Liver cancer cells: targeting and prolonged-release drug carriers consisting of mesoporous silica nanoparticles and alginate microspheres.

Science.gov (United States)

Liao, Yu-Te; Liu, Chia-Hung; Yu, Jiashing; Wu, Kevin C-W

2014-01-01

A new microsphere consisting of inorganic mesoporous silica nanoparticles (MSNs) and organic alginate (denoted as MSN@Alg) was successfully synthesized by air-dynamic atomization and applied to the intracellular drug delivery systems (DDS) of liver cancer cells with sustained release and specific targeting properties. MSN@Alg microspheres have the advantages of MSN and alginate, where MSN provides a large surface area for high drug loading and alginate provides excellent biocompatibility and COOH functionality for specific targeting. Rhodamine 6G was used as a model drug, and the sustained release behavior of the rhodamine 6G-loaded MSN@Alg microspheres can be prolonged up to 20 days. For targeting therapy, the anticancer drug doxorubicin was loaded into MSN@Alg microspheres, and the (lysine)4-tyrosine-arginine-glycine-aspartic acid (K4YRGD) peptide was functionalized onto the surface of MSN@Alg for targeting liver cancer cells, hepatocellular carcinoma (HepG2). The results of the 3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide (MTT) assay and confocal laser scanning microscopy indicate that the MSN@Alg microspheres were successfully uptaken by HepG2 without apparent cytotoxicity. In addition, the intracellular drug delivery efficiency was greatly enhanced (ie, 3.5-fold) for the arginine-glycine-aspartic acid (RGD)-labeled, doxorubicin-loaded MSN@Alg drug delivery system compared with the non-RGD case. The synthesized MSN@Alg microspheres show great potential as drug vehicles with high biocompatibility, sustained release, and targeting features for future intracellular DDS.

In situ targeted activation of an anticancer agent using ultrasound-triggered release of composite droplets.

Science.gov (United States)

Bezagu, Marine; Clarhaut, Jonathan; Renoux, Brigitte; Monti, Fabrice; Tanter, Mickael; Tabeling, Patrick; Cossy, Janine; Couture, Olivier; Papot, Sebastien; Arseniyadis, Stellios

2017-12-15

The efficiency of a drug is usually highly dependent on the way it is administered or delivered. As such, targeted-therapy, which requires conceiving drug-delivery vehicles that will change their state from a relatively stable structure with a very slow leak-rate to an unstable structure with a fast release, clearly improves the pharmacokinetics, the absorption, the distribution, the metabolism and the therapeutic index of a given drug. In this context, we have developed a particularly effective double stimuli-responsive drug-delivery method allowing an ultrasound-induced release of a monomethylauristatin E-glucuronide prodrug and its subsequent activation by a β-glucuronidase. This led to an increase of cytotoxicity of about 80% on cancer cells. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

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.

Liver cancer cells: targeting and prolonged-release drug carriers consisting of mesoporous silica nanoparticles and alginate microspheres

Directory of Open Access Journals (Sweden)

Liao YT

2014-06-01

Full Text Available Yu-Te Liao,1 Chia-Hung Liu,2 Jiashing Yu,1 Kevin C-W Wu1,3 1Department of Chemical Engineering, National Taiwan University, Taipei, Taiwan; 2Department of Urology, Taipei Medical University-Shuang Ho Hospital, New Taipei City, Taiwan; 3Division of Medical Engineering Research, National Health Research Institutes, Zhunan Township, Miaoli County, Taiwan Abstract: A new microsphere consisting of inorganic mesoporous silica nanoparticles (MSNs and organic alginate (denoted as MSN@Alg was successfully synthesized by air-dynamic atomization and applied to the intracellular drug delivery systems (DDS of liver cancer cells with sustained release and specific targeting properties. MSN@Alg microspheres have the advantages of MSN and alginate, where MSN provides a large surface area for high drug loading and alginate provides excellent biocompatibility and COOH functionality for specific targeting. Rhodamine 6G was used as a model drug, and the sustained release behavior of the rhodamine 6G-loaded MSN@Alg microspheres can be prolonged up to 20 days. For targeting therapy, the anticancer drug doxorubicin was loaded into MSN@Alg microspheres, and the (lysine4-tyrosine-arginine-glycine-aspartic acid (K4YRGD peptide was functionalized onto the surface of MSN@Alg for targeting liver cancer cells, hepatocellular carcinoma (HepG2. The results of the 3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide (MTT assay and confocal laser scanning microscopy indicate that the MSN@Alg microspheres were successfully uptaken by HepG2 without apparent cytotoxicity. In addition, the intracellular drug delivery efficiency was greatly enhanced (ie, 3.5-fold for the arginine-glycine-aspartic acid (RGD-labeled, doxorubicin-loaded MSN@Alg drug delivery system compared with the non-RGD case. The synthesized MSN@Alg microspheres show great potential as drug vehicles with high biocompatibility, sustained release, and targeting features for future intracellular DDS. Keywords

High-efficiency target-ion sources for RIB generation

International Nuclear Information System (INIS)

Alton, G.D.

1993-01-01

A brief review is given of high-efficiency ion sources which have been developed or are under development at ISOL facilities which show particular promise for use at existing, future, or radioactive ion beam (RIB) facilities now under construction. Emphasis will be placed on those sources which have demonstrated high ionization efficiency, species versatility, and operational reliability and which have been carefully designed for safe handling in the high level radioactivity radiation fields incumbent at such facilities. Brief discussions will also be made of the fundamental processes which affect the realizable beam intensities in target-ion sources. Among the sources which will be reviewed will be selected examples of state-of-the-art electron-beam plasma-type ion sources, thermal-ionization, surface-ionization, ECR, and selectively chosen ion source concepts which show promise for radioactive ion beam generation. A few advanced, chemically selective target-ion sources will be described, such as sources based on the use of laser-resonance ionization, which, in principle, offer a more satisfactory solution to isobaric contamination problems than conventional electromagnetic techniques. Particular attention will be given to the sources which have been selected for initial or future use at the Holifield Radioactive Ion Beam Facility now under construction at the Oak Ridge National Laboratory

Encapsulation of Volatile Citronella Essential Oil by Coacervation: Efficiency and Release Study

Science.gov (United States)

Manaf, M. A.; Subuki, I.; Jai, J.; Raslan, R.; Mustapa, A. N.

2018-05-01

The volatile citronella essential oil was encapsulated by simple coacervation and complex coacervation using Arabic gum and gelatin as wall material. Glutaraldehyde was used in the methodology as crosslinking agent. The citronella standard calibration graph obtained with R2 of 0.9523 was used for the accurate determination of encapsulation efficiency and release study. The release kinetic was analysed based on Fick"s law of diffusion for polymeric system and linear graph of Log fraction release over Log time was constructed to determine the release rate constant, k and diffusion coefficient, n. Both coacervation methods in the present study produce encapsulation efficiency around 94%. The produced capsules for both coacervation processes were discussed based on the capsules morphology and release kinetic mechanisms.

Multifunctional Polymer Nanoparticles for Dual Drug Release and Cancer Cell Targeting

Directory of Open Access Journals (Sweden)

Yu-Han Wen

2017-06-01

Full Text Available Multifunctional polymer nanoparticles have been developed for cancer treatment because they could be easily designed to target cancer cells and to enhance therapeutic efficacy according to cancer hallmarks. In this study, we synthesized a pH-sensitive polymer, poly(methacrylic acid-co-histidine/doxorubicin/biotin (HBD in which doxorubicin (DOX was conjugated by a hydrazone bond to encapsulate an immunotherapy drug, imiquimod (IMQ, to form dual cancer-targeting and dual drug-loaded nanoparticles. At low pH, polymeric nanoparticles could disrupt and simultaneously release DOX and IMQ. Our experimental results show that the nanoparticles exhibited pH-dependent drug release behavior and had an ability to target cancer cells via biotin and protonated histidine.

Building an Efficient Model for Afterburn Energy Release

Energy Technology Data Exchange (ETDEWEB)

Alves, S; Kuhl, A; Najjar, F; Tringe, J; McMichael, L; Glascoe, L

2012-02-03

Many explosives will release additional energy after detonation as the detonation products mix with the ambient environment. This additional energy release, referred to as afterburn, is due to combustion of undetonated fuel with ambient oxygen. While the detonation energy release occurs on a time scale of microseconds, the afterburn energy release occurs on a time scale of milliseconds with a potentially varying energy release rate depending upon the local temperature and pressure. This afterburn energy release is not accounted for in typical equations of state, such as the Jones-Wilkins-Lee (JWL) model, used for modeling the detonation of explosives. Here we construct a straightforward and efficient approach, based on experiments and theory, to account for this additional energy release in a way that is tractable for large finite element fluid-structure problems. Barometric calorimeter experiments have been executed in both nitrogen and air environments to investigate the characteristics of afterburn for C-4 and other materials. These tests, which provide pressure time histories, along with theoretical and analytical solutions provide an engineering basis for modeling afterburn with numerical hydrocodes. It is toward this end that we have constructed a modified JWL equation of state to account for afterburn effects on the response of structures to blast. The modified equation of state includes a two phase afterburn energy release to represent variations in the energy release rate and an afterburn energy cutoff to account for partial reaction of the undetonated fuel.

Intestinal Targeting of Ganciclovir Release Employing a Novel HEC-PAA Blended Lyomatrix.

Science.gov (United States)

Mabrouk, Mostafa; Mulla, Jameel A S; Kumar, Pradeep; Chejara, Dharmesh R; Badhe, Ravindra V; Choonara, Yahya E; du Toit, Lisa C; Pillay, Viness

2016-10-01

A hydroxyethylcellulose-poly(acrylic acid) (HEC-PAA) lyomatrix was developed for ganciclovir (GCV) intestine targeting to overcome its undesirable degradation in the stomach. GCV was encapsulated within the HEC-PAA lyomatrix prepared by lyophilization. Conventional tablets were also prepared with identical GCV concentrations in order to compare the GCV release behavior from the lyomatrix and tablets. GCV incorporation (75.12%) was confirmed using FTIR, DSC, and TGA. The effect of GCV loading on the microstructure properties of the lyomatrix was evaluated by SEM, AFM, and BET surface area measurements. The in vitro drug release study showed steady and rapid release profiles from the GCV-loaded lyomatrix compared with the tablet formulation at identical pH values. Minimum GCV release was observed at acidic pH (≤40%) and maximum release occurred at intestinal pH values (≥90%) proving the intestinal targeting ability of the lyomatrix. Kinetic modeling revealed that the GCV-loaded lyomatrix exhibited zero-order release kinetics (n = 1), while the tablets were best described via the Peppas model. Textural analysis highlighted enhanced matrix resilience and rigidity gradient (12.5%, 20 Pa) for the GCV-loaded lyomatrix compared to the pure (7%, 9.5 Pa) HEC-PAA lyomatrix. Bench-top MRI imaging was used to confirm the mechanism of GCV release behavior by monitoring the swelling and erosion rates. The swelling and erosion rate of the tablets was not sufficient to achieve rapid zero-order GCV release as with the lyomatrix. These combined results suggest that the HEC-PAA lyomatrix may be suitable for GCV intestinal targeting after oral administration.

An efficient targeted drug delivery through apotransferrin loaded nanoparticles.

Directory of Open Access Journals (Sweden)

Athuluri Divakar Sai Krishna

Full Text Available BACKGROUND: Cancerous state is a highly stimulated environment of metabolically active cells. The cells under these conditions over express selective receptors for assimilation of factors essential for growth and transformation. Such receptors would serve as potential targets for the specific ligand mediated transport of pharmaceutically active molecules. The present study demonstrates the specificity and efficacy of protein nanoparticle of apotransferrin for targeted delivery of doxorubicin. METHODOLOGY/PRINCIPAL FINDINGS: Apotransferrin nanoparticles were developed by sol-oil chemistry. A comparative analysis of efficiency of drug delivery in conjugated and non-conjugated forms of doxorubicin to apotransferrin nanoparticle is presented. The spherical shaped apotransferrin nanoparticles (nano have diameters of 25-50 etam, which increase to 60-80 etam upon direct loading of drug (direct-nano, and showed further increase in dimension (75-95 etam in conjugated nanoparticles (conj-nano. The competitive experiments with the transferrin receptor specific antibody showed the entry of both conj-nano and direct-nano into the cells through transferrin receptor mediated endocytosis. Results of various studies conducted clearly establish the superiority of the direct-nano over conj-nano viz. (a localization studies showed complete release of drug very early, even as early as 30 min after treatment, with the drug localizing in the target organelle (nucleus (b pharmacokinetic studies showed enhanced drug concentrations, in circulation with sustainable half-life (c the studies also demonstrated efficient drug delivery, and an enhanced inhibition of proliferation in cancer cells. Tissue distribution analysis showed intravenous administration of direct nano lead to higher drug localization in liver, and blood as compared to relatively lesser localization in heart, kidney and spleen. Experiments using rat cancer model confirmed the efficacy of the formulation in

A smart multifunctional nanocomposite for intracellular targeted drug delivery and self-release

Science.gov (United States)

Wang, Chan; Lv, Piping; Wei, Wei; Tao, Shengyang; Hu, Tao; Yang, Jingbang; Meng, Changgong

2011-10-01

A multifunctional 'all-in-one' nanocomposite is fabricated using a colloid, template and surface-modification method. This material encompasses magnetic induced target delivery, cell uptake promotion and controlled drug release in one system. The nanocomposite is characterized by scanning electron microscopy, transmission electron microscopy, x-ray diffraction, N2 adsorption and vibrating sample magnetometry. The prepared material has a diameter of 350-400 nm, a high surface area of 420.29 m2 g - 1, a pore size of 1.91 nm and a saturation magnetization of 32 emu g - 1. Doxorubicin (DOX) is loaded in mesopores and acid-sensitive blockers are introduced onto the orifices of the mesopores by a Schiff base linker to implement pH-dependent self-release. Folate was also introduced to improve DOX targeted delivery and endocytosis. The linkers remained intact to block pores with ferrocene valves and inhibit the diffusion of DOX at neutral pH. However, in lysosomes of cancer cells, which have a weak acidic pH, hydrolysis of the Schiff base group removes the nanovalves and allows the trapped DOX to be released. These processes are demonstrated by UV-visible absorption spectra, confocal fluorescence microscopy images and methyl thiazolyl tetrazolium assays in vitro, which suggest that the smart nanocomposite successfully integrates targeted drug delivery with internal stimulus induced self-release and is a potentially useful material for nanobiomedicine.

