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Sample records for improving tumor-targeting capability

  1. A Tumor-Targeted Nanodelivery System to Improve Early MRI Detection of Cancer

    Directory of Open Access Journals (Sweden)

    Kathleen F. Pirollo

    2006-01-01

    Full Text Available The development of improvements in magnetic resonance imaging (MRI that would enhance sensitivity, leading to earlier detection of cancer and visualization of metastatic disease, is an area of intense exploration. We have devised a tumor-targeting, liposomal nanodelivery platform for use in gene medicine. This systemically administered nanocomplex has been shown to specifically and efficiently deliver both genes and oligonucleotides to primary and metastatic tumor cells, resulting in significant tumor growth inhibition and even tumor regression. Here we examine the effect on MRI of incorporating conventional MRI contrast agent Magnevist® into our anti-transferrin receptor single-chain antibody (TfRscFv liposomal complex. Both in vitro and in an in vivo orthotopic mouse model of pancreatic cancer, we show increased resolution and image intensity with the complexed Magnevist®. Using advanced microscopy techniques (scanning electron microscopy and scanning probe microscopy, we also established that the Magnevist® is in fact encapsulated by the liposome in the complex and that the complex still retains its nanodimensional size. These results demonstrate that this TfRscFv-liposome-Magnevist® nanocomplex has the potential to become a useful tool in early cancer detection.

  2. Improved tumor-targeting MRI contrast agents: Gd(DOTA) conjugates of a cycloalkane-based RGD peptide

    International Nuclear Information System (INIS)

    Park, Ji-Ae; Lee, Yong Jin; Ko, In Ok; Kim, Tae-Jeong; Chang, Yongmin; Lim, Sang Moo; Kim, Kyeong Min; Kim, Jung Young

    2014-01-01

    Highlights: • Development of improved tumor-targeting MRI contrast agents. • To increase the targeting ability of RGD, we developed cycloalkane-based RGD peptides. • Gd(DOTA) conjugates of cycloalkane-based RGD peptide show improved tumor signal enhancement in vivo MR images. - Abstract: Two new MRI contrast agents, Gd-DOTA-c(RGD-ACP-K) (1) and Gd-DOTA-c(RGD-ACH-K) (2), which were designed by incorporating aminocyclopentane (ACP)- or aminocyclohexane (ACH)-carboxylic acid into Gd-DOTA (gadolinium-tetraazacyclo dodecanetetraacetic acid) and cyclic RGDK peptides, were synthesized and evaluated for tumor-targeting ability in vitro and in vivo. Binding affinity studies showed that both 1 and 2 exhibited higher affinity for integrin receptors than cyclic RGDyK peptides, which were used as a reference. These complexes showed high relaxivity and good stability in human serum and have the potential to improve target-specific signal enhancement in vivo MR images

  3. Improved tumor-targeting MRI contrast agents: Gd(DOTA) conjugates of a cycloalkane-based RGD peptide

    Energy Technology Data Exchange (ETDEWEB)

    Park, Ji-Ae, E-mail: jpark@kirams.re.kr [Molecular Imaging Research Center, Korea Institute of Radiological and Medical Sciences, Seoul (Korea, Republic of); Lee, Yong Jin; Ko, In Ok [Molecular Imaging Research Center, Korea Institute of Radiological and Medical Sciences, Seoul (Korea, Republic of); Kim, Tae-Jeong; Chang, Yongmin [Institute of Biomedical Engineering, Kyungpook National University, Daegu (Korea, Republic of); Lim, Sang Moo [Department of Nuclear Medicine, Korea Institute of Radiological and Medical Sciences, Seoul (Korea, Republic of); Kim, Kyeong Min [Molecular Imaging Research Center, Korea Institute of Radiological and Medical Sciences, Seoul (Korea, Republic of); Kim, Jung Young, E-mail: jykim@kirams.re.kr [Molecular Imaging Research Center, Korea Institute of Radiological and Medical Sciences, Seoul (Korea, Republic of)

    2014-12-12

    Highlights: • Development of improved tumor-targeting MRI contrast agents. • To increase the targeting ability of RGD, we developed cycloalkane-based RGD peptides. • Gd(DOTA) conjugates of cycloalkane-based RGD peptide show improved tumor signal enhancement in vivo MR images. - Abstract: Two new MRI contrast agents, Gd-DOTA-c(RGD-ACP-K) (1) and Gd-DOTA-c(RGD-ACH-K) (2), which were designed by incorporating aminocyclopentane (ACP)- or aminocyclohexane (ACH)-carboxylic acid into Gd-DOTA (gadolinium-tetraazacyclo dodecanetetraacetic acid) and cyclic RGDK peptides, were synthesized and evaluated for tumor-targeting ability in vitro and in vivo. Binding affinity studies showed that both 1 and 2 exhibited higher affinity for integrin receptors than cyclic RGDyK peptides, which were used as a reference. These complexes showed high relaxivity and good stability in human serum and have the potential to improve target-specific signal enhancement in vivo MR images.

  4. Evaluation of cytotoxic and tumor targeting capability of (177)Lu-DOTATATE-nanoparticles: a trailblazing strategy in peptide receptor radionuclide therapy.

    Science.gov (United States)

    Arora, Geetanjali; Dubey, Priyanka; Shukla, Jaya; Ghosh, Sourabh; Bandopadhyaya, Gurupad

    2016-06-01

    We propose an innovative strategy of nanoparticle-mediated-peptide receptor radionuclide therapy (PRRT) employing PLGA-nanoparticles together with anti-β-hCG antibodies that can protect kidneys from radiation damage while simultaneously enhancing its tumor targeting and cytotoxic ability for somatostatin receptor (SSR) positive tumors. PEG-coated-(177)Lu-DOTATATE-PLGA-nanoparticles (PEG-LuD-NP) were formulated and characterized. In vitro toxicity of these particles was tested on human glioblastoma cell line U87MG over a radiation dose range of 19-78 Gy, using MTT assay and flow cytometry. To further enhance cytotoxicity and test the feasibility of active tumor targeting, apoptosis-inducing anti-β-hCG monoclonal antibodies were employed in vitro, after confirming expression of β-hCG on U87MG. In vivo tumor targeting ability of these particles, in comparison to uncoated particles and un-encapsulated (177)Lu-DOTATATE, was assessed by intravenous administration in tumor-induced wistar rats. Rats were first imaged in a gamma camera followed by euthanasia for organ extraction and counting in gamma counter. The particles were spherical in shape with mean diameter of 300 nm. Highest cytotoxicity that could be achieved with PEG-LuD-NP, on radio-resistant U87MG cells, was 35.8 % due to complex cellular response triggered by ionizing radiation. Interestingly, synergistic action of antibodies and PEG-LuD-NP doubled the cytotoxicity (80 %). PEG-LuD-NP showed the highest tumor uptake (4.3 ± 0.46 % ID/g) as compared to (177)Lu-DOTATATE (3.5 ± 0.31 %) and uncoated-(177)Lu-DOTATATE-nanoparticles (3.4 ± 0.35 %) in tumor-inoculated wistar rats (p targeting SSR positive tumors for enhanced cytoxicity and reduced renal radiation dose associated with conventional PRRT. To our knowledge of literature, this is the first study to establish in vitro and in vivo efficacy profile of nanoparticles in PRRT providing a stepping-stone for undergoing and future research

  5. An effective tumor-targeting strategy utilizing hypoxia-sensitive siRNA delivery system for improved anti-tumor outcome.

    Science.gov (United States)

    Kang, Lin; Fan, Bo; Sun, Ping; Huang, Wei; Jin, Mingji; Wang, Qiming; Gao, Zhonggao

    2016-10-15

    Hypoxia is a feature of most solid tumors, targeting hypoxia is considered as the best validated yet not extensively exploited strategy in cancer therapy. Here, we reported a novel tumor-targeting strategy using a hypoxia-sensitive siRNA delivery system. In the study, 2-nitroimidazole (NI), a hydrophobic component that can be converted to hydrophilic 2-aminoimidazole (AI) through bioreduction under hypoxic conditions, was conjugated to the alkylated polyethyleneimine (bPEI1.8k-C6) to form amphiphilic bPEI1.8k-C6-NI polycations. bPEI1.8k-C6-NI could self-assemble into micelle-like aggregations in aqueous, which contributed to the improved stability of the bPEI1.8k-C6-NI/siRNA polyplexes, resulted in increased cellular uptake. After being transported into the hypoxic tumor cells, the selective nitro-to-amino reduction would cause structural change and elicit a relatively loose structure to facilitate the siRNA dissociation in the cytoplasm, for enhanced gene silencing efficiency ultimately. Therefore, the conflict between the extracellular stability and the intracellular siRNA release ability of the polyplexes was solved by introducing the hypoxia-responsive unit. Consequently, the survivin-targeted siRNA loaded polyplexes shown remarkable anti-tumor effect not only in hypoxic cells, but also in tumor spheroids and tumor-bearing mice, indicating that the hypoxia-sensitive siRNA delivery system had great potential for tumor-targeted therapy. Hypoxia is one of the most remarkable features of most solid tumors, and targeting hypoxia is considered as the best validated strategy in cancer therapy. However, in the past decades, there were few reports about using this strategy in the drug delivery system, especially in siRNA delivery system. Therefore, we constructed a hypoxia-sensitive siRNA delivery system utilizing a hypoxia-responsive unit, 2-nitroimidazole, by which the unavoidable conflict between improved extracellular stability and promoted intracellular si

  6. Improved tumor targeting of anti-HER2 nanobody through N-succinimidyl 4-guanidinomethyl-3-iodobenzoate radiolabeling.

    Science.gov (United States)

    Pruszynski, Marek; Koumarianou, Eftychia; Vaidyanathan, Ganesan; Revets, Hilde; Devoogdt, Nick; Lahoutte, Tony; Lyerly, H Kim; Zalutsky, Michael R

    2014-04-01

    Nanobodies are approximately 15-kDa proteins based on the smallest functional fragments of naturally occurring heavy chain-only antibodies and represent an attractive platform for the development of molecularly targeted agents for cancer diagnosis and therapy. Because the human epidermal growth factor receptor type 2 (HER2) is overexpressed in breast and ovarian carcinoma, as well as in other malignancies, HER2-specific Nanobodies may be valuable radiodiagnostics and therapeutics for these diseases. The aim of the present study was to evaluate the tumor-targeting potential of anti-HER2 5F7GGC Nanobody after radioiodination with the residualizing agent N-succinimidyl 4-guanidinomethyl 3-(125/131)I-iodobenzoate (*I-SGMIB). The 5F7GGC Nanobody was radiolabeled using *I-SGMIB and, for comparison, with N(ε)-(3-*I-iodobenzoyl)-Lys(5)-N(α)-maleimido-Gly(1)-GEEEK (*I-IB-Mal-d-GEEEK), another residualizing agent, and by direct radioiodination using IODO-GEN ((125)I-Nanobody). The 3 labeled Nanobodies were evaluated in affinity measurements, and paired-label internalization assays were performed on HER2-expressing BT474M1 breast carcinoma cells and in paired-label tissue distribution measurements in mice bearing subcutaneous BT474M1 xenografts. *I-SGMIB-Nanobody was produced in 50.4% ± 3.6% radiochemical yield and exhibited a dissociation constant of 1.5 ± 0.5 nM. Internalization assays demonstrated that intracellular retention of radioactivity was up to 1.5-fold higher for *I-SGMIB-Nanobody than for coincubated (125)I-Nanobody or *I-IB-Mal-d-GEEEK-Nanobody. Peak tumor uptake for *I-SGMIB-Nanobody was 24.50% ± 9.89% injected dose/g at 2 h, 2- to 4-fold higher than observed with other labeling methods, and was reduced by 90% with trastuzumab blocking, confirming the HER2 specificity of localization. Moreover, normal-organ clearance was fastest for *I-SGMIB-Nanobody, such that tumor-to-normal-organ ratios greater than 50:1 were reached by 24 h in all tissues except lungs

  7. Improved decision making for prioritizing tumor targeting antibodies in human xenografts: Utility of fluorescence imaging to verify tumor target expression, antibody binding and optimization of dosage and application schedule.

    Science.gov (United States)

    Dobosz, Michael; Haupt, Ute; Scheuer, Werner

    2017-01-01

    Preclinical efficacy studies of antibodies targeting a tumor-associated antigen are only justified when the expression of the relevant antigen has been demonstrated. Conventionally, antigen expression level is examined by immunohistochemistry of formalin-fixed paraffin-embedded tumor tissue section. This method represents the diagnostic "gold standard" for tumor target evaluation, but is affected by a number of factors, such as epitope masking and insufficient antigen retrieval. As a consequence, variances and discrepancies in histological staining results can occur, which may influence decision-making and therapeutic outcome. To overcome these problems, we have used different fluorescence-labeled therapeutic antibodies targeting human epidermal growth factor receptor (HER) family members and insulin-like growth factor-1 receptor (IGF1R) in combination with fluorescence imaging modalities to determine tumor antigen expression, drug-target interaction, and biodistribution and tumor saturation kinetics in non-small cell lung cancer xenografts. For this, whole-body fluorescence intensities of labeled antibodies, applied as a single compound or antibody mixture, were measured in Calu-1 and Calu-3 tumor-bearing mice, then ex vivo multispectral tumor tissue analysis at microscopic resolution was performed. With the aid of this simple and fast imaging method, we were able to analyze the tumor cell receptor status of HER1-3 and IGF1R, monitor the antibody-target interaction and evaluate the receptor binding sites of anti-HER2-targeting antibodies. Based on this, the most suitable tumor model, best therapeutic antibody, and optimal treatment dosage and application schedule was selected. Predictions drawn from obtained imaging data were in excellent concordance with outcome of conducted preclinical efficacy studies. Our results clearly demonstrate the great potential of combined in vivo and ex vivo fluorescence imaging for the preclinical development and characterization of

  8. Tumor targeting using {sup 67}Ga-DOTA-Bz-folate - investigations of methods to improve the tissue distribution of radiofolates

    Energy Technology Data Exchange (ETDEWEB)

    Mueller, Cristina, E-mail: cristina.mueller@psi.ch [Center for Radiopharmaceutical Sciences ETH-PSI-USZ, Paul Scherrer Institute, 5232 Villigen-PSI (Switzerland); Vlahov, Iontcho R.; Santhapuram, Hari Krishna R.; Leamon, Christopher P. [Endocyte Inc., West Lafayette, IN 47906 (United States); Schibli, Roger [Center for Radiopharmaceutical Sciences ETH-PSI-USZ, Paul Scherrer Institute, 5232 Villigen-PSI (Switzerland); Department of Chemistry and Applied Biosciences, ETH Zurich, 8093 Zurich (Switzerland)

    2011-07-15

    Introduction: Use of folic acid radioconjugates for folate receptor (FR) targeting is a promising strategy for imaging purposes as well as for potential therapy of cancer and inflammatory diseases due to the frequent FR overexpression found on cancer cells and activated macrophages. Herein, we report on preclinical results using a novel DOTA-Bz-EDA-folate conjugate radiolabeled with [{sup 67}Ga]-gallium. Methods: DOTA-Bz-EDA-folate was prepared by conjugation of ethylenediamine-({gamma})-folate with 2-(p-isothiocyanobenzyl)-DOTA. Radiolabeling was carried out with {sup 67}GaCl{sub 3} according to standard procedures. Biodistribution studies of the tracer were performed in mice bearing FR-positive KB tumor xenografts. The effects on radiofolate biodistribution with coadministered renal uptake-blocking amino acids, diuretic agents, antifolates as well as different routes of administration were likewise investigated. Supportive imaging studies were performed using a small-animal single photon emission computed tomography (SPECT)/CT scanner. Results: {sup 67}Ga-DOTA-Bz-EDA-folate showed a high and specific accumulation in tumors (6.30%{+-}0.75% ID/g, 1 h pi and 6.08%{+-}0.89% ID/g, 4 h pi). Nonspecific radioactivity uptake in nontargeted tissues was negligible, but significant accumulation was found in FR-positive kidneys, which resulted in unfavorably low tumor-to-kidney ratios (<0.1). Coadministered amino acids or diuretics did not effectively reduce renal accumulation; in contrast, predosed pemetrexed did significantly reduce kidney uptake (<29% of control values). The SPECT/CT studies confirmed the excellent tumor-to-background contrast of {sup 67}Ga-radiofolate and the favorable reduction in kidney uptake (with improved imaging quality) resulting from pemetrexed administration. Conclusion: Conventional methods to reduce kidney uptake of radiofolates fail. However, the novel {sup 67}Ga-radiolabeled DOTA-Bz-EDA-folate can effectively be used to image FR

  9. Long-circulating and passively tumor-targeted polymer-drug conjugates improve the efficacy and reduce the toxicity of radiochemotherapy

    Czech Academy of Sciences Publication Activity Database

    Lammers, T.; Šubr, Vladimír; Ulbrich, Karel; Peschke, P.; Huber, P. E.; Hennink, W. E.; Storm, G.; Kiessling, F.

    2010-01-01

    Roč. 12, č. 9 (2010), B413-B421 ISSN 1438-1656 R&D Projects: GA MŠk 1M0505 Institutional research plan: CEZ:AV0Z40500505 Keywords : HPMA copolymers * targeting * tumor targeting Subject RIV: EI - Biotechnology ; Bionics Impact factor: 1.746, year: 2010

  10. OPSAID improvements and capabilities report.

    Energy Technology Data Exchange (ETDEWEB)

    Halbgewachs, Ronald D.; Chavez, Adrian R.

    2011-08-01

    Process Control System (PCS) and Industrial Control System (ICS) security is critical to our national security. But there are a number of technological, economic, and educational impediments to PCS owners implementing effective security on their systems. Sandia National Laboratories has performed the research and development of the OPSAID (Open PCS Security Architecture for Interoperable Design), a project sponsored by the US Department of Energy Office of Electricity Delivery and Energy Reliability (DOE/OE), to address this issue. OPSAID is an open-source architecture for PCS/ICS security that provides a design basis for vendors to build add-on security devices for legacy systems, while providing a path forward for the development of inherently-secure PCS elements in the future. Using standardized hardware, a proof-of-concept prototype system was also developed. This report describes the improvements and capabilities that have been added to OPSAID since an initial report was released. Testing and validation of this architecture has been conducted in another project, Lemnos Interoperable Security Project, sponsored by DOE/OE and managed by the National Energy Technology Laboratory (NETL).

  11. Tumor-targeting peptides from combinatorial libraries*

    Science.gov (United States)

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

    2018-01-01

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

  12. Carbohydrate plasma expanders for passive tumor targeting

    DEFF Research Database (Denmark)

    Hoffmann, Stefan; Caysa, Henrike; Kuntsche, Judith

    2013-01-01

    The objective of this study was to investigate the suitability of carbohydrate plasma volume expanders as a novel polymer platform for tumor targeting. Many synthetic polymers have already been synthesized for targeted tumor therapy, but potential advantages of these carbohydrates include inexpen...... was characterized in human colon carcinoma xenograft bearing nude mice. A tumor specific accumulation of HES 450 was observed, which proves it’s potential as carrier for passive tumor targeting....

  13. Improved DFIG Capability during Asymmetrical Grid Faults

    DEFF Research Database (Denmark)

    Zhou, Dao; Blaabjerg, Frede

    2015-01-01

    In the wind power application, different asymmetrical types of the grid fault can be categorized after the Y/d transformer, and the positive and negative components of a single-phase fault, phase-to-phase fault, and two-phase fault can be summarized. Due to the newly introduced negative and even...... the natural component of the Doubly-Fed Induction Generator (DFIG) stator flux during the fault period, their effects on the rotor voltage can be investigated. It is concluded that the phase-to-phase fault has the worst scenario due to its highest introduction of the negative stator flux. Afterwards......, the capability of a 2 MW DFIG to ride through asymmetrical grid faults can be estimated at the existing design of the power electronics converter. Finally, a control scheme aimed to improve the DFIG capability is proposed and the simulation results validate its feasibility....

  14. Brain tumor-targeted drug delivery strategies

    Directory of Open Access Journals (Sweden)

    Xiaoli Wei

    2014-06-01

    Full Text Available Despite the application of aggressive surgery, radiotherapy and chemotherapy in clinics, brain tumors are still a difficult health challenge due to their fast development and poor prognosis. Brain tumor-targeted drug delivery systems, which increase drug accumulation in the tumor region and reduce toxicity in normal brain and peripheral tissue, are a promising new approach to brain tumor treatments. Since brain tumors exhibit many distinctive characteristics relative to tumors growing in peripheral tissues, potential targets based on continuously changing vascular characteristics and the microenvironment can be utilized to facilitate effective brain tumor-targeted drug delivery. In this review, we briefly describe the physiological characteristics of brain tumors, including blood–brain/brain tumor barriers, the tumor microenvironment, and tumor stem cells. We also review targeted delivery strategies and introduce a systematic targeted drug delivery strategy to overcome the challenges.

  15. High efficiency diffusion molecular retention tumor targeting.

    Directory of Open Access Journals (Sweden)

    Yanyan Guo

    Full Text Available Here we introduce diffusion molecular retention (DMR tumor targeting, a technique that employs PEG-fluorochrome shielded probes that, after a peritumoral (PT injection, undergo slow vascular uptake and extensive interstitial diffusion, with tumor retention only through integrin molecular recognition. To demonstrate DMR, RGD (integrin binding and RAD (control probes were synthesized bearing DOTA (for (111 In(3+, a NIR fluorochrome, and 5 kDa PEG that endows probes with a protein-like volume of 25 kDa and decreases non-specific interactions. With a GFP-BT-20 breast carcinoma model, tumor targeting by the DMR or i.v. methods was assessed by surface fluorescence, biodistribution of [(111In] RGD and [(111In] RAD probes, and whole animal SPECT. After a PT injection, both probes rapidly diffused through the normal and tumor interstitium, with retention of the RGD probe due to integrin interactions. With PT injection and the [(111In] RGD probe, SPECT indicated a highly tumor specific uptake at 24 h post injection, with 352%ID/g tumor obtained by DMR (vs 4.14%ID/g by i.v.. The high efficiency molecular targeting of DMR employed low probe doses (e.g. 25 ng as RGD peptide, which minimizes toxicity risks and facilitates clinical translation. DMR applications include the delivery of fluorochromes for intraoperative tumor margin delineation, the delivery of radioisotopes (e.g. toxic, short range alpha emitters for radiotherapy, or the delivery of photosensitizers to tumors accessible to light.

  16. Improving the Agency's Software Acquisition Capability

    Science.gov (United States)

    Hankinson, Allen

    2003-01-01

    External development of software has oftc n led to unsatisfactory results and great frustration for the assurE 7ce community. Contracts frequently omit critical assuranc 4 processes or the right to oversee software development activitie: At a time when NASA depends more and more on software to in plement critical system functions, combination of three factors ex; cerbate this problem: I ) the ever-increasing trend to acquire rather than develop software in-house, 2) the trend toward performance based contracts, and 3) acquisition vehicles that only state softwar 2 requirements while leaving development standards and assur! ince methodologies up to the contractor. We propose to identify specific methods at d tools that NASA projects can use to mitigate the adverse el ects of the three problems. TWO broad classes of methoddt ols will be explored. The first will be those that provide NASA p ojects with insight and oversight into contractors' activities. The st cond will be those that help projects objectively assess, and thus i nprwe, their software acquisition capability. Of particular interest is the Software Engineering Institute's (SEI) Software Acqt isition Capability Maturity Model (SA-CMMO).

  17. Tumor targeting using liposomal antineoplastic drugs

    Directory of Open Access Journals (Sweden)

    Jörg Huwyler

    2008-03-01

    Full Text Available Jörg Huwyler1, Jürgen Drewe2, Stephan Krähenbühl21University of Applied Sciences Northwestern Switzerland, Institute of Pharma Technology, Muttenz, Switzerland; 2Department of Research and Division of Clinical Pharmacology, University Hospital Basel, Basel, SwitzerlandAbstract: During the last years, liposomes (microparticulate phospholipid vesicles have beenused with growing success as pharmaceutical carriers for antineoplastic drugs. Fields of application include lipid-based formulations to enhance the solubility of poorly soluble antitumordrugs, the use of pegylated liposomes for passive targeting of solid tumors as well as vector-conjugated liposomal carriers for active targeting of tumor tissue. Such formulation and drug targeting strategies enhance the effectiveness of anticancer chemotherapy and reduce at the same time the risk of toxic side-effects. The present article reviews the principles of different liposomal technologies and discusses current trends in this field of research.Keywords: tumor targeting, antineoplastic drugs, liposomes, pegylation, steric stabilization, immunoliposomes

  18. Polyethylene Glycol Modified, Cross-Linked Starch Coated Iron Oxide Nanoparticles for Enhanced Magnetic Tumor Targeting

    Science.gov (United States)

    Cole, Adam J.; David, Allan E.; Wang, Jianxin; Galbán, Craig J.; Hill, Hannah L.; Yang, Victor C.

    2010-01-01

    While successful magnetic tumor targeting of iron oxide nanoparticles has been achieved in a number of models, the rapid blood clearance of magnetically suitable particles by the reticuloendothelial system (RES) limits their availability for targeting. This work aimed to develop a long-circulating magnetic iron oxide nanoparticle (MNP) platform capable of sustained tumor exposure via the circulation and, thus, enhanced magnetic tumor targeting. Aminated, cross-linked starch (DN) and aminosilane (A) coated MNPs were successfully modified with 5 kDa (A5, D5) or 20 kDa (A20, D20) polyethylene glycol (PEG) chains using simple N-Hydroxysuccinimide (NHS) chemistry and characterized. Identical PEG-weight analogues between platforms (A5 & D5, A20 & D20) were similar in size (140–190 nm) and relative PEG labeling (1.5% of surface amines – A5/D5, 0.4% – A20/D20), with all PEG-MNPs possessing magnetization properties suitable for magnetic targeting. Candidate PEG-MNPs were studied in RES simulations in vitro to predict long-circulating character. D5 and D20 performed best showing sustained size stability in cell culture medium at 37°C and 7 (D20) to 10 (D5) fold less uptake in RAW264.7 macrophages when compared to previously targeted, unmodified starch MNPs (D). Observations in vitro were validated in vivo, with D5 (7.29 hr) and D20 (11.75 hr) showing much longer half-lives than D (0.12 hr). Improved plasma stability enhanced tumor MNP exposure 100 (D5) to 150 (D20) fold as measured by plasma AUC0-∞ Sustained tumor exposure over 24 hours was visually confirmed in a 9L-glioma rat model (12 mg Fe/kg) using magnetic resonance imaging (MRI). Findings indicate that both D5 and D20 are promising MNP platforms for enhanced magnetic tumor targeting, warranting further study in tumor models. PMID:21176955

  19. Work system innovation: Designing improvement methods for generative capability

    DEFF Research Database (Denmark)

    Hansen, David; Møller, Niels

    2013-01-01

    This paper explores how a work system’s capability for improvement is influenced by its improvement methods. Based on explorative case study at a Lean manufacturing facility, the methods problem solving and Appreciative Inquiry were compared through in-depth qualitative studies over a 12-month...

  20. Positron imaging system with improved count rate and tomographic capability

    International Nuclear Information System (INIS)

    1979-01-01

    A system with improved count rate capability for detecting the radioactive distribution of positron events within an organ of interest in a living subject is described. Objects of the invention include improving the scintillation crystal and pulse processing electronics, avoiding the limitations of collimators and provide an Arger camera positron imaging system that avoids the use of collimators. (U.K.)

  1. Positron imaging system with improved count rate and tomographic capability

    International Nuclear Information System (INIS)

    Muehllehner, G.; Buchin, M.P.

    1980-01-01

    Improvements to a positron camera imaging system are described. A pair of Angear-type scintillation cameras serve as the detectors, each camera being positioned on opposite sides of the organ of interest. Pulse shaping circuits reduce the pulse duration below 900 nanoseconds and the integration time below 500 noneseconds, improving the count rate capability and the counting statistics of the system and thus the image quality and processing speed. The invention also provides means for rotating the opposed camera heads about an axis which passes through the organ of interest. The cameras do not use collimators, and are capable of accepting radiation travelling in planes not perpendicular to the scintillation crystals. (LL)

  2. Annunciation - building product team capabilities to support utility operational improvement

    International Nuclear Information System (INIS)

    Doucet, R.; Brown, R.; Trask, D.; Leger, R.; Mitchel, G.; Judd, R.; Davey, E.

    2003-01-01

    The purpose of this paper is to describe an AECL initiative to enhance the capabilities to assist utilities with undertaking annunciation improvement. This initiative was undertaken to complement a recent annunciation product upgrade, and in anticipation of developing commercial opportunities to assist Canadian and foreign utilities with control room annunciation improvement. Utilities are relying more and more on external engineering product and service providers to meet their plant support needs as they reduce in-house staffing to lower ongoing support costs. This evolving commercial environment places new demands on product and service providers, and provides new opportunities for increasing the proportion of product and service provider participation in plant improvement projects. This paper outlines recent AECL experience in the annunciation product area. The paper discusses the rationale for product support capability improvement, discusses the approaches undertaken, describes lessons learned, and outlines a proposed utility support model for assisting with future annunciation improvements. (author)

  3. Process capability improvement through DMAIC for aluminum alloy wheel machining

    Science.gov (United States)

    Sharma, G. V. S. S.; Rao, P. Srinivasa; Babu, B. Surendra

    2017-07-01

    This paper first enlists the generic problems of alloy wheel machining and subsequently details on the process improvement of the identified critical-to-quality machining characteristic of A356 aluminum alloy wheel machining process. The causal factors are traced using the Ishikawa diagram and prioritization of corrective actions is done through process failure modes and effects analysis. Process monitoring charts are employed for improving the process capability index of the process, at the industrial benchmark of four sigma level, which is equal to the value of 1.33. The procedure adopted for improving the process capability levels is the define-measure-analyze-improve-control (DMAIC) approach. By following the DMAIC approach, the C p, C pk and C pm showed signs of improvement from an initial value of 0.66, -0.24 and 0.27, to a final value of 4.19, 3.24 and 1.41, respectively.

  4. Advancing theranostics with tumor-targeting peptides for precision otolaryngology

    Directory of Open Access Journals (Sweden)

    Chadwick L. Wright

    2016-06-01

    Full Text Available Worldwide, about 600,000 head and neck squamous cell carcinoma (HNSCC are detected annually, many of which involve high risk human papilloma virus (HPV. Surgery is the primary and desired first treatment option. Following surgery, the existence of cancer cells at the surgical margin is strongly associated with eventual recurrence of cancer and a poor outcome. Despite improved surgical methods (robotics, microsurgery, endoscopic/laparoscopic, and external imaging, surgeons rely only on their vision and touch to locate tumors during surgery. Diagnostic imaging systems like computed tomography (CT, magnetic resonance imaging (MRI, single-photon emission computed tomography (SPECT and positron-emission tomography (PET are too large, slow and costly to use efficiently during most surgeries and, ultrasound imaging, while fast and portable, is not cancer specific. This purpose of this article is to review the fundamental technologies that will radically advance Precision Otolaryngology practices to the benefit of patients with HNSCC. In particular, this article will address the potential for tumor-targeting peptides to enable more precise diagnostic imaging while simultaneously advancing new therapeutic paradigms for next generation image-guided surgery, tumor-specific chemotherapeutic delivery and tumor-selective targeted radiotherapy (i.e., theranostic. Keywords: Squamous cell carcinoma, Peptide, Optical surgical navigation, Diagnostic imaging, Theranostic

  5. Tumor-targeted nanomedicines for cancer theranostics

    Science.gov (United States)

    Lammers, Twan; Shi, Yang

    2017-01-01

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

  6. Improving global laboratory capabilities for emergency radionuclide bioassay

    International Nuclear Information System (INIS)

    Li, C.; Jourdain, J.; Kramer, G. H.

    2012-01-01

    During a radiological or nuclear emergency, first-responders and the general public may be internally contaminated with the radionuclide(s) involved. A timely radionuclide bioassay provides important information about contamination, for subsequent dose assessment and medical management. Both technical and operational gaps are discussed in this paper. As many people may need to be assessed in a short period of time, any single laboratory may find its capabilities insufficient. Laboratories from other regions or other countries may be called upon for assistance. This paper proposes a road-map to improve global capabilities in emergency radionuclide bioassay, suggesting a phased approach for establishing a global laboratory network. Existing international collaboration platforms could provide the base on which to build such a network. (authors)

  7. IMPROVE MACHINING PROCESS CAPABILITY BY USING SIX-SIGMA

    Directory of Open Access Journals (Sweden)

    Sanjit Ray

    2011-06-01

    Full Text Available Abstract: Six-Sigma is an improvement strategy for achieving customer satisfaction by reducing variation and thus producing products and services better, faster and cheaper. This study presents a Six-Sigma project of an automotive plant illustrating how the DMAIC methodology and statistical techniques were applied to resolve the issue of manufacturing process capability. This project has substantially benefit ted the organization by reducing the variation of bore size of crank case, achieving zero rejection and improving the on time delivery. By using appropriate qualitative and quantitative tools in different phases of the DMAIC methodology, the critical output, key process inputs and root causes were identified, analyzed and validated. This project methodology can be used in general to reduce process variation for any other manufacturing processes as well, which will help in improving customer satisfaction.

  8. Improving Effectiveness of Capabilities in EU Conflict Prevention

    DEFF Research Database (Denmark)

    Rodt, Annemarie Peen

    – severely challenging the Union’s current capabilities as an international security provider. The urgency of improving conflict preventive and crisis management measures is particularly pertinent in Africa, where the numbers affected by conflicts across the continent are staggering. This contribution sets...... out to answer whether – and if so how – EU responses to African conflicts have made a meaningful contribution to preventing (further) conflict. The Union’s efforts in Libya, South Sudan, Democratic Republic of Congo and Central African Republic are critically examined in a comparative case study...

  9. Mask manufacturing improvement through capability definition and bottleneck line management

    Science.gov (United States)

    Strott, Al

    1994-02-01

    In 1989, Intel's internal mask operation limited itself to research and development activities and re-inspection and pellicle application of externally manufactured masks. Recognizing the rising capital cost of mask manufacturing at the leading edge, Intel's Mask Operation management decided to offset some of these costs by manufacturing more masks internally. This was the beginning of the challenge they set to manufacture at least 50% of Intel's mask volume internally, at world class performance levels. The first step in responding to this challenge was the completion of a comprehensive operation capability analysis. A series of bottleneck improvements by focus teams resulted in an average cycle time improvement to less than five days on all product and less than two days on critical products.

  10. Improvements in TREAT hodoscope fuel-motion capabilities

    International Nuclear Information System (INIS)

    Fink, C.L.; Boyar, R.E.; Eichholz, J.J.; DeVolpi, A.

    1982-01-01

    The fast-neutron detection system of the hadoscope has been a major ingredient in the success of the hodoscope as a fuel-motion monitoring device. While the original Hornyak-button detector system has met most of the current fuel-motion needs, the more stringent requirements of improved reactor-safety codes, and of new experimental test facilities necessitate improved detection capabilities. Development efforts have centered on three areas: the construction of an array of proton-recoil proportional counters to be used in conjunction with the Hornyak-button detectors, the upgrading of the Hornyak-button detectors to increase linearity and signal-to-background ratio, and the intercalibration of detectors using a modified horizontal and a new vertical scan system

  11. Enhanced anticancer efficacy of paclitaxel through multistage tumor-targeting liposomes modified with RGD and KLA peptides

    Directory of Open Access Journals (Sweden)

    Sun J

    2017-02-01

    Full Text Available Jiawei Sun,1 Lei Jiang,2 Yi Lin,3 Ethan Michael Gerhard,4 Xuehua Jiang,1 Li Li,3 Jian Yang,4 Zhongwei Gu3 1West China School of Pharmacy, Sichuan University, Chengdu, Sichuan, 2Department of Pharmaceutics, China Pharmaceutical University, Nanjing, Jiangsu, 3National Engineering Research Center for Biomaterials, Sichuan University, Chengdu, Sichuan, People’s Republic of China; 4Department of Biomedical Engineering Materials Research Institute, The Huck Institutes of The Life Sciences, The Pennsylvania State University, University Park, PA, USA Abstract: Mitochondria serve as both “energy factories” and “suicide weapon stores” of cells. Targeted delivery of cytotoxic drugs to the mitochondria of tumor cells and tumor vascular cells is a promising strategy to improve the efficacy of chemotherapy. Here, multistage tumor-targeting liposomes containing two targeted peptide-modified lipids, cRGD-PEG2000-DSPE and KLA-PEG2000-DSPE, were developed for encapsulation of the anticancer drug paclitaxel (PTX, RGD-KLA/PTX-Lips. Compared with Taxol (free PTX, RGD/PTX-Lips and KLA/PTX-Lips, the half-maximal inhibitory concentration (IC50 value of RGD-KLA/PTX-Lips in vitro was 1.9-, 36.7- and 22.7-fold lower with 4T1 cells, respectively, because of higher levels of cellular uptake. Similar results were also observed with human umbilical vascular endothelial cells (HUVECs. An apoptosis assay showed that the total apoptotic ratio of RGD-KLA/PTX-Lips was the highest because of the mitochondria-targeted drug delivery and the activation of mitochondrial apoptosis pathways, as evidenced by visible mitochondrial localization, decreased mitochondrial membrane potential, release of cytochrome c and increased activities of caspase-9 and caspase-3. The strongest tumor growth inhibition (TGI; 80.6% and antiangiogenesis effects without systemic toxicity were also observed in RGD-KLA/PTX-Lip-treated 4T1 tumor xenograft BALB/c mice. In conclusion, these multistage

  12. Novel tumor-targeting, self-assembling peptide nanofiber as a carrier for effective curcumin delivery

    Directory of Open Access Journals (Sweden)

    Liu J

    2013-12-01

    Full Text Available Jianfeng Liu, Jinjian Liu, Hongyan Xu, Yumin Zhang, Liping Chu, Qingfen Liu, Naling Song, Cuihong YangTianjin Key Laboratory of Molecular Nuclear Medicine, Institute of Radiation Medicine, Chinese Academy of Medical Science and Peking Union Medical College, People's Republic of ChinaAbstract: The poor aqueous solubility and low bioavailability of curcumin restrict its clinical application for cancer treatment. In this study, a novel tumor-targeting nanofiber carrier was developed to improve the solubility and tumor-targeting ability of curcumin using a self-assembled Nap-GFFYG-RGD peptide. The morphologies of the peptide nanofiber and the curcumin-encapsulated nanofiber were visualized by transmission electron microscopy. The tumor-targeting activity of the curcumin-encapsulated Nap-GFFYG-RGD peptide nanofiber (f-RGD-Cur was studied in vitro and in vivo, using Nap-GFFYG-RGE peptide nanofiber (f-RGE-Cur as the control. Curcumin was encapsulated into the peptide nanofiber, which had a diameter of approximately 10–20 nm. Curcumin showed sustained-release behavior from the nanofibers in vitro. f-RGD-Cur showed much higher cellular uptake in αvβ3 integrin-positive HepG2 liver carcinoma cells than did non-targeted f-RGE-Cur, thereby leading to significantly higher cytotoxicity. Ex vivo studies further demonstrated that curcumin could accumulate markedly in mouse tumors after administration of f-RGD-Cur via the tail vein. These results indicate that Nap-GFFYG-RGD peptide self-assembled nanofibers are a promising hydrophobic drug delivery system for targeted treatment of cancer.Keywords: nanofiber, tumor-targeting, self-assembling, curcumin, drug delivery

  13. Hyaluronic acid-functionalized single-walled carbon nanotubes as tumor-targeting MRI contrast agent

    Directory of Open Access Journals (Sweden)

    Hou L

    2015-07-01

    Full Text Available Lin Hou,* Huijuan Zhang,* Yating Wang, Lili Wang, Xiaomin Yang, Zhenzhong ZhangSchool of Pharmaceutical Sciences, Zhengzhou University, Zhengzhou, People’s Republic of China*These authors contributed equally to this workAbstract: A tumor-targeting carrier, hyaluronic acid (HA-functionalized single-walled carbon nanotubes (SWCNTs, was explored to deliver magnetic resonance imaging (MRI contrast agents (CAs targeting to the tumor cells specifically. In this system, HA surface modification for SWCNTs was simply accomplished by amidation process and could make this nanomaterial highly hydrophilic. Cellular uptake was performed to evaluate the intracellular transport capabilities of HA-SWCNTs for tumor cells and the uptake rank was HA-SWCNTs> SWCNTs owing to the presence of HA, which was also evidenced by flow cytometry. The safety evaluation of this MRI CAs was investigated in vitro and in vivo. It revealed that HA-SWCNTs could stand as a biocompatible nanocarrier and gadolinium (Gd/HA-SWCNTs demonstrated almost no toxicity compared with free GdCl3. Moreover, GdCl3 bearing HA-SWCNTs could significantly increase the circulation time for MRI. Finally, to investigate the MRI contrast enhancing capabilities of Gd/HA-SWCNTs, T1-weighted MR images of tumor-bearing mice were acquired. The results suggested Gd/HA-SWCNTs had the highest tumor-targeting efficiency and T1-relaxivity enhancement, indicating HA-SWCNTs could be developed as a tumor-targeting carrier to deliver the CAs, GdCl3, for the identifiable diagnosis of tumor.Keywords: gadolinium, magnetic resonance, SWCNTs, hyaluronic acid, contrast agent

  14. [The development of novel tumor targeting delivery strategy].

    Science.gov (United States)

    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

  15. Improving emergency preparedness and crisis management capabilities in transportation.

    Science.gov (United States)

    2009-11-30

    Despite the heightened attention disaster preparedness and emergency management have received over the past decade, serious weaknesses in the United States emergency response capabilities remain at all levels of government and across a wide range ...

  16. Glucosylated polyethylenimine as a tumor-targeting gene carrier.

    Science.gov (United States)

    Park, In-Kyu; Cook, Seung-Eun; Kim, You-Kyoung; Kim, Hyun-Woo; Cho, Myung-Haing; Jeong, Hwan-Jeong; Kim, Eun-Mi; Nah, Jae-Woon; Bom, Hee-Seung; Cho, Chong-Su

    2005-11-01

    Glucosylated polyethylenimine (GPEI) was synthesized as a tumor-targeting gene carrier through facilitative glucose metabolism by tumor glucose transporter. Particle sizes of GPEI/DNA complex increased in proportion to glucose content of GPEI, whereas surface charge of the complex was not dependent on glucosylation, partially due to inefficient shielding of the short hydrophilic group introduced. GPEI with higher glucosylation (36 mol-%) had no cytotoxic effect on cells even at polymer concentrations higher than 200 microg/mL. Compared to unglucosylated PEI, glucosylation induced less than one-order decrease of transfection efficiency. Transfection of GPEI/DNA complex into tumor cells possibly occurred through specific interaction between glucose-related cell receptors and glucose moiety of GPEI. Gamma imaging technique revealed GPEI/DNA complex was distributed in liver, spleen, and tumors.

  17. PEGylated chitosan grafted with polyamidoaminedendron as tumor-targeted magnetic resonance imaging contrast agent

    International Nuclear Information System (INIS)

    Guangyue Zu; Xiaoyan Tong; Yi Cao; Ye Kuang; Yajie Zhang; Min Liu; Renjun Pei

    2017-01-01

    Macromolecular contrast agents labeled with targeting ligands are now receiving growing interest in tumor-targeted magnetic resonance imaging. In this study, a macromolecular contrast agent based on PEGylated chitosan was synthesized and characterized, and its application as an MRI contrast agent was then demonstrated both in vitro and in vivo. First, the chitosan backbone was partially grafted with poly(ethylene glycol), which was used to improve the in vivo stability, followed by modifying with azide groups. Second, alkynyl-terminated PAMAM dendron modified with gadolinium diethylenetriaminepentaacetic acid (Gd-DTPA) was synthesized and conjugated onto the chitosan backbone through click chemistry. Finally, the obtained mCA was further functionalized with folic acid to improve the target specificity. The obtained FA labeled mCA exhibited higher relaxivity (9.53 mM"-"1.s"-"1) relative to Gd-DTPA (4.25 mM"-"1.s"-"1) and showed negligible toxicity as determined by the WST assay. In vivo MRI results suggested that a relatively high signal enhancement was observed in the tumor region, which made it a promising candidate for tumor-targeted MRI CA. (authors)

  18. Improving offering strategies for wind farms enhanced with storage capability

    DEFF Research Database (Denmark)

    Ding, Huajie; Hu, Zechun; Song, Yonghua

    2015-01-01

    Due to the flexible charging and discharging capability, energy storage system (ESS) is thought of as a promising complement to wind farms (WF) in participating into electricity markets. This paper proposes a reserve-based real-time operation strategy of ESS to make arbitrage and to alleviate...... the wind power deviation from day-ahead contracts. Taking into account the operation strategy as well as two-price balancing market rules, a day-ahead bidding strategy of WF-ESS system is put forward and formulated. A modified gradient descent algorithm is described to solve the formulations. In the case...... studies, the computational efficiency of the algorithm is validated firstly. Moreover, a number of scenarios with/without considering the temporal dependence of wind power forecast error are designed and employed to compare the proposed strategy with other common ones in terms of profit....

  19. In vivo tomographic imaging with fluorescence and MRI using tumor-targeted dual-labeled nanoparticles

    Directory of Open Access Journals (Sweden)

    Zhang Y

    2013-12-01

    Full Text Available Yue Zhang,1 Bin Zhang,1 Fei Liu,1,2 Jianwen Luo,1,3 Jing Bai1 1Department of Biomedical Engineering, School of Medicine, 2Tsinghua-Peking Center for Life Sciences, 3Center for Biomedical Imaging Research, Tsinghua University, Beijing, People's Republic of China Abstract: Dual-modality imaging combines the complementary advantages of different modalities, and offers the prospect of improved preclinical research. The combination of fluorescence imaging and magnetic resonance imaging (MRI provides cross-validated information and direct comparison between these modalities. Here, we report on the application of a novel tumor-targeted, dual-labeled nanoparticle (NP, utilizing iron oxide as the MRI contrast agent and near infrared (NIR dye Cy5.5 as the fluorescent agent. Results of in vitro experiments verified the specificity of the NP to tumor cells. In vivo tumor targeting and uptake of the NPs in a mouse model were visualized by fluorescence and MR imaging collected at different time points. Quantitative analysis was carried out to evaluate the efficacy of MRI contrast enhancement. Furthermore, tomographic images were also acquired using both imaging modalities and cross-validated information of tumor location and size between these two modalities was revealed. The results demonstrate that the use of dual-labeled NPs can facilitate the dual-modal detection of tumors, information cross-validation, and direct comparison by combing fluorescence molecular tomography (FMT and MRI. Keywords: dual-modality, fluorescence molecular tomography (FMT, magnetic resonance imaging (MRI, nanoparticle

  20. Tumor Targeting and Drug Delivery by Anthrax Toxin

    Directory of Open Access Journals (Sweden)

    Christopher Bachran

    2016-07-01

    Full Text Available Anthrax toxin is a potent tripartite protein toxin from Bacillus anthracis. It is one of the two virulence factors and causes the disease anthrax. The receptor-binding component of the toxin, protective antigen, needs to be cleaved by furin-like proteases to be activated and to deliver the enzymatic moieties lethal factor and edema factor to the cytosol of cells. Alteration of the protease cleavage site allows the activation of the toxin selectively in response to the presence of tumor-associated proteases. This initial idea of re-targeting anthrax toxin to tumor cells was further elaborated in recent years and resulted in the design of many modifications of anthrax toxin, which resulted in successful tumor therapy in animal models. These modifications include the combination of different toxin variants that require activation by two different tumor-associated proteases for increased specificity of toxin activation. The anthrax toxin system has proved to be a versatile system for drug delivery of several enzymatic moieties into cells. This highly efficient delivery system has recently been further modified by introducing ubiquitin as a cytosolic cleavage site into lethal factor fusion proteins. This review article describes the latest developments in this field of tumor targeting and drug delivery.

  1. Tumor Targeting and Drug Delivery by Anthrax Toxin.

    Science.gov (United States)

    Bachran, Christopher; Leppla, Stephen H

    2016-07-01

    Anthrax toxin is a potent tripartite protein toxin from Bacillus anthracis. It is one of the two virulence factors and causes the disease anthrax. The receptor-binding component of the toxin, protective antigen, needs to be cleaved by furin-like proteases to be activated and to deliver the enzymatic moieties lethal factor and edema factor to the cytosol of cells. Alteration of the protease cleavage site allows the activation of the toxin selectively in response to the presence of tumor-associated proteases. This initial idea of re-targeting anthrax toxin to tumor cells was further elaborated in recent years and resulted in the design of many modifications of anthrax toxin, which resulted in successful tumor therapy in animal models. These modifications include the combination of different toxin variants that require activation by two different tumor-associated proteases for increased specificity of toxin activation. The anthrax toxin system has proved to be a versatile system for drug delivery of several enzymatic moieties into cells. This highly efficient delivery system has recently been further modified by introducing ubiquitin as a cytosolic cleavage site into lethal factor fusion proteins. This review article describes the latest developments in this field of tumor targeting and drug delivery.

  2. Tumor target amplification: Implications for nano drug delivery systems.

    Science.gov (United States)

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

    2018-04-10

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

  3. Improving capability, motivation and turnover of engineering personnel

    International Nuclear Information System (INIS)

    Alonso Zabalo, F.; Gonzalez Junco, J.

    1995-01-01

    The electricity sector today is continually improving the technical and economic performance of power plants and extending their operating life. This means that to serve the electricity industry, engineering companies must continually adapt and innovate in technology. Human resources are vital for today's engineering companies, to satisfy demand within the industry, and to remain strong in their home market and competitive abroad. A company can optimize the potential and cost-effectiveness of its people by balancing the experience and specialization of senior engineers, who can apply their abilities to new fields, and recruiting younger people with new methods and outlook. In parallel, the company must foster an environment in which staff share technical information, think positively about the future, avoid routine and welcome change and stimulating work. To harmonize individual and collective interests to achieve shared goals, the company must manage the knowledge, expertise and professional aspirations of each individual, rotate people among group without losing individuality, and promote in house and outside training. Weekly briefing give people a personal awareness of the technical and economic goals of the work group and its specific tasks and their cost, and a sense of responsibility, to give the organization the vitality it needs to succeed today. This presentation describes the procedures, and organizational and management tools needed to achieve these objectives and practical experience in applying them. (Author)

  4. Improving predictive capabilities of environmental change with GLOBE data

    Science.gov (United States)

    Robin, Jessica Hill

    This dissertation addresses two applications of Normalized Difference Vegetation Index (NDVI) essential for predicting environmental changes. The first study focuses on whether NDVI can improve model simulations of evapotranspiration for temperate Northern (>35°) regions. The second study focuses on whether NDVI can detect phenological changes in start of season (SOS) for high Northern (>60°) environments. The overall objectives of this research were to (1) develop a methodology for utilizing GLOBE data in NDVI research; and (2) provide a critical analysis of NDVI as a long-term monitoring tool for environmental change. GLOBE is an international partnership network of K-12 students, teachers, and scientists working together to study and understand the global environment. The first study utilized data collected by one GLOBE school in Greenville, Pennsylvania and the second utilized phenology observations made by GLOBE students in Alaska. Results from the first study showed NDVI could predict transpiration periods for environments like Greenville, Pennsylvania. In phenological terms, these environments have three distinct periods (QI, QII, and QIII). QI reflects onset of the growing season (mid March--mid May) when vegetation is greening up (NDVI 0.60). Results from the second study showed that a climate threshold of 153 +/- 22 growing degree days was a better predictor of SOS for Fairbanks than a NDVI threshold applied to temporal AVHRR and MODIS datasets. Accumulated growing degree days captured the interannual variability of SOS better than the NDVI threshold and most closely resembled actual SOS observations made by GLOBE students. Overall, biweekly composites and effects of clouds, snow, and conifers limit the ability of NDVI to monitor phenological changes in Alaska. Both studies did show that GLOBE data provides an important source of input and validation information for NDVI research.

  5. Conjugate of biotin with silicon(IV) phthalocyanine for tumor-targeting photodynamic therapy.

    Science.gov (United States)

    Li, Ke; Qiu, Ling; Liu, Qingzhu; Lv, Gaochao; Zhao, Xueyu; Wang, Shanshan; Lin, Jianguo

    2017-09-01

    In order to improve the efficacy of photodynamic therapy (PDT), biotin was axially conjugated with silicon(IV) phthalocyanine (SiPc) skeleton to develop a new tumor-targeting photosensitizer SiPc-biotin. The target compound SiPc-biotin showed much higher binding affinity toward BR-positive (biotin receptor overexpressed) HeLa human cervical carcinoma cells than its precursor SiPc-pip. However, when the biotin receptors of HeLa cells were blocked by free biotin, >50% uptake of SiPc-biotin was suppressed, demonstrating that SiPc-biotin could selectively accumulate in BR-positive cancer cells via the BR-mediated internalization. The confocal fluorescence images further confirmed the target binding ability of SiPc-biotin. As a consequence of specificity of SiPc-biotin toward BR-positive HeLa cells, the photodynamic effect was also largely dependent on the BR expression level of HeLa cells. The photodynamic activities of SiPc-biotin against HeLa cells were dramatically reduced when the biotin receptors were blocked by the free biotin (IC 50 : 0.18μM vs. 0.46μM). It is concluded that SiPc-biotin can selectively damage BR-positive cancer cells under irradiation. Furthermore, the dark toxicity of SiPc-biotin toward human normal liver cell lines LO2 was much lower than that of its precursor SiPc-pip. The targeting photodynamic activity and low dark toxicity suggest that SiPc-biotin is a promising photosensitizer for tumor-targeting photodynamic therapy. Copyright © 2017 Elsevier B.V. All rights reserved.

  6. Assessing organizational readiness for depression care quality improvement: relative commitment and implementation capability.

    Science.gov (United States)

    Rubenstein, Lisa V; Danz, Marjorie S; Crain, A Lauren; Glasgow, Russell E; Whitebird, Robin R; Solberg, Leif I

    2014-12-02

    Depression is a major cause of morbidity and cost in primary care patient populations. Successful depression improvement models, however, are complex. Based on organizational readiness theory, a practice's commitment to change and its capability to carry out the change are both important predictors of initiating improvement. We empirically explored the links between relative commitment (i.e., the intention to move forward within the following year) and implementation capability. The DIAMOND initiative administered organizational surveys to medical and quality improvement leaders from each of 83 primary care practices in Minnesota. Surveys preceded initiation of activities directed at implementation of a collaborative care model for improving depression care. To assess implementation capability, we developed composites of survey items for five types of organizational factors postulated to be collaborative care barriers and facilitators. To assess relative commitment for each practice, we averaged leader ratings on an identical survey question assessing practice priorities. We used multivariable regression analyses to assess the extent to which implementation capability predicted relative commitment. We explored whether relative commitment or implementation capability measures were associated with earlier initiation of DIAMOND improvements. All five implementation capability measures independently predicted practice leaders' relative commitment to improving depression care in the following year. These included the following: quality improvement culture and attitudes (p = 0.003), depression culture and attitudes (p commitment (p = 0.002) and prior depression quality improvement activities appeared to be associated with earlier participation in the DIAMOND initiative. The study supports the concept of organizational readiness to improve quality of care and the use of practice leader surveys to assess it. Practice leaders' relative commitment to depression care

  7. Optimization of Boiler Control to Improve the Load-following Capability of Power-plant Units

    OpenAIRE

    Mortensen, J. H.; Mølbak, T.; Andersen, Palle; Pedersen, Tom Søndergaard

    1998-01-01

    The capability to perform fast load changes has been an important issue in the power market, and will become increasingly more so due to the incresing commercialisation of the European power market. An optimizing control system for improving the load-following capability of power-plant units has therefore been developed. The system is implemented as a complement, producing control signals to be added to those of the existing boiler control system, a concept which has various practical advanta...

  8. Improving environmental performance through unit-level organizational citizenship behaviors for the environment: A capability perspective.

    Science.gov (United States)

    Alt, Elisa; Spitzeck, Heiko

    2016-11-01

    Organizational citizenship behaviors for the environment (OCBEs) are increasingly advocated as a means of complementing formal practices in improving environmental performance. Adopting a capability perspective, we propose that a firm's employee involvement capability translates into environmental performance through the manifestation of unit-level OCBEs, and that this relationship is amplified by a shared vision capability. In a cross-country and multi-industry sample of 170 firms, we find support for our hypotheses, shedding light on contextual determinants of OCBEs, and on how firms may engender a positive relationship between top-down environmental initiatives and bottom-up behaviors. Copyright © 2016 Elsevier Ltd. All rights reserved.

  9. Extension of ERIM multispectral data processing capabilities through improved data handling techniques

    Science.gov (United States)

    Kriegler, F. J.

    1973-01-01

    The improvement and extension of the capabilities of the Environmental Research Institute of Michigan processing facility in handling multispectral data are discussed. Improvements consisted of implementing hardware modifications which permitted more rapid access to the recorded data through improved numbering and indexing of such data. In addition, techniques are discussed for handling data from sources other than the ERIM M-5 and M-7 scanner systems.

  10. Bilayered near-infrared fluorescent nanoparticles based on low molecular weight PEI for tumor-targeted in vivo imaging

    Energy Technology Data Exchange (ETDEWEB)

    Liu, Hao; Li, Ke [Xi’an Jiaotong University, Key Laboratory of Biomedical Information Engineering of Education Ministry, School of Life Science and Technology (China); Xu, Liang [The University of Kansas, Department of Molecular Biosciences (United States); Wu, Daocheng, E-mail: wudaocheng@mail.xjtu.edu.cn [Xi’an Jiaotong University, Key Laboratory of Biomedical Information Engineering of Education Ministry, School of Life Science and Technology (China)

    2014-12-15

    To improve the tumor fluorescent imaging results in vivo, bilayered nanoparticles encapsulating a lipophilic near-infrared (NIR) fluorescent dye 1,1′-dioctadecyl-3,3,3′,3′-tetramethylindotri-carbocyanine iodide (DiR) were prepared using low molecular weight stearic acid-grafted polyethyleneimine and hyaluronic acid (DiR-PgSHA nanoparticles), which were investigated as a novel NIR fluorescent nano-probe for in vivo tumor-targeted optical imaging. These nanoparticles were characterized by transmission electron microscopy (TEM), infrared (IR) spectra, UV-visual absorption, and fluorescent emission spectra. Their cytotoxicity in vitro and hepatotoxicity in vivo were tested by MTT assay and histological study, respectively. In vivo NIR fluorescence imaging of the DiR-PgSHA nanoparticles was performed using a Carestream imaging system. The DiR-PgSHA nanoparticles were sphere shaped with a diameter of approximately 50 nm according to the TEM images. The DiR-PgSHA nanoparticles had a low cytotoxicity in vitro according to the MTT assay and low hepatotoxicity in vivo as determined in histological studies. The fluorescent emission of DiR-PgSHA nanoparticles was stable in pH values of 5–9 in solution, with only slight blue-shifts of the emission maxima at the basic pH range. The DiR-PgSHA nanoparticles exhibited a substantial tumor-targeting ability in the optical imaging with the use of tumor-bearing mice. These results demonstrated that the DiR-PgSHA nanoparticle is an excellent biocompatible nano-probe for in vivo tumor-targeted NIR fluorescence imaging with a potential for clinical applications.

  11. Bilayered near-infrared fluorescent nanoparticles based on low molecular weight PEI for tumor-targeted in vivo imaging

    International Nuclear Information System (INIS)

    Liu, Hao; Li, Ke; Xu, Liang; Wu, Daocheng

    2014-01-01

    To improve the tumor fluorescent imaging results in vivo, bilayered nanoparticles encapsulating a lipophilic near-infrared (NIR) fluorescent dye 1,1′-dioctadecyl-3,3,3′,3′-tetramethylindotri-carbocyanine iodide (DiR) were prepared using low molecular weight stearic acid-grafted polyethyleneimine and hyaluronic acid (DiR-PgSHA nanoparticles), which were investigated as a novel NIR fluorescent nano-probe for in vivo tumor-targeted optical imaging. These nanoparticles were characterized by transmission electron microscopy (TEM), infrared (IR) spectra, UV-visual absorption, and fluorescent emission spectra. Their cytotoxicity in vitro and hepatotoxicity in vivo were tested by MTT assay and histological study, respectively. In vivo NIR fluorescence imaging of the DiR-PgSHA nanoparticles was performed using a Carestream imaging system. The DiR-PgSHA nanoparticles were sphere shaped with a diameter of approximately 50 nm according to the TEM images. The DiR-PgSHA nanoparticles had a low cytotoxicity in vitro according to the MTT assay and low hepatotoxicity in vivo as determined in histological studies. The fluorescent emission of DiR-PgSHA nanoparticles was stable in pH values of 5–9 in solution, with only slight blue-shifts of the emission maxima at the basic pH range. The DiR-PgSHA nanoparticles exhibited a substantial tumor-targeting ability in the optical imaging with the use of tumor-bearing mice. These results demonstrated that the DiR-PgSHA nanoparticle is an excellent biocompatible nano-probe for in vivo tumor-targeted NIR fluorescence imaging with a potential for clinical applications

  12. Integrating the development of continuous improvement andinnovation capabilities into engineering education

    DEFF Research Database (Denmark)

    Jørgensen, Frances; Kofoed, Lise B.

    2007-01-01

    In this paper, a study is presented in which engineering students at a Danish university developed Continuous Improvement (CI) and innovation capabilities through action research and experientiallearning methods. The paper begins with a brief overview of the literature on CI and innovation...

  13. Optimization of Boiler Control to Improve the Load-following Capability of Power-plant Units

    DEFF Research Database (Denmark)

    Mortensen, J. H.; Mølbak, T.; Andersen, Palle

    The capability to perform fast load changes has been an important issue in the power market, and will become increasingly more so due to the incresing commercialisation of the European power market. An optimizing control system for improving the load-following capability of power-plant units has...... tests on a 265 MW coal-fired power-plant unit reveals that the maximum allowable load gradient that can be imposed on the plant, can be increased from 4 MW/min. to 8 MW/min....

  14. Optimization of Boiler Control to Improve the Load-following Capability of Power-plant Units

    DEFF Research Database (Denmark)

    Mortensen, J. H.; Mølbak, T.; Andersen, Palle

    1998-01-01

    The capability to perform fast load changes has been an important issue in the power market, and will become increasingly more so due to the incresing commercialisation of the European power market. An optimizing control system for improving the load-following capability of power-plant units has...... tests on a 265 MW coal-fired power-plant unit reveals that the maximum allowable load gradient that can be imposed on the plant, can be increased from 4 MW/min. to 8 MW/min....

  15. A DMAIC approach for process capability improvement an engine crankshaft manufacturing process

    Science.gov (United States)

    Sharma, G. V. S. S.; Rao, P. Srinivasa

    2014-05-01

    The define-measure-analyze-improve-control (DMAIC) approach is a five-strata approach, namely DMAIC. This approach is the scientific approach for reducing the deviations and improving the capability levels of the manufacturing processes. The present work elaborates on DMAIC approach applied in reducing the process variations of the stub-end-hole boring operation of the manufacture of crankshaft. This statistical process control study starts with selection of the critical-to-quality (CTQ) characteristic in the define stratum. The next stratum constitutes the collection of dimensional measurement data of the CTQ characteristic identified. This is followed by the analysis and improvement strata where the various quality control tools like Ishikawa diagram, physical mechanism analysis, failure modes effects analysis and analysis of variance are applied. Finally, the process monitoring charts are deployed at the workplace for regular monitoring and control of the concerned CTQ characteristic. By adopting DMAIC approach, standard deviation is reduced from 0.003 to 0.002. The process potential capability index ( C P) values improved from 1.29 to 2.02 and the process performance capability index ( C PK) values improved from 0.32 to 1.45, respectively.

  16. Recent Trends in Multifunctional Liposomal Nanocarriers for Enhanced Tumor Targeting

    Directory of Open Access Journals (Sweden)

    Federico Perche

    2013-01-01

    Full Text Available Liposomes are delivery systems that have been used to formulate a vast variety of therapeutic and imaging agents for the past several decades. They have significant advantages over their free forms in terms of pharmacokinetics, sensitivity for cancer diagnosis and therapeutic efficacy. The multifactorial nature of cancer and the complex physiology of the tumor microenvironment require the development of multifunctional nanocarriers. Multifunctional liposomal nanocarriers should combine long blood circulation to improve pharmacokinetics of the loaded agent and selective distribution to the tumor lesion relative to healthy tissues, remote-controlled or tumor stimuli-sensitive extravasation from blood at the tumor’s vicinity, internalization motifs to move from tumor bounds and/or tumor intercellular space to the cytoplasm of cancer cells for effective tumor cell killing. This review will focus on current strategies used for cancer detection and therapy using liposomes with special attention to combination therapies.

  17. THEORY OF REASONED ACTION FOR CONTINUOUS IMPROVEMENT CAPABILITIES: A BEHAVIORAL APPROACH

    Directory of Open Access Journals (Sweden)

    Janaina Siegler

    2012-09-01

    Full Text Available The importance of interaction between Operations Management (OM and Human Behavior has been recently re-addressed. This paper introduced the Reasoned Action Theory suggested by Froehle and Roth (2004 to analyze Operational Capabilities exploring the suitability of this model in the context of OM. It also seeks to discuss the behavioral aspects of operational capabilities from the perspective of organizational routines. This theory was operationalized using Fishbein and Ajzen (F/A behavioral model and a multi-case strategy was employed to analyze the Continuous Improvement (CI capability. The results posit that the model explains partially the CI behavior in an operational context and some contingency variables might influence the general relationsamong the variables involved in the F/A model. Thus intention might not be the determinant variable of behavior in this context.

  18. Applications of polymeric micelles with tumor targeted in chemotherapy

    International Nuclear Information System (INIS)

    Ding Hui; Wang Xiaojun; Zhang Song; Liu Xinli

    2012-01-01

    Polymeric micelles (PMs) have gained more progress as a carrier system with the quick development of biological and nanoparticle techniques. In particular, PMs with smart targeting can deliver anti-cancer drugs directly into tumor cells at a sustained rate. PMs with core–shell structure (with diameters of 10 ∼ 100 nm) have been prepared by a variety of biodegradable and biocompatible polymers via a self-assembly process. The preparation of polymeric micelles with stimuli-responsive block copolymers or modification of target molecules on polymeric micelles’ surface are able to significantly improve the efficiency of drug delivery. Polymeric micelles, which have been considered as a novel promising drug carrier for cancer therapeutics, are rapidly evolving and being introduced in an attempt to overcome several limitations of traditional chemotherapeutics, including water solubility, tumor-specific accumulation, anti-tumor efficacy, and non-specific toxicity. This review describes the preparation of polymeric micelles and the targeted modification which greatly enhance the effects of chemotherapeutic agents.

  19. Engineering of magnetic DNA nanoparticles for tumor-targeted therapy

    International Nuclear Information System (INIS)

    Hosseinkhani, Hossein; Chen Yiru; He Wenjie; Hong Poda; Yu, Dah-Shyong; Domb, Abraham J.

    2013-01-01

    This study aims to engineer novel targeted delivery system composed of magnetic DNA nanoparticles to be effective as an efficient targeted gene therapy vehicle for tumor therapy. A polysaccharide, dextran, was chosen as the vector of plasmid DNA-encoded NK4 that acts as an HGF-antagonist and anti-angiogenic regulator for inhibitions of tumor growth, invasion, and metastasis. Spermine (Sm) was chemically introduced to the hydroxyl groups of dextran to obtain dextran-Sm. When Fe 2+ solution was added to the mixture of dextran-Sm and a plasmid DNA, homogenous DNA nanoparticles were formed via chemical metal coordination bonding with average size of 230 nm. Characterization of DNA nanoparticles was performed via dynamic light scattering measurement, electrophoretic light scattering measurement, as well as transmission electron microscope. DNA nanoparticles effectively condensed plasmid DNA into nanoparticles and enhanced the stability of DNA, while significantly improved transfection efficiency in vitro and tumor accumulation in vivo. In addition, magnetic DNA nanoparticles exhibited high efficiency in antitumor therapy with regards to tumor growth as well as survival of animals evaluated in the presence of external magnetic field. We conclude that the magnetic properties of these DNA nanoparticles would enhance the tracking of non-viral gene delivery systems when administrated in vivo in a test model. These findings suggest that DNA nanoparticles effectively deliver DNA to tumor and thereby inhibiting tumor growth.

