order selection and the effects of additive white Gaussion noise are addressed.

Optimal Signal Processing of Frequency-Stepped CW Radar Data

NASA Technical Reports Server (NTRS)

Ybarra, Gary A.; Wu, Shawkang M.; Bilbro, Griff L.; Ardalan, Sasan H.; Hearn, Chase P.; Neece, Robert T.

1995-01-01

An optimal signal processing algorithm is derived for estimating the time delay and amplitude of each scatterer reflection using a frequency-stepped CW system. The channel is assumed to be composed of abrupt changes in the reflection coefficient profile. The optimization technique is intended to maximize the target range resolution achievable from any set of frequency-stepped CW radar measurements made in such an environment. The algorithm is composed of an iterative two-step procedure. First, the amplitudes of the echoes are optimized by solving an overdetermined least squares set of equations. Then, a nonlinear objective function is scanned in an organized fashion to find its global minimum. The result is a set of echo strengths and time delay estimates. Although this paper addresses the specific problem of resolving the time delay between the two echoes, the derivation is general in the number of echoes. Performance of the optimization approach is illustrated using measured data obtained from an HP-851O network analyzer. It is demonstrated that the optimization approach offers a significant resolution enhancement over the standard processing approach that employs an IFFT. Degradation in the performance of the algorithm due to suboptimal model order selection and the effects of additive white Gaussion noise are addressed.

Autophagy and Alzheimer’s Disease: From Molecular Mechanisms to Therapeutic Implications

PubMed Central

Uddin, Md. Sahab; Stachowiak, Anna; Mamun, Abdullah Al; Tzvetkov, Nikolay T.; Takeda, Shinya; Atanasov, Atanas G.; Bergantin, Leandro B.; Abdel-Daim, Mohamed M.; Stankiewicz, Adrian M.

2018-01-01

Alzheimer’s disease (AD) is the most common cause of progressive dementia in the elderly. It is characterized by a progressive and irreversible loss of cognitive abilities and formation of senile plaques, composed mainly of amyloid β (Aβ), and neurofibrillary tangles (NFTs), composed of tau protein, in the hippocampus and cortex of afflicted humans. In brains of AD patients the metabolism of Aβ is dysregulated, which leads to the accumulation and aggregation of Aβ. Metabolism of Aβ and tau proteins is crucially influenced by autophagy. Autophagy is a lysosome-dependent, homeostatic process, in which organelles and proteins are degraded and recycled into energy. Thus, dysfunction of autophagy is suggested to lead to the accretion of noxious proteins in the AD brain. In the present review, we describe the process of autophagy and its importance in AD. Additionally, we discuss mechanisms and genes linking autophagy and AD, i.e., the mTOR pathway, neuroinflammation, endocannabinoid system, ATG7, BCL2, BECN1, CDK5, CLU, CTSD, FOXO1, GFAP, ITPR1, MAPT, PSEN1, SNCA, UBQLN1, and UCHL1. We also present pharmacological agents acting via modulation of autophagy that may show promise in AD therapy. This review updates our knowledge on autophagy mechanisms proposing novel therapeutic targets for the treatment of AD. PMID:29441009

Atmospheric Pressure Ionization Using a High Voltage Target Compared to Electrospray Ionization.

PubMed

Lubin, Arnaud; Bajic, Steve; Cabooter, Deirdre; Augustijns, Patrick; Cuyckens, Filip

2017-02-01

A new atmospheric pressure ionization (API) source, viz. UniSpray, was evaluated for mass spectrometry (MS) analysis of pharmaceutical compounds by head-to-head comparison with electrospray ionization (ESI) on the same high-resolution MS system. The atmospheric pressure ionization source is composed of a grounded nebulizer spraying onto a high voltage, cylindrical stainless steel target. Molecules are ionized in a similar fashion to electrospray ionization, predominantly producing protonated or deprotonated species. Adduct formation (e.g., proton and sodium adducts) and in-source fragmentation is shown to be almost identical between the two sources. The performance of the new API source was compared with electrospray by infusion of a mix of 22 pharmaceutical compounds with a wide variety of functional groups and physico-chemical properties (molecular weight, logP, and pKa) in more than 100 different conditions (mobile phase strength, solvents, pH, and flow rate). The new API source shows an intensity gain of a factor 2.2 compared with ESI considering all conditions on all compounds tested. Finally, some hypotheses on the ionization mechanism, similarities, and differences with ESI, are discussed. Graphical Abstract ᅟ.

Blood Vessels in Allotransplantation.

PubMed

Abrahimi, P; Liu, R; Pober, J S

2015-07-01

Human vascularized allografts are perfused through blood vessels composed of cells (endothelium, pericytes, and smooth muscle cells) that remain largely of graft origin and are thus subject to host alloimmune responses. Graft vessels must be healthy to maintain homeostatic functions including control of perfusion, maintenance of permselectivity, prevention of thrombosis, and participation in immune surveillance. Vascular cell injury can cause dysfunction that interferes with these processes. Graft vascular cells can be activated by mediators of innate and adaptive immunity to participate in graft inflammation contributing to both ischemia/reperfusion injury and allograft rejection. Different forms of rejection may affect graft vessels in different ways, ranging from thrombosis and neutrophilic inflammation in hyperacute rejection, to endothelialitis/intimal arteritis and fibrinoid necrosis in acute cell-mediated or antibody-mediated rejection, respectively, and to diffuse luminal stenosis in chronic rejection. While some current therapies targeting the host immune system do affect graft vascular cells, direct targeting of the graft vasculature may create new opportunities for preventing allograft injury and loss. © Copyright 2015 The American Society of Transplantation and the American Society of Transplant Surgeons.

Candidate molten salt investigation for an accelerator driven subcritical core

NASA Astrophysics Data System (ADS)

Sooby, E.; Baty, A.; Beneš, O.; McIntyre, P.; Pogue, N.; Salanne, M.; Sattarov, A.

2013-09-01

We report a design for accelerator-driven subcritical fission in a molten salt core (ADSMS) that utilizes a fuel salt composed of NaCl and transuranic (TRU) chlorides. The ADSMS core is designed for fast neutronics (28% of neutrons >1 MeV) to optimize TRU destruction. The choice of a NaCl-based salt offers benefits for corrosion, operating temperature, and actinide solubility as compared with LiF-based fuel salts. A molecular dynamics (MD) code has been used to estimate properties of the molten salt system which are important for ADSMS design but have never been measured experimentally. Results from the MD studies are reported. Experimental measurements of fuel salt properties and studies of corrosion and radiation damage on candidate metals for the core vessel are anticipated. A special thanks is due to Prof. Paul Madden for introducing the ADSMS group to the concept of using the molten salt as the spallation target, rather than a conventional heavy metal spallation target. This feature helps to optimize this core as a Pu/TRU burner.

Atmospheric Pressure Ionization Using a High Voltage Target Compared to Electrospray Ionization

NASA Astrophysics Data System (ADS)

Lubin, Arnaud; Bajic, Steve; Cabooter, Deirdre; Augustijns, Patrick; Cuyckens, Filip

2017-02-01

A new atmospheric pressure ionization (API) source, viz. UniSpray, was evaluated for mass spectrometry (MS) analysis of pharmaceutical compounds by head-to-head comparison with electrospray ionization (ESI) on the same high-resolution MS system. The atmospheric pressure ionization source is composed of a grounded nebulizer spraying onto a high voltage, cylindrical stainless steel target. Molecules are ionized in a similar fashion to electrospray ionization, predominantly producing protonated or deprotonated species. Adduct formation (e.g., proton and sodium adducts) and in-source fragmentation is shown to be almost identical between the two sources. The performance of the new API source was compared with electrospray by infusion of a mix of 22 pharmaceutical compounds with a wide variety of functional groups and physico-chemical properties (molecular weight, logP, and pKa) in more than 100 different conditions (mobile phase strength, solvents, pH, and flow rate). The new API source shows an intensity gain of a factor 2.2 compared with ESI considering all conditions on all compounds tested. Finally, some hypotheses on the ionization mechanism, similarities, and differences with ESI, are discussed.

Crystal Structure of the Cul2-Rbx1-EloBC-VHL Ubiquitin Ligase Complex.

PubMed

Cardote, Teresa A F; Gadd, Morgan S; Ciulli, Alessio

2017-06-06

Cullin RING E3 ubiquitin ligases (CRLs) function in the ubiquitin proteasome system to catalyze the transfer of ubiquitin from E2 conjugating enzymes to specific substrate proteins. CRLs are large dynamic complexes and attractive drug targets for the development of small-molecule inhibitors and chemical inducers of protein degradation. The atomic details of whole CRL assembly and interactions that dictate subunit specificity remain elusive. Here we present the crystal structure of a pentameric CRL2 VHL complex, composed of Cul2, Rbx1, Elongin B, Elongin C, and pVHL. The structure traps a closed state of full-length Cul2 and a new pose of Rbx1 in a trajectory from closed to open conformation. We characterize hotspots and binding thermodynamics at the interface between Cul2 and pVHL-EloBC and identify mutations that contribute toward a selectivity switch for Cul2 versus Cul5 recognition. Our findings provide structural and biophysical insights into the whole Cul2 complex that could aid future drug targeting. Copyright © 2017 The Author(s). Published by Elsevier Ltd.. All rights reserved.

A "signal on" protection-displacement-hybridization-based electrochemical hepatitis B virus gene sequence sensor with high sensitivity and peculiar adjustable specificity.

PubMed

Li, Fengqin; Xu, Yanmei; Yu, Xiang; Yu, Zhigang; He, Xunjun; Ji, Hongrui; Dong, Jinghao; Song, Yongbin; Yan, Hong; Zhang, Guiling

2016-08-15

One "signal on" electrochemical sensing strategy was constructed for the detection of a specific hepatitis B virus (HBV) gene sequence based on the protection-displacement-hybridization-based (PDHB) signaling mechanism. This sensing system is composed of three probes, one capturing probe (CP) and one assistant probe (AP) which are co-immobilized on the Au electrode surface, and one 3-methylene blue (MB) modified signaling probe (SP) free in the detection solution. One duplex are formed between AP and SP with the target, a specific HBV gene sequence, hybridizing with CP. This structure can drive the MB labels close to the electrode surface, thereby producing a large detection current. Two electrochemical testing techniques, alternating current voltammetry (ACV) and cyclic voltammetry (CV), were used for characterizing the sensor. Under the optimized conditions, the proposed sensor exhibits a high sensitivity with the detection limit of ∼5fM for the target. When used for the discrimination of point mutation, the sensor also features an outstanding ability and its peculiar high adjustability. Copyright © 2016 Elsevier B.V. All rights reserved.

Differential Distributions of Synechococcus Subgroups Across the California Current System

PubMed Central

Paerl, Ryan W.; Johnson, Kenneth S.; Welsh, Rory M.; Worden, Alexandra Z.; Chavez, Francisco P.; Zehr, Jonathan P.

2011-01-01

Synechococcus is an abundant marine cyanobacterial genus composed of different populations that vary physiologically. Synechococcus narB gene sequences (encoding for nitrate reductase in cyanobacteria) obtained previously from isolates and the environment (e.g., North Pacific Gyre Station ALOHA, Hawaii or Monterey Bay, CA, USA) were used to develop quantitative PCR (qPCR) assays. These qPCR assays were used to quantify populations from specific narB phylogenetic clades across the California Current System (CCS), a region composed of dynamic zones between a coastal-upwelling zone and the oligotrophic Pacific Ocean. Targeted populations (narB subgroups) had different biogeographic patterns across the CCS, which appear to be driven by environmental conditions. Subgroups C_C1, D_C1, and D_C2 were abundant in coastal-upwelling to coastal-transition zone waters with relatively high to intermediate ammonium, nitrate, and chl. a concentrations. Subgroups A_C1 and F_C1 were most abundant in coastal-transition zone waters with intermediate nutrient concentrations. E_O1 and G_O1 were most abundant at different depths of oligotrophic open-ocean waters (either in the upper mixed layer or just below). E_O1, A_C1, and F_C1 distributions differed from other narB subgroups and likely possess unique ecologies enabling them to be most abundant in waters between coastal and open-ocean waters. Different CCS zones possessed distinct Synechococcus communities. Core California current water possessed low numbers of narB subgroups relative to counted Synechococcus cells, and coastal-transition waters contained high abundances of Synechococcus cells and total number of narB subgroups. The presented biogeographic data provides insight on the distributions and ecologies of Synechococcus present in an eastern boundary current system. PMID:21833315

A cyclic-RGD-BioShuttle functionalized with TMZ by DARinv “Click Chemistry” targeted to αvβ3 integrin for therapy

PubMed Central

Braun, Klaus; Wiessler, Manfred; Pipkorn, Rüdiger; Ehemann, Volker; Bäuerle, Tobias; Fleischhacker, Heinz; Müller, Gabriele; Lorenz, Peter; Waldeck, Waldemar

2010-01-01

Clinical experiences often document, that a successful tumor control requires high doses of drug applications. It is widely believed that unavoidable adverse reactions could be minimized by using gene-therapeutic strategies protecting the tumor-surrounding healthy tissue as well as the bone-marrow. One new approach in this direction is the use of “Targeted Therapies” realizing a selective drug targeting to gain effectual amounts at the target site, even with drastically reduced application doses. MCF-7 breast cancer cells expressing the αvβ3 [alpha(v)beta(3)] integrin receptor are considered as appropriate candidates for such a targeted therapy. The modularly composed BioShuttle carrier consisting of different units designed to facilitate the passage across the cell membranes and for subcellular addressing of diagnostic and/or therapeutic molecules could be considered as an eligible delivery platform. Here we used the cyclic RGD-BioShuttle as a carrier for temozolomide (TMZ) at the αvβ3 integrin receptor realizing local TMZ concentrations sufficient for cell killing. The IC50 values are 12 µMol/L in the case of cRGD-BioShuttle-TMZ and 100 µMol/L for underivatized TMZ, which confirms the advantage of TMZ reformulation to realize local concentrations sufficient for cell killing. Our paper focuses on the design, synthesis and application of the cRGD-BioShuttle conjugate composed of the cyclic RGD, a αvβ3 integrin-ligand, ligated to the cytotoxic drug TMZ. The ligation was carried out by the Diels Alder Reaction with inverse electron demand (DARinv). PMID:20922134

Ultrashort pulse laser deposition of thin films

DOEpatents

Perry, Michael D.; Banks, Paul S.; Stuart, Brent C.

2002-01-01

Short pulse PLD is a viable technique of producing high quality films with properties very close to that of crystalline diamond. The plasma generated using femtosecond lasers is composed of single atom ions with no clusters producing films with high Sp.sup.3 /Sp.sup.2 ratios. Using a high average power femtosecond laser system, the present invention dramatically increases deposition rates to up to 25 .mu.m/hr (which exceeds many CVD processes) while growing particulate-free films. In the present invention, deposition rates is a function of laser wavelength, laser fluence, laser spot size, and target/substrate separation. The relevant laser parameters are shown to ensure particulate-free growth, and characterizations of the films grown are made using several diagnostic techniques including electron energy loss spectroscopy (EELS) and Raman spectroscopy.

Quantitative Kα line spectroscopy for energy transport in ultra-intense laser plasma interaction

NASA Astrophysics Data System (ADS)

Zhang, Z.; Nishimura, H.; Namimoto, T.; Fujioka, S.; Arikawa, Y.; Nakai, M.; Koga, M.; Shiraga, H.; Kojima, S.; Azechi, H.; Ozaki, T.; Chen, H.; Pakr, J.; Williams, G. J.; Nishikino, M.; Kawachi, T.; Sagisaka, A.; Orimo, S.; Ogura, K.; Pirozhkov, A.; Yogo, A.; Kiriyama, H.; Kondo, K.; Okano, Y.

2012-10-01

X-ray line spectra ranging from 17 to 77 keV were quantitatively measured with a Laue spectrometer, composed of a cylindrically curved crystal and a detector. The absolute sensitivity of the spectrometer system was calibrated using pre-characterized laser-produced x-ray sources and radioisotopes, for the detectors and crystal respectively. The integrated reflectivity for the crystal is in good agreement with predictions by an open code for x-ray diffraction. The energy transfer efficiency from incident laser beams to hot electrons, as the energy transfer agency for Au Kα x-ray line emissions, is derived as a consequence of this work. By considering the hot electron temperature, the transfer efficiency from LFEX laser to Au plate target is about 8% to 10%.

A novel recombinant virus-like particle vaccine for prevention of porcine parvovirus-induced reproductive failure.

PubMed

Antonis, Adriaan F G; Bruschke, Christianne J M; Rueda, Paloma; Maranga, Luis; Casal, J Ignacio; Vela, Carmen; Hilgers, Luuk A Th; Belt, Peter B G M; Weerdmeester, Klaas; Carrondo, Manuel J T; Langeveld, Jan P M

2006-06-29

A novel vaccine against porcine parvovirus (PPV), composed of recombinant virus-like particles (PPV-VLPs) produced with the baculovirus expression vector system (BEVS) at industrial scale, was tested for its immunogenicity and protective potency. A formulation of submicrogram amounts of PPV-VLPs in a water-in-mineral oil adjuvant evoked high serum antibody titres in both guinea pigs, used as reference model, and target species, pigs. A single immunisation with 0.7microg of this antigen yielded complete foetal protection against PPV infection after challenge with a virulent strain of this virus. Furthermore, also in the presence of mild adjuvants the protective action of these PPV-VLPs is excellent. This recombinant subunit vaccine overcomes some of the drawbacks of classical PPV vaccines.

The Healthy Children, Strong Families Intervention: Design and Community Participation

ERIC Educational Resources Information Center

Adams, Alexandra K.; LaRowe, Tara L.; Cronin, Kate A.; Prince, Ronald J.; Wubben, Deborah P.; Parker, Tassy; Jobe, Jared B.

2012-01-01

Healthy Children, Strong Families (HCSF) is a 2-year, community-driven, family-based randomized controlled trial of a healthy lifestyles intervention conducted in partnership with four Wisconsin American Indian tribes. HCSF is composed of 1 year of targeted home visits to deliver nutritional and physical activity curricula. During Year 1, trained…

Potentialities of HTS Superconductor Technology in Telecommunication Satellites

DTIC Science & Technology

2005-07-13

satellites de télécommunications, utilisant des composants supraconducteurs à haute température critique et de l’électronique refroidie sont présentés... supraconducteur ) is the focal array of a receiving antenna (FAFR). The target application is a receive multi-beam satellite antenna in Ka-band. Small

Improving Expository Writing Skills with Explicit and Strategy Instructional Methods in Inclusive Middle School Classrooms

ERIC Educational Resources Information Center

Cihak, David F.; Castle, Kristin

2011-01-01

Forty eighth grade students with and without learning disabilities in an inclusive classroom participated in an adapted Step-Up to Writing (Auman, 2002) intervention program. The intervention targeted expository essays and composing topic, detail, transitional, and concluding sentences. A repeated-measures ANOVA indicated that both students with…

Improving Elementary Students' Spelling Achievement Using High-Frequency Words.

ERIC Educational Resources Information Center

Durnil, Christina; And Others

An action research study detailed a program for improving spelling achievement across the curriculum. The targeted population is composed of second and third grade students from a growing, middle class community located in a suburb of Chicago, Illinois. The problem of misspelled words in the students' writing was documented through students'…

Particle induced nuclear reaction calculations of Boron target nuclei

NASA Astrophysics Data System (ADS)

Tel, Eyyup; Sahan, Muhittin; Sarpün, Ismail Hakki; Kavun, Yusuf; Gök, Ali Armagan; Poyraz, Meltem

2017-09-01

Boron is usable element in many areas such as health, industry and energy. Especially, Boron neutron capture therapy (BNCT) is one of the medical applications. Boron target is irradiated with low energy thermal neutrons and at the end of reactions alpha particles occur. After this process recoiling lithium-7 nuclei is composed. In this study, charge particle induced nuclear reactions calculations of Boron target nuclei were investigated in the incident proton and alpha energy range of 5-50 MeV. The excitation functions for 10B target nuclei reactions have been calculated by using PCROSS Programming code. The semi-empirical calculations for (p,α) reactions have been done by using cross section formula with new coefficient obtained by Tel et al. The calculated results were compared with the experimental data from the literature.

Optical system design of solar-blind UV target receiver with large FOV

NASA Astrophysics Data System (ADS)

Chen, Yu; Huo, Furong; Zheng, Liqin

2014-11-01

Ultraviolet (UV) radiation of 200nm-300nm waveband from the sun is absorbed by atmosphere, which is often referred to the solar-blind region of the solar spectrum. Solar-blind characteristics of this waveband have important application value in forest-fire prevention, UV security communication, UV corona detection and other aspects. Especially in military fields such as missile warning, the application of solar-blind waveband has developed very rapidly, which is receiving more and more attention recently. In this paper, ZEMAX software is used to design an optical system of solar-blind UV target receiver with waveband 240nm-280nm, with which UV target signal can be detected. The optional materials are very few for UV optical systems to choose from, in which only CaF2 and JGS1 are commonly used. Various aberrations are not easy to be corrected. So it is very difficult to design a good UV system. Besides, doublet or triplet cannot be used in UV optical system considering possible cracking for different thermal expansion coefficients of different materials. So the doublet in initial structure is separated for this reason. During the optimization process, an aspheric surface is used to correct the aberrations. But this surface is removed before the design is finished to save production cost and enhance the precision of fabrication and test, which still keeps the image quality meeting the usage requirements. What we care for is the converging condition for different field of view from the far object on image plane. So this is an energy system. Spot diagram is taken as the evaluation criterion of image quality. The system is composed of 6 lenses with field of view (FOV) 31 degrees. In the final design results, the root mean square (RMS) radius for marginal FOV is less than 6.3 microns, while the value is only 4 microns for zero FOV. Point Spread Function and diffraction encircled energy diagram within the maximum FOV confirms the good performance of system further.

Privacy-preserving screen capture: towards closing the loop for health IT usability.

PubMed

Cooley, Joseph; Smith, Sean

2013-08-01

As information technology permeates healthcare (particularly provider-facing systems), maximizing system effectiveness requires the ability to document and analyze tricky or troublesome usage scenarios. However, real-world health IT systems are typically replete with privacy-sensitive data regarding patients, diagnoses, clinicians, and EMR user interface details; instrumentation for screen capture (capturing and recording the scenario depicted on the screen) needs to respect these privacy constraints. Furthermore, real-world health IT systems are typically composed of modules from many sources, mission-critical and often closed-source; any instrumentation for screen capture can rely neither on access to structured output nor access to software internals. In this paper, we present a tool to help solve this problem: a system that combines keyboard video mouse (KVM) capture with automatic text redaction (and interactively selectable unredaction) to produce precise technical content that can enrich stakeholder communications and improve end-user influence on system evolution. KVM-based capture makes our system both application-independent and OS-independent because it eliminates software-interface dependencies on capture targets. Using a corpus of EMR screenshots, we present empirical measurements of redaction effectiveness and processing latency to demonstrate system performances. We discuss how these techniques can translate into instrumentation systems that improve real-world health IT deployments. Copyright © 2013 Elsevier Inc. All rights reserved.

Uniqueness and characterization theorems for generalized entropies

NASA Astrophysics Data System (ADS)

Enciso, Alberto; Tempesta, Piergiulio

2017-12-01

The requirement that an entropy function be composable is key: it means that the entropy of a compound system can be calculated in terms of the entropy of its independent components. We prove that, under mild regularity assumptions, the only composable generalized entropy in trace form is the Tsallis one-parameter family (which contains Boltzmann-Gibbs as a particular case). This result leads to the use of generalized entropies that are not of trace form, such as Rényi’s entropy, in the study of complex systems. In this direction, we also present a characterization theorem for a large class of composable non-trace-form entropy functions with features akin to those of Rényi’s entropy.

Engineering of blended nanoparticle platform for delivery of mitochondria-acting therapeutics

PubMed Central

Marrache, Sean; Dhar, Shanta

2012-01-01

Mitochondrial dysfunctions cause numerous human disorders. A platform technology based on biodegradable polymers for carrying bioactive molecules to the mitochondrial matrix could be of enormous potential benefit in treating mitochondrial diseases. Here we report a rationally designed mitochondria-targeted polymeric nanoparticle (NP) system and its optimization for efficient delivery of various mitochondria-acting therapeutics by blending a targeted poly(d,l-lactic-co-glycolic acid)-block (PLGA-b)-poly(ethylene glycol) (PEG)-triphenylphosphonium (TPP) polymer (PLGA-b-PEG-TPP) with either nontargeted PLGA-b-PEG-OH or PLGA-COOH. An optimized formulation was identified through in vitro screening of a library of charge- and size-varied NPs, and mitochondrial uptake was studied by qualitative and quantitative investigations of cytosolic and mitochondrial fractions of cells treated with blended NPs composed of PLGA-b-PEG-TPP and a triblock copolymer containing a fluorescent quantum dot, PLGA-b-PEG-QD. The versatility of this platform was demonstrated by studying various mitochondria-acting therapeutics for different applications, including the mitochondria-targeting chemotherapeutics lonidamine and α-tocopheryl succinate for cancer, the mitochondrial antioxidant curcumin for Alzheimer’s disease, and the mitochondrial uncoupler 2,4-dinitrophenol for obesity. These biomolecules were loaded into blended NPs with high loading efficiencies. Considering efficacy, the targeted PLGA-b-PEG-TPP NP provides a remarkable improvement in the drug therapeutic index for cancer, Alzheimer’s disease, and obesity compared with the nontargeted construct or the therapeutics in their free form. This work represents the potential of a single, programmable NP platform for the diagnosis and targeted delivery of therapeutics for mitochondrial dysfunction-related diseases. PMID:22991470

Maneuver Algorithm for Bearings-Only Target Tracking with Acceleration and Field of View Constraints

NASA Astrophysics Data System (ADS)

Roh, Heekun; Shim, Sang-Wook; Tahk, Min-Jea

2018-05-01

This paper proposes a maneuver algorithm for the agent performing target tracking with bearing angle information only. The goal of the agent is to estimate the target position and velocity based only on the bearing angle data. The methods of bearings-only target state estimation are outlined. The nature of bearings-only target tracking problem is then addressed. Based on the insight from above-mentioned properties, the maneuver algorithm for the agent is suggested. The proposed algorithm is composed of a nonlinear, hysteresis guidance law and the estimation accuracy assessment criteria based on the theory of Cramer-Rao bound. The proposed guidance law generates lateral acceleration command based on current field of view angle. The accuracy criteria supply the expected estimation variance, which acts as a terminal criterion for the proposed algorithm. The aforementioned algorithm is verified with a two-dimensional simulation.

Assembling nanoparticle coatings to improve the drug delivery performance of lipid based colloids

NASA Astrophysics Data System (ADS)

Simovic, Spomenka; Barnes, Timothy J.; Tan, Angel; Prestidge, Clive A.

2012-02-01

Lipid based colloids (e.g. emulsions and liposomes) are widely used as drug delivery systems, but often suffer from physical instabilities and non-ideal drug encapsulation and delivery performance. We review the application of engineered nanoparticle layers at the interface of lipid colloids to improve their performance as drug delivery systems. In addition we focus on the creation of novel hybrid nanomaterials from nanoparticle-lipid colloid assemblies and their drug delivery applications. Specifically, nanoparticle layers can be engineered to enhance the physical stability of submicron lipid emulsions and liposomes, satbilise encapsulated active ingredients against chemical degradation, control molecular transport and improve the dermal and oral delivery characteristics, i.e. increase absorption, bioavailability and facilitate targeted delivery. It is feasible that hybrid nanomaterials composed of nanoparticles and colloidal lipids are effective encapsulation and delivery systems for both poorly soluble drugs and biological drugs and may form the basis for the next generation of medicines. Additional pre-clinical research including specific animal model studies are required to advance the peptide/protein delivery systems, whereas the silica lipid hybrid systems have now entered human clinical trials for poorly soluble drugs.

[Neurological disorders and the blood-brain barrier. Strategies and limitations for drug delivery to the brain].

PubMed

Domínguez, Alazne; Álvarez, Antonia; Suárez-Merino, Blanca; Goñi-de-Cerio, Felipe

2014-03-01

The incidence in the central nervous system diseases has increased with a growing elderly population. Unfortunately, conventional treatments used to treat the mentioned diseases are frequently ineffective due to the presence of the blood brain barrier. To illustrate the blood-brain barrier properties that limit drug transport into the brain and the main strategies employed to treat neurologic disorders. The blood-brain barrier is mainly composed of a specialized microvascular endothelium and of glial cells. It constitutes a valuable tool to separate the central nervous system from the rest of the body. Nevertheless, it also represents an obstacle to the delivery of therapeutic drugs to the brain. To be effective, drugs must reach their target in the brain. On one hand, therapeutic agents could be designed to be able to cross the blood brain barrier. On the other hand, drug delivery systems could be employed to facilitate the therapeutic agents' entry into the central nervous system. In vivo models of neurological diseases, in addition to in vitro models of the blood brain barrier, have been widely employed for the evaluation of drugs utilized to treat central nervous system diseases.

EGNOS Tran Solutions for River Information Services

NASA Astrophysics Data System (ADS)

Jandrisits, Marko; de Mateo Garcia, Juan Carlos; Abwerzger, Gunther

2005-03-01

Within the ESA Advanced Research Telecommunications program ARTES-5, the project GALEWAT (Galileo and EGNOS for Waterway Transport) aims at introducing EGNOS into River Information Systems (RIS) through the Automatic Identification System (AIS).The GALEWAT project is carried out by a consortium composed by via donau (Austria), responsible for the overall project coordination and the operations in Vienna; Kongsberg Seatex AS (Norway), mainly responsible for the ship and shore equipment provision and installation; TeleConsult Austria (Austria), responsible for the geodetic reference system and performance evaluation of the tests, and INOV (Portugal), responsible for software development, i.e. performance monitor software and web interface for the external segment.During the definition phase, the system architecture and user equipment have been defined, in line with standards and international recommendations. The activity is currently in its implementation phase. Three demo sites are targeted: Vienna (Austria), Lisbon (Portugal) and Constanta (Romania) in order to illustrate the system in different environments (river navigation, harbour approach, open sea). The objective of this paper is to present the results of the tests and demo trials that took place based on the EGNOS signals during the last quarter of 2004 in Vienna.

Enhancing interpretability of automatically extracted machine learning features: application to a RBM-Random Forest system on brain lesion segmentation.

PubMed

Pereira, Sérgio; Meier, Raphael; McKinley, Richard; Wiest, Roland; Alves, Victor; Silva, Carlos A; Reyes, Mauricio

2018-02-01

Machine learning systems are achieving better performances at the cost of becoming increasingly complex. However, because of that, they become less interpretable, which may cause some distrust by the end-user of the system. This is especially important as these systems are pervasively being introduced to critical domains, such as the medical field. Representation Learning techniques are general methods for automatic feature computation. Nevertheless, these techniques are regarded as uninterpretable "black boxes". In this paper, we propose a methodology to enhance the interpretability of automatically extracted machine learning features. The proposed system is composed of a Restricted Boltzmann Machine for unsupervised feature learning, and a Random Forest classifier, which are combined to jointly consider existing correlations between imaging data, features, and target variables. We define two levels of interpretation: global and local. The former is devoted to understanding if the system learned the relevant relations in the data correctly, while the later is focused on predictions performed on a voxel- and patient-level. In addition, we propose a novel feature importance strategy that considers both imaging data and target variables, and we demonstrate the ability of the approach to leverage the interpretability of the obtained representation for the task at hand. We evaluated the proposed methodology in brain tumor segmentation and penumbra estimation in ischemic stroke lesions. We show the ability of the proposed methodology to unveil information regarding relationships between imaging modalities and extracted features and their usefulness for the task at hand. In both clinical scenarios, we demonstrate that the proposed methodology enhances the interpretability of automatically learned features, highlighting specific learning patterns that resemble how an expert extracts relevant data from medical images. Copyright © 2017 Elsevier B.V. All rights reserved.

