Polarized deuterium internal target at AmPS (NIKHEF)

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

Ferro-Luzzi, M.; NIKHEF, P.O. Box 41882, 1009 DB Amsterdam; Zhou, Z.-L.

1998-01-20

We describe the polarized deuterium target internal to the NIKHEF medium-energy electron storage ring. Tensor polarized deuterium was produced in an atomic beam source and injected into a storage cell target. A Breit-Rabi polarimeter was used to monitor the injected atomic beam intensity and polarization. An electrostatic ion-extraction system and a Wien filter were utilized to measure on-line the atomic fraction of the target gas in the storage cell. This device was supplemented with a tensor polarization analyzer using the neutron anisotropy of the {sup 3}H(d,n){alpha} reaction at 60 keV. This method allows determining the density-averaged nuclear polarization of themore » target gas, independent of spatial and temporal variations. We address issues important for polarized hydrogen/deuterium internal targets, such as the effects of spin-exchange collisions and resonant transitions induced by the RF fields of the charged particle beam.« less

[Strategy Development for International Cooperation in the Clinical Laboratory Field].

PubMed

Kudo, Yoshiko; Osawa, Susumu

2015-10-01

The strategy of international cooperation in the clinical laboratory field was analyzed to improve the quality of intervention by reviewing documents from international organizations and the Japanese government. Based on the world development agenda, the target of action for health has shifted from communicable diseases to non-communicable diseases (NCD). This emphasizes the importance of comprehensive clinical laboratories instead of disease-specific examinations in developing countries. To achieve this goal, the World Health Organization (WHO) has disseminated to the African and Asian regions the Laboratory Quality Management System (LQMS), which is based on the same principles of the International Organization of Standardization (ISO) 15189. To execute this strategy, international experts must have competence in project management, analyze information regarding the target country, and develop a strategy for management of the LQMS with an understanding of the technical aspects of laboratory work. However, there is no appropriate pre- and post-educational system of international health for Japanese international workers. Universities and academic organizations should cooperate with the government to establish a system of education for international workers. Objectives of this education system must include: (1) training for the organization and understanding of global health issues, (2) education of the principles regarding comprehensive management of clinical laboratories, and (3) understanding the LQMS which was employed based on WHO's initiative. Achievement of these objectives will help improve the quality of international cooperation in the clinical laboratory field.

Polarized deuterium internal target at AmPS (NIKHEF)

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

Norum, Blaine; De Jager, Cornelis; Geurts, D.

1997-08-01

We describe the polarized deuterium target internal to the NIKHEF medium-energy electron storage ring. Tensor polarized deuterium was produced in an atomic beam source and injected into a storage cell target. A Breit-Rabi polarimeter was used to monitor the injected atomic beam intensity and polarization. An electrostatic ion-extraction system and a Wien filter were utilized to measure on-line the atomic fraction of the target gas in the storage cell. This device was supplemented with a tensor polarization analyzer using the neutron anisotropy of the 3H(d,n)sigma reaction at 60 keV. This method allows determining the density-averaged nuclear polarization of the targetmore » gas, independent of spatial and temporal variations. We address issues important for polarized hydrogen/deuterium internal targets, such as the effects of spin-exchange collisions and resonant transitions induced by the RF fields of the charged particle beam.« less

Ada (Trade Name) Compiler Validation Summary Report: International Business Machines Corporation. IBM Development System for the Ada Language System, Version 1.1.0, IBM 4381 under VM/SP CMS Host, IBM 4381 under MVS Target

DTIC Science & Technology

1988-05-20

AVF Control Number: AVF-VSR-84.1087 ’S (0 87-03-10-TEL I- Ada® COMPILER VALIDATION SUMMARY REPORT: International Business Machines Corporation IBM...System, Version 1.1.0, International Business Machines Corporation, Wright-Patterson AFB. IBM 4381 under VM/SP CMS, Release 3.6 (host) and IBM 4381...an IBM 4381 operating under MVS, Release 3.8. On-site testing was performed 18 May 1987 through 20 May 1987 at International Business Machines

Ada Compiler Validation Summary Report: Certificate Number 89020W1. 10073: International Business Machines Corporation, IBM Development System for the Ada Language, VM/CMS Ada Compiler, Version 2.1.1, IBM 3083 (Host and Target)

DTIC Science & Technology

1989-04-20

International Business Machines Corporation) IBM Development System for the Ada Language, VN11/CMS Ada Compiler, Version 2.1.1, Wright-Patterson AFB, IBM 3083...890420W1.10073 International Business Machines Corporation IBM Development System for the Ada Language VM/CMS Ada Compiler Version 2.1.1 IBM 3083... International Business Machines Corporation and reviewed by the validation team. The compiler was tested using all default option settings except for the

Ada Compiler Validation Summary Report: Certificate Number: 890420W1. 10075 International Business Machines Corporation. IBM Development System, for the Ada Language CMS/MVS Ada Cross Compiler, Version 2.1.1 IBM 3083 Host and IBM 4381 Target

DTIC Science & Technology

1989-04-20

International business Machines Corporati,:i IBM Development System for the Ada Language, CMS/MVS Ada Cross Compiler, Version 2.1.1, Wright-Patterson AFB, IBM...VALIDATION SUMMARY REPORT: Certificate Number: 890420W1.10075 International Business Machines Corporation IBM Development System for the Ada Language CMS...command scripts provided by International Business Machines Corporation and reviewed by the validation team. The compiler was tested using all default

Academic Culture, Business Culture, and Measuring Achievement Differences: Internal Auditing Views

ERIC Educational Resources Information Center

Roth, Benjamin S.

2012-01-01

This study explored whether university internal audit directors' views of culture and measuring achievement differences between their institutions and a business were related to how they viewed internal auditing priorities and uses. The Carnegie Classification system's 283 Doctorate-granting Universities were the target population.…

Future Targets for Female Sexual Dysfunction.

PubMed

Farmer, Melissa; Yoon, Hana; Goldstein, Irwin

2016-08-01

Female sexual function reflects a dynamic interplay of central and peripheral nervous, vascular, and endocrine systems. The primary challenge in the development of novel treatments for female sexual dysfunction is the identification and targeted modulation of excitatory sexual circuits using pharmacologic treatments that facilitate the synthesis, release, and/or receptor binding of neurochemicals, peptides, and hormones that promote female sexual function. To develop an evidence-based state-of-the-art consensus report that critically integrates current knowledge of the therapeutic potential for known molecular and cellular targets to facilitate the physiologic processes underlying female sexual function. State-of-the-art review representing the opinions of international experts developed in a consensus process during a 1-year period. Expert opinion was established by grading the evidence-based medical literature, intensive internal committee discussion, public presentation, and debate. Scientific investigation is urgently needed to expand knowledge and foster development of future treatments that maintain genital tissue integrity, enhance genital physiologic responsiveness, and optimize positive subjective appraisal of internal and external sexual cues. This article critically condenses the current knowledge of therapeutic manipulation of molecular and cellular targets within biological systems responsible for female sexual physiologic function. Future treatment targets include pharmacologic modulation of emotional learning circuits, restoration of normal tactile sensation, growth factor therapy, gene therapy, stem cell-based therapies, and regenerative medicine. Concurrent use of centrally and peripherally acting therapies could optimize treatment response. Copyright © 2016 International Society for Sexual Medicine. Published by Elsevier Inc. All rights reserved.

The control system of the polarized internal target of ANKE at COSY

NASA Astrophysics Data System (ADS)

Kleines, H.; Sarkadi, J.; Zwoll, K.; Engels, R.; Grigoryev, K.; Mikirtychyants, M.; Nekipelov, M.; Rathmann, F.; Seyfarth, H.; Kravtsov, P.; Vasilyev, A.

2006-05-01

The polarized internal target for the ANKE experiment at the Cooler Synchrotron COSY of the Forschungszentrum Jülich utilizes a polarized atomic beam source to feed a storage cell with polarized hydrogen or deuterium atoms. The nuclear polarization is measured with a Lamb-shift polarimeter. For common control of the two systems, industrial equipment was selected providing reliable, long-term support and remote control of the target as well as measurement and optimization of its operating parameters. The interlock system has been implemented on the basis of SIEMENS SIMATIC S7-300 family of programmable logic controllers. In order to unify the interfacing to the control computer, all front-end equipment is connected via the PROFIBUS DP fieldbus. The process control software was implemented using the Windows-based WinCC toolkit from SIEMENS. The variety of components, to be controlled, and the logical structure of the control and interlock system are described. Finally, a number of applications derived from the present development to other, new installations are briefly mentioned.

Ada Compiler Validation Summary Report: Certificate Number: 890420W1. 10074 International Business Machines Corporation, IBM Development System for the Ada Language MVS Ada Compiler, Version 2.1.1 IBM 4381 (Host and Target)

DTIC Science & Technology

1989-04-20

20. ARS1AAI . (Contimne on reverse side olnetessary *rwenPtif) by bfoci nur~be’) International Business Machines Corporation, IBM Development System...Number: AVF-VSR-261.0789 89-01-26-TEL Ada COMPILER VALIDATION SUMMARY REPORT: Certificate Number: 890420W1.10074 International Business Machines...computer. The compiler was tested using command scripts provided by International Business Machines Corporation and reviewed by the validation team. The

Development of a real-time internal and external marker tracking system for particle therapy: a phantom study using patient tumor trajectory data

PubMed Central

Cho, Junsang; Cheon, Wonjoong; Ahn, Sanghee; Jung, Hyunuk; Sheen, Heesoon; Park, Hee Chul

2017-01-01

Abstract Target motion–induced uncertainty in particle therapy is more complicated than that in X-ray therapy, requiring more accurate motion management. Therefore, a hybrid motion-tracking system that can track internal tumor motion and as well as an external surrogate of tumor motion was developed. Recently, many correlation tests between internal and external markers in X-ray therapy have been developed; however, the accuracy of such internal/external marker tracking systems, especially in particle therapy, has not yet been sufficiently tested. In this article, the process of installing an in-house hybrid internal/external motion-tracking system is described and the accuracy level of tracking system was acquired. Our results demonstrated that the developed in-house external/internal combined tracking system has submillimeter accuracy, and can be clinically used as a particle therapy system as well as a simulation system for moving tumor treatment. PMID:28201522

A survey of quantum Lyapunov control methods.

PubMed

Cong, Shuang; Meng, Fangfang

2013-01-01

The condition of a quantum Lyapunov-based control which can be well used in a closed quantum system is that the method can make the system convergent but not just stable. In the convergence study of the quantum Lyapunov control, two situations are classified: nondegenerate cases and degenerate cases. For these two situations, respectively, in this paper the target state is divided into four categories: the eigenstate, the mixed state which commutes with the internal Hamiltonian, the superposition state, and the mixed state which does not commute with the internal Hamiltonian. For these four categories, the quantum Lyapunov control methods for the closed quantum systems are summarized and analyzed. Particularly, the convergence of the control system to the different target states is reviewed, and how to make the convergence conditions be satisfied is summarized and analyzed.

Preliminary research on flow rate and free surface of the accelerator driven subcritical system gravity-driven dense granular-flow target

PubMed Central

Li, Xiaodong; Wan, Jiangfeng; Zhang, Sheng; Lin, Ping; Zhang, Yanshi; Yang, Guanghui; Wang, Mengke; Duan, Wenshan; Sun, Jian’an

2017-01-01

A spallation target is one of the three core parts of the accelerator driven subcritical system (ADS), which has already been investigated for decades. Recently, a gravity-driven Dense Granular-flow Target (DGT) is proposed, which consists of a cylindrical hopper and an internal coaxial cylindrical beam pipe. The research on the flow rate and free surface are important for the design of the target whether in Heavy Liquid Metal (HLM) targets or the DGT. In this paper, the relations of flow rate and the geometry of the DGT are investigated. Simulations based on the discrete element method (DEM) implementing on Graphics Processing Units (GPUs) and experiments are both performed. It is found that the existence of an internal pipe doesn’t influence the flow rate when the distance from the bottom of the pipe to orifice is large enough even in a larger system. Meanwhile, snapshots of the free surface formed just below the beam pipe are given. It is observed that the free surface is stable over time. The entire research is meaningful for the design of DGT. PMID:29095910

Preliminary research on flow rate and free surface of the accelerator driven subcritical system gravity-driven dense granular-flow target.

PubMed

Li, Xiaodong; Wan, Jiangfeng; Zhang, Sheng; Lin, Ping; Zhang, Yanshi; Yang, Guanghui; Wang, Mengke; Duan, Wenshan; Sun, Jian'an; Yang, Lei

2017-01-01

A spallation target is one of the three core parts of the accelerator driven subcritical system (ADS), which has already been investigated for decades. Recently, a gravity-driven Dense Granular-flow Target (DGT) is proposed, which consists of a cylindrical hopper and an internal coaxial cylindrical beam pipe. The research on the flow rate and free surface are important for the design of the target whether in Heavy Liquid Metal (HLM) targets or the DGT. In this paper, the relations of flow rate and the geometry of the DGT are investigated. Simulations based on the discrete element method (DEM) implementing on Graphics Processing Units (GPUs) and experiments are both performed. It is found that the existence of an internal pipe doesn't influence the flow rate when the distance from the bottom of the pipe to orifice is large enough even in a larger system. Meanwhile, snapshots of the free surface formed just below the beam pipe are given. It is observed that the free surface is stable over time. The entire research is meaningful for the design of DGT.

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.

Amplatzer Vascular Plug Anchoring Technique to Stabilize the Delivery System for Microcoil Embolization

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

Onozawa, Shiro, E-mail: onozawa@nms.ac.jp; Murata, Satoru, E-mail: genji@nms.ac.jp; Mine, Takahiko, E-mail: takahikomine@gmail.com

PurposeTo evaluate the feasibility of a novel embolization technique, the Amplatzer vascular plug (AVP) anchoring technique, to stabilize the delivery system for microcoil embolization.Materials and methodsThree patients were enrolled in this study, including two cases of internal iliac artery aneurysms and one case of internal iliac arterial occlusion prior to endovascular aortic repair. An AVP was used in each case for embolization of one target artery, and the AVP was left in place. The AVP detachment wire was then used as an anchor to stabilize the delivery system for microcoil embolization to embolize the second target artery adjacent to themore » first target artery. The microcatheter for the microcoils was inserted parallel to the AVP detachment wire in the guiding sheath or catheter used for the AVP.ResultsThe AVP anchoring technique was achieved and the microcatheter was easily advanced to the second target artery in all three cases.ConclusionThe AVP anchoring technique was found to be feasible to advance the microcatheter into the neighboring artery of an AVP-embolized artery.« less

The Visual System's Intrinsic Bias and Knowledge of Size Mediate Perceived Size and Location in the Dark

ERIC Educational Resources Information Center

Zhou, Liu; He, Zijiang J.; Ooi, Teng Leng

2013-01-01

Dimly lit targets in the dark are perceived as located about an implicit slanted surface that delineates the visual system's intrinsic bias (Ooi, Wu, & He, 2001). If the intrinsic bias reflects the internal model of visual space--as proposed here--its influence should extend beyond target localization. Our first 2 experiments demonstrated that…

Internal and External Triggering Mechanism of "Smart" Nanoparticle-Based DDSs in Targeted Tumor Therapy.

PubMed

Qiana, Xian-Ling; Li, Jun; Wei, Ran; Lin, Hui; Xiong, Li-Xia

2018-05-09

Anticancer chemotherapeutics have a lot of problems via conventional drug delivery systems (DDSs), including non-specificity, burst release, severe side-effects, and damage to normal cells. Owing to its potential to circumventing these problems, nanotechnology has gained increasing attention in targeted tumor therapy. Chemotherapeutic drugs or genes encapsulated in nanoparticles could be used to target therapies to the tumor site in three ways: "passive", "active", and "smart" targeting. To summarize the mechanisms of various internal and external "smart" stimulating factors on the basis of findings from in vivo and in vitro studies. A thorough search of PubMed was conducted in order to identify the majority of trials, studies and novel articles related to the subject. Activated by internal triggering factors (pH, redox, enzyme, hypoxia, etc.) or external triggering factors (temperature, light of different wavelengths, ultrasound, magnetic fields, etc.), "smart" DDSs exhibit targeted delivery to the tumor site, and controlled release of chemotherapeutic drugs or genes. In this review article, we summarize and classify the internal and external triggering mechanism of "smart" nanoparticle-based DDSs in targeted tumor therapy, and the most recent research advances are illustrated for better understanding. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

76 FR 22726 - Certain Multimedia Display and Navigation Devices and Systems, Components Thereof, and Products...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-04-22

... Determination To Extend the Target Date; Request for Supplemental Briefing AGENCY: U.S. International Trade... determined to extend the target date for completion of the above-captioned investigation from April 18, 2011... Commission determined to review the final ID in part. Target Date: The Commission has determined to extend...

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.

Evaluation of DNA damage induced by Auger electrons from 137Cs.

PubMed

Watanabe, Ritsuko; Hattori, Yuya; Kai, Takeshi

2016-11-01

To understand the biological effect of external and internal exposure from 137 Cs, DNA damage spectrum induced by directly emitted electrons (γ-rays, internal conversion electrons, Auger electrons) from 137 Cs was compared with that induced by 137 Cs γ-rays. Monte Carlo track simulation method was used to calculate the microscopic energy deposition pattern in liquid water. Simulation was performed for the two simple target systems in microscale. Radiation sources were placed inside for one system and outside for another system. To simulate the energy deposition by directly emitted electrons from 137 Cs placed inside the system, the multiple ejections of electrons after internal conversion were considered. In the target systems, induction process of DNA damage was modeled and simulated for both direct energy deposition and the water radical reaction on the DNA. The yield and spatial distribution of simple and complex DNA damage including strand breaks and base lesions were calculated for irradiation by electrons and γ-rays from 137 Cs. The simulation showed that the significant difference in DNA damage spectrum was not caused by directly ejected electrons and γ-rays from 137 Cs. The result supports the existing perception that the biological effects by internal and external exposure by 137 Cs are equivalent.

A Survey of Quantum Lyapunov Control Methods

PubMed Central

2013-01-01

The condition of a quantum Lyapunov-based control which can be well used in a closed quantum system is that the method can make the system convergent but not just stable. In the convergence study of the quantum Lyapunov control, two situations are classified: nondegenerate cases and degenerate cases. For these two situations, respectively, in this paper the target state is divided into four categories: the eigenstate, the mixed state which commutes with the internal Hamiltonian, the superposition state, and the mixed state which does not commute with the internal Hamiltonian. For these four categories, the quantum Lyapunov control methods for the closed quantum systems are summarized and analyzed. Particularly, the convergence of the control system to the different target states is reviewed, and how to make the convergence conditions be satisfied is summarized and analyzed. PMID:23766732

Ligand-directed profiling of organelles with internalizing phage libraries

PubMed Central

Dobroff, Andrey S.; Rangel, Roberto; Guzman-Roja, Liliana; Salmeron, Carolina C.; Gelovani, Juri G.; Sidman, Richard L.; Bologa, Cristian G.; Oprea, Tudor I.; Brinker, C. Jeffrey; Pasqualini, Renata; Arap, Wadih

2015-01-01

Phage display is a resourceful tool to, in an unbiased manner, discover and characterize functional protein-protein interactions, to create vaccines, and to engineer peptides, antibodies, and other proteins as targeted diagnostic and/or therapeutic agents. Recently, our group has developed a new class of internalizing phage (iPhage) for ligand-directed targeting of organelles and/or to identify molecular pathways within live cells. This unique technology is suitable for applications ranging from fundamental cell biology to drug development. Here we describe the method for generating and screening the iPhage display system, and explain how to select and validate candidate internalizing homing peptide. PMID:25640897

Smart Drug Delivery Systems in Cancer Therapy.

PubMed

Unsoy, Gozde; Gunduz, Ufuk

2018-02-08

Smart nanocarriers have been designed for tissue-specific targeted drug delivery, sustained or triggered drug release and co-delivery of synergistic drug combinations to develop safer and more efficient therapeutics. Advances in drug delivery systems provide reduced side effects, longer circulation half-life and improved pharmacokinetics. Smart drug delivery systems have been achieved successfully in the case of cancer. These nanocarriers can serve as an intelligent system by considering the differences of tumor microenvironment from healthy tissue, such as low pH, low oxygen level, or high enzymatic activity of matrix metalloproteinases. The performance of anti-cancer agents used in cancer diagnosis and therapy is improved by enhanced cellular internalization of smart nanocarriers and controlled drug release. Here, we review targeting, cellular internalization; controlled drug release and toxicity of smart drug delivery systems. We are also emphasizing the stimulus responsive controlled drug release from smart nanocarriers. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Development of a real-time internal and external marker tracking system for particle therapy: a phantom study using patient tumor trajectory data.

PubMed

Cho, Junsang; Cheon, Wonjoong; Ahn, Sanghee; Jung, Hyunuk; Sheen, Heesoon; Park, Hee Chul; Han, Youngyih

2017-09-01

Target motion-induced uncertainty in particle therapy is more complicated than that in X-ray therapy, requiring more accurate motion management. Therefore, a hybrid motion-tracking system that can track internal tumor motion and as well as an external surrogate of tumor motion was developed. Recently, many correlation tests between internal and external markers in X-ray therapy have been developed; however, the accuracy of such internal/external marker tracking systems, especially in particle therapy, has not yet been sufficiently tested. In this article, the process of installing an in-house hybrid internal/external motion-tracking system is described and the accuracy level of tracking system was acquired. Our results demonstrated that the developed in-house external/internal combined tracking system has submillimeter accuracy, and can be clinically used as a particle therapy system as well as a simulation system for moving tumor treatment. © The Author 2017. Published by Oxford University Press on behalf of The Japan Radiation Research Society and Japanese Society for Radiation Oncology.

A Global Perspective on Drinking-Water and Sanitation Classification: An Evaluation of Census Content

PubMed Central

Yu, Weiyu; Wardrop, Nicola A.; Bain, Robert E. S.; Lin, Yanzhao; Zhang, Ce; Wright, Jim A.

2016-01-01

Following the recent expiry of the United Nations’ 2015 Millennium Development Goals (MDGs), new international development agenda covering 2030 water, sanitation and hygiene (WASH) targets have been proposed, which imply new demands on data sources for monitoring relevant progress. This study evaluates drinking-water and sanitation classification systems from national census questionnaire content, based upon the most recent international policy changes, to examine national population census’s ability to capture drinking-water and sanitation availability, safety, accessibility, and sustainability. In total, 247 censuses from 83 low income and lower-middle income countries were assessed using a scoring system, intended to assess harmonised water supply and sanitation classification systems for each census relative to the typology needed to monitor the proposed post-2015 indicators of WASH targets. The results signal a lack of international harmonisation and standardisation in census categorisation systems, especially concerning safety, accessibility, and sustainability of services in current census content. This suggests further refinements and harmonisation of future census content may be necessary to reflect ambitions for post-2015 monitoring. PMID:26986472

A Global Perspective on Drinking-Water and Sanitation Classification: An Evaluation of Census Content.

PubMed

Yu, Weiyu; Wardrop, Nicola A; Bain, Robert E S; Lin, Yanzhao; Zhang, Ce; Wright, Jim A

2016-01-01

Following the recent expiry of the United Nations' 2015 Millennium Development Goals (MDGs), new international development agenda covering 2030 water, sanitation and hygiene (WASH) targets have been proposed, which imply new demands on data sources for monitoring relevant progress. This study evaluates drinking-water and sanitation classification systems from national census questionnaire content, based upon the most recent international policy changes, to examine national population census's ability to capture drinking-water and sanitation availability, safety, accessibility, and sustainability. In total, 247 censuses from 83 low income and lower-middle income countries were assessed using a scoring system, intended to assess harmonised water supply and sanitation classification systems for each census relative to the typology needed to monitor the proposed post-2015 indicators of WASH targets. The results signal a lack of international harmonisation and standardisation in census categorisation systems, especially concerning safety, accessibility, and sustainability of services in current census content. This suggests further refinements and harmonisation of future census content may be necessary to reflect ambitions for post-2015 monitoring.

Development of internal models and predictive abilities for visual tracking during childhood

PubMed Central

Ego, Caroline; Yüksel, Demet

2015-01-01

The prediction of the consequences of our own actions through internal models is an essential component of motor control. Previous studies showed improvement of anticipatory behaviors with age for grasping, drawing, and postural control. Since these actions require visual and proprioceptive feedback, these improvements might reflect both the development of internal models and the feedback control. In contrast, visual tracking of a temporarily invisible target gives specific markers of prediction and internal models for eye movements. Therefore, we recorded eye movements in 50 children (aged 5–19 yr) and in 10 adults, who were asked to pursue a visual target that is temporarily blanked. Results show that the youngest children (5–7 yr) have a general oculomotor behavior in this task, qualitatively similar to the one observed in adults. However, the overall performance of older subjects in terms of accuracy at target reappearance and variability in their behavior was much better than the youngest children. This late maturation of predictive mechanisms with age was reflected into the development of the accuracy of the internal models governing the synergy between the saccadic and pursuit systems with age. Altogether, we hypothesize that the maturation of the interaction between smooth pursuit and saccades that relies on internal models of the eye and target displacement is related to the continuous maturation of the cerebellum. PMID:26510757

Development of internal models and predictive abilities for visual tracking during childhood.

PubMed

Ego, Caroline; Yüksel, Demet; Orban de Xivry, Jean-Jacques; Lefèvre, Philippe

2016-01-01

The prediction of the consequences of our own actions through internal models is an essential component of motor control. Previous studies showed improvement of anticipatory behaviors with age for grasping, drawing, and postural control. Since these actions require visual and proprioceptive feedback, these improvements might reflect both the development of internal models and the feedback control. In contrast, visual tracking of a temporarily invisible target gives specific markers of prediction and internal models for eye movements. Therefore, we recorded eye movements in 50 children (aged 5-19 yr) and in 10 adults, who were asked to pursue a visual target that is temporarily blanked. Results show that the youngest children (5-7 yr) have a general oculomotor behavior in this task, qualitatively similar to the one observed in adults. However, the overall performance of older subjects in terms of accuracy at target reappearance and variability in their behavior was much better than the youngest children. This late maturation of predictive mechanisms with age was reflected into the development of the accuracy of the internal models governing the synergy between the saccadic and pursuit systems with age. Altogether, we hypothesize that the maturation of the interaction between smooth pursuit and saccades that relies on internal models of the eye and target displacement is related to the continuous maturation of the cerebellum. Copyright © 2016 the American Physiological Society.

Estimating the Fully Burdened Cost of Fuel Using an Input-Output Model - A Micro-Level Analysis

DTIC Science & Technology

2011-09-01

The multilocation distribution model used by Lu and Rencheng to evaluate an international supply chain (From: Lu & Rencheng, 2007...IO model to evaluate an international supply chain specifically for a multilocation production system. Figure 2 illustrates such a system. vendor...vendor vendor Target markets Production plants Material vendor Figure 2. The multilocation distribution model used by Lu and Rencheng to

Ligand-based targeted therapy: a novel strategy for hepatocellular carcinoma

PubMed Central

Li, Min; Zhang, Weiyue; Wang, Birong; Gao, Yang; Song, Zifang; Zheng, Qi Chang

2016-01-01

Hepatocellular carcinoma (HCC) is the most common primary liver cancer with high morbidity and mortality worldwide. Chemotherapy is recommended to patients with intermediate or advanced stage cancer. However, the conventional chemotherapy yields low desired response rates due to multidrug resistance, fast clearance rate, nonspecific delivery, severe side effects, low drug concentration in cancer cells, and so on. Nanoparticle-mediated targeted drug delivery system can surmount the aforementioned obstacles through enhanced permeability and retention effect and active targeting as a novel approach of therapeutics for HCC in recent years. The active targeting is triggered by ligands on the delivery system, which recognize with and internalize into hepatoma cells with high specificity and efficiency. This review focuses on the latest targeted delivery systems for HCC and summarizes the ligands that can enhance the capacity of active targeting, to provide some insight into future research in nanomedicine for HCC. PMID:27920520

Work continues on Leonardo, the Multi-Purpose Logistics Module, in the Space Station Processing Faci

NASA Technical Reports Server (NTRS)

1999-01-01

Workers in the Space Station Processing Facility work on Leonardo, the Multipurpose Logistics Module (MPLM) built by the Agenzia Spaziale Italiana (ASI). The MPLM, a reusable logistics carrier, will be the primary delivery system used to resupply and return International Space Station cargo requiring a pressurized environment. Leonardo is the first of three MPLM carriers for the International Space Station. It is scheduled to be launched on Space Shuttle Mission STS-102, targeted for June 2000. Leonardo shares space in the SSPF with the Shuttle Radar Topography Mission (SRTM), targeted for launch in September 1999, and Destiny, the U.S. Lab module, targeted for mission STS-98 in late April 2000.

Label-Free Raman Microspectral Analysis for Comparison of Cellular Uptake and Distribution between Non-Targeted and EGFR-Targeted Biodegradable Polymeric Nanoparticles

PubMed Central

Chernenko, Tatyana; Buyukozturk, Fulden; Miljkovic, Milos; Carrier, Rebecca; Diem, Max; Amiji, Mansoor

2013-01-01

Active targeted delivery of nanoparticle-encapsulated agents to tumor cells in vivo is expected to enhance therapeutic effect with significantly less non-specific toxicity. Active targeting is based on surface modification of nanoparticles with ligands that bind with extracellular targets and enhance payload delivery in the cells. In this study, we have used label-free Raman micro-spectral analysis and kinetic modeling to study cellular interactions and intracellular delivery of C6-ceramide using a non-targeted and an epidermal growth factor receptor (EGFR) targeted biodegradable polymeric nano-delivery systems, in EGFR-expressing human ovarian adenocarcinoma (SKOV3) cells. The results show that EGFR peptide-modified nanoparticles were rapidly internalized in SKOV3 cells leading to significant intracellular accumulation as compared to non-specific uptake by the non-targeted nanoparticles. Raman micro-spectral analysis enables visualization and quantification of the carrier system, drug-load, and responses of the biological systems interrogated, without exogenous staining and labeling procedures. PMID:24298430

Design and Preliminary Testing of the International Docking Adapter's Peripheral Docking Target

NASA Technical Reports Server (NTRS)

Foster, Christopher W.; Blaschak, Johnathan; Eldridge, Erin A.; Brazzel, Jack P.; Spehar, Peter T.

2015-01-01

The International Docking Adapter's Peripheral Docking Target (PDT) was designed to allow a docking spacecraft to judge its alignment relative to the docking system. The PDT was designed to be compatible with relative sensors using visible cameras, thermal imagers, or Light Detection and Ranging (LIDAR) technologies. The conceptual design team tested prototype designs and materials to determine the contrast requirements for the features. This paper will discuss the design of the PDT, the methodology and results of the tests, and the conclusions pertaining to PDT design that were drawn from testing.

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.

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

PubMed

Sadekar, S; Figueroa, I; Tabrizi, M

2015-07-01

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

Enhancing Adoptive Cell Therapy of Cancer through Targeted Delivery of Small-Molecule Immunomodulators to Internalizing or Noninternalizing Receptors.

PubMed

Zheng, Yiran; Tang, Li; Mabardi, Llian; Kumari, Sudha; Irvine, Darrell J

2017-03-28

Adoptive cell therapy (ACT) has achieved striking efficacy in B-cell leukemias, but less success treating other cancers, in part due to the rapid loss of ACT T-cell effector function in vivo due to immunosuppression in solid tumors. Transforming growth factor-β (TGF-β) signaling is an important mechanism of immune suppression in the tumor microenvironment, but systemic inhibition of TGF-β is toxic. Here we evaluated the potential of targeting a small molecule inhibitor of TGF-β to ACT T-cells using PEGylated immunoliposomes. Liposomes were prepared that released TGF-β inhibitor over ∼3 days in vitro. We compared the impact of targeting these drug-loaded vesicles to T-cells via an internalizing receptor (CD90) or noninternalizing receptor (CD45). When lymphocytes were preloaded with immunoliposomes in vitro prior to adoptive therapy, vesicles targeted to both CD45 and CD90 promoted enhanced T-cell expression of granzymes relative to free systemic drug administration, but only targeting to CD45 enhanced accumulation of granzyme-expressing T-cells in tumors, which correlated with the greatest enhancement of T-cell antitumor activity. By contrast, when administered i.v. to target T-cells in vivo, only targeting of a CD90 isoform expressed exclusively by the donor T-cells led to greater tumor regression over equivalent doses of free systemic drug. These results suggest that in vivo, targeting of receptors uniquely expressed by donor T-cells is of paramount importance for maximal efficacy. This immunoliposome strategy should be broadly applicable to target exogenous or endogenous T-cells and defines parameters to optimize delivery of supporting (or suppressive) drugs to these important immune effectors.

Proceedings of the international workshop on the technology and thermal hydraulics of heavy liquid metals (Hg, Pb, Bi, and their eutectics)

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

Appleton, B.R.; Bauer, G.S.

1996-06-01

The International Workshop on the Technology and Thermal Hydraulics of Heavy Liquid Metals (Schruns Workshop) was organized to assess the R&D and technology problems associated with designing and building a heavy liquid metal target for a spallation neutron source. The European scientific community is completing a feasibility study for a future, accelerator-based, pulsed spallation neutron source that would deliver a beam power of 5 megawatts (MW) to a target. They have concluded that a liquid metal target is preferable to conventional solid targets for handling the extreme radiation environments, high heat loads, and pulsed power. Similarly, the ORNL has beenmore » funded by the DOE to design a high-power, pulsed spallation neutron source that would begin operation at about 1 MW but that could be upgraded to significantly higher powers in the future. Again, the most feasible target design appears to be a liquid metal target. Since the expertise needed to consider these problems resides in a number of disparate disciplines not normally covered by existing conferences, this workshop was organized to bring a small number of scientists and engineers together to assess the opportunities for building such a target. The objectives and goals of the Schruns Workshop were to: review and share existing information on the science and technology of heavy liquid metal systems. Evaluate the opportunities and limitations of materials compatibility, thermal hydraulics and heat transfer, chemical reactions, corrosion, radiation effects, liquid-gas mixtures, systems designs, and circuit components for a heavy liquid metal target. Establish the critical R & D and technology that is necessary to construct a liquid metal target. Explore opportunities for cooperative R & D among members of the international community that could expedite results, and share expertise and resources. Selected papers are indexed separately for inclusion in the Energy Science and Technology Database.« less

Stochastic inversion of cross-borehole radar data from metalliferous vein detection

NASA Astrophysics Data System (ADS)

Zeng, Zhaofa; Huai, Nan; Li, Jing; Zhao, Xueyu; Liu, Cai; Hu, Yingsa; Zhang, Ling; Hu, Zuzhi; Yang, Hui

2017-12-01

In the exploration and evaluation of the metalliferous veins with a cross-borehole radar system, traditional linear inversion methods (least squares inversion, LSQR) only get indirect parameters (permittivity, resistivity, or velocity) to estimate the target structure. They cannot accurately reflect the geological parameters of the metalliferous veins’ media properties. In order to get the intrinsic geological parameters and internal distribution, in this paper, we build a metalliferous veins model based on the stochastic effective medium theory, and carry out stochastic inversion and parameter estimation based on the Monte Carlo sampling algorithm. Compared with conventional LSQR, the stochastic inversion can get higher resolution inversion permittivity and velocity of the target body. We can estimate more accurately the distribution characteristics of abnormality and target internal parameters. It provides a new research idea to evaluate the properties of complex target media.

Epidermal growth factor targeting of bacteriophage to the choroid plexus for gene delivery to the central nervous system via cerebrospinal fluid.

PubMed

Gonzalez, Ana Maria; Leadbeater, Wendy; Podvin, Sonia; Borboa, Alexandra; Burg, Michael; Sawada, Ritsuko; Rayner, James; Sims, Karen; Terasaki, Tetsuya; Johanson, Conrad; Stopa, Edward; Eliceiri, Brian; Baird, Andrew

2010-11-04

Because the choroid plexus normally controls the production and composition of cerebrospinal fluid and, as such, its many functions of the central nervous system, we investigated whether ligand-mediated targeting could deliver genes to its secretory epithelium. We show here that when bacteriophages are targeted with epidermal growth factor, they acquire the ability to enter choroid epithelial cells grown in vitro as cell cultures, ex vivo as tissue explants or in vivo by intracerebroventricular injection. The binding and internalization of these particles activate EGF receptors on targeted cells, and the dose- and time-dependent internalization of particles is inhibited by the presence of excess ligand. When the phage genome is further reengineered to contain like green fluorescent protein or firefly luciferase under control of the cytomegalovirus promoter, gene expression is detectable in the choroid plexus and ependymal epithelium by immunohistochemistry or by noninvasive imaging, respectively. Taken together, these data support the hypothesis that reengineered ligand-mediated gene delivery should be considered a viable strategy to increase the specificity of gene delivery to the central nervous system and bypass the blood-brain barrier so as to exploit the biological effectiveness of the choroid plexus as a portal of entry into the brain. Copyright © 2010 Elsevier B.V. All rights reserved.

Global Fund-supported programmes contribution to international targets and the Millennium Development Goals: an initial analysis.

PubMed

Komatsu, Ryuichi; Low-Beer, Daniel; Schwartländer, Bernhard

2007-10-01

The Global Fund to Fight AIDS, Tuberculosis and Malaria is one of the largest funders to fight these diseases. This paper discusses the programmatic contribution of Global Fund-supported programmes towards achieving international targets and Millennium Development Goals, using data from Global Fund grants. Results until June 2006 of 333 grants supported by the Global Fund in 127 countries were aggregated and compared against international targets for HIV/AIDS, tuberculosis and malaria. Progress reports to the Global Fund secretariat were used as a basis to calculate results. Service delivery indicators for antiretrovirals (ARV) for HIV/AIDS, case detection under the DOTS strategy for tuberculosis (DOTS) and insecticide-treated nets (ITNs) for malaria prevention were selected to estimate programmatic contributions to international targets for the three diseases. Targets of Global Fund-supported programmes were projected based on proposals for Rounds 1 to 4 and compared to international targets for 2009. Results for Global Fund-supported programmes total 544,000 people on ARV, 1.4 million on DOTS and 11.3 million for ITNs by June 2006. Global Fund-supported programmes contributed 18% of international ARV targets, 29% of DOTS targets and 9% of ITNs in sub-Saharan Africa by mid-2006. Existing Global Fund-supported programmes have agreed targets that are projected to account for 19% of the international target for ARV delivery expected for 2009, 28% of the international target for DOTS and 84% of ITN targets in sub-Saharan Africa. Global Fund-supported programmes have already contributed substantially to international targets by mid-2006, but there is a still significant gap. Considerably greater financial support is needed, particularly for HIV, in order to achieve international targets for 2009.

On the performance of infrared sensors in earth observations

NASA Technical Reports Server (NTRS)

Johnson, L. F.

1972-01-01

The performance of infrared sensing systems is dependent upon the radiative properties of targets in addition to constraints imposed by system components. The unclassified state-of-the-art of infrared system performance figures is reviewed to indicate the relevance to system performance of target radiative properties. A theory of rough surface scattering is developed which allows the formulation of the reflective characteristics of extended targets. The thermal radiation emission from extended targets is formulated on the basis of internal radiation characteristics of natural materials and the transmissive scattering effects at the surface. Finally, the total radiative characteristics may be expressed as functions of material properties and incident and received directions, although the expressions are extremely complex functions and do not account for the effects of shadowing or multiple scattering. It is believed that the theory may be extended to include these effects and to incorporate the local radii of curvature of the surface.

Contextual cuing contributes to the independent modification of multiple internal models for vocal control

PubMed Central

Keough, Dwayne

2011-01-01

Research on the control of visually guided limb movements indicates that the brain learns and continuously updates an internal model that maps the relationship between motor commands and sensory feedback. A growing body of work suggests that an internal model that relates motor commands to sensory feedback also supports vocal control. There is evidence from arm-reaching studies that shows that when provided with a contextual cue, the motor system can acquire multiple internal models, which allows an animal to adapt to different perturbations in diverse contexts. In this study we show that trained singers can rapidly acquire multiple internal models regarding voice fundamental frequency (F0). These models accommodate different perturbations to ongoing auditory feedback. Participants heard three musical notes and reproduced each one in succession. The musical targets could serve as a contextual cue to indicate which direction (up or down) feedback would be altered on each trial; however, participants were not explicitly instructed to use this strategy. When participants were gradually exposed to altered feedback adaptation was observed immediately following vocal onset. Aftereffects were target specific and did not influence vocal productions on subsequent trials. When target notes were no longer a contextual cue, adaptation occurred during altered feedback trials and evidence for trial-by-trial adaptation was found. These findings indicate that the brain is exceptionally sensitive to the deviations between auditory feedback and the predicted consequence of a motor command during vocalization. Moreover, these results indicate that, with contextual cues, the vocal control system may maintain multiple internal models that are capable of independent modification during different tasks or environments. PMID:21346208

Differential intra-endothelial delivery of polymer nanocarriers targeted to distinct PECAM-1 epitopes

PubMed Central

Garnacho, Carmen; Albelda, Steven M.; Muzykantov, Vladimir R.; Muro, Silvia

2008-01-01

Coupling drug carriers to antibodies for targeting endothelial cells (ECs) may improve treatment of vascular and pulmonary diseases. Selecting antibodies that deliver carriers to the cell surface or intracellularly may further optimize specifcity of interventions. We studied antibody-directed targeting of nanocarriers to platelet–endothelial cell adhesion molecule (PECAM)-1, an endothelial glycoprotein containing 6 Ig-like extracellular domains. PECAM-1 antibodies bind to ECs without internalization, but ECs internalize by endocytosis nanocarriers carrying multiple copies of anti-PECAM (anti-PECAM/NCs). To determine whether binding and intracellular transport of anti-PECAM/NCs depend on the epitope engaged, we targeted five PECAM-1 epitopes: mAb35, mAb37 and mAb62 (membrane-distal Ig domain 1), mAbGi34 (Ig domains 2/3), and mAb4G6 (membrane-proximal Ig domain 6). The antibodies bound to ECs regardless of the epitope proximity to the plasmalemma, whereas 130 nm diameter nanocarriers only targeted effectively distal domains (mAb4G6/NCs did not bind to ECs). ECs internalized mAb35, mAb62, and mAbGi34 carriers regardless of their size (0.13 to 5 µm diameter), yet they did not internalize mAb37/NCs. After internalization, mAb62/NCs trafficked to lysosomes within 2–3 h, whereas mAb35/NCs had prolonged residence in pre-lysosomal vesicles. Therefore, endothelial binding, endocytosis, and intracellular transport of anti-PECAM/NCs are epitope-specific. This paradigm will guide the design of endothelial drug delivery systems providing specific cellular localizations. PMID:18606202

Why We Should Establish a National System of Standards.

ERIC Educational Resources Information Center

Hennen, Thomas J., Jr.

2000-01-01

Explains the need to establish a national system of standards for public libraries. Discusses local standards, state standards, and international standards, and suggests adopting a tiered approach including three levels: minimum standards; target standards; and benchmarking standards, as found in total quality management. (LRW)

International Society of Refractive Surgery of the American Academy of Ophthalmology

MedlinePlus

... Eye Drop Targets Miosis and Accommodation, Femtosecond Laser Lens Softening for Presbyopia Correction Read Outlook ... system below. Google Calendar Outlook or Apple Calendar Yahoo Calendar Note: ...

Path planning during combustion mode switch

DOEpatents

Jiang, Li; Ravi, Nikhil

2015-12-29

Systems and methods are provided for transitioning between a first combustion mode and a second combustion mode in an internal combustion engine. A current operating point of the engine is identified and a target operating point for the internal combustion engine in the second combustion mode is also determined. A predefined optimized transition operating point is selected from memory. While operating in the first combustion mode, one or more engine actuator settings are adjusted to cause the operating point of the internal combustion engine to approach the selected optimized transition operating point. When the engine is operating at the selected optimized transition operating point, the combustion mode is switched from the first combustion mode to the second combustion mode. While operating in the second combustion mode, one or more engine actuator settings are adjusted to cause the operating point of the internal combustion to approach the target operating point.

Intravenous phage display identifies peptide sequences that target the burn-injured intestine.

PubMed

Costantini, Todd W; Eliceiri, Brian P; Putnam, James G; Bansal, Vishal; Baird, Andrew; Coimbra, Raul

2012-11-01

The injured intestine is responsible for significant morbidity and mortality after severe trauma and burn; however, targeting the intestine with therapeutics aimed at decreasing injury has proven difficult. We hypothesized that we could use intravenous phage display technology to identify peptide sequences that target the injured intestinal mucosa in a murine model, and then confirm the cross-reactivity of this peptide sequence with ex vivo human gut. Four hours following 30% TBSA burn we performed an in vivo, intravenous systemic administration of phage library containing 10(12) phage in balb/c mice to biopan for gut-targeting peptides. In vivo assessment of the candidate peptide sequences identified after 4 rounds of internalization was performed by injecting 1×10(12) copies of each selected phage clone into sham or burned animals. Internalization into the gut was assessed using quantitative polymerase chain reaction. We then incubated this gut-targeting peptide sequence with human intestine and visualized fluorescence using confocal microscopy. We identified 3 gut-targeting peptide sequences which caused collapse of the phage library (4-1: SGHQLLLNKMP, 4-5: ILANDLTAPGPR, 4-11: SFKPSGLPAQSL). Sequence 4-5 was internalized into the intestinal mucosa of burned animals 9.3-fold higher than sham animals injected with the same sequence (2.9×10(5)vs. 3.1×10(4) particles per mg tissue). Sequences 4-1 and 4-11 were both internalized into the gut, but did not demonstrate specificity for the injured mucosa. Phage sequence 4-11 demonstrated cross-reactivity with human intestine. In the future, this gut-targeting peptide sequence could serve as a platform for the delivery of biotherapeutics. Copyright © 2012 Elsevier Inc. All rights reserved.

Guided molecular missiles for tumor-targeting chemotherapy--case studies using the second-generation taxoids as warheads.

PubMed

Ojima, Iwao

2008-01-01

A long-standing problem in cancer chemotherapy is the lack of tumor-specific treatments. Traditional chemotherapy relies on the premise that rapidly proliferating cancer cells are more likely to be killed by a cytotoxic agent. In reality, however, cytotoxic agents have very little or no specificity, which leads to systemic toxicity, causing undesirable severe side effects. Therefore, the development of innovative and efficacious tumor-specific drug delivery protocols or systems is urgently needed. A rapidly growing tumor requires various nutrients and vitamins. Thus, tumor cells overexpress many tumor-specific receptors, which can be used as targets to deliver cytotoxic agents into tumors. This Account presents our research program on the discovery and development of novel and efficient drug delivery systems, possessing tumor-targeting ability and efficacy against various cancer types, especially multidrug-resistant tumors. In general, a tumor-targeting drug delivery system consists of a tumor recognition moiety and a cytotoxic warhead connected directly or through a suitable linker to form a conjugate. The conjugate, which can be regarded as a "guided molecular missile", should be systemically nontoxic, that is, the linker must be stable in blood circulation, but upon internalization into the cancer cell, the conjugate should be readily cleaved to regenerate the active cytotoxic warhead. These novel "guided molecular missiles" are conjugates of the highly potent second-generation taxoid anticancer agents with tumor-targeting molecules through mechanism-based cleavable linkers. These conjugates are specifically delivered to tumors and internalized into tumor cells, and the potent taxoid anticancer agents are released from the linker into the cytoplasm. We have successfully used omega-3 polyunsaturated fatty acids, in particular DHA, and monoclonal antibodies (for EGFR) as tumor-targeting molecules for the conjugates, which exhibited remarkable efficacy against human tumor xenografts in animal models. We have developed self-immolative disulfide linkers wherein the glutathione-triggered cascade drug release takes place to generate the original anticancer agent. The use of disulfide linkers is attractive beacuse it takes into account the fact that the concentration of glutathione is much higher (>1000 times) in tumor cells than in blood plasma. In order to monitor and elucidate the mechanism of tumor-targeting, internalization, and drug release, several fluorescent and fluorogenic probes using biotin as the tumor-targeting module were developed and used. Then, the progressive occurrence of the designed receptor-mediated endocytosis, drug release, and drug binding to the target protein (microtubules) has been successfully observed and confirmed by means of confocal fluorescence microscopy. These "guided molecular missiles" provide bright prospects for the development of highly efficacious new generation drugs for cancer chemotherapy.

Results from the Maine 1992 foliage penetration experiment

NASA Astrophysics Data System (ADS)

Toups, Michael F.; Ayasli, Serpil

1993-11-01

In order to investigate the detection of targets which are hidden by foliage, an experiment was designed which utilized a forest region located near Portage, Maine. The experiment was designed to address four issues. First, the properties of the backscatter or clutter which competes with the desired target were investigated. Second, the foliage induced attenuation that is experienced by the radar energy traversing the foliage were measured. Third, the ability of a synthetic aperture radar system to focus on a target obscured by foliage was investigated. Fourth, target signatures of foliage obscured and unobscured targets were measured. The forest region was investigated using two different airborne synthetic aperture radar (SAR) systems. A UHF wide-band SAR operated by SRI International was used as well as a L-, C-, and X-band SAR installed on a P-3 aircraft operated by the U.S. Navy. The SRI system was used to collect data over 16 square kilometers with repeat passes for verification of system performance. The P-3 system was used to collect over 50 square kilometers of data at three different depression angles with several repeat passes.

Will international emissions trading help achieve the objectives of the Paris Agreement?

NASA Astrophysics Data System (ADS)

Fujimori, Shinichiro; Kubota, Izumi; Dai, Hancheng; Takahashi, Kiyoshi; Hasegawa, Tomoko; Liu, Jing-Yu; Hijioka, Yasuaki; Masui, Toshihiko; Takimi, Maho

2016-10-01

Under the Paris Agreement, parties set and implement their own emissions targets as nationally determined contributions (NDCs) to tackle climate change. International carbon emissions trading is expected to reduce global mitigation costs. Here, we show the benefit of emissions trading under both NDCs and a more ambitious reduction scenario consistent with the 2 °C goal. The results show that the global welfare loss, which was measured based on estimated household consumption change in 2030, decreased by 75% (from 0.47% to 0.16%), as a consequence of achieving NDCs through emissions trading. Furthermore, achieving the 2 °C targets without emissions trading led to a global welfare loss of 1.4%-3.4%, depending on the burden-sharing scheme used, whereas emissions trading reduced the loss to around 1.5% (from 1.4% to 1.7%). These results indicate that emissions trading is a valuable option for the international system, enabling NDCs and more ambitious targets to be achieved in a cost-effective manner.

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

Code of Federal Regulations, 2014 CFR

2014-04-01

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

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

Code of Federal Regulations, 2012 CFR

2012-04-01

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

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.

Practice-based learning can improve osteoporosis care.

PubMed

Hess, Brian J; Johnston, Mary M; Iobst, William F; Lipner, Rebecca S

2013-10-01

To examine physician engagement in practice-based learning using a self-evaluation module to assess and improve their care of individuals with or at risk of osteoporosis. Retrospective cohort study. Internal medicine and subspecialty clinics. Eight hundred fifty U.S. physicians with time-limited certification in general internal medicine or a subspecialty. Performance rates on 23 process measures and seven practice system domain scores were obtained from the American Board of Internal Medicine (ABIM) Osteoporosis Practice Improvement Module (PIM), an Internet-based self-assessment module that physicians use to improve performance on one targeted measure. Physicians remeasured performance on their targeted measures by conducting another medical chart review. Variability in performance on measures was found, with observed differences between general internists, geriatricians, and rheumatologists. Some practice system elements were modestly associated with measure performance; the largest association was between providing patient-centered self-care support and documentation of calcium intake and vitamin D estimation and counseling (correlation coefficients from 0.20 to 0.28, Ps < .002). For all practice types, the most commonly selected measure targeted for improvement was documentation of vitamin D level (38% of physicians). On average, physicians reported significant and large increases in performance on measures targeted for improvement. Gaps exist in the quality of osteoporosis care, and physicians can apply practice-based learning using the ABIM PIM to take action to improve the quality of care. © 2013, Copyright the Authors Journal compilation © 2013, The American Geriatrics Society.

Discussion and a new method of optical cryptosystem based on interference

NASA Astrophysics Data System (ADS)

Lu, Dajiang; He, Wenqi; Liao, Meihua; Peng, Xiang

2017-02-01

A discussion and an objective security analysis of the well-known optical image encryption based on interference are presented in this paper. A new method is also proposed to eliminate the security risk of the original cryptosystem. For a possible practical application, we expand this new method into a hierarchical authentication scheme. In this authentication system, with a pre-generated and fixed random phase lock, different target images indicating different authentication levels are analytically encoded into corresponding phase-only masks (phase keys) and amplitude-only masks (amplitude keys). For the authentication process, a legal user can obtain a specified target image at the output plane if his/her phase key, and amplitude key, which should be settled close against the fixed internal phase lock, are respectively illuminated by two coherent beams. By comparing the target image with all the standard certification images in the database, the system can thus verify the user's legality even his/her identity level. Moreover, in despite of the internal phase lock of this system being fixed, the crosstalk between different pairs of keys held by different users is low. Theoretical analysis and numerical simulation are both provided to demonstrate the validity of this method.

Temperature Measurements in Dynamically-loaded Systems Using Neutron Resonance Spectroscopy (NRS) at LANSCE

NASA Astrophysics Data System (ADS)

Yuan, V. W.

2002-12-01

In previous attempts to determine the internal temperature in systems subjected to dynamic loading, experimenters have usually relied on surface-based optical techniques that are often hampered by insufficient information regarding the emissivity of the surfaces under study. Neutron Resonance Spectroscopy (NRS) is a technique that uses Doppler-broadened neutron resonances to measure internal temperatures in dynamically-loaded samples. NRS has developed its own target-moderator assembly to provide single pulses with an order of magnitude higher brightness than the Lujan production target. The resonance line shapes from which temperature information is extracted are also influenced by non-temperature-dependent broadening from the moderator and detector phosphorescence. Dynamic NRS experiments have been performed to measure the temperature in a silver sheet jet and behind the passage of a shock wave in molybdenum.

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-CT imaging studies showed the preferential accumulation of these nanobins in an orthotopic model of breast cancer. Due to their biocompatibility, robustness, and extensive history in the clinic, liposomes are an ideal drug delivery vehicle for the development of targeted therapies. The data presented in this thesis demonstrates the potential for active targeting to increase the therapeutic index of nanoscale drug delivery systems by increasing antitumor effect while simultaneously preventing drug uptake in peripheral tissue. In particular, targeting nanoparticles to the uPA system is a promising strategy for the treatment of many advanced, metastatic cancers.

Multi-Target Tracking for Swarm vs. Swarm UAV Systems

DTIC Science & Technology

2012-09-01

Uhlmann, “Using covariance intersection for SLAM,” Robotics and Autonomous Systems, vol. 55, pp. 3–20, Jan. 2007. [10] R. B. G. Wolfgang Niehsen... Krause , J. Leskovec, and C. Guestrin, “Data association for topic intensity track- ing,” Proceedings of the 23rd international conference on Machine

Multicolor fluorescence "click"-chemistry as a means to select membrane targets for pre-targeting approaches by function of their receptor kinetics.

PubMed

van der Wal, Steffen; de Korne, Clarize M; Sand, Laurens L G; van Willigen, Danny M; Hogendoorn, Pancras C W; Szuhai, Karoly; van Leeuwen, Fijs W B; Buckle, Tessa

2018-06-04

Availability of a receptor for theranostic pre-targeting approaches was assessed using a novel "click" chemistry-based de-activatable fluorescence-quenching concept. Efficacy was evaluated in a cell-based model system that exhibits both membranous (available) and internalized (unavailable) receptor-fractions of the clinically relevant receptor chemokine receptor 4 (CXCR4). Proof of concept was based on a de-activatable tracer consisting out of a CXCR4 specific peptide functionalized with a Cy5 dye comprising a chemo-selective azide handle (N3-Cy5-AcTZ14011). Reaction with a Cy7 quencher dye (Cy7-DBCO) resulted in optically silent Cy7-["click"]-Cy5-AcTZ14011. In situ a >90% FRET-based reduction of signal intensity of N3-Cy5-AcTZ14011 (KD 222.4 ± 25.2 nM) was seen within minutes after quencher addition. In cells, discrimination between the membranous and internalized receptor-fraction could be made through quantitative assessment of quenching/internalization kinetics. As such, using this approach screening of membrane receptors and their applicability in receptor-(pre-)targeted theranostics can become straightforward. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Self-organizing team formation for target observation

NASA Astrophysics Data System (ADS)

Bowyer, Richard S.; Bogner, Robert E.

2001-08-01

Target observation is a problem where the application of multiple sensors can improve the probability of detection and observation of the target. Team formation is one method by which seemingly unsophisticated heterogeneous sensors may be organized to achieve a coordinated observation system. The sensors, which we shall refer to as agents, are situated in an area of interest with the goal of observing a moving target. We apply a team approach to this problem, which combines the strengths of individual agents into a cohesive entity - the team. In autonomous systems, the mechanisms that underlie the formation of a team are of interest. Teams may be formed by various mechanisms, which include an externally imposed grouping of agents, or an internally, self-organized (SO) grouping of agents. Internally motivated mechanisms are particularly challenging, but offer the benefit of being unsupervised, an important quality for groups of autonomous cooperating machines. This is the focus of our research. By studying natural systems such as colonies of ants, we obtain insight into these mechanisms of self organization. We propose that the team is an expression of a distributed agent-self, and that a particular realization of the agent-self exists, whilst the environmental conditions are conducive to that existence. We describe an algorithms for agent team formation that is inspired by the self-organizing behavior of ants, and describe simulation results for team formation amongst a lattice of networked sensors.

Management of high blood pressure in Blacks: an update of the International Society on Hypertension in Blacks consensus statement.

PubMed

Flack, John M; Sica, Domenic A; Bakris, George; Brown, Angela L; Ferdinand, Keith C; Grimm, Richard H; Hall, W Dallas; Jones, Wendell E; Kountz, David S; Lea, Janice P; Nasser, Samar; Nesbitt, Shawna D; Saunders, Elijah; Scisney-Matlock, Margaret; Jamerson, Kenneth A

2010-11-01

Since the first International Society on Hypertension in Blacks consensus statement on the "Management of High Blood Pressure in African American" in 2003, data from additional clinical trials have become available. We reviewed hypertension and cardiovascular disease prevention and treatment guidelines, pharmacological hypertension clinical end point trials, and blood pressure-lowering trials in blacks. Selected trials without significant black representation were considered. In this update, blacks with hypertension are divided into 2 risk strata, primary prevention, where elevated blood pressure without target organ damage, preclinical cardiovascular disease, or overt cardiovascular disease for whom blood pressure consistently <135/85 mm Hg is recommended, and secondary prevention, where elevated blood pressure with target organ damage, preclinical cardiovascular disease, and/or a history of cardiovascular disease, for whom blood pressure consistently <130/80 mm Hg is recommended. If blood pressure is ≤10 mm Hg above target levels, monotherapy with a diuretic or calcium channel blocker is preferred. When blood pressure is >15/10 mm Hg above target, 2-drug therapy is recommended, with either a calcium channel blocker plus a renin-angiotensin system blocker or, alternatively, in edematous and/or volume-overload states, with a thiazide diuretic plus a renin-angiotensin system blocker. Effective multidrug therapeutic combinations through 4 drugs are described. Comprehensive lifestyle modifications should be initiated in blacks when blood pressure is ≥115/75 mm Hg. The updated International Society on Hypertension in Blacks consensus statement on hypertension management in blacks lowers the minimum target blood pressure level for the lowest-risk blacks, emphasizes effective multidrug regimens, and de-emphasizes monotherapy.

Inertially confined fusion using heavy ion drivers

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

Herrmannsfeldt, W.B.; Bangerter, R.O.; Bock, R.

1991-10-01

The various technical issues of HIF will be briefly reviewed in this paper. It will be seen that there are numerous areas in common in all the approaches to HIF. In the recent International Symposium on Heavy Ion Inertial Fusion, the attendees met in specialized workshop sessions to consider the needs for research in each area. Each of the workshop groups considered the key questions of this report: (1) Is this an appropriate time for international collaboration in HIF (2) Which problems are most appropriate for such collaboration (3) Can the sharing of target design information be set aside untilmore » other driver and systems issues are better resolved, by which time it might be supposed that there could be a relaxation of classification of target issues (4) What form(s) of collaboration are most appropriate, e.g., bilateral or multilateral (5) Can international collaboration be sensibly attempted without significant increases in funding for HIF The authors of this report share the conviction that collaboration on a broad scale is mandatory for HIF to have the resources, both financial and personnel, to progress to a demonstration experiment. Ultimately it may be possible for a single driver with the energy, power, focusibility, and pulse shape to satisfy the needs of the international community for target physics research. Such a facility could service multiple experimental chambers with a variety of beam geometries and target concepts.« less

Inertially confined fusion using heavy ion drivers

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

Herrmannsfeldt, W.B.; Bangerter, R.O.; Bock, R.

1991-10-01

The various technical issues of HIF will be briefly reviewed in this paper. It will be seen that there are numerous areas in common in all the approaches to HIF. In the recent International Symposium on Heavy Ion Inertial Fusion, the attendees met in specialized workshop sessions to consider the needs for research in each area. Each of the workshop groups considered the key questions of this report: (1) Is this an appropriate time for international collaboration in HIF? (2) Which problems are most appropriate for such collaboration? (3) Can the sharing of target design information be set aside untilmore » other driver and systems issues are better resolved, by which time it might be supposed that there could be a relaxation of classification of target issues? (4) What form(s) of collaboration are most appropriate, e.g., bilateral or multilateral? (5) Can international collaboration be sensibly attempted without significant increases in funding for HIF? The authors of this report share the conviction that collaboration on a broad scale is mandatory for HIF to have the resources, both financial and personnel, to progress to a demonstration experiment. Ultimately it may be possible for a single driver with the energy, power, focusibility, and pulse shape to satisfy the needs of the international community for target physics research. Such a facility could service multiple experimental chambers with a variety of beam geometries and target concepts.« less

A pretargeted nanoparticle system for tumor cell labeling

PubMed Central

Gunn, Jonathan; Park, Steven I.; Veiseh, Omid; Press, Oliver W.; Zhang, Miqin

2011-01-01

Nanoparticle-based cancer diagnostics and therapeutics can be significantly enhanced by selective tissue localization, but the strategy can be complicated by the requirement of a targeting ligand conjugated on nanoparticles, that is specific to only one or a limited few types of neoplastic cells, necessitating the development of multiple nanoparticle systems for different diseases. Here, we present a new nanoparticle system that capitalizes on a targeting pretreatment strategy, where a circulating fusion protein (FP) selectively prelabels the targeted cellular epitope, and a biotinylated iron oxide nanoparticle serves as a secondary label that binds to the FP on the target cell. This approach enables a single nanoparticle formulation to be used with any one of existing fusion proteins to bind a variety of target cells. We demonstrated this approach with two fusion proteins against two model cancer cell lines: lymphoma (Ramos) and leukemia (Jurkat), which showed 72.2% and 91.1% positive labeling, respectively. Notably, TEM analysis showed that a large nanoparticle population was endocytosed via attachment to the non-internalizing CD20 epitope. PMID:21107453

A pretargeted nanoparticle system for tumor cell labeling.

PubMed

Gunn, Jonathan; Park, Steven I; Veiseh, Omid; Press, Oliver W; Zhang, Miqin

2011-03-01

Nanoparticle-based cancer diagnostics and therapeutics can be significantly enhanced by selective tissue localization, but the strategy can be complicated by the requirement of a targeting ligand conjugated on nanoparticles, that is specific to only one or a limited few types of neoplastic cells, necessitating the development of multiple nanoparticle systems for different diseases. Here, we present a new nanoparticle system that capitalizes on a targeting pretreatment strategy, where a circulating fusion protein (FP) selectively prelabels the targeted cellular epitope, and a biotinylated iron oxide nanoparticle serves as a secondary label that binds to the FP on the target cell. This approach enables a single nanoparticle formulation to be used with any one of existing fusion proteins to bind a variety of target cells. We demonstrated this approach with two fusion proteins against two model cancer cell lines: lymphoma (Ramos) and leukemia (Jurkat), which showed 72.2% and 91.1% positive labeling, respectively. Notably, TEM analysis showed that a large nanoparticle population was endocytosed via attachment to the non-internalizing CD20 epitope.

International Infantry and Joint Services Small Arms Systems Symposium, Exhibition and Firing Demonstration

DTIC Science & Technology

2009-05-21

range performance and PHit /PKill is essential ● System prepared for additional functionalities as technology matures Aimpoint BR8 – NATO Demo Aimpoint...have been delivered to FMV (Swedish Defence Materiel Administration) ● Demonstrated for NATO in Toledo 2007- 02-15: > 65% PHit at 1.2x1.2m targets...from 100 to 250m! ● Demonstrated in Sweden 2008-10-01: > 80% PHit at different targets from 120 to 150m! ● 100 units ordered in May 2009 for use on

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.

Cultural Adaptation of a Neurobiologically Informed Intervention in Local and International Contexts

ERIC Educational Resources Information Center

Pakulak, Eric; Hampton Wray, Amanda; Longoria, Zayra; Garcia Isaza, Alejandra; Stevens, Courtney; Bell, Theodore; Burlingame, Sarah; Klein, Scott; Berlinski, Samuel; Attanasio, Orazio; Neville, Helen

2017-01-01

The relationship between early adversity and numerous negative outcomes across the lifespan is evident in a wide range of societies and cultures (e.g., Pakulak, Stevens, & Neville, 2018). Among the most affected neural systems are those supporting attention, self-regulation, and stress regulation. As such, these systems represent targets for…

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

Code of Federal Regulations, 2011 CFR

2011-04-01

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

Economic mitigation challenges: how further delay closes the door for achieving climate targets

NASA Astrophysics Data System (ADS)

Luderer, Gunnar; Pietzcker, Robert C.; Bertram, Christoph; Kriegler, Elmar; Meinshausen, Malte; Edenhofer, Ottmar

2013-09-01

While the international community aims to limit global warming to below 2 ° C to prevent dangerous climate change, little progress has been made towards a global climate agreement to implement the emissions reductions required to reach this target. We use an integrated energy-economy-climate modeling system to examine how a further delay of cooperative action and technology availability affect climate mitigation challenges. With comprehensive emissions reductions starting after 2015 and full technology availability we estimate that maximum 21st century warming may still be limited below 2 ° C with a likely probability and at moderate economic impacts. Achievable temperature targets rise by up to ˜0.4 ° C if the implementation of comprehensive climate policies is delayed by another 15 years, chiefly because of transitional economic impacts. If carbon capture and storage (CCS) is unavailable, the lower limit of achievable targets rises by up to ˜0.3 ° C. Our results show that progress in international climate negotiations within this decade is imperative to keep the 2 ° C target within reach.

Systemic sclerosis-scleroderma.

