Composing in Public

ERIC Educational Resources Information Center

Heintz, Anne

2011-01-01

The central premise of this project is that researching student communication and composing actions in light of audience will illuminate particular features of student composing processes in 21st century interdisciplinary contexts. Students in this study took part in a six week inquiry unit about their local area. Data generated included student…

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.

The COMPOSE Project

NASA Astrophysics Data System (ADS)

Balletta, P.; Biagini, M.; Gallinaro, G.; Vernucci, A.

2003-07-01

This paper provides an overview of the on-going project COMPOSE, an EC co-funded project aiming to define, specify and validate an innovative mobile-services scenario in support of travellers, and to demonstrate the effectiveness of the new proposed location-based value-added services. COMPOSE is supported by organisations belonging to numerous categories covering, as a whole, the entire value-chain of infomobility services provision to the final user. The project team comprises, in addition to the affiliations of the authors, also Teleatlas (NL), ARS T&TT (NL), Alcatel-Bell Space (B), Skysoft (P), Hitech Marketing (A) and MobileGis (IR). The paper describes the services that will be offered to users, encompassing both the pre-trip and the on-trip framework, presents the overall hybrid system architecture also including a via-satellite component based upon the Wideband-CDMA (W-CDMA) technique adopted in UMTS, discusses the access solutions envisaged for that component permitting multiple feeder-link stations to share the CDMA multiplex capacity by directly transmitting their codes to the satellite, and illustrates the results of some computer simulations intended to assess the performance of said access solutions, with regard to the effects of the inevitable up- link frequency errors and transponder non-linearity.

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.

Creative Inspiration in Composers

ERIC Educational Resources Information Center

Gowan, John Curtis

1977-01-01

Discussed are sources of creative inspiration noted by composers such as Wagner, Strauss, and Puccini; and charted are discrete steps in creativity common to composers seen as producing works of genius. (IM)

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.

Composing the Curriculum: Teacher Identity

ERIC Educational Resources Information Center

Lewis, Rebecca

2012-01-01

What is composing and how is it valued? What does a good education in composing look like; what constraints hinder it and is it possible to overcome such constraints? Can composing be a personal, creative and valuable activity for the school student? What role does the teacher play in all of this? These are questions that I discuss in this…

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.

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.

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

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

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

Filmmaking as a Composing Process.

ERIC Educational Resources Information Center

Cox, Carole

1985-01-01

Discusses learning how to compose a film as one way children can learn the valuable lesson of how to give form to ideas and shape to thought. Presents the stages of composing a film and a sequence of filmmaking activities for introduction at progressive grade levels. (HTH)

Detection technique of targets for missile defense system

NASA Astrophysics Data System (ADS)

Guo, Hua-ling; Deng, Jia-hao; Cai, Ke-rong

2009-11-01

Ballistic missile defense system (BMDS) is a weapon system for intercepting enemy ballistic missiles. It includes ballistic-missile warning system, target discrimination system, anti-ballistic-missile guidance systems, and command-control communication system. Infrared imaging detection and laser imaging detection are widely used in BMDS for surveillance, target detection, target tracking, and target discrimination. Based on a comprehensive review of the application of target-detection techniques in the missile defense system, including infrared focal plane arrays (IRFPA), ground-based radar detection technology, 3-dimensional imaging laser radar with a photon counting avalanche photodiode (APD) arrays and microchip laser, this paper focuses on the infrared and laser imaging detection techniques in missile defense system, as well as the trends for their future development.

Hybrid-drive implosion system for ICF targets

DOEpatents

Mark, J.W.K.

1987-10-14

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

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.

Development of a microcapillary column for detecting targeted messenger RNA molecules.

PubMed

Ohnishi, Michihiro

2006-03-24

A capillary column in a rapid-flow system has been developed for detecting targeted messenger RNA (mRNA) molecules. The column has a structure made of two beds-one bed of porous microbeads and one bed of microbeads with a polythymidine base sequence. The targeted eukaryotic mRNA molecules are detected by two-step hybridization (sandwich hybridization) composed of polyadenosine selection of mRNA molecules and formation of a probe-target (targeted mRNA) hybrid. The sandwich hybridization, which is accomplished within 1 h, was tested using synthetic polydeoxynucleotides. Ten picomoles of the targeted polydeoxynucleotide were detected.

Guidance system for laser targets

DOEpatents

Porter, Gary D.; Bogdanoff, Anatoly

1978-01-01

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

The composing process in technical communication

NASA Technical Reports Server (NTRS)

Masse, R. E.

1981-01-01

The theory and application of the composing process in technical communications is addressed. The composing process of engineers, some implications for composing research for the teaching and research of technical communication, and an interpretation of the processes as creative experience are also discussed. Two areas of technical communications summarized concern: the rhetorical features of technical communications, and the theoretical background for a process-based view, a problem-solving approach to technical writing.

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

Allegany Ballistics Lab: sensor test target system

NASA Astrophysics Data System (ADS)

Eaton, Deran S.

2011-06-01

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

Hybrid-drive implosion system for ICF targets

DOEpatents

Mark, James W.

1988-08-02

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

Hybrid-drive implosion system for ICF targets

DOEpatents

Mark, James W.

1988-01-01

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

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.

Sequoias, Mavericks, Open Doors...Composing Joan Tower

ERIC Educational Resources Information Center

Allsup, Randall Everett

2011-01-01

This essay interview with Joan Tower is a meditation on the importance of composing, understood as a process larger than the making of new sound combinations or musical scores, suggesting that the compositional act is self-educative and self-forming. Tower's musical life, one of teaching and learning, one of composing and self-composing, is an…

Real-time target tracking and locating system for UAV

NASA Astrophysics Data System (ADS)

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

2017-07-01

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

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.

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.

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. �

Temperature Controller System for Gas Gun Targets

NASA Astrophysics Data System (ADS)

Bucholtz, Scott; Sheffield, Stephen

2005-07-01

A temperature controller system capable of heating and cooling gas gun targets over the range -75 C to +200 C was designed and tested. The system uses cold nitrogen gas from a liquid nitrogen Dewar for cooling and compressed air for heating. Two gas flow heaters control the gas temperature for both heating and cooling. One heater controls the temperature of the target mounting plate and the other the temperature of a copper tubing coil surrounding the target. Each heater is separately adjustable, so the target material will achieve a uniform temperature throughout its volume. A magnetic gauge with integrated thermocouples was developed to measure the internal temperature of the target. Using this system shock experiments, including equation-of-state measurements and shock initiation of high explosives, can be performed over a range of initial temperatures. Successful tests were completed on Teflon samples. This work was supported by the NNSA Enhanced Surveillance Campaign through contract DE-ACO4-01AL66850.

Temperature Controller System for Gas Gun Targets

NASA Astrophysics Data System (ADS)

Bucholtz, S. M.; Gehr, R. J.; Rupp, T. D.; Sheffield, S. A.; Robbins, D. L.

2006-07-01

A temperature controller system capable of heating and cooling gas gun targets over the range -75°C to +120°C was designed and tested. The system uses cold nitrogen gas from a liquid nitrogen Dewar for cooling and compressed air for heating. Two gas flow heaters control the gas temperature for both heating and cooling. One heater controls the temperature of the target mounting plate and the other the temperature of a copper tubing coil surrounding the target. Each heater is separately adjustable, so the target material will achieve a uniform temperature throughout its volume. A magnetic gauge membrane with integrated thermocouples was developed to measure the internal temperature of the target. Using this system, multiple magnetic gauge shock experiments, including equation-of-state measurements and shock initiation of high explosives, can be performed over a range of initial temperatures. Successful heating and cooling tests were completed on Teflon samples.

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

PubMed

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

2017-12-17

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

Target isolation system, high power laser and laser peening method and system using same

DOEpatents

Dane, C. Brent; Hackel, Lloyd A.; Harris, Fritz

2007-11-06

A system for applying a laser beam to work pieces, includes a laser system producing a high power output beam. Target delivery optics are arranged to deliver the output beam to a target work piece. A relay telescope having a telescope focal point is placed in the beam path between the laser system and the target delivery optics. The relay telescope relays an image between an image location near the output of the laser system and an image location near the target delivery optics. A baffle is placed at the telescope focal point between the target delivery optics and the laser system to block reflections from the target in the target delivery optics from returning to the laser system and causing damage.

A Virtual Composer in Every Classroom

ERIC Educational Resources Information Center

Hoffman, Adria R.; Carter, Bruce A.

2013-01-01

Previous generations applauded grant-funded programs that brought living composers into the lives of K-12 music students. The current economic climate, however, limits opportunities similar to those enjoyed in the past. We designed a virtual composer-in-residence experience that uses technology to overcome the barriers of funding limitations and…

Children Composing and the Tonal Idiom

ERIC Educational Resources Information Center

Roels, Johanna Maria; Van Petegem, Peter

2016-01-01

Existing studies have demonstrated how children compose, experiment and use their imagination within the conventions of the tonal idiom with functional harmony. However, one area of research that has hardly been explored is how tonality emerges in the compositions of children who compose by transforming their own non-musical ideas, such as their…

Adolescents' Dialogic Composing with Mobile Phones

ERIC Educational Resources Information Center

Warner, Julie

2016-01-01

This 14-month study examined the phone-based composing practice of three adolescents. Given the centrality of mobile phones to youth culture, the researcher sought to create a description of the participants' composing practices with these devices. Focal participants were users of Twitter and Instagram, two social media platforms that are usually…

The Composing Processes of Twelfth Graders.

ERIC Educational Resources Information Center

Emig, Janet

This inquiry examines the composing process of twelfth-grade writers, using a case study method. Eight twelfth graders were asked, in four sessions, each, to give autobiographies of their writing experiences and to compose aloud three times in the presence of a tape recorder and an investigator. Four hypotheses were formulated: (1) Twelfth-grade…

Cryogenic target system for hydrogen layering

DOE PAGES

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

2015-11-24

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

A Design for Composing and Extending Vehicle Models

NASA Technical Reports Server (NTRS)

Madden, Michael M.; Neuhaus, Jason R.

2003-01-01

The Systems Development Branch (SDB) at NASA Langley Research Center (LaRC) creates simulation software products for research. Each product consists of an aircraft model with experiment extensions. SDB treats its aircraft models as reusable components, upon which experiments can be built. SDB has evolved aircraft model design with the following goals: 1. Avoid polluting the aircraft model with experiment code. 2. Discourage the copy and tailor method of reuse. The current evolution of that architecture accomplishes these goals by reducing experiment creation to extend and compose. The architecture mechanizes the operational concerns of the model's subsystems and encapsulates them in an interface inherited by all subsystems. Generic operational code exercises the subsystems through the shared interface. An experiment is thus defined by the collection of subsystems that it creates ("compose"). Teams can modify the aircraft subsystems for the experiment using inheritance and polymorphism to create variants ("extend").

Multi-Stage System for Automatic Target Recognition

NASA Technical Reports Server (NTRS)

Chao, Tien-Hsin; Lu, Thomas T.; Ye, David; Edens, Weston; Johnson, Oliver

2010-01-01

A multi-stage automated target recognition (ATR) system has been designed to perform computer vision tasks with adequate proficiency in mimicking human vision. The system is able to detect, identify, and track targets of interest. Potential regions of interest (ROIs) are first identified by the detection stage using an Optimum Trade-off Maximum Average Correlation Height (OT-MACH) filter combined with a wavelet transform. False positives are then eliminated by the verification stage using feature extraction methods in conjunction with neural networks. Feature extraction transforms the ROIs using filtering and binning algorithms to create feature vectors. A feedforward back-propagation neural network (NN) is then trained to classify each feature vector and to remove false positives. The system parameter optimizations process has been developed to adapt to various targets and datasets. The objective was to design an efficient computer vision system that can learn to detect multiple targets in large images with unknown backgrounds. Because the target size is small relative to the image size in this problem, there are many regions of the image that could potentially contain the target. A cursory analysis of every region can be computationally efficient, but may yield too many false positives. On the other hand, a detailed analysis of every region can yield better results, but may be computationally inefficient. The multi-stage ATR system was designed to achieve an optimal balance between accuracy and computational efficiency by incorporating both models. The detection stage first identifies potential ROIs where the target may be present by performing a fast Fourier domain OT-MACH filter-based correlation. Because threshold for this stage is chosen with the goal of detecting all true positives, a number of false positives are also detected as ROIs. The verification stage then transforms the regions of interest into feature space, and eliminates false positives using an

Music and emotion-a composer's perspective.

PubMed

Douek, Joel

2013-01-01

This article takes an experiential and anecdotal look at the daily lives and work of film composers as creators of music. It endeavors to work backwards from what practitioners of the art and craft of music do instinctively or unconsciously, and try to shine a light on it as a conscious process. It examines the role of the film composer in his task to convey an often complex set of emotions, and communicate with an immediacy and universality that often sit outside of common language. Through the experiences of the author, as well as interviews with composer colleagues, this explores both concrete and abstract ways in which music can bring meaning and magic to words and images, and as an underscore to our daily lives.

Music and emotion—a composer's perspective

PubMed Central

Douek, Joel

2013-01-01

This article takes an experiential and anecdotal look at the daily lives and work of film composers as creators of music. It endeavors to work backwards from what practitioners of the art and craft of music do instinctively or unconsciously, and try to shine a light on it as a conscious process. It examines the role of the film composer in his task to convey an often complex set of emotions, and communicate with an immediacy and universality that often sit outside of common language. Through the experiences of the author, as well as interviews with composer colleagues, this explores both concrete and abstract ways in which music can bring meaning and magic to words and images, and as an underscore to our daily lives. PMID:24348344

Composing for Affect, Audience, and Identity: Toward a Multidimensional Understanding of Adolescents' Multimodal Composing Goals and Designs

ERIC Educational Resources Information Center

Smith, Blaine E.

2018-01-01

This study examined adolescents' perspectives on their multimodal composing goals and designs when creating digital projects in the context of an English Language Arts class. Sociocultural and social semiotics theoretical frameworks were integrated to understand six 12th grade students' viewpoints when composing three multimodal products--a…

Composing across Modes: A Comparative Analysis of Adolescents' Multimodal Composing Processes

ERIC Educational Resources Information Center

Smith, Blaine E.

2017-01-01

Although the shift from page to screen has dramatically redefined conceptions of writing, very little is known about how youth compose with multiple modes in digital environments. Integrating multimodality and multiliteracies theoretical frameworks, this comparative case study examined how urban twelfth-grade students collaboratively composed…

Unskilled Writers as Composers.

ERIC Educational Resources Information Center

Perl, Sondra

1979-01-01

Composition is not a straightforward, linear process; it involves a creative search for meaning that becomes clear only as the writer engages in the composing process. This suggests that teaching not dwell on the correctness of the finished product. (Author/SJL)

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 Multiple-Demand System in the Novelty of Musical Improvisation: Evidence from an MRI Study on Composers.

PubMed

Lu, Jing; Yang, Hua; He, Hui; Jeon, Seun; Hou, Changyue; Evans, Alan C; Yao, Dezhong

2017-01-01

The multiple-demand (MD) system has proven to be associated with creating structured mental programs in comprehensive behaviors, but the functional mechanisms of this system have not been clarified in the musical domain. In this study, we explored the hypothesis that the MD system is involved in a comprehensive music-related behavior known as musical improvisation. Under a functional magnetic resonance imaging (fMRI) paradigm, 29 composers were recruited to improvise melodies through visual imagery tasks according to familiar and unfamiliar cues. We found that the main regions of the MD system were significantly activated during both musical improvisation conditions. However, only a greater involvement of the intraparietal sulcus (IPS) within the MD system was shown when improvising with unfamiliar cues. Our results revealed that the MD system strongly participated in musical improvisation through processing the novelty of melodies, working memory, and attention. In particular, improvising with unfamiliar cues required more musical transposition manipulations. Moreover, both functional and structural analyses indicated evidence of neuroplasticity in MD regions that could be associated with musical improvisation training. These findings can help unveil the functional mechanisms of the MD system in musical cognition, as well as improve our understanding of musical improvisation.

Repetitive output laser system and method using target reflectivity

DOEpatents

Johnson, Roy R.

1978-01-01

An improved laser system and method for implosion of a thermonuclear fuel pellet in which that portion of a laser pulse reflected by the target pellet is utilized in the laser system to initiate a succeeding target implosion, and in which the energy stored in the laser system to amplify the initial laser pulse, but not completely absorbed thereby, is used to amplify succeeding laser pulses initiated by target reflection.

Active Multimodal Sensor System for Target Recognition and Tracking

PubMed Central

Zhang, Guirong; Zou, Zhaofan; Liu, Ziyue; Mao, Jiansen

2017-01-01

High accuracy target recognition and tracking systems using a single sensor or a passive multisensor set are susceptible to external interferences and exhibit environmental dependencies. These difficulties stem mainly from limitations to the available imaging frequency bands, and a general lack of coherent diversity of the available target-related data. This paper proposes an active multimodal sensor system for target recognition and tracking, consisting of a visible, an infrared, and a hyperspectral sensor. The system makes full use of its multisensor information collection abilities; furthermore, it can actively control different sensors to collect additional data, according to the needs of the real-time target recognition and tracking processes. This level of integration between hardware collection control and data processing is experimentally shown to effectively improve the accuracy and robustness of the target recognition and tracking system. PMID:28657609

The Research Progress of Targeted Drug Delivery Systems

NASA Astrophysics Data System (ADS)

Zhan, Jiayin; Ting, Xizi Liang; Zhu, Junjie

2017-06-01

Targeted drug delivery system (DDS) means to selectively transport drugs to targeted tissues, organs, and cells through a variety of drugs carrier. It is usually designed to improve the pharmacological and therapeutic properties of conventional drugs and to overcome problems such as limited solubility, drug aggregation, poor bio distribution and lack of selectivity, controlling drug release carrier and to reduce normal tissue damage. With the characteristics of nontoxic and biodegradable, it can increase the retention of drug in lesion site and the permeability, improve the concentration of the drug in lesion site. at present, there are some kinds of DDS using at test phase, such as slow controlled release drug delivery system, targeted drug delivery systems, transdermal drug delivery system, adhesion dosing system and so on. This paper makes a review for DDS.

Composing Interfering Abstract Protocols

DTIC Science & Technology

2016-04-01

Tecnologia , Universidade Nova de Lisboa, Caparica, Portugal. This document is a companion technical report of the paper, “Composing Interfering Abstract...a Ciência e Tecnologia (Portuguese Foundation for Science and Technology) through the Carnegie Mellon Portugal Program under grant SFRH / BD / 33765

Magnetic confinement system using charged ammonia targets

DOEpatents

Porter, Gary D.; Bogdanoff, Anatoly

1979-01-01

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

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

ERIC Educational Resources Information Center

Owen, Jane; Alterman, Jeff

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

The Composing Processes of Unskilled College Writers.

ERIC Educational Resources Information Center

Perl, Sondra

The findings from a study of five students undertaken to determine how unskilled college writers compose, whether their writing processes can be analyzed in a systematic manner, and what an increased understanding of those processes suggests about the nature of composing and about the manner in which writing is taught are presented in this paper.…

ILC TARGET WHEEL RIM FRAGMENT/GUARD PLATE IMPACT ANALYSIS

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

Hagler, L

2008-07-17

A positron source component is needed for the International Linear Collider Project. The leading design concept for this source is a rotating titanium alloy wheel whose spokes rotate through an intense localized magnetic field. The system is composed of an electric motor, flexible motor/drive-shaft coupling, stainless steel drive-shaft, two Plumber's Block tapered roller bearings, a titanium alloy target wheel, and electromagnet. Surrounding the target wheel and magnet is a steel frame with steel guarding plates intended to contain shrapnel in case of catastrophic wheel failure. Figure 1 is a layout of this system (guard plates not shown for clarity). Thismore » report documents the FEA analyses that were performed at LLNL to help determine, on a preliminary basis, the required guard plate thickness for three potential plate steels.« less

The Multiple-Demand System in the Novelty of Musical Improvisation: Evidence from an MRI Study on Composers

PubMed Central

Lu, Jing; Yang, Hua; He, Hui; Jeon, Seun; Hou, Changyue; Evans, Alan C.; Yao, Dezhong

2017-01-01

The multiple-demand (MD) system has proven to be associated with creating structured mental programs in comprehensive behaviors, but the functional mechanisms of this system have not been clarified in the musical domain. In this study, we explored the hypothesis that the MD system is involved in a comprehensive music-related behavior known as musical improvisation. Under a functional magnetic resonance imaging (fMRI) paradigm, 29 composers were recruited to improvise melodies through visual imagery tasks according to familiar and unfamiliar cues. We found that the main regions of the MD system were significantly activated during both musical improvisation conditions. However, only a greater involvement of the intraparietal sulcus (IPS) within the MD system was shown when improvising with unfamiliar cues. Our results revealed that the MD system strongly participated in musical improvisation through processing the novelty of melodies, working memory, and attention. In particular, improvising with unfamiliar cues required more musical transposition manipulations. Moreover, both functional and structural analyses indicated evidence of neuroplasticity in MD regions that could be associated with musical improvisation training. These findings can help unveil the functional mechanisms of the MD system in musical cognition, as well as improve our understanding of musical improvisation. PMID:29311776

The composing process of technical writers: A preliminary study

NASA Technical Reports Server (NTRS)

Mair, D.; Roundy, N.

1981-01-01

The assumption that technical writers compose as do other writers is tested. The literature on the composing process, not limited to the pure or applied sciences, was reviewed, yielding three areas of general agreement. The composing process (1) consists of several stages, (2) is reflexive, and (3) may be mastered by means of strategies. Data on the ways technical writers compose were collected, and findings were related to the three areas of agreement. Questionnaires and interviews surveying 70 writers were used. The disciplines represented by these writers included civil, chemical, agricultural, geological, mechanical, electrical, and petroleum engineering, chemistry, hydrology, geology, and biology. Those providing consulting services, or performing research. No technical editors or professional writers were surveyed, only technicians, engineers, and researchers whose jobs involved composing reports. Three pedagogical implications are included.

Systems genetics for drug target discovery

PubMed Central

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

2011-01-01

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

Surgical operation using lighting goggle composed of white LED arrays

NASA Astrophysics Data System (ADS)

Shimada, Junichi; Kawakami, Yoichi; Fujita, Shigeo

2001-12-01

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. To improve the color rendering in red colors, some adjustments should be given in the fluorescents layers. Design of goggle is also very important for cutting into the real practical market of white LEDs.

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.

Recent Advances in Aptamers Targeting Immune System.

PubMed

Hu, Piao-Ping

2017-02-01

The immune system plays important role in protecting the organism by recognizing non-self molecules from pathogen such as bacteria, parasitic worms, and viruses. When the balance of the host defense system is disturbed, immunodeficiency, autoimmunity, and inflammation occur. Nucleic acid aptamers are short single-stranded DNA (ssDNA) or RNA ligands that interact with complementary molecules with high specificity and affinity. Aptamers that target the molecules involved in immune system to modulate their function have great potential to be explored as new diagnostic and therapeutic agents for immune disorders. This review summarizes recent advances in the development of aptamers targeting immune system. The selection of aptamers with superior chemical and biological characteristics will facilitate their application in the diagnosis and treatment of immune disorders.

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.

Prospects for composability of models and simulations

NASA Astrophysics Data System (ADS)

Davis, Paul K.; Anderson, Robert B.

2004-08-01

This paper is the summary of a recent RAND study done at the request of the U.S. Defense Modeling and Simulation Office (DMSO). Commissioned in recognition that the last decade's efforts by DoD to achieve model "composability" have had only limited success (e.g., HLA-mediated exercises), and that fundamental problems remain, the study surveyed the underlying problems that make composability difficult. It then went on to recommend a series of improvement measures for DMSO and other DoD offices to consider. One strong recommendation was that DoD back away from an earlier tendency toward overselling composability, moving instead to a more particularized approach in which composability is sought within domains where it makes most sense substantively. Another recommendation was that DoD needs to recognize the shortcomings of standard software-engineering paradigms when dealing with "models" rather than pure software. Beyond this, the study had concrete recommendations dealing with science and technology, the base of human capital, management, and infrastructure. Many recommendations involved the need to align more closely with cutting edge technology and emerging standards in the private sector.

Targeting the Thioredoxin System for Cancer Therapy.

PubMed

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

2017-09-01

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

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

PubMed

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

2015-07-01

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

Tumor target amplification: Implications for nano drug delivery systems.

PubMed

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

2018-04-10

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

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.

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.

Fe₃O₄ Nanoparticles in Targeted Drug/Gene Delivery Systems.

PubMed

Shen, Lazhen; Li, Bei; Qiao, Yongsheng

2018-02-23

Fe₃O₄ nanoparticles (NPs), the most traditional magnetic nanoparticles, have received a great deal of attention in the biomedical field, especially for targeted drug/gene delivery systems, due to their outstanding magnetism, biocompatibility, lower toxicity, biodegradability, and other features. Naked Fe₃O₄ NPs are easy to aggregate and oxidize, and thus are often made with various coatings to realize superior properties for targeted drug/gene delivery. In this review, we first list the three commonly utilized synthesis methods of Fe₃O₄ NPs, and their advantages and disadvantages. In the second part, we describe coating materials that exhibit noticeable features that allow functionalization of Fe₃O₄ NPs and summarize their methods of drug targeting/gene delivery. Then our efforts will be devoted to the research status and progress of several different functionalized Fe₃O₄ NP delivery systems loaded with chemotherapeutic agents, and we present targeted gene transitive carriers in detail. In the following section, we illuminate the most effective treatment systems of the combined drug and gene therapy. Finally, we propose opportunities and challenges of the clinical transformation of Fe₃O₄ NPs targeting drug/gene delivery systems.

Composing a Research Life

ERIC Educational Resources Information Center

Cochran-Smith, Marilyn

2012-01-01

In this article about her early career development and the experiences that shaped her life as a scholar and researcher, the author describes the work lives of university-based teacher educators and what it means to compose a research life in this field. This article draws on the author's 30 years as a university-based teacher educator. In it, she…

Target tracking system based on preliminary and precise two-stage compound cameras

NASA Astrophysics Data System (ADS)

Shen, Yiyan; Hu, Ruolan; She, Jun; Luo, Yiming; Zhou, Jie

2018-02-01

Early detection of goals and high-precision of target tracking is two important performance indicators which need to be balanced in actual target search tracking system. This paper proposed a target tracking system with preliminary and precise two - stage compound. This system using a large field of view to achieve the target search. After the target was searched and confirmed, switch into a small field of view for two field of view target tracking. In this system, an appropriate filed switching strategy is the key to achieve tracking. At the same time, two groups PID parameters are add into the system to reduce tracking error. This combination way with preliminary and precise two-stage compound can extend the scope of the target and improve the target tracking accuracy and this method has practical value.

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

NASA Astrophysics Data System (ADS)

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

2001-10-01

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

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.

Radiation effects in IFMIF Li target diagnostic systems

NASA Astrophysics Data System (ADS)

Molla, J.; Vila, R.; Shikama, T.; Horiike, H.; Simakov, S.; Ciotti, M.; Ibarra, A.

2009-04-01

Diagnostics for the lithium target will be crucial for the operation of IFMIF. Several parameters as the lithium temperature, target thickness or wave pattern must be monitored during operation. Radiation effects may produce malfunctioning in any of these diagnostics due to the exposure to high radiation fields. The main diagnostic systems proposed for the operation of IFMIF are reviewed in this paper from the point of view of radiation damage. The main tools for the assessment of the performance of these diagnostics are the neutronics calculations by using specialised codes and the information accumulated during the last decades on the radiation effects in functional materials, components and diagnostics for ITER. This analysis allows to conclude that the design of some of the diagnostic systems must be revised to assure the high availability required for the target system.

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

PubMed Central

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

2016-01-01

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

Targeted activation of diverse CRISPR-Cas systems for mammalian genome editing via proximal CRISPR targeting.

PubMed

Chen, Fuqiang; Ding, Xiao; Feng, Yongmei; Seebeck, Timothy; Jiang, Yanfang; Davis, Gregory D

2017-04-07

Bacterial CRISPR-Cas systems comprise diverse effector endonucleases with different targeting ranges, specificities and enzymatic properties, but many of them are inactive in mammalian cells and are thus precluded from genome-editing applications. Here we show that the type II-B FnCas9 from Francisella novicida possesses novel properties, but its nuclease function is frequently inhibited at many genomic loci in living human cells. Moreover, we develop a proximal CRISPR (termed proxy-CRISPR) targeting method that restores FnCas9 nuclease activity in a target-specific manner. We further demonstrate that this proxy-CRISPR strategy is applicable to diverse CRISPR-Cas systems, including type II-C Cas9 and type V Cpf1 systems, and can facilitate precise gene editing even between identical genomic sites within the same genome. Our findings provide a novel strategy to enable use of diverse otherwise inactive CRISPR-Cas systems for genome-editing applications and a potential path to modulate the impact of chromatin microenvironments on genome modification.

Targeted activation of diverse CRISPR-Cas systems for mammalian genome editing via proximal CRISPR targeting

PubMed Central

Chen, Fuqiang; Ding, Xiao; Feng, Yongmei; Seebeck, Timothy; Jiang, Yanfang; Davis, Gregory D.

2017-01-01

Bacterial CRISPR–Cas systems comprise diverse effector endonucleases with different targeting ranges, specificities and enzymatic properties, but many of them are inactive in mammalian cells and are thus precluded from genome-editing applications. Here we show that the type II-B FnCas9 from Francisella novicida possesses novel properties, but its nuclease function is frequently inhibited at many genomic loci in living human cells. Moreover, we develop a proximal CRISPR (termed proxy-CRISPR) targeting method that restores FnCas9 nuclease activity in a target-specific manner. We further demonstrate that this proxy-CRISPR strategy is applicable to diverse CRISPR–Cas systems, including type II-C Cas9 and type V Cpf1 systems, and can facilitate precise gene editing even between identical genomic sites within the same genome. Our findings provide a novel strategy to enable use of diverse otherwise inactive CRISPR–Cas systems for genome-editing applications and a potential path to modulate the impact of chromatin microenvironments on genome modification. PMID:28387220

Naldemedine versus placebo for opioid-induced constipation (COMPOSE-1 and COMPOSE-2): two multicentre, phase 3, double-blind, randomised, parallel-group trials.

PubMed

Hale, Martin; Wild, James; Reddy, Jyotsna; Yamada, Tadaaki; Arjona Ferreira, Juan Camilo

2017-08-01

Opioid-induced constipation is a frequent side-effect of opioid treatment, and standard interventions have limited or inconsistent efficacy. This study assessed the efficacy and safety of naldemedine, a peripherally acting μ-opioid receptor antagonist, for the treatment of opioid-induced constipation in patients with chronic non-cancer pain. We report two double-blind, randomised, placebo-controlled trials in adults with chronic non-cancer pain and opioid-induced constipation. The first (COMPOSE-1) was done in 68 outpatient sites in seven countries and the second (COMPOSE-2) at 69 outpatient sites in six countries; both studies were done in Europe and the USA. Eligible patients were aged 18-80 years, did not use laxatives, and had a stable opioid regimen for treatment of chronic non-cancer pain with a total daily dose averaging at least 30 mg (morphine equivalent) for at least 1 month before screening. Patients were randomly assigned (1:1) to receive either oral naldemedine 0·2 mg or matching placebo once a day for 12 weeks. Randomisation was stratified by average total daily opioid dose (30-100 mg and >100 mg equivalents of oral morphine sulphate). The primary endpoint was proportion of responders. A responder had at least three spontaneous bowel movements (SBMs) per week with an increase from baseline of at least one SBM per week for at least 9 weeks of the 12-week treatment period including at least three of the last 4 weeks. Efficacy endpoints were analysed by intention to treat and the safety population included all patients who received at least one dose of study drug. These trials have both been completed and are registered with ClinicalTrials.gov, numbers NCT01965158 and NCT01993940. In COMPOSE-1, 547 patients were recruited between Aug 29, 2013, and Jan 22, 2015, and were randomly assigned to receive naldemedine (n=274) or placebo (n=273). Patients for COMPOSE-2 were recruited between Nov 4, 2013, and June 9, 2015; 553 patients were randomly assigned to

Composing chaotic music from the letter m

NASA Astrophysics Data System (ADS)

Sotiropoulos, Anastasios D.

Chaotic music is composed from a proposed iterative map depicting the letter m, relating the pitch, duration and loudness of successive steps. Each of the two curves of the letter m is based on the classical logistic map. Thus, the generating map is xn+1 = r xn(1/2 - xn) for xn between 0 and 1/2 defining the first curve, and xn+1 = r (xn - 1/2)(1 - xn) for xn between 1/2 and 1 representing the second curve. The parameter r which determines the height(s) of the letter m varies from 2 to 16, the latter value ensuring fully developed chaotic solutions for the whole letter m; r = 8 yielding full chaotic solutions only for its first curve. The m-model yields fixed points, bifurcation points and chaotic regions for each separate curve, as well as values of the parameter r greater than 8 which produce inter-fixed points, inter-bifurcation points and inter-chaotic regions from the interplay of the two curves. Based on this, music is composed from mapping the m- recurrence model solutions onto actual notes. The resulting musical score strongly depends on the sequence of notes chosen by the composer to define the musical range corresponding to the range of the chaotic mathematical solutions x from 0 to 1. Here, two musical ranges are used; one is the middle chromatic scale and the other is the seven- octaves range. At the composer's will and, for aesthetics, within the same composition, notes can be the outcome of different values of r and/or shifted in any octave. Compositions with endings of non-repeating note patterns result from values of r in the m-model that do not produce bifurcations. Scores of chaotic music composed from the m-model and the classical logistic model are presented.

16 CFR 303.24 - Pile fabrics and products composed thereof.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 16 Commercial Practices 1 2010-01-01 2010-01-01 false Pile fabrics and products composed thereof... CONGRESS RULES AND REGULATIONS UNDER THE TEXTILE FIBER PRODUCTS IDENTIFICATION ACT § 303.24 Pile fabrics and products composed thereof. The fiber content of pile fabrics or products composed thereof may be...

Grammar for College Writing: A Sentence-Composing Approach

ERIC Educational Resources Information Center

Killgallon, Don; Killgallon, Jenny

2010-01-01

Across America, in thousands of classrooms, from elementary school to high school, the time-tested sentence-composing approach has given students tools to become better writers. Now the authors present a much anticipated sentence-composing grammar worktext for college writing. This book presents a new and easier way to understand grammar: (1) Noun…

IGF system targeted therapy: Therapeutic opportunities for ovarian cancer.

PubMed

Liefers-Visser, J A L; Meijering, R A M; Reyners, A K L; van der Zee, A G J; de Jong, S

2017-11-01

The insulin-like growth factor (IGF) system comprises multiple growth factor receptors, including insulin-like growth factor 1 receptor (IGF-1R), insulin receptor (IR) -A and -B. These receptors are activated upon binding to their respective growth factor ligands, IGF-I, IGF-II and insulin, and play an important role in development, maintenance, progression, survival and chemotherapeutic response of ovarian cancer. In many pre-clinical studies anti-IGF-1R/IR targeted strategies proved effective in reducing growth of ovarian cancer models. In addition, anti-IGF-1R targeted strategies potentiated the efficacy of platinum based chemotherapy. Despite the vast amount of encouraging and promising pre-clinical data, anti-IGF-1R/IR targeted strategies lacked efficacy in the clinic. The question is whether targeting the IGF-1R/IR signaling pathway still holds therapeutic potential. In this review we address the complexity of the IGF-1R/IR signaling pathway, including receptor heterodimerization within and outside the IGF system and downstream signaling. Further, we discuss the implications of this complexity on current targeted strategies and indicate therapeutic opportunities for successful targeting of the IGF-1R/IR signaling pathway in ovarian cancer. Multiple-targeted approaches circumventing bidirectional receptor tyrosine kinase (RTK) compensation and prevention of system rewiring are expected to have more therapeutic potential. Copyright © 2017 The Author(s). Published by Elsevier Ltd.. All rights reserved.

Prioritized System Science Targets for Heliophysics

NASA Astrophysics Data System (ADS)

Spann, J. F.; Christensen, A. B.; St Cyr, O. C.; Posner, A.; Giles, B. L.

2009-12-01

Heliophysics is a discipline that investigates the science at work from the interface of Earth and space, to the core of the Sun, and to the outer edge of our solar system. This solar-interplanetary-planetary system is vast and inherently coupled on many spatial, temporal and energy scales. The Sun’s explosive energy output creates complicated field and plasma structures that when coupled with our terrestrial magnetized space, generates an extraordinary complex environment that has practical implications for humanity as we are becoming increasingly dependent on space-based assets. This immense volume of our cosmic neighborhood is the domain of heliophysics. Understanding this domain and the dominant mechanisms that control the transfer of mass and energy requires a system approach that addresses all aspects and regions of the system. The 2009 NASA Heliophysics Roadmap presents a science-focused strategic approach to advance the goal of heliophysics: why does the Sun vary; how do the Earth and heliosphere respond; and what are the impacts on humanity? This talk will present the top 6 prioritized science targets to understand the coupled heliophysics system as presented in the 2009 NASA Heliophysics Roadmap. An exposition of each science target and how it addresses outstanding questions in heliophysics will be discussed.

Prioritized System Science Targets for Heliophysics

NASA Technical Reports Server (NTRS)

Spann, James Frederick; Christensen, Andrew B.; SaintCyr, Orville Chris; Posner, Arik; Giles, Barbara L.

2009-01-01

Heliophysics is a discipline that investigates the science at work from the interface of Earth and space, to the core of the Sun, and to the outer edge of our solar system. This solar-interplanetary-planetary system is vast and inherently coupled on many spatial, temporal and energy scales. The Sun's explosive energy output creates complicated field and plasma structures that when coupled with our terrestrial magnetized space, generates an extraordinary complex environment that has practical implications for humanity as we are becoming increasingly dependent on space-based assets. This immense volume of our cosmic neighborhood is the domain of heliophysics. Understanding this domain and the dominant mechanisms that control the transfer of mass and energy requires a system approach that addresses all aspects and regions of the system. The 2009 NASA Heliophysics Roadmap presents a science-focused strategic approach to advance the goal of heliophysics: why does the Sun vary; how do the Earth and heliosphere respond; and what are the impacts on humanity? This talk will present the top 6 prioritized science targets to understand the coupled heliophysics system as presented in the 2009 NASA Heliophysics Roadmap. An exposition of each science target and how it addresses outstanding questions in heliophysics will be discussed.

Customer systems group 1996 target summaries: Information systems and telecommunications. Revision 4

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

NONE

1995-06-15

The target summaries give planning information on the new business systems development; customer service applications and infrastructure; and advanced information systems and telecommunications research, architecture and standards factions of Information Systems & Telecommunications.

Celebration of Black Composers: Black Music at the Philharmonic

ERIC Educational Resources Information Center

Current, Gloster B.

1978-01-01

The five-day celebration of black composers at the New York Philharmonic included a panel discussion of black music and three symphonic concerts featuring the premieres of new works by celebrated black composers. (Author/AM)

Composing Models of Geographic Physical Processes

NASA Astrophysics Data System (ADS)

Hofer, Barbara; Frank, Andrew U.

Processes are central for geographic information science; yet geographic information systems (GIS) lack capabilities to represent process related information. A prerequisite to including processes in GIS software is a general method to describe geographic processes independently of application disciplines. This paper presents such a method, namely a process description language. The vocabulary of the process description language is derived formally from mathematical models. Physical processes in geography can be described in two equivalent languages: partial differential equations or partial difference equations, where the latter can be shown graphically and used as a method for application specialists to enter their process models. The vocabulary of the process description language comprises components for describing the general behavior of prototypical geographic physical processes. These process components can be composed by basic models of geographic physical processes, which is shown by means of an example.