  20. Phenylalanine-coupled solid lipid nanoparticles for brain tumor targeting

    Energy Technology Data Exchange (ETDEWEB)

    Kharya, Parul; Jain, Ashish; Gulbake, Arvind; Shilpi, Satish; Jain, Ankit; Hurkat, Pooja [Dr. Hari Singh Gour University, Pharmaceutical Research Projects Laboratory, Department of Pharmaceutical Sciences (India); Majumdar, Subrata [Bose Institute, Division of Molecular Medicine (India); Jain, Sanjay K., E-mail: drskjainin@yahoo.com [Dr. Hari Singh Gour University, Pharmaceutical Research Projects Laboratory, Department of Pharmaceutical Sciences (India)

    2013-11-15

    The purpose of this study is to investigate the targeting potential of amino acid (phenylalanine)-coupled solid lipid nanoparticles (SLN) loaded with ionically complexed doxorubicin HCl (Dox). Ionic complexation was used to enhance the loading efficiency and release characteristics of water soluble form of Dox. l-Type amino acid transporters (LAT1) are highly expressed on blood brain barrier as well as on many brain cancer cells, thus targeting LAT1 using phenylalanine improved anticancer activity of prepared nanocarrier. The phenylalanine-coupled SLN were characterized by fourier transform infrared spectroscopy, scanning electron microscope, transmission electron microscopy, particle size, zeta potential, entrapment efficiency and in vitro release. The particle size of the resulting SLN was found to be in the range of 163.3 ± 5.2 to 113.0 ± 2.6 nm, with a slightly negative surface charge. In ex vivo study on C6 glioma cell lines, the cellular cytotoxicity of the SLN was highly increased when coupled with phenylalanine. In addition, stealthing sheath of PEG present on the surface of the SLN enhanced the cellular uptake of the SLN on C6 glioma cell line. Results of biodistribution and fluorescence studies clearly revealed that phenylalanine-coupled SLN could deliver high amount of drug into the brain tumor cells and showed the brain-targeting potential.

  1. Engineering of magnetic DNA nanoparticles for tumor-targeted therapy

    Energy Technology Data Exchange (ETDEWEB)

    Hosseinkhani, Hossein, E-mail: hosseinkhani@yahoo.com [Graduate Institute of Biomedical Engineering, National Taiwan University of Science and Technology (Taiwan Tech) (China); Chen Yiru [National Yang-Ming University, Department of Biomedical Engineering (China); He Wenjie; Hong Poda [Graduate Institute of Biomedical Engineering, National Taiwan University of Science and Technology (Taiwan Tech) (China); Yu, Dah-Shyong [Nanomedicine Research Center, National Defense Medical Center (China); Domb, Abraham J. [Institute of Drug Research, The Center for Nanoscience and Nanotechnology, School of Pharmacy, Faculty of Medicine, Hebrew University of Jerusalem (Israel)

    2013-01-15

    This study aims to engineer novel targeted delivery system composed of magnetic DNA nanoparticles to be effective as an efficient targeted gene therapy vehicle for tumor therapy. A polysaccharide, dextran, was chosen as the vector of plasmid DNA-encoded NK4 that acts as an HGF-antagonist and anti-angiogenic regulator for inhibitions of tumor growth, invasion, and metastasis. Spermine (Sm) was chemically introduced to the hydroxyl groups of dextran to obtain dextran-Sm. When Fe{sup 2+} solution was added to the mixture of dextran-Sm and a plasmid DNA, homogenous DNA nanoparticles were formed via chemical metal coordination bonding with average size of 230 nm. Characterization of DNA nanoparticles was performed via dynamic light scattering measurement, electrophoretic light scattering measurement, as well as transmission electron microscope. DNA nanoparticles effectively condensed plasmid DNA into nanoparticles and enhanced the stability of DNA, while significantly improved transfection efficiency in vitro and tumor accumulation in vivo. In addition, magnetic DNA nanoparticles exhibited high efficiency in antitumor therapy with regards to tumor growth as well as survival of animals evaluated in the presence of external magnetic field. We conclude that the magnetic properties of these DNA nanoparticles would enhance the tracking of non-viral gene delivery systems when administrated in vivo in a test model. These findings suggest that DNA nanoparticles effectively deliver DNA to tumor and thereby inhibiting tumor growth.

  2. GLUT1-mediated selective tumor targeting with fluorine containing platinum(II) glycoconjugates.

    Science.gov (United States)

    Liu, Ran; Fu, Zheng; Zhao, Meng; Gao, Xiangqian; Li, Hong; Mi, Qian; Liu, Pengxing; Yang, Jinna; Yao, Zhi; Gao, Qingzhi

    2017-06-13

    Increased glycolysis and overexpression of glucose transporters (GLUTs) are physiological characteristics of human malignancies. Based on the so-called Warburg effect, 18flurodeoxyglucose-positron emission tomography (FDG-PET) has successfully developed as clinical modality for the diagnosis and staging of many cancers. To leverage this glucose transporter mediated metabolic disparity between normal and malignant cells, in the current report, we focus on the fluorine substituted series of glucose, mannose and galactose-conjugated (trans-R,R-cyclohexane-1,2-diamine)-2-flouromalonato-platinum(II) complexes for a comprehensive evaluation on their selective tumor targeting. Besides highly improved water solubility, these sugar-conjugates presented improved cytotoxicity than oxaliplatin in glucose tranporters (GLUTs) overexpressing cancer cell lines and exhibited no cross-resistance to cisplatin. For the highly water soluble glucose-conjugated complex (5a), two novel in vivo assessments were conducted and the results revealed that 5a was more efficacious at a lower equitoxic dose (70% MTD) than oxaliplatin (100% MTD) in HT29 xenograft model, and it was significantly more potent than oxaliplatin in leukemia-bearing DBA/2 mice as well even at equimolar dose levels (18% vs 90% MTD). GLUT inhibitor mediated cell viability analysis, GLUT1 knockdown cell line-based cytotoxicity evaluation, and platinum accumulation study demonstrated that the cellular uptake of the sugar-conjugates was regulated by GLUT1. The higher intrinsic DNA reactivity of the sugar-conjugates was confirmed by kinetic study of platinum(II)-guanosine adduct formation. The mechanistic origin of the antitumor effect of the fluorine complexes was found to be forming the bifunctional Pt-guanine-guanine (Pt-GG) intrastrand cross-links with DNA. The results provide a rationale for Warburg effect targeted anticancer drug design.

  3. IMPROVEMENTS IN THE CAPABILITY PROFILE OF 3-D PRINTING: AN UPDATE

    Directory of Open Access Journals (Sweden)

    Dimitrov, Dimitar Marinov

    2014-08-01

    Full Text Available Knowledge about the capabilities of a production system is an important issue. The three- dimensional (3-D printing (drop-on-bed process has become a well-established Additive Manufacturing (AM technology. Initially intended for use mainly as a concept modeller, its scope of application has expanded to include, among others, fit and functional models, pattern-making for casting and moulding processes, rapid tooling, and medical and architectural models. This growth in applications has stimulated a reciprocal improvement in available materials and the technological capabilities of 3-D printing, such as accuracy, strength and elongation, surface finish, build time, and cost. These factors are of significance to users who want to control their processes better and to designers who want to define their expectations and determine their requirements. Thus this paper aims to provide a technical update, highlighting the influence level of different factors on a system’s capabilities. This paper uses the example of the ZPrinter 310 system from the Z Corporation, applies appropriate statistical techniques, and takes into consideration the latest material and machine developments, in order to report on the current improvements of the capability profile of this important process.

  4. Optimization of Boiler Control for Improvement of Load Following Capabilities of Existing Power Plants

    DEFF Research Database (Denmark)

    Mortensen, J. H.; Mølbak, T.; Pedersen, Tom Søndergaard

    1997-01-01

    An An optimizing control system for improving the load following capabilities of power plant units has been developed. The system is implemented as a complement producing additive control signals to the existing boiler control system, a concept which has various practical advantages in terms...... of implementation and commissioning. The optimizing control system takes into account the multivariable and nonlinear characteristics of the boiler process as a gain-scheduled LQG-controller is utilized. Simulation results indicate that a reduction of steam temperature deviations of about 75% can be obtained.......optimizing control system for improving the load following capabilities of power plant units has been developed. The system is implemented as a complement producing additive control signals to the existing boiler control system, a concept which has various practical advantages in terms of implementation...

  5. Novel method to improve power handling capability for coplanar waveguide high-temperature superconducting filter

    Energy Technology Data Exchange (ETDEWEB)

    Satoh, K; Koizumi, D; Narahashi, S [NTT DoCoMo, Inc., 3-5 Hikari-no-oka, 239-8536 Yokosuka (Japan)

    2006-06-01

    This paper proposes a novel method to improve the power handling capability of a coplanar waveguide (CPW) high-temperature superconducting (HTS) filter. The noteworthy point of the proposed method is that it is based on the concept that the power handling capability is improved by reducing the maximum current density of the filter. Numerical investigations confirm that a CPW HTS filter using 66-{omega} characteristic impedance resonators (66-{omega} CPW HTSF) reduces the maximum current density compared to that using conventional 50-{omega} resonators (50-{omega} CPW HTSF). We fabricated 5-GHz band four-pole Chevyshev CPW HTSFs based on the proposed and conventional methods. The fabricated 66-{omega} CPW HTSF exhibited the third-order intercept point (TOI) of + 61 dBm while the 50-{omega} CPW HTSF exhibited the TOI of + 54 dBm, both at 60 K. These results indicate the effectiveness of the proposed method.

  6. Novel functionalized nanoparticles for tumor-targeting co-delivery of doxorubicin and siRNA to enhance cancer therapy

    Directory of Open Access Journals (Sweden)

    Xia Y

    2017-12-01

    Full Text Available Yu Xia, Tiantian Xu, Changbing Wang, Yinghua Li, Zhengfang Lin, Mingqi Zhao, Bing Zhu Central Laboratory, Guangzhou Women and Children’s Medical Center, Guangzhou Medical University, Guangzhou, People’s Republic of China Abstract: Human homeobox protein (Nanog is highly expressed in most cancer cells and has gradually emerged as an excellent target in cancer therapy, owing to its regulation of cancer cell proliferation, metastasis and apoptosis. In this study, we prepared tumor-targeting functionalized selenium nanoparticles (RGDfC-SeNPs to load chemotherapeutic doxorubicin (DOX and Nanog siRNA. Herein, RGDfC peptide was used as a tumor-targeting moiety which could specifically bind to αvβ3 integrins overexpressed on various cancer cells. The sizes of RGDfC-SeNPs@DOX nanoparticles (~12 nm were confirmed by both dynamic light scattering and transmission electron microscopy. The chemical structure of RGDfC-SeNPs@DOX was characterized via Fourier-transform infrared spectroscopy. The RGDfC-SeNPs@DOX was compacted with siRNA (anti-Nanog by electrostatic interaction to fabricate the RGDfC-SeNPs@DOX/siRNA complex. The RGDfC-SeNPs@DOX/siRNA complex nanoparticles could efficiently enter into HepG2 cells via clathrin-associated endocytosis, and showed high gene transfection efficiency that resulted in enhanced gene silencing. The in vivo biodistribution experiment indicated that RGDfC-SeNPs@DOX/siRNA nanoparticles were capable of specifically accumulating in the tumor site. Furthermore, treatment with RGDfC-SeNPs@DOX/siRNA resulted in a more significant anticancer activity than the free DOX, RGDfC-SeNPs@DOX or RGDfC-SeNPs/siRNA in vitro and in vivo. In summary, this study shows a novel type of DOX and siRNA co-delivery system, thereby providing an alternative route for cancer treatment. Keywords: nanoparticles, tumor targeting, drug delivery, doxorubicin, Nanog siRNA

  7. Passive versus active tumor targeting using RGD- and NGR-modified polymeric nanomedicines

    NARCIS (Netherlands)

    Kunjachan, Sijumon; Pola, Robert; Gremse, Felix; Theek, Benjamin; Ehling, Josef; Moeckel, Diana; Hermanns-Sachweh, Benita; Pechar, Michal; Ulbrich, Karel; Hennink, Wim E.; Storm, Gert; Lederle, Wiltrud; Kiessling, Fabian; Lammers, Twan

    2014-01-01

    Enhanced permeability and retention (EPR) and the (over-) expression of angiogenesis-related surface receptors are key features of tumor blood vessels. As a consequence, EPR-mediated passive and Arg-Gly-Asp (RGD) and Asn-Gly-Arg (NGR) based active tumor targeting have received considerable attention

  8. In vivo imaging of passively tumor targeted polymer carrier and the enzymatically cleavable drug model

    Czech Academy of Sciences Publication Activity Database

    Pola, Robert; Heinrich, A. K.; Mueller, T.; Kostka, Libor; Mäder, K.; Pechar, Michal; Etrych, Tomáš

    2017-01-01

    Roč. 6, 4 (Suppl) (2017), s. 90 ISSN 2325-9604. [International Conference and Exhibition on Nanomedicine and Drug Delivery. 29.05.2017-31.05.2017, Osaka] R&D Projects: GA MZd(CZ) NV16-28594A Institutional support: RVO:61389013 Keywords : polymer drug carrier * tumor targeting * enzymatic release Subject RIV: FD - Oncology ; Hematology

  9. Radix Achyranthis Bidentatae improves learning and memory capabilities in ovariectomized rats

    Institute of Scientific and Technical Information of China (English)

    Yuefen Wang; Ya Xu; Yanshu Pan; Weihong Li; Wei Zhang; Yang Liu; Jing Jia; Pengtao Li

    2013-01-01

    Kidney-tonifying recipe can reduce the accumulation of advanced glycation end products, prevent neuronal degeneration and improve cognitive functions in ovariectomized rats. Radix Achyranthis Bidentatae alcohol extracts may dose-dependently inhibit non-enzymatic saccharification in vitro. This study aimed to examine the effect of Radix Achyranthis Bidentatae on advanced glycation end products and on learning and memory capabilities in ovariectomized rats. Ovariectomized rats were treated with Radix Achyranthis Bidentatae alcohol extracts (containing 1.5 g/kg crude drug) or 0.1% aminoguanidine for 12 weeks and behavioral testing was performed with the Y-electrical maze. This test revealed that Radix Achyranthis Bidentatae and aminoguanidine could improve the learning and memory capabilities of ovariectomized rats. Results of competitive enzyme-linked immunosorbent assay showed that treatment with Radix Achyranthis Bidentatae or aminoguanidine reduced the accumulation of advanced glycation end products in the frontal cortex of ovariectomized rats, while increasing content in the blood and urine. Biochemical tests showed that treatment with Radix Achyranthis Bidentatae or aminoguanidine decreased superoxide dismutase activity in the serum and frontal cortex, and increased serum levels of glutathione peroxidase in ovariectomized rats. In addition, there was no apparent effect on malondialdehyde levels. These experimental findings indicate that Radix Achyranthis Bidentatae inhibits production of advanced glycation end products and its accumulation in brain tissue, and improves learning and memory capabilities in ovariectomized rats. These effects may be associated with an anti-oxidative action of the extract.

  10. Photoacoustic imaging of tumor targeting with biotin conjugated nanostructured phthalocyanine assemblies

    Science.gov (United States)

    Lee, Seunghyun; Li, Xingshu; Lee, Dayoung; Yoon, Juyoung; Kim, Chulhong

    2018-02-01

    Visualizing biological markers and delivering bioactive agents to living organisms are important to biological research. In recent decades, photoacoustic imaging (PAI) has been significantly improved in the area of molecular imaging, which provides high-resolution volume imaging with high optical absorption contrast. To demonstrate the ability of nanoprobes to target tumors using PAI, we synthesize convertible nanostructured agents with strong photothermal and photoacoustic properties and linked the nanoprobe with biotin to target tumors in small animal model. Interestingly, these nanoprobes allow partial to disassemble in the presence of targeted proteins that switchable photoactivity, thus the nanoprobes provides a fluorescent-cancer imaging with high signal-to-background ratios. The proposed nanoprobe produce a much stronger PA signal compared to the same concentration of methylene blue (MB), which is widely used in clinical study and contrast agent for PAI. The biotin conjugated nanoprobe has high selectivity for biotin receptor positive cancer cells such as A549 (human lung cancer). Then we subsequently examined the PA properties of the nanoprobe that are inherently suitable for in vivo PAI. After injecting of the nanoprobe via intravenous method, we observed the mice's whole body by PA imaging and acquired the PA signal near the cancer. The PA signal increased linearly with time after injection and the fluorescence signal near the cancer was confirmed by fluorescence imaging. The ability to target a specific cancer of the nanoprobe was well verified by PA imaging. This study provides valuable perspective on the advancement of clinical translations and in the design of tumor-targeting phototheranostic agents that could act as new nanomedicines.

  11. Improving Coastal Ocean Color Validation Capabilities through Application of Inherent Optical Properties (IOPs)

    Science.gov (United States)

    Mannino, Antonio

    2008-01-01

    Understanding how the different components of seawater alter the path of incident sunlight through scattering and absorption is essential to using remotely sensed ocean color observations effectively. This is particularly apropos in coastal waters where the different optically significant components (phytoplankton, detrital material, inorganic minerals, etc.) vary widely in concentration, often independently from one another. Inherent Optical Properties (IOPs) form the link between these biogeochemical constituents and the Apparent Optical Properties (AOPs). understanding this interrelationship is at the heart of successfully carrying out inversions of satellite-measured radiance to biogeochemical properties. While sufficient covariation of seawater constituents in case I waters typically allows empirical algorithms connecting AOPs and biogeochemical parameters to behave well, these empirical algorithms normally do not hold for case I1 regimes (Carder et al. 2003). Validation in the context of ocean color remote sensing refers to in-situ measurements used to verify or characterize algorithm products or any assumption used as input to an algorithm. In this project, validation capabilities are considered those measurement capabilities, techniques, methods, models, etc. that allow effective validation. Enhancing current validation capabilities by incorporating state-of-the-art IOP measurements and optical models is the purpose of this work. Involved in this pursuit is improving core IOP measurement capabilities (spectral, angular, spatio-temporal resolutions), improving our understanding of the behavior of analytical AOP-IOP approximations in complex coastal waters, and improving the spatial and temporal resolution of biogeochemical data for validation by applying biogeochemical-IOP inversion models so that these parameters can be computed from real-time IOP sensors with high sampling rates. Research cruises supported by this project provides for collection and

  12. Statistical methods for quality assurance basics, measurement, control, capability, and improvement

    CERN Document Server

    Vardeman, Stephen B

    2016-01-01

    This undergraduate statistical quality assurance textbook clearly shows with real projects, cases and data sets how statistical quality control tools are used in practice. Among the topics covered is a practical evaluation of measurement effectiveness for both continuous and discrete data. Gauge Reproducibility and Repeatability methodology (including confidence intervals for Repeatability, Reproducibility and the Gauge Capability Ratio) is thoroughly developed. Process capability indices and corresponding confidence intervals are also explained. In addition to process monitoring techniques, experimental design and analysis for process improvement are carefully presented. Factorial and Fractional Factorial arrangements of treatments and Response Surface methods are covered. Integrated throughout the book are rich sets of examples and problems that help readers gain a better understanding of where and how to apply statistical quality control tools. These large and realistic problem sets in combination with the...

  13. A study on improvement of measurement capability for gravimetric flowmeter calibrator

    International Nuclear Information System (INIS)

    Lee, Dong Keun; Park, Jong Ho

    2009-01-01

    The calibration of flowmeter is a very important procedure to set up traceability from the national or international standards. The uncertainty of flow measurement defines reliability for measurement results. The uncertainty of gravimetric method combines uncertainties of each independent variable, including mass, time, water density, air density and the density of dead weight. In this study, it has been found that the uncertainties of mass and time measurement in the gravimetric method have dominant influence on the total measurement uncertainty. After improvements of a constant head tank and a diverter, the best measurement capability for K-water's calibration facility has been reached less than 0.1%.

  14. Improving Fault Ride-Through Capability of Variable Speed Wind Turbines in Distribution Networks

    DEFF Research Database (Denmark)

    Mokryani, Geev; Siano, P.; Piccolo, Antonio

    2013-01-01

    In this paper, a fuzzy controller for improving the fault ride-through (FRT) capability of variable speed wind turbines (WTs) equipped with a doubly fed induction generator (DFIG) is presented. DFIGs can be used as reactive power sources to control the voltage at the point of common coupling (PCC......). The controller is designed to compensate for the voltage at the PCC by simultaneously regulating the reactive and active power generated by WTs. The performance of the controller is evaluated in different case studies considering a different number of wind farms in different locations. Simulations carried out...

  15. Nano-Engineered Mesenchymal Stem Cells Increase Therapeutic Efficacy of Anticancer Drug Through True Active Tumor Targeting.

    Science.gov (United States)

    Layek, Buddhadev; Sadhukha, Tanmoy; Panyam, Jayanth; Prabha, Swayam

    2018-06-01

    Tumor-targeted drug delivery has the potential to improve therapeutic efficacy and mitigate non-specific toxicity of anticancer drugs. However, current drug delivery approaches rely on inefficient passive accumulation of the drug carrier in the tumor. We have developed a unique, truly active tumor-targeting strategy that relies on engineering mesenchymal stem cells (MSC) with drug-loaded nanoparticles. Our studies using the A549 orthotopic lung tumor model show that nano-engineered MSCs carrying the anticancer drug paclitaxel (PTX) home to tumors and create cellular drug depots that release the drug payload over several days. Despite significantly lower doses of PTX, nano-engineered MSCs resulted in significant inhibition of tumor growth and superior survival. Anticancer efficacy of nano-engineered MSCs was confirmed in immunocompetent C57BL/6 albino female mice bearing orthotopic Lewis Lung Carcinoma (LL/2-luc) tumors. Furthermore, at doses that resulted in equivalent therapeutic efficacy, nano-engineered MSCs had no effect on white blood cell count, whereas PTX solution and PTX nanoparticle treatments caused leukopenia. Biodistribution studies showed that nano-engineered MSCs resulted in greater than 9-fold higher AUC lung of PTX (1.5 μg.day/g) than PTX solution and nanoparticles (0.2 and 0.1 μg.day/g tissue, respectively) in the target lung tumors. Furthermore, the lung-to-liver and the lung-to-spleen ratios of PTX were several folds higher for nano-engineered MSCs relative to those for PTX solution and nanoparticle groups, suggesting that nano-engineered MSCs demonstrate significantly less off-target deposition. In summary, our results demonstrate that nano-engineered MSCs can serve as an efficient carrier for tumor-specific drug delivery and significantly improved anti-cancer efficacy of conventional chemotherapeutic drugs. Mol Cancer Ther; 17(6); 1196-206. ©2018 AACR . ©2018 American Association for Cancer Research.

  16. RCGVS design improvement and depressurization capability tests for Ulchin nuclear power plant units 3 and 4

    Energy Technology Data Exchange (ETDEWEB)

    Sung, Kang Sik; Seong, Ho Je; Jeong, Won Sang; Seo, Jong Tae; Lee, Sang Keun [Korea Power Engineering Company, Inc., Seoul (Korea, Republic of); Lim, Keun Hyo; Choi, Kwon Sik; Oh, Chul Sung [Korea Electric Power Cooperation, Taejon (Korea, Republic of)

    1999-12-31

    The Reactor Coolant Gas Vent System(RCGVS) design for Ulchin Nuclear Power Plant Units 3 and 4 (UCN 3 and 4) has been improved from the Yonggwang Nuclear Power Plant Units 3 and 4 (YGN 3 and 4) based on the evaluation results for depressurization capability tests performed at YGN 3 and 4. There has been a series of plant safety analyses for Natural Circulation Cooldown(NCC) event and thermo-dynamic analyses with RELAP5 code for the steam blowdown phenomena in order to optimize the orifice size of UCN 3 and 4 RCGVS. Based on these analyses results, the RCGVS orifics size for UCN 3 and 4 has been reduced to 9/32 inch from the 11/32 inch for YGN 3 and 4. The depressurization capability tests, which were performed at UCN 3 in order to verify the FSAR NCC analysis results, show that the RCGVS depressurization rates are being within the acceptable ranges. Therefore, it is concluded that the orificed flow path of UCN 3 and 4 RCGVS is adequately designed, and can provide the safety-grade depressurization capability required for a safe plant operation. 6 refs., 5 figs., 1 tab. (Author)

  17. RCGVS design improvement and depressurization capability tests for Ulchin nuclear power plant units 3 and 4

    Energy Technology Data Exchange (ETDEWEB)

    Sung, Kang Sik; Seong, Ho Je; Jeong, Won Sang; Seo, Jong Tae; Lee, Sang Keun [Korea Power Engineering Company, Inc., Seoul (Korea, Republic of); Lim, Keun Hyo; Choi, Kwon Sik; Oh, Chul Sung [Korea Electric Power Cooperation, Taejon (Korea, Republic of)

    1998-12-31

    The Reactor Coolant Gas Vent System(RCGVS) design for Ulchin Nuclear Power Plant Units 3 and 4 (UCN 3 and 4) has been improved from the Yonggwang Nuclear Power Plant Units 3 and 4 (YGN 3 and 4) based on the evaluation results for depressurization capability tests performed at YGN 3 and 4. There has been a series of plant safety analyses for Natural Circulation Cooldown(NCC) event and thermo-dynamic analyses with RELAP5 code for the steam blowdown phenomena in order to optimize the orifice size of UCN 3 and 4 RCGVS. Based on these analyses results, the RCGVS orifics size for UCN 3 and 4 has been reduced to 9/32 inch from the 11/32 inch for YGN 3 and 4. The depressurization capability tests, which were performed at UCN 3 in order to verify the FSAR NCC analysis results, show that the RCGVS depressurization rates are being within the acceptable ranges. Therefore, it is concluded that the orificed flow path of UCN 3 and 4 RCGVS is adequately designed, and can provide the safety-grade depressurization capability required for a safe plant operation. 6 refs., 5 figs., 1 tab. (Author)

  18. Mesenchymal Stem Cell-Based Tumor-Targeted Gene Therapy in Gastrointestinal Cancer

    OpenAIRE

    Bao, Qi; Zhao, Yue; Niess, Hanno; Conrad, Claudius; Schwarz, Bettina; Jauch, Karl-Walter; Huss, Ralf; Nelson, Peter J.; Bruns, Christiane J.

    2012-01-01

    Mesenchymal stem (or stromal) cells (MSCs) are nonhematopoietic progenitor cells that can be obtained from bone marrow aspirates or adipose tissue, expanded and genetically modified in vitro, and then used for cancer therapeutic strategies in vivo. Here, we review available data regarding the application of MSC-based tumor-targeted therapy in gastrointestinal cancer, provide an overview of the general history of MSC-based gene therapy in cancer research, and discuss potential problems associa...

  19. In vivo tumor targeting of gold nanoparticles: effect of particle type and dosing strategy.

    Science.gov (United States)

    Puvanakrishnan, Priyaveena; Park, Jaesook; Chatterjee, Deyali; Krishnan, Sunil; Tunnell, James W

    2012-01-01

    Gold nanoparticles (GNPs) have gained significant interest as nanovectors for combined imaging and photothermal therapy of tumors. Delivered systemically, GNPs preferentially accumulate at the tumor site via the enhanced permeability and retention effect, and when irradiated with near infrared light, produce sufficient heat to treat tumor tissue. The efficacy of this process strongly depends on the targeting ability of the GNPs, which is a function of the particle's geometric properties (eg, size) and dosing strategy (eg, number and amount of injections). The purpose of this study was to investigate the effect of GNP type and dosing strategy on in vivo tumor targeting. Specifically, we investigated the in vivo tumor-targeting efficiency of pegylated gold nanoshells (GNSs) and gold nanorods (GNRs) for single and multiple dosing. We used Swiss nu/nu mice with a subcutaneous tumor xenograft model that received intravenous administration for a single and multiple doses of GNS and GNR. We performed neutron activation analysis to quantify the gold present in the tumor and liver. We performed histology to determine if there was acute toxicity as a result of multiple dosing. Neutron activation analysis results showed that the smaller GNRs accumulated in higher concentrations in the tumor compared to the larger GNSs. We observed a significant increase in GNS and GNR accumulation in the liver for higher doses. However, multiple doses increased targeting efficiency with minimal effect beyond three doses of GNPs. These results suggest a significant effect of particle type and multiple doses on increasing particle accumulation and on tumor targeting ability.

  20. Integrated nanotechnology platform for tumor-targeted multimodal imaging and therapeutic cargo release.

    Science.gov (United States)

    Hosoya, Hitomi; Dobroff, Andrey S; Driessen, Wouter H P; Cristini, Vittorio; Brinker, Lina M; Staquicini, Fernanda I; Cardó-Vila, Marina; D'Angelo, Sara; Ferrara, Fortunato; Proneth, Bettina; Lin, Yu-Shen; Dunphy, Darren R; Dogra, Prashant; Melancon, Marites P; Stafford, R Jason; Miyazono, Kohei; Gelovani, Juri G; Kataoka, Kazunori; Brinker, C Jeffrey; Sidman, Richard L; Arap, Wadih; Pasqualini, Renata

    2016-02-16

    A major challenge of targeted molecular imaging and drug delivery in cancer is establishing a functional combination of ligand-directed cargo with a triggered release system. Here we develop a hydrogel-based nanotechnology platform that integrates tumor targeting, photon-to-heat conversion, and triggered drug delivery within a single nanostructure to enable multimodal imaging and controlled release of therapeutic cargo. In proof-of-concept experiments, we show a broad range of ligand peptide-based applications with phage particles, heat-sensitive liposomes, or mesoporous silica nanoparticles that self-assemble into a hydrogel for tumor-targeted drug delivery. Because nanoparticles pack densely within the nanocarrier, their surface plasmon resonance shifts to near-infrared, thereby enabling a laser-mediated photothermal mechanism of cargo release. We demonstrate both noninvasive imaging and targeted drug delivery in preclinical mouse models of breast and prostate cancer. Finally, we applied mathematical modeling to predict and confirm tumor targeting and drug delivery. These results are meaningful steps toward the design and initial translation of an enabling nanotechnology platform with potential for broad clinical applications.

  1. Improving Research Reactor Accident Response Capability at the Hungarian Nuclear Safety Authority

    International Nuclear Information System (INIS)

    Vegh, J.; Gajdos, F.; Horvath, Cs.; Matisz, A.; Nyisztor, D.

    2013-06-01

    The paper describes the design and implementation of an on-line operation monitoring and accident response support system to be used at the CERTA emergency response centre of Hungarian Atomic Energy Authority (HAEA). The monitored facility is the Budapest Research Reactor (BRR), which is a tank-type thermal reactor having 10 MW thermal power. The basic reason for the development of the on-line safety information system is to extend the emergency response capability of the CERTA crisis centre to include emergencies related to BRR, as well. CERTA is operated by HAEA at its Budapest headquarters and the centre already has an on-line system for monitoring the state of the four units of Paks NPP, Hungary. The system is called CERTA VITA and it is able to monitor the four VVER-440/V213 units during their normal operation, and during emergencies (including severe accidents). Ensuring appropriate emergency response capabilities, as well as improving the presently available systems and tools was one of the important recommendations resulting from the analyses following the severe accident at Fukushima. This task is valid not only for the operators of the nuclear facilities but also for the nuclear safety authorities, therefore HAEA decided to launch a project - together with the Centre for Energy Research, the operator of BRR - to establish an on-line information system similar to the CERTA VITA used for monitoring the four units of the Paks NPP. It is believed that by the introduction of this new on-line system the accident response capabilities of HAEA will be further enhanced and the BRR emergencies will be handled at the same professional level as potential emergencies at Paks NPP. (authors)

  2. Using simulation to improve the capability of undergraduate nursing students in mental health care.

    Science.gov (United States)

    Kunst, Elicia L; Mitchell, Marion; Johnston, Amy N B

    2017-03-01

    Mental health care is an increasing component of acute patient care and yet mental health care education can be limited in undergraduate nursing programs. The aim of this study was to establish if simulation learning can be an effective method of improving undergraduate nurses' capability in mental health care in an acute care environment. Undergraduate nursing students at an Australian university were exposed to several high-fidelity high-technology simulation activities that incorporated elements of acute emergency nursing practice and acute mental health intervention, scaffolded by theories of learning. This approach provided a safe environment for students to experience clinical practice, and develop their skills for dealing with complex clinical challenges. Using a mixed method approach, the primary domains of interest in this study were student confidence, knowledge and ability. These were self-reported and assessed before and after the simulation activities (intervention) using a pre-validated survey, to gauge the self-rated capacity of students to initiate and complete effective care episodes. Focus group interviews were subsequently held with students who attended placement in the emergency department to explore the impact of the intervention on student performance in this clinical setting. Students who participated in the simulation activity identified and reported significantly increased confidence, knowledge and ability in mental health care post-intervention. They identified key features of the intervention included the impact of its realism on the quality of learning. There is some evidence to suggest that the intervention had an impact on the performance and reflection of students in the clinical setting. This study provides evidence to support the use of simulation to enhance student nurses' clinical capabilities in providing mental health care in acute care environments. Nursing curriculum development should be based on best-evidence to ensure that

  3. Combining Capability Assessment and Value Engineering: a New Two-dimensional Method for Software Process Improvement

    Directory of Open Access Journals (Sweden)

    Pasi Ojala

    2008-02-01

    Full Text Available During the last decades software process improvement (SPI has been recognized as a usable possibility to increase the quality of software development. Implemented SPI investments have often indicated increased process capabilities as well. Recently more attention has been focused on the costs of SPI as well as on the cost-effectiveness and productivity of software development, although the roots of economic-driven software engineering originate from the very early days of software engineering research. This research combines Value Engineering and capability assessment into usable new method in order to better respond to the challenges that cost-effectiveness and productivity has brought to software companies. This is done in part by defining the concepts of value, worth and cost and in part by defining the Value Engineering process and different enhancements it has seen to offer to software assessment. The practical industrial cases show that proposed two-dimensional method works in practise and is useful to assessed companies.

  4. Improved thermal source term generation capability for use in performance assessment and system studies

    International Nuclear Information System (INIS)

    King, J.; Rhodes, C.

    1994-01-01

    This paper describes work performed by the Civilian Radioactive Waste Management System (CRWMS) Management and Operating (M ampersand O) Contractor to improve spent nuclear fuel (SNF) waste stream characterization for system studies. It discusses how these new capabilities may be exploited for thermal source term generation for use in repository performance assessment modeling. SNF historical discharges have been exhaustively tracked, and significant effort has gone into capturing, verifying, and electronically managing spent fuel inventory data. Future discharge projections are produced annually by the Energy Information Administration (EIA) using sophisticated computer models. The output of these models is coupled with annually updated SNF historical discharges to produce what is referred to as the open-quotes reactor database.close quotes This database and related data are published in a variety of ways including on magnetic media for consistent use by analysts or other interested parties

  5. Accuracy Improvement Capability of Advanced Projectile Based on Course Correction Fuze Concept

    Directory of Open Access Journals (Sweden)

    Ahmed Elsaadany

    2014-01-01

    Full Text Available Improvement in terminal accuracy is an important objective for future artillery projectiles. Generally it is often associated with range extension. Various concepts and modifications are proposed to correct the range and drift of artillery projectile like course correction fuze. The course correction fuze concepts could provide an attractive and cost-effective solution for munitions accuracy improvement. In this paper, the trajectory correction has been obtained using two kinds of course correction modules, one is devoted to range correction (drag ring brake and the second is devoted to drift correction (canard based-correction fuze. The course correction modules have been characterized by aerodynamic computations and flight dynamic investigations in order to analyze the effects on deflection of the projectile aerodynamic parameters. The simulation results show that the impact accuracy of a conventional projectile using these course correction modules can be improved. The drag ring brake is found to be highly capable for range correction. The deploying of the drag brake in early stage of trajectory results in large range correction. The correction occasion time can be predefined depending on required correction of range. On the other hand, the canard based-correction fuze is found to have a higher effect on the projectile drift by modifying its roll rate. In addition, the canard extension induces a high-frequency incidence angle as canards reciprocate at the roll motion.

  6. Accuracy improvement capability of advanced projectile based on course correction fuze concept.

    Science.gov (United States)

    Elsaadany, Ahmed; Wen-jun, Yi

    2014-01-01

    Improvement in terminal accuracy is an important objective for future artillery projectiles. Generally it is often associated with range extension. Various concepts and modifications are proposed to correct the range and drift of artillery projectile like course correction fuze. The course correction fuze concepts could provide an attractive and cost-effective solution for munitions accuracy improvement. In this paper, the trajectory correction has been obtained using two kinds of course correction modules, one is devoted to range correction (drag ring brake) and the second is devoted to drift correction (canard based-correction fuze). The course correction modules have been characterized by aerodynamic computations and flight dynamic investigations in order to analyze the effects on deflection of the projectile aerodynamic parameters. The simulation results show that the impact accuracy of a conventional projectile using these course correction modules can be improved. The drag ring brake is found to be highly capable for range correction. The deploying of the drag brake in early stage of trajectory results in large range correction. The correction occasion time can be predefined depending on required correction of range. On the other hand, the canard based-correction fuze is found to have a higher effect on the projectile drift by modifying its roll rate. In addition, the canard extension induces a high-frequency incidence angle as canards reciprocate at the roll motion.

  7. Mach Stability Improvements Using an Existing Second Throat Capability at the National Transonic Facility

    Science.gov (United States)

    Chan, David T.; Balakrishna, Sundareswara; Walker, Eric L.; Goodliff, Scott L.

    2015-01-01

    Recent data quality improvements at the National Transonic Facility have an intended goal of reducing the Mach number variation in a data point to within plus or minus 0.0005, with the ultimate goal of reducing the data repeatability of the drag coefficient for full-span subsonic transport models at transonic speeds to within half a drag count. This paper will discuss the Mach stability improvements achieved through the use of an existing second throat capability at the NTF to create a minimum area at the end of the test section. These improvements were demonstrated using both the NASA Common Research Model and the NTF Pathfinder-I model in recent experiments. Sonic conditions at the throat were verified using sidewall static pressure data. The Mach variation levels from both experiments in the baseline tunnel configuration and the choked tunnel configuration will be presented and the correlation between Mach number and drag will also be examined. Finally, a brief discussion is given on the consequences of using the second throat in its location at the end of the test section.

  8. HST/WFC3: new capabilities, improved IR detector calibrations, and long-term performance stability

    Science.gov (United States)

    MacKenty, John W.; Baggett, Sylvia M.; Brammer, Gabriel; Hilbert, Bryan; Long, Knox S.; McCullough, Peter; Riess, Adam G.

    2014-08-01

    Wide Field Camera 3 (WFC3) is the most used instrument on board the Hubble Space Telescope. Providing a broad range of high quality imaging capabilities from 200 to 1700mn using Silicon CCD and HgCdTe IR detectors, WFC3 is fulfilling both our expectations and its formal requirements. With the re-establishment of the observatory level "spatial scan" capability, we have extended the scientific potential ofWFC3 in multiple directions. These controlled scans, often in combination with low resolution slit-less spectroscopy, enable extremely high precision differential photometric measurements of transiting exo-planets and direct measurement of sources considerably brighter than originally anticipated. In addition, long scans permit the measurement of the separation of star images to accuracies approaching 25 micro-arc seconds (a factor of 10 better than prior FGS or imaging measurements) enables direct parallax observations out to 4 kilo-parsecs. In addition, we have employed this spatial scan capability to both assess and improve the mid­ spatial frequency flat field calibrations. WFC3 uses a Teledyne HgCdTe 1014xl014 pixel Hawaii-lR infrared detector array developed for this mission. One aspect of this detector with implications for many types of science observations is the localized trapping of charge. This manifests itself as both image persistence lasting several hours and as an apparent response variation with photon arrival rate over a large dynamic range. Beyond a generally adopted observing strategy of obtaining multiple observations with small spatial offsets, we have developed a multi-parameter model that accounts for source flux, accumulated signal level, and decay time to predict image persistence at the pixel level. Using a running window through the entirety of the acquired data, we now provide observers with predictions for each individual exposure within several days of its acquisition. Ongoing characterization of the sources on infrared background and

  9. Hybrid Intelligent Control Method to Improve the Frequency Support Capability of Wind Energy Conversion Systems

    Directory of Open Access Journals (Sweden)

    Shin Young Heo

    2015-10-01

    Full Text Available This paper presents a hybrid intelligent control method that enables frequency support control for permanent magnet synchronous generators (PMSGs wind turbines. The proposed method for a wind energy conversion system (WECS is designed to have PMSG modeling and full-scale back-to-back insulated-gate bipolar transistor (IGBT converters comprising the machine and grid side. The controller of the machine side converter (MSC and the grid side converter (GSC are designed to achieve maximum power point tracking (MPPT based on an improved hill climb searching (IHCS control algorithm and de-loaded (DL operation to obtain a power margin. Along with this comprehensive control of maximum power tracking mode based on the IHCS, a method for kinetic energy (KE discharge control of the supporting primary frequency control scheme with DL operation is developed to regulate the short-term frequency response and maintain reliable operation of the power system. The effectiveness of the hybrid intelligent control method is verified by a numerical simulation in PSCAD/EMTDC. Simulation results show that the proposed approach can improve the frequency regulation capability in the power system.

  10. A static VAR compensator model for improved ride-through capability of wind farms

    Energy Technology Data Exchange (ETDEWEB)

    Akhmatov, V.; Soebrink, K.

    2004-12-01

    Dynamic reactive compensation is associated with reactive power and voltage control of induction generator based wind turbines. With regard to wind power, application areas of dynamic reactive compensation can be improvement of the power quality and the voltage stability, the control of the reactive power exchange between the wind farm and the power grid in the wind farm connection point as well as improvement of the ride-through capability of the wind farm. This article presents a model of a Static VAR Compensator (SVC) with dynamic generic control that is a kind of dynamic reactive compensation device. The term 'generic' implies that the model is general and must cover a variety of the SVC units and their specific controls from different manufacturers. The SVC model with dynamic generic control is implemented by Eltra in the simulation tool Powerfactory and validated from the SVC model in the tool PSCAD/EMTDC. Implementation in the tool Powerfactory makes it possible to apply the SVC model with dynamic generic control in investigations of power system stability with regard to establishment of large wind farms without restrictions on the model size of the power grid. (Author)

  11. Hybrid modeling approach to improve the forecasting capability for the gaseous radionuclide in a nuclear site

    International Nuclear Information System (INIS)

    Jeong, Hyojoon; Hwang, Wontae; Kim, Eunhan; Han, Moonhee

    2012-01-01

    Highlights: ► This study is to improve the reliability of air dispersion modeling. ► Tracer experiments assumed gaseous radionuclides were conducted at a nuclear site. ► The performance of a hybrid modeling combined ISC with ANFIS was investigated.. ► Hybrid modeling approach shows better performance rather than a single ISC model. - Abstract: Predicted air concentrations of radioactive materials are important for an environmental impact assessment for the public health. In this study, the performance of a hybrid modeling combined with the industrial source complex (ISC) model and an adaptive neuro-fuzzy inference system (ANFIS) for predicting tracer concentrations was investigated. Tracer dispersion experiments were performed to produce the field data assuming the accidental release of radioactive material. ANFIS was trained in order that the outputs of the ISC model are similar to the measured data. Judging from the higher correlation coefficients between the measured and the calculated ones, the hybrid modeling approach could be an appropriate technique for an improvement of the modeling capability to predict the air concentrations for radioactive materials.

  12. Investing in lean to improve basic capabilities: A strategy for system supply?

    Directory of Open Access Journals (Sweden)

    Inga-Lill Carlsson

    2017-04-01

    Full Text Available Purpose: This paper describes the perceived effects of implementing lean production in a Swedish SME contract manufacturer. Especially focused are the effects on, and possible trade-offs between, cost-efficiency and flexibility. Design/methodology/approach: SME suppliers need basic capabilities of qualitative production performance which may then be stepping-stones to develop more system supplier capabilities for added customer value: leadership to manage systems and processes, SCM, communications and relations management. Development of stable production processes is seen as a way to reach stable basic performance, efficient and with higher resource utilization. Quality is a precursor to delivery performance as well as to cost reduction and flexibility. This is a longitudinal single case study of a SME supplier striving to become a system supplier. Two main sources of data collection are used: interviews and the main author’s presence as employee and business developer, participating in and following up the ongoing change process. Findings: Two specific findings appeared: (1 An initial effect was an important “eye-opener” for the balance between cost efficiency and flexibility in the organization. (2 Process orientation, as the basis of both lean and agile approaches, allows many improvements without any conflicts or trade-offs between these two goals. Stability in the production leads to increased controllability, initially resulting in both higher cost-efficiency and higher flexibility. As the organization develops however, strategic considerations relating to the chosen market strategy might occur: cost leadership or differentiation.    Research limitations/implications: These results reflect the experiences of one SME supplier and further studies are needed for generalizability. Originality/value: The study increases the understanding of how a SME may develop stable processes in its different supplier-customer contexts. The study

  13. Mesenchymal Stem Cell-Based Tumor-Targeted Gene Therapy in Gastrointestinal Cancer

    Science.gov (United States)

    Bao, Qi; Zhao, Yue; Niess, Hanno; Conrad, Claudius; Schwarz, Bettina; Jauch, Karl-Walter; Huss, Ralf; Nelson, Peter J.

    2012-01-01

    Mesenchymal stem (or stromal) cells (MSCs) are nonhematopoietic progenitor cells that can be obtained from bone marrow aspirates or adipose tissue, expanded and genetically modified in vitro, and then used for cancer therapeutic strategies in vivo. Here, we review available data regarding the application of MSC-based tumor-targeted therapy in gastrointestinal cancer, provide an overview of the general history of MSC-based gene therapy in cancer research, and discuss potential problems associated with the utility of MSC-based therapy such as biosafety, immunoprivilege, transfection methods, and distribution in the host. PMID:22530882

  14. RGD-modified poly(D,L-lactic acid nanoparticles enhance tumor targeting of oridonin

    Directory of Open Access Journals (Sweden)

    Xu J

    2012-01-01

    -PLA-NPs or ORI solution. Consistent with these observations, ORI-PLA-RGD-NPs showed greater antitumor efficacy than ORI-PLA-RGD-NPs or ORI solution, as reflected by the decreased tumor growth and the prolonged survival time of mice bearing H22 tumors.Conclusion: The tumor-targeting efficiency and subsequent antitumor efficacy of ORI is increased by incorporation into ORI-PLA-RGD-NPs.Keywords: ORI, antitumor activity, RGD, poly(D,L-lactic acid, nanoparticles

  15. Application of indices Cp and Cpk to improve quality control capability in clinical biochemistry laboratories.

    Science.gov (United States)

    Chen, Ming-Shu; Wu, Ming-Hsun; Lin, Chih-Ming

    2014-04-30

    The traditional criteria for acceptability of analytic quality may not be objective in clinical laboratories. To establish quality control procedures intended to enhance Westgard multi-rules for improving the quality of clinical biochemistry tests, we applied the Cp and Cpk quality-control indices to monitor tolerance fitting and systematic variation of clinical biochemistry test results. Daily quality-control data of a large Taiwanese hospital in 2009 were analyzed. The test items were selected based on an Olympus biochemistry machine and included serum albumin, aspartate aminotransferase, cholesterol, glucose and potassium levels. Cp and Cpk values were calculated for normal and abnormal levels, respectively. The tolerance range was estimated with data from 50 laboratories using the same instruments and reagents. The results showed a monthly trend of variation for the five items under investigation. The index values of glucose were lower than those of the other items, and their values were usually quality control, but also for revealing inter-laboratory qualitycontrol capability differences.

  16. Improvement of RETRAN-MASTER-TORC transient capability and coupling optimization

    International Nuclear Information System (INIS)

    Cho, J. Y.; Song, J. S.; Joo, H. G.; Seo, K. W.; Whang, D. H.; Lee, C. C.; Zee, S. Q.

    2003-11-01

    This work is to improve MASTER-TORC transient calculation capability by complementing the previously developed consolidated code system RETRAN- MASTER-TORC, and to reduce the computing time by coupling optimization. The coupling soundness and optimization performance of the consolidated code system are evaluated by solving a YGN3 control bank ejection accident and the OECD Main Steam Line Break(MSLB) benchmark problems. The YGN3 control bank ejection accident is analyzed by the MASTER-TORC system. Most of all results including the transient core power, peak power and time are similar with those from the MASTER-COBRA system. In the computing time, the MASTER- TORC system is proved to be same as the MASTER-COBRA system, which means the coupling is sound and well-optimized. In the analysis of the OECD MSLB benchmark problem, the RETRAN-MASTER-TORC system shows the very similar results with the RETRAN-MASTER-COBRA system. However, minor differences due to fuel conductivity and thermal capacity model are noticed. In TORC, these parameters are treated as constants, while they are modeled as temperature dependent functions in COBRA. Therefore, in the future, TORC need to complement the temperature dependent thermal properties for accurate fuel and cladding temperature calculation. In the computing time for this problem, RETRAN-MASTER-TORC system shows a little bit faster than COBRA case

  17. Torque capability improvement of sensorless FOC induction machine in field weakening for propulsion purposes

    Directory of Open Access Journals (Sweden)

    Nisha G.K.

    2017-05-01

    Full Text Available An electric propulsion system is generally based on torque controlled electric drive and DC series motors are traditionally used for propulsion system. Induction machines, which are reliable, low cost and have less maintenance, satisfy the characteristics of the propulsion and reinstating the DC series motor. Field oriented control (FOC of induction machines can decouple its torque control from field control which allows the induction motor to act like a separately excited DC motor. In this paper, the characteristic control of induction motor is achieved through appropriate design modification of induction motor by varying magnetizing current to produce maximum torque in field weakening (FW region. Thus to improve the torque capability of induction machine in FW region by varying machine parameters. The sensorless operation of the induction motor is carried out by adopting model reference adaptive system (MRAS using sliding mode control (SMC and a FW algorithm based on the voltage and current constraints. The simulation of the induction motor drive models based on the design options have been carried out and analyzed the simulation results.

  18. Improvement of neutronic calculations on a Masurca core using adaptive mesh refinement capabilities

    International Nuclear Information System (INIS)

    Fournier, D.; Archier, P.; Le Tellier, R.; Suteau, C.

    2011-01-01

    The simulation of 3D cores with homogenized assemblies in transport theory remains time and memory consuming for production calculations. With a multigroup discretization for the energy variable and a discrete ordinate method for the angle, a system of about 10"4 coupled hyperbolic transport equations has to be solved. For these equations, we intend to optimize the spatial discretization. In the framework of the SNATCH solver used in this study, the spatial problem is dealt with by using a structured hexahedral mesh and applying a Discontinuous Galerkin Finite Element Method (DGFEM). This paper shows the improvements due to the development of Adaptive Mesh Refinement (AMR) methods. As the SNATCH solver uses a hierarchical polynomial basis, p−refinement is possible but also h−refinement thanks to non conforming capabilities. Besides, as the flux spatial behavior is highly dependent on the energy, we propose to adapt differently the spatial discretization according to the energy group. To avoid dealing with too many meshes, some energy groups are joined and share the same mesh. The different energy-dependent AMR strategies are compared to each other but also with the classical approach of a conforming and highly refined spatial mesh. This comparison is carried out on different quantities such as the multiplication factor, the flux or the current. The gain in time and memory is shown for 2D and 3D benchmarks coming from the ZONA2B experimental core configuration of the MASURCA mock-up at CEA Cadarache. (author)

  19. Improving the forming capability of laser dynamic forming by using rubber as a forming medium

    Science.gov (United States)

    Shen, Zongbao; Liu, Huixia; Wang, Xiao; Wang, Cuntang

    2016-04-01

    Laser dynamic forming (LDF) is a novel high velocity forming technique, which employs laser-generated shock wave to load the sample. The forming velocity induced by the high energy laser pulse may exceed the critical forming velocity, resulting in the occurrence of premature fracture. To avoid the above premature fracture, rubber is introduced in LDF as a forming medium to prolong the loading duration in this paper. Laser induced shock wave energy is transferred to the sample in different forming stages, so the forming velocity can be kept below the critical forming velocity when the initial laser energy is high for fracture. Bulge forming experiments with and without rubber were performed to study the effect of rubber on loading duration. The experimental results show that, the shock wave energy attenuates during the propagation through the rubber layer, the rubber can avoid the premature fracture. So the plastic deformation can continue, the forming capability of LDF is improved. Due to the severe plastic deformation under rubber compression, adiabatic shear bands (ASB) occur in LDF with rubber. The material softening in ASB leads to the irregular fracture, which is different from the premature fracture pattern (regular fracture) in LDF without rubber. To better understand this deformation behavior, Johnson-Cook model is used to simulate the dynamic response and the evolution of ASB of copper sample. The simulation results also indicate the rubber can prolong the loading duration.

  20. pH-Responsive Tumor-Targetable Theranostic Nanovectors Based on Core Crosslinked (CCL Micelles with Fluorescence and Magnetic Resonance (MR Dual Imaging Modalities and Drug Delivery Performance

    Directory of Open Access Journals (Sweden)

    Sidan Tian

    2016-06-01

    Full Text Available The development of novel theranostic nanovectors is of particular interest in treating formidable diseases (e.g., cancers. Herein, we report a new tumor-targetable theranostic agent based on core crosslinked (CCL micelles, possessing tumor targetable moieties and fluorescence and magnetic resonance (MR dual imaging modalities. An azide-terminated diblock copolymer, N3-POEGMA-b-P(DPA-co-GMA, was synthesized via consecutive atom transfer radical polymerization (ATRP, where OEGMA, DPA, and GMA are oligo(ethylene glycolmethyl ether methacrylate, 2-(diisopropylaminoethyl methacrylate, and glycidyl methacrylate, respectively. The resulting diblock copolymer was further functionalized with DOTA(Gd (DOTA is 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetrakisacetic acid or benzaldehyde moieties via copper(I-catalyzed alkyne-azide cycloaddition (CuAAC chemistry, resulting in the formation of DOTA(Gd-POEGMA-b-P(DPA-co-GMA and benzaldehyde-POEGMA-b-P(DPA-co-GMA copolymers. The resultant block copolymers co-assembled into mixed micelles at neutral pH in the presence of tetrakis[4-(2-mercaptoethoxyphenyl]ethylene (TPE-4SH, which underwent spontaneous crosslinking reactions with GMA residues embedded within the micellar cores, simultaneously switching on TPE fluorescence due to the restriction of intramolecular rotation. Moreover, camptothecin (CPT was encapsulated into the crosslinked cores at neutral pH, and tumor-targeting pH low insertion peptide (pHLIP, sequence: AEQNPIYWARYADWLFTTPLLLLDLALLVDADEGTCG moieties were attached to the coronas through the Schiff base chemistry, yielding a theranostic nanovector with fluorescence and MR dual imaging modalities and tumor-targeting capability. The nanovectors can be efficiently taken up by A549 cells, as monitored by TPE fluorescence. After internalization, intracellular acidic pH triggered the release of loaded CPT, killing cancer cells in a selective manner. On the other hand, the nanovectors labeled with DOTA

  1. Liposomal Tumor Targeting in Drug Delivery Utilizing MMP-2- and MMP-9-Binding Ligands

    Directory of Open Access Journals (Sweden)

    Oula Penate Medina

    2011-01-01

    Full Text Available Nanotechnology offers an alternative to conventional treatment options by enabling different drug delivery and controlled-release delivery strategies. Liposomes being especially biodegradable and in most cases essentially nontoxic offer a versatile platform for several different delivery approaches that can potentially enhance the delivery and targeting of therapies to tumors. Liposomes penetrate tumors spontaneously as a result of fenestrated blood vessels within tumors, leading to known enhanced permeability and subsequent drug retention effects. In addition, liposomes can be used to carry radioactive moieties, such as radiotracers, which can be bound at multiple locations within liposomes, making them attractive carriers for molecular imaging applications. Phage display is a technique that can deliver various high-affinity and selectivity peptides to different targets. In this study, gelatinase-binding peptides, found by phage display, were attached to liposomes by covalent peptide-PEG-PE anchor creating a targeted drug delivery vehicle. Gelatinases as extracellular targets for tumor targeting offer a viable alternative for tumor targeting. Our findings show that targeted drug delivery is more efficient than non-targeted drug delivery.

  2. Improving English Language Arts and Mathematics Teachers' Capabilities for Teaching Integrated Information Literacy Skills

    Science.gov (United States)

    Ballard, Kevin

    2013-01-01

    Teachers in a large Illinois suburban school district will soon have to integrate the teaching of the Common Core State Standards into their content classes and may not feel prepared to do this effectively. Stephenson's definition of capability was used as the conceptual framework for this study, which holds that capable teachers are those who…

  3. Organizational Context and Capabilities for Integrating Care: A Framework for Improvement

    Directory of Open Access Journals (Sweden)

    Jenna M. Evans

    2016-08-01

    Full Text Available Background: Interventions aimed at integrating care have become widespread in healthcare; however, there is significant variability in their success. Differences in organizational contexts and associated capabilities may be responsible for some of this variability. Purpose: This study develops and validates a conceptual framework of organizational capabilities for integrating care, identifies which of these capabilities may be most important, and explores the mechanisms by which they influence integrated care efforts.  Methods: The Context and Capabilities for Integrating Care (CCIC Framework was developed through a literature review, and revised and validated through interviews with leaders and care providers engaged in integrated care networks in Ontario, Canada. Interviews involved open-ended questions and graphic elicitation. Quantitative content analysis was used to summarize the data.  Results: The CCIC Framework consists of eighteen organizational factors in three categories: Basic Structures, People and Values, and Key Processes. The three most important capabilities shaping the capacity of organizations to implement integrated care interventions include Leadership Approach, Clinician Engagement and Leadership, and Readiness for Change. The majority of hypothesized relationships among organizational capabilities involved Readiness for Change and Partnering, emphasizing the complexity, interrelatedness and importance of these two factors to integrated care efforts.  Conclusions: Organizational leaders can use the framework to determine readiness to integrate care, develop targeted change management strategies, and select appropriate partners with overlapping or complementary profiles on key capabilities. Researchers may use the results to test and refine the proposed framework, with a focus on the hypothesized relationships among organizational capabilities and between organizational capabilities and performance outcomes.

  4. Organizational Context and Capabilities for Integrating Care: A Framework for Improvement

    Science.gov (United States)

    Grudniewicz, Agnes; Baker, G. Ross; Wodchis, Walter P.

    2016-01-01

    Background: Interventions aimed at integrating care have become widespread in healthcare; however, there is significant variability in their success. Differences in organizational contexts and associated capabilities may be responsible for some of this variability. Purpose: This study develops and validates a conceptual framework of organizational capabilities for integrating care, identifies which of these capabilities may be most important, and explores the mechanisms by which they influence integrated care efforts. Methods: The Context and Capabilities for Integrating Care (CCIC) Framework was developed through a literature review, and revised and validated through interviews with leaders and care providers engaged in integrated care networks in Ontario, Canada. Interviews involved open-ended questions and graphic elicitation. Quantitative content analysis was used to summarize the data. Results: The CCIC Framework consists of eighteen organizational factors in three categories: Basic Structures, People and Values, and Key Processes. The three most important capabilities shaping the capacity of organizations to implement integrated care interventions include Leadership Approach, Clinician Engagement and Leadership, and Readiness for Change. The majority of hypothesized relationships among organizational capabilities involved Readiness for Change and Partnering, emphasizing the complexity, interrelatedness and importance of these two factors to integrated care efforts. Conclusions: Organizational leaders can use the framework to determine readiness to integrate care, develop targeted change management strategies, and select appropriate partners with overlapping or complementary profiles on key capabilities. Researchers may use the results to test and refine the proposed framework, with a focus on the hypothesized relationships among organizational capabilities and between organizational capabilities and performance outcomes. PMID:28413366

  5. Improving emergency preparedness and crisis management capabilities in transportation : year 2.

    Science.gov (United States)

    2013-03-01

    While disaster preparedness and emergency management have had a high public : profile over the past decade, Hurricane Katrina revealed serious weaknesses in the : United States emergency response capabilities. There is thus much left to do : befor...

  6. Neglected Capabilities in the DoD: Using Agency Theory to Improve Guidance. Policy Analysis Exercise

    National Research Council Canada - National Science Library

    Presley, Doug; Stinton, Anthony

    2008-01-01

    .... Yet the strength and culture of the military services can also create agency problems which interfere with the Secretary of Defense's ability to guide the acquisition of necessary capabilities...

  7. Brain Tumor Targeting of Magnetic Nanoparticles for Potential Drug Delivery: Effect of Administration Route and Magnetic Field Topography

    Science.gov (United States)

    Chertok, Beata; David, Allan E.; Yang, Victor C.

    2011-01-01

    Our previous studies demonstrated feasibility of magnetically-mediated retention of iron-oxide nanoparticles in brain tumors after intravascular administration. The purpose of this study was to elucidate strategies for further improvement of this promising approach. In particular, we explored administration of the nanoparticles via a non-occluded carotid artery as a way to increase the passive exposure of tumor vasculature to nanoparticles for subsequent magnetic entrapment. However, aggregation of nanoparticles in the afferent vasculature interfered with tumor targeting. The magnetic setup employed in our experiments was found to generate a relatively uniform magnetic flux density over a broad range, exposing the region of the afferent vasculature to high magnetic force. To overcome this problem, the magnetic setup was modified with a 9-mm diameter cylindrical NdFeB magnet to exhibit steeper magnetic field topography. Six-fold reduction of the magnetic force at the injection site, achieved with this modification, alleviated the aggregation problem under the conditions of intact carotid blood flow. Using this setup, carotid administration was found to present 1.8-fold increase in nanoparticle accumulation in glioma compared to the intravenous route at 350 mT. This increase was found to be in reasonable agreement with the theoretically estimated 1.9-fold advantage of carotid administration, Rd. The developed approach is expected to present an even greater advantage when applied to drug-loaded nanoparticles exhibiting higher values of Rd. PMID:21763736

  8. A Functional Iron Oxide Nanoparticles Modified with PLA-PEG-DG as Tumor-Targeted MRI Contrast Agent.

    Science.gov (United States)

    Xiong, Fei; Hu, Ke; Yu, Haoli; Zhou, Lijun; Song, Lina; Zhang, Yu; Shan, Xiuhong; Liu, Jianping; Gu, Ning

    2017-08-01

    Tumor targeting could greatly promote the performance of magnetic nanomaterials as MRI (Magnetic Resonance Imaging) agent for tumor diagnosis. Herein, we reported a novel magnetic nanoparticle modified with PLA (poly lactic acid)-PEG (polyethylene glycol)-DG (D-glucosamine) as Tumor-targeted MRI Contrast Agent. In this work, we took use of the D-glucose passive targeting on tumor cells, combining it on PLA-PEG through amide reaction, and then wrapped the PLA-PEG-DG up to the Fe 3 O 4 @OA NPs. The stability and anti phagocytosis of Fe 3 O 4 @OA@PLA-PEG-DG was tested in vitro; the MRI efficiency and toxicity was also detected in vivo. These functional magnetic nanoparticles demonstrated good biocompatibility and stability both in vitro and in vivo. Cell experiments showed that Fe 3 O 4 @OA@PLA-PEG-DG nanoparticles exist good anti phagocytosis and high targetability. In vivo MRI images showed that the contrast effect of Fe 3 O 4 @OA@PLA-PEG-DG nanoparticles prevailed over the commercial non tumor-targeting magnetic nanomaterials MRI agent at a relatively low dose. The DG can validly enhance the tumor-targetting effect of Fe 3 O 4 @OA@PLA-PEG nanoparticle. Maybe MRI agents with DG can hold promise as tumor-targetting development in the future.

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

    Science.gov (United States)

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

    2016-05-01

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

  10. Oligo-branched peptides for tumor targeting: from magic bullets to magic forks.

    Science.gov (United States)

    Falciani, Chiara; Pini, Alessandro; Bracci, Luisa

    2009-02-01

    Selective targeting of tumor cells is the final goal of research and drug discovery for cancer diagnosis, imaging and therapy. After the invention of hybridoma technology, the concept of magic bullet was introduced into the field of oncology, referring to selective killing of tumor cells, by specific antibodies. More recently, small molecules and peptides have also been proposed as selective targeting agents. We analyze the state of the art of tumor-selective agents that are presently available and tested in clinical settings. A novel approach based on 'armed' oligo-branched peptides as tumor targeting agents, is discussed and compared with existing tumor-selective therapies mediated by antibodies, small molecules or monomeric peptides. Oligo-branched peptides could be novel drugs that combine the advantages of antibodies and small molecules.

  11. Canine parvovirus-like particles, a novel nanomaterial for tumor targeting

    Directory of Open Access Journals (Sweden)

    Destito Giuseppe

    2006-02-01

    Full Text Available Abstract Specific targeting of tumor cells is an important goal for the design of nanotherapeutics for the treatment of cancer. Recently, viruses have been explored as nano-containers for specific targeting applications, however these systems typically require modification of the virus surface using chemical or genetic means to achieve tumor-specific delivery. Interestingly, there exists a subset of viruses with natural affinity for receptors on tumor cells that could be exploited for nanotechnology applications. For example, the canine parvovirus (CPV utilizes transferrin receptors (TfRs for binding and cell entry into canine as well as human cells. TfRs are over-expressed by a variety of tumor cells and are widely being investigated for tumor-targeted drug delivery. We explored whether the natural tropism of CPV to TfRs could be harnessed for targeting tumor cells. Towards this goal, CPV virus-like particles (VLPs produced by expression of the CPV-VP2 capsid protein in a baculovirus expression system were examined for attachment of small molecules and delivery to tumor cells. Structural modeling suggested that six lysines per VP2 subunit are presumably addressable for bioconjugation on the CPV capsid exterior. Between 45 and 100 of the possible 360 lysines/particle could be routinely derivatized with dye molecules depending on the conjugation conditions. Dye conjugation also demonstrated that the CPV-VLPs could withstand conditions for chemical modification on lysines. Attachment of fluorescent dyes neither impaired binding to the TfRs nor affected internalization of the 26 nm-sized VLPs into several human tumor cell lines. CPV-VLPs therefore exhibit highly favorable characteristics for development as a novel nanomaterial for tumor targeting.

  12. Multifunctional nanosheets based on folic acid modified manganese oxide for tumor-targeting theranostic application

    Science.gov (United States)

    Hao, Yongwei; Wang, Lei; Zhang, Bingxiang; Zhao, Hongjuan; Niu, Mengya; Hu, Yujie; Zheng, Cuixia; Zhang, Hongling; Chang, Junbiao; Zhang, Zhenzhong; Zhang, Yun

    2016-01-01

    It is highly desirable to develop smart nanocarriers with stimuli-responsive drug-releasing and diagnostic-imaging functions for cancer theranostics. Herein, we develop a reduction and pH dual-responsive tumor theranostic platform based on degradable manganese dioxide (MnO2) nanosheets. The MnO2 nanosheets with a size of 20-60 nm were first synthesized and modified with (3-Aminopropyl) trimethoxysilane (APTMS) to get amine-functionalized MnO2, and then functionalized by NH2-PEG2000-COOH (PEG). The tumor-targeting group, folic acid (FA), was finally conjugated with the PEGylated MnO2 nanosheets. Then, doxorubicin (DOX), a chemotherapeutic agent, was loaded onto the modified nanosheets through a physical adsorption, which was designated as MnO2-PEG-FA/DOX. The prepared MnO2-PEG-FA/DOX nanosheets with good biocompatibility can not only efficiently deliver DOX to tumor cells in vitro and in vivo, leading to enhanced anti-tumor efficiency, but can also respond to a slightly acidic environment and high concentration of reduced glutathione (GSH), which caused degradation of MnO2 into manganese ions enabling magnetic resonance imaging (MRI). The longitudinal relaxation rate r 1 was 2.26 mM-1 s-1 at pH 5.0 containing 2 mM GSH. These reduction and pH dual-responsive biodegradable nanosheets combining efficient MRI and chemotherapy provide a novel and promising platform for tumor-targeting theranostic application.

  13. Innovations that influence the pharmacology of monoclonal antibody guided tumor targeting

    International Nuclear Information System (INIS)

    Schlom, J.; Hand, P.H.; Greiner, J.W.; Colcher, D.; Shrivastav, S.; Carrasquillo, J.A.; Reynolds, J.C.; Larson, S.M.; Raubitschek, A.

    1990-01-01

    Tumor targeting by monoclonal antibodies (MAbs) can be enhanced by (a) increasing the percentage of injected dose taken up by the tumor and/or (b) increasing the tumor:nontumor ratios. Several groups have demonstrated that one can increase tumor to nontumor ratios by the use of antibody fragments or the administration of second antibodies. Several other modalities are also possible: (a) the use of recombinant interferons to up-regulate the expression of specific tumor associated antigens such as carcinoembryonic antigen or TAG-72 on the surface of carcinoma cells and thus increase MAb tumor binding has proved successful in both in vitro and in vivo studies; (b) the intracavitary administration of MAbs. Recent studies have demonstrated that when radiolabeled B72.3 is administered i.p. to patients with carcinoma of the peritoneal cavity, it localizes tumor masses with greater efficiency than does concurrent i.v. administered antibody. Studies involving the comparative pharmacology of intracavitary administration of radiolabeled MAb in patients and several animal models will be discussed; (c) it has been reported that prior exposure of hepatoma to external beam radiation will increase radiolabeled MAb tumor targeting. We and others have not been able to duplicate this phenomenon with a human colon cancer xenograft model and radiolabeled MAbs to two different colon carcinoma associated antigens. The possible reasons for these differences will be discussed; (d) the cloning and expression of recombinant MAbs with human constant regions and subsequent size modification constructs will also undoubtedly alter the pharmacology of MAb tumor binding in both diagnostic and therapeutic applications. 66 references

  14. Improved fault ride through capability of DFIG based wind turbines using synchronous reference frame control based dynamic voltage restorer.