A smart multifunctional nanocomposite for intracellular targeted drug delivery and self-release

International Nuclear Information System (INIS)

Wang Chan; Tao Shengyang; Hu Tao; Yang Jingbang; Meng Changgong; Lv Piping; Wei Wei

2011-01-01

A multifunctional 'all-in-one' nanocomposite is fabricated using a colloid, template and surface-modification method. This material encompasses magnetic induced target delivery, cell uptake promotion and controlled drug release in one system. The nanocomposite is characterized by scanning electron microscopy, transmission electron microscopy, x-ray diffraction, N 2 adsorption and vibrating sample magnetometry. The prepared material has a diameter of 350-400 nm, a high surface area of 420.29 m 2 g -1 , a pore size of 1.91 nm and a saturation magnetization of 32 emu g -1 . Doxorubicin (DOX) is loaded in mesopores and acid-sensitive blockers are introduced onto the orifices of the mesopores by a Schiff base linker to implement pH-dependent self-release. Folate was also introduced to improve DOX targeted delivery and endocytosis. The linkers remained intact to block pores with ferrocene valves and inhibit the diffusion of DOX at neutral pH. However, in lysosomes of cancer cells, which have a weak acidic pH, hydrolysis of the Schiff base group removes the nanovalves and allows the trapped DOX to be released. These processes are demonstrated by UV-visible absorption spectra, confocal fluorescence microscopy images and methyl thiazolyl tetrazolium assays in vitro, which suggest that the smart nanocomposite successfully integrates targeted drug delivery with internal stimulus induced self-release and is a potentially useful material for nanobiomedicine.

Target-ion source unit ionization efficiency measurement by method of stable ion beam implantation

CERN Document Server

Panteleev, V.N; Fedorov, D.V; Moroz, F.V; Orlov, S.Yu; Volkov, Yu.M

The ionization efficiency is one of the most important parameters of an on-line used target-ion source system exploited for production of exotic radioactive beams. The ionization efficiency value determination as a characteristic of a target-ion source unit in the stage of its normalizing before on-line use is a very important step in the course of the preparation for an on-line experiment. At the IRIS facility (Petersburg Nuclear Physics Institute, Gatchina) a reliable and rather precise method of the target-ion source unit ionization efficiency measurement by the method of stable beam implantation has been developed. The method worked out exploits an off-line mass-separator for the implantation of the ion beams of selected stable isotopes of different elements into a tantalum foil placed inside the Faraday cup in the focal plane of the mass-separator. The amount of implanted ions has been measured with a high accuracy by the current integrator connected to the Faraday cup. After the implantation of needed a...

Targeted delivery and controlled release of Paclitaxel for the treatment of lung cancer using single-walled carbon nanotubes

International Nuclear Information System (INIS)

Yu, Baodan; Tan, Li; Zheng, Runhui; Tan, Huo; Zheng, Lixia

2016-01-01

A new type of drug delivery system (DDS) based on single-walled carbon nanotubes (SWNTs) for controlled-release of the anti-cancer drug Paclitaxel (PTX) was constructed in this study. Chitosan (CHI) was non-covalently attached to the SWNTs to improve biocompatibility. Biocompatible hyaluronan was also combined to the outer CHI layer to realise the specific targeting property. The results showed that the release of PTX was pH-triggered and was better at lower pH (pH 5.5). The modified SWNTs showed a significant improvement in intracellular reactive oxygen species (ROS), which may have enhanced mitogen-activated protein kinase activation and further promoted cell apoptosis. The results of western blotting indicated that the apoptosis-related proteins were abundantly expressed in A549 cells. Lactate dehydrogenase (LDH) release assay and cell viability assay demonstrated that PTX-loaded SWNTs could destroy cell membrane integrity, thus inducing lower cell viability of the A549 cells. Thus, this targeting DDS could effectively inhibit cell proliferation and kill A549 cells, is a promising system for cancer therapy. - Highlights: • Chitosan and hyaluronan modified single-walled carbon nanotubes (SWNTs) were prepared for delivery of Paclitaxel (PTX). • Morphology, drug loading efficiency and drug release amount of the nanotubes were studied. • Cell viability, LDH, intracellular ROS levels and western blotting were evaluated. • The drug delivery system could effectively inhibit A549 cells proliferation.

Targeted delivery and controlled release of Paclitaxel for the treatment of lung cancer using single-walled carbon nanotubes

Energy Technology Data Exchange (ETDEWEB)

Yu, Baodan; Tan, Li; Zheng, Runhui; Tan, Huo, E-mail: tanhuo.2008@163.com; Zheng, Lixia, E-mail: 66593953@qq.com

2016-11-01

A new type of drug delivery system (DDS) based on single-walled carbon nanotubes (SWNTs) for controlled-release of the anti-cancer drug Paclitaxel (PTX) was constructed in this study. Chitosan (CHI) was non-covalently attached to the SWNTs to improve biocompatibility. Biocompatible hyaluronan was also combined to the outer CHI layer to realise the specific targeting property. The results showed that the release of PTX was pH-triggered and was better at lower pH (pH 5.5). The modified SWNTs showed a significant improvement in intracellular reactive oxygen species (ROS), which may have enhanced mitogen-activated protein kinase activation and further promoted cell apoptosis. The results of western blotting indicated that the apoptosis-related proteins were abundantly expressed in A549 cells. Lactate dehydrogenase (LDH) release assay and cell viability assay demonstrated that PTX-loaded SWNTs could destroy cell membrane integrity, thus inducing lower cell viability of the A549 cells. Thus, this targeting DDS could effectively inhibit cell proliferation and kill A549 cells, is a promising system for cancer therapy. - Highlights: • Chitosan and hyaluronan modified single-walled carbon nanotubes (SWNTs) were prepared for delivery of Paclitaxel (PTX). • Morphology, drug loading efficiency and drug release amount of the nanotubes were studied. • Cell viability, LDH, intracellular ROS levels and western blotting were evaluated. • The drug delivery system could effectively inhibit A549 cells proliferation.

Safety aspects of targets for ADTT: Activity, volatile products, residual heat release

International Nuclear Information System (INIS)

Gai, E.V.; Ignatyuk, A.V.; Lunev, V.P.; Shubin, Yu.N.

1999-01-01

Safety aspects of heavy metal liquid targets for the accelerator driven systems connected with the activity accumulation and residual energy release due to the irradiation with high energy proton beam are discussed. The results obtained for the lead-bismuth target that are under construction in IPPE now in the frame of ISTC Project No. 559 are briefly presented. The calculations and the analysis of the accumulation of the spallation reaction products, activity and energy release at various moments after the accelerator shutdown are presented. The concentrations of the reaction products, the total and partial activities, the activities of volatile products are determined. The contributions of the short-lived nuclides important for the prediction of the facility behaviour in regimes with the accelerator beam trips. The calculations and analysis of the residual energy release due to different decay type have been performed. The conclusions are as follows. The obtained results showed that long lived radioactivity accumulates mainly due to primary nuclear reactions. Secondary reactions are responsible for the production of small number of long-lived isotopes Bi-207, Po-210 and some others, being generated by radiative capture of low energy neutrons. It is possible to make a conclusion that neutrons in the energy range 20 - 800 MeV and protons with energy above 100 MeV give main contribution to the total activity generation although these parts of spectra inside the target give comparatively small contribution to the total flux. The correct consideration of short-lived nuclides contribution is the main problem in the analysis of the target behaviour in the case of short accelerator shutdowns. They make the determining contribution to the both activity and the heat release at the first moments after the accelerator shutdown, creating the intermediate links and additional channels for the long-lived nuclides accumulation chains. The strong dependence of calculated

A multifunctional magnetic nanocarrier bearing fluorescent dye for targeted drug delivery by enhanced two-photon triggered release

International Nuclear Information System (INIS)

Banerjee, Shashwat S; Chen, D-H

2009-01-01

We report a novel nanoformulation for targeted drug delivery which utilizes nanophotonics through the fusion of nanotechnology with biomedical application. The approach involves an energy-transferring magnetic nanoscopic co-assembly fabricated of rhodamine B (RDB) fluorescent dye grafted gum arabic modified Fe 3 O 4 magnetic nanoparticle and photosensitive linker by which dexamethasone drug is conjugated to the magnetic nano-assembly. The advantage offered by this nanoformulation is the indirect photo-triggered-on-demand drug release by efficient up-converting energy of the near-IR (NIR) light to higher energy and intraparticle energy transfer from the dye grafted magnetic nanoparticle to the linker for drug release by cleavage. The synthesized nanoparticles were found to be of ultra-small size (13.33 nm) and are monodispersed in an aqueous suspension. Dexamethasone (Dexa) drug conjugated to RDB-GAMNP by photosensitive linker showed appreciable release of Dexa by photo-triggered response on exposure to radiation having a wavelength in the NIR region whereas no detectable release was observed in the dark. Photo-triggered response for the nanoformulation not bearing the rhodamine B dye was drastically less as less Dexa was released on exposure to NIR radiation which suggest that the photo-cleavage of linker and release of Dexa mainly originated from the indirect excitation through the uphill energy conversions based on donor-acceptor model FRET. The promising pathway of nanophotonics for the on-demand release of the drug makes this nanocarrier very promising for applications in nanomedicine.

Advances in research of targeting delivery and controlled release of drug-loaded nanoparticles

International Nuclear Information System (INIS)

Tan Zhonghua

2003-01-01

Biochemistry drug, at present, is still the main tool that human struggle to defeat the diseases. So, developing safe and efficacious technique of drug targeting delivery and controlled release is key to enhance curative effect, decrease drug dosage, and lessen its side effect. Drug-loaded nanoparticles, which is formed by conjugate between nanotechnology and modern pharmaceutics, is a new fashioned pharmic delivery carrier. Because of advantages in pharmic targeting transport and controlled or slow release and improving bioavailability, it has been one of developing trend of modern pharmaceutical dosage forms

A smart multifunctional nanocomposite for intracellular targeted drug delivery and self-release

Energy Technology Data Exchange (ETDEWEB)

Wang Chan; Tao Shengyang; Hu Tao; Yang Jingbang; Meng Changgong [School of Chemical Engineering, Dalian University of Technology, Dalian, Liaoning (China); Lv Piping; Wei Wei, E-mail: taosy@dlut.edu.cn [National Key Laboratory of Biochemical Engineering, Institute of Process Engineering, Chinese Academy of Sciences, Beijing (China)

2011-10-14

A multifunctional 'all-in-one' nanocomposite is fabricated using a colloid, template and surface-modification method. This material encompasses magnetic induced target delivery, cell uptake promotion and controlled drug release in one system. The nanocomposite is characterized by scanning electron microscopy, transmission electron microscopy, x-ray diffraction, N{sub 2} adsorption and vibrating sample magnetometry. The prepared material has a diameter of 350-400 nm, a high surface area of 420.29 m{sup 2} g{sup -1}, a pore size of 1.91 nm and a saturation magnetization of 32 emu g{sup -1}. Doxorubicin (DOX) is loaded in mesopores and acid-sensitive blockers are introduced onto the orifices of the mesopores by a Schiff base linker to implement pH-dependent self-release. Folate was also introduced to improve DOX targeted delivery and endocytosis. The linkers remained intact to block pores with ferrocene valves and inhibit the diffusion of DOX at neutral pH. However, in lysosomes of cancer cells, which have a weak acidic pH, hydrolysis of the Schiff base group removes the nanovalves and allows the trapped DOX to be released. These processes are demonstrated by UV-visible absorption spectra, confocal fluorescence microscopy images and methyl thiazolyl tetrazolium assays in vitro, which suggest that the smart nanocomposite successfully integrates targeted drug delivery with internal stimulus induced self-release and is a potentially useful material for nanobiomedicine.