PubMed

Haustein, U-F

2002-06-01

Systemic sclerosis is a clinically heterogeneous, systemic disorder which affects the connective tissue of the skin, internal organs and the walls of blood vessels. It is characterized by alterations of the microvasculature, disturbances of the immune system and by massive deposition of collagen and other matrix substances in the connective tissue. This review discusses epidemiology and survival, clinical features including subsets and internal organ involvement, pathophysiology and genetics, microvasculature, immunobiology, fibroblasts and connective tissue metabolism and environmental factors. Early diagnosis and individually tailored therapy help to manage this disorder, which is treatable, but not curable. Therapy involves immunomodulation as well as the targeting of blood vessel mechanics and fibrosis. Physical therapy and psychotherapy are also important adjunctive therapies in this multifactorial disease.

Charomers—Interleukin-6 Receptor Specific Aptamers for Cellular Internalization and Targeted Drug Delivery

PubMed Central

2017-01-01

Interleukin-6 (IL-6) is a key player in inflammation and the main factor for the induction of acute phase protein biosynthesis. Further to its central role in many aspects of the immune system, IL-6 regulates a variety of homeostatic processes. To interfere with IL-6 dependent diseases, such as various autoimmune diseases or certain cancers like multiple myeloma or hepatocellular carcinoma associated with chronic inflammation, it might be a sensible strategy to target human IL-6 receptor (hIL-6R) presenting cells with aptamers. We therefore have selected and characterized different DNA and RNA aptamers specifically binding IL-6R. These IL-6R aptamers, however, do not interfere with the IL-6 signaling pathway but are internalized with the receptor and thus can serve as vehicles for the delivery of different cargo molecules like therapeutics. We succeeded in the construction of a chlorin e6 derivatized aptamer to be delivered for targeted photodynamic therapy (PDT). Furthermore, we were able to synthesize an aptamer intrinsically comprising the cytostatic 5-Fluoro-2′-deoxy-uridine for targeted chemotherapy. The α6β4 integrin specific DNA aptamer IDA, also selected in our laboratory is internalized, too. All these aptamers can serve as vehicles for targeted drug delivery into cells. We call them charomers—in memory of Charon, the ferryman in Greek mythology, who ferried the deceased into the underworld. PMID:29211023

Charomers-Interleukin-6 Receptor Specific Aptamers for Cellular Internalization and Targeted Drug Delivery.

PubMed

Hahn, Ulrich

2017-12-06

Interleukin-6 (IL-6) is a key player in inflammation and the main factor for the induction of acute phase protein biosynthesis. Further to its central role in many aspects of the immune system, IL-6 regulates a variety of homeostatic processes. To interfere with IL-6 dependent diseases, such as various autoimmune diseases or certain cancers like multiple myeloma or hepatocellular carcinoma associated with chronic inflammation, it might be a sensible strategy to target human IL-6 receptor (hIL-6R) presenting cells with aptamers. We therefore have selected and characterized different DNA and RNA aptamers specifically binding IL-6R. These IL-6R aptamers, however, do not interfere with the IL-6 signaling pathway but are internalized with the receptor and thus can serve as vehicles for the delivery of different cargo molecules like therapeutics. We succeeded in the construction of a chlorin e6 derivatized aptamer to be delivered for targeted photodynamic therapy (PDT). Furthermore, we were able to synthesize an aptamer intrinsically comprising the cytostatic 5-Fluoro-2'-deoxy-uridine for targeted chemotherapy. The α6β4 integrin specific DNA aptamer IDA, also selected in our laboratory is internalized, too. All these aptamers can serve as vehicles for targeted drug delivery into cells. We call them charomers-in memory of Charon, the ferryman in Greek mythology, who ferried the deceased into the underworld.

An efficient PEGylated liposomal nanocarrier containing cell-penetrating peptide and pH-sensitive hydrazone bond for enhancing tumor-targeted drug delivery.

PubMed

Ding, Yuan; Sun, Dan; Wang, Gui-Ling; Yang, Hong-Ge; Xu, Hai-Feng; Chen, Jian-Hua; Xie, Ying; Wang, Zhi-Qiang

2015-01-01

Cell-penetrating peptides (CPPs) as small molecular transporters with abilities of cell penetrating, internalization, and endosomal escape have potential prospect in drug delivery systems. However, a bottleneck hampering their application is the poor specificity for cells. By utilizing the function of hydration shell of polyethylene glycol (PEG) and acid sensitivity of hydrazone bond, we constructed a kind of CPP-modified pH-sensitive PEGylated liposomes (CPPL) to improve the selectivity of these peptides for tumor targeting. In CPPL, CPP was directly attached to liposome surfaces via coupling with stearate (STR) to avoid the hindrance of PEG as a linker on the penetrating efficiency of CPP. A PEG derivative by conjugating PEG with STR via acid-degradable hydrazone bond (PEG2000-Hz-STR, PHS) was synthesized. High-performance liquid chromatography and flow cytometry demonstrated that PHS was stable at normal neutral conditions and PEG could be completely cleaved from liposome surface to expose CPP under acidic environments in tumor. An optimal CPP density on liposomes was screened to guaranty a maximum targeting efficiency on tumor cells as well as not being captured by normal cells that consequently lead to a long circulation in blood. In vitro and in vivo studies indicated, in 4 mol% CPP of lipid modified system, that CPP exerted higher efficiency on internalizing the liposomes into targeted subcellular compartments while remaining inactive and free from opsonins at a maximum extent in systemic circulation. The 4% CPPL as a drug delivery system will have great potential in the clinical application of anticancer drugs in future.

An efficient PEGylated liposomal nanocarrier containing cell-penetrating peptide and pH-sensitive hydrazone bond for enhancing tumor-targeted drug delivery

PubMed Central

Ding, Yuan; Sun, Dan; Wang, Gui-Ling; Yang, Hong-Ge; Xu, Hai-Feng; Chen, Jian-Hua; Xie, Ying; Wang, Zhi-Qiang

2015-01-01

Cell-penetrating peptides (CPPs) as small molecular transporters with abilities of cell penetrating, internalization, and endosomal escape have potential prospect in drug delivery systems. However, a bottleneck hampering their application is the poor specificity for cells. By utilizing the function of hydration shell of polyethylene glycol (PEG) and acid sensitivity of hydrazone bond, we constructed a kind of CPP-modified pH-sensitive PEGylated liposomes (CPPL) to improve the selectivity of these peptides for tumor targeting. In CPPL, CPP was directly attached to liposome surfaces via coupling with stearate (STR) to avoid the hindrance of PEG as a linker on the penetrating efficiency of CPP. A PEG derivative by conjugating PEG with STR via acid-degradable hydrazone bond (PEG2000-Hz-STR, PHS) was synthesized. High-performance liquid chromatography and flow cytometry demonstrated that PHS was stable at normal neutral conditions and PEG could be completely cleaved from liposome surface to expose CPP under acidic environments in tumor. An optimal CPP density on liposomes was screened to guaranty a maximum targeting efficiency on tumor cells as well as not being captured by normal cells that consequently lead to a long circulation in blood. In vitro and in vivo studies indicated, in 4 mol% CPP of lipid modified system, that CPP exerted higher efficiency on internalizing the liposomes into targeted subcellular compartments while remaining inactive and free from opsonins at a maximum extent in systemic circulation. The 4% CPPL as a drug delivery system will have great potential in the clinical application of anticancer drugs in future. PMID:26491292

Hierarchical Targeting Strategy for Enhanced Tumor Tissue Accumulation/Retention and Cellular Internalization.

PubMed

Wang, Sheng; Huang, Peng; Chen, Xiaoyuan

2016-09-01

Targeted delivery of therapeutic agents is an important way to improve the therapeutic index and reduce side effects. To design nanoparticles for targeted delivery, both enhanced tumor tissue accumulation/retention and enhanced cellular internalization should be considered simultaneously. So far, there have been very few nanoparticles with immutable structures that can achieve this goal efficiently. Hierarchical targeting, a novel targeting strategy based on stimuli responsiveness, shows good potential to enhance both tumor tissue accumulation/retention and cellular internalization. Here, the recent design and development of hierarchical targeting nanoplatforms, based on changeable particle sizes, switchable surface charges and activatable surface ligands, will be introduced. In general, the targeting moieties in these nanoplatforms are not activated during blood circulation for efficient tumor tissue accumulation, but re-activated by certain internal or external stimuli in the tumor microenvironment for enhanced cellular internalization. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Research on energy transmission calculation problem on laser detecting submarine

NASA Astrophysics Data System (ADS)

Fu, Qiang; Li, Yingchao; Zhang, Lizhong; Wang, Chao; An, Yan

2014-12-01

The laser detection and identification is based on the method of using laser as the source of signal to scan the surface of ocean. If the laser detection equipment finds out the target, it will immediately reflect the returning signal, and then through receiving and disposing the returning signal by the receiving system, to realize the function of detection and identification. Two mediums channels should be though in the process of laser detection transmission, which are the atmosphere and the seawater. The energy loss in the process of water transport, mainly considering the surface reflection and scattering attenuation and internal attenuation factors such as seawater. The energy consumption though atmospheric transmission, mainly considering the absorption of atmospheric and the attenuation causing by scattering, the energy consumption though seawater transmission, mainly considering the element such as surface reflection, the attenuation of scattering and internal attenuation of seawater. On the basis of the analysis and research, through the mode of establishment of atmospheric scattering, the model of sea surface reflection and the model of internal attenuation of seawater, determine the power dissipation of emitting lasers system, calculates the signal strength that reaches the receiver. Under certain conditions, the total attenuation of -98.92 dB by calculation, and put forward the related experiment scheme by the use of Atmospheric analog channel, seawater analog channel. In the experiment of the theory, we use the simulation pool of the atmosphere and the sea to replace the real environment where the laser detection system works in this kind of situation. To start with, we need to put the target in the simulating seawater pool of 10 meters large and then control the depth of the target in the sea level. We, putting the laser detection system in position where it is 2 kilometers far from one side, secondly use the equipment to aim at the target in some distance. Lastly, by launching and detecting the signal of returning wave, identify the effect of the image produced by the system.

Scaling up towards international targets for AIDS, tuberculosis, and malaria: contribution of global fund-supported programs in 2011-2015.

PubMed

Katz, Itamar; Komatsu, Ryuichi; Low-Beer, Daniel; Atun, Rifat

2011-02-23

The paper projects the contribution to 2011-2015 international targets of three major pandemics by programs in 140 countries funded by the Global Fund to Fight AIDS, Tuberculosis and Malaria, the largest external financier of tuberculosis and malaria programs and a major external funder of HIV programs in low and middle income countries. Estimates, using past trends, for the period 2011-2015 of the number of persons receiving antiretroviral (ARV) treatment, tuberculosis case detection using the internationally approved DOTS strategy, and insecticide-treated nets (ITNs) to be delivered by programs in low and middle income countries supported by the Global Fund compared to international targets established by UNAIDS, Stop TB Partnership, Roll Back Malaria Partnership and the World Health Organisation. Global Fund-supported programs are projected to provide ARV treatment to 5.5-5.8 million people, providing 30%-31% of the 2015 international target. Investments in tuberculosis and malaria control will enable reaching in 2015 60%-63% of the international target for tuberculosis case detection and 30%-35% of the ITN distribution target in sub-Saharan Africa. Global Fund investments will substantially contribute to the achievement by 2015 of international targets for HIV, TB and malaria. However, additional large scale international and domestic financing is needed if these targets are to be reached by 2015.

Highly efficient, nonpeptidic oligoguanidinium vectors that selectively internalize into mitochondria.

PubMed

Fernández-Carneado, Jimena; Van Gool, Michiel; Martos, Vera; Castel, Susanna; Prados, Pilar; de Mendoza, Javier; Giralt, Ernest

2005-01-26

Oligoguanidinium-based cell delivery systems have gained broad interest in the drug delivery field since one decade ago. Thus, arginine-containing peptides as Tat or Antp, oligoarginine peptides, and derived peptoids have been described as shuttles for delivering nonpermeant drugs inside cancer cells. Herein we report a new family of tetraguanidinium cell penetrating vectors efficiently internalized in human tumor cells. Their high internalization, studied by confocal microscopy and flow cytometry, as well as their specific accumulation in mitochondria makes these new vectors likely vehicles for the targeted delivery of anticancer drugs to mitochondria.

N-acetylgalactosamine-functionalized dendrimers as hepatic cancer cell-targeted carriers.

PubMed

Medina, Scott H; Tekumalla, Venkatesh; Chevliakov, Maxim V; Shewach, Donna S; Ensminger, William D; El-Sayed, Mohamed E H

2011-06-01

There is an urgent need for novel polymeric carriers that can selectively deliver a large dose of chemotherapeutic agents into hepatic cancer cells to achieve high therapeutic activity with minimal systemic side effects. PAMAM dendrimers are characterized by a unique branching architecture and a large number of chemical surface groups suitable for coupling of chemotherapeutic agents. In this article, we report the coupling of N-acetylgalactosamine (NAcGal) to generation 5 (G5) of poly(amidoamine) (PAMAM-NH₂) dendrimers via peptide and thiourea linkages to prepare NAcGal-targeted carriers used for targeted delivery of chemotherapeutic agents into hepatic cancer cells. We describe the uptake of NAcGal-targeted and non-targeted G5 dendrimers into hepatic cancer cells (HepG2) as a function of G5 concentration and incubation time. We examine the contribution of the asialoglycoprotein receptor (ASGPR) to the internalization of NAcGal-targeted dendrimers into hepatic cancer cells through a competitive inhibition assay. Our results show that uptake of NAcGal-targeted G5 dendrimers into hepatic cancer cells occurs via ASGPR-mediated endocytosis. Internalization of these targeted carriers increased with the increase in G5 concentration and incubation time following Michaelis-Menten kinetics characteristic of receptor-mediated endocytosis. These results collectively indicate that G5-NAcGal conjugates function as targeted carriers for selective delivery of chemotherapeutic agents into hepatic cancer cells. Copyright © 2011 Elsevier Ltd. All rights reserved.

Mathematical modeling of vesicle drug delivery systems 2: targeted vesicle interactions with cells, tumors, and the body.

PubMed

Ying, Chong T; Wang, Juntian; Lamm, Robert J; Kamei, Daniel T

2013-02-01

Vesicles have been studied for several years in their ability to deliver drugs. Mathematical models have much potential in reducing time and resources required to engineer optimal vesicles, and this review article summarizes these models that aid in understanding the ability of targeted vesicles to bind and internalize into cancer cells, diffuse into tumors, and distribute in the body. With regard to binding and internalization, radiolabeling and surface plasmon resonance experiments can be performed to determine optimal vesicle size and the number and type of ligands conjugated. Binding and internalization properties are also inputs into a mathematical model of vesicle diffusion into tumor spheroids, which highlights the importance of the vesicle diffusion coefficient and the binding affinity of the targeting ligand. Biodistribution of vesicles in the body, along with their half-life, can be predicted with compartmental models for pharmacokinetics that include the effect of targeting ligands, and these predictions can be used in conjunction with in vivo models to aid in the design of drug carriers. Mathematical models can prove to be very useful in drug carrier design, and our hope is that this review will encourage more investigators to combine modeling with quantitative experimentation in the field of vesicle-based drug delivery.

Systematic evaluation of antibody-mediated siRNA delivery using an industrial platform of THIOMAB–siRNA conjugates

PubMed Central

Cuellar, Trinna L.; Barnes, Dwight; Nelson, Christopher; Tanguay, Joshua; Yu, Shang-Fan; Wen, Xiaohui; Scales, Suzie J.; Gesch, Julie; Davis, David; van Brabant Smith, Anja; Leake, Devin; Vandlen, Richard; Siebel, Christian W.

2015-01-01

Delivery of siRNA is a key hurdle to realizing the therapeutic promise of RNAi. By targeting internalizing cell surface antigens, antibody–siRNA complexes provide a possible solution. However, initial reports of antibody–siRNA complexes relied on non-specific charged interactions and have not been broadly applicable. To assess and improve this delivery method, we built on an industrial platform of therapeutic antibodies called THIOMABs, engineered to enable precise covalent coupling of siRNAs. We report that such coupling generates monomeric antibody–siRNA conjugates (ARCs) that retain antibody and siRNA activities. To broadly assess this technology, we generated a battery of THIOMABs against seven targets that use multiple internalization routes, enabling systematic manipulation of multiple parameters that impact delivery. We identify ARCs that induce targeted silencing in vitro and extend tests to target prostate carcinoma cells following systemic administration in mouse models. However, optimal silencing was restricted to specific conditions and only observed using a subset of ARCs. Trafficking studies point to ARC entrapment in endocytic compartments as a limiting factor, independent of the route of antigen internalization. Our broad characterization of multiple parameters using therapeutic-grade conjugate technology provides a thorough assessment of this delivery technology, highlighting both examples of success as well as remaining challenges. PMID:25550431

6TH Saint Petersburg International Conference on Integrated Navigation Systems. (6eme Conference Internationale de Saint Petersbourg sur les Systemes de Navigation Integree)

DTIC Science & Technology

1999-10-01

Kharisov V.N., Perov A.I., Boldin V.A. (editors). 1977. The global satelllite radio-navigational system 20. Wu W.-R. Target tracking with glint...the coordinates of the OP techniques for their searching and extracting in deep seas. These techniques. have yielded Researches have shown that, an OP

Discovery of peptide drug carrier candidates for targeted multi-drug delivery into prostate cancer cells.

PubMed

Bashari, O; Redko, B; Cohen, A; Luboshits, G; Gellerman, G; Firer, M A

2017-11-01

Metastatic castration-resistant prostate cancer (mCRPC) remains essentially incurable. Targeted Drug Delivery (TDD) systems may overcome the limitations of current mCRPC therapies. We describe the use of strict criteria to isolate novel prostate cancer cell targeting peptides that specifically deliver drugs into target cells. Phage from a libraries displaying 7mer peptides were exposed to PC-3 cells and only internalized phage were recovered. The ability of these phage to internalize into other prostate cancer cells (LNCaP, DU-145) was validated. The displayed peptides of selected phage clones were synthesized and their specificity for target cells was validated in vitro and in vivo. One peptide (P12) which specifically targeted PC-3 tumors in vivo was incorporated into mono-drug (Chlorambucil, Combretastatin or Camptothecin) and dual-drug (Chlorambucil/Combretastatin or Chlorambucil/Camptothecin) PDCs and the cytotoxic efficacy of these conjugates for target cells was tested. Conjugation of P12 into dual-drug PDCs allowed discovery of new drug combinations with synergistic effects. The use of strict selection criteria can lead to discovery of novel peptides for use as drug carriers for TDD. PDCs represent an effective alternative to current modes of free drug chemotherapy for prostate cancer. Copyright © 2017. Published by Elsevier B.V.

Evolution of Magnetized Liner Inertial Fusion (MagLIF) Targets

DOE PAGES

Fooks, J. A.; Carlson, L. C.; Fitzsimmons, P.; ...

2017-12-19

Here, the magnetized liner inertial fusion (MagLIF) experimental campaign conducted at the University of Rochester’s Laboratory for Laser Energetics (LLE) has evolved significantly since its start in 2014. Scientific requirements and OMEGA EP system technology both have progressed, resulting in necessary and available updates to the target design. These include, but are not limited to: optimizing target dimensions and aspect ratios to maximize survival at desired pressures; coating target components to enhance physics diagnosis; precision-machining diagnostic windows along the axis of the target; improving fiducial placement reproducibility and reducing subsequent assembly time by 50%; and implementing gas-pressure transducers on themore » targets. In addition, target fabrication techniques have changed and improved, allowing for simpler target reproducibility and decreased assembly time. To date, eleven variations of targets have been fabricated, with successful target fielding ranging from 1 to 20atm internal pressure and a maximum survivability of 33atm.« less

Evolution of Magnetized Liner Inertial Fusion (MagLIF) Targets

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

Fooks, J. A.; Carlson, L. C.; Fitzsimmons, P.

Here, the magnetized liner inertial fusion (MagLIF) experimental campaign conducted at the University of Rochester’s Laboratory for Laser Energetics (LLE) has evolved significantly since its start in 2014. Scientific requirements and OMEGA EP system technology both have progressed, resulting in necessary and available updates to the target design. These include, but are not limited to: optimizing target dimensions and aspect ratios to maximize survival at desired pressures; coating target components to enhance physics diagnosis; precision-machining diagnostic windows along the axis of the target; improving fiducial placement reproducibility and reducing subsequent assembly time by 50%; and implementing gas-pressure transducers on themore » targets. In addition, target fabrication techniques have changed and improved, allowing for simpler target reproducibility and decreased assembly time. To date, eleven variations of targets have been fabricated, with successful target fielding ranging from 1 to 20atm internal pressure and a maximum survivability of 33atm.« less

STS-95 Day 06 Highlights

NASA Technical Reports Server (NTRS)

1998-01-01

On this sixth day of the STS-95 mission, the flight crew, Cmdr. Curtis L. Brown, Pilot Steven W. Lindsey, Mission Specialists Scott E. Parazynski, Stephen K. Robinson, and Pedro Duque, and Payload Specialists Chiaki Mukai and John H. Glenn, test a device called the Video Guidance Sensor, a component of an automated docking system being prepared for use on the International Space Station. As Discovery closes in on Spartan, the astronauts will use a laser system that provides precise measurements of how far away the shuttle is from a target and how fast it is moving toward or away from the target.

Familial risk and sibling mentalization: Links with preschoolers' internalizing problems.

PubMed

Rodrigues, Michelle; Binnoon-Erez, Noam; Prime, Heather; Perlman, Michal; Jenkins, Jennifer M

2017-09-01

The current study explored whether older sibling mentalization moderated the relationship between familial risk for internalizing symptoms and the development of future internalizing problems in the younger siblings, referred to as target children. Data were collected on 397 older siblings at Time 1 (T1) when target children were newborn and their older siblings were on average 2.61 years old (SD = .75). Target children were on average 1.60 years old at Time 2 (T2). Internalizing problems were assessed via mother and partner reports. Familial risk was operationalized as the average of all older siblings' level of internalizing problems. Older sibling mentalization, indexed by internal state talk and reasoning, was observed and coded during a sibling pretend-play interaction at T2. Results revealed a significant interaction between familial risk of internalizing problems and older siblings' mentalizing abilities, showing that familial risk was related to target children's internalizing problems in the absence of sibling mentalization. Familial risk was not associated with target children's internalizing problems when siblings demonstrated mentalizing abilities. Findings support the need to consider sibling mentalization as a protective factor for children's internalizing problems. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

Advanced traveler information system capabilities : human factors research needs : summary report

DOT National Transportation Integrated Search

2003-09-01

The number and intensity of domestic and international terrorist events, along with the September 11, 2001, attacks, change the way Americans think and live. Terrorists attack targets where human casualties and economic consequences are likely to be ...

Calibration and tests of commercial wireless infrared thermometers

USDA-ARS?s Scientific Manuscript database

Applications of infrared thermometers (IRTs) in large agricultural fields require wireless data transmission, and IRT target temperature should have minimal sensitivity to internal detector temperature. To meet these objectives, a prototype wireless IRT system was developed at USDA Agricultural Rese...

The Decibel Report: Acoustic Sound Measurement Modeling and the Effects of Sonar on Marine Mammals

DTIC Science & Technology

2010-06-21

flow noise and shipborne internal noise are other relevant factors. For active systems, transmit and receive apparatus, target echo reflectivity...ambient noise, hydrodynamic flow noise, shipborne internal noise, and reverberation interference are the other relevant factors. The "L" terms expressed...speed, that is, hydrodynamic flow , dependent. 27 5. ND1 : dB - These symbols are read as receiving directivity index in units of decibels. The

International Infantry and Joint Services Small Arms Systems Symposium: Exhibition and Firing Demonstration

DTIC Science & Technology

2008-05-22

operation of weapon system) Phit Weapon System (e.g. dispersion) Most important influence ● Operator ● Distance to target together with ballistic...Suitable for a variety of weapons where ballistical correction to improve range performance and PHit /PKill is essential ● Prepare system for additional...status ● Prototypes have been delivered to FMV (Swedish Defence Materiel Administration) ● Demonstrated for NATO in Toledo 2007-02-15: > 65% PHit

Target Trailing With Safe Navigation for Maritime Autonomous Surface Vehicles

NASA Technical Reports Server (NTRS)

Wolf, Michael; Kuwata, Yoshiaki; Zarzhitsky, Dimitri V.

2013-01-01

This software implements a motion-planning module for a maritime autonomous surface vehicle (ASV). The module trails a given target while also avoiding static and dynamic surface hazards. When surface hazards are other moving boats, the motion planner must apply International Regulations for Avoiding Collisions at Sea (COLREGS). A key subset of these rules has been implemented in the software. In case contact with the target is lost, the software can receive and follow a "reacquisition route," provided by a complementary system, until the target is reacquired. The programmatic intention is that the trailed target is a submarine, although any mobile naval platform could serve as the target. The algorithmic approach to combining motion with a (possibly moving) goal location, while avoiding local hazards, may be applicable to robotic rovers, automated landing systems, and autonomous airships. The software operates in JPL s CARACaS (Control Architecture for Robotic Agent Command and Sensing) software architecture and relies on other modules for environmental perception data and information on the predicted detectability of the target, as well as the low-level interface to the boat controls.

First Experiments with the Polarized Internal Gas Target (PIT) at ANKE/COSY

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

Engels, R.; Lorentz, B.; Prasuhn, D.

2008-02-06

For future few-nucleon interaction studies with polarized beams and targets at COSY-Juelich, a polarized internal storage-cell gas target was implemented at the magnet spectrometer ANKE in summer 2005. First commissioning of the polarized Atomic Beam Source (ABS) at ANKE was carried out and some improvements of the system have been done. Storage-cell tests to determine the COSY beam dimensions have been performed. Electron cooling combined with stacking and stochastic cooling have been studied. Experiments with N{sub 2} gas in the storage cell to simulate the background produced by beam interaction with the aluminum cell walls were performed to investigate themore » beam heating by the target gas. The analysis of the d-vector p-vector {yields}dp and d-vector p-vector{yields}(dp{sub sp}){pi}{sup 0} reactions showed that events from the extended target can be clearly identified in the ANKE detector system.The polarization of the atomic beam of the ABS, positioned close to the strong dipole magnet D2 of ANKE, was tuned with a Lamb-shift polarimeter (LSP) beneath the target chamber. With use of the known analyzing powers of the quasi-free np{yields}d{pi}{sup 0} reaction, the polarization in the storage cell was measured to be Q{sub y} = 0.79{+-}0.07 in the vertical stray field of the D2 magnet acting as a holding field. The achieved target thickness was 2x10{sup 13} atoms/cm{sup 2} for one hyperfine state populated in the ABS beam only. With a COSY beam intensity of 6x10{sup 9} stored polarized deuterons in the ring, the luminosity for double polarized experiments was 1x10{sup 29} cm{sup -2} s{sup -1}.« less

First Experiments with the Polarized Internal Gas Target (PIT) at ANKE/COSY

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

Engels, R.; Lorentz, B.; Prasuhn, D.

2009-08-04

For future few-nucleon interaction studies with polarized beams and targets at COSY-Juelich, a polarized internal storage-cell gas target was implemented at the magnet spectrometer ANKE. First commissioning of the polarized Atomic Beam Source (ABS) at ANKE was carried out and some improvements of the system have been done. Storage-cell tests to determine the COSY beam dimensions have been performed. Electron cooling combined with stacking and stochastic cooling have been studied. Experiments with N{sub 2} gas in the storage cell to simulate the background produced by beam interaction with the aluminum cell walls were performed to investigate the beam heating bymore » the target gas. The analysis of the d-vectorp-vector->dp and d-vectorp-vector->(dp{sub sp})pi{sup 0} reactions showed that events from different positions of the extended target can be clearly identified in the ANKE detector system. The polarization of the atomic beam of the ABS, positioned close to the strong dipole magnet D2 of ANKE, was tuned with a Lamb-shift polarimeter (LSP) beneath the target chamber. With use of the known analyzing powers of the quasi-free np->dpi{sup 0} reaction, the polarization in the storage cell was measured to be Q{sub y} = 0.79+-0.07 in the vertical stray field of the D2 magnet acting as a holding field. The target thickness achieved was 2x10{sup 13} atoms/cm{sup 2} for one hyperfine state populated in the ABS beam only. With a COSY beam intensity of 6x10{sup 9} stored polarized deuterons in the ring, the luminosity for double polarized experiments was 1x10{sup 29} cm{sup -2} s{sup -1}.« less

Internal Light Source-Driven Photoelectrochemical 3D-rGO/Cellulose Device Based on Cascade DNA Amplification Strategy Integrating Target Analog Chain and DNA Mimic Enzyme.

PubMed

Lan, Feifei; Liang, Linlin; Zhang, Yan; Li, Li; Ren, Na; Yan, Mei; Ge, Shenguang; Yu, Jinghua

2017-11-01

In this work, a chemiluminescence-driven collapsible greeting card-like photoelectrochemical lab-on-paper device (GPECD) with hollow channel was demonstrated, in which target-triggering cascade DNA amplification strategy was ingeniously introduced. The GPECD had the functions of reagents storage and signal collection, and the change of configuration could control fluidic path, reaction time and alterations in electrical connectivity. In addition, three-dimentional reduced graphene oxide affixed Au flower was in situ grown on paper cellulose fiber for achieving excellent conductivity and biocompatibility. The cascade DNA amplification strategy referred to the cyclic formation of target analog chain and its trigger action to hybridization chain reaction (HCR), leading to the formation of numerous hemin/G-quadruplex DNA mimic enzyme with the presence of hemin. Subjected to the catalysis of hemin/G-quadruplex, the strong chemiluminiscence of luminol-H 2 O 2 system was obtained, which then was used as internal light source to excite photoactive materials realizing the simplification of instrument. In this analyzing process, thrombin served as proof-of-concept, and the concentration of target was converted into the DNA signal output by the specific recognition of aptamer-protein and target analog chain recycling. The target analog chain was produced in quantity with the presence of target, which further triggered abundant HCR and introduced hemin/G-quadruplex into the system. The photocurrent signal was obtained after the nitrogen-doped carbon dots sensitized ZnO was stimulated by chemiluminescence. The proposed GPECD exhibited excellent specificity and sensitivity toward thrombin with a detection limit of 16.7 fM. This judiciously engineered GPECD paved a luciferous way for detecting other protein with trace amounts in bioanalysis and clinical biomedicine.

Preliminary analysis for integration of spot-scanning proton beam therapy and real-time imaging and gating.

PubMed

Shimizu, S; Matsuura, T; Umezawa, M; Hiramoto, K; Miyamoto, N; Umegaki, K; Shirato, H

2014-07-01

Spot-scanning proton beam therapy (PBT) can create good dose distribution for static targets. However, there exists larger uncertainty for tumors that move due to respiration, bowel gas or other internal circumstances within the patients. We have developed a real-time tumor-tracking radiation therapy (RTRT) system that uses an X-ray linear accelerator gated to the motion of internal fiducial markers introduced in the late 1990s. Relying on more than 10 years of clinical experience and big log data, we established a real-time image gated proton beam therapy system dedicated to spot scanning. Using log data and clinical outcomes derived from the clinical usage of the RTRT system since 1999, we have established a library to be used for in-house simulation for tumor targeting and evaluation. Factors considered to be the dominant causes of the interplay effects related to the spot scanning dedicated proton therapy system are listed and discussed. Total facility design, synchrotron operation cycle, and gating windows were listed as the important factors causing the interplay effects contributing to the irradiation time and motion-induced dose error. Fiducial markers that we have developed and used for the RTRT in X-ray therapy were suggested to have the capacity to improve dose distribution. Accumulated internal motion data in the RTRT system enable us to improve the operation and function of a Spot-scanning proton beam therapy (SSPT) system. A real-time-image gated SSPT system can increase accuracy for treating moving tumors. The system will start clinical service in early 2014. Copyright © 2014 Associazione Italiana di Fisica Medica. Published by Elsevier Ltd. All rights reserved.

A novel in vivo method for isolating antibodies from a phage display library by neuronal retrograde transport selectively yields antibodies against p75(NTR.).

PubMed

Tani, Hiroaki; Osbourn, Jane K; Walker, Edward H; Rush, Robert A; Ferguson, Ian A

2013-01-01

The neurotrophin receptor p75(NTR) is utilized by a variety of pathogens to gain entry into the central nervous system (CNS). We tested if this entry portal might be exploited using a phage display library to isolate internalizing antibodies that target the CNS in vivo. By applying a phage library that expressed human single chain variable fragment (scFv) antibodies on their surface to a transected sciatic nerve, we showed that (1) phage conjugated to anti-p75(NTR) antibody or phage scFv library pre-panned against p75(NTR) are internalized by neurons expressing p75(NTR); (2) subsequent retrograde axonal transport separates internalized phage from the applied phage; and, (3) internalized phage can be recovered from a proximal ligature made on a nerve. This approach resulted in 13-fold increase in the number of phage isolated from the injured nerve compared with the starting population, and isolation of 18 unique internalizing p75(NTR) antibodies that were transported from the peripheral nerve into the spinal cord, through the blood-brain barrier. In addition, antibodies recognizing other potentially internalized antigens were identified through in vivo selection using a fully diverse library. Because p75(NTR) expression is upregulated in motor neurons in response to injury and in disease, the p75(NTR) antibodies may have substantial potential for cell-targeted drug/gene delivery. In addition, this novel selection method provides the potential to generate panels of antibodies that could be used to identify further internalization targets, which could aid drug delivery across the blood-brain barrier.

A novel in vivo method for isolating antibodies from a phage display library by neuronal retrograde transport selectively yields antibodies against p75NTR

PubMed Central

Tani, Hiroaki; Osbourn, Jane K.; Walker, Edward H.; Rush, Robert A.; Ferguson, Ian A.

2013-01-01

The neurotrophin receptor p75NTR is utilized by a variety of pathogens to gain entry into the central nervous system (CNS). We tested if this entry portal might be exploited using a phage display library to isolate internalizing antibodies that target the CNS in vivo. By applying a phage library that expressed human single chain variable fragment (scFv) antibodies on their surface to a transected sciatic nerve, we showed that (1) phage conjugated to anti-p75NTR antibody or phage scFv library pre-panned against p75NTR are internalized by neurons expressing p75NTR; (2) subsequent retrograde axonal transport separates internalized phage from the applied phage; and, (3) internalized phage can be recovered from a proximal ligature made on a nerve. This approach resulted in 13-fold increase in the number of phage isolated from the injured nerve compared with the starting population, and isolation of 18 unique internalizing p75NTR antibodies that were transported from the peripheral nerve into the spinal cord, through the blood-brain barrier. In addition, antibodies recognizing other potentially internalized antigens were identified through in vivo selection using a fully diverse library. Because p75NTR expression is upregulated in motor neurons in response to injury and in disease, the p75NTR antibodies may have substantial potential for cell-targeted drug/gene delivery. In addition, this novel selection method provides the potential to generate panels of antibodies that could be used to identify further internalization targets, which could aid drug delivery across the blood-brain barrier. PMID:23549155

APT Blanket Thermal Analyses of Top Horizontal Row 1 Modules

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

Shadday, M.A.

1999-09-20

The Accelerator Production of Tritium (APT) cavity flood system (CFS) is designed to be the primary safeguard for the integrity of the blanket modules during loss of coolant accidents (LOCAs). For certain large break LOCAs the CFS also provides backup for the residual heat removal systems (RHRs) in cooling the target assemblies. In the unlikely event that the internal flow passages in a blanket module or target assembly dryout, decay heat in the metal structures will be dissipated to the CFS through the module or assembly walls (i.e., rung outer walls). The target assemblies consist of tungsten targets encased inmore » steel conduits, and they can safely sustain high metal temperatures. Under internally dry conditions, the cavity flood fluid will cool the target assemblies with vigorous nucleate boiling on the external surfaces. However, the metal structures in the blanket modules consist of lead cladded in aluminum, and they have a long-term exposure temperature limit currently set to 150 degrees C. Simultaneous LOCAs in both the target and blanket heat removal systems (HRS) could result in dryout of the target ladders, as well as the horizontal blanket modules above the target. The cavity flood coolant would boil on the outside surfaces of the target ladder rungs, and the resultant steam could reduce the effectiveness of convection heat transfer from the blanket modules to the cavity flood coolant. A two-part analysis was conducted to ascertain if the cavity flood system can adequately cool the blanket modules above the targets, even when boiling is occurring on the outer surfaces of the target ladder rungs. The first part of the analysis was to model transient thermal conduction in the front top horizontal row 1 module (i.e. top horizontal modules nearest the incoming beam), while varying parametrically the convection heat transfer coefficient (htc) for the external surfaces exposed to the cavity flood flow. This part of the analysis demonstrated that the module could adequately conduct heat to the outer module surfaces, given reasonable values for the convection heat transfer coefficients. The second part of the analysis consisted of two-phase flow modeling of the natural circulation of the cavity flood fluid past the top modules. Slots in the top shield allow the cavity flood fluid to circulate. The required width for these slots, to prevent steam from backing up and blanketing the outer surfaces of the top modules, was determined.« less

Rapid and reliable detection and identification of GM events using multiplex PCR coupled with oligonucleotide microarray.

PubMed

Xu, Xiaodan; Li, Yingcong; Zhao, Heng; Wen, Si-yuan; Wang, Sheng-qi; Huang, Jian; Huang, Kun-lun; Luo, Yun-bo

2005-05-18

To devise a rapid and reliable method for the detection and identification of genetically modified (GM) events, we developed a multiplex polymerase chain reaction (PCR) coupled with a DNA microarray system simultaneously aiming at many targets in a single reaction. The system included probes for screening gene, species reference gene, specific gene, construct-specific gene, event-specific gene, and internal and negative control genes. 18S rRNA was combined with species reference genes as internal controls to assess the efficiency of all reactions and to eliminate false negatives. Two sets of the multiplex PCR system were used to amplify four and five targets, respectively. Eight different structure genes could be detected and identified simultaneously for Roundup Ready soybean in a single microarray. The microarray specificity was validated by its ability to discriminate two GM maizes Bt176 and Bt11. The advantages of this method are its high specificity and greatly reduced false-positives and -negatives. The multiplex PCR coupled with microarray technology presented here is a rapid and reliable tool for the simultaneous detection of GM organism ingredients.

Biomechanical responses of PMHS in moderate-speed rear impacts and development of response targets for evaluating the internal and external biofidelity of ATDS.

PubMed

Kang, Yun-Seok; Bolte, John H; Moorhouse, Kevin; Donnelly, Bruce; Herriott, Rodney; Mallory, Ann

2012-10-01

The objectives of this study were to obtain biomechanical responses of post mortem human subjects (PMHS) by subjecting them to two moderate-speed rear impact sled test conditions (8.5g, 17 km/h; 10.5g, 24 km/h) while positioned in an experimental seat system, and to create biomechanical targets for internal and external biofidelity evaluation of rear impact ATDs. The experimental seat was designed to measure external loads on the head restraint (4 load cells), seat back (6 load cells), and seat pan (4 load cells) such that subject dynamic interaction with the seat could be evaluated. This seat system was capable of simulating the dynamic characteristics of modern vehicle seat backs by considering the moment-rotation properties of a typical passenger vehicle, thus providing a more realistic test environment than using a rigid seat with a non-rotating seat back as done in previous studies. Instrumentation used to measure biomechanical responses of the PMHS included both accelerometers and angular rate sensors (ARS). A total of fourteen sled tests using eight PMHS (males 175.8 ± 6.2 cm of stature and 78.4 ± 7.2 kg of weight) provided data sets of seven PMHS for both test conditions. The biomechanical responses are described at both speeds, and cervical spine injuries are documented. Biomechanical targets are also created for internal and external biofidelity evaluation of rear impact anthropomorphic test devices (ATDs).

Science observations with the IUE using the one-gyro mode

NASA Technical Reports Server (NTRS)

Imhoff, C.; Pitts, R.; Arquilla, R.; Shrader, Chris R.; Perez, M. R.; Webb, J.

1990-01-01

The International Ultraviolet Explorer (IUE) attitude control system originally included an inertial reference package containing six gyroscopes for three axis stabilization. The science instrument includes a prime and redundant Field Error Sensor (FES) camera for target acquisition and offset guiding. Since launch, four of the six gyroscopes have failed. The current attitude control system utilizes the remaining two gyros and a Fine Sun Sensor (FSS) for three axis stabilization. When the next gyro fails, a new attitude control system will be uplinked which will rely on the remaining gyro and the FSS for general three axis stabilization. In addition to the FSS, the FES cameras will be required to assist in maintaining fine attitude control during target acquisition. This has required thoroughly determining the characteristics of the FES cameras and the spectrograph aperture plate as well as devising new target acquisition procedures. The results of this work are presented.

Science observations with the IUE using the one-gyro mode

NASA Technical Reports Server (NTRS)

Imhoff, C.; Pitts, R.; Arquilla, R.; Shrader, C.; Perez, M.; Webb, J.

1990-01-01

The International Ultraviolet Explorer (IUE) attitude control system originally included an inertial reference package containing six gyroscopes for three axis stabilization. The science instrument includes a prime and redundant Field Error Sensor (FES) camera for target acquisition and offset guiding. Since launch, four of the six gyroscopes have failed. The current attitude control system utilizes the remaining two gyros and a Fine Sun Sensor (FSS) for three axis stabilization. When the next gyro fails, a new attitude control system will be uplinked, which will relay on the remaining gyro and the FSS for general three axis stabilization. In addition to the FSS, the FES cameras will be required to assist in maintaining fine attitude control during target acquisition. This has required thoroughly determining the characteristics of the FES cameras and the spectrograph aperture plate as well as devising new target acquisition procedures. The results of this work are presented.

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.

SU-F-J-45: Sparing Normal Tissue with Ultra-High Dose Rate in Radiation Therapy

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

Feng, Y

Purpose: To spare normal tissue by reducing the location uncertainty of a moving target, we proposed an ultra-high dose rate system and evaluated. Methods: High energy electrons generated with a linear accelerator were injected into a storage ring to be accumulated. The number of the electrons in the ring was determined based on the prescribed radiation dose. The dose was delivered within a millisecond, when an online imaging system found that the target was in the position that was consistent with that in a treatment plan. In such a short time period, the displacement of the target was negligible. Themore » margin added to the clinical target volume (CTV) could be reduced that was evaluated by comparing of volumes between CTV and ITV in 14 cases of lung stereotactic body radiation therapy (SBRT) treatments. A design of the ultra-high dose rate system was evaluated based clinical needs and the recent developments of low energy (a few MeV) electron storage ring. Results: This design of ultra-high dose rate system was feasible based on the techniques currently available. The reduction of a target volume was significant by reducing the margin that accounted the motion of the target. ∼50% volume reduction of the internal target volume (ITV) could be achieved in lung SBRT treatments. Conclusion: With this innovation of ultra-high dose rate system, the margin of target is able to be significantly reduced. It will reduce treatment time of gating and allow precisely specified gating window to improve the accuracy of dose delivering.« less

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.

A method for integrating multiple components in a decision support system

Treesearch

Donald Nute; Walter D. Potter; Zhiyuan Cheng; Mayukh Dass; Astrid Glende; Frederick Maierv; Cy Routh; Hajime Uchiyama; Jin Wang; Sarah Witzig; Mark Twery; Peter Knopp; Scott Thomasma; H. Michael Rauscher

2005-01-01

We present a flexible, extensible method for integrating multiple tools into a single large decision support system (DSS) using a forest ecosystem management DSS (NED-2) as an example. In our approach, a rich ontology for the target domain is developed and implemented in the internal data model for the DSS. Semi-autonomous agents control external components and...

3D optical phase reconstruction within PMMA samples using a spectral OCT system

NASA Astrophysics Data System (ADS)

Briones-R., Manuel d. J.; De La Torre-Ibarra, Manuel H.; Mendoza Santoyo, Fernando

2015-08-01

The optical coherence tomography (OCT) technique has proved to be a useful method in biomedical areas such as ophthalmology, dentistry, dermatology, among many others. In all these applications the main target is to reconstruct the internal structure of the samples from which the physician's expertise may recognize and diagnose the existence of a disease. Nowadays OCT has been applied one step further and is used to study the mechanics of some particular type of materials, where the resulting information involves more than just their internal structure and the measurement of parameters such as displacements, stress and strain. Here we report on a spectral OCT system used to image the internal 3D microstructure and displacement maps from a PMMA (Poly-methyl-methacrylate) sample, subjected to a deformation by a controlled three point bending and tilting. The internal mechanical response of the polymer is shown as consecutive 2D images.

Design of a New Acceleration System for High-Current Pulsed Proton Beams from an ECR Source

NASA Astrophysics Data System (ADS)

Cooper, Andrew L.; Pogrebnyak, Ivan; Surbrook, Jason T.; Kelly, Keegan J.; Carlin, Bret P.; Champagne, Arthur E.; Clegg, Thomas B.

2014-03-01

A primary objective for accelerators at TUNL's Laboratory for Experimental Nuclear Astrophysics (LENA) is to maximize target beam intensity to ensure a high rate of nuclear events during each experiment. Average proton target currents of several mA are needed from LENA's electron cyclotron resonance (ECR) ion source because nuclear cross sections decrease substantially at energies of interest <200 keV. We seek to suppress undesired continuous environmental background by pulsing the beam and detecting events only during beam pulses. To improve beam intensity and transport, we installed a more powerful, stable microwave system for the ECR plasma, and will install a new acceleration system. This system will: reduce defocusing effects of the beam's internal space charge; provide better vacuum with a high gas conductance accelerating column; suppress bremsstrahlung X-rays produced when backstreaming electrons strike internal acceleration tube structures; and provide better heat dissipation by using deionized water to provide the current drain needed to establish the accelerating tube's voltage gradient. Details of beam optical modeling calculations, proposed accelerating tube design, and initial beam pulsing tests will be described. Work supported in part by USDOE Office of HE and Nuclear Physics.

Therapeutic Innovations for Targeting Childhood Neuroblastoma: Implications of the Neurokinin-1 Receptor System.

PubMed

Berger, Michael; VON Schweinitz, Dietrich

2017-11-01

Neuroblastoma is the most common solid extracranial malignant tumor in children. Despite recent advances in the treatment of this heterogenous tumor with surgery and chemotherapy, the prognosis in advanced stages remains poor. Interestingly, neuroblastoma is one of the few solid tumors, to date, in which an effect for targeted immunotherapy has been proven in controlled clinical trials, giving hope for further advances in the treatment of this and other tumors by targeted therapy. A large array of novel therapeutic options for targeted therapy of neuroblastoma is on the horizon. To this repεrtoirε, the neurokinin-1 receptor (NK1R) system was recently added. The present article explores the most recent developments in targeting neuroblastoma cells via the NK1R and how this new knowledge could be helpful to create new anticancer therapies agains neuroblastoma and other cancers. Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

Nanoparticle hardness controls the internalization pathway for drug delivery

NASA Astrophysics Data System (ADS)

Li, Ye; Zhang, Xianren; Cao, Dapeng

2015-01-01

Nanoparticle (NP)-based drug delivery systems offer fundamental advantages over current therapeutic agents that commonly display a longer circulation time, lower toxicity, specific targeted release, and greater bioavailability. For successful NP-based drug delivery it is essential that the drug-carrying nanocarriers can be internalized by the target cells and transported to specific sites, and the inefficient internalization of nanocarriers is often one of the major sources for drug resistance. In this work, we use the dissipative particle dynamics simulation to investigate the effect of NP hardness on their internalization efficiency. Three simplified models of NP platforms for drug delivery, including polymeric NP, liposome and solid NP, are designed here to represent increasing nanocarrier hardness. Simulation results indicate that NP hardness controls the internalization pathway for drug delivery. Rigid NPs can enter the cell by a pathway of endocytosis, whereas for soft NPs the endocytosis process can be inhibited or frustrated due to wrapping-induced shape deformation and non-uniform ligand distribution. Instead, soft NPs tend to find one of three penetration pathways to enter the cell membrane via rearranging their hydrophobic and hydrophilic segments. Finally, we show that the interaction between nanocarriers and drug molecules is also essential for effective drug delivery.

Impact of an individualist vs. collectivist context on the social valorization of internal explanations.

PubMed

Testé, Benoît

2012-01-01

The theory of the norm of internality emphasizes the role of Western individualism in the normativity of internal explanations. The present study examines the link between the social value accorded to targets expressing internal vs. external explanations and individualist vs. collectivist contexts. Sixty-three male and female French management sciences students evaluated two targets (internal vs. external) in a simulated recruitment situation. The job vacancy was partially manipulated to create individualist vs. collectivist contexts. Participants were asked to state whether or not they would recruit the targets and to describe the targets on traits relating to social utility (market value) and social desirability (likeability). As expected, the results showed that the effect of the targets' internality on recruitment judgments and perceived social utility was stronger in the individualist context than in the collectivist context. However, the analysis also revealed that the participant's gender moderated the impact of the context on the evaluation of the targets. The results showed that the context strongly affected the men's judgments, whereas it had no effect on the women's judgments.

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.

Discovery of Regulators of Receptor Internalization with High-Throughput Flow Cytometry

PubMed Central

Tapia, Phillip H.; Fisher, Gregory W.; Simons, Peter C.; Strouse, J. Jacob; Foutz, Terry; Waggoner, Alan S.; Jarvik, Jonathan; Sklar, Larry A.

2012-01-01

We developed a platform combining fluorogen-activating protein (FAP) technology with high-throughput flow cytometry to detect real-time protein trafficking to and from the plasma membrane in living cells. The hybrid platform facilitates drug discovery for trafficking receptors such as G protein-coupled receptors and was validated with the β2-adrenergic receptor (β2AR) system. When a chemical library containing ∼1200 off-patent drugs was screened against cells expressing FAP-tagged β2ARs, all 33 known β2AR-active ligands in the library were successfully identified, together with a number of compounds that might regulate receptor internalization in a nontraditional manner. Results indicated that the platform identified ligands of target proteins regardless of the associated signaling pathway; therefore, this approach presents opportunities to search for biased receptor modulators and is suitable for screening of multiplexed targets for improved efficiency. The results revealed that ligands may be biased with respect to the rate or duration of receptor internalization and that receptor internalization may be independent of activation of the mitogen-activated protein kinase pathway. PMID:22767611

Challenges of Sustaining the International Space Station Through 2020 and Beyond: Reassessing Confidence Targets for System Availability

NASA Technical Reports Server (NTRS)

Lutomski, Michael G.; Carter-Journet, Katrina; Anderson, Leif; Box, Neil; Harrington, Sean; Jackson, David; DiFilippo, Denise

2012-01-01

The International Space Station (ISS) was originally designed to operate until 2015 with a plan for deorbiting the ISS in 2016. Currently, the international partnership has agreed to extend the operations until 2020 and discussions are underway to extend the life even further to 2028. Each partner is responsible for the sustaining engineering, sparing, and maintenance of their own segments. National Aeronautics and Space Administration's (NASA's) challenge is to purchase the needed number of spares to maintain the functional availability of the ISS systems necessary for the United States On-Orbit Segment s contribution. This presentation introduces an analytical approach to assessing uncertainty in ISS hardware necessary to extend the life of the vehicle. Some key areas for consideration are: establishing what confidence targets are required to ensure science can be continuously carried out on the ISS, defining what confidence targets are reasonable to ensure vehicle survivability, considering what is required to determine if the confidence targets are too high, and whether sufficient number of spares are purchased. The results of the analysis will provide a methodological basis for reassessing vehicle subsystem confidence targets. This analysis compares the probability of existing spares exceeding the total expected unit demand of the Orbital Replacement Unit (ORU) in functional hierarchies approximating the vehicle subsystems. In cases where the functional hierarchies' availability does not meet subsystem confidence targets, the analysis will further identify which ORUs may require additional spares to extend the life of the ISS. The resulting probability is dependent upon hardware reliability estimates. However, the ISS hardware fleet carries considerable epistemic uncertainty which must be factored into the development and execution of sparing risk postures. In addition, it is also recognized that uncertainty in the assessment is due to disconnects between modeled functions and actual subsystem operations. Perhaps most importantly, it is acknowledged that conservative confidence targets per subsystem are currently accepted. This presentation will also discuss how subsystem confidence targets may be relaxed based on calculating the level of uncertainty for each corresponding ORU-function. The presentation will conclude with the various strengths and limitations for implementing the analytical approach in sustaining the ISS through end of life; 2020 and beyond.

Liver cell-targeted delivery of therapeutic molecules.

PubMed

Kang, Jeong-Hun; Toita, Riki; Murata, Masaharu

2016-01-01

The liver is the largest internal organ in mammals and is involved in metabolism, detoxification, synthesis of proteins and lipids, secretion of cytokines and growth factors and immune/inflammatory responses. Hepatitis, alcoholic or non-alcoholic liver disease, hepatocellular carcinoma, hepatic veno-occlusive disease, and liver fibrosis and cirrhosis are the most common liver diseases. Safe and efficient delivery of therapeutic molecules (drugs, genes or proteins) into the liver is very important to increase the clinical efficacy of these molecules and to reduce their side effects in other organs. Several liver cell-targeted delivery systems have been developed and tested in vivo or ex vivo/in vitro. In this review, we discuss the literature concerning liver cell-targeted delivery systems, with a particular emphasis on the results of in vivo studies.

Polarized internal target apparatus

DOEpatents

Holt, Roy J.

1986-01-01

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

Present status of the liquid lithium target facility in the international fusion materials irradiation facility (IFMIF)

NASA Astrophysics Data System (ADS)

Nakamura, Hiroo; Riccardi, B.; Loginov, N.; Ara, K.; Burgazzi, L.; Cevolani, S.; Dell'Orco, G.; Fazio, C.; Giusti, D.; Horiike, H.; Ida, M.; Ise, H.; Kakui, H.; Matsui, H.; Micciche, G.; Muroga, T.; Nakamura, Hideo; Shimizu, K.; Sugimoto, M.; Suzuki, A.; Takeuchi, H.; Tanaka, S.; Yoneoka, T.

2004-08-01

During the three year key element technology phase of the International Fusion Materials Irradiation Facility (IFMIF) project, completed at the end of 2002, key technologies have been validated. In this paper, these results are summarized. A water jet experiment simulating Li flow validated stable flow up to 20 m/s with a double reducer nozzle. In addition, a small Li loop experiment validated stable Li flow up to 14 m/s. To control the nitrogen content in Li below 10 wppm will require surface area of a V-Ti alloy getter of 135 m 2. Conceptual designs of diagnostics have been carried out. Moreover, the concept of a remote handling system to replace the back wall based on `cut and reweld' and `bayonet' options has been established. Analysis by FMEA showed safe operation of the target system. Recent activities in the transition phase, started in 2003, and plan for the next phase are also described.

Investigations of internal noise levels for different target sizes, contrasts, and noise structures

NASA Astrophysics Data System (ADS)

Han, Minah; Choi, Shinkook; Baek, Jongduk

2014-03-01

To describe internal noise levels for different target sizes, contrasts, and noise structures, Gaussian targets with four different sizes (i.e., standard deviation of 2,4,6 and 8) and three different noise structures(i.e., white, low-pass, and highpass) were generated. The generated noise images were scaled to have standard deviation of 0.15. For each noise type, target contrasts were adjusted to have the same detectability based on NPW, and the detectability of CHO was calculated accordingly. For human observer study, 3 trained observers performed 2AFC detection tasks, and correction rate, Pc, was calculated for each task. By adding proper internal noise level to numerical observer (i.e., NPW and CHO), detectability of human observer was matched with that of numerical observers. Even though target contrasts were adjusted to have the same detectability of NPW observer, detectability of human observer decreases as the target size increases. The internal noise level varies for different target sizes, contrasts, and noise structures, demonstrating different internal noise levels should be considered in numerical observer to predict the detection performance of human observer.

[Target volume margins for lung cancer: internal target volume/clinical target volume].

PubMed

Jouin, A; Pourel, N

2013-10-01

The aim of this study was to carry out a review of margins that should be used for the delineation of target volumes in lung cancer, with a focus on margins from gross tumour volume (GTV) to clinical target volume (CTV) and internal target volume (ITV) delineation. Our review was based on a PubMed literature search with, as a cornerstone, the 2010 European Organisation for Research and Treatment of Cancer (EORTC) recommandations by De Ruysscher et al. The keywords used for the search were: radiotherapy, lung cancer, clinical target volume, internal target volume. The relevant information was categorized under the following headings: gross tumour volume definition (GTV), CTV-GTV margin (first tumoural CTV then nodal CTV definition), in field versus elective nodal irradiation, metabolic imaging role through the input of the PET scanner for tumour target volume and limitations of PET-CT imaging for nodal target volume definition, postoperative radiotherapy target volume definition, delineation of target volumes after induction chemotherapy; then the internal target volume is specified as well as tumoural mobility for lung cancer and respiratory gating techniques. Finally, a chapter is dedicated to planning target volume definition and another to small cell lung cancer. For each heading, the most relevant and recent clinical trials and publications are mentioned. Copyright © 2013. Published by Elsevier SAS.

Advanced MicroObserver UGS integration with and cueing of the BattleHawk squad level loitering munition and UAV

NASA Astrophysics Data System (ADS)

Steadman, Bob; Finklea, John; Kershaw, James; Loughman, Cathy; Shaffner, Patti; Frost, Dean; Deller, Sean

2014-06-01

Textron's Advanced MicroObserver(R) is a next generation remote unattended ground sensor system (UGS) for border security, infrastructure protection, and small combat unit security. The original MicroObserver(R) is a sophisticated seismic sensor system with multi-node fusion that supports target tracking. This system has been deployed in combat theaters. The system's seismic sensor nodes are uniquely able to be completely buried (including antennas) for optimal covertness. The advanced version adds a wireless day/night Electro-Optic Infrared (EOIR) system, cued by seismic tracking, with sophisticated target discrimination and automatic frame capture features. Also new is a field deployable Gateway configurable with a variety of radio systems and flexible networking, an important upgrade that enabled the research described herein. BattleHawkTM is a small tube launched Unmanned Air Vehicle (UAV) with a warhead. Using transmitted video from its EOIR subsystem an operator can search for and acquire a target day or night, select a target for attack, and execute terminal dive to destroy the target. It is designed as a lightweight squad level asset carried by an individual infantryman. Although BattleHawk has the best loiter time in its class, it's still relatively short compared to large UAVs. Also it's a one-shot asset in its munition configuration. Therefore Textron Defense Systems conducted research, funded internally, to determine if there was military utility in having the highly persistent MicroObserver(R) system cue BattleHawk's launch and vector it to beyond visual range targets for engagement. This paper describes that research; the system configuration implemented, and the results of field testing that was performed on a government range early in 2013. On the integrated system that was implemented, MicroObserver(R) seismic detections activated that system's camera which then automatically captured images of the target. The geo-referenced and time-tagged MicroObserver(R) target reports and images were then automatically forwarded to the BattleHawk Android-based controller. This allowed the operator to see the intruder (classified and geo-located) on the map based display, assess the intruder as likely hostile (via the image), and launch BattleHawk with the pre-loaded target coordinates. The operator was thus able to quickly acquire the intended target (without a search) and initiate target engagement immediately. System latencies were a major concern encountered during the research.

Polarized internal target apparatus

DOEpatents

Holt, R.J.

1984-10-10

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

Multileaf collimator tracking integrated with a novel x-ray imaging system and external surrogate monitoring

NASA Astrophysics Data System (ADS)

Krauss, Andreas; Fast, Martin F.; Nill, Simeon; Oelfke, Uwe

2012-04-01

We have previously developed a tumour tracking system, which adapts the aperture of a Siemens 160 MLC to electromagnetically monitored target motion. In this study, we exploit the use of a novel linac-mounted kilovoltage x-ray imaging system for MLC tracking. The unique in-line geometry of the imaging system allows the detection of target motion perpendicular to the treatment beam (i.e. the directions usually featuring steep dose gradients). We utilized the imaging system either alone or in combination with an external surrogate monitoring system. We equipped a Siemens ARTISTE linac with two flat panel detectors, one directly underneath the linac head for motion monitoring and the other underneath the patient couch for geometric tracking accuracy assessments. A programmable phantom with an embedded metal marker reproduced three patient breathing traces. For MLC tracking based on x-ray imaging alone, marker position was detected at a frame rate of 7.1 Hz. For the combined external and internal motion monitoring system, a total of only 85 x-ray images were acquired prior to or in between the delivery of ten segments of an IMRT beam. External motion was monitored with a potentiometer. A correlation model between external and internal motion was established. The real-time component of the MLC tracking procedure then relied solely on the correlation model estimations of internal motion based on the external signal. Geometric tracking accuracies were 0.6 mm (1.1 mm) and 1.8 mm (1.6 mm) in directions perpendicular and parallel to the leaf travel direction for the x-ray-only (the combined external and internal) motion monitoring system in spite of a total system latency of ˜0.62 s (˜0.51 s). Dosimetric accuracy for a highly modulated IMRT beam-assessed through radiographic film dosimetry-improved substantially when tracking was applied, but depended strongly on the respective geometric tracking accuracy. In conclusion, we have for the first time integrated MLC tracking with x-ray imaging in the in-line geometry and demonstrated highly accurate respiratory motion tracking.

G3-C12 Peptide Reverses Galectin-3 from Foe to Friend for Active Targeting Cancer Treatment.

PubMed

Sun, Wei; Li, Lian; Yang, Qingqing; Shan, Wei; Zhang, Zhirong; Huang, Yuan

2015-11-02

Galectin-3 is overexpressed by numerous carcinomas and is a potential target for active tumor treatments. On the other hand, galectin-3 also plays a key role in cancer progression and prevents cells from undergoing apoptosis, thereby offsetting the benefits of active targeting drugs. However, the relative contribution of the protective antiapoptotic effects of galectin-3 and the proapoptotic effects of galectin-3-targeted therapies has remained yet unrevealed. Here, we show that a galectin-3-binding peptide G3-C12 could reverse galectin-3 from foe to friend for active targeting delivery system. Results showed G3-C12 modified N-(2-hydroxypropyl)methacrylamide copolymer doxorubicin conjugates (G3-C12-HPMA-Dox) could internalize into galectin-3 overexpressed PC-3 cells via a highly specific ligand-receptor pathway (2.2 times higher cellular internalization than HPMA-Dox). The internalized Dox stimulated the translocation of galectin-3 to the mitochondria to prevent from apoptosis. In turn, this caused G3-C12-HPMA-Dox to concentrate into the mitochondria after binding to galectin-3 intracellularly. Initially, mitochondrial galectin-3 weakened Dox-induced mitochondrial damage; however, as time progressed, G3-C12 active-mediation allowed increasing amounts of Dox to be delivered to the mitochondria, which eventually induced higher level of apoptosis than nontargeted copolymers. In addition, G3-C12 downregulates galectin-3 expression, 0.43 times lower than control cells, which could possibly be responsible for the suppressed cell migration. Thus, G3-C12 peptide exerts sequential targeting to both cell membrane and mitochondria via regulating galectin-3, and eventually reverses and overcomes the protective effects of galectin-3; therefore, it could be a promising agent for the treatment of galectin-3-overexpressing cancers.

IO CAREERS - Home

Science.gov Websites

international organization as a federal employee ‹ › Search Jobs Professional Field: -- Any Indonesia Iran Iraq Israel Italy Jamaica Japan Jordan Kazakhstan Kenya Kosovo Kuwait Kyrgyzstan Laos Lebanon System / UNDP, - (Multiple D/S) Targeted Students and Young Professionals Most professional posts in

Locating the optimal internal jugular target site for central venous line placement.

PubMed

Giordano, Chris R; Murtagh, Kevin R; Mills, Jaime; Deitte, Lori A; Rice, Mark J; Tighe, Patrick J

2016-09-01

Historically, the placement of internal jugular central venous lines has been accomplished by using external landmarks to help identify target-rich locations in order to steer clear of dangerous structures. This paradigm is largely being displaced, as ultrasound has become routine practice, raising new considerations regarding target locations and risk mitigation. Most human anatomy texts depict the internal jugular vein as a straight columnar structure that exits the cranial vault the same size that it enters the thoracic cavity. We dispute the notion that the internal jugulars are cylindrical columns that symmetrically descend into the thoracic cavity, and purport that they are asymmetric conical structures. The primary aim of this study was to evaluate 100 consecutive adult chest and neck computed tomography exams that were imaged at an inpatient hospital. We measured the internal jugular on the left and right sides at three different levels to look for differences in size as the internal jugular descends into the thoracic cavity. We revealed that as the internal jugular descends into the thorax, the area of the vessel increases and geometrically resembles a conical structure. We also reconfirmed that the left internal jugular is smaller than the right internal jugular. Understanding that the largest target area for central venous line placement is the lower portion of the right internal jugular vein will help to better target vascular access for central line placement. This is the first study the authors are aware of that depicts the internal jugular as a conical structure as opposed to the commonly depicted symmetrical columnar structure frequently illustrated in anatomy textbooks. This target area does come with additional risk, as the closer you get to the thoracic cavity, the greater the chances for lung injury. Copyright © 2016 Elsevier Inc. All rights reserved.

Geometry-Based Observability Metric

NASA Technical Reports Server (NTRS)

Eaton, Colin; Naasz, Bo

2012-01-01

The Satellite Servicing Capabilities Office (SSCO) is currently developing and testing Goddard s Natural Feature Image Recognition (GNFIR) software for autonomous rendezvous and docking missions. GNFIR has flight heritage and is still being developed and tailored for future missions with non-cooperative targets: (1) DEXTRE Pointing Package System on the International Space Station, (2) Relative Navigation System (RNS) on the Space Shuttle for the fourth Hubble Servicing Mission.

Design Development of a Combined Deployment and Pointing System for the International Space Station Neutron Star Interior Composition Explorer Telescope

NASA Technical Reports Server (NTRS)

Budinoff, Jason; Gendreau, Keith; Arzoumanian, Zaven; Baker, Charles; Berning, Robert; Colangelo, Todd; Holzinger, John; Lewis, Jesse; Liu, Alice; Mitchell, Alissa;

Design Development of a Combined Deployment and Pointing System for the International Space Station Neutron Star Interior Composition Explorer Telescope

NASA Technical Reports Server (NTRS)

Budinoff, Jason; Gendreau, Keith; Arzoumanian, Zaven; Baker, Charles; Berning, Robert; Colangelo, TOdd; Holzinger, John; Lewis, Jesse; Liu, Alice; Mitchell, Alissa;

Aquaculture expansion in Brazilian freshwaters against the Aichi Biodiversity Targets.

PubMed

Lima Junior, Dilermando Pereira; Magalhães, André Lincoln Barroso; Pelicice, Fernando Mayer; Vitule, Jean Ricardo Simões; Azevedo-Santos, Valter M; Orsi, Mário Luís; Simberloff, Daniel; Agostinho, Angelo Antônio

2018-05-01

The Convention on Biological Diversity proposed the Aichi Biodiversity Targets to improve conservation policies and to balance economic development, social welfare, and the maintenance of biodiversity/ecosystem services. Brazil is a signatory of the Aichi Biodiversity Targets and is the most diverse country in terms of freshwater fish, but its national policies have supported the development of unsustainable commercial and ornamental aquaculture, which has led to serious disturbances to inland ecosystems and natural resources. We analyzed the development of Brazilian aquaculture to show how current aquaculture expansion conflicts with all 20 Aichi Targets. This case suggests that Brazil and many other megadiverse developing countries will not meet international conservation targets, stressing the need for new strategies, such as the environmental management system, to improve biodiversity conservation.