    Science.gov (United States)

    Rini Ann Jerin, A; Kaliannan, Palanisamy; Subramaniam, Umashankar

    2017-09-01

    Fault ride through (FRT) capability in wind turbines to maintain the grid stability during faults has become mandatory with the increasing grid penetration of wind energy. Doubly fed induction generator based wind turbine (DFIG-WT) is the most popularly utilized type of generator but highly susceptible to the voltage disturbances in grid. Dynamic voltage restorer (DVR) based external FRT capability improvement is considered. Since DVR is capable of providing fast voltage sag mitigation during faults and can maintain the nominal operating conditions for DFIG-WT. The effectiveness of the DVR using Synchronous reference frame (SRF) control is investigated for FRT capability in DFIG-WT during both balanced and unbalanced fault conditions. The operation of DVR is confirmed using time-domain simulation in MATLAB/Simulink using 1.5MW DFIG-WT. Copyright © 2017 ISA. Published by Elsevier Ltd. All rights reserved.

  15. ROV: improving remotely operated vehicle (ROV) intervention capabilities for blowout preventer override systems

    Energy Technology Data Exchange (ETDEWEB)

    Lazar, Stephen [Christopher S. Mancini, Tomball, TX (United States)

    2012-07-01

    Events during 2010 have focused attention on increased ROV/BOP Intervention capabilities and standardization of BOP/ROV interfaces in the oil and gas offshore industry. Currently no enforced set standards for ROV intervention panels or manifold types for use on BOP Override systems are specified. The industry offers multiple configurations at present. This abstract will discuss the advantages and disadvantages of the various configurations in existence, trending toward suggested industry standards taking shape as requirements in the near term. Standards for the offshore industry or a set specification must be made to increase safety and functionality of BOP control systems. To date, ROV override capabilities have been added to existing engineered BOP systems. BOP designed closing times were not a critical consideration, only that the access was there to allow for ROV override. Increased ROV flow and pressure capabilities: no current minimum flow requirements for Emergency BOP Override pumps are established. Based on stack valving and configuration, a minimum, 7 gpm may be required to shift valving fully to allow BOP operator function. IADC/API minimum requirements may be proposed at 10 gpm at 3000psi. Based on shear pressures exceeding 3000psi, pressures of 5000psi should be considered. Current intervention skids/pump capabilities will be required if ROVs must achieve API 16D BOP minimum closing times. Remote or isolated accumulation for increased intervention capabilities offers possibilities when ANY ROV of opportunity can trigger a function (such as small inspection type ROVs). Increased volumes will be required. This is critical in functioning stack rams with an ROV of opportunity to achieve API 16D closing times. We now understand that higher flows and pressures are required along with standardization of stab types. Current recommendations: API 17H Hi-Flow manifolds should be added to essential ROV overrides. ROV skids will have a minimum requirement of 10gpm

  16. SAFARI new and improved: extending the capabilities of SPICA's imaging spectrometer

    Science.gov (United States)

    Roelfsema, Peter; Giard, Martin; Najarro, Francisco; Wafelbakker, Kees; Jellema, Willem; Jackson, Brian; Sibthorpe, Bruce; Audard, Marc; Doi, Yasuo; di Giorgio, Anna; Griffin, Matthew; Helmich, Frank; Kamp, Inga; Kerschbaum, Franz; Meyer, Michael; Naylor, David; Onaka, Takashi; Poglitch, Albrecht; Spinoglio, Luigi; van der Tak, Floris; Vandenbussche, Bart

    2014-08-01

    The Japanese SPace Infrared telescope for Cosmology and Astrophysics, SPICA, aims to provide astronomers with a truly new window on the universe. With a large -3 meter class- cold -6K- telescope, the mission provides a unique low background environment optimally suited for highly sensitive instruments limited only by the cosmic background itself. SAFARI, the SpicA FAR infrared Instrument SAFARI, is a Fourier Transform imaging spectrometer designed to fully exploit this extremely low far infrared background environment. The SAFARI consortium, comprised of European and Canadian institutes, has established an instrument reference design based on a Mach-Zehnder interferometer stage with outputs directed to three extremely sensitive Transition Edge Sensor arrays covering the 35 to 210 μm domain. The baseline instrument provides R > 1000 spectroscopic imaging capabilities over a 2' by 2' field of view. A number of modifications to the instrument to extend its capabilities are under investigation. With the reference design SAFARI's sensitivity for many objects is limited not only by the detector NEP but also by the level of broad band background radiation - the zodiacal light for the shorter wavelengths and satellite baffle structures for the longer wavelengths. Options to reduce this background are dedicated masks or dispersive elements which can be inserted in the optics as required. The resulting increase in sensitivity can directly enhance the prime science goals of SAFARI; with the expected enhanced sensitivity astronomers would be in a better position to study thousands of galaxies out to redshift 3 and even many hundreds out to redshifts of 5 or 6. Possibilities to increase the wavelength resolution, at least for the shorter wavelength bands, are investigated as this would significantly enhance SAFARI's capabilities to study star and planet formation in our own galaxy.

  17. Physico-Chemical Strategies to Enhance Stability and Drug Retention of Polymeric Micelles for Tumor-Targeted Drug Delivery

    NARCIS (Netherlands)

    Shi, Y.; Lammers, Twan Gerardus Gertudis Maria; Storm, Gerrit; Hennink, W.E.

    2017-01-01

    Polymeric micelles (PM) have been extensively used for tumor-targeted delivery of hydrophobic anti-cancer drugs. The lipophilic core of PM is naturally suitable for loading hydrophobic drugs and the hydrophilic shell endows them with colloidal stability and stealth properties. Decades of research on

  18. In vivo tumor targeting and imaging with engineered trivalent antibody fragments containing collagen-derived sequences.

    Directory of Open Access Journals (Sweden)

    Angel M Cuesta

    Full Text Available There is an urgent need to develop new and effective agents for cancer targeting. In this work, a multivalent antibody is characterized in vivo in living animals. The antibody, termed "trimerbody", comprises a single-chain antibody (scFv fragment connected to the N-terminal trimerization subdomain of collagen XVIII NC1 by a flexible linker. As indicated by computer graphic modeling, the trimerbody has a tripod-shaped structure with three highly flexible scFv heads radially outward oriented. Trimerbodies are trimeric in solution and exhibited multivalent binding, which provides them with at least a 100-fold increase in functional affinity than the monovalent scFv. Our results also demonstrate the feasibility of producing functional bispecific trimerbodies, which concurrently bind two different ligands. A trimerbody specific for the carcinoembryonic antigen (CEA, a classic tumor-associated antigen, showed efficient tumor targeting after systemic administration in mice bearing CEA-positive tumors. Importantly, a trimerbody that recognizes an angiogenesis-associated laminin epitope, showed excellent tumor localization in several cancer types, including fibrosarcomas and carcinomas. These results illustrate the potential of this new antibody format for imaging and therapeutic applications, and suggest that some laminin epitopes might be universal targets for cancer targeting.

  19. Bioconjugated PLGA-4-arm-PEG branched polymeric nanoparticles as novel tumor targeting carriers

    International Nuclear Information System (INIS)

    Ding Hong; Yong, Ken-Tye; Roy, Indrajit; Hu Rui; Zhao Lingling; Law, Wing-Cheung; Ji Wei; Liu Liwei; Bergey, Earl J; Prasad, Paras N; Wu Fang; Zhao Weiwei

    2011-01-01

    In this study, we have developed a novel carrier, micelle-type bioconjugated PLGA-4-arm-PEG branched polymeric nanoparticles (NPs), for the detection and treatment of pancreatic cancer. These NPs contained 4-arm-PEG as corona, and PLGA as core, the particle surface was conjugated with cyclo(arginine-glycine-aspartate) (cRGD) as ligand for in vivo tumor targeting. The hydrodynamic size of the NPs was determined to be 150-180 nm and the critical micellar concentration (CMC) was estimated to be 10.5 mg l -1 . Our in vitro study shows that these NPs by themselves had negligible cytotoxicity to human pancreatic cancer (Panc-1) and human glioblastoma (U87) cell lines. Near infrared (NIR) microscopy and flow cytometry demonstrated that the cRGD conjugated PLGA-4-arm-PEG polymeric NPs were taken up more efficiently by U87MG glioma cells, over-expressing the α v β 3 integrin, when compared with the non-targeted NPs. Whole body imaging showed that the cRGD conjugated PLGA-4-arm-PEG branched polymeric NPs had the highest accumulation in the pancreatic tumor site of mice at 48 h post-injection. Physical, hematological, and pathological assays indicated low in vivo toxicity of this NP formulation. These studies on the ability of these bioconjugated PLGA-4-arm-PEG polymeric NPs suggest that the prepared polymeric NPs may serve as a promising platform for detection and targeted drug delivery for pancreatic cancer.

  20. Development of tumor-targeted near infrared probes for fluorescence guided surgery.

    Science.gov (United States)

    Kelderhouse, Lindsay E; Chelvam, Venkatesh; Wayua, Charity; Mahalingam, Sakkarapalayam; Poh, Scott; Kularatne, Sumith A; Low, Philip S

    2013-06-19

    Complete surgical resection of malignant disease is the only reliable method to cure cancer. Unfortunately, quantitative tumor resection is often limited by a surgeon's ability to locate all malignant disease and distinguish it from healthy tissue. Fluorescence-guided surgery has emerged as a tool to aid surgeons in the identification and removal of malignant lesions. While nontargeted fluorescent dyes have been shown to passively accumulate in some tumors, the resulting tumor-to-background ratios are often poor, and the boundaries between malignant and healthy tissues can be difficult to define. To circumvent these problems, our laboratory has developed high affinity tumor targeting ligands that bind to receptors that are overexpressed on cancer cells and deliver attached molecules selectively into these cells. In this study, we explore the use of two tumor-specific targeting ligands (i.e., folic acid that targets the folate receptor (FR) and DUPA that targets prostate specific membrane antigen (PSMA)) to deliver near-infrared (NIR) fluorescent dyes specifically to FR and PSMA expressing cancers, thereby rendering only the malignant cells highly fluorescent. We report here that all FR- and PSMA-targeted NIR probes examined bind cultured cancer cells in the low nanomolar range. Moreover, upon intravenous injection into tumor-bearing mice with metastatic disease, these same ligand-NIR dye conjugates render receptor-expressing tumor tissues fluorescent, enabling their facile resection with minimal contamination from healthy tissues.

  1. Hyaluronate tethered, "smart" multiwalled carbon nanotubes for tumor-targeted delivery of doxorubicin.

    Science.gov (United States)

    Datir, Satyajit R; Das, Manasmita; Singh, Raman Preet; Jain, Sanyog

    2012-11-21

    The present study reports the optimized synthesis, physicochemical characterization, and biological evaluation of a novel, multiwalled carbon nanotube-hyaluronic acid (MWCNT-HA) conjugate, complexed with an anticancer agent, Doxorubicin (DOX) via π-π stacking interaction. The therapeutic conjugate was concomitantly labeled with a near-infrared fluorescent dye, Alexa-Flour-647 (AF-647), and radiotracer Technetium-99m ((99m)Tc) to track its whereabouts both in vitro and in vivo via optical and scintigraphic imaging techniques. Covalent functionalization of MWCNTs with HA facilitated their internalization into human lung adenocarcinoma, A549 cells via hyaluronan receptors (HR) mediated endocytosis. Internalized nanotubes showed lysosomal trafficking, followed by low pH-triggered DOX release under endolysosomal conditions. Consequently, DOX-loaded HA-MWCNTs exhibited 3.2 times higher cytotoxicity and increased apoptotic activity than free DOX in equivalent concentrations. Organ distribution studies in Ehlrich ascites tumor (EAT) bearing mice model indicated that tumor specific localization of (99m)Tc-MWCNT-HA-DOX is significantly higher than both free drug and nontargeted MWCNTs. Pharmacodynamic studies in chemically breast-cancer-induced rats showed that the tumor-growth inhibitory effect of HA-MWCNT-DOX was 5 times higher than free DOX in equivalent concentration. DOX delivered through HA-MWCNTs was devoid of any detectable cardiotoxity, hepatotoxicity, or nephrotoxicity. All these promising attributes make HA-MWCNTs a "smart" platform for tumor-targeted delivery of anticancer agents.

  2. Analysis and modeling of localized heat generation by tumor-targeted nanoparticles (Monte Carlo methods)

    Science.gov (United States)

    Sanattalab, Ehsan; SalmanOgli, Ahmad; Piskin, Erhan

    2016-04-01

    We investigated the tumor-targeted nanoparticles that influence heat generation. We suppose that all nanoparticles are fully functionalized and can find the target using active targeting methods. Unlike the commonly used methods, such as chemotherapy and radiotherapy, the treatment procedure proposed in this study is purely noninvasive, which is considered to be a significant merit. It is found that the localized heat generation due to targeted nanoparticles is significantly higher than other areas. By engineering the optical properties of nanoparticles, including scattering, absorption coefficients, and asymmetry factor (cosine scattering angle), the heat generated in the tumor's area reaches to such critical state that can burn the targeted tumor. The amount of heat generated by inserting smart agents, due to the surface Plasmon resonance, will be remarkably high. The light-matter interactions and trajectory of incident photon upon targeted tissues are simulated by MIE theory and Monte Carlo method, respectively. Monte Carlo method is a statistical one by which we can accurately probe the photon trajectories into a simulation area.

  3. Fabrication of a nanocarrier system through self-assembly of plasma protein and its tumor targeting

    International Nuclear Information System (INIS)

    Gong Guangming; Zhi Feng; Wang Kaikai; Tang Xiaolei; Yuan Ahu; Zhao Lili; Ding Dawei; Hu Yiqiao

    2011-01-01

    Human serum albumin (HSA) nanoparticles hold great promise as a nanocarrier system for targeted drug delivery. The objective of this study was to explore the possibility of preparing size controllable albumin nanoparticles using the disulfide bond breaking reagent β-mercaptoethanol (β-ME). The results showed that the protein concentration and temperature had positive effects on the sizes of the albumin nanoparticles, while pH had a negative effect on the rate of nanoparticle formation. The addition of β-ME induced changes in HSA secondary structure and exposed the hydrophobic core of HSA, leading to the formation of nanoparticles. Human serum albumin nanoparticles could be internalized by MCF-7 cells and mainly accumulated in cytoplasm. After injection in tumor bearing mice, the HSA nanoparticles accumulated in tumor tissues, demonstrating the targeting ability of the nanoparticles. Therefore, human serum albumin can be fabricated into nanoparticles by breaking the disulfide bonds and these nanoparticles exhibit high tumor targeting ability. Human serum albumin nanoparticles could be ideal for the targeted delivery of pharmacologically active substances.

  4. RGD-modified lipid disks as drug carriers for tumor targeted drug delivery

    Science.gov (United States)

    Gao, Jie; Xie, Cao; Zhang, Mingfei; Wei, Xiaoli; Yan, Zhiqiang; Ren, Yachao; Ying, Man; Lu, Weiyue

    2016-03-01

    Melittin, the major component of the European bee venom, is a potential anticancer candidate due to its lytic properties. However, in vivo applications of melittin are limited due to its main side effect, hemolysis, especially when applied through intravenous administration. The polyethylene glycol-stabilized lipid disk is a novel type of nanocarrier, and the rim of lipid disks has a high affinity to amphiphilic peptides. In our study, a c(RGDyK) modified lipid disk was developed as a tumor targeted drug delivery system for melittin. Cryo-TEM was used to confirm the shape and size of lipid disks with or without c(RGDyK) modification. In vitro and in vivo hemolysis analyses revealed that the hemolysis effect significantly decreased after melittin associated with lipid disks. Importantly, the results of our in vivo biodistribution and tumor growth inhibitory experiments showed that c(RGDyK) modification increased the distribution of lipid disks in the tumor and the anticancer efficacy of melittin loaded lipid disks. Thus, we successfully achieved a targeted drug delivery system for melittin and other amphiphilic peptides with a good therapeutic effect and low side effects.

  5. Premature drug release of polymeric micelles and its effects on tumor targeting.

    Science.gov (United States)

    Miller, Tobias; Breyer, Sandra; van Colen, Gwenaelle; Mier, Walter; Haberkorn, Uwe; Geissler, Simon; Voss, Senta; Weigandt, Markus; Goepferich, Achim

    2013-03-10

    Based on the enhanced permeability and retention (EPR) effect, nanoparticles are believed to accumulate in tumors. In this conjunction, the stability of drug encapsulation is assumed to be sufficient. For clarification purposes, PEGylated poly-(D,L-lactic acid) (PEG-PDLLA) micelles which incorporated the hydrophobic model drug dechloro-4-iodo-fenofibrate (IFF) were investigated. H2N-PEG-PDLLA was synthesized, coupled to 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) and labeled with 111-indium. From this polymeric species, mixed micelles with H3CO-PEG-PDLLA were prepared which encapsulated the 125-iodine or 131-iodine labeled drug IFF. Bioimaging and biodistribution experiments in healthy and AR42J-tumor bearing mice were carried out to quantify the uptake of the drug and its carrier in single organs. As a result, upon injection of this system, a rapid dissociation of the polymeric carrier and the incorporated drug (system allowed for successful solubilization of the hydrophobic drug by physical incorporation into micelles whereas the tumor targeting properties of the drug delivery system could not be sufficiently shown. Copyright © 2013 Elsevier B.V. All rights reserved.

  6. Enhancing the effect of radionuclide tumor targeting, using lysosomotropic weak bases

    International Nuclear Information System (INIS)

    Sundberg, Asa Liljegren; Steffen, Ann-Charlott

    2007-01-01

    Purpose: The aim of the present study was to investigate if treatment with lysosomotropic weak bases could increase the intracellular retention of radiohalogens and thereby increase the therapeutic effect of radionuclide tumor targeting. Methods and Materials: Four different lysosomotropic bases, chloroquine, ammonium chloride, amantadine, and thioridazine, were investigated for their ability to increase radiohalogen retention in vitro. The two most promising substances, chloroquine and ammonium chloride, were studied in several cell lines (A431, U343MGaCl2:6, SKOV-3, and SKBR-3) in combination with radiolabeled epidermal growth factor (EGF) or the HER2 binding affibody (Z HER2:4 ) 2 . Results: The uptake and retention of radionuclides was found to be substantially increased by simultaneous treatment with the lysosomotropic bases. The effect was, however, more pronounced in the epidermal growth factor:epidermal growth factor receptor (EGF:EGFR) system than in the (Z HER2:4 ) 2 :HER2 system. The therapeutic effect of ammonium chloride treatment combined with 211 At-EGF was also studied. The effect obtained after combined treatment was found to be much better than after 211 At-EGF treatment alone. Conclusions: The encouraging results from the present study indicate that the use of lysosomotropic weak bases is a promising approach for increasing the therapeutic effect of radionuclide targeting with radiohalogens

  7. Hybrid protein-inorganic nanoparticles: From tumor-targeted drug delivery to cancer imaging.

    Science.gov (United States)

    Elzoghby, Ahmed O; Hemasa, Ayman L; Freag, May S

    2016-12-10

    Recently, a great interest has been paid to the development of hybrid protein-inorganic nanoparticles (NPs) for drug delivery and cancer diagnostics in order to combine the merits of both inorganic and protein nanocarriers. This review primarily discusses the most outstanding advances in the applications of the hybrids of naturally-occurring proteins with iron oxide, gadolinium, gold, silica, calcium phosphate NPs, carbon nanotubes, and quantum dots in drug delivery and cancer imaging. Various strategies that have been utilized for the preparation of protein-functionalized inorganic NPs and the mechanisms involved in the drug loading process are discussed. How can the protein functionalization overcome the limitations of colloidal stability, poor dispersibility and toxicity associated with inorganic NPs is also investigated. Moreover, issues relating to the influence of protein hybridization on the cellular uptake, tumor targeting efficiency, systemic circulation, mucosal penetration and skin permeation of inorganic NPs are highlighted. A special emphasis is devoted to the novel approaches utilizing the protein-inorganic nanohybrids in combined cancer therapy, tumor imaging, and theranostic applications as well as stimuli-responsive drug release from the nanohybrids. Copyright © 2016 Elsevier B.V. All rights reserved.

  8. Enhanced tumor targeting of cRGD peptide-conjugated albumin nanoparticles in the BxPC-3 cell line.

    Science.gov (United States)

    Yu, Xinzhe; Song, Yunlong; Di, Yang; He, Hang; Fu, Deliang; Jin, Chen

    2016-08-12

    The emerging albumin nanoparticle brings new hope for the delivery of antitumor drugs. However, a lack of robust tumor targeting greatly limits its application. In this paper, cyclic arginine-glycine-aspartic-conjugated, gemcitabine-loaded human serum albumin nanoparticles (cRGD-Gem-HSA-NPs) were successfully prepared, characterized, and tested in vitro in the BxPC-3 cell line. Initially, 4-N-myristoyl-gemcitabine (Gem-C14) was formed by conjugating myristoyl to the 4-amino group of gemcitabine. Then, cRGD-HSA was synthesized using sulfosuccinimidyl-(4-N-maleimidomethyl)cyclohexane-1-carboxylate (Sulfo-SMCC) cross-linkers. Finally, cRGD-Gem-HSA-NPs were formulated based on the nanoparticle albumin-bound (nab) technology. The resulting NPs were characterized for particle size, zeta potential, morphology, encapsulation efficiency, and drug loading efficiency. In vitro cellular uptake and inhibition studies were conducted to compare Gem-HSA-NPs and cRGD-Gem-HSA-NPs in a human pancreatic cancer cell line (BxPC-3). The cRGD-Gem-HSA-NPs exhibited an average particle size of 160 ± 23 nm. The encapsulation rate and drug loading rate were approximately 83 ± 5.6% and 11 ± 4.2%, respectively. In vitro, the cRGD-anchored NPs exhibited a significantly greater affinity for the BxPC-3 cells compared to non-targeted NPs and free drug. The cRGD-Gem-HSA-NPs also showed the strongest inhibitory effect in the BxPC-3 cells among all the analyzed groups. The improved efficacy of cRGD-Gem-HSA-NPs in the BxPC-3 cell line warrants further in vivo investigations.

  9. A Self-Peeling Vat for Improved Release Capabilities During DLP Materials Processing

    DEFF Research Database (Denmark)

    Pedersen, David Bue; Zhang, Yang; Nielsen, Jakob Skov

    2016-01-01

    for an eased release of the manufactured part from the vat by means of a flexible membrane system. A membrane of fluorinated ethylene polymer will through elastic deformation automatically peel off the part as the part is lifted during layer changes. Peeling has been qualified by means of a truncated inverted...... cone as test geometry. As the cross-sectional diameter of the cone increase throughout the build-job, the geometry will release from the glass based build platform at the point where the peeling force exceed the adhesion force between platform and part. At failure point the lateral surface area...... of the top and bottom of the truncated cone is used as a measure of the performance of the vat with respect to release-capability. This has been tested at increasing manufacturing rates. The new self-peeling vat outperformed industrial state-of-the-art vats by 814% percent....

  10. Improved Trajectory Search Capability for Multi-Rendezvous and Flyby Missions

    Data.gov (United States)

    National Aeronautics and Space Administration — This work made vital improvements to a primitive trajectory search algorithm known as NASA Exhaustive Lambert Lattice Search (NELLS). NELLS was created to work hand...

  11. Accuracy Improvement Capability of Advanced Projectile Based on Course Correction Fuze Concept

    OpenAIRE

    Elsaadany, Ahmed; Wen-jun, Yi

    2014-01-01

    Improvement in terminal accuracy is an important objective for future artillery projectiles. Generally it is often associated with range extension. Various concepts and modifications are proposed to correct the range and drift of artillery projectile like course correction fuze. The course correction fuze concepts could provide an attractive and cost-effective solution for munitions accuracy improvement. In this paper, the trajectory correction has been obtained using two kinds of course corr...

  12. Improvement of voltage holding capability in the 500 keV negative ion source for JT-60SA.

    Science.gov (United States)

    Tanaka, Y; Hanada, M; Kojima, A; Akino, N; Shimizu, T; Ohshima, K; Inoue, T; Watanabe, K; Taniguchi, M; Kashiwagi, M; Umeda, N; Tobari, H; Grisham, L R

    2010-02-01

    Voltage holding capability of JT-60 negative ion source that has a large electrostatic negative ion accelerator with 45 cm x 1.1 m acceleration grids was experimentally examined and improved to realize 500 keV, 22 A, and 100 s D- ion beams for JT-60 Super Advanced. The gap lengths in the acceleration stages were extended to reduce electric fields in a gap between the large grids and at the corner of the support flanges from the original 4-5 to 3-4 kV/mm. As a result, the voltage holding capability without beam acceleration has been successfully improved from 400 to 500 kV. The pulse duration to hold 500 kV reached 40 s of the power supply limitation.

  13. Improving National Capability in Biogeochemical Flux Modelling: the UK Environmental Virtual Observatory (EVOp)

    Science.gov (United States)

    Johnes, P.; Greene, S.; Freer, J. E.; Bloomfield, J.; Macleod, K.; Reaney, S. M.; Odoni, N. A.

    2012-12-01

    The best outcomes from watershed management arise where policy and mitigation efforts are underpinned by strong science evidence, but there are major resourcing problems associated with the scale of monitoring needed to effectively characterise the sources rates and impacts of nutrient enrichment nationally. The challenge is to increase national capability in predictive modelling of nutrient flux to waters, securing an effective mechanism for transferring knowledge and management tools from data-rich to data-poor regions. The inadequacy of existing tools and approaches to address these challenges provided the motivation for the Environmental Virtual Observatory programme (EVOp), an innovation from the UK Natural Environment Research Council (NERC). EVOp is exploring the use of a cloud-based infrastructure in catchment science, developing an exemplar to explore N and P fluxes to inland and coastal waters in the UK from grid to catchment and national scale. EVOp is bringing together for the first time national data sets, models and uncertainty analysis into cloud computing environments to explore and benchmark current predictive capability for national scale biogeochemical modelling. The objective is to develop national biogeochemical modelling capability, capitalising on extensive national investment in the development of science understanding and modelling tools to support integrated catchment management, and supporting knowledge transfer from data rich to data poor regions, The AERC export coefficient model (Johnes et al., 2007) has been adapted to function within the EVOp cloud environment, and on a geoclimatic basis, using a range of high resolution, geo-referenced digital datasets as an initial demonstration of the enhanced national capacity for N and P flux modelling using cloud computing infrastructure. Geoclimatic regions are landscape units displaying homogenous or quasi-homogenous functional behaviour in terms of process controls on N and P cycling

  14. Gossiping Capabilities

    DEFF Research Database (Denmark)

    Mogensen, Martin; Frey, Davide; Guerraoui, Rachid

    Gossip-based protocols are now acknowledged as a sound basis to implement collaborative high-bandwidth content dissemination: content location is disseminated through gossip, the actual contents being subsequently pulled. In this paper, we present HEAP, HEterogeneity Aware gossip Protocol, where...... nodes dynamically adjust their contribution to gossip dissemination according to their capabilities. Using a continuous, itself gossip-based, approximation of relative capabilities, HEAP dynamically leverages the most capable nodes by (a) increasing their fanouts (while decreasing by the same proportion...... declare a high capability in order to augment their perceived quality without contributing accordingly. We evaluate HEAP in the context of a video streaming application on a 236 PlanetLab nodes testbed. Our results shows that HEAP improves the quality of the streaming by 25% over a standard gossip...

  15. Improvement of analytical capabilities of neutron activation analysis laboratory at the Colombian Geological Survey

    Science.gov (United States)

    Parrado, G.; Cañón, Y.; Peña, M.; Sierra, O.; Porras, A.; Alonso, D.; Herrera, D. C.; Orozco, J.

    2016-07-01

    The Neutron Activation Analysis (NAA) laboratory at the Colombian Geological Survey has developed a technique for multi-elemental analysis of soil and plant matrices, based on Instrumental Neutron Activation Analysis (INAA) using the comparator method. In order to evaluate the analytical capabilities of the technique, the laboratory has been participating in inter-comparison tests organized by Wepal (Wageningen Evaluating Programs for Analytical Laboratories). In this work, the experimental procedure and results for the multi-elemental analysis of four soil and four plant samples during participation in the first round on 2015 of Wepal proficiency test are presented. Only elements with radioactive isotopes with medium and long half-lives have been evaluated, 15 elements for soils (As, Ce, Co, Cr, Cs, Fe, K, La, Na, Rb, Sb, Sc, Th, U and Zn) and 7 elements for plants (Br, Co, Cr, Fe, K, Na and Zn). The performance assessment by Wepal based on Z-score distributions showed that most results obtained |Z-scores| ≤ 3.

  16. Improvement of analytical capabilities of neutron activation analysis laboratory at the Colombian Geological Survey

    Energy Technology Data Exchange (ETDEWEB)

    Parrado, G., E-mail: gparrado@sgc.gov.co; Cañón, Y.; Peña, M., E-mail: mlpena@sgc.gov.co; Sierra, O., E-mail: osierra@sgc.gov.co; Porras, A.; Alonso, D.; Herrera, D. C., E-mail: dherrera@sgc.gov.co; Orozco, J. [Colombian Geological Survey, Nuclear Affairs Technical Division, Neutron Activation Analysis Laboratory, Bogota D. C. (Colombia)

    2016-07-07

    The Neutron Activation Analysis (NAA) laboratory at the Colombian Geological Survey has developed a technique for multi-elemental analysis of soil and plant matrices, based on Instrumental Neutron Activation Analysis (INAA) using the comparator method. In order to evaluate the analytical capabilities of the technique, the laboratory has been participating in inter-comparison tests organized by Wepal (Wageningen Evaluating Programs for Analytical Laboratories). In this work, the experimental procedure and results for the multi-elemental analysis of four soil and four plant samples during participation in the first round on 2015 of Wepal proficiency test are presented. Only elements with radioactive isotopes with medium and long half-lives have been evaluated, 15 elements for soils (As, Ce, Co, Cr, Cs, Fe, K, La, Na, Rb, Sb, Sc, Th, U and Zn) and 7 elements for plants (Br, Co, Cr, Fe, K, Na and Zn). The performance assessment by Wepal based on Z-score distributions showed that most results obtained |Z-scores| ≤ 3.

  17. Clinical coaching in primary care: Capable of improving control in patients with type 2 diabetes mellitus?

    Science.gov (United States)

    González-Guajardo, Eduardo Enrique; Salinas-Martínez, Ana María; Botello-García, Antonio; Mathiew-Quiros, Álvaro

    2016-06-01

    Few clinical coaching studies are both endorsed by real cases and focused on reducing suboptimal diabetes control. We evaluated the effectiveness of coaching on improving type 2 diabetes goals after 3 years of implementation in primary care. A cross-sectional study with follow up was conducted during 2008-2011. Coaching consisted of guiding family doctors to improve their clinical abilities, and it was conducted by a medical doctor trained in skill building, experiential learning, and goal setting. Effectiveness was assessed by means of fasting plasma glucose and glycosylated hemoglobin outcomes. The main analysis consisted of 1×3 and 2×3 repeated measures ANOVAs. A significant coaching×time interaction was observed, indicating that the difference in glucose between primary care units with and without coaching increased over time (Wilks' lambda multivariate test, PCoaching increased 1.4 times (95%CI 1.3, 1.5) the possibility of reaching the fasting glucose goal after controlling for baseline values. There was also a significant improvement in glycosylated hemoglobin (Bonferroni-corrected p-value for pairwise comparisons, Pcoaching was found to be worth the effort to improve type 2 diabetes control in primary care. Copyright © 2015 Primary Care Diabetes Europe. Published by Elsevier Ltd. All rights reserved.

  18. Improved Screening Mammogram Workflow by Maximizing PACS Streamlining Capabilities in an Academic Breast Center.

    Science.gov (United States)

    Pham, Ramya; Forsberg, Daniel; Plecha, Donna

    2017-04-01

    The aim of this study was to perform an operational improvement project targeted at the breast imaging reading workflow of mammography examinations at an academic medical center with its associated breast centers and satellite sites. Through careful analysis of the current workflow, two major issues were identified: stockpiling of paperwork and multiple worklists. Both issues were considered to cause significant delays to the start of interpreting screening mammograms. Four workflow changes were suggested (scanning of paperwork, worklist consolidation, use of chat functionality, and tracking of case distribution among trainees) and implemented in July 2015. Timestamp data was collected 2 months before (May-Jun) and after (Aug-Sep) the implemented changes. Generalized linear models were used to analyze the data. The results showed significant improvements for the interpretation of screening mammograms. The average time elapsed for time to open a case reduced from 70 to 28 min (60 % decrease, p workflow for diagnostic mammograms at large unaltered even with increased volume of mammography examinations (31 % increase of 4344 examinations for May-Jun to 5678 examinations for Aug-Sep). In conclusion, targeted efforts to improve the breast imaging reading workflow for screening mammograms in a teaching environment provided significant performance improvements without affecting the workflow of diagnostic mammograms.

  19. A comparison of prostate tumor targeting strategies using magnetic resonance imaging-targeted, transrectal ultrasound-guided fusion biopsy.

    Science.gov (United States)

    Martin, Peter R; Cool, Derek W; Fenster, Aaron; Ward, Aaron D

    2018-03-01

    Magnetic resonance imaging (MRI)-targeted, three-dimensional (3D) transrectal ultrasound (TRUS)-guided prostate biopsy aims to reduce the 21-47% false-negative rate of clinical two-dimensional (2D) TRUS-guided systematic biopsy, but continues to yield false-negative results. This may be improved via needle target optimization, accounting for guidance system errors and image registration errors. As an initial step toward the goal of optimized prostate biopsy targeting, we investigated how needle delivery error impacts tumor sampling probability for two targeting strategies. We obtained MRI and 3D TRUS images from 49 patients. A radiologist and radiology resident assessed these MR images and contoured 81 suspicious regions, yielding tumor surfaces that were registered to 3D TRUS. The biopsy system's root-mean-squared needle delivery error (RMSE) and systematic error were modeled using an isotropic 3D Gaussian distribution. We investigated two different prostate tumor-targeting strategies using (a) the tumor's centroid and (b) a ring in the lateral-elevational plane. For each simulation, targets were spaced at equal arc lengths on a ring with radius equal to the systematic error magnitude. A total of 1000 biopsy simulations were conducted for each tumor, with RMSE and systematic error magnitudes ranging from 1 to 6 mm. The difference in median tumor sampling probability and probability of obtaining a 50% core involvement was determined for ring vs centroid targeting. Our simulation results indicate that ring targeting outperformed centroid targeting in situations where systematic error exceeds RMSE. In these instances, we observed statistically significant differences showing 1-32% improvement in sampling probability due to ring targeting. Likewise, we observed statistically significant differences showing 1-39% improvement in 50% core involvement probability due to ring targeting. Our results suggest that the optimal targeting scheme for prostate biopsy depends on

  20. Improving Neutron Measurement Capabilities; Expanding the Limits of Correlated Neutron Counting

    Energy Technology Data Exchange (ETDEWEB)

    Santi, Peter Angelo [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Geist, William H. [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Dougan, Arden [National Nuclear Security Administration (NNSA), Washington, DC (United States)

    2015-11-05

    A number of technical and practical limitations exist within the neutron correlated counting techniques used in safeguards, especially within the algorithms that are used to process and analyze the detected neutron signals. A multi-laboratory effort is underway to develop new and improved analysis and data processing algorithms based on fundamental physics principles to extract additional or more accurate information about nuclear material bearing items.

  1. Recombinant expression and purification of a tumor-targeted toxin in Bacillus anthracis

    International Nuclear Information System (INIS)

    Bachran, Christopher; Abdelazim, Suzanne; Fattah, Rasem J.; Liu, Shihui; Leppla, Stephen H.

    2013-01-01

    Highlights: ► Non-infectious and protease-deficient Bacillus anthracis protein expression system. ► Successful expression and purification of a tumor-targeted fusion protein drug. ► Very low endotoxin contamination of purified protein. ► Efficient protein secretion simplifies purification. ► Functional anti-tumor fusion protein purified. -- Abstract: Many recombinant therapeutic proteins are purified from Escherichia coli. While expression in E. coli is easily achieved, some disadvantages such as protein aggregation, formation of inclusion bodies, and contamination of purified proteins with the lipopolysaccharides arise. Lipopolysaccharides have to be removed to prevent inflammatory responses in patients. Use of the Gram-positive Bacillus anthracis as an expression host offers a solution to circumvent these problems. Using the multiple protease-deficient strain BH460, we expressed a fusion of the N-terminal 254 amino acids of anthrax lethal factor (LFn), the N-terminal 389 amino acids of diphtheria toxin (DT389) and human transforming growth factor alpha (TGFα). The resulting fusion protein was constitutively expressed and successfully secreted by B. anthracis into the culture supernatant. Purification was achieved by anion exchange chromatography and proteolytic cleavage removed LFn from the desired fusion protein (DT389 fused to TGFα). The fusion protein showed the intended specific cytotoxicity to epidermal growth factor receptor-expressing human head and neck cancer cells. Final analyses showed low levels of lipopolysaccharides, originating most likely from contamination during the purification process. Thus, the fusion to LFn for protein secretion and expression in B. anthracis BH460 provides an elegant tool to obtain high levels of lipopolysaccharide-free recombinant protein.

  2. 188Re labeling and biodistribution of magnetic nanoparticles for the tumor targeting

    International Nuclear Information System (INIS)

    Li Guiping; Zhang Hui; Wang Yongxian; Zhang Chunfu

    2006-01-01

    Objective: To prepare 188 Re labeled monoclonal antibody (Herceptin)-coated magnetic nanoparticles for tumor targeting and to study its biodistribution in mice. Methods: Herceptin and histidine were covalently linked to the amine group upon silica-coated magnetic nanoparticles modified by N-[3-(trimethyoxysilyl)prowl]-ethylenediamine using glutaraldehyde method. The Herceptin-coated magnetic nanoparticles and Herceptin were radiolabeled with 188 Re by a direct labelling method, whereas the histidine-coated magnetic nanoparticles was radiolabeled with 188 Re using fac-[ 188 Re(CO) 3 (H 2 0) 3 ] + as a precursor. The labelling efficiency and immunoreactivity as well as labelling stability were determined. Also, the biodistribution of 188 Re-magnetic and 188 Re-Herceptin-magnetic nanoparticles were observed in mice. Results: Herceptin-coated magnetic nanoparticles was characterized by transmission electron microscope (TEM) with diameter about 60 nm, while histidine-coated magnetic nanoparticles about 30 nm. The labeling efficiency for 188 Re-Herceptin, 188 Re-magnetic nanoparticles and 188 Re-Herceptin-magnetic nanoparticles were all > 90% and had a better stability in vitro. The immunoreactivity of Herceptin linked to magnetic nanoparticles was still high. The biodistribution in mice was shown that 188 Re-magnetic nanoparticles and 188 Re-Herceptin- magnetic nanoparticles had higher radioactivity levels in blood. Magnetic nanoparticles with diameter of 30 or 60 nm had a long half-life in blood stream and were accumulated in liver. Conclusion: The efficiency and stability of labelling Herceptin-coated magnetic nanoparticles and labelling magnetic nanoparticles with 188 Re are suitable for in vivo study in tumor-beating nude mice models. (authors)

  3. Recombinant expression and purification of a tumor-targeted toxin in Bacillus anthracis

    Energy Technology Data Exchange (ETDEWEB)

    Bachran, Christopher; Abdelazim, Suzanne; Fattah, Rasem J.; Liu, Shihui [National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892 (United States); Leppla, Stephen H., E-mail: sleppla@niaid.nih.gov [National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892 (United States)

    2013-01-04

    Highlights: Black-Right-Pointing-Pointer Non-infectious and protease-deficient Bacillus anthracis protein expression system. Black-Right-Pointing-Pointer Successful expression and purification of a tumor-targeted fusion protein drug. Black-Right-Pointing-Pointer Very low endotoxin contamination of purified protein. Black-Right-Pointing-Pointer Efficient protein secretion simplifies purification. Black-Right-Pointing-Pointer Functional anti-tumor fusion protein purified. -- Abstract: Many recombinant therapeutic proteins are purified from Escherichia coli. While expression in E. coli is easily achieved, some disadvantages such as protein aggregation, formation of inclusion bodies, and contamination of purified proteins with the lipopolysaccharides arise. Lipopolysaccharides have to be removed to prevent inflammatory responses in patients. Use of the Gram-positive Bacillus anthracis as an expression host offers a solution to circumvent these problems. Using the multiple protease-deficient strain BH460, we expressed a fusion of the N-terminal 254 amino acids of anthrax lethal factor (LFn), the N-terminal 389 amino acids of diphtheria toxin (DT389) and human transforming growth factor alpha (TGF{alpha}). The resulting fusion protein was constitutively expressed and successfully secreted by B. anthracis into the culture supernatant. Purification was achieved by anion exchange chromatography and proteolytic cleavage removed LFn from the desired fusion protein (DT389 fused to TGF{alpha}). The fusion protein showed the intended specific cytotoxicity to epidermal growth factor receptor-expressing human head and neck cancer cells. Final analyses showed low levels of lipopolysaccharides, originating most likely from contamination during the purification process. Thus, the fusion to LFn for protein secretion and expression in B. anthracis BH460 provides an elegant tool to obtain high levels of lipopolysaccharide-free recombinant protein.

  4. Bioconjugated PLGA-4-arm-PEG branched polymeric nanoparticles as novel tumor targeting carriers

    Energy Technology Data Exchange (ETDEWEB)

    Ding Hong; Yong, Ken-Tye; Roy, Indrajit; Hu Rui; Zhao Lingling; Law, Wing-Cheung; Ji Wei; Liu Liwei; Bergey, Earl J; Prasad, Paras N [Department of Chemistry, Institute for Lasers, Photonics and Biophotonics, University at Buffalo, State University of New York, Buffalo, NY 14260 (United States); Wu Fang [Department of Pharmaceutical Sciences, University at Buffalo, State University of New York, Buffalo, NY 14260 (United States); Zhao Weiwei, E-mail: bergeye@buffalo.edu, E-mail: pnprasad@buffalo.edu [Department of Microbiology and Immunology, University at Buffalo, State University of New York, Buffalo, NY 14215 (United States)

    2011-04-22

    In this study, we have developed a novel carrier, micelle-type bioconjugated PLGA-4-arm-PEG branched polymeric nanoparticles (NPs), for the detection and treatment of pancreatic cancer. These NPs contained 4-arm-PEG as corona, and PLGA as core, the particle surface was conjugated with cyclo(arginine-glycine-aspartate) (cRGD) as ligand for in vivo tumor targeting. The hydrodynamic size of the NPs was determined to be 150-180 nm and the critical micellar concentration (CMC) was estimated to be 10.5 mg l{sup -1}. Our in vitro study shows that these NPs by themselves had negligible cytotoxicity to human pancreatic cancer (Panc-1) and human glioblastoma (U87) cell lines. Near infrared (NIR) microscopy and flow cytometry demonstrated that the cRGD conjugated PLGA-4-arm-PEG polymeric NPs were taken up more efficiently by U87MG glioma cells, over-expressing the {alpha}{sub v{beta}3} integrin, when compared with the non-targeted NPs. Whole body imaging showed that the cRGD conjugated PLGA-4-arm-PEG branched polymeric NPs had the highest accumulation in the pancreatic tumor site of mice at 48 h post-injection. Physical, hematological, and pathological assays indicated low in vivo toxicity of this NP formulation. These studies on the ability of these bioconjugated PLGA-4-arm-PEG polymeric NPs suggest that the prepared polymeric NPs may serve as a promising platform for detection and targeted drug delivery for pancreatic cancer.

  5. Improved mirror coatings for use in the Lyman Ultraviolet to enhance astronomical instrument capabilities

    Science.gov (United States)

    Quijada, Manuel A.; del Hoyo, Javier; Boris, David R.; Walton, Scott G.

    2017-09-01

    This paper will describe efforts at developing broadband mirror coatings with high performance that will extend from infrared wavelengths down to the Far-Ultraviolet (FUV) spectral region. These mirror coatings would be realized by passivating the surface of freshly made aluminum coatings with fluorine ions in order to form a thin AlF3 overcoat that will protect the aluminum from oxidation and, hence, realize the high-reflectance of this material down to its intrinsic cut-off wavelength of 90 nm. Improved reflective coatings for optics, particularly in the FUV region (90-120 nm), could yield dramatically more sensitive instruments and permit more instrument design freedom.

  6. Improving accuracy and capabilities of X-ray fluorescence method using intensity ratios

    Energy Technology Data Exchange (ETDEWEB)

    Garmay, Andrey V., E-mail: andrew-garmay@yandex.ru; Oskolok, Kirill V.

    2017-04-15

    An X-ray fluorescence analysis algorithm is proposed which is based on a use of ratios of X-ray fluorescence lines intensities. Such an analytical signal is more stable and leads to improved accuracy. Novel calibration equations are proposed which are suitable for analysis in a broad range of matrix compositions. To apply the algorithm to analysis of samples containing significant amount of undetectable elements a use of a dependence of a Rayleigh-to-Compton intensity ratio on a total content of these elements is suggested. The technique's validity is shown by analysis of standard steel samples, model metal oxides mixture and iron ore samples.

  7. Hydrogen Addition for Improved Lean Burn Capability on Natural Gas Engine

    Energy Technology Data Exchange (ETDEWEB)

    Andersson, Tobias [Lund Inst. of Technology (Sweden). Dept. of Heat and Power Engineering

    2002-12-01

    Lean burn spark ignition (SI) engines powered by natural gas is an attractive alternative to the Diesel engine, especially in urban traffic, where reduction of tailpipe emissions are of great importance. A major benefit is the large reduction in soot (PM). Lean burn spark ignition (SI) engines yield high fuel conversion efficiency and also relatively low NO{sub x} emissions at full load. In order to improve the engine operating characteristics at lower loads, the {lambda}-value is normally reduced to some degree, with increased NO{sub x} emissions and reduced efficiency as a result. This is a drawback for the lean burn engines, especially in urban applications such as in city buses and distribution trucks for urban use. So, it is desirable to find ways to extend the lean limit at low loads. One way to improve these part load properties is to add hydrogen to the natural gas in order to improve the combustion characteristics of the fuel. It is possible to extend the lean limit of a natural gas engine by addition of hydrogen to the primary fuel. This report presents measurements made on a single cylinder 1.6 liter natural gas engine. Two combustion chambers, one slow and one fast burning, were tested with various amounts of hydrogen (0 to 20 %-vol) added to natural gas. Three operating conditions were investigated for each combustion chamber and each hydrogen content level; idle, wide open throttle (WOT) and a high load condition (simulated turbo charging). For all three operating conditions, the air/fuel ratio was varied between stoichiometric and the lean limit. For each operating point, the ignition timing was swept in order to find maximum brake torque (MBT) timing. In some cases were the ignition timing limited by knock. Heat release rate calculations were made in order to assess the influence of hydrogen addition on burn rate. Addition of hydrogen showed an increase in burn rate for both combustion chambers, resulting in more stable combustion close to the lean

  8. Change of tumor target volume during waiting time for intensity-modulated radiotherapy (IMRT) in nasopharyngeal carcinoma

    International Nuclear Information System (INIS)

    Chen Bo; Yi Junlin; Gao Li; Xu Guozhen; Huang Xiaodong; Zhang Zhong; Luo Jingwei; Li Suyan

    2007-01-01

    Objective: To determine the influence of change in tumor target volume of nasopharyngeal carcinoma (NPC) while waiting for intensity modulated radiation therapy (IMRT). Methods: From March 2005 to December 2005, 31 patients with nasopharyngeal carcinoma received IMRT as the initial treatment at the Cancer Hospital of Chinese Academic of Medical Sciences. The original simulation CT scan was acquired before IMRT planning. A second CT scan was acquired before the start of radiotherapy. Wait- ing time was defined as the duration between CT simulation and start of radiotherapy. CT-CT fusion was used to minimize the error of delineation between the first tumor target volume (GTV) and the second tumor target volume (sGTV). Tumor target volume was calculated by treatment planning system. T test was carried out to analyse the difference between GTV and sGTV. Pearson correlation and multivariate linear regression was used to analyse the influence factor of the change betweent GTV and sGTV. Results: Median waiting time was 18 days (range, 9-27 days). There were significant differences between GTV and sGTV of both primary tumor (P=0.009) and metastatic lymphoma (P=0.005 ). Both Pearson correlation and multivariate linear regression showed that the change of primary tumor target volume had significant correlation with the first tumor target volume but had no significant correlation with the waiting time, sex, age, T stage and N stage (1992 Chinese Fuzhou Staging Classification). Conclusions: Within the range of the waiting time ob- served in our study, large volume primary tumor would have had a significant increase in volume, but whether the therapeutic effect would be influenced or not would need to be proved by study of large number of cases. Patients with large volume tumor should be considered to reduce the influence of waiting time by enlarging gross target volume and clinical targe volume and by neoadjuveant chemotherapy. For avoiding the unnecessary high-dose to normal

  9. The culture of care within psychiatric services: tackling inequalities and improving clinical and organisational capabilities.

    Science.gov (United States)

    Ascoli, Micol; Palinski, Andrea; Owiti, John Arianda; De Jongh, Bertine; Bhui, Kamaldeep S

    2012-09-28

    Cultural Consultation is a clinical process that emerged from anthropological critiques of mental healthcare. It includes attention to therapeutic communication, research observations and research methods that capture cultural practices and narratives in mental healthcare. This essay describes the work of a Cultural Consultation Service (ToCCS) that improves service user outcomes by offering cultural consultation to mental health practitioners. The setting is a psychiatric service with complex and challenging work located in an ethnically diverse inner city urban area. Following a period of 18 months of cultural consultation, we gather the dominant narratives that emerged during our evaluation of our service. These narratives highlight how culture is conceptualized and acted upon in the day-to-day practices of individual health and social care professionals, specialist psychiatric teams and in care systems. The findings reveal common narratives and themes about culture, ethnicity, race and their perceived place and meaningfulness in clinical care. These narratives express underlying assumptions and covert rules for managing, and sometimes negating, dilemmas and difficulties when considering "culture" in the presentation and expression of mental distress. The narratives reveal an overall "culture of understanding cultural issues" and specific "cultures of care". These emerged as necessary foci of intervention to improve service user outcomes. Understanding the cultures of care showed that clinical and managerial over-structuring of care prioritises organisational proficiency, but it leads to inflexibility. Consequently, the care provided is less personalised and less accommodating of cultural issues, therefore, professionals are unable to see or consider cultural influences in recovery.

  10. Capabilities of gravitational surgery for improvement of treatment results in patients with diabetic foot syndrome

    Directory of Open Access Journals (Sweden)

    M B Akhmedov

    2018-06-01

    Full Text Available Aim. Improvement of complex treatment results in patients with diabetic foot syndrome by introducing methods of gravitational surgery and α-lipoic acid. Methods. The results of treatment were analyzed for 558 patients with diabetic foot syndrome treated in Scientific Centre of Surgery named after M.A. Topchubashov (Baku, Azerbaijan from 1988 to 2015. The age varied from 28 to 83 years. The patients included 416 men and 142 women. The control group included 90 patients who at the perioperative period underwent basic therapy including antibiotics, anticoagulants, antiaggregants, dextrans, angioprotectors, spasmolytics, corticosteroids, narcotic and non-narcotic analgesics. The study group included 468 patients, along with traditional therapy receiving efferent methods (plasmapheresis, ultraviolet blood irradiation, ozone therapy and α-lipoic acid. 282 patients of the study group received outpatient treatment and 186 - complex inpatient surgical treatment. A comparative evaluation of the results was performed separately in three groups: angiopathy, neuropathy, angioneuropathy. The results were evaluated by clinical and instrumental examinations before and after treatment (6, 12, 60 months and more. Results. In the study group a satisfactory result of treatment was registered in 85.5% of patients, in the control group - in 62.2%, unsatisfactory in 14.5 and 37.8% of patients, respectively (p=0.046. Conclusion. The use of efferent methods and α-lipoic acid provided prompt elimination of numerous pathogenetic disorders observed in diabetes mellitus, decrease of amputation frequency and improvement of complex surgical treatment results in patients with diabetic foot syndrome.

  11. The culture of care within psychiatric services: tackling inequalities and improving clinical and organisational capabilities

    Directory of Open Access Journals (Sweden)

    Ascoli Micol

    2012-09-01

    Full Text Available Abstract Introduction Cultural Consultation is a clinical process that emerged from anthropological critiques of mental healthcare. It includes attention to therapeutic communication, research observations and research methods that capture cultural practices and narratives in mental healthcare. This essay describes the work of a Cultural Consultation Service (ToCCS that improves service user outcomes by offering cultural consultation to mental health practitioners. The setting is a psychiatric service with complex and challenging work located in an ethnically diverse inner city urban area. Following a period of 18 months of cultural consultation, we gather the dominant narratives that emerged during our evaluation of our service. Results These narratives highlight how culture is conceptualized and acted upon in the day-to-day practices of individual health and social care professionals, specialist psychiatric teams and in care systems. The findings reveal common narratives and themes about culture, ethnicity, race and their perceived place and meaningfulness in clinical care. These narratives express underlying assumptions and covert rules for managing, and sometimes negating, dilemmas and difficulties when considering “culture” in the presentation and expression of mental distress. The narratives reveal an overall “culture of understanding cultural issues” and specific “cultures of care”. These emerged as necessary foci of intervention to improve service user outcomes. Conclusion Understanding the cultures of care showed that clinical and managerial over-structuring of care prioritises organisational proficiency, but it leads to inflexibility. Consequently, the care provided is less personalised and less accommodating of cultural issues, therefore, professionals are unable to see or consider cultural influences in recovery.

  12. Gcg-XTEN: an improved glucagon capable of preventing hypoglycemia without increasing baseline blood glucose.

    Directory of Open Access Journals (Sweden)

    Nathan C Geething

    2010-04-01

    Full Text Available While the majority of current diabetes treatments focus on reducing blood glucose levels, hypoglycemia represents a significant risk associated with insulin treatment. Glucagon plays a major regulatory role in controlling hypoglycemia in vivo, but its short half-life and hyperglycemic effects prevent its therapeutic use for non-acute applications. The goal of this study was to identify a modified form of glucagon suitable for prophylactic treatment of hypoglycemia without increasing baseline blood glucose levels.Through application of the XTEN technology, we report the construction of a glucagon fusion protein with an extended exposure profile (Gcg-XTEN. The in vivo half-life of the construct was tuned to support nightly dosing through design and testing in cynomolgus monkeys. Efficacy of the construct was assessed in beagle dogs using an insulin challenge to induce hypoglycemia. Dose ranging of Gcg-XTEN in fasted beagle dogs demonstrated that the compound was biologically active with a pharmacodynamic profile consistent with the designed half-life. Prophylactic administration of 0.6 nmol/kg Gcg-XTEN to dogs conferred resistance to a hypoglycemic challenge at 6 hours post-dose without affecting baseline blood glucose levels. Consistent with the designed pharmacokinetic profile, hypoglycemia resistance was not observed at 12 hours post-dose. Importantly, the solubility and stability of the glucagon peptide were also significantly improved by fusion to XTEN.The data show that Gcg-XTEN is effective in preventing hypoglycemia without the associated hyperglycemia expected for unmodified glucagon. While the plasma clearance of this Gcg-XTEN has been optimized for overnight dosing, specifically for the treatment of nocturnal hypoglycemia, constructs with significantly longer exposure profiles are feasible. Such constructs may have multiple applications such as allowing for more aggressive insulin treatment regimens, treating hypoglycemia due to insulin

  13. Health Worker Focused Distributed Simulation for Improving Capability of Health Systems in Liberia.

    Science.gov (United States)

    Gale, Thomas C E; Chatterjee, Arunangsu; Mellor, Nicholas E; Allan, Richard J

    2016-04-01

    The main goal of this study was to produce an adaptable learning platform using virtual learning and distributed simulation, which can be used to train health care workers, across a wide geographical area, key safety messages regarding infection prevention control (IPC). A situationally responsive agile methodology, Scrum, was used to develop a distributed simulation module using short 1-week iterations and continuous synchronous plus asynchronous communication including end users and IPC experts. The module contained content related to standard IPC precautions (including handwashing techniques) and was structured into 3 distinct sections related to donning, doffing, and hazard perception training. Using Scrum methodology, we were able to link concepts applied to best practices in simulation-based medical education (deliberate practice, continuous feedback, self-assessment, and exposure to uncommon events), pedagogic principles related to adult learning (clear goals, contextual awareness, motivational features), and key learning outcomes regarding IPC, as a rapid response initiative to the Ebola outbreak in West Africa. Gamification approach has been used to map learning mechanics to enhance user engagement. The developed IPC module demonstrates how high-frequency, low-fidelity simulations can be rapidly designed using scrum-based agile methodology. Analytics incorporated into the tool can help demonstrate improved confidence and competence of health care workers who are treating patients within an Ebola virus disease outbreak region. These concepts could be used in a range of evolving disasters where rapid development and communication of key learning messages are required.

  14. Design of a Control Scheme for Distribution Static Synchronous Compensators with Power-Quality Improvement Capability

    Directory of Open Access Journals (Sweden)

    Pedro Roncero-Sànchez

    2014-04-01

    Full Text Available Electric power systems are among the greatest achievements of the last century. Today, important issues, such as an ever-increasing demand, the flexible and reliable integration of distributed generation or a growth in disturbing loads, must be borne in mind. In this context, smart grids play a key role, allowing better efficiency of power systems. Power electronics provides solutions to the aforementioned matters, since it allows various energy sources to be integrated into smart grids. Nevertheless, the design of the various control schemes that are necessary for the correct operation of the power-electronic interface is a very important issue that must always be taken into consideration. This paper deals with the design of the control system of a distribution static synchronous compensator (DSTATCOM based on flying-capacitor multilevel converters. The control system is tailored to compensate for both voltage sags by means of reactive-power injection and voltage imbalances caused by unbalanced loads. The design of the overall control is carried out by using the root-locus and frequency-response techniques, improving both the transient response and the steady-state error of the closed-loop system. Simulation results obtained using PSCADTM/EMTDCTM (Manitoba Hydro International Ltd., Commerce Drive, Winnipeg, MB, Canada show the resultant voltage regulation.

  15. Graphene–cyclodextrin–cytochrome c layered assembly with improved electron transfer rate and high supramolecular recognition capability

    Energy Technology Data Exchange (ETDEWEB)

    Gong, Cheng-Bin; Guo, Cong-Cong; Jiang, Dan; Tang, Qian, E-mail: qiantang@swu.edu.cn; Liu, Chang-Hua; Ma, Xue-Bing

    2014-06-01

    This study aimed to develop a new graphene-based layered assembly, named graphene–cyclodextrin–cytochrome c with improved electron transfer rate. This assembly has combined high conductivity of graphene nanosheets (GNs), selectively binding properties and electronegativity of cyclodextrins (CDs), as well as electropositivity of cytochrome c (Cyt c). This assembly can also mimic the confined environments of the intermembrane space of mitochondria. A β-cyclodextrin (β-CD) functionalized GN (GN–CD) assembly was initially prepared by a simple wet-chemical strategy, i.e., in situ thermal reduction of graphene oxide with hydrazine hydrate in the presence of β-CD. Cyt c was then intercalated to the GN–CD assembly to form a layered self-assembled structure, GN–CD–Cyt c, through electrostatic interaction. Compared with GNs and GN–CD, GN–CD–Cyt c assembly displayed improved electron transfer rate and high supramolecular recognition capability toward six probe molecules. - Highlights: • A new tertiary layered assembly named GN–CD–Cyt c was prepared. • Compared with GNs and GN–CD, GN–CD–Cyt c shows improved electron transfer rate. • GN–CD–Cyt c displays high supramolecular recognition capability.

  16. Graphene–cyclodextrin–cytochrome c layered assembly with improved electron transfer rate and high supramolecular recognition capability

    International Nuclear Information System (INIS)

    Gong, Cheng-Bin; Guo, Cong-Cong; Jiang, Dan; Tang, Qian; Liu, Chang-Hua; Ma, Xue-Bing

    2014-01-01

    This study aimed to develop a new graphene-based layered assembly, named graphene–cyclodextrin–cytochrome c with improved electron transfer rate. This assembly has combined high conductivity of graphene nanosheets (GNs), selectively binding properties and electronegativity of cyclodextrins (CDs), as well as electropositivity of cytochrome c (Cyt c). This assembly can also mimic the confined environments of the intermembrane space of mitochondria. A β-cyclodextrin (β-CD) functionalized GN (GN–CD) assembly was initially prepared by a simple wet-chemical strategy, i.e., in situ thermal reduction of graphene oxide with hydrazine hydrate in the presence of β-CD. Cyt c was then intercalated to the GN–CD assembly to form a layered self-assembled structure, GN–CD–Cyt c, through electrostatic interaction. Compared with GNs and GN–CD, GN–CD–Cyt c assembly displayed improved electron transfer rate and high supramolecular recognition capability toward six probe molecules. - Highlights: • A new tertiary layered assembly named GN–CD–Cyt c was prepared. • Compared with GNs and GN–CD, GN–CD–Cyt c shows improved electron transfer rate. • GN–CD–Cyt c displays high supramolecular recognition capability

  17. Macromolecular pHPMA-based nanoparticles with cholesterol for solid tumor targeting: behavior in HSA protein environment

    Czech Academy of Sciences Publication Activity Database

    Zhang, X.; Niebuur, B.-J.; Chytil, Petr; Etrych, Tomáš; Filippov, Sergey K.; Kikhney, A.; Wieland, D. C. F.; Svergun, D. I.; Papadakis, C. M.

    2018-01-01

    Roč. 19, č. 2 (2018), s. 470-480 ISSN 1525-7797 R&D Projects: GA ČR(CZ) GC15-10527J; GA MZd(CZ) NV16-28594A; GA MŠk(CZ) LO1507 Institutional support: RVO:61389013 Keywords : polymer carriers * N-(2-hydroxypropyl)methacrylamide * tumor targeting Subject RIV: CD - Macromolecular Chemistry OBOR OECD: Polymer science Impact factor: 5.246, year: 2016

  18. Passive tumor targeting of polymer therapeutics: in vivo imaging of both the polymer carrier and the enzymatically cleavable drug model

    Czech Academy of Sciences Publication Activity Database

    Pola, Robert; Heinrich, A. K.; Mueller, T.; Kostka, Libor; Mäder, K.; Pechar, Michal; Etrych, Tomáš

    2016-01-01

    Roč. 16, č. 11 (2016), s. 1577-1582 ISSN 1616-5187 R&D Projects: GA ČR(CZ) GA15-02986S; GA ČR(CZ) GA16-17207S; GA MŠk(CZ) LO1507 Institutional support: RVO:61389013 Keywords : polymer drug carriers * tumor targeting * enzymatic release Subject RIV: CD - Macromolecular Chemistry Impact factor: 3.238, year: 2016

  19. High molecular weight chitosan derivative polymeric micelles encapsulating superparamagnetic iron oxide for tumor-targeted magnetic resonance imaging

    Directory of Open Access Journals (Sweden)

    Xiao Y

    2015-02-01

    Full Text Available Yunbin Xiao,1,* Zuan Tao Lin,2,* Yanmei Chen,1 He Wang,1 Ya Li Deng,2 D Elizabeth Le,3 Jianguo Bin,1 Meiyu Li,1 Yulin Liao,1 Yili Liu,1 Gangbiao Jiang,2 Jianping Bin1 1State Key Laboratory of Organ Failure Research, Division of Cardiology, Nanfang Hospital, Southern Medical University, Guangzhou, People’s Republic of China; 2Department of Pharmaceutical Engineering, South China Agricultural University, Guangzhou, People’s Republic of China; 3Cardiovascular Division, Oregon Health and Science University, Portland, OR, USA *These authors contributed equally to this work Abstract: Magnetic resonance imaging (MRI contrast agents based on chitosan derivatives have great potential for diagnosing diseases. However, stable tumor-targeted MRI contrast agents using micelles prepared from high molecular weight chitosan derivatives are seldom reported. In this study, we developed a novel tumor-targeted MRI vehicle via superparamagnetic iron oxide nanoparticles (SPIONs encapsulated in self-aggregating polymeric folate-conjugated N-palmitoyl chitosan (FAPLCS micelles. The tumor-targeting ability of FAPLCS/SPIONs was demonstrated in vitro and in vivo. The results of dynamic light scattering experiments showed that the micelles had a relatively narrow size distribution (136.60±3.90 nm and excellent stability. FAPLCS/SPIONs showed low cytotoxicity and excellent biocompatibility in cellular toxicity tests. Both in vitro and in vivo studies demonstrated that FAPLCS/SPIONs bound specifically to folate receptor-positive HeLa cells, and that FAPLCS/SPIONs accumulated predominantly in established HeLa-derived tumors in mice. The signal intensities of T2-weighted images in established HeLa-derived tumors were reduced dramatically after intravenous micelle administration. Our study indicates that FAPLCS/SPION micelles can potentially serve as safe and effective MRI contrast agents for detecting tumors that overexpress folate receptors. Keywords: superparamagnetic

  20. Technical Study on Improvement of Endurance Capability of Limit Short-circuit Current of Charge Control SMART Meter

    Science.gov (United States)

    Li, W. W.; Du, Z. Z.; Yuan, R. m.; Xiong, D. Z.; Shi, E. W.; Lu, G. N.; Dai, Z. Y.; Chen, X. Q.; Jiang, Z. Y.; Lv, Y. G.

    2017-10-01

    Smart meter represents the development direction of energy-saving smart grid in the future. The load switch, one of the core parts of smart meter, should be of high reliability, safety and endurance capability of limit short-circuit current. For this reason, this paper discusses the quick simulation of relationship between attraction and counterforce of load switch without iteration, establishes dual response surface model of attraction and counterforce and optimizes the design scheme of load switch for charge control smart meter, thus increasing electromagnetic attraction and spring counterforce. In this way, this paper puts forward a method to improve the withstand capacity of limit short-circuit current.

  1. Power Quality Improvement and LVRT Capability Enhancement of Wind Farms by Means of an Inductive Filtering Method

    Directory of Open Access Journals (Sweden)

    Yanjian Peng

    2016-04-01

    Full Text Available Unlike the traditional method for power quality improvement and low-voltage ride through (LVRT capability enhancement of wind farms, this paper proposes a new wind power integrated system by means of an inductive filtering method, especially if it contains a grid-connected transformer, a static synchronous compensator (STATCOM and fully-tuned (FT branches. First, the main circuit topology of the new wind power integrated system is presented. Then, the mathematical model is established to reveal the mechanism of harmonic suppression and the reactive compensation of the proposed wind power integrated system, and then the realization conditions of the inductive filtering method is obtained. Further, the control strategy of STATCOM is introduced. Based on the measured data for a real wind farm, the simulation studies are carried out to illustrate the performance of the proposed new wind power integrated system. The results indicate that the new system can not only enhance the LVRT capability of wind farms, but also prevent harmonic components flowing into the primary (grid winding of the grid-connected transformer. Moreover, since the new method can compensate for reactive power in a wind farm, the power factor at the grid side can be improved effectively.

  2. An Innovative Control Strategy to Improve the Fault Ride-Through Capability of DFIGs Based on Wind Energy Conversion Systems

    Directory of Open Access Journals (Sweden)

    Vandai Le

    2016-01-01

    Full Text Available An innovative control strategy is proposed for enhancing the low voltage ride-through (LVRT capability of a doubly fed induction generator based on wind energy conversion systems (DFIG-WECS. Within the proposed control method, the current control loops of the rotor side converter (RSC are developed based on passivity theory. The control scheme for the grid side converter (GSC is designed based on a two-term approach to keep the DC-link voltage close to a given value. The first term based on the maximal voltage of GSC is introduced in the GSC control loops as a reference reactive current. The second one reflecting the instantaneous unbalanced power flow between the RSC and GSC is also introduced in the GSC control loops as a disturbance considering the instantaneous power of the grid filter to compensate the instantaneous rotor power. The effectiveness of the proposed control strategy is verified via time domain simulation of a 2.0 MW-575 V DFIG-WECS using PSCAD/EMTP. Simulation results show that the control of the DFIG with the proposed approach can improve the LVRT capability better than with the conventional one.

  3. Supporting Data for Multifunctional all-in-one drug delivery systems for tumor targeting and sequential release of three different anti-tumor drugs

    Directory of Open Access Journals (Sweden)

    Guowei Wu

    2016-06-01

    Full Text Available Although nanoparticulate drug delivery systems (NDDSs can preferentially accumulate in tumors, active targeting by targeting ligands (e.g. monoclonal antibody is necessary for increasing its targeting efficacy in vivo. We conjugated mAb198.3 on the SiO2@AuNP system surface to make it obtain active targeting efficacy. The FAT1 targeting capability of SiO2@AuNP system is the first issue to be solved. Thus, flow cytometry analysis was attempted to demonstrate that the SiO2@AuNP system could bind to native FAT1 molecules on the surface of Colo205 cells. Also, together with the drug release behavior study of self-decomposable SiO2 NPs, the continuous morphological evolution needed to be clarified. Therefore, to characterize the morphological evolution in vitro, we analyzed the morphology of inner self-decomposable NPs in different time intervals using transmission electron microscopy (TEM. A more comprehensive analysis of this data may be obtained from the article “Multifunctional all-in-one drug delivery systems for tumor targeting and sequential release of three different anti-tumor drugs” in Biomaterials.