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.

Neural Network Target Identification System for False Alarm Reduction

NASA Technical Reports Server (NTRS)

Ye, David; Edens, Weston; Lu, Thomas T.; Chao, Tien-Hsin

2009-01-01

A multi-stage automated target recognition (ATR) system has been designed to perform computer vision tasks with adequate proficiency in mimicking human vision. The system is able to detect, identify, and track targets of interest. Potential regions of interest (ROIs) are first identified by the detection stage using an Optimum Trade-off Maximum Average Correlation Height (OT-MACH) filter combined with a wavelet transform. False positives are then eliminated by the verification stage using feature extraction methods in conjunction with neural networks. Feature extraction transforms the ROIs using filtering and binning algorithms to create feature vectors. A feed forward back propagation neural network (NN) is then trained to classify each feature vector and remove false positives. This paper discusses the test of the system performance and parameter optimizations process which adapts the system to various targets and datasets. The test results show that the system was successful in substantially reducing the false positive rate when tested on a sonar image dataset.

A thermo- and pH-sensitive hydrogel composed of quaternized chitosan/glycerophosphate.

PubMed

Wu, Jie; Su, Zhi-Guo; Ma, Guang-Hui

2006-06-06

The quaternized chitosan was synthesized by the reaction of chitosan and glycidyltrimethylammonium chloride (GTMAC) and named as N-[(2-hydroxy-3-trimethylammonium) propyl] chitosan chloride (HTCC). A novel hydrogel system composed of HTCC/glycerophosphate (HTCC/GP) with thermo- and pH-sensitivity was synthesized and used as an intelligent drug carrier. The formulation was solution below or at room temperature, which allowed it injectable and to incorporate living cells, proteins, enzymes or other therapeutic drugs easily. Once the surrounding temperature was up to 37 degrees C, the system was transformed to a non-flowing hydrogel, and the formed hydrogel can release the trapped drug as a function of pH values. The swelling behavior of the system and the release profiles of doxorubicin hydrochloride (DX) as a model drug at different pH values were investigated. At acidic condition the hydrogel dissolved and released drug quickly, while it absorbed water and released drug slowly at neutral or basic conditions. Hydrogel composed of chitosan hydrochloride and glycerophosphate (CS/GP) was also prepared to compare with HTCC/GP hydrogel. The HTCC/GP hydrogel in this study was transparent which made it suitable for some specific uses such as ocular drug formulation.

Optical memory development. Volume 3: The membrane light value page composer

NASA Technical Reports Server (NTRS)

Cosentino, L. S.; Nagle, E. M.; Stewart, W. C.

1972-01-01

The feasibility of producing a page composer for optical memory systems using thin, deformable, membrane-mirror elements as light valves was investigated. The electromechanical and optical performances of such elements were determined both analytically and experimentally. It was found that fast switching (approximately 10 microseconds), high-contrast (10 or greater), fatigue-free operation over missions of cycles, and efficient utilization of input light could be obtained with membrane light valves. Several arrays of 64 elements were made on substrates with feedthroughs, allowing access to individual elements from the backside of the substrate. Single light valves on such arrays were successfully operated with the transistors designed and produced for selection and storage at each bit location. This simulated the operation of a prototype page composer with semiconductor chips beam-lead bonded to the back of the substrate.

Dynamics of quadruple systems composed of two binaries: stars, white dwarfs, and implications for Ia supernovae

NASA Astrophysics Data System (ADS)

Fang, Xiao; Thompson, Todd A.; Hirata, Christopher M.

2018-05-01

We investigate the long-term secular dynamics and Lidov-Kozai (LK) eccentricity oscillations of quadruple systems composed of two binaries at quadrupole and octupole orders in the perturbing Hamiltonian. We show that the fraction of systems reaching high eccentricities is enhanced relative to triple systems, over a broader range of parameter space. We show that this fraction grows with time, unlike triple systems evolved at quadrupole order. This is fundamentally because with their additional degrees of freedom, quadruple systems do not have a maximal set of commuting constants of the motion, even in secular theory at quadrupole order. We discuss these results in the context of star-star and white dwarf-white dwarf (WD) binaries, with emphasis on WD-WD mergers and collisions relevant to the Type Ia supernova problem. For star-star systems, we find that more than 30 per cent of systems reach high eccentricity within a Hubble time, potentially forming triple systems via stellar mergers or close binaries. For WD-WD systems, taking into account general relativistic and tidal precession and dissipation, we show that the merger rate is enhanced in quadruple systems relative to triple systems by a factor of 3.5-10, and that the long-term evolution of quadruple systems leads to a delay-time distribution ˜1/t for mergers and collisions. In gravitational wave-driven mergers of compact objects, we classify the mergers by their evolutionary patterns in phase space and identify a regime in about 8 per cent of orbital shrinking mergers, where eccentricity oscillations occur on the general relativistic precession time-scale, rather than the much longer LK time-scale. Finally, we generalize previous treatments of oscillations in the inner binary eccentricity (evection) to eccentric mutual orbits. We assess the merger rate in quadruple and triple systems and the implications for their viability as progenitors of stellar mergers and Type Ia supernovae.

Dimensions of the Composing Process.

ERIC Educational Resources Information Center

Freedman, Aviva

As a by-product of a study concerning how university level writers develop new genres of discourse, a study was undertaken to examine what factors or dimensions affect the composing process of university writers. Six undergraduate students at Carleton University in Ottawa participated, making available to researchers information about how they…

Finding a Target with an Accessible Global Positioning System

ERIC Educational Resources Information Center

Ponchillia, Paul E.; MacKenzie, Nancy; Long, Richard G.; Denton-Smith, Pamela; Hicks, Thomas L.; Miley, Priscilla

2007-01-01

This article presents two target-location experiments. In the first experiment, 19 participants located a 25-foot chalk circle 93% of the time with a Global Positioning System (GPS) compared to 12% of the time without it. In a single-subject follow-up experiment, the participant came within 1 foot of the target on all GPS trials. Target-location…

Advances in Orion's On-Orbit Guidance and Targeting System Architecture

NASA Technical Reports Server (NTRS)

Scarritt, Sara K.; Fill, Thomas; Robinson, Shane

2015-01-01

NASA's manned spaceflight programs have a rich history of advancing onboard guidance and targeting technology. In order to support future missions, the guidance and targeting architecture for the Orion Multi-Purpose Crew Vehicle must be able to operate in complete autonomy, without any support from the ground. Orion's guidance and targeting system must be sufficiently flexible to easily adapt to a wide array of undecided future missions, yet also not cause an undue computational burden on the flight computer. This presents a unique design challenge from the perspective of both algorithm development and system architecture construction. The present work shows how Orion's guidance and targeting system addresses these challenges. On the algorithm side, the system advances the state-of-the-art by: (1) steering burns with a simple closed-loop guidance strategy based on Shuttle heritage, and (2) planning maneuvers with a cutting-edge two-level targeting routine. These algorithms are then placed into an architecture designed to leverage the advantages of each and ensure that they function in concert with one another. The resulting system is characterized by modularity and simplicity. As such, it is adaptable to the on-orbit phases of any future mission that Orion may attempt.

Structural systems pharmacology: a new frontier in discovering novel drug targets.

PubMed

Tan, Hepan; Ge, Xiaoxia; Xie, Lei

2013-08-01

The modern target-based drug discovery process, characterized by the one-drug-one-gene paradigm, has been of limited success. In contrast, phenotype-based screening produces thousands of active compounds but gives no hint as to what their molecular targets are or which ones merit further research. This presents a question: What is a suitable target for an efficient and safe drug? In this paper, we argue that target selection should take into account the proteome-wide energetic and kinetic landscape of drug-target interactions, as well as their cellular and organismal consequences. We propose a new paradigm of structural systems pharmacology to deconvolute the molecular targets of successful drugs as well as to identify druggable targets and their drug-like binders. Here we face two major challenges in structural systems pharmacology: How do we characterize and analyze the structural and energetic origins of drug-target interactions on a proteome scale? How do we correlate the dynamic molecular interactions to their in vivo activity? We will review recent advances in developing new computational tools for biophysics, bioinformatics, chemoinformatics, and systems biology related to the identification of genome-wide target profiles. We believe that the integration of these tools will realize structural systems pharmacology, enabling us to both efficiently develop effective therapeutics for complex diseases and combat drug resistance.

A Fast MEANSHIFT Algorithm-Based Target Tracking System

PubMed Central

Sun, Jian

2012-01-01

Tracking moving targets in complex scenes using an active video camera is a challenging task. Tracking accuracy and efficiency are two key yet generally incompatible aspects of a Target Tracking System (TTS). A compromise scheme will be studied in this paper. A fast mean-shift-based Target Tracking scheme is designed and realized, which is robust to partial occlusion and changes in object appearance. The physical simulation shows that the image signal processing speed is >50 frame/s. PMID:22969397

Advances in Bone-targeted Drug Delivery Systems for Neoadjuvant Chemotherapy for Osteosarcoma.

PubMed

Li, Cheng-Jun; Liu, Xiao-Zhou; Zhang, Lei; Chen, Long-Bang; Shi, Xin; Wu, Su-Jia; Zhao, Jian-Ning

2016-05-01

Targeted therapy for osteosarcoma includes organ, cell and molecular biological targeting; of these, organ targeting is the most mature. Bone-targeted drug delivery systems are used to concentrate chemotherapeutic drugs in bone tissues, thus potentially resolving the problem of reaching the desired foci and minimizing the toxicity and adverse effects of neoadjuvant chemotherapy. Some progress has been made in bone-targeted drug delivery systems for treatment of osteosarcoma; however, most are still at an experimental stage and there is a long transitional period to clinical application. Therefore, determining how to combine new, polymolecular and multi-pathway targets is an important research aspect of designing new bone-targeted drug delivery systems in future studies. The purpose of this article was to review the status of research on targeted therapy for osteosarcoma and to summarize the progress made thus far in developing bone-targeted drug delivery systems for neoadjuvant chemotherapy for osteosarcoma with the aim of providing new ideas for highly effective therapeutic protocols with low toxicity for patients with osteosarcoma. © 2016 Chinese Orthopaedic Association and John Wiley & Sons Australia, Ltd.

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.

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

Constraints in distortion-invariant target recognition system simulation

NASA Astrophysics Data System (ADS)

Iftekharuddin, Khan M.; Razzaque, Md A.

2000-11-01

Automatic target recognition (ATR) is a mature but active research area. In an earlier paper, we proposed a novel ATR approach for recognition of targets varying in fine details, rotation, and translation using a Learning Vector Quantization (LVQ) Neural Network (NN). The proposed approach performed segmentation of multiple objects and the identification of the objects using LVQNN. In this current paper, we extend the previous approach for recognition of targets varying in rotation, translation, scale, and combination of all three distortions. We obtain the analytical results of the system level design to show that the approach performs well with some constraints. The first constraint determines the size of the input images and input filters. The second constraint shows the limits on amount of rotation, translation, and scale of input objects. We present the simulation verification of the constraints using DARPA's Moving and Stationary Target Recognition (MSTAR) images with different depression and pose angles. The simulation results using MSTAR images verify the analytical constraints of the system level design.

Engineering of the Magnetized Target Fusion Propulsion System

NASA Technical Reports Server (NTRS)

Statham, G.; White, S.; Adams, R. B.; Thio, Y. C. F.; Santarius, J.; Alexander, R.; Fincher, S.; Polsgrove, T.; Chapman, J.; Philips, A.

2002-01-01

Engineering details are presented for a magnetized target fusion (MTF) propulsion system designed to support crewed missions to the outer solar system. Structural, thermal and radiation-management design details are presented. Propellant storage and supply options are also discussed and a propulsion system mass estimate is given.

Real-Time Target Motion Animation for Missile Warning System Testing

DTIC Science & Technology

2006-04-01

T. Perkins, R. Sundberg, J. Cordell, Z. Tun , and M. Owen, Real-time Target Motion Animation for Missile Warning System Testing, Proc. SPIE Vol 6208...Z39-18 Real-time target motion animation for missile warning system testing Timothy Perkins*a, Robert Sundberga, John Cordellb, Zaw Tunb, Mark

Radiological Protection and Nuclear Engineering Studies in Multi-MW Target Systems

NASA Astrophysics Data System (ADS)

Luis, Raul Fernandes

Several innovative projects involving nuclear technology have emerged around the world in recent years, for applications such as spallation neutron sources, accelerator-driven systems for the transmutation of nuclear waste and radioactive ion beam (RIB) production. While the available neutron Wuxes from nuclear reactors did not increase substantially in intensity over the past three decades, the intensities of neutron sources produced in spallation targets have increased steadily, and should continue to do so during the 21st century. Innovative projects like ESS, MYRRHA and EURISOL lie at the forefront of the ongoing pursuit for increasingly bright neutron sources; driven by proton beams with energies up to 2 GeV and intensities up to several mA, the construction of their proposed facilities involves complex Nuclear Technology and Radiological Protection design studies executed by multidisciplinary teams of scientists and engineers from diUerent branches of Science. The intense neutron Wuxes foreseen for those facilities can be used in several scientiVc research Velds, such as Nuclear Physics and Astrophysics, Medicine and Materials Science. In this work, the target systems of two facilitites for the production of RIBs using the Isotope Separation On-Line (ISOL) method were studied in detail: ISOLDE, operating at CERN since 1967, and EURISOL, the next-generation ISOL facility to be built in Europe. For the EURISOL multi-MW target station, a detailed study of Radiological Protection was carried out using the Monte Carlo code FLUKA. Simulations were done to assess neutron Wuences, Vssion rates, ambient dose equivalent rates during operation and after shutdown and the production of radioactive nuclei in the targets and surrounding materials. DiUerent materials were discussed for diUerent components of the target system, aiming at improving its neutronics performance while keeping the residual activities resulting from material activation as low as possible. The second

Opto-mechanical system design of test system for near-infrared and visible target

NASA Astrophysics Data System (ADS)

Wang, Chunyan; Zhu, Guodong; Wang, Yuchao

2014-12-01

Guidance precision is the key indexes of the guided weapon shooting. The factors of guidance precision including: information processing precision, control system accuracy, laser irradiation accuracy and so on. The laser irradiation precision is an important factor. This paper aimed at the demand of the precision test of laser irradiator，and developed the laser precision test system. The system consists of modified cassegrain system, the wide range CCD camera, tracking turntable and industrial PC, and makes visible light and near infrared target imaging at the same time with a Near IR camera. Through the analysis of the design results, when it exposures the target of 1000 meters that the system measurement precision is43mm, fully meet the needs of the laser precision test.

Collaborative Composing in High School String Chamber Music Ensembles

ERIC Educational Resources Information Center

Hopkins, Michael T.

2015-01-01

The purpose of this study was to examine collaborative composing in high school string chamber music ensembles. Research questions included the following: (a) How do high school string instrumentalists in chamber music ensembles use verbal and musical forms of communication to collaboratively compose a piece of music? (b) How do selected variables…

An intelligent re-shieldable targeting system for enhanced tumor accumulation.

PubMed

Hu, Zhenpeng; Ma, Jinlong; Fu, Fei; Cui, Chen; Li, Xiaomin; Wang, Xinyu; Wang, Wei; Wan, Yeda; Yuan, Zhi

2017-12-28

Programmed ligand targeting strategy promotes the blood circulation stability of nanoparticles by shielding the ligand. However, the irreversible shielding causes the deshielded nanoparticles to be easily recognized and cleared by the reticuloendothelial system (RES), impeding their further retention in the tumor. Here, we for the first time prove the superiority of the intelligent re-shieldable targeting system that is based on the pH-responsive self-assembly/disassembly of gold nanoparticles. The system can enhance the stability of gold nanoparticles in the blood circulation (2.6-fold at 24h), reduce uptake by the RES (35% lower) and improve tumor accumulation (41% higher by analysis of gold content in tumor) effectively compared with the conventional irreversible system. Furthermore, preliminary study indicates that the system could be applied as computed tomography contrast agent in tumor imaging. The in vivo validity of the intelligent re-shieldable targeting system provides inspiration for the design of nanomaterials for cancer diagnosis and treatment. Copyright © 2017. Published by Elsevier B.V.

Composability-Centered Convolutional Neural Network Pruning

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

Shen, Xipeng; Guan, Hui; Lim, Seung-Hwan

This work studies the composability of the building blocks ofstructural CNN models (e.g., GoogleLeNet and Residual Networks) in thecontext of network pruning. We empirically validate that a networkcomposed of pre-trained building blocks (e.g. residual blocks andInception modules) not only gives a better initial setting fortraining, but also allows the training process to converge at asignificantly higher accuracy in much less time. Based on thatinsight, we propose a {\\em composability-centered} design for CNNnetwork pruning. Experiments show that this new scheme shortens theconfiguration process in CNN network pruning by up to 186.8X forResNet-50 and up to 30.2X for Inception-V3, and meanwhile, themore » modelsit finds that meet the accuracy requirement are significantly morecompact than those found by default schemes.« less

Research-to-Resource: Programming Ensemble Literature Composed by Women

ERIC Educational Resources Information Center

Baker, Vicki; Biggers, Carter

2018-01-01

Research has indicated that a gender imbalance exists in the field of music composition. This inequitable distribution is clearly demonstrated in a state-mandated repertoire list in which women represent 3% of the wind band composers and 12% of the choral composers (all voicings). Ensemble directors are in a position to affect a change by…

Progress and Challenges in Developing Aptamer-Functionalized Targeted Drug Delivery Systems

PubMed Central

Jiang, Feng; Liu, Biao; Lu, Jun; Li, Fangfei; Li, Defang; Liang, Chao; Dang, Lei; Liu, Jin; He, Bing; Atik Badshah, Shaikh; Lu, Cheng; He, Xiaojuan; Guo, Baosheng; Zhang, Xiao-Bing; Tan, Weihong; Lu, Aiping; Zhang, Ge

2015-01-01

Aptamers, which can be screened via systematic evolution of ligands by exponential enrichment (SELEX), are superior ligands for molecular recognition due to their high selectivity and affinity. The interest in the use of aptamers as ligands for targeted drug delivery has been increasing due to their unique advantages. Based on their different compositions and preparation methods, aptamer-functionalized targeted drug delivery systems can be divided into two main categories: aptamer-small molecule conjugated systems and aptamer-nanomaterial conjugated systems. In this review, we not only summarize recent progress in aptamer selection and the application of aptamers in these targeted drug delivery systems but also discuss the advantages, challenges and new perspectives associated with these delivery systems. PMID:26473828

Progress and Challenges in Developing Aptamer-Functionalized Targeted Drug Delivery Systems.

PubMed

Jiang, Feng; Liu, Biao; Lu, Jun; Li, Fangfei; Li, Defang; Liang, Chao; Dang, Lei; Liu, Jin; He, Bing; Badshah, Shaikh Atik; Lu, Cheng; He, Xiaojuan; Guo, Baosheng; Zhang, Xiao-Bing; Tan, Weihong; Lu, Aiping; Zhang, Ge

2015-10-09

Aptamers, which can be screened via systematic evolution of ligands by exponential enrichment (SELEX), are superior ligands for molecular recognition due to their high selectivity and affinity. The interest in the use of aptamers as ligands for targeted drug delivery has been increasing due to their unique advantages. Based on their different compositions and preparation methods, aptamer-functionalized targeted drug delivery systems can be divided into two main categories: aptamer-small molecule conjugated systems and aptamer-nanomaterial conjugated systems. In this review, we not only summarize recent progress in aptamer selection and the application of aptamers in these targeted drug delivery systems but also discuss the advantages, challenges and new perspectives associated with these delivery systems.

Achromatic illumination system for small targets

DOEpatents

Sigler, Robert D.

1979-01-01

A pair of light beams is directed to provide illumination that is substantially uniform from all directions on a small target by a system comprising a pair of corrector windows, a pair of planar reflecting surfaces, a pair of paraboloidal mirrors and a reflecting mirror cavity. The components are arranged so that each of the beams passes through a corrector and is reflected from the planar surface to the paraboloidal mirror, from which it is focused through a hole in the planar surface to the interior of the cavity. The surface of the interior portion of the cavity is shaped to reflect the focused beam three times before the focused reflected beam strikes the target.

Trends, Vibes, and Energies: Building on Students' Strengths in Visual Composing

ERIC Educational Resources Information Center

Kurtyka, Faith

2015-01-01

This article examines the composing practices of two members of a social sorority who use visual images on the media of Tumblr and YouTube to teach potential new members about the kind of sorority experience they will have. From interviews with these composers and analyses of the artifacts they create, I distill three composing principles used to…

Future System Science Mission Targets for Heliophysics

NASA Technical Reports Server (NTRS)

Spann, James; Christensen, Andrew B.; SaintCyr, O. C.; Giles, Barbara I.; Posner, Arik

2009-01-01

Heliophysics is a discipline that investigates the science at work from the interface of Earth and space, to the core of the Sun, and to the outer edge of our solar system. This solar-interplanetary-planetary system is vast and inherently coupled on many spatial, temporal and energy scales. The Sun's explosive energy output creates complicated field and plasma structures that when coupled without terrestrial magnetized space, generates an extraordinary complex environment that has practical implications for humanity as we are becoming increasingly dependent on space-based assets. The immense volume of our cosmic neighborhood is the domain of heliophysics. Understanding this domain and the dominant mechanisms that control the transfer of mass and energy requires a system approach that addresses all aspects and regions of the system. The 2009 NASA Heliophysics Roadmap presents a science-focused strategic approach to advance the goal of heliophysics: why does the Sun vary; how do the Earth and heliosphere respond; and what are the impacts on humanity? This talk will present the top 6 prioritized science targets to understand the coupled heliophysics system as presented in the 2009 NASA Heliophysics Roadmap. An exposition of each science target and how it addresses outstanding questions in heliophysics will be discussed.

Engineering of the Magnetized Target Fusion Propulsion System

NASA Technical Reports Server (NTRS)

Statham, G.; White, S.; Adams, R. B.; Thio, Y. C. F.; Santarius, J.; Alexander, R.; Chapman, J.; Fincher, S.; Philips, A.; Polsgrove, T.

2003-01-01

Engineering details are presented for a magnetized target fusion (MTF) propulsion system designed to support crewed missions to the outer solar system. Basic operation of an MTF propulsion system is introduced. Structural, thermal, radiation-management and electrical design details are presented. The propellant storage and supply system design is also presented. A propulsion system mass estimate and associated performance figures are given. The advantages of helium-3 as a fusion fuel for an advanced MTF system are discussed.

Research on regional intrusion prevention and control system based on target tracking

NASA Astrophysics Data System (ADS)

Liu, Yanfei; Wang, Jieling; Jiang, Ke; He, Yanhui; Wu, Zhilin

2017-08-01

In view of the fact that China’s border is very long and the border prevention and control measures are single, we designed a regional intrusion prevention and control system which based on target-tracking. The system consists of four parts: solar panel, radar, electro-optical equipment, unmanned aerial vehicle and intelligent tracking platform. The solar panel provides independent power for the entire system. The radar detects the target in real time and realizes the high precision positioning of suspicious targets, then through the linkage of electro-optical equipment, it can achieve full-time automatic precise tracking of targets. When the target appears within the range of detection, the drone will be launched to continue the tracking. The system is mainly to realize the full time, full coverage, whole process integration and active realtime control of the border area.

Synchronization transition of a coupled system composed of neurons with coexisting behaviors near a Hopf bifurcation

NASA Astrophysics Data System (ADS)

Jia, Bing

2014-05-01

The coexistence of a resting condition and period-1 firing near a subcritical Hopf bifurcation point, lying between the monostable resting condition and period-1 firing, is often observed in neurons of the central nervous systems. Near such a bifurcation point in the Morris—Lecar (ML) model, the attraction domain of the resting condition decreases while that of the coexisting period-1 firing increases as the bifurcation parameter value increases. With the increase of the coupling strength, and parameter and initial value dependent synchronization transition processes from non-synchronization to compete synchronization are simulated in two coupled ML neurons with coexisting behaviors: one neuron chosen as the resting condition and the other the coexisting period-1 firing. The complete synchronization is either a resting condition or period-1 firing dependent on the initial values of period-1 firing when the bifurcation parameter value is small or middle and is period-1 firing when the parameter value is large. As the bifurcation parameter value increases, the probability of the initial values of a period-1 firing neuron that lead to complete synchronization of period-1 firing increases, while that leading to complete synchronization of the resting condition decreases. It shows that the attraction domain of a coexisting behavior is larger, the probability of initial values leading to complete synchronization of this behavior is higher. The bifurcations of the coupled system are investigated and discussed. The results reveal the complex dynamics of synchronization behaviors of the coupled system composed of neurons with the coexisting resting condition and period-1 firing, and are helpful to further identify the dynamics of the spatiotemporal behaviors of the central nervous system.

[Mental disease in two classical music composers].

PubMed

Rempelakos, L; Poulakou-Rebelakou, E; Ploumpidis, D

2012-01-01

A study οn two neglected classical music composers suffering a not syphilitic mental disease, is attempted here, syphilis of the central nervous system being frequent in that time. A brief overview on the psychiatric ailments of many great composers reveals suicide attempts and more or less severe depression following external events. The issue of a possible relationship between mental disease and (musical) creativity can be discussed, as mood swings and a certain tendency to melancholia are frequent features of a talented brain (a fact that can also be detected in their works). The first case presented here is Hans Rott from Austria, the beloved student of Anton Bruckner, who was considered to be at least equal to his famous classmate Gustav Mahler. The great expectations of his teacher and his friends suddenly came to an end, when he suffered a crisis of schizophrenia and was hospitalized in an insane asylum in Lower Austria. The tragic psychiatric adventure of the young musician lasted almost four years. He was diagnosed as a case of "hallucinatory insanity" and "persecution mania" by the medical staff, before dying of tuberculosis, aged only 26, and having completed only one symphony and several smaller works. His name came again on surface only a century after his death, when in 1989 his Symphony in E Major was discovered and premiered with great success, permitting to its creator a posthumous recognition, among Bruckner and Mahler. The second case of mental illness is that of the Armenian Komitas Vardapet. He was an orphan who grew up in theological schools and became a monk and later a priest, though he spent some years in Berlin in order to develop his musical skills. He is considered to be an authority of Armenian ecclesiastic music, introducing polyphony in the Armenian Church's music and collecting numerous traditional songs from all parts of Armenia. In 1915, during the Armenian genocide he was deported, tortured but finally saved, due to interventions

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.

Logical Structure and the Composing Process.

ERIC Educational Resources Information Center

Russow, Lilly-Marlene

An important aspect of the composing process is the element of organization--the coherent development of ideas and considerations of relevance. Most investigations of this aspect have focused on prewriting behavior or on "heuristics,""frames," or other approaches that presuppose that organization is something imposed from the…

Targeted systemic gene therapy and molecular imaging of cancer contribution of the vascular-targeted AAVP vector.

PubMed

Hajitou, Amin

2010-01-01

Gene therapy and molecular-genetic imaging have faced a major problem: the lack of an efficient systemic gene delivery vector. Unquestionably, eukaryotic viruses have been the vectors of choice for gene delivery to mammalian cells; however, they have had limited success in systemic gene therapy. This is mainly due to undesired uptake by the liver and reticuloendothelial system, broad tropism for mammalian cells causing toxicity, and their immunogenicity. On the other hand, prokaryotic viruses such as bacteriophage (phage) have no tropism for mammalian cells, but can be engineered to deliver genes to these cells. However, phage-based vectors have inherently been considered poor vectors for mammalian cells. We have reported a new generation of vascular-targeted systemic hybrid prokaryotic-eukaryotic vectors as chimeras between an adeno-associated virus (AAV) and targeted bacteriophage (termed AAV/phage; AAVP). In this hybrid vector, the targeted bacteriophage serves as a shuttle to deliver the AAV transgene cassette inserted in an intergenomic region of the phage DNA genome. As a proof of concept, we assessed the in vivo efficacy of vector in animal models of cancer by displaying on the phage capsid the cyclic Arg-Gly-Asp (RGD-4C) ligand that binds to alphav integrin receptors specifically expressed on the angiogenic blood vessels of tumors. The ligand-directed vector was able to specifically deliver imaging and therapeutic transgenes to tumors in mice, rats, and dogs while sparing the normal organs. This chapter reviews some gene transfer strategies and the potential of the vascular-targeted AAVP vector for enhancing the effectiveness of existing systemic gene delivery and genetic-imaging technologies. Copyright (c) 2010 Elsevier Inc. All rights reserved.

Endocannabinoid system: potential novel targets for treatment of schizophrenia.

PubMed

Saito, Atsushi; Ballinger, Michael D L; Pletnikov, Mikhail V; Wong, Dean F; Kamiya, Atsushi

2013-05-01

Accumulating epidemiological evidences suggest that cannabis use during adolescence is a potential environmental risk for the development of psychosis, including schizophrenia. Consistently, clinical and preclinical studies, using pharmacological approaches and genetically engineered animals to target endocannabinoid signaling, reveal the multiple varieties of endocannabinoid system-mediated human and animal behaviors, including cognition and emotion. Recently, there has been substantial progress in understanding the molecular mechanisms of the endocannabinoid system for synaptic communications in the central nervous system. Furthermore, the impact of endocannabinoid signaling on diverse cellular processes during brain development has emerged. Thus, although schizophrenia has etiological complexities, including genetic heterogeneities and multiple environmental factors, it now becomes crucial to explore molecular pathways of convergence of genetic risk factors and endocannabinoid signaling, which may provide us with clues to find novel targets for therapeutic intervention. In this review, epidemiological, clinical, and pathological evidences on the role of the endocannabinoid system in the pathophysiologies of schizophrenia will be presented. We will also make a brief overview of the recent progress in understanding molecular mechanisms of the endocannabinoid system for brain development and function, with particular focus on cannabinoid receptor type 1 (CB1R)-mediated cascade, the most well-characterized cannabinoid receptor. Lastly, we will discuss the potential of the endocannabinoid system in finding novel therapeutic targets for prevention and treatment of schizophrenia. Copyright © 2012 Elsevier Inc. All rights reserved.

Emerging drugs which target the renin-angiotensin-aldosterone system.

PubMed

Steckelings, Ulrike Muscha; Paulis, Ludovit; Unger, Thomas; Bader, Michael

2011-12-01

The renin-angiotensin-aldosterone system (RAAS) is already the most important target for drugs in the cardiovascular system. However, still new developments are underway to interfere with the system on different levels. The novel strategies to interfere with RAAS aim to reduce the synthesis of the two major RAAS effector hormones, angiotensin (Ang) II and aldosterone, or interfere with their receptors, AT1 and mineralocorticoid receptor, respectively. Moreover, novel targets have been identified in RAAS, such as the (pro)renin receptor, and molecules, which counteract the classical actions of Ang II and are therefore beneficial in cardiovascular diseases. These include the AT2 receptor and the ACE2/Ang-(1-7)/Mas axis. The search for drugs activating these tissue-protective arms of RAAS is therefore the most innovative field in RAAS pharmacology. Most of the novel pharmacological strategies to inhibit the classical RAAS need to prove their superiority above the existing treatment in clinical trials and then have to compete against these now quite cheap drugs in a competitive market. The newly discovered targets have functions beyond the cardiovascular system opening up novel therapeutic areas for drugs interfering with RAAS components.

Soil CO2 flux in alley-cropping systems composed of black locust and poplar trees, Germany

NASA Astrophysics Data System (ADS)

Medinski, Tetiana; Freese, Dirk; Boehm, Christian

2013-04-01

The understanding of soil carbon dynamics after establishment of alley-cropping systems is crucial for mitigation of greenhouse CO2 gas. This study investigates soil CO2 fluxes in alley-cropping systems composed of strips of black locust (Robinia pseudoacacia L.) and poplar (Max 1) trees and adjacent to them crop strips (Lupinus). Soil CO2 flux was measured monthly over a period from March to November 2012, using a LI-COR LI-8100A automated device. Concurrently with CO2 flux measurements, soil and air temperature and soil moisture were recorded within 10 cm of each collar. Soil samples were collected nearby each soil collar for microbial C and hot water-extractable C analyses. At each study plot, root biomass was measured to a depth of 15 cm. In all vegetation types, soil CO2 flux increased from May to August, showing a significant positive correlation with air and soil temperature, which can be a reflection of increase in photosynthesis over the warm summer months. CO2 flux was the highest in poplar followed by black locust and lupines. The relationships between CO2 flux, microbial biomass and hot water-extractable carbon were not straightforward. Among the measured parameters, root density was found to be the main factor to explain the higher CO2 flux in tree strips.

Multiple operating system rotation environment moving target defense

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

Evans, Nathaniel; Thompson, Michael

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

System transfer modelling for automatic target recognizer evaluations

NASA Astrophysics Data System (ADS)

Clark, Lloyd G.

1991-11-01

Image processing to accomplish automatic recognition of military vehicles has promised increased weapons systems effectiveness and reduced timelines for a number of Department of Defense missions. Automatic Target Recognizers (ATR) are often claimed to be able to recognize many different ground vehicles as possible targets in military air-to- surface targeting applications. The targeting scenario conditions include different vehicle poses and histories as well as a variety of imaging geometries, intervening atmospheres, and background environments. Testing these ATR subsystems in most cases has been limited to a handful of the scenario conditions of interest, as is represented by imagery collected with the desired imaging sensor. The question naturally arises as to how robust the performance of the ATR is for all scenario conditions of interest, not just for the set of imagery upon which an algorithm was trained.

Rethinking Joseph Janangelo's "Joseph Cornell and the Artistry of Composing Persuasive Hypertexts"

ERIC Educational Resources Information Center

College Composition and Communication, 2007

2007-01-01

This article presents several excerpts from an article written by Joseph Janangelo titled "Joseph Cornell and the Artistry of Composing Persuasive Hypertexts." In his article, Janangelo suggested that Cornell's work and ideas about composing model intelligent ways to composing persuasive nonsequential text. Janangelo also wondered if the use of…

The Contexts of Composing: A Dynamic Scene with Movable Centers.

ERIC Educational Resources Information Center

Wiley, Mark L.

An examination of the transformations that the concept of genius undergoes when viewed through the apparently incommensurable expressivistic and social views of composing helps to reconcile phenomenologically objective descriptions of composing with value-laden descriptions of the self in the act of writing. When the description of composition is…

A Novel Aqueous Micellar Two-Phase System Composed of Surfactant and Sorbitol for Purification of Pectinase Enzyme from Psidium guajava and Recycling Phase Components

PubMed Central

Murshid, Fara Syazana; Manap, Mohd Yazid; Hussin, Muhaini

2015-01-01

A novel aqueous two-phase system composed of a surfactant and sorbitol was employed for the first time to purify pectinase from Psidium guajava. The influences of different parameters, including the type and concentration of the surfactant and the concentration and composition of the surfactant/sorbitol ratio, on the partitioning behavior and recovery of pectinase were investigated. Moreover, the effects of system pH and the crude load on purification fold and the yield of purified pectinase were studied. The experimental results indicated that the pectinase was partitioned into surfactant-rich top phase, and the impurities were partitioned into the sorbitol-rich bottom phase with the novel method involving an ATPS composed of 26% (w/w) Triton X-100 and 23% (w/w) sorbitol at 54.2% of the TLL crude load of 20% (w/w) at pH 6.0. The enzyme was successfully recovered by this method with a high purification factor of 15.2 and a yield of 98.3%, whereas the phase components were also recovered and recycled at rates above 96%. This study demonstrated that this novel ATPS method can be used as an efficient and economical alternative to the traditional ATPS for the purification and recovery of the valuable enzyme. PMID:25756051

A novel aqueous micellar two-phase system composed of surfactant and sorbitol for purification of pectinase enzyme from Psidium guajava and recycling phase components.

PubMed

Amid, Mehrnoush; Murshid, Fara Syazana; Manap, Mohd Yazid; Hussin, Muhaini

2015-01-01

A novel aqueous two-phase system composed of a surfactant and sorbitol was employed for the first time to purify pectinase from Psidium guajava. The influences of different parameters, including the type and concentration of the surfactant and the concentration and composition of the surfactant/sorbitol ratio, on the partitioning behavior and recovery of pectinase were investigated. Moreover, the effects of system pH and the crude load on purification fold and the yield of purified pectinase were studied. The experimental results indicated that the pectinase was partitioned into surfactant-rich top phase, and the impurities were partitioned into the sorbitol-rich bottom phase with the novel method involving an ATPS composed of 26% (w/w) Triton X-100 and 23% (w/w) sorbitol at 54.2% of the TLL crude load of 20% (w/w) at pH 6.0. The enzyme was successfully recovered by this method with a high purification factor of 15.2 and a yield of 98.3%, whereas the phase components were also recovered and recycled at rates above 96%. This study demonstrated that this novel ATPS method can be used as an efficient and economical alternative to the traditional ATPS for the purification and recovery of the valuable enzyme.

A Secure and Privacy-Preserving Targeted Ad-System

NASA Astrophysics Data System (ADS)

Androulaki, Elli; Bellovin, Steven M.

Thanks to its low product-promotion cost and its efficiency, targeted online advertising has become very popular. Unfortunately, being profile-based, online advertising methods violate consumers' privacy, which has engendered resistance to the ads. However, protecting privacy through anonymity seems to encourage click-fraud. In this paper, we define consumer's privacy and present a privacy-preserving, targeted ad system (PPOAd) which is resistant towards click fraud. Our scheme is structured to provide financial incentives to all entities involved.

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 Composer's Program Note for Newly Written Classical Music: Content and Intentions.

PubMed

Blom, Diana M; Bennett, Dawn; Stevenson, Ian

2016-01-01

In concerts of western classical music the provision of a program note is a widespread practice dating back to the 18th century and still commonly in use. Program notes tend to inform listeners and performers about historical context, composer biographical details, and compositional thinking. However, the scant program note research conducted to date reveals that program notes may not foster understanding or enhance listener enjoyment as previously assumed. In the case of canonic works, performers and listeners may already be familiar with much of the program note information. This is not so in the case of newly composed works, which formed the basis of the exploratory study reported here. This article reports the views of 17 living contemporary composers on their writing of program notes for their own works. In particular, the study sought to understand the intended recipient, role and the content of composer-written program notes. Participating composers identified three main roles for their program notes: to shape a performer's interpretation of the work; to guide, engage or direct the listener and/or performer; and as collaborative mode of communication between the composer, performer, and listener. For some composers, this collaboration was intended to result in "performative listening" in which listeners were actively engaged in bringing each composition to life. This was also described as a form of empathy that results in the co-construction of the musical experience. Overall, composers avoided giving too much personal information and they provided performers with more structural information. However, composers did not agree on whether the same information should be provided to both performers and listeners. Composers' responses problematize the view of a program note as a simple statement from writer to recipient, indicating instead a more complex set of relations at play between composer, performer, listener, and the work itself. These relations are

16 CFR 300.26 - Pile fabrics and products composed thereof.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 16 Commercial Practices 1 2010-01-01 2010-01-01 false Pile fabrics and products composed thereof... CONGRESS RULES AND REGULATIONS UNDER THE WOOL PRODUCTS LABELING ACT OF 1939 Labeling § 300.26 Pile fabrics and products composed thereof. The fiber content of pile fabrics or products made thereof may be...

Composing in Public: The Ambient Audiences of a Writing Lab

ERIC Educational Resources Information Center

Hall, Matthew

2015-01-01

Although scholars have investigated the ways youths individually enact composing practices and the impact of audience on these practices, this study examines the impact of an audience physically present while composing in a shared, public space--an ambient audience. Blurring the line between traditional notions of audience and collaborator through…

Remote liquid target loading system for LANL two-stage gas gun

NASA Astrophysics Data System (ADS)

Gibson, L. L.; Bartram, B.; Dattelbaum, D. M.; Sheffield, S. A.; Stahl, D. B.