Cybersecurity in Hospitals: A Systematic, Organizational Perspective

PubMed Central

Kaiser, Jessica P

2018-01-01

Background Cybersecurity incidents are a growing threat to the health care industry in general and hospitals in particular. The health care industry has lagged behind other industries in protecting its main stakeholder (ie, patients), and now hospitals must invest considerable capital and effort in protecting their systems. However, this is easier said than done because hospitals are extraordinarily technology-saturated, complex organizations with high end point complexity, internal politics, and regulatory pressures. Objective The purpose of this study was to develop a systematic and organizational perspective for studying (1) the dynamics of cybersecurity capability development at hospitals and (2) how these internal organizational dynamics interact to form a system of hospital cybersecurity in the United States. Methods We conducted interviews with hospital chief information officers, chief information security officers, and health care cybersecurity experts; analyzed the interview data; and developed a system dynamics model that unravels the mechanisms by which hospitals build cybersecurity capabilities. We then use simulation analysis to examine how changes to variables within the model affect the likelihood of cyberattacks across both individual hospitals and a system of hospitals. Results We discuss several key mechanisms that hospitals use to reduce the likelihood of cybercriminal activity. The variable that most influences the risk of cyberattack in a hospital is end point complexity, followed by internal stakeholder alignment. Although resource availability is important in fueling efforts to close cybersecurity capability gaps, low levels of resources could be compensated for by setting a high target level of cybersecurity. Conclusions To enhance cybersecurity capabilities at hospitals, the main focus of chief information officers and chief information security officers should be on reducing end point complexity and improving internal stakeholder alignment. These strategies can solve cybersecurity problems more effectively than blindly pursuing more resources. On a macro level, the cyber vulnerability of a country’s hospital infrastructure is affected by the vulnerabilities of all individual hospitals. In this large system, reducing variation in resource availability makes the whole system less vulnerable—a few hospitals with low resources for cybersecurity threaten the entire infrastructure of health care. In other words, hospitals need to move forward together to make the industry less attractive to cybercriminals. Moreover, although compliance is essential, it does not equal security. Hospitals should set their target level of cybersecurity beyond the requirements of current regulations and policies. As of today, policies mostly address data privacy, not data security. Thus, policy makers need to introduce policies that not only raise the target level of cybersecurity capabilities but also reduce the variability in resource availability across the entire health care system. PMID:29807882

Fluids and Combustion Facility: Fluids Integrated Rack Modal Model Correlation

NASA Technical Reports Server (NTRS)

McNelis, Mark E.; Suarez, Vicente J.; Sullivan, Timothy L.; Otten, Kim D.; Akers, James C.

2005-01-01

The Fluids Integrated Rack (FIR) is one of two racks in the Fluids and Combustion Facility on the International Space Station. The FIR is dedicated to the scientific investigation of space system fluids management supporting NASA s Exploration of Space Initiative. The FIR hardware was modal tested and FIR finite element model updated to satisfy the International Space Station model correlation criteria. The final cross-orthogonality results between the correlated model and test mode shapes was greater than 90 percent for all primary target modes.

Mobile camera-space manipulation

NASA Technical Reports Server (NTRS)

Seelinger, Michael J. (Inventor); Yoder, John-David S. (Inventor); Skaar, Steven B. (Inventor)

2001-01-01

The invention is a method of using computer vision to control systems consisting of a combination of holonomic and nonholonomic degrees of freedom such as a wheeled rover equipped with a robotic arm, a forklift, and earth-moving equipment such as a backhoe or a front-loader. Using vision sensors mounted on the mobile system and the manipulator, the system establishes a relationship between the internal joint configuration of the holonomic degrees of freedom of the manipulator and the appearance of features on the manipulator in the reference frames of the vision sensors. Then, the system, perhaps with the assistance of an operator, identifies the locations of the target object in the reference frames of the vision sensors. Using this target information, along with the relationship described above, the system determines a suitable trajectory for the nonholonomic degrees of freedom of the base to follow towards the target object. The system also determines a suitable pose or series of poses for the holonomic degrees of freedom of the manipulator. With additional visual samples, the system automatically updates the trajectory and final pose of the manipulator so as to allow for greater precision in the overall final position of the system.

Graphene quantum dots for cancer targeted drug delivery.

PubMed

Iannazzo, Daniela; Pistone, Alessandro; Salamò, Marina; Galvagno, Signorino; Romeo, Roberto; Giofré, Salvatore V; Branca, Caterina; Visalli, Giuseppa; Di Pietro, Angela

2017-02-25

A biocompatible and cell traceable drug delivery system Graphene Quantum Dots (GQD) based, for the targeted delivery of the DNA intercalating drug doxorubicin (DOX) to cancer cells, is here reported. Highly dispersible and water soluble GQD, synthesized by acidic oxidation and exfoliation of multi-walled carbon nanotubes (MWCNT), were covalently linked to the tumor targeting module biotin (BTN), able to efficiently recognize biotin receptors over-expressed on cancer cells and loaded with DOX. Biological test performed on A549 cells reported a very low toxicity of the synthesized carrier (GQD and GQD-BTN). In GQD-BTN-DOX treated cancer cells, the cytotoxicity was strongly dependent from cell uptake which was greater and delayed after treatment with GQD-BTN-DOX system with respect to what observed for cells treated with the same system lacking of the targeting module BTN (GQD-DOX) or with the free drug alone. A delayed nuclear internalization of the drug is reported, due to the drug detachment from the nanosystem, triggered by the acidic environment of cancer cells. Copyright © 2017 Elsevier B.V. All rights reserved.

ManPortable and UGV LIVAR: advances in sensor suite integration bring improvements to target observation and identification for the electronic battlefield

NASA Astrophysics Data System (ADS)

Lynam, Jeff R.

2001-09-01

A more highly integrated, electro-optical sensor suite using Laser Illuminated Viewing and Ranging (LIVAR) techniques is being developed under the Army Advanced Concept Technology- II (ACT-II) program for enhanced manportable target surveillance and identification. The ManPortable LIVAR system currently in development employs a wide-array of sensor technologies that provides the foot-bound soldier and UGV significant advantages and capabilities in lightweight, fieldable, target location, ranging and imaging systems. The unit incorporates a wide field-of-view, 5DEG x 3DEG, uncooled LWIR passive sensor for primary target location. Laser range finding and active illumination is done with a triggered, flash-lamp pumped, eyesafe micro-laser operating in the 1.5 micron region, and is used in conjunction with a range-gated, electron-bombarded CCD digital camera to then image the target objective in a more- narrow, 0.3$DEG, field-of-view. Target range determination is acquired using the integrated LRF and a target position is calculated using data from other onboard devices providing GPS coordinates, tilt, bank and corrected magnetic azimuth. Range gate timing and coordinated receiver optics focus control allow for target imaging operations to be optimized. The onboard control electronics provide power efficient, system operations for extended field use periods from the internal, rechargeable battery packs. Image data storage, transmission, and processing performance capabilities are also being incorporated to provide the best all-around support, for the electronic battlefield, in this type of system. The paper will describe flash laser illumination technology, EBCCD camera technology with flash laser detection system, and image resolution improvement through frame averaging.

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

Extended producer responsibility for consumer waste: the gap between economic theory and implementation.

PubMed

Dubois, Maarten

2012-09-01

Although economic theory supports the use of extended producer responsibility (EPR) to stimulate prevention and recycling of waste, EPR systems implemented in Europe are often criticized as a result of weak incentives for prevention and green product design. Using a stylized economic model, this article evaluates the efficiency of European EPR systems. The model reveals that the introduction of static collection targets creates a gap between theory and implementation. Static targets lead to inefficient market outcomes and weak incentives for prevention and green product design. The minimum collection targets should be complemented with a tax on producers for the non-collected waste fraction. Because such a tax internalizes the cost of waste disposal, more efficient price signals will lead to better incentives for waste management in a complex and dynamic market.

Leveraging Our Expertise To Inform International RE Roadmaps | Energy

Science.gov Websites

energy targets to support Mexico's renewable energy goal. NREL and its Mexico partners developed the institutions need to take to determine how the electricity infrastructure and systems must change to accommodate high levels of renewables. The roadmap focuses on analysis methodologies-including grid expansion

Improving Aid Effectiveness or Transforming the Global Capitalist System

ERIC Educational Resources Information Center

Ginsburg, Mark

2010-01-01

In the introduction to his article, "Aid, Development, and Education," Klees (2010) poses the question, has the "hundreds of billions of dollars in international aid... loaned to [or otherwise targeted to "assist"] developing countries through bilateral and multilateral mechanisms... helped?" He then posits the question to be "too complicated to…

Internal combustion engine run on biogas is a potential solution to meet Indonesia emission target

NASA Astrophysics Data System (ADS)

Ambarita, Himsar

2017-09-01

Indonesia has released two different Greenhouse Gas (GHG) emissions reduction targets. The first target, released in 2009, is reduction GHG emissions 26% from Business-as-Usual (BAU) level using own budget and up 41% if supported international aids by 2020. The second target is reduction 29% and 41% from BAU by 2030 using own budget and with international support, respectively. In this paper, the BAU emissions and emissions reduction target of these two targets are elaborated. In addition, the characteristics of emissions from transportation sector are discussed. One of the potential mitigation actions is switching fuel in transportation sector. The results the most promising mitigation action in the transportation is switching oil fuel with biofuel. The Government of Indonesia (GoI) focuses on using biodiesel and bioethanol to run internal combustion engine in transportation sector and biogas is aimed to fuel power plant unit. However, there is very limited of success stories on using biogas in the power plant. The barriers and challenges will be discussed here. It is suggested to run internal combustion engine with biogas.

Modular cell-internalizing aptamer nanostructure enables targeted delivery of large functional RNAs in cancer cell lines.

PubMed

Porciani, David; Cardwell, Leah N; Tawiah, Kwaku D; Alam, Khalid K; Lange, Margaret J; Daniels, Mark A; Burke, Donald H

2018-06-11

Large RNAs and ribonucleoprotein complexes have powerful therapeutic potential, but effective cell-targeted delivery tools are limited. Aptamers that internalize into target cells can deliver siRNAs (<15 kDa, 19-21 nt/strand). We demonstrate a modular nanostructure for cellular delivery of large, functional RNA payloads (50-80 kDa, 175-250 nt) by aptamers that recognize multiple human B cell cancer lines and transferrin receptor-expressing cells. Fluorogenic RNA reporter payloads enable accelerated testing of platform designs and rapid evaluation of assembly and internalization. Modularity is demonstrated by swapping in different targeting and payload aptamers. Both modules internalize into leukemic B cell lines and remained colocalized within endosomes. Fluorescence from internalized RNA persists for ≥2 h, suggesting a sizable window for aptamer payloads to exert influence upon targeted cells. This demonstration of aptamer-mediated, cell-internalizing delivery of large RNAs with retention of functional structure raises the possibility of manipulating endosomes and cells by delivering large aptamers and regulatory RNAs.

Air intake side secondary air supply system for an internal combustion engine with a duty ratio control operation

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

Kawanabe, T.; Asakura, M.; Shina, T.

1987-09-01

An air intake side secondary air supply system is described for an internal combustion engine having an air intake passage with a carburetor and an exhaust passage, comprising: an air intake side secondary air supply passage communicating with the air intake passage on the downstream side of the carburetor; an open/close valve disposed in the air intake side secondary air supply passage; an oxygen concentration sensor disposed in the exhaust passage; and detection and control means for detecting whether an air-fuel ratio of mixture to be supplied to the engine is leaner or richer with respect to a target air-fuelmore » ratio through a level of an output signal of the oxygen concentration sensor and for periodically actuating the open/close valve, the detection and control means decreasing a valve open period of the open/close valve within each cyclic period by a first predetermined amount when a detected air-fuel ratio of mixture is leaner than the target air-fuel ratio and increasing the valve open period by a second predetermined amount when the detected air-fuel ratio of mixture is richer than the target air-fuel ratio. The second predetermined amount is different from the first predetermined amount.« less

Can representational trajectory reveal the nature of an internal model of gravity?

PubMed

De Sá Teixeira, Nuno; Hecht, Heiko

2014-05-01

The memory for the vanishing location of a horizontally moving target is usually displaced forward in the direction of motion (representational momentum) and downward in the direction of gravity (representational gravity). Moreover, this downward displacement has been shown to increase with time (representational trajectory). However, the degree to which different kinematic events change the temporal profile of these displacements remains to be determined. The present article attempts to fill this gap. In the first experiment, we replicate the finding that representational momentum for downward-moving targets is bigger than for upward motions, showing, moreover, that it increases rapidly during the first 300 ms, stabilizing afterward. This temporal profile, but not the increased error for descending targets, is shown to be disrupted when eye movements are not allowed. In the second experiment, we show that the downward drift with time emerges even for static targets. Finally, in the third experiment, we report an increased error for upward-moving targets, as compared with downward movements, when the display is compatible with a downward ego-motion by including vection cues. Thus, the errors in the direction of gravity are compatible with the perceived event and do not merely reflect a retinotopic bias. Overall, these results provide further evidence for an internal model of gravity in the visual representational system.

CRISPR: From Prokaryotic Immune Systems to Plant Genome Editing Tools.

PubMed

Bandyopadhyay, Anindya; Mazumdar, Shamik; Yin, Xiaojia; Quick, William Paul

2017-01-01

The clustered regularly interspaced short palindromic repeats (CRISPR) system is a prokaryotic adaptive immune system that has the ability to identify specific locations on the bacteriophage (phage) genome to create breaks in it, and internalize the phage genome fragments in its own genome as CRISPR arrays for memory-dependent resistance. Although CRISPR has been used in the dairy industry for a long time, it recently gained importance in the field of genome editing because of its ability to precisely target locations in a genome. This system has further been modified to locate and target any region of a genome of choice due to modifications in the components of the system. By changing the nucleotide sequence of the 20-nucleotide target sequence in the guide RNA, targeting any location is possible. It has found an application in the modification of plant genomes with its ability to generate mutations and insertions, thus helping to create new varieties of plants. With the ability to introduce specific sequences into the plant genome after cleavage by the CRISPR system and subsequent DNA repair through homology-directed repair (HDR), CRISPR ensures that genome editing can be successfully applied in plants, thus generating stronger and more improved traits. Also, the use of the CRISPR editing system can generate plants that are transgene-free and have mutations that are stably inherited, thus helping to circumvent current GMO regulations.

Inhibitors of SARS-CoV Entry - Identification using an Internally-Controlled Dual Envelope Pseudovirion Assay

PubMed Central

Zhou, Yanchen; Agudelo, Juliet; Lu, Kai; Goetz, David H.; Hansell, Elizabeth; Chen, Yen Ting; Roush, William R.; McKerrow, James; Craik, Charles S.; Amberg, Sean M.; Simmons, Graham

2011-01-01

Severe acute respiratory syndrome-associated coronavirus (SARS-CoV) emerged as the causal agent of an endemic atypical pneumonia, infecting thousands of people worldwide. Although a number of promising potential vaccines and therapeutic agents for SARS-CoV have been described, no effective antiviral drug against SARS-CoV is currently available. The intricate, sequential nature of the viral entry process provides multiple valid targets for drug development. Here, we describe a rapid and safe cell-based high-throughput screening system, Dual Envelope Pseudovirion (DEP) Assay, for specifically screening inhibitors of viral entry. The assay system employs a novel dual envelope strategy, using lentiviral pseudovirions as targets whose entry is driven by the SARS-CoV Spike glycoprotein. A second, unrelated viral envelope is used as an internal control to reduce the number of false positives. As an example of the power of this assay a class of inhibitors is reported with the potential to inhibit SARS-CoV at two steps of the replication cycle, viral entry and particle assembly. This assay system can be easily adapted to screen entry inhibitors against other viruses with the careful selection of matching partner virus envelopes. PMID:21820471

ICAM-1 Targeting of Doxorubicin-Loaded PLGA Nanoparticles to Lung Epithelial Cells

PubMed Central

Chuda, Chittasupho; Sheng-Xue, Xie; Abdulgader, Baoum; Tatyana, Yakovleva; Teruna, Siahaan J.; Cory, Berkland

2009-01-01

Interaction of leukocyte function associated antigen-1 (LFA-1) on T-lymphoctytes and intercellular adhesion molecule-1 (ICAM-1) on epithelial cells controls leukocyte adhesion, spreading, and extravasation. This process plays an important role in leukocyte recruitment to a specific site of inflammation and has been indentified as a biomarker for certain types of carcinomas. Cyclo-(1,12)-PenITDGEATDSGC (cLABL) has been shown to inhibit LFA-1 and ICAM-1 interaction via binding to ICAM-1. In addition, cLABL has been shown to internalize after binding ICAM-1. The possibility of using cLABL conjugated nanoparticles (cLABL-NP) as a targeted and controlled release drug delivery system has been investigated in this study. The cLABL peptide was conjugated to a modified Pluronic® surfactant on poly (DL-lactic-co-glycolic acid) (PLGA) nanoparticles. The cLABL-NP showed more rapid cellular uptake by A549 lung epithelial cells compared to nanoparticles without peptide. The specificity of ICAM-1 mediated internalization was confirmed by blocking the uptake of cLABL-NP to ICAM-1 using free cLABL peptide to block the binding of cLABL-NP to ICAM-1 on the cell surface. Cell studies suggested that cLABL-NPs targeted encapsulated doxorubicin to ICAM-1 expressing cells. Cytotoxicity assay confirmed the activity of the drug incorporated in nanoparticles. Sustained release of doxorubicin afforded by PLGA nanoparticles may enable cLABL-NP as a targeted, controlled release drug delivery system. PMID:19429421

A tactile display for international space station (ISS) extravehicular activity (EVA).

PubMed

Rochlis, J L; Newman, D J

2000-06-01

A tactile display to increase an astronaut's situational awareness during an extravehicular activity (EVA) has been developed and ground tested. The Tactor Locator System (TLS) is a non-intrusive, intuitive display capable of conveying position and velocity information via a vibrotactile stimulus applied to the subject's neck and torso. In the Earth's 1 G environment, perception of position and velocity is determined by the body's individual sensory systems. Under normal sensory conditions, redundant information from these sensory systems provides humans with an accurate sense of their position and motion. However, altered environments, including exposure to weightlessness, can lead to conflicting visual and vestibular cues, resulting in decreased situational awareness. The TLS was designed to provide somatosensory cues to complement the visual system during EVA operations. An EVA task was simulated on a computer graphics workstation with a display of the International Space Station (ISS) and a target astronaut at an unknown location. Subjects were required to move about the ISS and acquire the target astronaut using either an auditory cue at the outset, or the TLS. Subjects used a 6 degree of freedom input device to command translational and rotational motion. The TLS was configured to act as a position aid, providing target direction information to the subject through a localized stimulus. Results show that the TLS decreases reaction time (p = 0.001) and movement time (p = 0.001) for simulated subject (astronaut) motion around the ISS. The TLS is a useful aid in increasing an astronaut's situational awareness, and warrants further testing to explore other uses, tasks and configurations.

Predictive Models for Dynamic Brittle Fracture and Damage at High-velocity Impact in Multilayered Targets

DTIC Science & Technology

2016-11-01

layered glass/PC systems,Functionally Graded Materials (FGMs), polycrystalline AlON, and fiber-reinforced composite (FRC) materials. For the first time we...multi-layered glass/PC systems,Functionally Graded Materials (FGMs), polycrystalline AlON, and fiber-reinforced composite (FRC) materials. For the... Composite Lamina with Peridynamics, International Journal for Multiscale Computational Engineering, (12 2011): 0. doi: Florin Bobaru, Youn Doh Ha

A novel sensitive pathogen detection system based on Microbead Quantum Dot System.

PubMed

Wu, Tzong-Yuan; Su, Yi-Yu; Shu, Wei-Hsien; Mercado, Augustus T; Wang, Shi-Kwun; Hsu, Ling-Yi; Tsai, Yow-Fu; Chen, Chung-Yung

2016-04-15

A fast and accurate detection system for pathogens can provide immediate measurements for the identification of infectious agents. Therefore, the Microbead Quantum-dots Detection System (MQDS) was developed to identify and measure target DNAs of pathogenic microorganisms and eliminated the need of PCR amplifications. This nanomaterial-based technique can detect different microorganisms by flow cytometry measurements. In MQDS, pathogen specific DNA probes were designed to form a hairpin structure and conjugated on microbeads. In the presence of the complementary target DNA sequence, the probes will compete for binding with the reporter probes but will not interfere with the binding between the probe and internal control DNA. To monitor the binding process by flow cytometry, both the reporter probes and internal control probes were conjugated with Quantum dots that fluoresce at different emission wavelengths using the click reaction. When MQDS was used to detect the pathogens in environmental samples, a high correlation coefficient (R=0.994) for Legionella spp., with a detection limit of 0.1 ng of the extracted DNAs and 10 CFU/test, can be achieved. Thus, this newly developed technique can also be applied to detect other pathogens, particularly viruses and other genetic diseases. Copyright © 2015 Elsevier B.V. All rights reserved.

KSC-2010-1312

NASA Image and Video Library

2010-01-18

CAPE CANAVERAL, Fla. - In Orbiter Processing Facility 1 at NASA's Kennedy Space Center in Florida, a crane lowers the orbiter boom sensor system, or OBSS, into space shuttle Atlantis' payload bay where it will be installed. The OBSS' inspection boom assembly, or IBA, is removed from the arm every other processing flow for a detailed inspection. After five consecutive flights, all IBA internal components are submitted to a thorough electrical checkout in the Remote Manipulator System Lab. The 50-foot-long OBSS attaches to the end of the shuttle’s robotic arm and supports the cameras and laser systems used to inspect the shuttle’s thermal protection system while in space. Atlantis is next slated to deliver an Integrated Cargo Carrier and Russian-built Mini Research Module to the International Space Station on the STS-132 mission. Launch is targeted for May 14. Photo credit: NASA/Jim Grossmann

KSC-2010-1314

NASA Image and Video Library

2010-01-18

CAPE CANAVERAL, Fla. - In Orbiter Processing Facility 1 at NASA's Kennedy Space Center in Florida, installation of the orbiter boom sensor system, or OBSS, into space shuttle Atlantis' payload bay is under way. The OBSS' inspection boom assembly, or IBA, is removed from the arm every other processing flow for a detailed inspection. After five consecutive flights, all IBA internal components are submitted to a thorough electrical checkout in the Remote Manipulator System Lab. The 50-foot-long OBSS attaches to the end of the shuttle’s robotic arm and supports the cameras and laser systems used to inspect the shuttle’s thermal protection system while in space. Atlantis is next slated to deliver an Integrated Cargo Carrier and Russian-built Mini Research Module to the International Space Station on the STS-132 mission. Launch is targeted for May 14. Photo credit: NASA/Jim Grossmann

KSC-2010-1313

NASA Image and Video Library

2010-01-18

CAPE CANAVERAL, Fla. - In Orbiter Processing Facility 1 at NASA's Kennedy Space Center in Florida, technicians prepare to install the orbiter boom sensor system, or OBSS, into space shuttle Atlantis' payload bay. The OBSS' inspection boom assembly, or IBA, is removed from the arm every other processing flow for a detailed inspection. After five consecutive flights, all IBA internal components are submitted to a thorough electrical checkout in the Remote Manipulator System Lab. The 50-foot-long OBSS attaches to the end of the shuttle’s robotic arm and supports the cameras and laser systems used to inspect the shuttle’s thermal protection system while in space. Atlantis is next slated to deliver an Integrated Cargo Carrier and Russian-built Mini Research Module to the International Space Station on the STS-132 mission. Launch is targeted for May 14. Photo credit: NASA/Jim Grossmann

KSC-2010-1317

NASA Image and Video Library

2010-01-18

CAPE CANAVERAL, Fla. - In Orbiter Processing Facility 1 at NASA's Kennedy Space Center in Florida, the orbiter boom sensor system, or OBSS, is installed in space shuttle Atlantis' payload bay. The OBSS' inspection boom assembly, or IBA, is removed from the arm every other processing flow for a detailed inspection. After five consecutive flights, all IBA internal components are submitted to a thorough electrical checkout in the Remote Manipulator System Lab. The 50-foot-long OBSS attaches to the end of the shuttle’s robotic arm and supports the cameras and laser systems used to inspect the shuttle’s thermal protection system while in space. Atlantis is next slated to deliver an Integrated Cargo Carrier and Russian-built Mini Research Module to the International Space Station on the STS-132 mission. Launch is targeted for May 14. Photo credit: NASA/Jim Grossmann

Online polarimetry of the Nuclotron internal deuteron and proton beams

NASA Astrophysics Data System (ADS)

Isupov, A. Yu

2017-12-01

The spin studies at Nuclotron require fast and precise determination of the deuteron and proton beam polarization. For these purposes new powerful VME-based data acquisition (DAQ) system has been designed for the Deuteron Spin Structure setup placed at the Nuclotron Internal Target Station. The DAQ system is built using the netgraph-based data acquisition and processing framework ngdp. The software dealing with VME hardware is a set of netgraph nodes in form of the loadable kernel modules, so works in the operating system kernel context. The specific for current implementation nodes and user context utilities are described. The online events representation by ROOT classes allows us to generalize code for histograms filling and polarization calculations. The DAQ system was successfully used during 53rd and 54th Nuclotron runs, and their suitability for online polarimetry is demonstrated.

Assuring long-term reliability of concentrator PV systems

NASA Astrophysics Data System (ADS)

McConnell, R.; Garboushian, V.; Brown, J.; Crawford, C.; Darban, K.; Dutra, D.; Geer, S.; Ghassemian, V.; Gordon, R.; Kinsey, G.; Stone, K.; Turner, G.

2009-08-01

Concentrator PV (CPV) systems have attracted significant interest because these systems incorporate the world's highest efficiency solar cells and they are targeting the lowest cost production of solar electricity for the world's utility markets. Because these systems are just entering solar markets, manufacturers and customers need to assure their reliability for many years of operation. There are three general approaches for assuring CPV reliability: 1) field testing and development over many years leading to improved product designs, 2) testing to internationally accepted qualification standards (especially for new products) and 3) extended reliability tests to identify critical weaknesses in a new component or design. Amonix has been a pioneer in all three of these approaches. Amonix has an internal library of field failure data spanning over 15 years that serves as the basis for its seven generations of CPV systems. An Amonix product served as the test CPV module for the development of the world's first qualification standard completed in March 2001. Amonix staff has served on international standards development committees, such as the International Electrotechnical Commission (IEC), in support of developing CPV standards needed in today's rapidly expanding solar markets. Recently Amonix employed extended reliability test procedures to assure reliability of multijunction solar cell operation in its seventh generation high concentration PV system. This paper will discuss how these three approaches have all contributed to assuring reliability of the Amonix systems.

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.

NASA'S Solar System Exploration Research Virtual Institute: An international approach toward bringing science and human exploration together for mutual benefit

NASA Astrophysics Data System (ADS)

Schmidt, Gregory

2016-07-01

The NASA Solar System Exploration Research Virtual Institute (SSERVI) is a virtual institute focused on research at the intersection of science and explora-tion, training the next generation of lunar scientists, and community development. The institute is a hub for opportunities that engage the larger scientific and exploration communities in order to form new interdis-ciplinary, research-focused collaborations. Its relative-ly large domestic teams work together along with in-ternational partners in both traditional and virtual set-tings to bring disparate approaches together for mutual benefit. This talk will describe the research efforts of the nine domestic teams that constitute the U.S. com-plement of the Institute and how it is engaging the in-ternational science and exploration communities through workshops, conferences, online seminars and classes, student exchange programs and internships. The Institute is centered on the scientific aspects of exploration as they pertain to the Moon, Near Earth Asteroids (NEAs) and the moons of Mars. It focuses on interdisciplinary, exploration-related science cen-tered around all airless bodies targeted as potential human destinations. Areas of study reported here will represent the broad spectrum of lunar, NEA, and Mar-tian moon sciences encompassing investigations of the surface, interior, exosphere, and near-space environ-ments as well as science uniquely enabled from these bodies. The technical focus ranges from investigations of plasma physics, geology/geochemistry, technology integration, solar system origins/evolution, regolith geotechnical properties, analogues, volatiles, ISRU and exploration potential of the target bodies. SSERVI enhances the widening knowledgebase of planetary research by acting as a bridge between several differ-ent groups and bringing together researchers from the scientific and exploration communities, multiple disci-plines across the full range of planetary sciences, and domestic and international communities and partner-ships.

PREFACE: 1st Tensor Polarized Solid Target Workshop

NASA Astrophysics Data System (ADS)

2014-10-01

These are the proceedings of the first Tensor Spin Observables Workshop that was held in March 2014 at the Thomas Jefferson National Accelerator Facility in Newport News, Virginia. The conference was convened to study the physics that can be done with the recently approved E12-13-011 polarized target. A tensor polarized target holds the potential of initiating a new generation of tensor spin physics at Jefferson Lab. Experiments which utilize tensor polarized targets can help clarify how nuclear properties arise from partonic degrees of freedom, provide unique insight into short-range correlations and quark angular momentum, and also help pin down the polarization of the quark sea with a future Electron Ion Collider. This three day workshop was focused on tensor spin observables and the associated tensor target development. The workshop goals were to stimulate progress in the theoretical treatment of polarized spin-1 systems, foster the development of new proposals, and to reach a consensus on the optimal polarized target configuration for the tensor spin program. The workshop was sponsored by the University of New Hampshire, the Jefferson Science Associates, Florida International University, and Jefferson Lab. It was organized by Karl Slifer (chair), Patricia Solvignon, and Elena Long of the University of New Hampshire, Douglas Higinbotham and Christopher Keith of Jefferson Lab, and Misak Sargsian of the Florida International University. These proceedings represent the effort put forth by the community to begin exploring the possibilities that a high-luminosity, high-tensor polarized solid target can offer.

KSC-2010-1316

NASA Image and Video Library

2010-01-18

CAPE CANAVERAL, Fla. - In Orbiter Processing Facility 1 at NASA's Kennedy Space Center in Florida, technicians install the orbiter boom sensor system, or OBSS, in space shuttle Atlantis' payload bay across from the remote manipulator system arm. The OBSS' inspection boom assembly, or IBA, is removed from the arm every other processing flow for a detailed inspection. After five consecutive flights, all IBA internal components are submitted to a thorough electrical checkout in the Remote Manipulator System Lab. The 50-foot-long OBSS attaches to the end of the shuttle’s robotic arm and supports the cameras and laser systems used to inspect the shuttle’s thermal protection system while in space. Atlantis is next slated to deliver an Integrated Cargo Carrier and Russian-built Mini Research Module to the International Space Station on the STS-132 mission. Launch is targeted for May 14. Photo credit: NASA/Jim Grossmann

Validation of microwave radiometry for measuring the internal temperature profile of human tissue

NASA Astrophysics Data System (ADS)

Levick, A.; Land, D.; Hand, J.

2011-06-01

A phantom target with a known linear temperature gradient has been developed for validating microwave radiometry for measuring internal temperature profiles within human tissue. The purpose of the phantom target is to simulate the temperature gradient found within the surface layers of a baby's brain during hypothermal neuroprotection therapy, in which the outer surface of the phantom represents the skin surface and the inner surface the brain core. The target comprises a volume of phantom tissue material with similar dielectric properties to high water-content human tissue, contained between two copper plates at known temperatures. The antenna of a microwave radiometer is in contact with one surface of the phantom material. We have measured the microwave temperature of the phantom with microwave radiometry in a frequency band of 3.0-3.5 GHz. Our microwave temperature measurements have small 0.05 °C (type A) uncertainties associated with random effects and provide temperatures consistent with values determined using theoretical models of the antenna-target system within uncertainties. The measurements are in good agreement with the major signal contribution being formed over a near plane-wave response within the material with a much smaller contribution from close to the antenna face.

26 CFR 1.338-11 - Effect of section 338 election on insurance company targets.

Code of Federal Regulations, 2010 CFR

2010-04-01

... section is limited to the excess, if any, of— (i) The fair market value of old target's assets acquired by... company targets. 1.338-11 Section 1.338-11 Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE... section 338 election on insurance company targets. (a) In general. This section provides rules that apply...

Cancer cell-selective, clathrin-mediated endocytosis of aptamer decorated nanoparticles

PubMed Central

Engelberg, Shira; Modrejewski, Julia; Walter, Johanna G.; Livney, Yoav D.; Assaraf, Yehuda G.

2018-01-01

Lung cancer is the leading cause of cancer mortality worldwide, resulting in 88% deaths of all diagnosed patients. Hence, novel therapeutic modalities are urgently needed. Single-stranded oligonucleotide-based aptamers (APTs) are excellent ligands for tumor cell targeting. However, the molecular mechanisms underlying their internalization into living cells have been poorly studied. Towards the application of APTs for active drug targeting to cancer cells, we herein studied the mechanism underlying S15-APT internalization into human non-small cell lung cancer A549 cells. We thus delineated the mode of entry of a model nanomedical system based on quantum dots (QDs) decorated with S15-APTs as a selective targeting moiety for uptake by A549 cells. These APT-decorated QDs displayed selective binding to, and internalization by target A549 cells, but not by normal human bronchial epithelial BEAS2B, cervical carcinoma (HeLa) and colon adenocarcinoma CaCo-2 cells, hence demonstrating high specificity. Flow cytometric analysis revealed a remarkably low dissociation constant of S15-APTs-decorated QDs to A549 cells (Kd = 13.1 ± 1.6 nM). Through the systematic application of a series of established inhibitors of known mechanisms of endocytosis, we show that the uptake of S15-APTs proceeds via a classical clathrin-dependent receptor-mediated endocytosis. This cancer cell-selective mode of entry could possibly be used in the future to evade plasma membrane-localized multidrug resistance efflux pumps, thereby overcoming an important mechanism of cancer multidrug resistance. PMID:29765515

Cancer cell-selective, clathrin-mediated endocytosis of aptamer decorated nanoparticles.

PubMed

Engelberg, Shira; Modrejewski, Julia; Walter, Johanna G; Livney, Yoav D; Assaraf, Yehuda G

2018-04-20

Lung cancer is the leading cause of cancer mortality worldwide, resulting in 88% deaths of all diagnosed patients. Hence, novel therapeutic modalities are urgently needed. Single-stranded oligonucleotide-based aptamers (APTs) are excellent ligands for tumor cell targeting. However, the molecular mechanisms underlying their internalization into living cells have been poorly studied. Towards the application of APTs for active drug targeting to cancer cells, we herein studied the mechanism underlying S15-APT internalization into human non-small cell lung cancer A549 cells. We thus delineated the mode of entry of a model nanomedical system based on quantum dots (QDs) decorated with S15-APTs as a selective targeting moiety for uptake by A549 cells. These APT-decorated QDs displayed selective binding to, and internalization by target A549 cells, but not by normal human bronchial epithelial BEAS2B, cervical carcinoma (HeLa) and colon adenocarcinoma CaCo-2 cells, hence demonstrating high specificity. Flow cytometric analysis revealed a remarkably low dissociation constant of S15-APTs-decorated QDs to A549 cells (K d = 13.1 ± 1.6 nM). Through the systematic application of a series of established inhibitors of known mechanisms of endocytosis, we show that the uptake of S15-APTs proceeds via a classical clathrin-dependent receptor-mediated endocytosis. This cancer cell-selective mode of entry could possibly be used in the future to evade plasma membrane-localized multidrug resistance efflux pumps, thereby overcoming an important mechanism of cancer multidrug resistance.

The IUE Science Operations Ground System

NASA Technical Reports Server (NTRS)

Pitts, Ronald E.; Arquilla, Richard

1994-01-01

The International Ultraviolet Explorer (IUE) Science Operations System provides full realtime operations capabilities and support to the operations staff and astronomer users. The components of this very diverse and extremely flexible hardware and software system have played a major role in maintaining the scientific efficiency and productivity of the IUE. The software provides the staff and user with all the tools necessary for pre-visit and real-time planning and operations analysis for any day of the year. Examples of such tools include the effects of spacecraft constraints on target availability, maneuver times between targets, availability of guide stars, target identification, coordinate transforms, e-mail transfer of Observatory forms and messages, and quick-look analysis of image data. Most of this extensive software package can also be accessed remotely by individual users for information, scheduling of shifts, pre-visit planning, and actual observing program execution. Astronomers, with a modest investment in hardware and software, may establish remote observing sites. We currently have over 20 such sites in our remote observers' network.

Human immune cell targeting of protein nanoparticles - caveospheres

NASA Astrophysics Data System (ADS)

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

2016-04-01

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

Model MTF for the mosaic window

NASA Astrophysics Data System (ADS)

Xing, Zhenchong; Hong, Yongfeng; Zhang, Bao

2017-10-01

An electro-optical targeting system mounted either within an airframe or housed in separate pods requires a window to form an environmental barrier to the outside world. In current practice, such windows usually use a mosaic or segmented window. When scanning the target, internally gimbaled systems sweep over the window, which can affect the modulation transfer function (MTF) due to wave-front division and optical path differences arising from the thickness/wedge differences between panes. In this paper, a mathematical model of the MTF of the mosaic window is presented that allows an analysis of influencing factors; we show how the model may be integrated into ZEMAX® software for optical design. The model can be used to guide both the design and the tolerance analysis of optical systems that employ a mosaic window.

Reducing Internalizing Symptoms among High-Risk, Hispanic Adolescents: Mediators of a Preventive Family Intervention

PubMed Central

Perrino, Tatiana; Brincks, Ahnalee; Howe, George; Brown, C. Hendricks; Prado, Guillermo; Pantin, Hilda

2016-01-01

Familias Unidas is a family-focused preventive intervention that has been found to reduce drug use and sexual risk behaviors among Hispanic adolescents. In some trials, Familias Unidas has also been found to be efficacious in reducing adolescent internalizing symptoms (i.e., depressive and anxiety symptoms), even though the intervention did not specifically target internalizing symptoms. This study examines potential mediators or mechanisms by which Familias Unidas influences internalizing symptoms, specifically the role of intervention-targeted improvements in parent-adolescent communication and reductions in youth externalizing behaviors. A total of 213 Hispanic eighth grade students with a history of externalizing behavior problems and their primary caregivers were recruited from the public school system. Participants, with a mean age of 13.8 years, were randomized into the Familias Unidas intervention or community practice control condition, and assessed at baseline, 6-months, 18-months, and 30-months post-baseline. A cascading mediation model was tested in which the Familias Unidas intervention was hypothesized to decrease adolescent internalizing symptoms through two mediators: improvements in parent-adolescent communication leading to decreases in externalizing behaviors. Findings show that the intervention had significant direct effects on youth internalizing symptoms at 30-months post-baseline. In addition, the cascading mediation model was supported in which the Familias Unidas intervention predicted significant improvements in parent-adolescent communication at 6-months, subsequently decreasing externalizing behaviors at 18-months, and ultimately reducing youth internalizing symptoms at 30-months post-baseline. Implications for prevention interventions are discussed. PMID:27154768

Tandem internal models execute motor learning in the cerebellum.

PubMed

Honda, Takeru; Nagao, Soichi; Hashimoto, Yuji; Ishikawa, Kinya; Yokota, Takanori; Mizusawa, Hidehiro; Ito, Masao

2018-06-25

In performing skillful movement, humans use predictions from internal models formed by repetition learning. However, the computational organization of internal models in the brain remains unknown. Here, we demonstrate that a computational architecture employing a tandem configuration of forward and inverse internal models enables efficient motor learning in the cerebellum. The model predicted learning adaptations observed in hand-reaching experiments in humans wearing a prism lens and explained the kinetic components of these behavioral adaptations. The tandem system also predicted a form of subliminal motor learning that was experimentally validated after training intentional misses of hand targets. Patients with cerebellar degeneration disease showed behavioral impairments consistent with tandemly arranged internal models. These findings validate computational tandemization of internal models in motor control and its potential uses in more complex forms of learning and cognition. Copyright © 2018 the Author(s). Published by PNAS.

Anticipation from sensation: using anticipating synchronization to stabilize a system with inherent sensory delay.

PubMed

Eberle, Henry; Nasuto, Slawomir J; Hayashi, Yoshikatsu

2018-03-01

We present a novel way of using a dynamical model for predictive tracking control that can adapt to a wide range of delays without parameter update. This is achieved by incorporating the paradigm of anticipating synchronization (AS), where a 'slave' system predicts a 'master' via delayed self-feedback. By treating the delayed output of the plant as one half of a 'sensory' AS coupling, the plant and an internal dynamical model can be synchronized such that the plant consistently leads the target's motion. We use two simulated robotic systems with differing arrangements of the plant and internal model ('parallel' and 'serial') to demonstrate that this form of control adapts to a wide range of delays without requiring the parameters of the controller to be changed.

Autonomous learning by simple dynamical systems with delayed feedback.

PubMed

Kaluza, Pablo; Mikhailov, Alexander S

2014-09-01

A general scheme for the construction of dynamical systems able to learn generation of the desired kinds of dynamics through adjustment of their internal structure is proposed. The scheme involves intrinsic time-delayed feedback to steer the dynamics towards the target performance. As an example, a system of coupled phase oscillators, which can, by changing the weights of connections between its elements, evolve to a dynamical state with the prescribed (low or high) synchronization level, is considered and investigated.

Double targeting and aptamer-assisted controlled release delivery of epirubicin to cancer cells by aptamers-based dendrimer in vitro and in vivo.

PubMed

Taghdisi, Seyed Mohammad; Danesh, Noor Mohammad; Ramezani, Mohammad; Lavaee, Parirokh; Jalalian, Seyed Hamid; Robati, Rezvan Yazdian; Abnous, Khalil

2016-05-01

Clinical use of epirubicin (Epi) in the treatment of cancer has been limited, due to its cardiotoxicity. Targeted delivery of chemotherapeutic agents could increase their efficacy and reduce their off-target effects. High drug loading and excellent stability of DNA dendrimers make these DNA nanostructures unique candidates for biological applications. In this study a modified and promoted dendrimer using three kinds of aptamers (MUC1, AS1411 and ATP aptamers) was designed for targeted delivery of Epi and its efficacy was evaluated in target cells including MCF-7 cells (breast cancer cell) and C26 cells (murine colon carcinoma cell). Aptamers (Apts)-Dendrimer-Epi complex formation was analyzed by fluorometric analysis and gel retardation assay. Release profiles of Epi from the designed complex were assessed at pHs 5.4 and 7.4. For MTT assay (cytotoxic study) MCF-7 and C26 cells (target cells) and CHO cells (Chinese hamster ovary cell, nontarget) were treated with Epi, Apts-Dendrimer-Epi complex and Apts-Dendrimer conjugate. Internalization was evaluated using flow cytometry analysis. Finally, the developed complex was used for inhibition of tumor growth in vivo. 25μM Epi was efficiently intercalated to 1μM dendrimer. Epi was released from the Apts-Dendrimer-Epi complex in a pH-sensitive manner (more release at pH 5.5). The results of flow cytometry analysis indicated that the designed complex was efficiently internalized into target cells, but not into control cells. The internalization data were confirmed by the results of MTT assay. Apts-Dendrimer-Epi complex had less cytotoxicity in CHO cells compared to Epi alone. The complex had more cytotoxicity in C26 and MCF-7 cells compared to Epi alone. Moreover, the Apts-Dendrimer-Epi complex could efficiently prohibit tumor growth in vivo. In conclusion, the designed targeted drug delivery system inherited characteristics of pH-dependent drug release, high drug loading and tumor targeting in vitro and in vivo. Copyright © 2016 Elsevier B.V. All rights reserved.

Self-Tuning Fully-Connected PID Neural Network System for Distributed Temperature Sensing and Control of Instrument with Multi-Modules.

PubMed

Zhang, Zhen; Ma, Cheng; Zhu, Rong

2016-10-14

High integration of multi-functional instruments raises a critical issue in temperature control that is challenging due to its spatial-temporal complexity. This paper presents a multi-input multi-output (MIMO) self-tuning temperature sensing and control system for efficiently modulating the temperature environment within a multi-module instrument. The smart system ensures that the internal temperature of the instrument converges to a target without the need of a system model, thus making the control robust. The system consists of a fully-connected proportional-integral-derivative (PID) neural network (FCPIDNN) and an on-line self-tuning module. The experimental results show that the presented system can effectively control the internal temperature under various mission scenarios, in particular, it is able to self-reconfigure upon actuator failure. The system provides a new scheme for a complex and time-variant MIMO control system which can be widely applied for the distributed measurement and control of the environment in instruments, integration electronics, and house constructions.

Cellular Internalization of Therapeutic Oligonucleotides by Peptide Amphiphile Nanofibers and Nanospheres.

PubMed

Mumcuoglu, Didem; Sardan Ekiz, Melis; Gunay, Gokhan; Tekinay, Turgay; Tekinay, Ayse B; Guler, Mustafa O

2016-05-11

Oligonucleotides are promising drug candidates due to the exceptionally high specificity they exhibit toward their target DNA and RNA sequences. However, their poor pharmacokinetic and pharmacodynamic properties, in conjunction with problems associated with their internalization by cells, necessitates their delivery through specialized carrier systems for efficient therapy. Here, we investigate the effects of carrier morphology on the cellular internalization mechanisms of oligonucleotides by using self-assembled fibrous or spherical peptide nanostructures. Size and geometry were both found to be important parameters for the oligonucleotide internalization process; direct penetration was determined to be the major mechanism for the internalization of nanosphere carriers, whereas nanofibers were internalized by clathrin- and dynamin-dependent endocytosis pathways. We further showed that glucose conjugation to carrier nanosystems improved cellular internalization in cancer cells due to the enhanced glucose metabolism associated with oncogenesis, and the internalization of the glucose-conjugated peptide/oligonucleotide complexes was found to be dependent on glucose transporters present on the surface of the cell membrane.

Targeting International Terrorism with the Law of Armed Conflict: An Alternative Strategy

DTIC Science & Technology

1991-02-11

AD-A236 582 D TIC III IBII IH IH JUNI 1. 1991. (Unclassified Paper) NAVAL WAR COLLEGE Newport, R.I. TARGETING INTERNATIONAL TERRORISM WITH THE LAW OF...11. TITLE OWN11110 Secrty Ceu4ifction) TARGETING INTERNATIONAL TERRORISM WITH THE LAW OF ARMED CONFLICT: AN ALTERNATIVE STRATEGY (1.) 12, PERSONAL...lawegieforcoperatiosb re forcdaigwt nes.nItiofurther rorimmendgfral rbetos msesnt ofte thkede easuc-tresa en ocnrotadrsodttate-sponsored terrorism . Ti a

A unified dynamic neural field model of goal directed eye movements

NASA Astrophysics Data System (ADS)

Quinton, J. C.; Goffart, L.

2018-01-01

Primates heavily rely on their visual system, which exploits signals of graded precision based on the eccentricity of the target in the visual field. The interactions with the environment involve actively selecting and focusing on visual targets or regions of interest, instead of contemplating an omnidirectional visual flow. Eye-movements specifically allow foveating targets and track their motion. Once a target is brought within the central visual field, eye-movements are usually classified into catch-up saccades (jumping from one orientation or fixation to another) and smooth pursuit (continuously tracking a target with low velocity). Building on existing dynamic neural field equations, we introduce a novel model that incorporates internal projections to better estimate the current target location (associated to a peak of activity). Such estimate is then used to trigger an eye movement, leading to qualitatively different behaviours depending on the dynamics of the whole oculomotor system: (1) fixational eye-movements due to small variations in the weights of projections when the target is stationary, (2) interceptive and catch-up saccades when peaks build and relax on the neural field, (3) smooth pursuit when the peak stabilises near the centre of the field, the system reaching a fixed point attractor. Learning is nevertheless required for tracking a rapidly moving target, and the proposed model thus replicates recent results in the monkey, in which repeated exercise permits the maintenance of the target within in the central visual field at its current (here-and-now) location, despite the delays involved in transmitting retinal signals to the oculomotor neurons.

Confocal Raman microspectroscopic study of folate receptor-targeted delivery of 6-mercaptopurine-embedded gold nanoparticles in a single cell.

PubMed

Park, Jin; Jeon, Won Il; Lee, So Yeong; Ock, Kwang-Su; Seo, Ji Hye; Park, Jinho; Ganbold, Erdene-Ochir; Cho, Keunchang; Song, Nam Woong; Joo, Sang-Woo

2012-05-01

We investigate the cellular uptake behaviors and efficacy of folate-coated gold nanoparticles (AuNPs) for the targeted drug delivery system in human cancer cells. Folate-conjugated AuNPs embedded with a purine analogue cancer drug of 6-mercaptopurine (6MP) were assembled via a 1-ethyl-3-[3-dimethylaminopropyl] carbodiimide hydrochloride (EDC) coupling reaction between the amino group of 4-aminobenzenethiol (ABT) and the carboxyl group of folic acid. The assembly of folate and 6MP on AuNPs has been examined by absorption spectroscopy, transmission electron microscopy (TEM), and confocal Raman spectroscopy. The internalization of the conjugated AuNPs inside the folate receptor-positive HeLa and KB cells was checked by TEM and dark-field microscopy (DFM) combined with label-free confocal spectroscopy over the depth variable z at a micrometer resolution. DFM live cell imaging of folate-conjugated AuNPs in HeLa cells indicated that the targeted AuNPs appeared to attach on the cell surfaces and enter into the cell with an hour. The cell viability was also compared to estimate the efficacy of folate-conjugated AuNP delivery systems. Folate receptor-targeted AuNP systems appeared to decrease cancer cell viability both in vitro and in vivo more than did the use of the 6MP-coated AuNPs drug without any targeting systems. Copyright © 2012 Wiley Periodicals, Inc.

Internal model of gravity for hand interception: parametric adaptation to zero-gravity visual targets on Earth.

PubMed

Zago, Myrka; Lacquaniti, Francesco

2005-08-01

Internal model is a neural mechanism that mimics the dynamics of an object for sensory motor or cognitive functions. Recent research focuses on the issue of whether multiple internal models are learned and switched to cope with a variety of conditions, or single general models are adapted by tuning the parameters. Here we addressed this issue by investigating how the manual interception of a moving target changes with changes of the visual environment. In our paradigm, a virtual target moves vertically downward on a screen with different laws of motion. Subjects are asked to punch a hidden ball that arrives in synchrony with the visual target. By using several different protocols, we systematically found that subjects do not develop a new internal model appropriate for constant speed targets, but they use the default gravity model and reduce the central processing time. The results imply that adaptation to zero-gravity targets involves a compression of temporal processing through the cortical and subcortical regions interconnected with the vestibular cortex, which has previously been shown to be the site of storage of the internal model of gravity.

Perceptual Factors Influence Visual Search for Meaningful Symbols in Individuals with Intellectual Disabilities and Down Syndrome or Autism Spectrum Disorders

ERIC Educational Resources Information Center

Wilkinson, Krista M.; McIlvane, William J.

2013-01-01

Augmentative and alternative communication (AAC) systems often supplement oral communication for individuals with intellectual and communication disabilities. Research with preschoolers without disabilities has demonstrated that two visual--perceptual factors influence speed and/or accuracy of finding a target: the internal color and spatial…

A Case Study: Innovation of Internal Teaching and Learning Evaluation System in Higher Education Institutions

ERIC Educational Resources Information Center

Huiru, Yin

2009-01-01

The ultimate target of the education and teaching reform in higher education institutions is to improve the quality of teaching and talent training. As a key comprehensive university under the jurisdiction of the provincial government, Heilongjiang University sees its responsibility as training qualified talent to promote local economic…

Middle Atmosphere Program. Handbook for MAP. Volume 30: International School on Atmospheric Radar

NASA Technical Reports Server (NTRS)

Fukao, Shoichiro (Editor)

1989-01-01

Broad, tutorial coverage is given to the technical and scientific aspects of mesosphere stratosphere troposphere (MST) meteorological radar systems. Control issues, signal processing, atmospheric waves, the historical aspects of radar atmospheric dynamics, incoherent scatter radars, radar echoes, radar targets, and gravity waves are among the topics covered.

Melting, vaporization, and energy partitioning for impacts on asteroidal and planetary objects

NASA Technical Reports Server (NTRS)

Smither, Catherine L.; Ahrens, Thomas J.

1992-01-01

A three-dimensional smoothed particle hydrodynamics code was used to model normal and oblique impacts of silicate projectiles on asteroidal and planetary bodies. The energy of the system, initially in the kinetic energy of the impactor, is partitioned after impact into internal and kinetic energy of the impactor and the target body. These simulations show that, unlike the case of impacts onto a half-space, a significant amount of energy remains in the kinetic energy of the impacting body, as parts of it travel past the main planet and escape the system. This effect is greater for more oblique impacts, and for impacts onto the small planets. Melting and vaporization of both bodies were also examined. The amount of the target body melted was much greater in the case of smaller targets than for an impact of a similar scale on a larger body.

Targeting receptor-mediated endocytotic pathways with nanoparticles: rationale and advances

PubMed Central

Xu, Shi; Olenyuk, Bogdan Z.; Okamoto, Curtis T.; Hamm-Alvarez, Sarah F.

2012-01-01

Targeting of drugs and their carrier systems by using receptor-mediated endocytotic pathways was in its nascent stages 25 years ago. In the intervening years, an explosion of knowledge focused on design and synthesis of nanoparticulate delivery systems as well as elucidation of the cellular complexity of what was previously-termed receptor-mediated endocytosis has now created a situation when it has become possible to design and test the feasibility of delivery of highly specific nanoparticle drug carriers to specific cells and tissue. This review outlines the mechanisms governing the major modes of receptor-mediated endocytosis used in drug delivery and highlights recent approaches using these as targets for in vivo drug delivery of nanoparticles. The review also discusses some of the inherent complexity associated with the simple shift from a ligand-drug conjugate versus a ligand-nanoparticle conjugate, in terms of ligand valency and its relationship to the mode of receptor-mediated internalization. PMID:23026636

Single-Molecule Analysis for RISC Assembly and Target Cleavage.

PubMed

Sasaki, Hiroshi M; Tadakuma, Hisashi; Tomari, Yukihide

2018-01-01

RNA-induced silencing complex (RISC) is a small RNA-protein complex that mediates silencing of complementary target RNAs. Biochemistry has been successfully used to characterize the molecular mechanism of RISC assembly and function for nearly two decades. However, further dissection of intermediate states during the reactions has been warranted to fill in the gaps in our understanding of RNA silencing mechanisms. Single-molecule analysis with total internal reflection fluorescence (TIRF) microscopy is a powerful imaging-based approach to interrogate complex formation and dynamics at the individual molecule level with high sensitivity. Combining this technique with our recently established in vitro reconstitution system of fly Ago2-RISC, we have developed a single-molecule observation system for RISC assembly. In this chapter, we summarize the detailed protocol for single-molecule analysis of chaperone-assisted assembly of fly Ago2-RISC as well as its target cleavage reaction.

Folate-targeted nanoparticles for rheumatoid arthritis therapy.

PubMed

Nogueira, Eugénia; Gomes, Andreia C; Preto, Ana; Cavaco-Paulo, Artur

2016-05-01

Rheumatoid arthritis (RA) is the most common inflammatory rheumatic disease, affecting almost 1% of the world population. Although the cause of RA remains unknown, the complex interaction between immune mediators (cytokines and effector cells) is responsible for the joint damage that begins at the synovial membrane. Activated macrophages are critical in the pathogenesis of RA and showed specifically express a receptor for the vitamin folic acid (FA), folate receptor β (FRβ). This particular receptor allows internalization of FA-coupled cargo. In this review we will address the potential of nanoparticles as an effective drug delivery system for therapies that will directly target activated macrophages. Special attention will be given to stealth degree of the nanoparticles as a strategy to avoid clearance by macrophages of the mononuclear phagocytic system (MPS). This review summarizes the application of FA-target nanoparticles as drug delivery systems for RA and proposes prospective future directions. Rheumatoid arthritis is a debilitating autoimmune disease of the joints which affects many people worldwide. Up till now, there is a lack of optimal therapy against this disease. In this review article, the authors outlined in depth the current mechanism of disease for rheumatoid arthritis and described the latest research in using folic acid-targeted nanoparticles to target synovial macrophages in the fight against rheumatoid arthritis. Copyright © 2016 Elsevier Inc. All rights reserved.

Biological and targeted therapies of systemic lupus erythematosus: evidence and the state of the art.

PubMed

Mok, Chi Chiu

2017-07-01

Systemic lupus erythematosus (SLE) is a multi-systemic disease characterized by an unpredictable disease course and periods of remission and flare, leading to organ damage and mortality. Novel biological agents are being developed (targeting the lymphocytes, accessory molecules and cytokines) that aim to enhance the therapeutic efficacy when combined with standard therapies. Areas covered: This article updates recent data on the use of biological and targeted therapies in SLE. Expert commentary: B cells remain the main target of development of novel therapeutics in SLE. Similar to the intravenous preparation, subcutaneous belimumab has been shown to be superior to placebo when added to the standard of care in SLE. However, two phase III trials of epratuzumab and blisibimod did not meet their primary endpoints. Recent data on the inhibition of type I interferons (anifrolumab) appear promising. Newer calcineurin inhibitors and combination strategies using conventional immunosuppressive agents are being tested in lupus nephritis. Finally, international groups are developing consensus definitions on disease remission and low disease activity state to explore the benefits of the treat-to-target strategy in SLE. Hopefully, the armamentarium for the treatment of SLE can be expanded in the near future, so that the longevity and quality of life of patients can be further improved.

Development and characterization of multifunctional nanoparticles for drug delivery to cancer cells

NASA Astrophysics Data System (ADS)

Nahire, Rahul Rajaram

Lipid and polymeric nanoparticles, although proven to be effective drug delivery systems compared to free drugs, have shown considerable limitations pertaining to their uptake and release at tumor sites. Spatial and temporal control over the delivery of anticancer drugs has always been challenge to drug delivery scientists. Here, we have developed and characterized multifunctional nanoparticles (liposomes and polymersomes) which are targeted specifically to cancer cells, and release their contents with tumor specific internal triggers. To enable these nanoparticles to be tracked in blood circulation, we have imparted them with echogenic characteristic. Echogenicity of nanoparticles is evaluated using ultrasound scattering and imaging experiments. Nanoparticles demonstrated effective release with internal triggers such as elevated levels of MMP-9 enzyme found in the extracellular matrix of tumor cells, decreased pH of lysosome, and differential concentration of reducing agents in cytosol of cancer cells. We have also successfully demonstrated the sensitivity of these particles towards ultrasound to further enhance the release with internal triggers. To ensure the selective uptake by folate receptor- overexpressing cancer cells, we decorated these nanoparticles with folic acid on their surface. Fluorescence microscopic images showed significantly higher uptake of folate-targeted nanoparticles by MCF-7 (breast cancer) and PANC-1 (pancreatic cancer) cells compared to particles without any targeting ligand on their surface. To demonstrate the effectiveness of these nanoparticles to carry the drugs inside and kill cancer cells, we encapsulated doxorubicin and/or gemcitabine employing the pH gradient method. Drug loaded nanoparticles showed significantly higher killing of the cancer cells compared to their non-targeted counterparts and free drugs. With further development, these nanoparticles certainly have potential to be used as a multifunctional nanocarriers for image guided, targeted delivery of anticancer drugs.

Laboratory Calibration Studies in Support of ORGANICS on the International Space Station: Evolution of Organic Matter in Space

NASA Technical Reports Server (NTRS)

Ruiterkamp, R.; Ehrenfreund, P.; Halasinski, T.; Salama, F.; Foing, B.; Schmidt, W.

2002-01-01

This paper describes the scientific overview and current status of ORGANICS an exposure experiment performed on the International Space Station (ISS) to study the evolution of organic matter in space (PI: P. Ehrenfreund), with supporting laboratory experiments performed at NASA Ames. ORGANICS investigates the chemical evolution of samples submitted to long-duration exposure to space environment in near-Earth orbit. This experiment will provide information on the nature, evolution, and survival of carbon species in the interstellar medium (ISM) and in solar system targets.

Glycolipid-Dependent, Protease Sensitive Internalization of Pseudomonas aeruginosa Into Cultured Human Respiratory Epithelial Cells

PubMed Central

Emam, Aufaugh; Carter, William G; Lingwood, Clifford

2010-01-01

Internalization of PAK strain Pseudomonas aeruginosa into human respiratory epithelial cell lines and HeLa cervical cancer cells in vitro was readily demonstrable via a gentamycin protection assay. Depletion of target cell glycosphingolipids (GSLs) using a glucosyl ceramide synthase inhibitor, P4, completely prevented P. aeruginosa internalization. In contrast, P4 treatment had no effect on the internalization of Salmonella typhimurium into HeLa cells. Internalized P. aeruginosa were within membrane vacuoles, often containing microvesicles, between the bacterium and the limiting membrane. P. aeruginosa internalization was markedly enhanced by target cell pretreatment with the exogenous GSL, deacetyl gangliotetraosyl ceramide (Gg4). Gg4 binds the lipid raft marker, GM1 ganglioside. Target cell pretreatment with TLCK, but not other (serine) protease inhibitors, prevented both P. aeruginosa host cell binding and internalization. NFkB inhibition also prevented internalization. A GSL-containing lipid-raft model of P. aeruginosa host cell binding/internalization is proposed PMID:21270937

Treating juvenile idiopathic arthritis to target: recommendations of an international task force.

PubMed

Ravelli, Angelo; Consolaro, Alessandro; Horneff, Gerd; Laxer, Ronald M; Lovell, Daniel J; Wulffraat, Nico M; Akikusa, Jonathan D; Al-Mayouf, Sulaiman M; Antón, Jordi; Avcin, Tadej; Berard, Roberta A; Beresford, Michael W; Burgos-Vargas, Ruben; Cimaz, Rolando; De Benedetti, Fabrizio; Demirkaya, Erkan; Foell, Dirk; Itoh, Yasuhiko; Lahdenne, Pekka; Morgan, Esi M; Quartier, Pierre; Ruperto, Nicolino; Russo, Ricardo; Saad-Magalhães, Claudia; Sawhney, Sujata; Scott, Christiaan; Shenoi, Susan; Swart, Joost F; Uziel, Yosef; Vastert, Sebastiaan J; Smolen, Josef S

2018-06-01

Recent therapeutic advances in juvenile idiopathic arthritis (JIA) have made remission an achievable goal for most patients. Reaching this target leads to improved outcomes. The objective was to develop recommendations for treating JIA to target. A Steering Committee formulated a set of recommendations based on evidence derived from a systematic literature review. These were subsequently discussed, amended and voted on by an international Task Force of 30 paediatric rheumatologists in a consensus-based, Delphi-like procedure. Although the literature review did not reveal trials that compared a treat-to-target approach with another or no strategy, it provided indirect evidence regarding an optimised approach to therapy that facilitated development of recommendations. The group agreed on six overarching principles and eight recommendations. The main treatment target, which should be based on a shared decision with parents/patients, was defined as remission, with the alternative target of low disease activity. The frequency and timeline of follow-up evaluations to ensure achievement and maintenance of the target depend on JIA category and level of disease activity. Additional recommendations emphasise the importance of ensuring adequate growth and development and avoiding long-term systemic glucocorticoid administration to maintain the target. All items were agreed on by more than 80% of the members of the Task Force. A research agenda was formulated. The Task Force developed recommendations for treating JIA to target, being aware that the evidence is not strong and needs to be expanded by future research. These recommendations can inform various stakeholders about strategies to reach optimal outcomes for JIA. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

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

NASA Technical Reports Server (NTRS)

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

1983-01-01

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

KSC-98pc1776

NASA Image and Video Library

1998-12-03

KENNEDY SPACE CENTER, FLA. -- Participants pose for a photo at the Space Station Processing Facility ceremony transferring the "Leonardo" Multipurpose Logistics Module (MPLM) from the Italian Space Agency, Agenzia Spaziale Italiana (ASI), to NASA. From left, they are astronaut Jim Voss, European Space Agency astronauts Umberto Guidoni of Italy and Christer Fuglesang of Sweden, NASA International Space Station Program Manager Randy Brinkley, NASA Administrator Daniel S. Goldin, ASI President Sergio De Julio and Stephen Francois, director, International Space Station Launch Site Support at KSC. The MPLM, a reusable logistics carrier, will be the primary delivery system used to resupply and return International Space Station cargo requiring a pressurized environment. Leonardo is the first of three MPLM carriers for the International Space Station. It is scheduled to be launched on Space Shuttle Mission STS-100, targeted for April 2000

26 CFR 1.338-7 - Allocation of redetermined ADSP and AGUB among target assets.

Code of Federal Regulations, 2010 CFR

2010-04-01

...: Asset class Asset Fair market value V Building $ 100 V Stock of X (not a target) 200 Total 300 (B) T has... target assets. 1.338-7 Section 1.338-7 Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE... redetermined ADSP and AGUB among target assets. (a) Scope. ADSP and AGUB are redetermined at such time and in...

Laboratory-Scale Internal Wave Apparatus for Studying Copepod Behavior

NASA Astrophysics Data System (ADS)

Jung, S.; Webster, D. R.; Haas, K. A.; Yen, J.

2016-02-01

Internal waves are ubiquitous features in coastal marine environments and have been observed to mediate vertical distributions of zooplankton in situ. Internal waves create fine-scale hydrodynamic cues that copepods and other zooplankton are known to sense, such as fluid density gradients and velocity gradients (quantified as shear deformation rate). The role of copepod behavior in response to cues associated with internal waves is largely unknown. The objective is to provide insight to the bio-physical interaction and the role of biological versus physical forcing in mediating organism distributions. We constructed a laboratory-scale internal wave apparatus to facilitate fine-scale observations of copepod behavior in flows that replicate in situ conditions of internal waves in two-layer stratification. Two cases were chosen with density jump of 1 and 1.5 sigma-t units. Analytical analysis of the two-layer system provided guidance to the target forcing frequency needed to generate a standing internal wave with a single dominate frequency of oscillation. Flow visualization and signal processing of the interface location were used to quantify the wave characteristics. The results show a close match to the target wave parameters. Marine copepod (mixed population of Acartia tonsa, Temora longicornis, and Eurytemora affinis) behavior assays were conducted for three different physical arrangements: (1) no density stratification, (2) stagnant two-layer density stratification, and (3) two-layer density stratification with internal wave motion. Digitized trajectories of copepod swimming behavior indicate that in the control (case 1) the animals showed no preferential motion in terms of direction. In the stagnant density jump treatment (case 2) copepods preferentially moved horizontally, parallel to the density interface. In the internal wave treatment (case 3) copepods demonstrated orbital trajectories near the density interface.

KSC-2010-1315

NASA Image and Video Library

2010-01-18

CAPE CANAVERAL, Fla. - In Orbiter Processing Facility 1 at NASA's Kennedy Space Center in Florida, technicians ensure that the installation of the orbiter boom sensor system, or OBSS, into space shuttle Atlantis' payload bay meets the correct specifications. The OBSS' inspection boom assembly, or IBA, is removed from the arm every other processing flow for a detailed inspection. After five consecutive flights, all IBA internal components are submitted to a thorough electrical checkout in the Remote Manipulator System Lab. The 50-foot-long OBSS attaches to the end of the shuttle’s robotic arm and supports the cameras and laser systems used to inspect the shuttle’s thermal protection system while in space. Atlantis is next slated to deliver an Integrated Cargo Carrier and Russian-built Mini Research Module to the International Space Station on the STS-132 mission. Launch is targeted for May 14. Photo credit: NASA/Jim Grossmann

A planetary telescope at the ISS

NASA Astrophysics Data System (ADS)

Korablev, O.; Moroz, V.; Avanesov, G.; Rodin, V.; Bellucci, G.; Vid Machenko, A.; Tejfel, V.