Stroke, music, and creative output: Alfred Schnittke and other composers.

PubMed

Zagvazdin, Yuri

2015-01-01

Alfred Schnittke (1934-1998), a celebrated Russian composer of the twentieth century, suffered from several strokes which affected his left cerebral hemisphere. The disease, however, did not diminish his musical talent. Moreover, he stated that his illness in a way facilitated his work. The composer showed amazingly high productivity after his first and second injuries of the central nervous system. The main topic of this chapter is the effect of strokes on Schnittke's output, creativity, and style of music. A brief biography of the composer with the chronology of his brain hemorrhages is included. In addition, the influence of cerebrovascular lesions on creative potential of other prominent composers such as Benjamin Britten, Jean Langlais, Vissarion Shebalin, Igor Stravinsky, and Ira Randall Thompson is discussed. © 2015 Elsevier B.V. All rights reserved.

The charged black-hole bomb: A lower bound on the charge-to-mass ratio of the explosive scalar field

NASA Astrophysics Data System (ADS)

Hod, Shahar

2016-04-01

The well-known superradiant amplification mechanism allows a charged scalar field of proper mass μ and electric charge q to extract the Coulomb energy of a charged Reissner-Nordström black hole. The rate of energy extraction can grow exponentially in time if the system is placed inside a reflecting cavity which prevents the charged scalar field from escaping to infinity. This composed black-hole-charged-scalar-field-mirror system is known as the charged black-hole bomb. Previous numerical studies of this composed physical system have shown that, in the linearized regime, the inequality q / μ > 1 provides a necessary condition for the development of the superradiant instability. In the present paper we use analytical techniques to study the instability properties of the charged black-hole bomb in the regime of linearized scalar fields. In particular, we prove that the lower bound q/μ>√{rm /r- - 1/ rm /r+ - 1 } provides a necessary condition for the development of the superradiant instability in this composed physical system (here r± are the horizon radii of the charged Reissner-Nordström black hole and rm is the radius of the confining mirror). This analytically derived lower bound on the superradiant instability regime of the composed black-hole-charged-scalar-field-mirror system is shown to agree with direct numerical computations of the instability spectrum.

Photopolymerization Synthesis of Magnetic Nanoparticle Embedded Nanogels for Targeted Biotherapeutic Delivery

NASA Astrophysics Data System (ADS)

Denmark, Daniel J.

Conventional therapeutic techniques treat the patient by delivering a biotherapeutic to the entire body rather than the target tissue. In the case of chemotherapy, the biotherapeutic is a drug that kills healthy and diseased cells indiscriminately which can lead to undesirable side effects. With targeted delivery, biotherapeutics can be delivered directly to the diseased tissue significantly reducing exposure to otherwise healthy tissue. Typical composite delivery devices are minimally composed of a stimuli responsive polymer, such as poly(N-isopropylacrylamide), allowing for triggered release when heated beyond approximately 32 °C, and magnetic nanoparticles which enable targeting as well as provide a mechanism for stimulus upon alternating magnetic field heating. Although more traditional methods, such as emulsion polymerization, have been used to realize these composite devices, the synthesis is problematic. Poisonous surfactants that are necessary to prevent agglomeration must be removed from the finished polymer, increasing the time and cost of the process. This study seeks to further explore non-toxic, biocompatible, non-residual, photochemical methods of creating stimuli responsive nanogels to advance the targeted biotherapeutic delivery field. Ultraviolet photopolymerization promises to be more efficient, while ensuring safety by using only biocompatible substances. The reactants selected for nanogel fabrication were N -isopropylacrylamide as monomer, methylene bisacrylamide as cross-linker, and Irgacure 2959 as ultraviolet photo-initiator. The superparamagnetic nanoparticles for encapsulation were approximately 10 nm in diameter and composed of magnetite to enable remote delivery and enhanced triggered release properties. Early investigations into the interactions of the polymer and nanoparticles employ a pioneering experimental setup, which allows for coincident turbidimetry and alternating magnetic field heating of an aqueous solution containing both materials. Herein, a low-cost, scalable, and rapid, custom ultraviolet photo-reactor with in-situ, spectroscopic monitoring system is used to observe the synthesis as the sample undergoes photopolymerization. This method also allows in-situ encapsulation of the magnetic nanoparticles simplifying the process. Size characterization of the resulting nanogels was performed by Transmission Electron Microscopy revealing size-tunable nanogel spheres between 50 and 800 nm by varying the ratio and concentration of the reactants. Nano-Tracking Analysis indicates that the nanogels exhibit minimal agglomeration as well as provides a temperature-dependent particle size distribution. Optical characterization utilized Fourier Transform Infrared and Ultraviolet Spectroscopy to confirm successful polymerization. When samples of the nanogels encapsulating magnetic nanoparticles were subjected to an alternating magnetic field a temperature increase was observed indicating that triggered release is possible. Furthermore, a model, based on linear response theory that innovatively utilizes size distribution data, is presented to explain alternating magnetic field heating results. The results presented here will advance targeted biotherapeutic delivery and have a wide range of applications in medical sciences like oncology, gene delivery, cardiology and endocrinology.

Improving the Army’s Joint Platform Allocation Tool (JPAT)

DTIC Science & Technology

2013-09-01

INTENTIONALLY LEFT BLANK ix LIST OF FIGURES Figure 1. Three example systems composed of platforms P1, P2, and P3, and sensors SN1, SN2 , SN3, and SN4...Figure 1. Three example systems composed of platforms P1, P2, and P3, and sensors SN1, SN2 , SN3, and SN4 (from Craparo et al., 2013) Figure 2. A

Two conceptual designs of helical fusion reactor FFHR-d1A based on ITER technologies and challenging ideas

NASA Astrophysics Data System (ADS)

Sagara, A.; Miyazawa, J.; Tamura, H.; Tanaka, T.; Goto, T.; Yanagi, N.; Sakamoto, R.; Masuzaki, S.; Ohtani, H.; The FFHR Design Group

2017-08-01

The Fusion Engineering Research Project (FERP) at the National Institute for Fusion Science (NIFS) is conducting conceptual design activities for the LHD-type helical fusion reactor FFHR-d1A. This paper newly defines two design options, ‘basic’ and ‘challenging.’ Conservative technologies, including those that will be demonstrated in ITER, are chosen in the basic option in which two helical coils are made of continuously wound cable-in-conduit superconductors of Nb3Sn strands, the divertor is composed of water-cooled tungsten monoblocks, and the blanket is composed of water-cooled ceramic breeders. In contrast, new ideas that would possibly be beneficial for making the reactor design more attractive are boldly included in the challenging option in which the helical coils are wound by connecting high-temperature REBCO superconductors using mechanical joints, the divertor is composed of a shower of molten tin jets, and the blanket is composed of molten salt FLiNaBe including Ti powers to increase hydrogen solubility. The main targets of the challenging option are early construction and easy maintenance of a large and three-dimensionally complicated helical structure, high thermal efficiency, and, in particular, realistic feasibility of the helical reactor.

Range optimization for mono- and bi-energetic proton modulated arc therapy with pencil beam scanning

NASA Astrophysics Data System (ADS)

Sanchez-Parcerisa, Daniel; Kirk, Maura; Fager, Marcus; Burgdorf, Brendan; Stowe, Malorie; Solberg, Tim; Carabe, Alejandro

2016-11-01

The development of rotational proton therapy plans based on a pencil-beam-scanning (PBS) system has been limited, among several other factors, by the energy-switching time between layers, a system-dependent parameter that ranges between a fraction of a second and several seconds. We are investigating mono- and bi-energetic rotational proton modulated arc therapy (PMAT) solutions that would not be affected by long energy switching times. In this context, a systematic selection of the optimal proton energy for each arc is vital. We present a treatment planning comparison of four different range selection methods, analyzing the dosimetric outcomes of the resulting treatment plans created with the ranges obtained. Given the patient geometry and arc definition (gantry and couch trajectories, snout elevation) our in-house treatment planning system (TPS) FoCa was used to find the maximum, medial and minimum water-equivalent thicknesses (WETs) of the target viewed from all possible field orientations. Optimal ranges were subsequently determined using four methods: (1) by dividing the max/min WET interval into equal steps, (2) by taking the average target midpoints from each field, (3) by taking the average WET of all voxels from all field orientations, and (4) by minimizing the fraction of the target which cannot be reached from any of the available angles. After the range (for mono-energetic plans) or ranges (for bi-energetic plans) were selected, the commercial clinical TPS in use in our institution (Varian Eclipse™) was used to produce the PMAT plans using multifield optimization. Linear energy transfer (LET) distributions of all plans were also calculated using FoCa and compared among the different methods. Mono- and bi-energetic PMAT plans, composed of a single 180° arc, were created for two patient geometries: a C-shaped target located in the mediastinal area of a thoracic tissue-equivalent phantom and a small brain tumor located directly above the brainstem. All plans were optimized using the same procedure to (1) achieve target coverage, (2) reduce dose to OAR and (3) limit dose hot spots in the target. Final outcomes were compared in terms of the resulting dose and LET distributions. Data shows little significant differences among the four studied methods, with superior results obtained with mono-energetic plans. A streamlined systematic method has been implemented in an in-house TPS to find the optimal range to maximize target coverage with rotational mono- or bi-energetic PBS rotational plans by minimizing the fraction of the target that cannot be reached by any direction.

Current nonclinical testing paradigm enables safe entry to First-In-Human clinical trials: The IQ consortium nonclinical to clinical translational database.

PubMed

Monticello, Thomas M; Jones, Thomas W; Dambach, Donna M; Potter, David M; Bolt, Michael W; Liu, Maggie; Keller, Douglas A; Hart, Timothy K; Kadambi, Vivek J

2017-11-01

The contribution of animal testing in drug development has been widely debated and challenged. An industry-wide nonclinical to clinical translational database was created to determine how safety assessments in animal models translate to First-In-Human clinical risk. The blinded database was composed of 182 molecules and contained animal toxicology data coupled with clinical observations from phase I human studies. Animal and clinical data were categorized by organ system and correlations determined. The 2×2 contingency table (true positive, false positive, true negative, false negative) was used for statistical analysis. Sensitivity was 48% with a 43% positive predictive value (PPV). The nonhuman primate had the strongest performance in predicting adverse effects, especially for gastrointestinal and nervous system categories. When the same target organ was identified in both the rodent and nonrodent, the PPV increased. Specificity was 84% with an 86% negative predictive value (NPV). The beagle dog had the strongest performance in predicting an absence of clinical adverse effects. If no target organ toxicity was observed in either test species, the NPV increased. While nonclinical studies can demonstrate great value in the PPV for certain species and organ categories, the NPV was the stronger predictive performance measure across test species and target organs indicating that an absence of toxicity in animal studies strongly predicts a similar outcome in the clinic. These results support the current regulatory paradigm of animal testing in supporting safe entry to clinical trials and provide context for emerging alternate models. Copyright © 2017 Elsevier Inc. All rights reserved.

A fast and simple label-free immunoassay based on a smartphone.

PubMed

Giavazzi, Fabio; Salina, Matteo; Ceccarello, Erica; Ilacqua, Andrea; Damin, Francesco; Sola, Laura; Chiari, Marcella; Chini, Bice; Cerbino, Roberto; Bellini, Tommaso; Buscaglia, Marco

2014-08-15

Despite the continuous advancements in bio-molecular detection and fluidic systems integration, the realization of portable and high performance devices for diagnostic applications still presents major difficulties, mostly because of the need to combine adequate sensitivity with low cost of production and operational simplicity and speed. In this context, we propose a compact device composed of a smartphone and a custom-designed cradle, containing only a disposable sensing cartridge, a tiny magnetic stirrer and a few passive optical components. The detection principle is the previously proposed Reflective Phantom Interface that is based on measuring the intensity of light reflected by the surface of an amorphous fluoropolymer substrate, which has a refractive index very close to that of the aqueous sample solution and hosts various antibodies immobilized within spots. The reflectivity of dozens of spots is monitored in real time by the phone׳s camera using the embedded flash LED as the illumination source. We test the performance of the combined device targeting heterologous immunoglobulins and antigens commonly used as markers for diagnoses of hepatitis B and HIV. Target concentrations as low as a few ng/ml can be rapidly and robustly determined by comparing the rate of increase of the signal after the addition of the sample with that measured after the subsequent addition of a standard solution with known concentration. The features of the proposed system enable the realization of novel handheld biosensing devices suitable for those applications where multiple targets have to be rapidly detected even without the presence of trained personnel. Copyright © 2014 Elsevier B.V. All rights reserved.

Numerical simulations of impacts involving porous bodies. II. Comparison with laboratory experiments

NASA Astrophysics Data System (ADS)

Jutzi, Martin; Michel, Patrick; Hiraoka, Kensuke; Nakamura, Akiko M.; Benz, Willy

2009-06-01

In this paper, we compare the outcome of high-velocity impact experiments on porous targets, composed of pumice, with the results of simulations by a 3D SPH hydrocode in which a porosity model has been implemented. The different populations of small bodies of our Solar System are believed to be composed, at least partially, of objects with a high degree of porosity. To describe the fragmentation of such porous objects, a different model is needed than that used for non-porous bodies. In the case of porous bodies, the impact process is not only driven by the presence of cracks which propagate when a stress threshold is reached, it is also influenced by the crushing of pores and compaction. Such processes can greatly affect the whole body's response to an impact. Therefore, another physical model is necessary to improve our understanding of the collisional process involving porous bodies. Such a model has been developed recently and introduced successfully in a 3D SPH hydrocode [Jutzi, M., Benz, W., Michel, P., 2008. Icarus 198, 242-255]. Basic tests have been performed which already showed that it is implemented in a consistent way and that theoretical solutions are well reproduced. However, its full validation requires that it is also capable of reproducing the results of real laboratory impact experiments. Here we present simulations of laboratory experiments on pumice targets for which several of the main material properties have been measured. We show that using the measured material properties and keeping the remaining free parameters fixed, our numerical model is able to reproduce the outcome of these experiments carried out under different impact conditions. This first complete validation of our model, which will be tested for other porous materials in the future, allows us to start addressing problems at larger scale related to small bodies of our Solar System, such as collisions in the Kuiper Belt or the formation of a family by the disruption of a porous parent body in the main asteroid belt.

40 CFR 255.11 - Criteria for identifying agencies.

Code of Federal Regulations, 2011 CFR

2011-07-01

...) Be a representative organization composed of, or whose membership is composed of, individuals at... waste management system and comprehensive planning which -addresses trade-offs among various media. (e... waste to supply disposal or recovery facilities should be addressed. The Agency providing such...

Development of a method to screen and isolate potential xanthine oxidase inhibitors from Panax japlcus var via ultrafiltration liquid chromatography combined with counter-current chromatography.

PubMed

Li, Sainan; Tang, Ying; Liu, Chunming; Li, Jing; Guo, Liping; Zhang, Yuchi

2015-03-01

Panax japlcus var is a typical Chinese herb with a large number of saponins existing in all parts of it. The common methods of screening and isolating saponins are mostly labor-intensive and time-consuming. In this study, a new assay based on ultrafiltration-liquid chromatography-mass spectrometry (UF-LC-MS) was developed for the rapid screening and identifying of the ligands for xanthine oxidase from the extract of P. japlcus. Six saponins were identified as xanthine oxidase inhibitors from the extract. Subsequently, the specific binding ligands, namely, 24 (R)-majoroside R1, chikusetsusaponin IVa, oleanolic acid-28-O-β-D-glucopyranoside, notoginsenoside Fe, ginsenoside Rb2 and ginsenoside Rd (the purities of them were 95.74%, 96.12%, 93.19%, 94.83%, 95.07% and 94.62%, respectively) were separated by high-speed counter-current chromatography (HSCCC). The component ratio of the solvent system of HSCCC was calculated with the help of a multiexponential function model was optimized. The partition coefficient (K) values of the target compounds and resolutions of peaks were employed as the research indicators, and exponential function and binomial formulas were used to optimize the solvent system and flow rate of the mobile phases in a two-stage separation. An optimized two-phase solvent system composed of ethyl acetate, isopropanol, 0.1% aqueous formic acid (1.9:1.0:1.3, v/v/v, for the first-stage) and that composed of methylene chloride, acetonitrile, isopropanol, 0.1% aqueous formic acid (5.6:1.0:2.4:5.2, v/v/v/v, for the second-stage) were used to isolate the six compounds from P. japlcus. The targeted compounds isolated, collected and purified by HSCCC were analyzed by high performance liquid chromatography (UPLC), and the chemical structures of all the six compounds were identified by UV, MS and NMR. The results demonstrate that UF-LC-MS combined with HSCCC might provide not only a powerful tool for screening and isolating xanthine oxidase inhibitors in complex samples but also a useful platform for discovering bioactive compounds for the prevention and treatment of gout. Copyright © 2014 Elsevier B.V. All rights reserved.

Systemic surfaceome profiling identifies target antigens for immune-based therapy in subtypes of advanced prostate cancer

PubMed Central

Lee, John K.; Bangayan, Nathanael J.; Chai, Timothy; Smith, Bryan A.; Pariva, Tiffany E.; Yun, Sangwon; Vashisht, Ajay; Zhang, Qingfu; Park, Jung Wook; Corey, Eva; Huang, Jiaoti; Wohlschlegel, James; Witte, Owen N.

2018-01-01

Prostate cancer is a heterogeneous disease composed of divergent molecular and histologic subtypes, including prostate adenocarcinoma (PrAd) and neuroendocrine prostate cancer (NEPC). While PrAd is the major histology in prostate cancer, NEPC can evolve from PrAd as a mechanism of treatment resistance that involves a transition from an epithelial to a neurosecretory cancer phenotype. Cell surface markers are often associated with specific cell lineages and differentiation states in normal development and cancer. Here, we show that PrAd and NEPC can be broadly discriminated by cell-surface profiles based on the analysis of prostate cancer gene expression datasets. To overcome a dependence on predictions of human cell-surface genes and an assumed correlation between mRNA levels and protein expression, we integrated transcriptomic and cell-surface proteomic data generated from a panel of prostate cancer cell lines to nominate cell-surface markers associated with these cancer subtypes. FXYD3 and CEACAM5 were validated as cell-surface antigens enriched in PrAd and NEPC, respectively. Given the lack of effective treatments for NEPC, CEACAM5 appeared to be a promising target for cell-based immunotherapy. As a proof of concept, engineered chimeric antigen receptor T cells targeting CEACAM5 induced antigen-specific cytotoxicity in NEPC cell lines. Our findings demonstrate that the surfaceomes of PrAd and NEPC reflect unique cancer differentiation states and broadly represent vulnerabilities amenable to therapeutic targeting. PMID:29686080

Alkylation sensitivity screens reveal a conserved cross-species functionome

PubMed Central

Svilar, David; Dyavaiah, Madhu; Brown, Ashley R.; Tang, Jiang-bo; Li, Jianfeng; McDonald, Peter R.; Shun, Tong Ying; Braganza, Andrea; Wang, Xiao-hong; Maniar, Salony; St Croix, Claudette M.; Lazo, John S.; Pollack, Ian F.; Begley, Thomas J.; Sobol, Robert W.

2013-01-01

To identify genes that contribute to chemotherapy resistance in glioblastoma, we conducted a synthetic lethal screen in a chemotherapy-resistant glioblastoma derived cell line with the clinical alkylator temozolomide (TMZ) and an siRNA library tailored towards “druggable” targets. Select DNA repair genes in the screen were validated independently, confirming the DNA glycosylases UNG and MYH as well as MPG to be involved in the response to high dose TMZ. The involvement of UNG and MYH is likely the result of a TMZ-induced burst of reactive oxygen species. We then compared the human TMZ sensitizing genes identified in our screen with those previously identified from alkylator screens conducted in E. coli and S. cerevisiae. The conserved biological processes across all three species composes an Alkylation Functionome that includes many novel proteins not previously thought to impact alkylator resistance. This high-throughput screen, validation and cross-species analysis was then followed by a mechanistic analysis of two essential nodes: base excision repair (BER) DNA glycosylases (UNG, human and mag1, S. cerevisiae) and protein modification systems, including UBE3B and ICMT in human cells or pby1, lip22, stp22 and aim22 in S. cerevisiae. The conserved processes of BER and protein modification were dual targeted and yielded additive sensitization to alkylators in S. cerevisiae. In contrast, dual targeting of BER and protein modification genes in human cells did not increase sensitivity, suggesting an epistatic relationship. Importantly, these studies provide potential new targets to overcome alkylating agent resistance. PMID:23038810

A SURVEY OF THE HIGH ORDER MULTIPLICITY OF NEARBY SOLAR-TYPE BINARY STARS WITH Robo-AO

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

Riddle, Reed L.; Bui, Khanh; Dekany, Richard G.

2015-01-20

We conducted a survey of nearby binary systems composed of main sequence stars of spectral types F and G in order to improve our understanding of the hierarchical nature of multiple star systems. Using Robo-AO, the first robotic adaptive optics instrument, we collected high angular resolution images with deep and well-defined detection limits in the Sloan Digital Sky Survey i' band. A total of 695 components belonging to 595 systems were observed. We prioritized observations of faint secondary components with separations over 10'' to quantify the still poorly constrained frequency of their subsystems. Of the 214 secondaries observed, 39 containmore » such subsystems; 19 of those were discovered with Robo-AO. The selection-corrected frequency of secondary subsystems with periods from 10{sup 3.5} to 10{sup 5} days is 0.12 ± 0.03, the same as the frequency of such companions to the primary. Half of the secondary pairs belong to quadruple systems where the primary is also a close pair, showing that the presence of subsystems in both components of the outer binary is correlated. The relatively large abundance of 2+2 quadruple systems is a new finding, and will require more exploration of the formation mechanism of multiple star systems. We also targeted close binaries with periods less than 100 yr, searching for their distant tertiary components, and discovered 17 certain and 2 potential new triples. In a subsample of 241 close binaries, 71 have additional outer companions. The overall frequency of tertiary components is not enhanced, compared to all (non-binary) targets, but in the range of outer periods from 10{sup 6} to 10{sup 7.5} days (separations on the order of 500 AU), the frequency of tertiary components is 0.16 ± 0.03, exceeding the frequency of similar systems among all targets (0.09) by almost a factor of two. Measurements of binary stars with Robo-AO allowed us to compute first orbits for 9 pairs and to improve orbits of another 11 pairs.« less

Deconvolution of Energy Spectra in the ATIC Experiment

NASA Technical Reports Server (NTRS)

Batkov, K. E.; Panov, A. D.; Adams, J. H.; Ahn, H. S.; Bashindzhagyan, G. L.; Chang, J.; Christl, M.; Fazley, A. R.; Ganel, O.; Gunasigha, R. M.;

Design of an electron-accelerator-driven compact neutron source for non-destructive assay

NASA Astrophysics Data System (ADS)

Murata, A.; Ikeda, S.; Hayashizaki, N.

2017-09-01

The threat of nuclear and radiological terrorism remains one of the greatest challenges to international security, and the threat is constantly evolving. In order to prevent nuclear terrorism, it is important to avoid unlawful import of nuclear materials, such as uranium and plutonium. Development of technologies for non-destructive measurement, detection and recognition of nuclear materials is essential for control at national borders. At Tokyo Institute of Technology, a compact neutron source system driven by an electron-accelerator has been designed for non-destructive assay (NDA). This system is composed of a combination of an S-band (2.856 GHz) RF-gun, a tungsten target to produce photons by bremsstrahlung, a beryllium target, which is suitable for use in generating neutrons because of the low threshold energy of photonuclear reactions, and a moderator to thermalize the fast neutrons. The advantage of this system can accelerate a short pulse beam with a pulse width less than 1 μs which is difficult to produce by neutron generators. The amounts of photons and neutron produced by electron beams were simulated using the Monte Carlo simulation code PHITS 2.82. When the RF-gun is operated with an average electron beam current of 0.1 mA, it is expected that the neutron intensities are 1.19 × 109 n/s and 9.94 × 109 n/s for incident electron beam energies of 5 MeV and 10 MeV, respectively.

Redox Regulation of Endothelial Cell Fate

PubMed Central

Song, Ping; Zou, Ming-Hui

2014-01-01

Endothelial cells (ECs) are present throughout blood vessels and have variable roles in both physiological and pathological settings. EC fate is altered and regulated by several key factors in physiological or pathological conditions. Reactive nitrogen species and reactive oxygen species derived from NAD(P)H oxidases, mitochondria, or nitric oxide-producing enzymes are not only cytotoxic but also compose a signaling network in the redox system. The formation, actions, key molecular interactions, and physiological and pathological relevance of redox signals in ECs remain unclear. We review the identities, sources, and biological actions of oxidants and reductants produced during EC function or dysfunction. Further, we discuss how ECs shape key redox sensors and examine the biological functions, transcriptional responses, and post-translational modifications evoked by the redox system in ECs. We summarize recent findings regarding the mechanisms by which redox signals regulate the fate of ECs and address the outcome of altered EC fate in health and disease. Future studies will examine if the redox biology of ECs can be targeted in pathophysiological conditions. PMID:24633153

Measurement system of the refractive power of spherical and sphero-cylindrical lenses with the magnification ellipse fitting method.

PubMed

Ko, Wooseok; Kim, Soohyun

2009-11-01

This paper proposes a new measurement system for measuring the refractive power of spherical and sphero-cylindrical lenses with a six-point light source, which is composed of a light emitting diode and a six-hole pattern aperture, and magnification ellipse fitting method. The position of the six light sources is changed into a circular or elliptical form subjected to the lens refractive power and meridian rotation angle. The magnification ellipse fitting method calculates the lens refractive power based on the ellipse equation with magnifications that are the ratios between initial diagonal lengths and measured diagonal lengths of the conjugated light sources changed by the target lens. The refractive powers of the spherical and sphero-cylindrical lenses certified in the Korea Research Institute of Standard and Science were measured to verify the measurement performance. The proposed method is estimated to have a repeatability of +/-0.01 D and an error value below 1%.

A Consideration of Stable Operating Power Limits of HVDC System Composed of Voltage Source Converters

NASA Astrophysics Data System (ADS)

Konishi, Hiroo; Takahashi, Choei; Kishibe, Hideto; Sato, Hiromichi

The stable operating power limits of a small scale HVDC system composed of voltage source converters (VSC-HVDC system) are analyzed with a simple model. The VSC-HVDC system could operate where the AC system must be somewhat larger in capacity than the VSC-HVDC system capacity. The stable operating power limits were between one and two times the SCR (short circuit ratio). When the inverter of the VSC-HVDC system was operated with lead reactive (capacitive) power control conditions, the stable operating limits were increased through AC voltage stabilization. When the inverter was a STATCOM operation, it could operate regardless of the SCR but regions within allowable AC voltage variations.

Accelerating a MPEG-4 video decoder through custom software/hardware co-design

NASA Astrophysics Data System (ADS)

Díaz, Jorge L.; Barreto, Dacil; García, Luz; Marrero, Gustavo; Carballo, Pedro P.; Núñez, Antonio

2007-05-01

In this paper we present a novel methodology to accelerate an MPEG-4 video decoder using software/hardware co-design for wireless DAB/DMB networks. Software support includes the services provided by the embedded kernel μC/OS-II, and the application tasks mapped to software. Hardware support includes several custom co-processors and a communication architecture with bridges to the main system bus and with a dual port SRAM. Synchronization among tasks is achieved at two levels, by a hardware protocol and by kernel level scheduling services. Our reference application is an MPEG-4 video decoder composed of several software functions and written using a special C++ library named CASSE. Profiling and space exploration techniques were used previously over the Advanced Simple Profile (ASP) MPEG-4 decoder to determinate the best HW/SW partition developed here. This research is part of the ARTEMI project and its main goal is the establishment of methodologies for the design of real-time complex digital systems using Programmable Logic Devices with embedded microprocessors as target technology and the design of multimedia systems for broadcasting networks as reference application.

EAGLE: relay mirror technology development

NASA Astrophysics Data System (ADS)

Hartman, Mary; Restaino, Sergio R.; Baker, Jeffrey T.; Payne, Don M.; Bukley, Jerry W.

2002-06-01

EAGLE (Evolutionary Air & Space Global Laser Engagement) is the proposed high power weapon system with a high power laser source, a relay mirror constellation, and the necessary ground and communications links. The relay mirror itself will be a satellite composed of two optically-coupled telescopes/mirrors used to redirect laser energy from ground, air, or space based laser sources to distant points on the earth or space. The receiver telescope captures the incoming energy, relays it through an optical system that cleans up the beam, then a separate transmitter telescope/mirror redirects the laser energy at the desired target. Not only is it a key component in extending the range of DoD's current laser weapon systems, it also enables ancillary missions. Furthermore, if the vacuum of space is utilized, then the atmospheric effects on the laser beam propagation will be greatly attenuated. Finally, several critical technologies are being developed to make the EAGLE/Relay Mirror concept a reality, and the Relay Mirror Technology Development Program was set up to address them. This paper will discuss each critical technology, the current state of the work, and the future implications of this program.

Integration of Si-CMOS embedded photo detector array and mixed signal processing system with embedded optical waveguide input

NASA Astrophysics Data System (ADS)

Kim, Daeik D.; Thomas, Mikkel A.; Brooke, Martin A.; Jokerst, Nan M.

2004-06-01

Arrays of embedded bipolar junction transistor (BJT) photo detectors (PD) and a parallel mixed-signal processing system were fabricated as a silicon complementary metal oxide semiconductor (Si-CMOS) circuit for the integration optical sensors on the surface of the chip. The circuit was fabricated with AMI 1.5um n-well CMOS process and the embedded PNP BJT PD has a pixel size of 8um by 8um. BJT PD was chosen to take advantage of its higher gain amplification of photo current than that of PiN type detectors since the target application is a low-speed and high-sensitivity sensor. The photo current generated by BJT PD is manipulated by mixed-signal processing system, which consists of parallel first order low-pass delta-sigma oversampling analog-to-digital converters (ADC). There are 8 parallel ADCs on the chip and a group of 8 BJT PDs are selected with CMOS switches. An array of PD is composed of three or six groups of PDs depending on the number of rows.

Text Coherence in Translation

ERIC Educational Resources Information Center

Zheng, Yanping

2009-01-01

In the thesis a coherent text is defined as a continuity of senses of the outcome of combining concepts and relations into a network composed of knowledge space centered around main topics. And the author maintains that in order to obtain the coherence of a target language text from a source text during the process of translation, a translator can…

Toward Market Education: Are Vouchers or Tax Credits the Better Path? Policy Analysis No. 392.

ERIC Educational Resources Information Center

Coulson, Andrew J.

This paper compares voucher and tax credit programs on how well they manifest the necessary conditions for market education and allow all families to participate in that market. Voucher programs include targeted and universal programs. The tax credit proposal is a nonrefundable, education credit composed of: a parental choice credit for taxpayers…

3D mouse shape reconstruction based on phase-shifting algorithm for fluorescence molecular tomography imaging system.

PubMed

Zhao, Yue; Zhu, Dianwen; Baikejiang, Reheman; Li, Changqing

2015-11-10

This work introduces a fast, low-cost, robust method based on fringe pattern and phase shifting to obtain three-dimensional (3D) mouse surface geometry for fluorescence molecular tomography (FMT) imaging. We used two pico projector/webcam pairs to project and capture fringe patterns from different views. We first calibrated the pico projectors and the webcams to obtain their system parameters. Each pico projector/webcam pair had its own coordinate system. We used a cylindrical calibration bar to calculate the transformation matrix between these two coordinate systems. After that, the pico projectors projected nine fringe patterns with a phase-shifting step of 2π/9 onto the surface of a mouse-shaped phantom. The deformed fringe patterns were captured by the corresponding webcam respectively, and then were used to construct two phase maps, which were further converted to two 3D surfaces composed of scattered points. The two 3D point clouds were further merged into one with the transformation matrix. The surface extraction process took less than 30 seconds. Finally, we applied the Digiwarp method to warp a standard Digimouse into the measured surface. The proposed method can reconstruct the surface of a mouse-sized object with an accuracy of 0.5 mm, which we believe is sufficient to obtain a finite element mesh for FMT imaging. We performed an FMT experiment using a mouse-shaped phantom with one embedded fluorescence capillary target. With the warped finite element mesh, we successfully reconstructed the target, which validated our surface extraction approach.