2009-06-01

A Remote Liquid Loading System (RLLS) was designed to load high hazard liquid materials into targets for gas-gun driven impact experiments. These high hazard liquids tend to react with confining materials in a short period of time, degrading target assemblies and potentially building up pressure through the evolution of gas in the reactions. Therefore, the ability to load a gas gun target in place immediately prior to firing the gun, provides the most stable and reliable target fielding approach. We present the design and evaluation of a RLLS built for the LANL two-stage gas gun. Targets for the gun are made of PMMA and assembled to form a liquid containment cell with a volume of approximately 25 cc. The compatibility of materials was a major consideration in the design of the system, particularly for its use with highly concentrated hydrogen peroxide. Teflon and 304-stainless steel were the two most compatible materials with the materials to be tested. Teflon valves and tubing, as well as stainless steel tubing, were used to handle the liquid, along with a stainless steel reservoir. Preliminary testing was done to ensure proper flow rate and safety. The system has been used to successfully load 97.5 percent hydrogen peroxide into a target cell just prior to a successful multiple magnetic gauge experiment. TV cameras on the target verified the bubble-free filling operation.

When Computer Writers Compose by Hand.

ERIC Educational Resources Information Center

Collier, Richard; Werier, Clifford

1995-01-01

Reviews videotapes of three professional writers composing several essays from start to finish, both by hand and by computer. Discusses similarities and differences among the completed essays. Finds that writing appears to be governed by deep cognitive models that are little influenced by the mode of text production or by the writer's preference…

Fe3O4 Nanoparticles in Targeted Drug/Gene Delivery Systems

PubMed Central

Shen, Lazhen; Li, Bei; Qiao, Yongsheng

2018-01-01

Fe3O4 nanoparticles (NPs), the most traditional magnetic nanoparticles, have received a great deal of attention in the biomedical field, especially for targeted drug/gene delivery systems, due to their outstanding magnetism, biocompatibility, lower toxicity, biodegradability, and other features. Naked Fe3O4 NPs are easy to aggregate and oxidize, and thus are often made with various coatings to realize superior properties for targeted drug/gene delivery. In this review, we first list the three commonly utilized synthesis methods of Fe3O4 NPs, and their advantages and disadvantages. In the second part, we describe coating materials that exhibit noticeable features that allow functionalization of Fe3O4 NPs and summarize their methods of drug targeting/gene delivery. Then our efforts will be devoted to the research status and progress of several different functionalized Fe3O4 NP delivery systems loaded with chemotherapeutic agents, and we present targeted gene transitive carriers in detail. In the following section, we illuminate the most effective treatment systems of the combined drug and gene therapy. Finally, we propose opportunities and challenges of the clinical transformation of Fe3O4 NPs targeting drug/gene delivery systems. PMID:29473914

Performance Measurement and Target-Setting in California's Safety Net Health Systems.

PubMed

Hemmat, Shirin; Schillinger, Dean; Lyles, Courtney; Ackerman, Sara; Gourley, Gato; Vittinghoff, Eric; Handley, Margaret; Sarkar, Urmimala

Health policies encourage implementing quality measurement with performance targets. The 2010-2015 California Medicaid waiver mandated quality measurement and reporting. In 2013, California safety net hospitals participating in the waiver set a voluntary performance target (the 90th percentile for Medicare preferred provider organization plans) for mammography screening and cholesterol control in diabetes. They did not reach the target, and the difference-in-differences analysis suggested that there was no difference for mammography ( P = .39) and low-density lipoprotein control ( P = .11) performance compared to measures for which no statewide quality improvement initiative existed. California's Medicaid waiver was associated with improved performance on a number of metrics, but this performance was not attributable to target setting on specific health conditions. Performance may have improved because of secular trends or systems improvements related to waiver funding. Relying on condition-specific targets to measure performance may underestimate improvements and disadvantage certain health systems. Achieving ambitious targets likely requires sustained fiscal, management, and workforce investments.

Polarization effects on hard target calibration of lidar systems

NASA Technical Reports Server (NTRS)

Kavaya, Michael J.

1987-01-01

The theory of hard target calibration of lidar backscatter data, including laboratory measurements of the pertinent target reflectance parameters, is extended to include the effects of polarization of the transmitted and received laser radiation. The bidirectional reflectance-distribution function model of reflectance is expanded to a 4 x 4 matrix allowing Mueller matrix and Stokes vector calculus to be employed. Target reflectance parameters for calibration of lidar backscatter data are derived for various lidar system polarization configurations from integrating sphere and monostatic reflectometer measurements. It is found that correct modeling of polarization effects is mandatory for accurate calibration of hard target reflectance parameters and, therefore, for accurate calibration of lidar backscatter data.

The Links between Handwriting and Composing for Y6 Children

ERIC Educational Resources Information Center

Medwell, Jane; Strand, Steve; Wray, David

2009-01-01

Although handwriting is often considered a matter of presentation, a substantial body of international research suggests that the role of handwriting in children's composing has been neglected. Automaticity in handwriting is now seen as of key importance in composing but this proposition is relatively untested in the UK and the assumption has been…

Multi-Draft Composing: An Iterative Model for Academic Argument Writing

ERIC Educational Resources Information Center

Eckstein, Grant; Chariton, Jessica; McCollum, Robb Mark

2011-01-01

Post-secondary writing teachers in composition and English as a second language (ESL) writing programs are likely familiar with multi-draft composing. Both composition and ESL writing programs share nearly identical multi-draft models despite the very unique and different cultures of each group. We argue that multi-draft composing as it is…

Coding the Composing Process: A Guide for Teachers and Researchers.

ERIC Educational Resources Information Center

Perl, Sondra

Designed for teachers and researchers interested in the study of the composing process, this guide introduces a method of analysis that can be applied to data from a range of different cases. Specifically, the guide offers a simple, direct coding scheme for describing the movements occurring during composing that involves four procedures: teaching…

Resolution verification targets for airborne and spaceborne imaging systems at the Stennis Space Center

NASA Astrophysics Data System (ADS)

McKellip, Rodney; Yuan, Ding; Graham, William; Holland, Donald E.; Stone, David; Walser, William E.; Mao, Chengye

1997-06-01

The number of available spaceborne and airborne systems will dramatically increase over the next few years. A common systematic approach toward verification of these systems will become important for comparing the systems' operational performance. The Commercial Remote Sensing Program at the John C. Stennis Space Center (SSC) in Mississippi has developed design requirements for a remote sensing verification target range to provide a means to evaluate spatial, spectral, and radiometric performance of optical digital remote sensing systems. The verification target range consists of spatial, spectral, and radiometric targets painted on a 150- by 150-meter concrete pad located at SSC. The design criteria for this target range are based upon work over a smaller, prototypical target range at SSC during 1996. This paper outlines the purpose and design of the verification target range based upon an understanding of the systems to be evaluated as well as data analysis results from the prototypical target range.

Ion implantation system and process for ultrasensitive determination of target isotopes

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

Farmer, III, Orville T.; Liezers, Martin

2016-09-13

A system and process are disclosed for ultrasensitive determination of target isotopes of analytical interest in a sample. Target isotopes may be implanted in an implant area on a high-purity substrate to pre-concentrate the target isotopes free of contaminants. A known quantity of a tracer isotope may also be implanted. Target isotopes and tracer isotopes may be determined in a mass spectrometer. The present invention provides ultrasensitive determination of target isotopes in the sample.

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

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.

The Composing Processes of Mature Adults.

ERIC Educational Resources Information Center

Crabbe, Katharyn

The study examined 41 students (24 male, 17 female) in a beginning writing course for adults. Data were collected by (1) taping four workshop sessions in which all students participated in small groups, (2) interviewing all the students, and (3) observing four students writing in the classroom. The adult writers composed in two models: the…

Target-Tracking Camera for a Metrology System

NASA Technical Reports Server (NTRS)

Liebe, Carl; Bartman, Randall; Chapsky, Jacob; Abramovici, Alexander; Brown, David

2009-01-01

An analog electronic camera that is part of a metrology system measures the varying direction to a light-emitting diode that serves as a bright point target. In the original application for which the camera was developed, the metrological system is used to determine the varying relative positions of radiating elements of an airborne synthetic aperture-radar (SAR) antenna as the airplane flexes during flight; precise knowledge of the relative positions as a function of time is needed for processing SAR readings. It has been common metrology system practice to measure the varying direction to a bright target by use of an electronic camera of the charge-coupled-device or active-pixel-sensor type. A major disadvantage of this practice arises from the necessity of reading out and digitizing the outputs from a large number of pixels and processing the resulting digital values in a computer to determine the centroid of a target: Because of the time taken by the readout, digitization, and computation, the update rate is limited to tens of hertz. In contrast, the analog nature of the present camera makes it possible to achieve an update rate of hundreds of hertz, and no computer is needed to determine the centroid. The camera is based on a position-sensitive detector (PSD), which is a rectangular photodiode with output contacts at opposite ends. PSDs are usually used in triangulation for measuring small distances. PSDs are manufactured in both one- and two-dimensional versions. Because it is very difficult to calibrate two-dimensional PSDs accurately, the focal-plane sensors used in this camera are two orthogonally mounted one-dimensional PSDs.

Activity of Nanobins Targeted to the Urokinase Plasminogen Activator System

NASA Astrophysics Data System (ADS)

Hankins, Patrick Leon

While innovations in nanotechnology have resulted in numerous medical advancements for the treatment of cancer, there remains an urgent unmet need for safe and efficient molecular platforms that facilitate the delivery of potent therapeutics to solid tumors. Nanoscale formulations help to overcome the poor bioavailability and systemic organ toxicity associated with many small molecule drugs. Of these nanoparticle drug delivery systems, the greatest clinical successes to date have employed simple nanoscale lipid bilayer assemblies which encase large payloads of chemotherapeutic. While the nanobin platform we have developed has seen initial success through the passive accumulation into tumors, actively targeting nanobins to tumor specific antigens has the potential to increase the therapeutic index of these nanoparticle drugs. We have identified the urokinase plasminogen activator (uPA) and its cell surface bound receptor (uPAR) as ideal targets for drug delivery due to their selective overexpression in metastatic cancers and their important role in tumor progression. From a panel of monoclonal antibodies targeted to uPA and uPAR, we have selected ATN291 and ATN658 as lead candidates for nanobin targeting based on their tumor cell binding and ability to be internalized by cells. A novel method of conjugating antibodies to liposomes was developed for our nanobin platform that preserves the high binding affinity and specificity of these antibodies. We evaluated these uPA- and uPAR-targeted nanobins in several xenograft tumor models and found that they were well-tolerated over a wide range of doses and demonstrated significantly increased antitumor efficacy over untargeted nanobins in multiple tumor types. Preliminary studies suggest that uPA-targeted nanobins are readily internalized by tumor cells, and we believe this is the mechanism for their increased antitumor effect. A method for radiolabeling nanobins with gallium-67 was developed, and preliminary SPECT

Size-tunable drug-delivery capsules composed of a magnetic nanoshell.

PubMed

Fuchigami, Teruaki; Kitamoto, Yoshitaka; Namiki, Yoshihisa

2012-01-01

Nano-sized FePt capsules with two types of ultrathin shell were fabricated using a template method for use in a nano-scale drug delivery system. One capsule was composed of an inorganic-organic hybrid shell of a water-soluble polymer and FePt nanoparticles, and the other capsule was composed of a network of fused FePt nanoparticles. We demonstrated that FePt nanoparticles selectively accumulated on the polymer molecules adsorbed on the template silica particles, and investigated the morphologies of the particle accumulation by changing the concentration of the polymer solution with which the template particles were treated. Capsular size was reduced from 340 to less than 90 nm by changing the size of the silica template particles, and the shell thickness was controlled by changing the amount of FePt nanoparticles adsorbed on the template particles. The hybrid shell was maintained by the connection of FePt nanoparticles and polymer molecules, and the shell thickness was 10 nm at the maximum. The FePt network shell was fabricated by hydrothermal treatment of the FePt/polymer-modified silica composite particles. The FePt network shell was produced from only the FePt alloy, and the shell thickness was 3 nm. Water-soluble anti-cancer drugs could be loaded into the hollow space of FePt network capsules, and lipid-coated FePt network capsules loaded with anti-cancer drugs showed cellular toxicity. The nano-sized capsular structure and the ultrathin shell suggest applicability as a drug carrier in magnetically guided drug delivery systems.

Size-tunable drug-delivery capsules composed of a magnetic nanoshell

PubMed Central

Fuchigami, Teruaki; Kitamoto, Yoshitaka; Namiki, Yoshihisa

2012-01-01

Nano-sized FePt capsules with two types of ultrathin shell were fabricated using a template method for use in a nano-scale drug delivery system. One capsule was composed of an inorganic-organic hybrid shell of a water-soluble polymer and FePt nanoparticles, and the other capsule was composed of a network of fused FePt nanoparticles. We demonstrated that FePt nanoparticles selectively accumulated on the polymer molecules adsorbed on the template silica particles, and investigated the morphologies of the particle accumulation by changing the concentration of the polymer solution with which the template particles were treated. Capsular size was reduced from 340 to less than 90 nm by changing the size of the silica template particles, and the shell thickness was controlled by changing the amount of FePt nanoparticles adsorbed on the template particles. The hybrid shell was maintained by the connection of FePt nanoparticles and polymer molecules, and the shell thickness was 10 nm at the maximum. The FePt network shell was fabricated by hydrothermal treatment of the FePt/polymer-modified silica composite particles. The FePt network shell was produced from only the FePt alloy, and the shell thickness was 3 nm. Water-soluble anti-cancer drugs could be loaded into the hollow space of FePt network capsules, and lipid-coated FePt network capsules loaded with anti-cancer drugs showed cellular toxicity. The nano-sized capsular structure and the ultrathin shell suggest applicability as a drug carrier in magnetically guided drug delivery systems. PMID:23507895

Targeted mutagenesis in Zea mays using TALENs and the CRISPR/Cas system.

PubMed

Liang, Zhen; Zhang, Kang; Chen, Kunling; Gao, Caixia

2014-02-20

Transcription activator-like effector nucleases (TALENs) and clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated (Cas) systems have emerged as powerful tools for genome editing in a variety of species. Here, we report, for the first time, targeted mutagenesis in Zea mays using TALENs and the CRISPR/Cas system. We designed five TALENs targeting 4 genes, namely ZmPDS, ZmIPK1A, ZmIPK, ZmMRP4, and obtained targeting efficiencies of up to 23.1% in protoplasts, and about 13.3% to 39.1% of the transgenic plants were somatic mutations. Also, we constructed two gRNAs targeting the ZmIPK gene in maize protoplasts, at frequencies of 16.4% and 19.1%, respectively. In addition, the CRISPR/Cas system induced targeted mutations in Z. mays protoplasts with efficiencies (13.1%) similar to those obtained with TALENs (9.1%). Our results show that both TALENs and the CRISPR/Cas system can be used for genome modification in maize. Copyright © 2013. Published by Elsevier Ltd.

Mitochondrion: A Promising Target for Nanoparticle-Based Vaccine Delivery Systems

PubMed Central

Wen, Ru; Umeano, Afoma C.; Francis, Lily; Sharma, Nivita; Tundup, Smanla; Dhar, Shanta

2016-01-01

Vaccination is one of the most popular technologies in disease prevention and eradication. It is promising to improve immunization efficiency by using vectors and/or adjuvant delivery systems. Nanoparticle (NP)-based delivery systems have attracted increasing interest due to enhancement of antigen uptake via prevention of vaccine degradation in the biological environment and the intrinsic immune-stimulatory properties of the materials. Mitochondria play paramount roles in cell life and death and are promising targets for vaccine delivery systems to effectively induce immune responses. In this review, we focus on NPs-based delivery systems with surfaces that can be manipulated by using mitochondria targeting moieties for intervention in health and disease. PMID:27258316

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.

Functional Requirements of a Target Description System for Vulnerability Analysis

DTIC Science & Technology

1979-11-01

called GIFT .1,2 Together the COMGEOM description model and GIFT codes make up the BRL’s target description system. The significance of a target...and modifying target descriptions are described. 1 Lawrence W. Bain, Jr. and Mathew J. Reisinger, "The GIFT Code User Manual; Volume 1...34The GIFT Code User Manual; Volume II, The Output Options," unpublished draft of BRL report. II. UNDERLYING PHILOSOPHY The BRL has a computer

Combined protein construct and synthetic gene engineering for heterologous protein expression and crystallization using Gene Composer

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

Raymond, Amy; Lovell, Scott; Lorimer, Don

2009-12-01

With the goal of improving yield and success rates of heterologous protein production for structural studies we have developed the database and algorithm software package Gene Composer. This freely available electronic tool facilitates the information-rich design of protein constructs and their engineered synthetic gene sequences, as detailed in the accompanying manuscript. In this report, we compare heterologous protein expression levels from native sequences to that of codon engineered synthetic gene constructs designed by Gene Composer. A test set of proteins including a human kinase (P38{alpha}), viral polymerase (HCV NS5B), and bacterial structural protein (FtsZ) were expressed in both E. colimore » and a cell-free wheat germ translation system. We also compare the protein expression levels in E. coli for a set of 11 different proteins with greatly varied G:C content and codon bias. The results consistently demonstrate that protein yields from codon engineered Gene Composer designs are as good as or better than those achieved from the synonymous native genes. Moreover, structure guided N- and C-terminal deletion constructs designed with the aid of Gene Composer can lead to greater success in gene to structure work as exemplified by the X-ray crystallographic structure determination of FtsZ from Bacillus subtilis. These results validate the Gene Composer algorithms, and suggest that using a combination of synthetic gene and protein construct engineering tools can improve the economics of gene to structure research.« less

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.

System considerations for detection and tracking of small targets using passive sensors

NASA Astrophysics Data System (ADS)

DeBell, David A.

1991-08-01

Passive sensors provide only a few discriminants to assist in threat assessment of small targets. Tracking of the small targets provides additional discriminants. This paper discusses the system considerations for tracking small targets using passive sensors, in particular EO sensors. Tracking helps establish good versus bad detections. Discussed are the requirements to be placed on the sensor system's accuracy, with respect to knowledge of the sightline direction. The detection of weak targets sets a requirement for two levels of tracking in order to reduce processor throughput. A system characteristic is the need to track all detections. For low thresholds, this can mean a heavy track burden. Therefore, thresholds must be adaptive in order not to saturate the processors. Second-level tracks must develop a range estimate in order to assess threat. Sensor platform maneuvers are required if the targets are moving. The need for accurate pointing, good stability, and a good update rate will be shown quantitatively, relating to track accuracy and track association.

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-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

Receptor-Mediated Drug Delivery Systems Targeting to Glioma

PubMed Central

Wang, Shanshan; Meng, Ying; Li, Chengyi; Qian, Min; Huang, Rongqin

2015-01-01

Glioma has been considered to be the most frequent primary tumor within the central nervous system (CNS). The complexity of glioma, especially the existence of the blood-brain barrier (BBB), makes the survival and prognosis of glioma remain poor even after a standard treatment based on surgery, radiotherapy, and chemotherapy. This provides a rationale for the development of some novel therapeutic strategies. Among them, receptor-mediated drug delivery is a specific pattern taking advantage of differential expression of receptors between tumors and normal tissues. The strategy can actively transport drugs, such as small molecular drugs, gene medicines, and therapeutic proteins to glioma while minimizing adverse reactions. This review will summarize recent progress on receptor-mediated drug delivery systems targeting to glioma, and conclude the challenges and prospects of receptor-mediated glioma-targeted therapy for future applications. PMID:28344260

Beacon Collision Avoidance System (BCAS) Alternative Concepts for Determining Target Positions

DOT National Transportation Integrated Search

1978-09-01

The (Litchford) Beacon-based Collision Avoidance System concept requires the computation of target range and bearing relative to the BCAS aircraft. Techniques for determining target range and bearing under four different assumptions about the ground ...

Colon-targeted oral drug delivery systems: design trends and approaches.

PubMed

Amidon, Seth; Brown, Jack E; Dave, Vivek S

2015-08-01

Colon-specific drug delivery systems (CDDS) are desirable for the treatment of a range of local diseases such as ulcerative colitis, Crohn's disease, irritable bowel syndrome, chronic pancreatitis, and colonic cancer. In addition, the colon can be a potential site for the systemic absorption of several drugs to treat non-colonic conditions. Drugs such as proteins and peptides that are known to degrade in the extreme gastric pH, if delivered to the colon intact, can be systemically absorbed by colonic mucosa. In order to achieve effective therapeutic outcomes, it is imperative that the designed delivery system specifically targets the drugs into the colon. Several formulation approaches have been explored in the development colon-targeted drug delivery systems. These approaches involve the use of formulation components that interact with one or more aspects of gastrointestinal (GI) physiology, such as the difference in the pH along the GI tract, the presence of colonic microflora, and enzymes, to achieve colon targeting. This article highlights the factors influencing colon-specific drug delivery and colonic bioavailability, and the limitations associated with CDDS. Further, the review provides a systematic discussion of various conventional, as well as relatively newer formulation approaches/technologies currently being utilized for the development of CDDS.

Polymeric nanoparticles for targeted drug delivery system for cancer therapy.

PubMed

Masood, Farha

2016-03-01

A targeted delivery system based on the polymeric nanoparticles as a drug carrier represents a marvelous avenue for cancer therapy. The pivotal characteristics of this system include biodegradability, biocompatibility, non-toxicity, prolonged circulation and a wide payload spectrum of a therapeutic agent. Other outstanding features are their distinctive size and shape properties for tissue penetration via an active and passive targeting, specific cellular/subcellular trafficking pathways and facile control of cargo release by sophisticated material engineering. In this review, the current implications of encapsulation of anticancer agents within polyhydroxyalkanoates, poly-(lactic-co-glycolic acid) and cyclodextrin based nanoparticles to precisely target the tumor site, i.e., cell, tissue and organ are highlighted. Furthermore, the promising perspectives in this emerging field are discussed. Copyright © 2015 Elsevier B.V. All rights reserved.

Systems biology-embedded target validation: improving efficacy in drug discovery.

PubMed

Vandamme, Drieke; Minke, Benedikt A; Fitzmaurice, William; Kholodenko, Boris N; Kolch, Walter

2014-01-01

The pharmaceutical industry is faced with a range of challenges with the ever-escalating costs of drug development and a drying out of drug pipelines. By harnessing advances in -omics technologies and moving away from the standard, reductionist model of drug discovery, there is significant potential to reduce costs and improve efficacy. Embedding systems biology approaches in drug discovery, which seek to investigate underlying molecular mechanisms of potential drug targets in a network context, will reduce attrition rates by earlier target validation and the introduction of novel targets into the currently stagnant market. Systems biology approaches also have the potential to assist in the design of multidrug treatments and repositioning of existing drugs, while stratifying patients to give a greater personalization of medical treatment. © 2013 Wiley Periodicals, Inc.

Enhancement of tracking performance in electro-optical system based on servo control algorithm

NASA Astrophysics Data System (ADS)

Choi, WooJin; Kim, SungSu; Jung, DaeYoon; Seo, HyoungKyu

2017-10-01

Modern electro-optical surveillance and reconnaissance systems require tracking capability to get exact images of target or to accurately direct the line of sight to target which is moving or still. This leads to the tracking system composed of image based tracking algorithm and servo control algorithm. In this study, we focus on the servo control function to minimize the overshoot in the tracking motion and do not miss the target. The scheme is to limit acceleration and velocity parameters in the tracking controller, depending on the target state information in the image. We implement the proposed techniques by creating a system model of DIRCM and simulate the same environment, validate the performance on the actual equipment.

Point target detection utilizing super-resolution strategy for infrared scanning oversampling system

NASA Astrophysics Data System (ADS)

Wang, Longguang; Lin, Zaiping; Deng, Xinpu; An, Wei

2017-11-01

To improve the resolution of remote sensing infrared images, infrared scanning oversampling system is employed with information amount quadrupled, which contributes to the target detection. Generally the image data from double-line detector of infrared scanning oversampling system is shuffled to a whole oversampled image to be post-processed, whereas the aliasing between neighboring pixels leads to image degradation with a great impact on target detection. This paper formulates a point target detection method utilizing super-resolution (SR) strategy concerning infrared scanning oversampling system, with an accelerated SR strategy proposed to realize fast de-aliasing of the oversampled image and an adaptive MRF-based regularization designed to achieve the preserving and aggregation of target energy. Extensive experiments demonstrate the superior detection performance, robustness and efficiency of the proposed method compared with other state-of-the-art approaches.

Image-guided ex-vivo targeting accuracy using a laparoscopic tissue localization system

NASA Astrophysics Data System (ADS)

Bieszczad, Jerry; Friets, Eric; Knaus, Darin; Rauth, Thomas; Herline, Alan; Miga, Michael; Galloway, Robert; Kynor, David

2007-03-01

In image-guided surgery, discrete fiducials are used to determine a spatial registration between the location of surgical tools in the operating theater and the location of targeted subsurface lesions and critical anatomic features depicted in preoperative tomographic image data. However, the lack of readily localized anatomic landmarks has greatly hindered the use of image-guided surgery in minimally invasive abdominal procedures. To address these needs, we have previously described a laser-based system for localization of internal surface anatomy using conventional laparoscopes. During a procedure, this system generates a digitized, three-dimensional representation of visible anatomic surfaces in the abdominal cavity. This paper presents the results of an experiment utilizing an ex-vivo bovine liver to assess subsurface targeting accuracy achieved using our system. During the experiment, several radiopaque targets were inserted into the liver parenchyma. The location of each target was recorded using an optically-tracked insertion probe. The liver surface was digitized using our system, and registered with the liver surface extracted from post-procedure CT images. This surface-based registration was then used to transform the position of the inserted targets into the CT image volume. The target registration error (TRE) achieved using our surface-based registration (given a suitable registration algorithm initialization) was 2.4 mm +/- 1.0 mm. A comparable TRE (2.6 mm +/- 1.7 mm) was obtained using a registration based on traditional fiducial markers placed on the surface of the same liver. These results indicate the potential of fiducial-free, surface-to-surface registration for image-guided lesion targeting in minimally invasive abdominal surgery.

Q&A: The AI composer

NASA Astrophysics Data System (ADS)

Spinney, Laura

2017-09-01

Computer scientist Luc Steels uses artificial intelligence to explore the origins and evolution of language. He is best known for his 1999-2001 Talking Heads Experiment, in which robots had to construct a language from scratch to communicate with each other. Now Steels, who works at the Free University of Brussels (VUB), has composed an opera based on the legend of Faust, with a twenty-first-century twist. He talks about Mozart as a nascent computer programmer, how music maps onto language, and the blurred boundaries of a digitized world.

HS 2231+2441: an HW Vir system composed of a low-mass white dwarf and a brown dwarf★

NASA Astrophysics Data System (ADS)

Almeida, L. A.; Damineli, A.; Rodrigues, C. V.; Pereira, M. G.; Jablonski, F.

2017-12-01

HW Vir systems are rare evolved eclipsing binaries composed of a hot compact star and a low-mass main sequence star in a close orbit. These systems provide a direct way to measure the fundamental properties, e.g. masses and radii, of their components, hence they are crucial in studying the formation of subdwarf B stars and low-mass white dwarfs, the common-envelope phase and the pre-phase of cataclysmic variables. Here, we present a detailed study of HS 2231+2441, an HW Vir type system, by analysing BVRCIC photometry and phase-resolved optical spectroscopy. The spectra of this system, which are dominated by the primary component features, were fitted using non-local thermodynamic equilibrium models providing an effective temperature Teff = 28 500 ± 500 K, surface gravity log g = 5.40 ± 0.05 cm s-2 and helium abundance log (n(He)/n(H)) = -2.52 ± 0.07. The geometrical orbit and physical parameters were derived by simultaneously modelling the photometric and spectroscopic data using the Wilson-Devinney code. We derive two possible solutions for HS 2231+2441 that provide the component masses: M1 = 0.19 M⊙ and M2 = 0.036 M⊙ or M1 = 0.288 M⊙ and M2 = 0.046 M⊙. Considering the possible evolutionary channels for forming a compact hot star, the primary of HS 2231+2441 probably evolved through the red-giant branch scenario and does not have a helium-burning core, which is consistent with a low-mass white dwarf. Both solutions are consistent with a brown dwarf as the secondary.

LHRH-Targeted Drug Delivery Systems for Cancer Therapy.

PubMed

Li, Xiaoning; Taratula, Oleh; Taratula, Olena; Schumann, Canan; Minko, Tamara

2017-01-01

Targeted delivery of therapeutic and diagnostic agents to cancer sites has significant potential to improve the therapeutic outcome of treatment while minimizing severe side effects. It is widely accepted that decoration of the drug delivery systems with targeting ligands that bind specifically to the receptors on the cancer cells is a promising strategy that may substantially enhance accumulation of anticancer agents in the tumors. Due to the transformed cellular nature, cancer cells exhibit a variety of overexpressed cell surface receptors for peptides, hormones, and essential nutrients, providing a significant number of target candidates for selective drug delivery. Among others, luteinizing hormonereleasing hormone (LHRH) receptors are overexpressed in the majority of cancers, while their expression in healthy tissues, apart from pituitary cells, is limited. The recent studies indicate that LHRH peptides can be employed to efficiently guide anticancer and imaging agents directly to cancerous cells, thereby increasing the amount of these substances in tumor tissue and preventing normal cells from unnecessary exposure. This manuscript provides an overview of the targeted drug delivery platforms that take advantage of the LHRH receptors overexpression by cancer cells.

Multimodal Composing in Classrooms: Learning and Teaching for the Digital World

ERIC Educational Resources Information Center

Miller, Suzanne M., Ed.; McVee, Mary B., Ed.

2012-01-01

Taking a close look at multimodal composing as an essential new literacy in schools, this volume draws from contextualized case studies across educational contexts to provide detailed portraits of teachers and students at work in classrooms. Authors elaborate key issues in transforming classrooms with student multimodal composing, including…

Multiple-target tracking implementation in the ebCMOS camera system: the LUSIPHER prototype

NASA Astrophysics Data System (ADS)

Doan, Quang Tuyen; Barbier, Remi; Dominjon, Agnes; Cajgfinger, Thomas; Guerin, Cyrille

2012-06-01

The domain of the low light imaging systems progresses very fast, thanks to detection and electronic multiplication technology evolution, such as the emCCD (electron multiplying CCD) or the ebCMOS (electron bombarded CMOS). We present an ebCMOS camera system that is able to track every 2 ms more than 2000 targets with a mean number of photons per target lower than two. The point light sources (targets) are spots generated by a microlens array (Shack-Hartmann) used in adaptive optics. The Multiple-Target-Tracking designed and implemented on a rugged workstation is described. The results and the performances of the system on the identification and tracking are presented and discussed.

A Retrieval System for Radioactive Target Materials at the NIF

NASA Astrophysics Data System (ADS)

Krieger, M.; Shibata, K.; Fallica, J.; Henchen, R.; Pogozelski, E.; Padalino, S.; Sangster, T. C.; Suny Collaboration; Laboratory Collaboration

2011-10-01

Currently, solid radioactive material collection from the NIF target chamber is performed via the DIM. The retrieval process takes several hours to complete. To decrease this time for short lived radioisotopes, the Target Materials Retrieval System (TMRS) is being designed to move a radioactive sample from the target chamber to the counting station in less than 50 seconds, using a closed-loop helium filled RaPToRS system. The TMRS consists of three components: the retrieval apparatus, RaPToRS and the counting station. Starting at 0.5 meters from TCC, the sample will move from the vacuum chamber, travel through 60 meters of 10 centimeter diameter RaPToRS tubes, reaching speeds of 10 m/s. The sample will then arrive at the counting station, where it be robotically placed in front of a gamma ray detector. The use of helium will decrease background gamma radiation produced by activated N2 normally found in a pressurized air system. This work was supported in part by the US Department of Energy through the LLE.

Optical cell monitoring system for underwater targets

NASA Astrophysics Data System (ADS)

Moon, SangJun; Manzur, Fahim; Manzur, Tariq; Demirci, Utkan

2008-10-01

We demonstrate a cell based detection system that could be used for monitoring an underwater target volume and environment using a microfluidic chip and charge-coupled-device (CCD). This technique allows us to capture specific cells and enumerate these cells on a large area on a microchip. The microfluidic chip and a lens-less imaging platform were then merged to monitor cell populations and morphologies as a system that may find use in distributed sensor networks. The chip, featuring surface chemistry and automatic cell imaging, was fabricated from a cover glass slide, double sided adhesive film and a transparent Polymethlymetacrylate (PMMA) slab. The optically clear chip allows detecting cells with a CCD sensor. These chips were fabricated with a laser cutter without the use of photolithography. We utilized CD4+ cells that are captured on the floor of a microfluidic chip due to the ability to address specific target cells using antibody-antigen binding. Captured CD4+ cells were imaged with a fluorescence microscope to verify the chip specificity and efficiency. We achieved 70.2 +/- 6.5% capturing efficiency and 88.8 +/- 5.4% specificity for CD4+ T lymphocytes (n = 9 devices). Bright field images of the captured cells in the 24 mm × 4 mm × 50 μm microfluidic chip were obtained with the CCD sensor in one second. We achieved an inexpensive system that rapidly captures cells and images them using a lens-less CCD system. This microfluidic device can be modified for use in single cell detection utilizing a cheap light-emitting diode (LED) chip instead of a wide range CCD system.

The eisosome core is composed of BAR domain proteins

PubMed Central

Olivera-Couto, Agustina; Graña, Martin; Harispe, Laura; Aguilar, Pablo S.

2011-01-01

Eisosomes define sites of plasma membrane organization. In Saccharomyces cerevisiae, eisosomes delimit furrow-like plasma membrane invaginations that concentrate sterols, transporters, and signaling molecules. Eisosomes are static macromolecular assemblies composed of cytoplasmic proteins, most of which have no known function. In this study, we used a bioinformatics approach to analyze a set of 20 eisosome proteins. We found that the core components of eisosomes, paralogue proteins Pil1 and Lsp1, are distant homologues of membrane-sculpting Bin/amphiphysin/Rvs (BAR) proteins. Consistent with this finding, purified recombinant Pil1 and Lsp1 tubulated liposomes and formed tubules when the proteins were overexpressed in mammalian cells. Structural homology modeling and site-directed mutagenesis indicate that Pil1 positively charged surface patches are needed for membrane binding and liposome tubulation. Pil1 BAR domain mutants were defective in both eisosome assembly and plasma membrane domain organization. In addition, we found that eisosome-associated proteins Slm1 and Slm2 have F-BAR domains and that these domains are needed for targeting to furrow-like plasma membrane invaginations. Our results support a model in which BAR domain protein–mediated membrane bending leads to clustering of lipids and proteins within the plasma membrane. PMID:21593205

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

PubMed

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

2014-08-01

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

Optimization of a Multi-Stage ATR System for Small Target Identification

NASA Technical Reports Server (NTRS)

Lin, Tsung-Han; Lu, Thomas; Braun, Henry; Edens, Western; Zhang, Yuhan; Chao, Tien- Hsin; Assad, Christopher; Huntsberger, Terrance

2010-01-01

An Automated Target Recognition system (ATR) was developed to locate and target small object in images and videos. The data is preprocessed and sent to a grayscale optical correlator (GOC) filter to identify possible regionsof- interest (ROIs). Next, features are extracted from ROIs based on Principal Component Analysis (PCA) and sent to neural network (NN) to be classified. The features are analyzed by the NN classifier indicating if each ROI contains the desired target or not. The ATR system was found useful in identifying small boats in open sea. However, due to "noisy background," such as weather conditions, background buildings, or water wakes, some false targets are mis-classified. Feedforward backpropagation and Radial Basis neural networks are optimized for generalization of representative features to reduce false-alarm rate. The neural networks are compared for their performance in classification accuracy, classifying time, and training time.

The application of carbon nanotubes in target drug delivery systems for cancer therapies

NASA Astrophysics Data System (ADS)

Zhang, Wuxu; Zhang, Zhenzhong; Zhang, Yingge

2011-10-01

Among all cancer treatment options, chemotherapy continues to play a major role in killing free cancer cells and removing undetectable tumor micro-focuses. Although chemotherapies are successful in some cases, systemic toxicity may develop at the same time due to lack of selectivity of the drugs for cancer tissues and cells, which often leads to the failure of chemotherapies. Obviously, the therapeutic effects will be revolutionarily improved if human can deliver the anticancer drugs with high selectivity to cancer cells or cancer tissues. This selective delivery of the drugs has been called target treatment. To realize target treatment, the first step of the strategies is to build up effective target drug delivery systems. Generally speaking, such a system is often made up of the carriers and drugs, of which the carriers play the roles of target delivery. An ideal carrier for target drug delivery systems should have three pre-requisites for their functions: (1) they themselves have target effects; (2) they have sufficiently strong adsorptive effects for anticancer drugs to ensure they can transport the drugs to the effect-relevant sites; and (3) they can release the drugs from them in the effect-relevant sites, and only in this way can the treatment effects develop. The transporting capabilities of carbon nanotubes combined with appropriate surface modifications and their unique physicochemical properties show great promise to meet the three pre-requisites. Here, we review the progress in the study on the application of carbon nanotubes as target carriers in drug delivery systems for cancer therapies.

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

PubMed

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

2017-11-27

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

An automatic target recognition system based on SAR image

NASA Astrophysics Data System (ADS)

Li, Qinfu; Wang, Jinquan; Zhao, Bo; Luo, Furen; Xu, Xiaojian

2009-10-01

In this paper, an automatic target recognition (ATR) system based on synthetic aperture radar (SAR) is proposed. This ATR system can play an important role in the simulation of up-to-data battlefield environment and be used in ATR research. To establish an integral and available system, the processing of SAR image was divided into four main stages which are de-noise, detection, cluster-discrimination and segment-recognition, respectively. The first three stages are used for searching region of interest (ROI). Once the ROIs are extracted, the recognition stage will be taken to compute the similarity between the ROIs and the templates in the electromagnetic simulation software National Electromagnetic Scattering Code (NESC). Due to the lack of the SAR raw data, the electromagnetic simulated images are added to the measured SAR background to simulate the battlefield environment8. The purpose of the system is to find the ROIs which can be the artificial military targets such as tanks, armored cars and so on and to categorize the ROIs into the right classes according to the existing templates. From the results we can see that the proposed system achieves a satisfactory result.

Composing Networks: Writing Practices on Mobile Devices

ERIC Educational Resources Information Center

Swarts, Jason

2016-01-01

This article is an investigation of composing practices through which people create networks with mobile phones. By looking through the lens of actor-network theory, the author portrays the networking activity of mobile phone users as translation, what Latour describes as an infralanguage to which different disciplinary perspectives can be…

Polymeric micelles with stimuli-triggering systems for advanced cancer drug targeting.

PubMed

Nakayama, Masamichi; Akimoto, Jun; Okano, Teruo

2014-08-01

Since the 1990s, nanoscale drug carriers have played a pivotal role in cancer chemotherapy, acting through passive drug delivery mechanisms and subsequent pharmaceutical action at tumor tissues with reduction of adverse effects. Polymeric micelles, as supramolecular assemblies of amphiphilic polymers, have been considerably developed as promising drug carrier candidates, and a number of clinical studies of anticancer drug-loaded polymeric micelle carriers for cancer chemotherapy applications are now in progress. However, these systems still face several issues; at present, the simultaneous control of target-selective delivery and release of incorporated drugs remains difficult. To resolve these points, the introduction of stimuli-responsive mechanisms to drug carrier systems is believed to be a promising approach to provide better solutions for future tumor drug targeting strategies. As possible trigger signals, biological acidic pH, light, heating/cooling and ultrasound actively play significant roles in signal-triggering drug release and carrier interaction with target cells. This review article summarizes several molecular designs for stimuli-responsive polymeric micelles in response to variation of pH, light and temperature and discusses their potentials as next-generation tumor drug targeting systems.