We present the development of a 40-cm telescope to be deployed at the Russian segment of International Space Station (ISS) dedicated to the observations of planets of Solar system, which primary goal will be tracking climate-related changes and other variable phenomena on planets. The most effective will be the observations of Venus, Mars, Jupiter, Saturn, and comets, while other interesting targets will be certainly considered. This space-based observatory will perform monitoring of Solar System objects on regular basis The observatory includes the 40-cm narrow-field (f:20) telescope at a pointing platform with guidance system assuring pointing accuracy of ~10", and an internal tracking system with an accuracy inferior to 1" during tens of minutes. Four focal plane instruments, a camera, two spectrometers and a spectropolarimeter, will perform imaging and spectral observations in the range from ~200 nm to ~3 μm.

Are national policies on global health in fact national policies on global health governance? A comparison of policy designs from Norway and Switzerland.

PubMed

Jones, Catherine M; Clavier, Carole; Potvin, Louise

2017-01-01

Since the signing of the Oslo Ministerial Declaration in 2007, the idea that foreign policy formulation should include health considerations has gained traction on the United Nations agenda as evidenced by annual General Assembly resolutions on global health and foreign policy. The adoption of national policies on global health (NPGH) is one way that some member states integrate health and foreign policymaking. This paper explores what these policies intend to do and how countries plan to do it. Using a most similar systems design, we carried out a comparative study of two policy documents formally adopted in 2012. We conducted a directed qualitative content analysis of the Norwegian White Paper on Global health in foreign and development policy and the Swiss Health Foreign Policy using Schneider and Ingram's policy design framework. After replicating analysis methods for each document, we analysed them side by side to explore the commonalities and differences across elements of NPGH design. Analyses indicate that NPGH expect to influence change outside their borders. Targeting the international level, they aim to affect policy venues, multilateral partnerships and international institutions. Instruments for supporting desired changes are primarily those of health diplomacy, proposed as a tool for negotiating interests and objectives for global health between multiple sectors, used internally in Switzerland and externally in Norway. Findings suggest that NPGH designs contribute to constructing the global health governance system by identifying it as a policy target, and policy instruments may elude the health sector actors unless implementation rules explicitly include them. Research should explore how future NPGH designs may construct different kinds of targets as politicised groups of actors on which national governments seek to exercise influence for global health decision-making.

Are national policies on global health in fact national policies on global health governance? A comparison of policy designs from Norway and Switzerland

PubMed Central

Clavier, Carole; Potvin, Louise

2017-01-01

Background Since the signing of the Oslo Ministerial Declaration in 2007, the idea that foreign policy formulation should include health considerations has gained traction on the United Nations agenda as evidenced by annual General Assembly resolutions on global health and foreign policy. The adoption of national policies on global health (NPGH) is one way that some member states integrate health and foreign policymaking. This paper explores what these policies intend to do and how countries plan to do it. Methods Using a most similar systems design, we carried out a comparative study of two policy documents formally adopted in 2012. We conducted a directed qualitative content analysis of the Norwegian White Paper on Global health in foreign and development policy and the Swiss Health Foreign Policy using Schneider and Ingram's policy design framework. After replicating analysis methods for each document, we analysed them side by side to explore the commonalities and differences across elements of NPGH design. Results Analyses indicate that NPGH expect to influence change outside their borders. Targeting the international level, they aim to affect policy venues, multilateral partnerships and international institutions. Instruments for supporting desired changes are primarily those of health diplomacy, proposed as a tool for negotiating interests and objectives for global health between multiple sectors, used internally in Switzerland and externally in Norway. Conclusion Findings suggest that NPGH designs contribute to constructing the global health governance system by identifying it as a policy target, and policy instruments may elude the health sector actors unless implementation rules explicitly include them. Research should explore how future NPGH designs may construct different kinds of targets as politicised groups of actors on which national governments seek to exercise influence for global health decision-making. PMID:28589007

[The economics of health care in developing countries: what the fight against the AIDS epidemics has changed].

PubMed

Moatti, Jean Paul

2008-12-01

Since the start of the new century, development aid targeted on health care has seen an unprecedented rise, driven by the fight against AIDS. This article shows how this struggle has been accompanied with a renewal of the economic paradigms governing international action in favour of health care in developing countries: the idea that an improvement in health care constitutes an unavoidable prerequisite to macroeconomic growth, rather than a consequence; the insistence on the founding of mechanisms for health insurance to finance the costs of health care, rather than covering the costs at the point of use by the health care users; a concern to impose price differentials for access to medicine in developing countries, and to introduce flexibility in the regulation of international intellectual property law; the priority to vertical programmes targeted on certain illnesses, thought to act as levers for a global reinforcement of health care systems. This article discusses the pertinence of these new paradigms in light of the evolution of the AIDS/HIV epidemic, and the international context.

An expanded view of energy homeostasis: Neural integration of metabolic, cognitive, and emotional drives to eat

PubMed Central

Shin, Andrew C.; Zheng, Huiyuan; Berthoud, Hans-Rudolf

2009-01-01

The traditional view of neural regulation of body energy homeostasis focuses on internal feedback signals integrated in the hypothalamus and brainstem and in turn leading to balanced activation of behavioral, autonomic, and endocrine effector pathways leading to changes in food intake and energy expenditure. Recent observations have demonstrated that many of these internal signals encoding energy status have much wider effects on the brain, particularly sensory and cortico-limbic systems that process information from the outside world by detecting and interpreting food cues, forming, storing, and recalling representations of experience with food, and assigning hedonic and motivational value to conditioned and unconditioned food stimuli. Thus, part of the metabolic feedback from the internal milieu regulates food intake and energy balance by acting on extrahypothalamic structures, leading to an expanded view of neural control of energy homeostasis taking into account the need to adapt to changing conditions in the environment. The realization that metabolic signals act directly on these non-traditional targets of body energy homeostasis brings opportunities for novel drug targets for the fight against obesity and eating disorders. PMID:19419661

Cybersecurity in Hospitals: A Systematic, Organizational Perspective.

PubMed

Jalali, Mohammad S; Kaiser, Jessica P

2018-05-28

Cybersecurity incidents are a growing threat to the health care industry in general and hospitals in particular. The health care industry has lagged behind other industries in protecting its main stakeholder (ie, patients), and now hospitals must invest considerable capital and effort in protecting their systems. However, this is easier said than done because hospitals are extraordinarily technology-saturated, complex organizations with high end point complexity, internal politics, and regulatory pressures. The purpose of this study was to develop a systematic and organizational perspective for studying (1) the dynamics of cybersecurity capability development at hospitals and (2) how these internal organizational dynamics interact to form a system of hospital cybersecurity in the United States. We conducted interviews with hospital chief information officers, chief information security officers, and health care cybersecurity experts; analyzed the interview data; and developed a system dynamics model that unravels the mechanisms by which hospitals build cybersecurity capabilities. We then use simulation analysis to examine how changes to variables within the model affect the likelihood of cyberattacks across both individual hospitals and a system of hospitals. We discuss several key mechanisms that hospitals use to reduce the likelihood of cybercriminal activity. The variable that most influences the risk of cyberattack in a hospital is end point complexity, followed by internal stakeholder alignment. Although resource availability is important in fueling efforts to close cybersecurity capability gaps, low levels of resources could be compensated for by setting a high target level of cybersecurity. To enhance cybersecurity capabilities at hospitals, the main focus of chief information officers and chief information security officers should be on reducing end point complexity and improving internal stakeholder alignment. These strategies can solve cybersecurity problems more effectively than blindly pursuing more resources. On a macro level, the cyber vulnerability of a country's hospital infrastructure is affected by the vulnerabilities of all individual hospitals. In this large system, reducing variation in resource availability makes the whole system less vulnerable-a few hospitals with low resources for cybersecurity threaten the entire infrastructure of health care. In other words, hospitals need to move forward together to make the industry less attractive to cybercriminals. Moreover, although compliance is essential, it does not equal security. Hospitals should set their target level of cybersecurity beyond the requirements of current regulations and policies. As of today, policies mostly address data privacy, not data security. Thus, policy makers need to introduce policies that not only raise the target level of cybersecurity capabilities but also reduce the variability in resource availability across the entire health care system. ©Mohammad S Jalali, Jessica P Kaiser. Originally published in the Journal of Medical Internet Research (http://www.jmir.org), 28.05.2018.

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

PubMed

Gibiansky, Leonid; Gibiansky, Ekaterina

2018-02-01

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

Fault Detection and Diagnosis System for the Air-conditioning

NASA Astrophysics Data System (ADS)

Nakahara, Nobuo

The fault detection and diagnosis system, the FDD system, for the HVAC was initiated around the middle of 1970s in Japan but it still remains at the elementary stage. The HVAC is really one of the most complicated and large scaled system for the FDD system. Besides, the maintenance engineering was never focussed as the target of the academic study since after the war, but the FDD system for some kinds of the components and subsystems has been developed for the sake of the practical industrial needs. Recently, international cooperative study in the IEA Annex 25 on the energy conservation for the building and community targetted on the BOFD, the building optimization, fault detection and diagnosis. Not a few academic peaple from various engineering field got interested and, moreover, some national projects seem to start in the European countries. The author has reviewed the state of the art of the FDD and BO as well based on the references and the experience at the IEA study.

Fibronectin Attachment Protein (FAP) From Bacillus Calmette-Guerin As Targeting Agent For Bladder Tumor Cells

PubMed Central

Coon, Brian G.; Crist, Scott; González-Bonet, Andrés M.; Kim, Hee-Kwon; Sowa, Jennifer; Thompson, David H.; Ratliff, Timothy L.; Aguilar, R. Claudio

2011-01-01

The adjuvant therapy of choice for superficial bladder cancer is the intravesical instillation of live Mycobacterium bovis Bacillus Calmette-Guerin (BCG). In spite of the fact that this therapy is the most effective treatment for superficial bladder cancer, intravesical administration of BCG is associated with high local morbidity and the potential for systemic infection. Therefore, there is a need for the development of safer, less toxic approaches to fight this disease. Since fibronectin attachment protein (FAP) is a key element in BCG retention and targeting to cells, we hypothesize that this protein can be used as targeting agent to deliver cytotoxic cargo for the treatment of bladder tumors. Here we evaluated the ability of bladder tumor cells to bind and endocytose FAP via fibronectin-integrin complexes. We found that microaggregation induced by an anti-FAP polyclonal antibody accelerated FAP uptake by T24 bladder tumor cells. FAP was determined to be internalized via a clathrin-independent, caveolae-dependent mechanism. Further, once within the endosomal compartment, FAP was targeted to the lysosomal compartment with negligible recycling to the plasma membrane. Importantly, we demonstrated that FAP microaggregation and internalization could also be triggered by multivalent Ni2+NTA-bearing liposomes. Overall, our studies validate the use of FAP as a targeting vector and provide the foundation for the design of more effective, less toxic bladder cancer therapeutics. PMID:21901746

Common Infrastructure for Neo Scientific and Planetary Defense Missions

NASA Technical Reports Server (NTRS)

Adams, Robert; Wilks, Rodney

2009-01-01

While defending the Earth against collisions with asteroids and comets has garnered increasing attention over the past few decades, our knowledge of the threats and methods of mitigation remain inadequate. There exists a considerable gap in knowledge regarding the size, composition, location, internal structure and formation of near earth asteroids and comets. Although estimates have been made, critical experiments have not yet been conducted on the effectiveness of various proposed mitigation techniques. Closing this knowledge gap is of interest to both the planetary defense and planetary science communities. Increased scientific knowledge of asteroid and comet composition and structure can confirm or advance current theories about the formation of the solar system. This proposal suggests a joint effort between these two communities to provide an economical architecture that supports multiple launches of characterization and mitigation payloads with minimal response time. The science community can use this architecture for characterization missions of opportunity when multiple scientific targets or targets of uncommon scientific value present themselves, while the planetary defense community would be able to fire characterization or mitigation payloads at targets that present a threat to the Earth. Both communities would benefit from testing potential mitigation techniques, which would reveal information on the internal structure of asteroids and comets. In return, the Earth would have the beginnings of a viable response system should an impact threat prove real in the near future.

Target Trailing With Safe Navigation With Colregs for Maritime Autonomous Surface Vehicles

NASA Technical Reports Server (NTRS)

Kuwata, Yoshiaki (Inventor); Aghazarian, Hrand (Inventor); Huntsberger, Terrance L. (Inventor); Howard, Andrew B. (Inventor); Wolf, Michael T. (Inventor); Zarzhitsky, Dimitri V. (Inventor)

2014-01-01

Systems and methods for operating autonomous waterborne vessels in a safe manner. The systems include hardware for identifying the locations and motions of other vessels, as well as the locations of stationary objects that represent navigation hazards. By applying a computational method that uses a maritime navigation algorithm for avoiding hazards and obeying COLREGS using Velocity Obstacles to the data obtained, the autonomous vessel computes a safe and effective path to be followed in order to accomplish a desired navigational end result, while operating in a manner so as to avoid hazards and to maintain compliance with standard navigational procedures defined by international agreement. The systems and methods have been successfully demonstrated on water with radar and stereo cameras as the perception sensors, and integrated with a higher level planner for trailing a maneuvering target.

Folic acid-conjugated amphiphilic alternating copolymer as a new active tumor targeting drug delivery platform.

PubMed

Li, Xia; Szewczuk, Myron R; Malardier-Jugroot, Cecile

2016-01-01

Targeted drug delivery using polymeric nanostructures is an emerging cancer research area, engineered for safer, more efficient, and effective use of chemotherapeutic drugs. A pH-responsive, active targeting delivery system was designed using folic acid functionalized amphiphilic alternating copolymer poly(styrene-alt-maleic anhydride) (FA-DABA-SMA) via a biodegradable linker 2,4-diaminobutyric acid (DABA). The polymeric template is pH responsive, forming amphiphilic nanostructures at pH 7, allowing the encapsulation of hydrophobic drugs on its interior. Moreover, the structure is stable only at neutral pH and collapses in the acidic tumor microenvironment, releasing drugs on-site from its core. The delivery vehicle is investigated using human pancreatic PANC-1 cancer cells and RAW-Blue™ mouse macrophage reporter cell line, both of which have overly expression of folic acid receptors. To trace the cellular uptake by both cell lines, curcumin was selected as a dye and drug mimic owing to its fluorescence nature and hydrophobic properties. Fluorescent microscopy of FA-DABA-SMA loaded with curcumin revealed a significant internalization of the dye by human pancreatic PANC-1 cancer cells compared to those with unfunctionalized polymers (SMA). Moreover, the FA-DABA-SMA polymers exhibit rodlike association specific to the cells. Both empty SMA and FA-DABA-SMA show little toxicity to PANC-1 cells as characterized by WST-1 cell proliferation assay. These results clearly indicate that FA-DABA-SMA polymers show potential as an active tumor targeting drug delivery system with the ability to internalize hydrophobic chemotherapeutics after they specifically attach to cancer cells.

Successful amplification of DNA aboard the International Space Station.

PubMed

Boguraev, Anna-Sophia; Christensen, Holly C; Bonneau, Ashley R; Pezza, John A; Nichols, Nicole M; Giraldez, Antonio J; Gray, Michelle M; Wagner, Brandon M; Aken, Jordan T; Foley, Kevin D; Copeland, D Scott; Kraves, Sebastian; Alvarez Saavedra, Ezequiel

2017-01-01

As the range and duration of human ventures into space increase, it becomes imperative that we understand the effects of the cosmic environment on astronaut health. Molecular technologies now widely used in research and medicine will need to become available in space to ensure appropriate care of astronauts. The polymerase chain reaction (PCR) is the gold standard for DNA analysis, yet its potential for use on-orbit remains under-explored. We describe DNA amplification aboard the International Space Station (ISS) through the use of a miniaturized miniPCR system. Target sequences in plasmid, zebrafish genomic DNA, and bisulfite-treated DNA were successfully amplified under a variety of conditions. Methylation-specific primers differentially amplified bisulfite-treated samples as would be expected under standard laboratory conditions. Our findings establish proof of concept for targeted detection of DNA sequences during spaceflight and lay a foundation for future uses ranging from environmental monitoring to on-orbit diagnostics.

The importance of workforce surveillance, research evidence and political advocacy in the context of international migration of dentists.

PubMed

Balasubramanian, M; Brennan, D S; Spencer, A J; Watkins, K; Short, S D

2015-03-01

The international migration of dentists is an issue of pressing significance that poses several complex policy challenges. Policy-making is mainly constrained by the lack of workforce surveillance, research evidence and political advocacy - all three are required to work together, yet with different purposes. We first discuss the inconsistencies in migrant dentist surveillance in major country-level governmental systems (immigration departments, dentist registration authorities and workforce agencies). We argue that the limitations in surveillance collections affect independent research and in turn scholarly contributions to dental workforce policy. Differences in country-level surveillance collections also hinder valid cross-country comparisons on migrant dentist data, impeding global policy efforts. Due to these limitations, advocacy, or the political process to influence health policy, suffers, but is integral to future challenges on dentist migration. Country-level advocacy is best targeted at improving migrant dentist surveillance systems. Research interest can be invigorated through targeted funding allocations for migration research and by improving the availability of dentist surveillance data for research purposes. At the global level, the WHOs global code of practice for international recruitment of health personnel (a crucial advocacy tool) needs to be strengthened. Global organisations such as the FDI World Dental Federation have an important role to play in advocating for improved migrant dentist workforce surveillance and research evidence, especially in low- and middle-income countries.

Simple method for production of internal control DNA for Mycobacterium tuberculosis polymerase chain reaction assays.

PubMed Central

deWit, D; Wootton, M; Allan, B; Steyn, L

1993-01-01

A simple method for the production of internal control DNA for two well-established Mycobacterium tuberculosis polymerase chain reaction assays is described. The internal controls were produced from Mycobacterium kansasii DNA with the same primers but at a lower annealing temperature than that used in the standard assays. In both assays, therefore, the internal control DNA has the same primer-binding sequences at the target DNA. One-microgram quantities of internal control DNA which was not contaminated with target DNA could easily be produced by this method. The inclusion of the internal control in the reaction mixture did not affect the efficiency of amplification of the target DNA. The method is simple and rapid and should be adaptable to most M. tuberculosis polymerase chain reaction assays. Images PMID:8370752

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

PubMed

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

2017-02-10

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

Subliminal repetition primes help detection of phonemes in a picture: Evidence for a phonological level of the priming effects.

PubMed

Manoiloff, Laura; Segui, Juan; Hallé, Pierre

2016-01-01

In this research, we combine a cross-form word-picture visual masked priming procedure with an internal phoneme monitoring task to examine repetition priming effects. In this paradigm, participants have to respond to pictures whose names begin with a prespecified target phoneme. This task unambiguously requires retrieving the word-form of the target picture's name and implicitly orients participants' attention towards a phonological level of representation. The experiments were conducted within Spanish, whose highly transparent orthography presumably promotes fast and automatic phonological recoding of subliminal, masked visual word primes. Experiments 1 and 2 show that repetition primes speed up internal phoneme monitoring in the target, compared to primes beginning with a different phoneme from the target, or sharing only their first phoneme with the target. This suggests that repetition primes preactivate the phonological code of the entire target picture's name, hereby speeding up internal monitoring, which is necessarily based on such a code. To further qualify the nature of the phonological code underlying internal phoneme monitoring, a concurrent articulation task was used in Experiment 3. This task did not affect the repetition priming effect. We propose that internal phoneme monitoring is based on an abstract phonological code, prior to its translation into articulation.

Modeling Cell and Tumor-Metastasis Dosimetry with the Particle and Heavy Ion Transport Code System (PHITS) Software for Targeted Alpha-Particle Radionuclide Therapy.

PubMed

Lee, Dongyoul; Li, Mengshi; Bednarz, Bryan; Schultz, Michael K

2018-06-26

The use of targeted radionuclide therapy for cancer is on the rise. While beta-particle-emitting radionuclides have been extensively explored for targeted radionuclide therapy, alpha-particle-emitting radionuclides are emerging as effective alternatives. In this context, fundamental understanding of the interactions and dosimetry of these emitted particles with cells in the tumor microenvironment is critical to ascertaining the potential of alpha-particle-emitting radionuclides. One important parameter that can be used to assess these metrics is the S-value. In this study, we characterized several alpha-particle-emitting radionuclides (and their associated radionuclide progeny) regarding S-values in the cellular and tumor-metastasis environments. The Particle and Heavy Ion Transport code System (PHITS) was used to obtain S-values via Monte Carlo simulation for cell and tumor metastasis resulting from interactions with the alpha-particle-emitting radionuclides, lead-212 ( 212 Pb), actinium-225 ( 225 Ac) and bismuth-213 ( 213 Bi); these values were compared to the beta-particle-emitting radionuclides yttrium-90 ( 90 Y) and lutetium-177 ( 177 Lu) and an Auger-electron-emitting radionuclide indium-111 ( 111 In). The effect of cellular internalization on S-value was explored at increasing degree of internalization for each radionuclide. This aspect of S-value determination was further explored in a cell line-specific fashion for six different cancer cell lines based on the cell dimensions obtained by confocal microscopy. S-values from PHITS were in good agreement with MIRDcell S-values (cellular S-values) and the values found by Hindié et al. (tumor S-values). In the cellular model, 212 Pb and 213 Bi decay series produced S-values that were 50- to 120-fold higher than 177 Lu, while 225 Ac decay series analysis suggested S-values that were 240- to 520-fold higher than 177 Lu. S-values arising with 100% cellular internalization were two- to sixfold higher for the nucleus when compared to 0% internalization. The tumor dosimetry model defines the relative merit of radionuclides and suggests alpha particles may be effective for large tumors as well as small tumor metastases. These results from PHITS modeling substantiate emerging evidence that alpha-particle-emitting radionuclides may be an effective alternative to beta-particle-emitting radionuclides for targeted radionuclide therapy due to preferred dose-deposition profiles in the cellular and tumor metastasis context. These results further suggest that internalization of alpha-particle-emitting radionuclides via radiolabeled ligands may increase the relative biological effectiveness of radiotherapeutics.

Science case for the Asteroid Impact Mission (AIM): A component of the Asteroid Impact & Deflection Assessment (AIDA) mission

NASA Astrophysics Data System (ADS)

Michel, Patrick; Cheng, A.; Küppers, M.; Pravec, P.; Blum, J.; Delbo, M.; Green, S. F.; Rosenblatt, P.; Tsiganis, K.; Vincent, J. B.; Biele, J.; Ciarletti, V.; Hérique, A.; Ulamec, S.; Carnelli, I.; Galvez, A.; Benner, L.; Naidu, S. P.; Barnouin, O. S.; Richardson, D. C.; Rivkin, A.; Scheirich, P.; Moskovitz, N.; Thirouin, A.; Schwartz, S. R.; Campo Bagatin, A.; Yu, Y.

2016-06-01

The Asteroid Impact & Deflection Assessment (AIDA) mission is a joint cooperation between European and US space agencies that consists of two separate and independent spacecraft that will be launched to a binary asteroid system, the near-Earth asteroid Didymos, to test the kinetic impactor technique to deflect an asteroid. The European Asteroid Impact Mission (AIM) is set to rendezvous with the asteroid system to fully characterize the smaller of the two binary components a few months prior to the impact by the US Double Asteroid Redirection Test (DART) spacecraft. AIM is a unique mission as it will be the first time that a spacecraft will investigate the surface, subsurface, and internal properties of a small binary near-Earth asteroid. In addition it will perform various important technology demonstrations that can serve other space missions. The knowledge obtained by this mission will have great implications for our understanding of the history of the Solar System. Having direct information on the surface and internal properties of small asteroids will allow us to understand how the various processes they undergo work and transform these small bodies as well as, for this particular case, how a binary system forms. Making these measurements from up close and comparing them with ground-based data from telescopes will also allow us to calibrate remote observations and improve our data interpretation of other systems. With DART, thanks to the characterization of the target by AIM, the mission will be the first fully documented impact experiment at asteroid scale, which will include the characterization of the target's properties and the outcome of the impact. AIDA will thus offer a great opportunity to test and refine our understanding and models at the actual scale of an asteroid, and to check whether the current extrapolations of material strength from laboratory-scale targets to the scale of AIDA's target are valid. Moreover, it will offer a first check of the validity of the kinetic impactor concept to deflect a small body and lead to improved efficiency for future kinetic impactor designs. This paper focuses on the science return of AIM, the current knowledge of its target from ground-based observations, and the instrumentation planned to get the necessary data.

Monitoring drinking water, sanitation, and hygiene in non-household settings: Priorities for policy and practice.

PubMed

Cronk, Ryan; Slaymaker, Tom; Bartram, Jamie

2015-11-01

Inadequate drinking water, sanitation, and hygiene (WaSH) in non-household settings, such as schools, health care facilities, and workplaces impacts the health, education, welfare, and productivity of populations, particularly in low and middle-income countries. There is limited knowledge on the status of WaSH in such settings. To address this gap, we reviewed international standards, international and national actors, and monitoring initiatives; developed the first typology of non-household settings; and assessed the viability of monitoring. Based on setting characteristics, non-household settings include six types: schools, health care facilities, workplaces, temporary use settings, mass gatherings, and dislocated populations. To-date national governments and international actors have focused monitoring of non-household settings on schools and health care facilities with comparatively little attention given to other settings such as workplaces and markets. Nationally representative facility surveys and national management information systems are the primary monitoring mechanisms. Data suggest that WaSH coverage is generally poor and often lower than in corresponding household settings. Definitions, indicators, and data sources are underdeveloped and not always comparable between countries. While not all countries monitor non-household settings, examples are available from countries on most continents suggesting that systematic monitoring is achievable. Monitoring WaSH in schools and health care facilities is most viable. Monitoring WaSH in other non-household settings would be viable with: technical support from local and national actors in addition to international organizations such as WHO and UNICEF; national prioritization through policy and financing; and including WaSH indicators into monitoring initiatives to improve cost-effectiveness. International consultations on targets and indicators for global monitoring of WaSH post-2015 identified non-household settings as a priority. National and international monitoring systems will be important to better understand status, trends, to identify priorities and target resources accordingly, and to improve accountability for progressive improvements in WaSH in non-household settings. Copyright © 2015 Elsevier GmbH. All rights reserved.

The Crew Earth Observations Experiment: Earth System Science from the ISS

NASA Technical Reports Server (NTRS)

Stefanov, William L.; Evans, Cynthia A.; Robinson, Julie A.; Wilkinson, M. Justin

2007-01-01

This viewgraph presentation reviews the use of Astronaut Photography (AP) as taken from the International Space Station (ISS) in Earth System Science (ESS). Included are slides showing basic remote sensing theory, data characteristics of astronaut photography, astronaut training and operations, crew Earth observations group, targeting sites and acquisition, cataloging and database, analysis and applications for ESS, image analysis of particular interest urban areas, megafans, deltas, coral reefs. There are examples of the photographs and the analysis.

Cultural Adaptation of a Neurobiologically Informed Intervention in Local and International Contexts.

PubMed

Pakulak, Eric; Hampton Wray, Amanda; Longoria, Zayra; Garcia Isaza, Alejandra; Stevens, Courtney; Bell, Theodore; Burlingame, Sarah; Klein, Scott; Berlinski, Samuel; Attanasio, Orazio; Neville, Helen

2017-12-01

The relationship between early adversity and numerous negative outcomes across the lifespan is evident in a wide range of societies and cultures (e.g., Pakulak, Stevens, & Neville, 2018). Among the most affected neural systems are those supporting attention, self-regulation, and stress regulation. As such, these systems represent targets for neurobiologically informed interventions addressing early adversity. In prior work with monolingual native English-speaking families, we showed that a two-generation intervention targeting these systems in families improves outcomes across multiple domains including child brain function for selective attention (for detail, see Neville et al., 2013). Here, we discuss the translation and cultural adaptation (CA) of this intervention in local and international contexts, which required systematic consideration of cultural differences that could affect program acceptability. First, we conducted a translation and CA of our program to serve Latino families in the United States using the Cultural Adaptation Process (CAP), a model that works closely with stakeholders in a systematic, iterative process. Second, to implement the adapted program in Medellín, Colombia, we conducted a subsequent adaptation for Colombian culture using the same CAP. Our experience underscores the importance of consideration of cultural differences and a systematic approach to adaptation before assessing the efficacy of neurobiologically informed interventions in different cultural contexts. © 2017 Wiley Periodicals, Inc.

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

The transformation of targeted killing and international order.

PubMed

Senn, Martin; Troy, Jodok

2017-05-04

This article introduces the special issue's question of whether and how the current transformation of targeted killing is transforming the global international order and provides the conceptual ground for the individual contributions to the special issue. It develops a two-dimensional concept of political order and introduces a theoretical framework that conceives the maintenance and transformation of international order as a dynamic interplay between its behavioral dimension in the form of violence and discursive processes and its institutional dimension in the form of ideas, norms, and rules. The article also conceptualizes targeted killing and introduces a typology of targeted-killing acts on the basis of their legal and moral legitimacy. Building on this conceptual groundwork, the article takes stock of the current transformation of targeted killing and summarizes the individual contributions to this special issue.

An explosives detection system for airline security using coherent x-ray scattering technology

NASA Astrophysics Data System (ADS)

Madden, Robert W.; Mahdavieh, Jacob; Smith, Richard C.; Subramanian, Ravi

2008-08-01

L-3 Communications Security and Detection Systems (SDS) has developed a new system for automated alarm resolution in airline baggage Explosive Detection Systems (EDS) based on coherent x-ray scattering spectroscopy. The capabilities of the system were demonstrated in tests with concealed explosives at the Transportation Security Laboratory and airline passenger baggage at Orlando International Airport. The system uses x-ray image information to identify suspicious objects and performs targeted diffraction measurements to classify them. This extra layer of detection capability affords a significant reduction in the rate of false alarm objects that must presently be resolved by opening passenger bags for hand inspection.

Intracellular Delivery System for Antibody–Peptide Drug Conjugates

PubMed Central

Berguig, Geoffrey Y; Convertine, Anthony J; Frayo, Shani; Kern, Hanna B; Procko, Erik; Roy, Debashish; Srinivasan, Selvi; Margineantu, Daciana H; Booth, Garrett; Palanca-Wessels, Maria Corinna; Baker, David; Hockenbery, David; Press, Oliver W; Stayton, Patrick S

2015-01-01

Antibodies armed with biologic drugs could greatly expand the therapeutic potential of antibody–drug conjugates for cancer therapy, broadening their application to disease targets currently limited by intracellular delivery barriers. Additional selectivity and new therapeutic approaches could be realized with intracellular protein drugs that more specifically target dysregulated pathways in hematologic cancers and other malignancies. A multifunctional polymeric delivery system for enhanced cytosolic delivery of protein drugs has been developed that incorporates endosomal-releasing activity, antibody targeting, and a biocompatible long-chain ethylene glycol component for optimized safety, pharmacokinetics, and tumor biodistribution. The pH-responsive polymeric micelle carrier, with an internalizing anti-CD22 monoclonal targeting antibody, effectively delivered a proapoptotic Bcl-2 interacting mediator (BIM) peptide drug that suppressed tumor growth for the duration of treatment and prolonged survival in a xenograft mouse model of human B-cell lymphoma. Antitumor drug activity was correlated with a mechanistic induction of the Bcl-2 pathway biomarker cleaved caspase-3 and a marked decrease in the Ki-67 proliferation biomarker. Broadening the intracellular target space by more effective delivery of protein/peptide drugs could expand the repertoire of antibody–drug conjugates to currently undruggable disease-specific targets and permit tailored drug strategies to stratified subpopulations and personalized medicines. PMID:25669432

The relationship between external and local governance systems: the case of health care associated infections and medication errors in one NHS trust.

PubMed

Ramsay, Angus; Magnusson, Carin; Fulop, Naomi

2010-12-01

'Organisational governance'--the systems, processes, behaviours and cultures by which an organisation leads and controls its functions to achieve its objectives--is seen as an important influence on patient safety. The features of 'good' governance remain to be established, partly because the relationship between governance and safety requires more investigation. To describe external governance systems--for example, national targets and regulatory bodies--and an NHS Trust's formal governance systems for Health Care Associated Infections (HCAIs) and medication errors; to consider the relationships between these systems. External governance systems and formal internal governance systems for both medication errors and HCAIs were analysed based on documentary analysis and interviews with relevant hospital staff. Nationally, HCAIs appeared to be a higher priority than medication errors, reflected in national targets and the focus of regulatory bodies. Locally, HCAIs were found to be the focus of committees at all levels of the organisation and, unlike medication errors, a central component of the Trust's performance management system; medication errors were discussed in appropriate governance committees, but most governance of medication errors took place at divisional or ward level. The data suggest a relationship between national and local prioritisation of the safety issues examined: national targets on HCAIs influence the behaviour of regulators and professional organisations; and these, in turn, have a significant impact on Trust activity. A contributory factor might be that HCAIs are more amenable to measurement than medication errors, meaning HCAIs lend themselves better to target-setting.

Validation of a newly developed hexaplex real-time PCR assay for screening for presence of GMOs in food, feed and seed.

PubMed

Bahrdt, C; Krech, A B; Wurz, A; Wulff, D

2010-03-01

For years, an increasing number and diversity of genetically modified plants has been grown on a commercial scale. The need for detection and identification of these genetically modified organisms (GMOs) calls for broad and at the same time flexible high throughput testing methods. Here we describe the development and validation of a hexaplex real-time polymerase chain reaction (PCR) screening assay covering more than 100 approved GMOs containing at least one of the GMO targets of the assay. The assay comprises detection systems for Cauliflower Mosaic Virus 35S promoter, Agrobacterium tumefaciens NOS terminator, Figwort Mosaic Virus 34S promoter and two construct-specific sequences present in novel genetically modified soybean and maize that lack common screening elements. Additionally a detection system for an internal positive control (IPC) indicating the presence or absence of PCR inhibiting substances was included. The six real-time PCR systems were allocated to five detection channels showing no significant crosstalk between the detection channels. As part of an extensive validation, a limit of detection (LOD(abs)) < or = ten target copies was proven in hexaplex format. A sensitivity < or = ten target copies of each GMO detection system was still shown in highly asymmetric target situations in the presence of 1,000 copies of all other GMO targets of each detection channel. Furthermore, the applicability to a broad sample spectrum and reliable indication of inhibition by the IPC system was demonstrated. The presented hexaplex assay offers sensitive and reliable detection of GMOs in processed and unprocessed food, feed and seed samples with high efficiency.

The ceremonial transfer of Leonardo, the first MPLM, from ASI to NASA

NASA Technical Reports Server (NTRS)

1998-01-01

Participants pose for a photo at the Space Station Processing Facility ceremony transferring the 'Leonardo' Multipurpose Logistics Module (MPLM) from the Italian Space Agency, Agenzia Spaziale Italiana (ASI), to NASA. From left, they are astronaut Jim Voss, European Space Agency astronauts Umberto Guidoni of Italy and Christer Fuglesang of Sweden, NASA International Space Station Program Manager Randy Brinkley, NASA Administrator Daniel S. Goldin, ASI President Sergio De Julio and Stephen Francois, director, International Space Station Launch Site Support at KSC. The MPLM, a reusable logistics carrier, will be the primary delivery system used to resupply and return International Space Station cargo requiring a pressurized environment. Leonardo is the first of three MPLM carriers for the International Space Station. It is scheduled to be launched on Space Shuttle Mission STS-100, targeted for April 2000.

Challenging the current approaches to multiple myeloma- and other cancer-related bone diseases: from bisphosphonates to targeted therapy.

PubMed

Kleber, Martina; Udi, Josefina; Metzke, Barbara; Terpos, Evangelos; Roodmann, G David; Morgan, Gareth; Dispenzieri, Angela; Einsele, Hermann; Wäsch, Ralph; Engelhardt, Monika

2012-06-01

An international myeloma meeting entitled "Challenging the current approaches to multiple myeloma- and other cancer-related bone diseases: from bisphosphonates to targeted therapy" was held in Freiburg, Germany in July 2011 to discuss novel insights into and approaches to myeloma bone disease and other bone-seeking tumors. This review briefly summarizes the most prominent data of the meeting and current literature on our understanding of bone disease, the role of imaging techniques, operative interventions and systemic bone-seeking treatment, all of which should further improve our future therapeutic choices.

Differential cellular internalization of anti-CD19 and -CD22 immunotoxins results in different cytotoxic activity.

PubMed

Du, Xing; Beers, Richard; Fitzgerald, David J; Pastan, Ira

2008-08-01

B-cell malignancies routinely express surface antigens CD19 and CD22. Immunotoxins against both antigens have been evaluated, and the immunotoxins targeting CD22 are more active. To understand this disparity in cytotoxicity and guide the screening of therapeutic targets, we compared two immunotoxins, FMC63(Fv)-PE38-targeting CD19 and RFB4(Fv)-PE38 (BL22)-targeting CD22. Six lymphoma cell lines have 4- to 9-fold more binding sites per cell for CD19 than for CD22, but BL22 is 4- to 140-fold more active than FMC63(Fv)-PE38, although they have a similar cell binding affinity (Kd, approximately 7 nmol/L). In 1 hour, large amounts of BL22 are internalized (2- to 3-fold more than the number of CD22 molecules on the cell surface), whereas only 5.2% to 16.6% of surface-bound FMC63(Fv)-PE38 is internalized. The intracellular reservoir of CD22 decreases greatly after immunotoxin internalization, indicating that it contributes to the uptake of BL22. Treatment of cells with cycloheximide does not reduce the internalization of BL22. Both internalized immunotoxins are located in the same vesicles. Our results show that the rapid internalization of large amounts of BL22 bound to CD22 makes CD22 a better therapeutic target than CD19 for immunotoxins and probably for other immunoconjugates that act inside cells.

Neuropeptide Y Y1 receptors meditate targeted delivery of anticancer drug with encapsulated nanoparticles to breast cancer cells with high selectivity and its potential for breast cancer therapy.

PubMed

Li, Juan; Shen, Zheyu; Ma, Xuehua; Ren, Wenzhi; Xiang, Lingchao; Gong, An; Xia, Tian; Guo, Junming; Wu, Aiguo

2015-03-11

By enabling nanoparticle-based drug delivery system to actively target cancer cells with high selectivity, active targeted molecules have attracted great attention in the application of nanoparticles for anticancer drug delivery. However, the clinical application of most active targeted molecules in breast cancer therapy is limited, due to the low expression of their receptors in breast tumors or coexpression in the normal and tumor breast tissues. Here, a neuropeptide Y Y1 receptors ligand PNBL-NPY, as a novel targeted molecule, is conjugated with anticancer drug doxorubicin encapsulating albumin nanoparticles to investigate the effect of Y1 receptors on the delivery of drug-loaded nanoparticles to breast cancer cells and its potential for breast cancer therapy. The PNBL-NPY can actively recognize and bind to the Y1 receptors that are significantly overexpressed on the surface of the breast cancer cells, and the drug-loaded nanoparticles are delivered directly into the cancer cells through internalization. This system is highly selective and able to distinguish the breast cancer cells from the normal cells, due to normal breast cells that express Y2 receptors only. It is anticipated that this study may provide a guidance in the development of Y1 receptor-based nanoparticulate drug delivery system for a safer and more efficient breast cancer therapy.

Single-element ultrasound transducer for combined vessel localization and ablation.

PubMed

Chen, Wen-Shiang; Shen, Che-Chou; Wang, Jen-Chieh; Ko, Chung-Ting; Liu, Hao-Li; Ho, Ming-Chih; Chen, Chiung-Nien; Yeh, Chih-Kuang

2011-04-01

This report describes a system that utilizes a single high-intensity focused ultrasound (HIFU) transducer for both the localization and ablation of arteries with internal diameters of 0.5 and 1.3 mm. In vitro and in vivo tests were performed to demonstrate both the imaging and ablation functionalities of this system. For imaging mode, pulsed acoustic waves (3 cycles for in vitro and 10 cycles for in vivo tests, 2 MPa peak pressure) were emitted from the 2-MHz HIFU transducer, and the backscattered ultrasonic signal was collected by the same transducer to calculate Doppler shifts in the target region. The maximum signal amplitude of the Doppler shift was used to determine the location of the target vessel. The operation mode was then switched to the therapeutic mode and vessel occlusion was successfully produced by high-intensity continuous HIFU waves (12 MPa) for 60 s. The system was then switched back to imaging mode for residual flow to determine the need for a second ablation treatment. The new system might be used to target and occlude unwanted vessels such as vasculature around tumors, and to help with tumor destruction. © 2011 IEEE

ROGER a potential orbital space debris removal system

NASA Astrophysics Data System (ADS)

Starke, Juergen; Bischof, Bernd; Foth, W.-O.; -J., J.; Günther

The previous activities in the field of On Orbit Servicing studied in the 1990's included in partic-ular the capability of vehicles in GEO to capture and support satellites (mainly communication satellites) to enable repair and continuation of operations, and finally the controlled transfer the target into a permanent graveyard orbit. The specific capture tools for these applications were mostly based on robotic systems to capture and fix the target under specific dynamic constraints (e.g. slowly tumbling target) without damage, and to allow the stabilization, re-orientation and potential repair of the target and subsequent release or transport to the final disposal orbit. Due to the drastically increasing number of debris particularly in the Low Earth Orbits (SSO) the active debris removal is now necessary to counteract to the predicted debris production cascade (Kessler Syndrome), which means the pollution of the total sphere in low earth orbit and not only the SSO area. In most of the debris congresses it was recommended to start removal with the still integrated systems as soon as possible. In the case of large debris objects, the soft capture system can be replaced by a simpler and robust system able to operate from a safe distance to the target and flexible enough to capture and hold different types of targets such as deactivated and/or defective satellites, upper stages and big fragments. These nominally non -cooperative targets might be partially destroyed by the capture process, but the production of additional debris shall be avoided. A major argument for the commercial applications is a multi-target mission potential, which is possible at GEO because the transfer propellant requirement to the disposal orbit and the return to the orbit of the next potential target is relative low (orbits with similar inclination and altitude). The proposed ROGER system is designed as a spacecraft with rendezvous capabilities including inspection in the vicinity of the target and stabilization and transportation features for the combined configuration. The capture system is a deployable and closable net. The net is ejected from the mother spacecraft at a safe distance to prevent any collision with the target. After transport to the disposal orbit the net will be cut and the spacecraft will return to the operational orbit of the next target. An initial down-scaled demonstration is planned for the net capture system on a parabolic flight in autumn 2010. Further representative demonstrations including, for example, one in LEO are under discussion. The capture system can be used operationally also in other orbits e.g. LEO, but the propellant requirements for transport of the target into a direct controlled re-entry orbit and the subsequent return of the mother spacecraft to a new target orbit will be very high. This could impact the multi mission capability of the system. The potential applications are under discussion with different customers including satellite operators, insurance companies and international organisations. juergen.starke@astrium.eads.net Tel.: +49-421-539-4573

Anti-DR5 monoclonal antibody-mediated DTIC-loaded nanoparticles combining chemotherapy and immunotherapy for malignant melanoma: target formulation development and in vitro anticancer activity.

PubMed

Ding, Baoyue; Wu, Xin; Fan, Wei; Wu, Zhaoyong; Gao, Jing; Zhang, Wei; Ma, Lulu; Xiang, Wang; Zhu, Quangang; Liu, Jiyong; Ding, Xueying; Gao, Shen

2011-01-01

The increased incidence of malignant melanoma in recent decades, along with its high mortality rate and pronounced resistance to therapy pose an enormous challenge. Novel therapeutic strategies, such as immunotherapy and targeted therapy, are urgently needed for melanoma. In this study, a new active targeting drug delivery system was constructed to combine chemotherapy and active specific immunotherapy. The chemotherapeutic drug, dacarbazine (DTIC), that induces apoptosis through the intrinsic pathway which typically responds to severe DNA damage, was used as a model drug to prepare DTIC-loaded polylactic acid (PLA) nanoparticles (DTIC-NPs), which were covalently conjugated to a highly specific targeting functional TRAIL-receptor 2 (DR5) monoclonal antibody (mAb) that can contribute directly to cancer cell apoptosis or growth inhibition through the extrinsic pathway. Our in vitro experiments demonstrated that DTIC-PLA-DR5 mAb nanoparticles (DTIC-NPs-DR5 mAb) are an active targeting drug delivery system which can specifically target DR5-overexpressing malignant melanoma cells and become efficiently internalized. Most strikingly, compared with conventional DTIC-NPs, DTIC-NPs-DR5 mAb showed significantly enhanced cytotoxicity and increased cell apoptosis in DR5-positive malignant melanoma cells. The DTIC-NPs-DR5 mAb described in this paper might be a potential formulation for targeting chemotherapy and immunotherapy to DR5-overexpressing metastatic melanoma.

Simultaneous analysis of multiple classes of antimicrobials in environmental water samples using SPE coupled with UHPLC-ESI-MS/MS and isotope dilution.

PubMed

Tran, Ngoc Han; Chen, Hongjie; Do, Thanh Van; Reinhard, Martin; Ngo, Huu Hao; He, Yiliang; Gin, Karina Yew-Hoong

2016-10-01

A robust and sensitive analytical method was developed for the simultaneous analysis of 21 target antimicrobials in different environmental water samples. Both single SPE and tandem SPE cartridge systems were investigated to simultaneously extract multiple classes of antimicrobials. Experimental results showed that good extraction efficiencies (84.5-105.6%) were observed for the vast majority of the target analytes when extraction was performed using the tandem SPE cartridge (SB+HR-X) system under an extraction pH of 3.0. HPLC-MS/MS parameters were optimized for simultaneous analysis of all the target analytes in a single injection. Quantification of target antimicrobials in water samples was accomplished using 15 isotopically labeled internal standards (ILISs), which allowed the efficient compensation of the losses of target analytes during sample preparation and correction of matrix effects during UHPLC-MS/MS as well as instrument fluctuations in MS/MS signal intensity. Method quantification limit (MQL) for most target analytes based on SPE was below 5ng/L for surface waters, 10ng/L for treated wastewater effluents, and 15ng/L for raw wastewater. The method was successfully applied to detect and quantify the occurrence of the target analytes in raw influent, treated effluent and surface water samples. Copyright © 2016 Elsevier B.V. All rights reserved.

Health research systems: promoting health equity or economic competitiveness?

PubMed

Pratt, Bridget; Loff, Bebe

2012-01-01

International collaborative health research is justifiably expected to help reduce global health inequities. Investment in health policy and systems research in developing countries is essential to this process but, currently, funding for international research is mainly channelled towards the development of new medical interventions. This imbalance is largely due to research legislation and policies used in high-income countries. These policies have increasingly led these countries to invest in health research aimed at boosting national economic competitiveness rather than reducing health inequities. In the United States of America and the United Kingdom of Great Britain and Northern Ireland, the regulation of research has encouraged a model that: leads to products that can be commercialized; targets health needs that can be met by profitable, high-technology products; has the licensing of new products as its endpoint; and does not entail significant research capacity strengthening in other countries. Accordingly, investment in international research is directed towards pharmaceutical trials and product development public-private partnerships for neglected diseases. This diverts funding away from research that is needed to implement existing interventions and to strengthen health systems, i.e. health policy and systems research. Governments must restructure their research laws and policies to increase this essential research in developing countries.

Incineration of nuclear waste by accelerator

NASA Astrophysics Data System (ADS)

Martino, J.; Fioni, G.; Leray, S.

1998-10-01

An important international effort is devoted to find a suitable solution to incinerate radioactive nuclear waste issued from conventional power plants and from nuclear disarmament. Practically all innovative projects consist of a sub critical system driven by an external neutron source obtained by spallation induced by a high intensity proton accelerator irradiating a heavy target. New nuclear data measurements are necessary for the realization of these systems, in particular a good knowledge of the spallation process and of the neutron cross sections for transuranic elements are essential.

Development and Function of the Drosophila Tracheal System.

PubMed

Hayashi, Shigeo; Kondo, Takefumi

2018-06-01

The tracheal system of insects is a network of epithelial tubules that functions as a respiratory organ to supply oxygen to various target organs. Target-derived signaling inputs regulate stereotyped modes of cell specification, branching morphogenesis, and collective cell migration in the embryonic stage. In the postembryonic stages, the same set of signaling pathways controls highly plastic regulation of size increase and pattern elaboration during larval stages, and cell proliferation and reprograming during metamorphosis. Tracheal tube morphogenesis is also regulated by physicochemical interaction of the cell and apical extracellular matrix to regulate optimal geometry suitable for air flow. The trachea system senses both the external oxygen level and the metabolic activity of internal organs, and helps organismal adaptation to changes in environmental oxygen level. Cellular and molecular mechanisms underlying the high plasticity of tracheal development and physiology uncovered through research on Drosophila are discussed. Copyright © 2018 by the Genetics Society of America.

ExoDat Information System at CeSAM

NASA Astrophysics Data System (ADS)

Agneray, F.; Moreau, C.; Chabaud, P.; Damiani, C.; Deleuil, M.

2014-05-01

CoRoT (Convection Rotation and planetary transits) is a space based mission led by French space agency (CNES) in association with French and international laboratories. One of CoRoT's goal is to detect exoplanets by the transit method. The Exoplanet Database (Exodat) is a VO compliant information system for the CoRoT exoplanet program. The main functions of ExoDat are to provide a source catalog for the observation fields and targets selection; to characterize the CoRoT targets (spectral type, variability , contamination...);and to support follow up programs. ExoDat is built using the AstroNomical Information System (ANIS) developed by the CeSAM (Centre de donneeS Astrophysique de Marseille). It offers download of observation catalogs and additional services like: search, extract and display data by using a combination of criteria, object list, and cone-search interfaces. Web services have been developed to provide easy access for user's softwares and pipelines.

[Development of pseudoviral competitive internal controls for RT-PCR detection of dengue virus].

PubMed

Hang, Xiao-Tong; Li, Jian-Dong; Zhang, Quan-Fu; Li, Chuan; Zhang, Shuo; Liang, Mi-Fang; Li, De-Xin

2010-02-01

Development of pseudoviral competitive internal controls for RT-PCR laboratory detection of dengue virus. The internal controls target gene were obtained by insertion of a 180 bp non-related DNA fragment into RT-PCR detection target of dengue virus between the forward and reverse PCR primer binding regions. A yellow florescence protein reporter gene was induced at downstream of internal controls target gene via internal ribosome entry site gene. HEK 293T cells were transfected with plasmid containing this whole cassette and lentiviral packaging support plasmid. Pseudoviral particle was recovered from the supernatant and analyzed quantitatively and qualitatively in simulated samples at the same tube under different experimental conditions. The established pseudoviral competitive internal controls can be used in the RT-PCR detection of different serotype dengue virus and the whole detection process can be monitored. The obtained fragment is easy to be differentiated in agarose electrophoresis. The pseudoviral competitive internal controls could be used for the quality control of the laboratory diagnosis process, simple to prepare, stable for storage, easy to be transformed into internal controls for other RNA virus.

Reaching for the Unknown: Multiple Target Encoding and Real-Time Decision-Making in a Rapid Reach Task

ERIC Educational Resources Information Center

Chapman, Craig S.; Gallivan, Jason P.; Wood, Daniel K.; Milne, Jennifer L.; Culham, Jody C.; Goodale, Melvyn A.

2010-01-01

Decision-making is central to human cognition. Fundamental to every decision is the ability to internally represent the available choices and their relative costs and benefits. The most basic and frequent decisions we make occur as our motor system chooses and executes only those actions that achieve our current goals. Although these interactions…

Women Farmers' Perceptions of the Economic Problems Influencing Their Productivity in Agricultural Systems: Meme Division of the Southwest Province, Cameroon.

ERIC Educational Resources Information Center

Endeley, Joyce B.

Women farmers produce about 60% of the food in Cameroon, but face more problems and constraints than men in performing their agricultural activities. Cash crop farmers (mostly men) are the targeted beneficiaries of government and international aids, and have better access to extension services, loans, subsidized production input (herbicides,…

Primary School Teachers' Views on a Holistic Approach to Facilitating the Acquisition of Musical Cultural Values

ERIC Educational Resources Information Center

Badjanova, Jelena

2013-01-01

Recent tendencies in education highlight the need to align the system of general education in Latvia with the tenets of sustainability. In keeping with this broad target orientation, this paper re-examines international and Latvian experiences and perspectives on the application of a holistic approach to the content of primary education. This…

Tracing the U.S. Deficit in PISA Reading Skills to Early Childhood: Evidence from the United States and Canada

ERIC Educational Resources Information Center

Merry, Joseph J.

2013-01-01

Why does the United States lag behind so many other countries on international education assessments? The traditional view targets school-based explanations--U.S. schools attract poorer teachers and lack the proper incentives. But the U.S. educational system may also serve children with comparatively greater academic challenges as a result of…

STS-104 Emergency Egress Training (Launch) at Bldg.9, CCT

NASA Image and Video Library

2001-02-27

JSC2001-E-06419 (27 February 2001) --- Astronaut Janet L. Kavandi, mission specialist, during mission training at the Johnson Space Center’s Systems Integration Facility. The STS-104 mission to the International Space Station (ISS) represents the Space Shuttle Atlantis’ first flight using a new engine and is targeted for a liftoff no earlier than June 14, 2001.

The ACCE Position Statement on Media Enriched Learning Communities: "If We're Not Standing on the Edge and Thinking Ahead We're Taking up Too Much Room"

ERIC Educational Resources Information Center

Kember, Deborah; Brandenburg, Tony; Murphy, Angela

2007-01-01

The ACCE position statement for creating media enriched learning communities targets all stakeholders in educational policy and practice who influence the future of learning, schools, and systems. Stakeholders include policy-makers in government, national and international organisations, professional networks and institutions, school leaders,…

Noninvasive and real-time monitoring of molecular targeting therapy for lymph node and peritoneal metastasis in nude mice bearing xenografts of human colorectal cancer cells tagged with GFP and DsRed

NASA Astrophysics Data System (ADS)

Nakanishi, Hayao; Hara, Masayasu; Ikehara, Yuzuru; Tatematsu, Masae

2007-02-01

We have developed an in vivo imaging system consisting of GFP- and DsRed-tagged human colonic cancer cell line, which has peritoneal and lymph node metastatic potential and show high sensitivity to EGFR targeting drugs, and convenient detection devices for GFP and DsRed. The latter includes a small handy fluorescence detection device for external monitoring of the therapeutic effect of the drug and a convenient stereo fluorescent microscope for internal visualization of micrometastases. We applied this imaging system to investigate anti-metastatic effects of EGFR targeting drugs such as gefitinib (Iressa). This system allowed sensitive detection of the development of peritoneal and lymph node metastases from the micrometastasis stage at the cellular level and also permited noninvasive, non-anesthetic monitoring of anti-metastatic effect of the drug in an animal facility without any pretreatment. Significant decreases in the intraabdominal metastatic tumor growth and prevention of inguinal lymph node metastasis by gefitinib treatment could be clearly monitored. These results suggest that convenient, low-cost, true real-time monitoring of therapeutic effect using such a fluorescence-mediated whole body imaging system seems to enhance the speed of preclinical study for novel anti-cancer agents and will allow us to understand the action mechanism of molecular targeting drugs.

The transformation of targeted killing and international order

PubMed Central

Senn, Martin; Troy, Jodok

2017-01-01

ABSTRACT This article introduces the special issue’s question of whether and how the current transformation of targeted killing is transforming the global international order and provides the conceptual ground for the individual contributions to the special issue. It develops a two-dimensional concept of political order and introduces a theoretical framework that conceives the maintenance and transformation of international order as a dynamic interplay between its behavioral dimension in the form of violence and discursive processes and its institutional dimension in the form of ideas, norms, and rules. The article also conceptualizes targeted killing and introduces a typology of targeted-killing acts on the basis of their legal and moral legitimacy. Building on this conceptual groundwork, the article takes stock of the current transformation of targeted killing and summarizes the individual contributions to this special issue. PMID:29097903

Rendezvous and Proximity Operations of the Space Shuttle

NASA Technical Reports Server (NTRS)

Goodman, John L.

2005-01-01

Space Shuttle rendezous missions presented unique challenges that were not fully recognized when the Shuttle was designed. Rendezvous targets could be passive (i.e., no lights or transponders), and not designed to facilitate Shuttle rendezvous, proximity operations and retrieval. Shuttle reaction control system jet plume impingement on target spacecraft presented induced dynamics, structural loading and contamination concerns. These issues, along with limited forward reaction control system propellant, drove a change from the Gemimi/Apollo coelliptic profile heritage to a stable orbit profile, and the development of new proximity operations techniques. Multiple scientific and on-orbit servicing missions and crew exchange, assembly and replinishment flights to Mir and to the International Space Station drove further profile and piloting technique changes, including new relative navigation sensors and new computer generated piloting cues.

Development and validation of InnoQuant™, a sensitive human DNA quantitation and degradation assessment method for forensic samples using high copy number mobile elements Alu and SVA.

PubMed

Pineda, Gina M; Montgomery, Anne H; Thompson, Robyn; Indest, Brooke; Carroll, Marion; Sinha, Sudhir K

2014-11-01

There is a constant need in forensic casework laboratories for an improved way to increase the first-pass success rate of forensic samples. The recent advances in mini STR analysis, SNP, and Alu marker systems have now made it possible to analyze highly compromised samples, yet few tools are available that can simultaneously provide an assessment of quantity, inhibition, and degradation in a sample prior to genotyping. Currently there are several different approaches used for fluorescence-based quantification assays which provide a measure of quantity and inhibition. However, a system which can also assess the extent of degradation in a forensic sample will be a useful tool for DNA analysts. Possessing this information prior to genotyping will allow an analyst to more informatively make downstream decisions for the successful typing of a forensic sample without unnecessarily consuming DNA extract. Real-time PCR provides a reliable method for determining the amount and quality of amplifiable DNA in a biological sample. Alu are Short Interspersed Elements (SINE), approximately 300bp insertions which are distributed throughout the human genome in large copy number. The use of an internal primer to amplify a segment of an Alu element allows for human specificity as well as high sensitivity when compared to a single copy target. The advantage of an Alu system is the presence of a large number (>1000) of fixed insertions in every human genome, which minimizes the individual specific variation possible when using a multi-copy target quantification system. This study utilizes two independent retrotransposon genomic targets to obtain quantification of an 80bp "short" DNA fragment and a 207bp "long" DNA fragment in a degraded DNA sample in the multiplex system InnoQuant™. The ratio of the two quantitation values provides a "Degradation Index", or a qualitative measure of a sample's extent of degradation. The Degradation Index was found to be predictive of the observed loss of STR markers and alleles as degradation increases. Use of a synthetic target as an internal positive control (IPC) provides an additional assessment for the presence of PCR inhibitors in the test sample. In conclusion, a DNA based qualitative/quantitative/inhibition assessment system that accurately predicts the status of a biological sample, will be a valuable tool for deciding which DNA test kit to utilize and how much target DNA to use, when processing compromised forensic samples for DNA testing. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

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

PubMed

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

2007-08-20

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

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

NASA Astrophysics Data System (ADS)

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

2007-08-01

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

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

DOE PAGES

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

2007-08-16

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

Activity targets for nanostructured platinum-group-metal-free catalysts in hydroxide exchange membrane fuel cells.

PubMed

Setzler, Brian P; Zhuang, Zhongbin; Wittkopf, Jarrid A; Yan, Yushan

2016-12-06

Fuel cells are the zero-emission automotive power source that best preserves the advantages of gasoline automobiles: low upfront cost, long driving range and fast refuelling. To make fuel-cell cars a reality, the US Department of Energy has set a fuel cell system cost target of US$30 kW -1 in the long-term, which equates to US$2,400 per vehicle, excluding several major powertrain components (in comparison, a basic, but complete, internal combustion engine system costs approximately US$3,000). To date, most research for automotive applications has focused on proton exchange membrane fuel cells (PEMFCs), because these systems have demonstrated the highest power density. Recently, however, an alternative technology, hydroxide exchange membrane fuel cells (HEMFCs), has gained significant attention, because of the possibility to use stable platinum-group-metal-free catalysts, with inherent, long-term cost advantages. In this Perspective, we discuss the cost profile of PEMFCs and the advantages offered by HEMFCs. In particular, we discuss catalyst development needs for HEMFCs and set catalyst activity targets to achieve performance parity with state-of-the-art automotive PEMFCs. Meeting these targets requires careful optimization of nanostructures to pack high surface areas into a small volume, while maintaining high area-specific activity and favourable pore-transport properties.

Activity targets for nanostructured platinum-group-metal-free catalysts in hydroxide exchange membrane fuel cells

NASA Astrophysics Data System (ADS)

Setzler, Brian P.; Zhuang, Zhongbin; Wittkopf, Jarrid A.; Yan, Yushan

2016-12-01

Fuel cells are the zero-emission automotive power source that best preserves the advantages of gasoline automobiles: low upfront cost, long driving range and fast refuelling. To make fuel-cell cars a reality, the US Department of Energy has set a fuel cell system cost target of US$30 kW-1 in the long-term, which equates to US$2,400 per vehicle, excluding several major powertrain components (in comparison, a basic, but complete, internal combustion engine system costs approximately US$3,000). To date, most research for automotive applications has focused on proton exchange membrane fuel cells (PEMFCs), because these systems have demonstrated the highest power density. Recently, however, an alternative technology, hydroxide exchange membrane fuel cells (HEMFCs), has gained significant attention, because of the possibility to use stable platinum-group-metal-free catalysts, with inherent, long-term cost advantages. In this Perspective, we discuss the cost profile of PEMFCs and the advantages offered by HEMFCs. In particular, we discuss catalyst development needs for HEMFCs and set catalyst activity targets to achieve performance parity with state-of-the-art automotive PEMFCs. Meeting these targets requires careful optimization of nanostructures to pack high surface areas into a small volume, while maintaining high area-specific activity and favourable pore-transport properties.

Targeted microbubbles: a novel application for the treatment of kidney stones.

PubMed

Ramaswamy, Krishna; Marx, Vanessa; Laser, Daniel; Kenny, Thomas; Chi, Thomas; Bailey, Michael; Sorensen, Mathew D; Grubbs, Robert H; Stoller, Marshall L

2015-07-01

Kidney stone disease is endemic. Extracorporeal shockwave lithotripsy was the first major technological breakthrough where focused shockwaves were used to fragment stones in the kidney or ureter. The shockwaves induced the formation of cavitation bubbles, whose collapse released energy at the stone, and the energy fragmented the kidney stones into pieces small enough to be passed spontaneously. Can the concept of microbubbles be used without the bulky machine? The logical progression was to manufacture these powerful microbubbles ex vivo and inject these bubbles directly into the collecting system. An external source can be used to induce cavitation once the microbubbles are at their target; the key is targeting these microbubbles to specifically bind to kidney stones. Two important observations have been established: (i) bisphosphonates attach to hydroxyapatite crystals with high affinity; and (ii) there is substantial hydroxyapatite in most kidney stones. The microbubbles can be equipped with bisphosphonate tags to specifically target kidney stones. These bubbles will preferentially bind to the stone and not surrounding tissue, reducing collateral damage. Ultrasound or another suitable form of energy is then applied causing the microbubbles to induce cavitation and fragment the stones. This can be used as an adjunct to ureteroscopy or percutaneous lithotripsy to aid in fragmentation. Randall's plaques, which also contain hydroxyapatite crystals, can also be targeted to pre-emptively destroy these stone precursors. Additionally, targeted microbubbles can aid in kidney stone diagnostics by virtue of being used as an adjunct to traditional imaging methods, especially useful in high-risk patient populations. This novel application of targeted microbubble technology not only represents the next frontier in minimally invasive stone surgery, but a platform technology for other areas of medicine. © 2014 The Authors BJU International © 2014 BJU International Published by John Wiley & Sons Ltd.

Strategic management system in a healthcare setting--moving from strategy to results.

PubMed

Devitt, Rob; Klassen, Wolf; Martalog, Julian

2005-01-01

One of the historical challenges in the healthcare system has been the identification and collection of meaningful data to measure an organization's progress towards the achievement of its strategic goals and the concurrent alignment of internal operating practices with this strategy. Over the last 18 months the Toronto East General Hospital (TEGH) has adopted a strategic management system and organizing framework that has led to a metric-based strategic plan. It has allowed for formal and measurable linkages across a full range of internal business processes, from the annual operating plan to resource allocation decisions, to the balanced scorecard and individual performance evaluations. The Strategic Management System (SMS) aligns organizational planning and performance measurement, facilitates an appropriate balance between organizational priorities and resolving "local" problems, and encourages behaviours that are consistent with the values upon which the organization is built. The TEGH Accountability Framework serves as the foundation for the entire system. A key tool of the system is the rolling three-year strategic plan for the organization that sets out specific annual improvement targets on a number of key strategic measures. Individual program/department plans with corresponding measures ensure that the entire organization is moving forward strategically. Each year, all plans are reviewed, with course adjustments made to reflect changes in the hospital's environment and with re-calibration of performance targets for the next three years to ensure continued improvement and organizational progress. This system has been used through one annual business cycle. Results from the past year show measurable success. The hospital has improved on 12 of the 15 strategic plan metrics, including achieving the targeted 1% operating surplus while operating in an environment of tremendous change and uncertainty. This article describes the strategic management system used at TEGH and demonstrates the formal integration of the plan into its operating and decision making processes. It also provides examples of the metrics, their use in decision-making and the variance reporting and improvement mechanisms. The article also demonstrates that a measurement-oriented approach to the planning and delivery of community hospital service is both achievable and valuable in terms of accountability and organizational responsiveness.

Development, Characterization and Validation of Trastuzumab-Modified Gold Nanoparticles for Molecularly Targeted Radiosensitization of Breast Cancer

NASA Astrophysics Data System (ADS)

Chattopadhyay, Niladri

The overexpression of the human epidermal growth factor receptor-2 (HER-2) in 20--25% of human breast cancers was investigated as a target for development of a gold nanoparticle (AuNP) based radiosensitizer for improving the efficacy of neoadjuvant X-radiation therapy of the disease. HER-2 targeted AuNPs were developed by covalently conjugating trastuzumab, a Health Canada approved monoclonal antibody for the treatment of HER-2-overexpressing breast cancer, to 30 nm AuNPs. Trastuzumab conjugated AuNPs were efficiently internalized by HER-2-overexpressing breast cancer cells (as assessed by darkfield microscopy and transmission electron microscopy) and increased DNA damage from X-radiation in these cells by more than 5-fold. To optimize delivery of AuNPs to HER-2-overexpressing tumors, high resolution microSPECT/CT imaging was used to track the in vivo fate of 111In-labelled non-targeted and HER-2 targeted AuNPs following intravenous (i.v.) or intratumoral (i.t.) injection. For i.v. injection, the effects of GdCl3 (for deactivation of macrophages) and non-specific (anti-CD20) antibody rituximab (for blocking of Fc mediated liver and spleen uptake) were studied. It was found that HER-2 targeting via attachment of trastuzumab paradoxically decreased tumor uptake as a result of faster elimination of the targeted AuNPs from the blood while improving internalization in HER-2-positive tumor cells as compared to non-targeted AuNPs. This phenomenon could be attributed to Fc-mediated recognition and subsequent sequestration of trastuzumab conjugated AuNP by the reticuloendothelial system (RES). Blocking of the RES did not increase tumor uptake of either HER-2 targeted or non-targeted AuNPs. Following i.t. injection, our results suggest that Au-NTs redistribute over time and traffick to the liver via the ipsilateral axillary lymph node leading to comparable exposure as seen with i.v. administration. In contrast, targeted AuNPs are bound and internalized by HER-2-overexpressing tumor cells following i.t. injection, with a lower proportion of AuNPs redistributing to normal tissues. In vivo, the combination of HER-2 targeted AuNPs injected i.t. and X-radiation (11 Gy) yielded a 46% decrease in tumor size over a 4 month period in contrast to an 11.5% increase in tumor size for X-radiation treatment alone. Toxicology studies (evaluated through complete blood cell counts, by serum transaminase and creatinine measurements and by monitoring the body weight) demonstrated no apparent normal organ toxicity from the combination of HER-2 targeted AuNPs and X-radiation. These results are promising for the clinical translation of HER-2-targeted AuNPs for radiosensitization of tumors to X-radiation.