Miniature Sensor Probe for O2, CO2, and H2O Monitoring in Portable Life Support Systems

NASA Technical Reports Server (NTRS)

Delgado, Jesus; Chambers, Antja

2013-01-01

A miniature sensor probe, composed of four sensors which monitor the partial pressure of O2, CO2, H2O, and temperature, designed to operate in the portable life support system (PLSS), has been demonstrated. The probe provides an important advantage over existing technology in that it is able to operate reliably while wet. These luminescence-based fiber optic sensors consist of an indicator chemistry immobilized in a polymeric film, whose emission lifetime undergoes a strong change upon a reversible interaction with the target gas. Each sensor includes chemistry specifically sensitive to one target parameter. All four sensors are based on indicator chemistries that include luminescent dyes from the same chemical family, and therefore exhibit similar photochemical properties, which allow performing measurements of all the sensors by a single, compact, low-power optoelectronic unit remotely connected to the sensors by an electromagnetic interference-proof optical fiber cable. For space systems, using these miniature sensor elements with remote optoelectronics provides unmatched design flexibility for measurements in highly constrained volume systems such as the PLSS. A 10 mm diameter and 15 mm length prototype multiparameter probe was designed, fabricated, tested, and demonstrated over a wide operational range of gas concentration, humidity, and temperature relevant to operation in the PLSS. The sensors were evaluated for measurement range, precision, accuracy, and response time in temperatures ranging from 50 aF-150 aF and relative humidity from dry to 100% RH. Operation of the sensors in water condensation conditions was demonstrated wherein the sensors not only tolerated liquid water but actually operated while wet.

Characteristics comparison between a cyclotron-based neutron source and KUR-HWNIF for boron neutron capture therapy

NASA Astrophysics Data System (ADS)

Tanaka, H.; Sakurai, Y.; Suzuki, M.; Masunaga, S.; Kinashi, Y.; Kashino, G.; Liu, Y.; Mitsumoto, T.; Yajima, S.; Tsutsui, H.; Maruhashi, A.; Ono, K.

2009-06-01

At Kyoto University Research Reactor Institute (KURRI), 275 clinical trials of boron neutron capture therapy (BNCT) have been performed as of March 2006, and the effectiveness of BNCT has been revealed. In order to further develop BNCT, it is desirable to supply accelerator-based epithermal-neutron sources that can be installed near the hospital. We proposed the method of filtering and moderating fast neutrons, which are emitted from the reaction between a beryllium target and 30-MeV protons accelerated by a cyclotron accelerator, using an optimum moderator system composed of iron, lead, aluminum and calcium fluoride. At present, an epithermal-neutron source is under construction from June 2008. This system consists of a cyclotron accelerator, beam transport system, neutron-yielding target, filter, moderator and irradiation bed. In this article, an overview of this system and the properties of the treatment neutron beam optimized by the MCNPX Monte Carlo neutron transport code are presented. The distribution of biological effect weighted dose in a head phantom compared with that of Kyoto University Research Reactor (KUR) is shown. It is confirmed that for the accelerator, the biological effect weighted dose for a deeply situated tumor in the phantom is 18% larger than that for KUR, when the limit dose of the normal brain is 10 Gy-eq. The therapeutic time of the cyclotron-based neutron sources are nearly one-quarter of that of KUR. The cyclotron-based epithermal-neutron source is a promising alternative to reactor-based neutron sources for treatments by BNCT.

Magnetic-Fe/Fe(3)O(4)-nanoparticle-bound SN38 as carboxylesterase-cleavable prodrug for the delivery to tumors within monocytes/macrophages.

PubMed

Wang, Hongwang; Shrestha, Tej B; Basel, Matthew T; Dani, Raj Kumar; Seo, Gwi-Moon; Balivada, Sivasai; Pyle, Marla M; Prock, Heidy; Koper, Olga B; Thapa, Prem S; Moore, David; Li, Ping; Chikan, Viktor; Troyer, Deryl L; Bossmann, Stefan H

2012-01-01

The targeted delivery of therapeutics to the tumor site is highly desirable in cancer treatment, because it is capable of minimizing collateral damage. Herein, we report the synthesis of a nanoplatform, which is composed of a 15 ± 1 nm diameter core/shell Fe/Fe(3)O(4) magnetic nanoparticles (MNPs) and the topoisomerase I blocker SN38 bound to the surface of the MNPs via a carboxylesterase cleavable linker. This nanoplatform demonstrated high heating ability (SAR = 522 ± 40 W/g) in an AC-magnetic field. For the purpose of targeted delivery, this nanoplatform was loaded into tumor-homing double-stable RAW264.7 cells (mouse monocyte/macrophage-like cells (Mo/Ma)), which have been engineered to express intracellular carboxylesterase (InCE) upon addition of doxycycline by a Tet-On Advanced system. The nanoplatform was taken up efficiently by these tumor-homing cells. They showed low toxicity even at high nanoplatform concentration. SN38 was released successfully by switching on the Tet-On Advanced system. We have demonstrated that this nanoplatform can be potentially used for thermochemotherapy. We will be able to achieve the following goals: (1) Specifically deliver the SN38 prodrug and magnetic nanoparticles to the cancer site as the payload of tumor-homing double-stable RAW264.7 cells; (2) Release of chemotherapeutic SN38 at the cancer site by means of the self-containing Tet-On Advanced system; (3) Provide localized magnetic hyperthermia to enhance the cancer treatment, both by killing cancer cells through magnetic heating and by activating the immune system.

Dual linear accelerator system for use in sterilization of medical disposable supplies

NASA Astrophysics Data System (ADS)

Sadat, Theo

1991-05-01

Accelerators can be used for sterilization or decontamination (medical disposables, food, plastics, hospital waste, etc.). Most of these accelerators are located in an industrial environment and must have a high availability. A dual accelerator system (composed of two accelerators) offers optimal flexibility and reliability. The main advantage of this system is "all-in all-out" because it does not need a turnover of products. Such a dual system, composed of two 10 MeV 20 kW linear accelerators (instead of one 40 kW linac), has been chosen by a Swedish company (Mölnlycke).

Modular Power Standard for Space Explorations Missions

NASA Technical Reports Server (NTRS)

Oeftering, Richard C.; Gardner, Brent G.

2016-01-01

Future human space exploration will most likely be composed of assemblies of multiple modular spacecraft elements with interconnected electrical power systems. An electrical system composed of a standardized set modular building blocks provides significant development, integration, and operational cost advantages. The modular approach can also provide the flexibility to configure power systems to meet the mission needs. A primary goal of the Advanced Exploration Systems (AES) Modular Power System (AMPS) project is to establish a Modular Power Standard that is needed to realize these benefits. This paper is intended to give the space exploration community a "first look" at the evolving Modular Power Standard and invite their comments and technical contributions.

User-composable Electronic Health Record Improves Efficiency of Clinician Data Viewing for Patient Case Appraisal: A Mixed-Methods Study.

PubMed

Senathirajah, Yalini; Kaufman, David; Bakken, Suzanne

2016-01-01

Challenges in the design of electronic health records (EHRs) include designing usable systems that must meet the complex, rapidly changing, and high-stakes information needs of clinicians. The ability to move and assemble elements together on the same page has significant human-computer interaction (HCI) and efficiency advantages, and can mitigate the problems of negotiating multiple fixed screens and the associated cognitive burdens. We compare MedWISE-a novel EHR that supports user-composable displays-with a conventional EHR in terms of the number of repeat views of data elements for patient case appraisal. The study used mixed-methods for examination of clinical data viewing in four patient cases. The study compared use of an experimental user-composable EHR with use of a conventional EHR, for case appraisal. Eleven clinicians used a user-composable EHR in a case appraisal task in the laboratory setting. This was compared with log file analysis of the same patient cases in the conventional EHR. We investigated the number of repeat views of the same clinical information during a session and across these two contexts, and compared them using Fisher's exact test. There was a significant difference (p<.0001) in proportion of cases with repeat data element viewing between the user-composable EHR (14.6 percent) and conventional EHR (72.6 percent). Users of conventional EHRs repeatedly viewed the same information elements in the same session, as revealed by log files. Our findings are consistent with the hypothesis that conventional systems require that the user view many screens and remember information between screens, causing the user to forget information and to have to access the information a second time. Other mechanisms (such as reduction in navigation over a population of users due to interface sharing, and information selection) may also contribute to increased efficiency in the experimental system. Systems that allow a composable approach that enables the user to gather together on the same screen any desired information elements may confer cognitive support benefits that can increase productive use of systems by reducing fragmented information. By reducing cognitive overload, it can also enhance the user experience.

3-D Modeling of Planar Target-Mount Perturbation Experiments on OMEGA

NASA Astrophysics Data System (ADS)

Collins, T. J. B.; Marshall, F. J.; Marozas, J. A.; Bonino, M. J.; Forties, R.; Goncharov, V. N.; Igumenshchev, I. V.; McKenty, P. W.; Smalyuk, V. A.

2008-11-01

OMEGA cryogenic targets are suspended in the target chamber using four spider silks attached to a C-shaped mount. The spider silks are typically composed of two entwined protein strands comparable to 1 μm in diameter. The silks and mount refract the incident laser light and cast shadows on the target surface. Experiments to measure the effects of the silks on target illumination have been performed in planar geometry using silks suspended parallel to a 20-μm-thick laser-driven target. The evolution of the surface perturbations introduced by the silks was measured using x-ray backlighting. The results of these experiments will be compared to simulations performed with DRACO, employing three-dimensional (3-D) planar hydrodynamics and a new 3-D refractive ray-trace package written specifically for this geometry. This work was supported by the U.S. Department of Energy Office of Inertial Confinement Fusion under Cooperative Agreement No. DE-FC52-08NA28302.

Selective Targeting of Proteins within Secretory Pathway for Endoplasmic Reticulum-associated Degradation

PubMed Central

Vecchi, Lara; Petris, Gianluca; Bestagno, Marco; Burrone, Oscar R.

2012-01-01

The endoplasmic reticulum-associated degradation (ERAD) is a cellular quality control mechanism to dispose of misfolded proteins of the secretory pathway via proteasomal degradation. SEL1L is an ER-resident protein that participates in identification of misfolded molecules as ERAD substrates, therefore inducing their ER-to-cytosol retrotranslocation and degradation. We have developed a novel class of fusion proteins, termed degradins, composed of a fragment of SEL1L fused to a target-specific binding moiety located on the luminal side of the ER. The target-binding moiety can be a ligand of the target or derived from specific mAbs. Here, we describe the ability of degradins with two different recognition moieties to promote degradation of a model target. Degradins recognize the target protein within the ER both in secretory and membrane-bound forms, inducing their degradation following retrotranslocation to the cytosol. Thus, degradins represent an effective technique to knock-out proteins within the secretory pathway with high specificity. PMID:22523070

Design and characterization of a real time particle radiography system based on scintillating optical fibers

NASA Astrophysics Data System (ADS)

Longhitano, F.; Lo Presti, D.; Bonanno, D. L.; Bongiovanni, D. G.; Leonora, E.; Randazzo, N.; Reito, S.; Sipala, V.; Gallo, G.

2017-02-01

The fabrication and characterization of a charged particle imaging system composed of a tracker and a residual range detector (RRD) is described. The tracker is composed of four layers of scintillating fibers (SciFi), 500 μm side square section, arranged to form two planes orthogonal to each other. The fibers are coupled to two Multi-Pixel Photon Counter (MPPC) arrays by means of a channel reduction system patented by the Istituto Nazionale di Fisica Nucleare (INFN) (Presti, 2015) [1]. Sixty parallel layers of the same fibers used in the tracker compose the RRD. The various layers are optically coupled to a MPPC array by means of wavelength shifting (WLS) fibers. The sensitive area of the two detectors is 9×9 cm2. The results of the measurements, acquired by the prototypes with CATANA (Cirrone, 2008) [2] proton beam, and a comparison with the simulations of the detectors are presented.

950 keV X-Band Linac For Material Recognition Using Two-Fold Scintillator Detector As A Concept Of Dual-Energy X-Ray System

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

Lee, Kiwoo; Natsui, Takuya; Hirai, Shunsuke

2011-06-01

One of the advantages of applying X-band linear accelerator (Linac) is the compact size of the whole system. That shows us the possibility of on-site system such as the custom inspection system in an airport. As X-ray source, we have developed X-band Linac and achieved maximum X-ray energy 950 keV using the low power magnetron (250 kW) in 2 {mu}s pulse length. The whole size of the Linac system is 1x1x1 m{sup 3}. That is realized by introducing X-band system. In addition, we have designed two-fold scintillator detector in dual energy X-ray concept. Monte carlo N-particle transport (MCNP) code wasmore » used to make up sensor part of the design with two scintillators, CsI and CdWO4. The custom inspection system is composed of two equipments: 950 keV X-band Linac and two-fold scintillator and they are operated simulating real situation such as baggage check in an airport. We will show you the results of experiment which was performed with metal samples: iron and lead as targets in several conditions.« less

Neurosyphilis in Anglo-American Composers and Jazz Musicians.

PubMed

Breitenfeld, Darko; Kust, Davor; Breitenfeld, Tomislav; Prpić, Marin; Lucijanić, Marko; Zibar, Davor; Hostić, Vedran; Franceschi, Maja; Bolanča, Ante

2017-09-01

Syphilis is a sexually transmitted, systemic disease caused by the spirochete bacterium Treponema pallidum. The most common mechanism of transmission is sexual intercourse. Although there are several hypotheses, the exact origin of the disease remains unknown. Newly published evidence suggests that the hypothesis supporting the theory of the American origin of the disease is the valid one. Among 1500 analyzed pathographies of composers and musicians, data on ten Anglo-American composers and jazz musicians having suffered from neurosyphilis (tertiary stage of the disease) were extracted for this report. In this group of Anglo-American composers and musicians, most of them died from progressive paralysis while still in the creative phase of life. Additionally, diagnoses of eleven other famous neurosyphilitic composers, as well as basic biographic data on ten less known composers that died from neurosyphilis-progressive paralysis are also briefly mentioned. In conclusion, neurosyphilis can cause serious neurological damage, as well as permanent disability or death, preventing further work and skill improvement.

Prioritising health service innovation investments using public preferences: a discrete choice experiment.

PubMed

Erdem, Seda; Thompson, Carl

2014-08-28

Prioritising scarce resources for investment in innovation by publically funded health systems is unavoidable. Many healthcare systems wish to foster transparency and accountability in the decisions they make by incorporating the public in decision-making processes. This paper presents a unique conceptual approach exploring the public's preferences for health service innovations by viewing healthcare innovations as 'bundles' of characteristics. This decompositional approach allows policy-makers to compare numerous competing health service innovations without repeatedly administering surveys for specific innovation choices. A Discrete Choice Experiment (DCE) was used to elicit preferences. Individuals chose from presented innovation options that they believe the UK National Health Service (NHS) should invest the most in. Innovations differed according to: (i) target population; (ii) target age; (iii) implementation time; (iv) uncertainty associated with their likely effects; (v) potential health benefits; and, (vi) cost to a taxpayer. This approach fosters multidimensional decision-making, rather than imposing a single decision criterion (e.g., cost, target age) in prioritisation. Choice data was then analysed using scale-adjusted Latent Class models to investigate variability in preferences and scale and valuations amongst respondents. Three latent classes with considerable heterogeneity in the preferences were present. Each latent class is composed of two consumer subgroups varying in the level of certainty in their choices. All groups preferred scientifically proven innovations, those with potential health benefits that cost less. There were, however, some important differences in their preferences for innovation investment choices: Class-1 (54%) prefers innovations benefitting adults and young people and does not prefer innovations targeting people with 'drug addiction' and 'obesity'. Class- 2 (34%) prefers innovations targeting 'cancer' patients only and has negative preferences for innovations targeting elderly, and Class-3 (12%) prefers spending on elderly and cancer patients the most. DCE can help policy-makers incorporate public preferences for health service innovation investment choices into decision making. The findings provide useful information on the public's valuation and acceptability of potential health service innovations. Such information can be used to guide innovation prioritisation decisions by comparing competing innovation options. The approach in this paper makes, these often implicit and opaque decisions, more transparent and explicit.

[Advances in nanoparticle-targeting tumor associated macrophages for cancer imaging and therapy].

PubMed

Fengliang, Guo; Guping, Tang; Qinglian, H U

2017-03-25

Tumor tissues are composed of tumor cells and complicate microenvironment. Tumor associated macrophages (TAMs) as an important component in tumor microenvironment, play fundamental roles in tumor progression, metastasis and microenvironment regulation. Recently, studies have found that nanotechnology, as an emerging platform, provides unique potential for cancer imaging and therapy. With the nanotechnology, TAMs imaging presents direct evidence for cancer development, progression, and the effectiveness of cancer treatments; it also can regulate the immunosuppression of tumor microenvironment and improve therapeutic efficiency through TAMs targeted killing or phenotypic transformation. In this article, we illustrate the function of TAMs and review the latest development in nano-carriers and their applications in tumor associated macrophage targeting cancer imaging and therapy.

Non-deterministic quantum CNOT gate with double encoding

NASA Astrophysics Data System (ADS)

Gueddana, Amor; Attia, Moez; Chatta, Rihab

2013-09-01

We define an Asymmetric Partially Polarizing Beam Splitter (APPBS) to be a linear optical component having different reflectivity (transmittance) coefficients, on the upper and the lower arms, for horizontally and vertically Polarized incident photons. Our CNOT model is composed by two APPBSs, one Half Wave Plate (HWP), two Polarizing Beam Splitters (PBSs), a Beam Splitter (BS) and a -phase rotator for specific wavelength. Control qubit operates with dual rail encoding while target qubit is based on polarization encoding. To perform CNOT operation in 4/27 of the cases, input and target incoming photons are injected with different wavelengths.

A Component-based Programming Model for Composite, Distributed Applications

NASA Technical Reports Server (NTRS)

Eidson, Thomas M.; Bushnell, Dennis M. (Technical Monitor)

2001-01-01

The nature of scientific programming is evolving to larger, composite applications that are composed of smaller element applications. These composite applications are more frequently being targeted for distributed, heterogeneous networks of computers. They are most likely programmed by a group of developers. Software component technology and computational frameworks are being proposed and developed to meet the programming requirements of these new applications. Historically, programming systems have had a hard time being accepted by the scientific programming community. In this paper, a programming model is outlined that attempts to organize the software component concepts and fundamental programming entities into programming abstractions that will be better understood by the application developers. The programming model is designed to support computational frameworks that manage many of the tedious programming details, but also that allow sufficient programmer control to design an accurate, high-performance application.

AAA gunnermodel based on observer theory. [predicting a gunner's tracking response

NASA Technical Reports Server (NTRS)

Kou, R. S.; Glass, B. C.; Day, C. N.; Vikmanis, M. M.

1978-01-01

The Luenberger observer theory is used to develop a predictive model of a gunner's tracking response in antiaircraft artillery systems. This model is composed of an observer, a feedback controller and a remnant element. An important feature of the model is that the structure is simple, hence a computer simulation requires only a short execution time. A parameter identification program based on the least squares curve fitting method and the Gauss Newton gradient algorithm is developed to determine the parameter values of the gunner model. Thus, a systematic procedure exists for identifying model parameters for a given antiaircraft tracking task. Model predictions of tracking errors are compared with human tracking data obtained from manned simulation experiments. Model predictions are in excellent agreement with the empirical data for several flyby and maneuvering target trajectories.

Design of an Acoustic Target Intrusion Detection System Based on Small-Aperture Microphone Array.

PubMed

Zu, Xingshui; Guo, Feng; Huang, Jingchang; Zhao, Qin; Liu, Huawei; Li, Baoqing; Yuan, Xiaobing

2017-03-04

Automated surveillance of remote locations in a wireless sensor network is dominated by the detection algorithm because actual intrusions in such locations are a rare event. Therefore, a detection method with low power consumption is crucial for persistent surveillance to ensure longevity of the sensor networks. A simple and effective two-stage algorithm composed of energy detector (ED) and delay detector (DD) with all its operations in time-domain using small-aperture microphone array (SAMA) is proposed. The algorithm analyzes the quite different velocities between wind noise and sound waves to improve the detection capability of ED in the surveillance area. Experiments in four different fields with three types of vehicles show that the algorithm is robust to wind noise and the probability of detection and false alarm are 96.67% and 2.857%, respectively.

An online model composition tool for system biology models

PubMed Central

2013-01-01

Background There are multiple representation formats for Systems Biology computational models, and the Systems Biology Markup Language (SBML) is one of the most widely used. SBML is used to capture, store, and distribute computational models by Systems Biology data sources (e.g., the BioModels Database) and researchers. Therefore, there is a need for all-in-one web-based solutions that support advance SBML functionalities such as uploading, editing, composing, visualizing, simulating, querying, and browsing computational models. Results We present the design and implementation of the Model Composition Tool (Interface) within the PathCase-SB (PathCase Systems Biology) web portal. The tool helps users compose systems biology models to facilitate the complex process of merging systems biology models. We also present three tools that support the model composition tool, namely, (1) Model Simulation Interface that generates a visual plot of the simulation according to user’s input, (2) iModel Tool as a platform for users to upload their own models to compose, and (3) SimCom Tool that provides a side by side comparison of models being composed in the same pathway. Finally, we provide a web site that hosts BioModels Database models and a separate web site that hosts SBML Test Suite models. Conclusions Model composition tool (and the other three tools) can be used with little or no knowledge of the SBML document structure. For this reason, students or anyone who wants to learn about systems biology will benefit from the described functionalities. SBML Test Suite models will be a nice starting point for beginners. And, for more advanced purposes, users will able to access and employ models of the BioModels Database as well. PMID:24006914

Crystal structure of the Csm3-Csm4 subcomplex in the type III-A CRISPR-Cas interference complex.

PubMed

Numata, Tomoyuki; Inanaga, Hideko; Sato, Chikara; Osawa, Takuo

2015-01-30

Clustered, regularly interspaced, short palindromic repeat (CRISPR) loci play a pivotal role in the prokaryotic host defense system against invading genetic materials. The CRISPR loci are transcribed to produce CRISPR RNAs (crRNAs), which form interference complexes with CRISPR-associated (Cas) proteins to target the invading nucleic acid for degradation. The interference complex of the type III-A CRISPR-Cas system is composed of five Cas proteins (Csm1-Csm5) and a crRNA, and targets invading DNA. Here, we show that the Csm1, Csm3, and Csm4 proteins from Methanocaldococcus jannaschii form a stable subcomplex. We also report the crystal structure of the M. jannaschii Csm3-Csm4 subcomplex at 3.1Å resolution. The complex structure revealed the presence of a basic concave surface around their interface, suggesting the RNA and/or DNA binding ability of the complex. A gel retardation analysis showed that the Csm3-Csm4 complex binds single-stranded RNA in a non-sequence-specific manner. Csm4 structurally resembles Cmr3, a component of the type III-B CRISPR-Cas interference complex. Based on bioinformatics, we constructed a model structure of the Csm1-Csm4-Csm3 ternary complex, which provides insights into its role in the Csm interference complex. Copyright © 2014 Elsevier Ltd. All rights reserved.

Estimation of absolute water surface temperature based on atmospherically corrected thermal infrared multispectral scanner digital data

NASA Technical Reports Server (NTRS)

Anderson, James E.

1986-01-01

Airborne remote sensing systems, as well as those on board Earth orbiting satellites, sample electromagnetic energy in discrete wavelength regions and convert the total energy sampled into data suitable for processing by digital computers. In general, however, the total amount of energy reaching a sensor system located at some distance from the target is composed not only of target related energy, but, in addition, contains a contribution originating from the atmosphere itself. Thus, some method must be devised for removing or at least minimizing the effects of the atmosphere. The LOWTRAN-6 Program was designed to estimate atmospheric transmittance and radiance for a given atmospheric path at moderate spectral resolution over an operational wavelength region from 0.25 to 28.5 microns. In order to compute the Thermal Infrared Multispectral Scanner (TIMS) digital values which were recorded in the absence of the atmosphere, the parameters derived from LOWTRAN-6 are used in a correction equation. The TIMS data were collected at 1:00 a.m. local time on November 21, 1983, over a recirculating cooling pond for a power plant in southeastern Mississippi. The TIMS data were analyzed before and after atmospheric corrections were applied using a band ratioing model to compute the absolute surface temperature of various points on the power plant cooling pond. The summarized results clearly demonstrate the desirability of applying atmospheric corrections.

Biomimetic interfaces based on S-layer proteins, lipid membranes and functional biomolecules

PubMed Central

Schuster, Bernhard; Sleytr, Uwe B.

2014-01-01

Designing and utilization of biomimetic membrane systems generated by bottom-up processes is a rapidly growing scientific and engineering field. Elucidation of the supramolecular construction principle of archaeal cell envelopes composed of S-layer stabilized lipid membranes led to new strategies for generating highly stable functional lipid membranes at meso- and macroscopic scale. In this review, we provide a state-of-the-art survey of how S-layer proteins, lipids and polymers may be used as basic building blocks for the assembly of S-layer-supported lipid membranes. These biomimetic membrane systems are distinguished by a nanopatterned fluidity, enhanced stability and longevity and, thus, provide a dedicated reconstitution matrix for membrane-active peptides and transmembrane proteins. Exciting areas in the (lab-on-a-) biochip technology are combining composite S-layer membrane systems involving specific membrane functions with the silicon world. Thus, it might become possible to create artificial noses or tongues, where many receptor proteins have to be exposed and read out simultaneously. Moreover, S-layer-coated liposomes and emulsomes copying virus envelopes constitute promising nanoformulations for the production of novel targeting, delivery, encapsulation and imaging systems. PMID:24812051

Interactive orbital proximity operations planning system instruction and training guide

NASA Technical Reports Server (NTRS)

Grunwald, Arthur J.; Ellis, Stephen R.

1994-01-01

This guide instructs users in the operation of a Proximity Operations Planning System. This system uses an interactive graphical method for planning fuel-efficient rendezvous trajectories in the multi-spacecraft environment of the space station and allows the operator to compose a multi-burn transfer trajectory between orbit initial chaser and target trajectories. The available task time (window) of the mission is predetermined and the maneuver is subject to various operational constraints, such as departure, arrival, spatial, plume impingement, and en route passage constraints. The maneuvers are described in terms of the relative motion experienced in a space station centered coordinate system. Both in-orbital plane as well as out-of-orbital plane maneuvering is considered. A number of visual optimization aids are used for assisting the operator in reaching fuel-efficient solutions. These optimization aids are based on the Primer Vector theory. The visual feedback of trajectory shapes, operational constraints, and optimization functions, provided by user-transparent and continuously active background computations, allows the operator to make fast, iterative design changes that rapidly converge to fuel-efficient solutions. The planning tool is an example of operator-assisted optimization of nonlinear cost functions.

Remote hardware-reconfigurable robotic camera

NASA Astrophysics Data System (ADS)

Arias-Estrada, Miguel; Torres-Huitzil, Cesar; Maya-Rueda, Selene E.

2001-10-01

In this work, a camera with integrated image processing capabilities is discussed. The camera is based on an imager coupled to an FPGA device (Field Programmable Gate Array) which contains an architecture for real-time computer vision low-level processing. The architecture can be reprogrammed remotely for application specific purposes. The system is intended for rapid modification and adaptation for inspection and recognition applications, with the flexibility of hardware and software reprogrammability. FPGA reconfiguration allows the same ease of upgrade in hardware as a software upgrade process. The camera is composed of a digital imager coupled to an FPGA device, two memory banks, and a microcontroller. The microcontroller is used for communication tasks and FPGA programming. The system implements a software architecture to handle multiple FPGA architectures in the device, and the possibility to download a software/hardware object from the host computer into its internal context memory. System advantages are: small size, low power consumption, and a library of hardware/software functionalities that can be exchanged during run time. The system has been validated with an edge detection and a motion processing architecture, which will be presented in the paper. Applications targeted are in robotics, mobile robotics, and vision based quality control.

MACRO: a combined microchip-PCR and microarray system for high-throughput monitoring of genetically modified organisms.

PubMed

Shao, Ning; Jiang, Shi-Meng; Zhang, Miao; Wang, Jing; Guo, Shu-Juan; Li, Yang; Jiang, He-Wei; Liu, Cheng-Xi; Zhang, Da-Bing; Yang, Li-Tao; Tao, Sheng-Ce

2014-01-21

The monitoring of genetically modified organisms (GMOs) is a primary step of GMO regulation. However, there is presently a lack of effective and high-throughput methodologies for specifically and sensitively monitoring most of the commercialized GMOs. Herein, we developed a multiplex amplification on a chip with readout on an oligo microarray (MACRO) system specifically for convenient GMO monitoring. This system is composed of a microchip for multiplex amplification and an oligo microarray for the readout of multiple amplicons, containing a total of 91 targets (18 universal elements, 20 exogenous genes, 45 events, and 8 endogenous reference genes) that covers 97.1% of all GM events that have been commercialized up to 2012. We demonstrate that the specificity of MACRO is ~100%, with a limit of detection (LOD) that is suitable for real-world applications. Moreover, the results obtained of simulated complex samples and blind samples with MACRO were 100% consistent with expectations and the results of independently performed real-time PCRs, respectively. Thus, we believe MACRO is the first system that can be applied for effectively monitoring the majority of the commercialized GMOs in a single test.

Protecting and Leaving Functions of Trimethylsilyl Groups in Trimethylsilylated Silicates for the Synthesis of Alkoxysiloxane Oligomers.

PubMed

Yoshikawa, Masashi; Tamura, Yasuhiro; Wakabayashi, Ryutaro; Tamai, Misa; Shimojima, Atsushi; Kuroda, Kazuyuki

2017-11-06

The concept of protecting groups and leaving groups in organic synthesis was applied to the synthesis of siloxane-based molecules. Alkoxy-functionalized siloxane oligomers composed of SiO 4 , RSiO 3 , or R 2 SiO 2 units were chosen as targets (R: functional groups, such as Me and Ph). Herein we describe a novel synthesis of alkoxysiloxane oligomers based on the substitution reaction of trimethylsilyl (TMS) groups with alkoxysilyl groups. Oligosiloxanes possessing TMS groups were reacted with alkoxychlorosilane in the presence of BiCl 3 as a catalyst. TMS groups were substituted with alkoxysilyl groups, leading to the synthesis of alkoxysiloxane oligomers. Siloxane oligomers composed of RSiO 3 and R 2 SiO 2 units were synthesized more efficiently than those composed of SiO 4 units, suggesting that the steric hindrance around the TMS groups of the oligosiloxanes makes a difference in the degree of substitution. This reaction uses TMS groups as both protecting and leaving groups for SiOH/SiO - groups. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Intelligent Tutoring Systems: Machine Learning Research

DTIC Science & Technology

1991-07-01

is composed of cutin . Ki: Cutin is impermeable to gases. Does the cuticle restrict water loss from the leaf? Domain Expert: Yes, that’s right. Kl...transported from inside the Leaf Epidermis to the atmosphere outside of the Leaf Epidermis. Rule 1: If an object is composed of cutin , then it is

Exploring the Experiences of African American Women in an Undergraduate Summer Research Program Designed to Address the Underrepresentation of Women and Minorities in Neuroscience: A Qualitative Analysis

ERIC Educational Resources Information Center

Reid, Ericka L.