  4. Dual actions of albumin packaging and tumor targeting enhance the antitumor efficacy and reduce the cardiotoxicity of doxorubicin in vivo

    Directory of Open Access Journals (Sweden)

    Zheng K

    2015-08-01

    Full Text Available Ke Zheng,1 Rui Li,2 Xiaolei Zhou,2 Ping Hu,2 Yaxin Zhang,2 Yunmei Huang,3 Zhuo Chen,2 Mingdong Huang2 1College of Chemistry, Fuzhou University, Fuzhou, People’s Republic of China; 2State Key Laboratory of Structural Chemistry, Fujian Institute of Research on the Structure of Matter, Chinese Academy of Sciences, Fuzhou, People’s Republic of China; 3Fujian Academy of Integrative Medicine, Fujian University of Traditional Chinese Medicine, Fuzhou, People’s Republic of China Abstract: Doxorubicin (DOX is an effective chemotherapy drug used to treat different types of cancers. However, DOX has severe side effects, especially life-threatening cardiotoxicity. We herein report a new approach to reduce the toxicity of DOX by embedding DOX inside human serum albumin (HSA. HSA is further fused by a molecular biology technique with a tumor-targeting agent, amino-terminal fragment of urokinase (ATF. ATF binds with a high affinity to urokinase receptor, which is a cell-surface receptor overexpressed in many types of tumors. The as-prepared macromolecule complex (ATF–HSA:DOX was not as cytotoxic as free DOX to cells in vitro, and was mainly localized in cell cytosol in contrast to DOX that was localized in cell nuclei. However, in tumor-bearing mice, ATF–HSA:DOX was demonstrated to have an enhanced tumor-targeting and antitumor efficacy compared with free DOX. More importantly, histopathological examinations of the hearts from the mice treated with ATF–HSA:DOX showed a significantly reduced cardiotoxicity compared with hearts from mice treated with free DOX. These results demonstrate the feasibility of this approach in reducing the cardiotoxicity of DOX while strengthening its antitumor efficacy. Such a tumor-targeted albumin packaging strategy can also be applied to other antitumor drugs. Keywords: amino-terminal fragment of urokinase, urokinase receptor, drug carrier, human serum albumin, doxorubicin, cytotoxicity

  5. Chondroitin sulfate-functionalized polyamidoamine as a tumor-targeted carrier for miR-34a delivery.

    Science.gov (United States)

    Chen, Wenqi; Liu, Yong; Liang, Xiao; Huang, Yu; Li, Quanshun

    2017-07-15

    Chondroitin sulfate (CS) was modified on a polyamidoamine dendrimer (PAMAM) through Michael addition to construct a tumor-targeted carrier CS-PAMAM for miR-34a delivery. The derivative CS-PAMAM was demonstrated to achieve an efficient cellular uptake of miR-34a in a CD44-dependent endocytosis way and further facilitate the endosomal escape of miR-34a after 4h. Through the miR-34a delivery, obvious inhibition of cell proliferation could be detected which was attributed to the enhancement of cell apoptosis and cell cycle arrest, and meanwhile the cell migration and invasion has been observed to be inhibited. Finally, the intravenous injection of CS-PAMAM/miR-34a formulation into mice bearing human lung adenocarcinoma cell A549 xenografts could efficiently inhibit the tumor growth and induce the tumor apoptosis owing to the enhanced accumulation of miR-34a in tumor tissue. Overall, CS-PAMAM is potential to be used as a tumor-targeted oligonucleotide carrier for achieving tumor gene therapy. The cationic dendrimer PAMAM was modified by chondroitin sulfate (CS) through Michael addition to construct a tumor-targeted carrier CS-PAMAM for miR-34a delivery. The introduction of CS could achieve an efficient cellular uptake and intracellular transfection of miR-34a in a CD44-dependent endocytosis manner. The miR-34a delivery could execute the anti-proliferation activity by simultaneously inducing cell apoptosis and cell cycle arrest, and also the anti-migration activity. The CS-PAMAM-mediated systemic delivery of miR-34a showed significant inhibition of tumor growth and induction of tumor apoptosis using a mice model of subcutaneously implanted tumors. Copyright © 2017 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

  6. Graphene-cyclodextrin-cytochrome c layered assembly with improved electron transfer rate and high supramolecular recognition capability.

    Science.gov (United States)

    Gong, Cheng-Bin; Guo, Cong-Cong; Jiang, Dan; Tang, Qian; Liu, Chang-Hua; Ma, Xue-Bing

    2014-06-01

    This study aimed to develop a new graphene-based layered assembly, named graphene-cyclodextrin-cytochrome c with improved electron transfer rate. This assembly has combined high conductivity of graphene nanosheets (GNs), selectively binding properties and electronegativity of cyclodextrins (CDs), as well as electropositivity of cytochrome c (Cyt c). This assembly can also mimic the confined environments of the intermembrane space of mitochondria. A β-cyclodextrin (β-CD) functionalized GN (GN-CD) assembly was initially prepared by a simple wet-chemical strategy, i.e., in situ thermal reduction of graphene oxide with hydrazine hydrate in the presence of β-CD. Cyt c was then intercalated to the GN-CD assembly to form a layered self-assembled structure, GN-CD-Cyt c, through electrostatic interaction. Compared with GNs and GN-CD, GN-CD-Cyt c assembly displayed improved electron transfer rate and high supramolecular recognition capability toward six probe molecules. Copyright © 2014 Elsevier B.V. All rights reserved.

  7. Global view of the mechanisms of improved learning and memory capability in mice with music-exposure by microarray.

    Science.gov (United States)

    Meng, Bo; Zhu, Shujia; Li, Shijia; Zeng, Qingwen; Mei, Bing

    2009-08-28

    Music has been proved beneficial to improve learning and memory in many species including human in previous research work. Although some genes have been identified to contribute to the mechanisms, it is believed that the effect of music is manifold, behind which must concern a complex regulation network. To further understand the mechanisms, we exposed the mice to classical music for one month. The subsequent behavioral experiments showed improvement of spatial learning capability and elevation of fear-motivated memory in the mice with music-exposure as compared to the naïve mice. Meanwhile, we applied the microarray to compare the gene expression profiles of the hippocampus and cortex between the mice with music-exposure and the naïve mice. The results showed approximately 454 genes in cortex (200 genes up-regulated and 254 genes down-regulated) and 437 genes in hippocampus (256 genes up-regulated and 181 genes down-regulated) were significantly affected in music-exposing mice, which mainly involved in ion channel activity and/or synaptic transmission, cytoskeleton, development, transcription, hormone activity. Our work may provide some hints for better understanding the effects of music on learning and memory.

  8. Application of data assimilation to improve the forecasting capability of an atmospheric dispersion model for a radioactive plume

    International Nuclear Information System (INIS)

    Jeong, H.J.; Han, M.H.; Hwang, W.T.; Kim, E.H.

    2008-01-01

    Modeling an atmospheric dispersion of a radioactive plume plays an influential role in assessing the environmental impacts caused by nuclear accidents. The performance of data assimilation techniques combined with Gaussian model outputs and measurements to improve forecasting abilities are investigated in this study. Tracer dispersion experiments are performed to produce field data by assuming a radiological emergency. Adaptive neuro-fuzzy inference system (ANFIS) and linear regression filter are considered to assimilate the Gaussian model outputs with measurements. ANFIS is trained so that the model outputs are likely to be more accurate for the experimental data. Linear regression filter is designed to assimilate measurements similar to the ANFIS. It is confirmed that ANFIS could be an appropriate method for an improvement of the forecasting capability of an atmospheric dispersion model in the case of a radiological emergency, judging from the higher correlation coefficients between the measured and the assimilated ones rather than a linear regression filter. This kind of data assimilation method could support a decision-making system when deciding on the best available countermeasures for public health from among emergency preparedness alternatives

  9. Application of Composite Indices for Improving Joint Detection Capabilities of Instrumented Roof Bolt Drills in Underground Mining and Construction

    Science.gov (United States)

    Liu, Wenpeng; Rostami, Jamal; Elsworth, Derek; Ray, Asok

    2018-03-01

    Roof bolts are the dominant method of ground support in mining and tunneling applications, and the concept of using drilling parameters from the bolter for ground characterization has been studied for a few decades. This refers to the use of drilling data to identify geological features in the ground including joints and voids, as well as rock classification. Rock mass properties, including distribution of joints/voids and strengths of rock layers, are critical factors for proper design of ground support to avoid instability. The goal of this research was to improve the capability and sensitivity of joint detection programs based on the updated pattern recognition algorithms in sensing joints with smaller than 3.175 mm (0.125 in.) aperture while reducing the number of false alarms, and discriminating rock layers with different strengths. A set of concrete blocks with different strengths were used to simulate various rock layers, where the gap between the blocks would represent the joints in laboratory tests. Data obtained from drilling through these blocks were analyzed to improve the reliability and precision of joint detection systems. While drilling parameters can be used to detect the gaps, due to low accuracy of the results, new composite indices have been introduced and used in the analysis to improve the detection rates. This paper briefly discusses ongoing research on joint detection by using drilling parameters collected from a roof bolter in a controlled environment. The performances of the new algorithms for joint detection are also examined by comparing their ability to identify existing joints and reducing false alarms.

  10. Biological Evaluation of 99mTc-HYNIC-EDDA/tricine-(Ser)-D4 Peptide for Tumor Targeting.

    Science.gov (United States)

    Kazemi, Ziba; Zahmatkesh, Mona Haddad; Abedi, Seyed Mohammad; Hosseinimehr, Seyed Jalal

    2017-08-24

    D4 small peptide (Leu-Ala-Arg-Leu-Leu-Thr) was selected as an appropriate agent for specific targeting of epidermal growth factor receptor (EGFR). The aim of study was to investigate the 99mTc-labeled D4 peptide for non-small cell lung tumor targeting. HYNIC-(Ser)3-D4 peptide was labeled with 99mTc using mixture of tricine and ethylenediamine diacetic acid (EDDA) as co-ligands. The in vitro cellular uptake of radiolabeled peptide was evaluated by blocking test on human non-small cell lung cancer (A-549) cell line and its biodistribution was evaluated in A-549 xenografted nude mice. This conjugated peptide was labeled with 99mTc in high radiochemical purity and it was highly stable in buffer and serum. The un-blocked to blocked cellular radioactivity ratio was 4- fold that showed a specific binding of this radiolabeled peptide on A-549 cell. Animal biodistribution in A-549 xenografted nude mice showed rapid clearance from blood and other non-target organs. Tumor uptake values as %ID/g (percentage of injection dose per gram of tissue) were 2.47% and 1.30% at 1 and 4 h after injection. This study showed the 99mTc-EDDA/tricine-HYNIC-(Ser)3-D4 peptide had tumor targeting on the non-small cell lung tumor. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  11. Multiple cues on the physiochemical, mesenchymal, and intracellular trafficking interactions with nanocarriers to maximize tumor target efficiency

    Directory of Open Access Journals (Sweden)

    Kim SW

    2015-06-01

    Full Text Available Sang-Woo Kim, Dongwoo Khang Nanomedicine Laboratory, Department of Molecular Medicine, School of Medicine, Gachon University, Incheon, South Korea Abstract: Over the past 60 years, numerous medical strategies have been employed to overcome neoplasms. In fact, with the exception of lung, bronchial, and pancreatic cancers, the 5-year survival rate of most cancers currently exceeds 70%. However, the quality of life of patients during chemotherapy remains unsatisfactory despite the increase in survival rate. The side effects of current chemotherapies stem from poor target efficiency at tumor sites due to the uncontrolled biodistribution of anticancer agents (ie, conventional or current approved nanodrugs. This review discusses the effective physiochemical factors for determining biodistribution of nanocarriers and, ultimately, increasing tumor-targeting probability by avoiding the reticuloendothelial system. Second, stem cell-conjugated nanotherapeutics was addressed to maximize the tumor searching ability and to inhibit tumor growth. Lastly, physicochemical material properties of anticancer nanodrugs were discussed for targeting cellular organelles with modulation of drug-release time. A better understanding of suggested topics will increase the tumor-targeting ability of anticancer drugs and, ultimately, promote the quality of life of cancer patients during chemotherapy. Keywords: cancer, anticancer nanodrugs, mesenchymal stem cell, intracellular trafficking

  12. A pre-protective strategy for precise tumor targeting and efficient photodynamic therapy with a switchable DNA/upconversion nanocomposite.

    Science.gov (United States)

    Yu, Zhengze; Ge, Yegang; Sun, Qiaoqiao; Pan, Wei; Wan, Xiuyan; Li, Na; Tang, Bo

    2018-04-14

    Tumor-specific targeting based on folic acid (FA) is one of the most common and significant approaches in cancer therapy. However, the expression of folate receptors (FRs) in normal tissues will lead to unexpected targeting and unsatisfactory therapeutic effect. To address this issue, we develop a pre-protective strategy for precise tumor targeting and efficient photodynamic therapy (PDT) using a switchable DNA/upconversion nanocomposite, which can be triggered in the acidic tumor microenvironment. The DNA/upconversion nanocomposite is composed of polyacrylic acid (PAA) coated upconversion nanoparticles (UCNPs), the surface of which is modified using FA and chlorin e6 (Ce6) functionalized DNA sequences with different lengths. Initially, FA on the shorter DNA was protected by a longer DNA to prevent the bonding to FRs on normal cells. Once reaching the acidic tumor microenvironment, C base-rich longer DNA forms a C-quadruplex, resulting in the exposure of the FA groups and the bonding of FA and FRs on cancer cell membranes to achieve precise targeting. Simultaneously, the photosensitizer chlorin e6 (Ce6) gets close to the surface of UCNPs, enabling the excitation of Ce6 to generate singlet oxygen ( 1 O 2 ) under near infrared light via Förster resonance energy transfer (FRET). In vivo experiments indicated that higher tumor targeting efficiency was achieved and the tumor growth was greatly inhibited through the pre-protective strategy.

  13. Nano-sized metabolic precursors for heterogeneous tumor-targeting strategy using bioorthogonal click chemistry in vivo.

    Science.gov (United States)

    Lee, Sangmin; Jung, Seulhee; Koo, Heebeom; Na, Jin Hee; Yoon, Hong Yeol; Shim, Man Kyu; Park, Jooho; Kim, Jong-Ho; Lee, Seulki; Pomper, Martin G; Kwon, Ick Chan; Ahn, Cheol-Hee; Kim, Kwangmeyung

    2017-12-01

    Herein, we developed nano-sized metabolic precursors (Nano-MPs) for new tumor-targeting strategy to overcome the intrinsic limitations of biological ligands such as the limited number of biological receptors and the heterogeneity in tumor tissues. We conjugated the azide group-containing metabolic precursors, triacetylated N-azidoacetyl-d-mannosamine to generation 4 poly(amidoamine) dendrimer backbone. The nano-sized dendrimer of Nano-MPs could generate azide groups on the surface of tumor cells homogeneously regardless of cell types via metabolic glycoengineering. Importantly, these exogenously generated 'artificial chemical receptors' containing azide groups could be used for bioorthogonal click chemistry, regardless of phenotypes of different tumor cells. Furthermore, in tumor-bearing mice models, Nano-MPs could be mainly localized at the target tumor tissues by the enhanced permeation and retention (EPR) effect, and they successfully generated azide groups on tumor cells in vivo after an intravenous injection. Finally, we showed that these azide groups on tumor tissues could be used as 'artificial chemical receptors' that were conjugated to bioorthogonal chemical group-containing liposomes via in vivo click chemistry in heterogeneous tumor-bearing mice. Therefore, overall results demonstrated that our nano-sized metabolic precursors could be extensively applied to new alternative tumor-targeting technique for molecular imaging and drug delivery system, regardless of the phenotype of heterogeneous tumor cells. Copyright © 2017 Elsevier Ltd. All rights reserved.

  14. Capability Paternalism

    NARCIS (Netherlands)

    Claassen, R.J.G.|info:eu-repo/dai/nl/269266224

    A capability approach prescribes paternalist government actions to the extent that it requires the promotion of specific functionings, instead of the corresponding capabilities. Capability theorists have argued that their theories do not have much of these paternalist implications, since promoting

  15. Using a Simple Binomial Model to Assess Improvement in Predictive Capability: Sequential Bayesian Inference, Hypothesis Testing, and Power Analysis

    Energy Technology Data Exchange (ETDEWEB)

    Sigeti, David E. [Los Alamos National Laboratory; Pelak, Robert A. [Los Alamos National Laboratory

    2012-09-11

    We present a Bayesian statistical methodology for identifying improvement in predictive simulations, including an analysis of the number of (presumably expensive) simulations that will need to be made in order to establish with a given level of confidence that an improvement has been observed. Our analysis assumes the ability to predict (or postdict) the same experiments with legacy and new simulation codes and uses a simple binomial model for the probability, {theta}, that, in an experiment chosen at random, the new code will provide a better prediction than the old. This model makes it possible to do statistical analysis with an absolute minimum of assumptions about the statistics of the quantities involved, at the price of discarding some potentially important information in the data. In particular, the analysis depends only on whether or not the new code predicts better than the old in any given experiment, and not on the magnitude of the improvement. We show how the posterior distribution for {theta} may be used, in a kind of Bayesian hypothesis testing, both to decide if an improvement has been observed and to quantify our confidence in that decision. We quantify the predictive probability that should be assigned, prior to taking any data, to the possibility of achieving a given level of confidence, as a function of sample size. We show how this predictive probability depends on the true value of {theta} and, in particular, how there will always be a region around {theta} = 1/2 where it is highly improbable that we will be able to identify an improvement in predictive capability, although the width of this region will shrink to zero as the sample size goes to infinity. We show how the posterior standard deviation may be used, as a kind of 'plan B metric' in the case that the analysis shows that {theta} is close to 1/2 and argue that such a plan B should generally be part of hypothesis testing. All the analysis presented in the paper is done with a

  16. Equally sloped X-ray microtomography of living insects with low radiation dose and improved resolution capability

    International Nuclear Information System (INIS)

    Yao, Shengkun; Fan, Jiadong; Zong, Yunbing; Sun, Zhibin; Zhang, Jianhua; Jiang, Huaidong; He, You; Zhou, Guangzhao; Xiao, Tiqiao; Huang, Qingjie

    2016-01-01

    Three-dimensional X-ray imaging of living specimens is challenging due to the limited resolution of conventional absorption contrast X-ray imaging and potential irradiation damage of biological specimens. In this letter, we present microtomography of a living specimen combining phase-contrast imaging and a Fourier-based iterative algorithm termed equally sloped tomography. Non-destructive 3D imaging of an anesthetized living yellow mealworm Tenebrio molitor was demonstrated with a relatively low dose using synchrotron generated X-rays. Based on the high-quality 3D images, branching tracheoles and different tissues of the insect in a natural state were identified and analyzed, demonstrating a significant advantage of the technique over conventional X-ray radiography or histotomy. Additionally, the insect survived without problem after a 1.92-s X-ray exposure and subsequent absorbed radiation dose of ∼1.2 Gy. No notable physiological effects were observed after reviving the insect from anesthesia. The improved static tomographic method demonstrated in this letter shows advantage in the non-destructive structural investigation of living insects in three dimensions due to the low radiation dose and high resolution capability, and offers many potential applications in biological science.

  17. Equally sloped X-ray microtomography of living insects with low radiation dose and improved resolution capability

    Science.gov (United States)

    Yao, Shengkun; Fan, Jiadong; Zong, Yunbing; He, You; Zhou, Guangzhao; Sun, Zhibin; Zhang, Jianhua; Huang, Qingjie; Xiao, Tiqiao; Jiang, Huaidong

    2016-03-01

    Three-dimensional X-ray imaging of living specimens is challenging due to the limited resolution of conventional absorption contrast X-ray imaging and potential irradiation damage of biological specimens. In this letter, we present microtomography of a living specimen combining phase-contrast imaging and a Fourier-based iterative algorithm termed equally sloped tomography. Non-destructive 3D imaging of an anesthetized living yellow mealworm Tenebrio molitor was demonstrated with a relatively low dose using synchrotron generated X-rays. Based on the high-quality 3D images, branching tracheoles and different tissues of the insect in a natural state were identified and analyzed, demonstrating a significant advantage of the technique over conventional X-ray radiography or histotomy. Additionally, the insect survived without problem after a 1.92-s X-ray exposure and subsequent absorbed radiation dose of ˜1.2 Gy. No notable physiological effects were observed after reviving the insect from anesthesia. The improved static tomographic method demonstrated in this letter shows advantage in the non-destructive structural investigation of living insects in three dimensions due to the low radiation dose and high resolution capability, and offers many potential applications in biological science.

  18. Citrus aurantium Naringenin Prevents Osteosarcoma Progression and Recurrence in the Patients Who Underwent Osteosarcoma Surgery by Improving Antioxidant Capability

    Directory of Open Access Journals (Sweden)

    Lirong Zhang

    2018-01-01

    Full Text Available Citrus aurantium is rich in flavonoids, which may prevent osteosarcoma progression, but its related molecular mechanism remains unclear. Flavonoids were extracted from C. aurantium and purified by reparative HPLC. Each fraction was identified by using electrospray ionisation mass spectrometry (ESI-MS. Three main components (naringin, naringenin, and hesperetin were isolated from C. aurantium. Naringenin inhibited the growth of MG-63 cells, whereas naringin and hesperetin had no inhibitory function on cell growth. ROS production was increased in naringin- and hesperetin-treated groups after one day of culture while the level was always lowest in the naringenin-treated group after three days of culture. 95 osteosarcoma patients who underwent surgery were assigned into two groups: naringenin group (NG, received 20 mg naringenin daily, n=47 and control group (CG, received 20 mg placebo daily, n=48. After an average of two-year follow-up, osteosarcoma volumes were smaller in the NG group than in the CG group (P>0.01. The rate of osteosarcoma recurrence was also lower in the NG group than in CG group. ROS levels were lower in the NG group than in the CG group. Thus, naringenin from Citrus aurantium inhibits osteosarcoma progression and local recurrence in the patients who underwent osteosarcoma surgery by improving antioxidant capability.

  19. Citrus aurantium Naringenin Prevents Osteosarcoma Progression and Recurrence in the Patients Who Underwent Osteosarcoma Surgery by Improving Antioxidant Capability.

    Science.gov (United States)

    Zhang, Lirong; Xu, Xiaohua; Jiang, Tiechao; Wu, Kunzhe; Ding, Chuanbo; Liu, Zhen; Zhang, Xuanhe; Yu, Tianhua; Song, Changlong

    2018-01-01

    Citrus aurantium is rich in flavonoids, which may prevent osteosarcoma progression, but its related molecular mechanism remains unclear. Flavonoids were extracted from C. aurantium and purified by reparative HPLC. Each fraction was identified by using electrospray ionisation mass spectrometry (ESI-MS). Three main components (naringin, naringenin, and hesperetin) were isolated from C. aurantium . Naringenin inhibited the growth of MG-63 cells, whereas naringin and hesperetin had no inhibitory function on cell growth. ROS production was increased in naringin- and hesperetin-treated groups after one day of culture while the level was always lowest in the naringenin-treated group after three days of culture. 95 osteosarcoma patients who underwent surgery were assigned into two groups: naringenin group (NG, received 20 mg naringenin daily, n = 47) and control group (CG, received 20 mg placebo daily, n = 48). After an average of two-year follow-up, osteosarcoma volumes were smaller in the NG group than in the CG group ( P > 0.01). The rate of osteosarcoma recurrence was also lower in the NG group than in CG group. ROS levels were lower in the NG group than in the CG group. Thus, naringenin from Citrus aurantium inhibits osteosarcoma progression and local recurrence in the patients who underwent osteosarcoma surgery by improving antioxidant capability.

  20. Equally sloped X-ray microtomography of living insects with low radiation dose and improved resolution capability

    Energy Technology Data Exchange (ETDEWEB)

    Yao, Shengkun; Fan, Jiadong; Zong, Yunbing; Sun, Zhibin; Zhang, Jianhua; Jiang, Huaidong, E-mail: hdjiang@sdu.edu.cn [State Key Laboratory of Crystal Materials, Shandong University, Jinan 250100 (China); He, You; Zhou, Guangzhao; Xiao, Tiqiao [Shanghai Synchrotron Radiation Facility, Shanghai Institute of Applied Physics, Chinese Academy of Sciences, Shanghai 201800 (China); Huang, Qingjie [School of Information Science and Engineering, Shandong University, Jinan 250100 (China)

    2016-03-21

    Three-dimensional X-ray imaging of living specimens is challenging due to the limited resolution of conventional absorption contrast X-ray imaging and potential irradiation damage of biological specimens. In this letter, we present microtomography of a living specimen combining phase-contrast imaging and a Fourier-based iterative algorithm termed equally sloped tomography. Non-destructive 3D imaging of an anesthetized living yellow mealworm Tenebrio molitor was demonstrated with a relatively low dose using synchrotron generated X-rays. Based on the high-quality 3D images, branching tracheoles and different tissues of the insect in a natural state were identified and analyzed, demonstrating a significant advantage of the technique over conventional X-ray radiography or histotomy. Additionally, the insect survived without problem after a 1.92-s X-ray exposure and subsequent absorbed radiation dose of ∼1.2 Gy. No notable physiological effects were observed after reviving the insect from anesthesia. The improved static tomographic method demonstrated in this letter shows advantage in the non-destructive structural investigation of living insects in three dimensions due to the low radiation dose and high resolution capability, and offers many potential applications in biological science.

  1. Exploring the potential of a multi-level approach to improve capability for continuous organizational improvement and learning in a Swedish healthcare region.

    Science.gov (United States)

    Nyström, M E; Höög, E; Garvare, R; Andersson Bäck, M; Terris, D D; Hansson, J

    2018-05-24

    Eldercare and care of people with functional impairments is organized by the municipalities in Sweden. Improving care in these areas is complex, with multiple stakeholders and organizations. Appropriate strategies to develop capability for continuing organizational improvement and learning (COIL) are needed. The purpose of our study was to develop and pilot-test a flexible, multilevel approach for COIL capability building and to identify what it takes to achieve changes in key actors' approaches to COIL. The approach, named "Sustainable Improvement and Development through Strategic and Systematic Approaches" (SIDSSA), was applied through an action-research and action-learning intervention. The SIDSSA approach was tested in a regional research and development (R&D) unit, and in two municipalities handling care of the elderly and people with functional impairments. Our approach included a multilevel strategy, development loops of five flexible phases, and an action-learning loop. The approach was designed to support systems understanding, strategic focus, methodological practices, and change process knowledge - all of which required double-loop learning. Multiple qualitative methods, i.e., repeated interviews, process diaries, and documents, provided data for conventional content analyses. The new approach was successfully tested on all cases and adopted and sustained by the R&D unit. Participants reported new insights and skills. The development loop facilitated a sense of coherence and control during uncertainty, improved planning and problem analysis, enhanced mapping of context and conditions, and supported problem-solving at both the individual and unit levels. The systems-level view and structured approach helped participants to explain, motivate, and implement change initiatives, especially after working more systematically with mapping, analyses, and goal setting. An easily understood and generalizable model internalized by key organizational actors is an

  2. Substrate decoration for improvement of current-carrying capabilities of YBa2Cu3Ox thin films

    International Nuclear Information System (INIS)

    Khoryushin, Alexey V.; Mozhaev, Peter B.; Mozhaeva, Julia E.; Bdikin, Igor K.; Zhao, Yue; Andersen, Niels H.; Jacobsen, Claus S.; Hansen, Jørn Bindslev

    2013-01-01

    Highlights: ► Effects of substrate decoration on properties of YBCO thin films were studied. ► Y 2 O 3 nanoparticles, ultra-thin Y 2 O 3 and Y:ZrO 2 layers were used as decoration layer. ► Decoration improves j C (5 T and 50 K) up to 0.97 MA/cm 2 vs. 0.76 MA/cm 2 for a reference film. ► Ultra-thin layer of yttria and yttria nanoparticles have a similar effect on YBCO. ► Y 2 O 3 decoration results in power law coefficient α = 0.3 vs. α = 0.4 for a reference film. -- Abstract: The effects of substrate decoration with yttria and Y:ZrO 2 on the structural and electrical properties of the YBa 2 Cu 3 O x (YBCO) thin films are studied. The films were deposited on (LaAlO 3 ) 3 –(Sr 2 AlTaO 8 ) 7 substrates by pulsed laser deposition. Two different structures of decoration layer were applied, a template layer of nanoparticles and an uniform ultra-thin layer. Significant improvement of current-carrying capabilities was observed, especially at high external magnetic fields. Structural studies of these films reveal the presence of extended linear defects in the YBCO matrix. The formation of these structures is attributed to seeding of randomly oriented YBCO grains due to suppression of epitaxy in the very beginning of the deposition. The films of both kinds of decoration layers show nearly the same improvement of j C over the reference film at 77 and 50 K: j C (5T and 50 K) reaches 0.92 and 0.97 MA/cm 2 for uniform and template decoration layers. At 5 and 20 K the effect of template decoration layers is more beneficial: j C (5T and 20 K) values are 3.5 and 4.1 MA/cm 2 , j C (5T and 5 K) values are 6.4 and 7.9 MA/cm 2 , for uniform and template decoration layers, respectively

  3. Imitation-tumor targeting based on continuous-wave near-infrared tomography.

    Science.gov (United States)

    Liu, Dan; Liu, Xin; Zhang, Yan; Wang, Qisong; Lu, Jingyang; Sun, Jinwei

    2017-12-01

    Continuous-wave Near-Infrared (NIR) optical spectroscopy has shown great diagnostic capability in the early tumor detection with advantages of low-cost, portable, non-invasive, and non-radiative. In this paper, Modified Lambert-Beer Theory is deployed to address the low-resolution issues of the NIR technique and to design the tumor detecting and imaging system. Considering that tumor tissues have features such as high blood flow and hypoxia, the proposed technique can detect the location, size, and other information of the tumor tissues by comparing the absorbance between pathological and normal tissues. Finally, the tumor tissues can be imaged through tomographic method. The simulation experiments prove that the proposed technique and designed system can efficiently detect the tumor tissues, achieving imaging precision within 1 mm. The work of the paper has shown great potential in the diagnosis of tumor close to body surface.

  4. Recent Developments in Active Tumor Targeted Multifunctional Nanoparticles for Combination Chemotherapy in Cancer Treatment and Imaging

    Science.gov (United States)

    Glasgow, Micah D. K.; Chougule, Mahavir B.

    2016-01-01

    Nanotechnology and combination therapy are two major fields that show great promise in the treatment of cancer. The delivery of drugs via nanoparticles helps to improve drug’s therapeutic effectiveness while reducing adverse side effects associated with high dosage by improving their pharmacokinetics. Taking advantage of molecular markers over-expressing on tumor tissues compared to normal cells, an “active” molecular marker targeted approach would be beneficial for cancer therapy. These actively targeted nanoparticles would increase drug concentration at the tumor site, improving efficacy while further reducing chemo-resistance. The multidisciplinary approach may help to improve the overall efficacy in cancer therapy. This review article summarizes recent developments of targeted multifunctional nanoparticles in the delivery of various drugs for a combinational chemotherapy approach to cancer treatment and imaging. PMID:26554150

  5. Improved the lithium storage capability of BaLi2Ti6O14 by electroless silver coating

    International Nuclear Information System (INIS)

    Lin, Xiaoting; Wang, Pengfei; Li, Peng; Yu, Haoxiang; Qian, Shangshu; Shui, Miao; Wang, Dongjie; Long, Nengbing; Shu, Jie

    2015-01-01

    Highlights: • BaLi 2 Ti 6 O 14 /Ag is fabricated via a facile electroless deposition. • Highly dispersed Ag nanoparticles are successively coated on BaLi 2 Ti 6 O 14 . • BaLi 2 Ti 6 O 14 /Ag is used as anode material for lithium storage. • BaLi 2 Ti 6 O 14 /Ag exhibits improved lithium storage capability. - Abstract: To form BaLi 2 Ti 6 O 14 /Ag, highly dispersed Ag nanoparticles are successfully deposited on the surface of BaLi 2 Ti 6 O 14 by a simple chemical deposition method. The morphology, quantity and size of Ag nanoparticles in BaLi 2 Ti 6 O 14 /Ag composites are significantly influenced by the Ag coating contents. Electrochemical results show that Ag nanoparticles play a positive role in reducing redox polarization and improving electrical conductivity of BaLi 2 Ti 6 O 14 during lithiation/delithiation processes. Among all the as-obtained products, 6 wt.% Ag coated BaLi 2 Ti 6 O 14 shows the highest initial charge specific capacity of 160 mAh g −1 at the current density of 100 mA g −1 (1C), which is much higher than the 149.1 mAh g −1 for bare BaLi 2 Ti 6 O 14 . After 100 charge/discharge cycles, the reversible capacity can be maintained at 117.0 mAh g −1 . Moreover, this sample also shows excellent rate performance with high reversible charge capacities of 147.5, 139.7, 132.6, and 126.7 mAh g −1 at the rates of 2C, 3C, 4C and 5C, respectively. Compared with bare BaLi 2 Ti 6 O 14 , the superior electrochemical performance indicates that BaLi 2 Ti 6 O 14 /Ag can be a good anode material in lithium ion batteries.

  6. Intrinsically active nanobody-modified polymeric micelles for tumor-targeted combination therapy

    NARCIS (Netherlands)

    Talelli, M.; Oliveira, S.; Rijcken, C.J.; Pieters, E.H.; Etrych, T.; Ulbrich, K.; van Nostrum, C.F.; Storm, Gerrit; Hennink, W.E.; Lammers, Twan Gerardus Gertudis Maria

    2013-01-01

    Various different passively and actively targeted nanomedicines have been designed and evaluated over the years, in particular for the treatment of cancer. Reasoning that the potential of ligand-modified nanomedicines can be substantially improved if intrinsically active targeting moieties are used,

  7. In Vivo Tumor Targeting by the B-Subunit of Shiga Toxin

    Directory of Open Access Journals (Sweden)

    Thomas Viel

    2008-11-01

    Full Text Available Delivery of drugs to the appropriate target cells would improve efficacy and reduce potential side effects. The nontoxic B-subunit of the intestinal pathogen-produced Shiga toxin (STxB binds specifically to the glycosphingolipid Gb3, overex-pressed in membranes of certain tumor cells, and enters these cells through the retrograde pathway. Therefore, STxB binding to Gb3 receptors may be useful for cell-specific vectorization or imaging purposes. Here we labeled STxB with a fluorophore to evaluate its potential as an in vivo cell-specific targeting reagent in two different models of human colorectal carcinoma. Fluorescent STxB was administered systemically to xenografted nude mice, and its biodistribution was studied by optical imaging. The use of fluorescent STxB allowed the combination of the macroscopic observations with analyses at the cellular level using confocal microscopy. After administration, the fluorescent STxB was slowly eliminated by renal excretion. However, it accumulated in the tumor area. Furthermore, STxB was demonstrated to enter the Gb3-expressing tumoral cells, as well as the epithelial cells of the neovascularization and the monocytes and macrophages surrounding the xenografts.

  8. hTe exciting potential of nanotherapy in brain-tumor targeted drug delivery approaches

    Institute of Scientific and Technical Information of China (English)

    Vivek Agrahari

    2017-01-01

    Delivering therapeutics to the central nervous system (CNS) and brain-tumor has been a major challenge. hTe current standard treatment approaches for the brain-tumor comprise of surgical resection followed by immunotherapy, radiotherapy, and chemotherapy. However, the current treatments are limited in provid-ing signiifcant beneifts to the patients and despite recent technological advancements; brain-tumor is still challenging to treat. Brain-tumor therapy is limited by the lack of effective and targeted strategies to deliver chemotherapeutic agents across the blood-brain barrier (BBB). hTe BBB is the main obstacle that must be overcome to allow compounds to reach their targets in the brain. Recent advances have boosted the nan-otherapeutic approaches in providing an attractive strategy in improving the drug delivery across the BBB and into the CNS. Compared to conventional formulations, nanoformulations offer signiifcant ad vantages in CNS drug delivery approaches. Considering the above facts, in this review, the physiological/anatomical features of the brain-tumor and the BBB are brielfy discussed. hTe drug transport mechanisms at the BBB are outlined. hTe approaches to deliver chemotherapeutic drugs across the CNS into the brain-tumor using nanocarriers are summarized. In addition, the challenges that need to be addressed in nanotherapeutic ap-proaches for their enhanced clinical application in brain-tumor therapy are discussed.

  9. The exciting potential of nanotherapy in brain-tumor targeted drug delivery approaches

    Directory of Open Access Journals (Sweden)

    Vivek Agrahari

    2017-01-01

    Full Text Available Delivering therapeutics to the central nervous system (CNS and brain-tumor has been a major challenge. The current standard treatment approaches for the brain-tumor comprise of surgical resection followed by immunotherapy, radiotherapy, and chemotherapy. However, the current treatments are limited in providing significant benefits to the patients and despite recent technological advancements; brain-tumor is still challenging to treat. Brain-tumor therapy is limited by the lack of effective and targeted strategies to deliver chemotherapeutic agents across the blood-brain barrier (BBB. The BBB is the main obstacle that must be overcome to allow compounds to reach their targets in the brain. Recent advances have boosted the nanotherapeutic approaches in providing an attractive strategy in improving the drug delivery across the BBB and into the CNS. Compared to conventional formulations, nanoformulations offer significant advantages in CNS drug delivery approaches. Considering the above facts, in this review, the physiological/anatomical features of the brain-tumor and the BBB are briefly discussed. The drug transport mechanisms at the BBB are outlined. The approaches to deliver chemotherapeutic drugs across the CNS into the brain-tumor using nanocarriers are summarized. In addition, the challenges that need to be addressed in nanotherapeutic approaches for their enhanced clinical application in brain-tumor therapy are discussed.

  10. Adaptive reactive power control of PV power plants for improved power transfer capability under ultra-weak grid conditions

    DEFF Research Database (Denmark)

    Yang, Dongsheng; Wang, Xiongfei; Liu, Fangcheng

    2017-01-01

    The Photovoltaic (PV) power plants are usually deployed in remote areas with the high solar irradiance, and their power transfer capabilities can be greatly limited by the large impedance of long-distance transmission lines. This paper investigates first the power transfer limit of the PV power p...

  11. Orotracheal administration of contrast agents: a new protocol for brain tumor targeting.

    Science.gov (United States)

    Bianchi, Andrea; Moncelet, Damien; Lux, François; Plissonneau, Marie; Rizzitelli, Silvia; Ribot, Emeline Julie; Tassali, Nawal; Bouchaud, Véronique; Tillement, Olivier; Voisin, Pierre; Crémillieux, Yannick

    2015-06-01

    The development of new non-invasive diagnostic and therapeutic approaches is of paramount importance in order to improve the outcome of patients with glioblastoma (GBM). In this work we investigated a completely non-invasive pre-clinical protocol to effectively target and detect brain tumors through the orotracheal route, using ultra-small nanoparticles (USRPs) and MRI. A mouse model of GBM was developed. In vivo MRI acquisitions were performed before and after intravenous or orotracheal administration of the nanoparticles to identify and segment the tumor. The accumulation of the nanoparticles in neoplastic lesions was assessed ex vivo through fluorescence microscopy. Before the administration of contrast agents, MR images allowed the identification of the presence of abnormal brain tissue in 73% of animals. After orotracheal or intravenous administration of USRPs, in all the mice an excellent co-localization of the position of the tumor with MRI and histology was observed. The elimination time of the USRPs from the tumor after the orotracheal administration was approximately 70% longer compared with intravenous injection. MRI and USRPs were shown to be powerful imaging tools able to detect, quantify and longitudinally monitor the development of GBMs. The absence of ionizing radiation and high resolution of MRI, along with the complete non-invasiveness and good reproducibility of the proposed protocol, make this technique potentially translatable to humans. To our knowledge, this is the first time that the advantages of a needle-free orotracheal administration route have been demonstrated for the investigation of the pathomorphological changes due to GBMs. Copyright © 2015 John Wiley & Sons, Ltd.

  12. Capability ethics

    OpenAIRE

    Robeyns, Ingrid

    2012-01-01

    textabstractThe capability approach is one of the most recent additions to the landscape of normative theories in ethics and political philosophy. Yet in its present stage of development, the capability approach is not a full-blown normative theory, in contrast to utilitarianism, deontological theories, virtue ethics, or pragmatism. As I will argue in this chapter, at present the core of the capability approach is an account of value, which together with some other (more minor) normative comm...

  13. Preparation of a folate-mediated tumor targeting ultraparamagnetic polymeric micelles and its in vitro experimental study

    International Nuclear Information System (INIS)

    Hong Guobin; Zhou Jingxing; Shen Jun; Liang Biling; Yuan Renxu; Shuai Xintao

    2008-01-01

    Objective: To evaluate the tumor targeting characteristic of the Folate-SPIO-DOX- Micelles by in vitro studies, and to test the feasibility of monitor tumor targeting using it and clinical MRI. Methods: The polymeric micelles, Folate-SPIO-DOXO-Micelles were prepared. The in vitro tumor cell targeting efficacy of these folate modified and DOX or SPIO-loaded micelles (Folate-SPIO-DOX- MiceUes) was evaluated by observing the cellular uptake of micelles by human hepatic carcinoma cells (Bel 7402 cells) which overexpressed folate surface receptors. Cell suspensions were incubated with Folate-SPIO- DOXO-Micelles for 1 h. Prussian blue staining was performed to show intracellular irons. Flow cytometry was used to further quantify the cellular uptake of the nanoparticles into Bel 7402 cells. MRI was performed to show the signal intensity changes by using T 2 WI sequences at a clinical 1.5 T MR system. Results Prussian blue staining showed much more intracellular iron in cells incubated with Folate-SPIO-DOX- Micelles than the cells incubated with the non-targeting SPIO-DOX-Micelles. As revealed by flow cytometry, the mean fluorescence intensity of cells in the folate group and the non-folate group were 117.88 and 46. 33, respectively. The T 2 signal intensity in MRI of cells treated with the folate targeting micelles decreased significantly(when the concentration of SPIO in cell culture medium was 5, 10, 20, 40, and 80 μg/ml, respectively, T 2 signal intensity decreased by -5.02%, -23.58%, -45.89%, -70.34%, and -92.41%, respectively). In contrast, T 2 signal intensity did not show obvious decrease for cells treated with the folate-free micelles (when the concentration of SPIO in cell culture medium was at 5, 10, 20, 40, and 80 μg/ml, respectively, T 2 signal intensity decreased by -3.77%, -2.16%, -2.18%, -2.74% and -19.77%, respectively). Conclusion: The polymeric micelles, Folate-SPIO-DOX-Micelles has good targeting ability to the hepatic carcinoma cells in vitro, and

  14. Dosimetric evaluation of a moving tumor target in intensity-modulated radiation therapy (IMRT) for lung cancer patients

    Science.gov (United States)

    Kim, Sung Kyu; Kang, Min Kyu; Yea, Ji Woon; Oh, Se An

    2013-07-01

    Immobilization plays an important role in intensity-modulated radiation therapy (IMRT). The application of IMRT in lung cancer patients is very difficult due to the movement of the tumor target. Patient setup in radiation treatment demands high accuracy because IMRT employs a treatment size of a 1mm pixel unit. Hence, quality assurance of the dose delivered to patients must be at its highest. The radiation dose was evaluated for breathing rates of 9, 14, and 18 breaths per minute (bpm) for tumor targets moving up and down by 1.0 cm and 1.5 cm. The dose of the moving planned target volume (PTV) was measured by using a thermo-luminescent dosimeter (TLD) and Gafchromic™ EBT film. The measurement points were 1.0 cm away from the top, the bottom and the left and the right sides of the PTV center. The evaluated dose differences ranged from 94.2 to 103.8%, from 94.4 to 105.4%, and from 90.7 to 108.5% for 9, 14 and 18 bpm, respectively, for a tumor movement of 1.0 cm. The mean values of the doses were 101.4, 99.9, and 99.5% for 9, 14 and 18 bpm, respectively, for a tumor movement of 1.0 cm. Meanwhile, the evaluated dose differences ranged from 93.6 to 105.8%, from 95.9 to 111.5%, and from 96.2 to 111.7% for 9, 14 and 18 bpm, respectively, for a tumor movement of 1.5 cm. The mean values of the doses were 102.3, 103.4, and 103.1% for 9, 14 and 18 bpm, respectively, for a tumor movement of 1.5 cm. Therefore, we suggest that IMRT can be used in the treatment of lung cancer patients with vertical target movements within the range of 1.0 to 1.5 cm.

  15. Dynamic Capabilities

    DEFF Research Database (Denmark)

    Grünbaum, Niels Nolsøe; Stenger, Marianne

    2013-01-01

    The findings reveal a positive relationship between dynamic capabilities and innovation performance in the case enterprises, as we would expect. It was, however, not possible to establish a positive relationship between innovation performance and profitability. Nor was there any positive...... relationship between dynamic capabilities and profitability....

  16. Capability ethics

    NARCIS (Netherlands)

    I.A.M. Robeyns (Ingrid)

    2012-01-01

    textabstractThe capability approach is one of the most recent additions to the landscape of normative theories in ethics and political philosophy. Yet in its present stage of development, the capability approach is not a full-blown normative theory, in contrast to utilitarianism, deontological

  17. Styrene-maleic acid-copolymer conjugated zinc protoporphyrin as a candidate drug for tumor-targeted therapy and imaging.

    Science.gov (United States)

    Fang, Jun; Tsukigawa, Kenji; Liao, Long; Yin, Hongzhuan; Eguchi, Kanami; Maeda, Hiroshi

    2016-01-01

    Previous studies indicated the potential of zinc protoporphyrin (ZnPP) as an antitumor agent targeting to the tumor survival factor heme oxygenase-1, and/or for photodynamic therapy (PDT). In this study, to achieve tumor-targeted delivery, styrene-maleic acid-copolymer conjugated ZnPP (SMA-ZnPP) was synthesized via amide bond, which showed good water solubility, having ZnPP loading of 15%. More importantly, it forms micelles in aqueous solution with a mean particle size of 111.6 nm, whereas it has an apparent Mw of 65 kDa. This micelle formation was not detracted by serum albumin, suggesting it is stable in circulation. Further SMA-ZnPP conjugate will behave as an albumin complex in blood with much larger size (235 kDa) by virtue of the albumin binding property of SMA. Consequently, SMA-ZnPP conjugate exhibited prolonged circulating retention and preferential tumor accumulation by taking advantage of enhanced permeability and retention (EPR) effect. Clear tumor imaging was thus achieved by detecting the fluorescence of ZnPP. In addition, the cytotoxicity and PDT effect of SMA-ZnPP conjugate was confirmed in human cervical cancer HeLa cells. Light irradiation remarkably increased the cytotoxicity (IC50, from 33 to 5 μM). These findings may provide new options and knowledge for developing ZnPP based anticancer theranostic drugs.

  18. Tumor targeted gene therapy

    International Nuclear Information System (INIS)

    Kang, Joo Hyun

    2006-01-01

    Knowledge of molecular mechanisms governing malignant transformation brings new opportunities for therapeutic intervention against cancer using novel approaches. One of them is gene therapy based on the transfer of genetic material to an organism with the aim of correcting a disease. The application of gene therapy to the cancer treatment had led to the development of new experimental approaches such as suicidal gene therapy, inhibition of oncogenes and restoration of tumor-suppressor genes. Suicidal gene therapy is based on the expression in tumor cells of a gene encoding an enzyme that converts a prodrug into a toxic product. Representative suicidal genes are Herpes simplex virus type 1 thymidine kinase (HSV1-tk) and cytosine deaminase (CD). Especially, physicians and scientists of nuclear medicine field take an interest in suicidal gene therapy because they can monitor the location and magnitude, and duration of expression of HSV1-tk and CD by PET scanner

  19. Improvement of the field-trapping capabilities of bulk Nd Ba Cu O superconductors using Ba Cu O substrates

    Science.gov (United States)

    Matsui, Motohide; Nariki, Shinya; Sakai, Naomichi; Iwafuchi, Kengo; Murakami, Masato

    2006-07-01

    We used Ba-Cu-O substrates to fabricate bulk Nd-Ba-Cu-O superconductors using a top-seeded melt-growth method. There were several advantages for the use of Ba-Cu-O substrate compared to conventional substrate materials such as MgO, ZrO2, Al2O3, RE123 and RE211 (RE = rare earth). The Ba-Cu-O did not react with the precursor and minimized liquid loss. Accordingly, the introduction of large-sized cracks was suppressed. We also found that Tc values were high at the bottom regions, which was ascribed to the beneficial effect of Ba-Cu-O in suppressing Nd/Ba substitution. As a result, we obtained bulk Nd-Ba-Cu-O superconductors that exhibited fairly good field-trapping capabilities, even at the bottom surfaces.

  20. Adaptive Reactive Power Control of PV Power Plants for Improved Power Transfer Capability under Ultra-Weak Grid Conditions

    DEFF Research Database (Denmark)

    Yang, Dongsheng; Wang, Xiongfei; Liu, Fangcheng

    2018-01-01

    with the unity power factor. Then, considering the reactive power compensation from PV inverters, the minimum SCR in respect to Power Factor (PF) is derived, and the optimized coordination of the active and reactive power is exploited. It is revealed that the power transfer capability of PV power plant under...... of a 200 MW PV power plant demonstrate that the proposed method can ensure the rated power transfer of PV power plant with the SCR of 1.25, provided that the PV inverters are operated with the minimal PF=0.9.......This paper analyzes the power transfer limitation of the PV power plant under the ultra-weak grid condition, i.e., when the Short-Circuit Ratio (SCR) is close to 1. It explicitly identifies that a minimum SCR of 2 is required for the PV power plant to deliver the rated active power when operating...

  1. Anti-EGFR-iRGD recombinant protein conjugated silk fibroin nanoparticles for enhanced tumor targeting and antitumor efficiency

    Directory of Open Access Journals (Sweden)

    Bian X

    2016-05-01

    Full Text Available Xinyu Bian,* Puyuan Wu,* Huizi Sha, Hanqing Qian, Qing Wang, Lei Cheng, Yang Yang, Mi Yang, Baorui LiuComprehensive Cancer Center of Drum-Tower Hospital, Medical School of Nanjing University, Clinical Cancer Institute of Nanjing University, Nanjing, People’s Republic of China*These authors contributed equally to this workAbstract: In this study, we report a novel kind of targeting with paclitaxel (PTX-loaded silk fibroin nanoparticles conjugated with iRGD–EGFR nanobody recombinant protein (anti-EGFR-iRGD. The new nanoparticles (called A-PTX-SF-NPs were prepared using the carbodiimide-mediated coupling procedure and their characteristics were evaluated. The cellular cytotoxicity and cellular uptake of A-PTX-SF-NPs were also investigated. The results in vivo suggested that NPs conjugated with the recombinant protein exhibited more targeting and anti-neoplastic property in cells with high EGFR expression. In the in vivo antitumor efficacy assay, the A-PTX-SF-NPs group showed slower tumor growth and smaller tumor volumes than PTX-SF-NPs in a HeLa xenograft mouse model. A real-time near-infrared fluorescence imaging study showed that A-PTX-SF-NPs could target the tumor more effectively. These results suggest that the anticancer activity and tumor targeting of A-PTX-SF-NPs were superior to those of PTX-SF-NPs and may have the potential to be used for targeted delivery for tumor therapies. Keywords: EGFR, nanobody, iRGD, recombinant protein, targeting drug carriers, antitumor efficiency

  2. Tumor-targeted inhibition by a novel strategy - mimoretrovirus expressing siRNA targeting the Pokemon gene.

    Science.gov (United States)

    Tian, Zhiqiang; Wang, Huaizhi; Jia, Zhengcai; Shi, Jinglei; Tang, Jun; Mao, Liwei; Liu, Hongli; Deng, Yijing; He, Yangdong; Ruan, Zhihua; Li, Jintao; Wu, Yuzhang; Ni, Bing

    2010-12-01

    Pokemon gene has crucial but versatile functions in cell differentiation, proliferation and tumorigenesis. It is a master regulator of the ARF-HDM2-p53 and Rb-E2F pathways. The facts that the expression of Pokemon is essential for tumor formation and many kinds of tumors over-express the Pokemon gene make it an attractive target for therapeutic intervention for cancer treatment. In this study, we used an RNAi strategy to silence the Pokemon gene in a cervical cancer model. To address the issues involving tumor specific delivery and durable expression of siRNA, we applied the Arg-Gly-Asp (RGD) peptide ligand and polylysine (K(18)) fusion peptide to encapsulate a recombinant retrovirus plasmid expressing a siRNA targeting the Pokemon gene and produced the 'mimoretrovirus'. At charge ratio 2.0 of fusion peptide/plasmid, the mimoretrovirus formed stable and homogenous nanoparticles, and provided complete DNase I protection and complete gel retardation. This nanoparticle inhibited SiHa cell proliferation and invasion, while it promoted SiHa cell apoptosis. The binding of the nanoparticle to SiHa cells was mediated via the RGD-integrin α(v)β(3) interaction, as evidenced by the finding that unconjugated RGD peptide inhibited this binding significantly. This tumor-targeting mimoretrovirus exhibited excellent anti-tumor capacity in vivo in a nude mouse model. Moreover, the mimoretrovirus inhibited tumor growth with a much higher efficiency than recombinant retrovirus expressing siRNA or the K(18)/P4 nanoparticle lacking the RGD peptide. Results suggest that the RNAi/RGD-based mimoretrovirus developed in this study represents a novel anti-tumor strategy that may be applicable to most research involving cancer therapy and, thus, has promising potential as a cervical cancer treatment.

  3. 99mTc-HYNIC-(tricine/EDDA)-FROP peptide for MCF-7 breast tumor targeting and imaging.

    Science.gov (United States)

    Ahmadpour, Sajjad; Noaparast, Zohreh; Abedi, Seyed Mohammad; Hosseinimehr, Seyed Jalal

    2018-02-19

    Breast cancer is the most common malignancy among women in the world. Development of novel tumor-specific radiopharmaceuticals for early breast tumor diagnosis is highly desirable. In this study we developed 99m Tc-HYNIC-(tricine/EDDA)-Lys-FROP peptide with the ability of specific binding to MCF-7 breast tumor. The FROP-1 peptide was conjugated with the bifunctional chelator hydrazinonicotinamide (HYNIC) and labeled with 99m Tc using tricine/EDDA co-ligand. The cellular specific binding of 99m Tc-HYNIC-FROP was evaluated on different cell lines as well as with blocking experiment on MCF-7 (human breast adenocarcinoma). The tumor targeting and imaging of this labeled peptide were performed on MCF-7 tumor bearing mice. Radiochemical purity for 99m Tc-HYNIC-(tricine/EDDA)-FROP was 99% which was determined with ITLC method. This radiolabeled peptide showed high stability in normal saline and serum about 98% which was monitored with HPLC method. In saturation binding experiments, the binding constant (K d ) to MCF-7 cells was determined to be 158 nM. Biodistribution results revealed that the 99m Tc-HYNIC-FROP was mainly exerted from urinary route. The maximum tumor uptake was found after 30 min post injection (p.i.); however maximum tumor/muscle ratio was seen at 15 min p.i. The tumor uptake of this labeled peptide was specific and blocked by co-injection of excess FROP. According to the planar gamma imaging result, tumor was clearly visible due to the tumor uptake of 99m Tc-HYNIC-(tricine/EDDA)-FROP in mouse after 15 min p.i. The 99m Tc-HYNIC-(tricine/EDDA)-FROP is considered a promising probe with high specific binding to MCF-7 breast cancer cells.

  4. Synthesis and Bioevaluation of Iodine-131 Directly Labeled Cyclic RGD-PEGylated Gold Nanorods for Tumor-Targeted Imaging

    Directory of Open Access Journals (Sweden)

    Yingying Zhang

    2017-01-01

    Full Text Available Introduction. Radiolabeled gold nanoparticles play an important role in biomedical application. The aim of this study was to prepare iodine-131 (131I-labeled gold nanorods (GNRs conjugated with cyclic RGD and evaluate its biological characteristics for targeted imaging of integrin αvβ3-expressing tumors. Methods. HS-PEG(5000-COOH molecules were applied to replace CTAB covering the surface of bare GNRs for better biocompatibility, and c(RGDfK peptides were conjugated onto the carboxyl terminal of GNR-PEG-COOH via EDC/NHS coupling reactions. The nanoconjugate was characterized, and 131I was directly tagged on the surface of GNRs via AuI bonds for SPECT/CT imaging. We preliminarily studied the characteristics of the probe and its feasibility for tumor-targeting SPECT/CT imaging. Results. The [131I]GNR-PEG-cRGD probe was prepared in a simple and rapid manner and was stable in both PBS and fetal bovine serum. It targeted selectively and could be taken up by tumor cells mainly via integrin αvβ3-receptor-mediated endocytosis. In vivo imaging, biodistribution, and autoradiography results showed evident tumor uptake in integrin αvβ3-expressing tumors. Conclusions. These promising results showed that this smart nanoprobe can be used for angiogenesis-targeted SPECT/CT imaging. Furthermore, the nanoprobe possesses a remarkable capacity for highly efficient photothermal conversion in the near-infrared region, suggesting its potential as a multifunctional theranostic agent.

  5. Improving rate capability and reducing over-potential of lithium-oxygen batteries through optimization of Dimethylsulfoxide-N/N-dimethylacetamide mixed electrolyte

    International Nuclear Information System (INIS)

    Chen, Chunguang; Li, Liangyu; Su, Junming; Zhang, Congcong; Chen, Xiang; Huang, Tao; Yu, Aishui

    2017-01-01

    Although dimethylsulfoxide (DMSO) solvent has been widely researched in rechargeable lithium-oxygen (Li-O 2 ) batteries, high polarization voltage and low rate capability limited its application. In this work, we reported a DMSO-based electrolyte system by adding N, N-dimethylacetamide (DMA) to adjust its physical and electrochemical properties. The ionic conductivity, viscosity, oxygen solubility and diffusion coefficient of the mixed electrolytes as well as their electrochemical performance in Li-O 2 batteries are researched. The electrochemical tests show that the optimized DMSO/DMA volume ratio is 30 to 70 based on the rate performance and polarization voltage of the cell. Compared with that of the pure DMSO-based electrolyte, the cell with the mixed electrolyte shows improved rate capability and reduced charge-discharge over-potential. When increasing current density from 0.2 to 0.5 mA cm −2 , the capability retention improves from 32% to 59%. Meanwhile, the charge-discharge voltage gap drops from 1.4V to 0.9V at a current density of 0.2 mA cm −2 . The improved electrochemical performance could be attributed to low viscosity, high oxygen solubility and diffusion coefficient as well as the low charge-transfer resistance with the mixed electrolyte.

  6. PSORTb 3.0: improved protein subcellular localization prediction with refined localization subcategories and predictive capabilities for all prokaryotes.

    Science.gov (United States)

    Yu, Nancy Y; Wagner, James R; Laird, Matthew R; Melli, Gabor; Rey, Sébastien; Lo, Raymond; Dao, Phuong; Sahinalp, S Cenk; Ester, Martin; Foster, Leonard J; Brinkman, Fiona S L

    2010-07-01

    PSORTb has remained the most precise bacterial protein subcellular localization (SCL) predictor since it was first made available in 2003. However, the recall needs to be improved and no accurate SCL predictors yet make predictions for archaea, nor differentiate important localization subcategories, such as proteins targeted to a host cell or bacterial hyperstructures/organelles. Such improvements should preferably be encompassed in a freely available web-based predictor that can also be used as a standalone program. We developed PSORTb version 3.0 with improved recall, higher proteome-scale prediction coverage, and new refined localization subcategories. It is the first SCL predictor specifically geared for all prokaryotes, including archaea and bacteria with atypical membrane/cell wall topologies. It features an improved standalone program, with a new batch results delivery system complementing its web interface. We evaluated the most accurate SCL predictors using 5-fold cross validation plus we performed an independent proteomics analysis, showing that PSORTb 3.0 is the most accurate but can benefit from being complemented by Proteome Analyst predictions. http://www.psort.org/psortb (download open source software or use the web interface). psort-mail@sfu.ca Supplementary data are available at Bioinformatics online.

  7. Internet-based home training is capable to improve balance in multiple sclerosis: a randomized controlled trial.

    Science.gov (United States)

    Frevel, D; Mäurer, M

    2015-02-01

    Balance disorders are common in multiple sclerosis. Aim of the study is to investigate the effectiveness of an Internet-based home training program (e-Training) to improve balance in patients with multiple sclerosis. A randomized, controlled study. Academic teaching hospital in cooperation with the therapeutic riding center Gut Üttingshof, Bad Mergentheim. Eighteen multiple sclerosis patients (mean EDSS 3,5) took part in the trial. Outcome of patients using e-Training (N.=9) was compared to the outcome of patients receiving hippotherapy (N.=9), which can be considered as an advanced concept for the improvement of balance and postural control in multiple sclerosis. After simple random allocation patients received hippotherapy or Internet-based home training (balance, postural control and strength training) twice a week for 12 weeks. Assessments were done before and after the intervention and included static and dynamic balance (primary outcome). Isometric muscle strength of the knee and trunk extension/flexion (dynamometer), walking capacity, fatigue and quality of life served as secondary outcome parameters. Both intervention groups showed comparable and highly significant improvement in static and dynamic balance capacity, no difference was seen between the both intervention groups. However looking at fatigue and quality of life only the group receiving hippotherapy improved significantly. Since e-Training shows even comparable effects to hippotherapy to improve balance, we believe that the established Internet-based home training program, specialized on balance and postural control training, is feasible for a balance and strength training in persons with multiple sclerosis. We demonstrated that Internet-based home training is possible in patients with multiple sclerosis.

  8. Capability approach

    DEFF Research Database (Denmark)

    Jensen, Niels Rosendal; Kjeldsen, Christian Christrup

    Lærebogen er den første samlede danske præsentation af den af Amartya Sen og Martha Nussbaum udviklede Capability Approach. Bogen indeholder en præsentation og diskussion af Sen og Nussbaums teoretiske platform. I bogen indgår eksempler fra såvel uddannelse/uddannelsespolitik, pædagogik og omsorg....

  9. Improved interface quality and luminescence capability of InGaN/GaN quantum wells with Mg pretreatment

    Energy Technology Data Exchange (ETDEWEB)

    Wu, Zhengyuan; Shen, Xiyang; Xiong, Huan; Li, Qingfei; Kang, Junyong; Fang, Zhilai [Xiamen University, Collaborative Innovation Center for Optoelectronic Semiconductors and Efficient Devices, Department of Physics, Xiamen (China); Lin, Feng; Yang, Bilan; Lin, Shilin [San' an Optoelectronics Co., Ltd, Xiamen (China); Shen, Wenzhong [Shanghai Jiao Tong University, Key Laboratory of Artificial Structures and Quantum Control (Ministry of Education), Department of Physics, Shanghai (China); Zhang, Tong-Yi [Shanghai University, Shanghai University Materials Genome Institute and Shanghai Materials Genome Institute, Shanghai (China)

    2016-02-15

    Interface modification of high indium content InGaN/GaN quantum wells was carried out by Mg pretreatment of the GaN barrier surface. The indium in the Mg-pretreated InGaN layer was homogeneously distributed, making the interfaces abrupt. The improved interface quality greatly enhanced light emission capacity. The cathodoluminescence intensity of the Mg-pretreated InGaN/GaN quantum wells was correspondingly much stronger than those of the InGaN/GaN quantum wells without Mg pretreatment. (orig.)

  10. ENTREPRENEURIAL CAPABILITIES

    DEFF Research Database (Denmark)

    Rasmussen, Lauge Baungaard; Nielsen, Thorkild

    2003-01-01

    The aim of this article is to analyse entrepreneurship from an action research perspective. What is entrepreneurship about? Which are the fundamental capabilities and processes of entrepreneurship? To answer these questions the article includes a case study of a Danish entrepreneur and his networ....... Finally, the article discuss, how more long term action research methods could be integrated into the entrepreneurial processes and the possible impacts of such an implementation?...

  11. Dual Functional Capability of Dendritic Cells - Cytokine-Induced Killer Cells in Improving Side Effects of Colorectal Cancer Therapy.

    Science.gov (United States)

    Mosińska, Paula; Gabryelska, Agata; Zasada, Malwina; Fichna, Jakub

    2017-01-01

    The aim of cancer therapy is to eradicate cancer without affecting healthy tissues. Current options available for treating colorectal cancer (CRC), including surgery, chemotherapy or radiotherapy, usually elicit multiple adverse effects and frequently fail to completely remove the tumor cells. Thus, there is a constant need for seeking cancer cell-specific therapeutics to improve the course of cancer therapy and reduce the risk of relapse. In this review we elaborate on the mechanisms underlying the immunotherapy with dendritic cells (DCs) and cytokine-induced killer (CIK) cells, and summarize their effectiveness and tolerability available clinical studies. Finally, we discuss the up-to-date combinatorial adoptive anti-cancer immunotherapy with CIK cells co-cultured with DCs that recently showed encouraging efficacy and usefulness in treating malignant disease, including CRC.

  12. Multifunctional non-viral gene vectors with enhanced stability, improved cellular and nuclear uptake capability, and increased transfection efficiency

    Science.gov (United States)

    Yang, Zhe; Jiang, Zhaozhong; Cao, Zhong; Zhang, Chao; Gao, Di; Luo, Xingen; Zhang, Xiaofang; Luo, Huiyan; Jiang, Qing; Liu, Jie

    2014-08-01

    We have developed a new multifunctional, non-viral gene delivery platform consisting of cationic poly(amine-co-ester) (PPMS) for DNA condensation, PEG shell for nanoparticle stabilization, poly(γ-glutamic acid) (γ-PGA) and mTAT (a cell-penetrating peptide) for accelerated cellular uptake, and a nuclear localization signal peptide (NLS) for enhanced intracellular transport of DNA to the nucleus. In vitro study showed that coating of the binary PPMS/DNA polyplex with γ-PGA promotes cellular uptake of the polyplex particles, particularly by γ-glutamyl transpeptidase (GGT)-positive cells through the GGT-mediated endocytosis pathway. Conjugating PEG to the γ-PGA led to the formation of a ternary PPMS/DNA/PGA-g-PEG polyplex with decreased positive charges on the surface of the polyplex particles and substantially higher stability in serum-containing aqueous medium. The cellular uptake rate was further improved by incorporating mTAT into the ternary polyplex system. Addition of the NLS peptide was designed to facilitate intracellular delivery of the plasmid to the nucleus--a rate-limiting step in the gene transfection process. As a result, compared with the binary PPMS/LucDNA polyplex, the new mTAT-quaternary PPMS/LucDNA/NLS/PGA-g-PEG-mTAT system exhibited reduced cytotoxicity, remarkably faster cellular uptake rate, and enhanced transport of DNA to the nucleus. All these advantageous functionalities contribute to the remarkable gene transfection efficiency of the mTAT-quaternary polyplex both in vitro and in vivo, which exceeds that of the binary polyplex and commercial Lipofectamine™ 2000/DNA lipoplex. The multifunctional mTAT-quaternary polyplex system with improved efficiency and reduced cytotoxicity represents a new type of promising non-viral vectors for the delivery of therapeutic genes to treat tumors.We have developed a new multifunctional, non-viral gene delivery platform consisting of cationic poly(amine-co-ester) (PPMS) for DNA condensation, PEG shell

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

    Directory of Open Access Journals (Sweden)

    Ding Y

    2015-10-01

    Full Text Available Yuan Ding,1,* Dan Sun,1,* Gui-Ling Wang,1 Hong-Ge Yang,1 Hai-Feng Xu,1 Jian-Hua Chen,2 Ying Xie,1,3 Zhi-Qiang Wang4 1Beijing Key Laboratory of Molecular Pharmaceutics and New Drug Delivery Systems, School of Pharmaceutical Sciences, Peking University, Beijing, 2School of Medicine, Jianghan University, Wuhan, 3State Key Laboratory of Natural and Biomimetic Drugs, Peking University, Beijing, People’s Republic of China; 4Department of Chemistry and Biochemistry, Kent State University Geauga, Burton, OH, USA *These authors contributed equally to this work Abstract: 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

  14. iRGD-modified lipid–polymer hybrid nanoparticles loaded with isoliquiritigenin to enhance anti-breast cancer effect and tumor-targeting ability

    Directory of Open Access Journals (Sweden)

    Gao F

    2017-06-01

    Full Text Available Fei Gao,1–3 Jinming Zhang,3 Chaomei Fu,3 Xiaoming Xie,4 Fu Peng,1–3 Jieshu You,1,2 Hailin Tang,1,2,4 Zhiyu Wang,5 Peng Li,6 Jianping Chen1–3 1School of Chinese Medicine, Li Ka Shing Faculty of Medicine, University of Hong Kong, Hong Kong, 2Shenzhen Institute of Research and Innovation, University of Hong Kong, Shenzhen, 3College of Pharmacy, Chengdu University of Chinese Medicine, Chengdu, 4Department of Breast Oncology, Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, 5Department of Mammary Disease, Guangdong Provincial Hospital of Chinese Medicine, Guangzhou, 6State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macau, People’s Republic of China Abstract: Isoliquiritigenin (ISL, a natural anti-breast cancer dietary compound, has poor delivery characteristics and low bioavailability. In order to promote the therapeutic outcome of ISL, a tumor-targeting lipid–polymer hybrid nanoparticle (NP system modified by tumor-homing iRGD peptides has been developed. The hybrid NPs were prepared by a modified single-step nanoprecipitation method to encapsulate ISL. iRGD peptides were anchored on the surface by a postinsertion method (ISL-iRGD NPs. The stable lipid–polymer structure of ISL-iRGD NPs, with high encapsulation and loading efficiency, was confirmed. Compared to free ISL and non-iRGD-modified counterparts, ISL-iRGD NPs showed higher cytotoxicity and cell apoptosis against the different type of breast cancer cells. This was attributable to higher cellular accumulation mediated by the iRGD-integrin recognition and the nanoscale effect. More importantly, based on the active tumor-tissue accumulation by iRGD peptides and the prolonged in vivo circulation by the stealth nanostructure, ISL-iRGD NPs displayed higher tumor-growth inhibition efficiency in 4T1-bearing breast-tumor mouse

  15. NASA GISS Climate Change Research Initiative: A Multidisciplinary Vertical Team Model for Improving STEM Education by Using NASA's Unique Capabilities.