Designing polymers with sugar-based advantages for bioactive delivery applications.

PubMed

Zhang, Yingyue; Chan, Jennifer W; Moretti, Alysha; Uhrich, Kathryn E

2015-12-10

Sugar-based polymers have been extensively explored as a means to increase drug delivery systems' biocompatibility and biodegradation. Here,we review he use of sugar-based polymers for drug delivery applications, with a particular focus on the utility of the sugar component(s) to provide benefits for drug targeting and stimuli responsive systems. Specifically, numerous synthetic methods have been developed to reliably modify naturally-occurring polysaccharides, conjugate sugar moieties to synthetic polymer scaffolds to generate glycopolymers, and utilize sugars as a multifunctional building block to develop sugar-linked polymers. The design of sugar-based polymer systems has tremendous implications on both the physiological and biological properties imparted by the saccharide units and are unique from synthetic polymers. These features include the ability of glycopolymers to preferentially target various cell types and tissues through receptor interactions, exhibit bioadhesion for prolonged residence time, and be rapidly recognized and internalized by cancer cells. Also discussed are the distinct stimuli-sensitive properties of saccharide-modified polymers to mediate drug release under desired conditions. Saccharide-based systems with inherent pH- and temperature-sensitive properties, as well as enzyme-cleavable polysaccharides for targeted bioactive delivery, are covered. Overall, this work emphasizes inherent benefits of sugar-containing polymer systems for bioactive delivery.

Optical Remote Sensing for Fence-Line Monitoring using Open-Path Quantum Cascade Laser (QCL) mono-static system for multiple target compounds in the Mid IR 7-13um (Fingerprint) region.

NASA Astrophysics Data System (ADS)

Zemek, P. G.

2017-12-01

Quantum Cascade Lasers (QCLs) are quickly replacing Tunable Diode Lasers (TDL) for multi-target species identification and quantification in both extractive and open-path (OP) Optical Remote Sensing (ORS) fence-line instrumentation. As was seen with TDL incorporation and pricing drops as the adoption by the telecommunications industry and its current scaling has improved robustness and pricing, the QCL is also, albiet more slowly, becoming a mature market. There are several advantages of QCLs over conventional TDLs such as improved brightness and beam density, high resolution, as well as the incorporation of external etalons or internal gratings to scan over wide spectral areas. QCLs typically operate in the Mid infra-red (MIR) as opposed to the Near-Infrared (NIR) region used with TDL. The MidIR is a target rich absorption band area where compounds have high absorbtivity coefficients resulting in better detection limits as compared to TDL instruments. The use of novel chemometrics and more sensitive non-cryo-cooled detectors has allowed some of the first QCL open-path instruments in both active and passive operation. Data and field studies of one of the newest QCL OP systems is presented that allows one system to measure multiple target compounds. Multiple QCL spectral regions may be stitched together to increase the capability of QCLs over TDL OP systems. A comparison of several ORS type systems will be presented.

Human Centered Autonomous and Assistant Systems Testbed for Exploration Operations

NASA Technical Reports Server (NTRS)

Malin, Jane T.; Mount, Frances; Carreon, Patricia; Torney, Susan E.

2001-01-01

The Engineering and Mission Operations Directorates at NASA Johnson Space Center are combining laboratories and expertise to establish the Human Centered Autonomous and Assistant Systems Testbed for Exploration Operations. This is a testbed for human centered design, development and evaluation of intelligent autonomous and assistant systems that will be needed for human exploration and development of space. This project will improve human-centered analysis, design and evaluation methods for developing intelligent software. This software will support human-machine cognitive and collaborative activities in future interplanetary work environments where distributed computer and human agents cooperate. We are developing and evaluating prototype intelligent systems for distributed multi-agent mixed-initiative operations. The primary target domain is control of life support systems in a planetary base. Technical approaches will be evaluated for use during extended manned tests in the target domain, the Bioregenerative Advanced Life Support Systems Test Complex (BIO-Plex). A spinoff target domain is the International Space Station (ISS) Mission Control Center (MCC). Prodl}cts of this project include human-centered intelligent software technology, innovative human interface designs, and human-centered software development processes, methods and products. The testbed uses adjustable autonomy software and life support systems simulation models from the Adjustable Autonomy Testbed, to represent operations on the remote planet. Ground operations prototypes and concepts will be evaluated in the Exploration Planning and Operations Center (ExPOC) and Jupiter Facility.

The national ignition facility high-energy ultraviolet laser system

NASA Astrophysics Data System (ADS)

Moses, Edward I.

2004-09-01

The National Ignition Facility (NIF), currently under construction at the Lawrence Livermore National Laboratory, is a stadium-sized facility containing a 192-beam, 1.8 MJ, 500 TW, ultraviolet laser system together with a 10-m diameter target chamber with room for nearly 100 experimental diagnostics. When completed, NIF will be the world's largest and most energetic laser experimental system, providing an international center to study inertial confinement fusion and the physics of matter at extreme energy densities and pressures. NIF's 192 energetic laser beams will compress fusion targets to conditions required for thermonuclear burn, liberating more energy than required to initiate the fusion reactions. Other NIF experiments will allow the study of physical processes at temperatures approaching 10 8 K and 10 11 Bar, conditions that exist naturally only in the interior of stars, planets and in nuclear weapons. NIF is now entering the first phases of its laser commissioning program. The first four beams of the NIF laser system have generated 106 kJ of infrared light and over 10 kJ at the third harmonic (351 nm). NIF's target experimental systems are also being installed in preparation for experiments to begin in late 2003. This paper provides a detailed look the NIF laser systems, the significant laser and optical systems breakthroughs that were developed, the results of recent laser commissioning shots, and plans for commissioning diagnostics for experiments on NIF.

Polymeric micelles and nanoemulsions as tumor-targeted drug carriers: Insight through intravital imaging.

PubMed

Rapoport, Natalya; Gupta, Roohi; Kim, Yoo-Shin; O'Neill, Brian E

2015-05-28

Intravital imaging of nanoparticle extravasation and tumor accumulation has revealed, for the first time, detailed features of carrier and drug behavior in circulation and tissue that suggest new directions for optimization of drug nanocarriers. Using intravital fluorescent microscopy, the extent of the extravasation, diffusion in the tissue, internalization by tissue cells, and uptake by the RES system were studied for polymeric micelles, nanoemulsions, and nanoemulsion-encapsulated drug. Discrimination of vascular and tissue compartments in the processes of micelle and nanodroplet extravasation and tissue accumulation was possible. A simple 1-D continuum model was suggested that allowed discriminating between various kinetic regimes of nanocarrier (or released drug) internalization in tumors of various sizes and cell density. The extravasation and tumor cell internalization occurred much faster for polymeric micelles than for nanoemulsion droplets. Fast micelle internalization resulted in the formation of a perivascular fluorescent coating around blood vessels. A new mechanism of micelle extravasation and internalization was suggested, based on the fast extravasation and internalization rates of copolymer unimers while maintaining micelle/unimer equilibrium in the circulation. The data suggested that to be therapeutically effective, nanoparticles with high internalization rate should manifest fast diffusion in the tumor tissue in order to avoid generation of concentration gradients that induce drug resistance. However an extra-fast diffusion should be avoided as it may result in the flow of extravasated nanoparticles from the tumor to normal organs, which would compromise targeting efficiency. The extravasation kinetics were different for nanodroplets and nanodroplet-encapsulated drug F-PTX suggesting a premature release of some fraction of the drug from the carrier. In conclusion, the development of an "ideal" drug carrier should involve the optimization of both drug retention and carrier diffusion parameters. Copyright © 2015 Elsevier B.V. All rights reserved.

A graphitic hollow carbon nitride nanosphere as a novel photochemical internalization agent for targeted and stimuli-responsive cancer therapy

NASA Astrophysics Data System (ADS)

Liu, Chaoqun; Chen, Zhaowei; Wang, Zhenzhen; Li, Wei; Ju, Enguo; Yan, Zhengqing; Liu, Zhen; Ren, Jinsong; Qu, Xiaogang

2016-06-01

As a novel technique, photochemical internalization (PCI) has been employed as a new approach to overcome endo/lysosomal restriction, which is one of the main difficulties in both drug and gene delivery. However, the complicated synthesis procedure (usually requiring the self-assembly of polymers, photosensitizers and cargos) and payload specificity greatly limit its further application. In this paper, we employ a highly fluorescent graphitic hollow carbon nitride nanosphere (GHCNS) to simultaneously serve as a PCI photosensitizer, an imaging agent and a drug carrier. The surface modification of GHCNS with multifunctional polysaccharide hyaluronic acid (HA) endows the system with colloidal stability, biocompatibility and cancer cell targeting ability. After CD44 receptor-mediated endocytosis, the nanosystem is embedded in endo/lysosomal vesicles and HA could be specially degraded by hyaluronidase (Hyal), inducing open pores. In the following, with visible light illumination, GHCNS could produce ROS that effectively induced lipid peroxidation and caused endo/lysosomal membrane break, accelerating the cytoplasmic release of the drug in the targeted and irradiated cells. As a result, significantly increased therapeutic potency and specificity against cancer cells could be achieved.As a novel technique, photochemical internalization (PCI) has been employed as a new approach to overcome endo/lysosomal restriction, which is one of the main difficulties in both drug and gene delivery. However, the complicated synthesis procedure (usually requiring the self-assembly of polymers, photosensitizers and cargos) and payload specificity greatly limit its further application. In this paper, we employ a highly fluorescent graphitic hollow carbon nitride nanosphere (GHCNS) to simultaneously serve as a PCI photosensitizer, an imaging agent and a drug carrier. The surface modification of GHCNS with multifunctional polysaccharide hyaluronic acid (HA) endows the system with colloidal stability, biocompatibility and cancer cell targeting ability. After CD44 receptor-mediated endocytosis, the nanosystem is embedded in endo/lysosomal vesicles and HA could be specially degraded by hyaluronidase (Hyal), inducing open pores. In the following, with visible light illumination, GHCNS could produce ROS that effectively induced lipid peroxidation and caused endo/lysosomal membrane break, accelerating the cytoplasmic release of the drug in the targeted and irradiated cells. As a result, significantly increased therapeutic potency and specificity against cancer cells could be achieved. Electronic supplementary information (ESI) available. See DOI: 10.1039/c5nr07719b

Evaluation of the internal and external biofidelity of current rear impact ATDs to response targets developed from moderate-speed rear impacts of PMHS.

PubMed

Moorhouse, Kevin; Donnelly, Bruce; Kang, Yun-Seok; Bolte, John H; Herriott, Rodney

2012-10-01

The goal of this study is to evaluate both the internal and external biofidelity of existing rear impact anthropomorphic test devices (BioRID II, RID3D, Hybrid III 50th) in two moderate-speed rear impact sled test conditions (8.5g, 17 km/h; 10.5g, 24 km/h) by quantitatively comparing the ATD responses to biomechanical response targets developed from PMHS testing in a corresponding study. The ATDs and PMHS were tested in an experimental seat system that is capable of simulating the dynamic seat back rotation response of production seats. The experimental seat contains a total of fourteen load cells installed such that external loads from the ATDs and PMHS can be measured to evaluate external biofidelity. The PMHS were instrumented to correspond to the instrumentation contained in the ATDs so that direct comparison between ATDs and PMHS could be made to evaluate internal biofidelity. The NHTSA Biofidelity Ranking system was used to quantitatively evaluate the biofidelity of the ATDs and an additional tool was introduced and utilized which allows for the biofidelity score to be partitioned into components of amplitude, phase, and shape. For internal biofidelity, the BioRID II and RID3D were more biofidelic than the Hybrid III in the 17 km/h test, and the BioRID II was most biofidelic in the 24 km/h test. For external biofidelity, the BioRID II was most biofidelic in the 17 km/h test, while both the BioRID II and the RID3D were more biofidelic than the Hybrid III in the 24 km/h test. Overall, the BioRID II demonstrated the best biofidelity in both the 17 km/h and 24 km/h tests.

Converting an AEG Cyclotron to H- Acceleration and Extraction

NASA Astrophysics Data System (ADS)

Ramsey, Fred; Carroll, Lewis; Rathmann, Tom; Huenges, Ernst; Bechtold, Matthias Mentler Volker

2009-03-01

Clinical Trials are under way to evaluate agents labeled with the nuclide 225Ac and its decay product 213Bi, in targeted alpha-immuno-therapy [1]. 225Ac can be produced on a medium-energy cyclotron via the nuclear reaction 226Ra(p,n)225Ac. To demonstrate proof-of-principle, a vintage AEG cyclotron, Model E33 [2], with an internal target, had been employed in a pilot production program at the Technical University of Munich (TUM). To enhance production capability and further support the clinical studies, the TUM facility has recently been refurbished and upgraded, adding a new external beam-line, automated target irradiation and transport systems, new laboratories, hot cells, etc. [3]. An improved high-power rotating target has been built and installed [4]. The AEG cyclotron itself has also been modified and upgraded to accelerate and extract H- ions. We have designed, built, and tested a new axial Penning-type ion source which is optimized for the production of H- ions. The ion source has continued to evolve through experiment and experience. Steady improvements in materials and mechanics have led to enhanced source stability, life-time, and H- production. We have also designed and built a precision H- charge-exchange beam-extraction system which is equipped with a vacuum lock. To fit within the tight mechanical constraint imposed by the narrow magnet gap, the system incorporates a novel chain-drive foil holder and foil-changer mechanism. The reconfigured cyclotron system has now been in operation for more than 1 year. Three long-duration target irradiations have been conducted. The most recent bombardment ran 160 continuous hours at a beam on target of ˜80 microamperes for a total yield of ˜70 milli-curies of 225Ac.

An international observational study suggests that artificial intelligence for clinical decision support optimizes anemia management in hemodialysis patients.

PubMed

Barbieri, Carlo; Molina, Manuel; Ponce, Pedro; Tothova, Monika; Cattinelli, Isabella; Ion Titapiccolo, Jasmine; Mari, Flavio; Amato, Claudia; Leipold, Frank; Wehmeyer, Wolfgang; Stuard, Stefano; Stopper, Andrea; Canaud, Bernard

2016-08-01

Managing anemia in hemodialysis patients can be challenging because of competing therapeutic targets and individual variability. Because therapy recommendations provided by a decision support system can benefit both patients and doctors, we evaluated the impact of an artificial intelligence decision support system, the Anemia Control Model (ACM), on anemia outcomes. Based on patient profiles, the ACM was built to recommend suitable erythropoietic-stimulating agent doses. Our retrospective study consisted of a 12-month control phase (standard anemia care), followed by a 12-month observation phase (ACM-guided care) encompassing 752 patients undergoing hemodialysis therapy in 3 NephroCare clinics located in separate countries. The percentage of hemoglobin values on target, the median darbepoetin dose, and individual hemoglobin fluctuation (estimated from the intrapatient hemoglobin standard deviation) were deemed primary outcomes. In the observation phase, median darbepoetin consumption significantly decreased from 0.63 to 0.46 μg/kg/month, whereas on-target hemoglobin values significantly increased from 70.6% to 76.6%, reaching 83.2% when the ACM suggestions were implemented. Moreover, ACM introduction led to a significant decrease in hemoglobin fluctuation (intrapatient standard deviation decreased from 0.95 g/dl to 0.83 g/dl). Thus, ACM support helped improve anemia outcomes of hemodialysis patients, minimizing erythropoietic-stimulating agent use with the potential to reduce the cost of treatment. Copyright © 2016 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.

A proposed new international convention supporting the rights of pregnant women and girls and their newborn infants.

PubMed

Winrow, Benjamin; Bile, Khalif; Hafeez, Assad; Davies, Hugh; Brown, Nick; Zafar, Shamsa; Cham, Mamady; Phillips, Barbara; MacDonald, Rhona; Southall, David P

2012-05-01

For a multitude of eminently modifiable reasons, death rates for pregnant women and girls and their newborn infants in poorly resourced countries remain unacceptably high. The concomitant high morbidity rates compound the situation. The rights of these vulnerable individuals are incompletely protected by existing United Nations human rights conventions, which many countries have failed to implement. The authors propose a novel approach grounded on both human rights and robust evidence-based clinical guidelines to create a 'human rights convention specifically for pregnant women and girls and their newborn infants'. The approach targets the 'right to health' of these large, vulnerable and neglected populations. The proposed convention is designed so that it can be monitored, audited and evaluated objectively. It should also foster a sense of national ownership and accountability as it is designed to be relevant to local situations and to be incorporated into local clinical governance systems. It may be of particular value to those countries that are not yet on target to meet the Millennium Development Goals (MDGs), especially MDGs 4 and 5, which target child and maternal mortality, respectively. To foster a sense of international responsibility, two additional initiatives are integral to its philosophy: the promotion of twinning between well and poorly resourced regions and a raising of awareness of how some well-resourced countries can damage the health of mothers and babies, for example, through the recruitment of health workers trained by national governments and taken from the public health system.

New developments of a knowledge based system (VEG) for inferring vegetation characteristics

NASA Technical Reports Server (NTRS)

Kimes, D. S.; Harrison, P. A.; Harrison, P. R.

1992-01-01

An extraction technique for inferring physical and biological surface properties of vegetation using nadir and/or directional reflectance data as input has been developed. A knowledge-based system (VEG) accepts spectral data of an unknown target as input, determines the best strategy for inferring the desired vegetation characteristic, applies the strategy to the target data, and provides a rigorous estimate of the accuracy of the inference. Progress in developing the system is presented. VEG combines methods from remote sensing and artificial intelligence, and integrates input spectral measurements with diverse knowledge bases. VEG has been developed to (1) infer spectral hemispherical reflectance from any combination of nadir and/or off-nadir view angles; (2) test and develop new extraction techniques on an internal spectral database; (3) browse, plot, or analyze directional reflectance data in the system's spectral database; (4) discriminate between user-defined vegetation classes using spectral and directional reflectance relationships; and (5) infer unknown view angles from known view angles (known as view angle extension).

Towards a high sensitivity small animal PET system based on CZT detectors (Conference Presentation)

NASA Astrophysics Data System (ADS)

Abbaszadeh, Shiva; Levin, Craig

2017-03-01

Small animal positron emission tomography (PET) is a biological imaging technology that allows non-invasive interrogation of internal molecular and cellular processes and mechanisms of disease. New PET molecular probes with high specificity are under development to target, detect, visualize, and quantify subtle molecular and cellular processes associated with cancer, heart disease, and neurological disorders. However, the limited uptake of these targeted probes leads to significant reduction in signal. There is a need to advance the performance of small animal PET system technology to reach its full potential for molecular imaging. Our goal is to assemble a small animal PET system based on CZT detectors and to explore methods to enhance its photon sensitivity. In this work, we reconstruct an image from a phantom using a two-panel subsystem consisting of six CZT crystals in each panel. For image reconstruction, coincidence events with energy between 450 and 570 keV were included. We are developing an algorithm to improve sensitivity of the system by including multiple interaction events.

Creep stability of the proposed AIDA mission target 65803 Didymos: I. Discrete cohesionless granular physics model

NASA Astrophysics Data System (ADS)

Zhang, Yun; Richardson, Derek C.; Barnouin, Olivier S.; Maurel, Clara; Michel, Patrick; Schwartz, Stephen R.; Ballouz, Ronald-Louis; Benner, Lance A. M.; Naidu, Shantanu P.; Li, Junfeng

2017-09-01

As the target of the proposed Asteroid Impact & Deflection Assessment (AIDA) mission, the near-Earth binary asteroid 65803 Didymos represents a special class of binary asteroids, those whose primaries are at risk of rotational disruption. To gain a better understanding of these binary systems and to support the AIDA mission, this paper investigates the creep stability of the Didymos primary by representing it as a cohesionless self-gravitating granular aggregate subject to rotational acceleration. To achieve this goal, a soft-sphere discrete element model (SSDEM) capable of simulating granular systems in quasi-static states is implemented and a quasi-static spin-up procedure is carried out. We devise three critical spin limits for the simulated aggregates to indicate their critical states triggered by reshaping and surface shedding, internal structural deformation, and shear failure, respectively. The failure condition and mode, and shear strength of an aggregate can all be inferred from the three critical spin limits. The effects of arrangement and size distribution of constituent particles, bulk density, spin-up path, and interparticle friction are numerically explored. The results show that the shear strength of a spinning self-gravitating aggregate depends strongly on both its internal configuration and material parameters, while its failure mode and mechanism are mainly affected by its internal configuration. Additionally, this study provides some constraints on the possible physical properties of the Didymos primary based on observational data and proposes a plausible formation mechanism for this binary system. With a bulk density consistent with observational uncertainty and close to the maximum density allowed for the asteroid, the Didymos primary in certain configurations can remain geo-statically stable without requiring cohesion.

On certain development aspects of an ipsas-based system-target approach to evaluation of net asset sustainability level projects in high-rise construction

NASA Astrophysics Data System (ADS)

Kazaryan, Ruben

2018-03-01

Problems of accounting and reporting of net assets and the procedure of their formation taking into account the specifics of the economic and legal status of property of a non-commercial autonomous institution are some of the most controversial in the accounting for entities of the public sector. The study focuses on justification of accounting rules for net assets of public sector entities. The methods used in the study are as follows: comparison, synthesis, analysis, logical approach, and system approach. The article examines legal aspects and specifics of recognition of assets of public sector entities in accordance with IPSAS standards (International Public Sector Accounting Standards are a set of accounting standards issued by IPSASB (Council for International Financial Reporting Standards for Public Sector Organizations) used by state-owned enterprises worldwide in preparation of financial statements as of the 31st of August, 2015. The most crucial factor in the modeling of key performance indicators of the system-target approach to estimation of the sustainability level of net assets on the basis of IPSAS is a multicriterial evaluation of the basic management strategy for quality system elements used in operational and strategic planning projects operations in high-rise construction. We offer an alternative evaluation of assets due to be returned to the right holder (the state controller) in the event of liquidation of a public sector entity.

First internal and external experiments at COSY Juelich

NASA Astrophysics Data System (ADS)

Prasuhn, D.; Maier, R.; Bechstedt, U.; Dietrich, J.; Hacker, U.; Martin, S.; Stockhorst, H.; Tölle, R.; Grzonka, D.; Nake, C.; Mosel, F.

1995-02-01

The inauguration of the cooler synchrotron COSY Jülich was celebrated on April 1st, 1993. After the first successful acceleration to proton momenta above 800 GeV/ c, beamtimes for experiments were scheduled in parallel to further machine development. The first experiment was the internal target experiment EDDA, which investigated the energy dependence of the p-p interaction. It makes use of a 3 × 4 μm 2 thin CH 2 fiber as an internal target. The thickness of the fiber is more than adequate to achieve high luminosities, so the intensity of the stored beam has to be reduced to 10 7 p. On the other hand, it is thin enough to achieve beam lifetimes of 3 s at 1.4 GeV/ c. Details of the target fabrication and the first experimental results will be discussed. Both external experimental facilities at COSY, the time-of-flight spectrometer, and the magnetic spectrometer BIG KARL use a liquid hydrogen (deuterium) target. The first experiments were carried out at proton energies between 300 MeV and 500 MeV. Also, these experimental data will be presented. Two further internal experiments are prepared for the installation into the COSY ring. The target for the first experiment is a gas-jet target, the second experiment uses ribbon targets for the interaction. The status of both experimental setups will be shown.

An assessment of interactions between global health initiatives and country health systems.

PubMed

Samb, Badara; Evans, Tim; Dybul, Mark; Atun, Rifat; Moatti, Jean-Paul; Nishtar, Sania; Wright, Anna; Celletti, Francesca; Hsu, Justine; Kim, Jim Yong; Brugha, Ruairi; Russell, Asia; Etienne, Carissa

2009-06-20

Since 2000, the emergence of several large disease-specific global health initiatives (GHIs) has changed the way in which international donors provide assistance for public health. Some critics have claimed that these initiatives burden health systems that are already fragile in countries with few resources, whereas others have asserted that weak health systems prevent progress in meeting disease-specific targets. So far, most of the evidence for this debate has been provided by speculation and anecdotes. We use a review and analysis of existing data, and 15 new studies that were submitted to WHO for the purpose of writing this Report to describe the complex nature of the interplay between country health systems and GHIs. We suggest that this Report provides the most detailed compilation of published and emerging evidence so far, and provides a basis for identification of the ways in which GHIs and health systems can interact to mutually reinforce their effects. On the basis of the findings, we make some general recommendations and identify a series of action points for international partners, governments, and other stakeholders that will help ensure that investments in GHIs and country health systems can fulfil their potential to produce comprehensive and lasting results in disease-specific work, and advance the general public health agenda. The target date for achievement of the health-related Millennium Development Goals is drawing close, and the economic downturn threatens to undermine the improvements in health outcomes that have been achieved in the past few years. If adjustments to the interactions between GHIs and country health systems will improve efficiency, equity, value for money, and outcomes in global public health, then these opportunities should not be missed.

Targets and processes for fabricating same

DOEpatents

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

2012-07-24

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

Targets and processes for fabricating same

DOEpatents

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

2016-05-17

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

Targets and processes for fabricating same

DOEpatents

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

2014-06-10

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

How much importance do we give to target audiences in article writing?

PubMed

Nedjat, Sima; Nedjat, Saharnaz; Gholami, Jaleh; Ashoorkhani, Mahnaz; Maleki, Katayoun; Hejrie, Soroush Mortaz; Majdzadeh, Reza

2010-01-01

Writing papers can be used as a means to convey a message. Knowledge transfer is also about conveying the right message to the right target audience. The aim of this study was to determine the proportion of articles that had mentioned a clear message and the target audience in the abstract and the article as a whole, and also to examine their association with different determinant factors. Articles published from 2001 to 2006 that were based on clinical and health system research conducted on Iranian populations and on maternal care, diabetes and tuberculosis were searched systematically in domestic and international databases. Eventually checklists (Additional file 1) were completed for 795 articles. Overall, 98.5% of articles had a clear message, whereas 12.5% had addressed the direct target audience. Presence of a clear message in formatted abstracts were seen 3.6 times more (CI95%: 1.5-8.7) than in articles without formatted abstracts (p = 0.005). Addressing of the direct target audience was seen twice as much in health system research articles as compared to clinical studies, odds ratio was 2.3 (CI95%: 1.47-3.48, p<0.001). Creating a format for journal abstracts seems to be an effective intervention for presenting the message in articles.

In Vivo Bio-distribution and Efficient Tumor Targeting of Gelatin/Silica Nanoparticles for Gene Delivery

NASA Astrophysics Data System (ADS)

Zhao, Xueqin; Wang, Jun; Tao, SiJie; Ye, Ting; Kong, Xiangdong; Ren, Lei

2016-04-01

The non-viral gene delivery system is an attractive alternative to cancer therapy. The clinical success of non-viral gene delivery is hampered by transfection efficiency and tumor targeting, which can be individually overcome by addition of functional modules such as cell penetration or targeting. Here, we first engineered the multifunctional gelatin/silica (GS) nanovectors with separately controllable modules, including tumor-targeting aptamer AGRO100, membrane-destabilizing peptide HA2, and polyethylene glycol (PEG), and then studied their bio-distribution and in vivo transfection efficiencies by contrast resonance imaging (CRI). The results suggest that the sizes and zeta potentials of multifunctional gelatin/silica nanovectors were 203-217 nm and 2-8 mV, respectively. Functional GS-PEG nanoparticles mainly accumulated in the liver and tumor, with the lowest uptake by the heart and brain. Moreover, the synergistic effects of tumor-targeting aptamer AGRO100 and fusogenic peptide HA2 promoted the efficient cellular internalization in the tumor site. More importantly, the combined use of AGRO100 and PEG enhanced tumor gene expression specificity and effectively reduced toxicity in reticuloendothelial system (RES) organs after intravenous injection. Additionally, low accumulation of GS-PEG was observed in the heart tissues with high gene expression levels, which could provide opportunities for non-invasive gene therapy.

G protein-coupled receptor internalization assays in the high-content screening format.

PubMed

Haasen, Dorothea; Schnapp, Andreas; Valler, Martin J; Heilker, Ralf

2006-01-01

High-content screening (HCS), a combination of fluorescence microscopic imaging and automated image analysis, has become a frequently applied tool to study test compound effects in cellular disease-modeling systems. This chapter describes the measurement of G protein-coupled receptor (GPCR) internalization in the HCS format using a high-throughput, confocal cellular imaging device. GPCRs are the most successful group of therapeutic targets on the pharmaceutical market. Accordingly, the search for compounds that interfere with GPCR function in a specific and selective way is a major focus of the pharmaceutical industry today. This chapter describes methods for the ligand-induced internalization of GPCRs labeled previously with either a fluorophore-conjugated ligand or an antibody directed against an N-terminal tag of the GPCR. Both labeling techniques produce robust assay formats. Complementary to other functional GPCR drug discovery assays, internalization assays enable a pharmacological analysis of test compounds. We conclude that GPCR internalization assays represent a valuable medium/high-throughput screening format to determine the cellular activity of GPCR ligands.

Perceptual Factors Influence Visual Search for Meaningful Symbols In Individuals with Intellectual Disabilities and Down Syndrome or Autism Spectrum Disorders

PubMed Central

Wilkinson, Krista M.; McIlvane, William J.

2013-01-01

Augmentative and alternative communication (AAC) systems often supplement oral communication of individuals with intellectual and communication disabilities. Research with nondisabled preschoolers has demonstrated that two visual perceptual factors influence speed and/or accuracy of finding a target - the internal color and spatial organization of symbols. Twelve participants with Down syndrome and 12 with ASD underwent two search tasks. In one, the symbols were clustered by internal color; in the other the identical symbols had no arrangement cue. Visual search was superior in participants with ASD compared to those with Down syndrome. In both groups, responses were significantly faster when the symbols were clustered by internal color. Construction of aided AAC displays may benefit from attention to their physical/perceptual features. PMID:24245729

Innovative Technology Development for Comprehensive Air Quality Characterization from Open Burning

DTIC Science & Technology

2012-04-01

Burning/Open Detonation (OB/OD) has been used as a safe, effective , and economic way to demilitarize munitions for energetic material disposal. Field...target analyte i (lb/lb i in ordnance) ERDC-CERL Engineer Research Development Center, Construction Engineering Research Laboratory GC/FID gas ...chromatograph(y) - flame ionization detector GC/MS gas chromatography/mass spectrometry GPS global positioning system ISO International Organization for

Advanced Training Techniques Using Computer Generated Imagery.

DTIC Science & Technology

1983-02-28

described in this report has been made and is submitted along with this report. Unfortunately, the quality possible on standard monochromic 525 line...video tape is not representative of the quality of the presentations as displayed on a color beam penetration visual system, but one can, through the...YORK - LAGUARDIA (TWILIGHT) SEA SURFACE AND WAKE MINNEAPOLIS - ST. PAUL KC-135 TANKER INTERNATIONAL (TWILIGHT) MINNEAPOLIS - ST. PAUL GROUND TARGETS

STS-104 crewmembers in Building 9NW

NASA Image and Video Library

2001-01-17

JSC2001-00082 (January 2001) --- Astronauts Michael L. Gernhardt (left) and Janet L. Kavandi, both mission specialists, are pictured while in training at the Systems Integration Facility at Johnson Space Center (JSC). The STS-104 mission to the International Space Station (ISS) represents the Space Shuttle Atlantis' first flight using a new engine and is targeted for a liftoff no earlier than June 14, 2001.

Who Must We Target Now to Minimize Future Cardiovascular Events and Total Mortality?: Lessons From the Surveillance, Prevention and Management of Diabetes Mellitus (SUPREME-DM) Cohort Study.

PubMed

Desai, Jay R; Vazquez-Benitez, Gabriela; Xu, Zhiyuan; Schroeder, Emily B; Karter, Andrew J; Steiner, John F; Nichols, Gregory A; Reynolds, Kristi; Xu, Stanley; Newton, Katherine; Pathak, Ram D; Waitzfelder, Beth; Lafata, Jennifer Elston; Butler, Melissa G; Kirchner, H Lester; Thomas, Abraham; O'Connor, Patrick J

2015-09-01

Examining trends in cardiovascular events and mortality in US health systems can guide the design of targeted clinical and public health strategies to reduce cardiovascular events and mortality rates. We conducted an observational cohort study from 2005 to 2011 among 1.25 million diabetic subjects and 1.25 million nondiabetic subjects from 11 health systems that participate in the Surveillance, Prevention and Management of Diabetes Mellitus (SUPREME-DM) DataLink. Annual rates (per 1000 person-years) of myocardial infarction/acute coronary syndrome (International Classification of Diseases-Ninth Revision, 410.0–410.91, 411.1–411.8), stroke (International Classification of Diseases-Ninth Revision, 430–432.9, 433–434.9), heart failure (International Classification of Diseases-Ninth Revision, 428–428.9), and all-cause mortality were monitored by diabetes mellitus (DM) status, age, sex, race/ethnicity, and a prior cardiovascular history. We observed significant declines in cardiovascular events and mortality rates in subjects with and without DM. However, there was substantial variation by age, sex, race/ethnicity, and prior cardiovascular history. Mortality declined from 44.7 to 27.1 (P<0.0001) for those with DM and cardiovascular disease (CVD), from 11.2 to 10.9 (P=0.03) for those with DM only, and from 18.9 to 13.0 (P<0.0001) for those with CVD only. Yet, in the [almost equal to]85% of subjects with neither DM nor CVD, overall mortality (7.0 to 6.8; P=0.10) and stroke rates (1.6–1.6; P=0.77) did not decline and heart failure rates increased (0.9–1.15; P=0.0005). To sustain improvements in myocardial infarction, stroke, heart failure, and mortality, health systems that have successfully focused on care improvement in high-risk adults with DM or CVD must broaden their improvement strategies to target lower risk adults who have not yet developed DM or CVD.

Surrogate target cells expressing surface anti-idiotype antibody for the clinical evaluation of an internalizing CD22-specific antibody.

PubMed

Leung, Shui-On; Gao, Kai; Wang, Guang Yu; Cheung, Benny Ka-Wa; Lee, Kwan-Yeung; Zhao, Qi; Cheung, Wing-Tai; Wang, Jun Zhi

2015-01-01

SM03, a chimeric antibody that targets the B-cell restricted antigen CD22, is currently being clinically evaluated for the treatment of lymphomas and other autoimmune diseases in China. SM03 binding to surface CD22 leads to rapid internalization, making the development of an appropriate cell-based bioassay for monitoring changes in SM03 bioactivities during production, purification, storage, and clinical trials difficult. We report herein the development of an anti-idiotype antibody against SM03. Apart from its being used as a surrogate antigen for monitoring SM03 binding affinities, the anti-idiotype antibody was engineered to express as fusion proteins on cell surfaces in a non-internalizing manner, and the engineered cells were used as novel "surrogate target cells" for SM03. SM03-induced complement-mediated cytotoxicity (CMC) against these "surrogate target cells" proved to be an effective bioassay for monitoring changes in Fc functions, including those resulting from minor structural modifications borne within the Fc-appended carbohydrates. The approach can be generally applied for antibodies that target rapidly internalizing or non-surface bound antigens. The combined use of the anti-idiotype antibody and the surrogate target cells could help evaluate clinical parameters associated with safety and efficacies, and possibly the mechanisms of action of SM03.

Essential biodiversity variables

USGS Publications Warehouse

Pereira, H.M.; Ferrier, S.; Walters, M.; Geller, G.N.; Jongman, R.H.G.; Scholes, Robert J.; Bruford, M.W.; Brummitt, N.; Butchart, S.H.M.; Cardoso, A.C.; Coops, N.C.; Dulloo, E.; Faith, D.P.; Freyhof, J.; Gregory, R.D.; Heip, C.; Höft, R.; Hurtt, G.; Jetz, W.; Karp, D.S.; McGeoch, M.A.; Obura, D.; Onada, Y.; Pettorelli, N.; Reyers, B.; Sayre, R.; Scharlemann, J.P.W.; Stuart, S.N.; Turak, E.; Walpole, M.; Wegmann, M.

2013-01-01

Reducing the rate of biodiversity loss and averting dangerous biodiversity change are international goals, reasserted by the Aichi Targets for 2020 by Parties to the United Nations (UN) Convention on Biological Diversity (CBD) after failure to meet the 2010 target (1, 2). However, there is no global, harmonized observation system for delivering regular, timely data on biodiversity change (3). With the first plenary meeting of the Intergovernmental Science-Policy Platform on Biodiversity and Ecosystem Services (IPBES) soon under way, partners from the Group on Earth Observations Biodiversity Observation Network (GEO BON) (4) are developing—and seeking consensus around—Essential Biodiversity Variables (EBVs) that could form the basis of monitoring programs worldwide.

Nanoparticles in the ocular drug delivery

PubMed Central

Zhou, Hong-Yan; Hao, Ji-Long; Wang, Shuang; Zheng, Yu; Zhang, Wen-Song

2013-01-01

Ocular drug transport barriers pose a challenge for drug delivery comprising the ocular surface epithelium, the tear film and internal barriers of the blood-aqueous and blood-retina barriers. Ocular drug delivery efficiency depends on the barriers and the clearance from the choroidal, conjunctival vessels and lymphatic. Traditional drug administration reduces the clinical efficacy especially for poor water soluble molecules and for the posterior segment of the eye. Nanoparticles (NPs) have been designed to overcome the barriers, increase the drug penetration at the target site and prolong the drug levels by few internals of drug administrations in lower doses without any toxicity compared to the conventional eye drops. With the aid of high specificity and multifunctionality, DNA NPs can be resulted in higher transfection efficiency for gene therapy. NPs could target at cornea, retina and choroid by surficial applications and intravitreal injection. This review is concerned with recent findings and applications of NPs drug delivery systems for the treatment of different eye diseases. PMID:23826539

Multifunctional High Drug Loading Nanocarriers for Cancer Drug Delivery

NASA Astrophysics Data System (ADS)

Jin, Erlei

2011-12-01

Most anticancer drugs have poor water-solubility, rapid blood clearance, low tumor-selectivity and severe systemic toxicity to healthy tissues. Thus, polymeric nanocarriers have been widely explored for anticancer drugs to solve these problems. However, polymer nanocarriers developed to date still suffer drawbacks including low drug loading contents, premature drug release, slow cellular internalization, slow intracellular drug release and thereby low therapeutic efficiency in cancer thermotherapy. Accordingly, in this dissertation, functional nanocapsules and nanoparticles including high drug loading liposome-like nanocapsules, high drug loading phospholipid-mimic nanocapsules with fast intracellular drug release, high drug loading charge-reversal nanocapsules, TAT based long blood circulation nanoparticles and charge-reversal nuclear targeted nanoparticles are designed and synthesized. These functional carriers have advantages such as high drug loading contents without premature drug release, fast cellular internalization and intracellular drug release, nuclear targeted delivery and long blood circulation. As a result, all these drug carriers show much higher in vitro and in vivo anti-cancer activities.

Targeted opportunities to address the climate-trade dilemma in China

NASA Astrophysics Data System (ADS)

Liu, Zhu; Davis, Steven J.; Feng, Kuishuang; Hubacek, Klaus; Liang, Sai; Anadon, Laura Diaz; Chen, Bin; Liu, Jingru; Yan, Jinyue; Guan, Dabo

2016-02-01

International trade has become the fastest growing driver of global carbon emissions, with large quantities of emissions embodied in exports from emerging economies. International trade with emerging economies poses a dilemma for climate and trade policy: to the extent emerging markets have comparative advantages in manufacturing, such trade is economically efficient and desirable. However, if carbon-intensive manufacturing in emerging countries such as China entails drastically more CO2 emissions than making the same product elsewhere, then trade increases global CO2 emissions. Here we show that the emissions embodied in Chinese exports, which are larger than the annual emissions of Japan or Germany, are primarily the result of China’s coal-based energy mix and the very high emissions intensity (emission per unit of economic value) in a few provinces and industry sectors. Exports from these provinces and sectors therefore represent targeted opportunities to address the climate-trade dilemma by either improving production technologies and decarbonizing the underlying energy systems or else reducing trade volumes.

New insights on food intake control by olfactory processes: the emerging role of the endocannabinoid system.

PubMed

Soria-Gomez, Edgar; Bellocchio, Luigi; Marsicano, Giovanni

2014-11-01

The internal state of the organism is an important modulator of perception and behavior. The link between hunger, olfaction and feeding behavior is one of the clearest examples of these connections. At the neurobiological level, olfactory circuits are the targets of several signals (i.e. hormones and nutrients) involved in energy balance. This indicates that olfactory areas are potential sensors of the internal state of the organism. Thus, the aim of this manuscript is to review the literature showing the interplay between metabolic signals in olfactory circuits and its impact on food intake. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Freeform array projection

NASA Astrophysics Data System (ADS)

Michaelis, D.; Schreiber, P.; Li, C.; Bräuer, A.; Gross, H.

2015-09-01

The concept of multichannel array projection is generalized in order to realize an ultraslim, highly efficient optical system for structured illumination with high lumen output, where additionally the Köhler illumination principle is utilized and source light homogenization occurs. The optical system consists of a multitude of neighboring optical channels. In each channel two optical freeforms generate a real or a virtual spatial light pattern and furthermore, the ray directions are modified to enable Köhler illumination of a subsequent projection lens. The internal light pattern may be additionally influenced by absorbing apertures or slides. The projection lens transfers the resulting light pattern to a target, where the total target distribution is produced by superposition of all individual channel output pattern. The optical system without absorbing apertures can be regarded as a generalization of a fly's eye condenser for structured illumination. In this case light pattern is exclusively generated by freeform light redistribution. The commonly occurring blurring effect for freeform beamshaping is reduced due to the creation of a virtual object light structure by means of the two freeform surfaces and its imaging towards the target. But, the remaining blurring inhibits very high spatial frequencies at the target. In order to create target features with very high spatial resolution the absorbing apertures can be utilized. In this case the freeform beamshaping can be used for an enhanced light transmission through the absorbing apertures. The freeform surfaces are designed by a generalized approach of Cartesian oval representation.

Effect of tumor amplitude and frequency on 4D modeling of Vero4DRT system.

PubMed

Miura, Hideharu; Ozawa, Shuichi; Hayata, Masahiro; Tsuda, Shintaro; Yamada, Kiyoshi; Nagata, Yasushi

2017-01-01

An important issue in indirect dynamic tumor tracking with the Vero4DRT system is the accuracy of the model predictions of the internal target position based on surrogate infrared (IR) marker measurement. We investigated the predictive uncertainty of 4D modeling using an external IR marker, focusing on the effect of the target and surrogate amplitudes and periods. A programmable respiratory motion table was used to simulate breathing induced organ motion. Sinusoidal motion sequences were produced by a dynamic phantom with different amplitudes and periods. To investigate the 4D modeling error, the following amplitudes (peak-to-peak: 10-40 mm) and periods (2-8 s) were considered. The 95th percentile 4D modeling error (4D- E 95% ) between the detected and predicted target position ( μ  + 2SD) was calculated to investigate the 4D modeling error. 4D- E 95% was linearly related to the target motion amplitude with a coefficient of determination R 2  = 0.99 and ranged from 0.21 to 0.88 mm. The 4D modeling error ranged from 1.49 to 0.14 mm and gradually decreased with increasing target motion period. We analyzed the predictive error in 4D modeling and the error due to the amplitude and period of target. 4D modeling error substantially increased with increasing amplitude and decreasing period of the target motion.

Anti-DR5 monoclonal antibody-mediated DTIC-loaded nanoparticles combining chemotherapy and immunotherapy for malignant melanoma: target formulation development and in vitro anticancer activity

PubMed Central

Ding, Baoyue; Wu, Xin; Fan, Wei; Wu, Zhaoyong; Gao, Jing; Zhang, Wei; Ma, Lulu; Xiang, Wang; Zhu, Quangang; Liu, Jiyong; Ding, Xueying; Gao, Shen

2011-01-01

Background The increased incidence of malignant melanoma in recent decades, along with its high mortality rate and pronounced resistance to therapy pose an enormous challenge. Novel therapeutic strategies, such as immunotherapy and targeted therapy, are urgently needed for melanoma. In this study, a new active targeting drug delivery system was constructed to combine chemotherapy and active specific immunotherapy. Methods The chemotherapeutic drug, dacarbazine (DTIC), that induces apoptosis through the intrinsic pathway which typically responds to severe DNA damage, was used as a model drug to prepare DTIC-loaded polylactic acid (PLA) nanoparticles (DTIC-NPs), which were covalently conjugated to a highly specific targeting functional TRAIL-receptor 2 (DR5) monoclonal antibody (mAb) that can contribute directly to cancer cell apoptosis or growth inhibition through the extrinsic pathway. Results Our in vitro experiments demonstrated that DTIC-PLA-DR5 mAb nanoparticles (DTIC-NPs-DR5 mAb) are an active targeting drug delivery system which can specifically target DR5-overexpressing malignant melanoma cells and become efficiently internalized. Most strikingly, compared with conventional DTIC-NPs, DTIC-NPs-DR5 mAb showed significantly enhanced cytotoxicity and increased cell apoptosis in DR5-positive malignant melanoma cells. Conclusion The DTIC-NPs-DR5 mAb described in this paper might be a potential formulation for targeting chemotherapy and immunotherapy to DR5-overexpressing metastatic melanoma. PMID:21976975

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

First results on the measurements of the proton beam polarization at internal target at Nuclotron1

NASA Astrophysics Data System (ADS)

Ladygin, V. P.; Gurchin, Yu V.; Isupov, A. Yu; Janek, M.; Khrenov, A. N.; Kurilkin, P. K.; Livanov, A. N.; Piyadin, S. M.; Reznikov, S. G.; Skhomenko, Ya T.; Terekhin, A. A.; Tishevsky, A. V.; Averyanov, A. V.; Bazylev, S. N.; Belov, A. S.; Butenko, A. V.; Chernykh, E. V.; Filatov, Yu N.; Fimushkin, V. V.; Krivenkov, D. O.; Kondratenko, A. M.; Kondratenko, M. A.; Kovalenko, A. D.; Slepnev, I. V.; Slepnev, V. M.; Shutov, A. V.; Sidorin, A. O.; Vnukov, I. E.; Volkov, V. S.

2017-12-01

The spin program at NICA using SPD and MPD requires high intensity polarized proton beam with high value of the beam polarization. First results on the measurements of the proton beam polarization performed at internal target at Nuclotron are reported. The polarization of the proton beam provided by new source of polarized ions has been measured at 500 MeV using quasielastic proton-proton scattering and DSS setup at internal target. The obtained value of the vertical polarization of ∼35% is consistent with the calculations taking into account the current magnetic optics of the Nuclotron injection line.

Recommendations of the Global Multiple System Atrophy Research Roadmap Meeting.

PubMed

Walsh, Ryan R; Krismer, Florian; Galpern, Wendy R; Wenning, Gregor K; Low, Phillip A; Halliday, Glenda; Koroshetz, Walter J; Holton, Janice; Quinn, Niall P; Rascol, Olivier; Shaw, Leslie M; Eidelberg, David; Bower, Pam; Cummings, Jeffrey L; Abler, Victor; Biedenharn, Judy; Bitan, Gal; Brooks, David J; Brundin, Patrik; Fernandez, Hubert; Fortier, Philip; Freeman, Roy; Gasser, Thomas; Hewitt, Art; Höglinger, Günter U; Huentelman, Matt J; Jensen, Poul H; Jeromin, Andreas; Kang, Un Jung; Kaufmann, Horacio; Kellerman, Lawrence; Khurana, Vikram; Klockgether, Thomas; Kim, Woojin Scott; Langer, Carol; LeWitt, Peter; Masliah, Eliezer; Meissner, Wassilios; Melki, Ronald; Ostrowitzki, Susanne; Piantadosi, Steven; Poewe, Werner; Robertson, David; Roemer, Cyndi; Schenk, Dale; Schlossmacher, Michael; Schmahmann, Jeremy D; Seppi, Klaus; Shih, Lily; Siderowf, Andrew; Stebbins, Glenn T; Stefanova, Nadia; Tsuji, Shoji; Sutton, Sharon; Zhang, Jing

2018-01-09

Multiple system atrophy (MSA) is a rare neurodegenerative disorder with substantial knowledge gaps despite recent gains in basic and clinical research. In order to make further advances, concerted international collaboration is vital. In 2014, an international meeting involving leaders in the field and MSA advocacy groups was convened in Las Vegas, Nevada, to identify critical research areas where consensus and progress was needed to improve understanding, diagnosis, and treatment of the disease. Eight topic areas were defined: pathogenesis, preclinical modeling, target identification, endophenotyping, clinical measures, imaging biomarkers, nonimaging biomarkers, treatments/trial designs, and patient advocacy. For each topic area, an expert served as a working group chair and each working group developed priority-ranked research recommendations with associated timelines and pathways to reach the intended goals. In this report, each groups' recommendations are provided. Copyright © 2017 American Academy of Neurology.

Accumulation, internalization and therapeutic efficacy of neuropilin-1-targeted liposomes

PubMed Central

Paoli, Eric E.; Ingham, Elizabeth S.; Zhang, Hua; Mahakian, Lisa M.; Fite, Brett Z.; Gagnon, M. Karen; Tam, Sarah; Kheirolomoom, Azadeh; Cardiff, Robert D.; Ferrara, Katherine W.

2014-01-01

Advancements in liposomal drug delivery have produced long circulating and very stable drug formulations. These formulations minimize systemic exposure; however, unfortunately, therapeutic efficacy has remained limited due to the slow diffusion of liposomal particles within the tumor and limited release or uptake of the encapsulated drug. Here, the carboxyl-terminated CRPPR peptide, with affinity for the receptor neuropilin-1 (NRP), which is expressed on both endothelial and cancer cells, was conjugated to liposomes to enhance the tumor accumulation. Using a pH sensitive probe, liposomes were optimized for specific NRP binding and subsequent cellular internalization using in vitro cellular assays. Liposomes conjugated with the carboxyl-terminated CRPPR peptide (termed C-LPP liposomes) bound to the NRP-positive primary prostatic carcinoma cell line (PPC-1) but did not bind to the NRP-negative PC-3 cell line, and binding was observed with liposomal peptide concentrations as low as 0.16 mol%. Binding of the C-LPP liposomes was receptor-limited, with saturation observed at high liposome concentrations. The identical peptide sequence bearing an amide terminus did not bind specifically, accumulating only with a high (2.5 mol%) peptide concentration and adhering equally to NRP positive and negative cell lines. The binding of C-LPP liposomes conjugated with 0.63 mol% of the peptide was 83-fold greater than liposomes conjugated with the amide version of the peptide. Cellular internalization was also enhanced with C-LPP liposomes, with 80% internalized following 3hr incubation. Additionally, fluorescence in the blood pool (~40% of the injected dose) was similar for liposomes conjugated with 0.63 mol% of carboxyl-terminated peptide and non-targeted liposomes at 24 hr after injection, indicating stable circulation. Prior to doxorubicin treatment, in vivo tumor accumulation and vascular targeting were increased for peptide-conjugated liposomes compared to non-targeted liposomes based on confocal imaging of a fluorescent cargo, and the availability of the vascular receptor was confirmed with ultrasound molecular imaging. Finally, over a 4-week course of therapy, tumor knockdown resulting from doxorubicin-loaded, C-LPP liposomes was similar to non-targeted liposomes in syngeneic tumor-bearing FVB mice and C-LPP liposomes reduced doxorubicin accumulation in the skin and heart and eliminated skin toxicity. Taken together, our results demonstrate that a carboxyl-terminated RXXR peptide sequence, conjugated to liposomes at a concentration of 0.63 mol%, retains long circulation but enhances binding and internalization, and reduces toxicity. PMID:24434424

Production of Astatine-211 at the Duke University Medical Center for its regional distribution

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

Zalutsky, Michael

Systemic targeted radiation therapy and radioimmunotherapy continue to be important tools in the treatment of certain cancers. Because of their high energy and short path length, alpha particle emitters such as 211At are more effective than either external beam x- ray or in vivo beta radiation in delivering potentially curative doses of radiation. The limited clinical trials that have been conducted to date have yielded encouraging responses in some patients, e.g., malignant brain tumors. In order to escalate the additional necessary research and development in radiochemistry, radiobiology and efficacy evaluation of alpha particle radiotherapeutics, it is universally agreed that accessmore » to an affordable, reliable supply of 211At is warranted. In conjunction with the Department of Energy's intent to enhance stable and radioactive isotope availability for research applications, it is the primary objective of this project to improve 211At production and purification capabilities at Duke so that this radionuclide can be supplied to researchers at other institutions throughout the US.The most widely used 211At production method involves the α,2n reaction on Bismuth using a cyclotron with beams ≤ 28 MeV. Yields can be enhanced with use of an internal target that allows for a higher alpha fluence plus efficient heat dissipation in the target. Both of these items are in place at Duke; however, in order to support production for multi-institutional use, irradiation campaigns in excess of 50 µAp and four hours duration will be needed. Further, post-irradiation processing equipment is lacking that will enable the distribution process. Financial support is sought for i) a shielded, ventilated processing/containment hood; ii) development of a post-irradiation target retrieval system; iii) fabrication of a 211At distillation and recovery module and iv) a performance review and, where needed, an enhancement of seven major subsystems that comprise the CS-30 Cyclotron. With these modifications in place, routine production of ≥200 mCi of At-211 should be readily achievable, given our methodological development of At-211 target preparation, internal target irradiation and dry distillation to recover the radionuclide.« less

Application of Targeted Mass Spectrometry for the Quantification of Sirtuins in the Central Nervous System

NASA Astrophysics Data System (ADS)

Jayasena, T.; Poljak, A.; Braidy, N.; Zhong, L.; Rowlands, B.; Muenchhoff, J.; Grant, R.; Smythe, G.; Teo, C.; Raftery, M.; Sachdev, P.

2016-10-01

Sirtuin proteins have a variety of intracellular targets, thereby regulating multiple biological pathways including neurodegeneration. However, relatively little is currently known about the role or expression of the 7 mammalian sirtuins in the central nervous system. Western blotting, PCR and ELISA are the main techniques currently used to measure sirtuin levels. To achieve sufficient sensitivity and selectivity in a multiplex-format, a targeted mass spectrometric assay was developed and validated for the quantification of all seven mammalian sirtuins (SIRT1-7). Quantification of all peptides was by multiple reaction monitoring (MRM) using three mass transitions per protein-specific peptide, two specific peptides for each sirtuin and a stable isotope labelled internal standard. The assay was applied to a variety of samples including cultured brain cells, mammalian brain tissue, CSF and plasma. All sirtuin peptides were detected in the human brain, with SIRT2 being the most abundant. Sirtuins were also detected in human CSF and plasma, and guinea pig and mouse tissues. In conclusion, we have successfully applied MRM mass spectrometry for the detection and quantification of sirtuin proteins in the central nervous system, paving the way for more quantitative and functional studies.

Evidence for transcriptional interference in a dual-luciferase reporter system.

PubMed

Wu, Guo-Qing; Wang, Xiao; Zhou, Hong-Ying; Chai, Ke-Qun; Xue, Qian; Zheng, Ai-Hong; Zhu, Xiu-Ming; Xiao, Jian-Yong; Ying, Xu-Hua; Wang, Fu-Wei; Rui, Tao; Xu, Li-Yun; Zhang, Yong-Kui; Liao, Yi-Ji; Xie, Dan; Lu, Li-Qin; Huang, Dong-Sheng

2015-12-01

The dual-luciferase reporter assay is widely used for microRNA target identification and the functional validation of predicted targets. To determine whether curcumin regulates expression of the histone methyltransferase enhancer of zeste homolog 2 (EZH2) by targeting its 3'untranslated region (3'UTR), two luciferase reporter systems containing exactly the same sequence of the EZH2 3'UTR were used to perform dual-luciferase reporter assays. Surprisingly, there were certain discrepancies between the luciferase activities derived from these two reporter constructs. We normalized luciferase activity to an internal control to determine the amount of the reporter construct successfully transfected into cells, induced a transcriptional block with flavopiridol, quantified renilla luciferase mRNA levels, and compared the absolute luciferase activity among the different groups. The results suggested that curcumin promoted the transcription of the luciferase genes located downstream of the simian vacuolating virus 40 (SV40) early enhancer/promoter, but not those located downstream of the human cytomegalovirus (CMV) immediate-early or the herpes simplex virus thymidine kinase (HSV-TK) promoters. These results explain the discrepancies between the two luciferase reporter systems. The current study underscores the importance of taking caution when interpreting the results of dual-luciferase reporter assays and provides strategies to overcome the potential pitfall accompanying dual-luciferase reporter systems.

Evidence for transcriptional interference in a dual-luciferase reporter system

PubMed Central

Wu, Guo-Qing; Wang, Xiao; Zhou, Hong-Ying; Chai, Ke-Qun; Xue, Qian; Zheng, Ai-Hong; Zhu, Xiu-Ming; Xiao, Jian-Yong; Ying, Xu-Hua; Wang, Fu-Wei; Rui, Tao; Xu, Li-Yun; Zhang, Yong-Kui; Liao, Yi-Ji; Xie, Dan; Lu, Li-Qin; Huang, Dong-Sheng

2015-01-01

The dual-luciferase reporter assay is widely used for microRNA target identification and the functional validation of predicted targets. To determine whether curcumin regulates expression of the histone methyltransferase enhancer of zeste homolog 2 (EZH2) by targeting its 3′untranslated region (3′UTR), two luciferase reporter systems containing exactly the same sequence of the EZH2 3′UTR were used to perform dual-luciferase reporter assays. Surprisingly, there were certain discrepancies between the luciferase activities derived from these two reporter constructs. We normalized luciferase activity to an internal control to determine the amount of the reporter construct successfully transfected into cells, induced a transcriptional block with flavopiridol, quantified renilla luciferase mRNA levels, and compared the absolute luciferase activity among the different groups. The results suggested that curcumin promoted the transcription of the luciferase genes located downstream of the simian vacuolating virus 40 (SV40) early enhancer/promoter, but not those located downstream of the human cytomegalovirus (CMV) immediate-early or the herpes simplex virus thymidine kinase (HSV-TK) promoters. These results explain the discrepancies between the two luciferase reporter systems. The current study underscores the importance of taking caution when interpreting the results of dual-luciferase reporter assays and provides strategies to overcome the potential pitfall accompanying dual-luciferase reporter systems. PMID:26620302

Mechanism-Based Tumor-Targeting Drug Delivery System. Validation of Efficient Vitamin Receptor-Mediated Endocytosis and Drug Release

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

Chen, S.; Wong, S.; Zhao, X.

An efficient mechanism-based tumor-targeting drug delivery system, based on tumor-specific vitamin-receptor mediated endocytosis, has been developed. The tumor-targeting drug delivery system is a conjugate of a tumor-targeting molecule (biotin: vitamin H or vitamin B-7), a mechanism-based self-immolative linker and a second-generation taxoid (SB-T-1214) as the cytotoxic agent. This conjugate (1) is designed to be (i) specific to the vitamin receptors overexpressed on tumor cell surface and (ii) internalized efficiently through receptor-mediated endocytosis, followed by smooth drug release via glutathione-triggered self-immolation of the linker. In order to monitor and validate the sequence of events hypothesized, i.e., receptor-mediated endocytosis of the conjugate,more » drug release, and drug-binding to the target protein (microtubules), three fluorescent/fluorogenic molecular probes (2, 3, and 4) were designed and synthesized. The actual occurrence of these processes was unambiguously confirmed by means of confocal fluorescence microscopy (CFM) and flow cytometry using L1210FR leukemia cells, overexpressing biotin receptors. The molecular probe 4, bearing the taxoid linked to fluorescein, was also used to examine the cell specificity (i.e., efficacy of receptor-based cell targeting) for three cell lines, L1210FR (biotin receptors overexpressed), L1210 (biotin receptors not overexpressed), and WI38 (normal human lung fibroblast, biotin receptor negative). As anticipated, the molecular probe 4 exhibited high specificity only to L1210FR. To confirm the direct correlation between the cell-specific drug delivery and anticancer activity of the probe 4, its cytotoxicity against these three cell lines was also examined. The results clearly showed a good correlation between the two methods. In the same manner, excellent cell-specific cytotoxicity of the conjugate 1 (without fluorescein attachment to the taxoid) against the same three cell lines was confirmed. This mechanism-based tumor-targeting drug delivery system will find a range of applications.« less

Targeted Killing as an Element of U.S. Foreign Policy in the War On Terror

DTIC Science & Technology

2006-05-25

terrorists. Given the level of secrecy and lack of transparency involved in this policy and its implementation, how can we judge the moral and legal ...killing’ morally justifiable and legal under both US domestic and international law? Can the United States maintain international legitimacy while...Rights Law and International Humanitarian Law to determine the legality of a policy of targeted killing. iii TABLE OF CONTENTS INTRODUCTION

Balancing cellular redox metabolism in microbial electrosynthesis and electro fermentation - A chance for metabolic engineering.

PubMed

Kracke, Frauke; Lai, Bin; Yu, Shiqin; Krömer, Jens O

2018-01-01

More and more microbes are discovered that are capable of extracellular electron transfer, a process in which they use external electrodes as electron donors or acceptors for metabolic reactions. This feature can be used to overcome cellular redox limitations and thus optimizing microbial production. The technologies, termed microbial electrosynthesis and electro-fermentation, have the potential to open novel bio-electro production platforms from sustainable energy and carbon sources. However, the performance of reported systems is currently limited by low electron transport rates between microbes and electrodes and our limited ability for targeted engineering of these systems due to remaining knowledge gaps about the underlying fundamental processes. Metabolic engineering offers many opportunities to optimize these processes, for instance by genetic engineering of pathways for electron transfer on the one hand and target product synthesis on the other hand. With this review, we summarize the status quo of knowledge and engineering attempts around chemical production in bio-electrochemical systems from a microbe perspective. Challenges associated with the introduction or enhancement of extracellular electron transfer capabilities into production hosts versus the engineering of target compound synthesis pathways in natural exoelectrogens are discussed. Recent advances of the research community in both directions are examined critically. Further, systems biology approaches, for instance using metabolic modelling, are examined for their potential to provide insight into fundamental processes and to identify targets for metabolic engineering. Copyright © 2017 International Metabolic Engineering Society. Published by Elsevier Inc. All rights reserved.

IGRT/ART phantom with programmable independent rib cage and tumor motion

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

Haas, Olivier C. L., E-mail: o.haas@coventry.ac.uk; Mills, John A.; Land, Imke

2014-02-15

Purpose: This paper describes the design and experimental evaluation of the Methods and Advanced Equipment for Simulation and Treatment in Radiation Oncology (MAESTRO) thorax phantom, a new anthropomorphic moving ribcage combined with a 3D tumor positioning system to move target inserts within static lungs. Methods: The new rib cage design is described and its motion is evaluated using Vicon Nexus, a commercial 3D motion tracking system. CT studies at inhale and exhale position are used to study the effect of rib motion and tissue equivalence. Results: The 3D target positioning system and the rib cage have millimetre accuracy. Each axismore » of motion can reproduce given trajectories from files or individually programmed sinusoidal motion in terms of amplitude, period, and phase shift. The maximum rib motion ranges from 7 to 20 mm SI and from 0.3 to 3.7 mm AP with LR motion less than 1 mm. The repeatability between cycles is within 0.16 mm root mean square error. The agreement between CT electron and mass density for skin, ribcage, spine hard and inner bone as well as cartilage is within 3%. Conclusions: The MAESTRO phantom is a useful research tool that produces programmable 3D rib motions which can be synchronized with 3D internal target motion. The easily accessible static lungs enable the use of a wide range of inserts or can be filled with lung tissue equivalent and deformed using the target motion system.« less

KSC-02pd0537

NASA Image and Video Library

2002-04-22

KENNEDY SPACE CENTER, FLA. -- Inside the Orbiter Processing Facility, spectators watch as Endeavour is rolled out of the bay on top of a transporter. The orbiter is being moved to the Vehicle Assembly Building for mating to the External Tank/Solid Rocket Boosters atop the Mobile Launcher Platform. Endeavour is targeted to launch May 30, 2002, on mission STS-111 to the International Space Station. Mission goals include delivering and installing the Mobile Base System to complete the Canadian Mobile Service System and carrying the Expedition 5 crew to the Station for rotation with Expedition 4.

Towards an integration of affiliated companies energy audit process system at P.T Astra International

NASA Astrophysics Data System (ADS)

Telaga, Abdi Suryadinata; Hartanto, Indra Dwi; Audina, Debby Rizky; Prabowo, Fransiscus Dimas

2017-06-01

Environmental awareness, stringent regulation and soaring energy costs, together make energy efficiency as an important pillar for every company. Particularly, in 2020, the ministry of energy and mineral resources of Indonesia has set a target to reduce carbon emission by 26%. For that reason, companies in Indonesia have to comply with the emission target. However, there is trade-off between company's productivity and carbon emission. Therefore, the companies' productivity must be weighed against the environmental effect such as carbon emission. Nowadays, distinguish excessive energy in a company is still challenging. The company rarely has skilled person that capable to audit energy consumed in the company. Auditing energy consumption in a company is a lengthy and time consuming process. As PT Astra International (AI) have 220 affiliated companies (AFFCOs). Occasionally, direct visit to audit energy consumption in AFFCOs is inevitable. However, capability to conduct on-site energy audit was limited by the availability of PT AI energy auditors. For that reason, PT AI has developed a set of audit energy tools or Astra green energy (AGEn) tools to aid the AFFCOs auditor to be able to audit energy in their own company. Fishbone chart was developed as an analysis tool to gather root cause of audit energy problem. Following the analysis results, PT AI made an improvement by developing an AGEn web-based system. The system has capability to help AFFCOs to conduct energy audit on-site. The system was developed using prototyping methodology, object-oriented system analysis and design (OOSAD), and three-tier architecture. The implementation of system used ASP.NET, Microsoft SQL Server 2012 database, and web server IIS 8.