Spatial Release from Masking with a Moving Target

Directory of Open Access Journals (Sweden)

M. Torben Pastore

2017-12-01

Full Text Available In the visual domain, a stationary object that is difficult to detect usually becomes far more salient if it moves while the objects around it do not. This “pop out” effect is important for parsing the visual world into figure/ground relationships that allow creatures to detect food, threats, etc. We tested for an auditory correlate to this visual effect by asking listeners to identify a single word, spoken by a female, embedded with two or four masking words spoken by males. Percentage correct scores were analyzed and compared between conditions where target and maskers were presented from the same position vs. when the target was presented from one position while maskers were presented from different positions. In some trials, the target word was moved across the speaker array using amplitude panning, while in other trials that target was played from a single, static position. Results showed a spatial release from masking for all conditions where the target and maskers were not located at the same position, but there was no statistically significant difference between identification performance when the target was moving vs. when it was stationary. These results suggest that, at least for short stimulus durations (0.75 s for the stimuli in this experiment, there is unlikely to be a “pop out” effect for moving target stimuli in the auditory domain as there is in the visual domain.

MHI-148 Cyanine Dye Conjugated Chitosan Nanomicelle with NIR Light-Trigger Release Property as Cancer Targeting Theranostic Agent.

Science.gov (United States)

Thomas, Reju George; Moon, Myeong Ju; Surendran, Suchithra Poilil; Park, Hyeong Ju; Park, In-Kyu; Lee, Byeong-Il; Jeong, Yong Yeon

2018-02-15

Paclitaxel (PTX) loaded hydrophobically modified glycol chitosan (HGC) micelle is biocompatible in nature, but it requires cancer targeting ability and stimuli release property for better efficiency. To improve tumor retention and drug release characteristic of HGC-PTX nanomicelles, we conjugated cancer targeting heptamethine dye, MHI-148, which acts as an optical imaging agent, targeting moiety and also trigger on-demand drug release on application of NIR 808 nm laser. The amine group of glycol chitosan modified with hydrophobic 5β-cholanic acid and the carboxyl group of MHI-148 were bonded by 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide/N-hydroxysuccinimide chemistry. Paclitaxel was loaded to MHI-HGC nanomicelle by an oil-in-water emulsion method, thereby forming MHI-HGC-PTX. Comparison of near infrared (NIR) dyes, MHI-148, and Flamma-774 conjugated to HGC showed higher accumulation for MHI-HGC in 4T1 tumor and 4T1 tumor spheroid. In vitro studies showed high accumulation of MHI-HGC-PTX in 4T1 and SCC7 cancer cell lines compared to NIH3T3 cell line. In vivo fluorescence imaging of the 4T1 and SCC7 tumor showed peak accumulation of MHI-HGC-PTX at day 1 and elimination from the body at day 6. MHI-HGC-PTX showed good photothermal heating ability (50.3 °C), even at a low concentration of 33 μg/ml in 1 W/cm 2 808 nm laser at 1 min time point. Tumor reduction studies in BALB/c nude mice with SCC7 tumor showed marked reduction in MHI-HGC-PTX in the PTT group combined with photothermal therapy compared to MHI-HGC-PTX in the group without PTT. MHI-HGC-PTX is a cancer theranostic agent with cancer targeting and optical imaging capability. Our studies also showed that it has cancer targeting property independent of tumor type and tumor reduction property by combined photothermal and chemotherapeutic effects.

Criteria for selection of target materials and design of high-efficiency-release targets for radioactive ion beam generation

CERN Document Server

Alton, G D; Liu, Y

1999-01-01

In this report, we define criteria for choosing target materials and for designing, mechanically stable, short-diffusion-length, highly permeable targets for generation of high-intensity radioactive ion beams (RIBs) for use at nuclear physics and astrophysics research facilities based on the ISOL principle. In addition, lists of refractory target materials are provided and examples are given of a number of successful targets, based on these criteria, that have been fabricated and tested for use at the Holifield Radioactive Ion Beam Facility (HRIBF).

Nordic views on the next generation of EU energy efficiency targets

Energy Technology Data Exchange (ETDEWEB)

NONE

2012-11-15

EU has a target for energy efficiency for 2020, namely a 20 % reduction in the primary energy consumption relative to the PRIMES 2007 forecast for 2020. According to the new energy efficiency directive, that was agreed upon in June 2012, the target is that primary energy consumption must be no more than 1,474 Mtoe or that final energy consumption must be no more than 1,078 Mtoe by 2020. This is an absolute target for EU as a whole. There are no binding targets for member states. Due to the time lapse from goal setting, to policy formulation and practical implementation it is found that 2020 is just around the corner, and that it is high time to start discussion about the next goals. This could be concrete targets for 2030 and indicative targets for 2050. In this report target design and policy instruments are discussed from a Nordic perspective: Is it relevant to have an energy efficiency target? Should targets for energy efficiency be set in terms of primary energy or final energy? In absolute numbers or in relative numbers? Whether and how to divide the burden sharing? What are the Nordic positions of strength with regard to policy instruments? (LN)

Comparison of the calcium release channel of cardiac and skeletal muscle sarcoplasmic reticulum by target inactivation analysis

International Nuclear Information System (INIS)

McGrew, S.G.; Inui, Makoto; Chadwick, C.C.; Boucek, R.J. Jr.; Jung, C.Y.; Fleischer, S.

1989-01-01

The calcium release channel of sarcoplasmic reticulum which triggers muscle contraction in excitation-contraction coupling has recently been isolated. The channel has been found to be morphologically identical with the feet structures of the junctional face membrane of terminal cisternae and consists of an oligomer of a unique high molecular weight polypeptide. In this study, the authors compare the target size of the calcium release channel from heart and skeletal muscle using target inactivation analysis. The target molecular weights of the calcium release channel estimated by measuring ryanodine binding after irradiation are similar for heart (139,000) and skeletal muscle (143,000) and are smaller than the monomeric unit (estimated to be about 360,000). The target size, estimated by measuring polypeptide remaining after irradiation, was essentially the same for heart and skeletal muscle, 1,061,000 and 1,070,000, respectively, indicating an oligomeric association of protomers. Thus, the calcium release channel of both cardiac and skeletal muscle reacts uniquely with regard to target inactivation analysis in that (1) the size by ryanodine binding is smaller than the monomeric unit and (2) a single hit leads to destruction of more than one polypeptide, by measuring polypeptide remaining. The target inactivation analysis studies indicate that heart and skeletal muscle receptors are structurally very similar

Kinetic analysis of the effects of target structure on siRNA efficiency

Science.gov (United States)

Chen, Jiawen; Zhang, Wenbing

2012-12-01

RNAi efficiency for target cleavage and protein expression is related to the target structure. Considering the RNA-induced silencing complex (RISC) as a multiple turnover enzyme, we investigated the effect of target mRNA structure on siRNA efficiency with kinetic analysis. The 4-step model was used to study the target cleavage kinetic process: hybridization nucleation at an accessible target site, RISC-mRNA hybrid elongation along with mRNA target structure melting, target cleavage, and enzyme reactivation. At this model, the terms accounting for the target accessibility, stability, and the seed and the nucleation site effects are all included. The results are in good agreement with that of experiments which show different arguments about the structure effects on siRNA efficiency. It shows that the siRNA efficiency is influenced by the integrated factors of target's accessibility, stability, and the seed effects. To study the off-target effects, a simple model of one siRNA binding to two mRNA targets was designed. By using this model, the possibility for diminishing the off-target effects by the concentration of siRNA was discussed.

Photometric Calibration of the Barium Cloud Image in a Space Active Experiment: Determining the Release Efficiency

International Nuclear Information System (INIS)

Xie Liang-Hai; Li Lei; Wang Jing-Dong; Tao Ran; Cheng Bing-Jun; Zhang Yi-Teng

2014-01-01

The barium release experiment is an effective method to explore the near-earth environment and to study all kinds of space physics processes. The first space barium release experiment in China was successfully carried out by a sounding rocket on April 5, 2013. This work is devoted to calculating the release efficiency of the barium release by analyzing the optical image observed during the experiment. First, we present a method to calibrate the images grey value of barium cloud with the reference stars to obtain the radiant fluxes at different moments. Then the release efficiency is obtained by a curve fitting with the theoretical evolution model of barium cloud. The calculated result is basically consistent with the test value on ground

Enhancing bioactive peptide release and identification using targeted enzymatic hydrolysis of milk proteins.

Science.gov (United States)

Nongonierma, Alice B; FitzGerald, Richard J

2018-06-01

Milk proteins have been extensively studied for their ability to yield a range of bioactive peptides following enzymatic hydrolysis/digestion. However, many hurdles still exist regarding the widespread utilization of milk protein-derived bioactive peptides as health enhancing agents for humans. These mostly arise from the fact that most milk protein-derived bioactive peptides are not highly potent. In addition, they may be degraded during gastrointestinal digestion and/or have a low intestinal permeability. The targeted release of bioactive peptides during the enzymatic hydrolysis of milk proteins may allow the generation of particularly potent bioactive hydrolysates and peptides. Therefore, the development of milk protein hydrolysates capable of improving human health requires, in the first instance, optimized targeted release of specific bioactive peptides. The targeted hydrolysis of milk proteins has been aided by a range of in silico tools. These include peptide cutters and predictive modeling linking bioactivity to peptide structure [i.e., molecular docking, quantitative structure activity relationship (QSAR)], or hydrolysis parameters [design of experiments (DOE)]. Different targeted enzymatic release strategies employed during the generation of milk protein hydrolysates are reviewed herein and their limitations are outlined. In addition, specific examples are provided to demonstrate how in silico tools may help in the identification and discovery of potent milk protein-derived peptides. It is anticipated that the development of novel strategies employing a range of in silico tools may help in the generation of milk protein hydrolysates containing potent and bioavailable peptides, which in turn may be used to validate their health promoting effects in humans. Graphical abstract The targeted enzymatic hydrolysis of milk proteins may allow the generation of highly potent and bioavailable bioactive peptides.

Competitive release and outbreaks of non-target pests associated with transgenic Bt cotton.

Science.gov (United States)

Zeilinger, Adam R; Olson, Dawn M; Andow, David A

2016-06-01

The adoption of transgenic Bt cotton has, in some cases, led to environmental and economic benefits through reduced insecticide use. However, the distribution of these benefits and associated risks among cotton growers and cotton-growing regions has been uneven due in part to outbreaks of non-target or secondary pests, thereby requiring the continued use of synthetic insecticides. In the southeastern USA, Bt cotton adoption has resulted in increased abundance of and damage from stink bug pests, Euschistus servus and Nezara viridula (Heteroptera: Pentatomidae). While the impact of increased stink bug abundance has been well-documented, the causes have remained unclear. We hypothesize that release from competition with Bt-susceptible target pests may drive stink bug outbreaks in Bt cotton. We first examined the evidence for competitive release of stink bugs through meta-analysis of previous studies. We then experimentally tested if herbivory by Bt-susceptible Helicoverpa zea increases stink bug leaving rates and deters oviposition on non-Bt cotton. Consistent with previous studies, we found differences in leaving rates only for E servus, but we found that both species strongly avoided ovipositing on H. zea-damaged plants. Considering all available evidence, competitive release of stink bug populations in Bt cotton likely contributes to outbreaks, though the relative importance of competitive release remains an open question. Ecological risk assessments of Bt crops and other transgenic insecticidal crops would benefit from greater understanding of the ecological mechanisms underlying non-target pest outbreaks and greater attention to indirect ecological effects more broadly.

The dependence of neuronal encoding efficiency on Hebbian plasticity and homeostatic regulation of neurotransmitter release

Science.gov (United States)

Faghihi, Faramarz; Moustafa, Ahmed A.