    Science.gov (United States)

    Pearce, M. D.

    2017-12-01

    programing that improve STEM instruction, increase and sustain youth and public engagement in STEM, enhance STEM experience of undergraduate students, better serve groups under-represented groups in STEM fields and design graduate education for tomorrow's STEM workforce.

  16. Unlocking community capabilities for improving maternal and newborn health: participatory action research to improve birth preparedness, health facility access, and newborn care in rural Uganda

    Directory of Open Access Journals (Sweden)

    Elizabeth Ekirapa-Kiracho

    2016-11-01

    Full Text Available Abstract Background Community capacities and resources must be harnessed to complement supply side initiatives addressing high maternal and neonatal mortality rates in Uganda. This paper reflects on gains, challenges and lessons learnt from working with communities to improve maternal and newborn health in rural Uganda. Methods A participatory action research project was supported from 2012 to 2015 in three eastern districts. This project involved working with households, saving groups, sub county and district leaders, transporters and village health teams in diagnosing causes of maternal and neonatal mortality and morbidity, developing action plans to address these issues, taking action and learning from action in a cyclical manner. This paper draws from project experience and documentation, as well as thematic analysis of 20 interviews with community and district stakeholders and 12 focus group discussions with women who had recently delivered and men whose wives had recently delivered. Results Women and men reported increased awareness about birth preparedness, improved newborn care practices and more male involvement in maternal and newborn health. However, additional direct communication strategies were required to reach more men beyond the minority who attended community dialogues and home visits. Saving groups and other saving modalities were strengthened, with money saved used to meet transport costs, purchase other items needed for birth and other routine household needs. However saving groups required significant support to improve income generation, management and trust among members. Linkages between savings groups and transport providers improved women’s access to health facilities at reduced cost. Although village health teams were a key resource for providing information, their efforts were constrained by low levels of education, inadequate financial compensation and transportation challenges. Ensuring that the village health

  17. Preclinical evaluation of isostructural Tc-99m- and Re-188-folate-Gly-Gly-Cys-Glu for folate receptor-positive tumor targeting.

    Science.gov (United States)

    Kim, Woo Hyoung; Kim, Chang Guhn; Kim, Myoung Hyoun; Kim, Dae-Weung; Park, Cho Rong; Park, Ji Yong; Lee, Yun-Sang; Youn, Hyewon; Kang, Keon Wook; Jeong, Jae Min; Chung, June-Key

    2016-06-01

    -188-folate-GGCE. The tumor uptake of these molecules was completely suppressed when excess free folate was co-administered. Isostructural Tc-99m- and Re-188-folate-GGCE showed high and FR-specific uptake by tumors and generally favorable tumor:normal organ ratios. The tumor targeting capabilities of Tc-99m- and Re-188-folate-GGCE were clearly evident on serial imaging studies. This isostructural pair may have potential diagnostic and theranostic applications for FR-positive tumors.

  18. Improving the capability of an integrated CA-Markov model to simulate spatio-temporal urban growth trends using an Analytical Hierarchy Process and Frequency Ratio

    Science.gov (United States)

    Aburas, Maher Milad; Ho, Yuek Ming; Ramli, Mohammad Firuz; Ash'aari, Zulfa Hanan

    2017-07-01

    The creation of an accurate simulation of future urban growth is considered one of the most important challenges in urban studies that involve spatial modeling. The purpose of this study is to improve the simulation capability of an integrated CA-Markov Chain (CA-MC) model using CA-MC based on the Analytical Hierarchy Process (AHP) and CA-MC based on Frequency Ratio (FR), both applied in Seremban, Malaysia, as well as to compare the performance and accuracy between the traditional and hybrid models. Various physical, socio-economic, utilities, and environmental criteria were used as predictors, including elevation, slope, soil texture, population density, distance to commercial area, distance to educational area, distance to residential area, distance to industrial area, distance to roads, distance to highway, distance to railway, distance to power line, distance to stream, and land cover. For calibration, three models were applied to simulate urban growth trends in 2010; the actual data of 2010 were used for model validation utilizing the Relative Operating Characteristic (ROC) and Kappa coefficient methods Consequently, future urban growth maps of 2020 and 2030 were created. The validation findings confirm that the integration of the CA-MC model with the FR model and employing the significant driving force of urban growth in the simulation process have resulted in the improved simulation capability of the CA-MC model. This study has provided a novel approach for improving the CA-MC model based on FR, which will provide powerful support to planners and decision-makers in the development of future sustainable urban planning.

  19. Improved positive electrode materials for lithium-ion batteries: Exploring the high specific capacity of lithium cobalt dioxide and the high rate capability of lithium iron phosphate

    Science.gov (United States)

    Chen, Zhaohui

    During the past decade, the search for better electrode materials for Li-ion batteries has been of a great commercial interest, especially since Li-ion technology has become a major rechargeable battery technology with a market value of $3 billion US dollars per year. This thesis focuses on improving two positive electrode materials: one is a traditional positive electrode material--LiCoO2; the other is a new positive electrode material--LiFePO 4. Cho et al. reported that coating LiCoO2 with oxides can improve the capacity retention of LiCoO2 cycled to 4.4 V. The study of coatings in this thesis confirms this effect and shows that further improvement (30% higher energy density than that used in a commercial cell with excellent capacity retention) can be obtained. An in-situ XRD study proves that the mechanism of the improvement in capacity retention by coating proposed by Cho et al. is incorrect. Further experiments identify the suppression of impedance growth in the cell as the key reason for the improvement caused by coating. Based on this, other methods to improve the energy density of LiCoO2, without sacrificing capacity retention, are also developed. Using an XRD study, the structure of the phase between the O3-phase Li 1-xCoO2 (x > 0.5) and the O1 phase CoO2 was measured experimentally for the first time. XRD results confirmed the prediction of an H1-3 phase by Ceder's group. Apparently, because of the structural changes between the O3 phase and the H1-3 phase, good capacity retention cannot be attained for cycling LiCoO2 to 4.6 V with respect to Li metal. An effort was also made to reduce the carbon content in a LiFePO 4/C composite without sacrificing its rate capability. It was found that about 3% carbon by weight maintains both a good rate capability and a high pellet density for the composite.

  20. A tumor-targeting p53 nanodelivery system limits chemoresistance to temozolomide prolonging survival in a mouse model of glioblastoma multiforme.

    Science.gov (United States)

    Kim, Sang-Soo; Rait, Antonina; Kim, Eric; Pirollo, Kathleen F; Chang, Esther H

    2015-02-01

    Development of temozolomide (TMZ) resistance contributes to the poor prognosis for glioblastoma multiforme (GBM) patients. It was previously demonstrated that delivery of exogenous wild-type tumor suppressor gene p53 via a tumor-targeted nanocomplex (SGT-53) which crosses the blood-brain barrier could sensitize highly TMZ-resistant GBM tumors to TMZ. Here we assessed whether SGT-53 could inhibit development of TMZ resistance. SGT-53 significantly chemosensitized TMZ-sensitive human GBM cell lines (U87 and U251), in vitro and in vivo. Furthermore, in an intracranial GBM tumor model, two cycles of concurrent treatment with systemically administered SGT-53 and TMZ inhibited tumor growth, increased apoptosis and most importantly, significantly prolonged median survival. In contrast TMZ alone had no significant effect on median survival compared to a single cycle of TMZ. These results suggest that combining SGT-53 with TMZ appears to limit development of TMZ resistance, prolonging its anti-tumor effect and could be a more effective therapy for GBM. Using human glioblastoma multiforma cell lines, this research team demonstrated that the delivery of exogenous wild-type tumor suppressor gene p53 via a tumor-targeted nanocomplex limited the development of temozolomide resistance and prolonged its anti-tumor effect, which may enable future human application of this or similar techniques. Copyright © 2015 Elsevier Inc. All rights reserved.

  1. In vivo tumor-targeted dual-modal fluorescence/CT imaging using a nanoprobe co-loaded with an aggregation-induced emission dye and gold nanoparticles.

    Science.gov (United States)

    Zhang, Jimei; Li, Chan; Zhang, Xu; Huo, Shuaidong; Jin, Shubin; An, Fei-Fei; Wang, Xiaodan; Xue, Xiangdong; Okeke, C I; Duan, Guiyun; Guo, Fengguang; Zhang, Xiaohong; Hao, Jifu; Wang, Paul C; Zhang, Jinchao; Liang, Xing-Jie

    2015-02-01

    As an intensely studied computed tomography (CT) contrast agent, gold nanoparticle has been suggested to be combined with fluorescence imaging modality to offset the low sensitivity of CT. However, the strong quenching of gold nanoparticle on fluorescent dyes requires complicated design and shielding to overcome. Herein, we report a unique nanoprobe (M-NPAPF-Au) co-loading an aggregation-induced emission (AIE) red dye and gold nanoparticles into DSPE-PEG(2000) micelles for dual-modal fluorescence/CT imaging. The nanoprobe was prepared based on a facile method of "one-pot ultrasonic emulsification". Surprisingly, in the micelles system, fluorescence dye (NPAPF) efficiently overcame the strong fluorescence quenching of shielding-free gold nanoparticles and retained the crucial AIE feature. In vivo studies demonstrated the nanoprobe had superior tumor-targeting ability, excellent fluorescence and CT imaging effects. The totality of present studies clearly indicates the significant potential application of M-NPAPF-Au as a dual-modal non-invasive fluorescence/X-ray CT nanoprobe for in vivo tumor-targeted imaging and diagnosis. Copyright © 2014 Elsevier Ltd. All rights reserved.

  2. PET Imaging of 64Cu-DOTA-scFv-Anti-PSMA Lipid Nanoparticles (LNPs): Enhanced Tumor Targeting over Anti-PSMA scFv or Untargeted LNPs

    Science.gov (United States)

    Wong, Patty; Li, Lin; Chea, Junie; Delgado, Melissa K.; Crow, Desiree; Poku, Erasmus; Szpikowska, Barbara; Bowles, Nicole; Channappa, Divya; Colcher, David; Wong, Jeffrey Y.C.; Shively, John E.; Yazaki, Paul J.

    2017-01-01

    Introduction Single chain (scFv) antibodies are ideal targeting ligands due to their modular structure, high antigen specificity and affinity. These monovalent ligands display rapid tumor targeting but have limitations due to their fast urinary clearance. Methods An anti-prostate membrane antigen (PSMA) scFv with a site-specific cysteine was expressed and evaluated in a prostate cancer xenograft model by Cu-64 PET imaging. To enhance tumor accumulation, the scFv-cys was conjugated to the co-polymer DSPE-PEG-maleimide that spontaneously assembled into a homogeneous multivalent lipid nanoparticle (LNP). Results The targeted LNP exhibited a 2-fold increase in tumor uptake compared to the scFv alone using two different thiol ester chemistries. The anti-PSMA scFv-LNP exhibited a 1.6 fold increase in tumor targeting over the untargeted LNP. Conclusions The targeted anti-PSMA scFv-LNP showed enhanced tumor accumulation over the scFv alone or the untargeted DOTA-micelle providing evidence for the development of this system for drug delivery. Advances in Knowledge and implications for patient care Anti-tumor scFv antibody fragments have not achieved their therapeutic potential due to their fast blood clearance. Conjugation to a LNP enables multivalency to the tumor antigen as well as increased molecular size for chemotherapy drug delivery. PMID:28126683

  3. PET imaging of 64Cu-DOTA-scFv-anti-PSMA lipid nanoparticles (LNPs): Enhanced tumor targeting over anti-PSMA scFv or untargeted LNPs

    International Nuclear Information System (INIS)

    Wong, Patty; Li, Lin; Chea, Junie; Delgado, Melissa K.; Crow, Desiree; Poku, Erasmus; Szpikowska, Barbara; Bowles, Nicole; Channappa, Divya; Colcher, David; Wong, Jeffrey Y.C.; Shively, John E.; Yazaki, Paul J.

    2017-01-01

    Introduction: Single chain (scFv) antibodies are ideal targeting ligands due to their modular structure, high antigen specificity and affinity. These monovalent ligands display rapid tumor targeting but have limitations due to their fast urinary clearance. Methods: An anti-prostate membrane antigen (PSMA) scFv with a site-specific cysteine was expressed and evaluated in a prostate cancer xenograft model by Cu-64 PET imaging. To enhance tumor accumulation, the scFv-cys was conjugated to the co-polymer DSPE-PEG-maleimide that spontaneously assembled into a homogeneous multivalent lipid nanoparticle (LNP). Results: The targeted LNP exhibited a 2-fold increase in tumor uptake compared to the scFv alone using two different thiol ester chemistries. The anti-PSMA scFv-LNP exhibited a 1.6 fold increase in tumor targeting over the untargeted LNP. Conclusions: The targeted anti-PSMA scFv-LNP showed enhanced tumor accumulation over the scFv alone or the untargeted DOTA-micelle providing evidence for the development of this system for drug delivery. Advances in knowledge and implications for patient care: Anti-tumor scFv antibody fragments have not achieved their therapeutic potential due to their fast blood clearance. Conjugation to an LNP enables multivalency to the tumor antigen as well as increased molecular size for chemotherapy drug delivery.

  4. Technological Capability's Predictor Variables

    Directory of Open Access Journals (Sweden)

    Fernanda Maciel Reichert

    2011-03-01

    Full Text Available The aim of this study was to identify the factors that influence in configuration of the technological capability of companies in sectors with medium-low technological intensity. To achieve the goal proposed in this article a survey was carried out. Based on the framework developed by Lall (1992 which classifies firms in basic, intermediate and advanced level of technological capability; it was found that the predominant technological capability is intermediate, with 83.7% of respondent companies (plastics companies in Brazil. It is believed that the main contribution of this study is the finding that the dependent variable named “Technological Capability” can be explained at a rate of 65% by six variables: development of new processes; selection of the best equipment supplier; sales of internally developed new technology to third parties; design and manufacture of equipment; study of the work methods and perform inventory control; and improvement of product quality.

  5. Pretreatment of lignocellulosic material with fungi capable of higher lignin degradation and lower carbohydrate degradation improves substrate acid hydrolysis and the eventual conversion to ethanol

    Energy Technology Data Exchange (ETDEWEB)

    Kuhar, S.; Nair, L.M.; Kuhad, R.C. [Delhi Univ., New Delhi (India). Dept. of Microbiology, Lignocellulose Biotechnology Laboratory

    2008-04-15

    Lignocellulosic biomass is the most abundant energy resource in the world and is a potential source of carbon substrate for the production of ethanol via fermentation. However, the presence of lignin restricts access to holocellulose. It is necessary to break or remove the lignin in plant residues prior to their hydrolysis. Pretreatment is needed to liberate cellulose and hemicellulose from the lignins. This paper discussed a biological delignification method that avoided the use of toxic and corrosive chemicals. The in situ microbial delignification process used white rot fungi as a basidiomycetes for biological pretreatment. The study examined the capability of 4 basidiomycetes fungi, notably: (1) Phanerochaete chrysosporium; (2) Pycnoporus cinnabarinus; (3) fungal isolate RCK-1; and (4) fungal isolate RCK-3. The fungi were used to delignify wheat straw and improve hydrolysis procedures. Attempts were also made to ferment the acid hydrolysates from fungal-pretreated lignocellulosic materials. Results of the experiment showed that higher yields of ethanol were obtained using selective lignin-degrading fungi as a pretreatment method. 39 refs., 3 tabs., 4 figs.

  6. Short-term Inundation Forecasting for Tsunamis Version 4.0 Brings Forecasting Speed, Accuracy, and Capability Improvements to NOAA's Tsunami Warning Centers

    Science.gov (United States)

    Sterling, K.; Denbo, D. W.; Eble, M. C.

    2016-12-01

    Short-term Inundation Forecasting for Tsunamis (SIFT) software was developed by NOAA's Pacific Marine Environmental Laboratory (PMEL) for use in tsunami forecasting and has been used by both U.S. Tsunami Warning Centers (TWCs) since 2012, when SIFTv3.1 was operationally accepted. Since then, advancements in research and modeling have resulted in several new features being incorporated into SIFT forecasting. Following the priorities and needs of the TWCs, upgrades to SIFT forecasting were implemented into SIFTv4.0, scheduled to become operational in October 2016. Because every minute counts in the early warning process, two major time saving features were implemented in SIFT 4.0. To increase processing speeds and generate high-resolution flooding forecasts more quickly, the tsunami propagation and inundation codes were modified to run on Graphics Processing Units (GPUs). To reduce time demand on duty scientists during an event, an automated DART inversion (or fitting) process was implemented. To increase forecasting accuracy, the forecasted amplitudes and inundations were adjusted to include dynamic tidal oscillations, thereby reducing the over-estimates of flooding common in SIFTv3.1 due to the static tide stage conservatively set at Mean High Water. Further improvements to forecasts were gained through the assimilation of additional real-time observations. Cabled array measurements from Bottom Pressure Recorders (BPRs) in the Oceans Canada NEPTUNE network are now available to SIFT for use in the inversion process. To better meet the needs of harbor masters and emergency managers, SIFTv4.0 adds a tsunami currents graphical product to the suite of disseminated forecast results. When delivered, these new features in SIFTv4.0 will improve the operational tsunami forecasting speed, accuracy, and capabilities at NOAA's Tsunami Warning Centers.

  7. Tumor-targeting properties of 90Y- and 177Lu-labeled α-melanocyte stimulating hormone peptide analogues in a murine melanoma model

    International Nuclear Information System (INIS)

    Miao Yubin; Hoffman, Timothy J.; Quinn, Thomas P.

    2005-01-01

    The purpose of this study was to compare the tumor-targeting properties of 90 Y-DOTA-Re(Arg 11 )CCMSH and 177 Lu-DOTA-Re(Arg 11 )CCMSH in a murine melanoma mouse model. Methods: The in vitro properties of cellular internalization and retention of 90 Y-DOTA-Re(Arg 11 )CCMSH and 177 Lu-DOTA-Re(Arg 11 )CCMSH were studied in B16/F1 murine melanoma cells. The pharmacokinetics of 90 Y-DOTA-Re(Arg 11 )CCMSH and 177 Lu-DOTA-Re(Arg 11 )CCMSH were determined in B16/F1 melanoma-bearing C57 mice. Results: 90 Y-DOTA-Re(Arg 11 )CCMSH and 177 Lu-DOTA-Re(Arg 11 )CCMSH exhibited fast cellular internalization and extended cellular retention in B16/F1 cells. High receptor-mediated tumor uptake and retention coupled with fast whole-body clearance of 90 Y-DOTA-Re(Arg 11 )CCMSH and 177 Lu-DOTA-Re(Arg 11 )CCMSH were demonstrated in B16/F1 tumor-bearing C57 mice. The tumor uptakes of 90 Y-DOTA-Re(Arg 11 )CCMSH and 177 Lu-DOTA-Re(Arg 11 )CCMSH were 25.70±4.64 and 14.48±0.85 %ID/g at 2 h, and 14.09±2.73 and 17.68±3.32 %ID/g at 4 h postinjection. There was little activity accumulated in normal organs except for kidney. Conclusions: High tumor-targeting properties of 90 Y-DOTA-Re(Arg 11 )CCMSH and 177 Lu-DOTA-Re(Arg 11 )CCMSH highlighted their potential as radiopharmaceuticals for targeted radionuclide therapy of melanoma in further investigations

  8. In vitro study of novel gadolinium-loaded liposomes guided by GBI-10 aptamer for promising tumor targeting and tumor diagnosis by magnetic resonance imaging

    Directory of Open Access Journals (Sweden)

    Gu MJ

    2015-08-01

    Full Text Available Meng-Jie Gu,1,* Kun-Feng Li,1,* Lan-Xin Zhang,1 Huan Wang,1 Li-Si Liu,2 Zhuo-Zhao Zheng,2 Nan-Yin Han,1 Zhen-Jun Yang,1 Tian-Yuan Fan1 1State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, 2Department of Radiology, Peking University Third Hospital, Beijing, People’s Republic of China *These authors contributed equally to this work Abstract: Novel gadolinium-loaded liposomes guided by GBI-10 aptamer were developed and evaluated in vitro to enhance magnetic resonance imaging (MRI diagnosis of tumor. Nontargeted gadolinium-loaded liposomes were achieved by incorporating amphipathic material, Gd (III [N,N-bis-stearylamidomethyl-N'-amidomethyl] diethylenetriamine tetraacetic acid, into the liposome membrane using lipid film hydration method. GBI-10, as the targeting ligand, was then conjugated onto the liposome surface to get GBI-10-targeted gadolinium-loaded liposomes (GTLs. Both nontargeted gadolinium-loaded liposomes and GTLs displayed good dispersion stability, optimal size, and zeta potential for tumor targeting, as well as favorable imaging properties with enhanced relaxivity compared with a commercial MRI contrast agent (CA, gadopentetate dimeglumine. The use of GBI-10 aptamer in this liposomal system was intended to result in increased accumulation of gadolinium at the periphery of C6 glioma cells, where the targeting extracellular matrix protein tenascin-C is overexpressed. Increased cellular binding of GTLs to C6 cells was confirmed by confocal microscopy, flow cytometry, and MRI, demonstrating the promise of this novel delivery system as a carrier of MRI contrast agent for the diagnosis of tumor. These studies provide a new strategy furthering the development of nanomedicine for both diagnosis and therapy of tumor. Keywords: magnetic resonance imaging, gadolinium, liposomes, tenascin-C, GBI-10 aptamer, tumor targeting

  9. Tumor-targeted polymeric nanostructured lipid carriers with precise ratiometric control over dual-drug loading for combination therapy in non-small-cell lung cancer.

    Science.gov (United States)

    Liang, Yan; Tian, Baocheng; Zhang, Jing; Li, Keke; Wang, Lele; Han, Jingtian; Wu, Zimei

    2017-01-01

    Gemcitabine (GEM) and paclitaxel (PTX) are effective combination anticancer agents against non-small-cell lung cancer (NSCLC). At the present time, a main challenge of combination treatment is the precision of control that will maximize the combined effects. Here, we report a novel method to load GEM (hydrophilic) and PTX (hydrophobic) into simplex tumor-targeted nanostructured lipid carriers (NLCs) for accurate control of the ratio of the two drugs. We covalently preconjugated the dual drugs through a hydrolyzable ester linker to form drug conjugates. N -acetyl-d-glucosamine (NAG) is a glucose receptor-targeting ligand. We added NAG to the formation of NAG-NLCs. In general, synthesis of poly(6- O -methacryloyl-d-galactopyranose)-GEM/PTX (PMAGP-GEM/PTX) conjugates was demonstrated, and NAG-NLCs were prepared using emulsification and solvent evaporation. NAG-NLCs displayed sphericity with an average diameter of 120.3±1.3 nm, a low polydispersity index of 0.233±0.04, and accurate ratiometric control over the two drugs. A cytotoxicity assay showed that the NAG-NLCs had better antitumor activity on NSCLC cells than normal cells. There was an optimal ratio of the two drugs, exhibiting the best cytotoxicity and combinatorial effects among all the formulations we tested. In comparison with both the free-drug combinations and separately nanopackaged drug conjugates, PMAGP-GEM/PTX NAG-NLCs (3:1) exhibited superior synergism. Flow cytometry and confocal laser scanning microscopy showed that NAG-NLCs exhibited higher uptake efficiency in A549 cells via glucose receptor-mediated endocytosis. This combinatorial delivery system settles problems with ratiometric coloading of hydrophilic and hydrophobic drugs for tumor-targeted combination therapy to achieve maximal anticancer efficacy in NSCLC.

  10. Substrate decoration for improvement of current-carrying capabilities of YBa{sub 2}Cu{sub 3}O{sub x} thin films

    Energy Technology Data Exchange (ETDEWEB)

    Khoryushin, Alexey V., E-mail: khoryushin@ya.ru [Department of Physics, Technical University of Denmark, DTU Building 309, Kgs. Lyngby DK-2800 (Denmark); Mozhaev, Peter B.; Mozhaeva, Julia E. [Department of Physics, Technical University of Denmark, DTU Building 309, Kgs. Lyngby DK-2800 (Denmark); Bdikin, Igor K. [Department of Mechanical Engineering, Centre for Mechanical Technology and Automation, University of Aveiro, 3810-193 Aveiro (Portugal); Zhao, Yue [Department of Energy Conversion and Storage, Technical University of Denmark, DK-4000 Roskilde (Denmark); Andersen, Niels H.; Jacobsen, Claus S.; Hansen, Jørn Bindslev [Department of Physics, Technical University of Denmark, DTU Building 309, Kgs. Lyngby DK-2800 (Denmark)

    2013-03-15

    Highlights: ► Effects of substrate decoration on properties of YBCO thin films were studied. ► Y{sub 2}O{sub 3} nanoparticles, ultra-thin Y{sub 2}O{sub 3} and Y:ZrO{sub 2} layers were used as decoration layer. ► Decoration improves j{sub C} (5 T and 50 K) up to 0.97 MA/cm{sup 2} vs. 0.76 MA/cm{sup 2} for a reference film. ► Ultra-thin layer of yttria and yttria nanoparticles have a similar effect on YBCO. ► Y{sub 2}O{sub 3} decoration results in power law coefficient α = 0.3 vs. α = 0.4 for a reference film. -- Abstract: The effects of substrate decoration with yttria and Y:ZrO{sub 2} on the structural and electrical properties of the YBa{sub 2}Cu{sub 3}O{sub x} (YBCO) thin films are studied. The films were deposited on (LaAlO{sub 3}){sub 3}–(Sr{sub 2}AlTaO{sub 8}){sub 7} substrates by pulsed laser deposition. Two different structures of decoration layer were applied, a template layer of nanoparticles and an uniform ultra-thin layer. Significant improvement of current-carrying capabilities was observed, especially at high external magnetic fields. Structural studies of these films reveal the presence of extended linear defects in the YBCO matrix. The formation of these structures is attributed to seeding of randomly oriented YBCO grains due to suppression of epitaxy in the very beginning of the deposition. The films of both kinds of decoration layers show nearly the same improvement of j{sub C} over the reference film at 77 and 50 K: j{sub C} (5T and 50 K) reaches 0.92 and 0.97 MA/cm{sup 2} for uniform and template decoration layers. At 5 and 20 K the effect of template decoration layers is more beneficial: j{sub C} (5T and 20 K) values are 3.5 and 4.1 MA/cm{sup 2}, j{sub C} (5T and 5 K) values are 6.4 and 7.9 MA/cm{sup 2}, for uniform and template decoration layers, respectively.

  11. Capitalizing on capabilities.

    Science.gov (United States)

    Ulrich, Dave; Smallwood, Norm

    2004-06-01

    By making the most of organizational capabilities--employees' collective skills and fields of expertise--you can dramatically improve your company's market value. Although there is no magic list of proficiencies that every organization needs in order to succeed, the authors identify 11 intangible assets that well-managed companies tend to have: talent, speed, shared mind-set and coherent brand identity, accountability, collaboration, learning, leadership, customer connectivity, strategic unity, innovation, and efficiency. Such companies typically excel in only three of these capabilities while maintaining industry parity in the other areas. Organizations that fall below the norm in any of the 11 are likely candidates for dysfunction and competitive disadvantage. So you can determine how your company fares in these categories (or others, if the generic list doesn't suit your needs), the authors explain how to conduct a "capabilities audit," describing in particular the experiences and findings of two companies that recently performed such audits. In addition to highlighting which intangible assets are most important given the organization's history and strategy, this exercise will gauge how well your company delivers on its capabilities and will guide you in developing an action plan for improvement. A capabilities audit can work for an entire organization, a business unit, or a region--indeed, for any part of a company that has a strategy to generate financial or customer-related results. It enables executives to assess overall company strengths and weaknesses, senior leaders to define strategy, midlevel managers to execute strategy, and frontline leaders to achieve tactical results. In short, it helps turn intangible assets into concrete strengths.

  12. Potential Development of Tumor-Targeted Oral Anti-Cancer Prodrugs: Amino Acid and Dipeptide Monoester Prodrugs of Gemcitabine.

    Science.gov (United States)

    Tsume, Yasuhiro; Drelich, Adam J; Smith, David E; Amidon, Gordon L

    2017-08-10

    One of the main obstacles for cancer therapies is to deliver medicines effectively to target sites. Since stroma cells are developed around tumors, chemotherapeutic agents have to go through stroma cells in order to reach tumors. As a method to improve drug delivery to the tumor site, a prodrug approach for gemcitabine was adopted. Amino acid and dipeptide monoester prodrugs of gemcitabine were synthesized and their chemical stability in buffers, resistance to thymidine phosphorylase and cytidine deaminase, antiproliferative activity, and uptake/permeability in HFF cells as a surrogate to stroma cells were determined and compared to their parent drug, gemcitabine. The activation of all gemcitabine prodrugs was faster in pancreatic cell homogenates than their hydrolysis in buffer, suggesting enzymatic action. All prodrugs exhibited great stability in HFF cell homogenate, enhanced resistance to glycosidic bond metabolism by thymidine phosphorylase, and deamination by cytidine deaminase compared to their parent drug. All gemcitabine prodrugs exhibited higher uptake in HFF cells and better permeability across HFF monolayers than gemcitabine, suggesting a better delivery to tumor sites. Cell antiproliferative assays in Panc-1 and Capan-2 pancreatic ductal cell lines indicated that the gemcitabine prodrugs were more potent than their parent drug gemcitabine. The transport and enzymatic profiles of gemcitabine prodrugs suggest their potential for delayed enzymatic bioconversion and enhanced resistance to metabolic enzymes, as well as for enhanced drug delivery to tumor sites, and cytotoxic activity in cancer cells. These attributes would facilitate the prolonged systemic circulation and improved therapeutic efficacy of gemcitabine prodrugs.

  13. People Capability Maturity Model. SM.

    Science.gov (United States)

    1995-09-01

    tailored so it consumes less time and resources than a traditional software process assessment or CMU/SEI-95-MM-02 People Capability Maturity Model...improved reputation or customer loyalty. CMU/SEI-95-MM-02 People Capability Maturity Model ■ L5-17 Coaching Level 5: Optimizing Activity 1...Maturity Model CMU/SEI-95-MM-62 Carnegie-Mellon University Software Engineering Institute DTIC ELECTE OCT 2 7 1995 People Capability Maturity

  14. Polyethylene glycol-conjugated chondroitin sulfate A derivative nanoparticles for tumor-targeted delivery of anticancer drugs.

    Science.gov (United States)

    Lee, Jae-Young; Park, Ju-Hwan; Lee, Jeong-Jun; Lee, Song Yi; Chung, Suk-Jae; Cho, Hyun-Jong; Kim, Dae-Duk

    2016-10-20

    Polyethylene glycol (PEG)-decorated chondroitin sulfate A-deoxycholic acid (CSD) nanoparticles (NPs) were fabricated for the selective delivery of doxorubicin (DOX) to ovarian cancer. CSD-PEG was synthesized via amide bond formation between the NH2 group of methoxypolyethylene glycol amine and the COOH group of CSD. CSD-PEG/DOX NPs with a 247nm mean diameter, negative zeta potential, and >90% drug encapsulation efficiency were prepared. Sustained and pH-dependent DOX release profiles from CSD-PEG NPs were observed in dissolution tests. Endocytosis of NPs by SKOV-3 cells (CD44 receptor-positive human ovarian cancer cells), based on the CSA-CD44 receptor interaction, was determined by flow cytometry and confocal laser scanning microscopy (CLSM) studies. PEGylation of NPs also resulted in reduced drug clearance (CL) in vivo and improved relative bioavailability, compared to non-PEGylated NPs, as determined by the pharmacokinetic study performed after intravenous administration in rats. Developed CSD-PEG NPs can be a promising delivery vehicle for the therapy of CD44 receptor-expressing ovarian cancers. Copyright © 2016 Elsevier Ltd. All rights reserved.

  15. Direct transport to a PCI-capable hospital is associated with improved survival after adult out-of-hospital cardiac arrest of medical aetiology.

    Science.gov (United States)

    McKenzie, Nicole; Williams, Teresa A; Ho, Kwok M; Inoue, Madoka; Bailey, Paul; Celenza, Antonio; Fatovich, Daniel; Jenkins, Ian; Finn, Judith

    2018-05-02

    To compare survival outcomes of adults with out-of-hospital cardiac arrest (OHCA) of medical aetiology directly transported to a percutaneous-coronary-intervention capable (PCI-capable) hospital (direct transport) with patients transferred to a PCI-capable hospital via another hospital without PCI services available (indirect transport) by emergency medical services (EMS). This retrospective cohort study used the St John Ambulance Western Australia OHCA Database and medical chart review. We included OHCA patients (≥18 years) admitted to any one of five PCI-capable hospitals in Perth between January 2012 and December 2015. Survival to hospital discharge (STHD) and survival up to 12-months after OHCA were compared between the direct and indirect transport groups using multivariable logistic and Cox-proportional hazards regression, respectively, while adjusting for so-called "Utstein variables" and other potential confounders. Of the 509 included patients, 404 (79.4%) were directly transported to a PCI-capable hospital and 105 (20.6%) transferred via another hospital to a PCI-capable hospital; 274/509 (53.8%) patients STHD and 253/509 (49.7%) survived to 12-months after OHCA. Direct transport patients were twice as likely to STHD (adjusted odds ratio 1.97, 95% confidence interval [CI] 1.13-3.43) than those transferred via another hospital. Indirect transport was also associated with a possible increased risk of death, up to 12-months, compared to direct transport (adjusted hazard ratio 1.36, 95% CI 1.00-1.84). Direct transport to a PCI-capable hospital for post-resuscitation care is associated with a survival advantage for adults with OHCA of medical aetiology. This has implications for EMS transport protocols for patients with OHCA. Copyright © 2018 Elsevier B.V. All rights reserved.

  16. c-MPL provides tumor-targeted T-cell receptor-transgenic T cells with costimulation and cytokine signals.

    Science.gov (United States)

    Nishimura, Christopher D; Brenner, Daniel A; Mukherjee, Malini; Hirsch, Rachel A; Ott, Leah; Wu, Meng-Fen; Liu, Hao; Dakhova, Olga; Orange, Jordan S; Brenner, Malcolm K; Lin, Charles Y; Arber, Caroline

    2017-12-21

    Adoptively transferred T-cell receptor (TCR)-engineered T cells depend on host-derived costimulation and cytokine signals for their full and sustained activation. However, in patients with cancer, both signals are frequently impaired. Hence, we developed a novel strategy that combines both essential signals in 1 transgene by expressing the nonlymphoid hematopoietic growth factor receptor c-MPL (myeloproliferative leukemia), the receptor for thrombopoietin (TPO), in T cells. c-MPL signaling activates pathways shared with conventional costimulatory and cytokine receptor signaling. Thus, we hypothesized that host-derived TPO, present in the tumor microenvironment, or pharmacological c-MPL agonists approved by the US Food and Drug Administration could deliver both signals to c-MPL-engineered TCR-transgenic T cells. We found that c-MPL + polyclonal T cells expand and proliferate in response to TPO, and persist longer after adoptive transfer in immunodeficient human TPO-transgenic mice. In TCR-transgenic T cells, c-MPL activation enhances antitumor function, T-cell expansion, and cytokine production and preserves a central memory phenotype. c-MPL signaling also enables sequential tumor cell killing, enhances the formation of effective immune synapses, and improves antileukemic activity in vivo in a leukemia xenograft model. We identify the type 1 interferon pathway as a molecular mechanism by which c-MPL mediates immune stimulation in T cells. In conclusion, we present a novel immunotherapeutic strategy using c-MPL-enhanced transgenic T cells responding to either endogenously produced TPO (a microenvironment factor in hematologic malignancies) or c-MPL-targeted pharmacological agents. © 2017 by The American Society of Hematology.

  17. Fabrication and evaluation of tumor-targeted positive MRI contrast agent based on ultrasmall MnO nanoparticles.

    Science.gov (United States)

    Huang, Haitao; Yue, Tao; Xu, Ke; Golzarian, Jafar; Yu, Jiahui; Huang, Jin

    2015-07-01

    Gd(III) chelate is currently used as positive magnetic resonance imaging (MRI) contrast agent in clinical diagnosis, but generally induces the risk of nephrogenic systemic fibrosis (NSF) due to the dissociated Gd(3+) from Gd(III) chelates. To develop a novel positive MRI contrast agent with low toxicity and high sensitivity, ultrasmall MnO nanoparticles were PEGylated via catechol-Mn chelation and conjugated with cRGD as active targeting function to tumor. Particularly, the MnO nanoparticles with a size of ca. 5nm were modified by α,β-poly(aspartic acid)-based graft polymer containing PEG and DOPA moieties and, meanwhile, conjugated with cRGD to produce the contrast agent with a size of ca. 100nm and a longitudinal relaxivity (r1) of 10.2mM(-1)S(-1). Such nanoscaled contrast agent integrated passive- and active-targeting function to tumor, and its efficient accumulation behavior in tumor was verified by in vivo distribution study. At the same time, the PEG moiety played a role of hydrophilic coating to improve the biocompatibility and stability under storing and physiological conditions, and especially might guarantee enough circulation time in blood. Moreover, in vivo MRI revealed a good and long-term effect of enhancing MRI signal for as-fabricated contrast agent while cell viability assay proved its acceptable cytotoxicity for MRI application. On the whole, the as-fabricated PEGylated and cRGD-functionalized contrast agent based on ultrasmall MnO nanoparticles showed a great potential to the T1-weighted MRI diagnosis of tumor. Crown Copyright © 2015. Published by Elsevier B.V. All rights reserved.

  18. Dual tumor-targeted poly(lactic-co-glycolic acid–polyethylene glycol–folic acid nanoparticles: a novel biodegradable nanocarrier for secure and efficient antitumor drug delivery

    Directory of Open Access Journals (Sweden)

    Chen J

    2017-08-01

    Full Text Available Jia Chen,1,2,* Qi Wu,1,* Li Luo,1 Yi Wang,1 Yuan Zhong,1 Han-Bin Dai,1 Da Sun,1,3 Mao-Ling Luo,4 Wei Wu,1 Gui-Xue Wang1 1Key Laboratory for Biorheological Science and Technology, Ministry of Education, State and Local Joint Engineering Laboratory for Vascular Implants, Bioengineering College, Chongqing University, Chongqing, 2Institute of Laboratory Animals, Sichuan Academy of Medical Science, Sichuan Provincial People’s Hospital, Chengdu, 3Institute of Life Sciences, Wenzhou University, Wenzhou, 4School of Medicine, Wuhan University, Wuhan, China *These authors contributed equally to this work Abstract: Further specific target-ability development of biodegradable nanocarriers is extremely important to promote their security and efficiency in antitumor drug-delivery applications. In this study, a facilely prepared poly(lactic-co-glycolic acid (PLGA–polyethylene glycol (PEG–folic acid (FA copolymer was able to self-assemble into nanoparticles with favorable hydrodynamic diameters of around 100 nm and negative surface charge in aqueous solution, which was expected to enhance intracellular antitumor drug delivery by advanced dual tumor-target effects, ie, enhanced permeability and retention induced the passive target, and FA mediated the positive target. Fluorescence-activated cell-sorting and confocal laser-scanning microscopy results confirmed that doxorubicin (model drug loaded into PLGA-PEG-FA nanoparticles was able to be delivered efficiently into tumor cells and accumulated at nuclei. In addition, all hemolysis, 3-(4,5-dimethylthiazol-2-yl-5-(3-carboxymethoxyphenyl-2-(4-sulfophenyl-2H-tetrazolium, and zebrafish-development experiments demonstrated that PLGA-PEG-FA nanoparticles were biocompatible and secure for biomedical applications, even at high polymer concentration (0.1 mg/mL, both in vitro and in vivo. Therefore, PLGA-PEG-FA nanoparticles provide a feasible controlled-release platform for secure and efficient antitumor drug

  19. Development of PLGA-lipid nanoparticles with covalently conjugated indocyanine green as a versatile nanoplatform for tumor-targeted imaging and drug delivery

    Directory of Open Access Journals (Sweden)

    Xin Y

    2016-11-01

    course of the treatment (1 month. The results obtained demonstrate the versatility of the NPs, featuring stable fluorescence and tumor-targeting characteristics, with promising future applications in cancer therapy. Keywords: indocyanine green, resveratrol, near-infrared nanoprobe, tumor targeting, fluorescence imaging, drug delivery 

  20. Tumor-targeted polymeric nanostructured lipid carriers with precise ratiometric control over dual-drug loading for combination therapy in non-small-cell lung cancer

    Directory of Open Access Journals (Sweden)

    Liang Y

    2017-03-01

    Full Text Available Yan Liang,1 Baocheng Tian,1 Jing Zhang,1 Keke Li,1 Lele Wang,1 Jingtian Han,1,* Zimei Wu2,* 1School of Pharmacy, Binzhou Medical University, 2School of Pharmacy, Yantai University, Yantai, China *These authors contributed equally to this work Abstract: Gemcitabine (GEM and paclitaxel (PTX are effective combination anticancer agents against non-small-cell lung cancer (NSCLC. At the present time, a main challenge of combination treatment is the precision of control that will maximize the combined effects. Here, we report a novel method to load GEM (hydrophilic and PTX (hydrophobic into simplex tumor-targeted nanostructured lipid carriers (NLCs for accurate control of the ratio of the two drugs. We covalently preconjugated the dual drugs through a hydrolyzable ester linker to form drug conjugates. N-acetyl-D-glucosamine (NAG is a glucose receptor-targeting ligand. We added NAG to the formation of NAG-NLCs. In general, synthesis of poly(6-O-methacryloyl-d-galactopyranose–GEM/PTX (PMAGP-GEM/PTX conjugates was demonstrated, and NAG-NLCs were prepared using emulsification and solvent evaporation. NAG-NLCs displayed sphericity with an average diameter of 120.3±1.3 nm, a low polydispersity index of 0.233±0.04, and accurate ratiometric control over the two drugs. A cytotoxicity assay showed that the NAG-NLCs had better antitumor activity on NSCLC cells than normal cells. There was an optimal ratio of the two drugs, exhibiting the best cytotoxicity and combinatorial effects among all the formulations we tested. In comparison with both the free-drug combinations and separately nanopackaged drug conjugates, PMAGP-GEM/PTX NAG-NLCs (3:1 exhibited superior synergism. Flow cytometry and confocal laser scanning microscopy showed that NAG-NLCs exhibited higher uptake efficiency in A549 cells via glucose receptor-mediated endocytosis. This combinatorial delivery system settles problems with ratiometric coloading of hydrophilic and hydrophobic drugs for tumor-targeted

  1. Research for new UAV capabilities

    Energy Technology Data Exchange (ETDEWEB)

    Canavan, G.H.; Leadabrand, R.

    1996-07-01

    This paper discusses research for new Unmanned Aerial Vehicles (UAV) capabilities. Findings indicate that UAV performance could be greatly enhanced by modest research. Improved sensors and communications enhance near term cost effectiveness. Improved engines, platforms, and stealth improve long term effectiveness.

  2. A theranostic nanoplatform: magneto-gold@fluorescence polymer nanoparticles for tumor targeting T1&T2-MRI/CT/NIR fluorescence imaging and induction of genuine autophagy mediated chemotherapy.

    Science.gov (United States)

    Wang, Guannan; Qian, Kun; Mei, Xifan

    2018-06-14

    Multifunctional nanoparticles, bearing low toxicity and tumor-targeting properties, coupled with multifunctional diagnostic imaging and enhanced treatment efficacy, have drawn tremendous attention due to their enormous potential for medical applications. Herein, we report a new kind of biocompatible and tumor-targeting magneto-gold@fluorescent polymer nanoparticle (MGFs-LyP-1), which is based on ultra-small magneto-gold (Fe 3 O 4 -Au) nanoparticles and NIR emissive fluorescent polymers by a solvent-mediated method. This kind of nanoparticle could be taken up efficiently and simultaneously serve for in vivo tumor targeting T 1 &T 2 -MRI/CT/near infrared (NIR) fluorescence bioimaging. Furthermore, the nanoparticles exhibit small size, higher tumor targeting accumulation, excellent cytocompatibility for long-term tracking, and no disturbing cell proliferation and differentiation. Moreover, clear and convincing evidence proves that as-synthesized MGFs-LyP-1 could elicit genuine autophagy via inducing autophagosome formation, which offers a definite synergistic effect to enhance cancer therapy with doxorubicin (DOX) at a nontoxic concentration through enhancement of the autophagy flux. Meanwhile, the as-prepared nanoparticles could be rapidly cleared from mice without any obvious organ impairment. The results indeed reveal a promising prospect of an MGFs-LyP-1 contrast agent with low toxicity and high efficiency for promising application in biomedicine.

  3. Tumor-targeting Salmonella typhimurium A1-R is a highly effective general therapeutic for undifferentiated soft tissue sarcoma patient-derived orthotopic xenograft nude-mouse models.

    Science.gov (United States)

    Igarashi, Kentaro; Kawaguchi, Kei; Kiyuna, Tasuku; Miyake, Kentaro; Miyake, Masuyo; Singh, Arun S; Eckardt, Mark A; Nelson, Scott D; Russell, Tara A; Dry, Sarah M; Li, Yunfeng; Yamamoto, Norio; Hayashi, Katsuhiro; Kimura, Hiroaki; Miwa, Shinji; Tsuchiya, Hiroyuki; Singh, Shree Ram; Eilber, Fritz C; Hoffman, Robert M

    2018-03-18

    Undifferentiated soft tissue sarcoma (USTS) is a recalcitrant and heterogeneous subgroup of soft tissue sarcoma with high risk of metastasis and recurrence. Due to heterogeneity of USTS, there is no reliably effective first-line therapy. We have generated tumor-targeting Salmonella typhimurium A1-R (S. typhimurium A1-R), which previously showed strong efficacy on single patient-derived orthotopic xenograft (PDOX) models of Ewing's sarcoma and follicular dendritic cell sarcoma. In the present study, tumor resected from 4 patients with a biopsy-proven USTS (2 undifferentiated pleomorphic sarcoma [UPS], 1 undifferentiated sarcoma not otherwise specified [NOS] and 1 undifferentiated spindle cell sarcoma [USS]) were grown orthotopically in the biceps femoris muscle of mice to establish PDOX models. One USS model and one UPS model were doxorubicin (DOX) resistant. One UPS and the NOS model were partially sensitive to DOX. DOX is first-line therapy for these diseases. S. typhimurium A1-R arrested tumor growth all 4 models. In addition to arresting tumor growth in each case, S. typhimurium A1-R was significantly more efficacious than DOX in each case, thereby surpassing first-line therapy. These results suggest that S. typhimurium A1-R can be a general therapeutic for USTS and possibly sarcoma in general. Published by Elsevier Inc.

  4. Rights, goals, and capabilities

    NARCIS (Netherlands)

    van Hees, M.V.B.P.M

    This article analyses the relationship between rights and capabilities in order to get a better grasp of the kind of consequentialism that the capability theory represents. Capability rights have been defined as rights that have a capability as their object (rights to capabilities). Such a

  5. Group Capability Model

    Science.gov (United States)

    Olejarski, Michael; Appleton, Amy; Deltorchio, Stephen

    2009-01-01

    The Group Capability Model (GCM) is a software tool that allows an organization, from first line management to senior executive, to monitor and track the health (capability) of various groups in performing their contractual obligations. GCM calculates a Group Capability Index (GCI) by comparing actual head counts, certifications, and/or skills within a group. The model can also be used to simulate the effects of employee usage, training, and attrition on the GCI. A universal tool and common method was required due to the high risk of losing skills necessary to complete the Space Shuttle Program and meet the needs of the Constellation Program. During this transition from one space vehicle to another, the uncertainty among the critical skilled workforce is high and attrition has the potential to be unmanageable. GCM allows managers to establish requirements for their group in the form of head counts, certification requirements, or skills requirements. GCM then calculates a Group Capability Index (GCI), where a score of 1 indicates that the group is at the appropriate level; anything less than 1 indicates a potential for improvement. This shows the health of a group, both currently and over time. GCM accepts as input head count, certification needs, critical needs, competency needs, and competency critical needs. In addition, team members are categorized by years of experience, percentage of contribution, ex-members and their skills, availability, function, and in-work requirements. Outputs are several reports, including actual vs. required head count, actual vs. required certificates, CGI change over time (by month), and more. The program stores historical data for summary and historical reporting, which is done via an Excel spreadsheet that is color-coded to show health statistics at a glance. GCM has provided the Shuttle Ground Processing team with a quantifiable, repeatable approach to assessing and managing the skills in their organization. They now have a common

  6. Mobile Test Capabilities

    Data.gov (United States)

    Federal Laboratory Consortium — The Electrical Power Mobile Test capabilities are utilized to conduct electrical power quality testing on aircraft and helicopters. This capability allows that the...

  7. Improving Capabilities for Irregular Warfare. Volume 2. Capabilities Analysis

    Science.gov (United States)

    2007-08-01

    ranged from the Israelis and other Jews buying up all the land in Iraq, to the Coca - Cola logo (sup- posedly owned by Jews) as saying “No Mecca, No...New recruits training as bomb makers may be detected by their handling of explosives. New recruits could be discouraged by widely advertising severe

  8. Study on Application of New Approach of Fault Current Limiters in Fault Ride through Capability Improvement of DFIG Based Wind Turbine

    DEFF Research Database (Denmark)

    Naderi, Seyed Behzad; Davari, Pooya; Zhou, Dao

    2018-01-01

    Due to salient advantages, Doubly-Fed Induction Generator (DFIG) has more application in power network compared to Fixed Speed Wind Turbine. Because of employing back-to-back converters, one of the important studies regarding new grid code requirements is Fault Ride-Through (FRT) capability....... The proposed FCL can insert a controllable resistance in fault current pass to not only restrict fault current level and compensate voltage sag in the stator but also consume pre-fault output active power of the DFIG regarding wind speed variation. Simulation results and analytics are presented to prove...

  9. Capabilities for Strategic Adaptation

    DEFF Research Database (Denmark)

    Distel, Andreas Philipp

    This dissertation explores capabilities that enable firms to strategically adapt to environmental changes and preserve competitiveness over time – often referred to as dynamic capabilities. While dynamic capabilities being a popular research domain, too little is known about what these capabiliti...

  10. Tumor-Targeting Salmonella typhimurium A1-R in Combination with Trastuzumab Eradicates HER-2-Positive Cervical Cancer Cells in Patient-Derived Mouse Models.

    Directory of Open Access Journals (Sweden)

    Yukihiko Hiroshima

    Full Text Available We have previously developed mouse models of HER-2-positive cervical cancer. Tumors in nude mice had histological structures similar to the original tumor and were stained by anti-HER-2 antibody in the same pattern as the patient's cancer. We have also previously developed tumor-targeting Salmonella typhimurium A1-R and have demonstrated its efficacy against patient-derived tumor mouse models, both alone and in combination. In the current study, we determined the efficacy of S. typhimurium A1-R in combination with trastuzumab on a patient-cancer nude-mouse model of HER-2 positive cervical cancer. Mice were randomized to 5 groups and treated as follows: (1 no treatment; (2 carboplatinum (30 mg/kg, ip, weekly, 5 weeks; (3 trastuzumab (20 mg/kg, ip, weekly, 5 weeks; (4 S. typhimurium A1-R (5 × 107 CFU/body, ip, weekly, 5 weeks; (5 S. typhimurium A1-R (5 × 107 CFU/body, ip, weekly, 5 weeks + trastuzumab (20 mg/kg, ip, weekly, 5 weeks. All regimens had significant efficacy compared to the untreated mice. The relative tumor volume of S. typhimurium A1-R + trastuzumab-treated mice was smaller compared to trastuzumab alone (p = 0.007 and S. typhimurium A1-R alone (p = 0.039. No significant body weight loss was found compared to the no treatment group except for carboplatinum-treated mice (p = 0.021. Upon histological examination, viable tumor cells were not detected, and replaced by stromal cells in the tumors treated with S. typhimurium A1-R + trastuzumab. The results of the present study suggest that S. typhimurium A1-R and trastuzumab in combination are highly effective against HER-2-expressing cervical cancer.

  11. Tumor-targeting Salmonella typhimurium A1-R Inhibits Osteosarcoma Angiogenesis in the In Vivo Gelfoam® Assay Visualized by Color-coded Imaging.

    Science.gov (United States)

    Kiyuna, Tasuku; Tome, Yasunori; Uehara, Fuminari; Murakami, Takashi; Zhang, Yong; Zhao, Ming; Kanaya, Fuminori; Hoffman, Robert M

    2018-01-01

    We previously developed a color-coded imaging model that can quantify the length of nascent blood vessels using Gelfoam® implanted in nestin-driven green fluorescent protein (ND-GFP) nude mice. In this model, nascent blood vessels selectively express GFP. We also previously showed that osteosarcoma cells promote angiogenesis in this assay. We have also previously demonstrated the tumor-targeting bacteria Salmonella typhimurium A1-R (S. typhimurium A1-R) can inhibit or regress all tested tumor types in mouse models. The aim of the present study was to determine if S. typhimurium A1-R could inhibit osteosarcoma angiogenesis in the in vivo Gelfoam® color-coded imaging assay. Gelfoam® was implanted subcutaneously in ND-GFP nude mice. Skin flaps were made 7 days after implantation and 143B-RFP human osteosarcoma cells expressing red fluorescent protein (RFP) were injected into the implanted Gelfoam. After establishment of tumors in the Gelfoam®, control-group mice were treated with phosphate buffered saline via tail-vein injection (iv) and the experimental group was treated with S. typhimurium A1-R iv Skin flaps were made at day 7, 14, 21, and 28 after implantation of the Gelfoam® to allow imaging of vascularization in the Gelfoam® using a variable-magnification small-animal imaging system and confocal fluorescence microscopy. Nascent blood vessels expressing ND-GFP extended into the Gelfoam® over time in both groups. However, the extent of nascent blood-vessel growth was significantly inhibited by S. typhimurium A1-R treatment by day 28. The present results indicate S. typhimurium A1-R has potential for anti-angiogenic targeted therapy of osteosarcoma. Copyright© 2018, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

  12. A business analytics capability framework

    Directory of Open Access Journals (Sweden)

    Ranko Cosic

    2015-09-01

    Full Text Available Business analytics (BA capabilities can potentially provide value and lead to better organisational performance. This paper develops a holistic, theoretically-grounded and practically relevant business analytics capability framework (BACF that specifies, defines and ranks the capabilities that constitute an organisational BA initiative. The BACF was developed in two phases. First, an a priori conceptual framework was developed based on the Resource-Based View theory of the firm and a thematic content analysis of the BA literature. Second, the conceptual framework was further developed and refined using a three round Delphi study involving 16 BA experts. Changes from the Delphi study resulted in a refined and confirmed framework including detailed capability definitions, together with a ranking of the capabilities based on importance. The BACF will help academic researchers and industry practitioners to better understand the capabilities that constitute an organisational BA initiative and their relative importance. In future work, the capabilities in the BACF will be operationalised to measure their as-is status, thus enabling organisations to identify key areas of strength and weakness and prioritise future capability improvement efforts.

  13. Dynamic capabilities, Marketing Capability and Organizational Performance

    Directory of Open Access Journals (Sweden)

    Adriana Roseli Wünsch Takahashi

    2017-01-01

    Full Text Available The goal of the study is to investigate the influence of dynamic capabilities on organizational performance and the role of marketing capabilities as a mediator in this relationship in the context of private HEIs in Brazil. As a research method we carried out a survey with 316 IES and data analysis was operationalized with the technique of structural equation modeling. The results indicate that the dynamic capabilities have influence on organizational performance only when mediated by marketing ability. The marketing capability has an important role in the survival, growth and renewal on educational services offerings for HEIs in private sector, and consequently in organizational performance. It is also demonstrated that mediated relationship is more intense for HEI with up to 3,000 students and other organizational profile variables such as amount of courses, the constitution, the type of institution and type of education do not significantly alter the results.

  14. WE-G-BRE-07: Proton Therapy Enhanced by Tumor-Targeting Gold Nanoparticles: A Pilot in Vivo Experiment at The Proton Therapy Center at MD Anderson Cancer Center

    Energy Technology Data Exchange (ETDEWEB)

    Wolfe, T; Grant, J; Wolfe, A; Gillin, M; Krishnan, S [MD Anderson Cancer Ctr., Houston, TX (United States)

    2014-06-15

    Purpose: Assess tumor-growth delay and survival in a mouse model of prostate cancer treated with tumor-targeting gold nanoparticles (AuNPs) and proton therapy. Methods: We first examined the accumulation of targeting nanoparticles within prostate tumors by imaging AuNPs with ultrasound-guided photoacoustics at 24h after the intravenous administration of goserelin-conjugated AuNPs (gAuNP) in three mice. Nanoparticles were also imaged at the cellular level with TEM in PC3 cells incubated with gAuNP for 24h. Pegylated AuNPs (pAuNP) were also imaged in vivo and in vitro for comparison. PC3 cells were then implanted subcutaneously in nude mice; 51mice with 8–10mm tumors were included. AuNPs were injected intravenously at 0.2%w/w final gold concentration 24h before irradiation. A special jig was designed to facilitate tumor irradiation perpendicular to the proton beam. Proton energy was set to 180MeV, the radiation field was 18×18cm{sup 2}, and 9cm or 13.5cm thick solid-water compensators were used to position the tumors at either the beam entrance (BE) or the SOBP. Physical doses of 5Gy were delivered to all tumors on a patient beam line at MD Anderson's Proton Therapy Center. Results: The photoacoustic experiment reveled that our nanoparticles leak from the tumor-feeding vasculature and accumulate within the tumor volume over time. Additionally, TEM images showed gAuNP are internalized in cancer cells, accumulating within the cytoplasm, whereas pAuNP are not. Tumor-growth was delayed by 11 or 32days in mice receiving gAuNP irradiated at the BE or the SOBP, relative to proton radiation alone. Survival curves (ongoing experiment) reveal that gAuNPs improved survival by 36% or 74% for tumors irradiated at the BE or SOBP. Conclusion: These important, albeit preliminary, in vivo findings reveal nanoparticles to be potent sensitizers to proton therapy. Further, conjugation of AuNPs to tumor-specific antigens that promote enhanced cellular internalization improved

  15. Building a clinical leadership community to drive improvement: a multi-case educational study to inform 21st century clinical commissioning, professional capability and patient care.

    Science.gov (United States)

    Lynch, Marion; Verner, Elizabeth

    2013-01-01

    The new NHS requires transformational leadership; people with the knowledge and motivation to make effective change combined with an understanding of the system they work in. The aim of the Practice Leaders' Programme (PLP) is to generate the conditions needed to focus the energy and collaborative creativity required for innovation to enhance leadership skills across the health economy improving patient care. The PLP engaged 60 local leaders from central England in a new approach enabling them to influence others. It has informed educational policy and practice and helped change professional behaviours. Each participant implemented improvements in care and participated in six action learning sets (ALS) and up to six coaching sessions. Evidence of progress, learning and impact was identified in project reports, reflective diaries and evaluations. The ALS brought together key individuals from clinical and management disciplines across a diverse organisation to redesign a system by developing a shared vision for improving the quality of patient care. The links forged, the projects initiated, and the skills cultivated through the PLP produced ongoing benefits and outcomes beyond the course itself. Coaching sessions helped participants focus their efforts to achieve maximum impact and to become resilient in managing service change effectively. The programme has evolved over four years, building on recommendations from external evaluation which identified statistically significant increases in leadership competences. Further enhancement of this programme secured an International Health Improvement Award. Three key findings of positive impact have emerged; personal growth, service improvement, and legacy and sustainability.

  16. Killing the snake of poverty : local perceptions of poverty and well-being and people’s capabilities to improve their lives in the Southern Andes of Peru

    NARCIS (Netherlands)

    Miyashita, A.

    2009-01-01

    Despite the generalised image of comuneros of the Southern Andes of Peru as living in poverty, a closer examination of the daily lives of the campesinos provides a more dynamic perspective. Some households claim that their lives are improving, others that their lives are the same, while many report

  17. The improvement of near-term CdTe processing and product capabilities and establishment of next-generation CdTe technology. Annual technical progress report, September 1, 1995--August 31, 1996

    Energy Technology Data Exchange (ETDEWEB)

    Kester, J.; Albright, S. [Golden Photon, Inc., CO (United States)

    1997-07-01

    The potential of photovoltaics to become a major global business enterprise still lingers outside the limits of industrial capabilities. For the Cadmium Sulfide/Cadmium Telluride (CdS/CdTe) system this potential has continued to focus on improvements in efficiency, stability, and cost reduction. This triad is the primary objective of the present subcontract with NREL entitled {open_quotes}The Improvement of Near-term CdTe Processing and Product Capabilities & Establishment of Next Generation CdTe Technology{close_quotes}. This subcontract represents an intermediate stage of NREL`s plan to assist the growth of the photovoltaic industry in overcoming the scientific and technical barriers to commercialization. This report outlines the progress that has been made during the period of August 1995 through August 1996. The objectives of this subcontract are to improve processing methods, quantify and understand efficiency improvement mechanisms, meet life-testing goals, and address cadmium safety concerns. Task and subtask goals are defined to meet these objectives in specific areas. The approach to fulfilling the subcontract goals is through a balanced plan of process improvement and mechanism identification. These are carried out and continued through monitoring under various long term and accelerated stress conditions. GPI maintains an on-going awareness of all safety related issues, can in particular, those involving cadmium.

  18. Improved capacity and rate capability of Ru-doped and carbon-coated Li4Ti5O12 anode material

    International Nuclear Information System (INIS)

    Lin, Chih-Yuan; Jhan, Yi-Ruei; Duh, Jenq-Gong

    2011-01-01

    Highlights: → By using a simple one-step solid-state reactions method synthesizes Li 4 Ru 0.01 Ti 4.99 O 12 /C anode material. → Combining the Ru-doped and carbon-coated techniques to fabricate Li 4 Ru 0.01 Ti 4.99 O 12 /C effectively enhance the diffusion rate of Li + and significantly reduce surface electronic resistance of Li 4 Ti 5 O 12 . → Li 4 Ru 0.01 Ti 4.99 O 12 /C delivers 120 and 110 mAh g -1 at 5 and 10 C charge/discharge rate, respectively, after 100 charge/discharge cycles. - Abstract: Pure Li 4 Ti 5 O 12 , modified Li 4 Ti 5 O 12 /C, Li 4 Ru 0.01 Ti 4.99 O 12 and Li 4 Ru 0.01 Ti 4.99 O 12 /C were successfully prepared by a modified solid-state method and its electrochemical properties were investigated. From the XRD patterns, the added sugar or doped Ru did not affect the spinel structure. The results of electrochemical properties revealed that Li 4 Ru 0.01 Ti 4.99 O 12 /C showed 120 and 110 mAh/g at 5 and 10 C rate after 100 charge/discharge cycles. Li 4 Ru 0.01 Ti 4.99 O 12 /C exhibited the best rate capability and the highest capacity at 5 and 10 C charge/discharge rate owing to the increase of electronic conductivity and the reduction of interface resistance between particles of Li 4 Ti 5 O 12 .It is expected that the Li 4 Ru 0.01 Ti 4.99 O 12 /C will be a promising anode material to be used in high-rate lithium ion battery.

  19. Supplementing female rats with DHA-lysophosphatidylcholine increases docosahexaenoic acid and acetylcholine contents in the brain and improves the memory and learning capabilities of the pups

    Energy Technology Data Exchange (ETDEWEB)

    Valenzuela, A.; Nieto, S.; Sanhueza, J.; Morgado, N.; Rojas, I.; Zanartu, P.

    2010-07-01

    Docosahexaenoic acid (Dha) is supplied to the foetus and newborn through the mother from their own reserves and their diet. No consensus about the best form to supplement DHA has been established. We propose that DHA containing lysophosphatidylcholine (DHA-LPC), obtained from DHA-rich eggs may be a suitable form of DHA and choline (the precursor of acetylcholine) supplementation. We evaluated the effectiveness of DHA-LPC to increase DHA and acetylcholine concentration in the brain of pups born from female rats supplemented with DHA-LPC before and during pregnancy. We also evaluated the effect of DHA supplementation on learning and memory capabilities of pups through the Skinner test for operant conditioning. Female Wistar rats received 40-day supplementation of DHA-LPC (8 mg DHA/kg b.w/daily.), before and during pregnancy. After delivery, plasma, erythrocyte, liver, and adipose tissue DHA and plasma choline were analyzed. Brains from 60 day-old pups separated into frontal cortex, cerebellum, striatum, hippocampus, and occipital cortex, were assessed for DHA, acetylcholine, and acetylcholine transferase (CAT) activity. Pups were subjected to the Skinner box test. DHA-LPC supplementation produces higher choline and liver DHA contents in the mothers plasma and increases the pups DHA and acetylcholine in the cerebellum and hippocampus. CAT was not modified by supplementation. The Skinner test shows that pups born from DHA-LPC supplemented mothers exhibit better scores of learning and memory than the controls. Conclusion: DHA-LPC may be an adequate form for DHA supplementation during the perinatal period. (Author) 66 refs.

  20. BATING A REFERENCE INSTALLATION BASED ON CONTROLLED-POTENTIAL COULOMETRY METOD IN THE FRAME OF IMPROVING THE STATE PRIMARY STANDARD GET 176 AND ITS MEASUREMENT CAPABILITIES

    Directory of Open Access Journals (Sweden)

    V. M. Zyskin

    2016-01-01

    Full Text Available The results of developing of reference installation, based on a controlled-potential coulometry, in the frame of improving the State primary standard of the units of mass (molar fraction and mass (molar concentration of a component in the liquid and solid substances and materials GET 176 are presented. The physical principles of controlled-potential coulometry, content and metrological characteristics of the developed installation are considered. Measurement results of copper, iron and lead contents in the certified reference materials of metals' solutions and CRM of brass produced by BAM, Germany, obtained using reference installation are given.

  1. Supplementing female rats with DHA-lysophosphatidylcholine increases docosahexaenoic acid and acetylcholine contents in the brain and improves the memory and learning capabilities of the pups.

    Directory of Open Access Journals (Sweden)

    Rojas, I.