Automated Rendezvous and Capture System Development and Simulation for NASA

NASA Technical Reports Server (NTRS)

Roe, Fred D.; Howard, Richard T.; Murphy, Leslie

2004-01-01

The United States does not have an Automated Rendezvous and Capture/Docking (AR and C) capability and is reliant on manned control for rendezvous and docking of orbiting spacecraft. This reliance on the labor intensive manned interface for control of rendezvous and docking vehicles has a significant impact on the cost of the operation of the International Space Station (ISS) and precludes the use of any U.S. expendable launch capabilities for Space Station resupply. The Soviets have the capability to autonomously dock in space, but their system produces a hard docking with excessive force and contact velocity. Automated Rendezvous and Capture/Docking has been identified as a key enabling technology for the Space Launch Initiative (SLI) Program, DARPA Orbital Express and other DOD Programs. The development and implementation of an AR&C capability can significantly enhance system flexibility, improve safety, and lower the cost of maintaining, supplying, and operating the International Space Station. The Marshall Space Flight Center (MSFC) has conducted pioneering research in the development of an automated rendezvous and capture (or docking) (AR and C) system for U.S. space vehicles. This AR&C system was tested extensively using hardware-in-the-loop simulations in the Flight Robotics Laboratory, and a rendezvous sensor, the Video Guidance Sensor was developed and successfully flown on the Space Shuttle on flights STS-87 and STS-95, proving the concept of a video- based sensor. Further developments in sensor technology and vehicle and target configuration have lead to continued improvements and changes in AR&C system development and simulation. A new Advanced Video Guidance Sensor (AVGS) with target will be utilized on the Demonstration of Autonomous Rendezvous Technologies (DART) flight experiment in 2004.

Health research systems: promoting health equity or economic competitiveness?

PubMed Central

Loff, Bebe

2012-01-01

Abstract International collaborative health research is justifiably expected to help reduce global health inequities. Investment in health policy and systems research in developing countries is essential to this process but, currently, funding for international research is mainly channelled towards the development of new medical interventions. This imbalance is largely due to research legislation and policies used in high-income countries. These policies have increasingly led these countries to invest in health research aimed at boosting national economic competitiveness rather than reducing health inequities. In the United States of America and the United Kingdom of Great Britain and Northern Ireland, the regulation of research has encouraged a model that: leads to products that can be commercialized; targets health needs that can be met by profitable, high-technology products; has the licensing of new products as its endpoint; and does not entail significant research capacity strengthening in other countries. Accordingly, investment in international research is directed towards pharmaceutical trials and product development public–private partnerships for neglected diseases. This diverts funding away from research that is needed to implement existing interventions and to strengthen health systems, i.e. health policy and systems research. Governments must restructure their research laws and policies to increase this essential research in developing countries. PMID:22271965

International Test Comparisons: Reviewing Translation Error in Different Source Language-Target Language Combinations

ERIC Educational Resources Information Center

Zhao, Xueyu; Solano-Flores, Guillermo; Qian, Ming

2018-01-01

This article addresses test translation review in international test comparisons. We investigated the applicability of the theory of test translation error--a theory of the multidimensionality and inevitability of test translation error--across source language-target language combinations in the translation of PISA (Programme of International…

A new target ligand Ser-Glu for PEPT1-overexpressing cancer imaging.

PubMed

Dai, Tongcheng; Li, Na; Zhang, Lingzhi; Zhang, Yuanxing; Liu, Qin

2016-01-01

Nanoparticles functionalized with active target ligands have been widely used for tumor-specific diagnosis and therapy. The target ligands include antibodies, peptides, proteins, small molecules, and nucleic acid aptamers. Here, we utilize dipeptide Ser-Glu (DIP) as a new ligand to functionalize polymer-based fluorescent nanoparticles (NPs) for pancreatic cancer target imaging. We demonstrate that in the first step, Ser-Glu-conjugated NPs (NPs-DIP) efficiently bind to AsPC-1 and in the following NPs-DIP are internalized into AsPC-1 in vitro. The peptide transporter 1 inhibition experiment reveals that the targeting effects mainly depend on the specific binding of DIP to peptide transporter 1, which is remarkably upregulated in pancreatic cancer cells compared with varied normal cells. Furthermore, NPs-DIP specifically accumulate in the site of pancreatic tumor xenograft and are further internalized into the tumor cells in vivo after intravenous administration, indicating that DIP successfully enhanced nanoparticles internalization efficacy into tumor cells in vivo. This work establishes Ser-Glu to be a new tumor-targeting ligand and provides a promising tool for future tumor diagnostic or therapeutic applications.

A potyvirus vector efficiently targets recombinant proteins to chloroplasts, mitochondria and nuclei in plant cells when expressed at the amino terminus of the polyprotein.

PubMed

Majer, Eszter; Navarro, José-Antonio; Daròs, José-Antonio

2015-09-01

Plant virus-based expression systems allow quick and efficient production of recombinant proteins in plant biofactories. Among them, a system derived from tobacco etch virus (TEV; genus potyvirus) permits coexpression of equimolar amounts of several recombinant proteins. This work analyzed how to target recombinant proteins to different subcellular localizations in the plant cell using this system. We constructed TEV clones in which green fluorescent protein (GFP), with a chloroplast transit peptide (cTP), a nuclear localization signal (NLS) or a mitochondrial targeting peptide (mTP) was expressed either as the most amino-terminal product or embedded in the viral polyprotein. Results showed that cTP and mTP mediated efficient translocation of GFP to the corresponding organelle only when present at the amino terminus of the viral polyprotein. In contrast, the NLS worked efficiently at both positions. Viruses expressing GFP in the amino terminus of the viral polyprotein produced milder symptoms. Untagged GFPs and cTP and NLS tagged amino-terminal GFPs accumulated to higher amounts in infected tissues. Finally, viral progeny from clones with internal GFPs maintained the extra gene better. These observations will help in the design of potyvirus-based vectors able to coexpress several proteins while targeting different subcellular localizations, as required in plant metabolic engineering. Copyright © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

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

NASA Astrophysics Data System (ADS)

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

2013-12-01

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

KSC-2009-4811

NASA Image and Video Library

2009-08-21

CAPE CANAVERAL, Fla. – In NASA Kennedy Space Center's Orbiter Processing Facility 1, technicians begin a functional test on the orbital docking system on space shuttle Atlantis. The STS-129 mission will deliver to the International Space Station two spare gyroscopes, two nitrogen tank assemblies, two pump modules, an ammonia tank assembly and a spare latching end effector for the station's robotic arm. STS-129 is targeted to launch Nov. 12. Photo credit: NASA/Kim Shiflett

KSC-2009-4806

NASA Image and Video Library

2009-08-21

CAPE CANAVERAL, Fla. – In NASA Kennedy Space Center's Orbiter Processing Facility 1, technicians prepare to test the orbital docking system on space shuttle Atlantis. The STS-129 mission will deliver to the International Space Station two spare gyroscopes, two nitrogen tank assemblies, two pump modules, an ammonia tank assembly and a spare latching end effector for the station's robotic arm. STS-129 is targeted to launch Nov. 12. Photo credit: NASA/Kim Shiflett

KSC-2009-4808

NASA Image and Video Library

2009-08-21

CAPE CANAVERAL, Fla. – In NASA Kennedy Space Center's Orbiter Processing Facility 1, technicians begin testing the orbital docking system on space shuttle Atlantis. The STS-129 mission will deliver to the International Space Station two spare gyroscopes, two nitrogen tank assemblies, two pump modules, an ammonia tank assembly and a spare latching end effector for the station's robotic arm. STS-129 is targeted to launch Nov. 12. Photo credit: NASA/Kim Shiflett

Human Issues in Manufacturing Technology

DTIC Science & Technology

1992-09-01

with the following comparison to make his point. Both plants are modern, automated, machine- centered production systems. General Motors ’ Hamtramck...The MIT text draws from 116 research monographs prepared by affiliates of the International Motor Vehicle Program. The study is replete with empirical...Japanese industrial culture. The target for their study was the state-of-the-art Mazda plant in Flat Rock, Michigan. In addition to their treatment of the

Human-Robot Interaction: A Survey

DTIC Science & Technology

2007-01-01

breaks with the monolithic sense- plan -act loop of a centralized system, and instead uses distributed sense-response loops to generate appropriate...one of the first modern robots, cour- tesy of SRI International, Menlo Park, CA [279]; Kismet — an anthropomorphic robot with exaggerated emotion...linguis- tics. A common autonomy approach is sometimes referred to as the sense- plan -act model of decision-making [196]. This model has been a target

Scientific Data as the Core Legacy of IPY

NASA Astrophysics Data System (ADS)

Parsons, M. A.

2008-12-01

The interdisciplinary breadth of the International Polar Year is unprecedented. The IPY has explicit objectives to link researchers across different fields to address questions and issues lying beyond the scope of individual disciplines and to strengthen international coordination of research and enhance international collaboration and cooperation. The IPY Data Policy and Management Subcommittee have developed a policy to help meet these objectives and an international collaboration of investigators and data managers, the IPY Data and Information Service, are working to make IPY data widely available. I will present an overview of the primary data management considerations for IPY and how diverse organizations are making IPY and related data available. Centralized discovery mechanisms for widely distributed data plus targeted access mechanisms for specific disciplines will be presented. These range from near real time access to satellite remote sensing data and GCM output to fair and appropriate access to traditional knowledge of the Arctic. These mechanisms reflect significant advancement in polar data management, but they belie the major challenges that remain. These challenges include fostering a culture change in science that puts greater value on data publication and open data access as well as developing sustained systems and business models for the long-term preservation of IPY data. This will be crucial to ensuring the legacy of IPY, a major objective of IPY sponsors, ICSU and WMO. New efforts to ensure this legacy include the development of the WMO Information System, the Sustained Arctic Observing Network, and the Global Earth Observing System of Systems; the reform of ICSU's World Data Center System; and the results of the Electronic Geophysical Year.

Multiplexed detection of anthrax-related toxin genes.

PubMed

Moser, Michael J; Christensen, Deanna R; Norwood, David; Prudent, James R

2006-02-01

Simultaneous analysis of three targets in three colors on any real-time polymerase chain reaction (PCR) instrument would increase the flexibility of real-time PCR. For the detection of Bacillus strains that can cause inhalation anthrax-related illness, this ability would be valuable because two plasmids confer virulence, and internal positive controls are needed to monitor the testing in cases lacking target-specific signals. Using a real-time PCR platform called MultiCode-RTx, multiple assays were developed that specifically monitor the presence of Bacillus anthracis-specific virulence plasmid-associated genes. In particular for use on LightCycler-1, two triplex RTx systems demonstrated high sensitivity with limits of detection nearing single-copy levels for both plasmids. Specificity was established using a combination of Ct values and correct amplicon melting temperatures. All reactions were further verified by detection of an internal positive control. For these two triplex RTx assays, the analytical detection limit was one to nine plasmid copy equivalents, 100% analytical specificity with a 95% confidence interval (CI) of 9%, and 100% analytical sensitivity with a CI of 2%. Although further testing using clinical or environmental samples will be required to assess diagnostic sensitivity and specificity, the RTx platform achieves similar results to those of probe-based real-time systems.

Molecular chaperone function of Mia40 triggers consecutive induced folding steps of the substrate in mitochondrial protein import

PubMed Central

Banci, Lucia; Bertini, Ivano; Cefaro, Chiara; Cenacchi, Lucia; Ciofi-Baffoni, Simone; Felli, Isabella Caterina; Gallo, Angelo; Gonnelli, Leonardo; Luchinat, Enrico; Sideris, Dionisia; Tokatlidis, Kostas

2010-01-01

Several proteins of the mitochondrial intermembrane space are targeted by internal targeting signals. A class of such proteins with α-helical hairpin structure bridged by two intramolecular disulfides is trapped by a Mia40-dependent oxidative process. Here, we describe the oxidative folding mechanism underpinning this process by an exhaustive structural characterization of the protein in all stages and as a complex with Mia40. Two consecutive induced folding steps are at the basis of the protein-trapping process. In the first one, Mia40 functions as a molecular chaperone assisting α-helical folding of the internal targeting signal of the substrate. Subsequently, in a Mia40-independent manner, folding of the second substrate helix is induced by the folded targeting signal functioning as a folding scaffold. The Mia40-induced folding pathway provides a proof of principle for the general concept that internal targeting signals may operate as a folding nucleus upon compartment-specific activation. PMID:21059946

Isolation of Mycobacterium massiliense from a corneal biopsy in India.

PubMed

Kulandai, Lily Therese; Lakshmipathy, Dhanurekha; Ramasubban, Gayathri; Rao, Madhavan Hajib Narahari

2014-12-01

Rapidly growing mycobacteria (RGM) are ubiquitous and are usually considered as saprophytes, and have been recovered from the environment, particularly in dust, watery soil and water distribution systems. However, Mycobacterium massiliense is a rare causative agent of ocular infection. We report a case of M. massiliense in a 44-year-old female with signs and symptoms of a corneal ulcer. We carried out PCR-based DNA sequencing targeting the hsp 65 gene for the identification of M. massiliense . To confirm the identification, we also performed PCR-based RFLP targeting the hsp65 gene and PCR-based DNA sequencing targeting the internal transcribed spacer region, which showed 97 % nucleotide identity with M. massiliense . To the best of our knowledge, this is the first study in India to report the detection of M. massiliense from a corneal biopsy.

Lujan Center Mark-IV Target Neutronics Design Internal Review Report

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

Lisowski, Paul W.; Gallmeier, Franz; Guber, Klaus

The 1L Target Moderator Reflector System (TMRS) at the Lujan Center will need to be replaced before the CY 2020 operating cycle. A Physics Division design team investigated options for improving the overall target performance for nuclear science research with minimal reduction in performance for materials science. This review concluded that devoting an optimized arrangement of the Lujan TMRS upper tier to nuclear science and using the lower tier for materials science can achieve those goals. This would open the opportunity for enhanced nuclear science research in an important neutron energy range for NNSA. There will be no other facilitymore » in the US that will compete in the keV energy range provided flight paths and instrumentation are developed to take advantage of the neutron flux and resolution.« less

Are condom-promotion interventions reaching internal migrants in China? Integrated evidence from two cross-sectional surveys.

PubMed

Liu, Xiaona; Erasmus, Vicki; van Genugten, Lenneke; Sun, Xinying; Tan, Jingguang; Richardus, Jan Hendrik

2016-09-01

Behavioral interventions containing behavior change techniques (BCTs) that do not reach the target populations sufficiently will fail to accomplish their desired outcome. To guide sexually transmitted infection prevention policy for internal migrants in China, this study examines the extent to which BCTs aiming at increasing condom use reach the migrants and investigates the preference of the target population for these techniques among 364 migrants and 44 healthcare workers (HCWs) in Shenzhen, China. The results show that condom-promotion techniques that had been offered by HCWs to internal migrants reached a limited proportion of the population (range of reach ratio: 17.6-55.0%), although there appears to be a good match between what is offered and what is preferred by Chinese internal migrants regarding condom-promotion techniques (rank difference ≤ 1). Our findings highlight the need to increase the reach of condom-promotion techniques among Chinese internal migrants, and suggest techniques that are likely to reach the target population and match their preferred health education approaches.

pH-driven colloidal transformations based on the vasoactive drug nicergoline.

PubMed

Salentinig, Stefan; Tangso, Kristian J; Hawley, Adrian; Boyd, Ben J

2014-12-16

The structure of colloidal self-assembled drug delivery systems can be influenced by intermolecular interactions between drug and amphiphilic molecules, and is important to understand in the context of designing improved delivery systems. Controlling these structures can enable controlled or targeted release systems for poorly water-soluble drugs. Here we present the interaction of the hydrophobic vasoactive drug nicergoline with the internal structure of nanostructured emulsion particles based on the monoglyceride-water system. Addition of this drug leads to modification of the internal bicontinuous cubic structure to generate highly pH-responsive systems. The colloidal structures were characterized with small-angle X-ray scattering and visualized using cryogenic transmission electron microscopy. Reversible transformations to inverse micelles at high pH, vesicles at low pH, and the modification of the spacing of the bicontinuous cubic structure at intermediate pH were observed, and enabled the in situ determination of an apparent pKa for the drug in this system--a difficult task using solution-based approaches. The characterization of this phase behavior is also highly interesting for the design of pH-responsive controlled release systems for poorly water-soluble drug molecules.

Improved methods of AAV-mediated gene targeting for human cell lines using ribosome-skipping 2A peptide

PubMed Central

Karnan, Sivasundaram; Ota, Akinobu; Konishi, Yuko; Wahiduzzaman, Md; Hosokawa, Yoshitaka; Konishi, Hiroyuki

2016-01-01

The adeno-associated virus (AAV)-based targeting vector has been one of the tools commonly used for genome modification in human cell lines. It allows for relatively efficient gene targeting associated with 1–4-log higher ratios of homologous-to-random integration of targeting vectors (H/R ratios) than plasmid-based targeting vectors, without actively introducing DNA double-strand breaks. In this study, we sought to improve the efficiency of AAV-mediated gene targeting by introducing a 2A-based promoter-trap system into targeting constructs. We generated three distinct AAV-based targeting vectors carrying 2A for promoter trapping, each targeting a GFP-based reporter module incorporated into the genome, PIGA exon 6 or PIGA intron 5. The absolute gene targeting efficiencies and H/R ratios attained using these vectors were assessed in multiple human cell lines and compared with those attained using targeting vectors carrying internal ribosome entry site (IRES) for promoter trapping. We found that the use of 2A for promoter trapping increased absolute gene targeting efficiencies by 3.4–28-fold and H/R ratios by 2–5-fold compared to values obtained with IRES. In CRISPR-Cas9-assisted gene targeting using plasmid-based targeting vectors, the use of 2A did not enhance the H/R ratios but did upregulate the absolute gene targeting efficiencies compared to the use of IRES. PMID:26657635

Management information systems--green light for better info.

PubMed

Foster, K; McBride, N

1992-02-27

An EIS gathers financial and non-financial data from a variety of sources, both internal and external to an organisation, and presents them accessibly and understandably. It should facilitate the presentation of data so that it is timely and relevant to senior managers' needs. Generally, there are three categories of EIS: Front-end tools, which enhance the presentation of output from existing systems. For example, they can take the output from a general ledger system and enhance its appearance but do not change the content. Internal consolidation tools, which take data from a number of internal sources (such as the general ledger), store it in a central database, and present it to users. This is often done in report book format to which all EIS style functions may be applied. Integrators of information, which integrate data from internal and external sources. Much of the data is non-financial and a major emphasis is on the users' ability to communicate with each other. The key functions that may be included within an EIS are: Drill down. The facility to explore increasingly detailed levels of data. Trends and variances against pre-set targets, such as financial budgets. Graphics and tabular reporting. Data integrity checking. Analysis of the data, modelling and the production of forecasts using time series analysis techniques. Exception reporting through the use of some form of alert. Incorporation of text into the output.

A verotoxin 1 B subunit-lambda CRO chimeric protein specifically binds both DNA and globotriaosylceramide (Gb(3)) to effect nuclear targeting of exogenous DNA in Gb(3) positive cells.

PubMed

Facchini, L M; Lingwood, C A

2001-09-10

Inefficient nuclear incorporation of foreign DNA remains a critical roadblock in the development of effective nonviral gene delivery systems. DNA delivered by traditional protocols remains within endosomal/lysosomal vesicles, or is rapidly degraded in the cytoplasm. Verotoxin I (VT), an AB(5) subunit toxin produced by enterohaemorrhagic Escherichia coli, binds to the cell surface glycolipid, globotriaosylceramide (Gb(3)) and is internalized into preendosomes. VT is then retrograde transported to the Golgi, endoplasmic reticulum (ER), and nucleus of highly VT-sensitive cells. We have utilized this nuclear targeting of VT to design a unique delivery system which transports exogenous DNA via vesicular traffic to the nucleus. The nontoxic VT binding subunit (VTB) was fused to the lambda Cro DNA-binding repressor, generating a 14-kDa VTB-Cro chimera. VTB-Cro binds specifically via the Cro domain to a 25-bp DNA fragment containing the consensus Cro operator. VTB-Cro demonstrates simultaneous specific binding to Gb(3). Treatment of Vero cells with fluorescent-labeled Cro operator DNA in the presence of VTB-Cro, results in DNA internalization to the Golgi, ER, and nucleus, whereas fluorescent DNA alone is incorporated poorly and randomly within the cytoplasm. VTB-Cro mediated nuclear DNA transport is prevented by brefeldin A, consistent with Golgi/ER intracellular routing. Pretreatment with filipin had no effect, indicating that caveoli are not involved. This novel VTB-Cro shuttle protein may find practical applications in the fields of intracellular targeting, gene delivery, and gene therapy. Copyright 2001 Academic Press.

AACR-NCI-EORTC - 27th International Symposium - Molecular Targets and Cancer Therapeutics (November 5-9, 2015 - Boston, Massachusetts, USA).

PubMed

Carceller, V

2015-11-01

The 27th joint meeting of the European Organization for Research and Treatment of Cancer, National Cancer Institute and the American Association of Cancer Research (EORTC-NCI-AACR) International Conference on Molecular Targets and Cancer Therapeutics was held this year in Boston. Approximately 3,000 international academics, scientists and pharmaceutical industry representatives discussed new discoveries in the field of molecular biology of cancer and presented the latest information on drug discovery, preclinical research, clinical research and target selection in oncology. This report summarizes data on advances in cancer drug discovery. Copyright 2015 Prous Science, S.A.U. or its licensors. All rights reserved.

SMART Careplan System for Continuum of Care

PubMed Central

Kim, Young Ah; Jang, Seon Young; Ahn, Meejung; Kim, Kyung Duck

2015-01-01

Objectives This paper describes the integrated Careplan system, designed to manage and utilize the existing Electronic Medical Record (EMR) system; the system also defines key items for interdisciplinary communication and continuity of patient care. Methods We structured the Careplan system to provide effective interdisciplinary communication for healthcare services. The design of the Careplan system architecture proceeded in four steps-defining target datasets; construction of conceptual framework and architecture; screen layout and storyboard creation; screen user interface (UI) design and development, and pilot test and step-by-step deployment. This Careplan system architecture consists of two parts, a server-side and client-side area. On the server-side, it performs the roles of data retrieval and storage from target EMRs. Furthermore, it performs the role of sending push notifications to the client depending on the careplan series. Also, the Careplan system provides various convenient modules to easily enter an individual careplan. Results Currently, Severance Hospital operates the Careplan system and provides a stable service dealing with dynamic changes (e.g., domestic medical certification, the Joint Commission International guideline) of EMR. Conclusions The Careplan system should go hand in hand with key items for strengthening interdisciplinary communication and information sharing within the EMR environment. A well-designed Careplan system can enhance user satisfaction and completed performance. PMID:25705559

SMART Careplan System for Continuum of Care.

PubMed

Kim, Young Ah; Jang, Seon Young; Ahn, Meejung; Kim, Kyung Duck; Kim, Sung Soo

2015-01-01

This paper describes the integrated Careplan system, designed to manage and utilize the existing Electronic Medical Record (EMR) system; the system also defines key items for interdisciplinary communication and continuity of patient care. We structured the Careplan system to provide effective interdisciplinary communication for healthcare services. The design of the Careplan system architecture proceeded in four steps-defining target datasets; construction of conceptual framework and architecture; screen layout and storyboard creation; screen user interface (UI) design and development, and pilot test and step-by-step deployment. This Careplan system architecture consists of two parts, a server-side and client-side area. On the server-side, it performs the roles of data retrieval and storage from target EMRs. Furthermore, it performs the role of sending push notifications to the client depending on the careplan series. Also, the Careplan system provides various convenient modules to easily enter an individual careplan. Currently, Severance Hospital operates the Careplan system and provides a stable service dealing with dynamic changes (e.g., domestic medical certification, the Joint Commission International guideline) of EMR. The Careplan system should go hand in hand with key items for strengthening interdisciplinary communication and information sharing within the EMR environment. A well-designed Careplan system can enhance user satisfaction and completed performance.

High definition versus standard definition white light endoscopy for detecting dysplasia in patients with Barrett's esophagus.

PubMed

Sami, S S; Subramanian, V; Butt, W M; Bejkar, G; Coleman, J; Mannath, J; Ragunath, K

2015-01-01

High-definition endoscopy systems provide superior image resolution. The aim of this study was to assess the utility of high definition compared with standard definition endoscopy system for detecting dysplastic lesions in patients with Barrett's esophagus. A retrospective cohort study of patients with non-dysplastic Barrett's esophagus undergoing routine surveillance was performed. Data were retrieved from the central hospital electronic database. Procedures performed for non-surveillance indications, Barrett's esophagus Prague C0M1 classification with no specialized intestinal metaplasia on histology, patients diagnosed with any dysplasia or cancer on index endoscopy, and procedures using advanced imaging techniques were excluded. Logistic regression models were constructed to estimate adjusted odds ratios and 95% confidence intervals comparing outcomes with standard definition and high-definition systems. The high definition was superior to standard definition system in targeted detection of all dysplastic lesions (odds ratio 3.27, 95% confidence interval 1.27-8.40) as well as overall dysplasia detected on both random and target biopsies (odds ratio 2.36, 95% confidence interval 1.50-3.72). More non-dysplastic lesions were detected with the high-definition system (odds ratio 1.16, 95% confidence interval 1.01-1.33). There was no difference between high definition and standard definition endoscopy in the overall (random and target) high-grade dysplasia or cancers detected (odds ratio 0.93, 95% confidence interval 0.83-1.04). Trainee endoscopists, number of biopsies taken, and male sex were all significantly associated with a higher yield for dysplastic lesions. The use of the high-definition endoscopy system is associated with better targeted detection of any dysplasia during routine Barrett's esophagus surveillance. However, high-definition endoscopy cannot replace random biopsies at present time. © 2014 International Society for Diseases of the Esophagus.

International Space Station End-of-Life Probabilistic Risk Assessment

NASA Technical Reports Server (NTRS)

Duncan, Gary W.

2014-01-01

The International Space Station (ISS) end-of-life (EOL) cycle is currently scheduled for 2020, although there are ongoing efforts to extend ISS life cycle through 2028. The EOL for the ISS will require deorbiting the ISS. This will be the largest manmade object ever to be de-orbited therefore safely deorbiting the station will be a very complex problem. This process is being planned by NASA and its international partners. Numerous factors will need to be considered to accomplish this such as target corridors, orbits, altitude, drag, maneuvering capabilities etc. The ISS EOL Probabilistic Risk Assessment (PRA) will play a part in this process by estimating the reliability of the hardware supplying the maneuvering capabilities. The PRA will model the probability of failure of the systems supplying and controlling the thrust needed to aid in the de-orbit maneuvering.

Lupus erythematosus: considerations about clinical, cutaneous and therapeutic aspects*

PubMed Central

Moura Filho, Jucélio Pereira; Peixoto, Raiza Luna; Martins, Lívia Gomes; de Melo, Sillas Duarte; de Carvalho, Ligiana Leite; Pereira, Ana Karine F. da Trindade C.; Freire, Eutilia Andrade Medeiros

2014-01-01

Systemic Lupus Erythematosus is a chronic inflammatory disease with multifactorial etiology. Although clinical manifestations are varied, the skin is an important target-organ, which contributes to the inclusion of skin lesions in 4 out of the 17 new criteria for the diagnosis of the disease, according to the Systemic Lupus International Collaborating Clinics. The cutaneous manifestations of lupus are pleomorphic. Depending on their clinical characteristics, they can be classified into Acute Cutaneous Lupus Erythematosus, Subacute Cutaneous Lupus Erythematosus, Chronic Cutaneous Lupus Erythematosus and Intermittent Cutaneous Lupus Erythematosus. Treatment is based on preventive measures, reversal of inflammation, prevention of damage to target organs and relief of adverse events due to pharmacological therapy. The most commonly used treatment options are topical, systemic and surgical treatment, as well as phototherapy. The correct handling of the cases depends on a careful evaluation of the morphology of the lesions and the patient's general status, always taking into consideration not only the benefits but also the side effects of each therapeutic proposal. PMID:24626656

Protection from feed-forward amplification in an amplified RNAi mechanism

PubMed Central

Pak, Julia; Maniar, Jay Mahesh; Mello, Cecilia Cabral; Fire, Andrew

2012-01-01

SUMMARY The effectiveness of RNA interference (RNAi) in many organisms is potentiated through the signal-amplifying activity of a targeted RNA directed RNA polymerase (RdRP) system that can convert a small population of exogenously-encountered dsRNA fragments into an abundant internal pool of small interfering RNA (siRNA). As for any biological amplification system, we expect an underlying architecture that will limit the ability of a randomly encountered trigger to produce an uncontrolled and self-escalating response. Investigating such limits in C. elegans, we find that feed-forward amplification is limited by a critical biosynthetic and structural distinction at the RNA level between (i) triggers that can produce amplification and (ii) siRNA products of the amplification reaction. By assuring that initial (primary) siRNAs can act as triggers but not templates for activation, and that the resulting (secondary) siRNAs can enforce gene silencing on additional targets without unbridled trigger amplification, the system achieves substantial but fundamentally limited signal amplification. PMID:23141544

Free-form surface design method for a collimator TIR lens.

PubMed

Tsai, Chung-Yu

2016-04-01

A free-form (FF) surface design method is proposed for a general axial-symmetrical collimator system consisting of a light source and a total internal reflection lens with two coupled FF boundary surfaces. The profiles of the boundary surfaces are designed using a FF surface construction method such that each incident ray is directed (refracted and reflected) in such a way as to form a specified image pattern on the target plane. The light ray paths within the system are analyzed using an exact analytical model and a skew-ray tracing approach. In addition, the validity of the proposed FF design method is demonstrated by means of ZEMAX simulations. It is shown that the illumination distribution formed on the target plane is in good agreement with that specified by the user. The proposed surface construction method is mathematically straightforward and easily implemented in computer code. As such, it provides a useful tool for the design and analysis of general axial-symmetrical optical systems.

Rendezvous and Proximity Operations of the Space Shuttle

NASA Technical Reports Server (NTRS)

Goodman, John L.

2005-01-01

Space Shuttle rendezvous missions present unique challenges that were not fully recognized when the Shuttle was designed. Rendezvous targets could be passive (i.e., no lights or transponders), and not designed to facilitate Shuttle rendezvous, proximity operations, and retrieval. Shuttle reaction control system jet plume impingement on target spacecraft presented induced dynamics, structural loading, and contamination concerns. These issues, along with limited reaction control system propellant in the Shuttle nose, drove a change from the legacy Gemini/Apollo coelliptic profile to a stable orbit profile, and the development of new proximity operations techniques. Multiple scientific and on-orbit servicing missions, and crew exchange, assembly and replenishment flights to Mir and to the International Space Station drove further profile and piloting technique changes. These changes included new proximity operations, relative navigation sensors, and new computer generated piloting cues. However, the Shuttle's baseline rendezvous navigation system has not required modification to place the Shuttle at the proximity operations initiation point for all rendezvous missions flown.

Delivery of Cancer Therapeutics Using Nanotechnology

PubMed Central

Lim, Eun-Kyung; Jang, Eunji; Lee, Kwangyeol; Haam, Seungjoo; Huh, Yong-Min

2013-01-01

Nanoparticles have been investigated as drug carriers, because they provide a great opportunity due to their advantageous features: (i) various formulations using organic/inorganic materials, (ii) easy modification of targeting molecules, drugs or other molecules on them, (iii) effective delivery to target sites, resulting in high therapeutic efficacy and (iv) controlling drug release by external/internal stimuli. Because of these features, therapeutic efficacy can be improved and unwanted side effects can be reduced. Theranostic nanoparticles have been developed by incorporating imaging agents in drug carriers as all-in-one system, which makes it possible to diagnose and treat cancer by monitoring drug delivery behavior simultaneously. Recently, stimuli-responsive, activatable nanomaterials are being applied that are capable of producing chemical or physical changes by external stimuli. By using these nanoparticles, multiple tasks can be carried out simultaneously, e.g., early and accurate diagnosis, efficient cataloguing of patient groups of personalized therapy and real-time monitoring of disease progress. In this paper, we describe various types of nanoparticles for drug delivery systems, as well as theranostic systems. PMID:24300452

Effect of compressibility on the hypervelocity penetration

NASA Astrophysics Data System (ADS)

Song, W. J.; Chen, X. W.; Chen, P.

2018-02-01

We further consider the effect of rod strength by employing the compressible penetration model to study the effect of compressibility on hypervelocity penetration. Meanwhile, we define different instances of penetration efficiency in various modified models and compare these penetration efficiencies to identify the effects of different factors in the compressible model. To systematically discuss the effect of compressibility in different metallic rod-target combinations, we construct three cases, i.e., the penetrations by the more compressible rod into the less compressible target, rod into the analogously compressible target, and the less compressible rod into the more compressible target. The effects of volumetric strain, internal energy, and strength on the penetration efficiency are analyzed simultaneously. It indicates that the compressibility of the rod and target increases the pressure at the rod/target interface. The more compressible rod/target has larger volumetric strain and higher internal energy. Both the larger volumetric strain and higher strength enhance the penetration or anti-penetration ability. On the other hand, the higher internal energy weakens the penetration or anti-penetration ability. The two trends conflict, but the volumetric strain dominates in the variation of the penetration efficiency, which would not approach the hydrodynamic limit if the rod and target are not analogously compressible. However, if the compressibility of the rod and target is analogous, it has little effect on the penetration efficiency.

Black gold and blackmail: The politics of international oil coercion

NASA Astrophysics Data System (ADS)

Kelanic, Rosemary Ann

Does oil hold potential as an instrument of international political coercion? Could a country use the threat of oil cutoff to blackmail other nations? If so, why, and under what circumstances is this likely to occur? I argue that oil coercion, under a narrow range of circumstances, offers great promise for a country to get its way in the international system. My argument consists of two main steps. First, I argue that oil is unique. No other strategic resource compares to petroleum when it comes to determining success on the battlefield. An adversary that can forcibly interdict the flow of oil to a belligerent in wartime could immobilize the target's military, essentially threatening the target with military defeat. The oil weapon is most potent when employed in this manner as a denial strategy of coercion. For a state to be at risk of oil coercion, it must have some degree of baseline vulnerability. I hypothesize that three variables determine a state's vulnerability to oil coercion. The first is its degree of dependence on foreign sources of oil. For oil coercion to be effective, the target must depend heavily on foreign sources of petroleum. Second, the target's geography matters greatly, because it affects a coercer's ability to block the flow of oil. Island states are particularly susceptible to military blockade. The third variable is the country's relative power, which determines whether or not the state can protect its supply lines. The second step of the argument explains why successful oil coercion is rare. I argue that states, as strategic actors, recognize the danger oil coercion poses to them. Consequently, they try to forestall coercion by taking anticipatory measures to safeguard their petroleum access before coercion can happen. States pursue four types of anticipatory strategies: internal measures, such as stockpiling; alliances with petroleum-producing countries; deterrence; and conquest of oil-producing regions. More often than not, these policies undermine the effectiveness of the oil weapon. As a result, when it comes to oil coercion, we see a paradox: coercive failures occur because states respond proactively to the potential of being coerced.

Targeted drug delivery and enhanced intracellular release using functionalized liposomes

NASA Astrophysics Data System (ADS)

Garg, Ashish

The ability to target cancer cells using an appropriate drug delivery system can significantly reduce the associated side effects from cancer therapies and can help in improving the overall quality of life, post cancer survival. Integrin alpha5beta1 is expressed on several types of cancer cells, including colon cancer and plays an important role in tumor growth and metastasis. Thus, the ability to target the integrin alpha 5beta1 using an appropriate drug delivery nano-vector can significantly help in inhibiting tumor growth and reducing tumor metastasis. The work in this thesis focuses on designing and optimizing, functionalized stealth liposomes (liposomes covered with polyethylene glycol (PEG)) that specifically target the integrin alpha5beta1. The PEG provides a steric barrier allowing the liposomes to circulate in the blood for longer duration and the functionalizing moiety, PR_b peptide specifically recognizes and binds to integrin alpha5beta1 expressing cells. The work demonstrates that by optimizing the amount of PEG and PR_b on the liposomal interface, nano-vectors can be engineered that bind to CT26.WT colon cancer cells in a specific manner and internalize through alpha 5beta1-mediated endocytosis. To further improve the efficacy of the system, PR_b functionalized pH-sensitive stealth liposomes that exhibit triggered release under mild acidic conditions present in endocytotic vesicles were designed. The study showed that PR_b functionalized pH-sensitive stealth liposomes, undergo destabilization under mildly acidic conditions and incorporation of the PR_b peptide does not significantly affect the pH-sensitivity of the liposomes. PR_b functionalized pH-sensitive stealth liposomes bind to CT26.WT colon carcinoma cells that express integrin alpha5beta 1, undergo cellular internalization, and release their load intracellularly in a short period of time as compared to other formulations. PR_b-targeted pH-sensitive stealth liposomes encapsulating 5-fluorouracil (5-FU) show significantly higher cytotoxicity than the PR_b-targeted inert stealth liposomes and the non-targeted stealth liposomes (both pH-sensitive and inert). The studies demonstrated that optimized PR_b functionalized pH sensitive liposomes have the potential to deliver a payload, such as chemotherapeutic agents, directly to colon cancer cells in an efficient and specific manner.

A real-time respiration position based passive breath gating equipment for gated radiotherapy: A preclinical evaluation

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

Hu Weigang; Xu Anjie; Li Guichao

2012-03-15

Purpose: To develop a passive gating system incorporating with the real-time position management (RPM) system for the gated radiotherapy. Methods: Passive breath gating (PBG) equipment, which consists of a breath-hold valve, a controller mechanism, a mouthpiece kit, and a supporting frame, was designed. A commercial real-time positioning management system was implemented to synchronize the target motion and radiation delivery on a linear accelerator with the patient's breathing cycle. The respiratory related target motion was investigated by using the RPM system for correlating the external markers with the internal target motion while using PBG for passively blocking patient's breathing. Six patientsmore » were enrolled in the preclinical feasibility and efficiency study of the PBG system. Results: PBG equipment was designed and fabricated. The PBG can be manually triggered or released to block or unblock patient's breathing. A clinical workflow was outlined to integrate the PBG with the RPM system. After implementing the RPM based PBG system, the breath-hold period can be prolonged to 15-25 s and the treatment delivery efficiency for each field can be improved by 200%-400%. The results from the six patients showed that the diaphragm motion caused by respiration was reduced to less than 3 mm and the position of the diaphragm was reproducible for difference gating periods. Conclusions: A RPM based PBG system was developed and implemented. With the new gating system, the patient's breath-hold time can be extended and a significant improvement in the treatment delivery efficiency can also be achieved.« less

Optimized swimmer tracking system based on a novel multi-related-targets approach

NASA Astrophysics Data System (ADS)

Benarab, D.; Napoléon, T.; Alfalou, A.; Verney, A.; Hellard, P.

2017-02-01

Robust tracking is a crucial step in automatic swimmer evaluation from video sequences. We designed a robust swimmer tracking system using a new multi-related-targets approach. The main idea is to consider the swimmer as a bloc of connected subtargets that advance at the same speed. If one of the subtargets is partially or totally occluded, it can be localized by knowing the position of the others. In this paper, we first introduce the two-dimensional direct linear transformation technique that we used to calibrate the videos. Then, we present the classical tracking approach based on dynamic fusion. Next, we highlight the main contribution of our work, which is the multi-related-targets tracking approach. This approach, the classical head-only approach and the ground truth are then compared, through testing on a database of high-level swimmers in training, national and international competitions (French National Championships, Limoges 2015, and World Championships, Kazan 2015). Tracking percentage and the accuracy of the instantaneous speed are evaluated and the findings show that our new appraoach is significantly more accurate than the classical approach.

Fundamental Biological Research on the International Space Station

NASA Technical Reports Server (NTRS)

Souza, K. A.; Yost, Bruce; Fletcher, L.; Dalton, Bonnie P. (Technical Monitor)

2000-01-01

The fundamental Biology Program of NASA's Life Sciences Division is chartered with enabling and sponsoring research on the International Space Station (ISS) in order to understand the effects of the space flight environment, particularly microgravity, on living systems. To accomplish this goal, NASA Ames Research Center (ARC) has been tasked with managing the development of a number of biological habitats, along with their support systems infrastructure. This integrated suite of habitats and support systems is being designed to support research requirements identified by the scientific community. As such, it will support investigations using cells and tissues, avian eggs, insects, plants, aquatic organisms and rodents. Studies following organisms through complete life cycles and over multiple generations will eventually be possible. As an adjunct to the development of these basic habitats, specific analytical and monitoring technologies are being targeted for maturation to complete the research cycle by transferring existing or emerging analytical techniques, sensors, and processes from the laboratory bench to the ISS research platform.

CTEPP STANDARD OPERATING PROCEDURE FOR PREPARATION OF SURROGATE RECOVERY STANDARD AND INTERNAL STANDARD SOLUTIONS FOR POLAR TARGET ANALYTES (SOP-5.26)

EPA Science Inventory

This SOP describes the method used for preparing surrogate recovery standard and internal standard solutions for the analysis of polar target analytes. It also describes the method for preparing calibration standard solutions for polar analytes used for gas chromatography/mass sp...

In vivo toxicity, biodistribution, and clearance of glutathione-coated gold nanoparticles.

PubMed

Simpson, Carrie A; Salleng, Kenneth J; Cliffel, David E; Feldheim, Daniel L

2013-02-01

Gold nanoparticles are emerging as promising materials from which to construct nanoscale therapeutics and therapeutic delivery systems. However, animal studies have shown that gold nanoparticles modified with certain thiol monolayers such as tiopronin can cause renal complications and morbidity. Although these effects may be eliminated by coadsorbing small amounts of polyethylene glycol (PEG) onto the nanoparticle surface, PEG can also lower cellular internalization efficiency and binding interactions with protein disease targets, significantly reducing the potential for using gold nanoparticles as therapeutics. Using ICP-MS analysis of blood, urine, and several organs, we show in this article that glutathione-coated gold nanoparticles (1.2 nm ± 0.9 nm) cause no morbidity at any concentration up to and including 60 μM and target primary organs although providing gradual dissipation and clearance over time. This study suggests that glutathione may be an attractive alternative to PEG in the design of gold nanoparticle therapeutics. This study describes the utility and toxicity of glutathione coated gold nanoparticles in comparison to PEGylated counterparts that are commonly used to increase "Stealth" properties and lower cytotoxicity. Too much PEG on the NPs can lead to lower cellular internalization efficiency and less efficient binding interactions with protein disease targets, significantly reducing the potential for using gold nanoparticles as therapeutics. Copyright © 2013 Elsevier Inc. All rights reserved.

Issues and controversies of hepatocellular carcinoma-targeted therapy clinical trials in Asia: experts' opinion.

PubMed

Chen, Pei-Jer; Furuse, Junji; Han, Kwang-Hyub; Hsu, Chiun; Lim, Ho-Yeong; Moon, Hanlim; Qin, Shukui; Ye, Sheng-Long; Yeoh, Ee-Min; Yeo, Winnie

2010-11-01

Asia has a disproportionate share of the world's burden of hepatocellular carcinoma (HCC). However, the highly regarded clinical practice guidelines and recommendations for the design and conduct of clinical trials for HCC largely reflect Western practice. In order to design mutually beneficial international clinical trials of promising targeted therapies, it is imperative to understand how the aetiology, staging and treatment of HCC differ between Asian and Western countries. Our group, comprising experts in oncology and hepatology from countries that constitute the Eastern Asian region, convened to compare and contrast our current practices, evaluate potential compliance with the clinical trial recommendations, and offer suggestions for modifications that would enhance international collaboration. Here, we describe the results of our discussions, including recommendations for appropriate patient stratification based on potentially important differences in HCC aetiology, identification of practices that may confound interpretation of clinical trial outcomes (traditional Chinese medicine; antivirals that target hepatitis B virus; heterogeneous embolization procedures), suggestions for utilizing a common staging system in study protocols, recognition that sorafenib usage is limited by financial constraints and potentially increased toxicity in Asian patients, and expansion of patient populations that should be eligible for initial clinical trials with new agents. © 2010 John Wiley & Sons A/S.

KSC-07pd2868

NASA Image and Video Library

2007-10-01

KENNEDY SPACE CENTER, FLA. -- In the Space Station Processing Facility at NASA's Kennedy Space Center, the starboard arm of the Special Purpose Dexterous Manipulator, known as Dextre, is lowered toward the base for installation. Dextre is a sophisticated dual-armed robot, which is part of Canada's contribution to the International Space Station (ISS). Along with Canadarm2, whose technical name is the Space Station Remote Manipulator System, and a moveable work platform called the Mobile Base System, these three elements form a robotic system called the Mobile Servicing System, or MSS. The three components have been designed to work together or independently. Dextre is part of the payload scheduled on mission STS-123, targeted to launch Feb. 14. Photo credit: NASA/George Shelton

STK Integrated Message Production List Editor (SIMPLE) for CEO Operations

NASA Technical Reports Server (NTRS)

Trenchard, Mike; Heydorn, James

2014-01-01

Late in fiscal year 2011, the Crew Earth Observations (CEO) team was tasked to upgrade and replace its mission planning and mission operations software systems, which were developed in the Space Shuttle era of the 1980s and 1990s. The impetuses for this change were the planned transition of all workstations to the Windows 7 64-bit operating system and the desire for more efficient and effective use of Satellite Tool Kit (STK) software required for reliable International Space Station (ISS) Earth location tracking. An additional requirement of this new system was the use of the same SQL database of CEO science sites from the SMMS, which was also being developed. STK Integrated Message Production List Editor (SIMPLE) is the essential, all-in-one tool now used by CEO staff to perform daily ISS mission planning to meet its requirement to acquire astronaut photography of specific sites on Earth. The sites are part of a managed, long-term database that has been defined and developed for scientific, educational, and public interest. SIMPLE's end product is a set of basic time and location data computed for an operator-selected set of targets that the ISS crew will be asked to photograph (photography is typically planned 12 to 36 hours out). The CEO operator uses SIMPLE to (a) specify a payload operations planning period; (b) acquire and validate the best available ephemeris data (vectors) for the ISS during the planning period; (c) ingest and display mission-specific site information from the CEO database; (d) identify and display potential current dynamic event targets as map features; (e) compute and display time and location information for each target; (f) screen and select targets based on known crew availability constraints, obliquity constraints, and real-time evaluated constraints to target visibility due to illumination (sun elevation) and atmospheric conditions (weather); and finally (g) incorporate basic, computed time and location information for each selected target into the daily CEO Target List product (message) for submission to ISS payload planning and integration teams for their review and approval prior to uplink. SIMPLE requires and uses the following resources: an ISS mission planning period Greenwich Mean Time start date/time and end date/time), the best available ISS mission ephemeris data (vectors) for that planning period, the STK software package configured for the ISS, and an ISS mission-specific subset of the CEO sites database. The primary advantages realized by the development and implementation of SIMPLE into the CEO payload operations support activity are a smooth transition to the Windows 7 operating system upon scheduled workstation refresh; streamlining of the input and verification of the current ISS ephemeris (vector data); seamless incorporation of selected contents of the SQL database of science sites; the ability to tag and display potential dynamic event opportunities on orbit track maps; simplification of the display and selection of encountered sites based on crew availability, illumination, obliquity, and weather constraints; the incorporation of high-quality mapping of the Earth with various satellite-based datasets for use in describing targets; and the ability to encapsulate and export the essential selected target elements in XML format for use by onboard Earth-location systems, such as Worldmap. SIMPLE is a carefully designed and crafted in-house software package that includes detailed help files for the user and meticulous internal documentation for future modifications. It was delivered in February 2012 for test and evaluation. Following acceptance, it was implemented for CEO mission operations support in May 2012.

Expert consensus document: Clinical and molecular diagnosis, screening and management of Beckwith-Wiedemann syndrome: an international consensus statement.

PubMed

Brioude, Frédéric; Kalish, Jennifer M; Mussa, Alessandro; Foster, Alison C; Bliek, Jet; Ferrero, Giovanni Battista; Boonen, Susanne E; Cole, Trevor; Baker, Robert; Bertoletti, Monica; Cocchi, Guido; Coze, Carole; De Pellegrin, Maurizio; Hussain, Khalid; Ibrahim, Abdulla; Kilby, Mark D; Krajewska-Walasek, Malgorzata; Kratz, Christian P; Ladusans, Edmund J; Lapunzina, Pablo; Le Bouc, Yves; Maas, Saskia M; Macdonald, Fiona; Õunap, Katrin; Peruzzi, Licia; Rossignol, Sylvie; Russo, Silvia; Shipster, Caroleen; Skórka, Agata; Tatton-Brown, Katrina; Tenorio, Jair; Tortora, Chiara; Grønskov, Karen; Netchine, Irène; Hennekam, Raoul C; Prawitt, Dirk; Tümer, Zeynep; Eggermann, Thomas; Mackay, Deborah J G; Riccio, Andrea; Maher, Eamonn R

2018-04-01

Beckwith-Wiedemann syndrome (BWS), a human genomic imprinting disorder, is characterized by phenotypic variability that might include overgrowth, macroglossia, abdominal wall defects, neonatal hypoglycaemia, lateralized overgrowth and predisposition to embryonal tumours. Delineation of the molecular defects within the imprinted 11p15.5 region can predict familial recurrence risks and the risk (and type) of embryonal tumour. Despite recent advances in knowledge, there is marked heterogeneity in clinical diagnostic criteria and care. As detailed in this Consensus Statement, an international consensus group agreed upon 72 recommendations for the clinical and molecular diagnosis and management of BWS, including comprehensive protocols for the molecular investigation, care and treatment of patients from the prenatal period to adulthood. The consensus recommendations apply to patients with Beckwith-Wiedemann spectrum (BWSp), covering classical BWS without a molecular diagnosis and BWS-related phenotypes with an 11p15.5 molecular anomaly. Although the consensus group recommends a tumour surveillance programme targeted by molecular subgroups, surveillance might differ according to the local health-care system (for example, in the United States), and the results of targeted and universal surveillance should be evaluated prospectively. International collaboration, including a prospective audit of the results of implementing these consensus recommendations, is required to expand the evidence base for the design of optimum care pathways.

Microsurgical and Endoscopic Anatomy for Intradural Temporal Bone Drilling and Applications of the Electromagnetic Navigation System: Various Extensions of the Retrosigmoid Approach.

PubMed

Matsushima, Ken; Komune, Noritaka; Matsuo, Satoshi; Kohno, Michihiro

2017-07-01

The use of the retrosigmoid approach has recently been expanded by several modifications, including the suprameatal, transmeatal, suprajugular, and inframeatal extensions. Intradural temporal bone drilling without damaging vital structures inside or beside the bone, such as the internal carotid artery and jugular bulb, is a key step for these extensions. This study aimed to examine the microsurgical and endoscopic anatomy of the extensions of the retrosigmoid approach and to evaluate the clinical feasibility of an electromagnetic navigation system during intradural temporal bone drilling. Five temporal bones and 8 cadaveric cerebellopontine angles were examined to clarify the anatomy of retrosigmoid intradural temporal bone drilling. Twenty additional cerebellopontine angles were dissected in a clinical setting with an electromagnetic navigation system while measuring the target registration errors at 8 surgical landmarks on and inside the temporal bone. Retrosigmoid intradural temporal bone drilling expanded the surgical exposure to allow access to the petroclival and parasellar regions (suprameatal), internal acoustic meatus (transmeatal), upper jugular foramen (suprajugular), and petrous apex (inframeatal). The electromagnetic navigation continuously guided the drilling without line of sight limitation, and its small devices were easily manipulated in the deep and narrow surgical field in the posterior fossa. Mean target registration error was less than 0.50 mm during these procedures. The combination of endoscopic and microsurgical techniques aids in achieving optimal exposure for retrosigmoid intradural temporal bone drilling. The electromagnetic navigation system had clear advantages with acceptable accuracy including the usability of small devices without line of sight limitation. Copyright © 2017 Elsevier Inc. All rights reserved.

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

Code of Federal Regulations, 2013 CFR

2013-04-01

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

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

Code of Federal Regulations, 2012 CFR

2012-04-01

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

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

Code of Federal Regulations, 2014 CFR

2014-04-01

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

[Revision of the TNM Stage Grouping in the Forthcoming Eighth Edition of the TNM Classification for Lung Cancer].

PubMed

Ye, Bo; Zhao, Heng

2016-06-20

The currently adopted staging system for lung cancer is the seventh edition of the TNM staging edited by Union for International Cancer Control (UICC) in January, 2009. In recent years, with the advances of techniques in lung cancer diagnosis and the treatment trends towards precision treatment modalities such as individualized therapy and molecular targeted therapy, the survival and prognosis of lung cancer has been significantly improved. The old staging standard is difficult to satisfy the currentrapidly developing clinical needs. Therefore, the International Lung Cancer Research Society (International Association for the Study of Lung Cancer, IASLC) updated the stage of lung cancer in 2015, and the forthcoming eighth edition of the TNM Classification for Lung Cancer, which will be formally adopted in Jan. 2017, has been published in Journal of Thoracic Oncology. The new staging system has adopted 35 databases from 16 countries, including 94,708 cases treated between 1999 and 2010. The advantages of the new staging lies in its higher prognosis prediction and clinical guidance value.

Data Mining FAERS to Analyze Molecular Targets of Drugs Highly Associated with Stevens-Johnson Syndrome.

PubMed

Burkhart, Keith K; Abernethy, Darrell; Jackson, David

2015-06-01

Drug features that are associated with Stevens-Johnson syndrome (SJS) have not been fully characterized. A molecular target analysis of the drugs associated with SJS in the FDA Adverse Event Reporting System (FAERS) may contribute to mechanistic insights into SJS pathophysiology. The publicly available version of FAERS was analyzed to identify disproportionality among the molecular targets, metabolizing enzymes, and transporters for drugs associated with SJS. The FAERS in-house version was also analyzed for an internal comparison of the drugs most highly associated with SJS. Cyclooxygenases 1 and 2, carbonic anhydrase 2, and sodium channel 2 alpha were identified as disproportionately associated with SJS. Cytochrome P450 (CYPs) 3A4 and 2C9 are disproportionately represented as metabolizing enzymes of the drugs associated with SJS adverse event reports. Multidrug resistance protein 1 (MRP-1), organic anion transporter 1 (OAT1), and PEPT2 were also identified and are highly associated with the transport of these drugs. A detailed review of the molecular targets identifies important roles for these targets in immune response. The association with CYP metabolizing enzymes suggests that reactive metabolites and oxidative stress may have a contributory role. Drug transporters may enhance intracellular tissue concentrations and also have vital physiologic roles that impact keratinocyte proliferation and survival. Data mining FAERS may be used to hypothesize mechanisms for adverse drug events by identifying molecular targets that are highly associated with drug-induced adverse events. The information gained may contribute to systems biology disease models.

Photodynamic therapy of tumors with pyropheophorbide-a-loaded polyethylene glycol-poly(lactic-co-glycolic acid) nanoparticles.

PubMed

Liu, Hui; Zhao, Mei; Wang, Jin; Pang, Mingpei; Wu, Zhenzhou; Zhao, Liqing; Yin, Zhinan; Hong, Zhangyong

Photodynamic therapy (PDT) has many advantages in treating cancers, but the lack of ideal photosensitizers continues to be a major limitation restricting the clinical utility of PDT. This study aimed to overcome this obstacle by generating pyropheophorbide- a -loaded polyethylene glycol-poly(lactic- co -glycolic acid) nanoparticles (NPs) for efficient tumor-targeted PDT. The fabricated NPs were efficiently internalized in the mitochondrion by cancer cells, and they efficiently killed cancer cells in a dose-dependent manner when activated with light. Systemically delivered NPs were highly enriched in tumor sites, and completely ablated the tumors in a xenograft KB tumor mouse model when illuminated with 680 nm light (156 mW/cm 2 , 10 minutes). The results suggested that this tumor-specific NP-delivery system for pyropheophorbide- a has the potential to be used in tumor-targeted PDT.

Photodynamic therapy of tumors with pyropheophorbide-a-loaded polyethylene glycol–poly(lactic-co-glycolic acid) nanoparticles

PubMed Central

Liu, Hui; Zhao, Mei; Wang, Jin; Pang, Mingpei; Wu, Zhenzhou; Zhao, Liqing; Yin, Zhinan; Hong, Zhangyong

2016-01-01

Photodynamic therapy (PDT) has many advantages in treating cancers, but the lack of ideal photosensitizers continues to be a major limitation restricting the clinical utility of PDT. This study aimed to overcome this obstacle by generating pyropheophorbide-a-loaded polyethylene glycol–poly(lactic-co-glycolic acid) nanoparticles (NPs) for efficient tumor-targeted PDT. The fabricated NPs were efficiently internalized in the mitochondrion by cancer cells, and they efficiently killed cancer cells in a dose-dependent manner when activated with light. Systemically delivered NPs were highly enriched in tumor sites, and completely ablated the tumors in a xenograft KB tumor mouse model when illuminated with 680 nm light (156 mW/cm2, 10 minutes). The results suggested that this tumor-specific NP-delivery system for pyropheophorbide-a has the potential to be used in tumor-targeted PDT. PMID:27729788

Thioredoxin and redox signaling: Roles of the thioredoxin system in control of cell fate.

PubMed

Matsuzawa, Atsushi

2017-03-01

Reactive oxygen species (ROS) are not only cytotoxic products from external and internal environment, but also important mediators of redox signaling. Therefore, thioredoxin (Trx) as an antioxidant maintains the balance of the thiol-related redox status, and also plays pivotal roles in the regulation of redox signaling. Trx senses and responds to environmental oxidative stress and ROS generated by cellular respiration, metabolism, and immune response, and then modulates the redox status, function, and activity of its target signaling proteins. Dysregulation of such the Trx system affects various cellular functions and cell fate such as survival and cell death, leading to human diseases including cancer and inflammation. This review focuses on Trx and its target proteins involved in redox signaling, which are critical for the control of cell fate such as cell survival and apoptosis, and addresses how Trx regulates those effector proteins and redox signaling. Copyright © 2016 Elsevier Inc. All rights reserved.

KSC-98pc1775

NASA Image and Video Library

1998-12-03

KENNEDY SPACE CENTER, FLA. -- Participants pose for a photo at the Space Station Processing Facility ceremony transferring the "Leonardo" Multipurpose Logistics Module (MPLM) from the Italian Space Agency, Agenzia Spaziale Italiana (ASI), to NASA. From left, they are astronaut Jim Voss, ASI President Sergio De Julio, European Space Agency astronaut Umberto Guidoni of Italy, NASA Administrator Daniel S. Goldin and European Space Agency astronaut Christer Fuglesang of Sweden. The MPLM, a reusable logistics carrier, will be the primary delivery system used to resupply and return International Space Station cargo requiring a pressurized environment. Leonardo is the first of three MPLM carriers for the International Space Station. It is scheduled to be launched on Space Shuttle Mission STS-100, targeted for April 2000

KSC-98pc1774

NASA Image and Video Library

1998-12-03

KENNEDY SPACE CENTER, FLA. -- Participants pose for a photo at the Space Station Processing Facility ceremony transferring the "Leonardo" Multipurpose Logistics Module (MPLM) from the Italian Space Agency, Agenzia Spaziale Italiana (ASI), to NASA. From left, they are astronaut Jim Voss, ASI President Sergio De Julio, European Space Agency astronaut Umberto Guidoni of Italy, NASA Administrator Daniel S. Goldin and European Space Agency astronaut Christer Fuglesang of Sweden. The MPLM, a reusable logistics carrier, will be the primary delivery system used to resupply and return International Space Station cargo requiring a pressurized environment. Leonardo is the first of three MPLM carriers for the International Space Station. It is scheduled to be launched on Space Shuttle Mission STS-100, targeted for April 2000

KSC-2010-4543

NASA Image and Video Library

2010-09-01

CAPE CANAVERAL, Fla. -- In the Space Station Processing Facility at NASA's Kennedy Space Center in Florida, an overhead crane is poised over the Alpha Magnetic Spectrometer, or AMS, to lift the Payload Attach System, or PAS, up to the AMS. The PAS provides a method of securely connecting the payload to the International Space Station. AMS, a state-of-the-art particle physics detector, is designed to operate as an external module on the International Space Station. It will use the unique environment of space to study the universe and its origin by searching for dark matter. AMS will fly to the station aboard space shuttle Endeavour's STS-134 mission targeted to launch Feb. 26, 2011. Photo credit: NASA/Jack Pfaller

Fast and compact internal scanning CMOS-based hyperspectral camera: the Snapscan

NASA Astrophysics Data System (ADS)

Pichette, Julien; Charle, Wouter; Lambrechts, Andy

2017-02-01

Imec has developed a process for the monolithic integration of optical filters on top of CMOS image sensors, leading to compact, cost-efficient and faster hyperspectral cameras. Linescan cameras are typically used in remote sensing or for conveyor belt applications. Translation of the target is not always possible for large objects or in many medical applications. Therefore, we introduce a novel camera, the Snapscan (patent pending), exploiting internal movement of a linescan sensor enabling fast and convenient acquisition of high-resolution hyperspectral cubes (up to 2048x3652x150 in spectral range 475-925 nm). The Snapscan combines the spectral and spatial resolutions of a linescan system with the convenience of a snapshot camera.

Evaluation of the impact of matrix effect on quantification of pesticides in foods by gas chromatography-mass spectrometry using isotope-labeled internal standards.

PubMed

Yarita, Takashi; Aoyagi, Yoshie; Otake, Takamitsu

2015-05-29

The impact of the matrix effect in GC-MS quantification of pesticides in food using the corresponding isotope-labeled internal standards was evaluated. A spike-and-recovery study of nine target pesticides was first conducted using paste samples of corn, green soybean, carrot, and pumpkin. The observed analytical values using isotope-labeled internal standards were more accurate for most target pesticides than that obtained using the external calibration method, but were still biased from the spiked concentrations when a matrix-free calibration solution was used for calibration. The respective calibration curves for each target pesticide were also prepared using matrix-free calibration solutions and matrix-matched calibration solutions with blank soybean extract. The intensity ratio of the peaks of most target pesticides to that of the corresponding isotope-labeled internal standards was influenced by the presence of the matrix in the calibration solution; therefore, the observed slope varied. The ratio was also influenced by the type of injection method (splitless or on-column). These results indicated that matrix-matching of the calibration solution is required for very accurate quantification, even if isotope-labeled internal standards were used for calibration. Copyright © 2015 Elsevier B.V. All rights reserved.

Towards environmentally sustainable human behaviour: targeting non-conscious and conscious processes for effective and acceptable policies

NASA Astrophysics Data System (ADS)

Marteau, Theresa M.

2017-05-01

Meeting climate change targets to limit global warming to 2°C requires rapid and large reductions in demand for products that most contribute to greenhouse gas (GHG) emissions. These include production of bulk materials (e.g. steel and cement), energy supply (e.g. fossil fuels) and animal source foods (particularly ruminants and their products). Effective strategies to meet these targets require transformative changes in supply as well as demand, involving changes in economic, political and legal systems at local, national and international levels, building on evidence from many disciplines. This paper outlines contributions from behavioural science in reducing demand. Grounded in dual-process models of human behaviour (involving non-conscious and conscious processes) this paper considers first why interventions aimed at changing population values towards the environment are usually insufficient or unnecessary for reducing demand although they may be important in increasing public acceptability of policies that could reduce demand. It then outlines two sets of evidence from behavioural science towards effective systems-based strategies, to identify interventions likely to be effective at: (i) reducing demand for products that contribute most to GHG emissions, mainly targeting non-conscious processes and (ii) increasing public acceptability for policy changes to enable these interventions, targeting conscious processes. This article is part of the themed issue 'Material demand reduction'.

Towards environmentally sustainable human behaviour: targeting non-conscious and conscious processes for effective and acceptable policies.

PubMed

Marteau, Theresa M

2017-06-13

Meeting climate change targets to limit global warming to 2°C requires rapid and large reductions in demand for products that most contribute to greenhouse gas (GHG) emissions. These include production of bulk materials (e.g. steel and cement), energy supply (e.g. fossil fuels) and animal source foods (particularly ruminants and their products). Effective strategies to meet these targets require transformative changes in supply as well as demand, involving changes in economic, political and legal systems at local, national and international levels, building on evidence from many disciplines. This paper outlines contributions from behavioural science in reducing demand. Grounded in dual-process models of human behaviour (involving non-conscious and conscious processes) this paper considers first why interventions aimed at changing population values towards the environment are usually insufficient or unnecessary for reducing demand although they may be important in increasing public acceptability of policies that could reduce demand. It then outlines two sets of evidence from behavioural science towards effective systems-based strategies, to identify interventions likely to be effective at: (i) reducing demand for products that contribute most to GHG emissions, mainly targeting non-conscious processes and (ii) increasing public acceptability for policy changes to enable these interventions, targeting conscious processes.This article is part of the themed issue 'Material demand reduction'. © 2017 The Authors.

Towards environmentally sustainable human behaviour: targeting non-conscious and conscious processes for effective and acceptable policies

PubMed Central

2017-01-01

Meeting climate change targets to limit global warming to 2°C requires rapid and large reductions in demand for products that most contribute to greenhouse gas (GHG) emissions. These include production of bulk materials (e.g. steel and cement), energy supply (e.g. fossil fuels) and animal source foods (particularly ruminants and their products). Effective strategies to meet these targets require transformative changes in supply as well as demand, involving changes in economic, political and legal systems at local, national and international levels, building on evidence from many disciplines. This paper outlines contributions from behavioural science in reducing demand. Grounded in dual-process models of human behaviour (involving non-conscious and conscious processes) this paper considers first why interventions aimed at changing population values towards the environment are usually insufficient or unnecessary for reducing demand although they may be important in increasing public acceptability of policies that could reduce demand. It then outlines two sets of evidence from behavioural science towards effective systems-based strategies, to identify interventions likely to be effective at: (i) reducing demand for products that contribute most to GHG emissions, mainly targeting non-conscious processes and (ii) increasing public acceptability for policy changes to enable these interventions, targeting conscious processes. This article is part of the themed issue ‘Material demand reduction’. PMID:28461435

Benchmarking management practices in Australian public healthcare.

PubMed

Agarwal, Renu; Green, Roy; Agarwal, Neeru; Randhawa, Krithika

2016-01-01

The purpose of this paper is to investigate the quality of management practices of public hospitals in the Australian healthcare system, specifically those in the state-managed health systems of Queensland and New South Wales (NSW). Further, the authors assess the management practices of Queensland and NSW public hospitals jointly and globally benchmark against those in the health systems of seven other countries, namely, USA, UK, Sweden, France, Germany, Italy and Canada. In this study, the authors adapt the unique and globally deployed Bloom et al. (2009) survey instrument that uses a "double blind, double scored" methodology and an interview-based scoring grid to measure and internationally benchmark the management practices in Queensland and NSW public hospitals based on 21 management dimensions across four broad areas of management - operations, performance monitoring, targets and people management. The findings reveal the areas of strength and potential areas of improvement in the Queensland and NSW Health hospital management practices when compared with public hospitals in seven countries, namely, USA, UK, Sweden, France, Germany, Italy and Canada. Together, Queensland and NSW Health hospitals perform best in operations management followed by performance monitoring. While target management presents scope for improvement, people management is the sphere where these Australian hospitals lag the most. This paper is of interest to both hospital administrators and health care policy-makers aiming to lift management quality at the hospital level as well as at the institutional level, as a vehicle to consistently deliver sustainable high-quality health services. This study provides the first internationally comparable robust measure of management capability in Australian public hospitals, where hospitals are run independently by the state-run healthcare systems. Additionally, this research study contributes to the empirical evidence base on the quality of management practices in the Australian public healthcare systems of Queensland and NSW.