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

PubMed

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

2014-01-01

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

Making Judgements: Investigating the Process of Composing and Receiving Peer Feedback

ERIC Educational Resources Information Center

McConlogue, Teresa

2015-01-01

Recent studies have argued that tutor feedback is failing to support students' progression. The potential for peer feedback, i.e. feedback composed by peer assessors, to support learning has been under researched. The aim of this paper was to explore a case study of a peer assessor composing and receiving peer feedback. The paper reports a case…

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.

Study on portable optical 3D coordinate measuring system

NASA Astrophysics Data System (ADS)

Ren, Tongqun; Zhu, Jigui; Guo, Yinbiao

2009-05-01

A portable optical 3D coordinate measuring system based on digital Close Range Photogrammetry (CRP) technology and binocular stereo vision theory is researched. Three ultra-red LED with high stability is set on a hand-hold target to provide measuring feature and establish target coordinate system. Ray intersection based field directional calibrating is done for the intersectant binocular measurement system composed of two cameras by a reference ruler. The hand-hold target controlled by Bluetooth wireless communication is free moved to implement contact measurement. The position of ceramic contact ball is pre-calibrated accurately. The coordinates of target feature points are obtained by binocular stereo vision model from the stereo images pair taken by cameras. Combining radius compensation for contact ball and residual error correction, object point can be resolved by transfer of axes using target coordinate system as intermediary. This system is suitable for on-field large-scale measurement because of its excellent portability, high precision, wide measuring volume, great adaptability and satisfying automatization. It is tested that the measuring precision is near to +/-0.1mm/m.

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.

An artificial photosynthesis anode electrode composed of a nanoparticulate photocatalyst film in a visible light responsive GaN-ZnO solid solution system

NASA Astrophysics Data System (ADS)

Imanaka, Yoshihiko; Anazawa, Toshihisa; Manabe, Toshio; Amada, Hideyuki; Ido, Sachio; Kumasaka, Fumiaki; Awaji, Naoki; Sánchez-Santolino, Gabriel; Ishikawa, Ryo; Ikuhara, Yuichi

2016-10-01

The artificial photosynthesis technology known as the Honda-Fujishima effect, which produces oxygen and hydrogen or organic energy from sunlight, water, and carbon dioxide, is an effective energy and environmental technology. The key component for the higher efficiency of this reaction system is the anode electrode, generally composed of a photocatalyst formed on a glass substrate from electrically conductive fluorine-doped tin oxide (FTO). To obtain a highly efficient electrode, a dense film composed of a nanoparticulate visible light responsive photocatalyst that usually has a complicated multi-element composition needs to be deposited and adhered onto the FTO. In this study, we discovered a method for controlling the electronic structure of a film by controlling the aerosol-type nanoparticle deposition (NPD) condition and thereby forming films of materials with a band gap smaller than that of the prepared raw material powder, and we succeeded in extracting a higher current from the anode electrode. As a result, we confirmed that a current approximately 100 times larger than those produced by conventional processes could be obtained using the same material. This effect can be expected not only from the materials discussed (GaN-ZnO) in this paper but also from any photocatalyst, particularly materials of solid solution compositions.

An artificial photosynthesis anode electrode composed of a nanoparticulate photocatalyst film in a visible light responsive GaN-ZnO solid solution system

PubMed Central

Imanaka, Yoshihiko; Anazawa, Toshihisa; Manabe, Toshio; Amada, Hideyuki; Ido, Sachio; Kumasaka, Fumiaki; Awaji, Naoki; Sánchez-Santolino, Gabriel; Ishikawa, Ryo; Ikuhara, Yuichi

2016-01-01

The artificial photosynthesis technology known as the Honda-Fujishima effect, which produces oxygen and hydrogen or organic energy from sunlight, water, and carbon dioxide, is an effective energy and environmental technology. The key component for the higher efficiency of this reaction system is the anode electrode, generally composed of a photocatalyst formed on a glass substrate from electrically conductive fluorine-doped tin oxide (FTO). To obtain a highly efficient electrode, a dense film composed of a nanoparticulate visible light responsive photocatalyst that usually has a complicated multi-element composition needs to be deposited and adhered onto the FTO. In this study, we discovered a method for controlling the electronic structure of a film by controlling the aerosol-type nanoparticle deposition (NPD) condition and thereby forming films of materials with a band gap smaller than that of the prepared raw material powder, and we succeeded in extracting a higher current from the anode electrode. As a result, we confirmed that a current approximately 100 times larger than those produced by conventional processes could be obtained using the same material. This effect can be expected not only from the materials discussed (GaN-ZnO) in this paper but also from any photocatalyst, particularly materials of solid solution compositions. PMID:27759108

Review article: the endocannabinoid system in liver disease, a potential therapeutic target.

PubMed

Basu, P P; Aloysius, M M; Shah, N J; Brown, R S

2014-04-01

Endocannabinoids are a family of potent lipid-soluble molecules, acting on the cannabinoid (CB) receptors that mediate the effects of marijuana. The CB receptors, endocannabinoids and the enzymes involved in their synthesis and degradation are located in the brain and peripheral tissues, including the liver. To review the current understanding of the role of the endocannabinoid system in liver disease-associated pathophysiological conditions, and drugs targeting the endocannabinoid system as therapy for liver disease. Original articles and reviews were used to summarise the relevant pre-clinical and clinical research findings relating to this topic. The endocannabinoid system as a whole plays an important role in liver diseases (i.e. non-alcoholic liver disease, alcoholic liver disease, hepatic encephalopathy and autoimmune hepatitis) and related pathophysiological conditions (i.e. altered hepatic haemodynamics, cirrhotic cardiomyopathy, metabolic syndrome and ischaemia/reperfusion disease). Pharmacological targeting of the endocannabinoid system has had success as treatment for patients with liver disease, but adverse events led to withdrawal of marketing approval. However, there is optimism over novel therapeutics targeting the endocannabinoid system currently in the pre-clinical stage of development. The endocannabinoid system plays an important role in the pathophysiology of liver disease and its associated conditions. While some drugs targeting the endocannabinoid system have deleterious neurological adverse events, there is promise for a newer generation of therapies that do not cross the blood-brain barrier. © 2014 John Wiley & Sons Ltd.

Composing for Digital Publication: Rhetoric, Design, Code

ERIC Educational Resources Information Center

Eyman, Douglas; Ball, Cheryl E.

2014-01-01

The authors discuss the state of digital publication with the claim that, at this historical moment, nearly all composition is digital composition. But, as a field, composition studies has not yet made that shift completely explicit in the discussions of composing processes and writing pedagogies. A deeper engagement with this very rapid shift in…

Enhancing Memory in Your Students: COMPOSE Yourself!

ERIC Educational Resources Information Center

Rotter, Kathleen M.

2009-01-01

The essence of teaching is, in fact, creating new memories for your students. The teacher's role is to help students store the correct information (memories) in ways that make recall and future access and use likely. Therefore, choosing techniques to enhance memory is possibly the most critical aspect of instructional design. COMPOSE is an acronym…

A Tupaia paramyxovirus vector system for targeting and transgene expression.

PubMed

Engeland, Christine E; Bossow, Sascha; Hudacek, Andrew W; Hoyler, Birgit; Förster, Judith; Veinalde, Rūta; Jäger, Dirk; Cattaneo, Roberto; Ungerechts, Guy; Springfeld, Christoph

2017-09-01

Viruses from the diverse family of Paramyxoviridae include important pathogens and are applied in gene therapy and for cancer treatment. The Tupaia paramyxovirus (TPMV), isolated from the kidney of a tree shrew, does not infect human cells and neutralizing antibodies against other Paramyxoviridae do not cross-react with TPMV. Here, we present a vector system for de novo generation of infectious TPMV that allows for insertion of additional genes as well as targeting using antibody single-chain variable fragments. We show that the recombinant TPMV specifically infect cells expressing the targeted receptor and replicate in human cells. This vector system provides a valuable tool for both basic research and therapeutic applications.

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

PubMed Central

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

2014-01-01

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

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.

Modeling and Composing Scenario-Based Requirements with Aspects

NASA Technical Reports Server (NTRS)

Araujo, Joao; Whittle, Jon; Ki, Dae-Kyoo

2004-01-01

There has been significant recent interest, within the Aspect-Oriented Software Development (AOSD) community, in representing crosscutting concerns at various stages of the software lifecycle. However, most of these efforts have concentrated on the design and implementation phases. We focus in this paper on representing aspects during use case modeling. In particular, we focus on scenario-based requirements and show how to compose aspectual and non-aspectual scenarios so that they can be simulated as a whole. Non-aspectual scenarios are modeled as UML sequence diagram. Aspectual scenarios are modeled as Interaction Pattern Specifications (IPS). In order to simulate them, the scenarios are transformed into a set of executable state machines using an existing state machine synthesis algorithm. Previous work composed aspectual and non-aspectual scenarios at the sequence diagram level. In this paper, the composition is done at the state machine level.

A Novel Aqueous Two Phase System Composed of Surfactant and Xylitol for the Purification of Lipase from Pumpkin (Cucurbita moschata) Seeds and Recycling of Phase Components.

PubMed

Amid, Mehrnoush; Manap, Mohd Yazid; Hussin, Muhaini; Mustafa, Shuhaimi

2015-06-17

Lipase is one of the more important enzymes used in various industries such as the food, detergent, pharmaceutical, textile, and pulp and paper sectors. A novel aqueous two-phase system composed of surfactant and xylitol was employed for the first time to purify lipase from Cucurbita moschata. The influence of different parameters such as type and concentration of surfactants, and the composition of the surfactant/xylitol mixtures on the partitioning behavior and recovery of lipase was investigated. Moreover, the effect of system pH and crude load on the degree of purification and yield of the purified lipase were studied. The results indicated that the lipase was partitioned into the top surfactant rich phase while the impurities partitioned into the bottom xylitol-rich phase using an aqueous two phase system composed of 24% (w/w) Triton X-100 and 20% (w/w) xylitol, at 56.2% of tie line length (TLL), (TTL is one of the important parameters in this study and it is determined from a bimodal curve in which the tie-line connects two nodes on the bimodal, that represent concentration of phase components in the top and bottom phases) and a crude load of 25% (w/w) at pH 8.0. Recovery and recycling of components was also measured in each successive step process. The enzyme was successfully recovered by the proposed method with a high purification factor of 16.4 and yield of 97.4% while over 97% of the phase components were also recovered and recycled. This study demonstrated that the proposed novel aqueous two phase system method is more efficient and economical than the traditional aqueous two phase system method for the purification and recovery of the valuable enzyme lipase.

Interactive display system having a scaled virtual target zone

DOEpatents

Veligdan, James T.; DeSanto, Leonard

2006-06-13

A display system includes a waveguide optical panel having an inlet face and an opposite outlet face. A projector and imaging device cooperate with the panel for projecting a video image thereon. An optical detector bridges at least a portion of the waveguides for detecting a location on the outlet face within a target zone of an inbound light spot. A controller is operatively coupled to the imaging device and detector for displaying a cursor on the outlet face corresponding with the detected location of the spot within the target zone.

Endocannabinoid System: A Multi-Facet Therapeutic Target.

PubMed

Kaur, Rimplejeet; Ambwani, Sneha R; Singh, Surjit

2016-01-01

the therapeutic targets for both cannabinoid receptor agonists and antagonists. One challenge is to develop drugs that target only cannabinoid receptors in a particular tissue and another is to invent drugs that act selectively on cannabinoid receptors located outside the blood brain barrier. Besides this, development of the suitable dosage forms with maximum efficacy and minimum adverse effects is also warranted. Another angle to be introspected for therapeutic abilities of this group of drugs is non-CB1 and non-CB2 receptor targets for cannabinoids. In order to successfully exploit the therapeutic potential of endocannabinoid system, it is imperative to further characterize the endocannabinoid system in terms of identification of the exact cellular location of cannabinoid receptors and their role as "protective" and "disease inducing substance", time-dependent changes in the expression of cannabinoid receptors.

HIV-1 Proteins, Tat and gp120, Target the Developing Dopamine System

PubMed Central

Fitting, Sylvia; Booze, Rosemarie M.; Mactutus, Charles F.

2015-01-01

In 2014, 3.2 million children (< 15 years of age) were estimated to be living with HIV and AIDS worldwide, with the 240,000 newly infected children in the past year, i.e., another child infected approximately every two minutes [1]. The primary mode of HIV infection is through mother-to-child transmission (MTCT), occurring either in utero, intrapartum, or during breastfeeding. The effects of HIV-1 on the central nervous system (CNS) are putatively accepted to be mediated, in part, via viral proteins, such as Tat and gp120. The current review focuses on the targets of HIV-1 proteins during the development of the dopamine (DA) system, which appears to be specifically susceptible in HIV-1-infected children. Collectively, the data suggest that the DA system is a clinically relevant target in chronic HIV-1 infection, is one of the major targets in pediatric HIV-1 CNS infection, and may be specifically susceptible during development. The present review discusses the development of the DA system, follows the possible targets of the HIV-1 proteins during the development of the DA system, and suggests potential therapeutic approaches. By coupling our growing understanding of the development of the CNS with the pronounced age-related differences in disease progression, new light may be shed on the neurological and neurocognitive deficits that follow HIV-1 infection. PMID:25613135

Analysis of A Drug Target-based Classification System using Molecular Descriptors.

PubMed

Lu, Jing; Zhang, Pin; Bi, Yi; Luo, Xiaomin

2016-01-01

Drug-target interaction is an important topic in drug discovery and drug repositioning. KEGG database offers a drug annotation and classification using a target-based classification system. In this study, we gave an investigation on five target-based classes: (I) G protein-coupled receptors; (II) Nuclear receptors; (III) Ion channels; (IV) Enzymes; (V) Pathogens, using molecular descriptors to represent each drug compound. Two popular feature selection methods, maximum relevance minimum redundancy and incremental feature selection, were adopted to extract the important descriptors. Meanwhile, an optimal prediction model based on nearest neighbor algorithm was constructed, which got the best result in identifying drug target-based classes. Finally, some key descriptors were discussed to uncover their important roles in the identification of drug-target classes.

The role of the vestibular system in manual target localization

NASA Technical Reports Server (NTRS)

Barry, Susan R.; Mueller, S. Alyssa

1995-01-01

Astronauts experience perceptual and sensory-motor disturbances during spaceflight and immediately after return to the 1-g environment of Earth. During spaceflight, sensory information from the eyes, limbs and vestibular organs is reinterpreted by the central nervous system so that astronauts can produce appropriate body movements in microgravity. Alterations in sensory-motor function may affect eye-head-hand coordination and, thus, the crewmember's ability to manually locate objects in extrapersonal space. Previous reports have demonstrated that crewmembers have difficulty in estimating joint and limb position and in pointing to memorized target positions on orbit and immediately postflight. One set of internal cues that may assist in the manual localization of objects is information from the vestibular system. This system contributes to our sense of the body's position in space by providing information on head position and movement and the orientation of the body with respect to gravity. Research on the vestibular system has concentrated on its role in oculo-motor control. Little is known about the role that vestibular information plays in manual motor control, such as reaching and pointing movements. Since central interpretation of vestibular information is altered in microgravity, it is important to determine its role in this process. This summer, we determined the importance of vestibular information in a subject's ability to point accurately toward a target in extrapersonal space. Subjects were passively rotated across the earth-vertical axis and then asked to point back to a previously-seen target. In the first paradigm, the subjects used both visual and vestibular cues for the pointing response, while, in the second paradigm, subjects used only vestibular information. Subjects were able to point with 85 percent accuracy to a target using vestibular information alone. We infer from this result that vestibular input plays a role in the spatial programming of

Surface polaritons in grating composed of left-handed materials

NASA Astrophysics Data System (ADS)

Tiwari, D. C.; Premlal, P. L.; Chaturvedi, Vandana

2018-01-01

In this work, we developed a unique mathematical model to solve dispersion relation for surface polaritons (SPs) in artificial composite materials grating. Here, we have taken two types of materials for analysis. In the first case, the grating composed of epsilon-negative (ENG) material and air interface. In second case, grating composed of left-handed materials (LHMs) and ENG medium interface is considered. The dispersion curves of both p and s polarized SPs modes are obtained analytically. In the case of ENG grating and air interface, polaritons dispersion curves exist for p-polarization only, whereas for LHM grating and ENG medium interface, the polaritons dispersion curves for both p and s polarization are observed.

Cuticular Poroma: A Poroma Mostly Composed of Cuticular Cells (Cuticuloma).

PubMed

Alegría-Landa, Victoria; Kutzner, Heinz; Requena, Luis

2017-12-28

Poromas are benign cutaneous adnexal neoplasms with differentiation toward excretory ducts of eccrine and apocrine glands. They are mainly composed of solid aggregates of small, monomorphous, round, and basophilic poroid cells, with a lower proportion of larger, squamous, eosinophilic cuticular cells, which are lining ductal structures with an eosinophilic luminal cuticle. In most cases of poromas, cuticular cells represent a small proportion of the neoplastic aggregates. We report 2 poromas mostly composed of cuticular cells, and on the basis of these findings, we have named cuticuloma to this histopathologic variant of poroma.

Gene composer: database software for protein construct design, codon engineering, and gene synthesis.

PubMed

Lorimer, Don; Raymond, Amy; Walchli, John; Mixon, Mark; Barrow, Adrienne; Wallace, Ellen; Grice, Rena; Burgin, Alex; Stewart, Lance

2009-04-21

To improve efficiency in high throughput protein structure determination, we have developed a database software package, Gene Composer, which facilitates the information-rich design of protein constructs and their codon engineered synthetic gene sequences. With its modular workflow design and numerous graphical user interfaces, Gene Composer enables researchers to perform all common bio-informatics steps used in modern structure guided protein engineering and synthetic gene engineering. An interactive Alignment Viewer allows the researcher to simultaneously visualize sequence conservation in the context of known protein secondary structure, ligand contacts, water contacts, crystal contacts, B-factors, solvent accessible area, residue property type and several other useful property views. The Construct Design Module enables the facile design of novel protein constructs with altered N- and C-termini, internal insertions or deletions, point mutations, and desired affinity tags. The modifications can be combined and permuted into multiple protein constructs, and then virtually cloned in silico into defined expression vectors. The Gene Design Module uses a protein-to-gene algorithm that automates the back-translation of a protein amino acid sequence into a codon engineered nucleic acid gene sequence according to a selected codon usage table with minimal codon usage threshold, defined G:C% content, and desired sequence features achieved through synonymous codon selection that is optimized for the intended expression system. The gene-to-oligo algorithm of the Gene Design Module plans out all of the required overlapping oligonucleotides and mutagenic primers needed to synthesize the desired gene constructs by PCR, and for physically cloning them into selected vectors by the most popular subcloning strategies. We present a complete description of Gene Composer functionality, and an efficient PCR-based synthetic gene assembly procedure with mis-match specific endonuclease

Gene Composer: database software for protein construct design, codon engineering, and gene synthesis

PubMed Central

Lorimer, Don; Raymond, Amy; Walchli, John; Mixon, Mark; Barrow, Adrienne; Wallace, Ellen; Grice, Rena; Burgin, Alex; Stewart, Lance

2009-01-01

Background To improve efficiency in high throughput protein structure determination, we have developed a database software package, Gene Composer, which facilitates the information-rich design of protein constructs and their codon engineered synthetic gene sequences. With its modular workflow design and numerous graphical user interfaces, Gene Composer enables researchers to perform all common bio-informatics steps used in modern structure guided protein engineering and synthetic gene engineering. Results An interactive Alignment Viewer allows the researcher to simultaneously visualize sequence conservation in the context of known protein secondary structure, ligand contacts, water contacts, crystal contacts, B-factors, solvent accessible area, residue property type and several other useful property views. The Construct Design Module enables the facile design of novel protein constructs with altered N- and C-termini, internal insertions or deletions, point mutations, and desired affinity tags. The modifications can be combined and permuted into multiple protein constructs, and then virtually cloned in silico into defined expression vectors. The Gene Design Module uses a protein-to-gene algorithm that automates the back-translation of a protein amino acid sequence into a codon engineered nucleic acid gene sequence according to a selected codon usage table with minimal codon usage threshold, defined G:C% content, and desired sequence features achieved through synonymous codon selection that is optimized for the intended expression system. The gene-to-oligo algorithm of the Gene Design Module plans out all of the required overlapping oligonucleotides and mutagenic primers needed to synthesize the desired gene constructs by PCR, and for physically cloning them into selected vectors by the most popular subcloning strategies. Conclusion We present a complete description of Gene Composer functionality, and an efficient PCR-based synthetic gene assembly procedure with mis

Performance of target detection algorithm in compressive sensing miniature ultraspectral imaging compressed sensing system

NASA Astrophysics Data System (ADS)

Gedalin, Daniel; Oiknine, Yaniv; August, Isaac; Blumberg, Dan G.; Rotman, Stanley R.; Stern, Adrian

2017-04-01

Compressive sensing theory was proposed to deal with the high quantity of measurements demanded by traditional hyperspectral systems. Recently, a compressive spectral imaging technique dubbed compressive sensing miniature ultraspectral imaging (CS-MUSI) was presented. This system uses a voltage controlled liquid crystal device to create multiplexed hyperspectral cubes. We evaluate the utility of the data captured using the CS-MUSI system for the task of target detection. Specifically, we compare the performance of the matched filter target detection algorithm in traditional hyperspectral systems and in CS-MUSI multiplexed hyperspectral cubes. We found that the target detection algorithm performs similarly in both cases, despite the fact that the CS-MUSI data is up to an order of magnitude less than that in conventional hyperspectral cubes. Moreover, the target detection is approximately an order of magnitude faster in CS-MUSI data.

Supercollimation in photonic crystals composed of silicon rods

NASA Astrophysics Data System (ADS)

Shih, Ta-Ming; Kurs, André; Dahlem, Marcus; Petrich, Gale; Soljačić, Marin; Ippen, Erich; Kolodziejski, Leslie; Hall, Katherine; Kesler, Morris

2008-09-01

Supercollimation is the propagation of light without diffraction using the properties of photonic crystals. We present the first experimental demonstration of supercollimation in a planar photonic crystal composed of nanoscale rods. Supercollimation was observed over distances of up to 1000 lattice periods.

Efficient Authorization of Rich Presence Using Secure and Composed Web Services

NASA Astrophysics Data System (ADS)

Li, Li; Chou, Wu

This paper presents an extended Role-Based Access Control (RBAC) model for efficient authorization of rich presence using secure web services composed with an abstract presence data model. Following the information symmetry principle, the standard RBAC model is extended to support context sensitive social relations and cascaded authority. In conjunction with the extended RBAC model, we introduce an extensible presence architecture prototype using WS-Security and WS-Eventing to secure rich presence information exchanges based on PKI certificates. Applications and performance measurements of our presence system are presented to show that the proposed RBAC framework for presence and collaboration is well suited for real-time communication and collaboration.

The influence of the earth radiation on space target detection system

NASA Astrophysics Data System (ADS)

Su, Xiaofeng; Chen, FanSheng; Cuikun, .; Liuyan, .

2017-05-01

In the view of space remote sensing such as satellite detection space debris detection etc. visible band is usually used in order to have the all-weather detection capability, long wavelength infrared (LWIR) detection is also an important supplement. However, in the tow wave band, the earth can be a very strong interference source, especially in the dim target detecting. When the target is close to the earth, especially the LEO target, the background radiation of the earth will also enter into the baffle, and became the stray light through reflection, the stray light can reduce the signal to clutter ratio (SCR) of the target and make it difficult to be detected. In the visible band, the solar albedo by the earth is the main clutter source while in the LWIR band the radiation of the earth is the main clutter source. So, in this paper, we establish the energy transformation from the earth background radiation to the detection system to assess the effects of the stray light. Firstly, we discretize the surface of the earth to different unit, and using MODTRAN to calculate the radiation of the discrete point in different light and climate conditions, then, we integral all the radiation which can reach the baffle in the same observation angles to get the energy distribution, finally, according the target energy and the non-uniformity of the detector, we can calculate the design requirement of the system stray light suppression, which provides the design basis for the optical system.

Comprehensive target populations for current active safety systems using national crash databases.

PubMed

Kusano, Kristofer D; Gabler, Hampton C

2014-01-01

The objective of active safety systems is to prevent or mitigate collisions. A critical component in the design of active safety systems is the identification of the target population for a proposed system. The target population for an active safety system is that set of crashes that a proposed system could prevent or mitigate. Target crashes have scenarios in which the sensors and algorithms would likely activate. For example, the rear-end crash scenario, where the front of one vehicle contacts another vehicle traveling in the same direction and in the same lane as the striking vehicle, is one scenario for which forward collision warning (FCW) would be most effective in mitigating or preventing. This article presents a novel set of precrash scenarios based on coded variables from NHTSA's nationally representative crash databases in the United States. Using 4 databases (National Automotive Sampling System-General Estimates System [NASS-GES], NASS Crashworthiness Data System [NASS-CDS], Fatality Analysis Reporting System [FARS], and National Motor Vehicle Crash Causation Survey [NMVCCS]) the scenarios developed in this study can be used to quantify the number of police-reported crashes, seriously injured occupants, and fatalities that are applicable to proposed active safety systems. In this article, we use the precrash scenarios to identify the target populations for FCW, pedestrian crash avoidance systems (PCAS), lane departure warning (LDW), and vehicle-to-vehicle (V2V) or vehicle-to-infrastructure (V2I) systems. Crash scenarios were derived using precrash variables (critical event, accident type, precrash movement) present in all 4 data sources. This study found that these active safety systems could potentially mitigate approximately 1 in 5 of all severity and serious injury crashes in the United States and 26 percent of fatal crashes. Annually, this corresponds to 1.2 million all severity, 14,353 serious injury (MAIS 3+), and 7412 fatal crashes. In addition

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.

Rethinking Composing in a Digital Age: Authoring Literate Identities through Multimodal Storytelling

ERIC Educational Resources Information Center

Vasudevan, Lalitha; Schultz, Katherine; Bateman, Jennifer

2010-01-01

In this article, the authors engage the theoretical lens of multimodality in rethinking the practices and processes of composing in classrooms. Specifically, they focus on how learning new composing practices led some fifth-grade students to author new literate identities--what they call authorial stances--in their classroom community. Their…

Targeted mutagenesis in cotton (Gossypium hirsutum L.) using the CRISPR/Cas9 system.

PubMed

Chen, Xiugui; Lu, Xuke; Shu, Na; Wang, Shuai; Wang, Junjuan; Wang, Delong; Guo, Lixue; Ye, Wuwei

2017-03-13

The CRISPR (Clustered Regularly Interspaced Short Palindromic Repeats)/Cas9 system has been widely used for genome editing in various plants because of its simplicity, high efficiency and design flexibility. However, to our knowledge, there is no report on the application of CRISPR/Cas9-mediated targeted mutagenesis in cotton. Here, we report the genome editing and targeted mutagenesis in upland cotton (Gossypium hirsutum L., hereafter cotton) using the CRISPR/Cas9 system. We designed two guide RNAs to target distinct sites of the cotton Cloroplastos alterados 1 (GhCLA1) and vacuolar H + -pyrophosphatase (GhVP) genes. Mutations in these two genes were detected in cotton protoplasts. Most of the mutations were nucleotide substitutions, with one nucleotide insertion and one substitution found in GhCLA1 and one deletion found in GhVP in cotton protoplasts. Subsequently, the two vectors were transformed into cotton shoot apexes through Agrobacterium-mediated transformation, resulting in efficient target gene editing. Most of the mutations were nucleotide deletions, and the mutation efficiencies were 47.6-81.8% in transgenic cotton plants. Evaluation using restriction-enzyme-PCR assay and sequence analysis detected no off-target mutations. Our results indicated that the CRISPR/Cas9 system was an efficient and specific tool for targeted mutagenesis of the cotton genome.

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

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.

A new EMI system for detection and classification of challenging targets

NASA Astrophysics Data System (ADS)

Shubitidze, F.; Fernández, J. P.; Barrowes, B. E.; O'Neill, K.

2013-06-01

Advanced electromagnetic induction (EMI) sensors currently feature multi-axis illumination of targets and tri-axial vector sensing (e.g., MetalMapper), or exploit multi-static array data acquisition (e.g., TEMTADS). They produce data of high density, quality, and diversity, and have been combined with advanced EMI models to provide superb classification performance relative to the previous generation of single-axis, monostatic sensors. However, these advances yet have to improve significantly our ability to classify small, deep, and otherwise challenging targets. Particularly, recent live-site discrimination studies at Camp Butner, NC and Camp Beale, CA have revealed that it is more challenging to detect and discriminate small munitions (with calibers ranging from 20 mm to 60 mm) than larger ones. In addition, a live-site test at the Massachusetts Military Reservation, MA highlighted the difficulties for current sensors to classify large, deep, and overlapping targets with high confidence. There are two main approaches to overcome these problems: 1) adapt advanced EMI models to the existing systems and 2) improve the detection limits of current sensors by modifying their hardware. In this paper we demonstrate a combined software/hardware approach that will provide extended detection range and spatial resolution to next-generation EMI systems; we analyze and invert EMI data to extract classification features for small and deep targets; and we propose a new system that features a large transmitter coil.

[Research and application of microcontroller system for target controlled infusion].

PubMed

Cheng, Yuke; Dou, Jianhong; Zhang, Xingan; Wang, Ruosong

2005-08-01

This paper presents a microcontroller system for target controlled infusion according to pharmacodynamic parameters of intravenous anesthetics. It can control the depth of anesthesia by adjusting the level of plasma concentrations. The system has the advantages of high precision, extending power and easy manipulation. It has been used in the clinical anesthesia.

Targeting Strategies for the Combination Treatment of Cancer Using Drug Delivery Systems

PubMed Central

Kydd, Janel; Jadia, Rahul; Velpurisiva, Praveena; Gad, Aniket; Paliwal, Shailee; Rai, Prakash

2017-01-01

Cancer cells have characteristics of acquired and intrinsic resistances to chemotherapy treatment—due to the hostile tumor microenvironment—that create a significant challenge for effective therapeutic regimens. Multidrug resistance, collateral toxicity to normal cells, and detrimental systemic side effects present significant obstacles, necessitating alternative and safer treatment strategies. Traditional administration of chemotherapeutics has demonstrated minimal success due to the non-specificity of action, uptake and rapid clearance by the immune system, and subsequent metabolic alteration and poor tumor penetration. Nanomedicine can provide a more effective approach to targeting cancer by focusing on the vascular, tissue, and cellular characteristics that are unique to solid tumors. Targeted methods of treatment using nanoparticles can decrease the likelihood of resistant clonal populations of cancerous cells. Dual encapsulation of chemotherapeutic drug allows simultaneous targeting of more than one characteristic of the tumor. Several first-generation, non-targeted nanomedicines have received clinical approval starting with Doxil® in 1995. However, more than two decades later, second-generation or targeted nanomedicines have yet to be approved for treatment despite promising results in pre-clinical studies. This review highlights recent studies using targeted nanoparticles for cancer treatment focusing on approaches that target either the tumor vasculature (referred to as ‘vascular targeting’), the tumor microenvironment (‘tissue targeting’) or the individual cancer cells (‘cellular targeting’). Recent studies combining these different targeting methods are also discussed in this review. Finally, this review summarizes some of the reasons for the lack of clinical success in the field of targeted nanomedicines. PMID:29036899

Multiple target laser ablation system

DOEpatents

Mashburn, D.N.

1996-01-09

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

Multiple target laser ablation system

DOEpatents

Mashburn, Douglas N.

1996-01-01

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

Update on B-cell targeted therapies for systemic lupus erythematosus.

PubMed

Mok, Chi Chiu

2014-06-01

Systemic lupus erythematosus (SLE) is a systemic autoimmune disease characterized by flares and remission, leading to accrual of organ damage over time as a result of persistent tissue inflammation and treatment-related complications. Novel therapies aiming at better treatment response and fewer adverse effects are being tested in the pipeline. This review summarizes the B-cell abnormalities observed in patients with SLE, and updates recent data on the efficacy and safety of B-cell targeted therapies in the treatment of SLE. The pitfalls of clinical trial design and future directions of the development of SLE therapeutics are discussed. The variability of clinical response to treatment in SLE reflects the clinical and immunological heterogeneity of the disease. The treatment plan for patients with SLE should be individualized with the aim of eradicating disease activity, preventing flares and minimizing treatment-related complications. Despite the disappointment of recent clinical trials, B-cell remains the promising target of future SLE therapies. Results from ongoing clinical trials on B-cell targeted biological agents are eagerly awaited.

A distributed automatic target recognition system using multiple low resolution sensors

NASA Astrophysics Data System (ADS)

Yue, Zhanfeng; Lakshmi Narasimha, Pramod; Topiwala, Pankaj

2008-04-01

In this paper, we propose a multi-agent system which uses swarming techniques to perform high accuracy Automatic Target Recognition (ATR) in a distributed manner. The proposed system can co-operatively share the information from low-resolution images of different looks and use this information to perform high accuracy ATR. An advanced, multiple-agent Unmanned Aerial Vehicle (UAV) systems-based approach is proposed which integrates the processing capabilities, combines detection reporting with live video exchange, and swarm behavior modalities that dramatically surpass individual sensor system performance levels. We employ real-time block-based motion analysis and compensation scheme for efficient estimation and correction of camera jitter, global motion of the camera/scene and the effects of atmospheric turbulence. Our optimized Partition Weighted Sum (PWS) approach requires only bitshifts and additions, yet achieves a stunning 16X pixel resolution enhancement, which is moreover parallizable. We develop advanced, adaptive particle-filtering based algorithms to robustly track multiple mobile targets by adaptively changing the appearance model of the selected targets. The collaborative ATR system utilizes the homographies between the sensors induced by the ground plane to overlap the local observation with the received images from other UAVs. The motion of the UAVs distorts estimated homography frame to frame. A robust dynamic homography estimation algorithm is proposed to address this, by using the homography decomposition and the ground plane surface estimation.

Targeting the endocannabinoid system to treat anxiety-related disorders.

PubMed

Korem, Nachshon; Zer-Aviv, Tomer Mizrachi; Ganon-Elazar, Eti; Abush, Hila; Akirav, Irit

2016-05-01

The endocannabinoid system plays an important role in the control of emotions, and its dysregulation has been implicated in several psychiatric disorders. The most common self-reported reason for using cannabis is rooted in its ability to reduce feelings of stress, tension, and anxiety. Nevertheless, there are only few studies in controlled clinical settings that confirm that administration of cannabinoids can benefit patients with a post-traumatic stress disorder (PTSD). There are considerable encouraging preclinical data to suggest that endocannabinoid-targeted therapeutics for anxiety disorders should continue. In this review, we will describe data supporting a role for the endocannabinoid system in preventing and treating anxiety-like behavior in animal models and PTSD patients. Cannabinoids have shown beneficial outcomes in rat and mouse models of anxiety and PTSD, but they also may have untoward effects that discourage their chronic usage, including anxiogenic effects. Hence, clinical and preclinical research on the endocannabinoid system should further study the effects of cannabinoids on anxiety and help determine whether the benefits of using exogenous cannabinoids outweigh the risks. In general, this review suggests that targeting the endocannabinoid system represents an attractive and novel approach to the treatment of anxiety-related disorders and, in particular, PTSD.

How One Class with One Computer Composed Music

ERIC Educational Resources Information Center

Siegel, Jack

2004-01-01

Music composition is a rewarding activity for students. Through composition, teachers not only address National Standard 4 (composing and arranging music within specified guidelines), but also cover other areas of the music curriculum such as singing, notation, improvisation, form, style, tempo, dynamics, music vocabulary, and assessment. During…

Microchimeric cells in systemic lupus erythematosus: targets or innocent bystanders?

PubMed

Stevens, A M

2006-01-01

During pregnancy maternal and fetal cells commute back and forth leading to fetal microchimerism in the mother and maternal microchimerism in the child that can persist for years after the birth. Chimeric fetal and maternal cells can be hematopoietic or can differentiate into somatic cells in multiple organs, potentially acting as targets for 'autoimmunity' and so have been implicated in the pathogenesis of autoimmune diseases that resemble graft-versus-host disease after stem cell transplantation. Fetal cells have been found in women with systemic lupus erythematosus, both in the blood and a target organ, the kidney, suggesting that they may be involved in pathogenesis. Future studies will address how the host immune system normally tolerates maternal and fetal cells or how the balance may change during autoimmunity.

Effects-based strategy development through center of gravity and target system analysis

NASA Astrophysics Data System (ADS)

White, Christopher M.; Prendergast, Michael; Pioch, Nicholas; Jones, Eric K.; Graham, Stephen

2003-09-01

This paper describes an approach to effects-based planning in which a strategic-theater-level mission is refined into operational-level and ultimately tactical-level tasks and desired effects, informed by models of the expected enemy response at each level of abstraction. We describe a strategy development system that implements this approach and supports human-in-the-loop development of an effects-based plan. This system consists of plan authoring tools tightly integrated with a suite of center of gravity (COG) and target system analysis tools. A human planner employs the plan authoring tools to develop a hierarchy of tasks and desired effects. Upon invocation, the target system analysis tools use reduced-order models of enemy centers of gravity to select appropriate target set options for the achievement of desired effects, together with associated indicators for each option. The COG analysis tools also provide explicit models of the causal mechanisms linking tasks and desired effects to one another, and suggest appropriate observable indicators to guide ISR planning, execution monitoring, and campaign assessment. We are currently implementing the system described here as part of the AFRL-sponsored Effects Based Operations program.

A Phase l Study of a Tumor-targeted Systemic Nanodelivery System, SGT-94, in Genitourinary Cancers

PubMed Central

Siefker-Radtke, Arlene; Zhang, Xin-qiao; Guo, Charles C; Shen, Yu; Pirollo, Kathleen F; Sabir, Sharjeel; Leung, Chris; Leong-Wu, Cindy; Ling, Chi-Ming; Chang, Esther H; Millikan, Randall E; Benedict, William F

2016-01-01

Gene therapy development has been limited by our inability to target multifocal cancer with systemic delivery. We developed a systemically administered, tumor-targeted liposomal nanodelivery complex (SGT-94) carrying a plasmid encoding RB94, a truncated form of the RB gene. In preclinical studies, RB94 showed marked cytotoxicity against tumor but not normal cells. SGT-94 was administered intravenously in a first-in-man study in metastatic genitourinary cancer. Minimal side effects were observed; dose-limiting toxicity (DLT) has not been reached in 11 evaluable patients. There was evidence of clinical activity at the 2.4 mg dose with one complete remission (CR) and one partial remission (PR). The patient in CR was retreated upon progression and had a second PR. Furthermore, there was tumor-specific targeting of the SGT-94 complex. One patient had wedge resections of two lung metastases which demonstrated RB94 expression at the DNA level by polymerase chain reaction (PCR) and at the protein level by Western blotting, with no RB94 present in normal contiguous lung. In conclusion, systemically delivered SGT-94 showed evidence of selective tumor targeting and was well tolerated with evidence of clinical activity. Additional studies are warranted to explore the activity of this drug as a single agent and in combination therapy. PMID:27480598

Penalty dynamic programming algorithm for dim targets detection in sensor systems.