2010-01-01

African American women compose a critical proportion of the potential science, technology, engineering, and mathematics (STEM) workforce of the future, yet are disproportionately represented and largely underutilized. While various programs and initiatives have been designed and implemented to target women and underrepresented minorities, the…

Pre- and post-harvest interventions to reduce pathogen contamination in the U.S. beef industry

USDA-ARS?s Scientific Manuscript database

Significant effort has been targeted at reducing the risk of pathogens in U.S. beef products since the mid-1990s. These efforts were focused on E. coli O157:H7 after it was declared an adulterant in ground beef or its components. Initial efforts were composed primarily of post-harvest interventions ...

Supporting Orthographic Learning at the Beginning Stage of Learning to Read Chinese as a Second Language

ERIC Educational Resources Information Center

Chang, Li-Yun; Xu, Yi; Perfetti, Charles A.; Zhang, Juan; Chen, Hsueh-Chih

2014-01-01

Learning to read a second language (L2) is especially challenging when a target L2 requires learning new graphic forms. Learning Chinese, which consists of thousands of characters composed of hundreds of basic writing units, presents such a challenge of orthographic learning for adult English speakers at the beginning stages of learning. In this…

Assessing the Impact of First-Year Experience Courses on Student Success in Community and Technical Colleges

ERIC Educational Resources Information Center

Robertson, Luv'Tesha L.

2016-01-01

This study examined the impact first-year experience courses have on first-year student performance when enrolled in these courses at public community and technical colleges in Kentucky. The target population for this research study was composed of freshman students participating in the course compared to students not participating in the same…

Study of meteoroid impact craters on various materials (AO 138-1). Attempt at dust debris collection with stacked detectors (AO 138-2)

NASA Technical Reports Server (NTRS)

Mandeville, Jean Claude

1991-01-01

Part of the Long Duration Exposure Facility (LDEF) tray allocated to French experiments, known as FRECOPA payload, was devoted to the study of dust particles. Two passive experiments were flown: one composed of a set of glass and metallic samples and one composed of multilayer thin foils detectors. In addition to these experiments, a broad variety of materials were exposed to the bombardment of microparticles and provide more data. Thick target experiment comprises selected metallic (Al, Au, Cu, W, Stainless Steel) 250 microns thick and glass surfaces 1.5 mm thick. Crater size distribution from these thick target experiments enable, with the aid of lab calibrations by solid particle accelerators, the evaluation of the incident microparticle flux in the near earth environment. The aim of the multiple foil penetration and collection experiment is primarily to study the feasibility of multilayer thin film detectors acting as energy sorters in order to collect micrometeoroids, if not in their original shape, at least as 'breakup' fragments suitable for chemical analysis. Foil thicknesses range from 0.75 to 5 microns of Al.

Targeting deficiencies in mitochondrial respiratory complex I and functional uncoupling exerts anti-seizure effects in a genetic model of temporal lobe epilepsy and in a model of acute temporal lobe seizures.

PubMed

Simeone, Kristina A; Matthews, Stephanie A; Samson, Kaeli K; Simeone, Timothy A

2014-01-01

Mitochondria actively participate in neurotransmission by providing energy (ATP) and maintaining normative concentrations of reactive oxygen species (ROS) in both presynaptic and postsynaptic elements. In human and animal epilepsies, ATP-producing respiratory rates driven by mitochondrial respiratory complex (MRC) I are reduced, antioxidant systems are attenuated and oxidative damage is increased. We report that MRCI-driven respiration and functional uncoupling (an inducible antioxidant mechanism) are reduced and levels of H2O2 are elevated in mitochondria isolated from KO mice. Experimental impairment of MRCI in WT hippocampal slices via rotenone reduces paired-pulse ratios (PPRs) at mossy fiber-CA3 synapses (resembling KO PPRs), and exacerbates seizure-like events in vitro. Daily treatment with AATP [a combination therapy composed of ascorbic acid (AA), alpha-tocopherol (T), sodium pyruvate (P) designed to synergistically target mitochondrial impairments] improved mitochondrial functions, mossy fiber PPRs, and reduced seizure burden index (SBI) scores and seizure incidence in KO mice. AATP pretreatment reduced severity of KA-induced seizures resulting in 100% protection from the severe tonic-clonic seizures in WT mice. These data suggest that restoration of bioenergetic homeostasis in the brain may represent a viable anti-seizure target for temporal lobe epilepsy. Copyright © 2013 Elsevier Inc. All rights reserved.

Targeted cancer exome sequencing reveals recurrent mutations in myeloproliferative neoplasms

PubMed Central

Tenedini, E; Bernardis, I; Artusi, V; Artuso, L; Roncaglia, E; Guglielmelli, P; Pieri, L; Bogani, C; Biamonte, F; Rotunno, G; Mannarelli, C; Bianchi, E; Pancrazzi, A; Fanelli, T; Malagoli Tagliazucchi, G; Ferrari, S; Manfredini, R; Vannucchi, A M; Tagliafico, E

2014-01-01

With the intent of dissecting the molecular complexity of Philadelphia-negative myeloproliferative neoplasms (MPN), we designed a target enrichment panel to explore, using next-generation sequencing (NGS), the mutational status of an extensive list of 2000 cancer-associated genes and microRNAs. The genomic DNA of granulocytes and in vitro-expanded CD3+T-lymphocytes, as a germline control, was target-enriched and sequenced in a learning cohort of 20 MPN patients using Roche 454 technology. We identified 141 genuine somatic mutations, most of which were not previously described. To test the frequency of the identified variants, a larger validation cohort of 189 MPN patients was additionally screened for these mutations using Ion Torrent AmpliSeq NGS. Excluding the genes already described in MPN, for 8 genes (SCRIB, MIR662, BARD1, TCF12, FAT4, DAP3, POLG and NRAS), we demonstrated a mutation frequency between 3 and 8%. We also found that mutations at codon 12 of NRAS (NRASG12V and NRASG12D) were significantly associated, for primary myelofibrosis (PMF), with highest dynamic international prognostic scoring system (DIPSS)-plus score categories. This association was then confirmed in 66 additional PMF patients composing a final dataset of 168 PMF showing a NRAS mutation frequency of 4.7%, which was associated with a worse outcome, as defined by the DIPSS plus score. PMID:24150215

A portable fluorescence microscopic imaging system for cholecystectomy

NASA Astrophysics Data System (ADS)

Ye, Jian; Yang, Chaoyu; Gan, Qi; Ma, Rong; Zhang, Zeshu; Chang, Shufang; Shao, Pengfei; Zhang, Shiwu; Liu, Chenhai; Xu, Ronald

2016-03-01

In this paper we proposed a portable fluorescence microscopic imaging system to prevent iatrogenic biliary injuries from occurring during cholecystectomy due to misidentification of the cystic structures. The system consisted of a light source module, a CMOS camera, a Raspberry Pi computer and a 5 inch HDMI LCD. Specifically, the light source module was composed of 690 nm and 850 nm LEDs, allowing the CMOS camera to simultaneously acquire both fluorescence and background images. The system was controlled by Raspberry Pi using Python programming with the OpenCV library under Linux. We chose Indocyanine green(ICG) as a fluorescent contrast agent and then tested fluorescence intensities of the ICG aqueous solution at different concentration levels by our fluorescence microscopic system compared with the commercial Xenogen IVIS system. The spatial resolution of the proposed fluorescence microscopic imaging system was measured by a 1951 USAF resolution target and the dynamic response was evaluated quantitatively with an automatic displacement platform. Finally, we verified the technical feasibility of the proposed system in mouse models of bile duct, performing both correct and incorrect gallbladder resection. Our experiments showed that the proposed system can provide clear visualization of the confluence between the cystic duct and common bile duct or common hepatic duct, suggesting that this is a potential method for guiding cholecystectomy. The proposed portable system only cost a total of $300, potentially promoting its use in resource-limited settings.

Single-target regulators form a minor group of transcription factors in Escherichia coli K-12.

PubMed

Shimada, Tomohiro; Ogasawara, Hiroshi; Ishihama, Akira

2018-05-04

The identification of regulatory targets of all TFs is critical for understanding the entire network of the genome regulation. The lac regulon of Escherichia coli K-12 W3110 is composed of the lacZYA operon and its repressor lacI gene, and has long been recognized as the seminal model of transcription regulation in bacteria with only one highly preferred target. After the Genomic SELEX screening in vitro of more than 200 transcription factors (TFs) from E. coli K-12, however, we found that most TFs regulate multiple target genes. With respect to the number of regulatory targets, a total of these 200 E. coli TFs form a hierarchy ranging from a single target to as many as 1000 targets. Here we focus a total of 13 single-target TFs, 9 known TFs (BetI, KdpE, LacI, MarR, NanR, RpiR, TorR, UlaR and UxuR) and 4 uncharacterized TFs (YagI, YbaO, YbiH and YeaM), altogether forming only a minor group of TFs in E. coli. These single-target TFs were classified into three groups based on their functional regulation.

Single-target regulators form a minor group of transcription factors in Escherichia coli K-12

PubMed Central

Shimada, Tomohiro; Ogasawara, Hiroshi; Ishihama, Akira

2018-01-01

Abstract The identification of regulatory targets of all TFs is critical for understanding the entire network of the genome regulation. The lac regulon of Escherichia coli K-12 W3110 is composed of the lacZYA operon and its repressor lacI gene, and has long been recognized as the seminal model of transcription regulation in bacteria with only one highly preferred target. After the Genomic SELEX screening in vitro of more than 200 transcription factors (TFs) from E. coli K-12, however, we found that most TFs regulate multiple target genes. With respect to the number of regulatory targets, a total of these 200 E. coli TFs form a hierarchy ranging from a single target to as many as 1000 targets. Here we focus a total of 13 single-target TFs, 9 known TFs (BetI, KdpE, LacI, MarR, NanR, RpiR, TorR, UlaR and UxuR) and 4 uncharacterized TFs (YagI, YbaO, YbiH and YeaM), altogether forming only a minor group of TFs in E. coli. These single-target TFs were classified into three groups based on their functional regulation. PMID:29529243

Solar hydrogen production by tandem cell system composed of metal oxide semiconductor film photoelectrode and dye-sensitized solar cell

NASA Astrophysics Data System (ADS)

Arakawa, H.; Shiraishi, C.; Tatemoto, M.; Kishida, H.; Usui, D.; Suma, A.; Takamisawa, A.; Yamaguchi, T.

2007-09-01

Photocatalytic and photoelectrochemical approaches to solar hydrogen production in our group were introduced. In photocatalytic water splitting system using NiO x/ TiO II powder photocatalyst with concentrated Na IICO 3 aqueous solution, solar energy conversion efficiency to H II and O II production (STH efficiency) was 0.016%. In addition, STH efficiency of visible light responding photocatalyst, NiOx/ promoted In 0.9Ni 0.1TaO 4, was estimated at 0.03%. In photoelectrochemical system using an oxide semiconductor film phptoelectrode, STH efficiencies of meosporous TiO II (Anatase) , mesoporous visible light responding S-doped TiO II (Anatase) and WO 3 film were 0.32-0.44% at applied potential of 0.35 V vs NHE, 0.14% at 0.55 V and 0.44% at 0.9 V, respectively. Finally, solar hydrogen production by tandem cell system composed of an oxide semiconductor photoelectrode, a Pt wire counter electrode and a dye-sensitized solar cell (DSC) was investigated. As photoelectrodes, meosporous TiO II (Anatase), mesoporous S-doped TiO II (Anatase), WO 3, BiVO 4 and Fe IIO 3 film were tested. STH efficiency of tandem cell system composed of a WO 3 film photoelectrode, and a two-series-connected DSC (Voc = 1.4 V) was 2.5-2.8%. In conclusion, it is speculated that more than 5% STH efficiency will be obtained by tandem cell system composed of an oxide semiconductor photoelectrode and a two-series-connected DSC in near future. This suggests a cost-effective and practical application of this system for solar hydrogen production.

Targeting of Gold Deposits in Amazonian Exploration Frontiers using Knowledge- and Data-Driven Spatial Modeling of Geophysical, Geochemical, and Geological Data

NASA Astrophysics Data System (ADS)

Magalhães, Lucíola Alves; Souza Filho, Carlos Roberto

2012-03-01

This paper reports the application of weights-of-evidence, artificial neural networks, and fuzzy logic spatial modeling techniques to generate prospectivity maps for gold mineralization in the neighborhood of the Amapari Au mine, Brazil. The study area comprises one of the last Brazilian mineral exploration frontiers. The Amapari mine is located in the Maroni-Itaicaiúnas Province, which regionally hosts important gold, iron, manganese, chromite, diamond, bauxite, kaolinite, and cassiterite deposits. The Amapari Au mine is characterized as of the orogenic gold deposit type. The highest gold grades are associated with highly deformed rocks and are concentrated in sulfide-rich veins mainly composed of pyrrhotite. The data used for the generation of gold prospectivity models include aerogeophysical and geological maps as well as the gold content of stream sediment samples. The prospectivity maps provided by these three methods showed that the Amapari mine stands out as an area of high potential for gold mineralization. The prospectivity maps also highlight new targets for gold exploration. These new targets were validated by means of detailed maps of gold geochemical anomalies in soil and by fieldwork. The identified target areas exhibit good spatial coincidence with the main soil geochemical anomalies and prospects, thus demonstrating that the delineation of exploration targets by analysis and integration of indirect datasets in a geographic information system (GIS) is consistent with direct prospecting. Considering that work of this nature has never been developed in the Amazonian region, this is an important example of the applicability and functionality of geophysical data and prospectivity analysis in regions where geologic and metallogenetic information is scarce.

Design of pH-sensitive methotrexate prodrug-targeted curcumin nanoparticles for efficient dual-drug delivery and combination cancer therapy.

PubMed

Xie, Jiajiang; Fan, Zhongxiong; Li, Yang; Zhang, Yinying; Yu, Fei; Su, Guanghao; Xie, Liya; Hou, Zhenqing

2018-01-01

We designed acid-labile methotrexate (MTX) targeting prodrug self-assembling nanoparticles loaded with curcumin (CUR) drug for simultaneous delivery of multi-chemotherapeutic drugs and combination cancer therapy. A dual-acting MTX, acting as both an anticancer drug and as a tumor-targeting ligand, was coupled to 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[aldehyde(polyethylene glycol)-2000] via Schiff's base reaction. The synthesized prodrug conjugate (DSPE-PEG-Imine-MTX) could be self-assembled into micellar nanoparticles (MTX-Imine-M) in aqueous solution, which encapsulated CUR into their core by hydrophobic interactions (MTX-Imine-M-CUR). The prepared MTX-Imine-M-CUR nanoparticles were composed of an inner hydrophobic DSPE/CUR core and an outside hydrophilic bishydroxyl poly (ethyleneglycol) (PEG) shell with a self-targeting MTX prodrug corona. The imine linker between 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[aldehyde(polyethyleneglycol)-2000] and MTX, as a dynamic covalent bond, was strong enough to remain intact in physiological pH, even though it is rapidly cleaved in acidic pH. The MTX-Imine-M-CUR could codeliver MTX and CUR selectively and efficiently into the cancer cells via folate receptor-mediated endocytosis followed by the rapid intracellular release of CUR and the active form of MTX via the acidity of endosomes/lysosomes. Moreover, the MTX-Imine-M-CUR resulted in significantly higher in vitro and in vivo anticancer activity than pH-insensitive DSPE-PEGAmide-MTX assembling nanoparticles loaded with CUR (MTX-Amide-M-CUR), MTX unconjugated DSPE-PEG assembling micellar nanoparticles loaded with CUR (M-CUR), combination of both free drugs, and individual free drugs. The smart system provided a simple, yet feasible, drug delivery strategy for targeted combination chemotherapy.

Drug Target Optimization in Chronic Myeloid Leukemia Using Innovative Computational Platform

PubMed Central

Chuang, Ryan; Hall, Benjamin A.; Benque, David; Cook, Byron; Ishtiaq, Samin; Piterman, Nir; Taylor, Alex; Vardi, Moshe; Koschmieder, Steffen; Gottgens, Berthold; Fisher, Jasmin

2015-01-01

Chronic Myeloid Leukemia (CML) represents a paradigm for the wider cancer field. Despite the fact that tyrosine kinase inhibitors have established targeted molecular therapy in CML, patients often face the risk of developing drug resistance, caused by mutations and/or activation of alternative cellular pathways. To optimize drug development, one needs to systematically test all possible combinations of drug targets within the genetic network that regulates the disease. The BioModelAnalyzer (BMA) is a user-friendly computational tool that allows us to do exactly that. We used BMA to build a CML network-model composed of 54 nodes linked by 104 interactions that encapsulates experimental data collected from 160 publications. While previous studies were limited by their focus on a single pathway or cellular process, our executable model allowed us to probe dynamic interactions between multiple pathways and cellular outcomes, suggest new combinatorial therapeutic targets, and highlight previously unexplored sensitivities to Interleukin-3. PMID:25644994

Drug Target Optimization in Chronic Myeloid Leukemia Using Innovative Computational Platform

NASA Astrophysics Data System (ADS)

Chuang, Ryan; Hall, Benjamin A.; Benque, David; Cook, Byron; Ishtiaq, Samin; Piterman, Nir; Taylor, Alex; Vardi, Moshe; Koschmieder, Steffen; Gottgens, Berthold; Fisher, Jasmin

2015-02-01

Chronic Myeloid Leukemia (CML) represents a paradigm for the wider cancer field. Despite the fact that tyrosine kinase inhibitors have established targeted molecular therapy in CML, patients often face the risk of developing drug resistance, caused by mutations and/or activation of alternative cellular pathways. To optimize drug development, one needs to systematically test all possible combinations of drug targets within the genetic network that regulates the disease. The BioModelAnalyzer (BMA) is a user-friendly computational tool that allows us to do exactly that. We used BMA to build a CML network-model composed of 54 nodes linked by 104 interactions that encapsulates experimental data collected from 160 publications. While previous studies were limited by their focus on a single pathway or cellular process, our executable model allowed us to probe dynamic interactions between multiple pathways and cellular outcomes, suggest new combinatorial therapeutic targets, and highlight previously unexplored sensitivities to Interleukin-3.

Needle Steering in Biological Tissue using Ultrasound-based Online Curvature Estimation

PubMed Central

Moreira, Pedro; Patil, Sachin; Alterovitz, Ron; Misra, Sarthak

2014-01-01

Percutaneous needle insertions are commonly performed for diagnostic and therapeutic purposes. Accurate placement of the needle tip is important to the success of many needle procedures. The current needle steering systems depend on needle-tissue-specific data, such as maximum curvature, that is unavailable prior to an interventional procedure. In this paper, we present a novel three-dimensional adaptive steering method for flexible bevel-tipped needles that is capable of performing accurate tip placement without previous knowledge about needle curvature. The method steers the needle by integrating duty-cycled needle steering, online curvature estimation, ultrasound-based needle tracking, and sampling-based motion planning. The needle curvature estimation is performed online and used to adapt the path and duty cycling. We evaluated the method using experiments in a homogenous gelatin phantom, a two-layer gelatin phantom, and a biological tissue phantom composed of a gelatin layer and in vitro chicken tissue. In all experiments, virtual obstacles and targets move in order to represent the disturbances that might occur due to tissue deformation and physiological processes. The average targeting error using our new adaptive method is 40% lower than using the conventional non-adaptive duty-cycled needle steering method. PMID:26229729

Target-mediated drug disposition model and its approximations for antibody-drug conjugates.

PubMed

Gibiansky, Leonid; Gibiansky, Ekaterina

2014-02-01

Antibody-drug conjugate (ADC) is a complex structure composed of an antibody linked to several molecules of a biologically active cytotoxic drug. The number of ADC compounds in clinical development now exceeds 30, with two of them already on the market. However, there is no rigorous mechanistic model that describes pharmacokinetic (PK) properties of these compounds. PK modeling of ADCs is even more complicated than that of other biologics as the model should describe distribution, binding, and elimination of antibodies with different toxin load, and also the deconjugation process and PK of the released toxin. This work extends the target-mediated drug disposition (TMDD) model to describe ADCs, derives the rapid binding (quasi-equilibrium), quasi-steady-state, and Michaelis-Menten approximations of the TMDD model as applied to ADCs, derives the TMDD model and its approximations for ADCs with load-independent properties, and discusses further simplifications of the system under various assumptions. The developed models are shown to describe data simulated from the available clinical population PK models of trastuzumab emtansine (T-DM1), one of the two currently approved ADCs. Identifiability of model parameters is also discussed and illustrated on the simulated T-DM1 examples.

Hyaluronan and calcium carbonate hybrid nanoparticles for colorectal cancer chemotherapy

NASA Astrophysics Data System (ADS)

Bai, Jinghui; Xu, Jian; Zhao, Jian; Zhang, Rui

2017-09-01

A hybrid drug delivery system (DDS) composed of hyaluronan and calcium carbonate (CC) was developed. By taking advantage of the tumor-targeting ability of hyaluronan and the drug-loading property of CC, the well-formed hyaluronan-CC nanoparticles were able to serve as a DDS targeting colorectal cancer with a decent drug loading content, which is beneficial in the chemotherapy of colorectal cancer. In this study, hyaluronan-CC nanoparticles smaller than 100 nm were successfully developed to load the wide-range anti-cancer drug adriamycin (Adr) to construct hyaluronan-CC/Adr nanoparticles. On the other hand, we also found that hyaluronan-CC/Adr nanoparticles can possibly increase the uptake ratio of Adr into HT29 colorectal cancer cells when compared with hyaluronan-free nanoparticles (CC/Adr) via the CD44 receptor-mediated endocytosis via competitive uptake and in vivo imaging assays. Note that both in vitro (CCK-8 assay on HT29 cells) and in vivo (anti-cancer assay on HT-29 tumor-bearing nude mice model) experiments revealed that hyaluronan-CC/Adr nanoparticles exhibited stronger anti-cancer activity than free Adr or CC/Adr nanoparticles with minimized toxic side effects and preferable cancer-suppression potential.

SiRNA Crosslinked Nanoparticles for the Treatment of Inflammation-induced Liver Injury.

PubMed

Tang, Yaqin; Zeng, Ziying; He, Xiao; Wang, Tingting; Ning, Xinghai; Feng, Xuli

2017-02-01

RNA interference mediated by small interfering RNA (siRNA) provides a powerful tool for gene regulation, and has a broad potential as a promising therapeutic strategy. However, therapeutics based on siRNA have had limited clinical success due to their undesirable pharmacokinetic properties. This study presents pH-sensitive nanoparticles-based siRNA delivery systems (PNSDS), which are positive-charge-free nanocarriers, composed of siRNA chemically crosslinked with multi-armed poly(ethylene glycol) carriers via acid-labile acetal linkers. The unique siRNA crosslinked structure of PNSDS allows it to have minimal cytotoxicity, high siRNA loading efficiency, and a stimulus-responsive property that enables the selective intracellular release of siRNA in response to pH conditions. This study demonstrates that PNSDS can deliver tumor necrosis factor alpha (TNF-α) siRNA into macrophages and induce the efficient down regulation of the targeted gene in complete cell culture media. Moreover, PNSDS with mannose targeting moieties can selectively accumulate in mice liver, induce specific inhibition of macrophage TNF-α expression in vivo, and consequently protect mice from inflammation-induced liver damages. Therefore, this novel siRNA delivering platform would greatly improve the therapeutic potential of RNAi based therapies.

Structure of the heterotrimeric complex that regulates type III secretion needle formation

PubMed Central

Quinaud, Manuelle; Plé, Sophie; Job, Viviana; Contreras-Martel, Carlos; Simorre, Jean-Pierre; Attree, Ina; Dessen, Andréa

2007-01-01

Type III secretion systems (T3SS), found in several Gram-negative pathogens, are nanomachines involved in the transport of virulence effectors directly into the cytoplasm of target cells. T3SS are essentially composed of basal membrane-embedded ring-like structures and a hollow needle formed by a single polymerized protein. Within the bacterial cytoplasm, the T3SS needle protein requires two distinct chaperones for stabilization before its secretion, without which the entire T3SS is nonfunctional. The 2.0-Å x-ray crystal structure of the PscE-PscF55–85-PscG heterotrimeric complex from Pseudomonas aeruginosa reveals that the C terminus of the needle protein PscF is engulfed within the hydrophobic groove of the tetratricopeptide-like molecule PscG, indicating that the macromolecular scaffold necessary to stabilize the T3SS needle is totally distinct from chaperoned complexes between pilus- or flagellum-forming molecules. Disruption of specific PscG–PscF interactions leads to impairment of bacterial cytotoxicity toward macrophages, indicating that this essential heterotrimer, which possesses homologs in a wide variety of pathogens, is a unique attractive target for the development of novel antibacterials. PMID:17470796

Updates in the Development of ImmunoRNases for the Selective Killing of Tumor Cells

PubMed Central

Jordaan, Sandra; Akinrinmade, Olusiji A.; Nachreiner, Thomas; Cremer, Christian; Naran, Krupa; Chetty, Shivan; Barth, Stefan

2018-01-01

Targeted cancer therapy includes, amongst others, antibody-based delivery of toxic payloads to selectively eliminate tumor cells. This payload can be either a synthetic small molecule drug composing an antibody-drug conjugate (ADC) or a cytotoxic protein composing an immunotoxin (IT). Non-human cytotoxic proteins, while potent, have limited clinical efficacy due to their immunogenicity and potential off-target toxicity. Humanization of the cytotoxic payload is essential and requires harnessing of potent apoptosis-inducing human proteins with conditional activity, which rely on targeted delivery to contact their substrate. Ribonucleases are attractive candidates, due to their ability to induce apoptosis by abrogating protein biosynthesis via tRNA degradation. In fact, several RNases of the pancreatic RNase A superfamily have shown potential as anti-cancer agents. Coupling of a human RNase to a humanized antibody or antibody derivative putatively eliminates the immunogenicity of an IT (now known as a human cytolytic fusion protein, hCFP). However, RNases are tightly regulated in vivo by endogenous inhibitors, controlling the ribonucleolytic balance subject to the cell’s metabolic requirements. Endogenous inhibition limits the efficacy with which RNase-based hCFPs induce apoptosis. However, abrogating the natural interaction with the natural inhibitors by mutation has been shown to significantly enhance RNase activity, paving the way toward achieving cytolytic potency comparable to that of bacterial immunotoxins. Here, we review the immunoRNases that have undergone preclinical studies as anti-cancer therapeutic agents. PMID:29510557

Updates in the Development of ImmunoRNases for the Selective Killing of Tumor Cells.

PubMed

Jordaan, Sandra; Akinrinmade, Olusiji A; Nachreiner, Thomas; Cremer, Christian; Naran, Krupa; Chetty, Shivan; Barth, Stefan

2018-03-05

Targeted cancer therapy includes, amongst others, antibody-based delivery of toxic payloads to selectively eliminate tumor cells. This payload can be either a synthetic small molecule drug composing an antibody-drug conjugate (ADC) or a cytotoxic protein composing an immunotoxin (IT). Non-human cytotoxic proteins, while potent, have limited clinical efficacy due to their immunogenicity and potential off-target toxicity. Humanization of the cytotoxic payload is essential and requires harnessing of potent apoptosis-inducing human proteins with conditional activity, which rely on targeted delivery to contact their substrate. Ribonucleases are attractive candidates, due to their ability to induce apoptosis by abrogating protein biosynthesis via tRNA degradation. In fact, several RNases of the pancreatic RNase A superfamily have shown potential as anti-cancer agents. Coupling of a human RNase to a humanized antibody or antibody derivative putatively eliminates the immunogenicity of an IT (now known as a human cytolytic fusion protein, hCFP). However, RNases are tightly regulated in vivo by endogenous inhibitors, controlling the ribonucleolytic balance subject to the cell's metabolic requirements. Endogenous inhibition limits the efficacy with which RNase-based hCFPs induce apoptosis. However, abrogating the natural interaction with the natural inhibitors by mutation has been shown to significantly enhance RNase activity, paving the way toward achieving cytolytic potency comparable to that of bacterial immunotoxins. Here, we review the immunoRNases that have undergone preclinical studies as anti-cancer therapeutic agents.

GEANT4-based full simulation of the PADME experiment at the DAΦNE BTF

NASA Astrophysics Data System (ADS)

Leonardi, E.; Kozhuharov, V.; Raggi, M.; Valente, P.

2017-10-01

A possible solution to the dark matter problem postulates that dark particles can interact with Standard Model particles only through a new force mediated by a “portal”. If the new force has a U(1) gauge structure, the “portal” is a massive photon-like vector particle, called dark photon or A‧. The PADME experiment at the DAΦNE Beam-Test Facility (BTF) in Frascati is designed to detect dark photons produced in positron on fixed target annihilations decaying to dark matter (e+e-→γA‧) by measuring the final state missing mass. The experiment will be composed of a thin active diamond target where a 550 MeV positron beam will impinge to produce e+e- annihilation events. The surviving beam will be deflected with a magnet while the photons produced in the annihilation will be measured by a calorimeter composed of BGO crystals. To reject the background from Bremsstrahlung gamma production, a set of segmented plastic scintillator vetoes will be used to detect positrons exiting the target with an energy lower than that of the beam, while a fast small angle calorimeter will be used to reject the e+e-→γγ(γ) background. To optimize the experimental layout in terms of signal acceptance and background rejection, the full layout of the experiment was modelled with the GEANT4 simulation package. In this paper we will describe the details of the simulation and report on the results obtained with the software.

Host-regulated Hepatitis B Virus Capsid Assembly in a Mammalian Cell-free System.

PubMed

Liu, Kuancheng; Hu, Jianming

2018-04-20

The hepatitis B virus (HBV) is an important global human pathogen and represents a major cause of hepatitis, liver cirrhosis and liver cancer. The HBV capsid is composed of multiple copies of a single viral protein, the capsid or core protein (HBc), plays multiple roles in the viral life cycle, and has emerged recently as a major target for developing antiviral therapies against HBV infection. Although several systems have been developed to study HBV capsid assembly, including heterologous overexpression systems like bacteria and insect cells, in vitro assembly using purified protein, and mammalian cell culture systems, the requirement for non-physiological concentrations of HBc and salts and the difficulty in manipulating host regulators of assembly presents major limitations for detailed studies on capsid assembly under physiologically relevant conditions. We have recently developed a mammalian cell-free system based on the rabbit reticulocyte lysate (RRL), in which HBc is expressed at physiological concentrations and assembles into capsids under near-physiological conditions. This system has already revealed HBc assembly requirements that are not anticipated based on previous assembly systems. Furthermore, capsid assembly in this system is regulated by endogenous host factors that can be readily manipulated. Here we present a detailed protocol for this cell-free capsid assembly system, including an illustration on how to manipulate host factors that regulate assembly.