2015-01-01

Synapses act as information filters by different molecular mechanisms including retrograde messenger that affect neuronal spiking activity. One of the well-known effects of retrograde messenger in presynaptic neurons is a change of the probability of neurotransmitter release. Hebbian learning describe a strengthening of a synapse between a presynaptic input onto a postsynaptic neuron when both pre- and postsynaptic neurons are coactive. In this work, a theory of homeostatic regulation of neurotransmitter release by retrograde messenger and Hebbian plasticity in neuronal encoding is presented. Encoding efficiency was measured for different synaptic conditions. In order to gain high encoding efficiency, the spiking pattern of a neuron should be dependent on the intensity of the input and show low levels of noise. In this work, we represent spiking trains as zeros and ones (corresponding to non-spike or spike in a time bin, respectively) as words with length equal to three. Then the frequency of each word (here eight words) is measured using spiking trains. These frequencies are used to measure neuronal efficiency in different conditions and for different parameter values. Results show that neurons that have synapses acting as band-pass filters show the highest efficiency to encode their input when both Hebbian mechanism and homeostatic regulation of neurotransmitter release exist in synapses. Specifically, the integration of homeostatic regulation of feedback inhibition with Hebbian mechanism and homeostatic regulation of neurotransmitter release in the synapses leads to even higher efficiency when high stimulus intensity is presented to the neurons. However, neurons with synapses acting as high-pass filters show no remarkable increase in encoding efficiency for all simulated synaptic plasticity mechanisms. This study demonstrates the importance of cooperation of Hebbian mechanism with regulation of neurotransmitter release induced by rapid diffused retrograde

Progress in target materials for high-efficiency X-ray backlight

International Nuclear Information System (INIS)

Du Ai; Zhou Bin; Li Longxiang; Zhu Xiurong; Li Yu'nong; Shen Jun; Gao Guohua; Zhang Zhihua; Wu Guangming

2012-01-01

The composition, microstructure and density of the target materials are the key parameters to determinate the photon energy and intensity of the laser-induced X-ray backlight. Thus the classification of backlight targets, the preparation of target materials and the interaction between targets and high power laser were introduced in this paper. Underdense targets were more competitive than traditional dense targets among the backlight targets. Nano-structured foam targets, which could be classified into nanofiber targets and aerogel targets, were regarded as novel high-efficiency underdense targets. Nanofiber, which was commonly prepared via electro spinning and thermal treatment, exhibited good formability and high concentration of emission atoms; while aerogel, which was prepared via sol-gel processes and supercritical fluid drying, possesses the advantages of homogeneous microstructure and theoretically high conversion efficiency, but accompanied with the disadvantages of complex synthetic processes and low concentration of emission atoms. To prepare monolithic aerogels with low density and high concentration of emission atoms via combined sol-gel theories may be the better design for the development of the laser-induced X-ray backlight. (authors)

Effects of Controlled-Release Urea on Grain Yield of Spring Maize, Nitrogen Use Efficiency and Nitrogen Balance

Directory of Open Access Journals (Sweden)

JI Jing-hong

2017-03-01

Full Text Available The effects of mixing controlled-released urea (CRU (release period of resin coated urea is 90 days and urea (U on maize yield, nitrogen use efficiency and nitrogen balance were studied by 4 plot experiments (site:Shuangcheng, Binxian, Harbin and Zhaoyuan in two years (from year 2011 to 2012 to clarify the effect of controlled release urea on spring maize and soil nitrogen balance. Results were as follow:Spring maize yield and nitrogen absorption were increased with the increasing nitrogen fertilizer. Compared with applying urea treatment, applying CRU could increase yield, nitrogen absorption, nitrogen use efficiency, agriculture efficiency of nitrogen and nitrogen contribution rate. Under the same amount of nitrogen (100%, 75%, 50%, compared with 100% U as basic fertilizer treatment, maize yield of 100% CRU treatment increased 391, 427, 291 kg·hm-2, nitrogen use efficiency increased by 5.9%,4.9% and 5.1%, agriculture efficiency of nitrogen increased 2.0, 2.6, 2.6 kg·kg-1, and nitrogen contribution rate increased 2.7%, 3.1% and 2.4%, respectively. The value of maize yield, nitrogen absorption, nitrogen use efficiency and agriculture efficiency of nitrogen between the treatment four (40% urea as basic fertilizer+60% urea as topdressing and treatment five (40% urea plus 60% controlled release urea as basic fertilizer were similar. Apparent profit and loss of nitrogen decreased with the increase of nitrogen nitrogen fertilizer. Nitrogen apparent loss by applying 100% controlled release urea was reduced of 15.0 kg·hm-2 than applying 100% U treatment;Nitrogen apparent loss amount was decreased of 23.9 kg·hm-2 under treatment five. The method of mixing 40% urea and 60% controlled release urea should be applied in maize production in Heilongjiang Province.

Limited mobility of target pests crucially lowers controllability when sterile insect releases are spatiotemporally biased.

Science.gov (United States)

Ikegawa, Yusuke; Himuro, Chihiro

2017-05-21

The sterile insect technique (SIT) is a genetic pest control method wherein mass-reared sterile insects are periodically released into the wild, thereby impeding the successful reproduction of fertile pests. In Okinawa Prefecture, Japan, the SIT has been implemented to eradicate the West Indian sweet potato weevil Euscepes postfasciatus (Fairmaire), which is a flightless agricultural pest of sweet potatoes. It is known that E. postfasciatus is much less mobile than other insects to which the SIT has been applied. However, previous theoretical studies have rarely examined effects of low mobility of target pests and variation in the spatiotemporal evenness of sterile insect releases. To theoretically examine the effects of spatiotemporal evenness on the regional eradication of less mobile pests, we constructed a simple two-patch population model comprised of a pest and sterile insect moving between two habitats, and numerically simulated different release strategies (varying the number of released sterile insects and release intervals). We found that spatially biased releases allowed the pest to spatially escape from the sterile insect, and thus intensively lowered its controllability. However, we showed that the temporally counterbalancing spatially biased releases by swapping the number of released insects in the two habitats at every release (called temporal balancing) could greatly mitigate this negative effect and promote the controllability. We also showed that the negative effect of spatiotemporally biased releases was a result of the limited mobility of the target insect. Although directed dispersal of the insects in response to habitats of differing quality could lower the controllability in the more productive habitat, the temporal balancing could promote and eventually maximize the controllability as released insects increased. Copyright © 2017 Elsevier Ltd. All rights reserved.

Rescue of HIV-1 release by targeting widely divergent NEDD4-type ubiquitin ligases and isolated catalytic HECT domains to Gag.

Directory of Open Access Journals (Sweden)

Eric R Weiss

2010-09-01

Full Text Available Retroviruses engage the ESCRT pathway through late assembly (L domains in Gag to promote virus release. HIV-1 uses a PTAP motif as its primary L domain, which interacts with the ESCRT-I component Tsg101. In contrast, certain other retroviruses primarily use PPxY-type L domains, which constitute ligands for NEDD4-type ubiquitin ligases. Surprisingly, although HIV-1 Gag lacks PPxY motifs, the release of HIV-1 L domain mutants is potently enhanced by ectopic NEDD4-2s, a native isoform with a naturally truncated C2 domain that appears to account for the residual titer of L domain-defective HIV-1. The reason for the unique potency of the NEDD4-2s isoform has remained unclear. We now show that the naturally truncated C2 domain of NEDD4-2s functions as an autonomous Gag-targeting module that can be functionally replaced by the unrelated Gag-binding protein cyclophilin A (CypA. The residual C2 domain of NEDD4-2s was sufficient to transfer the ability to stimulate HIV-1 budding to other NEDD4 family members, including the yeast homologue Rsp5, and even to isolated catalytic HECT domains. The isolated catalytic domain of NEDD4-2s also efficiently promoted HIV-1 budding when targeted to Gag via CypA. We conclude that the regions typically required for substrate recognition by HECT ubiquitin ligases are all dispensable to stimulate HIV-1 release, implying that the relevant target for ubiquitination is Gag itself or can be recognized by divergent isolated HECT domains. However, the mere ability to ubiquitinate Gag was not sufficient to stimulate HIV-1 budding. Rather, our results indicate that the synthesis of K63-linked ubiquitin chains is critical for ubiquitin ligase-mediated virus release.

The dependence of neuronal encoding efficiency on Hebbian plasticity and homeostatic regulation of neurotransmitter release

Directory of Open Access Journals (Sweden)

Faramarz eFaghihi

2015-04-01

Full Text Available Synapses act as information filters by different molecular mechanisms including retrograde messenger that affect neuronal spiking activity. One of the well-known effects of retrograde messenger in presynaptic neurons is a change of the probability of neurotransmitter release. Hebbian learning describe a strengthening of a synapse between a presynaptic input onto a postsynaptic neuron when both pre- and postsynaptic neurons are coactive. In this work, a theory of homeostatic regulation of neurotransmitter release by retrograde messenger and Hebbian plasticity in neuronal encoding is presented. Encoding efficiency was measured for different synaptic conditions. In order to gain high encoding efficiency, the spiking pattern of a neuron should be dependent on the intensity of the input and show low levels of noise. In this work, we represent spiking trains as zeros and ones (corresponding to non-spike or spike in a time bin, respectively as words with length equal to three. Then the frequency of each word (here eight words is measured using spiking trains. These frequencies are used to measure neuronal efficiency in different conditions and for different parameter values. Results show that neurons that have synapses acting as band-pass filters show the highest efficiency to encode their input when both Hebbian mechanism and homeostatic regulation of neurotransmitter release exist in synapses. Specifically, the integration of homeostatic regulation of feedback inhibition with Hebbian mechanism and homeostatic regulation of neurotransmitter release in the synapses leads to even higher efficiency when high stimulus intensity is presented to the neurons. However, neurons with synapses acting as high-pass filters show no remarkable increase in encoding efficiency for all simulated synaptic plasticity mechanisms.

Mechanism of energy release from nucleus-target in hadron-nucleus collision

International Nuclear Information System (INIS)

Strugalski, Z.; Strugalska-Gola, E.

2000-01-01

The collisions of hadrons (protons, mesons) with 131 Xe nucleus and arising light nuclear fragments as nuclear refraction products have been observed in bubble chamber. Mechanism of energy release during these collisions has been discussed. The quantitative calculations has proved that this phenomena can be treated as potential energy source with use of many different target materials

Efficient energy-saving targets for APEC economies

International Nuclear Information System (INIS)

Hu, J.-L.; Kao, C.-H.

2007-01-01

Energy-saving target ratios (ESTR) for 17 APEC economies during 1991-2000 are computed in a total-factor framework. All nominal variables are transformed into real variables by the purchasing power parity (PPP) at the 1995 price level. The data envelopment analysis (DEA) approach is used to find the energy-saving target (EST) for APEC economies without reducing their maximum potential gross domestic productions (GDPs) in each year. Energy, labor, and capital are the three inputs, while GDP is the single output. Our major findings are as follows: (1) China has the largest EST up to almost half of its current usage. (2) Hong Kong, the Philippines, and the United States have the highest energy efficiency. (3) The energy efficiency generally increases for APEC economies except for Canada and New Zealand. (4) Chile, Mexico, and Taiwan have significantly improved their energy efficiency in the last 5 years. (5) An inverted U-shape relation exists between per capita EST and per capita GDP. (6) ESTR has a positive relation with the value-added percentage of GDP of the industry sector and a negative relation with that of the service sector

Analysis and prospectives of the mechanism of release of energy efficiency titles

International Nuclear Information System (INIS)

Pastore, P.

2009-01-01

Starting from the Third annual report on the mechanism of release of energetic efficiency titles and considering the Decree Ministerial 21/12/2007, there is an analysis of the better aspects of the mechanism of release of energetic efficiency titles introduced from the norms regarding the previous annual relations. Particularly important is the role carried out from the Authority of the Electric Power and the Gas in the action of control and monitoring of the market. In this direction they have been formulated various deliberations. Analyzing the results obtained from the market of energetic efficiency titles in the course of 2007, it has been caught up 98% of the established objectives. In the course of the same year they have been cancelled many titles, as a result of verification activity. The obtained results refer to the geographic distribution, to the exchanged volumes and to the costs of the titles. At last some criticalities are placed in evidence that remain in the mechanism and that they can be resolved in order to improve the market. [it

Kepler Planet Detection Metrics: Per-Target Flux-Level Transit Injection Tests of TPS for Data Release 25

Science.gov (United States)

Burke, Christopher J.; Catanzarite, Joseph

2017-01-01

Quantifying the ability of a transiting planet survey to recover transit signals has commonly been accomplished through Monte-Carlo injection of transit signals into the observed data and subsequent running of the signal search algorithm (Gilliland et al., 2000; Weldrake et al., 2005; Burke et al., 2006). In order to characterize the performance of the Kepler pipeline (Twicken et al., 2016; Jenkins et al., 2017) on a sample of over 200,000 stars, two complementary injection and recovery tests are utilized:1. Injection of a single transit signal per target into the image or pixel-level data, hereafter referred to as pixel-level transit injection (PLTI), with subsequent processing through the Photometric Analysis (PA), Presearch Data Conditioning (PDC), Transiting Planet Search (TPS), and Data Validation (DV) modules of the Kepler pipeline. The PLTI quantification of the Kepler pipeline's completeness has been described previously by Christiansen et al. (2015, 2016); the completeness of the final SOC 9.3 Kepler pipeline acting on the Data Release 25 (DR25) light curves is described by Christiansen (2017).2. Injection of multiple transit signals per target into the normalized flux time series data with a subsequent transit search using a stream-lined version of the Transiting Planet Search (TPS) module. This test, hereafter referred to as flux-level transit injection (FLTI), is the subject of this document. By running a heavily modified version of TPS, FLTI is able to perform many injections on selected targets and determine in some detail which injected signals are recoverable. Significant numerical efficiency gains are enabled by precomputing the data conditioning steps at the onset of TPS and limiting the search parameter space (i.e., orbital period, transit duration, and ephemeris zero-point) to a small region around each injected transit signal.The PLTI test has the advantage that it follows transit signals through all processing steps of the Kepler pipeline, and

Release studies of a thin foil tantalum target for the production of short-lived radioactive nuclei

CERN Document Server

Bennett, J R J; Drumm, P V; Lettry, Jacques; Nilsson, T; Catherall, R; Jonsson, O C; Ravn, H L; Simon, H

2002-01-01

Measurements have been made at ISOLDE, of the release curves and yields of radioactive beams of lithium, sodium and beryllium from a target constructed from 2 $\\mu$m thick foils. The release curves have been analysed by fitting to a mathematical model to determine the coefficients of diffusion of the particles in the foils and effusion through the target and ionizer at several temperatures. Through a better understanding of the rate of transport of the particles, it is possible to design targets and ionizers with improved yields. This is most important for the rare, short-lived isotopes in which there is considerable interest for physics experiments. This target has demonstrated large increases in the yields of $^{11}$Li and $^{12}$Be, in agreement with the predictions of the model. (11 refs).