PubMed

Huang, Dayu; Xue, Anke; Guo, Yunfei

2012-01-01

In order to detect and track multiple maneuvering dim targets in sensor systems, an improved dynamic programming track-before-detect algorithm (DP-TBD) called penalty DP-TBD (PDP-TBD) is proposed. The performances of tracking techniques are used as a feedback to the detection part. The feedback is constructed by a penalty term in the merit function, and the penalty term is a function of the possible target state estimation, which can be obtained by the tracking methods. With this feedback, the algorithm combines traditional tracking techniques with DP-TBD and it can be applied to simultaneously detect and track maneuvering dim targets. Meanwhile, a reasonable constraint that a sensor measurement can originate from one target or clutter is proposed to minimize track separation. Thus, the algorithm can be used in the multi-target situation with unknown target numbers. The efficiency and advantages of PDP-TBD compared with two existing methods are demonstrated by several simulations.

Penalty Dynamic Programming Algorithm for Dim Targets Detection in Sensor Systems

PubMed Central

Huang, Dayu; Xue, Anke; Guo, Yunfei

2012-01-01

In order to detect and track multiple maneuvering dim targets in sensor systems, an improved dynamic programming track-before-detect algorithm (DP-TBD) called penalty DP-TBD (PDP-TBD) is proposed. The performances of tracking techniques are used as a feedback to the detection part. The feedback is constructed by a penalty term in the merit function, and the penalty term is a function of the possible target state estimation, which can be obtained by the tracking methods. With this feedback, the algorithm combines traditional tracking techniques with DP-TBD and it can be applied to simultaneously detect and track maneuvering dim targets. Meanwhile, a reasonable constraint that a sensor measurement can originate from one target or clutter is proposed to minimize track separation. Thus, the algorithm can be used in the multi-target situation with unknown target numbers. The efficiency and advantages of PDP-TBD compared with two existing methods are demonstrated by several simulations. PMID:22666074

The MROI fast tip-tilt correction and target acquisition system

NASA Astrophysics Data System (ADS)

Young, John; Buscher, David; Fisher, Martin; Haniff, Christopher; Rea, Alexander; Seneta, Eugene B.; Sun, Xiaowei; Wilson, Donald; Farris, Allen; Olivares, Andres; Selina, Robert

2012-07-01

The fast tip-tilt correction system for the Magdalena Ridge Observatory Interferometer (MROI) is being designed and fabricated by the University of Cambridge. The design of the system is currently at an advanced stage and the performance of its critical subsystems has been verified in the laboratory. The system has been designed to meet a demanding set of specifications including satisfying all performance requirements in ambient temperatures down to -5 °C, maintaining the stability of the tip-tilt fiducial over a 5 °C temperature change without recourse to an optical reference, and a target acquisition mode with a 60” field-of-view. We describe the important technical features of the system, which uses an Andor electron-multiplying CCD camera protected by a thermal enclosure, a transmissive optical system with mounts incorporating passive thermal compensation, and custom control software running under Xenomai real-time Linux. We also report results from laboratory tests that demonstrate (a) the high stability of the custom optic mounts and (b) the low readout and compute latencies that will allow us to achieve a 40 Hz closed-loop bandwidth on bright targets.

A time domain simulation of a beam control system

NASA Astrophysics Data System (ADS)

Mitchell, J. R.

1981-02-01

The Airborne Laser Laboratory (ALL) is being developed by the Air Force to investigate the integration and operation of high energy laser components in a dynamic airborne environment and to study the propagation of laser light from an airborne vehicle to an airborne target. The ALL is composed of several systems; among these are the Airborne Pointing and Tracking System (APT) and the Automatic Alignment System (AAS). This report presents the results of performing a time domain dynamic simulation for an integrated beam control system composed of the APT and AAS. The simulation is performed on a digital computer using the MIMIC language. It includes models of the dynamics of the system and of disturbances. Also presented in the report are the rationales and developments of these models. The data from the simulation code is summarized by several plots. In addition results from massaging the data with waveform analysis packages are presented. The results are discussed and conclusions are drawn.

The swan-song phenomenon: last-works effects for 172 classical composers.

PubMed

Simonton, D K

1989-03-01

Creative individuals approaching their final years of life may undergo a transformation in outlook that is reflected in their last works. This hypothesized effect was quantitatively assessed for an extensive sample of 1,919 works by 172 classical composers. The works were independently gauged on seven aesthetic attributes (melodic originality, melodic variation, repertoire popularity, aesthetic significance, listener accessibility, performance duration, and thematic size), and potential last-works effects were operationally defined two separate ways (linearly and exponentially). Statistical controls were introduced for both longitudinal changes (linear, quadratic, and cubic age functions) and individual differences (eminence and lifetime productivity). Hierarchical regression analyses indicated that composers' swan songs tend to score lower in melodic originality and performance duration but higher in repertoire popularity and aesthetic significance. These last-works effects survive control for total compositional output, eminence, and most significantly, the composer's age when the last works were created.

Ideology and gender: observers' system justification and targets' gender as interactive predictors of citizenship expectations.

PubMed

Chiaburu, Dan S; Harris, T Brad; Smith, Troy A

2014-01-01

We integrate system justification and social role theory to explain how observers' system justification and target employees' gender interact to predict observers' expectations of targets' sportsmanship citizenship behaviors. In contrast with social role theory predictions, observers did not expect greater levels of sportsmanship from women compared to men. Yet observers expected more sportsmanship from women (a) when observers were ideologically motivated by gender-specific beliefs (gender-specific system justification; Study 1) and (b) when system justification was cued experimentally (Study 2). A heretofore-unexamined aspect, observers' ideology, modifies their expectations of sportsmanship citizenship across target genders. This has implications for system justification, social role, and organizational citizenship theoretical perspectives.

Application of the marine Ex-Bz transient system for delineating near shore resistive targets

NASA Astrophysics Data System (ADS)

Levi, Eldad; Goldman, Mark

2017-09-01

Under certain conditions, multidimensional coastal effect significantly enhances relative target response of the broadside transient marine Ex-Bz system. The effect is caused by a redistribution of the induced currents between the resistive target and the sea bottom compared to that existing in a 1-D geometry. As a result, the effect strongly depends on specific geoelectric conditions in the near-shore environment. The first study of the effect in the Mediterranean coast of central Israel was addressing shallow groundwater problem under specific geoelectric, hydrogeological and geomorphological conditions. Under different conditions (e.g. deep targets and sharp near-shore bathymetry), the influence of the effect on target response might be significantly different. More general analysis carried out in this study comprises various geoelectric scenarios that include both shallow and deep resistive targets at different distances from the shore line as well as various geometries of the target and the near-shore bathymetry. The study includes three major exploration aspects of the system, namely signal detectability, lateral and vertical resolution. Taking into account poor lateral resolution of the classical frequency domain CSEM and the limited application in shallow sea, the described broadside transient Ex-Bz system might represent a desired alternative for delineating shallow and deep resistive targets in transition zone.

A versatile targeting system with lentiviral vectors bearing the biotin-adaptor peptide

PubMed Central

Morizono, Kouki; Xie, Yiming; Helguera, Gustavo; Daniels, Tracy R.; Lane, Timothy F.; Penichet, Manuel L.; Chen, Irvin S. Y.

2010-01-01

Background Targeted gene transduction in vivo is the ultimate preferred method for gene delivery. We previously developed targeting lentiviral vectors that specifically recognize cell surface molecules with conjugated antibodies and mediate targeted gene transduction both in vitro and in vivo. Although effective in some experimental settings, the conjugation of virus with antibodies is mediated by the interaction between protein A and the Fc region of antibodies, which is not as stable as covalent conjugation. We have now developed a more stable conjugation strategy utilizing the interaction between avidin and biotin. Methods We inserted the biotin-adaptor-peptide, which was biotinylated by secretory biotin ligase at specific sites, into our targeting envelope proteins, enabling conjugation of the pseudotyped virus with avidin, streptavidin or neutravidin. Results When conjugated with avidin-antibody fusion proteins or the complex of avidin and biotinylated targeting molecules, the vectors could mediate specific transduction to targeted cells recognized by the targeting molecules. When conjugated with streptavidin-coated magnetic beads, transduction by the vectors was targeted to the locations of magnets. Conclusions This targeting vector system can be used for broad applications of targeted gene transduction using biotinylated targeting molecules or targeting molecules fused with avidin. PMID:19455593

Targeted mutagenesis in cotton (Gossypium hirsutum L.) using the CRISPR/Cas9 system

PubMed Central

Chen, Xiugui; Lu, Xuke; Shu, Na; Wang, Shuai; Wang, Junjuan; Wang, Delong; Guo, Lixue; Ye, Wuwei

2017-01-01

The CRISPR (Clustered Regularly Interspaced Short Palindromic Repeats)/Cas9 system has been widely used for genome editing in various plants because of its simplicity, high efficiency and design flexibility. However, to our knowledge, there is no report on the application of CRISPR/Cas9-mediated targeted mutagenesis in cotton. Here, we report the genome editing and targeted mutagenesis in upland cotton (Gossypium hirsutum L., hereafter cotton) using the CRISPR/Cas9 system. We designed two guide RNAs to target distinct sites of the cotton Cloroplastos alterados 1 (GhCLA1) and vacuolar H+-pyrophosphatase (GhVP) genes. Mutations in these two genes were detected in cotton protoplasts. Most of the mutations were nucleotide substitutions, with one nucleotide insertion and one substitution found in GhCLA1 and one deletion found in GhVP in cotton protoplasts. Subsequently, the two vectors were transformed into cotton shoot apexes through Agrobacterium-mediated transformation, resulting in efficient target gene editing. Most of the mutations were nucleotide deletions, and the mutation efficiencies were 47.6–81.8% in transgenic cotton plants. Evaluation using restriction-enzyme-PCR assay and sequence analysis detected no off-target mutations. Our results indicated that the CRISPR/Cas9 system was an efficient and specific tool for targeted mutagenesis of the cotton genome. PMID:28287154

An underwater ranging system based on photoacoustic effect occurring on target surface

NASA Astrophysics Data System (ADS)

Ni, Kai; Hu, Kai; Li, Xinghui; Wang, Lidai; Zhou, Qian; Wang, Xiaohao

2016-11-01

In this paper, an underwater ranging system based on photoacoustic effect occurring on target surface is proposed. In this proposal, laser pulse generated by blue-green laser is directly incident on target surface, where the photoacoustic effect occurs and a sound source is formed. And then the sound wave which is also called photoacoustic signal is received by the ultrasonic receiver after passing through water. According to the time delay between transmitting laser and receiving photoacoustic signal, and sound velocity in water, the distance between the target and the ultrasonic receiver can be calculated. Differing from underwater range finding by only laser, this approach can avoid backscattering of laser beam, so easier to implement. Experimental system according to this principle has been constructed to verify the feasibility of this technology. The experimental results showed that a ranging accuracy of 1 mm can be effectively achieved when the target is close to the ultrasonic receiver.

A time-of-flight system for the external target facility

NASA Astrophysics Data System (ADS)

Zhang, Xue-Heng; Yu, Yu-Hong; Sun, Zhi-Yu; Mao, Rui-Shi; Wang, Shi-Tao; Zhou, Yong; Yan, Duo; Liu, Long-Xiang

2013-05-01

A time-of-flight system with a plastic scintillator coupled to photomultipliers is developed for the external target facility (ETF). This system can satisfy the requirement of an ultrahigh vacuum (~10-9 mbar), a high counting rate (~106 particles per second) and a magnetic field environment. In the beam test experiment, a total time resolution of 580 ps FWHM was obtained for the whole system, and nuclei with a mass of up to 80 could be identified using this system.

Generating target system specifications from a domain model using CLIPS

NASA Technical Reports Server (NTRS)

Sugumaran, Vijayan; Gomaa, Hassan; Kerschberg, Larry

1991-01-01

The quest for reuse in software engineering is still being pursued and researchers are actively investigating the domain modeling approach to software construction. There are several domain modeling efforts reported in the literature and they all agree that the components that are generated from domain modeling are more conducive to reuse. Once a domain model is created, several target systems can be generated by tailoring the domain model or by evolving the domain model and then tailoring it according to the specified requirements. This paper presents the Evolutionary Domain Life Cycle (EDLC) paradigm in which a domain model is created using multiple views, namely, aggregation hierarchy, generalization/specialization hierarchies, object communication diagrams and state transition diagrams. The architecture of the Knowledge Based Requirements Elicitation Tool (KBRET) which is used to generate target system specifications is also presented. The preliminary version of KBRET is implemented in the C Language Integrated Production System (CLIPS).

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.

Interacting with target tracking algorithms in a gaze-enhanced motion video analysis system

NASA Astrophysics Data System (ADS)

Hild, Jutta; Krüger, Wolfgang; Heinze, Norbert; Peinsipp-Byma, Elisabeth; Beyerer, Jürgen

2016-05-01

Motion video analysis is a challenging task, particularly if real-time analysis is required. It is therefore an important issue how to provide suitable assistance for the human operator. Given that the use of customized video analysis systems is more and more established, one supporting measure is to provide system functions which perform subtasks of the analysis. Recent progress in the development of automated image exploitation algorithms allow, e.g., real-time moving target tracking. Another supporting measure is to provide a user interface which strives to reduce the perceptual, cognitive and motor load of the human operator for example by incorporating the operator's visual focus of attention. A gaze-enhanced user interface is able to help here. This work extends prior work on automated target recognition, segmentation, and tracking algorithms as well as about the benefits of a gaze-enhanced user interface for interaction with moving targets. We also propose a prototypical system design aiming to combine both the qualities of the human observer's perception and the automated algorithms in order to improve the overall performance of a real-time video analysis system. In this contribution, we address two novel issues analyzing gaze-based interaction with target tracking algorithms. The first issue extends the gaze-based triggering of a target tracking process, e.g., investigating how to best relaunch in the case of track loss. The second issue addresses the initialization of tracking algorithms without motion segmentation where the operator has to provide the system with the object's image region in order to start the tracking algorithm.

A Visual Language for Composable Simulation Scenarios

DTIC Science & Technology

2003-03-01

introduced by combining components of different levels of abstraction. However, the ideas presented in this research are applicable to all levels of...mission” [DMS95]. Finally, theater/campaign- level models predict the “outcomes of joint/ combined forces in a theatre/campaign level conflict” [DMS95...Other articles discussing composable simulation also gave more definitions and properties of components [DMS02d], [DMS02e], [BID00]. However, despite

Study on a novel laser target detection system based on software radio technique

NASA Astrophysics Data System (ADS)

Song, Song; Deng, Jia-hao; Wang, Xue-tian; Gao, Zhen; Sun, Ji; Sun, Zhi-hui

2008-12-01

This paper presents that software radio technique is applied to laser target detection system with the pseudo-random code modulation. Based on the theory of software radio, the basic framework of the system, hardware platform, and the implementation of the software system are detailed. Also, the block diagram of the system, DSP circuit, block diagram of the pseudo-random code generator, and soft flow diagram of signal processing are designed. Experimental results have shown that the application of software radio technique provides a novel method to realize the modularization, miniaturization and intelligence of the laser target detection system, and the upgrade and improvement of the system will become simpler, more convenient, and cheaper.

In fatal pursuit of immortal fame: Peer competition and early mortality of music composers.

PubMed

Borowiecki, Karol Jan; Kavetsos, Georgios

2015-06-01

We investigate the impact of peer competition on longevity using a unique historical data set of 144 prominent music composers born in the 19th century. We approximate for peer competition measuring (a) the number or (b) the share of composers located in the same area and time, (c) the time spent in one of the main cities for classical music, and (d) the quality of fellow composers. These measures suggest that composers' longevity is reduced, if they located in agglomerations with a larger group of peers or of a higher quality. The point estimates imply that, all else equal, a one percent increase in the number of composers reduces composer longevity by ∼ 7.2 weeks. Our analysis showed that the utilized concentration measures are stronger than the personal factors in determining longevity, indicating that individuals' backgrounds have minimal impact on mitigating the effect of experienced peer pressure. The negative externality of peer competition is experienced in all cities, fairly independent of their population size. Our results are reaffirmed using an instrumental variable approach and are consistent throughout a range of robustness tests. In addition to the widely known economic benefits associated with competition, these findings suggest that significant negative welfare externalities exist as well. Copyright © 2015 Elsevier Ltd. All rights reserved.

Non-Logical Discourse: Key to the Composing Process?

ERIC Educational Resources Information Center

Poulsen, Richard C.

One niche in which scholars have not looked for keys to the composing process is the sometimes illusory but vital area of nonlogical discourse, which includes fantasy, hallucination, dream, reverie, vision, trance, and meditation. Abundant evidence exists about the genesis, importance, and use of nonlogical discourse, but this evidence comes…

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

Composing the theme of city to be diverse and sustainable

NASA Astrophysics Data System (ADS)

Wiranegara, H. W.

2018-01-01

To give a path for developing a city needs a theme. City’s goal stated in a document of a spatial plan were too broad and insufficient detail in giving a direction. To make more detail and precise, every city has to compose a city theme. It is developed based on the potential, the uniqueness, the excellence, and the sustainability of its human resources, natural resources, and man-made resources. An integration among the three of resources which have the highest score become a theme of the city. The aim of this research was to formulate the conceptual framework to compose a city theme. The research design was the interview survey in Banda Aceh, Banjarmasin, and Kupang. Informants were the government officials, academics, figures, the private sector and public who considered related to the intended information being collected. Having set the conceptual framework, the interview directed to check the implementation in realities. The result was that the conceptual framework could accommodate the phenomenon of composing the theme of the city. Yet, it was a preliminary in nature and needed more research to get a complete result.

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

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.

Chromosomal targeting by CRISPR-Cas systems can contribute to genome plasticity in bacteria

PubMed Central

Dy, Ron L; Pitman, Andrew R; Fineran, Peter C

2013-01-01

The clustered regularly interspaced short palindromic repeats (CRISPR) and their associated (Cas) proteins form adaptive immune systems in bacteria to combat phage and other foreign genetic elements. Typically, short spacer sequences are acquired from the invader DNA and incorporated into CRISPR arrays in the bacterial genome. Small RNAs are generated that contain these spacer sequences and enable sequence-specific destruction of the foreign nucleic acids. Occasionally, spacers are acquired from the chromosome, which instead leads to targeting of the host genome. Chromosomal targeting is highly toxic to the bacterium, providing a strong selective pressure for a variety of evolutionary routes that enable host cell survival. Mutations that inactivate the CRISPR-Cas functionality, such as within the cas genes, CRISPR repeat, protospacer adjacent motifs (PAM), and target sequence, mediate escape from toxicity. This self-targeting might provide some explanation for the incomplete distribution of CRISPR-Cas systems in less than half of sequenced bacterial genomes. More importantly, self-genome targeting can cause large-scale genomic alterations, including remodeling or deletion of pathogenicity islands and other non-mobile chromosomal regions. While control of horizontal gene transfer is perceived as their main function, our recent work illuminates an alternative role of CRISPR-Cas systems in causing host genomic changes and influencing bacterial evolution. PMID:24251073

Is the Higgs boson composed of neutrinos?

DOE PAGES

Krog, Jens; Hill, Christopher T.

2015-11-09

We show that conventional Higgs compositeness conditions can be achieved by the running of large Higgs-Yukawa couplings involving right-handed neutrinos that become active at ~10 13–10 14 GeV. Together with a somewhat enhanced quartic coupling arising by a Higgs portal interaction to a dark matter sector, we can obtain a Higgs boson composed of neutrinos. Furthermore, this is a “next-to-minimal” dynamical electroweak symmetry breaking scheme.

Composing Songs for Teaching Science to College Students

ERIC Educational Resources Information Center

Yee Pinn Tsin, Isabel

2015-01-01

Recent studies have shown that songs may enhance learning as they function as mnemonic devices to increase memorability. In this research, songs based on the more difficult subtopics in Chemistry were composed, encompassing many formulas, equations and facts to be remembered. This technique of song composition can be used in any subject, any point…

When Did Classic Composers Make Their Best Work?

ERIC Educational Resources Information Center

Franses, Philip Hans

2016-01-01

This Research Note shows that classic composers created their best works when they were at a similar age when creators in other domains did their best work, namely when they were at an age that represented around 60% of their life span. This finding is very similar to earlier results for painters and authors.

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.

Systems Pharmacology-Based Discovery of Natural Products for Precision Oncology Through Targeting Cancer Mutated Genes.

PubMed

Fang, J; Cai, C; Wang, Q; Lin, P; Zhao, Z; Cheng, F

2017-03-01

Massive cancer genomics data have facilitated the rapid revolution of a novel oncology drug discovery paradigm through targeting clinically relevant driver genes or mutations for the development of precision oncology. Natural products with polypharmacological profiles have been demonstrated as promising agents for the development of novel cancer therapies. In this study, we developed an integrated systems pharmacology framework that facilitated identifying potential natural products that target mutated genes across 15 cancer types or subtypes in the realm of precision medicine. High performance was achieved for our systems pharmacology framework. In case studies, we computationally identified novel anticancer indications for several US Food and Drug Administration-approved or clinically investigational natural products (e.g., resveratrol, quercetin, genistein, and fisetin) through targeting significantly mutated genes in multiple cancer types. In summary, this study provides a powerful tool for the development of molecularly targeted cancer therapies through targeting the clinically actionable alterations by exploiting the systems pharmacology of natural products. © 2017 The Authors CPT: Pharmacometrics & Systems Pharmacology published by Wiley Periodicals, Inc. on behalf of American Society for Clinical Pharmacology and Therapeutics.

Transforming Experience: Negotiations of Sexual Identity in the Composing Processes of Gay Men

ERIC Educational Resources Information Center

Berry, William F.

2012-01-01

Negotiating meaning, knowledge, and identity is fundamental to composing processes. These negotiations occur both individually and socially for writers. Sexual identity is an intrinsic part of these negotiations, but is often overlooked by researchers. This study explored the phenomenon of negotiating sexual identity in the composing processes of…

Targeting bacterial secretion systems: benefits of disarmament in the microcosm.

PubMed

Baron, Christian; Coombes, Brian

2007-03-01

Secretion systems are used by many bacterial pathogens for the delivery of virulence factors to the extracellular space or directly into host cells. They are attractive targets for the development of novel anti-virulence drugs as their inactivation would lead to pathogen attenuation or avirulence, followed by clearance of the bacteria by the immune system. This review will present the state of knowledge on the assembly and function of type II, type III and type IV secretion systems in Gram-negative bacteria focusing on insights provided by structural analyses of several key components. The suitability of transcription factors regulating the expression of secretion system components and of ATPases, lytic transglycosylases and protein assembly factors as drug targets will be discussed. Recent progress using innovative in vivo as well as in vitro screening strategies led to a first set of secretion system inhibitors with potential for further development as anti-infectives. The discovery of such inhibitors offers exciting and innovative opportunities to further develop these anti-virulence drugs into monotherapy or in combination with classical antibiotics. Bacterial growth per se would not be inhibited by such drugs so that the selection for mutations causing resistance could be reduced. Secretion system inhibitors may therefore avoid many of the problems associated with classical antibiotics and may constitute a valuable addition to our arsenal for the treatment of bacterial infections.

"And Now That I Know Them": Composing Mutuality in a Service Learning Course.

ERIC Educational Resources Information Center

Welch, Nancy

2002-01-01

Turns to contemporary feminist object-relations theory to understand the efforts of students in a service learning course, to push beyond the usual subject-object, active-passive dualisms that pervade community-based literacy projects, and to compose instead complex representations in which all participants are composed as active, as knowing, and…

Environmental Management System Objectives & Targets Results Summary - FY 2015.

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

Vetter, Douglas W.

2016-02-01

Sandia National Laboratories (SNL) Environmental Management System is the integrated approach for members of the workforce to identify and manage environmental risks. Each Fiscal Year (FY) SNL performs an analysis to identify environmental aspects, and the environmental programs associated with them are charged with the task of routinely monitoring and measuring the objectives and targets that are established to mitigate potential impacts of SNL's operations on the environment. An annual summary of the results achieved towards meeting established Sandia Corporation and SNL Site-specific objectives and targets provides a connection to, and rational for, annually revised environmental aspects. The purpose ofmore » this document is to summarize the results achieved and documented in FY 2015.« less

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

Review of the Composability Problem for System Evaluation

DTIC Science & Technology

2004-11-01

burden estimate or any other aspect of this collection of information, including suggestions for reducing this burden, to Washington Headquarters Services ...directory services (e.g., the Lightweight Directory Access Protocol (LDAP)), authentication (e.g., Kerberos), databases, user interface (e.g...exemplifies this type of development, by its use of commercial components and systems for authentication, access management, directory services

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

Fuzzy System-Based Target Selection for a NIR Camera-Based Gaze Tracker

PubMed Central

Naqvi, Rizwan Ali; Arsalan, Muhammad; Park, Kang Ryoung

2017-01-01

Gaze-based interaction (GBI) techniques have been a popular subject of research in the last few decades. Among other applications, GBI can be used by persons with disabilities to perform everyday tasks, as a game interface, and can play a pivotal role in the human computer interface (HCI) field. While gaze tracking systems have shown high accuracy in GBI, detecting a user’s gaze for target selection is a challenging problem that needs to be considered while using a gaze detection system. Past research has used the blinking of the eyes for this purpose as well as dwell time-based methods, but these techniques are either inconvenient for the user or requires a long time for target selection. Therefore, in this paper, we propose a method for fuzzy system-based target selection for near-infrared (NIR) camera-based gaze trackers. The results of experiments performed in addition to tests of the usability and on-screen keyboard use of the proposed method show that it is better than previous methods. PMID:28420114

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

Laser-induced disruption of systemically administered liposomes for targeted drug delivery

NASA Astrophysics Data System (ADS)

Mackanos, Mark A.; Larabi, Malika; Shinde, Rajesh; Simanovskii, Dmitrii M.; Guccione, Samira; Contag, Christopher H.

2009-07-01

Liposomal formulations of drugs have been shown to enhance drug efficacy by prolonging circulation time, increasing local concentration and reducing off-target effects. Controlled release from these formulations would increase their utility, and hyperthermia has been explored as a stimulus for targeted delivery of encapsulated drugs. Use of lasers as a thermal source could provide improved control over the release of the drug from the liposomes with minimal collateral tissue damage. Appropriate methods for assessing local release after systemic delivery would aid in testing and development of better formulations. We use in vivo bioluminescence imaging to investigate the spatiotemporal distribution of luciferin, used as a model small molecule, and demonstrate laser-induced release from liposomes in animal models after systemic delivery. These liposomes were tested for luciferin release between 37 and 45 °C in PBS and serum using bioluminescence measurements. In vivo studies were performed on transgenic reporter mice that express luciferase constitutively throughout the body, thus providing a noninvasive readout for controlled release following systemic delivery. An Nd:YLF laser was used (527 nm) to heat tissues and induce rupture of the intravenously delivered liposomes in target tissues. These data demonstrate laser-mediated control of small molecule delivery using thermally sensitive liposomal formulations.

Active imaging system performance model for target acquisition

NASA Astrophysics Data System (ADS)

Espinola, Richard L.; Teaney, Brian; Nguyen, Quang; Jacobs, Eddie L.; Halford, Carl E.; Tofsted, David H.

2007-04-01

The U.S. Army RDECOM CERDEC Night Vision & Electronic Sensors Directorate has developed a laser-range-gated imaging system performance model for the detection, recognition, and identification of vehicle targets. The model is based on the established US Army RDECOM CERDEC NVESD sensor performance models of the human system response through an imaging system. The Java-based model, called NVLRG, accounts for the effect of active illumination, atmospheric attenuation, and turbulence effects relevant to LRG imagers, such as speckle and scintillation, and for the critical sensor and display components. This model can be used to assess the performance of recently proposed active SWIR systems through various trade studies. This paper will describe the NVLRG model in detail, discuss the validation of recent model components, present initial trade study results, and outline plans to validate and calibrate the end-to-end model with field data through human perception testing.

Targeted Mutagenesis in Rice Using TALENs and the CRISPR/Cas9 System.

PubMed

Endo, Masaki; Nishizawa-Yokoi, Ayako; Toki, Seiichi

2016-01-01

Sequence-specific nucleases (SSNs), such as zinc-finger nucleases (ZFNs), transcription activator-like effector nucleases (TALENs), and the clustered regularly interspersed short palindromic repeats (CRISPR)/CRISPR-associated protein 9 nuclease (Cas9) system, are powerful tools for understanding gene function and for developing novel traits in plants. In plant species for which transformation and regeneration systems using protoplasts are not yet established, direct delivery to nuclei of SSNs either in the form of RNA or protein is difficult. Thus, Agrobacterium-mediated transformation of SSN expression constructs in cultured cells is a practical means of delivering targeted mutagenesis in some plant species including rice. Because targeted mutagenesis occurs stochastically in transgenic cells and SSN-mediated targeted mutagenesis often leads to no selectable phenotype, identification of highly mutated cell lines is a critical step in obtaining regenerated plants with desired mutations.

Programmable Removal of Bacterial Strains by Use of Genome-Targeting CRISPR-Cas Systems

PubMed Central

Gomaa, Ahmed A.; Klumpe, Heidi E.; Luo, Michelle L.; Selle, Kurt; Barrangou, Rodolphe; Beisel, Chase L.

2014-01-01

ABSTRACT CRISPR (clustered regularly interspaced short palindromic repeats)-Cas (CRISPR-associated) systems in bacteria and archaea employ CRISPR RNAs to specifically recognize the complementary DNA of foreign invaders, leading to sequence-specific cleavage or degradation of the target DNA. Recent work has shown that the accidental or intentional targeting of the bacterial genome is cytotoxic and can lead to cell death. Here, we have demonstrated that genome targeting with CRISPR-Cas systems can be employed for the sequence-specific and titratable removal of individual bacterial strains and species. Using the type I-E CRISPR-Cas system in Escherichia coli as a model, we found that this effect could be elicited using native or imported systems and was similarly potent regardless of the genomic location, strand, or transcriptional activity of the target sequence. Furthermore, the specificity of targeting with CRISPR RNAs could readily distinguish between even highly similar strains in pure or mixed cultures. Finally, varying the collection of delivered CRISPR RNAs could quantitatively control the relative number of individual strains within a mixed culture. Critically, the observed selectivity and programmability of bacterial removal would be virtually impossible with traditional antibiotics, bacteriophages, selectable markers, or tailored growth conditions. Once delivery challenges are addressed, we envision that this approach could offer a novel means to quantitatively control the composition of environmental and industrial microbial consortia and may open new avenues for the development of “smart” antibiotics that circumvent multidrug resistance and differentiate between pathogenic and beneficial microorganisms. PMID:24473129

Nanodelivery Systems as New Tools for Immunostimulant or Vaccine Administration: Targeting the Fish Immune System

PubMed Central

Ji, Jie; Torrealba, Debora; Ruyra, Àngels; Roher, Nerea

2015-01-01

Fish disease treatments have progressed significantly over the last few years and have moved from the massive use of antibiotics to the development of vaccines mainly based on inactivated bacteria. Today, the incorporation of immunostimulants and antigens into nanomaterials provide us with new tools to enhance the performance of immunostimulation. Nanoparticles are dispersions or solid particles designed with specific physical properties (size, surface charge, or loading capacity), which allow controlled delivery and therefore improved targeting and stimulation of the immune system. The use of these nanodelivery platforms in fish is in the initial steps of development. Here we review the advances in the application of nanoparticles to fish disease prevention including: the type of biomaterial, the type of immunostimulant or vaccine loaded into the nanoparticles, and how they target the fish immune system. PMID:26492276

Recent Advances in Nanoparticle-Based Targeted Drug-Delivery Systems Against Cancer and Role of Tumor Microenvironment.

PubMed

Ashfaq, Usman Ali; Riaz, Muhammad; Yasmeen, Erum; Yousaf, Muhammad Zubair

2017-01-01

Cancer is one of the major causes of death worldwide. The silent activation of cellular factors responsible for deviation from normal regulatory pathways leads to the development of cancer. Nano-biotechnology is a novel drug-delivery system with high potential of efficacy and accuracy to target lethal cancers. Various biocompatible nanoparticle (NP)-based drug-delivery systems such as liposomes, dendrimers, micelles, silica, quantum dots, and magnetic, gold, and carbon nanotubes have already been reported for successful targeted cancer treatment. NPs are functionalized with different biological molecules, peptides, antibody, and protein ligands for targeted drug delivery. These systems include a hydrophilic central core, a target-oriented biocompatible outer layer, and a middle hydrophobic core where the drug destined to reach target site resides. Most of the NPs have the ability to maintain their structural shape and are constructed according to the cancer microenvironment. The self-assembling and colloidal properties of NPs have caused them to become the best vehicles for targeted drug delivery. The tumor microenvironment (TME) plays a major role in cancer progression, detection, and treatment. Due to its continuous complex behavior, the TME can hinder delivery systems, thus halting cancer treatment. Nonetheless, a successful biophysiological interaction between the NPs and the TME results in targeted release of drugs. Currently, a number of drugs and NP-based delivery systems against cancer are in clinical and preclinical trials and a few have been approved by Food and Drug Administration (FDA); for example: taxol, doxil, cerubidine, and adrucil. This review summarizes topical advances about the drugs being used for cancer treatment, their targeted delivery systems based on NPs, and the role of TME in this connection.

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

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.

What Reader-Oriented Literary and Cognitive Theories Have to Give to Composing Theory.

ERIC Educational Resources Information Center

Liebman-Kleine, JoAnne

In developing an interactive model of composing, this paper discusses three groups of reader-oriented theories, each of which provides composing theorists with some research and theory to use in developing such a model. First the paper discusses the main principle of the literary reader-response theorists--that the meaning and value of texts do…

The composition of precarity: 'emerging' composers' experiences of opportunity culture in contemporary classical music.

PubMed

Smith, Neil Thomas; Thwaites, Rachel

2018-02-28

This paper examines the precarious working lives of 'emerging' composers attempting to build a career in the world of new classical music in the UK. This topic is approached by considering the 'composition opportunity', success in which is seen as an important element in 'making it' in this sphere. We argue that such schemes in fact manifest a crucial tension in the nature of artistic labour, and are, at the very least, problematic in their function as conduits towards full professional identity. They may instead act to maintain the precarious working situation of composers in a neoliberal age. The working lives of artists are all too rarely illuminated, and new music composers are no exception; this survey of 47 emerging composers is the largest study of such individuals in the UK. © London School of Economics and Political Science 2018.

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

An Analytic Model for the Success Rate of a Robotic Actuator System in Hitting Random Targets.

PubMed

Bradley, Stuart

2015-11-20

Autonomous robotic systems are increasingly being used in a wide range of applications such as precision agriculture, medicine, and the military. These systems have common features which often includes an action by an "actuator" interacting with a target. While simulations and measurements exist for the success rate of hitting targets by some systems, there is a dearth of analytic models which can give insight into, and guidance on optimization, of new robotic systems. The present paper develops a simple model for estimation of the success rate for hitting random targets from a moving platform. The model has two main dimensionless parameters: the ratio of actuator spacing to target diameter; and the ratio of platform distance moved (between actuator "firings") to the target diameter. It is found that regions of parameter space having specified high success are described by simple equations, providing guidance on design. The role of a "cost function" is introduced which, when minimized, provides optimization of design, operating, and risk mitigation costs.

All-reflective optical target illumination system with high numerical aperture

DOEpatents

Sigler, Robert D.

1978-01-01

An all-reflective optical system for providing illumination of a target focal region at high numerical aperture from a pair of co-axially, confluent collimated light beams. A target cavity is defined by a pair of opposed inner ellipsoidal reflectors having respective first focal points within a target region and second focal points at a vertex opening in the opposing reflector. Outwardly of each inner reflector is the opposed combination of a spherical reflector, and an outer generally ellipsoidal reflector having an aberrated first focal point coincident with the focus of the opposing spherical reflector and a second focal point coincident with the second focal point of the opposing inner ellipsoidal reflector through a vertex opening in the spherical reflector. The confluent collimated beams are incident through vertex openings in the outer ellipsoidal reflectors onto respective opposing spherical reflectors. Each beam is reflected by the associated spherical reflector onto the opposing outer ellipsoidal reflector and focused thereby onto the opposing inner ellipsoidal reflector, and then onto the target region.

[The research on a pocket microcontroller system for target controlled infusion].

PubMed

Cheng, Yu-Ke; Zhang, Xin-An; Zhang, Yan-Wu; Wu, Qun-Ling; Dou, Jian-Hong; Wang, Rou-Shong

2005-05-01

This paper present a microcontroller system for target controlled infusion according to pharmacodynamic parameters of intravenous anesthetics. It can control the depth of anesthesia by adjusting the level of plasma concentrations. The system has the advantages of high precision, extended function and easy operation. It has been now used in the clinical anesthesia.

Staircase-scene-based nonuniformity correction in aerial point target detection systems.

PubMed

Huo, Lijun; Zhou, Dabiao; Wang, Dejiang; Liu, Rang; He, Bin

2016-09-01

Focal-plane arrays (FPAs) are often interfered by heavy fixed-pattern noise, which severely degrades the detection rate and increases the false alarms in airborne point target detection systems. Thus, high-precision nonuniformity correction is an essential preprocessing step. In this paper, a new nonuniformity correction method is proposed based on a staircase scene. This correction method can compensate for the nonlinear response of the detector and calibrate the entire optical system with computational efficiency and implementation simplicity. Then, a proof-of-concept point target detection system is established with a long-wave Sofradir FPA. Finally, the local standard deviation of the corrected image and the signal-to-clutter ratio of the Airy disk of a Boeing B738 are measured to evaluate the performance of the proposed nonuniformity correction method. Our experimental results demonstrate that the proposed correction method achieves high-quality corrections.

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.

Targeted gene deletion of miRNAs in mice by TALEN system.

PubMed

Takada, Shuji; Sato, Tempei; Ito, Yoshiaki; Yamashita, Satoshi; Kato, Tomoko; Kawasumi, Miyuri; Kanai-Azuma, Masami; Igarashi, Arisa; Kato, Tomomi; Tamano, Moe; Asahara, Hiroshi

2013-01-01

Mice are among the most valuable model animal species with an enormous amount of heritage in genetic modification studies. However, targeting genes in mice is sometimes difficult, especially for small genes, such as microRNAs (miRNAs) and targeting genes in repeat sequences. Here we optimized the application of TALEN system for mice and successfully obtained gene targeting technique in mice for intergenic region and series of microRNAs. Microinjection of synthesized RNA of TALEN targeting each gene in one cell stage of embryo was carried out and injected oocytes were transferred into pseudopregnant ICR female mice, producing a high success rate of the targeted deletion of miRNA genes. In our condition, TALEN RNA without poly(A) tail worked better than that of with poly(A) tail. This mutated allele in miRNA was transmitted to the next generation, suggesting the successful germ line transmission of this targeting method. Consistent with our notion of miRNAs maturation mechanism, in homozygous mutant mice of miR-10a, the non- mutated strand of miRNAs expression was completely diminished. This method will lead us to expand and accelerate our genetic research using mice in a high throughput way.

Cetuximab-conjugated nanodiamonds drug delivery system for enhanced targeting therapy and 3D Raman imaging.