Improving Common Security Risk Analysis (Amelioration d’un processus commun d’analyse de risques securite)

DTIC Science & Technology

2008-09-01

publication has been reproduced directly from material supplied by RTO or the authors. Published September 2008 Copyright © RTO/NATO 2008 All Rights...requirements are met at each level within the composed system, a chain of belief is formed which provides assurance that the composed system is in...FAILURE OF AIR-CONDITIONING x 12 – LOSS OF POWER SUPPLY x 13 – FAILURE OF TELECOMMUNICATION EQUIPMENT x 4 – Disturbance Due to

SoC: Une Nouvelle Approche de l’Amelioration des Performances des Systemes pour Combattre les Problemes de Disponibilite a Long Terme (SoC: A New Approach to Enhance System Performances and to Combat the Long-Term Availability Issue)

DTIC Science & Technology

2001-01-01

cin~tique Properties»> ou o IP »>. En fait, ces IP ne sont rien (exemple : un missile en vol libre ). Meme si on peut d’autres que des composants sur...probablement pas radicalement le problkme peuvent soit achet~s soit &tre issus de conceptions au niveau des composants 6lectroniques. pr&c~dentes. Les

In vivo genome editing via CRISPR/Cas9 mediated homology-independent targeted integration

PubMed Central

Suzuki, Keiichiro; Tsunekawa, Yuji; Hernandez-Benitez, Reyna; Wu, Jun; Zhu, Jie; Kim, Euiseok J.; Hatanaka, Fumiyuki; Yamamoto, Mako; Araoka, Toshikazu; Li, Zhe; Kurita, Masakazu; Hishida, Tomoaki; Li, Mo; Aizawa, Emi; Guo, Shicheng; Chen, Song; Goebl, April; Soligalla, Rupa Devi; Qu, Jing; Jiang, Tingshuai; Fu, Xin; Jafari, Maryam; Esteban, Concepcion Rodriguez; Berggren, W. Travis; Lajara, Jeronimo; Nuñez-Delicado, Estrella; Guillen, Pedro; Campistol, Josep M.; Matsuzaki, Fumio; Liu, Guang-Hui; Magistretti, Pierre; Zhang, Kun; Callaway, Edward M.; Zhang, Kang; Belmonte, Juan Carlos Izpisua

2017-01-01

Targeted genome editing via engineered nucleases is an exciting area of biomedical research and holds potential for clinical applications. Despite rapid advances in the field, in vivo targeted transgene integration is still infeasible because current tools are inefficient1, especially for non-dividing cells, which compose most adult tissues. This poses a barrier for uncovering fundamental biological principles and developing treatments for a broad range of genetic disorders2. Based on clustered regularly interspaced short palindromic repeat/Cas9 (CRISPR/Cas9)3,4 technology, here we devise a homology-independent targeted integration (HITI) strategy, which allows for robust DNA knock-in in both dividing and non-dividing cells in vitro and, more importantly, in vivo (for example, in neurons of postnatal mammals). As a proof of concept of its therapeutic potential, we demonstrate the efficacy of HITI in improving visual function using a rat model of the retinal degeneration condition retinitis pigmentosa. The HITI method presented here establishes new avenues for basic research and targeted gene therapies. PMID:27851729

Linear sine wave profiling to machine instability targets

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

Schmidt, Derek William; Martinez, John Israel

2016-08-01

Specialized machining processes and programming have been developed to deliver thin tin and copper Richtmyer-Meshkov instability targets that have different amplitude perturbations across the face of one 4-in.-diameter target. Typical targets have anywhere from two to five different regions of sine waves that have different amplitudes varying from 4 to 200 μm across the face of the target. The puck is composed of multiple rings that are zero press fit together and diamond turned to create a flat platform with a tolerance of 2 μm for the shock experiment. A custom software program was written in Labview to write themore » point-to-point program for the diamond-turning profiler through the X-Y-Z movements to cut the pure planar straight sine wave geometry. As a result, the software is optimized to push the profile of the whole part into the face while eliminating any unneeded passes that do not cut any material.« less

Targets Mask U-Net for Wind Turbines Detection in Remote Sensing Images

NASA Astrophysics Data System (ADS)

Han, M.; Wang, H.; Wang, G.; Liu, Y.

2018-04-01

To detect wind turbines precisely and quickly in very high resolution remote sensing images (VHRRSI) we propose target mask U-Net. This convolution neural network (CNN), which is carefully designed to be a wide-field detector, models the pixel class assignment to wind turbines and their context information. The shadow, which is the context information of the target in this study, has been regarded as part of a wind turbine instance. We have trained the target mask U-Net on training dataset, which is composed of down sampled image blocks and instance mask blocks. Some post-processes have been integrated to eliminate wrong spots and produce bounding boxes of wind turbine instances. The evaluation metrics prove the reliability and effectiveness of our method for the average F1-score of our detection method is up to 0.97. The comparison of detection accuracy and time consuming with the weakly supervised targets detection method based on CNN illustrates the superiority of our method.

An evolution based biosensor receptor DNA sequence generation algorithm.

PubMed

Kim, Eungyeong; Lee, Malrey; Gatton, Thomas M; Lee, Jaewan; Zang, Yupeng

2010-01-01

A biosensor is composed of a bioreceptor, an associated recognition molecule, and a signal transducer that can selectively detect target substances for analysis. DNA based biosensors utilize receptor molecules that allow hybridization with the target analyte. However, most DNA biosensor research uses oligonucleotides as the target analytes and does not address the potential problems of real samples. The identification of recognition molecules suitable for real target analyte samples is an important step towards further development of DNA biosensors. This study examines the characteristics of DNA used as bioreceptors and proposes a hybrid evolution-based DNA sequence generating algorithm, based on DNA computing, to identify suitable DNA bioreceptor recognition molecules for stable hybridization with real target substances. The Traveling Salesman Problem (TSP) approach is applied in the proposed algorithm to evaluate the safety and fitness of the generated DNA sequences. This approach improves efficiency and stability for enhanced and variable-length DNA sequence generation and allows extension to generation of variable-length DNA sequences with diverse receptor recognition requirements.

Selective complexation of K+ and Na+ in simple polarizable ion-ligating systems.

PubMed

Bostick, David L; Brooks, Charles L

2010-09-29

An influx of experimental and theoretical studies of ion transport protein structure has inspired efforts to understand underlying determinants of ionic selectivity. Design principles for selective ion binding can be effectively isolated and interrogated using simplified models composed of a single ion surrounded by a set of ion-ligating molecular species. While quantum mechanical treatments of such systems naturally incorporate electronic degrees of freedom, their computational overhead typically prohibits thorough dynamic sampling of configurational space and, thus, requires approximations when determining ion-selective free energy. As an alternative, we employ dynamical simulations with a polarizable force field to probe the structure and K(+)/Na(+) selectivity in simple models composed of one central K(+)/Na(+) ion surrounded by 0-8 identical model compounds: N-methylacetamide, formamide, or water. In the absence of external restraints, these models represent gas-phase clusters displaying relaxed coordination structures with low coordination number. Such systems display Na(+) selectivity when composed of more than ∼3 organic carbonyl-containing compounds and always display K(+) selectivity when composed of water molecules. Upon imposing restraints that solely enforce specific coordination numbers, we find all models are K(+)-selective when ∼7-8-fold ion coordination is achieved. However, when models composed of the organic compounds provide ∼4-6-fold coordination, they retain their Na(+) selectivity. From these trends, design principles emerge that are of basic importance in the behavior of K(+) channel selectivity filters and suggest a basis not only for K(+) selectivity but also for modulation of block and closure by smaller ions.

A Fisheries Application of a Dual-Frequency Identification Sonar Acoustic Camera

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

Moursund, Russell A.; Carlson, Thomas J.; Peters, Rock D.

2003-06-01

The uses of an acoustic camera in fish passage research at hydropower facilities are being explored by the U.S. Army Corps of Engineers. The Dual-Frequency Identification Sonar (DIDSON) is a high-resolution imaging sonar that obtains near video-quality images for the identification of objects underwater. Developed originally for the Navy by the University of Washington?s Applied Physics Laboratory, it bridges the gap between existing fisheries assessment sonar and optical systems. Traditional fisheries assessment sonars detect targets at long ranges but cannot record the shape of targets. The images within 12 m of this acoustic camera are so clear that one canmore » see fish undulating as they swim and can tell the head from the tail in otherwise zero-visibility water. In the 1.8 MHz high-frequency mode, this system is composed of 96 beams over a 29-degree field of view. This high resolution and a fast frame rate allow the acoustic camera to produce near video-quality images of objects through time. This technology redefines many of the traditional limitations of sonar for fisheries and aquatic ecology. Images can be taken of fish in confined spaces, close to structural or surface boundaries, and in the presence of entrained air. The targets themselves can be visualized in real time. The DIDSON can be used where conventional underwater cameras would be limited in sampling range to < 1 m by low light levels and high turbidity, and where traditional sonar would be limited by the confined sample volume. Results of recent testing at The Dalles Dam, on the lower Columbia River in Oregon, USA, are shown.« less

Contextual cueing of pop-out visual search: when context guides the deployment of attention.

PubMed

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

2010-05-01

Visual context information can guide attention in demanding (i.e., inefficient) search tasks. When participants are repeatedly presented with identically arranged ('repeated') displays, reaction times are faster relative to newly composed ('non-repeated') displays. The present article examines whether this 'contextual cueing' effect operates also in simple (i.e., efficient) search tasks and if so, whether there it influences target, rather than response, selection. The results were that singleton-feature targets were detected faster when the search items were presented in repeated, rather than non-repeated, arrangements. Importantly, repeated, relative to novel, displays also led to an increase in signal detection accuracy. Thus, contextual cueing can expedite the selection of pop-out targets, most likely by enhancing feature contrast signals at the overall-salience computation stage.

Yersinia type III effectors perturb host innate immune responses

PubMed Central

Pha, Khavong; Navarro, Lorena

2016-01-01

The innate immune system is the first line of defense against invading pathogens. Innate immune cells recognize molecular patterns from the pathogen and mount a response to resolve the infection. The production of proinflammatory cytokines and reactive oxygen species, phagocytosis, and induced programmed cell death are processes initiated by innate immune cells in order to combat invading pathogens. However, pathogens have evolved various virulence mechanisms to subvert these responses. One strategy utilized by Gram-negative bacterial pathogens is the deployment of a complex machine termed the type III secretion system (T3SS). The T3SS is composed of a syringe-like needle structure and the effector proteins that are injected directly into a target host cell to disrupt a cellular response. The three human pathogenic Yersinia spp. (Y. pestis, Y. enterocolitica, and Y. pseudotuberculosis) are Gram-negative bacteria that share in common a 70 kb virulence plasmid which encodes the T3SS. Translocation of the Yersinia effector proteins (YopE, YopH, YopT, YopM, YpkA/YopO, and YopP/J) into the target host cell results in disruption of the actin cytoskeleton to inhibit phagocytosis, downregulation of proinflammatory cytokine/chemokine production, and induction of cellular apoptosis of the target cell. Over the past 25 years, studies on the Yersinia effector proteins have unveiled tremendous knowledge of how the effectors enhance Yersinia virulence. Recently, the long awaited crystal structure of YpkA has been solved providing further insights into the activation of the YpkA kinase domain. Multisite autophosphorylation by YpkA to activate its kinase domain was also shown and postulated to serve as a mechanism to bypass regulation by host phosphatases. In addition, novel Yersinia effector protein targets, such as caspase-1, and signaling pathways including activation of the inflammasome were identified. In this review, we summarize the recent discoveries made on Yersinia effector proteins and their contribution to Yersinia pathogenesis. PMID:26981193

Exploring the Self through Songwriting: An Analysis of Songs Composed by People with Acquired Neurodisability in an Inpatient Rehabilitation Program.

PubMed

Baker, Felicity A; Tamplin, Jeanette; MacDonald, Raymond A R; Ponsford, Jennie; Roddy, Chantal; Lee, Claire; Rickard, Nikki

2017-03-01

Neurological trauma is associated with significant damage to people's pre-injury self-concept. Therapeutic songwriting has been linked with changes in self-concept and improved psychological well-being. This study analyzed the lyrics of songs composed by inpatients with neurological injuries who participated in a targeted songwriting program. The aim of this study was to understand which of the subdomains of the self-concept were the most frequently expressed in songs. An independent, deductive content analysis of 36 songs composed by 12 adults with spinal cord injury or brain injury (11 males, mean age 41 years +/- 13) were undertaken by authors 1 and 2. Deductive analysis indicated that when writing about the past self, people created songs that reflected a strong focus on family and descriptions of their personality. In contrast, there is a clear preoccupation with the physical self, on the personal self, and a tendency for spiritual and moral reflections to emerge during the active phase of rehabilitation (song about the present self). Statistical analyses confirmed a significant self-concept subdomain by song interaction, F(10, 110) = 5.98, p < .001, ηp2 = .35), which was primarily due to an increased focus on physical self-concept and a reduced focus on family self-concept in the present song, more than in either past or future songs. The analysis process confirmed that songwriting is a vehicle that allows for exploration of self-concept in individuals with neurological impairments. Songwriting may serve as a therapeutic tool to target the most prevalent areas of self-concept challenges for clients undergoing inpatient neurological rehabilitation programs. © the American Music Therapy Association 2017. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com

The Breakthrough Listen Search for Intelligent Life: Target Selection of Nearby Stars and Galaxies

NASA Astrophysics Data System (ADS)

Isaacson, Howard; Siemion, Andrew P. V.; Marcy, Geoffrey W.; Lebofsky, Matt; Price, Danny C.; MacMahon, David; Croft, Steve; DeBoer, David; Hickish, Jack; Werthimer, Dan; Sheikh, Sofia; Hellbourg, Greg; Enriquez, J. Emilio

2017-05-01

We present the target selection for the Breakthrough Listen search for extraterrestrial intelligence during the first year of observations at the Green Bank Telescope, Parkes Telescope, and Automated Planet Finder. On the way to observing 1,000,000 nearby stars in search of technological signals, we present three main sets of objects we plan to observe in addition to a smaller sample of exotica. We chose the 60 nearest stars, all within 5.1 pc from the Sun. Such nearby stars offer the potential to observe faint radio signals from transmitters that have a power similar to those on Earth. We add a list of 1649 stars drawn from the Hipparcos catalog that span the Hertzprung-Russell diagram, including all spectral types along the main sequence, subgiants, and giant stars. This sample offers diversity and inclusion of all stellar types, but with thoughtful limits and due attention to main sequence stars. Our targets also include 123 nearby galaxies composed of a “morphological-type-complete” sample of the nearest spirals, ellipticals, dwarf spherioidals, and irregulars. While their great distances hamper the detection of technological electromagnetic radiation, galaxies offer the opportunity to observe billions of stars simultaneously and to sample the bright end of the technological luminosity function. We will also use the Green Bank and Parkes telescopes to survey the plane and central bulge of the Milky Way. Finally, the complete target list includes several classes of exotica, including white dwarfs, brown dwarfs, black holes, neutron stars, and asteroids in our solar system.

Mitochondrial fumarate reductase as a target of chemotherapy: from parasites to cancer cells.

PubMed

Sakai, Chika; Tomitsuka, Eriko; Esumi, Hiroyasu; Harada, Shigeharu; Kita, Kiyoshi

2012-05-01

Recent research on respiratory chain of the parasitic helminth, Ascaris suum has shown that the mitochondrial NADH-fumarate reductase system (fumarate respiration), which is composed of complex I (NADH-rhodoquinone reductase), rhodoquinone and complex II (rhodoquinol-fumarate reductase) plays an important role in the anaerobic energy metabolism of adult parasites inhabiting hosts. The enzymes in these parasite-specific pathways are potential target for chemotherapy. We isolated a novel compound, nafuredin, from Aspergillus niger, which inhibits NADH-fumarate reductase in helminth mitochondria at nM order. It competes for the quinone-binding site in complex I and shows high selective toxicity to the helminth enzyme. Moreover, nafuredin exerts anthelmintic activity against Haemonchus contortus in in vivo trials with sheep indicating that mitochondrial complex I is a promising target for chemotherapy. In addition to complex I, complex II is a good target because its catalytic direction is reverse of succinate-ubiquionone reductase in the host complex II. Furthermore, we found atpenin and flutolanil strongly and specifically inhibit mitochondrial complex II. Interestingly, fumarate respiration was found not only in the parasites but also in some types of human cancer cells. Analysis of the mitochondria from the cancer cells identified an anthelminthic as a specific inhibitor of the fumarate respiration. Role of isoforms of human complex II in the hypoxic condition of cancer cells and fetal tissues is a challenge. This article is part of a Special Issue entitled Biochemistry of Mitochondria, Life and Intervention 2010. Copyright © 2011 Elsevier B.V. All rights reserved.

A GRAVITATIONAL DOUBLE-SCATTERING MECHANISM FOR GENERATING HIGH-VELOCITY OBJECTS DURING HALO MERGERS

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

Samsing, Johan; Department of Astrophysical Sciences, Princeton University, Peyton Hall, Princeton, NJ 08544

2015-02-01

We present a dynamical model that describes how halo particles can receive a significant energy kick from the merger between their own host halo and a target halo. This could provide a possible explanation for some high-velocity objects, including extended systems like globular clusters (GCs). In the model we especially introduce a double-scattering mechanism, where a halo particle receives a significant part of its total energy kick by first undergoing a gravitational deflection by the target halo and subsequently by its original host halo. This generates an energy kick that is due to the relative velocity between the halos duringmore » the deflections. We derive analytically the total kick energy of the particle, which is composed of energy from the double-scattering mechanism and tidal fields, as a function of its position in its original host halo just before merger. In the case of a 1:10 merger, we find that the presented mechanisms can easily generate particles with a velocity approximately two times the virial velocity of the target halo. This motivates us to suggest that the high velocity of the recently discovered GC HVGC-1 can be explained by a head-on halo merger. Finally, we illustrate the orbital evolution of high-velocity particles outside the virial sphere of the target halo by solving the equation of motion in an expanding universe. We find a sweet spot around a scale factor of 0.3-0.5 for ejecting particles into large orbits, which can easily reach beyond approximately five virial radii.« less

Remote magnetic targeting of iron oxide nanoparticles for cardiovascular diagnosis and therapeutic drug delivery: where are we now?

PubMed Central

Bietenbeck, Michael; Florian, Anca; Faber, Cornelius; Sechtem, Udo; Yilmaz, Ali

2016-01-01

Magnetic resonance imaging (MRI) allows for an accurate assessment of both functional and structural cardiac parameters, and thereby appropriate diagnosis and validation of cardiovascular diseases. The diagnostic yield of cardiovascular MRI examinations is often increased by the use of contrast agents that are almost exclusively based on gadolinium compounds. Another clinically approved contrast medium is composed of superparamagnetic iron oxide nanoparticles (IONs). These particles may expand the field of contrast-enhanced cardiovascular MRI as recently shown in clinical studies focusing on acute myocardial infarction (AMI) and atherosclerosis. Furthermore, IONs open up new research opportunities such as remote magnetic drug targeting (MDT). The approach of MDT relies on the coupling of bioactive molecules and magnetic nanoparticles to form an injectable complex. This complex, in turn, can be attracted to and retained at a desired target inside the body with the help of applied magnetic fields. In comparison to common systemic drug applications, MDT techniques promise both higher concentrations at the target site and lower concentrations elsewhere in the body. Moreover, concurrent or subsequent MRI can be used for noninvasive monitoring of drug distribution and successful delivery to the desired organ in vivo. This review does not only illustrate the basic conceptual and biophysical principles of IONs, but also focuses on new research activities and achievements in the cardiovascular field, mainly in the management of AMI. Based on the presentation of successful MDT applications in preclinical models of AMI, novel approaches and the translational potential of MDT are discussed. PMID:27486321

User-composable Electronic Health Record Improves Efficiency of Clinician Data Viewing for Patient Case Appraisal: A Mixed-Methods Study

PubMed Central

Senathirajah, Yalini; Kaufman, David; Bakken, Suzanne

2016-01-01

Background: Challenges in the design of electronic health records (EHRs) include designing usable systems that must meet the complex, rapidly changing, and high-stakes information needs of clinicians. The ability to move and assemble elements together on the same page has significant human-computer interaction (HCI) and efficiency advantages, and can mitigate the problems of negotiating multiple fixed screens and the associated cognitive burdens. Objective: We compare MedWISE—a novel EHR that supports user-composable displays—with a conventional EHR in terms of the number of repeat views of data elements for patient case appraisal. Design and Methods: The study used mixed-methods for examination of clinical data viewing in four patient cases. The study compared use of an experimental user-composable EHR with use of a conventional EHR, for case appraisal. Eleven clinicians used a user-composable EHR in a case appraisal task in the laboratory setting. This was compared with log file analysis of the same patient cases in the conventional EHR. We investigated the number of repeat views of the same clinical information during a session and across these two contexts, and compared them using Fisher’s exact test. Results: There was a significant difference (p<.0001) in proportion of cases with repeat data element viewing between the user-composable EHR (14.6 percent) and conventional EHR (72.6 percent). Discussion and Conclusion: Users of conventional EHRs repeatedly viewed the same information elements in the same session, as revealed by log files. Our findings are consistent with the hypothesis that conventional systems require that the user view many screens and remember information between screens, causing the user to forget information and to have to access the information a second time. Other mechanisms (such as reduction in navigation over a population of users due to interface sharing, and information selection) may also contribute to increased efficiency in the experimental system. Systems that allow a composable approach that enables the user to gather together on the same screen any desired information elements may confer cognitive support benefits that can increase productive use of systems by reducing fragmented information. By reducing cognitive overload, it can also enhance the user experience. PMID:27195306

Molecular Dynamics Modeling of Carbon Nanotube Composite Fracture Using ReaxFF

NASA Technical Reports Server (NTRS)

Jensen, Benjamin D.; Wise, Kristopher E.; Odegard, Gregory M.

2016-01-01

Carbon nanotube (CNT) fiber reinforced composites with specific tensile strengths and moduli approaching those of aerospace grade carbon fiber composites have recently been reported. This achievement was enabled by the emerging availability of high N/tex yarns in kilometer-scale quantities. While the production of this yarn is an impressive advance, its strength is still much lower than that of the individual CNTs comprising the yarn. Closing this gap requires understanding load transfer between CNTs at the nanometer dimensional scale. This work uses reactive molecular dynamics simulations to gain an understanding at the nanometer scale of the key factors that determine CNT nanocomposite mechanical performance, and to place more realistic upper bounds on the target properties. While molecular dynamics simulations using conventional force fields can predict elastic properties, the ReaxFF reactive forcefield can also model fracture behavior because of its ability to accurately describe bond breaking and formation during a simulation. The upper and lower bounds of CNT composite properties are investigated by comparing systems composed of CNTs continuously connected across the periodic boundary with systems composed of finite length CNTs. These lengths, effectively infinite for the continuous tubes and an aspect ratio of 13 for the finite length case, result from practical limitations on the number of atoms that can be included in a simulation. Experimentally measured aspect ratios are typically on the order of 100,000, so the calculated results should represent upper and lower limits on experimental mechanical properties. Finally, the effect of various degrees of covalent crosslinking between the CNTs and amorphous carbon matrix is considered to identify the amount of CNT-matrix covalent bonding that maximizes overall composite properties.

Context- and Template-Based Compression for Efficient Management of Data Models in Resource-Constrained Systems.

PubMed

Macho, Jorge Berzosa; Montón, Luis Gardeazabal; Rodriguez, Roberto Cortiñas

2017-08-01

The Cyber Physical Systems (CPS) paradigm is based on the deployment of interconnected heterogeneous devices and systems, so interoperability is at the heart of any CPS architecture design. In this sense, the adoption of standard and generic data formats for data representation and communication, e.g., XML or JSON, effectively addresses the interoperability problem among heterogeneous systems. Nevertheless, the verbosity of those standard data formats usually demands system resources that might suppose an overload for the resource-constrained devices that are typically deployed in CPS. In this work we present Context- and Template-based Compression (CTC), a data compression approach targeted to resource-constrained devices, which allows reducing the resources needed to transmit, store and process data models. Additionally, we provide a benchmark evaluation and comparison with current implementations of the Efficient XML Interchange (EXI) processor, which is promoted by the World Wide Web Consortium (W3C), and it is the most prominent XML compression mechanism nowadays. Interestingly, the results from the evaluation show that CTC outperforms EXI implementations in terms of memory usage and speed, keeping similar compression rates. As a conclusion, CTC is shown to be a good candidate for managing standard data model representation formats in CPS composed of resource-constrained devices.

Context- and Template-Based Compression for Efficient Management of Data Models in Resource-Constrained Systems

PubMed Central

Montón, Luis Gardeazabal

2017-01-01

The Cyber Physical Systems (CPS) paradigm is based on the deployment of interconnected heterogeneous devices and systems, so interoperability is at the heart of any CPS architecture design. In this sense, the adoption of standard and generic data formats for data representation and communication, e.g., XML or JSON, effectively addresses the interoperability problem among heterogeneous systems. Nevertheless, the verbosity of those standard data formats usually demands system resources that might suppose an overload for the resource-constrained devices that are typically deployed in CPS. In this work we present Context- and Template-based Compression (CTC), a data compression approach targeted to resource-constrained devices, which allows reducing the resources needed to transmit, store and process data models. Additionally, we provide a benchmark evaluation and comparison with current implementations of the Efficient XML Interchange (EXI) processor, which is promoted by the World Wide Web Consortium (W3C), and it is the most prominent XML compression mechanism nowadays. Interestingly, the results from the evaluation show that CTC outperforms EXI implementations in terms of memory usage and speed, keeping similar compression rates. As a conclusion, CTC is shown to be a good candidate for managing standard data model representation formats in CPS composed of resource-constrained devices. PMID:28763013

Marshall information retrieval and display system (MIRADS)

NASA Technical Reports Server (NTRS)

Groover, J. L.; Jones, S. C.; King, W. L.

1974-01-01

Program for data management system allows sophisticated inquiries while utilizing simplified language. Online system is composed of several programs. System is written primarily in COBOL with routines in ASSEMBLER and FORTRAN V.

Magnetic-Fe/Fe3O4-nanoparticle-bound SN38 as carboxylesterase-cleavable prodrug for the delivery to tumors within monocytes/macrophages

PubMed Central

Shrestha, Tej B; Basel, Matthew T; Dani, Raj Kumar; Seo, Gwi-Moon; Balivada, Sivasai; Pyle, Marla M; Prock, Heidy; Koper, Olga B; Thapa, Prem S; Moore, David; Li, Ping; Chikan, Viktor

2012-01-01

Summary The targeted delivery of therapeutics to the tumor site is highly desirable in cancer treatment, because it is capable of minimizing collateral damage. Herein, we report the synthesis of a nanoplatform, which is composed of a 15 ± 1 nm diameter core/shell Fe/Fe3O4 magnetic nanoparticles (MNPs) and the topoisomerase I blocker SN38 bound to the surface of the MNPs via a carboxylesterase cleavable linker. This nanoplatform demonstrated high heating ability (SAR = 522 ± 40 W/g) in an AC-magnetic field. For the purpose of targeted delivery, this nanoplatform was loaded into tumor-homing double-stable RAW264.7 cells (mouse monocyte/macrophage-like cells (Mo/Ma)), which have been engineered to express intracellular carboxylesterase (InCE) upon addition of doxycycline by a Tet-On Advanced system. The nanoplatform was taken up efficiently by these tumor-homing cells. They showed low toxicity even at high nanoplatform concentration. SN38 was released successfully by switching on the Tet-On Advanced system. We have demonstrated that this nanoplatform can be potentially used for thermochemotherapy. We will be able to achieve the following goals: (1) Specifically deliver the SN38 prodrug and magnetic nanoparticles to the cancer site as the payload of tumor-homing double-stable RAW264.7 cells; (2) Release of chemotherapeutic SN38 at the cancer site by means of the self-containing Tet-On Advanced system; (3) Provide localized magnetic hyperthermia to enhance the cancer treatment, both by killing cancer cells through magnetic heating and by activating the immune system. PMID:23016149

A secretome analysis reveals that PPARα is upregulated by fractionated-dose γ-irradiation in three-dimensional keratinocyte cultures

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

Lee, Jeeyong; Kim, Hyun-Ji; Yi, Jae Youn, E-mail: yjy_71@kcch.re.kr

Studies have shown that γ-irradiation induces various biological responses, including oxidative stress and apoptosis, as well as cellular repair and immune system responses. However, most such studies have been performed using traditional two-dimensional cell culture systems, which are limited in their ability to faithfully represent in vivo conditions. A three-dimensional (3D) environment composed of properly interconnected and differentiated cells that allow communication and cooperation among cells via secreted molecules would be expected to more accurately reflect cellular responses. Here, we investigated γ-irradiation–induced changes in the secretome of 3D-cultured keratinocytes. An analysis of keratinocyte secretome profiles following fractionated-dose γ-irradiation revealed changes inmore » genes involved in cell adhesion, angiogenesis, and the immune system. Notably, peroxisome proliferator-activated receptor-α (PPARα) was upregulated in response to fractionated-dose γ-irradiation. This upregulation was associated with an increase in the transcription of known PPARα target genes in secretome, including angiopoietin-like protein 4, dermokine and kallikrein-related peptide 12, which were differentially regulated by fractionated-dose γ-irradiation. Collectively, our data imply a mechanism linking γ-irradiation and secretome changes, and suggest that these changes could play a significant role in the coordinated cellular responses to harmful ionizing radiation, such as those associated with radiation therapy. This extension of our understanding of γ-irradiation-induced secretome changes has the potential to improve radiation therapy strategies. - Highlights: • γ-irradiation induced changes of cell adhesion, angiogenesis, and immune system in secretome of 3D-cultured keratinocytes. • Peroxisome proliferator-activated receptor-α (PPARα) was upregulated in response to fractionated-dose γ-irradiation. • The known PPARα target genes were differentially regulated by fractionated-dose γ-irradiation.« less

Medical lighting composed of LED arrays for surgical operation

NASA Astrophysics Data System (ADS)

Shimada, Junichi; Kawakami, Yoichi; Fujita, Shigeo

2001-05-01

Everywhere in the world, the highest quality and quantity of lighting is required during the surgical operations. However, the surgical approach has had many types and various angles, common ceiling surgical halogen lighting system cannot provide an adequate amount of beams because the surgeons' heads hinder the illuminations from reaching the operation field. Here, we newly design surgical lighting system composed of white LEDs equipped on both sides of goggles, which controls the lighting beams to the gazing point. With this system, it is just needed for surgeons to wear light plastic goggles with high quality LEDs made by Nichia. In fact, we have succeeded in the first internal shunt operation in the left forearm using the surgical LED lighting system on 11th Sept 2000. The electrical power for the system was supplied from lithium-ion battery for 2 hours. Since the white LEDs used were composed of InGaN- blue-emitters and YAG-yellow-phosphors, the color rendering property was not sufficient in the reddish colors. Therefore, in the next approach, it is very important to develop the spectral distribution of white LED to render inherent color of raw flesh such as skin, blood, fat tissue and internal organs.

Functional Biomimetic Architectures

NASA Astrophysics Data System (ADS)

Levine, Paul M.

N-substituted glycine oligomers, or 'peptoids,' are a class of sequence--specific foldamers composed of tertiary amide linkages, engendering proteolytic stability and enhanced cellular permeability. Peptoids are notable for their facile synthesis, sequence diversity, and ability to fold into distinct secondary structures. In an effort to establish new functional peptoid architectures, we utilize the copper-catalyzed azide-alkyne [3+2] cycloaddition (CuAAC) reaction to generate peptidomimetic assemblies bearing bioactive ligands that specifically target and modulate Androgen Receptor (AR) activity, a major therapeutic target for prostate cancer. Additionally, we explore chemical ligation protocols to generate semi-synthetic hybrid biomacromolecules capable of exhibiting novel structures and functions not accessible to fully biosynthesized proteins.

Measurement of positron annihilation lifetimes for positron burst by multi-detector array

NASA Astrophysics Data System (ADS)

Wang, B. Y.; Kuang, P.; Liu, F. Y.; Han, Z. J.; Cao, X. Z.; Zhang, P.

2018-03-01

It is currently impossible to exploit the timing information in a gamma-ray pulse generated within nanoseconds when a high-intensity positron burst annihilation event occurs in a target using conventional single-detector methods. A state-of-the-art solution to the problem is proposed in this paper. In this approach, a multi-detector array composed of many independent detection cells mounted spherically around the target is designed to detect the time distribution of the annihilated gamma rays generated following, in particular, a positron burst emitting huge amounts of positrons in a short pulse duration, even less than a few nano- or picoseconds.