    2010-03-01

    Full Text Available Docosahexaenoic acid (DHA is supplied to the foetus and newborn through the mother from their own reserves and their diet. No consensus about the best form to supplement DHA has been established. We propose that DHAcontaining lysophosphatidylcholine (DHA-LPC, obtained from DHA-rich eggs may be a suitable form of DHA and choline (the precursor of acetylcholine supplementation. We evaluated the effectiveness of DHA-LPC to increase DHA and acetylcholine concentration in the brain of pups born from female rats supplemented with DHA-LPC before and during pregnancy. We also evaluated the effect of DHA supplementation on learning and memory capabilities of pups through the Skinner test for operant conditioning. Female Wistar rats received 40-day supplementation of DHA-LPC (8 mg DHA/kg b.w/daily., before and during pregnancy. After delivery, plasma, erythrocyte, liver, and adipose tissue DHA and plasma choline were analyzed. Brains from 60 day-old pups separated into frontal cortex, cerebellum, striatum, hippocampus, and occipital cortex, were assessed for DHA, acetylcholine, and acetylcholine transferase (CAT activity. Pups were subjected to the Skinner box test. DHA-LPC supplementation produces higher choline and liver DHA contents in the mother’s plasma and increases the pups’ DHA and acetylcholine in the cerebellum and hippocampus. CAT was not modified by supplementation. The Skinner test shows that pups born from DHA-LPC supplemented mothers exhibit better scores of learning and memory than the controls. Conclusion: DHA-LPC may be an adequate form for DHA supplementation during the perinatal period.El ácido docosahexaenoico (DHA que requiere el feto y el recién nacido lo aporta la madre desde sus reservas y la dieta, por lo cual se sugiere suplementar a la madre con DHA. No hay consenso sobre la mejor forma de suplementación. Proponemos que un lisofosfolípido que contiene DHA y colina (DHA-LPC obtenido de huevos con alto contenido de DHA es

  2. ITERATIVE EVALUATION IN A MOBILE COUNSELING AND TESTING PROGRAM TO REACH PEOPLE OF COLOR AT RISK FOR HIV—NEW STRATEGIES IMPROVE PROGRAM ACCEPTABILITY, EFFECTIVENESS, AND EVALUATION CAPABILITIES

    Science.gov (United States)

    Spielberg, Freya; Kurth, Ann; Reidy, William; McKnight, Teka; Dikobe, Wame; Wilson, Charles

    2016-01-01

    This article highlights findings from an evaluation that explored the impact of mobile versus clinic-based testing, rapid versus central-lab based testing, incentives for testing, and the use of a computer counseling program to guide counseling and automate evaluation in a mobile program reaching people of color at risk for HIV. The program’s results show that an increased focus on mobile outreach using rapid testing, incentives and health information technology tools may improve program acceptability, quality, productivity and timeliness of reports. This article describes program design decisions based on continuous quality assessment efforts. It also examines the impact of the Computer Assessment and Risk Reduction Education computer tool on HIV testing rates, staff perception of counseling quality, program productivity, and on the timeliness of evaluation reports. The article concludes with a discussion of implications for programmatic responses to the Centers for Disease Control and Prevention’s HIV testing recommendations. PMID:21689041

  3. New chemical approach to obtain dense layer phosphate-based ionic conductor coating on negative electrode material surface: Synthesis way, outgassing and improvement of C-rate capability

    Energy Technology Data Exchange (ETDEWEB)

    Fleutot, Benoit, E-mail: benoit.fleutot@u-picardie.fr [Laboratoire de Réactivité et Chimie des Solides, Université de Picardie Jules Verne, CNRS UMR 7314, 33 rue Saint Leu, 80039 Amiens (France); Réseau sur le Stockage Electrochimique de l’Energie (RS2E), CNRS FR3459 (France); Davoisne, Carine; Gachot, Grégory; Cavalaglio, Sébastien; Grugeon, Sylvie; Viallet, Virginie [Laboratoire de Réactivité et Chimie des Solides, Université de Picardie Jules Verne, CNRS UMR 7314, 33 rue Saint Leu, 80039 Amiens (France); Réseau sur le Stockage Electrochimique de l’Energie (RS2E), CNRS FR3459 (France)

    2017-04-01

    Highlights: • Dense layer coating of based-phosphate ionic conductor obtained by spray-drying. • Influence of dense ionic conductor at the negative surface material on performances. • Impact of dense ionic conductor coating on outgassing phenomena. - Abstract: Li{sub 4}Ti{sub 5}O{sub 12} (LTO) based batteries have severe gassing behavior during charge/discharge and storage process, due to interfacial reactions between active material and electrolyte solution. In the same time, the electronic and ionic conductivity of pristine LTO is very poor and induces the use of nanoparticles which increase the outgassing phenomena. The coating of LTO particles could be a solution. For this the LTO spinel particles are modified with ionic conductor Li{sub 3}PO{sub 4} coating using a spray-drying method. For the first time a homogeneous thin dense layer phosphate based conductor is obtained without nanoparticles, as a thin film material. It is so possible to study the influence of ionic conductor deposited on the negative electrode material on performances by the controlled layer thickness. This coating was characterized by XRD, SEM, XPS and TEM. The electrochemical performance of Li{sub 3}PO{sub 4} coated Li{sub 4}Ti{sub 5}O{sub 12} is improved at high C-rate by the surface modification (improvement of 30 mAh g{sup −1} at 5 C-rate compared to pristine LTO for 5 nm of coating), inducing by a modification of surface energy. An optimum coating thickness was studied. This type of coating allows a significant decrease of outgassing phenomena due the conformal coating and opens the way to a great number of studies and new technologies.

  4. Reduced graphene oxide-NH2 modified low pressure nanofiltration composite hollow fiber membranes with improved water flux and antifouling capabilities

    Science.gov (United States)

    Li, Xipeng; Zhao, Changwei; Yang, Mei; Yang, Bin; Hou, Deyin; Wang, Tao

    2017-10-01

    Reduced graphene oxide-NH2 (R-GO-NH2), a kind of amino graphene oxide, was embedded into the polyamide (PA) layer of nanofiltration (NF) composite hollow fiber membranes via interfacial polymerization to enhance the permeate flux and antifouling properties of NF membranes under low pressure conditions. In addition, it could mitigate the poor compatibility issue between graphene oxide materials and PA layer. To evaluate the influence of R-GO-NH2 on the performance of the NF composite hollow fiber membrane, SEM, AFM, FTIR, XPS and Zeta potentials were used to characterize the membranes. The results indicated that the compatibility and interactions between R-GO-NH2 and PA layer were enhanced, which was mainly due to the polymerization reaction between amino groups of R-GO-NH2 and acyl chloride groups of TMC. Therefore, salts rejection of the current membranes was improved significantly, and the modified membranes with 50 mg/L R-GO-NH2 demonstrated highest performance in terms of the rejections, which were 26.9%, 98.5%, 98.1%, and 96.1%, for NaCl, Na2SO4, MgSO4, and CaCl2 respectively. It was found that with the R-GO-NH2 contents rasing from 0 to 50 mg/L, pure water flux increased from 30.44 ± 1.71 to 38.57 ± 2.01 L/(m2.h) at 2 bar. What's more, the membrane demonstrated improved antifouling properties.

  5. New chemical approach to obtain dense layer phosphate-based ionic conductor coating on negative electrode material surface: Synthesis way, outgassing and improvement of C-rate capability

    International Nuclear Information System (INIS)

    Fleutot, Benoit; Davoisne, Carine; Gachot, Grégory; Cavalaglio, Sébastien; Grugeon, Sylvie; Viallet, Virginie

    2017-01-01

    Highlights: • Dense layer coating of based-phosphate ionic conductor obtained by spray-drying. • Influence of dense ionic conductor at the negative surface material on performances. • Impact of dense ionic conductor coating on outgassing phenomena. - Abstract: Li_4Ti_5O_1_2 (LTO) based batteries have severe gassing behavior during charge/discharge and storage process, due to interfacial reactions between active material and electrolyte solution. In the same time, the electronic and ionic conductivity of pristine LTO is very poor and induces the use of nanoparticles which increase the outgassing phenomena. The coating of LTO particles could be a solution. For this the LTO spinel particles are modified with ionic conductor Li_3PO_4 coating using a spray-drying method. For the first time a homogeneous thin dense layer phosphate based conductor is obtained without nanoparticles, as a thin film material. It is so possible to study the influence of ionic conductor deposited on the negative electrode material on performances by the controlled layer thickness. This coating was characterized by XRD, SEM, XPS and TEM. The electrochemical performance of Li_3PO_4 coated Li_4Ti_5O_1_2 is improved at high C-rate by the surface modification (improvement of 30 mAh g"−"1 at 5 C-rate compared to pristine LTO for 5 nm of coating), inducing by a modification of surface energy. An optimum coating thickness was studied. This type of coating allows a significant decrease of outgassing phenomena due the conformal coating and opens the way to a great number of studies and new technologies.

  6. The development of educational for CA-RP (Cognitive Apprenticeeship-based Research Paper) to improve the research capabilities for majors students of radiological technology

    Energy Technology Data Exchange (ETDEWEB)

    Park, Hoon Hee; Chung, Hyun Suk; Lee, Yun Hee; Kim, Hyun Soo; Kang, Byung Sam; Son, Jin Hyun; Min, Jung Hwan; Lyu, Kwang Yeul [Shingu College, Sungnam (Korea, Republic of)

    2013-06-15

    In the medical field, the necessity of education growth for the professional Radiation Technologists has been emphasized to become experts on radiation and the radiation field is important of the society. Also, in hospitals and companies, important on thesis is getting higher in order to active and cope with rapidly changing internal and external environment and a more in-depth expert training, the necessity of new teaching and learning model that can cope with changes in a more proactive has become. Thesis writing classes brought limits to the in-depth learning as to start a semester and rely on only specific programs besides, inevitable on passive participation. In addition, it does not have a variety opportunity to present, an actual opportunity that can be written and discussed does not provide much caused by instructor-led classes. As well as, it has had a direct impact on the quality of the thesis, furthermore, having the opportunity to participate in various conferences showed the limitations. In order to solve these problems, in this study, writing thesis has organized training operations as a consistent gradual deepening of learning, at the same time, the operational idea was proposed based on the connectivity integrated operating and effective training program and instructional tool for improving the ability to perform the written actual thesis. The development of teaching and learning model consisted of 4 system modeling, scaffolding, articulation, exploration. Depending on the nature of the course, consisting team following the personal interest and the topic allow for connection subject, based on this, promote research capacity through a step-by-step evaluation and feedback and, fundamentally strengthen problem-solving skills through the journal studies, help not only solving the real-time problem by taking wiki-space but also efficient use of time, increase the quality of the thesis by activating cooperation through mentoring, as a result, it was to

  7. The development of educational for CA-RP (Cognitive Apprenticeeship-based Research Paper) to improve the research capabilities for majors students of radiological technology

    International Nuclear Information System (INIS)

    Park, Hoon Hee; Chung, Hyun Suk; Lee, Yun Hee; Kim, Hyun Soo; Kang, Byung Sam; Son, Jin Hyun; Min, Jung Hwan; Lyu, Kwang Yeul

    2013-01-01

    In the medical field, the necessity of education growth for the professional Radiation Technologists has been emphasized to become experts on radiation and the radiation field is important of the society. Also, in hospitals and companies, important on thesis is getting higher in order to active and cope with rapidly changing internal and external environment and a more in-depth expert training, the necessity of new teaching and learning model that can cope with changes in a more proactive has become. Thesis writing classes brought limits to the in-depth learning as to start a semester and rely on only specific programs besides, inevitable on passive participation. In addition, it does not have a variety opportunity to present, an actual opportunity that can be written and discussed does not provide much caused by instructor-led classes. As well as, it has had a direct impact on the quality of the thesis, furthermore, having the opportunity to participate in various conferences showed the limitations. In order to solve these problems, in this study, writing thesis has organized training operations as a consistent gradual deepening of learning, at the same time, the operational idea was proposed based on the connectivity integrated operating and effective training program and instructional tool for improving the ability to perform the written actual thesis. The development of teaching and learning model consisted of 4 system modeling, scaffolding, articulation, exploration. Depending on the nature of the course, consisting team following the personal interest and the topic allow for connection subject, based on this, promote research capacity through a step-by-step evaluation and feedback and, fundamentally strengthen problem-solving skills through the journal studies, help not only solving the real-time problem by taking wiki-space but also efficient use of time, increase the quality of the thesis by activating cooperation through mentoring, as a result, it was to

  8. Building Service Provider Capabilities

    DEFF Research Database (Denmark)

    Brandl, Kristin; Jaura, Manya; Ørberg Jensen, Peter D.

    2015-01-01

    In this paper we study whether and how the interaction between clients and the service providers contributes to the development of capabilities in service provider firms. In situations where such a contribution occurs, we analyze how different types of activities in the production process...... process. We find that clients influence the development of human capital capabilities and management capabilities in reciprocally produced services. While in sequential produced services clients influence the development of organizational capital capabilities and management capital capabilities....... of the services, such as sequential or reciprocal task activities, influence the development of different types of capabilities. We study five cases of offshore-outsourced knowledge-intensive business services that are distinguished according to their reciprocal or sequential task activities in their production...

  9. A joint time-invariant wavelet transform and kurtosis approach to the improvement of in-line oil debris sensor capability

    International Nuclear Information System (INIS)

    Fan, X; Liang, M; Yeap, T

    2009-01-01

    In-line oil debris sensors are important devices for the detection of machinery failures. However, two key issues remain to be addressed to more effectively make use of the existing oil debris sensors: the responsiveness to early machine failures and false alarms. The responsiveness level depends on the size of the debris that can be detected by an oil debris sensor. The detectable particle size in turn is mainly limited by the background noise. The false alarms are often caused by spurious impulses such as vibration-like signals. The challenge of improving the responsiveness and reducing false alarms lies in the very weak particle signals and their similarity to spurious signals. In this paper, a joint time-invariant wavelet transform and kurtosis analysis method is proposed to address the two issues simultaneously. The proposed method has been tested by extracting signatures of ultra-small metal particles from background noise and a wide range of simulated vibration-like and real vibration signals. Our test results have demonstrated that the proposed method can effectively detect very weak particle signals buried in strong background noise and eliminate vibration-like spurious signals. The implementation of the proposed method will substantially enhance many existing oil debris sensors

  10. In-situ grown CNTs modified SiO2/C composites as anode with improved cycling stability and rate capability for lithium storage

    Science.gov (United States)

    Wang, Siqi; Zhao, Naiqin; Shi, Chunsheng; Liu, Enzuo; He, Chunnian; He, Fang; Ma, Liying

    2018-03-01

    Silica (SiO2) is regarded as one of the most promising anode materials for lithium ion batteries owing to its high theoretical specific capacity, relatively low operation potentials, abundance, environmental benignity and low cost. However, the low intrinsic electrical conductivity and large volume change of SiO2 during the discharge/charge cycles usually results in poor electrochemical performance. In this work, carbon nanotubes (CNTs) modified SiO2/C composites have been fabricated through an in-situ chemical vapor deposition method. The results show that the electrical conductivity of the SiO2/C/CNTs is visibly enhanced through a robust connection between the CNTs and SiO2/C particles. Compared with the pristine SiO2 and SiO2/C composites, the SiO2/C/CNTs composites display a high initial capacity of 1267.2 mA h g-1. Besides, an excellent cycling stability with the capacity of 315.7 mA h g-1 is achieved after 1000th cycles at a rate of 1 A g-1. The significantly improved electrochemical properties of the SiO2/C/CNTs composites are mainly attributed to the formation of three dimensional CNT networks in the SiO2/C substrate, which can not only shorten the Li-ion diffusion path but also relieve the volume change during the lithium-ion insertion/extraction processes.

  11. In vivo tumor targeting and imaging with anti-vascular endothelial growth factor antibody-conjugated dextran-coated iron oxide nanoparticles

    Directory of Open Access Journals (Sweden)

    Hsieh WJ

    2012-06-01

    sections of tumor tissues stained for the iron constituent of the NPs with Prussian blue revealed a strong blue reaction in the tumors of anti-VEGF-NP-treated mice, but only a weak reaction in mice injected with NPs. In both groups, at all time points, Prussian blue-stained liver and spleen sections showed only light staining, while stained cells were rarely detected in kidney and lung sections. Transmission electron microscopy showed that many more electron-dense particles were present in endothelial cells, tumor cells, and extracellular matrix in tumor tissues in mice injected with anti-VEGF-NPs than in NP-injected mice.Conclusion: These results demonstrated in vivo tumor targeting and efficient accumulation of anti-VEGF-NPs in tumor tissues after systemic delivery in a colon cancer model, showing that anti-VEGF-NPs have potential for use as a molecular-targeted tumor imaging agent in vivo.Keywords: nanoparticles, vascular endothelial growth factor, colon tumor, magnetic resonance imaging, transmission electron microscopy

  12. Capability Handbook- offline metrology

    DEFF Research Database (Denmark)

    Islam, Aminul; Marhöfer, David Maximilian; Tosello, Guido

    This offline metrological capability handbook has been made in relation to HiMicro Task 3.3. The purpose of this document is to assess the metrological capability of the HiMicro partners and to gather the information of all available metrological instruments in the one single document. It provides...

  13. Dynamic Capabilities and Performance

    DEFF Research Database (Denmark)

    Wilden, Ralf; Gudergan, Siegfried P.; Nielsen, Bo Bernhard

    2013-01-01

    are contingent on the competitive intensity faced by firms. Our findings demonstrate the performance effects of internal alignment between organizational structure and dynamic capabilities, as well as the external fit of dynamic capabilities with competitive intensity. We outline the advantages of PLS...

  14. Developing Alliance Capabilities

    DEFF Research Database (Denmark)

    Heimeriks, Koen H.; Duysters, Geert; Vanhaverbeke, Wim

    This paper assesses the differential performance effects of learning mechanisms on the development of alliance capabilities. Prior research has suggested that different capability levels could be identified in which specific intra-firm learning mechanisms are used to enhance a firm's alliance...

  15. Telematics Options and Capabilities

    Energy Technology Data Exchange (ETDEWEB)

    Hodge, Cabell [National Renewable Energy Laboratory (NREL), Golden, CO (United States)

    2017-09-05

    This presentation describes the data tracking and analytical capabilities of telematics devices. Federal fleet managers can use the systems to keep their drivers safe, maintain a fuel efficient fleet, ease their reporting burden, and save money. The presentation includes an example of how much these capabilities can save fleets.

  16. FMEF/experimental capabilities

    International Nuclear Information System (INIS)

    Burgess, C.A.; Dronen, V.R.

    1981-01-01

    The Fuels and Materials Examination Facility (FMEF), under construction at the Hanford site north of Richland, Washington, will be one of the most modern facilities offering irradiated fuels and materials examination capabilities and fuel fabrication development technologies. Scheduled for completion in 1984, the FMEF will provide examination capability for fuel assemblies, fuel pins and test pins irradiated in the FFTF. Various functions of the FMEF are described, with emphasis on experimental data-gathering capabilities in the facility's Nondestructive and Destructive examination cell complex

  17. KSC Technical Capabilities Website

    Science.gov (United States)

    Nufer, Brian; Bursian, Henry; Brown, Laurette L.

    2010-01-01

    This document is the website pages that review the technical capabilities that the Kennedy Space Center (KSC) has for partnership opportunities. The purpose of this information is to make prospective customers aware of the capabilities and provide an opportunity to form relationships with the experts at KSC. The technical capabilities fall into these areas: (1) Ground Operations and Processing Services, (2) Design and Analysis Solutions, (3) Command and Control Systems / Services, (4) Materials and Processes, (5) Research and Technology Development and (6) Laboratories, Shops and Test Facilities.

  18. Improving the Current DHS Capabilities Framework

    Science.gov (United States)

    2008-09-01

    Laboratories ( PNL ) to establish the standards for the NIMS initiative. This entire situation creates another set of inconsistencies in criteria for...www.hsaj.org/?fullarticle=1.2.2, (accessed June 12, 2007), 8. 24 setting agencies: NFPA, PNL , American National Standards Institute (ANSI), and...with Pacific Northwest Laboratory ( PNL ) to develop the NIC standards. The Incident Management Standards Working Group (IMSWG) was established

  19. Architecture Capabilities to Improve Healthcare Environments

    Science.gov (United States)

    Ebrahimi, Ali; Mardomi, Karim; Hassanpour Rahimabad, Kasra

    2013-01-01

    Background The physical environment of healthcare buildings has great importance in issues such as patient safety, functional efficiency, user satisfaction, healthcare outcomes, and energy and resources consumption. Objectives The present study assesses physical environments of Iranian healthcare buildings. Materials and Methods This study was performed using a descriptive-analytical method. Data collection was carried out via a written questionnaire. Results Based on the findings of this study, "functional efficiency", "user satisfaction", "environmental issues", "patient safety”, “accountability in incidents and disasters", and "flexibility" are regarded as the most issues in the country's hospitals. Also, none of the parameters is "without any problem" and has a "desirable status". Conclusions According to the responses, all of the healthcare buildings in this research had flaws in their physical environment, which require attention. Thus, it is necessary to review and pay more attention to the architecture of the country's healthcare buildings. PMID:24350145

  20. Resources, constraints and capabilities

    NARCIS (Netherlands)

    Dhondt, S.; Oeij, P.R.A.; Schröder, A.

    2018-01-01

    Human and financial resources as well as organisational capabilities are needed to overcome the manifold constraints social innovators are facing. To unlock the potential of social innovation for the whole society new (social) innovation friendly environments and new governance structures

  1. a Capability approach

    African Journals Online (AJOL)

    efforts towards gender equality in education as a means of achieving social justice. ... should mean that a lot of capability approach-oriented commentators are ... processes, their forms of exercising power, and their rules, unwritten cultures, ...

  2. Engineering Capabilities and Partnerships

    Science.gov (United States)

    Poulos, Steve

    2010-01-01

    This slide presentation reviews the engineering capabilities at Johnson Space Center, The presentation also reviews the partnerships that have resulted in successfully designed and developed projects that involved commercial and educational institutions.

  3. Brandishing Cyberattack Capabilities

    Science.gov (United States)

    2013-01-01

    Advertising cyberwar capabilities may be helpful. It may back up a deterrence strategy. It might dissuade other states from conventional mischief or...to enable the attack.5 Many of the instruments of the attack remain with the target system, nestled in its log files, or even in the malware itself...debat- able. Even if demonstrated, what worked yesterday may not work today. But difficult does not mean impossible. Advertising cyberwar capabilities

  4. CASL Dakota Capabilities Summary

    Energy Technology Data Exchange (ETDEWEB)

    Adams, Brian M. [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Simmons, Chris [Univ. of Texas, Austin, TX (United States); Williams, Brian J. [Los Alamos National Lab. (LANL), Los Alamos, NM (United States)

    2017-10-10

    The Dakota software project serves the mission of Sandia National Laboratories and supports a worldwide user community by delivering state-of-the-art research and robust, usable software for optimization and uncertainty quantification. These capabilities enable advanced exploration and riskinformed prediction with a wide range of computational science and engineering models. Dakota is the verification and validation (V&V) / uncertainty quantification (UQ) software delivery vehicle for CASL, allowing analysts across focus areas to apply these capabilities to myriad nuclear engineering analyses.

  5. The Impact of IT Capability on Employee Capability, Customer Value, Customer Satisfaction, and Business Performance

    Science.gov (United States)

    Chae, Ho-Chang

    2009-01-01

    This study empirically examines the impact of IT capability on firms' performance and evaluates whether firms' IT capabilities play a role in improving employee capability, customer value, customer satisfaction, and ultimately business performance. The results were based on comparing the business performance of the IT leader companies with that of…

  6. Space Logistics: Launch Capabilities

    Science.gov (United States)

    Furnas, Randall B.

    1989-01-01

    The current maximum launch capability for the United States are shown. The predicted Earth-to-orbit requirements for the United States are presented. Contrasting the two indicates the strong National need for a major increase in Earth-to-orbit lift capability. Approximate weights for planned payloads are shown. NASA is studying the following options to meet the need for a new heavy-lift capability by mid to late 1990's: (1) Shuttle-C for near term (include growth versions); and (2) the Advanced Lauching System (ALS) for the long term. The current baseline two-engine Shuttle-C has a 15 x 82 ft payload bay and an expected lift capability of 82,000 lb to Low Earth Orbit. Several options are being considered which have expanded diameter payload bays. A three-engine Shuttle-C with an expected lift of 145,000 lb to LEO is being evaluated as well. The Advanced Launch System (ALS) is a potential joint development between the Air Force and NASA. This program is focused toward long-term launch requirements, specifically beyond the year 2000. The basic approach is to develop a family of vehicles with the same high reliability as the Shuttle system, yet offering a much greater lift capability at a greatly reduced cost (per pound of payload). The ALS unmanned family of vehicles will provide a low end lift capability equivalent to Titan IV, and a high end lift capability greater than the Soviet Energia if requirements for such a high-end vehicle are defined.In conclusion, the planning of the next generation space telescope should not be constrained to the current launch vehicles. New vehicle designs will be driven by the needs of anticipated heavy users.

  7. Campus Capability Plan

    Energy Technology Data Exchange (ETDEWEB)

    Adams, C. [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States); Arsenlis, T. [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States); Bailey, A. [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States); Bergman, M. [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States); Brase, J. [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States); Brenner, J. [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States); Camara, L. [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States); Carlton, H. [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States); Cheng, J. [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States); Chrzanowski, P. [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States); Colson, J. [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States); East, D. [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States); Farrell, J. [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States); Ferranti, L. [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States); Gursahani, A. [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States); Hansen, R. [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States); Helms, L. L. [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States); Hernandez, M. [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States); Jeffries, J. [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States); Larson, D. [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States); Lu, K. [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States); McNabb, D. [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States); Mercer, M. [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States); Skeate, M. [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States); Sueksdorf, M. [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States); Zucca, B. [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States); Le, D. [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States); Ancria, R. [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States); Scott, J. [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States); Leininger, L. [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States); Gagliardi, F. [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States); Gash, A. [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States); Bronson, M. [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States); Chung, B. [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States); Hobson, B. [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States); Meeker, J. [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States); Sanchez, J. [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States); Zagar, M. [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States); Quivey, B. [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States); Sommer, S. [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States); Atherton, J. [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States)

    2017-06-06

    Lawrence Livermore National Laboratory Campus Capability Plan for 2018-2028. Lawrence Livermore National Laboratory (LLNL) is one of three national laboratories that are part of the National Nuclear Security Administration. LLNL provides critical expertise to strengthen U.S. security through development and application of world-class science and technology that: Ensures the safety, reliability, and performance of the U.S. nuclear weapons stockpile; Promotes international nuclear safety and nonproliferation; Reduces global danger from weapons of mass destruction; Supports U.S. leadership in science and technology. Essential to the execution and continued advancement of these mission areas are responsive infrastructure capabilities. This report showcases each LLNL capability area and describes the mission, science, and technology efforts enabled by LLNL infrastructure, as well as future infrastructure plans.

  8. Capabilities for innovation

    DEFF Research Database (Denmark)

    Nielsen, Peter; Nielsen, Rene Nesgaard; Bamberger, Simon Grandjean

    2012-01-01

    is a survey that collected information from 601 firms belonging to the private urban sector in Denmark. The survey was carried out in late 2010. Keywords: dynamic capabilities/innovation/globalization/employee/employer cooperation/Nordic model Acknowledgment: The GOPA study was financed by grant 20080053113......Technological developments combined with increasing levels of competition related to the ongoing globalization imply that firms find themselves in dynamic, changing environments that call for dynamic capabilities. This challenges the internal human and organizational resources of firms in general...

  9. Human push capability.

    Science.gov (United States)

    Barnett, Ralph L; Liber, Theodore

    2006-02-22

    Use of unassisted human push capability arises from time to time in the areas of crowd and animal control, the security of locked doors, the integrity of railings, the removal of tree stumps and entrenched vehicles, the manoeuvering of furniture, and athletic pursuits such as US football or wrestling. Depending on the scenario, human push capability involves strength, weight, weight distribution, push angle, footwear/floor friction, and the friction between the upper body and the pushed object. Simple models are used to establish the relationships among these factors.

  10. The Capability Approach

    OpenAIRE

    Robeyns, Ingrid

    2011-01-01

    textabstract In its most general description, the capability approach is a flexible and multi-purpose normative framework, rather than a precise theory of well-being, freedom or justice. At its core are two normative claims: first, the claim that the freedom to achieve well-being is of primary moral importance, and second, that freedom to achieve well-being is to be understood in terms of people’s capabilities, that is, their real opportunities to do and be what they have reason to value. Thi...

  11. Sandia QIS Capabilities.

    Energy Technology Data Exchange (ETDEWEB)

    Muller, Richard P. [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States)

    2017-07-01

    Sandia National Laboratories has developed a broad set of capabilities in quantum information science (QIS), including elements of quantum computing, quantum communications, and quantum sensing. The Sandia QIS program is built atop unique DOE investments at the laboratories, including the MESA microelectronics fabrication facility, the Center for Integrated Nanotechnologies (CINT) facilities (joint with LANL), the Ion Beam Laboratory, and ASC High Performance Computing (HPC) facilities. Sandia has invested $75 M of LDRD funding over 12 years to develop unique, differentiating capabilities that leverage these DOE infrastructure investments.

  12. Adult Financial Capability Framework. Second Edition

    Science.gov (United States)

    Basic Skills Agency, 2006

    2006-01-01

    Both the Financial Services Authority and the Basic Skills Agency are committed to supporting those individuals and organisations working to improve the financial capability of themselves and others. The development of the National Strategy for Financial Capability, coordinated by the Financial Services Authority, and the commissioning of a…

  13. ISOPHOT - Capabilities and performance

    DEFF Research Database (Denmark)

    Lemke, D.; Klaas, U.; Abolins, J.

    1996-01-01

    ISOPHOT covers the largest wavelength range on ISO from 2.5 to 240 mu m. Its scientific capabilities include multi filter and multi-aperture photometry, polarimetry, imaging and spectrophotometry. All modes can optionally include a focal plane chopper. The backbone of the photometric calibration...

  14. Capabilities for Intercultural Dialogue

    Science.gov (United States)

    Crosbie, Veronica

    2014-01-01

    The capabilities approach offers a valuable analytical lens for exploring the challenge and complexity of intercultural dialogue in contemporary settings. The central tenets of the approach, developed by Amartya Sen and Martha Nussbaum, involve a set of humanistic goals including the recognition that development is a process whereby people's…

  15. Capabilities and Special Needs

    DEFF Research Database (Denmark)

    Kjeldsen, Christian Christrup

    into international consideration in relation to the implementation of the UN convention on the rights of persons with disabilities. As for the theoretical basis, the research makes use of the sociological open-ended and relational concepts of Pierre Bourdieu and the normative yardstick of the Capability Approach...

  16. Metrology Measurement Capabilities

    Energy Technology Data Exchange (ETDEWEB)

    Dr. Glen E. Gronniger

    2007-10-02

    This document contains descriptions of Federal Manufacturing & Technologies (FM&T) Metrology capabilities, traceability flow charts, and the measurement uncertainty of each measurement capability. Metrology provides NIST traceable precision measurements or equipment calibration for a wide variety of parameters, ranges, and state-of-the-art uncertainties. Metrology laboratories conform to the requirements of the Department of Energy Development and Production Manual Chapter 13.2, ANSI/ISO/IEC ANSI/ISO/IEC 17025:2005, and ANSI/NCSL Z540-1. FM&T Metrology laboratories are accredited by NVLAP for the parameters, ranges, and uncertainties listed in the specific scope of accreditation under NVLAP Lab code 200108-0. See the Internet at http://ts.nist.gov/Standards/scopes/2001080.pdf. These parameters are summarized. The Honeywell Federal Manufacturing & Technologies (FM&T) Metrology Department has developed measurement technology and calibration capability in four major fields of measurement: (1) Mechanical; (2) Environmental, Gas, Liquid; (3) Electrical (DC, AC, RF/Microwave); and (4) Optical and Radiation. Metrology Engineering provides the expertise to develop measurement capabilities for virtually any type of measurement in the fields listed above. A strong audit function has been developed to provide a means to evaluate the calibration programs of our suppliers and internal calibration organizations. Evaluation includes measurement audits and technical surveys.

  17. The Capability Approach

    NARCIS (Netherlands)

    I.A.M. Robeyns (Ingrid)

    2011-01-01

    textabstract In its most general description, the capability approach is a flexible and multi-purpose normative framework, rather than a precise theory of well-being, freedom or justice. At its core are two normative claims: first, the claim that the freedom to achieve well-being is of primary

  18. Sensor Alerting Capability

    Science.gov (United States)

    Henriksson, Jakob; Bermudez, Luis; Satapathy, Goutam

    2013-04-01

    There is a large amount of sensor data generated today by various sensors, from in-situ buoys to mobile underwater gliders. Providing sensor data to the users through standardized services, language and data model is the promise of OGC's Sensor Web Enablement (SWE) initiative. As the amount of data grows it is becoming difficult for data providers, planners and managers to ensure reliability of data and services and to monitor critical data changes. Intelligent Automation Inc. (IAI) is developing a net-centric alerting capability to address these issues. The capability is built on Sensor Observation Services (SOSs), which is used to collect and monitor sensor data. The alerts can be configured at the service level and at the sensor data level. For example it can alert for irregular data delivery events or a geo-temporal statistic of sensor data crossing a preset threshold. The capability provides multiple delivery mechanisms and protocols, including traditional techniques such as email and RSS. With this capability decision makers can monitor their assets and data streams, correct failures or be alerted about a coming phenomena.

  19. Demonstration of New OLAF Capabilities and Technologies

    Science.gov (United States)

    Kingston, C.; Palmer, E.; Stone, J.; Neese, C.; Mueller, B.

    2017-06-01

    Upgrades to the On-Line Archiving Facility (OLAF) PDS tool are leading to improved usability and additional functionality by integration of JavaScript web app frameworks. Also included is the capability to upload tabular data as CSV files.

  20. Atmospheric Release Advisory Capability

    International Nuclear Information System (INIS)

    Dickerson, M.H.; Gudiksen, P.H.; Sullivan, T.J.

    1983-02-01

    The Atmospheric Release Advisory Capability (ARAC) project is a Department of Energy (DOE) sponsored real-time emergency response service available for use by both federal and state agencies in case of a potential or actual atmospheric release of nuclear material. The project, initiated in 1972, is currently evolving from the research and development phase to full operation. Plans are underway to expand the existing capability to continuous operation by 1984 and to establish a National ARAC Center (NARAC) by 1988. This report describes the ARAC system, its utilization during the past two years, and plans for its expansion during the next five to six years. An integral part of this expansion is due to a very important and crucial effort sponsored by the Defense Nuclear Agency to extend the ARAC service to approximately 45 Department of Defense (DOD) sites throughout the continental US over the next three years

  1. Expeditionary Rubber Removal Capability

    Science.gov (United States)

    2006-12-31

    the modified spray unit or system with equivalent capabilities. 24 25 9.8. A pressure sensor or caster wheels should be incorporated into the...DISCUSSION 18 8.0 CONCLUSIONS 23 9.0 RECOMMENDATIONS 24 APPENDIX A – DETAILED LIST OF EQUIPMENT AND MODIFICATIONS 26 APPENDIX B – LIST OF SOURCES FOR...tall Weight – 4820 lb (No Attachments) Top Speed – 18 mph High Flow Hydraulics (Optional) – 26 gpm Steering – All Wheel Steering Cargo Max Load

  2. Atmospheric release advisory capability

    International Nuclear Information System (INIS)

    Sullivan, T.J.

    1981-01-01

    The ARAC system (Atmospheric Release Advisory Capability) is described. The system is a collection of people, computers, computer models, topographic data and meteorological input data that together permits a calculation of, in a quasi-predictive sense, where effluent from an accident will migrate through the atmosphere, where it will be deposited on the ground, and what instantaneous and integrated dose an exposed individual would receive

  3. An NAD(P)H:quinone oxidoreductase 1 (NQO1) enzyme responsive nanocarrier based on mesoporous silica nanoparticles for tumor targeted drug delivery in vitro and in vivo

    Science.gov (United States)

    Gayam, Srivardhan Reddy; Venkatesan, Parthiban; Sung, Yi-Ming; Sung, Shuo-Yuan; Hu, Shang-Hsiu; Hsu, Hsin-Yun; Wu, Shu-Pao

    2016-06-01

    The synthesis and characterization of an NAD(P)H:quinone oxidoreductase 1 (NQO1) enzyme responsive nanocarrier based on mesoporous silica nanoparticles (MSNPs) for on-command delivery applications has been described in this paper. Gatekeeping of MSNPs is achieved by the integration of mechanically interlocked rotaxane nanovalves on the surface of MSNPs. The rotaxane nanovalve system is composed of a linear stalk anchoring on the surface of MSNPs, an α-cyclodextrin ring that encircles it and locks the payload ``cargo'' molecules in the mesopores, and a benzoquinone stopper incorporated at the end of the stalk. The gate opening and controlled release of the cargo are triggered by cleavage of the benzoquinone stopper using an endogenous NQO1 enzyme. In addition to having efficient drug loading and controlled release mechanisms, this smart biocompatible carrier system showed obvious uptake and consequent release of the drug in tumor cells, could selectively induce the tumor cell death and enhance the capability of inhibition of tumor growth in vivo. The controlled drug delivery system demonstrated its use as a potential theranostic material.The synthesis and characterization of an NAD(P)H:quinone oxidoreductase 1 (NQO1) enzyme responsive nanocarrier based on mesoporous silica nanoparticles (MSNPs) for on-command delivery applications has been described in this paper. Gatekeeping of MSNPs is achieved by the integration of mechanically interlocked rotaxane nanovalves on the surface of MSNPs. The rotaxane nanovalve system is composed of a linear stalk anchoring on the surface of MSNPs, an α-cyclodextrin ring that encircles it and locks the payload ``cargo'' molecules in the mesopores, and a benzoquinone stopper incorporated at the end of the stalk. The gate opening and controlled release of the cargo are triggered by cleavage of the benzoquinone stopper using an endogenous NQO1 enzyme. In addition to having efficient drug loading and controlled release mechanisms, this

  4. Tumor-Targeting Salmonella typhimurium A1-R Promotes Tumoricidal CD8+ T Cell Tumor Infiltration and Arrests Growth and Metastasis in a Syngeneic Pancreatic-Cancer Orthotopic Mouse Model.

    Science.gov (United States)

    Murakami, Takashi; Hiroshima, Yukihiko; Zhang, Yong; Zhao, Ming; Kiyuna, Tasuku; Hwang, Ho Kyoung; Miyake, Kentaro; Homma, Yuki; Mori, Ryutaro; Matsuyama, Ryusei; Chishima, Takashi; Ichikawa, Yasushi; Tanaka, Kuniya; Bouvet, Michael; Endo, Itaru; Hoffman, Robert M

    2018-01-01

    The present study determined the effect of the tumor-targeting strain Salmonella typhimurium A1-R (S. typhimurium A1-R) on CD8 + tumor-infiltrating lymphocytes (TILs) in a syngeneic pancreatic-cancer orthotopic mouse model. The effect of tumor-targeting S. typhimurium A1-R on CD8 + TILs was determined on the Pan02 murine pancreatic-adenocarcinoma implanted orthotopically in the pancreatic tail of C57BL/6 immunocompromised mice. Three weeks after orthotopic implantation, mice were randomized as follows G1: untreated control group (n = 8); and G2: S. typhimurium A1-R-treatment group (n = 8, 1 × 10 7 colony forming units [CFU]/body, iv, weekly, 3 weeks). On the 22nd day from initial treatment, all mice were sacrificed and tumors were harvested. The tumor-volume ratio was defined as ratio of tumor volume on the 22nd day relative to the 1st day. The tumor volume ratio was significantly lower in the S. typhimurium A1-R-treated group (G2) (3.0 ± 2.8) than the untreated control (G1) (39.9 ± 30.7, P R-treated mice (G2). Six mice in G1 had peritoneal dissemination, whereas no mice showed peritoneal dissemination in G2 (P R promotes CD8 + T cell infiltration and inhibition of tumor growth and metastasis. J. Cell. Biochem. 119: 634-639, 2018. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

  5. A produção enxuta como fator diferencial na capacidade de fornecimento de PMEs Lean production as a tool to improve the supply capability of the SMEs

    Directory of Open Access Journals (Sweden)

    Maria Letícia Sousa Correia Lima

    2003-01-01

    Full Text Available Face ao processo de reestruturação produtiva que a indústria automotiva brasileira tem vivenciado, notadamente a partir dos anos 1990, e à influência da filosofia enxuta de produção neste, o presente artigo traz um estudo realizado em pequenas e médias empresas (PMEs gaúchas sobre o impacto potencial da aplicação de uma ferramenta da produção enxuta, o Mapeamento do Fluxo de Valor, na capacidade de fornecimento destas. Foram analisadas sete empresas no Estado. O resultado obtido foi uma redução geral nos tempos de estoques de 23%, o mesmo ocorrendo para o tempo de agregação de valor, reduzido em 65%. Pode-se dizer, portanto, que os ganhos potenciais com a aplicação das propostas apresentadas possibilitariam às empresas não somente fornecer de acordo com a demanda do cliente e em fluxo contínuo, mas também aumentar sua capacidade de fornecimento, atendendo às exigências de preço, prazo e flexibilidade.The automotive industry, especially in the 90's, has been passed through a re-structure process of its productive base and supply relationship. Supporting such a process, there is a production philosophy coined lean production. This paper aims at pointing out some considerations about what could be done, regarding the production process, that may improve the supply capability of the autoparts firms in the RS state. Seven firms were analyzed and a lean production tool, the Value Stream Mapping, was applied. The results obtained were positive in all firms. The general stock reductions were of about 23%. Concerning value addition the reductions were of about 65%. Therefore, the potential gains from the implementation of the improvements suggested at Value Stream Map would make it possible not only to produce accordingly to the demand but also, to increase the supply capability of the firms.

  6. The value of oxygen-isotope data and multiple discharge records in calibrating a fully-distributed, physically-based rainfall-runoff model (CRUM3) to improve predictive capability

    Science.gov (United States)

    Neill, Aaron; Reaney, Sim

    2015-04-01

    those derived from the oxygen-18 data to see how well the model captured catchment dynamics. The value of incorporating the oxygen-18 data set, as well as discharge data sets from multiple as opposed to single gauging stations in each catchment, in the calibration process to improve the predictive capability of the model was then investigated. This was achieved by assessing by how much the identifiability of the model parameters and the ability of the model to represent the runoff processes operating in each catchment improved with the inclusion of the additional data sets with respect to the likely costs that would be incurred in obtaining the data sets themselves.

  7. The evolution of alliance capabilities

    NARCIS (Netherlands)

    Heimeriks, K.H.; Duysters, G.M.; Vanhaverbeke, W.P.M.

    2004-01-01

    This paper assesses the effectiveness and differential performance effects of learning mechanisms on the evolution of alliance capabilities. Relying on the concept of capability lifecycles, prior research has suggested that different capability levels could be identified in which different

  8. Building Server Capabilities

    DEFF Research Database (Denmark)

    Adeyemi, Oluseyi

    2013-01-01

    Many western companies have moved part of their operations to China in order to take advantage of cheap resources and/or to gain access to a high potential market. Depending on motive, offshore facilities usually start either as “sales-only” of products exported by headquarters or “production......-only”, exporting parts and components back to headquarter for sales in the home country. In the course of time, the role of offshore subsidiaries in a company’s operations network tends to change and, with that, the capabilities, of the subsidiaries. Focusing on Danish subsidiaries in China, the objective...

  9. Building server capabilities

    DEFF Research Database (Denmark)

    Adeyemi, Oluseyi

    Many western companies have moved part of their operations to China in order to take advantage of cheap resources and/or to gain access to a high potential market. Depending on motive, offshore facilities usually start either as “sales-only” of products exported by headquarters or “production......-only”, exporting parts and components back to headquarter for sales in the home country. In the course of time, the role of offshore subsidiaries in a company’s operations network tends to change and, with that, the capabilities, of the subsidiaries. Focusing on Danish subsidiaries in China, the objective...

  10. Tumor Targeting via Sialic Acid: [68Ga]DOTA-en-pba as a New Tool for Molecular Imaging of Cancer with PET.

    Science.gov (United States)

    Tsoukalas, Charalambos; Geninatti-Crich, Simonetta; Gaitanis, Anastasios; Tsotakos, Theodoros; Paravatou-Petsotas, Maria; Aime, Silvio; Jiménez-Juárez, Rogelio; Anagnostopoulos, Constantinos D; Djanashvili, Kristina; Bouziotis, Penelope

    2018-02-20

    The aim of this study was to demonstrate the potential of Ga-68-labeled macrocycle (DOTA-en-pba) conjugated with phenylboronic vector for tumor recognition by positron emission tomography (PET), based on targeting of the overexpressed sialic acid (Sia). The imaging reporter DOTA-en-pba was synthesized and labeled with Ga-68 at high efficiency. Cell binding assay on Mel-C and B16-F10 melanoma cells was used to evaluate melanin production and Sia overexpression to determine the best model for demonstrating the capability of [ 68 Ga]DOTA-en-pba to recognize tumors. The in vivo PET imaging was done with B16-F10 tumor-bearing SCID mice injected with [ 68 Ga]DOTA-en-pba intravenously. Tumor, blood, and urine metabolites were assessed to evaluate the presence of a targeting agent. The affinity of [ 68 Ga]DOTA-en-pba to Sia was demonstrated on B16-F10 melanoma cells, after the production of melanin as well as Sia overexpression was proved to be up to four times higher in this cell line compared to that in Mel-C cells. Biodistribution studies in B16-F10 tumor-bearing SCID mice showed blood clearance at the time points studied, while uptake in the tumor peaked at 60 min post-injection (6.36 ± 2.41 % ID/g). The acquired PET images were in accordance with the ex vivo biodistribution results. Metabolite assessment on tumor, blood, and urine samples showed that [ 68 Ga]DOTA-en-pba remains unmetabolized up to at least 60 min post-injection. Our work is the first attempt for in vivo imaging of cancer by targeting overexpression of sialic acid on cancer cells with a radiotracer in PET.

  11. Laboratory microfusion capability study

    International Nuclear Information System (INIS)

    1993-05-01

    The purpose of this study is to elucidate the issues involved in developing a Laboratory Microfusion Capability (LMC) which is the major objective of the Inertial Confinement Fusion (ICF) program within the purview of the Department of Energy's Defense Programs. The study was initiated to support a number of DOE management needs: to provide insight for the evolution of the ICF program; to afford guidance to the ICF laboratories in planning their research and development programs; to inform Congress and others of the details and implications of the LMC; to identify criteria for selection of a concept for the Laboratory Microfusion Facility and to develop a coordinated plan for the realization of an LMC. As originally proposed, the LMC study was divided into two phases. The first phase identifies the purpose and potential utility of the LMC, the regime of its performance parameters, driver independent design issues and requirements, its development goals and requirements, and associated technical, management, staffing, environmental, and other developmental and operational issues. The second phase addresses driver-dependent issues such as specific design, range of performance capabilities, and cost. The study includes four driver options; the neodymium-glass solid state laser, the krypton fluoride excimer gas laser, the light-ion accelerator, and the heavy-ion induction linear accelerator. The results of the Phase II study are described in the present report

  12. On the improvement of the response capability of the control room operator in a pressurized water reactor nuclear power plant in a severe earthquake through the use of emergency response guidelines

    International Nuclear Information System (INIS)

    Lee, S.

    1989-01-01

    Recent probabilistic risk assessment studies indicate that potential accidents initiated by large earthquakes are among the major contributors to public risk from nuclear power plants. During a severe earthquake, the symptoms presented to operators may be unreliable and may endanger the validity of actions in emergency response guidelines (ERGs). The objective of the present study is to improve the operator capability of responding to seismic damage through the use of ERGS. The methods used are to deterministically identify the possible weakness of ERGs, given a severe earthquake, and to probabilistically evaluate those identified weaknesses. Several cases are postulated. Each of them contains system failures with or without indicator failures and leads the core to meltdown conditions if the operator follows the ERGs strictly without any deviation. The likelihood of each case is estimated. A LISP program is developed to estimate the plant seismic risk with which the relative risk contribution of each postulated case is estimated. As a result, ten cases are postulated and possible remedies for each case are discussed. The likelihood of each case is estimated to be not negligible. The identified indicator failures should be considered in future refinement of the ERGS. The development of an expert system to provide remedial procedures should be considered after a more thorough study in which many more cases are postulated

  13. Analytical Chemistry Core Capability Assessment - Preliminary Report

    International Nuclear Information System (INIS)

    Barr, Mary E.; Farish, Thomas J.

    2012-01-01

    The concept of 'core capability' can be nebulous one. Even at a fairly specific level, where core capability equals maintaining essential services, it is highly dependent upon the perspective of the requestor. Samples are submitted to analytical services because the requesters do not have the capability to conduct adequate analyses themselves. Some requests are for general chemical information in support of R and D, process control, or process improvement. Many analyses, however, are part of a product certification package and must comply with higher-level customer quality assurance requirements. So which services are essential to that customer - just those for product certification? Does the customer also (indirectly) need services that support process control and improvement? And what is the timeframe? Capability is often expressed in terms of the currently utilized procedures, and most programmatic customers can only plan a few years out, at best. But should core capability consider the long term where new technologies, aging facilities, and personnel replacements must be considered? These questions, and a multitude of others, explain why attempts to gain long-term consensus on the definition of core capability have consistently failed. This preliminary report will not try to define core capability for any specific program or set of programs. Instead, it will try to address the underlying concerns that drive the desire to determine core capability. Essentially, programmatic customers want to be able to call upon analytical chemistry services to provide all the assays they need, and they don't want to pay for analytical chemistry services they don't currently use (or use infrequently). This report will focus on explaining how the current analytical capabilities and methods evolved to serve a variety of needs with a focus on why some analytes have multiple analytical techniques, and what determines the infrastructure for these analyses. This information will be

  14. Technological Innovation Capabilities and Firm Performance

    OpenAIRE

    Richard C.M. Yam; William Lo; Esther P.Y. Tang; Antonio; K.W. Lau

    2010-01-01

    Technological innovation capability (TIC) is defined as a comprehensive set of characteristics of a firm that facilities and supports its technological innovation strategies. An audit to evaluate the TICs of a firm may trigger improvement in its future practices. Such an audit can be used by the firm for self assessment or third-party independent assessment to identify problems of its capability status. This paper attempts to develop such an auditing framework that can...

  15. Preparation, radioiodination and in vitro evaluation of a nido-carborane-dextran conjugate, a potential residualizing label for tumor targeting proteins and peptides

    International Nuclear Information System (INIS)

    Tolmachev, V.; Bruskin, A.; Uppsala University; Sjoeberg, S.; Carlsson, J.; Lundqvist, H.

    2004-01-01

    Polysaccharides are not degradable by proteolytic enzymes in lysosomes and do not diffuse through cellular membranes. Thus, attached to an internalizing, targeting protein, such polysaccharide linkers, will remain intracellularly after protein degradation. They can be labeled with halogens and provide then a so called residualizing label. Such an approach improves tumor-to-non-tumor radioactivity ratio and, consequently, the results of radionuclide diagnostics and therapy. A new approach to obtain a stable halogenation of the polysaccharide dextran using 7-(3-amino-propyl)-7,8-dicarba-nido-undecaborate (-) (ANC) is presented. Dextran T10 was partially oxidized by metaperiodate, and ANC was coupled to dextran by reductive amination. The conjugate was then labeled with 125 I using either Chloramine-T or IodoGen as oxidants. Labeling efficiency was 69-85%. Stability of the label was evaluated in rat liver homogenates. Under these conditions, the ANC-dextran conjugate was found to be more stable than labeled albumin, which was used as a control protein. (author)

  16. Tumor-targeting magnetic lipoplex delivery of short hairpin RNA suppresses IGF-1R overexpression of lung adenocarcinoma A549 cells in vitro and in vivo.

    Science.gov (United States)

    Wang, Chunmao; Ding, Chao; Kong, Minjian; Dong, Aiqiang; Qian, Jianfang; Jiang, Daming; Shen, Zhonghua

    2011-07-08

    Liposomal magnetofection potentiates gene transfection by applying a magnetic field to concentrate magnetic lipoplexes onto target cells. Magnetic lipoplexes are self-assembling ternary complexes of cationic lipids with plasmid DNA associated with superparamagnetic iron oxide nanoparticles (SPIONs). Type1 insulin-like growth factor receptor (IGF-1R), an important oncogene, is frequently overexpressed in lung cancer and mediates cancer cell proliferation and tumor growth. In this study, we evaluated the transfection efficiency (percentage of transfected cells) and therapeutic potential (potency of IGF-1R knockdown) of liposomal magnetofection of plasmids expressing GFP and shRNAs targeting IGF-1R (pGFPshIGF-1Rs) in A549 cells and in tumor-bearing mice as compared to lipofection using Lipofectamine 2000. Liposomal magnetofection provided a threefold improvement in transgene expression over lipofection and transfected up to 64.1% of A549 cells in vitro. In vitro, IGF-1R specific-shRNA transfected by lipofection inhibited IGF-1R protein by 56.1±6% and by liposomal magnetofection by 85.1±3%. In vivo delivery efficiency of the pGFPshIGF-1R plasmid into the tumor was significantly higher in the liposomal magnetofection group than in the lipofection group. In vivo IGF-1R specific-shRNA by lipofection inhibited IGF-1R protein by an average of 43.8±5.3%; that by liposomal magnetofection inhibited IGF-1R protein by 43.4±5.7%, 56.3±9.6%, and 72.2±6.8%, at 24, 48, and 72 h, respectively, after pGFPshIGF-1R injection. Our findings indicate that liposomal magnetofection may be a promising method that allows the targeting of gene therapy to lung cancer. Copyright © 2011 Elsevier Inc. All rights reserved.

  17. Encapsulation of temozolomide in a tumor-targeting nanocomplex enhances anti-cancer efficacy and reduces toxicity in a mouse model of glioblastoma.

    Science.gov (United States)

    Kim, Sang-Soo; Rait, Antonina; Kim, Eric; DeMarco, James; Pirollo, Kathleen F; Chang, Esther H

    2015-12-01

    Although temozolomide (TMZ) is the current first-line chemotherapy for glioblastoma multiforme (GBM), most patients either do not respond or ultimately fail TMZ treatment. Both intrinsic tumor resistance and limited access of TMZ to brain tumors as a result of the blood-brain barrier (BBB) contribute to poor response and ultimately to poor prognosis for GBM patients. We have developed a "dual-targeting" nanomedicine that both actively crosses the BBB and actively targets cancer cells once in the brain parenchyma. This nanomedicine (termed scL-TMZ) is sized ~40 nm and comprised of a cationic liposome (DOTAP:DOPE) encapsulating TMZ. The surface of liposome is decorated with anti-transferrin receptor single-chain antibody fragments to facilitate the crossing of the BBB by the scL-TMZ in addition to targeting GBM in the brain. This novel formulation was found to be markedly more effective than standard TMZ in both TMZ-resistant and TMZ-sensitive GBM. Encapsulation of TMZ also markedly enhanced its efficacy in killing a variety of non-GBM tumor cells. The scL-TMZ nanocomplex was shown to target cancer stem cells, which have been linked to both drug resistance and recurrence in GBM. Most significantly, systemically administered scL-TMZ significantly prolonged survival in mice bearing intracranial GBM tumors. The improved efficacy of scL-TMZ compared to standard TMZ was accompanied by reduced toxicity, so we conclude that the scL-TMZ nanomedicine holds great promise as a more effective therapy for GBM and other tumor types. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  18. Comparative assessment of a 99mTc labeled H1299.2-HYNIC peptide bearing two different co-ligands for tumor-targeted imaging.

    Science.gov (United States)

    Torabizadeh, Seyedeh Atekeh; Abedi, Seyed Mohammad; Noaparast, Zohreh; Hosseinimehr, Seyed Jalal

    2017-05-01

    Peptides are a class of targeting agents that bind to cancer-specific cell surfaces. Since they specifically target cancer cells, they could be used as molecular imaging tools. In this study, the 15-mer peptide Ac-H1299.2 (YAAWPASGAWTGTAP) was conjugated with HYNIC via lysine amino acid on C-terminus and labeled with 99m Tc using tricine and EDDA/tricine as the co-ligands. These radiotracers were evaluated for potential utilization in diagnostic imaging of ovarian cancer cells (SKOV-3). The cell-specificity of these radiolabeled peptides was determined based on their binding on an ovarian cancer cell line (SKOV-3), and displaying a low affinity for lung adenocarcinoma cell line (A549) and breast cancer cell line (MCF7). Biodistribution studies were conducted in normal mice as well as in nude mice bearing SKOV-3 ovarian cancer xenografts. HYNIC-peptide was labeled with 99m Tc with more than 99% efficiency and showed high stability in buffer and serum. We observed nanomolar binding affinities for both radiolabeled peptides. The tumor uptakes were 3.27%±0.46% and 1.55%±0.20% for tricine and 2.34±1.1% and 1.09%±0.18% for EDDA/tricine at 1 and 4h after injection, respectively. A higher tumor to background ratio and lower radioactivity in the blood were observed for EDDA/tricine co-ligands, leading to clear tumor visualization in imaging with injection of this peptide. This new 99m Tc-labeled peptide selectively targeted ovarian cancer and introduction of a (EDDA/tricine) as a co-ligand improved the pharmacokinetics of 99m Tc-labeled H1299.2 for tumor imaging in animals. Copyright © 2017 Elsevier Ltd. All rights reserved.

  19. Aircraft Capability Management

    Science.gov (United States)

    Mumaw, Randy; Feary, Mike

    2018-01-01

    This presentation presents an overview of work performed at NASA Ames Research Center in 2017. The work concerns the analysis of current aircraft system management displays, and the initial development of an interface for providing information about aircraft system status. The new interface proposes a shift away from current aircraft system alerting interfaces that report the status of physical components, and towards displaying the implications of degradations on mission capability. The proposed interface describes these component failures in terms of operational consequences of aircraft system degradations. The research activity was an effort to examine the utility of different representations of complex systems and operating environments to support real-time decision making of off-nominal situations. A specific focus was to develop representations that provide better integrated information to allow pilots to more easily reason about the operational consequences of the off-nominal situations. The work is also seen as a pathway to autonomy, as information is integrated and understood in a form that automated responses could be developed for the off-nominal situations in the future.

  20. Production capability and supply

    International Nuclear Information System (INIS)

    Klemenic, J.

    1977-01-01

    The strong market for uranium of recent years is about to usher in a new era in domestic uranium production. The spot market price of uranium has remained relatively stable at a little over $40/lb for more than 18 months. Many of the recent contracts for delivery in the early 1980s are calling for prices in the range of $40 to $65 per lb in year-of-delivery dollars. Low-grade, high-cost projects, such as uranium recovery from mill tailings and the reopening of ''mined-out'' ore bodies, have already been initiated. New underground mines to produce at greater depths, and new surface mines to recover lower grade ores, are being developed or seriously planned. In keeping with this movement to recover uranium from low-grade ore and other high cost materials, the Grand Junction Office has examined, for the first time, the production capability of the domestic industry assuming a $30/lb (or less) ''forward cost'' resource base. As in the past, keep in mind that the market price needed to stimulate full production of a given resource base may be significantly higher than the estimated forward cost of producing that resource. Results of the $30/lb study are presented

  1. LHC Capabilities for Quarkonia

    CERN Document Server

    Petrushanko, Sergey

    2008-01-01

    The measurement of the charmonium and bottomonium resonances in nucleus-nucleus collisions provides crucial information on high-density QCD matter. First, the suppression of quarkonia production is generally agreed to be one of the most direct probes of quark-gluon plasma formation. The observation of anomalous J/$\\psi$ suppression at the CERN-SPS and at RHIC is well established but the clarification of some important remaining questions requires equivalent studies of the $\\Upsilon$ family, only possible at the LHC energies. Second, the production of heavy-quarks proceeds mainly via gluon-gluon fusion processes and, as such, is sensitive to saturation of the gluon density at low-x in the nucleus. Measured departures from the expected vacuum quarkonia cross-sections in Pb+Pb collisions at the LHC will thus provide valuable information not only on the thermodynamical state of the produced partonic medium, but also on the initial-state modifications of the nuclear parton distribution functions. The capabilities ...

  2. Mobile systems capability plan

    International Nuclear Information System (INIS)

    1996-09-01

    This plan was prepared to initiate contracting for and deployment of these mobile system services. 102,000 cubic meters of retrievable, contact-handled TRU waste are stored at many sites around the country. Also, an estimated 38,000 cubic meters of TRU waste will be generated in the course of waste inventory workoff and continuing DOE operations. All the defense TRU waste is destined for disposal in WIPP near Carlsbad NM. To ship TRU waste there, sites must first certify that the waste meets WIPP waste acceptance criteria. The waste must be characterized, and if not acceptable, subjected to additional processing, including repackaging. Most sites plan to use existing fixed facilities or open new ones between FY1997-2006 to perform these functions; small-quantity sites lack this capability. An alternative to fixed facilities is the use of mobile systems mounted in trailers or skids, and transported to sites. Mobile systems will be used for all characterization and certification at small sites; large sites can also use them. The Carlsbad Area Office plans to pursue a strategy of privatization of mobile system services, since this offers a number of advantages. To indicate the possible magnitude of the costs of deploying mobile systems, preliminary estimates of equipment, maintenance, and operating costs over a 10-year period were prepared and options for purchase, lease, and privatization through fixed-price contracts considered

  3. Strength capability while kneeling.

    Science.gov (United States)

    Haslegrave, C M; Tracy, M F; Corlett, E N

    1997-12-01

    Work sometimes has to be carried out kneeling, particularly where jobs are performed in confined spaces as is common for miners, aircraft baggage handlers and maintenance workers. In order to assess the risks in performing forceful tasks under such conditions, data is needed on strength capabilities of kneeling subjects. A study was undertaken to measure isometric strength in single-handed exertions for male subjects and to investigate the effects on this of task layout factors (direction of force exertion, reach distance, height of the workpiece and orientation relative to the subject's sagittal plane). The data has been tabulated to show the degree to which strength may be reduced in different situations and analysis of the task factors showed their influence to be complex with direction of exertion and reach distance having the greatest effect. The results also suggest that exertions are weaker when subjects are kneeling on two knees than when kneeling on one knee, although this needs to be confirmed by direct experimental comparison.

  4. MHTGR inherent heat transfer capability

    International Nuclear Information System (INIS)

    Berkoe, J.M.

    1992-01-01

    This paper reports on the Commercial Modular High Temperature Gas-Cooled Reactor (MHTGR) which achieves improved reactor safety performance and reliability by utilizing a completely passive natural convection cooling system called the RCCS to remove decay heat in the event that all active cooling systems fail to operate. For the highly improbable condition that the RCCS were to become non-functional following a reactor depressurization event, the plant would be forced to rely upon its inherent thermo-physical characteristics to reject decay heat to the surrounding earth and ambient environment. A computational heat transfer model was created to simulate such a scenario. Plant component temperature histories were computed over a period of 20 days into the event. The results clearly demonstrate the capability of the MHTGR to maintain core integrity and provide substantial lead time for taking corrective measures

  5. Tumor-targeting magnetic lipoplex delivery of short hairpin RNA suppresses IGF-1R overexpression of lung adenocarcinoma A549 cells in vitro and in vivo

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Chunmao; Ding, Chao; Kong, Minjian [Department of Cardiothoracic Surgery, Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310009 (China); Dong, Aiqiang, E-mail: dr_dongaiqiang@sina.com [Department of Cardiothoracic Surgery, Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310009 (China); Qian, Jianfang; Jiang, Daming; Shen, Zhonghua [Department of Cardiothoracic Surgery, Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310009 (China)

    2011-07-08

    Highlights: {yields} We compared lipofection with magnetofection about difference of transfection efficiency on delivery a therapeutic gene in vitro and in vivo. {yields} We investigated the difference of shRNA induced by magnetofection and lipofection into A549 cell and subcutaneous tumor to knockdown IGF-1R overexpressed in A549 cell and A549 tumor. {yields} We investigated in vivo shRNA silenced IGF-1R overexpression 24, 48, and 72 h after shRNA intravenous injection into tumor-bearing mice by way of magnetofection and lipofection. {yields} Our results showed that magnetofection could achieve therapeutic gene targeted delivery into special site, which contributed to targeted gene therapy of lung cancers. -- Abstract: Liposomal magnetofection potentiates gene transfection by applying a magnetic field to concentrate magnetic lipoplexes onto target cells. Magnetic lipoplexes are self-assembling ternary complexes of cationic lipids with plasmid DNA associated with superparamagnetic iron oxide nanoparticles (SPIONs). Type1insulin-like growth factor receptor (IGF-1R), an important oncogene, is frequently overexpressed in lung cancer and mediates cancer cell proliferation and tumor growth. In this study, we evaluated the transfection efficiency (percentage of transfected cells) and therapeutic potential (potency of IGF-1R knockdown) of liposomal magnetofection of plasmids expressing GFP and shRNAs targeting IGF-1R (pGFPshIGF-1Rs) in A549 cells and in tumor-bearing mice as compared to lipofection using Lipofectamine 2000. Liposomal magnetofection provided a threefold improvement in transgene expression over lipofection and transfected up to 64.1% of A549 cells in vitro. In vitro, IGF-1R specific-shRNA transfected by lipofection inhibited IGF-1R protein by 56.1 {+-} 6% and by liposomal magnetofection by 85.1 {+-} 3%. In vivo delivery efficiency of the pGFPshIGF-1R plasmid into the tumor was significantly higher in the liposomal magnetofection group than in the

  6. Tumor-targeting magnetic lipoplex delivery of short hairpin RNA suppresses IGF-1R overexpression of lung adenocarcinoma A549 cells in vitro and in vivo

    International Nuclear Information System (INIS)

    Wang, Chunmao; Ding, Chao; Kong, Minjian; Dong, Aiqiang; Qian, Jianfang; Jiang, Daming; Shen, Zhonghua

    2011-01-01

    Highlights: → We compared lipofection with magnetofection about difference of transfection efficiency on delivery a therapeutic gene in vitro and in vivo. → We investigated the difference of shRNA induced by magnetofection and lipofection into A549 cell and subcutaneous tumor to knockdown IGF-1R overexpressed in A549 cell and A549 tumor. → We investigated in vivo shRNA silenced IGF-1R overexpression 24, 48, and 72 h after shRNA intravenous injection into tumor-bearing mice by way of magnetofection and lipofection. → Our results showed that magnetofection could achieve therapeutic gene targeted delivery into special site, which contributed to targeted gene therapy of lung cancers. -- Abstract: Liposomal magnetofection potentiates gene transfection by applying a magnetic field to concentrate magnetic lipoplexes onto target cells. Magnetic lipoplexes are self-assembling ternary complexes of cationic lipids with plasmid DNA associated with superparamagnetic iron oxide nanoparticles (SPIONs). Type1insulin-like growth factor receptor (IGF-1R), an important oncogene, is frequently overexpressed in lung cancer and mediates cancer cell proliferation and tumor growth. In this study, we evaluated the transfection efficiency (percentage of transfected cells) and therapeutic potential (potency of IGF-1R knockdown) of liposomal magnetofection of plasmids expressing GFP and shRNAs targeting IGF-1R (pGFPshIGF-1Rs) in A549 cells and in tumor-bearing mice as compared to lipofection using Lipofectamine 2000. Liposomal magnetofection provided a threefold improvement in transgene expression over lipofection and transfected up to 64.1% of A549 cells in vitro. In vitro, IGF-1R specific-shRNA transfected by lipofection inhibited IGF-1R protein by 56.1 ± 6% and by liposomal magnetofection by 85.1 ± 3%. In vivo delivery efficiency of the pGFPshIGF-1R plasmid into the tumor was significantly higher in the liposomal magnetofection group than in the lipofection group. In vivo IGF-1R

  7. Dosimetric impact of inter-observer variability for 3D conformal radiotherapy and volumetric modulated arc therapy: the rectal tumor target definition case

    International Nuclear Information System (INIS)

    Lobefalo, Francesca; Cozzi, Luca; Scorsetti, Marta; Mancosu, Pietro; Bignardi, Mario; Reggiori, Giacomo; Tozzi, Angelo; Tomatis, Stefano; Alongi, Filippo; Fogliata, Antonella; Gaudino, Anna; Navarria, Piera

    2013-01-01

    . The introduction of guidelines increases the dosimetric consistency for both techniques, with greater improvements for RA technique

  8. Sandia Laboratories technical capabilities. Auxiliary capabilities: environmental health information science

    International Nuclear Information System (INIS)

    1975-09-01

    Sandia Laboratories is an engineering laboratory in which research, development, testing, and evaluation capabilities are integrated by program management for the generation of advanced designs. In fulfilling its primary responsibility to ERDA, Sandia Laboratories has acquired extensive research and development capabilities. The purpose of this series of documents is to catalog the many technical capabilities of the Laboratories. After the listing of capabilities, supporting information is provided in the form of highlights, which show applications. This document deals with auxiliary capabilities, in particular, environmental health and information science. (11 figures, 1 table) (RWR)

  9. Sandia Laboratories technical capabilities: testing

    International Nuclear Information System (INIS)

    Lundergan, C.D.

    1975-12-01

    The testing capabilities at Sandia Laboratories are characterized. Selected applications of these capabilities are presented to illustrate the extent to which they can be applied in research and development programs

  10. Sandia Laboratories technical capabilities: electronics

    International Nuclear Information System (INIS)

    Lundergan, C.D.

    1975-12-01

    This report characterizes the electronics capabilities at Sandia Laboratories. Selected applications of these capabilities are presented to illustrate the extent to which they can be applied in research and development programs

  11. The new MCNP6 depletion capability

    International Nuclear Information System (INIS)

    Fensin, M. L.; James, M. R.; Hendricks, J. S.; Goorley, J. T.

    2012-01-01

    The first MCNP based in-line Monte Carlo depletion capability was officially released from the Radiation Safety Information and Computational Center as MCNPX 2.6.0. Both the MCNP5 and MCNPX codes have historically provided a successful combinatorial geometry based, continuous energy, Monte Carlo radiation transport solution for advanced reactor modeling and simulation. However, due to separate development pathways, useful simulation capabilities were dispersed between both codes and not unified in a single technology. MCNP6, the next evolution in the MCNP suite of codes, now combines the capability of both simulation tools, as well as providing new advanced technology, in a single radiation transport code. We describe here the new capabilities of the MCNP6 depletion code dating from the official RSICC release MCNPX 2.6.0, reported previously, to the now current state of MCNP6. NEA/OECD benchmark results are also reported. The MCNP6 depletion capability enhancements beyond MCNPX 2.6.0 reported here include: (1) new performance enhancing parallel architecture that implements both shared and distributed memory constructs; (2) enhanced memory management that maximizes calculation fidelity; and (3) improved burnup physics for better nuclide prediction. MCNP6 depletion enables complete, relatively easy-to-use depletion calculations in a single Monte Carlo code. The enhancements described here help provide a powerful capability as well as dictate a path forward for future development to improve the usefulness of the technology. (authors)

  12. The New MCNP6 Depletion Capability

    International Nuclear Information System (INIS)

    Fensin, Michael Lorne; James, Michael R.; Hendricks, John S.; Goorley, John T.