A novel fluoride anion modified gelatin nanogel system for ultrasound-triggered drug release.

Science.gov (United States)

Wu, Daocheng; Wan, Mingxi

2008-01-01

Controlled drug release, especially tumor-targeted drug release, remains a great challenge. Here, we prepare a novel fluoride anion-modified gelatin nanogel system and investigate its characteristics of ultrasound-triggered drug release. Adriamycin gelatin nanogel modified with fluoride anion (ADM-GNMF) was prepared by a modified co-precipitation method with fluoride anion and sodium sulfate. The loading and encapsulation efficiency of the anti-neoplastic agent adriamycin (ADM) were measured by high performance liquid chromatography (HPLC). The size and shape of ADM-GNMF were determined by electron microscopy and photo-correlation spectroscopy. The size distribution and drug release efficiency of ADM-GNMF, before and after sonication, were measured by two designed measuring devices that consisted of either a submicron particle size analyzer and an ultrasound generator as well as an ultrasound generator, automatic sampler, and HPLC. The ADM-GNMF was stable in solution with an average diameter of 46+/-12 nm; the encapsulation and loading efficiency of adriamycin were 87.2% and 6.38%, respectively. The ultrasound-triggered drug release and size change were most efficient at a frequency of 20 kHz, power density of 0.4w/cm2, and a 1~2 min duration. Under this ultrasound-triggered condition, 51.5% of drug in ADM-GNMF was released within 1~2 min, while the size of ADM-GNMF changed from 46 +/- 12 nm to 1212 +/- 35 nm within 1~2 min of sonication and restored to its previous size in 2~3 min after the ultrasound stopped. In contrast, 8.2% of drug in ADM-GNMF was released within 2~3 min without sonication, and only negligible size changes were found. The ADM-GNMF system efficiently released the encompassed drug in response to ultrasound, offering a novel and promising controlled drug release system for targeted therapy for cancer or other diseases.

Biocompatible magnetic and molecular dual-targeting polyelectrolyte hybrid hollow microspheres for controlled drug release.

Science.gov (United States)

Du, Pengcheng; Zeng, Jin; Mu, Bin; Liu, Peng

2013-05-06

Well-defined biocompatible magnetic and molecular dual-targeting polyelectrolyte hybrid hollow microspheres have been accomplished via the layer-by-layer (LbL) self-assembly technique. The hybrid shell was fabricated by the electrostatic interaction between the polyelectrolyte cation, chitosan (CS), and the hybrid anion, citrate modified ferroferric oxide nanoparticles (Fe3O4-CA), onto the uniform polystyrene sulfonate microsphere templates. Then the magnetic hybrid core/shell composite particles were modified with a linear, functional poly(ethylene glycol) (PEG) monoterminated with a biotargeting molecule (folic acid (FA)). Afterward the dual targeting hybrid hollow microspheres were obtained after etching the templates by dialysis. The dual targeting hybrid hollow microspheres exhibit exciting pH response and stability in high salt-concentration media. Their pH-dependent controlled release of the drug molecule (anticancer drug, doxorubicin (DOX)) was also investigated in different human body fluids. As expected, the cell viability of the HepG2 cells which decreased more rapidly was treated by the FA modified hybrid hollow microspheres rather than the unmodified one in the in vitro study. The dual-targeting hybrid hollow microspheres demonstrate selective killing of the tumor cells. The precise magnetic and molecular targeting properties and pH-dependent controlled release offers promise for cancer treatment.

Munc13 controls the location and efficiency of dense-core vesicle release in neurons.

Science.gov (United States)

van de Bospoort, Rhea; Farina, Margherita; Schmitz, Sabine K; de Jong, Arthur; de Wit, Heidi; Verhage, Matthijs; Toonen, Ruud F

2012-12-10

Neuronal dense-core vesicles (DCVs) contain diverse cargo crucial for brain development and function, but the mechanisms that control their release are largely unknown. We quantified activity-dependent DCV release in hippocampal neurons at single vesicle resolution. DCVs fused preferentially at synaptic terminals. DCVs also fused at extrasynaptic sites but only after prolonged stimulation. In munc13-1/2-null mutant neurons, synaptic DCV release was reduced but not abolished, and synaptic preference was lost. The remaining fusion required prolonged stimulation, similar to extrasynaptic fusion in wild-type neurons. Conversely, Munc13-1 overexpression (M13OE) promoted extrasynaptic DCV release, also without prolonged stimulation. Thus, Munc13-1/2 facilitate DCV fusion but, unlike for synaptic vesicles, are not essential for DCV release, and M13OE is sufficient to produce efficient DCV release extrasynaptically.

Kepler Planet Detection Metrics: Per-Target Detection Contours for Data Release 25

Science.gov (United States)

Burke, Christopher J.; Catanzarite, Joseph

2017-01-01

A necessary input to planet occurrence calculations is an accurate model for the pipeline completeness (Burke et al., 2015). This document describes the use of the Kepler planet occurrence rate products in order to calculate a per-target detection contour for the measured Data Release 25 (DR25) pipeline performance. A per-target detection contour measures for a given combination of orbital period, Porb, and planet radius, Rp, what fraction of transit signals are recoverable by the Kepler pipeline (Twicken et al., 2016; Jenkins et al., 2017). The steps for calculating a detection contour follow the procedure outlined in Burke et al. (2015), but have been updated to provide improved accuracy enabled by the substantially larger database of transit injection and recovery tests that were performed on the final version (i.e., SOC 9.3) of the Kepler pipeline (Christiansen, 2017; Burke Catanzarite, 2017a). In the following sections, we describe the main inputs to the per-target detection contour and provide a worked example of the python software released with this document (Kepler Planet Occurrence Rate Tools KeplerPORTs)1 that illustrates the generation of a detection contour in practice. As background material for this document and its nomenclature, we recommend the reader be familiar with the previous method of calculating a detection contour (Section 2 of Burke et al.,2015), input parameters relevant for describing the data quantity and quality of Kepler targets (Burke Catanzarite, 2017b), and the extensive new transit injection and recovery tests of the Kepler pipeline (Christiansen et al., 2016; Burke Catanzarite, 2017a; Christiansen, 2017).

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.

Improved laser-to-proton conversion efficiency in isolated reduced mass targets

Energy Technology Data Exchange (ETDEWEB)

Morace, A. [Center for Energy Research, University of California, 9500 Gilman Drive, La Jolla, California 92093 (United States); Dipartimento di Fisica, Università degli Studi di Milano, via Celoria 16, 20133 Milano (Italy); Bellei, C.; Patel, P. K. [Lawrence Livermore National Laboratory, 7000 East Avenue, Livermore, California 94550 (United States); Bartal, T.; Kim, J.; Beg, F. N. [Center for Energy Research, University of California, 9500 Gilman Drive, La Jolla, California 92093 (United States); Willingale, L.; Maksimchuk, A.; Krushelnick, K. [University of Michigan, 2200 Bonisteel Blvd. Ann Arbor, Michigan 48109 (United States); Wei, M. S. [Center for Energy Research, University of California, 9500 Gilman Drive, La Jolla, California 92093 (United States); General Atomics, 3550 General Atomics Court, San Diego, California 92121 (United States); Batani, D. [Univ. Bordeaux, CNRS, CEA, CELIA (Centre Lasers Intenses et Applications), UMR 5107, F-33405 Talence (France); Piovella, N. [Dipartimento di Fisica, Università degli Studi di Milano, via Celoria 16, 20133 Milano (Italy); Stephens, R. B. [General Atomics, 3550 General Atomics Court, San Diego, California 92121 (United States)

2013-07-29

We present experimental results of laser-to-proton conversion efficiency as a function of lateral confinement of the refluxing electrons. Experiments were carried out using the T-Cubed laser at the Center for Ultrafast Optical Science, University of Michigan. We demonstrate that the laser-to-proton conversion efficiency increases by 50% with increased confinement of the target from surroundings with respect to a flat target of the same thickness. Three-dimensional hybrid particle-in-cell simulations using LSP code agree with the experimental data. The adopted target design is suitable for high repetition rate operation as well as for Inertial Confinement Fusion applications.

Targeting thyroid cancer with acid-triggered release of doxorubicin from silicon dioxide nanoparticles

Directory of Open Access Journals (Sweden)

Li SJ

2017-08-01

Full Text Available Shijie Li,1 Daqi Zhang,1 Shihou Sheng,2 Hui Sun1 1Department of Thyroid Surgery, 2Department of Gastrointestinal Colorectal and Anal Surgery, China–Japan Union Hospital of Jilin University, Chang Chun, People’s Republic of China Abstract: Currently, therapy for thyroid cancer mainly involves surgery and radioiodine therapy. However, chemotherapy can be used in advanced and aggressive thyroid cancer that cannot be treated by other options. Nevertheless, a major obstacle to the successful treatment of thyroid cancer is the delivery of drugs to the thyroid gland. Here, we present an example of the construction of silicon dioxide nanoparticles with thyroid–stimulating-hormone receptor-targeting ligand that can specifically target the thyroid cancer. Doxorubicin nanoparticles can be triggered by acid to release the drug payload for cancer therapy. These nanoparticles shrink the tumor size in vivo with less toxic side effects. This research paves the way toward effective chemotherapy for thyroid cancer. Keywords: thyroid cancer, silicon dioxide nanoparticle, doxorubicin, acid-triggered release

Effect of co-administration of probiotics with polysaccharide based colon targeted delivery systems to optimize site specific drug release.

Science.gov (United States)

Prudhviraj, G; Vaidya, Yogyata; Singh, Sachin Kumar; Yadav, Ankit Kumar; Kaur, Puneet; Gulati, Monica; Gowthamarajan, K

2015-11-01

Significant clinical success of colon targeted dosage forms has been limited by their inappropriate release profile at the target site. Their failure to release the drug completely in the colon may be attributed to changes in the colonic milieu because of pathological state, drug effect and psychological stress accompanying the diseased state or, a combination of these. Alteration in normal colonic pH and bacterial picture leads to incomplete release of drug from the designed delivery system. We report the effectiveness of a targeted delivery system wherein the constant replenishment of the colonic microbiota is achieved by concomitant administration of probiotics along with the polysaccharide based drug delivery system. Guar gum coated spheroids of sulfasalazine were prepared. In the dissolution studies, these spheroids showed markedly higher release in the simulated colonic fluid. In vivo experiments conducted in rats clearly demonstrated the therapeutic advantage of co-administration of probiotics with guar gum coated spheroids. Our results suggest that concomitant use of probiotics along with the polysaccharide based delivery systems can be a simple strategy to achieve satisfactory colon targeting of drugs. Copyright © 2015 Elsevier B.V. All rights reserved.

Setting up GHG-based energy efficiency targets in buildings: The Ecolabel

International Nuclear Information System (INIS)

José Vinagre Díaz, Juan; Richard Wilby, Mark; Belén Rodríguez González, Ana

2013-01-01

The European Union has recently updated the regulations for energy performance of buildings and on the certification of energy-related products. The world is in the process of constructing policy frameworks to underwrite carbon emission reduction targets, best exemplified by the Kyoto Protocol. This requires complex technical and economical concepts to be presented in an understandable, transparent, and justifiable format. A building's energy efficiency was traditionally determined based on its annual consumption relative to some average performance level. Emissions are calculated as a derivative of consumptions and their aggregated values allow verification of the level of fulfillment of the objectives. Here we take a different approach: considering that the greenhouse gas emissions (GHG) objectives must be achieved; hence, we fix the efficiency standard based on emissions objectives, and then derive the corresponding reference values of consumption. Accordingly, we propose a certification scheme for energy efficiency in buildings based on targets of GHG emissions levels. This proposed framework includes both a label, namely the Ecolabel, and a fiche showing a set of indices and complementary information. The Ecolabel is designed to provide a flexible, evolvable, simple to use at the point of application, and transparent framework. - Highlights: • In this paper we consider the interaction between greenhouse gas emission reduction targets and building energy efficiency. • Specifically we propose an ‘‘Ecolabel” for buildings that is a GHG emissions liability index, which forms a labeling process. • The label follows the Kyoto Protocol philosophy and translates national GHG targets to targets for each and every building. • The approach provides both a new form of efficiency rating on which emissions reduction policy can be based

High-Efficiency Retrofit Lessons for Retail from a SuperTarget: Preprint

Energy Technology Data Exchange (ETDEWEB)

Langner, R.; Deru, M.; Hirsch, A.; Williams, S.

2013-02-01

The National Renewable Energy Laboratory partnered with Target under the Commercial Building Program to design and implement a retrofit of a SuperTarget in Thornton, CO. The result was a retrofit design that predicted 37% energy savings over ASHRAE Standard 90.1-2004, and 29% compared to existing (pre-retrofit) store consumption. The largest savings came from energy efficient lighting, energy efficient cooling systems, improved refrigeration, and better control of plug loads.

Contemporary Targets for Control of Efficient Energy Use

Directory of Open Access Journals (Sweden)

Yu. S. Petrusha

2012-01-01

Full Text Available The paper describes main principles of the methodology for control of efficient energy use in power engineering and economy sectors as a whole. Targets for control of energy use at different levels have been considered in the paper. A special attention has been paid to technical, organizational and legal aspects of energy efficiency improvement. The paper contains an analysis of the history of the given issue, the present level of its development and near-term prospects under conditions of the Republic of Belarus.