A Framework for Adaptable Operating and Runtime Systems

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

Sterling, Thomas

The emergence of new classes of HPC systems where performance improvement is enabled by Moore’s Law for technology is manifest through multi-core-based architectures including specialized GPU structures. Operating systems were originally designed for control of uniprocessor systems. By the 1980s multiprogramming, virtual memory, and network interconnection were integral services incorporated as part of most modern computers. HPC operating systems were primarily derivatives of the Unix model with Linux dominating the Top-500 list. The use of Linux for commodity clusters was first pioneered by the NASA Beowulf Project. However, the rapid increase in number of cores to achieve performance gain throughmore » technology advances has exposed the limitations of POSIX general-purpose operating systems in scaling and efficiency. This project was undertaken through the leadership of Sandia National Laboratories and in partnership of the University of New Mexico to investigate the alternative of composable lightweight kernels on scalable HPC architectures to achieve superior performance for a wide range of applications. The use of composable operating systems is intended to provide a minimalist set of services specifically required by a given application to preclude overheads and operational uncertainties (“OS noise”) that have been demonstrated to degrade efficiency and operational consistency. This project was undertaken as an exploration to investigate possible strategies and methods for composable lightweight kernel operating systems towards support for extreme scale systems.« less

Landscape genetics for the empirical assessment of resistance surfaces: The European pine marten (Martes martes) as a target-species of a regional ecological network

Treesearch

Aritz Ruiz-Gonzalez; Mikel Gurrutxaga; Samuel A. Cushman; Maria Jose Madeira; Ettore Randi; Benjamin J. Gomez-Moliner

2014-01-01

Coherent ecological networks (EN) composed of core areas linked by ecological corridors are being developed worldwide with the goal of promoting landscape connectivity and biodiversity conservation. However, empirical assessment of the performance of EN designs is critical to evaluate the utility of these networks to mitigate effects of habitat loss and...

Complex Dynamic Scene Perception: Effects of Attentional Set on Perceiving Single and Multiple Event Types

ERIC Educational Resources Information Center

Sanocki, Thomas; Sulman, Noah

2013-01-01

Three experiments measured the efficiency of monitoring complex scenes composed of changing objects, or events. All events lasted about 4 s, but in a given block of trials, could be of a single type (single task) or of multiple types (multitask, with a total of four event types). Overall accuracy of detecting target events amid distractors was…

Systolic Algorithms for Imaging from Space

DTIC Science & Technology

1989-07-31

on a keystone or trapezoidal grid [ Arikan & Munson, 1987]. The image reconstruction algorithm then simply applies an inverse 2-D FFT to the stored...rithm composed of groups of point targets, and we determined the effects of windowing and incor- poration of a Jacobian weighting factor [ Arikan ...the impulse response of the desired filter [ Arikan & Munson, 1989]. The necessary filtering is then accomplished through the physical mechanism of the

Utilization and viability of biologically-inspired algorithms in a dynamic multiagent camera surveillance system

NASA Astrophysics Data System (ADS)

Mundhenk, Terrell N.; Dhavale, Nitin; Marmol, Salvador; Calleja, Elizabeth; Navalpakkam, Vidhya; Bellman, Kirstie; Landauer, Chris; Arbib, Michael A.; Itti, Laurent

2003-10-01

In view of the growing complexity of computational tasks and their design, we propose that certain interactive systems may be better designed by utilizing computational strategies based on the study of the human brain. Compared with current engineering paradigms, brain theory offers the promise of improved self-organization and adaptation to the current environment, freeing the programmer from having to address those issues in a procedural manner when designing and implementing large-scale complex systems. To advance this hypothesis, we discus a multi-agent surveillance system where 12 agent CPUs each with its own camera, compete and cooperate to monitor a large room. To cope with the overload of image data streaming from 12 cameras, we take inspiration from the primate"s visual system, which allows the animal to operate a real-time selection of the few most conspicuous locations in visual input. This is accomplished by having each camera agent utilize the bottom-up, saliency-based visual attention algorithm of Itti and Koch (Vision Research 2000;40(10-12):1489-1506) to scan the scene for objects of interest. Real time operation is achieved using a distributed version that runs on a 16-CPU Beowulf cluster composed of the agent computers. The algorithm guides cameras to track and monitor salient objects based on maps of color, orientation, intensity, and motion. To spread camera view points or create cooperation in monitoring highly salient targets, camera agents bias each other by increasing or decreasing the weight of different feature vectors in other cameras, using mechanisms similar to excitation and suppression that have been documented in electrophysiology, psychophysics and imaging studies of low-level visual processing. In addition, if cameras need to compete for computing resources, allocation of computational time is weighed based upon the history of each camera. A camera agent that has a history of seeing more salient targets is more likely to obtain computational resources. The system demonstrates the viability of biologically inspired systems in a real time tracking. In future work we plan on implementing additional biological mechanisms for cooperative management of both the sensor and processing resources in this system that include top down biasing for target specificity as well as novelty and the activity of the tracked object in relation to sensitive features of the environment.

Convergence Estimates for Multidisciplinary Analysis and Optimization

NASA Technical Reports Server (NTRS)

Arian, Eyal

1997-01-01

A quantitative analysis of coupling between systems of equations is introduced. This analysis is then applied to problems in multidisciplinary analysis, sensitivity, and optimization. For the sensitivity and optimization problems both multidisciplinary and single discipline feasibility schemes are considered. In all these cases a "convergence factor" is estimated in terms of the Jacobians and Hessians of the system, thus it can also be approximated by existing disciplinary analysis and optimization codes. The convergence factor is identified with the measure for the "coupling" between the disciplines in the system. Applications to algorithm development are discussed. Demonstration of the convergence estimates and numerical results are given for a system composed of two non-linear algebraic equations, and for a system composed of two PDEs modeling aeroelasticity.

Imaging Metastasis Using an Integrin-Targeting Chain-Shaped Nanoparticle

PubMed Central

Peiris, Pubudu M.; Toy, Randall; Doolittle, Elizabeth; Pansky, Jenna; Abramowski, Aaron; Tam, Morgan; Vicente, Peter; Tran, Emily; Hayden, Elliott; Camann, Andrew; Mayer, Aaron; Erokwu, Bernadette O.; Berman, Zachary; Wilson, David; Baskaran, Harihara; Flask, Chris A.; Keri, Ruth A.; Karathanasis, Efstathios

2012-01-01

While the enhanced permeability and retention effect may promote the preferential accumulation of nanoparticles into well-vascularized primary tumors, it is ineffective in the case of metastases hidden within a large population of normal cells. Due to their small size, high dispersion to organs, and low vascularization, metastatic tumors are less accessible to targeted nanoparticles. To tackle these challenges, we designed a nanoparticle for vascular targeting based on an αvβ3 integrin-targeted nanochain particle composed of four iron oxide nanospheres chemically linked in a linear assembly. The chain-shaped nanoparticles enabled enhanced ‘sensing’ of the tumor-associated remodeling of the vascular bed offering increased likelihood of specific recognition of metastatic tumors. Compared to spherical nanoparticles, the chain-shaped nanoparticles resulted in superior targeting of αvβ3 integrin due to geometrically enhanced multivalent docking. We performed multimodal in vivo imaging (Fluorescence Molecular Tomography and Magnetic Resonance Imaging) in a non-invasive and quantitative manner, which showed that the nanoparticles targeted metastases in the liver and lungs with high specificity in a highly aggressive breast tumor model in mice. PMID:23005348

Poly(NIPAm-AMPS) nanoparticles for targeted delivery of anti-inflammatory cell penetrating peptides

NASA Astrophysics Data System (ADS)

Bartlett, Rush Lloyd, II

Inflammatory diseases such as osteoarthritis and rheumatoid arthritis cause $127.8 billion in US healthcare expenditures each year and are the cause of disability for 27% of disabled persons in the United States. Current treatment options rarely halt disease progression and often result in significant unwanted and debilitating side effects. Our laboratory has previously developed a family of cell penetrating peptides (CPPs) which inhibit the activity of mitogen activated protein kinase activate protein kinase 2 (MK2). MK2 mediates the inflammatory response by activating Tristetraprline (TTP). Once activated, TTP rapidly stabilizes AU rich regions of pro-inflammatory cytokine mRNA which allows translation of pro-inflammatory cytokines to occur. Blocking MK2 with our labs CPPs yields a decrease in inflammatory activity but CPPs by are highly non specific and prone to rapid enzymatic degradation in vivo.. In order to increase the potency of MK2 inhibiting CPPs we have developed a novel nanoparticle drug carrier composed of poly(N-isopropylacrylamide-co-2-acrylamido-2-methyl-1-propanesulfonic acid). This drug carrier has been shown to have preliminary efficacy in vitro and ex vivo for suppressing pro-inflammatory cytokine production when releasing CPPs. This thesis will present progress made on three aims: Specific Aim 1) Create and validate a NIPAm based drug delivery system that mimics the binding and release previously observed between cell penetrating peptides and glycosaminoglycans. Specific Aim 2) Engineer degradability into poly(NIPAm-AMPS) nanoparticles to enable more drug to be released and qualify that system in vitro. Specific Aim 3) Validate poly(NIPAm-AMPS) nanoparticles for targeted drug delivery in an ex vivo inflammatory model. Overall we have developed a novel anionic nanoparticle system that is biocompatible and efficient at loading and releasing cell penetrating peptides to inflamed tissue. Once loaded with a CPP the nanoparticle drug complex is capable of targeting diseased tissue and preventing the production of pro-inflammatory cytokines in both in vitro and ex vivo models.

Miniaturized Temperature-Controlled Planar Chromatography (Micro-TLC) as a Versatile Technique for Fast Screening of Micropollutants and Biomarkers Derived from Surface Water Ecosystems and During Technological Processes of Wastewater Treatment.

PubMed

Ślączka-Wilk, Magdalena M; Włodarczyk, Elżbieta; Kaleniecka, Aleksandra; Zarzycki, Paweł K

2017-07-01

There is increasing interest in the development of simple analytical systems enabling the fast screening of target components in complex samples. A number of newly invented protocols are based on quasi separation techniques involving microfluidic paper-based analytical devices and/or micro total analysis systems. Under such conditions, the quantification of target components can be performed mainly due to selective detection. The main goal of this paper is to demonstrate that miniaturized planar chromatography has the capability to work as an efficient separation and quantification tool for the analysis of multiple targets within complex environmental samples isolated and concentrated using an optimized SPE method. In particular, we analyzed various samples collected from surface water ecosystems (lakes, rivers, and the Baltic Sea of Middle Pomerania in the northern part of Poland) in different seasons, as well as samples collected during key wastewater technological processes (originating from the "Jamno" wastewater treatment plant in Koszalin, Poland). We documented that the multiple detection of chromatographic spots on RP-18W microplates-under visible light, fluorescence, and fluorescence quenching conditions, and using the visualization reagent phosphomolybdic acid-enables fast and robust sample classification. The presented data reveal that the proposed micro-TLC system is useful, inexpensive, and can be considered as a complementary method for the fast control of treated sewage water discharged by a municipal wastewater treatment plant, particularly for the detection of low-molecular mass micropollutants with polarity ranging from estetrol to progesterone, as well as chlorophyll-related dyes. Due to the low consumption of mobile phases composed of water-alcohol binary mixtures (less than 1 mL/run for the simultaneous separation of up to nine samples), this method can be considered an environmentally friendly and green chemistry analytical tool. The described analytical protocol can be complementary to those involving classical column chromatography (HPLC) or various planar microfluidic devices.

Plant GSK3 proteins regulate xylem cell differentiation downstream of TDIF-TDR signalling

NASA Astrophysics Data System (ADS)

Kondo, Yuki; Ito, Tasuku; Nakagami, Hirofumi; Hirakawa, Yuki; Saito, Masato; Tamaki, Takayuki; Shirasu, Ken; Fukuda, Hiroo

2014-03-01

During plant radial growth typically seen in trees, procambial and cambial cells act as meristematic cells in the vascular system to self-proliferate and differentiate into xylem cells. These two processes are regulated by a signalling pathway composed of a peptide ligand and its receptor; tracheary element differentiation inhibitory factor (TDIF) and TDIF RECEPTOR (TDR). Here we show that glycogen synthase kinase 3 proteins (GSK3s) are crucial downstream components of the TDIF signalling pathway suppressing xylem differentiation from procambial cells. TDR interacts with GSK3s at the plasma membrane and activates GSK3s in a TDIF-dependent fashion. Consistently, a specific inhibitor of plant GSK3s strongly induces xylem cell differentiation through BRI1-EMS SUPPRESSOR 1 (BES1), a well-known target transcription factor of GSK3s. Our findings provide insight into the regulation of cell fate determination in meristem maintenance.

Modeling and experimental investigation of x-ray spectra from a liquid metal anode x-ray tube

NASA Astrophysics Data System (ADS)

David, Bernd R.; Thran, Axel; Eckart, Rainer

2004-11-01

This paper presents simulated and measured spectra of a novel type of x-ray tube. The bremsstrahlung generating principle of this tube is based on the interaction of high energetic electrons with a turbulently flowing liquid metal separated from the vacuum by a thin window. We simulated the interaction of 50-150 keV electrons with liquid metal targets composed of the elements Ga, In, Sn, as well as the solid elements C, W and Re used for the electron windows. We obtained x-ray spectra and energy loss curves for various liquid metal/window combinations and thicknesses of the window material. In terms of optimum heat transport a thin diamond window in combination with the liquid metal GaInSn is the best suited system. If photon flux is the optimization criteria, thin tungsten/rhenium windows cooled by GaInSn should be preferred.

Transformable liquid-metal nanomedicine

PubMed Central

Lu, Yue; Hu, Quanyin; Lin, Yiliang; Pacardo, Dennis B.; Wang, Chao; Sun, Wujin; Ligler, Frances S.; Dickey, Michael D.; Gu, Zhen

2015-01-01

To date, numerous inorganic nanocarriers have been explored for drug delivery systems (DDSs). However, the clinical application of inorganic formulations has often been hindered by their toxicity and failure to biodegrade. We describe here a transformable liquid-metal nanomedicine, based on a core–shell nanosphere composed of a liquid-phase eutectic gallium-indium core and a thiolated polymeric shell. This formulation can be simply produced through a sonication-mediated method with bioconjugation flexibility. The resulting nanoparticles loaded with doxorubicin (Dox) have an average diameter of 107 nm and demonstrate the capability to fuse and subsequently degrade under a mildly acidic condition, which facilitates release of Dox in acidic endosomes after cellular internalization. Equipped with hyaluronic acid, a tumour-targeting ligand, this formulation displays enhanced chemotherapeutic inhibition towards the xenograft tumour-bearing mice. This liquid metal-based DDS with fusible and degradable behaviour under physiological conditions provides a new strategy for engineering theranostic agents with low toxicity. PMID:26625944

Comparative microstructures and cytotoxicity assays for ballistic aerosols composed of micrometals and nanometals: respiratory health implications

PubMed Central

Machado, Brenda I; Suro, Raquel M; Garza, Kristine M; Murr, Lawrence E

2011-01-01

Aerosol particulates collected on filters from ballistic penetration and erosion events for W–Ni–Co and W–Ni–Fe kinetic energy rod projectiles penetrating steel target plates were observed to be highly cytotoxic to human epithelial A549 lung cells in culture after 48 hours of exposure. The aerosol consisted of micron-sized Fe particulates and nanoparticulate aggregates consisting of W, Ni or W, Co, and some Fe, characterized by scanning electron microscopy and transmission electron microscopy, and using energy-dispersive (X-ray) spectrometry for elemental analysis and mapping. Cytotoxic assays of manufactured micron-sized and nanosized metal particulates of W, Ni, Fe, and Co demonstrated that, consistent with many studies in the literature, only the nanoparticulate elements demonstrated measurable cytotoxicity. These results suggest the potential for very severe, short-term, human toxicity, in particular to the respiratory system on inhaling ballistic aerosols. PMID:21499416

Dynamic Integration of Task-Relevant Visual Features in Posterior Parietal Cortex

PubMed Central

Freedman, David J.

2014-01-01

Summary The primate visual system consists of multiple hierarchically organized cortical areas, each specialized for processing distinct aspects of the visual scene. For example, color and form are encoded in ventral pathway areas such as V4 and inferior temporal cortex, while motion is preferentially processed in dorsal pathway areas such as the middle temporal area. Such representations often need to be integrated perceptually to solve tasks which depend on multiple features. We tested the hypothesis that the lateral intraparietal area (LIP) integrates disparate task-relevant visual features by recording from LIP neurons in monkeys trained to identify target stimuli composed of conjunctions of color and motion features. We show that LIP neurons exhibit integrative representations of both color and motion features when they are task relevant, and task-dependent shifts of both direction and color tuning. This suggests that LIP plays a role in flexibly integrating task-relevant sensory signals. PMID:25199703

Quantify spatial relations to discover handwritten graphical symbols

NASA Astrophysics Data System (ADS)

Li, Jinpeng; Mouchère, Harold; Viard-Gaudin, Christian

2012-01-01

To model a handwritten graphical language, spatial relations describe how the strokes are positioned in the 2-dimensional space. Most of existing handwriting recognition systems make use of some predefined spatial relations. However, considering a complex graphical language, it is hard to express manually all the spatial relations. Another possibility would be to use a clustering technique to discover the spatial relations. In this paper, we discuss how to create a relational graph between strokes (nodes) labeled with graphemes in a graphical language. Then we vectorize spatial relations (edges) for clustering and quantization. As the targeted application, we extract the repetitive sub-graphs (graphical symbols) composed of graphemes and learned spatial relations. On two handwriting databases, a simple mathematical expression database and a complex flowchart database, the unsupervised spatial relations outperform the predefined spatial relations. In addition, we visualize the frequent patterns on two text-lines containing Chinese characters.

Assembly of the Human Signal Recognition Particle

NASA Astrophysics Data System (ADS)

Menichelli, Elena; Nagai, Kiyoshi

Large RNA-protein complexes (ribonucleoprotein particles or RNPs) control fundamental biological processes. Their correct assembly is essential for function and occurs by the ordered addition of proteins to the RNA. A good model system for studying RNP assembly is provided by the Signal Recognition Particle (SRP), an RNP conserved from bacteria to humans, with different degrees of complexity. Human SRP, composed of a single RNA molecule and six pro teins, is responsible for the co-translational targeting of secretory and membrane proteins to the endoplasmic reticulum membrane. In vitro studies reveal that the SRP proteins need to be added to the RNA sequentially. If the order of addition is altered, non-native particles are formed. The sequential association of proteins causes conformational changes in the RNA, allowing binding of other proteins. The in vivo assembly is regulated by the translocation of precursors between different cellular compartments. In this chapter we review the current understanding of the human SRP assembly mechanism.

Disrupting beta-amyloid aggregation for Alzheimer disease treatment.

PubMed

Estrada, L D; Soto, C

2007-01-01

Alzheimer's disease is a devastating degenerative disorder for which there is no cure or effective treatment. Although the etiology of Alzheimer's disease is not fully understood, compelling evidence indicates that deposition of aggregates composed by a misfolded form of the amyloid beta peptide (Abeta) is the central event in the disease pathogenesis. Therefore, an attractive therapeutic strategy is to prevent or reverse Abeta misfolding and aggregation. Diverse strategies have been described to identify inhibitors of this process, including screening of libraries of small molecules chemical compounds, rational design of synthetic peptides, assessment of natural Abeta-binding proteins and stimulation of the immune system by vaccination. In this article we describe these different approaches, their principles and their potential strengths and weaknesses. Overall the available data suggest that the development of drugs to interfere with Abeta misfolding and aggregation is a feasible target that hold great promise for the treatment of Alzheimer's disease.

Transformable liquid-metal nanomedicine

NASA Astrophysics Data System (ADS)

Lu, Yue; Hu, Quanyin; Lin, Yiliang; Pacardo, Dennis B.; Wang, Chao; Sun, Wujin; Ligler, Frances S.; Dickey, Michael D.; Gu, Zhen

2015-12-01

To date, numerous inorganic nanocarriers have been explored for drug delivery systems (DDSs). However, the clinical application of inorganic formulations has often been hindered by their toxicity and failure to biodegrade. We describe here a transformable liquid-metal nanomedicine, based on a core-shell nanosphere composed of a liquid-phase eutectic gallium-indium core and a thiolated polymeric shell. This formulation can be simply produced through a sonication-mediated method with bioconjugation flexibility. The resulting nanoparticles loaded with doxorubicin (Dox) have an average diameter of 107 nm and demonstrate the capability to fuse and subsequently degrade under a mildly acidic condition, which facilitates release of Dox in acidic endosomes after cellular internalization. Equipped with hyaluronic acid, a tumour-targeting ligand, this formulation displays enhanced chemotherapeutic inhibition towards the xenograft tumour-bearing mice. This liquid metal-based DDS with fusible and degradable behaviour under physiological conditions provides a new strategy for engineering theranostic agents with low toxicity.

Lipophilicity Assessment of Ruthenium(II)-Arene Complexes by the Means of Reversed-Phase Thin-Layer Chromatography and DFT Calculations

PubMed Central

Shweshein, Khalil Salem A. M.; Andrić, Filip; Radoičić, Aleksandra; Gruden-Pavlović, Maja; Tešić, Živoslav; Milojković-Opsenica, Dušanka

2014-01-01

The lipophilicity of ten ruthenium(II)-arene complexes was assessed by reversed-phase thin-layer chromatography (RP-TLC) on octadecyl silica stationary phase. The binary solvent systems composed of water and acetonitrile were used as mobile phase in order to determine chromatographic descriptors for lipophilicity estimation. Octanol-water partition coefficient, logK OW, of tested complexes was experimentally determined using twenty-eight standard solutes which were analyzed under the same chromatographic conditions as target substances. In addition, ab initio density functional theory (DFT) computational approach was employed to calculate logK OW values from the differences in Gibbs' free solvation energies of the solute transfer from n-octanol to water. A good overall agreement between DFT calculated and experimentally determined logK OW values was established (R 2 = 0.8024–0.9658). PMID:24587761

Environmental management on the basis of Complex Regional Indicators Concept: case of the Murmansk region

NASA Astrophysics Data System (ADS)

Kozlov, A.; Gutman, S.; Zaychenko, I.; Rytova, E.; Nijinskaya, P.

2015-09-01

The article presents an approach to sustainable environmental development of the Murmansk region of the Russian Federation based on the complex regional indicators as a transformation of a balance scorecard method. The peculiarities of Murmansk region connected with sustainable environmental development are described. The complex regional indicators approach allows to elaborate the general concept of complex regional development taking into consideration economic and non-economic factors with the focus on environmental aspects, accumulated environmental damage in particular. General strategic chart of sustainable environmental development of the Murmansk region worked out on the basis of complex regional indicators concept is composed. The key target indicators of sustainable ecological development of the Murmansk region are presented for the following strategic chart components: regional finance; society and market; industry and entrepreneurship; training, development and innovations. These charts are to be integrated with international environmental monitoring systems.

Circular economy of plastic packaging: Current practice and perspectives in Austria.

PubMed

Van Eygen, Emile; Laner, David; Fellner, Johann

2018-02-01

Plastics, especially from packaging, have gained increasing attention in waste management, driving many policy initiatives to improve the circularity of these materials in the economy to increase resource efficiency. In this context, the EU has proposed increasing targets to encourage the recycling of (plastic) packaging. To accurately calculate the recycling rates, detailed information on the flows of plastic packaging is needed. Therefore, the aim of this paper is to quantitatively and qualitatively investigate the waste management system for plastic packaging in Austria in 2013 using material flow analysis, taking into account the used product types and the polymer composition. The results show that 300,000 ± 3% t/a (35 kg/cap·a) of waste plastic packaging were produced, mainly composed of large and small films and small hollow bodies, including PET bottles. Correspondingly, the polymer composition of the waste stream was dominated by LDPE (46% ± 6%), PET (19% ± 4%) and PP (14% ± 6%). 58% ± 3% was collected separately, and regarding the final treatment, 26% ± 7% of the total waste stream was recovered as re-granulates, whereas the rest was thermally recovered in waste-to-energy plants (40% ± 3%) and the cement industry (33% ± 6%). The targets set by the EU and Austria were reached comfortably, although to reach the proposed future target major technological steps regarding collection and sorting will be needed. However, the current calculation point of the targets, i.e. on the input side of the recycling plant, is not deemed to be fully in line with the overall objective of the circular economy, namely to keep materials in the economy and prevent losses. It is therefore recommended that the targets be calculated with respect to the actual output of the recycling process, provided that the quality of the output products is maintained, to accurately assess the performance of the waste management system. Copyright © 2017 Elsevier Ltd. All rights reserved.

Markov Chain Analysis of Musical Dice Games

NASA Astrophysics Data System (ADS)

Volchenkov, D.; Dawin, J. R.

2012-07-01

A system for using dice to compose music randomly is known as the musical dice game. The discrete time MIDI models of 804 pieces of classical music written by 29 composers have been encoded into the transition matrices and studied by Markov chains. Contrary to human languages, entropy dominates over redundancy, in the musical dice games based on the compositions of classical music. The maximum complexity is achieved on the blocks consisting of just a few notes (8 notes, for the musical dice games generated over Bach's compositions). First passage times to notes can be used to resolve tonality and feature a composer.

Musical Markov Chains

NASA Astrophysics Data System (ADS)

Volchenkov, Dima; Dawin, Jean René

A system for using dice to compose music randomly is known as the musical dice game. The discrete time MIDI models of 804 pieces of classical music written by 29 composers have been encoded into the transition matrices and studied by Markov chains. Contrary to human languages, entropy dominates over redundancy, in the musical dice games based on the compositions of classical music. The maximum complexity is achieved on the blocks consisting of just a few notes (8 notes, for the musical dice games generated over Bach's compositions). First passage times to notes can be used to resolve tonality and feature a composer.

Molecular building blocks and their architecture in biologically/environmentally compatible soft matter chemical machinery.

PubMed

Toyota, Taro; Banno, Taisuke; Nitta, Sachiko; Takinoue, Masahiro; Nomoto, Tomonori; Natsume, Yuno; Matsumura, Shuichi; Fujinami, Masanori

2014-01-01

This review briefly summarizes recent developments in the construction of biologically/environmentally compatible chemical machinery composed of soft matter. Since environmental and living systems are open systems, chemical machinery must continuously fulfill its functions not only through the influx and generation of molecules but also via the degradation and dissipation of molecules. If the degradation or dissipation of soft matter molecular building blocks and biomaterial molecules/polymers can be achieved, soft matter particles composed of them can be used to realize chemical machinery such as selfpropelled droplets, drug delivery carriers, tissue regeneration scaffolds, protocell models, cell-/tissuemarkers, and molecular computing systems.

Association with Amino Acids Does Not Enhance Efficacy of Polymerized Liposomes As a System for Lung Gene Delivery

PubMed Central

Bandeira, Elga; Lopes-Pacheco, Miquéias; Chiaramoni, Nadia; Ferreira, Débora; Fernandez-Ruocco, Maria J.; Prieto, Maria J.; Maron-Gutierrez, Tatiana; Perrotta, Ramiro M.; de Castro-Faria-Neto, Hugo C.; Rocco, Patricia R. M.; Alonso, Silvia del Valle; Morales, Marcelo M.

2016-01-01

Development of improved drug and gene delivery systems directly into the lungs is highly desirable given the important burden of respiratory diseases. We aimed to evaluate the safety and efficacy of liposomes composed of photopolymerized lipids [1,2-bis-(tricosa-10,12-diynoyl)-sn-glycero-3-phosphocholine] associated with amino acids as vectors for gene delivery into the lungs of healthy animals. Lipopolymer vesicles, in particular, are more stable than other types of liposomes. In this study, lipopolymers were associated with l-arginine, l-tryptophan, or l-cysteine. We hypothesized that the addition of these amino acids would enhance the efficacy of gene delivery to the lungs by the lipopolymers. l-Arginine showed the highest association efficiency due to its positive charge and better surface interactions. None of the formulations caused inflammation or altered lung mechanics, suggesting that these lipopolymers can be safely administered as aerosols. All formulations were able to induce eGFP mRNA expression in lung tissue, but the addition of amino acids reduced delivery efficacy when compared with the simple lipopolymer particle. These results indicate that this system could be further explored for gene or drug delivery targeting lung diseases. PMID:27199766

ARCADE-R2 experiment on board BEXUS 17 stratospheric balloon

NASA Astrophysics Data System (ADS)

Barbetta, Marco; Boesso, Alessandro; Branz, Francesco; Carron, Andrea; Olivieri, Lorenzo; Prendin, Jacopo; Rodeghiero, Gabriele; Sansone, Francesco; Savioli, Livia; Spinello, Fabio; Francesconi, Alessandro

2015-09-01

This paper provides an overview of the ARCADE-R2 experiment, a technology demonstrator that aimed to prove the feasibility of small-scale satellite and/or aircraft systems with automatic (a) attitude determination, (b) control and (c) docking capabilities. The experiment embodies a simplified scenario in which an unmanned vehicle mock-up performs rendezvous and docking operations with a fixed complementary unit. The experiment is composed by a supporting structure, which holds a small vehicle with one translational and one rotational degree of freedom, and its fixed target. The dual system features three main custom subsystems: a relative infrared navigation sensor, an attitude control system based on a reaction wheel and a small-scale docking mechanism. The experiment bus is equipped with pressure and temperature sensors, and wind probes to monitor the external environmental conditions. The experiment flew on board the BEXUS 17 stratospheric balloon on October 10, 2013, where several navigation-control-docking sequences were executed and data on the external pressure, temperature, wind speed and direction were collected, characterizing the atmospheric loads applied to the vehicle. This paper describes the critical components of ARCADE-R2 as well as the main results obtained from the balloon flight.

Decoupled macro/micro-manipulator for fast and precise assembly operations: design and experiments

NASA Astrophysics Data System (ADS)

Hodac, Agathe; Siegwart, Roland Y.

1999-08-01

This paper presents a high performance single arm robot configuration, based on a macro-manipulator coupled with a micro-manipulator. The system is well suited to fast and precise positioning tasks for repetitive pick and place applications in the manufacturing industry. Firstly, the paper focuses on the design of the micro-manipulator, particularly on the selection of the proper micro-actuator type and location. We show that the micro-manipulator's design with an actuator placed between endpoint and ground and with a flexible suspension system can reduce the dynamic coupling between the macro-manipulator and the micro- manipulator. The overall system performance can then be improved. We describe two different designs of compact and fast micro-manipulators composed of voice coil actuators and a monolithic flexure suspension with notch hinges. Secondly, the paper presents a control strategy that allows both correction of possible misalignments of the end-effector relative to the target and compensation of tip oscillations. The dynamic interaction is analyzed and stability is verified. Finally, experimental results demonstrate significant improvements in acceleration, endpoint accuracy and settling time achieved by the novel configuration of the macro/micro-manipulator.

Cyto-molecular Tuning of Quantum Dots

NASA Astrophysics Data System (ADS)

Lee, Bong; Suresh, Sindhuja; Ekpenyong, Andrew

Quantum dots (QDs) are semiconductor nanoparticles composed of groups II-VI or III-V elements, with physical dimensions smaller than the exciton Bohr radius, and between 1-10 nm. Their applications and promising myriad applications in photovoltaic cells, biomedical imaging, targeted drug delivery, quantum computing, etc, have led to much research on their interactions with other systems. For biological systems, research has focused on biocompatibility and cytotoxicity of QDs in the context of imaging/therapy. However, there is a paucity of work on how biological systems might be used to tune QDs. Here, we hypothesize that the photo-electronic properties of QDs can be tuned by biological macromolecules following controlled changes in cellular activities. Using CdSe/ZnS core-shell QDs, we perform spectroscopic analysis of optically excited colloidal QDs with and without promyelocytic HL60 cells. Preliminary results show shifts in the emission spectra of the colloidal dispersions with and without cells. We will present results for activated HL60-derived cells where specific macromolecules produced by these cells perturb the electric dipole moments of the excited QDs and the associated electric fields, in ways that constitute what we describe as cyto-molecular tuning. Startup funds from the College of Arts and Sciences, Creighton University (to AEE).