Validation of a Janus role of methotrexate-based PEGylated chitosan nanoparticles in vitro

NASA Astrophysics Data System (ADS)

Luo, Fanghong; Li, Yang; Jia, Mengmeng; Cui, Fei; Wu, Hongjie; Yu, Fei; Lin, Jinyan; Yang, Xiangrui; Hou, Zhenqing; Zhang, Qiqing

2014-07-01

Recently, methotrexate (MTX) has been used to target to folate (FA) receptor-overexpressing cancer cells for targeted drug delivery. However, the systematic evaluation of MTX as a Janus-like agent has not been reported before. Here, we explored the validity of using MTX playing an early-phase cancer-specific targeting ligand cooperated with a late-phase therapeutic anticancer agent based on the PEGylated chitosan (CS) nanoparticles (NPs) as drug carriers. Some advantages of these nanoscaled drug delivery systems are as follows: (1) the NPs can ensure minimal premature release of MTX at off-target site to reduce the side effects to normal tissue; (2) MTX can function as a targeting ligand at target site prior to cellular uptake; and (3) once internalized by the target cell, the NPs can function as a prodrug formulation, releasing biologically active MTX inside the cells. The (MTX + PEG)-CS-NPs presented a sustained/proteases-mediated drug release. More importantly, compared with the PEG-CS-NPs and (FA + PEG)-CS-NPs, the (MTX + PEG)-CS-NPs showed a greater cellular uptake. Furthermore, the (MTX + PEG)-CS-NPs demonstrated a superior cytotoxicity compare to the free MTX. Our findings therefore validated that the MTX-loaded PEGylated CS-NPs can simultaneously target and treat FA receptor-overexpressing cancer cells.

A new matrix for scoring the functionality of national laboratory networks in Africa: introducing the LABNET scorecard.

PubMed

Ondoa, Pascale; Datema, Tjeerd; Keita-Sow, Mah-Sere; Ndihokubwayo, Jean-Bosco; Isadore, Jocelyn; Oskam, Linda; Nkengasong, John; Lewis, Kim

2016-01-01

Functional national laboratory networks and systems are indispensable to the achievement of global health security targets according to the International Health Regulations. The lack of indicators to measure the functionality of national laboratory network has limited the efficiency of past and current interventions to enhance laboratory capacity in resource-limited-settings. We have developed a matrix for the assessment of national laboratory network functionality and progress thereof, with support from the African Society of Laboratory Medicine and the Association of Public Health Laboratories. The laboratory network (LABNET) scorecard was designed to: (1) Measure the status of nine overarching core capabilities of laboratory network required to achieve global health security targets, as recommended by the main normative standards; (2) Complement the World Health Organization joint external evaluation tool for the assessment of health system preparedness to International Health Regulations (2005) by providing detailed information on laboratory systems; and (3) Serve as a clear roadmap to guide the stepwise implementation of laboratory capability to prevent, detect and act upon infectious threats. The application of the LABNET scorecard under the coordination of the African Society of Laboratory Medicine and the Association of Public Health Laboratories could contribute to the design, monitoring and evaluation of upcoming Global Health Security Agenda-supported laboratory capacity building programmes in sub Saharan-Africa and other resource-limited settings, and inform the development of national laboratory policies and strategic plans. Endorsement by the World Health Organization Regional Office for Africa is foreseen.

A cell-targeted, size-photocontrollable, nuclear-uptake nanodrug delivery system for drug-resistant cancer therapy.

PubMed

Qiu, Liping; Chen, Tao; Öçsoy, Ismail; Yasun, Emir; Wu, Cuichen; Zhu, Guizhi; You, Mingxu; Han, Da; Jiang, Jianhui; Yu, Ruqin; Tan, Weihong

2015-01-14

The development of multidrug resistance (MDR) has become an increasingly serious problem in cancer therapy. The cell-membrane overexpression of P-glycoprotein (P-gp), which can actively efflux various anticancer drugs from the cell, is a major mechanism of MDR. Nuclear-uptake nanodrug delivery systems, which enable intranuclear release of anticancer drugs, are expected to address this challenge by bypassing P-gp. However, before entering the nucleus, the nanocarrier must pass through the cell membrane, necessitating coordination between intracellular and intranuclear delivery. To accommodate this requirement, we have used DNA self-assembly to develop a nuclear-uptake nanodrug system carried by a cell-targeted near-infrared (NIR)-responsive nanotruck for drug-resistant cancer therapy. Via DNA hybridization, small drug-loaded gold nanoparticles (termed nanodrugs) can self-assemble onto the side face of a silver-gold nanorod (NR, termed nanotruck) whose end faces were modified with a cell type-specific internalizing aptamer. By using this size-photocontrollable nanodrug delivery system, anticancer drugs can be efficiently accumulated in the nuclei to effectively kill the cancer cells.

Far-infrared and 3D imaging for doneness assessment in chicken breast

NASA Astrophysics Data System (ADS)

Tao, Yang; Ibarra, Juan G.

2001-03-01

Sensor fusion of infrared imaging and range imaging was proposed to estimate internal temperature on just cooked chicken breasts. An infrared camera operating at 8-12 microns registered surface temperature of cooked meat samples, while a single line structured light system located the thickest region of the meat target. In this region of interest, a combined time series/neural network method is applied to correlate the internal and external temperatures during the cool-down process. Experimental verification in a pilot plant oven is presented. To ensure food safety, a mandatory regulation requires all poultry processors in the U.S.A to verify that all ready-to-eat products reach a minimum endpoint temperature (71¦C for chicken breast), but no current assay can do a non-invasively inspection of all the samples. The proposed system has the potential for on-line inspection of ready-to-eat meat for food quality and safety.

Current advancements in the diagnosis and treatment of chronic pelvic pain.

PubMed

Morrissey, Darlene; Ginzburg, Natasha; Whitmore, Kristene

2014-07-01

The diagnosis and treatment of chronic pelvic pain (CPP) have moved away from targeting a specific organ to multifactorial and multidisciplinary individualized approach to treatment strategies. The purpose of this article is to review the current advancements in diagnosis and treatment of CPP. Recognition that response to current treatment approach to CPP syndrome is variable; organizations such as the European Association of Urology, American Urologic Association, International Continence Society, International Association for the Study of Pain, and others have integrated the most current evidence and management strategies from multiple specialties (urology, gynecology, pain medicine, gastroenterology, colorectal surgery, neurology, physiotherapy, and psychology). The 1 World Congress on Pelvic Pain met in 2013 to further collaborate on diagnosis and management of CPP. A multimodal clinical phenotype system has also been implemented to help understand cause and guide therapy. New classification systems allow for overlap of mechanisms between conditions and a multidisciplinary treatment approach.

International Deep Planet Survey, 317 stars to determine the wide-separated planet frequency

NASA Astrophysics Data System (ADS)

Galicher, R.; Marois, C.; Macintosh, B.; Zuckerman, B.; Song, I.; Barman, T.; Patience, J.

2013-09-01

Since 2000, more than 300 nearby young stars were observed for the International Deep Planet Survey with adaptive optics systems at Gemini (NIRI/NICI), Keck (Nirc2), and VLT (Naco). Massive young AF stars were included in our sample whereas they have generally been neglected in first generation surveys because the contrast and target distances are less favorable to image substellar companions. The most significant discovery of the campaign is the now well-known HR 8799 multi-planet system. This remarkable finding allows, for the first time, an estimate of the Jovians planet population at large separations (further than a few AUs) instead of deriving upper limits. During my presentation, I will present the survey showing images of multiple stars and planets. I will then propose a statistic study of the observed stars deriving constraints on the Jupiter-like planet frequency at large separations.

Pharmaceutical applications of magnetic resonance imaging (MRI).

PubMed

Richardson, J Craig; Bowtell, Richard W; Mäder, Karsten; Melia, Colin D

2005-06-15

Magnetic resonance imaging (MRI) is a powerful imaging modality that provides internal images of materials and living organisms on a microscopic and macroscopic scale. It is non-invasive and non-destructive, and one of very few techniques that can observe internal events inside undisturbed specimens in situ. It is versatile, as a wide range of NMR modalities can be accessed, and 2D and 3D imaging can be undertaken. Despite widespread use and major advances in clinical MRI, it has seen limited application in the pharmaceutical sciences. In vitro studies have focussed on drug release mechanisms in polymeric delivery systems, but isolated studies of bioadhesion, tablet properties, and extrusion and mixing processes illustrate the wider potential. Perhaps the greatest potential however, lies in investigations of pharmaceuticals in vivo, where pilot human and animal studies have demonstrated we can obtain unique insights into the behaviour of gastrointestinal, topical, colloidal, and targeted drug delivery systems.

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.

Easy regulation of metabolic flux in Escherichia coli using an endogenous type I-E CRISPR-Cas system.

PubMed

Chang, Yizhao; Su, Tianyuan; Qi, Qingsheng; Liang, Quanfeng

2016-11-15

Clustered regularly interspaced short palindromic repeats interference (CRISPRi) is a recently developed powerful tool for gene regulation. In Escherichia coli, the type I CRISPR system expressed endogenously shall be easy for internal regulation without causing metabolic burden in compared with the widely used type II system, which expressed dCas9 as an additional plasmid. By knocking out cas3 and activating the expression of CRISPR-associated complex for antiviral defense (Cascade), we constructed a native CRISPRi system in E. coli. Downregulation of the target gene from 6 to 82% was demonstrated using green fluorescent protein. Regulation of the citrate synthase gene (gltA) in the TCA cycle affected host metabolism. The effect of metabolic flux regulation was demonstrated by the poly-3-hydroxbutyrate (PHB) accumulation in vivo. By regulating native gltA in E. coli using an engineered endogenous type I-E CRISPR system, we redirected metabolic flux from the central metabolic pathway to the PHB synthesis pathway. This study demonstrated that the endogenous type I-E CRISPR-Cas system is an easy and effective method for regulating internal metabolic pathways, which is useful for product synthesis.

Dual Target Design for CLAS12

NASA Astrophysics Data System (ADS)

Alam, Omair; Gilfoyle, Gerard; Christo, Steve

2015-10-01

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

The accuracy of an electromagnetic navigation system in lateral skull base approaches.

PubMed

Komune, Noritaka; Matsushima, Ken; Matsuo, Satoshi; Safavi-Abbasi, Sam; Matsumoto, Nozomu; Rhoton, Albert L

2017-02-01

Image-guided optical tracking systems are being used with increased frequency in lateral skull base surgery. Recently, electromagnetic tracking systems have become available for use in this region. However, the clinical accuracy of the electromagnetic tracking system has not been examined in lateral skull base surgery. This study evaluates the accuracy of electromagnetic navigation in lateral skull base surgery. Cadaveric and radiographic study. Twenty cadaveric temporal bones were dissected in a surgical setting under a commercially available, electromagnetic surgical navigation system. The target registration error (TRE) was measured at 28 surgical landmarks during and after performing the standard translabyrinthine and middle cranial fossa surgical approaches to the internal acoustic canal. In addition, three demonstrative procedures that necessitate navigation with high accuracy were performed; that is, canalostomy of the superior semicircular canal from the middle cranial fossa, 1 cochleostomy from the middle cranial fossa, 2 and infralabyrinthine approach to the petrous apex. 3 RESULTS: Eleven of 17 (65%) of the targets in the translabyrinthine approach and five of 11 (45%) of the targets in the middle fossa approach could be identified in the navigation system with TRE of less than 0.5 mm. Three accuracy-dependent procedures were completed without anatomical injury of important anatomical structures. The electromagnetic navigation system had sufficient accuracy to be used in the surgical setting. It was possible to perform complex procedures in the lateral skull base under the guidance of the electromagnetically tracked navigation system. N/A. Laryngoscope, 2016 127:450-459, 2017. © 2016 The American Laryngological, Rhinological and Otological Society, Inc.

Intercepting a moving target: On-line or model-based control?

PubMed

Zhao, Huaiyong; Warren, William H

2017-05-01

When walking to intercept a moving target, people take an interception path that appears to anticipate the target's trajectory. According to the constant bearing strategy, the observer holds the bearing direction of the target constant based on current visual information, consistent with on-line control. Alternatively, the interception path might be based on an internal model of the target's motion, known as model-based control. To investigate these two accounts, participants walked to intercept a moving target in a virtual environment. We degraded the target's visibility by blurring the target to varying degrees in the midst of a trial, in order to influence its perceived speed and position. Reduced levels of visibility progressively impaired interception accuracy and precision; total occlusion impaired performance most and yielded nonadaptive heading adjustments. Thus, performance strongly depended on current visual information and deteriorated qualitatively when it was withdrawn. The results imply that locomotor interception is normally guided by current information rather than an internal model of target motion, consistent with on-line control.

Selection criteria for patients with chronic ankle instability in controlled research: a position statement of the International Ankle Consortium.

PubMed

Gribble, Phillip A; Delahunt, Eamonn; Bleakley, Chris; Caulfield, Brian; Docherty, Carrie L; Fourchet, François; Fong, Daniel; Hertel, Jay; Hiller, Claire; Kaminski, Thomas W; McKeon, Patrick O; Refshauge, Kathryn M; van der Wees, Philip; Vicenzino, Bill; Wikstrom, Erik A

2013-08-01

The International Ankle Consortium is an international community of researchers and clinicians whose primary scholastic purpose is to promote scholarship and dissemination of research-informed knowledge related to pathologies of the ankle complex. The constituents of the International Ankle Consortium and other similar organizations have yet to properly define the clinical phenomenon known as chronic ankle instability (CAI) and its related characteristics for consistent patient recruitment and advancement of research in this area. Although research on CAI and awareness of its impact on society and healthcare systems have grown substantially in the last 2 decades, the inconsistency in participant/patient selection criteria across studies presents a potential obstacle to addressing the problem properly. This major gap within the literature limits the ability to generalize this evidence to the target patient population. Therefore, there is a need to provide standards for patient/participant selection criteria in research focused on CAI, with justifications using the best available evidence.

Internal combustion engine report: Spark ignited ICE GenSet optimization and novel concept development

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

Keller, J.; Blarigan, P. Van

1998-08-01

In this manuscript the authors report on two projects each of which the goal is to produce cost effective hydrogen utilization technologies. These projects are: (1) the development of an electrical generation system using a conventional four-stroke spark-ignited internal combustion engine generator combination (SI-GenSet) optimized for maximum efficiency and minimum emissions, and (2) the development of a novel internal combustion engine concept. The SI-GenSet will be optimized to run on either hydrogen or hydrogen-blends. The novel concept seeks to develop an engine that optimizes the Otto cycle in a free piston configuration while minimizing all emissions. To this end themore » authors are developing a rapid combustion homogeneous charge compression ignition (HCCI) engine using a linear alternator for both power take-off and engine control. Targeted applications include stationary electrical power generation, stationary shaft power generation, hybrid vehicles, and nearly any other application now being accomplished with internal combustion engines.« less

NASA's Solar System Exploration Research Virtual Institute: Science and Technology for Lunar Exploration

NASA Technical Reports Server (NTRS)

Schmidt, Greg; Bailey, Brad; Gibbs, Kristina

2015-01-01

The NASA Solar System Exploration Research Virtual Institute (SSERVI) is a virtual institute focused on research at the intersection of science and exploration, training the next generation of lunar scientists, and development and support of the international community. As part of its mission, SSERVI acts as a hub for opportunities that engage the larger scientific and exploration communities in order to form new interdisciplinary, research-focused collaborations. The nine domestic SSERVI teams that comprise the U.S. complement of the Institute engage with the international science and exploration communities through workshops, conferences, online seminars and classes, student exchange programs and internships. SSERVI represents a close collaboration between science, technology and exploration enabling a deeper, integrated understanding of the Moon and other airless bodies as human exploration moves beyond low Earth orbit. SSERVI centers on the scientific aspects of exploration as they pertain to the Moon, Near Earth Asteroids (NEAs) and the moons of Mars, with additional aspects of related technology development, including a major focus on human exploration-enabling efforts such as resolving Strategic Knowledge Gaps (SKGs). The Institute focuses on interdisciplinary, exploration-related science focused on airless bodies targeted as potential human destinations. Areas of study represent the broad spectrum of lunar, NEA, and Martian moon sciences encompassing investigations of the surface, interior, exosphere, and near-space environments as well as science uniquely enabled from these bodies. This research profile integrates investigations of plasma physics, geology/geochemistry, technology integration, solar system origins/evolution, regolith geotechnical properties, analogues, volatiles, ISRU and exploration potential of the target bodies. New opportunities for both domestic and international partnerships are continually generated through these research and community development efforts, and SSERVI can further serve as a model for joint international scientific efforts through its creation of bridges across disciplines and between countries. Since the inception of the NASA Lunar Science Institute (SSERVIs predecessor), it has and will continue to contribute in many ways toward the advancement of lunar science and the eventual human exploration of the Moon.

KSC-2009-3203

NASA Image and Video Library

2009-05-18

CAPE CANAVERAL, Fla. – In the Operations and Checkout Building's high bay, a large poster displays an image of the completed Orion crew module. Part of NASA's Constellation Program, the Orion spacecraft will return humans to the moon and prepare for future voyages to Mars and other destinations in our solar system. Orion is targeted to begin carrying humans to the International Space Station in 2015 and to the moon by 2020. Photo credit: NASA/Kim Shiflett

KSC-2009-3205

NASA Image and Video Library

2009-05-18

CAPE CANAVERAL, Fla. – In the Operations and Checkout Building's high bay, "skins" are being applied to the outer mold of the simulator Orion crew module. Part of NASA's Constellation Program, the Orion spacecraft will return humans to the moon and prepare for future voyages to Mars and other destinations in our solar system. Orion is targeted to begin carrying humans to the International Space Station in 2015 and to the moon by 2020. Photo credit: NASA/Kim Shiflett

Targeting of Drugs to ICAM for Treatment of Acute Lung Injury

DTIC Science & Technology

2005-04-01

cystein and aspartic immunoproteosome, and the hybrid proteosome), which proteases) [237, 239]. These proteases are extensively contain a common core...activation of the hybrid system, is clathrin-mediated internalization, although this proteosome (depending on ATP but not on ubiquitin) can also sort...21lbldIGNswsijceendoyti veicls . he cllswer thn wshe, inubaed t 3 0 C o a into a separate group to control for mechanical retention of second-dose

KSC-07pd2681

NASA Image and Video Library

2007-10-05

KENNEDY SPACE CENTER, FLA. -- On Launch Pad 39A, workers remove the rain gutters from space shuttle Discovery's payload bay. The gutters prevent leaks into the bay from rain while the shuttle is on the pad. Beneath is the orbital docking system. Mission STS-120 will bring the Harmony module that will provide attachment points for European and Japanese laboratory modules to the International Space Station. Launch of Discovery is targeted for Oct. 23. Photo credit: NASA/George Shelton

Internal Wave Apparatus for Copepod Behavior Assays

NASA Astrophysics Data System (ADS)

Jung, S.; Haas, K. A.; Webster, D. R.

2015-11-01

Internal waves are ubiquitous features in coastal marine environments and have been observed to mediate vertical distributions of zooplankton in situ. Internal waves are generated through oscillations of the pycnocline in stratified waters and thereby create fine-scale hydrodynamic cues that copepods and other zooplankton are known to sense, such as fluid density gradients and velocity gradients (quantified as shear deformation rate). The role of copepod behavior in response to cues associated with internal waves is largely unknown. Thus, a coupled quantification of copepod behavior and hydrodynamic cues will provide insight to the bio-physical interaction and the role of biological versus physical forcing in mediating organism distributions. We constructed a laboratory-scale internal wave apparatus to facilitate fine-scale observations of copepod behavior in flows that replicate in situ conditions of internal waves in a two-layer stratification. Three cases are chosen with density jump ranging between 0.75 - 1.5 kg/m3. Analytical analysis of the two-layer system provides guidance of the target forcing frequency to generate a standing internal wave with a single dominate frequency of oscillation. Flow visualization and signal processing of the interface location are used to quantify the wave characteristics. A copepod behavior assay is conducted, and sample trajectories are analyzed to identify copepod response to internal wave structure.

Internal Targeting and External Control: Phototriggered Targeting in Nanomedicine.

PubMed

Arrue, Lily; Ratjen, Lars

2017-12-07

The photochemical control of structure and reactivity bears great potential for chemistry, biology, and life sciences. A key feature of photochemistry is the spatiotemporal control over secondary events. Well-established applications of photochemistry in medicine are photodynamic therapy (PDT) and photopharmacology (PP). However, although both are highly localizable through the application of light, they lack cell- and tissue-specificity. The combination of nanomaterial-based drug delivery and targeting has the potential to overcome limitations for many established therapy concepts. Even more privileged seems the merger of nanomedicine and cell-specific targeting (internal targeting) controlled by light (external control), as it can potentially be applied to many different areas of medicine and pharmaceutical research, including the aforementioned PDT and PP. In this review a survey of the interface of photochemistry, medicine and targeted drug delivery is given, especially focusing on phototriggered targeting in nanomedicine. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Filling of a Poisson trap by a population of random intermittent searchers.

PubMed

Bressloff, Paul C; Newby, Jay M

2012-03-01

We extend the continuum theory of random intermittent search processes to the case of N independent searchers looking to deliver cargo to a single hidden target located somewhere on a semi-infinite track. Each searcher randomly switches between a stationary state and either a leftward or rightward constant velocity state. We assume that all of the particles start at one end of the track and realize sample trajectories independently generated from the same underlying stochastic process. The hidden target is treated as a partially absorbing trap in which a particle can only detect the target and deliver its cargo if it is stationary and within range of the target; the particle is removed from the system after delivering its cargo. As a further generalization of previous models, we assume that up to n successive particles can find the target and deliver its cargo. Assuming that the rate of target detection scales as 1/N, we show that there exists a well-defined mean-field limit N→∞, in which the stochastic model reduces to a deterministic system of linear reaction-hyperbolic equations for the concentrations of particles in each of the internal states. These equations decouple from the stochastic process associated with filling the target with cargo. The latter can be modeled as a Poisson process in which the time-dependent rate of filling λ(t) depends on the concentration of stationary particles within the target domain. Hence, we refer to the target as a Poisson trap. We analyze the efficiency of filling the Poisson trap with n particles in terms of the waiting time density f(n)(t). The latter is determined by the integrated Poisson rate μ(t)=∫(0)(t)λ(s)ds, which in turn depends on the solution to the reaction-hyperbolic equations. We obtain an approximate solution for the particle concentrations by reducing the system of reaction-hyperbolic equations to a scalar advection-diffusion equation using a quasisteady-state analysis. We compare our analytical results for the mean-field model with Monte Carlo simulations for finite N. We thus determine how the mean first passage time (MFPT) for filling the target depends on N and n.

Summary of the XIII International Workshop on Polarized Sources, Targets and Polarimetry

NASA Astrophysics Data System (ADS)

Rathmann, F.

2011-01-01

The workshops on polarized sources, targets, and polarimetry are held every two years. The present meeting took place in Ferrara, Italy, and was organized by the University of Ferrara. Sessions on Polarized Proton and Deuterium Sources, Polarized Electron Sources, Polarimetry, Polarized Solid Targets, and Polarized Internal Targets, highlighted topics, recent developments, and progress in the field. A session decicated to Future Facilities provided an overview of a number of new activities in the spin-physics sector at facilities that are currently in the planning stage. Besides presenting a broad overview of polarized ion sources, electron sources, solid and gaseous targets, and their neighboring fields, the workshop also addressed the application of polarized atoms in applied sciences and medicine that is becoming increasingly important.

Comparative analysis of the internalization of the macrophage receptor sialoadhesin in human and mouse primary macrophages and cell lines.

PubMed

De Schryver, Marjorie; Leemans, Annelies; Pintelon, Isabel; Cappoen, Davie; Maes, Louis; Caljon, Guy; Cos, Paul; Delputte, Peter L

2017-06-01

Sialoadhesin (Sn) is a surface receptor expressed on resident macrophages with the ability to bind with sialic acids. During inflammation, an upregulation of Sn is observed. Upon binding of monoclonal antibodies to Sn, the receptor becomes internalized and this has been observed in multiple species. The latter characteristic, combined with the strong upregulation of Sn on inflammatory macrophages and the fact that Sn-positive macrophages contribute to certain inflammatory diseases, makes Sn an interesting entry portal for phenotype-modulating or cytotoxic drugs. Such drugs or toxins can be linked to Sn-specific antibodies which should enable their targeted uptake by macrophages. However, the activity of such drugs depends not only on their internalization but also on the intracellular trafficking and final fate in the endolysosomal system. Although information is available for porcine Sn, the detailed mechanisms of human and mouse Sn internalization and subsequent intracellular trafficking are currently unknown. To allow development of Sn-targeted therapies, differences across species and cellular background need to be characterized in more detail. In the current report, we show that internalization of human and mouse Sn is dynamin-dependent and clathrin-mediated, both in primary macrophages and CHO cell lines expressing a recombinant Sn. In primary macrophages, internalized Sn-specific F(ab') 2 fragments are located mostly in the early endosomes. With Fc containing Sn-specific antibodies, there is a slight shift towards lysosomal localization in mouse macrophages, possibly because of an interaction with Fc receptors. Surprisingly, in CHO cell lines expressing Sn, there is a predominant lysosomal localization. Our results show that the mechanism of Sn internalization and intracellular trafficking is concurrent in the tested species. The cellular background in which Sn is expressed and the type of antibody used can affect the intracellular fate, which in turn can impact the activity of antibody-based therapeutic interventions via Sn. Copyright © 2016 Elsevier GmbH. All rights reserved.

Enhanced anti-tumoral activity of methotrexate-human serum albumin conjugated nanoparticles by targeting with Luteinizing Hormone-Releasing Hormone (LHRH) peptide.

PubMed

Taheri, Azade; Dinarvand, Rassoul; Atyabi, Fatemeh; Ahadi, Fatemeh; Nouri, Farank Salman; Ghahremani, Mohammad Hossein; Ostad, Seyed Nasser; Borougeni, Atefeh Taheri; Mansoori, Pooria

2011-01-01

Active targeting could increase the efficacy of anticancer drugs. Methotrexate-human serum albumin (MTX-HSA) conjugates, functionalized by luteinizing hormone-releasing hormone (LHRH) as targeting moieties, with the aim of specifically targeting the cancer cells, were prepared. Owing to the high expression of LHRH receptors in many cancer cells as compared to normal cells, LHRH was used as the targeting ligand in this study. LHRH was conjugated to MTX-HSA nanoparticles via a cross-linker. Three types of LHRH targeted nanoparticles with a mean particle size between 120-138 nm were prepared. The cytotoxicity of LHRH targeted and non-targeted nanoparticles were determined on the LHRH positive and negative cell lines. The internalization of the targeted and non-targeted nanoparticles in LHRH receptor positive and negative cells was investigated using flow cytometry analysis and fluorescence microscopy. The cytotoxicity of the LHRH targeted nanoparticles on the LHRH receptor positive cells were significantly more than non-targeted nanoparticles. LHRH targeted nanoparticles were also internalized by LHRH receptor positive cells significantly more than non-targeted nanoparticles. There were no significant differences between the uptake of targeted and non-targeted nanoparticles to the LHRH receptor negative cells. The active targeting procedure using LHRH targeted MTX-HSA nanoparticles could increase the anti-tumoral activity of MTX.

Revisiting ocean carbon sequestration by direct injection: a global carbon budget perspective

NASA Astrophysics Data System (ADS)

Reith, Fabian; Keller, David P.; Oschlies, Andreas

2016-11-01

In this study we look beyond the previously studied effects of oceanic CO2 injections on atmospheric and oceanic reservoirs and also account for carbon cycle and climate feedbacks between the atmosphere and the terrestrial biosphere. Considering these additional feedbacks is important since backfluxes from the terrestrial biosphere to the atmosphere in response to reducing atmospheric CO2 can further offset the targeted reduction. To quantify these dynamics we use an Earth system model of intermediate complexity to simulate direct injection of CO2 into the deep ocean as a means of emissions mitigation during a high CO2 emission scenario. In three sets of experiments with different injection depths, we simulate a 100-year injection period of a total of 70 GtC and follow global carbon cycle dynamics over another 900 years. In additional parameter perturbation runs, we varied the default terrestrial photosynthesis CO2 fertilization parameterization by ±50 % in order to test the sensitivity of this uncertain carbon cycle feedback to the targeted atmospheric carbon reduction through direct CO2 injections. Simulated seawater chemistry changes and marine carbon storage effectiveness are similar to previous studies. As expected, by the end of the injection period avoided emissions fall short of the targeted 70 GtC by 16-30 % as a result of carbon cycle feedbacks and backfluxes in both land and ocean reservoirs. The target emissions reduction in the parameter perturbation simulations is about 0.2 and 2 % more at the end of the injection period and about 9 % less to 1 % more at the end of the simulations when compared to the unperturbed injection runs. An unexpected feature is the effect of the model's internal variability of deep-water formation in the Southern Ocean, which, in some model runs, causes additional oceanic carbon uptake after injection termination relative to a control run without injection and therefore with slightly different atmospheric CO2 and climate. These results of a model that has very low internal climate variability illustrate that the attribution of carbon fluxes and accounting for injected CO2 may be very challenging in the real climate system with its much larger internal variability.

Anti-P-glycoprotein conjugated nanoparticles for targeting drug delivery in cancer treatment.

PubMed

Iangcharoen, Pantiwa; Punfa, Wanisa; Yodkeeree, Supachai; Kasinrerk, Watchara; Ampasavate, Chadarat; Anuchapreeda, Songyot; Limtrakul, Pornngarm

2011-10-01

Targeting therapeutics to specific sites can enhance the efficacy of drugs, reduce required doses as well as unwanted side effects. In this work, using the advantages of the specific affinity of an immobilized antibody to membrane P-gp in two different nanoparticle formulations were thus developed for targeted drug delivery to multi-drug resistant cervical carcinoma (KB-V1) cells. Further, this was compared to the human drug sensitive cervical carcinoma cell line (KB-3-1) cells. The two nanoparticle preparations were: NP1, anti-P-gp conjugated with poly (DL-lactic-coglycolic acid) (PLGA) nanoparticle and polyethylene glycol (PEG); NP2, anti-P-gp conjugated to a modified poloxamer on PLGA nanoparticles. The cellular uptake capacity of nanoparticles was confirmed by fluorescent microscopy. Comparing with each counterpart core particles, there was a higher fluorescence intensity of the targeted nanoparticles in KBV1 cells compared to KB-3-1 cells suggesting that the targeted nanoparticles were internalized into KB-V1 cells to a greater extent than KB-3-1 cell. The results had confirmed the specificity and the potential of the developed targeted delivery system for overcoming multi-drug resistance induced by overexpression of P-gp on the cell membrane.

Optical Imaging of Targeted β-Galactosidase in Brain Tumors to Detect EGFR Levels

PubMed Central

Broome, Ann-Marie; Ramamurthy, Gopal; Lavik, Kari; Liggett, Alexander; Kinstlinger, Ian; Basilion, James

2015-01-01

A current limitation in molecular imaging is that it often requires genetic manipulation of cancer cells for noninvasive imaging. Other methods to detect tumor cells in vivo using exogenously delivered and functionally active reporters, such as β-gal, are required. We report the development of a platform system for linking β-gal to any number of different ligands or antibodies for in vivo targeting to tissue or cells, without the requirement for genetic engineering of the target cells prior to imaging. Our studies demonstrate significant uptake in vitro and in vivo of an EGFR-targeted β-gal complex. We were then able to image orthotopic brain tumor accumulation and localization of the targeted enzyme when a fluorophore was added to the complex, as well as validate the internalization of the intravenously administered β-gal reporter complex ex vivo. After fluorescence imaging localized the β-gal complexes to the brain tumor, we topically applied a bioluminescent β-gal substrate to serial sections of the brain to evaluate the delivery and integrity of the enzyme. Finally, robust bioluminescence of the EGFR-targeted β-gal complex was captured within the tumor during noninvasive in vivo imaging. PMID:25775241

Optical imaging of targeted β-galactosidase in brain tumors to detect EGFR levels.

PubMed

Broome, Ann-Marie; Ramamurthy, Gopal; Lavik, Kari; Liggett, Alexander; Kinstlinger, Ian; Basilion, James

2015-04-15

A current limitation in molecular imaging is that it often requires genetic manipulation of cancer cells for noninvasive imaging. Other methods to detect tumor cells in vivo using exogenously delivered and functionally active reporters, such as β-gal, are required. We report the development of a platform system for linking β-gal to any number of different ligands or antibodies for in vivo targeting to tissue or cells, without the requirement for genetic engineering of the target cells prior to imaging. Our studies demonstrate significant uptake in vitro and in vivo of an EGFR-targeted β-gal complex. We were then able to image orthotopic brain tumor accumulation and localization of the targeted enzyme when a fluorophore was added to the complex, as well as validate the internalization of the intravenously administered β-gal reporter complex ex vivo. After fluorescence imaging localized the β-gal complexes to the brain tumor, we topically applied a bioluminescent β-gal substrate to serial sections of the brain to evaluate the delivery and integrity of the enzyme. Finally, robust bioluminescence of the EGFR-targeted β-gal complex was captured within the tumor during noninvasive in vivo imaging.

Polydopamine and peptide decorated doxorubicin-loaded mesoporous silica nanoparticles as a targeted drug delivery system for bladder cancer therapy.

PubMed

Wei, Yi; Gao, Li; Wang, Lu; Shi, Lin; Wei, Erdong; Zhou, Baotong; Zhou, Li; Ge, Bo

2017-11-01

We reported a simple polydopamine (PDA)-based surface modification method to prepare novel targeted doxorubicin-loaded mesoporous silica nanoparticles and peptide CSNRDARRC conjugation (DOX-loaded MSNs@PDA-PEP) for enhancing the therapeutic effects on bladder cancer. Drug-loaded NPs were characterized in terms of size, size distribution, zeta potential, transmission electron microscopy (TEM), Brunauer-Emmett-Teller (BET) surface area and drug loading content. In vitro drug release indicated that DOX-loaded MSNs@PDA and MSNs@PDA-PEP had similar release kinetic profiles of DOX. The PDA coating well controlled DOX release and was highly sensitive to pH value. Confocal laser scanning microscopy (CLSM) showed that drug-loaded MSNs could be internalized by human bladder cancer cell line HT-1376, and DOX-loaded MSNs@PDA-PEP had the highest cellular uptake efficiency due to ligand-receptor recognition. The antitumor effects of DOX-loaded nanoparticles were evaluated by the MTT assay in vitro and by a xenograft tumor model in vivo, demonstrating that targeted nanocarriers DOX-loaded MSNs@PDA-PEP were significantly superior to free DOX and DOX-loaded MSNs@PDA. The novel DOX-loaded MSNs@PDA-PEP, which specifically recognized HT-1376 cells, can be used as a potential targeted drug delivery system for bladder cancer therapy.

The verbal facilitation effect: re-reading person descriptions as a system variable to improve identification performance.

PubMed

Sporer, Siegfried L; Kaminski, Kristina S; Davids, Maike C; McQuiston, Dawn

2016-11-01

When witnesses report a crime, police usually ask for a description of the perpetrator. Several studies suggested that verbalising faces leads to a detriment in identification performance (verbal overshadowing effect [VOE]) but the effect has been difficult to replicate. Here, we sought to reverse the VOE by inducing context reinstatement as a system variable through re-reading one's own description before an identification task. Participants (N = 208) watched a video film and were then dismissed (control group), only described the perpetrator, or described and later re-read their own descriptions before identification in either target-present or target-absent lineups after a 2-day or a 5-week delay. Identification accuracy was significantly higher after re-reading (85.0%) than in the no description control group (62.5%) irrespective of target presence. Data were internally replicated using a second target and corroborated by several small meta-analyses. Identification accuracy was related to description quality. Moreover, there was a tendency towards a verbal facilitation effect (VFE) rather than a VOE. Receiver operating characteristic (ROC) curve analyses confirm that our findings are not due to a shift in response bias but truly reflect improvement of recognition performance. Differences in the ecological validity of study paradigms are discussed.

Optimization of cell receptor-specific targeting through multivalent surface decoration of polymeric nanocarriers

PubMed Central

D’Addio, Suzanne M.; Baldassano, Steven; Shi, Lei; Cheung, Lila; Adamson, Douglas H.; Bruzek, Matthew; Anthony, John E.; Laskin, Debra L.; Sinko, Patrick J.; Prud’homme, Robert K.

2013-01-01

Treatment of tuberculosis is impaired by poor drug bioavailability, systemic side effects, patient non-compliance, and pathogen resistance to existing therapies. The mannose receptor (MR) is known to be involved in the recognition and internalization of Mycobacterium tuberculosis. We present a new assembly process to produce nanocarriers with variable surface densities of mannose targeting ligands in a single step, using kinetically-controlled, block copolymer-directed assembly. Nanocarrier association with murine macrophage J774 cells expressing the MR is examined as a function of incubation time and temperature, nanocarrier size, dose, and PEG corona properties. Amphiphilic diblock copolymers are prepared with terminal hydroxyl, methoxy, or mannoside functionality and incorporated into nanocarrier formulations at specific ratios by Flash NanoPrecipitation. Association of nanocarriers protected by a hydroxyl-terminated PEG corona with J774 cells is size dependent, while nanocarriers with methoxy-terminated PEG coronas do not associate with cells, regardless of size. Specific targeting of the MR is investigated using nanocarriers having 0-75% mannoside-terminated PEG chains in the PEG corona. This is a wider range of mannose densities than has been previously studied. Maximum nanocarrier association is attained with 9% mannoside-terminated PEG chains, increasing uptake more than 3-fold compared to non-targeted nanocarriers with a 5 kg mol−1 methoxy-terminated PEG corona. While a 5 kg mol−1 methoxy-terminated PEG corona prevents non-specific uptake, a 1.8 kg mol−1 methoxy-terminated PEG corona does not sufficiently protect the nanocarriers from nonspecific association. There is continuous uptake of MR-targeted nanocarriers at 37°C, but a saturation of association at 4°C. The majority of targeted nanocarriers associate with J774E cells are internalized at 37°C and uptake is receptor-dependent, diminishing with competitive inhibition by dextran. This characterization of nanocarrier uptake and targeting provides promise for optimizing drug delivery to macrophages for TB treatment and establishes a general route for optimizing targeted formulations of nanocarriers for specific delivery at targeted sites. PMID:23419950

Development of an in vitro diaphragm motion reproduction system.

PubMed

Liao, Ai-Ho; Chuang, Ho-Chiao; Shih, Ming-Chih; Hsu, Hsiao-Yu; Tien, Der-Chi; Kuo, Chia-Chun; Jeng, Shiu-Chen; Chiou, Jeng-Fong

2017-07-01

This study developed an in vitro diaphragm motion reproduction system (IVDMRS) based on noninvasive and real-time ultrasound imaging to track the internal displacement of the human diaphragm and diaphragm phantoms with a respiration simulation system (RSS). An ultrasound image tracking algorithm (UITA) was used to retrieve the displacement data of the tracking target and reproduce the diaphragm motion in real time using a red laser to irradiate the diaphragm phantom in vitro. This study also recorded the respiration patterns in 10 volunteers. Both simulated and the respiration patterns in 10 human volunteers signals were input to the RSS for conducting experiments involving the reproduction of diaphragm motion in vitro using the IVDMRS. The reproduction accuracy of the IVDMRS was calculated and analyzed. The results indicate that the respiration frequency substantially affects the correlation between ultrasound and kV images, as well as the reproduction accuracy of the IVDMRS due to the system delay time (0.35s) of ultrasound imaging and signal transmission. The utilization of a phase lead compensator (PLC) reduced the error caused by this delay, thereby improving the reproduction accuracy of the IVDMRS by 14.09-46.98%. Applying the IVDMRS in clinical treatments will allow medical staff to monitor the target displacements in real time by observing the movement of the laser beam. If the target displacement moves outside the planning target volume (PTV), the treatment can be immediately stopped to ensure that healthy tissues do not receive high doses of radiation. Copyright © 2017 Associazione Italiana di Fisica Medica. Published by Elsevier Ltd. All rights reserved.

Methods and Simulations of Muon Tomography and Reconstruction

NASA Astrophysics Data System (ADS)

Schreiner, Henry Fredrick, III

This dissertation investigates imaging with cosmic ray muons using scintillator-based portable particle detectors, and covers a variety of the elements required for the detectors to operate and take data, from the detector internal communications and software algorithms to a measurement to allow accurate predictions of the attenuation of physical targets. A discussion of the tracking process for the three layer helical design developed at UT Austin is presented, with details of the data acquisition system, and the highly efficient data format. Upgrades to this system provide a stable system for taking images in harsh or inaccessible environments, such as in a remote jungle in Belize. A Geant4 Monte Carlo simulation was used to develop our understanding of the efficiency of the system, as well as to make predictions for a variety of different targets. The projection process is discussed, with a high-speed algorithm for sweeping a plane through data in near real time, to be used in applications requiring a search through space for target discovery. Several other projections and a foundation of high fidelity 3D reconstructions are covered. A variable binning scheme for rapidly varying statistics over portions of an image plane is also presented and used. A discrepancy in our predictions and the observed attenuation through smaller targets is shown, and it is resolved with a new measurement of low energy spectrum, using a specially designed enclosure to make a series of measurements underwater. This provides a better basis for understanding the images of small amounts of materials, such as for thin cover materials.

Object motion perception is shaped by the motor control mechanism of ocular pursuit.

PubMed

Schweigart, G; Mergner, T; Barnes, G R

2003-02-01

It is still a matter of debate whether the control of smooth pursuit eye movements involves an internal drive signal from object motion perception. We measured human target velocity and target position perceptions and compared them with the presumed pursuit control mechanism (model simulations). We presented normal subjects (Ns) and vestibular loss patients (Ps) with visual target motion in space. Concurrently, a visual background was presented, which was kept stationary or was moved with or against the target (five combinations). The motion stimuli consisted of smoothed ramp displacements with different dominant frequencies and peak velocities (0.05, 0.2, 0.8 Hz; 0.2-25.6 degrees /s). Subjects always pursued the target with their eyes. In a first experiment they gave verbal magnitude estimates of perceived target velocity in space and of self-motion in space. The target velocity estimates of both Ns and Ps tended to saturate at 0.8 Hz and with peak velocities >3 degrees /s. Below these ranges the velocity estimates showed a pronounced modulation in relation to the relative target-to-background motion ('background effect'; for example, 'background with'-motion decreased and 'against'-motion increased perceived target velocity). Pronounced only in Ps and not in Ns, there was an additional modulation in relation to the relative head-to-background motion, which co-varied with an illusion of self-motion in space (circular vection, CV) in Ps. In a second experiment, subjects performed retrospective reproduction of perceived target start and end positions with the same stimuli. Perceived end position was essentially veridical in both Ns and Ps (apart from a small constant offset). Reproduced start position showed an almost negligible background effect in Ns. In contrast, it showed a pronounced modulation in Ps, which again was related to CV. The results were compared with simulations of a model that we have recently presented for velocity control of eye pursuit. We found that the main features of target velocity perception (in terms of dynamics and modulation by background) closely correspond to those of the internal drive signal for target pursuit, compatible with the notion of a common source of both the perception and the drive signal. In contrast, the eye pursuit movement is almost free of the background effect. As an explanation, we postulate that the target-to-background component in the target pursuit drive signal largely neutralises the background-to-eye retinal slip signal (optokinetic reflex signal) that feeds into the eye premotor mechanism as a competitor of the target retinal slip signal. An extension of the model allowed us to simulate also the findings of the target position perception. It is assumed to be represented in a perceptual channel that is distinct from the velocity perception, building on an efference copy of the essentially accurate eye position. We hold that other visuomotor behaviour, such as target reaching with the hand, builds mainly on this target position percept and therefore is not contaminated by the background effect in the velocity percept. Generally, the coincidence of an erroneous velocity percept and an almost perfect eye pursuit movement during background motion is discussed as an instructive example of an action-perception dissociation. This dissociation cannot be taken to indicate that the two functions are internally represented in separate brain control systems, but rather reflects the intimate coupling between both functions.

Dental ablation with 1064 nm, 500 ps, Diode pumped solid state laser: A preliminary study.

PubMed

Sozzi, Michele; Fornaini, Carlo; Cucinotta, Annamaria; Merigo, Elisabetta; Vescovi, Paolo; Selleri, Stefano

2013-01-01

The Er:YAG laser in conservative dentistry is. good alternative to conventional instruments. Though several studies show the advantages of these devices, some drawbacks and unsolved problems are still present, such as the cost of the device and the large dimensions of the equipment. In the present study, the effectiveness of dental surface ablation with a picosecond infrared diode-pumped solid-state (DPSS) laser was investigated. In vitro tests on extracted human teeth were carried out, with assessment of the ablation quality in the tooth and thermal increase inside the pulp chamber. A solid-state picosecond laser was used for the experiments. The samples were exposed to laser energy at 1064 nm at a frequency of 30 kHz and a 500 ps pulse width. The target teeth were cooled during exposures. The internal temperature of the pulp chamber was monitored with. thermocouple. Optical microscope images showed effective ablation with the absence of carbonisation and micro-cracks. The cooling maintained the temperature rise in the pulp chamber below the permitted 5.5°C. The main problem with the use of lasers in dentistry when teeth are the target is the heat generated in the pulp chamber of the target teeth. With lasers operating in the femtosecond mode, a better management of the internal temperature is possible, but is offset by the high cost of such devices. With the ps domain system used in the present study together with cooling using chilled water, effective and clean ablation could be achieved with a controlled thermal effect in the pulp chamber. In this preliminary study with a picosecond domain DPSS laser using water cooling for the target, effective hard tissue ablation was achieved keeping the thermal increase in the pulp within the permitted range. The results suggest that this system could be used in clinical practice with appropriate modifications.

Laboratory information management system for membrane protein structure initiative--from gene to crystal.

PubMed

Troshin, Petr V; Morris, Chris; Prince, Stephen M; Papiz, Miroslav Z

2008-12-01

Membrane Protein Structure Initiative (MPSI) exploits laboratory competencies to work collaboratively and distribute work among the different sites. This is possible as protein structure determination requires a series of steps, starting with target selection, through cloning, expression, purification, crystallization and finally structure determination. Distributed sites create a unique set of challenges for integrating and passing on information on the progress of targets. This role is played by the Protein Information Management System (PIMS), which is a laboratory information management system (LIMS), serving as a hub for MPSI, allowing collaborative structural proteomics to be carried out in a distributed fashion. It holds key information on the progress of cloning, expression, purification and crystallization of proteins. PIMS is employed to track the status of protein targets and to manage constructs, primers, experiments, protocols, sample locations and their detailed histories: thus playing a key role in MPSI data exchange. It also serves as the centre of a federation of interoperable information resources such as local laboratory information systems and international archival resources, like PDB or NCBI. During the challenging task of PIMS integration, within the MPSI, we discovered a number of prerequisites for successful PIMS integration. In this article we share our experiences and provide invaluable insights into the process of LIMS adaptation. This information should be of interest to partners who are thinking about using LIMS as a data centre for their collaborative efforts.

A FRET-guided, NIR-responsive bubble-generating liposomal system for in vivo targeted therapy with spatially and temporally precise controlled release.

PubMed

Chuang, Er-Yuan; Lin, Chia-Chen; Chen, Ko-Jie; Wan, De-Hui; Lin, Kun-Ju; Ho, Yi-Cheng; Lin, Po-Yen; Sung, Hsing-Wen

2016-07-01

The nonspecific distribution of therapeutic agents and nontargeted heating commonly produce undesirable side effects during cancer treatment since the optimal timing of triggering the carrier systems is unknown. This work proposes a multifunctional liposomal system that can intracellularly and simultaneously deliver the therapeutic drug doxorubicin (DOX), heat, and a bubble-generating agent (ammonium bicarbonate, ABC) into targeted tumor cells to have a cytotoxic effect. Gold nanocages that are encapsulated in liposomes effectively convert near-infrared light irradiation into localized heat, which causes the decomposition of ABC and generates CO2 bubbles, rapidly triggering the release of DOX. Additionally, a hybridized Mucin-1 aptamer is conjugated on the surface of the test liposomes, which then function as a recognition probe to enhance the uptake of those liposomes by cells, and as a molecular beacon to signal when the internalized particles have been maximized, which is the optimal time for photothermally triggering the release of the drug following the systemic administration of the liposomes. Empirical results reveal that this combined treatment effectively controls targeted drug release in a spatially and temporally precise fashion and so significantly increases the potency of the drug while minimizing unwanted side effects, making it a promising treatment for cancer. Copyright © 2016 Elsevier Ltd. All rights reserved.

Translation of Polioviral mRNA Is Inhibited by Cleavage of Polypyrimidine Tract-Binding Proteins Executed by Polioviral 3Cpro

PubMed Central

Back, Sung Hoon; Kim, Yoon Ki; Kim, Woo Jae; Cho, Sungchan; Oh, Hoe Rang; Kim, Jung-Eun; Jang, Sung Key

2002-01-01

The translation of polioviral mRNA occurs through an internal ribosomal entry site (IRES). Several RNA-binding proteins, such as polypyrimidine tract-binding protein (PTB) and poly(rC)-binding protein (PCBP), are required for the poliovirus IRES-dependent translation. Here we report that a poliovirus protein, 3Cpro (and/or 3CDpro), cleaves PTB isoforms (PTB1, PTB2, and PTB4). Three 3Cpro target sites (one major target site and two minor target sites) exist in PTBs. PTB fragments generated by poliovirus infection are redistributed to the cytoplasm from the nucleus, where most of the intact PTBs are localized. Moreover, these PTB fragments inhibit polioviral IRES-dependent translation in a cell-based assay system. We speculate that the proteolytic cleavage of PTBs may contribute to the molecular switching from translation to replication of polioviral RNA. PMID:11836431

Coulomb and nuclear excitations of narrow resonances in 17Ne

DOE PAGES

Marganiec, J.; Wamers, F.; Aksouh, F.; ...

2016-05-25

New experimental data for dissociation of relativistic 17Ne projectiles incident on targets of lead, carbon, and polyethylene targets at GSI are presented. Special attention is paid to the excitation and decay of narrow resonant states in 17Ne. Distributions of internal energy in the 15O+p +p three-body system have been determined together with angular and partial-energy correlations between the decay products in different energy regions. The analysis was done using existing experimental data on 17Ne and its mirror nucleus 17N. The isobaric multiplet mass equation is used for assignment of observed resonances and their spins and parities. A combination of datamore » from the heavy and light targets yielded cross sections and transition probabilities for the Coulomb excitations of the narrow resonant states. Finally, the resulting transition probabilities provide information relevant for a better understanding of the 17Ne structure.« less

The Implementation Challenge and the Learning Health System for SCI Initiative.

PubMed

Stucki, Gerold; Bickenbach, Jerome

2017-02-01

The paper introduces the special issue by linking the International Spinal Cord Injury (InSCI) Community Survey study to the Learning Health System for SCI Initiative (LHS-SCI). The LHS-SCI was designed to respond to the implementation challenge of bringing about policy reform in light of the targeted policy recommendations of World Health Organization's International Perspectives on SCI report as well as the call for action of WHO's Global Disability Action Plan. The paper reviews the components of LHS-SCI relevant to internationally comparable information, a theory of change to guide for action, and the tools for evidence-informed policy. The interplay between persons, their health needs, and the societal response to those needs provides the foundation for the organization of the LHS-SCI Initiative. Moreover, as the other articles in this special issue describe in detail, the rationale, conceptualization, and study design of the InSCI study are also informed by the rationale, and mission, of the LHS for SCI Initiative. The LHS-SCI, and the implementation challenge that motivates it, is responsible for the design of the InSCI study and the overall mission of LHS-SCI to continuously improve the lived experience of people living with SCI around the world through an international evidence- and rights-informed research and policy reform effort.

4D CT sorting based on patient internal anatomy

NASA Astrophysics Data System (ADS)

Li, Ruijiang; Lewis, John H.; Cerviño, Laura I.; Jiang, Steve B.

2009-08-01

Respiratory motion during free-breathing computed tomography (CT) scan may cause significant errors in target definition for tumors in the thorax and upper abdomen. A four-dimensional (4D) CT technique has been widely used for treatment simulation of thoracic and abdominal cancer radiotherapy. The current 4D CT techniques require retrospective sorting of the reconstructed CT slices oversampled at the same couch position. Most sorting methods depend on external surrogates of respiratory motion recorded by extra instruments. However, respiratory signals obtained from these external surrogates may not always accurately represent the internal target motion, especially when irregular breathing patterns occur. We have proposed a new sorting method based on multiple internal anatomical features for multi-slice CT scan acquired in the cine mode. Four features are analyzed in this study, including the air content, lung area, lung density and body area. We use a measure called spatial coherence to select the optimal internal feature at each couch position and to generate the respiratory signals for 4D CT sorting. The proposed method has been evaluated for ten cancer patients (eight with thoracic cancer and two with abdominal cancer). For nine patients, the respiratory signals generated from the combined internal features are well correlated to those from external surrogates recorded by the real-time position management (RPM) system (average correlation: 0.95 ± 0.02), which is better than any individual internal measures at 95% confidence level. For these nine patients, the 4D CT images sorted by the combined internal features are almost identical to those sorted by the RPM signal. For one patient with an irregular breathing pattern, the respiratory signals given by the combined internal features do not correlate well with those from RPM (correlation: 0.68 ± 0.42). In this case, the 4D CT image sorted by our method presents fewer artifacts than that from the RPM signal. Our 4D CT internal sorting method eliminates the need of externally recorded surrogates of respiratory motion. It is an automatic, accurate, robust, cost efficient and yet simple method and therefore can be readily implemented in clinical settings.

Complexity in graduate medical education: a collaborative education agenda for internal medicine and geriatric medicine.

PubMed

Chang, Anna; Fernandez, Helen; Cayea, Danelle; Chheda, Shobhina; Paniagua, Miguel; Eckstrom, Elizabeth; Day, Hollis

2014-06-01

Internal medicine residents today face significant challenges in caring for an increasingly complex patient population within ever-changing education and health care environments. As a result, medical educators, health care system leaders, payers, and patients are demanding change and accountability in graduate medical education (GME). A 2012 Society of General Internal Medicine (SGIM) retreat identified medical education as an area for collaboration between internal medicine and geriatric medicine. The authors first determined a short-term research agenda for resident education by mapping selected internal medicine reporting milestones to geriatrics competencies, and listing available sample learner assessment tools. Next, the authors proposed a strategy for long-term collaboration in three priority areas in clinical medicine that are challenging for residents today: (1) team-based care, (2) transitions and readmissions, and (3) multi-morbidity. The short-term agenda focuses on learner assessment, while the long-term agenda allows for program evaluation and improvement. This model of collaboration in medical education combines the resources and expertise of internal medicine and geriatric medicine educators with the goal of increasing innovation and improving outcomes in GME targeting the needs of our residents and their patients.

[New international initiatives to create systems of effective risk prediction and food safety].

PubMed

Efimochkinal, N R; Bagryantseva, E C; Dupouy, E C; Khotimchenko, S A; Permyakov, E V; Sheveleva, S A; Arnautov, O V

2016-01-01

Ensuring food safety is one of the most important problems that is directly related to health protection of the population. The problem is particularly relevant on aglobalscale because ofincreasingnumberoffood-borne diseases andimportance of the health consequence early detection. In accordance with the position of the Codex Alimentarius Commission, food safety concept also includes quality. In this case, creation of the national, supranational and international early warning systems related to the food safety, designed with the purpose to prevent or minimize risks on different stages of the food value chain in various countries, regions and climate zones specific to national nutrition and lifestyle in different groups of population, gains particular importance. The article describes the principles and working examples of international, supranational and national food safety early warning systems. Great importance is given to the hazards of microbial origin - emergent pathogens. Example of the rapid reaction to the appearance of cases, related to the melanin presence in infant formula, are presented. Analysis of the current food safety and quality control system in Russian Federation shows that main improvements are mostly related to the development of the efficient monitoring, diagnostics and rapid alert procedures forfood safety on interregional and international levels that will allow to estimate real contamination of food with the most dangerous pathogens, chemical and biological contaminants, and the development of the electronic database and scientifically proved algorithms for food safety and quality management for targeted prevention activities against existing and emerging microbiological and other etiology risks, and public health protection.

The impact of HIV prevalence, conflict, corruption, and GDP/capita on treatment cascades: data from 137 countries.

PubMed

Levi, Jacob; Pozniak, Anton; Heath, Katherine; Hill, Andrew

2018-04-01

In 2014, UNAIDS and partners set the 90-90-90 targets for the HIV treatment cascade. Multiple social, political and structural factors might influence progress towards these targets. We assessed how close countries and regions are to reaching these targets, and compared cascade outcomes with HIV prevalence, gross domestic product (GDP)/capita, conflict and corruption. Country-level HIV cascade data on diagnosis, ART coverage and viral suppression, from 2010 to 2016 were extracted from national reports, published papers and the www.AIDSinfoOnline database, and analysed. Weighted least-squares regression was used to assess predictors of cascade achievement: region, HIV prevalence, GDP/capita, the 2016 Corruption Perceptions Index (CPI), which is an international ranking system, and the 2016 Global Peace Index (GPI), which ranks all countries based on three main categories: societal safety, militarisation and conflict. Data were available for diagnosis for 84 countries, ART coverage for 137 countries, and viral suppression for 94 countries. Regions with the lowest ART coverage were South-east Asia and Pacific (36%), Eastern Europe and Central Asia (17%), and Middle East and North Africa (13%). Lower HIV prevalence was associated with poorer cascade results. Countries with higher GDP/capita achieved higher ART coverage ( P <0.001). Furthermore, countries with lower levels of peace and higher corruption had lower ART coverage ( P <0.001). Countries with a GPI >2.5 all had ART coverage of <40%. Only one country has reached the UNAIDS 90-90-90 targets. International comparison remains difficult due to heterogeneous data reporting. Difficulty meeting UNAIDS targets is associated with lower GDP/capita, lower HIV prevalence, higher corruption and conflict levels.

Improving external beam radiotherapy by combination with internal irradiation.

PubMed

Dietrich, A; Koi, L; Zöphel, K; Sihver, W; Kotzerke, J; Baumann, M; Krause, M

2015-07-01

The efficacy of external beam radiotherapy (EBRT) is dose dependent, but the dose that can be applied to solid tumour lesions is limited by the sensitivity of the surrounding tissue. The combination of EBRT with systemically applied radioimmunotherapy (RIT) is a promising approach to increase efficacy of radiotherapy. Toxicities of both treatment modalities of this combination of internal and external radiotherapy (CIERT) are not additive, as different organs at risk are in target. However, advantages of both single treatments are combined, for example, precise high dose delivery to the bulk tumour via standard EBRT, which can be increased by addition of RIT, and potential targeting of micrometastases by RIT. Eventually, theragnostic radionuclide pairs can be used to predict uptake of the radiotherapeutic drug prior to and during therapy and find individual patients who may benefit from this treatment. This review aims to highlight the outcome of pre-clinical studies on CIERT and resultant questions for translation into the clinic. Few clinical data are available until now and reasons as well as challenges for clinical implementation are discussed.

The relative importance of external and internal features of facial composites.

PubMed

Frowd, Charlie; Bruce, Vicki; McIntyre, Alex; Hancock, Peter

2007-02-01

Three experiments are reported that compare the quality of external with internal regions within a set of facial composites using two matching-type tasks. Composites are constructed with the aim of triggering recognition from people familiar with the targets, and past research suggests internal face features dominate representations of familiar faces in memory. However the experiments reported here show that the internal regions of composites are very poorly matched against the faces they purport to represent, while external feature regions alone were matched almost as well as complete composites. In Experiments 1 and 2 the composites used were constructed by participant-witnesses who were unfamiliar with the targets and therefore were predicted to demonstrate a bias towards the external parts of a face. In Experiment 3 we compared witnesses who were familiar or unfamiliar with the target items, but for both groups the external features were much better reproduced in the composites, suggesting it is the process of composite construction itself which is responsible for the poverty of the internal features. Practical implications of these results are discussed.

Dynamics of Receptor-Mediated Nanoparticle Internalization into Endothelial Cells

PubMed Central

Gonzalez-Rodriguez, David; Barakat, Abdul I.

2015-01-01

Nanoparticles offer a promising medical tool for targeted drug delivery, for example to treat inflamed endothelial cells during the development of atherosclerosis. To inform the design of such therapeutic strategies, we develop a computational model of nanoparticle internalization into endothelial cells, where internalization is driven by receptor-ligand binding and limited by the deformation of the cell membrane and cytoplasm. We specifically consider the case of nanoparticles targeted against ICAM-1 receptors, of relevance for treating atherosclerosis. The model computes the kinetics of the internalization process, the dynamics of binding, and the distribution of stresses exerted between the nanoparticle and the cell membrane. The model predicts the existence of an optimal nanoparticle size for fastest internalization, consistent with experimental observations, as well as the role of bond characteristics, local cell mechanical properties, and external forces in the nanoparticle internalization process. PMID:25901833

An efficient method for generation of bi-allelic null mutant mouse embryonic stem cells and its application for investigating epigenetic modifiers

PubMed Central

Cho, Lily Ting-yin; Andrews, Robert; Carroll, Thomas; Iyer, Vivek; Tate, Peri; Rosen, Barry; Stunnenberg, Hendrik G.; Fisher, Amanda G.; Skarnes, William C.

2017-01-01

Abstract Mouse embryonic stem (ES) cells are a popular model system to study biological processes, though uncovering recessive phenotypes requires inactivating both alleles. Building upon resources from the International Knockout Mouse Consortium (IKMC), we developed a targeting vector for second allele inactivation in conditional-ready IKMC ‘knockout-first’ ES cell lines. We applied our technology to several epigenetic regulators, recovering bi-allelic targeted clones with a high efficiency of 60% and used Flp recombinase to restore expression in two null cell lines to demonstrate how our system confirms causality through mutant phenotype reversion. We designed our strategy to select against re-targeting the ‘knockout-first’ allele and identify essential genes in ES cells, including the histone methyltransferase Setdb1. For confirmation, we exploited the flexibility of our system, enabling tamoxifen inducible conditional gene ablation while controlling for genetic background and tamoxifen effects. Setdb1 ablated ES cells exhibit severe growth inhibition, which is not rescued by exogenous Nanog expression or culturing in naive pluripotency ‘2i’ media, suggesting that the self-renewal defect is mediated through pluripotency network independent pathways. Our strategy to generate null mutant mouse ES cells is applicable to thousands of genes and repurposes existing IKMC Intermediate Vectors. PMID:28981838

UAS Detection Classification and Neutralization: Market Survey 2015

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

Birch, Gabriel Carisle; Griffin, John Clark; Erdman, Matthew Kelly

The purpose of this document is to briefly frame the challenges of detecting low, slow, and small (LSS) unmanned aerial systems (UAS). The conclusion drawn from internal discussions and external reports is the following; detection of LSS UAS is a challenging problem that can- not be achieved with a single detection modality for all potential targets. Classification of LSS UAS, especially classification in the presence of background clutter (e.g., urban environment) or other non-threating targets (e.g., birds), is under-explored. Though information of avail- able technologies is sparse, many of the existing options for UAS detection appear to be in theirmore » infancy (when compared to more established ground-based air defense systems for larger and/or faster threats). Companies currently providing or developing technologies to combat the UAS safety and security problem are certainly worth investigating, however, no company has provided the statistical evidence necessary to support robust detection, identification, and/or neutralization of LSS UAS targets. The results of a market survey are included that highlights potential commercial entities that could contribute some technology that assists in the detection, classification, and neutral- ization of a LSS UAS. This survey found no clear and obvious commercial solution, though recommendations are given for further investigation of several potential systems.« less

Epidermal growth factor receptor-targeted lipid nanoparticles retain self-assembled nanostructures and provide high specificity

NASA Astrophysics Data System (ADS)

Zhai, Jiali; Scoble, Judith A.; Li, Nan; Lovrecz, George; Waddington, Lynne J.; Tran, Nhiem; Muir, Benjamin W.; Coia, Gregory; Kirby, Nigel; Drummond, Calum J.; Mulet, Xavier

2015-02-01

Next generation drug delivery utilising nanoparticles incorporates active targeting to specific sites. In this work, we combined targeting with the inherent advantages of self-assembled lipid nanoparticles containing internal nano-structures. Epidermal growth factor receptor (EGFR)-targeting, PEGylated lipid nanoparticles using phytantriol and 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-PEG-maleimide amphiphiles were created. The self-assembled lipid nanoparticles presented here have internal lyotropic liquid crystalline nano-structures, verified by synchrotron small angle X-ray scattering and cryo-transmission electron microscopy, that offer the potential of high drug loading and enhanced cell penetration. Anti-EGFR Fab' fragments were conjugated to the surface of nanoparticles via a maleimide-thiol reaction at a high conjugation efficiency and retained specificity following conjugation to the nanoparticles. The conjugated nanoparticles were demonstrated to have high affinity for an EGFR target in a ligand binding assay.Next generation drug delivery utilising nanoparticles incorporates active targeting to specific sites. In this work, we combined targeting with the inherent advantages of self-assembled lipid nanoparticles containing internal nano-structures. Epidermal growth factor receptor (EGFR)-targeting, PEGylated lipid nanoparticles using phytantriol and 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-PEG-maleimide amphiphiles were created. The self-assembled lipid nanoparticles presented here have internal lyotropic liquid crystalline nano-structures, verified by synchrotron small angle X-ray scattering and cryo-transmission electron microscopy, that offer the potential of high drug loading and enhanced cell penetration. Anti-EGFR Fab' fragments were conjugated to the surface of nanoparticles via a maleimide-thiol reaction at a high conjugation efficiency and retained specificity following conjugation to the nanoparticles. The conjugated nanoparticles were demonstrated to have high affinity for an EGFR target in a ligand binding assay. Electronic supplementary information (ESI) available: Fig. S1-S4. See DOI: 10.1039/c4nr05200e

Impact of Spot Size and Spacing on the Quality of Robustly Optimized Intensity Modulated Proton Therapy Plans for Lung Cancer.