Improved Algorithms for Blending Dam Releases to Meet Downstream Water-Temperature Targets in the CE-QUAL-W2 Water-Quality Model

Science.gov (United States)

Rounds, S. A.; Buccola, N. L.

2014-12-01

The two-dimensional (longitudinal, vertical) water-quality model CE-QUAL-W2, version 3.7, was enhanced with new features to help dam operators and managers efficiently explore and optimize potential solutions for temperature management downstream of thermally stratified reservoirs. Such temperature management often is accomplished by blending releases from multiple dam outlets that access water of different temperatures at different depths in the reservoir. The original blending algorithm in this version of the model was limited to mixing releases from two outlets at a time, and few constraints could be imposed. The new enhanced blending algorithm allows the user to (1) specify a time-series of target release temperatures, (2) designate from 2 to 10 floating or fixed-elevation outlets for blending, (3) impose maximum head constraints as well as minimum and maximum flow constraints for any blended outlet, and (4) set a priority designation for each outlet that allows the model to choose which outlets to use and how to balance releases among them. The modified model was tested against a previously calibrated model of Detroit Lake on the North Santiam River in northwestern Oregon, and the results compared well. The enhanced model code is being used to evaluate operational and structural scenarios at multiple dam/reservoir systems in the Willamette River basin in Oregon, where downstream temperature management for endangered fish is a high priority for resource managers and dam operators. These updates to the CE-QUAL-W2 blending algorithm allow scenarios involving complicated dam operations and/or hypothetical outlet structures to be evaluated more efficiently with the model, with decreased need for multiple/iterative model runs or preprocessing of model inputs to fully characterize the operational constraints.

Target selection for the HRIBF Project

International Nuclear Information System (INIS)

Dellwo, J.; Alton, G.D.; Batchelder, J.C.

1994-01-01

Experiments are in progress at the Oak Ridge National Laboratory (ORNL) which are designed to select the most appropriate target materials for generating particular radioactive ion beams for the Holifield Radioactive Ion Beam Facility (HRIBF). The 25-MV tandem accelerator is used to implant stable complements of interesting radioactive elements into refractory targets mounted in a high-temperature FEBIAD ion source which is on-line at the UNISOR facility. These experiments permit selection of the target material most appropriate for the rapid release of the element of interest, as well as realistic estimates of the efficiency of the FEBIAD source. From diffusion release data information on the release times and diffusion coefficients can be derived. Diffusion coefficients for CI implanted into and diffused from CeS and Zr 5 Si 3 and As, Br, and Se implanted into and diffused from Zr 5 Ge 3 have been derived from the resulting intensity versus time profiles

Enhancing cognate target elution efficiency in gel-free chemical proteomics

Directory of Open Access Journals (Sweden)

Branka Radic-Sarikas

2015-12-01

Full Text Available Gel-free liquid chromatography mass spectrometry coupled to chemical proteomics is a powerful approach for characterizing cellular target profiles of small molecules. We have previously described a fast and efficient elution protocol; however, altered target profiles were observed. We hypothesised that elution conditions critically impact the effectiveness of disrupting drug-protein interactions. Thus, a number of elution conditions were systematically assessed with the aim of improving the recovery of all classes of proteins whilst maintaining compatibility with immunoblotting procedures. A double elution with formic acid combined with urea emerged as the most efficient and generically applicable elution method for chemical proteomics

Targeting utility customers to improve energy savings from conservation and efficiency programs

International Nuclear Information System (INIS)

Taylor, Nicholas W.; Jones, Pierce H.; Kipp, M. Jennison

2014-01-01

Highlights: • Improving DSM program impacts by targeting high energy users. • DSM energy savings potential hinges on pre-participation performance. • Targeting can benefit different utilities and energy efficiency programs. • Overall performance can be improved by up to 250% via targeting strategies. - Abstract: Electric utilities, government agencies, and private interests in the US have committed and continue to invest substantial resources – including billions of dollars of financial capital – in the pursuit of energy efficiency and conservation through demand-side management (DSM) programs. While most of these programs are deemed to be cost effective, and therefore in the public interest, opportunities exist to improve cost effectiveness by targeting programs to those customers with the greatest potential for energy savings. This article details an analysis of three DSM programs offered by three Florida municipal electric utilities to explore such opportunities. First, we estimate programs’ energy savings impacts; second, we measure and compare energy savings across subgroups of program participants as determined by their pre-intervention energy performance, and third, we explore potential changes in program impacts that might be realized by targeting specific customers for participation in the DSM programs. All three programs resulted in statistically significant average (per-participant) energy savings, yet average savings varied widely, with the customers who performed best (i.e., most efficient) before the intervention saving the least energy and those who performed worst (i.e., least efficient) before the intervention saving the most. Assessment of alternative program participation scenarios with varying levels of customer targeting suggests that program impacts could be increased by as much as 80% for a professional energy audit program, just over 100% for a high-efficiency heat pump upgrade program, and nearly 250% for an attic insulation

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

Mesoporous Fe3O4/hydroxyapatite composite for targeted drug delivery

International Nuclear Information System (INIS)

Gu, Lina; He, Xiaomei; Wu, Zhenyu

2014-01-01

Highlights: • Mesoporous Fe 3 O 4 /hydroxyapatite composite was synthesized by a simple, efficient and environmental friendly method. • The prepared material had a large surface area, high pore volume, and good magnetic separability. • DOX-loaded Fe 3 O 4 /hydroxyapatite composite exhibited surprising slow drug release behavior and pH-dependent behavior. - Abstract: In this contribution, we introduced a simple, efficient, and green method of preparing a mesoporous Fe 3 O 4 /hydroxyapatite (HA) composite. The as-prepared material had a large surface area, high pore volume, and good magnetic separability, which made it suitable for targeted drug delivery systems. The chemotherapeutic agent doxorubicin (DOX) was used to investigate the drug release behavior of Fe 3 O 4 /HA composite. The drug release profiles displayed a little burst effect and pH-dependent behavior. The release rate of DOX at pH 5.8 was larger than that at pH 7.4, which could be attributed to DOX protonation in acid medium. In addition, the released DOX concentrations remained at 0.83 and 1.39 μg/ml at pH 7.4 and 5.8, respectively, which indicated slow, steady, and safe release rates. Therefore, the as-prepared Fe 3 O 4 /hydroxyapatite composite could be an efficient platform for targeted anticancer drug delivery

Thermo-sensitively and magnetically ordered mesoporous carbon nanospheres for targeted controlled drug release and hyperthermia application.

Science.gov (United States)

Chen, Lin; Zhang, Huan; Zheng, Jing; Yu, Shiping; Du, Jinglei; Yang, Yongzhen; Liu, Xuguang

2018-03-01

A multifunctional nanoplatform based on thermo-sensitively and magnetically ordered mesoporous carbon nanospheres (TMOMCNs) is developed for effective targeted controlled release of doxorubicin hydrochloride (DOX) and hyperthermia in this work. The morphology, specific surface area, porosity, thermo-stability, thermo-sensitivity, as well as magnetism properties of TMOMCNs were verified by high resolution transmission electron microscopy, field emission scanning electron microscopy, thermo-gravimetric analysis, X-ray diffraction, Brunauer-Emmeltt-Teller surface area analysis, dynamic light scattering and vibrating sample magnetometry measurement. The results indicate that TMOMCNs have an average diameter of ~146nm with a lower critical solution temperature at around 39.5°C. They are superparamagnetic with a magnetization of 10.15emu/g at 20kOe. They generate heat when inductive magnetic field is applied to them and have a normalized specific absorption rate of 30.23W/g at 230kHz and 290Oe, showing good potential for hyperthermia. The DOX loading and release results illustrate that the loading capacity is 135.10mg/g and release performance could be regulated by changing pH and temperature. The good targeting, DOX loading and release and hyperthermia properties of TMOMCNs offer new probabilities for high effectiveness and low toxicity of cancer chemotherapy. Copyright © 2017 Elsevier B.V. All rights reserved.

Community Targets for JWST's Early Release Science Program: Evaluation of Transiting Exoplanet WASP-63b.

Science.gov (United States)

Kilpatrick, Brian; Cubillos, Patricio; Bruno, Giovanni; Lewis, Nikole K.; Stevenson, Kevin B.; Wakeford, Hannah; Blecic, Jasmina; Burrows, Adam Seth; Deming, Drake; Heng, Kevin; Line, Michael R.; Madhusudhan, Nikku; Morley, Caroline; Waldmann, Ingo P.; Transiting Exoplanet Early Release Science Community

2017-06-01

We present observations of the Hubble Space Telescope (HST) ``A Preparatory Program to Identify the Single Best Transiting Exoplanet for JWST Early Release Science" for WASP-63b, one of the community targets proposed for the James Webb Space Telescope (JWST) Early Release Science (ERS) program. A large collaboration of transiting exoplanet scientists identified a set of ``community targets" which meet a certain set of criteria for ecliptic latitude, period, host star brightness, well constrained orbital parameters, and strength of spectroscopic features. WASP-63b was one of the targets identified as a potential candidate for the ERS program. It is presented as an inflated planet with a large signal. It will be accessible to JWST approximately six months after the planned start of Cycle 1/ERS in April 2019 making it an ideal candidate should there be any delays in the JWST timetable. Here, we observe WASP-63b to evaluate its suitability as the best target to test the capabilities of JWST. Ideally, a clear atmosphere will be best suited for bench marking the instruments ability to detect spectroscopic features. We can use the strength of the water absorption feature at 1.4 μm as a way to determine the presence of obscuring clouds/hazes. The results of atmospheric retrieval are presented along with a discussion on the suitability of WASP-63b as the best target to be observed during the ERS Program.

Highly Complementary Target RNAs Promote Release of Guide RNAs from Human Argonaute2

Science.gov (United States)

De, Nabanita; Young, Lisa; Lau, Pick-Wei; Meisner, Nicole-Claudia; Morrissey, David V.; MacRae, Ian J.

2013-01-01

SUMMARY Argonaute proteins use small RNAs to guide the silencing of complementary target RNAs in many eukaryotes. Although small RNA biogenesis pathways are well studied, mechanisms for removal of guide RNAs from Argonaute are poorly understood. Here we show that the Argonaute2 (Ago2) guide RNA complex is extremely stable, with a half-life on the order of days. However, highly complementary target RNAs destabilize the complex and significantly accelerate release of the guide RNA from Ago2. This “unloading” activity can be enhanced by mismatches between the target and the guide 5′ end and attenuated by mismatches to the guide 3′ end. The introduction of 3′ mismatches leads to more potent silencing of abundant mRNAs in mammalian cells. These findings help to explain why the 3′ ends of mammalian microRNAs (miRNAs) rarely match their targets, suggest a mechanism for sequence-specific small RNA turnover, and offer insights for controlling small RNAs in mammalian cells. PMID:23664376

Iontophoresis on minoxidil sulphate-loaded chitosan nanoparticles accelerates drug release, decreasing their targeting effect to hair follicles

Directory of Open Access Journals (Sweden)

Breno N. Matos

Full Text Available The experiments described in this paper tested the hypothesis whether iontophoresis applied on a chitosan nanoparticle formulation could combine the enhanced drug accumulation into the follicular casts obtained using iontophoresis and the sustained drug release, reducing dermal exposure, provided by nanoparticles. Results showed that even though iontophoresis presented comparable minoxidil targeting potential to hair follicles than passive delivery of chitosan-nanoparticles (4.1 ± 0.9 and 5.3 ± 1.0 µg cm-2, respectively, it was less effective on preventing dermal exposure, since chitosan-nanoparticles presented a drug permeation in the receptor solution of 15.3 ± 4.3 µg cm-2 after 6 h of iontophoresis, while drug amounts from passive nanoparticle delivery were not detected. Drug release experiments showed particles were not able to sustain the drug release under the influence of a potential gradient. In conclusion, the application of MXS-loaded chitosan nanoparticles remains the best way to target MXS to the hair follicles while preventing dermal exposure.

Energy efficiency improvement target for SIC 34 - fabricated metal products. Revised target support document

Energy Technology Data Exchange (ETDEWEB)

Byrer, T. G.; Billhardt, C. F.; Farkas, M. S.

1977-02-15

In accordance with section 374 of the Energy Policy and Conservation Act (EPCA), Pub. L. 94-163, the Federal Energy Administration (FEA) proposed industrial energy efficiency improvement targets for the ten most energy-consumptive manufacturing industries in the U.S. Following public hearings and a review of the comments made, the final targets for Fabricated Metal Products (SIC 34) were established and are described. Using 1972 data on the energy consumed to produce specific metal products, it was concluded that a 24% reduction in energy consumption for SIC 34 is a viable goal for achievement by 1980. (ERA citation 04:045006)

Target-responsive aptamer release from manganese dioxide nanosheets for electrochemical sensing of cocaine with target recycling amplification.