    2012-01-01

    The first MCNP based inline Monte Carlo depletion capability was officially released from the Radiation Safety Information and Computational Center as MCNPX 2.6.0. Both the MCNP5 and MCNPX codes have historically provided a successful combinatorial geometry based, continuous energy, Monte Carlo radiation transport solution for advanced reactor modeling and simulation. However, due to separate development pathways, useful simulation capabilities were dispersed between both codes and not unified in a single technology. MCNP6, the next evolution in the MCNP suite of codes, now combines the capability of both simulation tools, as well as providing new advanced technology, in a single radiation transport code. We describe here the new capabilities of the MCNP6 depletion code dating from the official RSICC release MCNPX 2.6.0, reported previously, to the now current state of MCNP6. NEA/OECD benchmark results are also reported. The MCNP6 depletion capability enhancements beyond MCNPX 2.6.0 reported here include: (1) new performance enhancing parallel architecture that implements both shared and distributed memory constructs; (2) enhanced memory management that maximizes calculation fidelity; and (3) improved burnup physics for better nuclide prediction. MCNP6 depletion enables complete, relatively easy-to-use depletion calculations in a single Monte Carlo code. The enhancements described here help provide a powerful capability as well as dictate a path forward for future development to improve the usefulness of the technology.

  13. Structural Capability of an Organization toward Innovation Capability

    DEFF Research Database (Denmark)

    Nielsen, Susanne Balslev; Momeni, Mostafa

    2016-01-01

    The scholars in the field of strategic management have developed two major approaches for attainment of competitive advantage: an approach based on environmental opportunities, and another one based on internal capabilities of an organization. Some investigations in the last two decades have...... indicated that the advantages relying on the internal capabilities of organizations may determine the competitive position of organizations better than environmental opportunities do. Characteristics of firms shows that one of the most internal capabilities that lead the organizations to the strongest...... competitive advantage in the organizations is the innovation capability. The innovation capability is associated with other organizational capabilities, and many organizations have focused on the need to identify innovation capabilities.This research focuses on recognition of the structural aspect...

  14. Pharmacological and physical vessel modulation strategies to improve EPR-mediated drug targeting to tumors.

    Science.gov (United States)

    Ojha, Tarun; Pathak, Vertika; Shi, Yang; Hennink, Wim E; Moonen, Chrit T W; Storm, Gert; Kiessling, Fabian; Lammers, Twan

    2017-09-15

    The performance of nanomedicine formulations depends on the Enhanced Permeability and Retention (EPR) effect. Prototypic nanomedicine-based drug delivery systems, such as liposomes, polymers and micelles, aim to exploit the EPR effect to accumulate at pathological sites, to thereby improve the balance between drug efficacy and toxicity. Thus far, however, tumor-targeted nanomedicines have not yet managed to achieve convincing therapeutic results, at least not in large cohorts of patients. This is likely mostly due to high inter- and intra-patient heterogeneity in EPR. Besides developing (imaging) biomarkers to monitor and predict EPR, another strategy to address this heterogeneity is the establishment of vessel modulation strategies to homogenize and improve EPR. Over the years, several pharmacological and physical co-treatments have been evaluated to improve EPR-mediated tumor targeting. These include pharmacological strategies, such as vessel permeabilization, normalization, disruption and promotion, as well as physical EPR enhancement via hyperthermia, radiotherapy, sonoporation and phototherapy. In the present manuscript, we summarize exemplary studies showing that pharmacological and physical vessel modulation strategies can be used to improve tumor-targeted drug delivery, and we discuss how these advanced combination regimens can be optimally employed to enhance the (pre-) clinical performance of tumor-targeted nanomedicines. Copyright © 2017 Elsevier B.V. All rights reserved.

  15. The Capability to Hold Property

    NARCIS (Netherlands)

    Claassen, Rutger

    2015-01-01

    This paper discusses the question of whether a capability theory of justice (such as that of Martha Nussbaum) should accept a basic “capability to hold property.” Answering this question is vital for bridging the gap between abstract capability theories of justice and their institutional

  16. Building Airport Surface HITL Simulation Capability

    Science.gov (United States)

    Chinn, Fay Cherie

    2016-01-01

    FutureFlight Central is a high fidelity, real-time simulator designed to study surface operations and automation. As an air traffic control tower simulator, FFC allows stakeholders such as the FAA, controllers, pilots, airports, and airlines to develop and test advanced surface and terminal area concepts and automation including NextGen and beyond automation concepts and tools. These technologies will improve the safety, capacity and environmental issues facing the National Airspace system. FFC also has extensive video streaming capabilities, which combined with the 3-D database capability makes the facility ideal for any research needing an immersive virtual and or video environment. FutureFlight Central allows human in the loop testing which accommodates human interactions and errors giving a more complete picture than fast time simulations. This presentation describes FFCs capabilities and the components necessary to build an airport surface human in the loop simulation capability.

  17. Uncertainces in tumor target definition using PET

    International Nuclear Information System (INIS)

    Kirov, A.

    2013-01-01

    Full text: Introduction: PET entered into the clinics for radiation therapy as a means of displaying the metabolically active part of the tumor. However this advantage, PET has a number of shortcomings that prevent its use for precise determination of the tumor boundaries. What you will learn: The aim of the lecture is to present: the requirements for the accuracy of the determination of tumor boundaries in radiation therapy; the main phenomena which bring uncertainty using PET and a brief overview of methods for segmentation of tumors and their problems

  18. Capability-based computer systems

    CERN Document Server

    Levy, Henry M

    2014-01-01

    Capability-Based Computer Systems focuses on computer programs and their capabilities. The text first elaborates capability- and object-based system concepts, including capability-based systems, object-based approach, and summary. The book then describes early descriptor architectures and explains the Burroughs B5000, Rice University Computer, and Basic Language Machine. The text also focuses on early capability architectures. Dennis and Van Horn's Supervisor; CAL-TSS System; MIT PDP-1 Timesharing System; and Chicago Magic Number Machine are discussed. The book then describes Plessey System 25

  19. Transforming organizational capabilities in strategizing

    DEFF Research Database (Denmark)

    Jørgensen, Claus; Friis, Ole Uhrskov; Koch, Christian

    2014-01-01

    Offshored and networked enterprises are becoming an important if not leading organizational form and this development seriously challenges their organizational capabilities. More specifically, over the last years, SMEs have commenced entering these kinds of arrangements. As the organizational...... capabilities of SMEs are limited at the outset, even more emphasis is needed regarding the issues of developing relevant organizational capabilities. This paper aims at investigating how capabilities evolve during an offshoring process of more than 5 years in two Danish SMEs, i.e. not only short- but long......-term evolvements within the companies. We develop our framework of understanding organizational capabilities drawing on dynamic capability, relational capability and strategy as practice concepts, appreciating the performative aspects of developing new routines. Our two cases are taken from one author’s Ph...

  20. Review and evaluation of the Nuclear Materials Management and Safeguards System (NMMSS). Volume 1. Comparison of DOE nuclear materials information system requirements with NMMSS capabilities and recommendations for NMMSS improvements

    International Nuclear Information System (INIS)

    1984-03-01

    This report documents the result of a review of the Nuclear Materials Management and Safeguards System (NMMSS), a Department of Energy nuclear materials control and accountability data base and information processing system. This review was performed to determine what data are required from the NMMSS, how it is collected, and how it is used. Based upon the review, NMMSS deficiencies and excess capabilities were identified and a draft set of requirements for the nuclear materials information system that the Office of Safeguards and Security (OSS) should be supporting as well as recommendations for attaining that capability

  1. Extension of TRIGA reactor capabilities

    International Nuclear Information System (INIS)

    Gietzen, A.J.

    1980-01-01

    The first TRIGA reactor went into operation at 10 kW about 22 years ago. Since that time 55 TRIGAs have been put into operation including steady-state powers up to 14,000 kW and pulsing reactors that pulse to 20,000,000 kW. Five more are under construction and a proposal will soon be submitted for a reactor of 25,000 kW. Along with these increases in power levels (and the corresponding fluxes) the experimental facilities have also been expanded. In addition to the installation of new TRIGA reactors with enhanced capabilities many of the older reactors have been modified and upgraded. Also, a number of reactors originally fueled with plate fuel were converted to TRIGA fuel to take advantage of the improved technical and safety characteristics, including the ability for pulsed operation. In order to accommodate increased power and performance the fuel has undergone considerable evolution. Most of the changes have been in the geometry, enrichment and cladding material. However, more recently further development on the UZrH alloy has been carried out to extend the uranium content up to 45% by weight. This increased U content is necessary to allow the use of less than 20% enrichment in the higher powered reactors while maintaining longer core lifetime. The instrumentation and control system has undergone remarkable improvement as the electronics technology has evolved so rapidly in the last two decades. The information display and the circuitry logic has also undergone improvements for enhanced ease of operation and safety. (author)

  2. Human Capital, (Human) Capabilities and Higher Education

    Science.gov (United States)

    Le Grange, L.

    2011-01-01

    In this article I initiate a debate into the (de)merits of human capital theory and human capability theory and discuss implications of the debate for higher education. Human capital theory holds that economic growth depends on investment in education and that economic growth is the basis for improving the quality of human life. Human capable…

  3. Impact of Personnel Capabilities on Organizational Innovation Capability

    DEFF Research Database (Denmark)

    Nielsen, Susanne Balslev; Momeni, Mostafa

    2016-01-01

    in this rapidly changing world. This research focuses on definition of the personnel aspect of innovation capability, and proposes a conceptual model based on the scientific articles of academic literature on organisations innovation capability. This paper includes an expert based validation in three rounds...... of the Delphi method. And for the purpose of a better appreciation of the relationship dominating the factors of the model, it has distributed the questionnaire to Iranian companies in the Food industry. This research proposed a direct relationship between Innovation Capability and the Personnel Capability...

  4. Using Porterian Activity Analysis to Understand Organizational Capabilities

    DEFF Research Database (Denmark)

    Sheehan, Norman T.; Foss, Nicolai Juul

    2017-01-01

    conceptualized by Porter’s writings on the activity-based view. Porterian activity analysis is becoming more accepted in the strategy literature, but no strategy scholar has explicitly used Porter’s activities, and particularly his concept of drivers, to understand and analyze organizational capabilities....... Introducing Porterian activities into the discussion of capabilities improves strategy scholars’ understanding of the bases of capability heterogeneity, offers academics future directions for research, and provides managers with guidance to enhance their organizations’ capabilities....

  5. Land Capability Evaluation of Upper Sekampung Watersheds

    Directory of Open Access Journals (Sweden)

    Irwan Sukri Banuwa

    2008-05-01

    Full Text Available Land degradation is a serious problem in the Upper Sekampung Watersheds. This is because the farmers cultivated in steep land to coffee crops without in adequate soil and water conservation practices. The land degradation is mostly caused by erosion. The erosion problem not only stripping the most fertile top soil and decreasing crop production, but also resulting problems in lowland. Therefore, the reorientation land management should be improved to produce agriculture sustainability. The first step is to evaluated land capability this area. The objectives of the research were evaluate land capability of Upper Sekampung Watersheds. The results showed that the Upper Sekampung Watersheds were dominated with class and subclass land capability of III-l2 about 17.630,51 ha (41,58%. All of the constrain for each land capability in this area is erosion hazard, especially land slope. From this research, cultivated land to coffee base crops were allowed in land capability II-l1.e1, III-l2, IV-l3, and VI-l4, with in adequate soil and water conservation practices. In contrary, the land capability of VII-l5 unsuitable for agriculture, they should be a nature or for conservation forest.

  6. Technological Dynamics and Social Capability

    DEFF Research Database (Denmark)

    Fagerberg, Jan; Feldman, Maryann; Srholec, Martin

    2014-01-01

    for the sample as a whole between 1998 and 2008. The results indicate that social capabilities, such as well-developed public knowledge infrastructure, an egalitarian distribution of income, a participatory democracy and prevalence of public safety condition the growth of technological capabilities. Possible...

  7. Identifying 21st Century Capabilities

    Science.gov (United States)

    Stevens, Robert

    2012-01-01

    What are the capabilities necessary to meet 21st century challenges? Much of the literature on 21st century skills focuses on skills necessary to meet those challenges associated with future work in a globalised world. The result is a limited characterisation of those capabilities necessary to address 21st century social, health and particularly…

  8. Developing Collaborative Product Development Capabilities

    DEFF Research Database (Denmark)

    Mahnke, Volker; Tran, Yen

    2012-01-01

    innovation strategies’. Our analyses suggest that developing such collaboration capabilities benefits from the search for complementary practices, the combination of learning styles, and the development of weak and strong ties. Results also underscore the crucial importance of co-evolution of multi......Collaborative product development capabilities support a company’s product innovation activities. In the context of the fast fashion sector, this paper examines the development of the product development capabilities (PDC) that align product development capabilities in a dual innovation context......, one, slow paced, where the firm is well established and the other, fast paced, which represents a new competitive arena in which the company competes. To understand the process associated with collaborative capability development, we studied three Scandinavian fashion companies pursuing ‘dual...

  9. Marketing Capability in Strategy Research

    DEFF Research Database (Denmark)

    Ritter, Thomas; Distel, Andreas Philipp

    Following the call for a demand-side perspective of strategic management (e.g., Priem et al., 2012), a firm’s marketing capability, i.e. its ability to interact with down-stream stakeholders, becomes a pivotal element in explaining a firm’s competitiveness. While marketing capability is recognized...... in the strategic management literature as an important driver of firm performance, our review of 86 articles reveals a lack of a generally accepted definition of marketing capability, a lack of a common conceptualization as well as differences in the measurement of marketing capability. In order to build a common...... ground for advancing marketing capability research and thus supporting the demand-side perspective in strategic management, we develop an integrative framework to explain the differences and propose a research agenda for developing the field....

  10. Capabilities and Incapabilities of the Capabilities Approach to Health Justice.

    Science.gov (United States)

    Selgelid, Michael J

    2016-01-01

    This first part of this article critiques Sridhar Venkatapuram's conception of health as a capability. It argues that Venkatapuram relies on the problematic concept of dignity, implies that those who are unhealthy lack lives worthy of dignity (which seems politically incorrect), sets a low bar for health, appeals to metaphysically problematic thresholds, fails to draw clear connections between appealed-to capabilities and health, and downplays the importance/relevance of health functioning. It concludes by questioning whether justice entitlements should pertain to the capability for health versus health achievements, challenging Venkatapuram's claims about the strength of health entitlements, and demonstrating that the capabilities approach is unnecessary to address social determinants of health. © 2016 John Wiley & Sons Ltd.

  11. Indigenous Technological Innovation : Capability and ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    Indigenous Technological Innovation : Capability and Competitiveness in China's ... IDRC and key partners will showcase critical work on adaptation and ... Call for new OWSD Fellowships for Early Career Women Scientists now open.

  12. Synthesis of star-branched PLA-b-PMPC copolymer micelles as long blood circulation vectors to enhance tumor-targeted delivery of hydrophobic drugs in vivo

    Energy Technology Data Exchange (ETDEWEB)

    Long, Li-xia [Tianjin Key Laboratory of Composite and Functional Materials, School of Materials Science & Engineering, Tianjin University, Tianjin 300072 (China); Zhao, Jin, E-mail: zhaojin@tju.edu.cn [Tianjin Key Laboratory of Composite and Functional Materials, School of Materials Science & Engineering, Tianjin University, Tianjin 300072 (China); Li, Ke; He, Li-gang; Qian, Xiao-ming; Liu, Chao-yong; Wang, Li-mei; Yang, Xin-qi [Tianjin Key Laboratory of Composite and Functional Materials, School of Materials Science & Engineering, Tianjin University, Tianjin 300072 (China); Sun, Jinjin [Department of General Surgery, The Second Hospital of Tianjin Medical University, Tianjin 300211 (China); Ren, Yu [Tianjin Research Center of Basic Medical Science, Tianjin Medical University, Tianjin 300070 (China); Kang, Chun-sheng, E-mail: kang97061@yahoo.com [Department of Neurosurgery, Tianjin Medical University General Hospital, Tianjin 300052 (China); Yuan, Xu-bo, E-mail: xbyuan@tju.edu.cn [Tianjin Key Laboratory of Composite and Functional Materials, School of Materials Science & Engineering, Tianjin University, Tianjin 300072 (China)

    2016-09-01

    Star-branched amphiphilic copolymer nanocarriers with high-density zwitterionic shell show great promise in drug delivery due to their controllable small size and excellent anti-biofouling properties. This gives the hydrophobic cargo with high stability and long blood circulation in vivo. In the present study, star-branched polylactic acid and poly(2-methacryloyloxyethyl phosphorylcholine) copolymers with (AB{sub 3}){sub 3}–type architecture (PLA-b-PMPC{sub 3}){sub 3} were conceived as drug vectors, and the copolymers were synthesized by an “arm-first” approach via the combination of ring opening polymerization (ROP), atom transfer radical polymerization (ATRP) and the click reaction. The self-assembled star-branched copolymer micelles (sCPM) had an average diameter of about 64.5 nm and exhibited an ultra-hydrophilic surface with an ultralow water contact angle of about 12.7°, which efficiently suppressed the adhesion of serum proteins. In vivo experiments showed that the sCPM loading strongly enhanced the blood circulation time of DiI and the plasma half-life of DiI in sCPM was 19.3 h. The relative accumulation concentration in tumor of DiI delivered by sCPM was 2.37-fold higher than that of PLA-PEG, at 4 h after intravenous injection. These results demonstrated that the star-branched copolymer (PLA-b-PMPC{sub 3}){sub 3} is a promising alternative carrier material for intravenous delivery versus classic PEG-modified strategies. - Highlights: • Star-branched amphiphilic copolymer micelles (sCPM) with zwitterionic shells were prepared. • sCPM possess an ultra-hydrophilic surface and thus inhibited the protein absorption. • sCPM can effectively prolong the cargo’s plasma circulation time. • sCPM can enhance the cargo’s passive tumor-targeted delivery.

  13. Earth Science Capability Demonstration Project

    Science.gov (United States)

    Cobleigh, Brent

    2006-01-01

    A viewgraph presentation reviewing the Earth Science Capability Demonstration Project is shown. The contents include: 1) ESCD Project; 2) Available Flight Assets; 3) Ikhana Procurement; 4) GCS Layout; 5) Baseline Predator B Architecture; 6) Ikhana Architecture; 7) UAV Capability Assessment; 8) The Big Picture; 9) NASA/NOAA UAV Demo (5/05 to 9/05); 10) NASA/USFS Western States Fire Mission (8/06); and 11) Suborbital Telepresence.

  14. ANTECEDENTS OF CUSTOMER RELATIONSHIP MANAGEMENT CAPABILITIES

    Directory of Open Access Journals (Sweden)

    Tuleu Daniela

    2015-07-01

    Full Text Available Customer relationship management, as a process to manage customer relationship initiation, maintenance and termination to maximize the value of the relationship portfolio, is an evolving process. In recent years, the development of interactive technologies (social media have revolutionized the interaction between firms and their customers and between customers. The impact of technology on CRM is improving ways of collecting and processing customer information and transforming communication with customers. In the context of the development of social networks, the introduction of social media applications in customer relationship management activities bring important changes in this area. Thus, managers need to pay attention to the interaction management as an important process of CRM and enhance the customer relationship management capabilities. The study propose a conceptual research model of several antecedents of customer relationship managements capabilities and provide the linkage between this antecedents and CRM capabilities. First, following review of existing research literature related to customer relationship management, there are some conceptual clarification on customer relationship management. Second, are presented the working concepts: the adoption of interactive technologies, customer concept, customer empowerment, customer relationship orientation and customer-centric management system. Then, it is proposed the conceptual model and finally are presented conclusions, managerial implications, limitations and research directions. From a theoretical perspective, this paper highlights the importance of marketing actions at the individual customer level and reveal the impact of adoption by companies of interactive technologies so that organizations have the opportunity to engage in conversations with customers and respond in real time the requirements that they launched the online environment. Nowadays, customers feel empowered and play

  15. Accelerator and Electrodynamics Capability Review

    International Nuclear Information System (INIS)

    Jones, Kevin W.

    2010-01-01

    Los Alamos National Laboratory (LANL) uses capability reviews to assess the science, technology and engineering (STE) quality and institutional integration and to advise Laboratory Management on the current and future health of the STE. Capability reviews address the STE integration that LANL uses to meet mission requirements. The Capability Review Committees serve a dual role of providing assessment of the Laboratory's technical contributions and integration towards its missions and providing advice to Laboratory Management. The assessments and advice are documented in reports prepared by the Capability Review Committees that are delivered to the Director and to the Principal Associate Director for Science, Technology and Engineering (PADSTE). Laboratory Management will use this report for STE assessment and planning. LANL has defined fifteen STE capabilities. Electrodynamics and Accelerators is one of the seven STE capabilities that LANL Management (Director, PADSTE, technical Associate Directors) has identified for review in Fiscal Year (FY) 2010. Accelerators and electrodynamics at LANL comprise a blend of large-scale facilities and innovative small-scale research with a growing focus on national security applications. This review is organized into five topical areas: (1) Free Electron Lasers; (2) Linear Accelerator Science and Technology; (3) Advanced Electromagnetics; (4) Next Generation Accelerator Concepts; and (5) National Security Accelerator Applications. The focus is on innovative technology with an emphasis on applications relevant to Laboratory mission. The role of Laboratory Directed Research and Development (LDRD) in support of accelerators/electrodynamics will be discussed. The review provides an opportunity for interaction with early career staff. Program sponsors and customers will provide their input on the value of the accelerator and electrodynamics capability to the Laboratory mission.

  16. Accelerator and electrodynamics capability review

    Energy Technology Data Exchange (ETDEWEB)

    Jones, Kevin W [Los Alamos National Laboratory

    2010-01-01

    Los Alamos National Laboratory (LANL) uses capability reviews to assess the science, technology and engineering (STE) quality and institutional integration and to advise Laboratory Management on the current and future health of the STE. Capability reviews address the STE integration that LANL uses to meet mission requirements. The Capability Review Committees serve a dual role of providing assessment of the Laboratory's technical contributions and integration towards its missions and providing advice to Laboratory Management. The assessments and advice are documented in reports prepared by the Capability Review Committees that are delivered to the Director and to the Principal Associate Director for Science, Technology and Engineering (PADSTE). Laboratory Management will use this report for STE assessment and planning. LANL has defined fifteen STE capabilities. Electrodynamics and Accelerators is one of the seven STE capabilities that LANL Management (Director, PADSTE, technical Associate Directors) has identified for review in Fiscal Year (FY) 2010. Accelerators and electrodynamics at LANL comprise a blend of large-scale facilities and innovative small-scale research with a growing focus on national security applications. This review is organized into five topical areas: (1) Free Electron Lasers; (2) Linear Accelerator Science and Technology; (3) Advanced Electromagnetics; (4) Next Generation Accelerator Concepts; and (5) National Security Accelerator Applications. The focus is on innovative technology with an emphasis on applications relevant to Laboratory mission. The role of Laboratory Directed Research and Development (LDRD) in support of accelerators/electrodynamics will be discussed. The review provides an opportunity for interaction with early career staff. Program sponsors and customers will provide their input on the value of the accelerator and electrodynamics capability to the Laboratory mission.

  17. Technological Capability and Firm Performance

    Directory of Open Access Journals (Sweden)

    Fernanda Maciel Reichert

    2014-08-01

    Full Text Available This research aims to investigate the relationship between investments in technological capability and economic performance in Brazilian firms. Based on economic development theory and on developed countries history, it is assumed that this relationship is positive. Through key indicators, 133 Brazilian firms have been analyzed. Given the economic circumstances of an emerging economy, which the majority of businesses are primarily based on low and medium-low-technology industries, it is not possible to affirm the existence of a positive relation between technological capability and firm performance. There are other elements that allow firms to achieve such results. Firms of lower technological intensity industries performed above average in the economic performance indicators, adversely, they invested below average in technological capability. These findings do not diminish the merit of firms’ and country’s success. They in fact confirm a historical tradition of a country that concentrates its efforts on basic industries.

  18. Functional capability of piping systems

    International Nuclear Information System (INIS)

    Terao, D.; Rodabaugh, E.C.

    1992-11-01

    General Design Criterion I of Appendix A to Part 50 of Title 10 of the Code of Federal Regulations requires, in part, that structures, systems, and components important to safety be designed to withstand the effects of earthquakes without a loss of capability to perform their safety function. ne function of a piping system is to convey fluids from one location to another. The functional capability of a piping system might be lost if, for example, the cross-sectional flow area of the pipe were deformed to such an extent that the required flow through the pipe would be restricted. The objective of this report is to examine the present rules in the American Society of Mechanical Engineers Boiler and Pressure Vessel Code, Section III, and potential changes to these rules, to determine if they are adequate for ensuring the functional capability of safety-related piping systems in nuclear power plants

  19. Upgrading of TREAT experimental capabilities

    International Nuclear Information System (INIS)

    Dickerman, C.E.; Rose, D.; Bhattacharyya, S.K.

    1982-01-01

    The TREAT facility at the Argonne National Laboratory site in the Idaho National Engineering Laboratory is being upgraded to provide capabilities for fast-reactor-safety transient experiments not possible at any other experimental facility. Principal TREAT Upgrade (TU) goal is provision for 37-pin size experiments on energetics of core-disruptive accidents (CDA) in fast breeder reactor cores with moderate sodium void coefficients. this goal requires a significant enhancement of the capabilities of the TREAT facility, specifically including reactor control, hardened neutron spectrum incident on the test sample, and enlarged building. The upgraded facility will retain the capability for small-size experiments of the types currently being performed in TREAT. Reactor building and crane upgrading have been completed. TU schedules call for the components of the upgraded reactor system to be finished in 1984, including upgraded TREAT fuel and control system, and expanded coverage by the hodoscope fuel-motion diagnostics system

  20. Nanofabrication principles, capabilities and limits

    CERN Document Server

    Cui, Zheng

    2017-01-01

    This second edition of Nanofabrication is one of the most comprehensive introductions on nanofabrication technologies and processes. A practical guide and reference, this book introduces readers to all of the developed technologies that are capable of making structures below 100nm. The principle of each technology is introduced and illustrated with minimum mathematics involved. Also analyzed are the capabilities of each technology in making sub-100nm structures, and the limits of preventing a technology from going further down the dimensional scale. This book provides readers with a toolkit that will help with any of their nanofabrication challenges.

  1. Judgmental Forecasting of Operational Capabilities

    DEFF Research Database (Denmark)

    Hallin, Carina Antonia; Tveterås, Sigbjørn; Andersen, Torben Juul

    This paper explores a new judgmental forecasting indicator, the Employee Sensed Operational Capabilities (ESOC). The purpose of the ESOC is to establish a practical prediction tool that can provide early signals about changes in financial performance by gauging frontline employees’ sensing...... of changes in the firm’s operational capabilities. We present the first stage of the development of ESOC by applying a formative measurement approach to test the index in relation to financial performance and against an organizational commitment scale. We use distributed lag models to test whether the ESOC...

  2. Provisions for Climate Change Technological Capability in the ...

    African Journals Online (AJOL)

    organisational) that enable farm or actors to efficiently use equipment and information and improve technology. The paper reviewed the climate change technological capability provisions in agricultural policies, acts and initiatives in Nigeria. The technological capabilities examined were production, investment, minor ...

  3. E-Learning Capability Maturity Level in Kingdom of Bahrain

    Science.gov (United States)

    Al-Ammary, Jaflah; Mohammed, Zainab; Omran, Fatima

    2016-01-01

    Despite the effectiveness of using e-learning, educational institutions are still facing many challenges with the e-learning infrastructure and technical aspects, practices and capabilities, and improvement in learning outcome. Hence, a need for framework to benchmark the e-learning capability maturity level and measure the extent to what it is…

  4. System Reliability Analysis Capability and Surrogate Model Application in RAVEN

    Energy Technology Data Exchange (ETDEWEB)

    Rabiti, Cristian [Idaho National Lab. (INL), Idaho Falls, ID (United States); Alfonsi, Andrea [Idaho National Lab. (INL), Idaho Falls, ID (United States); Huang, Dongli [Idaho National Lab. (INL), Idaho Falls, ID (United States); Gleicher, Frederick [Idaho National Lab. (INL), Idaho Falls, ID (United States); Wang, Bei [Idaho National Lab. (INL), Idaho Falls, ID (United States); Adbel-Khalik, Hany S. [Idaho National Lab. (INL), Idaho Falls, ID (United States); Pascucci, Valerio [Idaho National Lab. (INL), Idaho Falls, ID (United States); Smith, Curtis L. [Idaho National Lab. (INL), Idaho Falls, ID (United States)

    2015-11-01

    This report collect the effort performed to improve the reliability analysis capabilities of the RAVEN code and explore new opportunity in the usage of surrogate model by extending the current RAVEN capabilities to multi physics surrogate models and construction of surrogate models for high dimensionality fields.

  5. Effects of the Program Caring for the Caregiver in improving caring capability Efectos del Programa Cuidando al Cuidador, en la mejora de la habilidad de cuidado Efeitos do Programa Cuidando o cuidador, na melhora da capacidade de cuidado

    Directory of Open Access Journals (Sweden)

    MORALES PADILLA ORFA NINETH

    2008-12-01

    Full Text Available Objective of the Study: to evaluate the effectiveness of the Program Caring for the Caregiver to strengthen capabilities with similar groups cared for in Hospital Nacional de Ortopedia y Rehabilitación Dr. Jorge von Ahn,in León,Guatemala. Methodology: quantitative, quasi-experimental method, with the participation of one sample and one control group. Results: both, experimental and control groups had a high general care capability in the pre-test, except for value. In the post-test, both groups enhanced knowledge and patience, the latter to a lesser extend. Discussion: Women continue assuming the care for their relatives, with a high degree of knowledge and patience which may be associated to social and demographic characteristics and low value, because, probably, the instrument has assessment problems. Although in the post-test the group in general reached a maximum score in the two dimensions previously described and low strengthening of value, which supports the need to continue developing the Program Caring for the Caregiver and to promote the creation of a new tool, taking into consideration the product obtained. Conclusions: the experimental Group and the control Group obtained a good initial care capability. When executing the program, an increase in knowledge and patience is observed and to a lesser extend in dimension of value, deducing from this that the latter is not really an area sensitive for the treatment carried out.Objetivo del estudio: evaluar la efectividad del Programa Cuidando al Cuidador, para el fortalecimiento de habilidades con grupos similares atendidos en el Hospital Nacional de Ortopedia y Rehabilitación Dr. Jorge von Ahn, de León, Guatemala. Metodología: cuantitativa de tipo cuasi experimental, con participación de un grupo muestra y otro de control. Resultados: tanto el grupo experimental como el de control tuvieron en la preprueba una alta habilidad de cuidado general, exceptuando el

  6. Efectos del Programa Cuidando al Cuidador, en la mejora de la habilidad de cuidado Efeitos do Programa Cuidando o cuidador, na melhora da capacidade de cuidado Effects of the Program Caring for the Caregiver in improving caring capability

    Directory of Open Access Journals (Sweden)

    ORFA NINETH MORALES PADILLA

    2008-12-01

    valor. Na pós-prova ambos os grupos aumentaram o conhecimento e paciência; o último em menor escala. Discussão: o gênero feminino continua assumindo o cuidado de seus familiares, com alto conhecimento e paciência que poderiam estar vinculadas com características sóciodemográficas, e baixo valor porque o instrumento, talvez, a presenta problemas na hora de ser avaliado. Embora na pós-prova o grupo em geral atingiu a pontuação máxima nas duas dimensões descritas com antecedência e pouco fortalecimento do valor, o que argumenta a necessidade de continuar desenvolvendo o Programa Cuidando ao Cuidador e promover a criação de uma nova ferramenta, considerando o produto obtido. Conclusões: o grupo experimental e o de controle conseguiram um bom nível de capacidade de cuidado inicial. Com a execução do programa se observa o incremento em conhecimento e paciência e, em menor grau, na dimensão de valor, é por isso que concluímos que essa é uma área não tão sensível ao tratamento efetuado.Objective of the Study: to evaluate the effectiveness of the Program Caring for the Caregiver to strengthen capabilities with similar groups cared for in Hospital Nacional de Ortopedia y Rehabilitación Dr. Jorge von Ahn,in León,Gua-temala. Methodology: quantitative, quasi-experimental method, with the participation of one sample and one control group. Results: both, experimental and control groups had a high general care capability in the pre-test, except for value. In the post-test, both groups enhanced knowledge and patience, the latter to a lesser extend. Discussion: Women continue assuming the care for their relatives, with a high degree of knowledge and patience which may be associated to social and demographic characteristics and low value, because, probably, the instrument has assessment problems. Although in the post-test the group in general reached a maximum score in the two dimensions previously described and low strengthening of value, which supports

  7. Tweaking Dendrimers and Dendritic Nanoparticles for Controlled Nano-bio Interactions: Potential Nanocarriers for Improved Cancer Targeting

    Science.gov (United States)

    Bugno, Jason; Hsu, Hao-Jui; Hong, Seungpyo

    2016-01-01

    Nanoparticles have shown great promise in the treatment of cancer, with a demonstrated potential in targeted drug delivery. Among a myriad of nanocarriers that have been recently developed, dendrimers have attracted a great deal of scientific interests due to their unique chemical and structural properties that allow for precise engineering of their characteristics. Despite this, the clinical translation of dendrimers has been hindered due to their drawbacks, such as scale-up issues, rapid systemic elimination, inefficient tumor accumulation, and limited drug loading. In order to overcome these limitations, a series of reengineered dendrimers have been recently introduced using various approaches, including: i) modifications of structure and surfaces; ii) integration with linear polymers; and iii) hybridization with other types of nanocarriers. Chemical modifications and surface engineering have tailored dendrimers to improve their pharmacokinetics and tissue permeation. Copolymerization of dendritic polymers with linear polymers has resulted in various amphiphilic copolymers with self-assembly capabilities and improved drug loading efficiencies. Hybridization with other nanocarriers integrates advantageous characteristics of both systems, which includes prolonged plasma circulation times and enhanced tumor targeting. This review provides a comprehensive summary of the newly emerging drug delivery systems that involve reengineering of dendrimers in an effort to precisely control their nano-bio interactions, mitigating their inherent weaknesses. PMID:26453160

  8. Building server capabilities in China

    DEFF Research Database (Denmark)

    Adeyemi, Oluseyi; Slepniov, Dmitrij; Wæhrens, Brian Vejrum

    2012-01-01

    The purpose of this paper is to further our understanding of multinational companies building server capabilities in China. The paper is based on the cases of two western companies with operations in China. The findings highlight a number of common patterns in the 1) managerial challenges related...

  9. Microfoundations of Routines and Capabilities

    DEFF Research Database (Denmark)

    Felin, Teppo; Foss, Nicolai Juul; Heimriks, Koen H.

    We discuss the microfoundations of routines and capabilities, including why a microfoundations view is needed and how it may inform work on organizational and competitive heterogeneity. Building on extant research, we identify three primary categories of micro-level components underlying routines...

  10. Microfoundations of Routines and Capabilities

    DEFF Research Database (Denmark)

    Felin, Tippo; Foss, Nicolai Juul; Heimericks, Koen H.

    2012-01-01

    This article introduces the Special Issue and discusses the microfoundations of routines and capabilities, including why a microfoundations view is needed and how it may inform work on organizational and competitive heterogeneity. Building on extant research, we identify three primary categories ...

  11. Capability and Learning to Choose

    Science.gov (United States)

    LeBmann, Ortrud

    2009-01-01

    The Capability Approach (henceforth CA) is in the first place an approach to the evaluation of individual well-being and social welfare. Many disciplines refer to the CA, first and foremost welfare economics, development studies and political philosophy. Educational theory was not among the first disciplines that took notice of the CA, but has a…

  12. Capability maturity models for offshore organisational management.

    Science.gov (United States)

    Strutt, J E; Sharp, J V; Terry, E; Miles, R

    2006-12-01

    The goal setting regime imposed by the UK safety regulator has important implications for an organisation's ability to manage health and safety related risks. Existing approaches to safety assurance based on risk analysis and formal safety assessments are increasingly considered unlikely to create the step change improvement in safety to which the offshore industry aspires and alternative approaches are being considered. One approach, which addresses the important issue of organisational behaviour and which can be applied at a very early stage of design, is the capability maturity model (CMM). The paper describes the development of a design safety capability maturity model, outlining the key processes considered necessary to safety achievement, definition of maturity levels and scoring methods. The paper discusses how CMM is related to regulatory mechanisms and risk based decision making together with the potential of CMM to environmental risk management.

  13. Imaging capabilities of germanium gamma cameras

    International Nuclear Information System (INIS)

    Steidley, J.W.

    1977-01-01

    Quantitative methods of analysis based on the use of a computer simulation were developed and used to investigate the imaging capabilities of germanium gamma cameras. The main advantage of the computer simulation is that the inherent unknowns of clinical imaging procedures are removed from the investigation. The effects of patient scattered radiation were incorporated using a mathematical LSF model which was empirically developed and experimentally verified. Image modifying effects of patient motion, spatial distortions, and count rate capabilities were also included in the model. Spatial domain and frequency domain modeling techniques were developed and used in the simulation as required. The imaging capabilities of gamma cameras were assessed using low contrast lesion source distributions. The results showed that an improvement in energy resolution from 10% to 2% offers significant clinical advantages in terms of improved contrast, increased detectability, and reduced patient dose. The improvements are of greatest significance for small lesions at low contrast. The results of the computer simulation were also used to compare a design of a hypothetical germanium gamma camera with a state-of-the-art scintillation camera. The computer model performed a parametric analysis of the interrelated effects of inherent and technological limitations of gamma camera imaging. In particular, the trade-off between collimator resolution and collimator efficiency for detection of a given low contrast lesion was directly addressed. This trade-off is an inherent limitation of both gamma cameras. The image degrading effects of patient motion, camera spatial distortions, and low count rate were shown to modify the improvements due to better energy resolution. Thus, based on this research, the continued development of germanium cameras to the point of clinical demonstration is recommended

  14. Development of students learning capabilities and professional capabilities

    DEFF Research Database (Denmark)

    Ringtved, Ulla Lunde; Wahl, Christian; Belle, Gianna

    This paper describes the work-in-progress on a project that aims todevelop a tool that via learning analytic methods enable studentsto enhance, document and assess the development of their learningcapabilities and professional capabilities in consequence of theirself-initiated study activities...... during their bachelor educations. Thetool aims at enhancing the development of students’ capabilities toself-initiate, self-regulate and self-assess their study activities.The tool uses the concept of collective intelligence as source formotivation and inspiration in self-initiating study activities...... as wellas self-assessing them. The tool is based on a heutagogical approachto support reflection on learning potential in these activities. Thisenhances the educational use of students self-initiated learningactivities by bringing visibility and evidence to them, and therebybringing value to the assessment...

  15. Developing a Dual-Level Capabilities Approach: Using Constructivist Grounded Theory and Feminist Ethnography to Enhance the Capabilities Approaches

    Science.gov (United States)

    Hall, Kia M. Q.

    2014-01-01

    In this study, a dual-level capabilities approach to development is introduced. This approach intends to improve upon individual-focused capabilities approaches developed by Amartya Sen and Martha Nussbaum. Based upon seven months of ethnographic research in the Afro-descendant, autochthonous Garifuna community of Honduras, constructivist grounded…

  16. Innovation capabilities and governance in the agri-food sector

    NARCIS (Netherlands)

    Tepic, M.

    2012-01-01

    Company performance is increasingly dependent on continuous improvement and innovation. In order to manage innovation projects effectively, a number of internal and external business capabilities are important: The results of this study show that functional, and in particular integrative firm

  17. An Integrative Approach to Developing Organisational Capabilities and Individual Skills

    OpenAIRE

    Murnane, Sinéad; Thornley, Clare

    2017-01-01

    The tightly coupled relationship between organisational capability and the skills and competences of the individuals working in that organisation has long been recognised in both the academic literature and by the practitioner community. Simply improving individuals’ skills and hoping that the organisation’s capability automatically improves in tandem is not sufficient, however. This relationship is non-trivial and needs to be actively managed, meaning that people need to have shared goals ...

  18. Recent Investments by NASA's National Force Measurement Technology Capability

    Science.gov (United States)

    Commo, Sean A.; Ponder, Jonathan D.

    2016-01-01

    The National Force Measurement Technology Capability (NFMTC) is a nationwide partnership established in 2008 and sponsored by NASA's Aeronautics Evaluation and Test Capabilities (AETC) project to maintain and further develop force measurement capabilities. The NFMTC focuses on force measurement in wind tunnels and provides operational support in addition to conducting balance research. Based on force measurement capability challenges, strategic investments into research tasks are designed to meet the experimental requirements of current and future aerospace research programs and projects. This paper highlights recent and force measurement investments into several areas including recapitalizing the strain-gage balance inventory, developing balance best practices, improving calibration and facility capabilities, and researching potential technologies to advance balance capabilities.

  19. Ensuring US National Aeronautics Test Capabilities

    Science.gov (United States)

    Marshall, Timothy J.

    2010-01-01

    process; and the reductions in wind tunnel testing requirements within the largest consumer of ATP wind tunnel test time, the Aeronautics Research Mission Directorate (ARMD). Retirement of the Space Shuttle Program and recent perturbations of NASA's Constellation Program will exacerbate this downward trend. Therefore it is crucial that ATP periodically revisit and determine which of its test capabilities are strategically important, which qualify as low-risk redundancies that could be put in an inactive status or closed, and address the challenges associated with both sustainment and improvements to the test capabilities that must remain active. This presentation will provide an overview of the ATP vision, mission, and goals as well as the challenges and opportunities the program is facing both today and in the future. We will discuss the strategy ATP is taking over the next five years to address the National aeronautics test capability challenges and what the program will do to capitalize on its opportunities to ensure a ready, robust and relevant portfolio of National aeronautics test capabilities.

  20. Human-Centered Design Capability

    Science.gov (United States)

    Fitts, David J.; Howard, Robert

    2009-01-01

    For NASA, human-centered design (HCD) seeks opportunities to mitigate the challenges of living and working in space in order to enhance human productivity and well-being. Direct design participation during the development stage is difficult, however, during project formulation, a HCD approach can lead to better more cost-effective products. HCD can also help a program enter the development stage with a clear vision for product acquisition. HCD tools for clarifying design intent are listed. To infuse HCD into the spaceflight lifecycle the Space and Life Sciences Directorate developed the Habitability Design Center. The Center has collaborated successfully with program and project design teams and with JSC's Engineering Directorate. This presentation discusses HCD capabilities and depicts the Center's design examples and capabilities.

  1. Developing Acquisition IS Integration Capabilities

    DEFF Research Database (Denmark)

    Wynne, Peter J.

    2016-01-01

    An under researched, yet critical challenge of Mergers and Acquisitions (M&A), is what to do with the two organisations’ information systems (IS) post-acquisition. Commonly referred to as acquisition IS integration, existing theory suggests that to integrate the information systems successfully......, an acquiring company must leverage two high level capabilities: diagnosis and integration execution. Through a case study, this paper identifies how a novice acquirer develops these capabilities in anticipation of an acquisition by examining its use of learning processes. The study finds the novice acquirer...... applies trial and error, experimental, and vicarious learning processes, while actively avoiding improvisational learning. The results of the study contribute to the acquisition IS integration literature specifically by exploring it from a new perspective: the learning processes used by novice acquirers...

  2. LOFT Augmented Operator Capability Program

    International Nuclear Information System (INIS)

    Hollenbeck, D.A.; Krantz, E.A.; Hunt, G.L.; Meyer, O.R.

    1980-01-01

    The outline of the LOFT Augmented Operator Capability Program is presented. This program utilizes the LOFT (Loss-of-Fluid Test) reactor facility which is located at the Idaho National Engineering Laboratory and the LOFT operational transient experiment series as a test bed for methods of enhancing the reactor operator's capability for safer operation. The design of an Operational Diagnotics and Display System is presented which was backfit to the existing data acquisition computers. Basic color-graphic displays of the process schematic and trend type are presented. In addition, displays were developed and are presented which represent safety state vector information. A task analysis method was applied to LOFT reactor operating procedures to test its usefulness in defining the operator's information needs and workload

  3. Exploration Medical Capability - Technology Watch

    Science.gov (United States)

    Krihak, Michael; Watkins, Sharmila; Barr, Yael; Barsten, Kristina; Fung, Paul; Baumann, David

    2011-01-01

    The objectives of the Technology Watch process are to identify emerging, high-impact technologies that augment current ExMC development efforts, and to work with academia, industry, and other government agencies to accelerate the development of medical care and research capabilities for the mitigation of potential health issues that could occur during space exploration missions. The establishment of collaborations with these entities is beneficial to technology development, assessment and/or insertion. Such collaborations also further NASA s goal to provide a safe and healthy environment for human exploration. The Tech Watch project addresses requirements and capabilities identified by knowledge and technology gaps that are derived from a discrete set of medical conditions that are most likely to occur on exploration missions. These gaps are addressed through technology readiness level assessments, market surveys, collaborations and distributed innovation opportunities. Ultimately, these gaps need to be closed with respect to exploration missions, and may be achieved through technology development projects. Information management is a key aspect to this process where Tech Watch related meetings, research articles, collaborations and partnerships are tracked by the HRP s Exploration Medical Capabilities (ExMC) Element. In 2011, ExMC will be introducing the Tech Watch external website and evidence wiki that will provide access to ExMC technology and knowledge gaps, technology needs and requirements documents.

  4. Evolving Capabilities for Virtual Globes

    Science.gov (United States)

    Glennon, A.

    2006-12-01

    Though thin-client spatial visualization software like Google Earth and NASA World Wind enjoy widespread popularity, a common criticism is their general lack of analytical functionality. This concern, however, is rapidly being addressed; standard and advanced geographic information system (GIS) capabilities are being developed for virtual globes--though not centralized into a single implementation or software package. The innovation is mostly originating from the user community. Three such capabilities relevant to the earth science, education, and emergency management communities are modeling dynamic spatial phenomena, real-time data collection and visualization, and multi-input collaborative databases. Modeling dynamic spatial phenomena has been facilitated through joining virtual globe geometry definitions--like KML--to relational databases. Real-time data collection uses short scripts to transform user-contributed data into a format usable by virtual globe software. Similarly, collaborative data collection for virtual globes has become possible by dynamically referencing online, multi-person spreadsheets. Examples of these functions include mapping flows within a karst watershed, real-time disaster assessment and visualization, and a collaborative geyser eruption spatial decision support system. Virtual globe applications will continue to evolve further analytical capabilities, more temporal data handling, and from nano to intergalactic scales. This progression opens education and research avenues in all scientific disciplines.

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

    Science.gov (United States)

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

    2017-05-01

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

  6. Benchmarking Organisational Capability using The 20 Keys

    Directory of Open Access Journals (Sweden)

    Dino Petrarolo

    2012-01-01

    Full Text Available Organisations have over the years implemented many improvement initiatives, many of which were applied individually with no real, lasting improvement. Approaches such as quality control, team activities, setup reduction and many more seldom changed the fundamental constitution or capability of an organisation. Leading companies in the world have come to realise that an integrated approach is required which focuses on improving more than one factor at the same time - by recognising the importance of synergy between different improvement efforts and the need for commitment at all levels of the company to achieve total system-wide improvement.

    The 20 Keys approach offers a way to look at the strenqth of organisations and to systemically improve it, one step at a time by focusing on 20 different but interrelated aspects. One feature of the approach is the benchmarking system which forms the main focus of this paper. The benchmarking system is introduced as an important part of the 20 Keys philosophy in measuring organisational strength. Benchmarking results from selected South African companies are provided, as well as one company's results achieved through the adoption of the 20 Keys philosophy.

  7. Menstrual cycle length: a surrogate measure of reproductive health capable of improving the accuracy of biochemical/sonographical ovarian reserve test in estimating the reproductive chances of women referred to ART.

    Science.gov (United States)

    Gizzo, Salvatore; Andrisani, Alessandra; Noventa, Marco; Quaranta, Michela; Esposito, Federica; Armanini, Decio; Gangemi, Michele; Nardelli, Giovanni B; Litta, Pietro; D'Antona, Donato; Ambrosini, Guido

    2015-04-10

    Aim of the study was to investigate whether menstrual cycle length may be considered as a surrogate measure of reproductive health, improving the accuracy of biochemical/sonographical ovarian reserve test in estimating the reproductive chances of women referred to ART. A retrospective-observational-study in Padua' public tertiary level Centre was conducted. A total of 455 normo-ovulatory infertile women scheduled for their first fresh non-donor IVF/ICSI treatment. The mean menstrual cycle length (MCL) during the preceding 6 months was calculated by physicians on the basis of information contained in our electronic database (first day of menstrual cycle collected every month by telephonic communication by single patients). We evaluated the relations between MCL, ovarian response to stimulation protocol, oocytes fertilization ratio, ovarian sensitivity index (OSI) and pregnancy rate in different cohorts of patients according to the class of age and the estimated ovarian reserve. In women younger than 35 years, MCL over 31 days may be associated with an increased risk of OHSS and with a good OSI. In women older than 35 years, and particularly than 40 years, MCL shortening may be considered as a marker of ovarian aging and may be associated with poor ovarian response, low OSI and reduced fertilization rate. When AMH serum value is lower than 1.1 ng/ml in patients older than 40 years, MCL may help Clinicians discriminate real from expected poor responders. Considering the pool of normoresponders, MCL was not correlated with pregnancy rate while a positive association was found with patients' age. MCL diary is more predictive than chronological age in estimating ovarian biological age and response to COH and it is more predictive than AMH in discriminating expected from real poor responders. In women older than 35 years MCL shortening may be considered as a marker of ovarian aging while chronological age remains most accurate parameter in predicting pregnancy.

  8. Adapting and improving resilience to climate change in communities (moravian community as a pilot), by creating new capabilities based on the implementation of a new water culture; protection and management of natural resources

    Science.gov (United States)

    Campos Gallo, A.

    2015-04-01

    Water, in all its dimensions and scope, concerns humans as civilization, individuals and communities immersed in an environment that faces serious environmental threats and changes. The efficient way to deal with this crisis is education of present and future generations, breaking paradigms, creating awareness and new development models, seeking community groups and forces to empower their water resource and care, manage and renew it in an efficient and sustainable manner. The multiple uses of water in personal uses, irrigation, agro-industry and clean energy production, transforms this resource in a strategic element to any nation. With support from the Centro Nacional de Alta Tecnologia (CeNAT), it was possible to formulate the "Agenda Ambiental de Moravia", agreeing to be the "Consejo Tecnico de Fuerzas Vivas" (CTFV) from Moravia - articulated network of stakeholders - the one that coordinate all actions refered to water Resources, pollution and cleaner technologies and protected Areas. CeNAT and CTFV have developed distinguished efforts to improve the Moravians quality of life, and this has led the initiative of constitution of a whole education and training project in rescuing the Upper Basin of the Rio Tarcoles, through the implementation of an ecological - recreative garden ("Parque Comunitario Pulmon Verde de Moravia"), fostersing good use of natural resources, and also works as a platform for training and awareness program in Sustainable Development, based on "Hacia una Nueva Cultura del Agua" (powered through the United Nations by Dr. Pedro Arrojo Agudo and his " Feria de Aguas, Rios y Pueblos", presented in many countries). This initiative is projected to the national and international communities, through the "Water International Conference", which propel initiatives, laws and decisions which enable the development of Costa Rica and other countries under a sustainable model, focused on this essential component for life on the planet.

  9. Capability Development in an Offshoring Context

    DEFF Research Database (Denmark)

    Jaura, Manya

    Capability development can be defined as deliberate firm-level investment involving a search and learning process aimed at modifying or enhancing existing capabilities. Increasingly, firms are relocating advanced services to offshore locations resulting in the challenge of capability development ...

  10. Unpacking dynamic capability : a design perspective

    NARCIS (Netherlands)

    Mulders, D.E.M.; Romme, A.G.L.; Bøllingtoft, A.; Håkonsson, D.D.; Nielsen, J.F.; Snow, C.C; Ulhøi, J.

    2009-01-01

    This chapter reviews the dynamic capability literature to explore relationships between definition, operationalization, and measurement of dynamic capability. Subsequently, we develop a design-oriented approach toward dynamic capability that distinguishes between design rules, recurrent patterns of

  11. Summary of Sandia Laboratories technical capabilities

    International Nuclear Information System (INIS)

    1977-05-01

    The technical capabilities of Sandia Laboratories are detailed in a series of companion reports. In this summary the use of the capabilities in technical programs is outlined and the capabilities are summarized. 25 figures, 3 tables

  12. Developing A/E Capabilities

    International Nuclear Information System (INIS)

    Gonzalez, A.; Gurbindo, J.

    1987-01-01

    During the last few years, the methods used by EMPRESARIOS AGRUPADOS and INITEC to perform Architect-Engineering work in Spain for nuclear projects has undergone a process of significant change in project management and engineering approaches. Specific practical examples of management techniques and design practices which represent a good record of results will be discussed. They are identified as areas of special interest in developing A/E capabilities for nuclear projects . Command of these areas should produce major payoffs in local participation and contribute to achieving real nuclear engineering capabities in the country. (author)

  13. Dynamic capabilities and network benefits

    Directory of Open Access Journals (Sweden)

    Helge Svare

    2017-01-01

    Full Text Available The number of publicly funded initiatives to establish or strengthen networks and clusters, in order to enhance innovation, has been increasing. Returns on such investments vary, and the aim of this study is to explore to what extent the variation in benefits for firms participating in networks or clusters can be explained by their dynamic capabilities (DC. Based on survey data from five Norwegian networks, the results suggest that firms with higher DC are more successful in harvesting the potential benefits of being member of a network.

  14. PROGRAMS WITH DATA MINING CAPABILITIES

    Directory of Open Access Journals (Sweden)

    Ciobanu Dumitru

    2012-03-01

    Full Text Available The fact that the Internet has become a commodity in the world has created a framework for anew economy. Traditional businesses migrate to this new environment that offers many features and options atrelatively low prices. However competitiveness is fierce and successful Internet business is tied to rigorous use of allavailable information. The information is often hidden in data and for their retrieval is necessary to use softwarecapable of applying data mining algorithms and techniques. In this paper we want to review some of the programswith data mining capabilities currently available in this area.We also propose some classifications of this softwareto assist those who wish to use such software.

  15. Technological capability at the Brazilian official pharmaceutical laboratories

    Directory of Open Access Journals (Sweden)

    José Vitor Bomtempo Martins

    2008-10-01

    Full Text Available This paper studies the technological capability in the Brazilian Official Pharmaceutical Laboratories [OPL]. The technological capability analysis could contribute to organization strategies and governmental actions in order to improve OPL basic tasks as well to incorporate new ones, particularly concerning the innovation management. Inspired in Figueiredo (2000, 2003a, 2003b and Figueiredo and Ariffin (2003, a framework was drawn and adapted to pharmaceutical industry characteristics and current sanitary and health legislation. The framework allows to map different dimensions of the technological capability (installations, processes, products, equipments, organizational capability and knowledge management and the level attained by OPL (ordinary or innovating capability. OPL show a good development of ordinary capabilities, particularly in Product and Processes. Concerning the other dimensions, OPL are quite diverse. In general, innovating capabilities are not much developed. In the short term, it was identified a dispersion in the capacitating efforts. Considering their present level and the absorption efforts, good perspectives can be found in Installations, Processes and Organizational Capability. A lower level of efforts in Products and Knowledge Management could undermine these capabilities in the future.

  16. Detection capabilities. Some historical footnotes

    International Nuclear Information System (INIS)

    Currie, L.A.

    2017-01-01

    Part I Summary of relevant topics from 1923 to present-including: Currie (Anal Chem 40:586-593, 1968) detection concepts and capabilities; International detection and uncertainty standards; Failure of classical "1"4C dating and birth of new scientific disciplines; Exploratory nuclear data analysis of "8"5Kr monitors found coincident with the collapse of the Iron Curtain (1989); Faulty statistics proved responsible for mistaken assertions that Currie's LC yields excessive false positives; Low-level counting and AMS for atmospheric "3"7Ar and µmolar fossil/biomass carbon in the environment; Erroneous assumption that our low-level background is a Poisson Process, linked to ∼8 % spurious anticoincidence events. Part II. Exact treatment of bivariate Poisson data-solved in 1930s by Przyborowski and Wilenski, Krakow University, for detecting extreme trace amounts of a malicious contaminant (dodder) in high purity seed standards. We adapted their treatment to detection capabilities in ultra-low-level nuclear counting. The timing of their work had great historical significance, marking the start of World War II, with the invasion of Poland (1939). (author)

  17. WFPC2 Science Capability Report

    Science.gov (United States)

    Brown, David I.

    2001-01-01

    In the following pages, a brief outline of the salient science features of Wide Field/Planetary Camera 2 (WFPC2) that impact the proposal writing process and conceptual planning of observations is presented. At the time of writing, WFPC2, while having been better defined than in the past, is far from being at the stage where science and engineering details are well enough known that concrete observational/operational sequences can be plannned with assurance. Conceptual issues are another matter. The thrust of the Science Capability Report at this time is to outline the known performance parameters and capabilities of WFPC2, filling in with specifications when necessary to hold a place for these items as they become known. Also, primary scientific and operational differences between WFPC 1 and 2 are discussed section-by-section, along with issues that remain to be determined and idiosyncrasies when known. Clearly the determination of the latter awaits some form of testing, most likely thermal/vacuum testing. All data in this report should be viewed with a jaundiced eye at this time.

  18. A Call to Action for National Foreign Language Capabilities

    Science.gov (United States)

    US Department of Defense, 2005

    2005-01-01

    The terrorist attacks of September 11th, the Global War on Terrorism, and the continued threat to the Homeland have defined the critical need to take action to improve the foreign language and cultural capabilities of the Nation. The government must act now to improve the gathering and analysis of information, advance international diplomacy, and…

  19. Author's capabilities in author indexing

    International Nuclear Information System (INIS)

    Ooi, Shoichi

    1988-01-01

    The purpose of this paper is to provide a author capability of current author indexing practices in journal literature indexing practices in 'Journal of Nuclear Science and Technology of Japan'. This Journal employed keywords freely assigned by author and not taken from INIS Thesaurus or other vocabulary list. Author examined 413 literatures, comparing keywords assigned by the literatures' authors with descriptor's (ATOMINDEX) assigned by an experienced professional indexer. The results of the comparisons showed that the average set of terms assigned by author included about 70% of all the terms assigned to the same literature by the professional indexer. Authors eventually would contribute, for the most effective point to create reference to information is at the time of its generation. Consequently, it may be possible to transfer them easily to descriptors in every secondary information system. (author)

  20. Amartya Sen's Capability Approach and Education

    Science.gov (United States)

    Walker, Melanie

    2005-01-01

    The human capabilities approach developed by the economist Amartya Sen links development, quality of life and freedom. This article explores the key ideas in the capability approach of: capability, functioning, agency, human diversity and public participation in generating valued capabilities. It then considers how these ideas relate specifically…

  1. Strengthening Homeland Security through Improved Foreign Language Capability

    Science.gov (United States)

    2011-12-01

    several languages.‖ See Merriam-Webster Online, s.v. ―linguist,‖ accessed 16 MAY 11, http://www.merriam-webster.com/ dictionary /linguist. 7 Ambrose...proficiency.362 Given that one observer has aptly characterized America as ―Profoundly Monolingual ,‖363 such changes in public opinion are unlikely...93 language proficiency,365 organizations will continue to produce less-than-professional- level linguists, and America may prove itself monolingual

  2. Improved capability of U-ZrH fuels

    Energy Technology Data Exchange (ETDEWEB)

    Gietzen, A J [General Atomic Company, San Diego, CA (United States)

    1983-08-01

    This paper provides a brief background on TRIGA fuels and a summary of the development of U-ZrH fuels utilizing higher uranium loadings in the alloy. Most of the development work was reported two years ago; however, in this paper some emphasis will be placed upon applications that General Atomic Company is now making with these higher alloy fuels. They are referred to as higher uranium content alloys because their development was not really LEU development; the TRIGA fuel has used low enrichment since its inception.

  3. Mali’s Next Battle: Improving Counterterrorism Capabilities

    Science.gov (United States)

    2017-01-01

    involved in training Malian troops (who were among those who deserted in massive numbers) failed to train them in “values, ethics and a military...French deployment is taking place in a region in which the factors of instability—ethnic, demographic, ecological , economic—are deep, durable, and

  4. Improving Air Force Depot Programming by Linking Resources to Capabilities

    Science.gov (United States)

    2012-01-01

    thank Rick Grisenthwaite at Warner Robins Air Logistics Center, Jamie Jeter at Okla- homa City Air Logistics Center, and Glen Brown at Ogden Air...consistency, we use the term block cycle instead of SCU in our F-16 discussions. 4 8 Im p ro vin g A ir Fo rce D ep o t Pro g ram m in g b y Lin kin...Requirements RAND TR905-B.8 Figure B.9 Depot Purchased Equipment Maintenance Model Output: Projected Aircraft Availability RAND TR905-B.9 A ir cr af t av

  5. Hybrid coils having an improved heat transfer capability

    NARCIS (Netherlands)

    2008-01-01

    A hybrid coil ( 11 ) employs a wire layer ( 22 ), a wire layer ( 23 ) adjacent the wire layer ( 22 ), and a wire layer ( 24 ) adjacent the wire layer ( 23 ). The hybrid coil ( 11 ) further employs a thermal conductive insulator ( 42 ) physically disposed within a space between the wire layer ( 22 )

  6. How Chinese Semantics Capability Improves Interpretation in Visual Communication

    Science.gov (United States)

    Cheng, Chu-Yu; Ou, Yang-Kun; Kin, Ching-Lung

    2017-01-01

    A visual representation involves delivering messages through visually communicated images. The study assumed that semantic recognition can affect visual interpretation ability, and the result showed that students graduating from a general high school achieve satisfactory results in semantic recognition and image interpretation tasks than students…

  7. Therapeutic games to improve attachment capabilities and protect sexual health.

    Science.gov (United States)

    Beier, Klaus M; Rebensburg, Klaus; Behrmann, Malte

    2010-01-01

    From the very beginning of life, man's fundamental needs for acceptance, security, trust, warmth and closeness can only be satisfied in relationships [1]. During infancy this is accomplished by body contact and the emotional experience of being taken care of, for instance by the sheltering manner in which an infant is held during breast-feeding. Through this parental loving care the modus of satisfying psychosocial fundamental needs by skin contact is learned by the infant and reinforced on a neuronal level, the way all processes of learning elementary skills generally are. According to present knowledge, chronic lack of security transmitted by frustration of psychosocial fundamental needs increases the probability of developing psychological and physical disorders. Furthermore it hinders overcoming prevailing diseases [2]. In developing therapeutic computer games this phylogenetically established programming for attachment in order to fulfill fundamental psychosocial needs will be the focus of interaction, cognitive triggers and strategic as well as emotional rules to be applied in the games which are designed in a modular way for difficult developmental phases (e.g. adolescence) or various chronic diseases. This is a new approach transferring sexological clinical experience into therapeutic computer games for prevention purposes and protection of sexual health.

  8. Improving the Distortional Deformation Capabilities of Aerospace Composite Networks

    Science.gov (United States)

    2011-02-28

    and 44DDS/DGEBA will be simulated and compared to experimental analysis. Additionally, matrices of hexamethylene diamine ( HDA ) and bis(hexamethylene...simulation in terms of defining secondary forces, such as hydrogen bonding, and make matrices even more rigid. Our hypothesis was that the HDA /DGEBA and...DGEBA (a) and 33DDS/DGEBA (b). HDA /DGEBA and B-HTA/DGEBA Experimental vs. Simulation Comparison Tensile Modulus, Tg, and density of HDA /DGEBA and B

  9. Improving NATO’S Capabilities: A Roadmap to 2020

    Science.gov (United States)

    2012-12-14

    Australia and El Salvador . Today, according to the official NATO web site, there are 50 contributing countries to the mission.48 The US has contributed... earthquake . Furthermore, in his research on NATO transformation, David Rudd underlined the employment of the NRF as one of the burden-sharing flaws : the

  10. Organizational Economics of Capability and Heterogeneity

    DEFF Research Database (Denmark)

    Argyres, Nicholas S.; Felin, Teppo; Foss, Nicolai Juul

    2012-01-01

    For decades, the literatures on firm capabilities and organizational economics have been at odds with each other, specifically relative to explaining organizational boundaries and heterogeneity. We briefly trace the history of the relationship between the capabilities literature and organizational...... economics, and we point to the dominance of a “capabilities first” logic in this relationship. We argue that capabilities considerations are inherently intertwined with questions about organizational boundaries and internal organization, and we use this point to respond to the prevalent capabilities first...... logic. We offer an integrative research agenda that focuses first on the governance of capabilities and then on the capability of governance....

  11. Paclitaxel-loaded redox-sensitive nanoparticles based on hyaluronic acid-vitamin E succinate conjugates for improved lung cancer treatment.

    Science.gov (United States)

    Song, Yu; Cai, Han; Yin, Tingjie; Huo, Meirong; Ma, Ping; Zhou, Jianping; Lai, Wenfang

    2018-01-01

    Lung cancer is the primary cause of cancer-related death worldwide. A redox-sensitive nanocarrier system was developed for tumor-targeted drug delivery and sufficient drug release of the chemotherapeutic agent paclitaxel (PTX) for improved lung cancer treatment. The redox-sensitive nanocarrier system constructed from a hyaluronic acid-disulfide-vitamin E succinate (HA-SS-VES, HSV) conjugate was synthesized and PTX was loaded in the delivery system. The physicochemical properties of the HSV nanoparticles were characterized. The redox-sensitivity, tumor-targeting and intracellular drug release capability of the HSV nanoparticles were evaluated. Furthermore, in vitro and in vivo antitumor activity of the PTX-loaded HSV nanoparticles was investigated in a CD44 over-expressed A549 tumor model. This HSV conjugate was successfully synthesized and self-assembled to form nanoparticles in aqueous condition with a low critical micelle concentration of 36.3 μg mL -1 . Free PTX was successfully entrapped into the HSV nanoparticles with a high drug loading of 33.5% (w/w) and an entrapment efficiency of 90.6%. Moreover, the redox-sensitivity of the HSV nanoparticles was confirmed by particle size change of the nanoparticles along with in vitro release profiles in different reducing environment. In addition, the HA-receptor mediated endocytosis and the potency of redox-sensitivity for intracellular drug delivery were further verified by flow cytometry and confocal laser scanning microscopic analysis. The antitumor activity results showed that compared to redox-insensitive nanoparticles and Taxol ® , PTX-loaded redox-sensitive nanoparticles exhibited much greater in vitro cytotoxicity and apoptosis-inducing ability against CD44 over-expressed A549 tumor cells. In vivo, the PTX-loaded HSV nanoparticles possessed much higher antitumor efficacy in an A549 mouse xenograft model and demonstrated improved safety profile. In summary, our PTX-loaded redox-sensitive HSV nanoparticles

  12. BIG DATA RESOURCES, MARKETING CAPABILITIES, AND FIRM PERFORMANCE.

    OpenAIRE

    Suoniemi, Samppa; Meyer-Waarden, Lars; Munzel, Andreas

    2017-01-01

    RESEARCH QUESTION Big data may significantly improve the efficiency and effectiveness of the firm's marketing capabilities. However, firms must overcome technological, skill-based and organisational challenges to become data-driven. Academic research has not empirically investigated how strategic big data resources, and to what extent, influence strategic marketing capabilities and, by extension, firm performance. The primary objective of this research is to remedy this crucial knowledge ...

  13. MINAC, A new radiographic inspection capability

    International Nuclear Information System (INIS)

    Lapides, M.E.; Schonberg, R.

    1983-01-01

    In service, radiographic inspection of thick section, metallic components has historically been limited to the capabilities of radioisotopic sources such as cobalt and iridium. Although practical in many applications, these sources tend to be restricted by output intensity, by resolution obtainable, and by the physical size and weight of necessary transport shielding. In nuclear plant applications, any radiography is also frequently inhibited by the presence of a radiation background from activated corrosion products on the inspection object which may fog the film before the desired exposure is achieved. In recognition of these limitations and the need for improved capability in the conduct of mandated ten-year inspection of U.S. nuclear plant components such as reactor coolant pumps, pressure vessel nozzles and valve bodies, the Electric Power Research Institute (EPRI) undertook the development of a high energy, X-ray device appropriate for in service inspection of thick section (up to approximately 30 cm of steel) components. The development was conducted by Schonberg Radiation (U.S.A). The product, MINAC, a miniaturized linear accelerator system, has been in use in many plant inspections since April 1981. This paper describes the development and typical applications of MINAC

  14. Atmospheric Release Advisory Capability (ARAC)

    International Nuclear Information System (INIS)

    Dickerson, M.H.