Development and applications of an acoustic package for deep-sea sub-bottom profiling and detailed seafloor imaging

NASA Astrophysics Data System (ADS)

Nishimura, Kiyokazu; Kisimoto, Kiyoyuki; Joshima, Masato; Arai, Kohsaku

In the deep-sea geological survey, good survey results are difficult to obtain by a conventional surface-towed acoustic survey system, because the horizontal resolution is limited due to the long distance between the sensor and the target (seafloor). In order to improve the horizontal resolution, a deep-tow system, which tows the sensor in the vicinity of seafloor, is most practical, and many such systems have been developed and used until today. It is not easy, however, to carry out a high-density survey in a small area by maneuvering the towing body altitude sufficiently close to the seafloor with rugged topography. A ROV (Remotely Operated Vehicle) can be used to solve this problem. The ROV makes a high-density 2D survey feasible because of its maneuverability, although a long-distance survey is difficult with it. Accordingly, we have developed an acoustic survey system installed on a ROV. The system named DAIPACK (Deep-sea Acoustic Imaging Package) consists of (1) a deep-sea sub-bottom profiler and (2) a deep-sea sidescan sonar. (1) Deep-sea sub-bottom profiler A light-weight and compact sub-bottom profiler for shallow water was chosen to improve and repackage for the deep sea usage. The system is composed of three units; a transducer, an electronic unit and a notebook computer for system control and data acquisition. The source frequency is 10kHz. To convert the system for the deep sea, the transducer was exchanged for the deep sea model, and the electronic unit was improved accordingly. The electronic unit and the notebook computer were installed in a spherical pressure vessel. (2) Deep-sea sidescan sonar We remodeled a compact shallow sea sidescan sonar(water depth limitation is 30m ) into a deep sea one. This sidescan sonar is composed of a sonar towfish (transducers and an electronic unit ), a cable and a notebook computer (data processor). To accommodate in the deep water, the transducers were remodeled into a high pressure resistance type, and the electronic unit and the computer unit were stored in a spherical pressure vessel. The frequency output of the sidescan sonar is 330kHz, and the ranging distance is variable from 15m to 120m (one side).

Theory of adsorption in a polydisperse templated porous material: Hard sphere systems

NASA Astrophysics Data System (ADS)

RŻysko, Wojciech; Sokołowski, Stefan; Pizio, Orest

2002-03-01

A theoretical description of adsorption in a templated porous material, formed by an equilibrium quench of a polydisperse fluid composed of matrix and template particles and subsequent removal of the template particles is presented. The approach is based on the solution of the replica Ornstein-Zernike equations with Percus-Yevick and hypernetted chain closures. The method of solution uses expansions of size-dependent correlation functions into Fourier series, as described by Lado [J. Chem. Phys. 108, 6441 (1998)]. Specific calculations have been carried out for model systems, composed of hard spheres.

Structure–function studies of STAR family Quaking proteins bound to their in vivo RNA target sites

PubMed Central

Teplova, Marianna; Hafner, Markus; Teplov, Dmitri; Essig, Katharina; Tuschl, Thomas; Patel, Dinshaw J.

2013-01-01

Mammalian Quaking (QKI) and its Caenorhabditis elegans homolog, GLD-1 (defective in germ line development), are evolutionarily conserved RNA-binding proteins, which post-transcriptionally regulate target genes essential for developmental processes and myelination. We present X-ray structures of the STAR (signal transduction and activation of RNA) domain, composed of Qua1, K homology (KH), and Qua2 motifs of QKI and GLD-1 bound to high-affinity in vivo RNA targets containing YUAAY RNA recognition elements (RREs). The KH and Qua2 motifs of the STAR domain synergize to specifically interact with bases and sugar-phosphate backbones of the bound RRE. Qua1-mediated homodimerization generates a scaffold that enables concurrent recognition of two RREs, thereby plausibly targeting tandem RREs present in many QKI-targeted transcripts. Structure-guided mutations reduced QKI RNA-binding affinity in vitro and in vivo, and expression of QKI mutants in human embryonic kidney cells (HEK293) significantly decreased the abundance of QKI target mRNAs. Overall, our studies define principles underlying RNA target selection by STAR homodimers and provide insights into the post-transcriptional regulatory function of mammalian QKI proteins. PMID:23630077

Achievement of a high-mobility FET with a cloud-aligned composite oxide semiconductor

NASA Astrophysics Data System (ADS)

Yamazaki, Shunpei; Shima, Yukinori; Hosaka, Yasuharu; Okazaki, Kenichi; Koezuka, Junichi

2016-11-01

We have recently discovered that films of a widely used In-Ga-Zn oxide (IGZO) with \\text{In}:\\text{Ga}:\\text{Zn} = 1:1:1 have different material composition states when sputter-deposited under different conditions using the same polycrystalline IGZO target. Significant improvements in on-state current and mobility (as high as 40 cm2·V-1·s-1) are obtained. The results of local composition analysis indicate that the deposited film is not composed of any known homogeneous IGZO compound and that the components of this film are separated into two types of nanoparticle regions: one type is composed mainly of GaO x and GaZnO x , which contribute to on/off (switching) characteristics, and the other is composed mainly of InO x and InZnO x , which contribute to on-state characteristics. These regions constitute a new type of oxide semiconductor (OS) film. The nanoparticles with a blurry boundary extend like a cloud, probably complementing one another. We consider that this OS film has a novel composition, which can be described as a “cloud-aligned composite OS” (CAC-OS).

Tutorial: Reactive high power impulse magnetron sputtering (R-HiPIMS)

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

Anders, André

High Power Impulse Magnetron Sputtering (HiPIMS) is a coating technology that combines magnetron sputtering with pulsed power concepts. Furthermore, by applying power in pulses of high amplitude and a relatively low duty cycle, large fractions of sputtered atoms and near-target gases are ionized. In contrast to conventional magnetron sputtering, HiPIMS is characterized by self-sputtering or repeated gas recycling for high and low sputter yield materials, respectively, and both for most intermediate materials. The dense plasma in front of the target has the dual function of sustaining the discharge and providing plasma-assistance to film growth, affecting the microstructure of growing films.more » Many technologically interesting thin films are compound films, which are composed of one or more metals and a reactive gas, most often oxygen or nitrogen. When reactive gas is added, non-trivial consequences arise for the system because the target may become “poisoned,” i.e., a compound layer forms on the target surface affecting the sputtering yield and the yield of secondary electron emission and thereby all other parameters. It is emphasized that the target state depends not only on the reactive gas' partial pressure (balanced via gas flow and pumping) but also on the ion flux to the target, which can be controlled by pulse parameters. This is a critical technological opportunity for reactive HiPIMS (R-HiPIMS). The scope of this tutorial is focused on plasma processes and mechanisms of operation and only briefly touches upon film properties. It introduces R-HiPIMS in a systematic, step-by-step approach by covering sputtering, magnetron sputtering, reactive magnetron sputtering, pulsed reactive magnetron sputtering, HiPIMS, and finally R-HiPIMS. The tutorial is concluded by considering variations of R-HiPIMS known as modulated pulsed power magnetron sputtering and deep-oscillation magnetron sputtering and combinations of R-HiPIMS with superimposed dc magnetron sputtering.« less

Tutorial: Reactive high power impulse magnetron sputtering (R-HiPIMS)

DOE PAGES

Anders, André

2017-03-21

High Power Impulse Magnetron Sputtering (HiPIMS) is a coating technology that combines magnetron sputtering with pulsed power concepts. Furthermore, by applying power in pulses of high amplitude and a relatively low duty cycle, large fractions of sputtered atoms and near-target gases are ionized. In contrast to conventional magnetron sputtering, HiPIMS is characterized by self-sputtering or repeated gas recycling for high and low sputter yield materials, respectively, and both for most intermediate materials. The dense plasma in front of the target has the dual function of sustaining the discharge and providing plasma-assistance to film growth, affecting the microstructure of growing films.more » Many technologically interesting thin films are compound films, which are composed of one or more metals and a reactive gas, most often oxygen or nitrogen. When reactive gas is added, non-trivial consequences arise for the system because the target may become “poisoned,” i.e., a compound layer forms on the target surface affecting the sputtering yield and the yield of secondary electron emission and thereby all other parameters. It is emphasized that the target state depends not only on the reactive gas' partial pressure (balanced via gas flow and pumping) but also on the ion flux to the target, which can be controlled by pulse parameters. This is a critical technological opportunity for reactive HiPIMS (R-HiPIMS). The scope of this tutorial is focused on plasma processes and mechanisms of operation and only briefly touches upon film properties. It introduces R-HiPIMS in a systematic, step-by-step approach by covering sputtering, magnetron sputtering, reactive magnetron sputtering, pulsed reactive magnetron sputtering, HiPIMS, and finally R-HiPIMS. The tutorial is concluded by considering variations of R-HiPIMS known as modulated pulsed power magnetron sputtering and deep-oscillation magnetron sputtering and combinations of R-HiPIMS with superimposed dc magnetron sputtering.« less

Tutorial: Reactive high power impulse magnetron sputtering (R-HiPIMS)

NASA Astrophysics Data System (ADS)

Anders, André

2017-05-01

High Power Impulse Magnetron Sputtering (HiPIMS) is a coating technology that combines magnetron sputtering with pulsed power concepts. By applying power in pulses of high amplitude and a relatively low duty cycle, large fractions of sputtered atoms and near-target gases are ionized. In contrast to conventional magnetron sputtering, HiPIMS is characterized by self-sputtering or repeated gas recycling for high and low sputter yield materials, respectively, and both for most intermediate materials. The dense plasma in front of the target has the dual function of sustaining the discharge and providing plasma-assistance to film growth, affecting the microstructure of growing films. Many technologically interesting thin films are compound films, which are composed of one or more metals and a reactive gas, most often oxygen or nitrogen. When reactive gas is added, non-trivial consequences arise for the system because the target may become "poisoned," i.e., a compound layer forms on the target surface affecting the sputtering yield and the yield of secondary electron emission and thereby all other parameters. It is emphasized that the target state depends not only on the reactive gas' partial pressure (balanced via gas flow and pumping) but also on the ion flux to the target, which can be controlled by pulse parameters. This is a critical technological opportunity for reactive HiPIMS (R-HiPIMS). The scope of this tutorial is focused on plasma processes and mechanisms of operation and only briefly touches upon film properties. It introduces R-HiPIMS in a systematic, step-by-step approach by covering sputtering, magnetron sputtering, reactive magnetron sputtering, pulsed reactive magnetron sputtering, HiPIMS, and finally R-HiPIMS. The tutorial is concluded by considering variations of R-HiPIMS known as modulated pulsed power magnetron sputtering and deep-oscillation magnetron sputtering and combinations of R-HiPIMS with superimposed dc magnetron sputtering.

Artificial small RNA for sequence specific cleavage of target RNA through RNase III endonuclease Dicer

PubMed Central

Liu, Yali; Liu, Li; Zhan, Yonghao; Zhuang, Chengle; Lin, Junhao; Chen, Mingwei; Li, Jianfa; Cai, Zhiming; Huang, Weiren; Zhang, Yong

2016-01-01

CRISPR-Cas9 system uses a guide RNA which functions in conjunction with Cas9 proteins to target a DNA and cleaves double-strand DNA. This phenomenon raises a question whether an artificial small RNA (asRNA), composed of a Dicer–binding RNA element and an antisense RNA, could also be used to induce Dicer to process and degrade a specific RNA. If so, we could develop a new method which is named DICERi for gene silencing or RNA editing. To prove the feasibility of asRNA, we selected MALAT-1 as target and used Hela and MDA-MB-231 cells as experimental models. The results of qRT-PCR showed that the introduction of asRNA decreased the relative expression level of target gene significantly. Next, we analyzed cell proliferation using CCK-8 and EdU staining assays, and then cell migration using wound scratch and Transwell invasion assays. We found that cell proliferation and cell migration were both suppressed remarkably after asRNA was expressed in Hela and MDA-MB-231 cells. Cell apoptosis was also detected through Hoechst staining and ELISA assays and the data indicated that he numbers of apoptotic cell in experimental groups significantly increased compared with negative controls. In order to prove that the gene silencing effects were caused by Dicer, we co-transfected shRNA silencing Dicer and asRNA. The relative expression levels of Dicer and MALAT-1 were both detected and the results indicated that when the cleavage role of Dicer was silenced, the relative expression level of MALAT-1 was not affected after the introduction of asRNA. All the above results demonstrated that these devices directed by Dicer effectively excised target RNA and repressed the target genes, thus causing phenotypic changes. Our works adds a new dimension to gene regulating technologies and may have broad applications in construction of gene circuits. PMID:27231846

Artificial small RNA for sequence specific cleavage of target RNA through RNase III endonuclease Dicer.

PubMed

Xu, Wen; Liu, Yuchen; Liu, Yali; Liu, Li; Zhan, Yonghao; Zhuang, Chengle; Lin, Junhao; Chen, Mingwei; Li, Jianfa; Cai, Zhiming; Huang, Weiren; Zhang, Yong

2016-08-23

CRISPR-Cas9 system uses a guide RNA which functions in conjunction with Cas9 proteins to target a DNA and cleaves double-strand DNA. This phenomenon raises a question whether an artificial small RNA (asRNA), composed of a Dicer-binding RNA element and an antisense RNA, could also be used to induce Dicer to process and degrade a specific RNA. If so, we could develop a new method which is named DICERi for gene silencing or RNA editing. To prove the feasibility of asRNA, we selected MALAT-1 as target and used Hela and MDA-MB-231 cells as experimental models. The results of qRT-PCR showed that the introduction of asRNA decreased the relative expression level of target gene significantly. Next, we analyzed cell proliferation using CCK-8 and EdU staining assays, and then cell migration using wound scratch and Transwell invasion assays. We found that cell proliferation and cell migration were both suppressed remarkably after asRNA was expressed in Hela and MDA-MB-231 cells. Cell apoptosis was also detected through Hoechst staining and ELISA assays and the data indicated that he numbers of apoptotic cell in experimental groups significantly increased compared with negative controls. In order to prove that the gene silencing effects were caused by Dicer, we co-transfected shRNA silencing Dicer and asRNA. The relative expression levels of Dicer and MALAT-1 were both detected and the results indicated that when the cleavage role of Dicer was silenced, the relative expression level of MALAT-1 was not affected after the introduction of asRNA. All the above results demonstrated that these devices directed by Dicer effectively excised target RNA and repressed the target genes, thus causing phenotypic changes. Our works adds a new dimension to gene regulating technologies and may have broad applications in construction of gene circuits.

Therapeutic Potential of Phytomedicines and Novel Polymeric Strategies for Significant Management of Candidiasis.

PubMed

Rohilla, Surbhi; Bhatt, D C; Gupta, Aditi

2018-05-23

Candidiasis is one of the most common opportunistic fungal infections caused by genus Candida. The genus composed of around 200 species. The most virulent among all are, Candida albicans followed by various non-albicans species. Despite of various treatments available, the incidence of severe systemic fungal infections is increasing, and with it the related morbidity and mortality, in relation to the misuse of antimicrobials and the emergence of drug-resistant fungal species. Therefore, various novel therapeutic approaches need to be developed and explored to overcome these limitations and effective management of candidiasis. In this review, we focused on natural herbal remedies and significance of novel formulation approaches for the treatment of candidiasis. The reported studies suggested the promising role of phytomedicines and novel polymeric drug delivery systems in therapeutic management of candidiasis. Phytomedicines are effective substitute of synthetic drugs as they are inexpensive with lesser number of side effects. Various novel particulate approaches can be successfully used to reduce the fungal burden at the target site. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Folic acid-functionalized magnetic ZnFe2O4 hollow microsphere core/mesoporous silica shell composite particles: synthesis and application in drug release.

PubMed

Yang, Dandan; Wei, Kaiwei; Liu, Qi; Yang, Yong; Guo, Xue; Rong, Hongren; Cheng, Mei-Ling; Wang, Guoxiu

2013-07-01

A drug delivery system was designed by deliberately combining the useful functions into one entity, which was composed of magnetic ZnFe2O4 hollow microsphere as the core, and mesoporous silica with folic acid molecules as the outer shell. Amine groups coated magnetic ZnFe2O4 hollow microsphere core/mesoporous silica shell (MZHM-MSS-NH2) composite particles were first synthesized by a one-pot direct co-condensation method. Subsequently a novel kind of folic acid-functionalized magnetic ZnFe2O4 hollow microsphere core/mesoporous silica shell (MZHM-MSS-NHFA) composite particles were synthesized by conjugating folic acid as targeted molecule to MZHM-MSS-NH2. Ibuprofen, a well-known antiphlogistic drug, was used as a model drug to assess the loading and releasing behavior of the composite microspheres. The results show that the MZHM-MSS-NHFA system has the higher capacity of drug storage and good sustained drug-release property. Copyright © 2013 Elsevier B.V. All rights reserved.

Central nervous system

MedlinePlus

The central nervous system is composed of the brain and spinal cord. Your brain and spinal cord serve as the main "processing center" for your entire nervous system. They control all the workings of your body.

An ERTS multispectral scanner experiment for mapping iron compounds

NASA Technical Reports Server (NTRS)

Vincent, R. K. (Principal Investigator)

1972-01-01

There are no author-identified significant results in this report. An experimental plan for enhancing spectral features related to the chemical composition of geological targets in ERTS multispectral scanner data is described. The experiment is designed to produce visible-reflective infrared ratio images from ERTS-1 data. Iron compounds are promising remote sensing targets because they display prominent spectral features in the visible-reflective infrared wavelength region and are geologically significant. The region selected for this ERTS experiment is the southern end of the Wind River Range in Wyoming. If this method proves successful it should prove useful for regional geologic mapping, mineralogical exploration, and soil mapping. It may also be helpful to ERTS users in scientific disciplines other than geology, especially to those concerned with targets composed of mixtures of live vegetation and soil or rock.

Targeting Dysbiosis for the Treatment of Liver Disease.

PubMed

Anand, Gobind; Zarrinpar, Amir; Loomba, Rohit

2016-02-01

The gut microbiome is composed of a vast number of microbes in the gastrointestinal tract, which benefit host metabolism, aid in digestion, and contribute to normal immune function. Alterations in microbial composition can result in intestinal dysbiosis, which has been implicated in several diseases including obesity, inflammatory bowel disease, and liver diseases. Over the past several years, significant interactions between the intestinal microbiota and liver have been discovered, with possible mechanisms for the development as well as progression of liver disease and promising therapeutic targets to either prevent or halt the progression of liver disease. In this review the authors examine mechanisms of dysbiosis-induced liver disease; highlight current knowledge regarding the role of dysbiosis in nonalcoholic liver disease, alcoholic liver disease, and cirrhosis; and discuss potential therapeutic targets. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Beam dynamic simulation and optimization of the CLIC positron source and the capture linac

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

Bayar, C., E-mail: cafer.bayar@cern.ch; CERN, Geneva; Doebert, S., E-mail: Steffen.Doebert@cern.ch

2016-03-25

The CLIC Positron Source is based on the hybrid target composed of a crystal and an amorphous target. Simulations have been performed from the exit of the amorphous target to the end of pre-injector linac which captures and accelerates the positrons to an energy of 200 MeV. Simulations are performed by the particle tracking code PARMELA. The magnetic field of the AMD is represented in PARMELA by simple coils. Two modes are applied in this study. The first one is accelerating mode based on acceleration after the AMD. The second one is decelerating mode based on deceleration in the first acceleratingmore » structure. It is shown that the decelerating mode gives a higher yield for the e{sup +} beam in the end of the Pre-Injector Linac.« less

Temporal information partitioning: Characterizing synergy, uniqueness, and redundancy in interacting environmental variables

NASA Astrophysics Data System (ADS)

Goodwell, Allison E.; Kumar, Praveen

2017-07-01

Information theoretic measures can be used to identify nonlinear interactions between source and target variables through reductions in uncertainty. In information partitioning, multivariate mutual information is decomposed into synergistic, unique, and redundant components. Synergy is information shared only when sources influence a target together, uniqueness is information only provided by one source, and redundancy is overlapping shared information from multiple sources. While this partitioning has been applied to provide insights into complex dependencies, several proposed partitioning methods overestimate redundant information and omit a component of unique information because they do not account for source dependencies. Additionally, information partitioning has only been applied to time-series data in a limited context, using basic pdf estimation techniques or a Gaussian assumption. We develop a Rescaled Redundancy measure (Rs) to solve the source dependency issue, and present Gaussian, autoregressive, and chaotic test cases to demonstrate its advantages over existing techniques in the presence of noise, various source correlations, and different types of interactions. This study constitutes the first rigorous application of information partitioning to environmental time-series data, and addresses how noise, pdf estimation technique, or source dependencies can influence detected measures. We illustrate how our techniques can unravel the complex nature of forcing and feedback within an ecohydrologic system with an application to 1 min environmental signals of air temperature, relative humidity, and windspeed. The methods presented here are applicable to the study of a broad range of complex systems composed of interacting variables.

Morphology of mucosa-associated lymphoid tissue in odontocetes.

PubMed

Silva, Fernanda M O; Guimarães, Juliana P; Vergara-Parente, Jociery E; Carvalho, Vitor L; Carolina, Ana; Meirelles, O; Marmontel, Miriam; Oliveira, Bruno S S P; Santos, Silvanise M; Becegato, Estella Z; Evangelista, Janaina S A M; Miglino, Maria Angelica

2016-09-01

This study describes the mucosa-associated lymphoid tissue (MALT) in odontocetes from the Brazilian coast and freshwater systems. Seven species were evaluated and tissue samples were analyzed by light, scanning and transmission electron microscopy, and immunohistochemistry. Laryngeal tonsil was a palpable oval mass located in the larynx, composed of a lymphoepithelial complex. Dense collections of lymphocytes were found in the skin of male fetus and calf. Clusters of lymphoid tissue were found in the uterine cervix of a reproductively active juvenile female and along the pulmonary artery of an adult female. Lymphoid tissues associated with the gastrointestinal tract were characterized by diffusely arranged or organized lymphocytes. The anal tonsil was composed of an aggregate of lymphoid tissue occurring exclusively in the anal canal, being composed of squamous epithelium branches. MALT was present in different tissues and organic systems of cetaceans, providing constant protection against mucosal pathogens present in their environment. © 2016 Wiley Periodicals, Inc.

System Identification Methods for Aircraft Flight Control Development and Validation

DOT National Transportation Integrated Search

1995-10-01

System-identification methods compose a mathematical model, or series of models, : from measurements of inputs and outputs of dynamic systems. This paper : discusses the use of frequency-domain system-identification methods for the : development and ...

15 years of genetic approaches in vivo for addiction research: Opioid receptor and peptide gene knockout in mouse models of drug abuse.

PubMed

Charbogne, Pauline; Kieffer, Brigitte L; Befort, Katia

2014-01-01

The endogenous opioid system is expressed throughout the brain reinforcement circuitry, and plays a major role in reward processing, mood control and the development of addiction. This neuromodulator system is composed of three receptors, mu, delta and kappa, interacting with a family of opioid peptides derived from POMC (β-endorphin), preproenkephalin (pEnk) and preprodynorphin (pDyn) precursors. Knockout mice targeting each gene of the opioid system have been created almost two decades ago. Extending classical pharmacology, these mutant mice represent unique tools to tease apart the specific role of each opioid receptor and peptide in vivo, and a powerful approach to understand how the opioid system modulates behavioral effects of drugs of abuse. The present review summarizes these studies, with a focus on major drugs of abuse including morphine/heroin, cannabinoids, psychostimulants, nicotine or alcohol. Genetic data, altogether, set the mu receptor as the primary target for morphine and heroin. In addition, this receptor is essential to mediate rewarding properties of non-opioid drugs of abuse, with a demonstrated implication of β-endorphin for cocaine and nicotine. Delta receptor activity reduces levels of anxiety and depressive-like behaviors, and facilitates morphine-context association. pEnk is involved in these processes and delta/pEnk signaling likely regulates alcohol intake. The kappa receptor mainly interacts with pDyn peptides to limit drug reward, and mediate dysphoric effects of cannabinoids and nicotine. Kappa/dynorphin activity also increases sensitivity to cocaine reward under stressful conditions. The opioid system remains a prime candidate to develop successful therapies in addicted individuals, and understanding opioid-mediated processes at systems level, through emerging genetic and imaging technologies, represents the next challenging goal and a promising avenue in addiction research. This article is part of a Special Issue entitled 'NIDA 40th Anniversary Issue'. Copyright © 2013 Elsevier Ltd. All rights reserved.

Artificial immune system approach for air combat maneuvering

NASA Astrophysics Data System (ADS)

Kaneshige, John; Krishnakumar, Kalmanje

2007-04-01

Since future air combat missions will involve both manned and unmanned aircraft, the primary motivation for this research is to enable unmanned aircraft with intelligent maneuvering capabilities. During air combat maneuvering, pilots use their knowledge and experience of maneuvering strategies and tactics to determine the best course of action. As a result, we try to capture these aspects using an artificial immune system approach. The biological immune system protects the body against intruders by recognizing and destroying harmful cells or molecules. It can be thought of as a robust adaptive system that is capable of dealing with an enormous variety of disturbances and uncertainties. However, another critical aspect of the immune system is that it can remember how previous encounters were successfully defeated. As a result, it can respond faster to similar encounters in the future. This paper describes how an artificial immune system is used to select and construct air combat maneuvers. These maneuvers are composed of autopilot mode and target commands, which represent the low-level building blocks of the parameterized system. The resulting command sequences are sent to a tactical autopilot system, which has been enhanced with additional modes and an aggressiveness factor for enabling high performance maneuvers. Just as vaccinations train the biological immune system how to combat intruders, training sets are used to teach the maneuvering system how to respond to different enemy aircraft situations. Simulation results are presented, which demonstrate the potential of using immunized maneuver selection for the purposes of air combat maneuvering.

Fluidized Bed Opposed Jet Mill System for Processing Inorganic Materials

NASA Astrophysics Data System (ADS)

Al-Nuzal, S. M. D.; Mohammed, M. I.

2017-08-01

A jet mill system was built aiming to give values for processing inorganic materials, to be used for different industry. The milling housing of the system is composed of; milling chamber, compressed air nozzles which deliver compressed air in the milling chamber to accelerate sample particles. The classifier wheel is composed of two concentric pieces welded together under argon and coupled to a AC Motor, 0 - 9000 rpm, 2 kW, with AC frequencies convertor. The performances of this jet mill system were tried on five cheap locally available materials, viz. white sand, glass, iron oxide, black carbon and alum. It is possible to get particle sizes of less than 1 μm with narrow distribution of particle sizes.

Deaf-And-Mute Sign Language Generation System

NASA Astrophysics Data System (ADS)

Kawai, Hideo; Tamura, Shinichi

1984-08-01

We have developed a system which can recognize speech and generate the corresponding animation-like sign language sequence. The system is implemented in a popular personal computer. This has three video-RAM's and a voice recognition board which can recognize only registered voice of a specific speaker. Presently, fourty sign language patterns and fifty finger spellings are stored in two floppy disks. Each sign pattern is composed of one to four sub-patterns. That is, if the pattern is composed of one sub-pattern, it is displayed as a still pattern. If not, it is displayed as a motion pattern. This system will help communications between deaf-and-mute persons and healthy persons. In order to display in high speed, almost programs are written in a machine language.

Cardiovascular system

MedlinePlus Videos and Cool Tools

The cardiovascular system is composed of the heart and the network of arteries, veins, and capillaries that transport blood throughout the ... carries waste products from the tissues to the systems of the body through which they are eliminated. ...

Demonstrator of atmospheric reentry system with hyperbolic velocity—DASH

NASA Astrophysics Data System (ADS)

Morita, Yasuhiro; Kawaguchi, Jun'ichiro; Inatani, Yoshifumi; Abe, Takashi

2003-01-01

Among a wide variety of challenging projects planned for the coming decade is the MUSES-C mission designed by the ISAS of Japan. Despite huge amount of data collected by the previous interplanetary spacecraft and probes, the origin and evolution of the solar system still remains unveiled due to their limited information. Thus, our concern has been directed toward a sample return to carry sample from an asteroid back to the earth, which will contribute to better understanding of the system. One of the keys to success is considered the reentry technology with hyperbolic velocity, which has not been demonstrated yet. With this as background, the demonstrator of atmospheric reentry system with hyperbolic velocity, DASH, has been given a commitment to demonstrate the high-speed reentry technology, which will be launched in summer of next year by Japan's H-IIA rocket in a piggyback configuration. The spaceship, composed of a reentry capsule and its carrier, will be injected into a geostationary transfer orbit (GTO) and after several revolutions it will deorbit by burn of a solid propellant deorbit motor. The capsule, identical to that of the sample return mission, can experience the targeted level of thermal environment even from the GTO by tracing a specially designed reentry trajectory.

Design of experiments for the development of poly( d, l-lactide- co-glycolide) nanoparticles loaded with Uncaria tomentosa

NASA Astrophysics Data System (ADS)

Ribeiro, Ana Ferreira; Ferreira, Carina Torres Garruth; dos Santos, Juliana Fernandes; Cabral, Lúcio Mendes; de Sousa, Valéria Pereira

2015-02-01

Polymeric nanoparticles have been shown to be effective carriers for natural substances that possess anticancer properties. Incorporation of these natural substances into polymeric nanoparticles increases targeting of these drugs, thus reducing side effects. Uncaria tomentosa (UT) is a Peruvian Amazon plant (existing in the Brazilian Amazon rainforest) that possesses promising anti-tumor activity. This paper describes the development of poly( d, l-lactide- co-glycolide) (PLGA) nanoparticles loaded with UT extract. The emulsion solvent evaporation method was utilized and the initial conditions were determined for the organic phase (OP) and the aqueous phase (AP). The influence of surfactant (type and concentration), PLGA concentration and AP volume on nanoparticle size, polydispersity index (PI), and entrapment efficiency (EE) was determined using a fractional factorial design (FFD). In addition, the formulation was optimized using a Box-Behnken design. After the conditions were optimized, UT nanoparticles were obtained using an OP composed of an ethyl acetate:acetone (3:2) mixture which contained the UT alkaloids and PLGA, and an AP composed of a buffered solution of Poloxamer 188 (pH 7.5). The optimized formulation produced an EE of 64.6 %, a particle size of 107.4 nm and a PI of 0.163. The preliminary experiments provided important information regarding the behavior of the nanoparticulate system and the FFD used in this study greatly facilitated the selection of the most optimal conditions for formulation development.

Strategy Developed for Selecting Optimal Sensors for Monitoring Engine Health

NASA Technical Reports Server (NTRS)

2004-01-01

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

Photogrammetric Metrology for the James Webb Space Telescope Integrated Science Instrument Module

NASA Technical Reports Server (NTRS)

Nowak, Maria; Crane, Allen; Davila, Pam; Eichhorn, William; Gill, James; Herrera, Acey; Hill, Michael; Hylan, Jason; Jetten, Mark; Marsh, James;

Targeted Delivery of Drugs to Brain Tumors (LBNL Summer Lecture Series)

ScienceCinema

Forte, Trudy [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States). Life Sciences Division; Children’s Hospital Oakland Research Inst. (CHORI), Oakland, CA (United States)

2017-12-15

Summer Lecture Series 2007: Trudy Forte of Berkeley Lab's Life Sciences Division will discuss her work developing nano-sized low-density lipoprotein (LDL) particles that can be used as a safe and effective means of delivering anticancer drugs to brain tumors, particularly glioblastoma multiforme. This is the most common malignant brain tumor in adults and one of the deadliest forms of cancer. Her research team found that the synthetic LDL particles can target and kill such tumors cells in vitro. The nanoparticles are composed of a lipid core surrounded by a peptide. The peptide contains an amino acid sequence that recognizes the LDL receptor, and the lipid core has the ability to accumulate anti-cancer drugs.