Science.gov (United States)

Chen, Zongbao; Lu, Minghua

2016-11-01

A novel electrochemical sensing platform based on manganese dioxide (MnO2) nanosheets was developed for sensitive screening of target cocaine with the signal amplification. Ferrocene-labeled cocaine aptamers were initially immobilized onto MnO2 nanosheets-modified screen-printed carbon electrode because of π-stacking interaction between nucleobases and nanosheets. The immobilized ferrocene-aptamer activated the electrical contact with the electrode, thereby resulting in the sensor circuit to switch on. Upon target cocaine introduction, the analyte reacted with the aptamer and caused the dissociation of ferrocene-aptamer from the electrode, thus giving rise to the detection circuit to switch off. The released aptamer was cleaved by DNase I with target recycling. Under optimal conditions, the decreasing percentage of the electronic signal relative to background current increased with the increasing cocaine concentration in the dynamic range of 0.1-20nM, and the detection limit was 32pM. The reproducibility, selectivity and method accuracy were acceptable. Importantly, this concept offers promise for rapid, simple, and cost-effective analysis of cocaine biological samples without the needs of sample separation and multiple washing steps. Copyright © 2016 Elsevier B.V. All rights reserved.

Biodegradable protein-based rockets for drug transportation and light-triggered release.

Science.gov (United States)

Wu, Zhiguang; Lin, Xiankun; Zou, Xian; Sun, Jianmin; He, Qiang

2015-01-14

We describe a biodegradable, self-propelled bovine serum albumin/poly-l-lysine (PLL/BSA) multilayer rocket as a smart vehicle for efficient anticancer drug encapsulation/delivery to cancer cells and near-infrared light controlled release. The rockets were constructed by a template-assisted layer-by-layer assembly of the PLL/BSA layers, followed by incorporation of a heat-sensitive gelatin hydrogel containing gold nanoparticles, doxorubicin, and catalase. These rockets can rapidly deliver the doxorubicin to the targeted cancer cell with a speed of up to 68 μm/s, through a combination of biocatalytic bubble propulsion and magnetic guidance. The photothermal effect of the gold nanoparticles under NIR irradiation enable the phase transition of the gelatin hydrogel for rapid release of the loaded doxorubicin and efficient killing of the surrounding cancer cells. Such biodegradable and multifunctional protein-based microrockets provide a convenient and efficient platform for the rapid delivery and controlled release of therapeutic drugs.

Hydrodynamic efficiency and thermal transport in planar target experiments at LLE

International Nuclear Information System (INIS)

Boehly, T.; Goldman, L.M.; Seka, W.; Craxton, R.S.

1984-01-01

The authors report the results of single beam irradiation of thin CH foils at laser intensities of 10 13 to 10 15 W/cm 2 in 0.8 ns pulses containing 20 to 50 J of 350 nm and 1054 nm light. They also discuss the hydrodynamic efficiency, thermal transport and preheat in these targets. Included is the measurement of the ion blowoff energy distribution and velocity. The efficient acceleration by short wavelength radiation causes target displacements comparable to the spot size resulting in two-dimension effects. The results are adequately modeled with the 2-D hydrocode SAGE using a flux limiter of f=0.04

An Energy-Efficient Sleep Strategy for Target Tracking Sensor Networks

Directory of Open Access Journals (Sweden)

Juan FENG

2014-02-01

Full Text Available Energy efficiency is very important for sensor networks since sensor nodes have limited energy supply from battery. So far, many researches have been focused on this issue, while less emphasis was placed on the optimal sleep time of each node. This paper proposed an adaptive energy conservation strategy for target tracking based on a grid network structure, where each node autonomously determines when and if to sleep. It allows sensor nodes far away from targets to sleep to save energy and guarantee the tracking accuracy. The proposed approach extend network lifetime by adopting an adaptive sleep scheduling scheme that combines the local power management (PM and the adaptive coordinate PM strategies to schedule the activities of sensor nodes. And each node can choose an optimal sleep time so as to make system adaptive and energy-efficient. We show the performance of our approach in terms of energy drop, comparing it to a naive approach, dynamic PM with fixed sleep time and the coordinate PM strategies. From the experimental results, it is readily seen that the efficiency of the proposed approach.

Mannosylated Chitosan Nanoparticles Based Macrophage-Targeting Gene Delivery System Enhanced Cellular Uptake and Improved Transfection Efficiency.

Science.gov (United States)

Peng, Yixing; Yao, Wenjun; Wang, Bo; Zong, Li

2015-04-01

Gene transfer mediated by mannosylated chitosan (MCS) is a safe and promising approach for gene and vaccine delivery. MCS nanoparticles based gene delivery system showed high in vivo delivery efficiency and elicited strong immune responses in mice. However, little knowledge about the cell binding, transfection efficiency and intracellular trafficking of MCS nanoparticles had been acquired. In this study, using gastrin-releasing peptide as a model plasmid (pGRP), the binding of MCS/pGRP nanoparticles to macrophages and the intracellular trafficking of MCS/pGRP nanoparticles in macrophages were investigated. MCS-mediated transfection efficiency in macrophages was also evaluated using pGL-3 as a reporter gene. The results showed that the binding and transfection efficiency of MCS nanoparticles in macrophages was higher than that of CS, which was attributed to the interaction between mannose ligands in MCS and mannose receptors on the surface of macrophages. Observation with a confocal laser scanning microscope indicated the cellular uptake of MCS/pGRP nanoparticles were more than that of CS/pGRP nanoparticles in macrophages. MCS/pGRP nanoparticles were taken up by macrophages and most of them were entrapped in endosomal/lysosomal compartments. After the nanoparticles escaping from endosomal/lysosomal compartments, naked pGRP entered the nucleus, and a few MCS might enter the nucleus in terms of nanoparticles. Overall, MCS has the potential to be an excellent macrophage-targeting gene delivery carrier.

Monitoring of released radioactive gaseous and liquid effluent at Rokkasho Reprocessing Plant

International Nuclear Information System (INIS)

Oka, M.; Keta, S.; Nagai, S.; Kano, M.; Ishihara, N.; Moriyama, T.; Ogaki, K.; Noda, K.

2009-01-01

Rokkasho Reprocessing Plant (RRP) Rokkasho Reprocessing Plant started its active tests with spent fuel at the end of March 2006. When spent fuels are sheared and dissolved, radioactive gaseous effluent and radioactive liquid effluent such as krypton-85, tritium, etc. are released into the environment. In order to limit the public dose as low as reasonably achievable in an efficient way, RRP removes radioactive material by evaporation, rinsing, filtering, etc., and then releases it through the main stack and the sea discharge pipeline that allow to make dispersion and dilution very efficiently. Also, concerning the radioactive gaseous and liquid effluent to be released into the environment, the target values of annual release have been defined in the Safety Rule based on the estimated annual release evaluated at the safety review of RRP. By monitoring the radioactive material in gaseous exhaust and liquid effluent RRP controls it not to exceed the target values. RRP reprocessed 430 tUpr of spent fuel during Active Test (March 2006 to October 2008). In this report, we report about: The outline of gaseous and liquid effluent monitoring. The amount of radioactive gaseous and liquid effluent during the active test. The performance of removal of radioactive materials in gaseous and liquid effluents. The impact on the public from radioactive effluents during the active test. (author)

Orthogonal Clickable Iron Oxide Nanoparticle Platform for Targeting, Imaging, and On-Demand Release.

Science.gov (United States)

Guldris, Noelia; Gallo, Juan; García-Hevia, Lorena; Rivas, José; Bañobre-López, Manuel; Salonen, Laura M

2018-04-12

A versatile iron oxide nanoparticle platform is reported that can be orthogonally functionalized to obtain highly derivatized nanomaterials required for a wide variety of applications, such as drug delivery, targeted therapy, or imaging. Facile functionalization of the nanoparticles with two ligands containing isocyanate moieties allows for high coverage of the surface with maleimide and alkyne groups. As a proof-of-principle, the nanoparticles were subsequently functionalized with a fluorophore as a drug model and with biotin as a targeting ligand towards tumor cells through Diels-Alder and azide-alkyne cycloaddition reactions, respectively. The thermoreversibility of the Diels-Alder product was exploited to induce the on-demand release of the loaded molecules by magnetic hyperthermia. Additionally, the nanoparticles were shown to target cancer cells through in vitro experiments, as analyzed by magnetic resonance imaging. © 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Stimuli-responsive PEGylated prodrugs for targeted doxorubicin delivery

Energy Technology Data Exchange (ETDEWEB)

Xu, Minghui; Qian, Junmin, E-mail: jmqian@mail.xjtu.edu.cn; Liu, Xuefeng; Liu, Ting; Wang, Hongjie

2015-05-01

In recent years, stimuli-sensitive prodrugs have been extensively studied for the rapid “burst” release of antitumor drugs to enhance chemotherapeutic efficiency. In this study, a novel stimuli-sensitive prodrug containing galactosamine as a targeting moiety, poly(ethylene glycol)–doxorubicin (PEG–DOX) conjugate, was developed for targeting HepG2 human liver cancer cells. To obtain the PEG–DOX conjugate, both galactosamine-decorated poly(ethylene glycol) aldehyde (Gal-PEG-CHO) and methoxy poly(ethylene glycol) aldehyde (mPEG-CHO) were firstly synthesized and functionalized with dithiodipropionate dihydrazide (TPH) through direct reductive amination via Schiff's base formation, and then DOX molecules were chemically conjugated to the hydrazide end groups of TPH-functionalized Gal-/m-PEG chains via pH-sensitive hydrazone linkages. The chemical structures of TPH-functionalized PEG and PEG–DOX prodrug were confirmed by {sup 1}H NMR analysis. The PEG–DOX conjugate could self-assemble into spherical nanomicelles with a mean diameter of 140 nm, as indicated by transmission electron microscopy and dynamic light scattering. The drug loading content and loading efficiency in the prodrug nanomicelles were as high as 20 wt.% and 75 wt.%, respectively. In vitro drug release studies showed that DOX was released rapidly from the prodrug nanomicelles at the intracellular levels of pH and reducing agent. Cellular uptake and MTT experiments demonstrated that the galactosamine-decorated prodrug nanomicelles were more efficiently internalized into HepG2 cells via a receptor-mediated endocytosis process and exhibited a higher toxicity, compared with pristine prodrug nanomicelles. These results suggest that the novel Gal-PEG–DOX prodrug nanomicelles have tremendous potential for targeted liver cancer therapy. - Highlights: • A novel stimuli-responsive PEGylated prodrugs is synthesized. • PEGylated prodrugs can self-assemble into spherical nanoparticles (140 nm

Mesoporous Fe{sub 3}O{sub 4}/hydroxyapatite composite for targeted drug delivery

Energy Technology Data Exchange (ETDEWEB)

Gu, Lina; He, Xiaomei; Wu, Zhenyu, E-mail: zhenyuwuhn@sina.com

2014-11-15

Highlights: • Mesoporous Fe{sub 3}O{sub 4}/hydroxyapatite composite was synthesized by a simple, efficient and environmental friendly method. • The prepared material had a large surface area, high pore volume, and good magnetic separability. • DOX-loaded Fe{sub 3}O{sub 4}/hydroxyapatite composite exhibited surprising slow drug release behavior and pH-dependent behavior. - Abstract: In this contribution, we introduced a simple, efficient, and green method of preparing a mesoporous Fe{sub 3}O{sub 4}/hydroxyapatite (HA) composite. The as-prepared material had a large surface area, high pore volume, and good magnetic separability, which made it suitable for targeted drug delivery systems. The chemotherapeutic agent doxorubicin (DOX) was used to investigate the drug release behavior of Fe{sub 3}O{sub 4}/HA composite. The drug release profiles displayed a little burst effect and pH-dependent behavior. The release rate of DOX at pH 5.8 was larger than that at pH 7.4, which could be attributed to DOX protonation in acid medium. In addition, the released DOX concentrations remained at 0.83 and 1.39 μg/ml at pH 7.4 and 5.8, respectively, which indicated slow, steady, and safe release rates. Therefore, the as-prepared Fe{sub 3}O{sub 4}/hydroxyapatite composite could be an efficient platform for targeted anticancer drug delivery.

Method for detecting binding efficiencies of synthetic oligonucleotides: Targeting bacteria and insects

Science.gov (United States)

Expanding applications of gene-based targeting biotechnology in functional genomics and the treatment of plants, animals, and microbes has synergized the need for new methods to measure binding efficiencies of these products to their genetic targets. The adaptation and innovative use of Cell–Penetra...

DASPfind: new efficient method to predict drug–target interactions

KAUST Repository

Ba Alawi, Wail

2016-03-16

Background Identification of novel drug–target interactions (DTIs) is important for drug discovery. Experimental determination of such DTIs is costly and time consuming, hence it necessitates the development of efficient computational methods for the accurate prediction of potential DTIs. To-date, many computational methods have been proposed for this purpose, but they suffer the drawback of a high rate of false positive predictions. Results Here, we developed a novel computational DTI prediction method, DASPfind. DASPfind uses simple paths of particular lengths inferred from a graph that describes DTIs, similarities between drugs, and similarities between the protein targets of drugs. We show that on average, over the four gold standard DTI datasets, DASPfind significantly outperforms other existing methods when the single top-ranked predictions are considered, resulting in 46.17 % of these predictions being correct, and it achieves 49.22 % correct single top ranked predictions when the set of all DTIs for a single drug is tested. Furthermore, we demonstrate that our method is best suited for predicting DTIs in cases of drugs with no known targets or with few known targets. We also show the practical use of DASPfind by generating novel predictions for the Ion Channel dataset and validating them manually. Conclusions DASPfind is a computational method for finding reliable new interactions between drugs and proteins. We show over six different DTI datasets that DASPfind outperforms other state-of-the-art methods when the single top-ranked predictions are considered, or when a drug with no known targets or with few known targets is considered. We illustrate the usefulness and practicality of DASPfind by predicting novel DTIs for the Ion Channel dataset. The validated predictions suggest that DASPfind can be used as an efficient method to identify correct DTIs, thus reducing the cost of necessary experimental verifications in the process of drug discovery. DASPfind

Self-targeting of TNF-releasing cancer cells in preclinical models of primary and metastatic tumors.