PubMed

Liu, Chenbin; Schild, Steven E; Chang, Joe Y; Liao, Zhongxing; Korte, Shawn; Shen, Jiajian; Ding, Xiaoning; Hu, Yanle; Kang, Yixiu; Keole, Sameer R; Sio, Terence T; Wong, William W; Sahoo, Narayan; Bues, Martin; Liu, Wei

2018-06-01

To investigate how spot size and spacing affect plan quality, robustness, and interplay effects of robustly optimized intensity modulated proton therapy (IMPT) for lung cancer. Two robustly optimized IMPT plans were created for 10 lung cancer patients: first by a large-spot machine with in-air energy-dependent large spot size at isocenter (σ: 6-15 mm) and spacing (1.3 σ), and second by a small-spot machine with in-air energy-dependent small spot size (σ: 2-6 mm) and spacing (5 mm). Both plans were generated by optimizing radiation dose to internal target volume on averaged 4-dimensional computed tomography scans using an in-house-developed IMPT planning system. The dose-volume histograms band method was used to evaluate plan robustness. Dose evaluation software was developed to model time-dependent spot delivery to incorporate interplay effects with randomized starting phases for each field per fraction. Patient anatomy voxels were mapped phase-to-phase via deformable image registration, and doses were scored using in-house-developed software. Dose-volume histogram indices, including internal target volume dose coverage, homogeneity, and organs at risk (OARs) sparing, were compared using the Wilcoxon signed-rank test. Compared with the large-spot machine, the small-spot machine resulted in significantly lower heart and esophagus mean doses, with comparable target dose coverage, homogeneity, and protection of other OARs. Plan robustness was comparable for targets and most OARs. With interplay effects considered, significantly lower heart and esophagus mean doses with comparable target dose coverage and homogeneity were observed using smaller spots. Robust optimization with a small spot-machine significantly improves heart and esophagus sparing, with comparable plan robustness and interplay effects compared with robust optimization with a large-spot machine. A small-spot machine uses a larger number of spots to cover the same tumors compared with a large-spot machine, which gives the planning system more freedom to compensate for the higher sensitivity to uncertainties and interplay effects for lung cancer treatments. Copyright © 2018 Elsevier Inc. All rights reserved.

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 manual responses.

Simulation of Mission Phases

NASA Technical Reports Server (NTRS)

Carlstrom, Nicholas Mercury

2016-01-01

This position with the Simulation and Graphics Branch (ER7) at Johnson Space Center (JSC) provided an introduction to vehicle hardware, mission planning, and simulation design. ER7 supports engineering analysis and flight crew training by providing high-fidelity, real-time graphical simulations in the Systems Engineering Simulator (SES) lab. The primary project assigned by NASA mentor and SES lab manager, Meghan Daley, was to develop a graphical simulation of the rendezvous, proximity operations, and docking (RPOD) phases of flight. The simulation is to include a generic crew/cargo transportation vehicle and a target object in low-Earth orbit (LEO). Various capsule, winged, and lifting body vehicles as well as historical RPOD methods were evaluated during the project analysis phase. JSC core mission to support the International Space Station (ISS), Commercial Crew Program (CCP), and Human Space Flight (HSF) influenced the project specifications. The simulation is characterized as a 30 meter +V Bar and/or -R Bar approach to the target object's docking station. The ISS was selected as the target object and the international Low Impact Docking System (iLIDS) was selected as the docking mechanism. The location of the target object's docking station corresponds with the RPOD methods identified. The simulation design focuses on Guidance, Navigation, and Control (GNC) system architecture models with station keeping and telemetry data processing capabilities. The optical and inertial sensors, reaction control system thrusters, and the docking mechanism selected were based on CCP vehicle manufacturer's current and proposed technologies. A significant amount of independent study and tutorial completion was required for this project. Multiple primary source materials were accessed using the NASA Technical Report Server (NTRS) and reference textbooks were borrowed from the JSC Main Library and International Space Station Library. The Trick Simulation Environment and User Training Materials version 2013.0 release was used to complete the Trick tutorial. Multiple network privilege and repository permission requests were required in order to access previous simulation models. The project was also an introduction to computer programming and the Linux operating system. Basic C++ and Python syntax was used during the completion of the Trick tutorial. Trick's engineering analysis and Monte Carlo simulation capabilities were observed and basic space mission planning procedures were applied in the conceptual design phase. Multiple professional development opportunities were completed in addition to project duties during this internship through the System for Administration, Training, and Education Resources for NASA (SATERN). Topics include: JSC Risk Management Workshop, CCP Risk Management, Basic Radiation Safety Training, X-Ray Radiation Safety, Basic Laser Safety, JSC Export Control, ISS RISE Ambassador, Basic SharePoint 2013, Space Nutrition and Biochemistry, and JSC Personal Protective Equipment. Additionally, this internship afforded the opportunity for formal project presentation and public speaking practice. This was my first experience at a NASA center. After completing this internship I have a much clearer understanding of certain aspects of the agency's processes and procedures, as well as a deeper appreciation from spaceflight simulation design and testing. I will continue to improve my technical skills so that I may have another opportunity to return to NASA and Johnson Space Center.

Gene delivery nanocarriers of bioactive glass with unique potential to load BMP2 plasmid DNA and to internalize into mesenchymal stem cells for osteogenesis and bone regeneration

NASA Astrophysics Data System (ADS)

Kim, Tae-Hyun; Singh, Rajendra K.; Kang, Min Sil; Kim, Joong-Hyun; Kim, Hae-Won

2016-04-01

The recent development of bioactive glasses with nanoscale morphologies has spurred their specific applications in bone regeneration, for example as drug and gene delivery carriers. Bone engineering with stem cells genetically modified with this unique class of nanocarriers thus holds great promise in this avenue. Here we report the potential of the bioactive glass nanoparticle (BGN) system for the gene delivery of mesenchymal stem cells (MSCs) targeting bone. The composition of 15% Ca-added silica, proven to be bone-bioactive, was formulated into surface aminated mesoporous nanospheres with enlarged pore sizes, to effectively load and deliver bone morphogenetic protein-2 (BMP2) plasmid DNA. The enlarged mesopores were highly effective in loading BMP2-pDNA with an efficiency as high as 3.5 wt% (pDNA w.r.t. BGN), a level more than twice than for small-sized mesopores. The BGN nanocarriers released the genetic molecules in a highly sustained manner (for as long as 2 weeks). The BMP2-pDNA/BGN complexes were effectively internalized to rat MSCs with a cell uptake level of ~73%, and the majority of cells were transfected to express the BMP2 protein. Subsequent osteogenesis of the transfected MSCs was demonstrated by the expression of bone-related genes, including bone sialoprotein, osteopontin, and osteocalcin. The MSCs transfected with BMP2-pDNA/BGN were locally delivered inside a collagen gel to the target calvarium defects. The results showed significantly improved bone regeneration, as evidenced by the micro-computed tomographic, histomorphometric and immunohistochemical analyses. This study supports the excellent capacity of the BGN system as a pDNA-delivery nanocarrier in MSCs, and the engineered system, BMP2-pDNA/BGN with MSCs, may be considered a new promising candidate to advance the therapeutic potential of stem cells through genetic modification, targeting bone defects and diseases.The recent development of bioactive glasses with nanoscale morphologies has spurred their specific applications in bone regeneration, for example as drug and gene delivery carriers. Bone engineering with stem cells genetically modified with this unique class of nanocarriers thus holds great promise in this avenue. Here we report the potential of the bioactive glass nanoparticle (BGN) system for the gene delivery of mesenchymal stem cells (MSCs) targeting bone. The composition of 15% Ca-added silica, proven to be bone-bioactive, was formulated into surface aminated mesoporous nanospheres with enlarged pore sizes, to effectively load and deliver bone morphogenetic protein-2 (BMP2) plasmid DNA. The enlarged mesopores were highly effective in loading BMP2-pDNA with an efficiency as high as 3.5 wt% (pDNA w.r.t. BGN), a level more than twice than for small-sized mesopores. The BGN nanocarriers released the genetic molecules in a highly sustained manner (for as long as 2 weeks). The BMP2-pDNA/BGN complexes were effectively internalized to rat MSCs with a cell uptake level of ~73%, and the majority of cells were transfected to express the BMP2 protein. Subsequent osteogenesis of the transfected MSCs was demonstrated by the expression of bone-related genes, including bone sialoprotein, osteopontin, and osteocalcin. The MSCs transfected with BMP2-pDNA/BGN were locally delivered inside a collagen gel to the target calvarium defects. The results showed significantly improved bone regeneration, as evidenced by the micro-computed tomographic, histomorphometric and immunohistochemical analyses. This study supports the excellent capacity of the BGN system as a pDNA-delivery nanocarrier in MSCs, and the engineered system, BMP2-pDNA/BGN with MSCs, may be considered a new promising candidate to advance the therapeutic potential of stem cells through genetic modification, targeting bone defects and diseases. Electronic supplementary information (ESI) available. See DOI: 10.1039/c5nr07933k

International Space Station End-of-Life Probabilistic Risk Assessment

NASA Technical Reports Server (NTRS)

Duncan, Gary

2014-01-01

Although there are ongoing efforts to extend the ISS life cycle through 2028, the International Space Station (ISS) end-of-life (EOL) cycle is currently scheduled for 2020. The EOL for the ISS will require de-orbiting the ISS. This will be the largest manmade object ever to be de-orbited, therefore safely de-orbiting the station will be a very complex problem. This process is being planned by NASA and its international partners. Numerous factors will need to be considered to accomplish this such as target corridors, orbits, altitude, drag, maneuvering capabilities, debris mapping etc. The ISS EOL Probabilistic Risk Assessment (PRA) will play a part in this process by estimating the reliability of the hardware supplying the maneuvering capabilities. The PRA will model the probability of failure of the systems supplying and controlling the thrust needed to aid in the de-orbit maneuvering.

International Agreement on Planetary Protection

NASA Technical Reports Server (NTRS)

2000-01-01

The maintenance of a NASA policy, is consistent with international agreements. The planetary protection policy management in OSS, with Field Center support. The advice from internal and external advisory groups (NRC, NAC/Planetary Protection Task Force). The technology research and standards development in bioload characterization. The technology research and development in bioload reduction/sterilization. This presentation focuses on: forward contamination - research on the potential for Earth life to exist on other bodies, improved strategies for planetary navigation and collision avoidance, and improved procedures for sterile spacecraft assembly, cleaning and/or sterilization; and backward contamination - development of sample transfer and container sealing technologies for Earth return, improvement in sample return landing target assessment and navigation strategy, planning for sample hazard determination requirements and procedures, safety certification, (liaison to NEO Program Office for compositional data on small bodies), facility planning for sample recovery system, quarantine, and long-term curation of 4 returned samples.

Single mutation in Shine-Dalgarno-like sequence present in the amino terminal of lactate dehydrogenase of Plasmodium effects the production of an eukaryotic protein expressed in a prokaryotic system.

PubMed

Cicek, Mustafa; Mutlu, Ozal; Erdemir, Aysegul; Ozkan, Ebru; Saricay, Yunus; Turgut-Balik, Dilek

2013-06-01

One of the most important step in structure-based drug design studies is obtaining the protein in active form after cloning the target gene. In one of our previous study, it was determined that an internal Shine-Dalgarno-like sequence present just before the third methionine at N-terminus of wild type lactate dehydrogenase enzyme of Plasmodium falciparum prevent the translation of full length protein. Inspection of the same region in P. vivax LDH, which was overproduced as an active enzyme, indicated that the codon preference in the same region was slightly different than the codon preference of wild type PfLDH. In this study, 5'-GGAGGC-3' sequence of P. vivax that codes for two glycine residues just before the third methionine was exchanged to 5'-GGAGGA-3', by mimicking P. falciparum LDH, to prove the possible effects of having an internal SD-like sequence when expressing an eukaryotic protein in a prokaryotic system. Exchange was made by site-directed mutagenesis. Results indicated that having two glycine residues with an internal SD-like sequence (GGAGGA) just before the third methionine abolishes the enzyme activity due to the preference of the prokaryotic system used for the expression. This study emphasizes the awareness of use of a prokaryotic system to overproduce an eukaryotic protein.

Evaluating institutional capacity for research ethics in Africa: a case study from Botswana.

PubMed

Hyder, Adnan A; Zafar, Waleed; Ali, Joseph; Ssekubugu, Robert; Ndebele, Paul; Kass, Nancy

2013-07-30

The increase in the volume of research conducted in Low and Middle Income Countries (LMIC), has brought a renewed international focus on processes for ethical conduct of research. Several programs have been initiated to strengthen the capacity for research ethics in LMIC. However, most such programs focus on individual training or development of ethics review committees. The objective of this paper is to present an approach to institutional capacity assessment in research ethics and application of this approach in the form of a case study from an institution in Africa. We adapted the Octagon model originally used by the Swedish International Development Cooperation Agency to assess an organization along eight domains in research ethics: basic values and identity; structure and organization; ability to carry out activities; relevance of activities to stated goals; capacity of staff and management; administrative, financing and accounting systems; its relations with target groups; and the national context. We used a mixed methods approach to collect empirical data at the University of Botswana from March to December 2010. The overall shape of the external evaluation Octagon suggests that strengths of the University of Botswana are in the areas of structure, relevance, production and identity; while the university still needs more work in the areas of systems of finance, target groups, and environment. The Octagons also show the similarities and discrepancies between the 'external' and 'internal' evaluations and provide an opportunity for exploration of these different assessments. For example, the discrepant score for 'identity' between internal and external evaluations allows for an exploration of what constitutes a strong identity for research ethics at the University of Botswana and how it can be strengthened. There is a general lack of frameworks for evaluating research ethics capacity in LMICs. We presented an approach that stresses evaluation from both internal and external perspectives. This case study highlights the university's rapid progress in developing research ethics capacity and points to some notable areas for improvement. We believe that such an empirically-driven and participatory assessment allows a more holistic measurement and promotion of institutional capacity strengthening for research ethics in LMICs.

Evaluating institutional capacity for research ethics in Africa: a case study from Botswana

PubMed Central

2013-01-01

Background The increase in the volume of research conducted in Low and Middle Income Countries (LMIC), has brought a renewed international focus on processes for ethical conduct of research. Several programs have been initiated to strengthen the capacity for research ethics in LMIC. However, most such programs focus on individual training or development of ethics review committees. The objective of this paper is to present an approach to institutional capacity assessment in research ethics and application of this approach in the form of a case study from an institution in Africa. Methods We adapted the Octagon model originally used by the Swedish International Development Cooperation Agency to assess an organization along eight domains in research ethics: basic values and identity; structure and organization; ability to carry out activities; relevance of activities to stated goals; capacity of staff and management; administrative, financing and accounting systems; its relations with target groups; and the national context. We used a mixed methods approach to collect empirical data at the University of Botswana from March to December 2010. Results The overall shape of the external evaluation Octagon suggests that strengths of the University of Botswana are in the areas of structure, relevance, production and identity; while the university still needs more work in the areas of systems of finance, target groups, and environment. The Octagons also show the similarities and discrepancies between the 'external' and 'internal' evaluations and provide an opportunity for exploration of these different assessments. For example, the discrepant score for 'identity' between internal and external evaluations allows for an exploration of what constitutes a strong identity for research ethics at the University of Botswana and how it can be strengthened. Conclusions There is a general lack of frameworks for evaluating research ethics capacity in LMICs. We presented an approach that stresses evaluation from both internal and external perspectives. This case study highlights the university's rapid progress in developing research ethics capacity and points to some notable areas for improvement. We believe that such an empirically-driven and participatory assessment allows a more holistic measurement and promotion of institutional capacity strengthening for research ethics in LMICs. PMID:23899301

Internalization, Trafficking, Intracellular Processing and Actions of Antibody-Drug Conjugates.

PubMed

Xu, Shi

2015-11-01

This review discusses the molecular mechanism involved in the targeting and delivery of antibody-drug conjugates (ADCs), the new class of biopharmaceuticals mainly designed for targeted cancer therapy. this review goes over major progress in preclinical and clinical studies of ADCs, in the past 5 years. The pharmacokinetics and pharmacodynamics of ADCs involve multiple mechanisms, including internalization of ADCs by target cells, intracellular trafficking, release of conjugated drugs, and payload. These mechanisms actually jointly determine the efficacy of ADCs. Therefore, the optimization of ADCs should take them as necessary rationales.

Narrative review of current context of malaria and management strategies in Uganda (Part I).

PubMed

Kassam, Rosemin; Collins, John B; Liow, Eric; Rasool, Nabeela

2015-12-01

In accordance with international targets, the Uganda National Malaria Control Strategic Plan established specific targets to be achieved by 2010. For children under five, this included increasing the number of children sleeping under mosquito nets and those receiving a first-line antimalarial to 85%, and decreasing case fatality to 2%. This narrative review offers contextual information relevant to malaria management in Uganda since the advent of artemisinin combination therapy (ACT) as first-line antimalarial treatment in 2004. A comprehensive search using key words and phrases was conducted using the web search engines Google and Google Scholar, as well as the databases of PubMed, ERIC, EMBASE, CINAHL, OvidSP (MEDLINE), PSYC Info, Springer Link, Cochrane Central Register of Controlled Trials (CENTRAL), and Cochrane Database of Systematic Reviews were searched. A total of 147 relevant international and Ugandan literature sources meeting the inclusion criteria were included. This review provides an insightful understanding on six topic areas: global and local priorities, malarial pathology, disease burden, malaria control, treatment guidelines for uncomplicated malaria, and role of the health system in accessing antimalarial medicines. Plasmodium falciparum remains the most common cause of malaria in Uganda, with children under five being most vulnerable due to their underdeveloped immunity. While international efforts to scale up malaria control measures have resulted in considerable decline in malaria incidence and mortality in several regions of sub-Saharan Africa, this benefit has yet to be substantiated for Uganda. At the local level, key initiatives have included implementation of a new antimalarial drug policy in 2004 and strengthening of government health systems and programs. Examples of such programs include removal of user fees, training of frontline health workers, providing free ACT from government systems and subsidized ACT from licensed private outlets, and introduction of the integrated community case management program to bring diagnostics and treatment for malaria, pneumonia and diarrhea closer to the community. However despite notable efforts, Uganda is far from achieving its 2010 targets. Several challenges in the delivery of care and treatment remain, with those most vulnerable and living in rural settings remaining at greatest risk from malaria morbidity and mortality. Copyright © 2015 The Authors. Published by Elsevier B.V. All rights reserved.

Advances in Doppler recognition for ground moving target indication

NASA Astrophysics Data System (ADS)

Kealey, Paul G.; Jahangir, Mohammed

2006-05-01

Ground Moving Target Indication (GMTI) radar provides a day/night, all-weather, wide-area surveillance capability to detect moving vehicles and personnel. Current GMTI radar sensors are limited to only detecting and tracking targets. The exploitation of GMTI data would be greatly enhanced by a capability to recognize accurately the detections as significant classes of target. Doppler classification exploits the differential internal motion of targets, e.g. due to the tracks, limbs and rotors. Recently, the QinetiQ Bayesian Doppler classifier has been extended to include a helicopter class in addition to wheeled, tracked and personnel classes. This paper presents the performance for these four classes using a traditional low-resolution GMTI surveillance waveform with an experimental radar system. We have determined the utility of an "unknown output decision" for enhancing the accuracy of the declared target classes. A confidence method has been derived, using a threshold of the difference in certainties, to assign uncertain classifications into an "unknown class". The trade-off between fraction of targets declared and accuracy of the classifier has been measured. To determine the operating envelope of a Doppler classification algorithm requires a detailed understanding of the Signal-to-Noise Ratio (SNR) performance of the algorithm. In this study the SNR dependence of the QinetiQ classifier has been determined.

Identification of TMEM208 and PQLC2 as reference genes for normalizing mRNA expression in colorectal cancer treated with aspirin

PubMed Central

Zhu, Yuanyuan; Yang, Chao; Weng, Mingjiao; Zhang, Yan; Yang, Chunhui; Jin, Yinji; Yang, Weiwei; He, Yan; Wu, Yiqi; Zhang, Yuhua; Wang, Guangyu; RajkumarEzakiel Redpath, Riju James; Zhang, Lei; Jin, Xiaoming; Liu, Ying; Sun, Yuchun; Ning, Ning; Qiao, Yu; Zhang, Fengmin; Li, Zhiwei; Wang, Tianzhen; Zhang, Yanqiao; Li, Xiaobo

2017-01-01

Numerous evidences indicate that aspirin usage causes a significant reduction in colorectal cancer. However, the molecular mechanisms about aspirin preventing colon cancer are largely unknown. Quantitative reverse transcription polymerase chain reaction (qRT-PCR) is a most frequently used method to identify the target molecules regulated by certain compound. However, this method needs stable internal reference genes to analyze the expression change of the targets. In this study, the transcriptional stabilities of several traditional reference genes were evaluated in colon cancer cells treated with aspirin, and also, the suitable internal reference genes were screened by using a microarray and were further identified by using the geNorm and NormFinder softwares, and then were validated in more cell lines and xenografts. We have showed that three traditional internal reference genes, β-actin, GAPDH and α-tubulin, are not suitable for studying gene transcription in colon cancer cells treated with aspirin, and we have identified and validated TMEM208 and PQLC2 as the ideal internal reference genes for detecting the molecular targets of aspirin in colon cancer in vitro and in vivo. This study reveals stable internal reference genes for studying the target genes of aspirin in colon cancer, which will contribute to identify the molecular mechanism behind aspirin preventing colon cancer. PMID:28184026

Identification of TMEM208 and PQLC2 as reference genes for normalizing mRNA expression in colorectal cancer treated with aspirin.

PubMed

Zhu, Yuanyuan; Yang, Chao; Weng, Mingjiao; Zhang, Yan; Yang, Chunhui; Jin, Yinji; Yang, Weiwei; He, Yan; Wu, Yiqi; Zhang, Yuhua; Wang, Guangyu; RajkumarEzakiel Redpath, Riju James; Zhang, Lei; Jin, Xiaoming; Liu, Ying; Sun, Yuchun; Ning, Ning; Qiao, Yu; Zhang, Fengmin; Li, Zhiwei; Wang, Tianzhen; Zhang, Yanqiao; Li, Xiaobo

2017-04-04

Numerous evidences indicate that aspirin usage causes a significant reduction in colorectal cancer. However, the molecular mechanisms about aspirin preventing colon cancer are largely unknown. Quantitative reverse transcription polymerase chain reaction (qRT-PCR) is a most frequently used method to identify the target molecules regulated by certain compound. However, this method needs stable internal reference genes to analyze the expression change of the targets. In this study, the transcriptional stabilities of several traditional reference genes were evaluated in colon cancer cells treated with aspirin, and also, the suitable internal reference genes were screened by using a microarray and were further identified by using the geNorm and NormFinder softwares, and then were validated in more cell lines and xenografts. We have showed that three traditional internal reference genes, β-actin, GAPDH and α-tubulin, are not suitable for studying gene transcription in colon cancer cells treated with aspirin, and we have identified and validated TMEM208 and PQLC2 as the ideal internal reference genes for detecting the molecular targets of aspirin in colon cancer in vitro and in vivo. This study reveals stable internal reference genes for studying the target genes of aspirin in colon cancer, which will contribute to identify the molecular mechanism behind aspirin preventing colon cancer.

Bulk and dispersed aqueous behaviour of an endogenous lipid, selachyl alcohol: Effect of Tween 80 and Pluronic F127 on nanostructure.

PubMed

Younus, Mohammad; Hawley, Adrian; Boyd, Ben J; Rizwan, Shakila B

2018-05-07

Tween 80 has been reported to provide a means of targeting drug nanocarriers to the blood- brain barrier. This study investigated the influence of addition of Tween 80 on the formation of different bulk and dispersed lyotropic liquid crystalline phases in selachyl alcohol-based systems. The effect of increasing concentrations of Tween 80 and Pluronic F127 (as a control) (0-25% w/w relative to SA) on the bulk phase behaviour and dispersions of selachyl alcohol (SA) were investigated using small angle X-ray scattering, dynamic light scattering, and cryogenic transmission electron microscopy. The addition of Tween 80 to SA bulk phase samples triggered concentration-dependent phase changes with the structure sequentially evolving from a reverse hexagonal phase (H 2 ) to a mixed H 2 and inverse bicontinuous cubic (V 2 ) then a V 2 phase alone. In contrast, the addition of Pluronic F127 resulted in a phase change from H 2 phase to a mixed lamellar and H 2 phase system. The mean particle size of internally structured particles was 125-190 nm with low polydispersity indices (0.1-0.2). Nanoparticles retained the bulk phase internal structure in the presence of Tween 80, whereas in the presence of Pluronic F127, the additional lamellar phase that formed in bulk phase systems was not observed. Cryo-TEM revealed the formation of cubosomes and hexosomes by SA in excess water in the presence of Tween 80 and Pluronic F127 respectively. In summary, it was shown that stabilisation of SA dispersions using Tween 80 resulted in a decrease in negative curvature leading to a change in internal structure from H 2 to V 2 phase. The studies provide the core understanding of particle structure to progress these structured lipid nanocarriers into delivery studies with Tween 80 as a mechanism to target the blood-brain barrier. Crown Copyright © 2018. Published by Elsevier B.V. All rights reserved.

KSC-08pd0606

NASA Image and Video Library

2008-02-11

KENNEDY SPACE CENTER, FLA. -- In the Space Station Processing Facility at NASA's Kennedy Space Center, an overhead crane moves the Special Purpose Dexterous Manipulator, known as Dextre, to the payload canister for transfer to Launch Pad 39A. Dextre is a sophisticated dual-armed robot, which is part of Canada's contribution to the International Space Station. Along with Canadarm2, which is called the Space Station Remote Manipulator System, and a moveable work platform called the Mobile Base System, these three elements form a robotic system called the Mobile Servicing System. The three components have been designed to work together or independently. Dextre is part of the payload on space shuttle Endeavour's STS-123 mission, targeted for launch March 11. Photo courtesy of The Boeing Company

KSC-08pd0608

NASA Image and Video Library

2008-02-11

KENNEDY SPACE CENTER, FLA. -- In the Space Station Processing Facility at NASA's Kennedy Space Center, the Special Purpose Dexterous Manipulator, known as Dextre, moves nearer to the payload canister where it will be installed for transfer to Launch Pad 39A. Dextre is a sophisticated dual-armed robot, which is part of Canada's contribution to the International Space Station. Along with Canadarm2, which is called the Space Station Remote Manipulator System, and a moveable work platform called the Mobile Base System, these three elements form a robotic system called the Mobile Servicing System. The three components have been designed to work together or independently. Dextre is part of the payload on space shuttle Endeavour's STS-123 mission, targeted for launch March 11. Photo courtesy of The Boeing Company

KSC-08pd0604

NASA Image and Video Library

2008-02-11

KENNEDY SPACE CENTER, FLA. -- In the Space Station Processing Facility at NASA's Kennedy Space Center, the Special Purpose Dexterous Manipulator, known as Dextre, moves across the facility via an overhead crane to the payload canister for transfer to Launch Pad 39A. Dextre is a sophisticated dual-armed robot, which is part of Canada's contribution to the International Space Station. Along with Canadarm2, which is called the Space Station Remote Manipulator System, and a moveable work platform called the Mobile Base System, these three elements form a robotic system called the Mobile Servicing System. The three components have been designed to work together or independently. Dextre is part of the payload on space shuttle Endeavour's STS-123 mission, targeted for launch March 11. Photo courtesy of The Boeing Company

KSC-08pd0607

NASA Image and Video Library

2008-02-11

KENNEDY SPACE CENTER, FLA. -- In the Space Station Processing Facility at NASA's Kennedy Space Center, the Special Purpose Dexterous Manipulator, known as Dextre, moves closer to the payload canister where it will be installed for transfer to Launch Pad 39A. Dextre is a sophisticated dual-armed robot, which is part of Canada's contribution to the International Space Station. Along with Canadarm2, which is called the Space Station Remote Manipulator System, and a moveable work platform called the Mobile Base System, these three elements form a robotic system called the Mobile Servicing System. The three components have been designed to work together or independently. Dextre is part of the payload on space shuttle Endeavour's STS-123 mission, targeted for launch March 11. Photo courtesy of The Boeing Company

KSC-07pd2871

NASA Image and Video Library

2007-10-01

KENNEDY SPACE CENTER, FLA. -- In the Space Station Processing Facility at NASA's Kennedy Space Center, technicians help guide the starboard arm of the Special Purpose Dexterous Manipulator, known as Dextre, into place for installation on the base. Dextre is a sophisticated dual-armed robot, which is part of Canada's contribution to the International Space Station (ISS). Along with Canadarm2, whose technical name is the Space Station Remote Manipulator System, and a moveable work platform called the Mobile Base System, these three elements form a robotic system called the Mobile Servicing System, or MSS. The three components have been designed to work together or independently. Dextre is part of the payload scheduled on mission STS-123, targeted to launch Feb. 14. Photo credit: NASA/George Shelton

KSC-07pd2863

NASA Image and Video Library

2007-10-01

KENNEDY SPACE CENTER, FLA. -- In the Space Station Processing Facility at NASA's Kennedy Space Center, the starboard arm of the Special Purpose Dexterous Manipulator, known as Dextre, is ready to be installed on the base. Dextre is a sophisticated dual-armed robot, which is part of Canada's contribution to the International Space Station ISS. Along with Canadarm2, whose technical name is the Space Station Remote Manipulator System, and a moveable work platform called the Mobile Base System, these three elements form a robotic system called the Mobile Servicing System, or MSS. The three components have been designed to work together or independently. Dextre is part of the payload scheduled on mission STS-123, targeted to launch Feb. 14. Photo credit: NASA/George Shelton

KSC-07pd2870

NASA Image and Video Library

2007-10-01

KENNEDY SPACE CENTER, FLA. -- In the Space Station Processing Facility at NASA's Kennedy Space Center, technicians help guide the starboard arm of the Special Purpose Dexterous Manipulator, known as Dextre, into place for installation on the base. Dextre is a sophisticated dual-armed robot, which is part of Canada's contribution to the International Space Station (ISS). Along with Canadarm2, whose technical name is the Space Station Remote Manipulator System, and a moveable work platform called the Mobile Base System, these three elements form a robotic system called the Mobile Servicing System, or MSS. The three components have been designed to work together or independently. Dextre is part of the payload scheduled on mission STS-123, targeted to launch Feb. 14. Photo credit: NASA/George Shelton

KSC-07pd2866

NASA Image and Video Library

2007-10-01

KENNEDY SPACE CENTER, FLA. -- In the Space Station Processing Facility at NASA's Kennedy Space Center, the starboard arm of the Special Purpose Dexterous Manipulator, known as Dextre, is moved across the facility. The arm will be installed on the base. Dextre is a sophisticated dual-armed robot, which is part of Canada's contribution to the International Space Station (ISS). Along with Canadarm2, whose technical name is the Space Station Remote Manipulator System, and a moveable work platform called the Mobile Base System, these three elements form a robotic system called the Mobile Servicing System, or MSS. The three components have been designed to work together or independently. Dextre is part of the payload scheduled on mission STS-123, targeted to launch Feb. 14. Photo credit: NASA/George Shelton

[The development of novel tumor targeting delivery strategy].

PubMed

Gao, Hui-le; Jiang, Xin-guo

2016-02-01

Tumor is one of the most serious threats for human being. Although many anti-tumor drugs are approved for clinical use, the treatment outcome is still modest because of the poor tumor targeting efficiency and low accumulation in tumor. Therefore, it is important to deliver anti-tumor drug into tumor efficiently, elevate drug concentration in tumor tissues and reduce the drug distribution in normal tissues. And it has been one of the most attractive directions of pharmaceutical academy and industry. Many kinds of strategies, especially various nanoparticulated drug delivery systems, have been developed to address the critical points of complex tumor microenvironment, which are partially or mostly satisfied for tumor treatment. In this paper, we carefully reviewed the novel targeting delivery strategies developed in recent years. The most powerful method is passive targeting delivery based on the enhanced permeability and retention(EPR) effect, and most commercial nanomedicines are based on the EPR effect. However, the high permeability and retention require different particle sizes, thus several kinds of size-changeable nanoparticles are developed, such as size reducible particles and assemble particles, to satisfy the controversial requirement for particle size and enhance both tumor retention and penetration. Surface charge reversible nanoparticles also shows a high efficiency because the anionic charge in blood circulation and normal organs decrease the unintended internalization. The charge can change into positive in tumor microenvironment, facilitating drug uptake by tumor cells. Additionally, tumor microenvironment responsive drug release is important to decrease drug side effect, and many strategies are developed, such as p H sensitive release and enzyme sensitive release. Except the responsive nanoparticles, shaping tumor microenvironment could attenuate the barriers in drug delivery, for example, decreasing tumor collagen intensity and normalizing tumor microvessels to decrease the internal fluid pressure. All these strategies could enhance the accumulation and penetration of nanoparticles into tumor, leading to a homogenous distribution of drugs in tumor. To enhance the internalization by specific cells, active targeting delivery strategies are developed. There were many surface markers, receptors or carriers overexpressed on specific kinds of cells, thus the corresponding ligands were utilized to mediate active targeting to certain cells, including tumor cells, cancer stem cells, tumor neovasculatures, tumor associated macrophages and other tumor stroma cells. Targeting more than one cell type may provide an improved antitumor effect. Although these passive and active targeting strategies all have promising outcome in the treatment of tumor, some shortages are still unaddressed, such as the specificity of responsive is not good enough, and the active targeting may be diminished by the protein corona. Thus more research is required to promote the drug delivery study.

Anti-nociceptive effect of a conjugate of substance P and light chain of botulinum neurotoxin type A.

PubMed

Mustafa, Golam; Anderson, Ethan M; Bokrand-Donatelli, Yvonne; Neubert, John K; Caudle, Robert M

2013-11-01

Neuropathic pain is a debilitating condition resulting from damage to sensory transmission pathways in the peripheral and central nervous system. A potential new way of treating chronic neuropathic pain is to target specific pain-processing neurons based on their expression of particular receptor molecules. We hypothesized that a toxin-neuropeptide conjugate would alter pain by first being taken up by specific receptors for the neuropeptide expressed on the neuronal cells. Then, once inside the cell the toxin would inhibit the neurons' activity without killing the neurons, thereby providing pain relief without lesioning the nervous system. In an effort to inactivate the nociceptive neurons in the trigeminal nucleus caudalis in mice, we targeted the NK1 receptor (NK1R) using substance P (SP). The catalytically active light chain of botulinum neurotoxin type A (LC/A) was conjugated with SP. Our results indicate that the conjugate BoNT/A-LC:SP is internalized in cultured NK1R-expressing neurons and also cleaves the target of botulinum toxin, a component-docking motif necessary for release of neurotransmitters called SNAP-25. The conjugate was next tested in a murine model of Taxol-induced neuropathic pain. An intracisternal injection of BoNT/A-LC:SP decreased thermal hyperalgesia as measured by the operant orofacial nociception assay. These findings indicate that conjugates of the light chain of botulinum toxin are extremely promising agents for use in suppressing neuronal activity for extended time periods, and that BoNT/A-LC:SP may be a useful agent for treating chronic pain. Copyright © 2013 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.

PST 2009: XIII International Workshop on Polarized Sources Targets and Polarimetry

NASA Astrophysics Data System (ADS)

Lenisa, Paolo

2011-05-01

The workshops on polarized sources, targets, and polarimetry are held every two years. In 2009 the meeting took place in Ferrara, Italy, and was organized by the University of Ferrara and INFN. Sessions on Polarized Proton and Deuterium Sources, Polarized Electron Sources, Polarimetry, Polarized Solid Targets, and Polarized Internal Targets, highlighted topics, recent developments, and progress in the field. A session dedicated to Future Facilities provided an overview of a number of new activities in the spin-physics sector at facilities that are currently in the planning stage. Besides presenting a broad overview of polarized ion sources, electron sources, solid and gaseous targets, and their neighbouring fields, the workshop also addressed the application of polarized atoms in applied sciences and medicine that is becoming increasingly important.

Performance and blood monitoring in sports: the artificial intelligence evoking target testing in antidoping (AR.I.E.T.T.A.) project.

PubMed

Manfredini, A F; Malagoni, A M; Litmanen, H; Zhukovskaja, L; Jeannier, P; Dal Follo, D; Felisatti, M; Besseberg, A; Geistlinger, M; Bayer, P; Carrabre, J E

2011-03-01

Substances and methods used to increase oxygen blood transport and physical performance can be detected in the blood, but the screening of the athletes to be tested remains a critical issue for the International Federations. This project, AR.I.E.T.T.A., aimed to develop a software capable of analysing athletes' hematological and performance profiles to detect abnormal patterns. One-hundred eighty athletes belonging to the International Biathlon Union gave written informed consent to have their hematological data, previously collected according to anti-doping rules, used to develop the AR.I.E.T.T.A. software. Software was developed with the included sections: 1) log-in; 2) data-entry: where data are loaded, stored and grouped; 3) analysis: where data are analysed, validated scores are calculated, and parameters are simultaneously displayed as statistics, tables and graphs, and individual or subpopulation profiles; 4) screening: where an immediate evaluation of the risk score of the present sample and/or the athlete under study is obtained. The sample risk score or AR.I.E.T.T.A. score is calculated by a simple computational system combining different parameters (absolute values and intra-individual variations) considered concurrently. The AR.I.E.T.T.A. score is obtained by the sum of the deviation units derived from each parameter, considering the shift of the present value from the reference values, based on the number of standard deviations. AR.I.E.T.T.A. enables a quick evaluation of blood results assisting surveillance programs and perform timely target testing controls on athletes by the International Federations. Future studies aiming to validate the AR.I.E.T.T.A. score and improve the diagnostic accuracy will improve the system.

Defining the RNA Internal Loops Preferred by Benzimidazole Derivatives via Two-Dimensional Combinatorial Screening and Computational Analysis

PubMed Central

Velagapudi, Sai Pradeep; Seedhouse, Steven J.; French, Jonathan

2011-01-01

RNA is an important therapeutic target, however, RNA targets are generally underexploited due to a lack of understanding of the small molecules that bind RNA and the RNA motifs that bind small molecules. Herein, we describe the identification of the RNA internal loops derived from a 4096-member 3×3 nucleotide loop library that are the most specific and highest affinity binders to a series of four designer, drug-like benzimidazoles. These studies establish a potentially general protocol to define the highest affinity and most specific RNA motif targets for heterocyclic small molecules. Such information could be used to target functionally important RNAs in genomic sequence. PMID:21604752

Targets for production of the medical radioisotopes with alpha and proton or deuteron beams

NASA Astrophysics Data System (ADS)

Stolarz, Anna; Kowalska, J. A.; Jastrzebski, J.; Choiński, J.; Sitarz, M.; Szkliniarz, K.; Trzcińska, A.; Zipper, W.

2018-05-01

The research quantities of some medical radioisotopes were produced in reactions induced by 32 MeV internal alpha beam (211At, Sc isotopes), 16 MeV and 28 MeV proton beams (Sc isotopes) and 8 MeV deuteron beam (Sc isotopes). The frame-less targets used for irradiation with internal alpha beam were prepared from elemental (Bi for 211At) and compound (CaCO3 for Sc radioisotopes) materials. The CaCO3 powder targets were also used for production of Sc radioisotopes with proton or deuteron external beams. Methods developed for preparation of the targets suitable for the irradiating beam type are described in this work.

STS-104 Crew Training of Jim Reilly in EMU fit check

NASA Image and Video Library

2001-04-09

JSC2001-E-11692 (9 April 2001) --- Astronaut James F. Reilly, mission specialist, prepares to don his helmet for an Extravehicular Mobility Unit (EMU) fit check in one of the chambers in the Crew Systems Laboratory at the Johnson Space Center (JSC). The STS-104 mission to the International Space Station (ISS) represents the Space Shuttle Atlantis' first flight using a new engine and is targeted for a liftoff no earlier than June 14, 2001.

STS-104 Crew Training of Jim Reilly in EMU fit check

NASA Image and Video Library

2001-04-09

JSC2001-E-11699 (9 April 2001) --- Astronaut James F. Reilly, STS-104 mission specialist, participates in an Extravehicular Mobility Unit (EMU) fit check in one of the chambers in the Crew Systems Laboratory at the Johnson Space Center (JSC). The STS-104 mission to the International Space Station (ISS) represents the Space Shuttle Atlantis' first flight using a new engine and is targeted for a liftoff no earlier than June 14, 2001.

STS-104 Crew Training of Jim Reilly in EMU fit check

NASA Image and Video Library

2001-04-09

JSC2001-E-11702 (9 April 2001) --- Astronaut James F. Reilly, STS-104 mission specialist, participates in an Extravehicular Mobility Unit (EMU) fit check in one of the chambers in the Crew Systems Laboratory at the Johnson Space Center (JSC). The STS-104 mission to the International Space Station (ISS) represents the Space Shuttle Atlantis' first flight using a new engine and is targeted for a liftoff no earlier than June 14, 2001.

STS-104 Crew Training of Jim Reilly in EMU fit check

NASA Image and Video Library

2001-04-09

JSC2001-E-11696 (9 April 2001) --- Astronaut James F. Reilly, STS-104 mission specialist, participates in an Extravehicular Mobility Unit (EMU) fit check in one of the chambers in the Crew Systems Laboratory at the Johnson Space Center (JSC). The STS-104 mission to the International Space Station (ISS) represents the Space Shuttle Atlantis' first flight using a new engine and is targeted for a liftoff no earlier than June 14, 2001.

STS-104 Crew Training of Jim Reilly in EMU fit check

NASA Image and Video Library

2001-04-09

JSC2001-E-11697 (9 April 2001) --- Astronaut James F. Reilly, STS-104 mission specialist, participates in an Extravehicular Mobility Unit (EMU) fit check in one of the chambers in the Crew Systems Laboratory at the Johnson Space Center (JSC). The STS-104 mission to the International Space Station (ISS) represents the Space Shuttle Atlantis' first flight using a new engine and is targeted for a liftoff no earlier than June 14, 2001.

STS-104 Crew Training of Jim Reilly in EMU fit check

NASA Image and Video Library

2001-04-09

JSC2001-E-11698 (9 April 2001) --- Astronaut James F. Reilly, STS-104 mission specialist, participates in an Extravehicular Mobility Unit (EMU) fit check in one of the chambers in the Crew Systems Laboratory at the Johnson Space Center (JSC). The STS-104 mission to the International Space Station (ISS) represents the Space Shuttle Atlantis' first flight using a new engine and is targeted for a liftoff no earlier than June 14, 2001.

STS-104 Crew Training of Jim Reilly in EMU fit check

NASA Image and Video Library

2001-04-09

JSC2001-E-11703 (9 April 2001) --- Astronaut James F. Reilly, STS-104 mission specialist, participates in an Extravehicular Mobility Unit (EMU) fit check in one of the chambers in the Crew Systems Laboratory at the Johnson Space Center (JSC). The STS-104 mission to the International Space Station (ISS) represents the Space Shuttle Atlantis' first flight using a new engine and is targeted for a liftoff no earlier than June 14, 2001.

Education and the Asian Surge: A Comparison of the Education Systems in India and China

DTIC Science & Technology

2008-01-01

countries similar to those that other researchers have faced. For instance, Bardhan (2003) notes that fewer reliability checks and internal consistency tests...with a critical mass to take advantage of the software outsourcing boom 2 According to UNESCO, although the definition of literacy may vary from one...need to be targeted. For instance, too much emphasis on the study of information technology to take advantage of the current outsourcing trends could

KSC-2009-3207

NASA Image and Video Library

2009-05-18

CAPE CANAVERAL, Fla. – In the Operations and Checkout Building's high bay, technicians test how to put the "skins" on the outer mold of the simulator Orion crew module. Part of NASA's Constellation Program, the Orion spacecraft will return humans to the moon and prepare for future voyages to Mars and other destinations in our solar system. Orion is targeted to begin carrying humans to the International Space Station in 2015 and to the moon by 2020. Photo credit: NASA/Kim Shiflett

KSC-2009-3204

NASA Image and Video Library

2009-05-18

CAPE CANAVERAL, Fla. – In the Operations and Checkout Building's high bay, technicians begin testing how to put the "skins" on the outer mold of the simulator Orion crew module.Part of NASA's Constellation Program, the Orion spacecraft will return humans to the moon and prepare for future voyages to Mars and other destinations in our solar system. Orion is targeted to begin carrying humans to the International Space Station in 2015 and to the moon by 2020. Photo credit: NASA/Kim Shiflett

KSC-2009-3206

NASA Image and Video Library

2009-05-18

CAPE CANAVERAL, Fla. – In the Operations and Checkout Building's high bay, technicians pick up one of the "skins" to apply to the outer mold of the simulator Orion crew module. Part of NASA's Constellation Program, the Orion spacecraft will return humans to the moon and prepare for future voyages to Mars and other destinations in our solar system. Orion is targeted to begin carrying humans to the International Space Station in 2015 and to the moon by 2020. Photo credit: NASA/Kim Shiflett

KSC-2009-3208

NASA Image and Video Library

2009-05-18

CAPE CANAVERAL, Fla. – In the Operations and Checkout Building's high bay, technicians test how to put the "skins" on the outer mold of the simulator Orion crew module. Part of NASA's Constellation Program, the Orion spacecraft will return humans to the moon and prepare for future voyages to Mars and other destinations in our solar system. Orion is targeted to begin carrying humans to the International Space Station in 2015 and to the moon by 2020. Photo credit: NASA/Kim Shiflett

KSC-2013-3565

NASA Image and Video Library

2013-06-24

CAPE CANAVERAL, Fla. –Outredgeous red romaine lettuce plants grow inside the bellows of a prototype VEGGIE flight pillow. U.S. astronauts living and working aboard the International Space Station are going to receive a newly developed Vegetable Production System VEGGIE. VEGGIE is set to launch aboard SpaceX's Dragon capsule on NASA's third Commercial Resupply Services mission targeted to launch Dec. 9 from Space Launch Complex 40 at Cape Canaveral Air Force Station in Florida. Photo credit: NASA/Gioia Massa

KSC-2013-3562

NASA Image and Video Library

2011-06-29

CAPE CANAVERAL, Fla. – This prototype VEGGIE hardware was designed and built by Orbital Technologies Corp. of Madison, Wisc. U.S. astronauts living and working aboard the International Space Station are going to receive a newly developed Vegetable Production System VEGGIE. VEGGIE is set to launch aboard SpaceX's Dragon capsule on NASA's third Commercial Resupply Services mission targeted to launch Dec. 9 from Space Launch Complex 40 at Cape Canaveral Air Force Station in Florida. Photo credit: NASA/Gioia Massa

KSC-2013-3563

NASA Image and Video Library

2012-09-25

CAPE CANAVERAL, Fla. – A 28-day-old Outredgeous red romaine lettuce plant grows in a prototype VEGGIE flight pillow. U.S. astronauts living and working aboard the International Space Station are going to receive a newly developed Vegetable Production System VEGGIE. VEGGIE is set to launch aboard SpaceX's Dragon capsule on NASA's third Commercial Resupply Services mission targeted to launch Dec. 9 from Space Launch Complex 40 at Cape Canaveral Air Force Station in Florida. Photo credit: NASA/Gioia Massa

KSC-2013-3567

NASA Image and Video Library

2013-06-06

CAPE CANAVERAL, Fla. – Outredgeous red romaine lettuce plants grow inside the bellows of a prototype VEGGIE flight pillow. U.S. astronauts living and working aboard the International Space Station are going to receive a newly developed Vegetable Production System VEGGIE. VEGGIE is set to launch aboard SpaceX's Dragon capsule on NASA's third Commercial Resupply Services mission targeted to launch Dec. 9 from Space Launch Complex 40 at Cape Canaveral Air Force Station in Florida. Photo credit: NASA/Bryan Onate

Asteroids in the service of humanity

NASA Astrophysics Data System (ADS)

Crawford, Ian A.

2013-07-01

There are at least three compelling reasons for the human race to initiate a major programme to explore and better understand the 'minor planets' of the Solar System: (1) Enhancing scientific knowledge; (2) Mitigating the impact hazard; and (3) Utilizing extraterrestrial resources. Strong synergies exist between all three. Moreover, all these activities would benefit from greater international cooperation in space exploration by the World's space agencies, and the recognition that asteroids are important targets for human and robotic exploration.

KSC-07pd2680

NASA Image and Video Library

2007-10-05

KENNEDY SPACE CENTER, FLA. -- On Launch Pad 39A, workers are removing the rain gutters from space shuttle Discovery's payload bay. The gutters prevent leaks into the bay from rain while the shuttle is on the pad. Beneath is the orbital docking system. Mission STS-120 will bring the Harmony module that will provide attachment points for European and Japanese laboratory modules to the International Space Station. Launch of Discovery is targeted for Oct. 23. Photo credit: NASA/George Shelton

Conducting non-commercial international clinical trials: the ICR-CTSU experience.

PubMed

Fox, Lisa; Toms, Christy; Kernaghan, Sarah; Snowdon, Claire; Bliss, Judith M

2017-09-26

Academic clinical trials play a fundamental role in the development of new treatments, the repurposing of existing treatments and in addressing areas of unmet clinical need. With cancer treatments increasingly targeted at molecular subtypes, and with priority placed on developing new treatments for rare tumour types, the need for international trial participation to access sufficient patient numbers for successful trial conduct is growing. However, lack of harmonisation of international legal, ethical and financial systems can make this challenging and the cost and effort of conducting trials internationally can be considered prohibitive, particularly where the sample size is comparatively small. The Institute of Cancer Research - Clinical Trials and Statistics Unit (ICR-CTSU) is a UK-based academic clinical trials unit that specialises in the design, conduct and analysis of clinical trials of cancer treatments with an expanding portfolio of trials in molecular subtypes of breast and urological cancers and in other rare cancer types. Implementing appropriate mechanisms to enable international participation has therefore been imperative. In this article, we explain how we have approached the challenges involved and describe examples of successful international trial conduct, achieved through robust collaborations with academic and industry partners. Conducting academic trials internationally is challenging but can and should be achieved through appropriate governance mechanisms and strong collaborations.

The influence of reading expertise in mirror-letter perception: Evidence from beginning and expert readers

PubMed Central

Duñabeitia, Jon Andoni; Dimitropoulou, María; Estévez, Adelina; Carreiras, Manuel

2013-01-01

The visual word recognition system recruits neuronal systems originally developed for object perception which are characterized by orientation insensitivity to mirror reversals. It has been proposed that during reading acquisition beginning readers have to “unlearn” this natural tolerance to mirror reversals in order to efficiently discriminate letters and words. Therefore, it is supposed that this unlearning process takes place in a gradual way and that reading expertise modulates mirror-letter discrimination. However, to date no supporting evidence for this has been obtained. We present data from an eye-movement study that investigated the degree of sensitivity to mirror-letters in a group of beginning readers and a group of expert readers. Participants had to decide which of the two strings presented on a screen corresponded to an auditorily presented word. Visual displays always included the correct target word and one distractor word. Results showed that those distractors that were the same as the target word except for the mirror lateralization of two internal letters attracted participants’ attention more than distractors created by replacement of two internal letters. Interestingly, the time course of the effects was found to be different for the two groups, with beginning readers showing a greater tolerance (decreased sensitivity) to mirror-letters than expert readers. Implications of these findings are discussed within the framework of preceding evidence showing how reading expertise modulates letter identification. PMID:24273596

Sense of coherence, self-esteem, and health locus of control in subjects with type 1 diabetes mellitus with/without satisfactory metabolic control.

PubMed

Nuccitelli, C; Valentini, A; Caletti, M T; Caselli, C; Mazzella, N; Forlani, G; Marchesini, G

2018-03-01

Despite intensive training, a few individuals with Type 1 diabetes mellitus (T1DM) fail to reach the desired metabolic targets. To evaluate the association between disease-related emotional and cognitive aspects and metabolic control in subjects with T1DM. Health locus of control (HLOC), sense of coherence (SOC), and self-esteem were assessed in T1DM subjects using validated questionnaires. Sixty-seven consecutive subjects who did not attain the desired HbA1c target (mean HbA1c, 8.3% [67 mmol/mol]) were compared with 30 cases in satisfactory metabolic control (HbA1c levels <7%-53 mmol/mol). In the overall population, SOC was negatively associated with BMI and average HbA1c, as was the association of self-esteem with HbA1c. Subjects attaining the desired metabolic target were characterized by higher SOC scores, higher Internal HLOC and prevalent Internal vs. Powerful-others HLOC. Compared to subjects in good metabolic control, subjects with unsatisfactory control had lower scores of SOC, Internal HLOC and Self-esteem, with no difference in Powerful others, or Chance HLOC. In the same group, SOC in the upper tertile was significantly associated with self-esteem (OR 1.35; 95% CI 1.08-1.69) and PHLOC (OR 1.24; 95% CI 1.03-1.49), after adjustment for age, sex, educational level, and comorbidities. Patients who fail to reach a satisfactory metabolic control tend to rely on significant others, trusting in the physicians' skills or on the efficiency of the health-care system. Strategies aimed at increasing self-efficacy and SOC, based on personal ability, are eagerly awaited to help patients improve diabetes care.

Enhanced Anti-Tumoral Activity of Methotrexate-Human Serum Albumin Conjugated Nanoparticles by Targeting with Luteinizing Hormone-Releasing Hormone (LHRH) Peptide

PubMed Central

Taheri, Azade; Dinarvand, Rassoul; Atyabi, Fatemeh; Ahadi, Fatemeh; Nouri, Farank Salman; Ghahremani, Mohammad Hossein; Ostad, Seyed Nasser; Borougeni, Atefeh Taheri; Mansoori, Pooria

2011-01-01

Active targeting could increase the efficacy of anticancer drugs. Methotrexate-human serum albumin (MTX-HSA) conjugates, functionalized by luteinizing hormone-releasing hormone (LHRH) as targeting moieties, with the aim of specifically targeting the cancer cells, were prepared. Owing to the high expression of LHRH receptors in many cancer cells as compared to normal cells, LHRH was used as the targeting ligand in this study. LHRH was conjugated to MTX-HSA nanoparticles via a cross-linker. Three types of LHRH targeted nanoparticles with a mean particle size between 120–138 nm were prepared. The cytotoxicity of LHRH targeted and non-targeted nanoparticles were determined on the LHRH positive and negative cell lines. The internalization of the targeted and non-targeted nanoparticles in LHRH receptor positive and negative cells was investigated using flow cytometry analysis and fluorescence microscopy. The cytotoxicity of the LHRH targeted nanoparticles on the LHRH receptor positive cells were significantly more than non-targeted nanoparticles. LHRH targeted nanoparticles were also internalized by LHRH receptor positive cells significantly more than non-targeted nanoparticles. There were no significant differences between the uptake of targeted and non-targeted nanoparticles to the LHRH receptor negative cells. The active targeting procedure using LHRH targeted MTX-HSA nanoparticles could increase the anti-tumoral activity of MTX. PMID:21845098

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

Code of Federal Regulations, 2010 CFR

2010-04-01

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

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

Code of Federal Regulations, 2013 CFR

2013-04-01

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

KSC-2010-4545

NASA Image and Video Library

2010-09-01

CAPE CANAVERAL, Fla. -- Technicians in the Space Station Processing Facility at NASA's Kennedy Space Center in Florida, check the progress of the Payload Attach System, or PAS, as it is lifted up to the Alpha Magnetic Spectrometer, where it will be attached to the bottom of the AMS. The PAS provides a method of securely connecting the payload to the International Space Station. AMS, a state-of-the-art particle physics detector, is designed to operate as an external module on the International Space Station. It will use the unique environment of space to study the universe and its origin by searching for dark matter. AMS will fly to the station aboard space shuttle Endeavour's STS-134 mission targeted to launch Feb. 26, 2011. Photo credit: NASA/Jack Pfaller

KSC-2010-4546

NASA Image and Video Library

2010-09-01

CAPE CANAVERAL, Fla. -- In the Space Station Processing Facility at NASA's Kennedy Space Center in Florida, a technician monitors the progress of the Payload Attach System, or PAS, as it is lifted up to the Alpha Magnetic Spectrometer, or AMS, where it will be attached to the bottom of the AMS. The PAS provides a method of securely connecting the payload to the International Space Station. AMS, a state-of-the-art particle physics detector, is designed to operate as an external module on the International Space Station. It will use the unique environment of space to study the universe and its origin by searching for dark matter. AMS will fly to the station aboard space shuttle Endeavour's STS-134 mission targeted to launch Feb. 26, 2011. Photo credit: NASA/Jack Pfaller

KSC-2010-4544

NASA Image and Video Library

2010-09-01

CAPE CANAVERAL, Fla. -- Technicians in the Space Station Processing Facility at NASA's Kennedy Space Center in Florida, monitor the guide wires of the overhead crane as it lifts the Payload Attach System, or PAS, up to the Alpha Magnetic Spectrometer, or AMS, for installation. The PAS provides a method of securely connecting the payload to the International Space Station. AMS, a state-of-the-art particle physics detector, is designed to operate as an external module on the International Space Station. It will use the unique environment of space to study the universe and its origin by searching for dark matter. AMS will fly to the station aboard space shuttle Endeavour's STS-134 mission targeted to launch Feb. 26, 2011. Photo credit: NASA/Jack Pfaller

KSC-2010-4547

NASA Image and Video Library

2010-09-01

CAPE CANAVERAL, Fla. -- A technicians in the Space Station Processing Facility at NASA's Kennedy Space Center in Florida, check the progress of the Payload Attach System, or PAS, as it is lifted up to the Alpha Magnetic Spectrometer, or AMS, where it will be attached to the bottom of the AMS. The PAS provides a method of securely connecting the payload to the International Space Station. AMS, a state-of-the-art particle physics detector, is designed to operate as an external module on the International Space Station. It will use the unique environment of space to study the universe and its origin by searching for dark matter. AMS will fly to the station aboard space shuttle Endeavour's STS-134 mission targeted to launch Feb. 26, 2011. Photo credit: NASA/Jack Pfaller

DEAE-Dextran coated paclitaxel nanoparticles act as multifunctional nano system for intranuclear delivery to triple negative breast cancer through VEGF and NOTCH1 inhibition.

PubMed

Bakrania, Anita K; Variya, Bhavesh C; Rathod, Lalaji V; Patel, Snehal S

2018-01-01

Triple negative breast cancer revolution has identified a plethora of therapeutic targets making it apparent that a single target for its treatment could be rare hence creating an urge to develop robust technologies for combination drug therapy. Paclitaxel, hailed as the most significant advancement in chemotherapy faces several underpinnings due to its low solubility and permeability. Advancing research has demonstrated the role of interferons in cancer. DEAE-Dextran, an emerging molecule with evidence of interferon induction was utilized in the present study to develop a nanoformulation in conjugation with paclitaxel to target multiple therapeutic pathways, with diminution of paclitaxel adverse effects and develop a specific targeted nano system. Evidently, it was demonstrated that DEAE-Dextran coated nanoformulation portrays significant synergistic cytotoxicity in the various cell lines. Moreover, overcoming the activation of ROS by paclitaxel, the combination drug therapy more effectively inhibited ROS through β-interferon induction. The nanoformulation was further conjugated to FITC for internalization studies which subsequently indicated maximum cellular uptake at 60min post treatment demonstrated by green fluorescence from FITC lighting up the nuclear membrane. Precisely, the mechanistic approach of nuclear-targeted nanoformulation was evaluated by in vivo xenograft studies which showed a synergistic release of β-interferon at the target organ. Moreover, the combination nanoformulation inculcated multiple mechanistic approaches through VEGF and NOTCH1 inhibition along with dual β and γ-interferon overexpression. Overall, the combination therapy may be a promising multifunctional nanomaterial for intranuclear drug delivery in TNBC. Copyright © 2017 Elsevier B.V. All rights reserved.

Guidance Scheme for Modulation of Drag Devices to Enable Return from Low Earth Orbit

NASA Technical Reports Server (NTRS)

Dutta, Soumyo; Bowes, Angela L.; Cianciolo, Alicia D.; Glass, Christopher E.; Powell, Richard W.

2017-01-01

Passive drag devices provide opportunities to return payloads from low Earth orbits quickly without using onboard propulsive systems to de-orbit the spacecraft. However, one potential disadvantage of such systems has been the lack of landing accuracy. Drag modulation or changing the shape of the drag device during flight offer a way to control the de-orbit trajectory and target a specific landing location. This paper discusses a candidate passive drag based system, called Exo-brake, as well as efforts to model the dynamics of the vehicle as it de-orbits and guidance schemes used to control the trajectory. Such systems can enable quick return of payloads from low Earth orbit assets like the International Space Station without the use of large re-entry cargo capsules or propulsive systems.

Improved Lysosomal Trafficking Can Modulate the Potency of Antibody Drug Conjugates.

PubMed

DeVay, Rachel M; Delaria, Kathy; Zhu, Guoyun; Holz, Charles; Foletti, Davide; Sutton, Janette; Bolton, Gary; Dushin, Russell; Bee, Christine; Pons, Jaume; Rajpal, Arvind; Liang, Hong; Shelton, David; Liu, Shu-Hui; Strop, Pavel

2017-04-19

Antibody drug conjugates (ADCs) provide an efficacious and relatively safe means by which chemotherapeutic agents can be specifically targeted to cancer cells. In addition to the selection of antibody targets, ADCs offer a modular design that allows selection of ADC characteristics through the choice of linker chemistries, toxins, and conjugation sites. Many studies have indicated that release of toxins bound to antibodies via noncleavable linker chemistries relies on the internalization and intracellular trafficking of the ADC. While this can make noncleavable ADCs more stable in the serum, it can also result in lower efficacy when their respective targets are not internalized efficiently or are recycled back to the cell surface following internalization. Here, we show that a lysosomally targeted ADC against the protein APLP2 mediates cell killing, both in vitro and in vivo, more effectively than an ADC against Trop2, a protein with less efficient lysosomal targeting. We also engineered a bispecific ADC with one arm targeting HER2 for the purpose of directing the ADC to tumors, and the other arm targeting APLP2, whose purpose is to direct the ADC to lysosomes for toxin release. This proof-of-concept bispecific ADC demonstrates that this technology can be used to shift the intracellular trafficking of a constitutively recycled target by directing one arm of the antibody against a lysosomally delivered protein. Our data also show limitations of this approach and potential future directions for development.

Light-controlled endosomal escape of the novel CD133-targeting immunotoxin AC133-saporin by photochemical internalization - A minimally invasive cancer stem cell-targeting strategy.

PubMed

Bostad, Monica; Olsen, Cathrine Elisabeth; Peng, Qian; Berg, Kristian; Høgset, Anders; Selbo, Pål Kristian

2015-05-28

The cancer stem cell (CSC) marker CD133 is an attractive target to improve antitumor therapy. We have used photochemical internalization (PCI) for the endosomal escape of the novel CD133-targeting immunotoxin AC133-saporin (PCIAC133-saporin). PCI employs an endocytic vesicle-localizing photosensitizer, which generates reactive oxygen species upon light-activation causing a rupture of the vesicle membranes and endosomal escape of entrapped drugs. Here we show that AC133-saporin co-localizes with the PCI-photosensitizer TPCS2a, which upon light exposure induces cytosolic release of AC133-saporin. PCI of picomolar levels of AC133-saporin in colorectal adenocarcinoma WiDr cells blocked cell proliferation and induced 100% inhibition of cell viability and colony forming ability at the highest light doses, whereas no cytotoxicity was obtained in the absence of light. Efficient PCI-based CD133-targeting was in addition demonstrated in the stem-cell-like, triple negative breast cancer cell line MDA-MB-231 and in the aggressive malignant melanoma cell line FEMX-1, whereas no enhanced targeting was obtained in the CD133-negative breast cancer cell line MCF-7. PCIAC133-saporin induced mainly necrosis and a minimal apoptotic response based on assessing cleavage of caspase-3 and PARP, and the TUNEL assay. PCIAC133-saporin resulted in S phase arrest and reduced LC3-II conversion compared to control treatments. Notably, co-treatment with Bafilomycin A1 and PCIAC133-saporin blocked LC3-II conversion, indicating a termination of the autophagic flux in WiDr cells. For the first time, we demonstrate laser-controlled targeting of CD133 in vivo. After only one systemic injection of AC133-saporin and TPCS2a, a strong anti-tumor response was observed after PCIAC133-saporin. The present PCI-based endosomal escape technology represents a minimally invasive strategy for spatio-temporal, light-controlled targeting of CD133+ cells in localized primary tumors or metastasis. Copyright © 2015 Elsevier B.V. All rights reserved.

Educating international students about tuberculosis and infections associated with travel to visit friends and relatives (VFR-travel).

PubMed

Gibney, Katherine B; Brass, Amanda; Hume, Sam C; Leder, Karin

2014-01-01

International students in Victoria, Australia, originate from over 140 different countries. They are over-represented in disease notifications for tuberculosis and travel-associated infections, including enteric fever, hepatitis A, and malaria. We describe a public health initiative aimed to increase awareness of these illnesses among international students and their support staff. We identified key agencies including student support advisors, medical practitioners, health insurers, and government and professional organisations. We developed health education materials targeting international students regarding tuberculosis and travel-related infections to be disseminated via a number of different media, including electronic and printed materials. We sought informal feedback from personnel in all interested agencies regarding the materials developed, their willingness to deliver these materials to international students, and their preferred media for disseminating these materials. Education institutions with dedicated international student support staff and on-campus health clinics were more easily engaged to provide feedback and disseminate the health education materials than institutions without such dedicated personnel. Response to contacting off-campus medical practices was poor. Delivery of educational materials via electronic and social media was preferred over face-to-face education. It is feasible to provide health education messages targeting international students for dissemination via appropriately-staffed educational institutions. This initiative could be expanded in terms of age-group, geographic range, and health issues to be targeted. Copyright © 2013 Elsevier Ltd. All rights reserved.

ICANS-XIV. The fourteenth meeting of the international collaboration on advanced neutron sources.

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

Carpenter, J. M., ed.; Tobin, C. A., ed.

1999-02-10

The meeting began with a reception on Sunday evening. Monday's plenary sessions included status reports on the four operating spallation neutron sources, IPNS, ISIS, KENS, and the Lujan Center; on the INR source under construction at Troitsk; on the IBR-2 pulsed reactor at Dubna; and on proposals for five new installations. We also heard reports on spin-off activities: the ASTE tests (liquid mercury target tests at the AGS accelerator at Brookhaven), the ACoM activities (developments aimed to provide cold moderators suitable for high-power pulsed sources), and the International Workshop on Cold Moderators for Pulsed Neutron Sources, held in September 1997more » at Argonne. Jose Alonso and Bob Macek delivered enlightening invited talks overviewing linear accelerators and rings for spallation neutron sources. The rest of the meeting was devoted to targets and moderators and to instrumentation in a normal rotation of ICANS topics. There were altogether 84 oral reports and 23 poster presentations. On Tuesday and on Wednesday morning, we divided into separate series of sessions on Instrumentation and on Targets and Moderators. In the first, we had reports and discussions on instrumentation and techniques, on computer software, on instrument suites, and on new instruments and equipment. In the second series were sessions on liquid target systems, on solid target systems, on neutron production and target physics, on moderator physics and performance, and on target and moderator neutronics. The Tuesday evening meetings went on until 10:00, making for a 14-hour working day. That everyone willingly endured the long hours is a credit to the dedication of the attendees. On Wednesday afternoon, we boarded buses for the 1-hour trip to Argonne, where attendees toured IPNS and the Advanced Photon Source. Returning to Starved Rock, we enjoyed boat rides on the Illinois River and then a barbecue banquet dinner at the Lodge. All day Thursday and Friday morning, the attendees, in small working groups, discussed next-generation powder diffractometers, critical heat flux limitations on solid targets, monte carlo instrument simulation, prospects for high- and low-energy spectroscopy, small angle scattering and reflectometry, and the roles of solid and liquid targets in high-power pulsed spallation sources. Representatives of the laboratories participating in ICANS met Thursday evening to discuss the outcome of ICANS XIV and to decide whether, where, and when the next meeting would take place. They agreed to meet again in about 2 years in Japan. After the lunch break on Friday, the working group chairs presented the findings of their groups to the participants in a final plenary session, and the meeting adjourned with good feelings of accomplishment.« less