PubMed

Li, Dandan; Chen, Xin; Wang, Hong; Liu, Jie; Zheng, Meiling; Fu, Yang; Yu, Yuan; Zhi, Jinfang

2017-12-01

In this study, a multicomponent nanodiamonds (NDs)-based targeting drug delivery system, cetuximab-NDs-cisplatin bioconjugate, combining both specific targeting and enhanced therapeutic efficacy capabilities, is developed and characterized. The specific targeting ability of cetuximab-NDs-cisplatin system on human liver hepatocellular carcinoma (HepG2) cells is evaluated through epidermal growth factor receptor (EGFR) blocking experiments, since EGFR is over-expressed on HepG2 cell membrane. Besides, cytotoxic evaluation confirms that cetuximab-NDs-cisplatin system could significantly inhibit the growth of HepG2 cells, and the therapeutic activity of this system is proven to be better than that of both nonspecific NDs-cisplatin conjugate and specific EGF-NDs-cisplatin conjugate. Furthermore, a 3-dimensional (3D) Raman imaging technique is utilized to visualize the targeting efficacy and enhanced internalization of cetuximab-NDs-cisplatin system in HepG2 cells, using the NDs existing in the bioconjugate as Raman probes, based on the characteristic Raman signal of NDs at 1332 cm -1 . These advantageous properties of cetuximab-NDs-cisplatin system propose a prospective imaging and treatment tool for further diagnostic and therapeutic purposes. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

DrugECs: An Ensemble System with Feature Subspaces for Accurate Drug-Target Interaction Prediction

PubMed Central

Jiang, Jinjian; Wang, Nian; Zhang, Jun

2017-01-01

Background Drug-target interaction is key in drug discovery, especially in the design of new lead compound. However, the work to find a new lead compound for a specific target is complicated and hard, and it always leads to many mistakes. Therefore computational techniques are commonly adopted in drug design, which can save time and costs to a significant extent. Results To address the issue, a new prediction system is proposed in this work to identify drug-target interaction. First, drug-target pairs are encoded with a fragment technique and the software “PaDEL-Descriptor.” The fragment technique is for encoding target proteins, which divides each protein sequence into several fragments in order and encodes each fragment with several physiochemical properties of amino acids. The software “PaDEL-Descriptor” creates encoding vectors for drug molecules. Second, the dataset of drug-target pairs is resampled and several overlapped subsets are obtained, which are then input into kNN (k-Nearest Neighbor) classifier to build an ensemble system. Conclusion Experimental results on the drug-target dataset showed that our method performs better and runs faster than the state-of-the-art predictors. PMID:28744468

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.

Orally active-targeted drug delivery systems for proteins and peptides.

PubMed

Li, Xiuying; Yu, Miaorong; Fan, Weiwei; Gan, Yong; Hovgaard, Lars; Yang, Mingshi

2014-09-01

In the past decade, extensive efforts have been devoted to designing 'active targeted' drug delivery systems (ATDDS) to improve oral absorption of proteins and peptides. Such ATDDS enhance cellular internalization and permeability of proteins and peptides via molecular recognition processes such as ligand-receptor or antigen-antibody interaction, and thus enhance drug absorption. This review focuses on recent advances with orally ATDDS, including ligand-protein conjugates, recombinant ligand-protein fusion proteins and ligand-modified carriers. In addition to traditional intestinal active transport systems of substrates and their corresponding receptors, transporters and carriers, new targets such as intercellular adhesion molecule-1 and β-integrin are also discussed. ATDDS can improve oral absorption of proteins and peptides. However, currently, no clinical studies on ATDDS for proteins and peptides are underway, perhaps due to the complexity and limited knowledge of transport mechanisms. Therefore, more research is warranted to optimize ATDDS efficiency.

Tracking Organs Composed of One or Multiple Regions Using Geodesic Active Region Models

NASA Astrophysics Data System (ADS)

Martínez, A.; Jiménez, J. J.

In radiotherapy treatment it is very important to find out the target organs on the medical image sequence in order to determine and apply the proper dose. The techniques to achieve this goal can be classified into extrinsic and intrinsic. Intrinsic techniques only use image processing with medical images associated to the radiotherapy treatment, as we deal in this chapter. To accurately perform this organ tracking it is necessary to find out segmentation and tracking models that were able to be applied to several image modalities involved on a radiotherapy session (CT See Modality , MRI , etc.). The movements of the organs are mainly affected by two factors: breathing and involuntary movements associated with the internal organs or patient positioning. Among the several alternatives to track the organs of interest, a model based on geodesic active regions is proposed. This model has been tested over CT images from the pelvic, cardiac, and thoracic area. A new model for the segmentation of organs composed by more than one region is proposed.

All-reflective optical target illumination system with high numerical aperture

DOEpatents

Thomas, Carlton E.; Sigler, Robert D.; Hoeger, John G.

1979-01-01

An all-reflective optical system for providing illumination of a target focal region at high numerical aperture from a pair of confluent collimated light beams. The collimated beams are each incident upon an associated concave eccentric pupil paraboloidal reflective surface, and thereby each focused through an opening in an associated outer ellipsoidal reflective surface onto a plane reflector. Each beam is reflected by its associated plane reflector onto the opposing concave surface of the outer ellipsoids to be focused through an opening in the plane surface onto an opposing inner concave ellipsoidal reflective surface, and thence onto the target region.

Chromosomal Targeting by the Type III-A CRISPR-Cas System Can Reshape Genomes in Staphylococcus aureus

PubMed Central

Guan, Jing; Wang, Wanying

2017-01-01

ABSTRACT CRISPR-Cas (clustered regularly interspaced short palindromic repeat [CRISPR]-CRISPR-associated protein [Cas]) systems can provide protection against invading genetic elements by using CRISPR RNAs (crRNAs) as a guide to locate and degrade the target DNA. CRISPR-Cas systems have been classified into two classes and five types according to the content of cas genes. Previous studies have indicated that CRISPR-Cas systems can avoid viral infection and block plasmid transfer. Here we show that chromosomal targeting by the Staphylococcus aureus type III-A CRISPR-Cas system can drive large-scale genome deletion and alteration within integrated staphylococcal cassette chromosome mec (SCCmec). The targeting activity of the CRISPR-Cas system is associated with the complementarity between crRNAs and protospacers, and 10- to 13-nucleotide truncations of spacers partially block CRISPR attack and more than 13-nucleotide truncation can fully abolish targeting, suggesting that a minimal length is required to license cleavage. Avoiding base pairings in the upstream region of protospacers is also necessary for CRISPR targeting. Successive trinucleotide complementarity between the 5′ tag of crRNAs and protospacers can disrupt targeting. Our findings reveal that type III-A CRISPR-Cas systems can modulate bacterial genome stability and may serve as a high-efficiency tool for deleting resistance or virulence genes in bacteria. IMPORTANCE Staphylococcus aureus is a pathogen that can cause a wide range of infections in humans. Studies have suggested that CRISPR-Cas systems can drive the loss of integrated mobile genetic elements (MGEs) by chromosomal targeting. Here we demonstrate that CRISPR-mediated cleavage contributes to the partial deletion of integrated SCCmec in methicillin-resistant S. aureus (MRSA), which provides a strategy for the treatment of MRSA infections. The spacer within artificial CRISPR arrays should contain more than 25 nucleotides for immunity, and

Chromosomal Targeting by the Type III-A CRISPR-Cas System Can Reshape Genomes in Staphylococcus aureus.

PubMed

Guan, Jing; Wang, Wanying; Sun, Baolin

2017-01-01

CRISPR-Cas (clustered regularly interspaced short palindromic repeat [CRISPR]-CRISPR-associated protein [Cas]) systems can provide protection against invading genetic elements by using CRISPR RNAs (crRNAs) as a guide to locate and degrade the target DNA. CRISPR-Cas systems have been classified into two classes and five types according to the content of cas genes. Previous studies have indicated that CRISPR-Cas systems can avoid viral infection and block plasmid transfer. Here we show that chromosomal targeting by the Staphylococcus aureus type III-A CRISPR-Cas system can drive large-scale genome deletion and alteration within integrated staphylococcal cassette chromosome mec (SCC mec ). The targeting activity of the CRISPR-Cas system is associated with the complementarity between crRNAs and protospacers, and 10- to 13-nucleotide truncations of spacers partially block CRISPR attack and more than 13-nucleotide truncation can fully abolish targeting, suggesting that a minimal length is required to license cleavage. Avoiding base pairings in the upstream region of protospacers is also necessary for CRISPR targeting. Successive trinucleotide complementarity between the 5' tag of crRNAs and protospacers can disrupt targeting. Our findings reveal that type III-A CRISPR-Cas systems can modulate bacterial genome stability and may serve as a high-efficiency tool for deleting resistance or virulence genes in bacteria. IMPORTANCE Staphylococcus aureus is a pathogen that can cause a wide range of infections in humans. Studies have suggested that CRISPR-Cas systems can drive the loss of integrated mobile genetic elements (MGEs) by chromosomal targeting. Here we demonstrate that CRISPR-mediated cleavage contributes to the partial deletion of integrated SCC mec in methicillin-resistant S. aureus (MRSA), which provides a strategy for the treatment of MRSA infections. The spacer within artificial CRISPR arrays should contain more than 25 nucleotides for immunity, and consecutive

Composing Music with Complex Networks

NASA Astrophysics Data System (ADS)

Liu, Xiaofan; Tse, Chi K.; Small, Michael

In this paper we study the network structure in music and attempt to compose music artificially. Networks are constructed with nodes and edges corresponding to musical notes and their co-occurrences. We analyze sample compositions from Bach, Mozart, Chopin, as well as other types of music including Chinese pop music. We observe remarkably similar properties in all networks constructed from the selected compositions. Power-law exponents of degree distributions, mean degrees, clustering coefficients, mean geodesic distances, etc. are reported. With the network constructed, music can be created by using a biased random walk algorithm, which begins with a randomly chosen note and selects the subsequent notes according to a simple set of rules that compares the weights of the edges, weights of the nodes, and/or the degrees of nodes. The newly created music from complex networks will be played in the presentation.

A new comprehensive method for detection of livestock-related pathogenic viruses using a target enrichment system.

PubMed

Oba, Mami; Tsuchiaka, Shinobu; Omatsu, Tsutomu; Katayama, Yukie; Otomaru, Konosuke; Hirata, Teppei; Aoki, Hiroshi; Murata, Yoshiteru; Makino, Shinji; Nagai, Makoto; Mizutani, Tetsuya

2018-01-08

We tested usefulness of a target enrichment system SureSelect, a comprehensive viral nucleic acid detection method, for rapid identification of viral pathogens in feces samples of cattle, pigs and goats. This system enriches nucleic acids of target viruses in clinical/field samples by using a library of biotinylated RNAs with sequences complementary to the target viruses. The enriched nucleic acids are amplified by PCR and subjected to next generation sequencing to identify the target viruses. In many samples, SureSelect target enrichment method increased efficiencies for detection of the viruses listed in the biotinylated RNA library. Furthermore, this method enabled us to determine nearly full-length genome sequence of porcine parainfluenza virus 1 and greatly increased Breadth, a value indicating the ratio of the mapping consensus length in the reference genome, in pig samples. Our data showed usefulness of SureSelect target enrichment system for comprehensive analysis of genomic information of various viruses in field samples. Copyright © 2017 Elsevier Inc. All rights reserved.

Cytotoxic chromosomal targeting by CRISPR/Cas systems can reshape bacterial genomes and expel or remodel pathogenicity islands.

PubMed

Vercoe, Reuben B; Chang, James T; Dy, Ron L; Taylor, Corinda; Gristwood, Tamzin; Clulow, James S; Richter, Corinna; Przybilski, Rita; Pitman, Andrew R; Fineran, Peter C

2013-04-01

In prokaryotes, clustered regularly interspaced short palindromic repeats (CRISPRs) and their associated (Cas) proteins constitute a defence system against bacteriophages and plasmids. CRISPR/Cas systems acquire short spacer sequences from foreign genetic elements and incorporate these into their CRISPR arrays, generating a memory of past invaders. Defence is provided by short non-coding RNAs that guide Cas proteins to cleave complementary nucleic acids. While most spacers are acquired from phages and plasmids, there are examples of spacers that match genes elsewhere in the host bacterial chromosome. In Pectobacterium atrosepticum the type I-F CRISPR/Cas system has acquired a self-complementary spacer that perfectly matches a protospacer target in a horizontally acquired island (HAI2) involved in plant pathogenicity. Given the paucity of experimental data about CRISPR/Cas-mediated chromosomal targeting, we examined this process by developing a tightly controlled system. Chromosomal targeting was highly toxic via targeting of DNA and resulted in growth inhibition and cellular filamentation. The toxic phenotype was avoided by mutations in the cas operon, the CRISPR repeats, the protospacer target, and protospacer-adjacent motif (PAM) beside the target. Indeed, the natural self-targeting spacer was non-toxic due to a single nucleotide mutation adjacent to the target in the PAM sequence. Furthermore, we show that chromosomal targeting can result in large-scale genomic alterations, including the remodelling or deletion of entire pre-existing pathogenicity islands. These features can be engineered for the targeted deletion of large regions of bacterial chromosomes. In conclusion, in DNA-targeting CRISPR/Cas systems, chromosomal interference is deleterious by causing DNA damage and providing a strong selective pressure for genome alterations, which may have consequences for bacterial evolution and pathogenicity.

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.

Drivers' detection of roadside targets when driving vehicles with three headlight systems during high beam activation.

PubMed

Reagan, Ian J; Brumbelow, Matthew L

2017-02-01

A previous open-road experiment indicated that curve-adaptive HID headlights driven with low beams improved drivers' detection of low conspicuity targets compared with fixed halogen and fixed HID low beam systems. The current study used the same test environment and targets to assess whether drivers' detection of targets was affected by the same three headlight systems when using high beams. Twenty drivers search and responded for 60 8×12inch targets of high or low reflectance that were distributed evenly across straight and curved road sections as they drove at 30 mph on an unlit two-lane rural road. The results indicate that target detection performance was generally similar across the three systems. However, one interaction indicated that drivers saw low reflectance targets on straight road sections from further away when driving with the fixed halogen high beam condition compared with curve-adaptive HID high beam headlights and also indicated a possible benefit for the curve-adaptive HID high beams for high reflectance targets placed on the inside of curves. The results of this study conflict with the previous study of low beams, which showed a consistent benefit for the curve-adaptive HID low beams for targets placed on curves compared with fixed HID and fixed halogen low beam conditions. However, a comparison of mean detection distances from the two studies indicated uniformly longer mean target detection distances for participants driving with high beams and implicates the potential visibility benefits for systems that optimize proper high beam use. Copyright © 2016 Elsevier Ltd. All rights reserved.

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.

Systems biology approaches and tools for analysis of interactomes and multi-target drugs.

PubMed

Schrattenholz, André; Groebe, Karlfried; Soskic, Vukic

2010-01-01

Systems biology is essentially a proteomic and epigenetic exercise because the relatively condensed information of genomes unfolds on the level of proteins. The flexibility of cellular architectures is not only mediated by a dazzling number of proteinaceous species but moreover by the kinetics of their molecular changes: The time scales of posttranslational modifications range from milliseconds to years. The genetic framework of an organism only provides the blue print of protein embodiments which are constantly shaped by external input. Indeed, posttranslational modifications of proteins represent the scope and velocity of these inputs and fulfil the requirements of integration of external spatiotemporal signal transduction inside an organism. The optimization of biochemical networks for this type of information processing and storage results in chemically extremely fine tuned molecular entities. The huge dynamic range of concentrations, the chemical diversity and the necessity of synchronisation of complex protein expression patterns pose the major challenge of systemic analysis of biological models. One further message is that many of the key reactions in living systems are essentially based on interactions of moderate affinities and moderate selectivities. This principle is responsible for the enormous flexibility and redundancy of cellular circuitries. In complex disorders such as cancer or neurodegenerative diseases, which initially appear to be rooted in relatively subtle dysfunctions of multimodal physiologic pathways, drug discovery programs based on the concept of high affinity/high specificity compounds ("one-target, one-disease"), which has been dominating the pharmaceutical industry for a long time, increasingly turn out to be unsuccessful. Despite improvements in rational drug design and high throughput screening methods, the number of novel, single-target drugs fell much behind expectations during the past decade, and the treatment of "complex

Modeling the target acquisition performance of active imaging systems

NASA Astrophysics Data System (ADS)

Espinola, Richard L.; Jacobs, Eddie L.; Halford, Carl E.; Vollmerhausen, Richard; Tofsted, David H.

2007-04-01

Recent development of active imaging system technology in the defense and security community have driven the need for a theoretical understanding of its operation and performance in military applications such as target acquisition. In this paper, the modeling of active imaging systems, developed at the U.S. Army RDECOM CERDEC Night Vision & Electronic Sensors Directorate, is presented with particular emphasis on the impact of coherent effects such as speckle and atmospheric scintillation. Experimental results from human perception tests are in good agreement with the model results, validating the modeling of coherent effects as additional noise sources. Example trade studies on the design of a conceptual active imaging system to mitigate deleterious coherent effects are shown.

Modeling the target acquisition performance of active imaging systems.

PubMed

Espinola, Richard L; Jacobs, Eddie L; Halford, Carl E; Vollmerhausen, Richard; Tofsted, David H

2007-04-02

Recent development of active imaging system technology in the defense and security community have driven the need for a theoretical understanding of its operation and performance in military applications such as target acquisition. In this paper, the modeling of active imaging systems, developed at the U.S. Army RDECOM CERDEC Night Vision & Electronic Sensors Directorate, is presented with particular emphasis on the impact of coherent effects such as speckle and atmospheric scintillation. Experimental results from human perception tests are in good agreement with the model results, validating the modeling of coherent effects as additional noise sources. Example trade studies on the design of a conceptual active imaging system to mitigate deleterious coherent effects are shown.

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

[Advances of tumor targeting peptides drug delivery system with pH-sensitive activities].

PubMed

Ma, Yin-yun; Li, Li; Huang, Hai-feng; Gou, San-hu; Ni, Jing-man

2016-05-01

The pH-sensitive peptides drug delivery systems, which target to acidic extracellular environment of tumor tissue, have many advantages in drug delivery. They exhibit a high specificity to tumor and low cytotoxicity, which significantly increase the efficacy of traditional anti-cancer drugs. In recent years the systems have received a great attention. The pH-sensitive peptides drug delivery systems can be divided into five types according to the difference in pH-responsive mechanism,type of peptides and carrier materials. This paper summarizes the recent progresses in the field with a focus on the five types of pH-sensitive peptides in drug delivery systems. This may provide a guideline to design and application of tumor targeting drugs.

Hypoxia-inducible tumour-specific promoters as a dual-targeting transcriptional regulation system for cancer gene therapy

PubMed Central

Javan, Bita; Shahbazi, Majid

2017-01-01

Transcriptional targeting is the best approach for specific gene therapy. Hypoxia is a common feature of the tumour microenvironment. Therefore, targeting gene expression in hypoxic cells by placing transgene under the control of a hypoxia-responsive promoter can be a good strategy for cancer-specific gene therapy. The hypoxia-inducible gene expression system has been investigated more in suicide gene therapy and it can also be of great help in knocking down cancer gene therapy with siRNAs. However, this system needs to be optimised to have maximum efficacy with minimum side effects in normal tissues. The combination of tissue-/tumour-specific promoters with HRE core sequences has been found to enhance the specificity and efficacy of this system. In this review, hypoxia-inducible gene expression system as well as gene therapy strategies targeting tumour hypoxia will be discussed. This review will also focus on hypoxia-inducible tumour-specific promoters as a dual-targeting transcriptional regulation systems developed for cancer-specific gene therapy. PMID:28798809

[Targeted drug delivery system: potential application to resveratrol].

PubMed

Farghali, Hassan; Kameníková, Ludmila

2017-01-01

Drug delivery system (DDS) is intended to increasing effectiveness of drugs through targeted distribution and to reducing of unwanted effects. In this mini-review, the basic principles of nanotechnology that were developed for DDS were reported including sections on the present research in key areas that are important for future investigations. Attention is paid on resveratrol as a model phytochemical with interesting pharmacologic profile which was demonstrated in great numbers of studies and for its wide use as supplemental therapy. Due to complicated pharmacokinetic profile of resveratrol that is characterized by very low bioavailability in spite of high oral absorption, the effects of resveratrol is being studied in new nanotechnology preparations of pharmaceutical formulation. Herein we report on results of present in vitro and in vivo investigations with resveratrol in new types of drug formulations using different nanoparticles as liposomes, solid lipid particles, cyclodextrins and micelles.Key words: targeted drug delivery nanotechnology resveratrol.

Programmable removal of bacterial strains by use of genome-targeting CRISPR-Cas systems.

PubMed

Gomaa, Ahmed A; Klumpe, Heidi E; Luo, Michelle L; Selle, Kurt; Barrangou, Rodolphe; Beisel, Chase L

2014-01-28

CRISPR (clustered regularly interspaced short palindromic repeats)-Cas (CRISPR-associated) systems in bacteria and archaea employ CRISPR RNAs to specifically recognize the complementary DNA of foreign invaders, leading to sequence-specific cleavage or degradation of the target DNA. Recent work has shown that the accidental or intentional targeting of the bacterial genome is cytotoxic and can lead to cell death. Here, we have demonstrated that genome targeting with CRISPR-Cas systems can be employed for the sequence-specific and titratable removal of individual bacterial strains and species. Using the type I-E CRISPR-Cas system in Escherichia coli as a model, we found that this effect could be elicited using native or imported systems and was similarly potent regardless of the genomic location, strand, or transcriptional activity of the target sequence. Furthermore, the specificity of targeting with CRISPR RNAs could readily distinguish between even highly similar strains in pure or mixed cultures. Finally, varying the collection of delivered CRISPR RNAs could quantitatively control the relative number of individual strains within a mixed culture. Critically, the observed selectivity and programmability of bacterial removal would be virtually impossible with traditional antibiotics, bacteriophages, selectable markers, or tailored growth conditions. Once delivery challenges are addressed, we envision that this approach could offer a novel means to quantitatively control the composition of environmental and industrial microbial consortia and may open new avenues for the development of "smart" antibiotics that circumvent multidrug resistance and differentiate between pathogenic and beneficial microorganisms. Controlling the composition of microbial populations is a critical aspect in medicine, biotechnology, and environmental cycles. While different antimicrobial strategies, such as antibiotics, antimicrobial peptides, and lytic bacteriophages, offer partial solutions

Mercury Handling for the Target System for a Muon Collider

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

Graves, Van B; Mcdonald, K; Kirk, H.

2012-01-01

The baseline target concept for a Muon Collider or Neutrino Factory is a free-stream mercury jet being impacted by an 8-GeV proton beam. The target is located within a 20-T magnetic field, which captures the generated pions that are conducted to a downstream decay channel. Both the mercury and the proton beam are introduced at slight downward angles to the magnetic axis. A pool of mercury serves as a receiving reservoir for the mercury and a dump for the unexpended proton beam. The impact energy of the remaining beam and jet are substantial, and it is required that splashes andmore » waves be controlled in order to minimize the potential for interference of pion production at the target. Design issues discussed in this paper include the nozzle, splash mitigation in the mercury pool, the mercury containment vessel, and the mercury recirculation system.« less

Cytotoxic Chromosomal Targeting by CRISPR/Cas Systems Can Reshape Bacterial Genomes and Expel or Remodel Pathogenicity Islands

PubMed Central

Vercoe, Reuben B.; Chang, James T.; Dy, Ron L.; Taylor, Corinda; Gristwood, Tamzin; Clulow, James S.; Richter, Corinna; Przybilski, Rita; Pitman, Andrew R.; Fineran, Peter C.

2013-01-01

In prokaryotes, clustered regularly interspaced short palindromic repeats (CRISPRs) and their associated (Cas) proteins constitute a defence system against bacteriophages and plasmids. CRISPR/Cas systems acquire short spacer sequences from foreign genetic elements and incorporate these into their CRISPR arrays, generating a memory of past invaders. Defence is provided by short non-coding RNAs that guide Cas proteins to cleave complementary nucleic acids. While most spacers are acquired from phages and plasmids, there are examples of spacers that match genes elsewhere in the host bacterial chromosome. In Pectobacterium atrosepticum the type I-F CRISPR/Cas system has acquired a self-complementary spacer that perfectly matches a protospacer target in a horizontally acquired island (HAI2) involved in plant pathogenicity. Given the paucity of experimental data about CRISPR/Cas–mediated chromosomal targeting, we examined this process by developing a tightly controlled system. Chromosomal targeting was highly toxic via targeting of DNA and resulted in growth inhibition and cellular filamentation. The toxic phenotype was avoided by mutations in the cas operon, the CRISPR repeats, the protospacer target, and protospacer-adjacent motif (PAM) beside the target. Indeed, the natural self-targeting spacer was non-toxic due to a single nucleotide mutation adjacent to the target in the PAM sequence. Furthermore, we show that chromosomal targeting can result in large-scale genomic alterations, including the remodelling or deletion of entire pre-existing pathogenicity islands. These features can be engineered for the targeted deletion of large regions of bacterial chromosomes. In conclusion, in DNA–targeting CRISPR/Cas systems, chromosomal interference is deleterious by causing DNA damage and providing a strong selective pressure for genome alterations, which may have consequences for bacterial evolution and pathogenicity. PMID:23637624

Knowledge-based approach for generating target system specifications from a domain model

NASA Technical Reports Server (NTRS)

Gomaa, Hassan; Kerschberg, Larry; Sugumaran, Vijayan

1992-01-01

Several institutions in industry and academia are pursuing research efforts in domain modeling to address unresolved issues in software reuse. To demonstrate the concepts of domain modeling and software reuse, a prototype software engineering environment is being developed at George Mason University to support the creation of domain models and the generation of target system specifications. This prototype environment, which is application domain independent, consists of an integrated set of commercial off-the-shelf software tools and custom-developed software tools. This paper describes the knowledge-based tool that was developed as part of the environment to generate target system specifications from a domain model.

Bipartite recognition of target RNAs activates DNA cleavage by the Type III-B CRISPR–Cas system

PubMed Central

Elmore, Joshua R.; Sheppard, Nolan F.; Ramia, Nancy; Deighan, Trace; Li, Hong; Terns, Rebecca M.; Terns, Michael P.

2016-01-01

CRISPR–Cas systems eliminate nucleic acid invaders in bacteria and archaea. The effector complex of the Type III-B Cmr system cleaves invader RNAs recognized by the CRISPR RNA (crRNA ) of the complex. Here we show that invader RNAs also activate the Cmr complex to cleave DNA. As has been observed for other Type III systems, Cmr eliminates plasmid invaders in Pyrococcus furiosus by a mechanism that depends on transcription of the crRNA target sequence within the plasmid. Notably, we found that the target RNA per se induces DNA cleavage by the Cmr complex in vitro. DNA cleavage activity does not depend on cleavage of the target RNA but notably does require the presence of a short sequence adjacent to the target sequence within the activating target RNA (rPAM [RNA protospacer-adjacent motif]). The activated complex does not require a target sequence (or a PAM) in the DNA substrate. Plasmid elimination by the P. furiosus Cmr system also does not require the Csx1 (CRISPR-associated Rossman fold [CARF] superfamily) protein. Plasmid silencing depends on the HD nuclease and Palm domains of the Cmr2 (Cas10 superfamily) protein. The results establish the Cmr complex as a novel DNA nuclease activated by invader RNAs containing a crRNA target sequence and a rPAM. PMID:26848045

Lejaren A. Hiller, Jr.: A Memorial Tribute to a Chemist-Composer

NASA Astrophysics Data System (ADS)

Wamser, Christian A.; Wamser, Carl C.

1996-07-01

Lejaren Hiller (1924-1994) was trained in chemistry but maintained a lifelong love of music. Like Alexander Borodin, the Russian chemist-composer, but eventually dedicated his career solely to music. His early work on the chemistry of polymers with Fred Wall at the University of Illinois introduced him to the Illiac computer, with which he did Monte Carlo calculations of polymer conformations. He promptly collaborated with Leonard Isaacson, a graduate student also associated with the Wall group, to teach the Illiac to compose music. Using a modified Monte Carlo technique to select the notes and other aspects of the music, they applied increasingly complex rules to define what constituted acceptable music. The result was their String Quartet #4, produced in 1957, often called the Illiac Suite. It is generally acknowledged as the first piece of music composed by a computer. Hiller remained a pioneer in the field of copmuter composition during his distinguished career at the University of Illinois and the State University of New York at Buffalo. This paper traces Hiller's careers in chemistry and music and examines the connections between the two.

Peptide and low molecular weight proteins based kidney targeted drug delivery systems.

PubMed

Xu, Pengfei; Zhang, Hailiang; Dang, Ruili; Jiang, Pei

2018-05-30

Renal disease is a worldwide public health problem, and unfortunately, the therapeutic index of regular drugs is limited. Thus, it is a great need to develop effective treatment strategies. Among the reported strategies, kidney-targeted drug delivery system is a promising method to increase renal efficacy and reduce extra-renal toxicity. In recent years, working as vehicles for targeted drug delivery, low molecular weight proteins (LMWP) and peptide have received immense attention due to their many advantages, such as selective accumulation in kidney, high drug loading capability, control over routes of biodegradation, convenience in modification at the amino terminus, and good biocompatibility. In this review, we describe the current LMWP and peptide carriers for kidney targeted drug delivery systems. In addition, we discuss different linking strategies between carriers and drugs. Furthermore, we briefly outline the current status and attempt to give an outlook on the further study. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

The development of a multi-target compiler-writing system for flight software development

NASA Technical Reports Server (NTRS)

Feyock, S.; Donegan, M. K.

1977-01-01

A wide variety of systems designed to assist the user in the task of writing compilers has been developed. A survey of these systems reveals that none is entirely appropriate to the purposes of the MUST project, which involves the compilation of one or at most a small set of higher-order languages to a wide variety of target machines offering little or no software support. This requirement dictates that any compiler writing system employed must provide maximal support in the areas of semantics specification and code generation, the areas in which existing compiler writing systems as well as theoretical underpinnings are weakest. This paper describes an ongoing research and development effort to create a compiler writing system which will overcome these difficulties, thus providing a software system which makes possible the fast, trouble-free creation of reliable compilers for a wide variety of target computers.

Sequential Axon-derived Signals Couple Target Survival and Layer Specificity in the Drosophila Visual System

PubMed Central

Pecot, Matthew Y.; Chen, Yi; Akin, Orkun; Chen, Zhenqing; Tsui, C.Y. Kimberly; Zipursky, S. Lawrence

2015-01-01

SUMMARY Neural circuit formation relies on interactions between axons and cells within the target field. While it is well established that target-derived signals act on axons to regulate circuit assembly, the extent to which axon-derived signals control circuit formation is not known. In the Drosophila visual system, anterograde signals numerically match R1–R6 photoreceptors with their targets by controlling target proliferation and neuronal differentiation. Here we demonstrate that additional axon-derived signals selectively couple target survival with layer-specificity. We show that Jelly belly (Jeb) produced by R1–R6 axons interacts with its receptor, anaplastic lymphoma kinase (Alk), on budding dendrites to control survival of L3 neurons, one of three postsynaptic targets. L3 axons then produce Netrin, which regulates the layer-specific targeting of another neuron within the same circuit. We propose that a cascade of axon-derived signals, regulating diverse cellular processes, provides a strategy for coordinating circuit assembly across different regions of the nervous system. PMID:24742459

A new liposome-based gene delivery system targeting lung epithelial cells using endothelin antagonist.

PubMed

Allon, Nahum; Saxena, Ashima; Chambers, Carolyn; Doctor, Bhupendra P

2012-06-10

We formulated a new gene delivery system based on targeted liposomes. The efficacy of the delivery system was demonstrated in in vitro and in vivo models. The targeting moiety consists of a high-affinity 7-amino-acid peptide, covalently and evenly conjugated to the liposome surface. The targeting peptide acts as an endothelin antagonist, and accelerates liposome binding and internalization. It is devoid of other biological activity. Liposomes with high phosphatidyl serine (PS) were specially formulated to help their fusion with the endosomal membrane at low pH and enable release of the liposome payload into the cytoplasm. A DNA payload, pre-compressed by protamine, was encapsulated into the liposomes, which directed the plasmid into the cell's nucleus. Upon exposure to epithelial cells, binding of the liposomes occurred within 5-10 min, followed by facilitated internalization of the complex. Endosomal escape was complete within 30 min, followed by DNA accumulation in the nucleus 2h post-transfection. A549 lung epithelial cells transfected with plasmid encoding for GFP encapsulated in targeted liposomes expressed significantly more protein than those transfected with plasmid complexed with Lipofectamine. The intra-tracheal instillation of plasmid encoding for GFP encapsulated in targeted liposomes into rat lungs resulted in the expression of GFP in bronchioles and alveoli within 5 days. These results suggest that this delivery system has great potential in targeting genes to lungs. Copyright © 2011 Elsevier B.V. All rights reserved.

Design and Realization of a Three Degrees of Freedom Displacement Measurement System Composed of Hall Sensors Based on Magnetic Field Fitting by an Elliptic Function

PubMed Central

Zhao, Bo; Wang, Lei; Tan, Jiu-Bin

2015-01-01

This paper presents the design and realization of a three degrees of freedom (DOFs) displacement measurement system composed of Hall sensors, which is built for the XYθz displacement measurement of the short stroke stage of the reticle stage of lithography. The measurement system consists of three pairs of permanent magnets mounted on the same plane on the short stroke stage along the Y, Y, X directions, and three single axis Hall sensors correspondingly mounted on the frame of the reticle stage. The emphasis is placed on the decoupling and magnetic field fitting of the three DOFs measurement system. The model of the measurement system is illustrated, and the XY positions and θZ rotation of the short stroke stage can be obtained by decoupling the sensor outputs. A magnetic field fitting by an elliptic function-based compensation method is proposed. The practical field intensity of a permanent magnet at a certain plane height can be substituted for the output voltage of a Hall sensors, which can be expressed by the elliptic function through experimental data as the crucial issue to calculate the three DOFs displacement. Experimental results of the Hall sensor displacement measurement system are presented to validate the proposed three DOFs measurement system. PMID:26370993

Computer Instruction in Handwriting, Spelling, and Composing for Students with Specific Learning Disabilities in Grades 4 to 9.

PubMed

Berninger, Virginia W; Nagy, William; Tanimoto, Steve; Thompson, Rob; Abbott, Robert D

2015-02-01

Effectiveness of iPad computerized writing instruction was evaluated for 4 th to 9 th graders ( n =35) with diagnosed specific learning disabilities (SLDs) affecting writing: dysgraphia (impaired handwriting), dyslexia (impaired spelling), and oral and written language learning disability (OWL LD) (impaired syntax composing). Each of the 18 two-hour lessons had multiple learning activities aimed at improving subword - (handwriting), word - (spelling), and syntax - (sentence composing) level language skills by engaging all four language systems (listening, speaking, reading, and writing) to create a functional writing system. To evaluate treatment effectiveness, normed measures of handwriting, spelling, and composing were used with the exception of one non-normed alphabet writing task. Results showed that the sample as a whole improved significantly from pretest to posttest in three handwriting measures, four spelling measures, and both written and oral syntax construction measures. All but oral syntax was evaluated with pen and paper tasks, showing that the computer writing instruction transferred to better writing with pen and paper. Performance on learning activities during instruction correlated with writing outcomes; and individual students tended to improve in the impaired skill associated with their diagnosis. Thus, although computers are often used in upper elementary school and middle school in the United States (US) for accommodations (alternatives to pen and paper) for students with persisting SLDs affecting writing, this study shows computers can also be used for Tier 3 instruction to improve the writing skills of students in grades 4 to 9 with history of persisting writing disabilities.

Computer Instruction in Handwriting, Spelling, and Composing for Students with Specific Learning Disabilities in Grades 4 to 9

PubMed Central

Berninger, Virginia W.; Nagy, William; Tanimoto, Steve; Thompson, Rob; Abbott, Robert D.

2014-01-01

Effectiveness of iPad computerized writing instruction was evaluated for 4th to 9th graders (n=35) with diagnosed specific learning disabilities (SLDs) affecting writing: dysgraphia (impaired handwriting), dyslexia (impaired spelling), and oral and written language learning disability (OWL LD) (impaired syntax composing). Each of the 18 two-hour lessons had multiple learning activities aimed at improving subword- (handwriting), word- (spelling), and syntax- (sentence composing) level language skills by engaging all four language systems (listening, speaking, reading, and writing) to create a functional writing system. To evaluate treatment effectiveness, normed measures of handwriting, spelling, and composing were used with the exception of one non-normed alphabet writing task. Results showed that the sample as a whole improved significantly from pretest to posttest in three handwriting measures, four spelling measures, and both written and oral syntax construction measures. All but oral syntax was evaluated with pen and paper tasks, showing that the computer writing instruction transferred to better writing with pen and paper. Performance on learning activities during instruction correlated with writing outcomes; and individual students tended to improve in the impaired skill associated with their diagnosis. Thus, although computers are often used in upper elementary school and middle school in the United States (US) for accommodations (alternatives to pen and paper) for students with persisting SLDs affecting writing, this study shows computers can also be used for Tier 3 instruction to improve the writing skills of students in grades 4 to 9 with history of persisting writing disabilities. PMID:25378768

MO-A-BRD-05: Evaluation of Composed Lung Ventilation with 4DCT and Image Registration

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

Du, K; Bayouth, J; Reinhardt, J

Purpose: Regional pulmonary function can be derived using fourdimensional computed tomography (4DCT) combined with deformable image registration. However, only peak inhale and exhale phases have been used thus far while the lung ventilation during intermediate phases is not considered. In our previous work, we have investigated the spatiotemporal heterogeneity of lung ventilation and its dependence on respiration effort. In this study, composed ventilation is introduced using all inspiration phases and compared to direct ventilation. Both methods are evaluated against Xe-CT derived ventilation. Methods: Using an in-house tissue volume preserving deformable image registration, unlike the direct ventilation method, which computes frommore » end expiration to end inspiration, Jacobian ventilation maps were computed from one inhale phase to the next and then composed from all inspiration steps. The two methods were compared in both patients prior to RT and mechanically ventilated sheep subjects. In addition, they wereassessed for the correlation with Xe-CT derived ventilation in sheep subjects. Annotated lung landmarks were used to evaluate the accuracy of original and composed deformation field. Results: After registration, the landmark distance for composed deformation field was always higher than that for direct deformation field (0IN to 100IN average in human: 1.03 vs 1.53, p=0.001, and in sheep: 0.80 vs0.94, p=0.009), and both increased with longer phase interval. Direct and composed ventilation maps were similar in both sheep (gamma pass rate 87.6) and human subjects (gamma pass rate 71.9),and showed consistent pattern from ventral to dorsal when compared to Xe-CT derived ventilation. Correlation coefficient between Xe-CT and composed ventilation was slightly better than the direct method but not significant (average 0.89 vs 0.85, p=0.135). Conclusion: More strict breathing control in sheep subjects may explain higher similarity between direct and composed

Galloylated polyphenols efficiently reduce alpha-tocopherol radicals in a phospholipid model system composed of sodium dodecyl sulfate (SDS) micelles.