    1975-01-01

    The chief purpose of ARAC data acquisition program is to provide site officials, who are responsible for ensuring maximum health protection for the endangered site personnel and public, with estimates of the effects of atmospheric releases of hazardous material as rapidly and accurately as possible. ARAC is in the initial stages of being implemented and is therefore susceptible to changes before it reaches its final form. However the concept of ARAC is fully developed and was successfully demonstrated during a feasibility study conducted in June 1974, as a joint effort between the Savannah River Laboratory (SRL) and Lawrence Livermore Laboratory (LLL). Additional tests between SRL and LLL are scheduled for December 1975. While the immediate goal is the application of ARAC to assist a limited number of ERDA sites, the system is designed with sufficient flexibility to permit expanding the service to a large number of sites. Success in ARAC application should provide nuclear facilities with a means to handle better the urgent questions concerning the potential accidental hazards from atmospheric releases in addition to providing the sites with a capability to assess the effort of their normal operations

  15. Global dynamics, capabilities and the crisis

    Czech Academy of Sciences Publication Activity Database

    Fagerberg, J.; Srholec, Martin

    2016-01-01

    Roč. 26, č. 4 (2016), s. 765-784 ISSN 0936-9937 Institutional support: PRVOUK-P23 Keywords : technological capabilities * social capabilities * competitiveness Subject RIV: AH - Economics Impact factor: 0.862, year: 2016

  16. Liberalism, Humanism, and Feminism in Nussbaum's Capabilities ...

    African Journals Online (AJOL)

    A purely theoretical analysis of Martha Nussbaum's basis of the capabilities ... Since even a capabilities approach rooted in feminist justice is itself radical and must ... rhetoric of sex and social justice that has already been embraced by current

  17. Sandia Laboratories technical capabilities: systems analysis

    International Nuclear Information System (INIS)

    Lundergan, C.D.

    1975-06-01

    The systems analysis capabilities at Sandia Laboratories are summarized. Selected applications of these capabilities are presented to illustrate the extent to which they can be applied in research and development programs. (U.S.)

  18. Sandia Laboratories technical capabilities: engineering analysis

    International Nuclear Information System (INIS)

    Lundergan, C.D.

    1975-12-01

    This report characterizes the engineering analysis capabilities at Sandia Laboratories. Selected applications of these capabilities are presented to illustrate the extent to which they can be applied in research and development programs

  19. DDP-516 Computer Graphics System Capabilities

    Science.gov (United States)

    1972-06-01

    This report describes the capabilities of the DDP-516 Computer Graphics System. One objective of this report is to acquaint DOT management and project planners with the system's current capabilities, applications hardware and software. The Appendix i...

  20. Towards a dynamic concept of alliance capability

    OpenAIRE

    SLUYTS, Kim; MARTENS, Rudy; MATTHYSSENS, Paul

    2008-01-01

    This paper has a threefold purpose. First, we offer a literature review on alliance capability based on strategic and competence based management literature. Second, we extend existing literature on alliance capability by breaking this concept down into five sub capabilities, which are each linked to a stage of the alliance life cycle. Finally, we suggest how firms can support these capabilities through structural, technological and people-related tools and techniques. We argue that current l...

  1. Electron identification capabilities of CBM

    Energy Technology Data Exchange (ETDEWEB)

    Lebedev, Semen [GSI, Darmstadt (Germany)]|[JINR, Dubna (Russian Federation)

    2008-07-01

    The Compressed Baryonic Matter (CBM) experiment at the future FAIR facility at Darmstadt will measure dileptons emitted from the hot and dense phase in heavy-ion collisions. In case of an electron measurement, a high purity of identified electrons is required in order to suppress the background. Electron identification in CBM will be performed by a RICH and TRD detectors. In this contribution we will present routines which have been developed for electron identification in CBM. A RICH ring recognition algorithm based on the Hough Transform has been implemented. An ellipse fitting algorithm has been elaborated because most of the CBM RICH rings have elliptic shapes, moreover, it helps to improve ring-track matching and electron identification procedures. An Artificial Neural Network can be used in order to suppress fake rings. The electron identification in RICH is substantially improved by the use of TRD information for which 3 different algorithms are implemented. Results of primary electron identification are presented. All developed algorithms were tested on large statistics of simulated events and are included into the CBM software framework for common use.

  2. Combining Land Capability Evaluation, Geographic Information ...

    African Journals Online (AJOL)

    Combining Land Capability Evaluation, Geographic Information Systems, AnD Indigenous Technologies for Soil Conservation in Northern Ethiopia. ... Land capability and land use status were established following the procedures of a modified treatment-oriented capability classification using GIS. The case study ...

  3. Organisational Capability--What Does It Mean?

    Science.gov (United States)

    National Centre for Vocational Education Research (NCVER), 2006

    2006-01-01

    Organisational capability is rapidly becoming recognized as the key to organizational success. However, the lack of research on it has been well documented in the literature, and organizational capability remains an elusive concept. Yet an understanding of organizational capability can offer insights into how RTOs might work most effectively,…

  4. Selecting Capabilities for Quality of Life Measurement

    Science.gov (United States)

    Robeyns, Ingrid

    2005-01-01

    The capability approach advocates that interpersonal comparisons be made in the space of functionings and capabilities. However, Amartya Sen has not specified which capabilities should be selected as the relevant ones. This has provoked two types of criticism. The stronger critique is Martha Nussbaum's claim that Sen should endorse one specific…

  5. High resolution, monochromatic x-ray topography capability at CHESS

    Energy Technology Data Exchange (ETDEWEB)

    Finkelstein, K. D., E-mail: kdf1@cornell.edu; Pauling, A.; Brown, Z. [CHESS, Cornell University, Ithaca, NY (United States); Jones, R. [Department of Physics, University of Connecticut, Storrs, CT (United States); Tarun, A.; Misra, D. S. [IIa Technologies (Singapore); Jupitz, S. [St. Mary’s College of Maryland, St. Mary’s City, MD (United States); Sagan, D. C. [CLASSE, Cornell University, Ithaca, NY (United States)

    2016-07-27

    CHESS has a monochromatic x-ray topography capability serving continually expanding user interest. The setup consists of a beam expanding monochromator, 6-circle diffactometer, and CHESS designed CMOS camera with real time sample-alignment capability. This provides rocking curve mapping with angle resolution as small as 2 µradians, spatial resolution to 3 microns, and field of view up to 7mm. Thus far the capability has been applied for: improving CVD-diamond growth, evaluating perfection of ultra-thin diamond membranes, correlating performance of diamond-based electronics with crystal defect structure, and defect analysis of single crystal silicon carbide. This paper describes our topography system, explains its capabilities, and presents experimental results from several applications.

  6. High resolution, monochromatic x-ray topography capability at CHESS

    International Nuclear Information System (INIS)

    Finkelstein, K. D.; Pauling, A.; Brown, Z.; Jones, R.; Tarun, A.; Misra, D. S.; Jupitz, S.; Sagan, D. C.

    2016-01-01

    CHESS has a monochromatic x-ray topography capability serving continually expanding user interest. The setup consists of a beam expanding monochromator, 6-circle diffactometer, and CHESS designed CMOS camera with real time sample-alignment capability. This provides rocking curve mapping with angle resolution as small as 2 µradians, spatial resolution to 3 microns, and field of view up to 7mm. Thus far the capability has been applied for: improving CVD-diamond growth, evaluating perfection of ultra-thin diamond membranes, correlating performance of diamond-based electronics with crystal defect structure, and defect analysis of single crystal silicon carbide. This paper describes our topography system, explains its capabilities, and presents experimental results from several applications.

  7. Towards a National Space Weather Predictive Capability

    Science.gov (United States)

    Fox, N. J.; Ryschkewitsch, M. G.; Merkin, V. G.; Stephens, G. K.; Gjerloev, J. W.; Barnes, R. J.; Anderson, B. J.; Paxton, L. J.; Ukhorskiy, A. Y.; Kelly, M. A.; Berger, T. E.; Bonadonna, L. C. M. F.; Hesse, M.; Sharma, S.

    2015-12-01

    National needs in the area of space weather informational and predictive tools are growing rapidly. Adverse conditions in the space environment can cause disruption of satellite operations, communications, navigation, and electric power distribution grids, leading to a variety of socio-economic losses and impacts on our security. Future space exploration and most modern human endeavors will require major advances in physical understanding and improved transition of space research to operations. At present, only a small fraction of the latest research and development results from NASA, NOAA, NSF and DoD investments are being used to improve space weather forecasting and to develop operational tools. The power of modern research and space weather model development needs to be better utilized to enable comprehensive, timely, and accurate operational space weather tools. The mere production of space weather information is not sufficient to address the needs of those who are affected by space weather. A coordinated effort is required to support research-to-applications transition efforts and to develop the tools required those who rely on this information. In this presentation we will review the space weather system developed for the Van Allen Probes mission, together with other datasets, tools and models that have resulted from research by scientists at JHU/APL. We will look at how these, and results from future missions such as Solar Probe Plus, could be applied to support space weather applications in coordination with other community assets and capabilities.

  8. Distinctive Dynamic Capabilities for New Business Creation

    DEFF Research Database (Denmark)

    Rosenø, Axel; Enkel, Ellen; Mezger, Florian

    2013-01-01

    This study examines the distinctive dynamic capabilities for new business creation in established companies. We argue that these are very different from those for managing incremental innovation within a company's core business. We also propose that such capabilities are needed in both slow...... and fast-paced industries, and that similarities exist across industries. Hence, the study contributes to dynamic capabilities literature by: 1) identifying the distinctive dynamic capabilities for new business creation; 2) shifting focus away from dynamic capabilities in environments characterised by high...... clock-speed and uncertainty towards considering dynamic capabilities for the purpose of developing new businesses, which also implies a high degree of uncertainty. Based on interviews with 33 companies, we identify distinctive dynamic capabilities for new business creation, find that dynamic...

  9. Array capabilities and future arrays

    International Nuclear Information System (INIS)

    Radford, D.

    1993-01-01

    Early results from the new third-generation instruments GAMMASPHERE and EUROGAM are confirming the expectation that such arrays will have a revolutionary effect on the field of high-spin nuclear structure. When completed, GAMMASHPERE will have a resolving power am order of magnitude greater that of the best second-generation arrays. When combined with other instruments such as particle-detector arrays and fragment mass analysers, the capabilites of the arrays for the study of more exotic nuclei will be further enhanced. In order to better understand the limitations of these instruments, and to design improved future detector systems, it is important to have some intelligible and reliable calculation for the relative resolving power of different instrument designs. The derivation of such a figure of merit will be briefly presented, and the relative sensitivities of arrays currently proposed or under construction presented. The design of TRIGAM, a new third-generation array proposed for Chalk River, will also be discussed. It is instructive to consider how far arrays of Compton-suppressed Ge detectors could be taken. For example, it will be shown that an idealised open-quote perfectclose quotes third-generation array of 1000 detectors has a sensitivity an order of magnitude higher again than that of GAMMASPHERE. Less conventional options for new arrays will also be explored

  10. Conceptualizing innovation capabilities: A contingency perspective

    Directory of Open Access Journals (Sweden)

    Tor Helge Aas

    2017-01-01

    Full Text Available Empirical research has confirmed that a positive relationship exists between the implementation of innovation activities and the future performance of organizations. Firms utilize resources and capabilities to develop innovations in the form of new products, services or processes. Some firms prove to be better at reproducing innovation success than others, and the capacity to do so is referred to as innovation capability. However, the term innovation capability is ambiguously treated in extant literature. There are several different definitions of the concept and the distinction between innovation capabilities and other types of capabilities, such as dynamic capabilities, is neither explicitly stated, nor is the relationship between the concept and other resource- and capability-based concepts within strategy theory established. Although innovation is increasingly identified as crucial for a firm’s sustainable competitiveness in contemporary volatile and complex markets, the strategy-innovation link is underdeveloped in extant research. To overcome this challenge this paper raises the following research question: What type of innovation capabilities are required to innovate successfully? Due to the status of the extant research, we chose a conceptual research design to answer our research question and the paper contributes with a conceptual framework to discuss what innovation capabilities firms need to reproduce innovation success. Based on careful examination of current literature on innovation capability specifically, and the strategy-innovation link in general, we suggest that innovation capability must be viewed along two dimensions – innovation novelty and market characteristics. This framework enables the identification of four different contexts for innovation capabilities in a two-bytwo matrix. We discuss the types of innovation capabilities necessary within the four different contexts. This novel framework contributes to the

  11. University access for social justice: a capabilities perspective ...

    African Journals Online (AJOL)

    University access for social justice: a capabilities perspective. M Wilson-Strydom. Abstract. The closely related, but often contradictory, issues of increasing access to university and improving students' chances of success in their university studies have been and continue to be an important research focus within higher ...

  12. Simple process capability analysis and quality validation of ...

    African Journals Online (AJOL)

    Many ways can be applied to improve the process and one of them is by choosing the correct six sigma's design of experiment (DOE). In this study, Taguchi's experimental design was applied to achieve high percentage of cell viability in the fermentation experiment. The process capability of this study was later analyzed by ...

  13. Achieving a Launch on Demand Capability

    Science.gov (United States)

    Greenberg, Joel S.

    2002-01-01

    The ability to place payloads [satellites] into orbit as and when required, often referred to as launch on demand, continues to be an elusive and yet largely unfulfilled goal. But what is the value of achieving launch on demand [LOD], and what metrics are appropriate? Achievement of a desired level of LOD capability must consider transportation system thruput, alternative transportation systems that comprise the transportation architecture, transportation demand, reliability and failure recovery characteristics of the alternatives, schedule guarantees, launch delays, payload integration schedules, procurement policies, and other factors. Measures of LOD capability should relate to the objective of the transportation architecture: the placement of payloads into orbit as and when required. Launch on demand capability must be defined in probabilistic terms such as the probability of not incurring a delay in excess of T when it is determined that it is necessary to place a payload into orbit. Three specific aspects of launch on demand are considered: [1] the ability to recover from adversity [i.e., a launch failure] and to keep up with the steady-state demand for placing satellites into orbit [this has been referred to as operability and resiliency], [2] the ability to respond to the requirement to launch a satellite when the need arises unexpectedly either because of an unexpected [random] on-orbit satellite failure that requires replacement or because of the sudden recognition of an unanticipated requirement, and [3] the ability to recover from adversity [i.e., a launch failure] during the placement of a constellation into orbit. The objective of this paper is to outline a formal approach for analyzing alternative transportation architectures in terms of their ability to provide a LOD capability. The economic aspect of LOD is developed by establishing a relationship between scheduling and the elimination of on-orbit spares while achieving the desired level of on

  14. Graphical Visualization of Human Exploration Capabilities

    Science.gov (United States)

    Rodgers, Erica M.; Williams-Byrd, Julie; Arney, Dale C.; Simon, Matthew A.; Williams, Phillip A.; Barsoum, Christopher; Cowan, Tyler; Larman, Kevin T.; Hay, Jason; Burg, Alex

    2016-01-01

    NASA's pioneering space strategy will require advanced capabilities to expand the boundaries of human exploration on the Journey to Mars (J2M). The Evolvable Mars Campaign (EMC) architecture serves as a framework to identify critical capabilities that need to be developed and tested in order to enable a range of human exploration destinations and missions. Agency-wide System Maturation Teams (SMT) are responsible for the maturation of these critical exploration capabilities and help formulate, guide and resolve performance gaps associated with the EMC-identified capabilities. Systems Capability Organization Reporting Engine boards (SCOREboards) were developed to integrate the SMT data sets into cohesive human exploration capability stories that can be used to promote dialog and communicate NASA's exploration investments. Each SCOREboard provides a graphical visualization of SMT capability development needs that enable exploration missions, and presents a comprehensive overview of data that outlines a roadmap of system maturation needs critical for the J2M. SCOREboards are generated by a computer program that extracts data from a main repository, sorts the data based on a tiered data reduction structure, and then plots the data according to specified user inputs. The ability to sort and plot varying data categories provides the flexibility to present specific SCOREboard capability roadmaps based on customer requests. This paper presents the development of the SCOREboard computer program and shows multiple complementary, yet different datasets through a unified format designed to facilitate comparison between datasets. Example SCOREboard capability roadmaps are presented followed by a discussion of how the roadmaps are used to: 1) communicate capability developments and readiness of systems for future missions, and 2) influence the definition of NASA's human exploration investment portfolio through capability-driven processes. The paper concludes with a description

  15. Compilation of Sandia Laboratories technical capabilities

    International Nuclear Information System (INIS)

    Lundergan, C.D.; Mead, P.L.

    1975-11-01

    This report is a compilation of 17 individual documents that together summarize the technical capabilities of Sandia Laboratories. Each document in this compilation contains details about a specific area of capability. Examples of application of the capability to research and development problems are provided. An eighteenth document summarizes the content of the other seventeen. Each of these documents was issued with a separate report number (SAND 74-0073A through SAND 74-0091, except -0078)

  16. Understanding dynamic capabilities through knowledge management

    DEFF Research Database (Denmark)

    Nielsen, Anders Paarup

    2006-01-01

    In the paper eight knowledge management activities are identified; knowledge creation, acquisition, capture, assembly, sharing, integration, leverage and exploitation. These activities are assembled into the three dynamic capabilities of knowledge development, knowledge (re......)combination and knowledge use. The dynamic capabilities and the associated knowledge management activities create flows to and from the firm’s stock of knowledge and they support the creation and use of organizational capabilities....

  17. Compilation of Sandia Laboratories technical capabilities

    Energy Technology Data Exchange (ETDEWEB)

    Lundergan, C. D.; Mead, P. L. [eds.

    1975-11-01

    This report is a compilation of 17 individual documents that together summarize the technical capabilities of Sandia Laboratories. Each document in this compilation contains details about a specific area of capability. Examples of application of the capability to research and development problems are provided. An eighteenth document summarizes the content of the other seventeen. Each of these documents was issued with a separate report number (SAND 74-0073A through SAND 74-0091, except -0078). (RWR)

  18. Behavior Choice of Technology-motivated Mergers and Acquisitions for Enterprise Innovation Capability Improvement:Analysis Based on Internal Dynamic Mechanism%技术贸易中技术并购对企业创新能力提升的行为选择--基于内部动力机制的分析

    Institute of Scientific and Technical Information of China (English)

    陈磊

    2014-01-01

    论文针对技术并购提升企业创新能力的行为选择进行分析。通过对技术并购内涵的阐述,剖析技术并购的具体内容以及企业技术并购中知识资本互动的层次各维度,并就企业技术并购提升企业创新能力的内部动力机制、外部适用边界与技术并购成长路径选择条件进行深入分析。分别从知识资本的外部累进与更新、知识资本内部协同以及知识型人力资源与组织的动态构建等三方面深入剖析基于知识资本的技术并购内部动力机制,并在此基础上提出技术增强型、互补型与多元型三类技术并购模式,分析技术并购内部动力机制的创新效应。%This paper analyzes the behavior choice of technological merger and acquisition improving enterprise innovation capability. Based on elaboration of the connotation of technological merger and acquisition, this paper analyzes the specific content of technological merger and acquisition and the level of each dimension in technological merger and acquisition. It also analyzes the internal dynamic mechanism and external boundary conditions of technological merger and acquisition improving enterprise innovation capability and the growth path of technological merger and acquisition. The technological merger and acquisition internal dynamic mechanism based on knowledge capital is analyzed from external progression and update, internal coordination and dynamic construction of knowledge-based human resource and organization, and based on this, three technology acquisition modes are put forward namely technical enhancing, complementary and pluralistic to analyze the innovation effect of technological merger and acquisition internal dynamic mechanism.

  19. Methods of ecological capability evaluation of forest

    International Nuclear Information System (INIS)

    Hosseini, M.; Makhdoum, M.F.; Akbarnia, M.; Saghebtalebi, Kh.

    2000-01-01

    In this research common methods of ecological capability evaluation of forests were reviewed and limitations for performance were analysed. Ecological capability of forests is an index that show site potential in several role of wood production, soil conservation, flood control, biodiversity, conservation and water supply. This index is related to ecological characteristics of land, such as soil, micro climate, elevation, slope and aspect that affect potential of sites. Suitable method of ecological capability evaluation must be chosen according to the objective of forestry. Common methods for ecological capability evaluation include plant and animal diversity, site index curve, soil and land form, inter branches, index plants, leave analyses, analyses regeneration and ecological mapping

  20. Capabilities of Future Training Support Packages

    National Research Council Canada - National Science Library

    Burnside, Billy

    2004-01-01

    .... This report identifies and analyzes five key capabilities needed in future TSPs: rapid tailoring or modification, reach, simulated operating environment, performance measurement, and pretests/selection criteria...

  1. ATTITUDE ASSESSMENT USING PLEIADES-HR CAPABILITIES

    Directory of Open Access Journals (Sweden)

    J. M. Delevit

    2012-07-01

    Full Text Available Since SPOT1, the French national space centre (CNES has worked on improving the geometry of Earth observation spacecrafts. The accuracy of sensor calibration is one of the main key points for any Earth observation application such as orthorectification, DEM generation or surface change detection. For the last twenty years CNES has developed two families of methods: absolute methods and relative methods. These methods are used to characterize a pushbroom acquisition along the detector line and the time line. By this way, the viewing directions are measured and the residual of the spacecraft’s attitude angles (not restituted by the Attitude and Orbit Control System is estimated. This information can complete the geometric model of all the scenes acquired by the instrument and is used in all geometric applications. This paper presents new attitude assessment methods taking advantage of the capabilities of Pléiades-HR in terms of agility and focal plane arrangement – panchromatic band and multispectral (MS bands.

  2. Turning negotiation into a corporate capability.

    Science.gov (United States)

    Ertel, D

    1999-01-01

    Every company today exists in a complex web of relationships formed, one at a time, through negotiation. Purchasing and outsourcing contracts are negotiated with vendors. Marketing arrangements are negotiated with distributors. Product development agreements are negotiated with joint-venture partners. Taken together, the thousands of negotiations a typical company engages in have an enormous effect on both its strategy and its bottom line. But few companies think systematically about their negotiating activities as a whole. Instead they take a situational view, perceiving each negotiation to be a separate event with its own goals, tactics, and measures of success. Coordinating them all seems an overwhelming and impracticable job. In reality, the author argues, it is neither. A number of companies are successfully building coordinated negotiation capabilities by applying four broad changes in practice and perspective. First, they've established a company-wide negotiation infrastructure to apply the knowledge gained from forging past agreements to improve future ones. Second, they've broadened the measures they use to evaluate negotiators' performance beyond matters of cost and price. Third, they draw a clear distinction between the elements of an individual deal and the nature of the ongoing relationship between the parties. Fourth, they make their negotiators feel comfortable walking away from a deal when it's not in the company's best interests. These changes aren't radical steps. But taken together, they will let companies establish closer, more creative relationships with suppliers, customers, and other partners.

  3. Dynamic capabilities and innovation capabilities: The case of the ‘Innovation Clinic’

    Directory of Open Access Journals (Sweden)

    Fred Strønen

    2017-01-01

    Full Text Available In this explorative study, we investigate the relationship between dynamic capabilities and innovation capabilities. Dynamic capabilities are at the core of strategic management in terms of how firms can ensure adaptation to changing environments over time. Our paper follows two paths of argumentation. First, we review and discuss some major contributions to the theories on ordinary capabilities, dynamic capabilities, and innovation capabilities. We seek to identify different understandings of the concepts in question, in order to clarify the distinctions and relationships between dynamic capabilities and innovation capabilities. Second, we present a case study of the ’Innovation Clinic’ at a major university hospital, including four innovation projects. We use this case study to explore and discuss how dynamic capabilities can be extended, as well as to what extent innovation capabilities can be said to be dynamic. In our conclusion, we discuss the conditions for nurturing ‘dynamic innovation capabilities’ in organizations.

  4. Enhancement of EAST plasma control capabilities

    Energy Technology Data Exchange (ETDEWEB)

    Xiao, Bingjia, E-mail: bjxiao@ipp.ac.cn [Institute of Plasma Physics, Chinese Academy of Sciences, Hefei (China); School of Nuclear Science and Technology, University of Science and Technology of China, Hefei (China); Yuan, Qiping; Luo, Zhengping; Huang, Yao; Liu, Lei; Guo, Yong; Pei, Xiaofang; Chen, Shuliang [Institute of Plasma Physics, Chinese Academy of Sciences, Hefei (China); Humphreys, D.A.; Hyatt, A.W. [General Atomics, P.O. Box 85608, San Diego, CA 92186-5608 (United States); Mueller, Dennis [Princeton Plasma Physics Laboratory, Princeton, NJ (United States); Calabró, G.; Crisanti, F. [ENEA UnitàTecnicaFusione, C.R. Frascati, Via E. Fermi 45, 00044 Frascati, Roma (Italy); Albanese, R.; Ambrosino, R. [CREATE, Università di Napoli Federicao II, Università di Cassino and Università di Napoli Parthenope, Via Claudio 19, 80125 Napoli (Italy)

    2016-11-15

    Highlights: • Parallel plasma equilibrium reconstruction using GPU for real-time control on EAST. • Vertical control using Bang-bang + PID method to improve the response and minimize the oscillation caused by the latency. • Quasi-snow flake divertor plasma configuration has been demonstrated on EAST. - Abstract: In order to improve the plasma control performance and enhance the capability for advanced plasma control, new algorithms such as PEFIT/ISOFLUX plasma shape feedback control, quasi-snowflake plasma shape development and vertical control under new vertical control power supply, have been implemented and experimentally tested and verified in EAST 2014 campaign. P-EFIT is a rewritten version of EFIT aiming at fast real-time equilibrium reconstruction by using GPU for parallelized computation. Successful control using PEFIT/ISOFLUX was established in dedicated experiment. Snowfldivertor plasma shape has the advantage of spreading heat over the divertor target and a quasi-snowflake (QSF) configuration was achieved in discharges with I{sub p} = 0.25 MA and B{sub t} = 1.8T, κ∼1.9, by plasma position feedback control. The shape feedback control to achieve QSF shape has been preliminary implemented by using PEFIT and the initial experimental test has been done. For more robust vertical instability control, the inner coil (IC) and its power supply have been upgraded. A new control algorithm with the combination of Bang-bang and PID controllers has been developed. It is shown that new vertical control power supply together with the new control algorithms results in higher vertical controllability.

  5. Diagnostic and therapeutic capabilities of modern nuclear medicine

    International Nuclear Information System (INIS)

    Lee Myung-Chul, M.D

    2007-01-01

    growths, brain epilepsies and neurovascular disorders. In lung cancer and colorectal cancer, recurrence FDG-PET, now as FDG-PET/CT, is the method of choice in prostate cancer, impalpable axillary nodes in breast cancer and ovarian cancer. Peptide receptor scintigraphy stared in 1989 with the in vivo demonstration of somatostatin-receptor-positive tumors in patients using radioiodinated somatostatin analogue. Later, other radiolabeled somatostatin analogues were developed. [In-111-DTPA0]octreotide is a radiopharmaceutical with great potential for the visualization of somatostatin-receptor-positive tumors. Pain associated with bone metastases is a common clinical problem which contributes to patient morbidity and reduced quality of life. Symptoms associated with this pain include depression, anxiety, fear and loss of independence. The use of bone-seeking radiopharmaceutical was first reported almost 50 years ago, and there are now compelling data to support their use as an effective - and cost effective - approaches to pain palliation. With the ability of PET machines to capture direct images of cellular and molecular growth condition changes, research and treatment using PET systems quickly progressed in the United States, Europe, Korea and Japan. PET will play an active role in providing these molecular imaging techniques for refining the definition of radiation beams in RTP. Other areas of interest are the investigation of tumor-targeting agents, gene imaging and different PET tracers to improve the characterization of target cells. Technologic advances, such as the ability to acquire gated PET scans, will improve the accuracy of target cell characterization

  6. Development of a gamma ray spectroscopy capability at LANSCE

    International Nuclear Information System (INIS)

    Nelson, R.O.; Strottman, D.D.; Sterbenz, S.M.

    1998-01-01

    This is the final report of a one-year, Laboratory Directed Research and Development (LDRD) project at the Los Alamos National Laboratory (LANL). The goal of this project was to explore an upgrade to the GEANIE high-resolution gamma-ray spectrometer at the Los Alamos Neutron Science Center (LANSCE) to help build additional experimental capabilities. The improvements identified have significantly added to the capabilities of GEANIE and made the facility more attractive for studies supporting the core national security mission as well as for use by outside collaborators. These benefits apply to both basic and applied studies

  7. Various advanced capabilities of the RBS setup at IMEC

    International Nuclear Information System (INIS)

    Brijs, B.; Coster, W. de; Vandervorst, W.

    1992-01-01

    This article describes the various capabilities of the ion-beam analysis facility at IMEC which is designed to fulfill two needs. One is the high volume analysis service of material originating from the processing and material development groups at IMEC and the other is the research associated with gaining improved insight in the different analysis methods used for semiconductors, in particular all the aspects related with ion sputtering, and the development of improved analysis capabilities in order to cope with the demands from the analysis service. The latter includes the incorporation of a TOF spectrometer for heavy-ion RBS and ERD, the investigation towards the application of heavy-ion RBS for improved sensitivity, the application of angle resolved image scans for fast and certified channeling analysis and resonant analysis by automated energy scanning. (orig.)

  8. 77 FR 16585 - Open Meeting of the President's Advisory Council on Financial Capability

    Science.gov (United States)

    2012-03-21

    ... private sector in improving financial capability. DATES: The meeting will be held on April 9, 2012, at 10... appointed by the President with relevant backgrounds, such as financial services, consumer protection... federal government and the private sector can work together to improve the financial capability of...

  9. Developing maturity grids for assessing organisational capabilities

    DEFF Research Database (Denmark)

    Maier, Anja; Moultrie, James; Clarkson, P John

    2009-01-01

    Keyword: Maturity Model,Maturity Grid,Maturity Matrix,Organisational Capabilities,Benchmarking,New Product Development,Perfirmance Assessment......Keyword: Maturity Model,Maturity Grid,Maturity Matrix,Organisational Capabilities,Benchmarking,New Product Development,Perfirmance Assessment...

  10. Space Communications Capability Roadmap Interim Review

    Science.gov (United States)

    Spearing, Robert; Regan, Michael

    2005-01-01

    Contents include the following: Identify the need for a robust communications and navigation architecture for the success of exploration and science missions. Describe an approach for specifying architecture alternatives and analyzing them. Establish a top level architecture based on a network of networks. Identify key enabling technologies. Synthesize capability, architecture and technology into an initial capability roadmap.

  11. Global dynamics, capabilities and the crisis

    Czech Academy of Sciences Publication Activity Database

    Fagerberg, J.; Srholec, Martin

    2016-01-01

    Roč. 26, č. 4 (2016), s. 765-784 ISSN 0936-9937 R&D Projects: GA ČR GAP402/10/2310 Institutional support: RVO:67985998 Keywords : technological capabilities * social capabilities * competitiveness Subject RIV: AH - Economics Impact factor: 0.862, year: 2016

  12. Making Capability Lists: Philosophy versus Democracy

    NARCIS (Netherlands)

    Claassen, R.J.G.

    2011-01-01

    The article discusses a fundamental problem that has to be faced if the general capability approach is to be developed in the direction of a theory of justice: the selection and justification of a list of capabilities. The democratic solution to this problem (defended by Amartya Sen) is to leave the

  13. Networking capability and new product development

    NARCIS (Netherlands)

    Mu, J.; Di Benedetto, A.C.

    2012-01-01

    Current research on network theory remains largely focused on structures and outcomes without exploring the capability that firms need to build efficient and effective networks to their advantage. In this paper, we take a networking capability view in studying inter-firm relationships. We assume

  14. Cultivating Human Capabilities in Venturesome Learning Environments

    Science.gov (United States)

    Hogan, Padraig

    2013-01-01

    The notion of competencies has been a familiar feature of educational reform policies for decades. In this essay, Padraig Hogan begins by highlighting the contrasting notion of capabilities, pioneered by the research of Amartya Sen and Martha Nussbaum. An educational variant of the notion of capabilities then becomes the basis for exploring…

  15. A framework for offshore vendor capability development

    Science.gov (United States)

    Yusuf Wibisono, Yogi; Govindaraju, Rajesri; Irianto, Dradjad; Sudirman, Iman

    2016-02-01

    Offshore outsourcing is a common practice conducted by companies, especially in developed countries, by relocating one or more their business processes to other companies abroad, especially in developing countries. This practice grows rapidly owing to the ease of accessing qualified vendors with a lower cost. Vendors in developing countries compete more intensely to acquire offshore projects. Indonesia is still below India, China, Malaysia as main global offshore destinations. Vendor capability is among other factors that contribute to the inability of Indonesian vendor in competing with other companies in the global market. Therefore, it is essential to study how to increase the vendor's capability in Indonesia, in the context of global offshore outsourcing. Previous studies on the vendor's capability mainly focus on capabilities without considering the dynamic of capabilities due to the environmental changes. In order to be able to compete with competitors and maintain the competitive advantage, it is necessary for vendors to develop their capabilities continuously. The purpose of this study is to develop a framework that describes offshore vendor capability development along the client-vendor relationship stages. The framework consists of three main components, i.e. the stages of client-vendor relationship, the success of each stage, and the capabilities of vendor at each stage.

  16. Towards a national cybersecurity capability development model

    CSIR Research Space (South Africa)

    Jacobs, Pierre C

    2017-06-01

    Full Text Available to be broken down into its components, a model serves as a blueprint to ensure that those building the capability considers all components, allows for cost estimation and facilitates the evaluation of trade-offs. One national cybersecurity capability...

  17. Technology support for military capability based acquisition

    CSIR Research Space (South Africa)

    Thaba, Mphahlela

    2017-05-01

    Full Text Available gap between capability planning and acquisition of product systems in the SANDF. (Thaba J et al, 2015). The need for decision support tools and technologies to assist capability planners to close this gap and make sound decisions has become more...

  18. Building Organisational Capability the Private Provider Way

    Science.gov (United States)

    Guthrie, Hugh

    2008-01-01

    Organisational capability is recognised as a key to organisational success. The combination of human capital (peoples' skills and knowledge), social capital (relationships between people) and organisational capital (the organisation's processes), is central to building an organisation's capability. This paper, presented at the 2008 annual…

  19. Capabilities of Universities in Achieving the Agricultural ...

    African Journals Online (AJOL)

    All (100%) the respondents had no capability in acquiring machines and equipment needed for teaching and conducting researches on climate change. Majority (85%) of the respondents had no capability in terms of human resource development with regards to climate change. Funding/manpower (0.657), organizational ...

  20. Current Capability of Atomic Structure Theory

    International Nuclear Information System (INIS)

    Kim, Yong Ki

    1993-01-01

    Current capability of atomic structure theory is reviewed, and advantages, disadvantages and major features of popular atomic structure codes described. Comparisons between theoretical and experimental data on transition energies and lifetimes of excited levels are presented to illustrate the current capability of atomic structure codes.

  1. Knowledge Perspectives on Advancing Dynamic Capability

    NARCIS (Netherlands)

    van Reijsen, J.

    2014-01-01

    Dynamic Capability is the organizational capacity to timely adapt to a changing market environment by reconfiguring resources and routines in order to stay competitive. Although dynamic capability is considered the Holy Grail of strategic management, a connection to the knowledge management domain

  2. Capabilities and Equality of Health II

    DEFF Research Database (Denmark)

    Keiding, Hans

    The concept of capabilities, introduced originally by Sen, has inspired many researchers but has not found any simple formal representation which might be instrumental in the construction of a comprehensive theory of equality. In a previous paper (Keiding, 2005), we investigated whether preferences...... of the capability approach to questions of health or equality. In the present paper we extend the notion of rationalizing orderings of capabilities to a dynamical context, in the sense that the utility function is not yet revealed to the individual at the time when the capabilities are ordered. It turns out...... over capabilities as sets of functionings can be rationalized by maximization of a suitable utility function over the set of functionings. Such a rationalization turned out to be possible only in cases which must be considered exceptional and which do not allowfor interesting applications...

  3. Neural network fusion capabilities for efficient implementation of tracking algorithms

    Science.gov (United States)

    Sundareshan, Malur K.; Amoozegar, Farid

    1997-03-01

    The ability to efficiently fuse information of different forms to facilitate intelligent decision making is one of the major capabilities of trained multilayer neural networks that is now being recognized. While development of innovative adaptive control algorithms for nonlinear dynamical plants that attempt to exploit these capabilities seems to be more popular, a corresponding development of nonlinear estimation algorithms using these approaches, particularly for application in target surveillance and guidance operations, has not received similar attention. We describe the capabilities and functionality of neural network algorithms for data fusion and implementation of tracking filters. To discuss details and to serve as a vehicle for quantitative performance evaluations, the illustrative case of estimating the position and velocity of surveillance targets is considered. Efficient target- tracking algorithms that can utilize data from a host of sensing modalities and are capable of reliably tracking even uncooperative targets executing fast and complex maneuvers are of interest in a number of applications. The primary motivation for employing neural networks in these applications comes from the efficiency with which more features extracted from different sensor measurements can be utilized as inputs for estimating target maneuvers. A system architecture that efficiently integrates the fusion capabilities of a trained multilayer neural net with the tracking performance of a Kalman filter is described. The innovation lies in the way the fusion of multisensor data is accomplished to facilitate improved estimation without increasing the computational complexity of the dynamical state estimator itself.

  4. Evaluating Internal Technological Capabilities in Energy Companies

    Directory of Open Access Journals (Sweden)

    Mingook Lee

    2016-03-01

    Full Text Available As global competition increases, technological capability must be evaluated objectively as one of the most important factors for predominance in technological competition and to ensure sustainable business excellence. Most existing capability evaluation models utilize either quantitative methods, such as patent analysis, or qualitative methods, such as expert panels. Accordingly, they may be in danger of reflecting only fragmentary aspects of technological capabilities, and produce inconsistent results when different models are used. To solve these problems, this paper proposes a comprehensive framework for evaluating technological capabilities in energy companies by considering the complex properties of technological knowledge. For this purpose, we first explored various factors affecting technological capabilities and divided the factors into three categories: individual, organizational, and technology competitiveness. Second, we identified appropriate evaluation items for each category to measure the technological capability. Finally, by using a hybrid approach of qualitative and quantitative methods, we developed an evaluation method for each item and suggested a method to combine the results. The proposed framework was then verified with an energy generation and supply company to investigate its practicality. As one of the earliest attempts to evaluate multi-faceted technological capabilities, the suggested model can support technology and strategic planning.

  5. Community psychology and the capabilities approach.

    Science.gov (United States)

    Shinn, Marybeth

    2015-06-01

    What makes for a good life? The capabilities approach to this question has much to offer community psychology, particularly with respect to marginalized groups. Capabilities are freedoms to engage in valued social activities and roles-what people can do and be given both their capacities, and environmental opportunities and constraints. Economist Amartya Sen's focus on freedoms and agency resonates with psychological calls for empowerment, and philosopher Martha Nussbaum's specification of requirements for a life that is fully human provides an important guide for social programs. Community psychology's focus on mediating structures has much to offer the capabilities approach. Parallels between capabilities, as enumerated by Nussbaum, and settings that foster positive youth development, as described in a National Research Council Report (Eccles and Gootman (Eds) in Community programs to promote youth development. National Academy Press, Washington, 2002) suggest extensions of the approach to children. Community psychologists can contribute to theory about ways to create and modify settings to enhance capabilities as well as empowerment and positive youth development. Finally, capabilities are difficult to measure, because they involve freedoms to choose but only choices actually made or enacted can be observed. The variation in activities or goals across members of a setting provides a measure of the capabilities that the setting fosters.

  6. BURAR: Detection and signal processing capabilities

    International Nuclear Information System (INIS)

    Ghica, Daniela; Radulian, Mircea; Popa, Mihaela

    2004-01-01

    Since July 2002, a new seismic monitoring station, the Bucovina Seismic Array (BURAR), has been installed in the northern part of Romania, in a joint effort of the Air Force Technical Applications Center, USA, and the National Institute for Earth Physics (NIEP), Romania. The array consists of 10 seismic sensors (9 short-period and one broad band) located in boreholes and distributed in a 5 x 5 km 2 area. At present, the seismic data are continuously recorded by BURAR and transmitted in real-time to the Romanian National Data Centre (ROM N DC), in Bucharest and to the National Data Center of USA, in Florida. The statistical analysis for the seismic information gathered at ROM N DC by the BURAR in the August 2002 - December 2003 time interval points out a much better efficiency of the BURAR system in detecting teleseismic events and local events occurred in the N-NE part of Romanian territory, in comparison with the actual Romanian Telemetered Network. Furthermore, the BURAR monitoring system has proven to be an important source of reliable data for NIEP efforts in issuing the seismic bulletins. Signal processing capability of the system provides useful information in order to improve the location of the local seismic events, using the array beamforming procedure. This method increases significantly the signal-to-noise ratio by summing up the coherent signals from the array components. In this way, possible source nucleation phases can be detected. At the same time, using the slowness and back azimuth estimations by f-k analysis, locations for the seismic events can be established based only on the information recorded by the BURAR array, acting like a single seismic station recording system. (authors)

  7. BURAR: Detection and signal processing capabilities

    International Nuclear Information System (INIS)

    Ghica, Daniela; Radulian, Mircea; Popa, Mihaela

    2004-01-01

    Since July 2002, a new seismic monitoring station, the Bucovina Seismic Array (BURAR), has been installed in the northern part of Romania, in a joint effort of the Air Force Technical Applications Center, USA, and the National Institute for Earth Physics (NIEP), Romania. The array consists of 10 seismic sensors (9 short-period and one broad band) located in boreholes and distributed in a 5 x 5 km area. At present, the seismic data are continuously recorded by BURAR and transmitted in real-time to the Romanian National Data Centre (ROM N DC), at Bucharest and to the National Data Center of USA, in Florida. The statistical analysis for the seismic information gathered at ROM N DC by the BURAR in the August 2002 - December 2003 time interval points out a much better efficiency of the BURAR system in detecting teleseismic events and local events occurred in the N-NE part of Romanian territory, in comparison with the actual Romanian Telemetered Network. Furthermore, the BURAR monitoring system has proven to be an important source of reliable data for NIEP efforts in elaborating of the seismic bulletins. Signal processing capability of the system provides useful information in order to improve the location of the local seismic events, using the array beamforming facility. This method increases significantly the signal-to-noise ratio of the seismic signal by summing up the coherent signals from the array components. In this way, eventual source nucleation phases can be detected. At the same time, using the slowness and backazimuth estimations by f-k analysis, locations for the seismic events can be performed based only on the information recorded by the BURAR array, acting like a single seismic station recording system. Additionally, f-k analysis techniques are useful in the local site effects estimation and interpretation of the local geological structure. (authors)

  8. Capability maturity models in engineering companies: case study analysis

    Directory of Open Access Journals (Sweden)

    Titov Sergei

    2016-01-01

    Full Text Available In the conditions of the current economic downturn engineering companies in Russia and worldwide are searching for new approaches and frameworks to improve their strategic position, increase the efficiency of the internal business processes and enhance the quality of the final products. Capability maturity models are well-known tools used by many foreign engineering companies to assess the productivity of the processes, to elaborate the program of business process improvement and to prioritize the efforts to optimize the whole company performance. The impact of capability maturity model implementation on cost and time are documented and analyzed in the existing research. However, the potential of maturity models as tools of quality management is less known. The article attempts to analyze the impact of CMM implementation on the quality issues. The research is based on a case study methodology and investigates the real life situation in a Russian engineering company.

  9. Canadian national nuclear forensics capability project

    International Nuclear Information System (INIS)

    Ball, J.; Dimayuga, I.; Summerell, I.; Totland, M.; Jonkmans, G.; Whitlock, J.; El-jaby, A.; Inrig, E.

    2015-01-01

    Following the 2010 Nuclear Security Summit, Canada expanded its existing capability for nuclear forensics by establishing a national nuclear forensics laboratory network, which would include a capability to perform forensic analysis on nuclear and other radioactive material, as well as on traditional evidence contaminated with radioactive material. At the same time, the need for a national nuclear forensics library of signatures of nuclear and radioactive materials under Canadian regulatory control was recognized. The Canadian Safety and Security Program, administered by Defence Research and Development Canada's Centre for Security Science (DRDC CSS), funds science and technology initiatives to enhance Canada's preparedness for prevention of and response to potential threats. DRDC CSS, with assistance from Canadian Nuclear Laboratories, formerly Atomic Energy of Canada Limited, is leading the Canadian National Nuclear Forensics Capability Project to develop a coordinated, comprehensive, and timely national nuclear forensics capability. (author)

  10. Annual Industrial Capabilities Report to Congress

    National Research Council Canada - National Science Library

    2006-01-01

    .... Stable robust Department of Defense (DoD) funding is the primary factor in sustaining those industrial capabilities supporting defense because such funding focuses market demand across a broad spectrum of industry segments to meet emerging...

  11. The Capabilities of the Offshore Middlemen

    DEFF Research Database (Denmark)

    Mahnke, Volker; Wareham, Jonathan

    preliminary theoretical justification for the emergence of offshore intermediaries; describe how and why they develop intermediation capabilities; and offer initial evidence substantiating their function and processes in intermediating transnational offshoring relationships in software development...

  12. [Run the risk: social disadvantage or capability?

    Science.gov (United States)

    Muñoz-Duque, Luz Adriana

    2018-05-10

    This article discusses the notions of risk and risk acceptability from a social justice perspective, especially in light of the capability approach proposed by Amartya Sen. The article argues that risk can be the expression of restrictions on subjects' capabilities, deriving from social disadvantages that can be taken for granted in their daily realities. On the other hand, risk can be viewed as an expression of capability in cases where subjects have accepted or admitted the risk through the exercise of freedom, as long as the subjects that relate to the risk do so in keeping with their idea of a good life, the building of which implies the full development of capability for agency. The article concludes with some thoughts on the issues of risk and risk acceptability in the sphere of public health.

  13. Resistance capability of microaerobic granular sludge for ...

    African Journals Online (AJOL)

    enoh

    2012-02-08

    Feb 8, 2012 ... The resistance capability to pH shock of microaerobic granular sludge for pentachlorophenol (PCP) ... process with chlorine gas in pulp and paper, leather and spinning ... nitrifying bacteria in the aerobic zone, and then trans-.

  14. Establishing an infrared measurement and modelling capability

    CSIR Research Space (South Africa)

    Willers, CJ

    2011-04-01

    Full Text Available The protection of own aircraft assets against infrared missile threats requires a deep understanding of the vulnerability of these assets with regard to specific threats and specific environments of operation. A key capability in the protection...

  15. Bearding the Capability Deprivation Machine: The Pedagogical ...

    African Journals Online (AJOL)

    Bearding the Capability Deprivation Machine: The Pedagogical Deal for ... Africa are managing the task of higher education in an environment marked by poverty. ... are valuable in the full range of social spaces young South Africans inhabit.

  16. Geospatial Information System Capability Maturity Models

    Science.gov (United States)

    2017-06-01

    To explore how State departments of transportation (DOTs) evaluate geospatial tool applications and services within their own agencies, particularly their experiences using capability maturity models (CMMs) such as the Urban and Regional Information ...

  17. Assessing Contractor Capabilities for Streamlined Site Investigations

    Science.gov (United States)

    The purpose of this document is to familiarize and encourage brownfields decision makers to investigate and employ innovative methods for characterizing their sites, to assist brownfields decision makers in assessing contractors' capabilities.

  18. Canadian national nuclear forensics capability project

    Energy Technology Data Exchange (ETDEWEB)

    Ball, J.; Dimayuga, I., E-mail: joanne.ball@cnl.ca [Canadian Nuclear Laboratories, Chalk River, Ontario (Canada); Summerell, I. [Royal Canadian Mounted Police, Ottawa, Ontario (Canada); Totland, M. [Canadian Nuclear Laboratories, Chalk River, Ontario (Canada); Jonkmans, G. [Defence Research and Development Canada, Ottawa, Ontario (Canada); Whitlock, J. [Canadian Nuclear Laboratories, Chalk River, Ontario (Canada); El-jaby, A. [Canadian Nuclear Safety Commission, Ottawa, Ontario (Canada); Inrig, E. [Defence Research and Development Canada, Ottawa, Ontario (Canada)

    2015-06-15

    Following the 2010 Nuclear Security Summit, Canada expanded its existing capability for nuclear forensics by establishing a national nuclear forensics laboratory network, which would include a capability to perform forensic analysis on nuclear and other radioactive material, as well as on traditional evidence contaminated with radioactive material. At the same time, the need for a national nuclear forensics library of signatures of nuclear and radioactive materials under Canadian regulatory control was recognized. The Canadian Safety and Security Program, administered by Defence Research and Development Canada's Centre for Security Science (DRDC CSS), funds science and technology initiatives to enhance Canada's preparedness for prevention of and response to potential threats. DRDC CSS, with assistance from Canadian Nuclear Laboratories, formerly Atomic Energy of Canada Limited, is leading the Canadian National Nuclear Forensics Capability Project to develop a coordinated, comprehensive, and timely national nuclear forensics capability. (author)

  19. Perception Management: A Core IO Capability

    National Research Council Canada - National Science Library

    Zaman, Khyber

    2007-01-01

    This thesis postulates that in today's media environment, with adversaries skillfully using propaganda to skirt nations' resolve, Perception Management is key to military success and should be an Information Operations (IO) Core Capability...

  20. Facility Interface Capability Assessment (FICA) project report

    International Nuclear Information System (INIS)

    Pope, R.B.; MacDonald, R.R.; Viebrock, J.M.; Mote, N.

    1995-09-01

    The US Department of Energy's (DOE) Office of Civilian Radioactive Waste Management (OCRWM) is responsible for developing the Civilian Radioactive Waste Management System (CRWMS) to accept spent nuclear fuel from commercial facilities. The objective of the Facility Interface Capability Assessment (FICA) project was to assess the capability of each commercial spent nuclear fuel (SNF) storage facility, at which SNF is stored, to handle various SNF shipping casks. The purpose of this report is to present and analyze the results of the facility assessments completed within the FICA project. During Phase 1, the data items required to complete the facility assessments were identified and the database for the project was created. During Phase 2, visits were made to 122 facilities on 76 sites to collect data and information, the database was updated, and assessments of the cask-handling capabilities at each facility were performed. Each assessment of cask-handling capability contains three parts: the current capability of the facility (planning base); the potential enhanced capability if revisions were made to the facility licensing and/or administrative controls; and the potential enhanced capability if limited physical modifications were made to the facility. The main conclusion derived from the planning base assessments is that the current facility capabilities will not allow handling of any of the FICA Casks at 49 of the 122 facilities evaluated. However, consideration of potential revisions and/or modifications showed that all but one of the 49 facilities could be adapted to handle at least one of the FICA Casks. For this to be possible, facility licensing, administrative controls, and/or physical aspects of the facility would need to be modified

  1. Descriptors of server capabilities in China

    DEFF Research Database (Denmark)

    Adeyemi, Oluseyi; Slepniov, Dmitrij; Wæhrens, Brian Vejrum

    are relevant to determine subsidiary roles and as an indication of the capabilities required. These descriptors are identified through extensive literature review and validated by case studies of two Danish multinational companies subsidiaries operating in China. They provided the empirical basis......China with the huge market potential it possesses is an important issue for subsidiaries of western multinational companies. The objective of this paper is therefore to strengthen researchers’ and practitioners’ perspectives on what are the descriptors of server capabilities. The descriptors...

  2. Identity Building in Organisations: Proactive Capability Development

    DEFF Research Database (Denmark)

    Rasmussen, Lauge Baungaard

    2002-01-01

    Identity building in organisations is often viewed as legitimacy of value systems of the organisation. Based on empirical studies the task of this article is to argue that such a legitimacy approach risks failing in the longer perspective, if the proactive capability development is neglected....... The participatory scenario method presented in this article is one of the possible methods to enhance identity building based on proactive capability development....

  3. Porflow Capabilities, Usage, History, and Testing

    International Nuclear Information System (INIS)

    Collard, L.B.

    1998-05-01

    To support closure of the Savannah River Site High Level Waste tanks, the PORFLOW computer program is being applied to predict long term movement of residual contaminants from the tanks. The PORFLOW program has greater capabilities than simpler programs that have been used previously, and PORFLOW results have been accepted by state and federal regulators throughout the United States. This document briefly discusses the PORFLOW capabilities and presents lists of reports showing PORFLOW's usage history and testing

  4. Targeted NextGen Capabilities for 2025

    Science.gov (United States)

    2011-11-01

    increased arrival capacity to single runways by reducing longitudinal wake separation standards for Instrument Flight Rules ( IFR ) operations under certain...b. ABSTRACT unclassified c. THIS PAGE unclassified Standard Form 298 (Rev. 8-98) Prescribed by ANSI Std Z39-18 Targeted NextGen Capabilities...The examples cited are not intended to cover every aircraft and every flight. In some instances, the available capabilities for 2025 will not be

  5. Facility Interface Capability Assessment (FICA) project report

    Energy Technology Data Exchange (ETDEWEB)

    Pope, R.B. [ed.] [Oak Ridge National Lab., TN (United States); MacDonald, R.R. [ed.] [Civilian Radioactive Waste Management System, Vienna, VA (United States); Viebrock, J.M.; Mote, N. [Nuclear Assurance Corp., Norcross, GA (United States)

    1995-09-01

    The US Department of Energy`s (DOE) Office of Civilian Radioactive Waste Management (OCRWM) is responsible for developing the Civilian Radioactive Waste Management System (CRWMS) to accept spent nuclear fuel from commercial facilities. The objective of the Facility Interface Capability Assessment (FICA) project was to assess the capability of each commercial spent nuclear fuel (SNF) storage facility, at which SNF is stored, to handle various SNF shipping casks. The purpose of this report is to present and analyze the results of the facility assessments completed within the FICA project. During Phase 1, the data items required to complete the facility assessments were identified and the database for the project was created. During Phase 2, visits were made to 122 facilities on 76 sites to collect data and information, the database was updated, and assessments of the cask-handling capabilities at each facility were performed. Each assessment of cask-handling capability contains three parts: the current capability of the facility (planning base); the potential enhanced capability if revisions were made to the facility licensing and/or administrative controls; and the potential enhanced capability if limited physical modifications were made to the facility. The main conclusion derived from the planning base assessments is that the current facility capabilities will not allow handling of any of the FICA Casks at 49 of the 122 facilities evaluated. However, consideration of potential revisions and/or modifications showed that all but one of the 49 facilities could be adapted to handle at least one of the FICA Casks. For this to be possible, facility licensing, administrative controls, and/or physical aspects of the facility would need to be modified.

  6. Aging and DNA repair capability. [Review

    Energy Technology Data Exchange (ETDEWEB)

    Tice, R R

    1977-01-01

    A review of the literature on DNA repair processes in relation to aging is presented under the following headings: DNA repair processes; age-related occurrence of unrepaired DNA lesions; DNA repair capability as a function of age; tissue-specific DNA repair capability; acceleration of the aging process by exposure to DNA damaging agents; human genetic syndromes; and longevity and DNA repair processes. (HLW)

  7. Product development capability and marketing strategy for new durable products

    OpenAIRE

    Banerjee, Sumitro; Soberman, David A.

    2013-01-01

    Our objective is to understand how a firm’s product development capability (PDC) affects the launch strategy for a durable product that is sequentially improved over time in a market where consumers have heterogeneous valuations for quality. We show that the launch strategy of firms is affected by the degree to which consumers think ahead. However, only the strategy of firms with high PDC is affected by the observability of quality. When consumers are myopic and quality is observable, both hi...

  8. Quantumness-generating capability of quantum dynamics

    Science.gov (United States)

    Li, Nan; Luo, Shunlong; Mao, Yuanyuan

    2018-04-01

    We study quantumness-generating capability of quantum dynamics, where quantumness refers to the noncommutativity between the initial state and the evolving state. In terms of the commutator of the square roots of the initial state and the evolving state, we define a measure to quantify the quantumness-generating capability of quantum dynamics with respect to initial states. Quantumness-generating capability is absent in classical dynamics and hence is a fundamental characteristic of quantum dynamics. For qubit systems, we present an analytical form for this measure, by virtue of which we analyze several prototypical dynamics such as unitary dynamics, phase damping dynamics, amplitude damping dynamics, and random unitary dynamics (Pauli channels). Necessary and sufficient conditions for the monotonicity of quantumness-generating capability are also identified. Finally, we compare these conditions for the monotonicity of quantumness-generating capability with those for various Markovianities and illustrate that quantumness-generating capability and quantum Markovianity are closely related, although they capture different aspects of quantum dynamics.

  9. Health, vital goals, and central human capabilities.

    Science.gov (United States)

    Venkatapuram, Sridhar

    2013-06-01

    I argue for a conception of health as a person's ability to achieve or exercise a cluster of basic human activities. These basic activities are in turn specified through free-standing ethical reasoning about what constitutes a minimal conception of a human life with equal human dignity in the modern world. I arrive at this conception of health by closely following and modifying Lennart Nordenfelt's theory of health which presents health as the ability to achieve vital goals. Despite its strengths I transform Nordenfelt's argument in order to overcome three significant drawbacks. Nordenfelt makes vital goals relative to each community or context and significantly reflective of personal preferences. By doing so, Nordenfelt's conception of health faces problems with both socially relative concepts of health and subjectively defined wellbeing. Moreover, Nordenfelt does not ever explicitly specify a set of vital goals. The theory of health advanced here replaces Nordenfelt's (seemingly) empty set of preferences and society-relative vital goals with a human species-wide conception of basic vital goals, or 'central human capabilities and functionings'. These central human capabilities come out of the capabilities approach (CA) now familiar in political philosophy and economics, and particularly reflect the work of Martha Nussbaum. As a result, the health of an individual should be understood as the ability to achieve a basic cluster of beings and doings-or having the overarching capability, a meta-capability, to achieve a set of central or vital inter-related capabilities and functionings. © 2012 John Wiley & Sons Ltd.

  10. Innovations in monoclonal antibody tumor targeting; Diagnostic and therapeutic implications

    International Nuclear Information System (INIS)

    Schlom, J.

    1989-01-01

    The detection of carcinoma lesions not identified by conventional radiological and physical examinations remains a major problem in the treatment of many carcinomas. This article reviews potential new modalities and areas of research for carcinoma diagnosis and treatment. A case history is presented

  11. Tumor Targeting and Drug Delivery by Anthrax Toxin

    OpenAIRE

    Bachran, Christopher; Leppla, Stephen H.

    2016-01-01

    Anthrax toxin is a potent tripartite protein toxin from Bacillus anthracis. It is one of the two virulence factors and causes the disease anthrax. The receptor-binding component of the toxin, protective antigen, needs to be cleaved by furin-like proteases to be activated and to deliver the enzymatic moieties lethal factor and edema factor to the cytosol of cells. Alteration of the protease cleavage site allows the activation of the toxin selectively in response to the presence of tumor-associ...

  12. Polymeric micelles as a drug carrier for tumor targeting

    Directory of Open Access Journals (Sweden)

    Neha M Dand

    2013-01-01

    Full Text Available Polymeric micelle can be targeted to tumor site by passive and active mechanism. Some inherent properties of polymeric micelle such as size in nanorange, stability in plasma, longevity in vivo, and pathological characteristics of tumor make polymeric micelles to be targeted at the tumor site by passive mechanism called enhanced permeability and retention effect. Polymeric micelle formed from the amphiphilic block copolymer is suitable for encapsulation of poorly water soluble, hydrophobic anticancer drugs. Other characteristics of polymeric micelles such as separated functionality at the outer shell are useful for targeting the anticancer drug to tumor by active mechanisms. Polymeric micelles can be conjugated with many ligands such as antibodies fragments, epidermal growth factors, α2 -glycoprotein, transferrine, and folate to target micelles to cancer cells. Application of heat and ultrasound are the alternative methods to enhance drug accumulation in tumoral cells. Targeting using micelles can also be done to tumor angiogenesis which is the potentially promising target for anticancer drugs. This review summarizes about recently available information regarding targeting the anticancer drug to the tumor site using polymeric micelles.

  13. Capable design or designing capabilities? An exploration of service design as an emerging organizational capability in Telenor – Martinkenaite

    Directory of Open Access Journals (Sweden)

    Ieva Martinkenaite

    2017-01-01

    Full Text Available This empirical paper examines a process, starting with the managerial decision to make service design an organizational capability, and follows it as it unfolds over time within one organization. Service design has become an established business practice of how firms create new products and services to promote differentiation in an increasingly uncertain business landscape. Implicit in the literature on service design are assumptions about strategic implications of adopting the prescribed innovation methods and tools. However, little is known about how service design evolves into an organizational capability enabling firms to transform their existing businesses and sustain competitiveness. Through a longitudinal, exploratory case study of service design practices in one of the world’s largest telecommunications companies, we explicate mechanisms through which service design evolves into an organizational capability by exploring the research question: what are the mechanisms through which service design develops into an organizational capability? Our study reveals the effect of an initial introduction of service design tools, identification of boundaryspanning actors and co-alignment of dedicated resources between internal functions, as well as through co-creation with customers. Over time, these activities lead to the adoption of service design practices, and subsequently these practices spark incremental learning throughout the organization, alter managerial decisions and influence multiple paths for the development of new capabilities. Reporting on this process, we are able to describe how service design practices were disseminated and institutionalized within the organization we observed. This study thus contributes by informing how service design can evolve into an organizational capability, as well as by bridging the emerging literature on service design and design thinking with established strategy theory. Further research will have to

  14. The enhancements and testing for the MCNPX depletion capability

    International Nuclear Information System (INIS)

    Fensin, M. L.; Hendricks, J. S.; Anghaie, S.

    2008-01-01

    Monte Carlo-linked depletion methods have gained recent interest due to the ability to more accurately model true system physics and better track the evolution of temporal nuclide inventory by simulating the actual physical process. The integration of INDER90 into the MCNPX Monte Carlo radiation transport code provides a completely self-contained Monte- Carlo-linked depletion capability in a single Monte Carlo code that is compatible with most nuclear criticality (KCODE) particle tracking features in MCNPX. MCNPX depletion tracks all necessary reaction rates and follows as many isotopes as cross section data permits in order to achieve a highly accurate temporal nuclide inventory solution. We describe here the depletion methodology dating from the original linking of MONTEBURNS and MCNP to the first public release of the integrated capability (MCNPX 2. 6.B, June, 2006) that has been reported previously. Then we further detail the many new depletion capability enhancements since then leading to the present capability. The H.B. Robinson benchmark calculation results are also reported. The new MCNPX depletion capability enhancements include: (1) allowing the modeling of as large a system as computer memory capacity permits; (2) tracking every fission product available in ENDF/B VII. 0; (3) enabling depletion in repeated structures geometries such as repeated arrays of fuel pins; (4) including metastable isotopes in burnup; and (5) manually changing the concentrations of key isotopes during different time steps to simulate changing reactor control conditions such as dilution of poisons to maintain criticality during burnup. These enhancements allow better detail to model the true system physics and also improve the robustness of the capability. The H.B. Robinson benchmark calculation was completed in order to determine the accuracy of the depletion solution. Temporal nuclide computations of key actinide and fission products are compared to the results of other

  15. Exploration Medical Capability (ExMC) Projects

    Science.gov (United States)

    Wu, Jimmy; Watkins, Sharmila; Baumann, David

    2010-01-01

    During missions to the Moon or Mars, the crew will need medical capabilities to diagnose and treat disease as well as for maintaining their health. The Exploration Medical Capability Element develops medical technologies, medical informatics, and clinical capabilities for different levels of care during space missions. The work done by team members in this Element is leading edge technology, procedure, and pharmacological development. They develop data systems that protect patient's private medical information, aid in the diagnosis of medical conditions, and act as a repository of relevant NASA life sciences experimental studies. To minimize the medical risks to crew health the physicians and scientists in this Element develop models to quantify the probability of medical events occurring during a mission. They define procedures to treat an ill or injured crew member who does not have access to an emergency room and who must be cared for in a microgravity environment where both liquids and solids behave differently than on Earth. To support the development of these medical capabilities, the Element manages the development of medical technologies that prevent, monitor, diagnose, and treat an ill or injured crewmember. The Exploration Medical Capability Element collaborates with the National Space Biomedical Research Institute (NSBRI), the Department of Defense, other Government-funded agencies, academic institutions, and industry.

  16. Geometry and gravity influences on strength capability

    Science.gov (United States)

    Poliner, Jeffrey; Wilmington, Robert P.; Klute, Glenn K.

    1994-01-01

    Strength, defined as the capability of an individual to produce an external force, is one of the most important determining characteristics of human performance. Knowledge of strength capabilities of a group of individuals can be applied to designing equipment and workplaces, planning procedures and tasks, and training individuals. In the manned space program, with the high risk and cost associated with spaceflight, information pertaining to human performance is important to ensuring mission success and safety. Knowledge of individual's strength capabilities in weightlessness is of interest within many areas of NASA, including workplace design, tool development, and mission planning. The weightless environment of space places the human body in a completely different context. Astronauts perform a variety of manual tasks while in orbit. Their ability to perform these tasks is partly determined by their strength capability as demanded by that particular task. Thus, an important step in task planning, development, and evaluation is to determine the ability of the humans performing it. This can be accomplished by utilizing quantitative techniques to develop a database of human strength capabilities in weightlessness. Furthermore, if strength characteristics are known, equipment and tools can be built to optimize the operators' performance. This study examined strength in performing a simple task, specifically, using a tool to apply a torque to a fixture.

  17. Innovation Inspired by Nature: Capabilities, Potentials and Challenges

    Science.gov (United States)

    Bar-Cohen, Yoseph

    2012-01-01

    Through evolution, nature came up with many effective solutions to its challenges and continually improving them. By mimicking, coping and being inspired, humans have been using Nature's solutions to address their own challenges. In recent years, the implementation of nature's capabilities has intensified with our growing understanding of the various biological and nastic mechanisms and processes. Successes include even the making of humanlike robots that perform such lifelike tasks as walking, talking, making eye-contact, interpreting speech and facial expressions, as well as many other humanlike functions. Generally, once humans are able to implement a function then, thru rapid advances in technology, capabilities are developed that can significantly exceed the original source of inspiration in Nature. Examples include flight where there is no species that can fly as high, carry so much mass, has so large dimensions and fly so fast, and operate at as such extreme conditions as our aircraft and other aerospace systems. However, using the capabilities of today's technology, there are many challenges that are not feasible to address in mimicking characteristics of species and plants. In this manuscript, state-of-the-art of biomimetic capabilities, potentials and challenges are reviewed.

  18. Human Exploration Systems and Mobility Capability Roadmap Progress Review

    Science.gov (United States)

    Culbert, Chris; Taylor, Jeff

    2005-01-01

    Contents include the following: Capability Roadmap Team. Capability Description and Capability Breakdown Structure. Benefits of the Human Systems and Mobility Capability. Roadmap Process and Approach. Drivers and Assumptions for the whole team. Current State-of-the-Art, Assumptions and Requirements will be covered in the appropriate sections. Capability Presentations by Leads under Roadmap (Repeated for each capability under roadmap). Capability Description, Benefits, Current State-of-the-Art. Capability Requirements and Assumptions. Roadmap for Capability. Capability Readiness Level. Technology Readiness Level. Figures of Merit. Summary of Top Level Capability. Significant Technical Challenges. Summary and Forward Work.

  19. Cosmopolitan capabilities in the HE classroom

    Directory of Open Access Journals (Sweden)

    Veronica Crosbie

    2014-04-01

    Full Text Available This study, concerning the development of cosmopolitan citizenship, draws on theories of human development and capabilities (Sen 1999; Nussbaum 2000 from a social justice perspective, where individual wellbeing is articulated as having the freedom to live a life of one’s choosing. In the context of an English to Speakers of Other Languages (ESOL classroom this involves paying attention to pedagogical strategies, power dynamics and curriculum content as a means of developing valued beings and doings (or capabilities and functionings as they are described in the literature. Sample activities are presented and evaluated to see to what extent they achieve the desired end. These include critical pedagogical interventions, students’ artefacts and extracts from focus group interviews, class reports and reflective journals.  Results from the textual data offer research evidence of successful curriculum change, demonstrating that the learning that takes place there can make a difference: in terms of the learners’ identity development, capability enhancement and cosmopolitan citizenship.

  20. Personality Assessment: A Competency-Capability Perspective.

    Science.gov (United States)

    Kaslow, Nadine J; Finklea, J Tyler; Chan, Ginny

    2018-01-01

    This article begins by reviewing the proficiency of personality assessment in the context of the competencies movement, which has dominated health service psychology in recent years. It examines the value of including a capability framework for advancing this proficiency and enhancing the quality of personality assessments, including Therapeutic Assessment (Finn & Tonsager, 1997 ), that include a personality assessment component. This hybrid competency-capability framework is used to set the stage for the conduct of personality assessments in a variety of contexts and for the optimal training of personality assessment. Future directions are offered in terms of ways psychologists can strengthen their social contract with the public and offer a broader array of personality assessments in more diverse contexts and by individuals who are both competent and capable.