Laser-fusion targets for reactors

DOEpatents

Nuckolls, John H.; Thiessen, Albert R.

1987-01-01

A laser target comprising a thermonuclear fuel capsule composed of a centrally located quantity of fuel surrounded by at least one or more layers or shells of material for forming an atmosphere around the capsule by a low energy laser prepulse. The fuel may be formed as a solid core or hollow shell, and, under certain applications, a pusher-layer or shell is located intermediate the fuel and the atmosphere forming material. The fuel is ignited by symmetrical implosion via energy produced by a laser, or other energy sources such as an electron beam machine or ion beam machine, whereby thermonuclear burn of the fuel capsule creates energy for applications such as generation of electricity via a laser fusion reactor.

A statistical model for radar images of agricultural scenes

NASA Technical Reports Server (NTRS)

Frost, V. S.; Shanmugan, K. S.; Holtzman, J. C.; Stiles, J. A.

1982-01-01

The presently derived and validated statistical model for radar images containing many different homogeneous fields predicts the probability density functions of radar images of entire agricultural scenes, thereby allowing histograms of large scenes composed of a variety of crops to be described. Seasat-A SAR images of agricultural scenes are accurately predicted by the model on the basis of three assumptions: each field has the same SNR, all target classes cover approximately the same area, and the true reflectivity characterizing each individual target class is a uniformly distributed random variable. The model is expected to be useful in the design of data processing algorithms and for scene analysis using radar images.

Data communications in a parallel active messaging interface of a parallel computer

DOEpatents

Archer, Charles J; Blocksome, Michael A; Ratterman, Joseph D; Smith, Brian E

2014-02-11

Data communications in a parallel active messaging interface ('PAMI') or a parallel computer, the parallel computer including a plurality of compute nodes that execute a parallel application, the PAMI composed of data communications endpoints, each endpoint including a specification of data communications parameters for a thread of execution of a compute node, including specification of a client, a context, and a task, the compute nodes and the endpoints coupled for data communications instruction, the instruction characterized by instruction type, the instruction specifying a transmission of transfer data from the origin endpoint to a target endpoint and transmitting, in accordance witht the instruction type, the transfer data from the origin endpoin to the target endpoint.

Marine Tactical Command and Control System (MTACCS) Field Development System-1 (FDS-1) assessment: Final report

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

Avery, L.W.; Hunt, S.T.; Savage, S.F.

1992-04-01

The United State Marine Corps (USMC) is continuing the development and fielding of the Marine Corps Tactical Command and Control System (MTACCS), a system which exists in varying states of development, fielding, or modernization. MTACCS is currently composed of the following components: Tactical Combat Operations System (TCO) for ground command and control (C2), Intelligence Analysis System (IAS) with a Genser terminal connected to a TCO workstation for intelligence C2, Marine Integrated Personnel System (MIPS) and a TCO workstation using the Marine Combat Personnel System (MCPERS) software for personnel C2, Marine Integrated Logistics System (MILOGS) which is composed of the Landingmore » Force Asset Distribution System (LFADS), the Marine Air-Ground Task Force (MAGTF) II, and a TCO terminal using the Marine Combat Logistics System (MCLOG) for logistics C2, Marine Corps Fire Support System (MCFSS) for fire support C2, and Advanced Tactical Air Command Central (ATACC) and the Improved Direct Air Support Central for aviation C2.« less

A mathematical model for generating bipartite graphs and its application to protein networks

NASA Astrophysics Data System (ADS)

Nacher, J. C.; Ochiai, T.; Hayashida, M.; Akutsu, T.

2009-12-01

Complex systems arise in many different contexts from large communication systems and transportation infrastructures to molecular biology. Most of these systems can be organized into networks composed of nodes and interacting edges. Here, we present a theoretical model that constructs bipartite networks with the particular feature that the degree distribution can be tuned depending on the probability rate of fundamental processes. We then use this model to investigate protein-domain networks. A protein can be composed of up to hundreds of domains. Each domain represents a conserved sequence segment with specific functional tasks. We analyze the distribution of domains in Homo sapiens and Arabidopsis thaliana organisms and the statistical analysis shows that while (a) the number of domain types shared by k proteins exhibits a power-law distribution, (b) the number of proteins composed of k types of domains decays as an exponential distribution. The proposed mathematical model generates bipartite graphs and predicts the emergence of this mixing of (a) power-law and (b) exponential distributions. Our theoretical and computational results show that this model requires (1) growth process and (2) copy mechanism.

Where's Wally: the influence of visual salience on referring expression generation.

PubMed

Clarke, Alasdair D F; Elsner, Micha; Rohde, Hannah

2013-01-01

REFERRING EXPRESSION GENERATION (REG) PRESENTS THE CONVERSE PROBLEM TO VISUAL SEARCH: given a scene and a specified target, how does one generate a description which would allow somebody else to quickly and accurately locate the target?Previous work in psycholinguistics and natural language processing has failed to find an important and integrated role for vision in this task. That previous work, which relies largely on simple scenes, tends to treat vision as a pre-process for extracting feature categories that are relevant to disambiguation. However, the visual search literature suggests that some descriptions are better than others at enabling listeners to search efficiently within complex stimuli. This paper presents a study testing whether participants are sensitive to visual features that allow them to compose such "good" descriptions. Our results show that visual properties (salience, clutter, area, and distance) influence REG for targets embedded in images from the Where's Wally? books. Referring expressions for large targets are shorter than those for smaller targets, and expressions about targets in highly cluttered scenes use more words. We also find that participants are more likely to mention non-target landmarks that are large, salient, and in close proximity to the target. These findings identify a key role for visual salience in language production decisions and highlight the importance of scene complexity for REG.

Precision targeting in guided munition using IR sensor and MmW radar

NASA Astrophysics Data System (ADS)

Sreeja, S.; Hablani, H. B.; Arya, H.

2015-10-01

Conventional munitions are not guided with sensors and therefore miss the target, particularly if the target is mobile. The miss distance of these munitions can be decreased by incorporating sensors to detect the target and guide the munition during flight. This paper is concerned with a Precision Guided Munition(PGM) equipped with an infrared sensor and a millimeter wave radar [IR and MmW, for short]. Three-dimensional flight of the munition and its pitch and yaw motion models are developed and simulated. The forward and lateral motion of a target tank on the ground is modeled as two independent second-order Gauss-Markov process. To estimate the target location on the ground and the line-of-sight rate to intercept it an Extended Kalman Filter is composed whose state vector consists of cascaded state vectors of missile dynamics and target dynamics. The line-of-sight angle measurement from the infrared seeker is by centroiding the target image in 40 Hz. The centroid estimation of the images in the focal plane is at a frequency of 10 Hz. Every 10 Hz, centroids of four consecutive images are averaged, yielding a time-averaged centroid, implying some measurement delay. The miss distance achieved by including by image processing delays is 1:45m.

Precision targeting in guided munition using infrared sensor and millimeter wave radar

NASA Astrophysics Data System (ADS)

Sulochana, Sreeja; Hablani, Hari B.; Arya, Hemendra

2016-07-01

Conventional munitions are not guided with sensors and therefore miss the target, particularly if the target is mobile. The miss distance of these munitions can be decreased by incorporating sensors to detect the target and guide the munition during flight. This paper is concerned with a precision guided munition equipped with an infrared (IR) sensor and a millimeter wave radar (MmW). Three-dimensional flight of the munition and its pitch and yaw motion models are developed and simulated. The forward and lateral motion of a target tank on the ground is modeled as two independent second-order Gauss-Markov processes. To estimate the target location on the ground and the line-of-sight (LOS) rate to intercept it, an extended Kalman filter is composed whose state vector consists of cascaded state vectors of missile dynamics and target dynamics. The LOS angle measurement from the IR seeker is by centroiding the target image in 40 Hz. The centroid estimation of the images in the focal plane is at a frequency of 10 Hz. Every 10 Hz, centroids of four consecutive images are averaged, yielding a time-averaged centroid, implying some measurement delay. The miss distance achieved by including image processing delays is 1.45 m.

Synthetic Developments of Nontoxic Quantum Dots.

PubMed

Das, Adita; Snee, Preston T

2016-03-03

Semiconductor nanocrystals, or quantum dots (QDs), are candidates for biological sensing, photovoltaics, and catalysis due to their unique photophysical properties. The most studied QDs are composed of heavy metals like cadmium and lead. However, this engenders concerns over heavy metal toxicity. To address this issue, numerous studies have explored the development of nontoxic (or more accurately less toxic) quantum dots. In this Review, we select three major classes of nontoxic quantum dots composed of carbon, silicon and Group I-III-VI elements and discuss the myriad of synthetic strategies and surface modification methods to synthesize quantum dots composed of these material systems. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Injector design for liner-on-target gas-puff experiments

NASA Astrophysics Data System (ADS)

Valenzuela, J. C.; Krasheninnikov, I.; Conti, F.; Wessel, F.; Fadeev, V.; Narkis, J.; Ross, M. P.; Rahman, H. U.; Ruskov, E.; Beg, F. N.

2017-11-01

We present the design of a gas-puff injector for liner-on-target experiments. The injector is composed of an annular high atomic number (e.g., Ar and Kr) gas and an on-axis plasma gun that delivers an ionized deuterium target. The annular supersonic nozzle injector has been studied using Computational Fluid Dynamics (CFD) simulations to produce a highly collimated (M > 5), ˜1 cm radius gas profile that satisfies the theoretical requirement for best performance on ˜1-MA current generators. The CFD simulations allowed us to study output density profiles as a function of the nozzle shape, gas pressure, and gas composition. We have performed line-integrated density measurements using a continuous wave (CW) He-Ne laser to characterize the liner gas density. The measurements agree well with the CFD values. We have used a simple snowplow model to study the plasma sheath acceleration in a coaxial plasma gun to help us properly design the target injector.

Injector design for liner-on-target gas-puff experiments.

PubMed

Valenzuela, J C; Krasheninnikov, I; Conti, F; Wessel, F; Fadeev, V; Narkis, J; Ross, M P; Rahman, H U; Ruskov, E; Beg, F N

2017-11-01

We present the design of a gas-puff injector for liner-on-target experiments. The injector is composed of an annular high atomic number (e.g., Ar and Kr) gas and an on-axis plasma gun that delivers an ionized deuterium target. The annular supersonic nozzle injector has been studied using Computational Fluid Dynamics (CFD) simulations to produce a highly collimated (M > 5), ∼1 cm radius gas profile that satisfies the theoretical requirement for best performance on ∼1-MA current generators. The CFD simulations allowed us to study output density profiles as a function of the nozzle shape, gas pressure, and gas composition. We have performed line-integrated density measurements using a continuous wave (CW) He-Ne laser to characterize the liner gas density. The measurements agree well with the CFD values. We have used a simple snowplow model to study the plasma sheath acceleration in a coaxial plasma gun to help us properly design the target injector.

Crystal Ball Replica

NASA Astrophysics Data System (ADS)

Ajamian, John

2016-09-01

The A2 collaboration of the Institute for Nuclear Physics of Johannes Gutenberg University performs research on (multiple) meson photoproduction and nucleon structure and dynamics using a high energy polarized photon beam at specific targets. Particles scattered from the target are detected in the Crystal Ball, or CB. The CB is composed of 672 NaI crystals that surround the target and can analyze particle type and energy of ejected particles. Our project was to create a replica of the CB that could display what was happening in real time on a 3 Dimensional scale replica. Our replica was constructed to help explain the physics to the general public, be used as a tool when calibrating each of the 672 NaI crystals, and to better analyze the electron showering of particles coming from the target. This poster will focus on the hardware steps necessary to construct the replica and wire the 672 programmable LEDS in such a way that they can be mapped to correspond to the Crystal Ball elements. George Washington NSF Grant.

The influences of target properties and deposition times on pulsed laser deposited hydroxyapatite films

NASA Astrophysics Data System (ADS)

Bao, Quanhe; Chen, Chuanzhong; Wang, Diangang; Liu, Junming

2008-11-01

Hydroxyapatite films were produced by pulsed laser deposition from three kinds of hydroxyapatite targets and with different deposition times. A JXA-8800R electron probe microanalyzer (EPMA) with a Link ISIS300 energy spectrum analyzer was used to give the secondary electron image (SE) and determine the element composition of the films. The phases of thin film were analyzed by a D/max-γc X-ray diffractometer (XRD). The Fourier-transform infrared spectroscopy (FT-IR) was used to characterize the hydroxyl, phosphate and other functional groups. The results show that deposited films were amorphous which mainly composed of droplet-like particles and vibration of PO 43- groups. With the target sintering temperature deposition times increasing, the density of droplets is decreased. While with deposition times increasing, the density of droplets is increased. With the target sintering temperature and deposition time increasing, the ratio of Ca/P is increasing and higher than that of theoretical value of HA.

Genus-specific PCR Primers Targeting Intracellular Parasite Euduboscquella (Dinoflagellata: Syndinea)

NASA Astrophysics Data System (ADS)

Jung, Jae-Ho; Choi, Jung Min; Kim, Young-Ok

2018-03-01

We designed a genus-specific primer pair targeting the intracellular parasite Euduboscquella. To increase target specificity and inhibit untargeted PCR, two nucleotides were added at the 3' end of the reverse primer, one being a complementary nucleotide to the Euduboscquella-specific SNP (single-nucleotide polymorphism) and the other a deliberately mismatched nucleotide. Target specificity of the primer set was verified experimentally using PCR of two Euduboscquella species (positive controls) and 15 related species (negative controls composed of ciliates, diatoms and dinoflagellates), and analytical comparison with SILVA SSU rRNA gene database (release 119) in silico. In addition, we applied the Euduboscquella-specific primer set to four environmental samples previously determined by cytological staining to be either positive or negative for Euduboscquella. As expected, only positive controls and environmental samples known to contain Euduboscquella were successfully amplified by the primer set. An inferred SSU rRNA gene phylogeny placed environmental samples containing aloricate ciliates infected by Euduboscquella in a cluster discrete from Euduboscquella groups a-d previously reported from loricate, tintinnid ciliates.

Detection of proteins using a colorimetric bio-barcode assay.

PubMed

Nam, Jwa-Min; Jang, Kyung-Jin; Groves, Jay T

2007-01-01

The colorimetric bio-barcode assay is a red-to-blue color change-based protein detection method with ultrahigh sensitivity. This assay is based on both the bio-barcode amplification method that allows for detecting miniscule amount of targets with attomolar sensitivity and gold nanoparticle-based colorimetric DNA detection method that allows for a simple and straightforward detection of biomolecules of interest (here we detect interleukin-2, an important biomarker (cytokine) for many immunodeficiency-related diseases and cancers). The protocol is composed of the following steps: (i) conjugation of target capture molecules and barcode DNA strands onto silica microparticles, (ii) target capture with probes, (iii) separation and release of barcode DNA strands from the separated probes, (iv) detection of released barcode DNA using DNA-modified gold nanoparticle probes and (v) red-to-blue color change analysis with a graphic software. Actual target detection and quantification steps with premade probes take approximately 3 h (whole protocol including probe preparations takes approximately 3 days).

Design specification for the European Spallation Source neutron generating target element

NASA Astrophysics Data System (ADS)

Aguilar, A.; Sordo, F.; Mora, T.; Mena, L.; Mancisidor, M.; Aguilar, J.; Bakedano, G.; Herranz, I.; Luna, P.; Magan, M.; Vivanco, R.; Jimenez-Villacorta, F.; Sjogreen, K.; Oden, U.; Perlado, J. M.; Martinez, J. L.; Bermejo, F. J.

2017-06-01

The paper addresses some of the most relevant issues concerning the thermal hydraulics and radiation damage of the neutron generation target to be built at the European Spallation Source as recently approved after a critical design review. The target unit consists of a set of Tungsten blocks placed inside a wheel of 2.5 m diameter which rotates at some 0.5 Hz in order to distribute the heat generated from incoming protons which reach the target in the radial direction. The spallation material elements are composed of an array of Tungsten pieces which rest on a rotating steel support (the cassette) and are distributed in a cross-flow configuration. The thermal, mechanical and radiation effects resulting from the impact of a 2 GeV proton pulse are analysed in detail as well as an evaluation of the inventory of spallation products. The current design is found to conform to specifications and found to be robust enough to deal with several accident scenarios.

Synchronization behaviors of coupled systems composed of hidden attractors

NASA Astrophysics Data System (ADS)

Zhang, Ge; Wu, Fuqiang; Wang, Chunni; Ma, Jun

2017-10-01

Based on a class of chaotic system composed of hidden attractors, in which the equilibrium points are described by a circular function, complete synchronization between two identical systems, pattern formation and synchronization of network is investigated, respectively. A statistical factor of synchronization is defined and calculated by using the mean field theory, the dependence of synchronization on bifurcation parameters discussed in numerical way. By setting a chain network, which local kinetic is described by hidden attractors, synchronization approach is investigated. It is found that the synchronization and pattern formation are dependent on the coupling intensity and also the selection of coupling variables. In the end, open problems are proposed for readers’ extensive guidance and investigation.

Dual cameras acquisition and display system of retina-like sensor camera and rectangular sensor camera

NASA Astrophysics Data System (ADS)

Cao, Nan; Cao, Fengmei; Lin, Yabin; Bai, Tingzhu; Song, Shengyu

2015-04-01

For a new kind of retina-like senor camera and a traditional rectangular sensor camera, dual cameras acquisition and display system need to be built. We introduce the principle and the development of retina-like senor. Image coordinates transformation and interpolation based on sub-pixel interpolation need to be realized for our retina-like sensor's special pixels distribution. The hardware platform is composed of retina-like senor camera, rectangular sensor camera, image grabber and PC. Combined the MIL and OpenCV library, the software program is composed in VC++ on VS 2010. Experience results show that the system can realizes two cameras' acquisition and display.

Peptide-conjugated micelles as a targeting nanocarrier for gene delivery

NASA Astrophysics Data System (ADS)

Lin, Wen Jen; Chien, Wei Hsuan

2015-09-01

The aim of this study was to develop peptide-conjugated micelles possessing epidermal growth factor receptor (EGFR) targeting ability for gene delivery. A sequence-modified dodecylpeptide, GE11(2R), with enhancing EGF receptor binding affinity, was applied in this study as a targeting ligand. The active targeting micelles were composed of poly( d,l-lactide- co-glycolide)-poly(ethylene glycol) (PLGA-PEG) copolymer conjugated with GE11(2R)-peptide. The particle sizes of peptide-free and peptide-conjugated micelles were 277.0 ± 5.1 and 308.7 ± 14.5 nm, respectively. The peptide-conjugated micelles demonstrated the cellular uptake significantly higher than peptide-free micelles in EGFR high-expressed MDA-MB-231 and MDA-MB-468 cells due to GE11(2R)-peptide specificity. Furthermore, the peptide-conjugated micelles were able to encapsulate plasmid DNA and expressed cellular transfection higher than peptide-free micelles in EGFR high-expressed cells. The EGFR-targeting delivery micelles enhanced DNA internalized into cells and achieved higher cellular transfection in EGFR high-expressed cells.

Investigation of the hydrodynamics and emission of a laser heated tamped high-Z target

NASA Astrophysics Data System (ADS)

Gray, William J.; Foord, Mark E.; Schneider, Marilyn B.; Barrios, Maria A.; Brown, Greg V.; Heeter, Robert F.; Jarrott, L. Charlie; Liedahl, Duane A.; Marley, Ed V.; Mauche, Chris W.; Widmann, Klaus

2018-06-01

We investigate the hydrodynamic expansion and x-ray emission of a laser-heated buried-layer target. This work is motivated by our interest in developing an experimental platform for probing plasma properties under relatively uniform conditions, such as ionization and equation of state. Targets consist of a few thousand angstrom-thick layer of material, embedded in a few microns of the tamper material (typically beryllium), which are irradiated on both sides by an intense few-nanosecond laser pulse. The expansion and emission of our target, composed of a homogeneous mixture of iron, vanadium, and gold, are simulated using the 2-D LASNEX code. Reasonable agreement is found with the time history of the x-ray emission traces (DANTE). Both experiments and simulations exhibit an interesting reduction in the radial size of the emission region with time, as measured using face-on imaging. This is shown to be due to the ablation of the beryllium tamper, which affects the radial confinement of the embedded target. Simulations using a larger diameter beryllium tamper are found to mitigate this effect, improving the one-dimensionality of the expansion.

Physical and Chemical Strategies for Therapeutic Delivery by Using Polymeric Nanoparticles

PubMed Central

Morachis, José M.; Mahmoud, Enas A.

2012-01-01

A significant challenge that most therapeutic agents face is their inability to be delivered effectively. Nanotechnology offers a solution to allow for safe, high-dose, specific delivery of pharmaceuticals to the target tissue. Nanoparticles composed of biodegradable polymers can be designed and engineered with various layers of complexity to achieve drug targeting that was unimaginable years ago by offering multiple mechanisms to encapsulate and strategically deliver drugs, proteins, nucleic acids, or vaccines while improving their therapeutic index. Targeting of nanoparticles to diseased tissue and cells assumes two strategies: physical and chemical targeting. Physical targeting is a strategy enabled by nanoparticle fabrication techniques. It includes using size, shape, charge, and stiffness among other parameters to influence tissue accumulation, adhesion, and cell uptake. New methods to measure size, shape, and polydispersity will enable this field to grow and more thorough comparisons to be made. Physical targeting can be more economically viable when certain fabrication techniques are used. Chemical targeting can employ molecular recognition units to decorate the surface of particles or molecular units responsive to diseased environments or remote stimuli. In this review, we describe sophisticated nanoparticles designed for tissue-specific chemical targeting that use conjugation chemistry to attach targeting moieties. Furthermore, we describe chemical targeting using stimuli responsive nanoparticles that can respond to changes in pH, heat, and light. PMID:22544864

The relationship between target-class and the physicochemical properties of antibacterial drugs

PubMed Central

Mugumbate, Grace; Overington, John P.

2015-01-01

The discovery of novel mechanism of action (MOA) antibacterials has been associated with the concept that antibacterial drugs occupy a differentiated region of physicochemical space compared to human-targeted drugs. With, in broad terms, antibacterials having higher molecular weight, lower log P and higher polar surface area (PSA). By analysing the physicochemical properties of about 1700 approved drugs listed in the ChEMBL database, we show, that antibacterials for whose targets are riboproteins (i.e., composed of a complex of RNA and protein) fall outside the conventional human ‘drug-like’ chemical space; whereas antibacterials that modulate bacterial protein targets, generally comply with the ‘rule-of-five’ guidelines for classical oral human drugs. Our analysis suggests a strong target-class association for antibacterials—either protein-targeted or riboprotein-targeted. There is much discussion in the literature on the failure of screening approaches to deliver novel antibacterial lead series, and linkage of this poor success rate for antibacterials with the chemical space properties of screening collections. Our analysis suggests that consideration of target-class may be an underappreciated factor in antibacterial lead discovery, and that in fact bacterial protein-targets may well have similar binding site characteristics to human protein targets, and questions the assumption that larger, more polar compounds are a key part of successful future antibacterial discovery. PMID:25975639

Construction of proteins with molecular recognition capabilities using α3β3 de novo protein scaffolds.

PubMed

Okura, Hiromichi; Mihara, Hisakazu; Takahashi, Tsuyoshi

2013-10-01

The molecular recognition ability of proteins is essential in biological systems, and therefore a considerable amount of effort has been devoted to constructing desired target-binding proteins using a variety of naturally occurring proteins as scaffolds. However, since generating a binding site in a native protein can often affect its structural properties, highly stable de novo protein scaffolds may be more amenable than the native proteins. We previously reported the generation of de novo proteins comprising three α-helices and three β-strands (α3β3) from a genetic library coding simplified amino acid sets. Two α3β3 de novo proteins, vTAJ13 and vTAJ36, fold into a native-like stable and molten globule-like structures, respectively, even though the proteins have similar amino acid compositions. Here, we attempted to create binding sites for the vTAJ13 and vTAJ36 proteins to prove the utility of de novo designed artificial proteins as a molecular recognition tool. Randomization of six amino acids at two linker sites of vTAJ13 and vTAJ36 followed by biopanning generated binding proteins that recognize the target molecules, fluorescein and green fluorescent protein, with affinities of 10(-7)-10(-8) M. Of note, the selected proteins from the vTAJ13-based library tended to recognize the target molecules with high specificity, probably due to the native-like stable structure of vTAJ13. Our studies provide an example of the potential of de novo protein scaffolds, which are composed of a simplified amino acid set, to recognize a variety of target compounds.

Genetic algorithm in the structural design of Cooke triplet lenses

NASA Astrophysics Data System (ADS)

Hazra, Lakshminarayan; Banerjee, Saswatee

1999-08-01

This paper is in tune with our efforts to develop a systematic method for multicomponent lens design. Our aim is to find a suitable starting point in the final configuration space, so that popular local search methods like damped least squares (DLS) may directly lead to a useful solution. For 'ab initio' design problems, a thin lens layout specifying the powers of the individual components and the intercomponent separations are worked out analytically. Requirements of central aberration targets for the individual components in order to satisfy the prespecified primary aberration targets for the overall system are then determined by nonlinear optimization. The next step involves structural design of the individual components by optimization techniques. This general method may be adapted for the design of triplets and their derivatives. However, for the thin lens design of a Cooke triplet composed of three airspaced singlets, the two steps of optimization mentioned above may be combined into a single optimization procedure. The optimum configuration for each of the single set, catering to the required Gaussian specification and primary aberration targets for the Cooke triplet, are determined by an application of genetic algorithm (GA). Our implementation of this algorithm is based on simulations of some complex tools of natural evolution, like selection, crossover and mutation. Our version of GA may or may not converge to a unique optimum, depending on some of the algorithm specific parameter values. With our algorithm, practically useful solutions are always available, although convergence to a global optimum can not be guaranteed. This is perfectly in keeping with our need to allow 'floating' of aberration targets in the subproblem level. Some numerical results dealing with our preliminary investigations on this problem are presented.

A needle guidance system for biopsy and therapy using two-dimensional ultrasound

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

Bluvol, Nathan; Sheikh, Allison; Kornecki, Anat

2008-02-15

Image-guided needle biopsies are currently used to provide a definitive diagnosis of breast cancer; however, difficulties in tumor targeting exist as the ultrasound (United States) scan plane and biopsy needle must remain coplanar throughout the procedure to display the actual needle tip position. The additional time associated with aligning and maintaining this coplanar relationship results in increased patient discomfort. Biopsy procedural efficiency is further hindered since needle pathway interpretation is often difficult, especially for needle insertions at large depths that usually require multiple reinsertions. The authors developed a system that would increase the speed and accuracy of current breast biopsymore » procedures using readily available two-dimensional (2D) US technology. This system is composed of a passive articulated mechanical arm that attaches to a 2D US transducer. The arm is connected to a computer through custom electronics and software, which were developed as an interface for tracking the positioning of the mechanical components in real time. The arm couples to the biopsy needle and provides visual guidance for the physician performing the procedure in the form of a real-time projected needle pathway overlay on an US image of the breast. An agar test phantom, with stainless steel targets interspersed randomly throughout, was used to validate needle trajectory positioning accuracy. The biopsy needle was guided by both the software and hardware components to the targets. The phantom, with the needle inserted and device decoupled, was placed in an x-ray stereotactic mammography (SM) machine. The needle trajectory and bead target locations were determined in three dimensions from the SM images. Results indicated a mean needle trajectory accuracy error of 0.75{+-}0.42 mm. This is adequate to sample lesions that are <2 mm in diameter. Chicken tissue test phantoms were used to compare core needle biopsy procedure times between experienced radiologists and inexperienced resident radiologists using free-hand US and the needle guidance system. Cylindrical polyvinyl alcohol cryogel lesions, colored blue, were embedded in chicken tissue. Radiologists identified the lesions, visible as hypoechoic masses in the US images, and performed biopsy using a 14-gauge needle. Procedure times were compared based on experience and the technique performed. Using a pair-wise t test, lower biopsy procedure times were observed when using the guidance system versus the free-hand technique (t=12.59, p<0.001). The authors believe that with this improved biopsy guidance they will be able to reduce the ''false negative'' rate of biopsies, especially in the hands of less experienced physicians.« less

Systems and Methods for Composable Analytics

DTIC Science & Technology

2014-04-29

simplistic module that performs a mathematical operation on two numbers. The most important method is the Execute() method. This will get called when it is...addition, an input control is also specified in the example below. In this example, the mathematical operator can only be chosen from a preconfigured...approaches. Some of the industries that could benefit from Composable Analytics include pharmaceuticals, health care, insurance, actuaries , and

Gestalt perception modulates early visual processing.

PubMed

Herrmann, C S; Bosch, V

2001-04-17

We examined whether early visual processing reflects perceptual properties of a stimulus in addition to physical features. We recorded event-related potentials (ERPs) of 13 subjects in a visual classification task. We used four different stimuli which were all composed of four identical elements. One of the stimuli constituted an illusory Kanizsa square, another was composed of the same number of collinear line segments but the elements did not form a Gestalt. In addition, a target and a control stimulus were used which were arranged differently. These stimuli allow us to differentiate the processing of colinear line elements (stimulus features) and illusory figures (perceptual properties). The visual N170 in response to the illusory figure was significantly larger as compared to the other collinear stimulus. This is taken to indicate that the visual N170 reflects cognitive processes of Gestalt perception in addition to attentional processes and physical stimulus properties.

Use of spring-roll EAP actuator applied as end-effector of a hyper-redundant robot

NASA Astrophysics Data System (ADS)

Errico, Gianmarco; Fava, Victor; Resta, Ferruccio; Ripamonti, Francesco

2015-04-01

This paper presents a hyper-redundant continuous robot used to perform work in places which humans can not reach. This type of robot is generally a bio-inspired solution, it is composed by a lot of flexible segments driven by multiple actuators and its dynamics is described by a lot degrees of freedom. In this paper a model composed of some rigid links connected to each other by revolution joint is presented. In each link a torsional spring is added in order to simulate the resistant torque between the links and the interactions among the cables and the robot during the relative rotation. Moreover a type of EAP actuator, called spring roll, is used as the end-effector of the robot. Through a suitable sensor, such as a camera, the spring roll allows to track a target and it closes the control loop on the robot to follow it.

Biomimetic virus-based colourimetric sensors.

PubMed

Oh, Jin-Woo; Chung, Woo-Jae; Heo, Kwang; Jin, Hyo-Eon; Lee, Byung Yang; Wang, Eddie; Zueger, Chris; Wong, Winnie; Meyer, Joel; Kim, Chuntae; Lee, So-Young; Kim, Won-Geun; Zemla, Marcin; Auer, Manfred; Hexemer, Alexander; Lee, Seung-Wuk

2014-01-01

Many materials in nature change colours in response to stimuli, making them attractive for use as sensor platform. However, both natural materials and their synthetic analogues lack selectivity towards specific chemicals, and introducing such selectivity remains a challenge. Here we report the self-assembly of genetically engineered viruses (M13 phage) into target-specific, colourimetric biosensors. The sensors are composed of phage-bundle nanostructures and exhibit viewing-angle independent colour, similar to collagen structures in turkey skin. On exposure to various volatile organic chemicals, the structures rapidly swell and undergo distinct colour changes. Furthermore, sensors composed of phage displaying trinitrotoluene (TNT)-binding peptide motifs identified from a phage display selectively distinguish TNT down to 300 p.p.b. over similarly structured chemicals. Our tunable, colourimetric sensors can be useful for the detection of a variety of harmful toxicants and pathogens to protect human health and national security.