PubMed

Pazos, Manuel; Torres, Josep Lluís; Andersen, Mogens L; Skibsted, Leif H; Medina, Isabel

2009-06-10

The ability of several polyphenolic fractions from grape ( Vitis vinifera ) pomace, pine ( Pinus pinaster ) bark, and witch hazel ( Hammamelis virginiana ) bark to repair alpha-tocopherol (alpha-TOH) through reduction of the alpha-tocopheroxyl radical was investigated in a homogeneous hexane system and a phospholipid-like system based on SDS micelles. These natural polyphenols were compared with pure related phenolics (epicatechin, gallic acid, epigallocatechin gallate, quercetin, and rutin) and ascorbic acid, which is a substance with a well-recognized capacity for regenerating alpha-TOH. alpha-Tocopheroxyl radicals were monitored and quantified by electron spin resonance (ESR) spectroscopy in the absence and presence of phenolics. Polyphenols from grape and pine bark were essentially catechin monomers and proanthocyanidins differing in the content of galloyl residues; those from pine bark had a negligible degree of galloylation. Polyphenolic fractions from witch hazel bark were composed of approximately 80% hydrolyzable tannins rich in galloyl moieties, together with a smaller amount of catechin monomers and proanthocyanidins. In the homogeneous hexane system, polyphenols from grape and pine bark exhibited similar activities, reducing the alpha-tocopheroxyl radicals by over 27-40%, whereas phenols from witch hazel were more highly effective, reducing 80% of alpha-TOH. In contrast, pine bark polyphenols were found to be significantly less active than the grape fractions in SDS micelles, reducing 30 and 70% of alpha-tocopheroxyl radicals, respectively. Polyphenolic fractions from witch hazel were also able to reduce the highest amount of alpha-TOH in SDS-micelles. The reducing capacity on alpha-tocopheroxyl radical of polyphenolic fractions was found to be pH-dependent and more effective at higher pH in the range of pH studied (5.8-7.8). These results stress the potential role of polyphenols, in particular those rich in galloyl groups, to maintain intact endogenous

Ground target geolocation based on digital elevation model for airborne wide-area reconnaissance system

NASA Astrophysics Data System (ADS)

Qiao, Chuan; Ding, Yalin; Xu, Yongsen; Xiu, Jihong

2018-01-01

To obtain the geographical position of the ground target accurately, a geolocation algorithm based on the digital elevation model (DEM) is developed for an airborne wide-area reconnaissance system. According to the platform position and attitude information measured by the airborne position and orientation system and the gimbal angles information from the encoder, the line-of-sight pointing vector in the Earth-centered Earth-fixed coordinate frame is solved by the homogeneous coordinate transformation. The target longitude and latitude can be solved with the elliptical Earth model and the global DEM. The influences of the systematic error and measurement error on ground target geolocation calculation accuracy are analyzed by the Monte Carlo method. The simulation results show that this algorithm can improve the geolocation accuracy of ground target in rough terrain area obviously. The geolocation accuracy of moving ground target can be improved by moving average filtering (MAF). The validity of the geolocation algorithm is verified by the flight test in which the plane flies at a geodetic height of 15,000 m and the outer gimbal angle is <47°. The geolocation root mean square error of the target trajectory is <45 and <7 m after MAF.

Teaching Effective Communication Skills with ACE: Analyzing, Composing, & Evaluating

ERIC Educational Resources Information Center

Snyder, Lisa Gueldenzoph; Shwom, Barbara

2011-01-01

Most business communication classes teach students to use a writing process to compose effective documents. Students practice the process by applying it to various types of writing with various purposes-reports, presentations, bad news letters, persuasive memos, etc. However, unless students practice that process in other contexts outside of the…

Integrative FourD omics approach profiles the target network of the carbon storage regulatory system

PubMed Central

Sowa, Steven W.; Gelderman, Grant; Leistra, Abigail N.; Buvanendiran, Aishwarya; Lipp, Sarah; Pitaktong, Areen; Vakulskas, Christopher A.; Romeo, Tony; Baldea, Michael

2017-01-01

Abstract Multi-target regulators represent a largely untapped area for metabolic engineering and anti-bacterial development. These regulators are complex to characterize because they often act at multiple levels, affecting proteins, transcripts and metabolites. Therefore, single omics experiments cannot profile their underlying targets and mechanisms. In this work, we used an Integrative FourD omics approach (INFO) that consists of collecting and analyzing systems data throughout multiple time points, using multiple genetic backgrounds, and multiple omics approaches (transcriptomics, proteomics and high throughput sequencing crosslinking immunoprecipitation) to evaluate simultaneous changes in gene expression after imposing an environmental stress that accentuates the regulatory features of a network. Using this approach, we profiled the targets and potential regulatory mechanisms of a global regulatory system, the well-studied carbon storage regulatory (Csr) system of Escherichia coli, which is widespread among bacteria. Using 126 sets of proteomics and transcriptomics data, we identified 136 potential direct CsrA targets, including 50 novel ones, categorized their behaviors into distinct regulatory patterns, and performed in vivo fluorescence-based follow up experiments. The results of this work validate 17 novel mRNAs as authentic direct CsrA targets and demonstrate a generalizable strategy to integrate multiple lines of omics data to identify a core pool of regulator targets. PMID:28126921

An analytical approach of thermodynamic behavior in a gas target system on a medical cyclotron.

PubMed

Jahangiri, Pouyan; Zacchia, Nicholas A; Buckley, Ken; Bénard, François; Schaffer, Paul; Martinez, D Mark; Hoehr, Cornelia

2016-01-01

An analytical model has been developed to study the thermo-mechanical behavior of gas targets used to produce medical isotopes, assuming that the system reaches steady-state. It is based on an integral analysis of the mass and energy balance of the gas-target system, the ideal gas law, and the deformation of the foil. The heat transfer coefficients for different target bodies and gases have been calculated. Excellent agreement is observed between experiments performed at TRIUMF's 13 MeV cyclotron and the model. Copyright © 2015 Elsevier Ltd. All rights reserved.

Interferon-targeted therapy in systemic lupus erythematosus: Is this an alternative to targeting B and T cells?

PubMed

Kalunian, K C

2016-09-01

Clinical trials of investigational agents in systemic lupus erythematosus (SLE) have focused on targeting dysregulated B and T cells; however, recent translational research findings of the importance of the dysregulation of the innate immune system in SLE have led to clinical trials that target interferon. Three biologics that target type I interferons have been tested for their efficacy and safety in active SLE patients; these phase II trials have tested the hypothesis that down-regulation of interferon-regulated gene expression (the interferon signature) lessen the clinical burden of SLE. Rontalizumab, an anti-interferon-α monoclonal antibody, was studied in patients who had discontinued immunosuppressants. This study failed to show efficacy as assessed by both two outcome assessments; however, in low interferon signature patients, response was higher and corticosteroid usage was less in rontalizumab-treated patients. Sifalimumab, another anti-interferon-α monoclonal antibody, was studied in patients who remained on standard of care therapy. This study showed significantly better efficacy in patients treated with two sifalimumab dosages; significant differences were seen in the high interferon signature group. In a similar design and in a similar population as the sifalimumab study, anifrolumab, a monoclonal antibody that binds to a type I interferon receptor, was studied in patients who remained on standard of care therapy. In this study, one dosage group demonstrated efficacy and statistically significant effects were achieved in both tested dosage groups with secondary end points. Oral corticosteroid reduction to ≤7.5 mg daily was achieved in one of the tested dosage groups and organ-specific outcomes were significantly improved in that same group. For all studies, no significant differences in serious adverse effects were seen; although, herpes zoster infections were increased in sifalimumab- and anifrolumab-treated patients and influenza rates were

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.

Implementation of Kane's Method for a Spacecraft Composed of Multiple Rigid Bodies

NASA Technical Reports Server (NTRS)

Stoneking, Eric T.

2013-01-01

Equations of motion are derived for a general spacecraft composed of rigid bodies connected via rotary (spherical or gimballed) joints in a tree topology. Several supporting concepts are developed in depth. Basis dyads aid in the transition from basis-free vector equations to component-wise equations. Joint partials allow abstraction of 1-DOF, 2-DOF, 3-DOF gimballed and spherical rotational joints to a common notation. The basic building block consisting of an "inner" body and an "outer" body connected by a joint enables efficient organization of arbitrary tree structures. Kane's equation is recast in a form which facilitates systematic assembly of large systems of equations, and exposes a relationship of Kane's equation to Newton and Euler's equations which is obscured by the usual presentation. The resulting system of dynamic equations is of minimum dimension, and is suitable for numerical solution by computer. Implementation is ·discussed, and illustrative simulation results are presented.

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.

Inductance and resistance measurement method for vessel detection and coil powering in all-surface inductive heating systems composed of outer squircle coils

NASA Astrophysics Data System (ADS)

Kilic, Veli Tayfun; Unal, Emre; Demir, Hilmi Volkan

2017-05-01

In this work, we investigate a method proposed for vessel detection and coil powering in an all-surface inductive heating system composed of outer squircle coils. Besides conventional circular coils, coils with different shapes such as outer squircle coils are used for and enable efficient all-surface inductive heating. Validity of the method, which relies on measuring inductance and resistance values of a loaded coil at different frequencies, is experimentally demonstrated for a coil with shape different from conventional circular coil. Simple setup was constructed with a small coil to model an all-surface inductive heating system. Inductance and resistance maps were generated by measuring coil's inductance and resistance values at different frequencies loaded by a plate made of different materials and located at various positions. Results show that in an induction hob for various coil geometries it is possible to detect a vessel's presence, to identify its material type and to specify its position on the hob surface by considering inductance and resistance of the coil measured on at least two different frequencies. The studied method is important in terms of enabling safe, efficient and user flexible heating in an all-surface inductive heating system by automatically detecting the vessel's presence and powering on only the coils that are loaded by the vessel with predetermined current levels.

Study of a trussed girder composed of a reinforced plastic.

DOT National Transportation Integrated Search

1974-01-01

The structural behavior of a series of laboratory test specimens was investigated to determine the ultimate strength, the deformation characteristics, and the mode of failure of a trussed girder composed of glass fiber reinforced polyester resin. Com...

Adaptive target binarization method based on a dual-camera system

NASA Astrophysics Data System (ADS)

Lei, Jing; Zhang, Ping; Xu, Jiangtao; Gao, Zhiyuan; Gao, Jing

2018-01-01

An adaptive target binarization method based on a dual-camera system that contains two dynamic vision sensors was proposed. First, a preprocessing procedure of denoising is introduced to remove the noise events generated by the sensors. Then, the complete edge of the target is retrieved and represented by events based on an event mosaicking method. Third, the region of the target is confirmed by an event-to-event method. Finally, a postprocessing procedure of image open and close operations of morphology methods is adopted to remove the artifacts caused by event-to-event mismatching. The proposed binarization method has been extensively tested on numerous degraded images with nonuniform illumination, low contrast, noise, or light spots and successfully compared with other well-known binarization methods. The experimental results, which are based on visual and misclassification error criteria, show that the proposed method performs well and has better robustness on the binarization of degraded images.

Design of Student Information Management Database Application System for Office and Departmental Target Responsibility System

NASA Astrophysics Data System (ADS)

Zhou, Hui

It is the inevitable outcome of higher education reform to carry out office and departmental target responsibility system, in which statistical processing of student's information is an important part of student's performance review. On the basis of the analysis of the student's evaluation, the student information management database application system is designed by using relational database management system software in this paper. In order to implement the function of student information management, the functional requirement, overall structure, data sheets and fields, data sheet Association and software codes are designed in details.

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.

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.

Tigres Workflow Library: Supporting Scientific Pipelines on HPC Systems

DOE PAGES

Hendrix, Valerie; Fox, James; Ghoshal, Devarshi; ...

2016-07-21

The growth in scientific data volumes has resulted in the need for new tools that enable users to operate on and analyze data on large-scale resources. In the last decade, a number of scientific workflow tools have emerged. These tools often target distributed environments, and often need expert help to compose and execute the workflows. Data-intensive workflows are often ad-hoc, they involve an iterative development process that includes users composing and testing their workflows on desktops, and scaling up to larger systems. In this paper, we present the design and implementation of Tigres, a workflow library that supports the iterativemore » workflow development cycle of data-intensive workflows. Tigres provides an application programming interface to a set of programming templates i.e., sequence, parallel, split, merge, that can be used to compose and execute computational and data pipelines. We discuss the results of our evaluation of scientific and synthetic workflows showing Tigres performs with minimal template overheads (mean of 13 seconds over all experiments). We also discuss various factors (e.g., I/O performance, execution mechanisms) that affect the performance of scientific workflows on HPC systems.« less

Tigres Workflow Library: Supporting Scientific Pipelines on HPC Systems

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

Hendrix, Valerie; Fox, James; Ghoshal, Devarshi

The growth in scientific data volumes has resulted in the need for new tools that enable users to operate on and analyze data on large-scale resources. In the last decade, a number of scientific workflow tools have emerged. These tools often target distributed environments, and often need expert help to compose and execute the workflows. Data-intensive workflows are often ad-hoc, they involve an iterative development process that includes users composing and testing their workflows on desktops, and scaling up to larger systems. In this paper, we present the design and implementation of Tigres, a workflow library that supports the iterativemore » workflow development cycle of data-intensive workflows. Tigres provides an application programming interface to a set of programming templates i.e., sequence, parallel, split, merge, that can be used to compose and execute computational and data pipelines. We discuss the results of our evaluation of scientific and synthetic workflows showing Tigres performs with minimal template overheads (mean of 13 seconds over all experiments). We also discuss various factors (e.g., I/O performance, execution mechanisms) that affect the performance of scientific workflows on HPC systems.« less

Lead discovery and chemical biology approaches targeting the ubiquitin proteasome system.

PubMed

Akinjiyan, Favour A; Carbonneau, Seth; Ross, Nathan T

2017-10-15

Protein degradation is critical for proteostasis, and the addition of polyubiquitin chains to a substrate is necessary for its recognition by the 26S proteasome. Therapeutic intervention in the ubiquitin proteasome system has implications ranging from cancer to neurodegeneration. Novel screening methods and chemical biology tools for targeting E1-activating, E2-conjugating and deubiquitinating enzymes will be discussed in this review. Approaches for targeting E3 ligase-substrate interactions as well as the proteasome will also be covered, with a focus on recently described approaches. Copyright © 2017. Published by Elsevier Ltd.

Video camera system for locating bullet holes in targets at a ballistics tunnel

NASA Technical Reports Server (NTRS)

Burner, A. W.; Rummler, D. R.; Goad, W. K.

1990-01-01

A system consisting of a single charge coupled device (CCD) video camera, computer controlled video digitizer, and software to automate the measurement was developed to measure the location of bullet holes in targets at the International Shooters Development Fund (ISDF)/NASA Ballistics Tunnel. The camera/digitizer system is a crucial component of a highly instrumented indoor 50 meter rifle range which is being constructed to support development of wind resistant, ultra match ammunition. The system was designed to take data rapidly (10 sec between shoots) and automatically with little operator intervention. The system description, measurement concept, and procedure are presented along with laboratory tests of repeatability and bias error. The long term (1 hour) repeatability of the system was found to be 4 microns (one standard deviation) at the target and the bias error was found to be less than 50 microns. An analysis of potential errors and a technique for calibration of the system are presented.

Systemic p53 gene therapy of cancer with immunolipoplexes targeted by anti-transferrin receptor scFv.

PubMed Central

Xu, L.; Tang, W. H.; Huang, C. C.; Alexander, W.; Xiang, L. M.; Pirollo, K. F.; Rait, A.; Chang, E. H.

2001-01-01

BACKGROUND: A long-standing goal in genetic therapy for cancer is a systemic gene delivery system that selectively targets tumor cells, including metastases. Here we describe a novel cationic immunolipoplex system that shows high in vivo gene transfer efficiency and anti- tumor efficacy when used for systemic p53 gene therapy of cancer. MATERIALS AND METHODS: A cationic immunolipoplex incorporating a biosynthetically lipid-tagged, anti-transferrin receptor single-chain antibody (TfRscFv), was designed to target tumor cells both in vitro and in vivo. A human breast cancer metastasis model was employed to evaluate the in vivo efficacy of systemically administered, TfRscFv-immunolipoplex-mediated, p53 gene therapy in combination with docetaxel. RESULTS: The TfRscFv-targeting cationic immunolipoplex had a size of 60-100 nm, showed enhanced tumor cell binding, and improved targeted gene delivery and transfection efficiencies, both in vitro and in vivo. The p53 tumor suppressor gene was not only systemically delivered by the immunolipoplex to human tumor xenografts in nude mice but also functionally expressed. In the nude mouse breast cancer metastasis model, the combination of the p53 gene delivered by the systemic administration of the TfRscFv-immunolipoplex and docetaxel resulted in significantly improved efficacy with prolonged survival. CONCLUSIONS: This is the first report using scFv-targeting immunolipoplexes for systemic gene therapy. The TfRscFv has a number of advantages over the transferrin (Tf) molecule itself: (1) scFv has a much smaller size than Tf producing a smaller immunolipoplex giving better penetration into solid tumors; (2) unlike Tf, the scFv is a recombinant protein, not a blood product; (3) large scale production and strict quality control of the recombinant scFv, as well as scFv-immunolipoplex, are feasible. The sensitization of tumors to chemotherapy by this tumor-targeted and efficient p53 gene delivery method could lower the effective dose of

Optoelectronic System Measures Distances to Multiple Targets

NASA Technical Reports Server (NTRS)

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

2007-01-01

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

Organists and organ music composers.

PubMed

Foerch, Christian; Hennerici, Michael G

2015-01-01

Clinical case reports of patients with exceptional musical talent and education provide clues as to how the brain processes musical ability and aptitude. In this chapter, selected examples from famous and unknown organ players/composers are presented to demonstrate the complexity of modified musical performances as well as the capacities of the brain to preserve artistic abilities: both authors are active organists and academic neurologists with strong clinical experience, practice, and knowledge about the challenges to play such an outstanding instrument and share their interest to explore potentially instrument-related phenomena of brain modulation in specific transient or permanent impairments. We concentrate on the sites of lesions, suggested pathophysiology, separate positive (e.g., seizures, visual or auditory hallucinations, or synesthesia [an involuntary perception produced by stimulation of another sense]) and negative phenomena (e.g., amusia, aphasia, neglect, or sensory-motor deficits) and particularly address aspects of recent concepts of temporary and permanent network disorders. © 2015 Elsevier B.V. All rights reserved.

A system for the real-time display of radar and video images of targets

NASA Technical Reports Server (NTRS)

Allen, W. W.; Burnside, W. D.

1990-01-01

Described here is a software and hardware system for the real-time display of radar and video images for use in a measurement range. The main purpose is to give the reader a clear idea of the software and hardware design and its functions. This system is designed around a Tektronix XD88-30 graphics workstation, used to display radar images superimposed on video images of the actual target. The system's purpose is to provide a platform for tha analysis and documentation of radar images and their associated targets in a menu-driven, user oriented environment.

Pathogenic Inflammation and Its Therapeutic Targeting in Systemic Lupus Erythematosus

PubMed Central

Gottschalk, Timothy A.; Tsantikos, Evelyn; Hibbs, Margaret L.

2015-01-01

Systemic lupus erythematosus (SLE, lupus) is a highly complex and heterogeneous autoimmune disease that most often afflicts women in their child-bearing years. It is characterized by circulating self-reactive antibodies that deposit in tissues, including skin, kidneys, and brain, and the ensuing inflammatory response can lead to irreparable tissue damage. Over many years, clinical trials in SLE have focused on agents that control B- and T-lymphocyte activation, and, with the single exception of an agent known as belimumab which targets the B-cell survival factor BAFF, they have been disappointing. At present, standard therapy for SLE with mild disease is the agent hydroxychloroquine. During disease flares, steroids are often used, while the more severe manifestations with major organ involvement warrant potent, broad-spectrum immunosuppression with cyclophosphamide or mycophenolate. Current treatments have severe and dose-limiting toxicities and thus a more specific therapy targeting a causative factor or signaling pathway would be greatly beneficial in SLE treatment. Moreover, the ability to control inflammation alongside B-cell activation may be a superior approach for disease control. There has been a recent focus on the innate immune system and associated inflammation, which has uncovered key players in driving the pathogenesis of SLE. Delineating some of these intricate inflammatory mechanisms has been possible with studies using spontaneous mouse mutants and genetically engineered mice. These strains, to varying degrees, exhibit hallmarks of the human disease and therefore have been utilized to model human SLE and to test new drugs. Developing a better understanding of the initiation and perpetuation of disease in SLE may uncover suitable novel targets for therapeutic intervention. Here, we discuss the involvement of inflammation in SLE disease pathogenesis, with a focus on several key proinflammatory cytokines and myeloid growth factors, and review the known

Secular dynamics of hierarchical multiple systems composed of nested binaries, with an arbitrary number of bodies and arbitrary hierarchical structure - II. External perturbations: flybys and supernovae

NASA Astrophysics Data System (ADS)

Hamers, Adrian S.

2018-05-01

We extend the formalism of a previous paper to include the effects of flybys and instantaneous perturbations such as supernovae on the long-term secular evolution of hierarchical multiple systems with an arbitrary number of bodies and hierarchy, provided that the system is composed of nested binary orbits. To model secular encounters, we expand the Hamiltonian in terms of the ratio of the separation of the perturber with respect to the barycentre of the multiple system, to the separation of the widest orbit. Subsequently, we integrate over the perturber orbit numerically or analytically. We verify our method for secular encounters and illustrate it with an example. Furthermore, we describe a method to compute instantaneous orbital changes to multiple systems, such as asymmetric supernovae and impulsive encounters. The secular code, with implementation of the extensions described in this paper, is publicly available within AMUSE, and we provide a number of simple example scripts to illustrate its usage for secular and impulsive encounters and asymmetric supernovae. The extensions presented in this paper are a next step towards efficiently modelling the evolution of complex multiple systems embedded in star clusters.

Method of composing two-dimensional scanned spectra observed by the New Vacuum Solar Telescope

NASA Astrophysics Data System (ADS)

Cai, Yun-Fang; Xu, Zhi; Chen, Yu-Chao; Xu, Jun; Li, Zheng-Gang; Fu, Yu; Ji, Kai-Fan

2018-04-01

In this paper we illustrate the technique used by the New Vacuum Solar Telescope (NVST) to increase the spatial resolution of two-dimensional (2D) solar spectroscopy observations involving two dimensions of space and one of wavelength. Without an image stabilizer at the NVST, large scale wobble motion is present during the spatial scanning, whose instantaneous amplitude can reach 1.3″ due to the Earth’s atmosphere and the precision of the telescope guiding system, and seriously decreases the spatial resolution of 2D spatial maps composed with scanned spectra. We make the following effort to resolve this problem: the imaging system (e.g., the TiO-band) is used to record and detect the displacement vectors of solar image motion during the raster scan, in both the slit and scanning directions. The spectral data (e.g., the Hα line) which are originally obtained in time sequence are corrected and re-arranged in space according to those displacement vectors. Raster scans are carried out in several active regions with different seeing conditions (two rasters are illustrated in this paper). Given a certain spatial sampling and temporal resolution, the spatial resolution of the composed 2D map could be close to that of the slit-jaw image. The resulting quality after correction is quantitatively evaluated with two methods. A physical quantity, such as the line-of-sight velocities in multiple layers of the solar atmosphere, is also inferred from the re-arranged spectrum, demonstrating the advantage of this technique.

Dual systemic tumor targeting with ligand-directed phage and Grp78 promoter induces tumor regression.

PubMed

Kia, Azadeh; Przystal, Justyna M; Nianiaris, Nastasia; Mazarakis, Nicholas D; Mintz, Paul J; Hajitou, Amin

2012-12-01

The tumor-specific Grp78 promoter is overexpressed in aggressive tumors. Cancer patients would benefit greatly from application of this promoter in gene therapy and molecular imaging; however, clinical benefit is limited by lack of strategies to target the systemic delivery of Grp78-driven transgenes to tumors. This study aims to assess the systemic efficacy of Grp78-guided expression of therapeutic and imaging transgenes relative to the standard cytomegalovirus (CMV) promoter. Combination of ligand and Grp78 transcriptional targeting into a single vector would facilitate systemic applications of the Grp78 promoter. We generated a dual tumor-targeted phage containing the arginine-glycine-aspartic acid tumor homing ligand and Grp78 promoter. Next, we combined flow cytometry, Western blot analysis, bioluminescence imaging of luciferase, and HSVtk/ganciclovir gene therapy and compared efficacy to conventional phage carrying the CMV promoter in vitro and in vivo in subcutaneous models of rat and human glioblastoma. We show that double-targeted phage provides persistent transgene expression in vitro and in tumors in vivo after systemic administration compared with conventional phage. Next, we showed significant tumor killing in vivo using the HSVtk/ganciclovir gene therapy and found a systemic antitumor effect of Grp78-driven HSVtk against therapy-resistant tumors. Finally, we uncovered a novel mechanism of Grp78 promoter activation whereby HSVtk/ganciclovir therapy upregulates Grp78 and transgene expression via the conserved unfolded protein response signaling cascade. These data validate the potential of Grp78 promoter in systemic cancer gene therapy and report the efficacy of a dual tumor targeting phage that may prove useful for translation into gene therapy and molecular imaging applications.

[Study on liver targeted drug delivery system of the effective anticancer component from Bolbstemma paniculatum].

PubMed

Sun, Yi-Yi; Ll, Tong-Hui; Tang, Chen-Kang; Zhu, Zi-Ping; Chi, Qun; Hou, Shi-Xiang

2005-06-01

To study the liver targeted drug delivery system of TBMS--the effective anticancer component from Bolbstemma paniculatum, and to discuss the system's function of decreasing toxicity. BCA was used as carrier material. The preparation through overall feedback dynamic techniques. The properties of preparation and toxicology were also technology of nanoparticles was optimized studied. Thenanoparticles' targeting in mice vivo was observed with transmission electron microscopy. The function of decreasing toxicity was researched by the XXTX-2000 automatic quantitative analysis management system. D50 was 0.68 microm. Drug-loading rate and entrapment rate were 37.3% and 88.6% respectively. The release in vitro accorded with Weibull equation. The reaching release balance time and the t 1/2 extended 26 times and 19 times respectively comparing with injection. Nanoparticles mainly distributed in liver tissue. Their toxicity to lung and liver was evidently lower than injection. Nanoparticles' LD50 exceeded injection's by 13.5% and their stimulus was much lower than injection. The TBMS can be targeted to liver by liver targeted drug delivery system. At the same time, the problem about the toxicity hindering clinical application could be solved, which lays the foundation for the further studies on TBMS.

Integrative FourD omics approach profiles the target network of the carbon storage regulatory system.

PubMed

Sowa, Steven W; Gelderman, Grant; Leistra, Abigail N; Buvanendiran, Aishwarya; Lipp, Sarah; Pitaktong, Areen; Vakulskas, Christopher A; Romeo, Tony; Baldea, Michael; Contreras, Lydia M

2017-02-28

Multi-target regulators represent a largely untapped area for metabolic engineering and anti-bacterial development. These regulators are complex to characterize because they often act at multiple levels, affecting proteins, transcripts and metabolites. Therefore, single omics experiments cannot profile their underlying targets and mechanisms. In this work, we used an Integrative FourD omics approach (INFO) that consists of collecting and analyzing systems data throughout multiple time points, using multiple genetic backgrounds, and multiple omics approaches (transcriptomics, proteomics and high throughput sequencing crosslinking immunoprecipitation) to evaluate simultaneous changes in gene expression after imposing an environmental stress that accentuates the regulatory features of a network. Using this approach, we profiled the targets and potential regulatory mechanisms of a global regulatory system, the well-studied carbon storage regulatory (Csr) system of Escherichia coli, which is widespread among bacteria. Using 126 sets of proteomics and transcriptomics data, we identified 136 potential direct CsrA targets, including 50 novel ones, categorized their behaviors into distinct regulatory patterns, and performed in vivo fluorescence-based follow up experiments. The results of this work validate 17 novel mRNAs as authentic direct CsrA targets and demonstrate a generalizable strategy to integrate multiple lines of omics data to identify a core pool of regulator targets. © The Author(s) 2017. Published by Oxford University Press on behalf of Nucleic Acids Research.

Development of a systematic feedback isolation approach for targeted strains from mixed culture systems.

PubMed

Poudel, Pramod; Tashiro, Yukihiro; Miyamoto, Hirokuni; Miyamoto, Hisashi; Okugawa, Yuki; Sakai, Kenji

2017-01-01

Elucidation of functions of bacteria in a mixed culture system (MCS) such as composting, activated sludge system is difficult, since the system is complicating with many unisolated bacteria. Here, we developed a systematic feedback isolation strategy for the isolation and rapid screening of multiple targeted strains from MCS. Six major strains (Corynebacterium sphenisci, Bacillus thermocloacae, Bacillus thermoamylovorans, Bacillus smithii, Bacillus humi, and Bacillus coagulans), which are detected by denaturing gradient gel electrophoresis (DGGE) analysis in our previous study on MCS for l-lactic acid production, were targeted for isolation. Based on information of suitable cultivation conditions (e.g., media, pH, temperature) from the literature, feedback isolation was performed to form 136 colonies. The following direct colony matrix assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS) was optimised as the second screening to narrow down 20 candidate colonies from similar spectra patterns with six closest type strains. This step could distinguish bacteria at the species level with distance similarity scores ≥0.55 corresponding to 16S rRNA gene sequence similarity ≥98.2%, suggesting that this is an effective technique to minimize isolates close to targeted type strains. Analysis of 16S rRNA gene sequences indicated that two targeted strains and one strain related to the target had successfully been isolated, showing high similarities (99.5-100%) with the sequences from the DGGE bands, and that the other candidates were affiliated with three strains that were closely related to the target species. This study proposes a new method for systematic feedback isolation that may be useful for isolating targeted strains from MCS for further investigation. Copyright © 2016 The Society for Biotechnology, Japan. Published by Elsevier B.V. All rights reserved.

Research on target information optics communications transmission characteristic and performance in multi-screens testing system

NASA Astrophysics Data System (ADS)

Li, Hanshan

2016-04-01

To enhance the stability and reliability of multi-screens testing system, this paper studies multi-screens target optical information transmission link properties and performance in long-distance, sets up the discrete multi-tone modulation transmission model based on geometric model of laser multi-screens testing system and visible light information communication principle; analyzes the electro-optic and photoelectric conversion function of sender and receiver in target optical information communication system; researches target information transmission performance and transfer function of the generalized visible-light communication channel; found optical information communication transmission link light intensity space distribution model and distribution function; derives the SNR model of information transmission communication system. Through the calculation and experiment analysis, the results show that the transmission error rate increases with the increment of transmission rate in a certain channel modulation depth; when selecting the appropriate transmission rate, the bit error rate reach 0.01.

The innate and adaptive infiltrating immune systems as targets for breast cancer immunotherapy

PubMed Central

Law, Andrew M K; Lim, Elgene; Ormandy, Christopher J

2017-01-01

A cancer cell-centric view has long dominated the field of cancer biology. Research efforts have focussed on aberrant cancer cell signalling pathways and on changes to cancer cell DNA. Mounting evidence demonstrates that many cancer-associated cell types within the tumour stroma co-evolve and support tumour growth and development, greatly modifying cancer cell behaviour, facilitating invasion and metastasis and controlling dormancy and sensitivity to drug therapy. Thus, these stromal cells represent potential targets for cancer therapy. Among these cell types, immune cells have emerged as a promising target for therapy. The adaptive and the innate immune system play an important role in normal mammary development and breast cancer. The number of infiltrating adaptive immune system cells with tumour-rejecting capacity, primarily, T lymphocytes, is lower in breast cancer compared with other cancer types, but infiltration occurs in a large proportion of cases. There is strong evidence demonstrating the importance of the immunosuppressive role of the innate immune system during breast cancer progression. A consideration of components of both the innate and the adaptive immune system is essential for the design and development of immunotherapies in breast cancer. In this review, we focus on the importance of immunosuppressive myeloid-derived suppressor cells (MDSCs) as potential targets for breast cancer therapy. PMID:28193698

The innate and adaptive infiltrating immune systems as targets for breast cancer immunotherapy.

PubMed

Law, Andrew M K; Lim, Elgene; Ormandy, Christopher J; Gallego-Ortega, David

2017-04-01

A cancer cell-centric view has long dominated the field of cancer biology. Research efforts have focussed on aberrant cancer cell signalling pathways and on changes to cancer cell DNA. Mounting evidence demonstrates that many cancer-associated cell types within the tumour stroma co-evolve and support tumour growth and development, greatly modifying cancer cell behaviour, facilitating invasion and metastasis and controlling dormancy and sensitivity to drug therapy. Thus, these stromal cells represent potential targets for cancer therapy. Among these cell types, immune cells have emerged as a promising target for therapy. The adaptive and the innate immune system play an important role in normal mammary development and breast cancer. The number of infiltrating adaptive immune system cells with tumour-rejecting capacity, primarily, T lymphocytes, is lower in breast cancer compared with other cancer types, but infiltration occurs in a large proportion of cases. There is strong evidence demonstrating the importance of the immunosuppressive role of the innate immune system during breast cancer progression. A consideration of components of both the innate and the adaptive immune system is essential for the design and development of immunotherapies in breast cancer. In this review, we focus on the importance of immunosuppressive myeloid-derived suppressor cells (MDSCs) as potential targets for breast cancer therapy. © 2017 The authors.

An affinity-directed protein missile system for targeted proteolysis.

PubMed

Fulcher, Luke J; Macartney, Thomas; Bozatzi, Polyxeni; Hornberger, Annika; Rojas-Fernandez, Alejandro; Sapkota, Gopal P

2016-10-01

The von Hippel-Lindau (VHL) protein serves to recruit the hypoxia-inducible factor alpha (HIF1α) protein under normoxia to the CUL2 E3 ubiquitin ligase for its ubiquitylation and degradation through the proteasome. In this report, we modify VHL to engineer an affinity-directed protein missile (AdPROM) system to direct specific endogenous target proteins for proteolysis in mammalian cells. The proteolytic AdPROM construct harbours a cameloid anti-green fluorescence protein (aGFP) nanobody that is fused to VHL for either constitutive or tetracycline-inducible expression. For target proteins, we exploit CRISPR/Cas9 to rapidly generate human kidney HEK293 and U2OS osteosarcoma homozygous knock-in cells harbouring GFP tags at the VPS34 (vacuolar protein sorting 34) and protein associated with SMAD1 (PAWS1, aka FAM83G) loci, respectively. Using these cells, we demonstrate that the expression of the VHL-aGFP AdPROM system results in near-complete degradation of the endogenous GFP-VPS34 and PAWS1-GFP proteins through the proteasome. Additionally, we show that Tet-inducible destruction of GFP-VPS34 results in the degradation of its associated partner, UVRAG, and reduction in levels of cellular phosphatidylinositol 3-phosphate. © 2016 The Authors.

An affinity-directed protein missile system for targeted proteolysis

PubMed Central

Fulcher, Luke J.; Macartney, Thomas; Bozatzi, Polyxeni; Hornberger, Annika; Rojas-Fernandez, Alejandro

2016-01-01

The von Hippel–Lindau (VHL) protein serves to recruit the hypoxia-inducible factor alpha (HIF1α) protein under normoxia to the CUL2 E3 ubiquitin ligase for its ubiquitylation and degradation through the proteasome. In this report, we modify VHL to engineer an affinity-directed protein missile (AdPROM) system to direct specific endogenous target proteins for proteolysis in mammalian cells. The proteolytic AdPROM construct harbours a cameloid anti-green fluorescence protein (aGFP) nanobody that is fused to VHL for either constitutive or tetracycline-inducible expression. For target proteins, we exploit CRISPR/Cas9 to rapidly generate human kidney HEK293 and U2OS osteosarcoma homozygous knock-in cells harbouring GFP tags at the VPS34 (vacuolar protein sorting 34) and protein associated with SMAD1 (PAWS1, aka FAM83G) loci, respectively. Using these cells, we demonstrate that the expression of the VHL-aGFP AdPROM system results in near-complete degradation of the endogenous GFP-VPS34 and PAWS1-GFP proteins through the proteasome. Additionally, we show that Tet-inducible destruction of GFP-VPS34 results in the degradation of its associated partner, UVRAG, and reduction in levels of cellular phosphatidylinositol 3-phosphate. PMID:27784791

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

Particle production of a graphite target system for the intensity frontier

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

Ding, X.; Kirk, H.; McDonald, K. T.

2015-05-03

A solid graphite target system is considered for an intense muon and/or neutrino source in support of physics at the intensity frontier. We previously optimized the geometric parameters of the beam and target to maximize particle production at low energies by incoming protons with kinetic energy of 6.75 GeV and an rms geometric emittance of 5 mm-mrad using the MARS15(2014) code. In this study, we ran MARS15 with ROOT-based geometry and also considered a mercury-jet target as an upgrade option. The optimization was extended to focused proton beams with transverse emittances from 5 to 50 mm-mrad, showing that the particlemore » production decreases slowly with increasing emittance. We also studied beam-dump configurations to suppress the rate of undesirable high-energy secondary particles in the beam.« less

Advances in oral nano-delivery systems for colon targeted drug delivery in inflammatory bowel disease: selective targeting to diseased versus healthy tissue.

PubMed

Hua, Susan; Marks, Ellen; Schneider, Jennifer J; Keely, Simon

2015-07-01

Colon targeted drug delivery is an active area of research for local diseases affecting the colon, as it improves the efficacy of therapeutics and enables localized treatment, which reduces systemic toxicity. Targeted delivery of therapeutics to the colon is particularly advantageous for the treatment of inflammatory bowel disease (IBD), which includes ulcerative colitis and Crohn's disease. Advances in oral drug delivery design have significantly improved the bioavailability of drugs to the colon; however in order for a drug to have therapeutic efficacy during disease, considerations must be made for the altered physiology of the gastrointestinal (GI) tract that is associated with GI inflammation. Nanotechnology has been used in oral dosage formulation design as strategies to further enhance uptake into diseased tissue within the colon. This review will describe some of the physiological challenges faced by orally administered delivery systems in IBD, the important developments in orally administered nano-delivery systems for colon targeting, and the future advances of this research. Inflammatory Bowel Disease (IBD) poses a significant problem for a large number of patients worldwide. Current medical therapy mostly aims at suppressing the active inflammatory episodes. In this review article, the authors described and discussed the various approaches current nano-delivery systems can offer in overcoming the limitations of conventional drug formulations. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

Real-Time Implementation of an Asynchronous Vision-Based Target Tracking System for an Unmanned Aerial Vehicle

DTIC Science & Technology

2007-06-01

Chin Khoon Quek. “Vision Based Control and Target Range Estimation for Small Unmanned Aerial Vehicle.” Master’s Thesis, Naval Postgraduate School...December 2005. [6] Kwee Chye Yap. “Incorporating Target Mensuration System for Target Motion Estimation Along a Road Using Asynchronous Filter

A real-time tracking system of infrared dim and small target based on FPGA and DSP

NASA Astrophysics Data System (ADS)

Rong, Sheng-hui; Zhou, Hui-xin; Qin, Han-lin; Wang, Bing-jian; Qian, Kun

2014-11-01

A core technology in the infrared warning system is the detection tracking of dim and small targets with complicated background. Consequently, running the detection algorithm on the hardware platform has highly practical value in the military field. In this paper, a real-time detection tracking system of infrared dim and small target which is used FPGA (Field Programmable Gate Array) and DSP (Digital Signal Processor) as the core was designed and the corresponding detection tracking algorithm and the signal flow is elaborated. At the first stage, the FPGA obtain the infrared image sequence from the sensor, then it suppresses background clutter by mathematical morphology method and enhances the target intensity by Laplacian of Gaussian operator. At the second stage, the DSP obtain both the original image and the filtered image form the FPGA via the video port. Then it segments the target from the filtered image by an adaptive threshold segmentation method and gets rid of false target by pipeline filter. Experimental results show that our system can achieve higher detection rate and lower false alarm rate.

Highly efficient targeted mutagenesis in one-cell mouse embryos mediated by the TALEN and CRISPR/Cas systems.

PubMed

Yasue, Akihiro; Mitsui, Silvia Naomi; Watanabe, Takahito; Sakuma, Tetsushi; Oyadomari, Seiichi; Yamamoto, Takashi; Noji, Sumihare; Mito, Taro; Tanaka, Eiji

2014-07-16

Since the establishment of embryonic stem (ES) cell lines, the combined use of gene targeting with homologous recombination has aided in elucidating the functions of various genes. However, the ES cell technique is inefficient and time-consuming. Recently, two new gene-targeting technologies have been developed: the transcription activator-like effector nuclease (TALEN) system, and the clustered regularly interspaced short palindromic repeat (CRISPR)/CRISPR-associated protein (Cas) system. In addition to aiding researchers in solving conventional problems, these technologies can be used to induce site-specific mutations in various species for which ES cells have not been established. Here, by targeting the Fgf10 gene through RNA microinjection in one-cell mouse embryos with the TALEN and CRISPR/Cas systems, we produced the known limb-defect phenotypes of Fgf10-deficient embryos at the F0 generation. Compared to the TALEN system, the CRISPR/Cas system induced the limb-defect phenotypes with a strikingly higher efficiency. Our results demonstrate that although both gene-targeting technologies are useful, the CRISPR/Cas system more effectively elicits single-step biallelic mutations in mice.

The targeting of plant cellular systems by injected type III effector proteins.

PubMed

Lewis, Jennifer D; Guttman, David S; Desveaux, Darrell

2009-12-01

The battle between phytopathogenic bacteria and their plant hosts has revealed a diverse suite of strategies and mechanisms employed by the pathogen or the host to gain the higher ground. Pathogens continually evolve tactics to acquire host resources and dampen host defences. Hosts must evolve surveillance and defence systems that are sensitive enough to rapidly respond to a diverse range of pathogens, while reducing costly and damaging inappropriate misexpression. The primary virulence mechanism employed by many bacteria is the type III secretion system, which secretes and translocates effector proteins directly into the cells of their plant hosts. Effectors have diverse enzymatic functions and can target specific components of plant systems. While these effectors should favour bacterial fitness, the host may be able to thwart infection by recognizing the activity or presence of these foreign molecules and initiating retaliatory immune measures. We review the diverse host cellular systems exploited by bacterial effectors, with particular focus on plant proteins directly targeted by effectors. Effector-host interactions reveal different stages of the battle between pathogen and host, as well as the diverse molecular strategies employed by bacterial pathogens to hijack eukaryotic cellular systems.

An integrated CRISPR Bombyx mori genome editing system with improved efficiency and expanded target sites.

PubMed

Ma, Sanyuan; Liu, Yue; Liu, Yuanyuan; Chang, Jiasong; Zhang, Tong; Wang, Xiaogang; Shi, Run; Lu, Wei; Xia, Xiaojuan; Zhao, Ping; Xia, Qingyou

2017-04-01

Genome editing enabled unprecedented new opportunities for targeted genomic engineering of a wide variety of organisms ranging from microbes, plants, animals and even human embryos. The serial establishing and rapid applications of genome editing tools significantly accelerated Bombyx mori (B. mori) research during the past years. However, the only CRISPR system in B. mori was the commonly used SpCas9, which only recognize target sites containing NGG PAM sequence. In the present study, we first improve the efficiency of our previous established SpCas9 system by 3.5 folds. The improved high efficiency was also observed at several loci in both BmNs cells and B. mori embryos. Then to expand the target sites, we showed that two newly discovered CRISPR system, SaCas9 and AsCpf1, could also induce highly efficient site-specific genome editing in BmNs cells, and constructed an integrated CRISPR system. Genome-wide analysis of targetable sites was further conducted and showed that the integrated system cover 69,144,399 sites in B. mori genome, and one site could be found in every 6.5 bp. The efficiency and resolution of this CRISPR platform will probably accelerate both fundamental researches and applicable studies in B. mori, and perhaps other insects. Copyright © 2017 Elsevier Ltd. All rights reserved.

Hidden targets of ubiquitin proteasome system: To prevent diabetic nephropathy.

PubMed

Goru, Santosh Kumar; Kadakol, Almesh; Gaikwad, Anil Bhanudas

2017-06-01

Diabetic nephropathy (DN) is the major cause of end stage renal failure. Although, several therapeutic targets have emerged to prevent the progression of DN, the number of people with DN still continues to rise worldwide, suggesting an urgent need of novel targets to prevent DN completely. Currently, the role of ubiquitin proteasome system (UPS) has been highlighted in the pathogenesis and progression of various diseases like obesity, insulin resistance, atherosclerosis, cancers, neurodegerative disorders and including secondary complications of diabetes. UPS mainly involves in protein homeostatis through ubiquitination (post translational modification) and proteasomal degradation of various proteins. Ubiquitination, not only involves in proteasomal degradation, but also directs the substrate proteins to participate in multitude of cell signalling pathways. However, very little is known about ubiquitination and UPS in the progression of DN. This review mainly focuses on UPS and its components including E2 conjugating enzymes, E3 ligases and deubiquitinases (DUBs) in the development of DN and thus may help us to find novel therapeutic targets with in UPS to prevent DN completely in future. Copyright © 2017 Elsevier Ltd. All rights reserved.

Intellectual maturity and longevity: late-blooming composers and writers live longer than child prodigies

PubMed Central

Hafkamp, Maurits P.J.; Slaets, Joris P.J.; van Bodegom, David

2017-01-01

Life history theory links human physical and sexual development to longevity. However, there have been no studies on the association of intellectual development with longevity. This observational study investigates the relationship between the onset of intellectual maturity and lifespan through the life histories of composers and creative writers, whose intellectual development can be gauged through their compositions and writings. In these groups we model the relationship between the age at first creative work, and age at death using multilevel regression, adjusting for sex, date of birth, and nationality. Historical biographical records on 1110 musical composers and 1182 creative writers, born in the period 1400 AD through 1915 AD, were obtained from the Oxford Companion to Music and the Oxford Companion to English Literature. Composers and creative writers lived, respectively 0.16 (p = 0.02) and 0.18 (p < 0.01) years longer for each later year of age at first work. When completion of the first creative work is interpreted as a proxy for the onset of intellectual maturity in composers and creative writers, our findings indicate that a later onset of intellectual maturity is associated with higher longevity. PMID:28562321

Intellectual maturity and longevity: late-blooming composers and writers live longer than child prodigies.

PubMed

Hafkamp, Maurits P J; Slaets, Joris P J; van Bodegom, David

2017-05-30

Life history theory links human physical and sexual development to longevity. However, there have been no studies on the association of intellectual development with longevity. This observational study investigates the relationship between the onset of intellectual maturity and lifespan through the life histories of composers and creative writers, whose intellectual development can be gauged through their compositions and writings. In these groups we model the relationship between the age at first creative work, and age at death using multilevel regression, adjusting for sex, date of birth, and nationality. Historical biographical records on 1110 musical composers and 1182 creative writers, born in the period 1400 AD through 1915 AD, were obtained from the Oxford Companion to Music and the Oxford Companion to English Literature. Composers and creative writers lived, respectively 0.16 ( p = 0.02) and 0.18 ( p < 0.01) years longer for each later year of age at first work. When completion of the first creative work is interpreted as a proxy for the onset of intellectual maturity in composers and creative writers, our findings indicate that a later onset of intellectual maturity is associated with higher longevity.

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

Polarized Solid State Target

NASA Astrophysics Data System (ADS)

Dutz, Hartmut; Goertz, Stefan; Meyer, Werner

2017-01-01

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

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.

Targeting endogenous proteins for degradation through the affinity-directed protein missile system.

PubMed

Fulcher, Luke J; Hutchinson, Luke D; Macartney, Thomas J; Turnbull, Craig; Sapkota, Gopal P

2017-05-01

Targeted proteolysis of endogenous proteins is desirable as a research toolkit and in therapeutics. CRISPR/Cas9-mediated gene knockouts are irreversible and often not feasible for many genes. Similarly, RNA interference approaches necessitate prolonged treatments, can lead to incomplete knockdowns and are often associated with off-target effects. Targeted proteolysis can overcome these limitations. In this report, we describe an affinity-directed protein missile (AdPROM) system that harbours the von Hippel-Lindau (VHL) protein, the substrate receptor of the Cullin2 (CUL2) E3 ligase complex, tethered to polypeptide binders that selectively bind and recruit endogenous target proteins to the CUL2-E3 ligase complex for ubiquitination and proteasomal degradation. By using synthetic monobodies that selectively bind the protein tyrosine phosphatase SHP2 and a camelid-derived VHH nanobody that selectively binds the human ASC protein, we demonstrate highly efficient AdPROM-mediated degradation of endogenous SHP2 and ASC in human cell lines. We show that AdPROM-mediated loss of SHP2 in cells impacts SHP2 biology. This study demonstrates for the first time that small polypeptide binders that selectively recognize endogenous target proteins can be exploited for AdPROM-mediated destruction of the target proteins. © 2017 The Authors.

Targeting endogenous proteins for degradation through the affinity-directed protein missile system

PubMed Central

Fulcher, Luke J.; Hutchinson, Luke D.; Macartney, Thomas J.; Turnbull, Craig

2017-01-01

Targeted proteolysis of endogenous proteins is desirable as a research toolkit and in therapeutics. CRISPR/Cas9-mediated gene knockouts are irreversible and often not feasible for many genes. Similarly, RNA interference approaches necessitate prolonged treatments, can lead to incomplete knockdowns and are often associated with off-target effects. Targeted proteolysis can overcome these limitations. In this report, we describe an affinity-directed protein missile (AdPROM) system that harbours the von Hippel–Lindau (VHL) protein, the substrate receptor of the Cullin2 (CUL2) E3 ligase complex, tethered to polypeptide binders that selectively bind and recruit endogenous target proteins to the CUL2-E3 ligase complex for ubiquitination and proteasomal degradation. By using synthetic monobodies that selectively bind the protein tyrosine phosphatase SHP2 and a camelid-derived VHH nanobody that selectively binds the human ASC protein, we demonstrate highly efficient AdPROM-mediated degradation of endogenous SHP2 and ASC in human cell lines. We show that AdPROM-mediated loss of SHP2 in cells impacts SHP2 biology. This study demonstrates for the first time that small polypeptide binders that selectively recognize endogenous target proteins can be exploited for AdPROM-mediated destruction of the target proteins. PMID:28490657

Mucosal and systemic immune responses elicited by recombinant Lactococcus lactis expressing a fusion protein composed of pertussis toxin and filamentous hemagglutinin from Bordetella pertussis.

PubMed

Torkashvand, Ali; Bahrami, Fariborz; Adib, Minoo; Ajdary, Soheila

2018-05-05

We constructed a food-grade expression system harboring a F1S1 fusion protein of Bordetella pertussis to be produced in Lactococcus lactis NZ3900 as a new oral vaccine model against whooping cough, caused by B. pertussis. F1S1 was composed of N-terminally truncated S1 subunit of pertussis toxin and type I immunodominant domain of filamentous hemagglutinin which are both known as protective immunogens against pertussis. The recombinant L. lactis was administered via oral or intranasal routes to BALB/c mice and the related specific systemic and mucosal immune responses were then evaluated. The results indicated significantly higher levels of specific IgA in the lung extracts and IgG in sera of mucosally-immunized mice, compared to their controls. It was revealed that higher levels of IgG2a, compared to IgG1, were produced in all mucosally-immunized mice. Moreover, immunized mice developed Th1 responses with high levels of IFN-γ production by the spleen cells. These findings provide evidence for L. lactis to be used as a suitable vehicle for expression and delivery of F1S1 fusion protein to mucosa and induction of appropriate systemic and mucosal immune responses against pertussis. Copyright © 2018 Elsevier Ltd. All rights reserved.

Open-shell characters and second hyperpolarizabilities of one-dimensional graphene nanoflakes composed of trigonal graphene units.

PubMed

Yoneda, Kyohei; Nakano, Masayoshi; Fukui, Hitoshi; Minami, Takuya; Shigeta, Yasuteru; Kubo, Takashi; Botek, Edith; Champagne, Benoît

2011-06-20

The impact of topology on the open-shell characters and the second hyperpolarizabilities (γ) has been addressed for one-dimensional graphene nanoflakes (GNFs) composed of the smallest trigonal graphene (phenalenyl) units. The main results are: 1) These GNFs show not only diradical but also multiradical characters when increasing the number of linked units. 2) GNFs composed of an equivalent number of units can exhibit a wide range of open-shell characters-from nearly closed-shell to pure multiradical characters-depending on the linking pattern of the trigonal units. 3) This wide variation in open-shell characters is explained by their resonance structures and/or by their (HOMO-i)-(LUMO+i) gaps deduced from the orbital correlations. 4) The change in the linking structure of the units can effectively control their open-shell characters as well as their γ values, of which the longitudinal components are significantly enhanced for the singlet GNFs having intermediate open-shell characters. 5) Singlet alternately linked (AL) systems present intermediate multiradical characters even in the case of a large number of units, which creates a significant enhancement of γ with increasing the size, whereas nonalternately linked (NAL) systems, which present pure multiradical characters, possess much smaller γ values. Finally 6) by switching from the singlet to the highest spin states, the γ values of NAL systems hardly change, whereas those of AL systems exhibit large reductions. These fascinating structure-property relationships between the topology of the GNFs, their open-shell characters, and their γ values not only deepen the understanding of open-shell characters of GNFs but aim also at stimulating further design studies to achieve giant NLO responses based on open-shell graphene-like materials. Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

A Production System Model of Capturing Reactive Moving Targets. M.S. Thesis

NASA Technical Reports Server (NTRS)

Jagacinski, R. J.; Plamondon, B. D.; Miller, R. A.

1984-01-01

Subjects manipulated a control stick to position a cursor over a moving target that reacted with a computer-generated escape strategy. The cursor movements were described at two levels of abstraction. At the upper level, a production system described transitions among four modes of activity; rapid acquisition, close following, a predictive mode, and herding. Within each mode, differential equations described trajectory-generating mechanisms. A simulation of this two-level model captures the targets in a manner resembling the episodic time histories of human subjects.

The p38α mitogen-activated protein kinase as a central nervous system drug discovery target

PubMed Central

Borders, Aaron S; de Almeida, Lucia; Van Eldik, Linda J; Watterson, D Martin

2008-01-01

Protein kinases are critical modulators of a variety of cellular signal transduction pathways, and abnormal phosphorylation events can be a cause or contributor to disease progression in a variety of disorders. This has led to the emergence of protein kinases as an important new class of drug targets for small molecule therapeutics. A serine/threonine protein kinase, p38α mitogen-activated protein kinase (MAPK), is an established therapeutic target for peripheral inflammatory disorders because of its critical role in regulation of proinflammatory cytokine production. There is increasing evidence that p38α MAPK is also an important regulator of proinflammatory cytokine levels in the central nervous system, raising the possibility that the kinase may be a drug discovery target for central nervous system disorders where cytokine overproduction contributes to disease progression. Development of bioavailable, central nervous system-penetrant p38α MAPK inhibitors provides the required foundation for drug discovery campaigns targeting p38α MAPK in neurodegenerative disorders. PMID:19090985

The p38alpha mitogen-activated protein kinase as a central nervous system drug discovery target.

PubMed

Borders, Aaron S; de Almeida, Lucia; Van Eldik, Linda J; Watterson, D Martin

2008-12-03

Protein kinases are critical modulators of a variety of cellular signal transduction pathways, and abnormal phosphorylation events can be a cause or contributor to disease progression in a variety of disorders. This has led to the emergence of protein kinases as an important new class of drug targets for small molecule therapeutics. A serine/threonine protein kinase, p38alpha mitogen-activated protein kinase (MAPK), is an established therapeutic target for peripheral inflammatory disorders because of its critical role in regulation of proinflammatory cytokine production. There is increasing evidence that p38alpha MAPK is also an important regulator of proinflammatory cytokine levels in the central nervous system, raising the possibility that the kinase may be a drug discovery target for central nervous system disorders where cytokine overproduction contributes to disease progression. Development of bioavailable, central nervous system-penetrant p38alpha MAPK inhibitors provides the required foundation for drug discovery campaigns targeting p38alpha MAPK in neurodegenerative disorders.

Theranostic nanoparticles carrying doxorubicin attenuate targeting ligand specific antibody responses following systemic delivery.

PubMed

Yang, Emmy; Qian, Weiping; Cao, Zehong; Wang, Liya; Bozeman, Erica N; Ward, Christina; Yang, Bin; Selvaraj, Periasamy; Lipowska, Malgorzata; Wang, Y Andrew; Mao, Hui; Yang, Lily

2015-01-01

Understanding the effects of immune responses on targeted delivery of nanoparticles is important for clinical translations of new cancer imaging and therapeutic nanoparticles. In this study, we found that repeated administrations of magnetic iron oxide nanoparticles (IONPs) conjugated with mouse or human derived targeting ligands induced high levels of ligand specific antibody responses in normal and tumor bearing mice while injections of unconjugated mouse ligands were weakly immunogenic and induced a very low level of antibody response in mice. Mice that received intravenous injections of targeted and polyethylene glycol (PEG)-coated IONPs further increased the ligand specific antibody production due to differential uptake of PEG-coated nanoparticles by macrophages and dendritic cells. However, the production of ligand specific antibodies was markedly inhibited following systemic delivery of theranostic nanoparticles carrying a chemotherapy drug, doxorubicin. Targeted imaging and histological analysis revealed that lack of the ligand specific antibodies led to an increase in intratumoral delivery of targeted nanoparticles. Results of this study support the potential of further development of targeted theranostic nanoparticles for the treatment of human cancers.

Beyond the Enthymeme: Sorites, Critical Thinking, and the Composing Process.

ERIC Educational Resources Information Center

Hill, Carolyn

A teacher presents a writing exercise designed to facilitate audience-directed, critical thinking during the process of composing, that starts students thinking in terms of sorites and enthymemes. Students first read a CIA manual, "Psychological Operations in Guerrilla Warfare," that instructs the Contra guerrillas in illegal acts and…

Why Targeted Therapies are Necessary for Systemic Lupus Erythematosus

PubMed Central

Durcan, Laura; Petri, Michelle

2016-01-01

Systemic lupus erythematosus (SLE) continues to have important morbidity and accelerated mortality despite therapeutic advances. Targeted therapies offer the possibility of improved efficacy with fewer side-effects. Current management strategies rely heavily on non-specific immunosuppressive agents. Prednisone, in particular, is responsible for a considerable burden of later organ damage. There are a multitude of diverse mechanisms of disease activity, immunogenic abnormalities and clinical manifestations to take into consideration in SLE. Many targeted agents with robust mechanistic pre-clinical data and promising early phase studies have ultimately been disappointing in phase III randomized controlled studies. Recent efforts have focused on B cell therapies, in particular given the success of belimumab in clinical trials, with limited success. We remain optimistic regarding other specific therapies being evaluated including interferon alpha blockade. It is likely that in SLE, given the heterogeneity of the population involved, precision medicine is needed, rather than expecting that any single biologic will be universally effective. PMID:27497251

Exploiting the CRISPR/Cas9 System for Targeted Genome Mutagenesis in Petunia.

PubMed

Zhang, Bin; Yang, Xia; Yang, Chunping; Li, Mingyang; Guo, Yulong

2016-02-03

Recently, CRISPR/Cas9 technology has emerged as a powerful approach for targeted genome modification in eukaryotic organisms from yeast to human cell lines. Its successful application in several plant species promises enormous potential for basic and applied plant research. However, extensive studies are still needed to assess this system in other important plant species, to broaden its fields of application and to improve methods. Here we showed that the CRISPR/Cas9 system is efficient in petunia (Petunia hybrid), an important ornamental plant and a model for comparative research. When PDS was used as target gene, transgenic shoot lines with albino phenotype accounted for 55.6%-87.5% of the total regenerated T0 Basta-resistant lines. A homozygous deletion close to 1 kb in length can be readily generated and identified in the first generation. A sequential transformation strategy--introducing Cas9 and sgRNA expression cassettes sequentially into petunia--can be used to make targeted mutations with short indels or chromosomal fragment deletions. Our results present a new plant species amenable to CRIPR/Cas9 technology and provide an alternative procedure for its exploitation.

Clustered carbohydrates as a target for natural killer cells: a model system.

PubMed

Kovalenko, Elena I; Abakushina, Elena; Telford, William; Kapoor, Veena; Korchagina, Elena; Khaidukov, Sergei; Molotkovskaya, Irina; Sapozhnikov, Alexander; Vlaskin, Pavel; Bovin, Nicolai

2007-03-01

Membrane-associated oligosaccharides are known to take part in interactions between natural killer (NK) cells and their targets and modulate NK cell activity. A model system was therefore developed using synthetic glycoconjugates as tools to modify the carbohydrate pattern on NK target cell surfaces. NK cells were then assessed for function in response to synthetic glycoconjugates, using both cytolysis-associated caspase 6 activation measured by flow cytometry and IFN-gamma production. Lipophilic neoglycoconjugates were synthesized to provide their easy incorporation into the target cell membranes and to make carbohydrate residues available for cell-cell interactions. While incorporation was successful based on fluorescence monitoring, glycoconjugate incorporation did not evoke artifactual changes in surface antigen expression, and had no negative effect on cell viability. Glycoconjugates contained Le(x), sulfated Le(x), and Le(y) sharing the common structure motif trisaccharide Le(x) were revealed to enhance cytotoxicity mediated specifically by CD16 +CD56+NK cells. The glycoconjugate effects were dependent on saccharide presentation in a polymeric form. Only polymeric, or clustered, but not monomeric glycoconjugates resulted in alteration of cytotoxicity in our system, suggesting that appropriate presentation is critical for carbohydrate recognition and subsequent biological effects.

Exploiting the CRISPR/Cas9 System for Targeted Genome Mutagenesis in Petunia

PubMed Central

Zhang, Bin; Yang, Xia; Yang, Chunping; Li, Mingyang; Guo, Yulong

2016-01-01

Recently, CRISPR/Cas9 technology has emerged as a powerful approach for targeted genome modification in eukaryotic organisms from yeast to human cell lines. Its successful application in several plant species promises enormous potential for basic and applied plant research. However, extensive studies are still needed to assess this system in other important plant species, to broaden its fields of application and to improve methods. Here we showed that the CRISPR/Cas9 system is efficient in petunia (Petunia hybrid), an important ornamental plant and a model for comparative research. When PDS was used as target gene, transgenic shoot lines with albino phenotype accounted for 55.6%–87.5% of the total regenerated T0 Basta-resistant lines. A homozygous deletion close to 1 kb in length can be readily generated and identified in the first generation. A sequential transformation strategy—introducing Cas9 and sgRNA expression cassettes sequentially into petunia—can be used to make targeted mutations with short indels or chromosomal fragment deletions. Our results present a new plant species amenable to CRIPR/Cas9 technology and provide an alternative procedure for its exploitation. PMID:26837606

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.

The CRISPR/Cas9 system produces specific and homozygous targeted gene editing in rice in one generation.

PubMed

Zhang, Hui; Zhang, Jinshan; Wei, Pengliang; Zhang, Botao; Gou, Feng; Feng, Zhengyan; Mao, Yanfei; Yang, Lan; Zhang, Heng; Xu, Nanfei; Zhu, Jian-Kang

2014-08-01

The CRISPR/Cas9 system has been demonstrated to efficiently induce targeted gene editing in a variety of organisms including plants. Recent work showed that CRISPR/Cas9-induced gene mutations in Arabidopsis were mostly somatic mutations in the early generation, although some mutations could be stably inherited in later generations. However, it remains unclear whether this system will work similarly in crops such as rice. In this study, we tested in two rice subspecies 11 target genes for their amenability to CRISPR/Cas9-induced editing and determined the patterns, specificity and heritability of the gene modifications. Analysis of the genotypes and frequency of edited genes in the first generation of transformed plants (T0) showed that the CRISPR/Cas9 system was highly efficient in rice, with target genes edited in nearly half of the transformed embryogenic cells before their first cell division. Homozygotes of edited target genes were readily found in T0 plants. The gene mutations were passed to the next generation (T1) following classic Mendelian law, without any detectable new mutation or reversion. Even with extensive searches including whole genome resequencing, we could not find any evidence of large-scale off-targeting in rice for any of the many targets tested in this study. By specifically sequencing the putative off-target sites of a large number of T0 plants, low-frequency mutations were found in only one off-target site where the sequence had 1-bp difference from the intended target. Overall, the data in this study point to the CRISPR/Cas9 system being a powerful tool in crop genome engineering. © 2014 Society for Experimental Biology, Association of Applied Biologists and John Wiley & Sons Ltd.

Molecular Mechanisms of RNA-Targeting by Cas13-containing Type VI CRISPR-Cas Systems.

PubMed

O'Connell, Mitchell

2018-06-22

Prokaryotic adaptive immune systems use CRISPRs (Clustered Regularly Interspaced Short Palindromic Repeats) and CRISPR associated (Cas) proteins for RNA-guided cleavage of foreign genetic elements. The focus of this review, Type VI CRISPR-Cas systems, include a single protein known as Cas13 (formerly C2c2), that when assembled with a crRNA forms a crRNA-guided RNA-targeting effector complex. Type VI CRISPR-Cas systems can be divided into four subtypes (A-D) based on Cas13 phylogeny. All Cas13 proteins studied to date possess two enzymatically distinct ribonuclease activities that are required for optimal interference. One RNase is responsible for pre-crRNA processing to form mature Type VI interference complexes, while the other RNase activity provided by the two HEPN (Higher Eukaryotes and Prokaryotes Nucleotide-binding) domains, is required for degradation of target RNA during viral interference. In this review, I will compare and contrast what is known about the molecular architecture and behavior of Type VI (A-D) CRISPR-Cas13 interference complexes, how this allows them to carry out their RNA-targeting function, how Type VI accessory proteins are able to modulate Cas13 activity, and how together all of these features have led to the rapid development of a range of RNA-targeting applications. Throughout I will also discuss some of the outstanding questions regarding Cas13's molecular behavior, and its role in bacterial adaptive immunity and RNA-targeting applications. Copyright © 2018. Published by Elsevier Ltd.

Measurement of the target current by inductive probe during laser interaction on terawatt laser system PALS.

PubMed

Cikhardt, J; Krása, J; De Marco, M; Pfeifer, M; Velyhan, A; Krouský, E; Cikhardtová, B; Klír, D; Rezáč, K; Ullschmied, J; Skála, J; Kubeš, P; Kravárik, J

2014-10-01

Measurements of the return-current flowing through a solid target irradiated with the sub-nanosecond kJ-class Prague Asterix Laser System is reported. A new inductive target probe was developed which allows us measuring the target current derivative in a kA/ns range. The dependences of the target current on the laser pulse energy for cooper, graphite, and polyethylene targets are reported. The experiment shows that the target current is proportional to the deposited laser energy and is strongly affected by the shot-to-shot fluctuations. The corresponding maximum target charge exceeded a value of 10 μC. A return-current dependence of the electromagnetic pulse produced by the laser-target interaction is presented.

[The use of honey in the simple and composed drugs at Rhazés].

PubMed

Katouzian-Safadi, Mehrnaz; Bonmatin, Jean-Marc

2003-01-01

Rāzī or Rhazès for Latin people is one of the great scientists of ninth century. He left major works in medicine, pharmacy and in alchemy. We examine here, the use of honey by this scientist as a simple drug and as one of the essential substances included in composed medicines. That leads us to examine the notion of simple and of composed in this physician and alchemist.

A system for the measurement of gene targeting efficiency in human cell lines using an antibiotic resistance-GFP fusion gene.

PubMed

Konishi, Yuko; Karnan, Sivasundaram; Takahashi, Miyuki; Ota, Akinobu; Damdindorj, Lkhagvasuren; Hosokawa, Yoshitaka; Konishi, Hiroyuki

2012-09-01

Gene targeting in a broad range of human somatic cell lines has been hampered by inefficient homologous recombination. To improve this technology and facilitate its widespread application, it is critical to first have a robust and efficient research system for measuring gene targeting efficiency. Here, using a fusion gene consisting of hygromycin B phosphotransferase and 3'-truncated enhanced GFP (HygR-5' EGFP) as a reporter gene, we created a molecular system monitoring the ratio of homologous to random integration (H/R ratio) of targeting vectors into the genome. Cell clones transduced with a reporter vector containing HygR-5' EGFP were efficiently established from two human somatic cell lines. Established HygR-5' EGFP reporter clones retained their capacity to monitor gene targeting efficiency for a longer duration than a conventional reporter system using an unfused 5' EGFP gene. With the HygR-5' EGFP reporter system, we reproduced previous findings of gene targeting frequency being up-regulated by the use of an adeno-associated viral (AAV) backbone, a promoter-trap system, or a longer homology arm in a targeting vector, suggesting that this system accurately monitors H/R ratio. Thus, our HygR-5' EGFP reporter system will assist in the development of an efficient AAV-based gene targeting technology.

Feasibility Test of a Pulse Modulated Pressurization System for a High Altitude Supersonic Target Vehicle Propulsion System.

DTIC Science & Technology

1976-11-01

pressure switch . The system was tested for stability of operation and accuracy of pressure control, using a High Altitude Supersonic Target (HAST...stable and accurate to approximately the deadband of the pressure switch used, 2 psi. (Author)

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.

Enhancing Targeted Genomic DNA Editing in Chicken Cells Using the CRISPR/Cas9 System

PubMed Central

Wang, Ling; Yang, Likai; Guo, Yijie; Du, Weili; Yin, Yajun; Zhang, Tao; Lu, Hongzhao

2017-01-01

The CRISPR/Cas9 system has enabled highly efficient genome targeted editing for various organisms. However, few studies have focused on CRISPR/Cas9 nuclease-mediated chicken genome editing compared with mammalian genomes. The current study combined CRISPR with yeast Rad52 (yRad52) to enhance targeted genomic DNA editing in chicken DF-1 cells. The efficiency of CRISPR/Cas9 nuclease-induced targeted mutations in the chicken genome was increased to 41.9% via the enrichment of the dual-reporter surrogate system. In addition, the combined effect of CRISPR nuclease and yRad52 dramatically increased the efficiency of the targeted substitution in the myostatin gene using 50-mer oligodeoxynucleotides (ssODN) as the donor DNA, resulting in a 36.7% editing efficiency after puromycin selection. Furthermore, based on the effect of yRad52, the frequency of exogenous gene integration in the chicken genome was more than 3-fold higher than that without yRad52. Collectively, these results suggest that ssODN is an ideal donor DNA for targeted substitution and that CRISPR/Cas9 combined with yRad52 significantly enhances chicken genome editing. These findings could be extensively applied in other organisms. PMID:28068387

TargetVue: Visual Analysis of Anomalous User Behaviors in Online Communication Systems.

PubMed

Cao, Nan; Shi, Conglei; Lin, Sabrina; Lu, Jie; Lin, Yu-Ru; Lin, Ching-Yung

2016-01-01

Users with anomalous behaviors in online communication systems (e.g. email and social medial platforms) are potential threats to society. Automated anomaly detection based on advanced machine learning techniques has been developed to combat this issue; challenges remain, though, due to the difficulty of obtaining proper ground truth for model training and evaluation. Therefore, substantial human judgment on the automated analysis results is often required to better adjust the performance of anomaly detection. Unfortunately, techniques that allow users to understand the analysis results more efficiently, to make a confident judgment about anomalies, and to explore data in their context, are still lacking. In this paper, we propose a novel visual analysis system, TargetVue, which detects anomalous users via an unsupervised learning model and visualizes the behaviors of suspicious users in behavior-rich context through novel visualization designs and multiple coordinated contextual views. Particularly, TargetVue incorporates three new ego-centric glyphs to visually summarize a user's behaviors which effectively present the user's communication activities, features, and social interactions. An efficient layout method is proposed to place these glyphs on a triangle grid, which captures similarities among users and facilitates comparisons of behaviors of different users. We demonstrate the power of TargetVue through its application in a social bot detection challenge using Twitter data, a case study based on email records, and an interview with expert users. Our evaluation shows that TargetVue is beneficial to the detection of users with anomalous communication behaviors.

Texture-based measurement of spatial frequency response using the dead leaves target: extensions, and application to real camera systems

NASA Astrophysics Data System (ADS)

McElvain, Jon; Campbell, Scott P.; Miller, Jonathan; Jin, Elaine W.

2010-01-01

The dead leaves model was recently introduced as a method for measuring the spatial frequency response (SFR) of camera systems. The target consists of a series of overlapping opaque circles with a uniform gray level distribution and radii distributed as r-3. Unlike the traditional knife-edge target, the SFR derived from the dead leaves target will be penalized for systems that employ aggressive noise reduction. Initial studies have shown that the dead leaves SFR correlates well with sharpness/texture blur preference, and thus the target can potentially be used as a surrogate for more expensive subjective image quality evaluations. In this paper, the dead leaves target is analyzed for measurement of camera system spatial frequency response. It was determined that the power spectral density (PSD) of the ideal dead leaves target does not exhibit simple power law dependence, and scale invariance is only loosely obeyed. An extension to the ideal dead leaves PSD model is proposed, including a correction term to account for system noise. With this extended model, the SFR of several camera systems with a variety of formats was measured, ranging from 3 to 10 megapixels; the effects of handshake motion blur are also analyzed via the dead leaves target.

Through-the-Wall Localization of a Moving Target by Two Independent Ultra Wideband (UWB) Radar Systems

PubMed Central

Kocur, Dušan; Švecová, Mária; Rovňáková, Jana

2013-01-01

In the case of through-the-wall localization of moving targets by ultra wideband (UWB) radars, there are applications in which handheld sensors equipped only with one transmitting and two receiving antennas are applied. Sometimes, the radar using such a small antenna array is not able to localize the target with the required accuracy. With a view to improve through-the-wall target localization, cooperative positioning based on a fusion of data retrieved from two independent radar systems can be used. In this paper, the novel method of the cooperative localization referred to as joining intersections of the ellipses is introduced. This method is based on a geometrical interpretation of target localization where the target position is estimated using a properly created cluster of the ellipse intersections representing potential positions of the target. The performance of the proposed method is compared with the direct calculation method and two alternative methods of cooperative localization using data obtained by measurements with the M-sequence UWB radars. The direct calculation method is applied for the target localization by particular radar systems. As alternative methods of cooperative localization, the arithmetic average of the target coordinates estimated by two single independent UWB radars and the Taylor series method is considered. PMID:24021968

Through-the-wall localization of a moving target by two independent ultra wideband (UWB) radar systems.

PubMed

Kocur, Dušan; Svecová, Mária; Rovňáková, Jana

2013-09-09

In the case of through-the-wall localization of moving targets by ultra wideband (UWB) radars, there are applications in which handheld sensors equipped only with one transmitting and two receiving antennas are applied. Sometimes, the radar using such a small antenna array is not able to localize the target with the required accuracy. With a view to improve through-the-wall target localization, cooperative positioning based on a fusion of data retrieved from two independent radar systems can be used. In this paper, the novel method of the cooperative localization referred to as joining intersections of the ellipses is introduced. This method is based on a geometrical interpretation of target localization where the target position is estimated using a properly created cluster of the ellipse intersections representing potential positions of the target. The performance of the proposed method is compared with the direct calculation method and two alternative methods of cooperative localization using data obtained by measurements with the M-sequence UWB radars. The direct calculation method is applied for the target localization by particular radar systems. As alternative methods of cooperative localization, the arithmetic average of the target coordinates estimated by two single independent UWB radars and the Taylor series method is considered.

Children Composing and Their Visual-Spatial Approach to the Keyboard

ERIC Educational Resources Information Center

Roels, Johanna Maria; Van Petegem, Peter

2015-01-01

This study aims to contribute to the already existing findings of children's compositional strategies and products. Despite the abundance of research provided regarding the manner in which children approach composing, little has been found about how children deal, specifically, with the structure of the keyboard. Therefore, from a context in which…

16 CFR 300.26 - Pile fabrics and products composed thereof.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 16 Commercial Practices 1 2011-01-01 2011-01-01 false Pile fabrics and products composed thereof. 300.26 Section 300.26 Commercial Practices FEDERAL TRADE COMMISSION REGULATIONS UNDER SPECIFIC ACTS OF CONGRESS RULES AND REGULATIONS UNDER THE WOOL PRODUCTS LABELING ACT OF 1939 Labeling § 300.26 Pile fabrics...

The Composing Process: A Critical Review of Some Recent Studies.

ERIC Educational Resources Information Center

Crismore, Avon

Six of the 10 existing research studies that attempt to characterize the composing process by examining certain components and behaviors are critically reviewed in this paper. For each study, the aims and data gathering and sampling procedures are described, and the findings, interpretations, design, and rationale of the research are critically…

Morphological Effect of Non-targeted Biomolecule-Modified MNPs on Reticuloendothelial System

NASA Astrophysics Data System (ADS)

Li, Xiao; Hu, Yan; Xiao, Jie; Cheng, Dengfeng; Xiu, Yan; Shi, Hongcheng

2015-09-01

Magnetic nanoparticles (MNPs) with special morphology were commonly used as biomaterials, while morphological effects of non-targeted biomolecule-modified MNPs on biological behaviors were still unclear. In this research, spherical and rod-like Fe3O4 in a comparable size were synthesized and then surface-modified by bovine serum albumin (BSA) as a model of non-targeted biomolecule-modified MNPs. Morphological effects were featured by TEM and quantification of in vitro phagocytic uptake, as well as the in vivo quantification of particles in reticuloendothelial system (RES)-related organs of normal Kunming mice. For these non-targeted BSA-modified MNPs, intracellular distributions were the same, but the rod-like MNPs were more likely to be uptake by macrophages; furthermore, the BSA-modified MNPs gathered in RES-related organs soon after intravenous injection, but the rod-like ones were expelled from the lung more quickly and expelled from the spleen more slowly. These preliminary results may be referable if MNPs or other similar biomolecule-modified nanoparticles were used.

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

Assessment, Target Selection, and Intervention: Dynamic Interactions within a Systemic Perspective

ERIC Educational Resources Information Center

Williams, A. Lynn

2005-01-01

There are a number of clinical options available for speech-language pathologists to choose from to analyze a child's phonological system, select treatment targets, and design intervention. Frequently, each of these areas of clinical options is viewed independently of one another or approached within an eclectic framework. In this article, an…

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

PubMed

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

2017-01-01

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

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

PubMed Central

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

2017-01-01

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

Further studies of a trussed-web girder composed of reinforced plastics.

DOT National Transportation Integrated Search

1975-01-01

Three single section and one trisection girder, s eight feet long were fabricated and load tested to determine the deflection, strain, and creep characteristics of the members. One specimen fabricated with stranded elements composed of Kevlar 49 inst...

Composable languages for bioinformatics: the NYoSh experiment

PubMed Central

Simi, Manuele

2014-01-01

Language WorkBenches (LWBs) are software engineering tools that help domain experts develop solutions to various classes of problems. Some of these tools focus on non-technical users and provide languages to help organize knowledge while other workbenches provide means to create new programming languages. A key advantage of language workbenches is that they support the seamless composition of independently developed languages. This capability is useful when developing programs that can benefit from different levels of abstraction. We reasoned that language workbenches could be useful to develop bioinformatics software solutions. In order to evaluate the potential of language workbenches in bioinformatics, we tested a prominent workbench by developing an alternative to shell scripting. To illustrate what LWBs and Language Composition can bring to bioinformatics, we report on our design and development of NYoSh (Not Your ordinary Shell). NYoSh was implemented as a collection of languages that can be composed to write programs as expressive and concise as shell scripts. This manuscript offers a concrete illustration of the advantages and current minor drawbacks of using the MPS LWB. For instance, we found that we could implement an environment-aware editor for NYoSh that can assist the programmers when developing scripts for specific execution environments. This editor further provides semantic error detection and can be compiled interactively with an automatic build and deployment system. In contrast to shell scripts, NYoSh scripts can be written in a modern development environment, supporting context dependent intentions and can be extended seamlessly by end-users with new abstractions and language constructs. We further illustrate language extension and composition with LWBs by presenting a tight integration of NYoSh scripts with the GobyWeb system. The NYoSh Workbench prototype, which implements a fully featured integrated development environment for NYoSh is