Science.gov (United States)

Dondossola, Eleonora; Dobroff, Andrey S; Marchiò, Serena; Cardó-Vila, Marina; Hosoya, Hitomi; Libutti, Steven K; Corti, Angelo; Sidman, Richard L; Arap, Wadih; Pasqualini, Renata

2016-02-23

Circulating cancer cells can putatively colonize distant organs to form metastases or to reinfiltrate primary tumors themselves through a process termed "tumor self-seeding." Here we exploit this biological attribute to deliver tumor necrosis factor alpha (TNF), a potent antitumor cytokine, directly to primary and metastatic tumors in a mechanism that we have defined as "tumor self-targeting." For this purpose, we genetically engineered mouse mammary adenocarcinoma (TSA), melanoma (B16-F10), and Lewis lung carcinoma cells to produce and release murine TNF. In a series of intervention trials, systemic administration of TNF-expressing tumor cells was associated with reduced growth of both primary tumors and metastatic colonies in immunocompetent mice. We show that these malignant cells home to tumors, locally release TNF, damage neovascular endothelium, and induce massive cancer cell apoptosis. We also demonstrate that such tumor-cell-mediated delivery avoids or minimizes common side effects often associated with TNF-based therapy, such as acute inflammation and weight loss. Our study provides proof of concept that genetically modified circulating tumor cells may serve as targeted vectors to deliver anticancer agents. In a clinical context, this unique paradigm represents a personalized approach to be translated into applications potentially using patient-derived circulating tumor cells as self-targeted vectors for drug delivery.

Increased Energy Efficiency in Slovenian Industry - A Contribution to the Kyoto Target

International Nuclear Information System (INIS)

Selan, B.; Urbancic, A.

1998-01-01

In Slovenia the actual fast growth of greenhouse emissions will require substantial efforts to fulfil the target set in Kyoto. The end-use emissions in the in the industrial sectors represented one third of the total CO 2 emissions in the country in 1996. The cost-effective potential in the sector for CO 2 emission reduction is significant. In the paper, the most important ongoing energy efficiency activities in the industrial sector are presented: information and awareness building, energy advising to larger industrial consumers, energy audition programme, demonstration programme of energy efficiency technologies, financial incentives for energy efficiency investment and the energy efficiency investment fund. A CO 2 tax has been in force since 1997. The results of an evaluation of energy efficiency strategies in industry in the frame of the project 'Integrated resource planning for the energy efficiency in Slovenia' are discussed from the viewpoint of greenhouse gases reduction targets set by Slovenia, and a brief information on the ongoing and expected post Kyoto activities and studies is given. The most important points of the future GHG reduction strategy related to industrial sector in Slovenia will be focused on intensified energy efficiency programme, increased combined heat and power production (CHP), and the effects of incentives through the CO 2 tax. (author)

CRISPR-DT: designing gRNAs for the CRISPR-Cpf1 system with improved target efficiency and specificity

OpenAIRE

Liang, Chun; Zhu, Houxiang

2018-01-01

The CRISPR-Cpf1 system has been successfully applied in genome editing. However, target efficiency of the CRISPR-Cpf1 system varies among different gRNA sequences. We reanalyzed the published CRISPR-Cpf1 gRNAs data and found many sequence and structural features related to their target efficiency. Using machine learning technology, a SVM model was created to predict target efficiency for any given gRNAs. We have developed the first web service application, CRISPR-DT (CRISPR DNA Targeting), to...

An Energy-Efficient Target Tracking Framework in Wireless Sensor Networks

Directory of Open Access Journals (Sweden)

Zhijun Yu

2009-01-01

Full Text Available This study devises and evaluates an energy-efficient distributed collaborative signal and information processing framework for acoustic target tracking in wireless sensor networks. The distributed processing algorithm is based on mobile agent computing paradigm and sequential Bayesian estimation. At each time step, the short detection reports of cluster members will be collected by cluster head, and a sensor node with the highest signal-to-noise ratio (SNR is chosen there as reference node for time difference of arrive (TDOA calculation. During the mobile agent migration, the target state belief is transmitted among nodes and updated using the TDOA measurement of these fusion nodes one by one. The computing and processing burden is evenly distributed in the sensor network. To decrease the wireless communications, we propose to represent the belief by parameterized methods such as Gaussian approximation or Gaussian mixture model approximation. Furthermore, we present an attraction force function to handle the mobile agent migration planning problem, which is a combination of the node residual energy, useful information, and communication cost. Simulation examples demonstrate the estimation effectiveness and energy efficiency of the proposed distributed collaborative target tracking framework.

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

Toward high-efficiency and detailed Monte Carlo simulation study of the granular flow spallation target

Science.gov (United States)

Cai, Han-Jie; Zhang, Zhi-Lei; Fu, Fen; Li, Jian-Yang; Zhang, Xun-Chao; Zhang, Ya-Ling; Yan, Xue-Song; Lin, Ping; Xv, Jian-Ya; Yang, Lei

2018-02-01

The dense granular flow spallation target is a new target concept chosen for the Accelerator-Driven Subcritical (ADS) project in China. For the R&D of this kind of target concept, a dedicated Monte Carlo (MC) program named GMT was developed to perform the simulation study of the beam-target interaction. Owing to the complexities of the target geometry, the computational cost of the MC simulation of particle tracks is highly expensive. Thus, improvement of computational efficiency will be essential for the detailed MC simulation studies of the dense granular target. Here we present the special design of the GMT program and its high efficiency performance. In addition, the speedup potential of the GPU-accelerated spallation models is discussed.

THINK OUTSIDE THE COLOR BOX: PROBABILISTIC TARGET SELECTION AND THE SDSS-XDQSO QUASAR TARGETING CATALOG

International Nuclear Information System (INIS)

Bovy, Jo; Hogg, David W.; Weaver, Benjamin A.; Hennawi, Joseph F.; Myers, Adam D.; Kirkpatrick, Jessica A.; Schlegel, David J.; Ross, Nicholas P.; Sheldon, Erin S.; McGreer, Ian D.; Schneider, Donald P.

2011-01-01

We present the SDSS-XDQSO quasar targeting catalog for efficient flux-based quasar target selection down to the faint limit of the Sloan Digital Sky Survey (SDSS) catalog, even at medium redshifts (2.5 ∼ 3.5) quasar probabilities for all 160,904,060 point sources with dereddened i-band magnitude between 17.75 and 22.45 mag in the 14,555 deg 2 of imaging from SDSS Data Release 8. The catalog can be used to define a uniformly selected and efficient low- or medium-redshift quasar survey, such as that needed for the SDSS-III's Baryon Oscillation Spectroscopic Survey project. We show that the XDQSO technique performs as well as the current best photometric quasar-selection technique at low redshift, and outperforms all other flux-based methods for selecting the medium-redshift quasars of our primary interest. We make code to reproduce the XDQSO quasar target selection publicly available.

Think Outside The Color Box: Probabilistic Target Selection And The SDSS-XDQSO Quasar Targeting Catalog

International Nuclear Information System (INIS)

Bovy, J.; Sheldon, E.; Hennawi, J.F.; Hogg, D.W.; Myers, A.D.

2011-01-01

We present the SDSS-XDQSO quasar targeting catalog for efficient flux-based quasar target selection down to the faint limit of the Sloan Digital Sky Survey (SDSS) catalog, even at medium redshifts (2.5 ∼ 3.5) quasar probabilities for all 160,904,060 point sources with dereddened i-band magnitude between 17.75 and 22.45 mag in the 14,555 deg 2 of imaging from SDSS Data Release 8. The catalog can be used to define a uniformly selected and efficient low- or medium-redshift quasar survey, such as that needed for the SDSS-III's Baryon Oscillation Spectroscopic Survey project. We show that the XDQSO technique performs as well as the current best photometric quasar-selection technique at low redshift, and outperforms all other flux-based methods for selecting the medium-redshift quasars of our primary interest. We make code to reproduce the XDQSO quasar target selection publicly available.

O&M Best Practices - A Guide to Achieving Operational Efficiency (Release 2.0)

Energy Technology Data Exchange (ETDEWEB)

Sullivan, Gregory P.; Pugh, Ray; Melendez, Aldo P.; Hunt, W. D.

2004-07-31

This guide, sponsored by DOE's Federal Energy Management Program, highlights operations and maintenance (O&M) programs targeting energy efficiency that are estimated to save 5% to 20% on energy bills without a significant capital investment. The purpose of this guide is to provide the federal O&M energy manager and practitioner with useful information about O&M management, technologies, energy efficiency and cost-reduction approaches.

Efficiency of an LBE spallation target in an accelerator-driven molten salt subcritical reactor

Energy Technology Data Exchange (ETDEWEB)

Bak, Sang-In [Sungkyunkwan University, Suwon (Korea, Republic of); Hong, Seung-Woo [Sungkyunkwan University, Suwon (Korea, Republic of); Kadi, Yacine [CERN, Geneva (Switzerland)

2016-10-15

An Accelerator-Driven System (ADS) combined with a subcritical Molten Salt Reactor (MSR) is a type of hybrid reactor originally designed to breed uranium from thorium or to incinerate long-lived minor actinides in nuclear wastes. In an MSR, the salt material is used not only as a nuclear fuel but also as a primary coolant. In addition, this material is used as a target for inducing spallation neutrons in most AD-MSR concepts. A high energy proton beam impinges on a heavy metal target to induce spallation reactions and produces neutrons. Accordingly, a reliable proton accelerator is needed to feed the source neutrons. As ADSs have been criticized for requiring high power accelerators, minimization of beam power is an important aspect of ADS design. A primary concern associated with ADS development is stable high-power accelerators. We therefore studied the neutron source efficiencies of an AD-MSR involving chloride fuels by including a Pb-Bi eutectic (LBE) spallation target. The proton source efficiency and the accelerator beam power required have been studied for an AD-MSR. Adoption of an LBE spallation target induces an increase in proton source efficiencies in comparison to the case without a spallation target. Thus the presence of an efficient spallation target is useful in the reduction of the beam power of an accelerator. Almost 33 % of the beam power can be reduced in comparison to the case without the target for NaCl-Th/{sup 233}U fuel, and about 16 % for NaCl-U/TRU fuel. The beam power amplifications increase by 1.5 times for NaCl-Th/{sup 233}U and 1.2 times for NaCl-U/TRU in comparison with the no target AD-MSR.

Pharmaceutical micelles featured with singlet oxygen-responsive cargo release and mitochondrial targeting for enhanced photodynamic therapy

Science.gov (United States)

Zhang, Xin; Yan, Qi; Naer Mulatihan, Di; Zhu, Jundong; Fan, Aiping; Wang, Zheng; Zhao, Yanjun

2018-06-01

The efficacy of nanoparticulate photodynamic therapy is often compromised by the short life time and limited diffusion radius of singlet oxygen as well as uncontrolled intracellular distribution of photosensitizer. It was hypothesized that rapid photosensitizer release upon nanoparticle internalization and its preferred accumulation in mitochondria would address the above problems. Hence, the aim of this study was to engineer a multifunctional micellar nanosystem featured with singlet oxygen-responsive cargo release and mitochondria-targeting. An imidazole-bearing amphiphilic copolymer was employed as the micelle building block to encapsulate triphenylphosphonium-pyropheophorbide a (TPP-PPa) conjugate or PPa. Upon laser irradiation, the singlet oxygen produced by TPP-PPa/PPa oxidized the imidazole moiety to produce hydrophilic urea, leading to micelle disassembly and rapid cargo release. The co-localization analysis showed that the TPP moiety significantly enhanced the photosensitizer uptake by mitochondria, improved mitochondria depolarization upon irradiation, and hence boosted the cytotoxicity in 4T1 cells. The targeting strategy also dramatically reduced the intracellular ATP concentration as a consequence of mitochondria injury. The mitochondria damage was accompanied with the activation of the apoptosis signals (caspase 3 and caspase 9), whose level was directly correlated to the apoptosis extent. The current work provides a facile and robust means to enhance the efficacy of photodynamic therapy.

Efficient visualization of high-throughput targeted proteomics experiments: TAPIR.

Science.gov (United States)

Röst, Hannes L; Rosenberger, George; Aebersold, Ruedi; Malmström, Lars

2015-07-15

Targeted mass spectrometry comprises a set of powerful methods to obtain accurate and consistent protein quantification in complex samples. To fully exploit these techniques, a cross-platform and open-source software stack based on standardized data exchange formats is required. We present TAPIR, a fast and efficient Python visualization software for chromatograms and peaks identified in targeted proteomics experiments. The input formats are open, community-driven standardized data formats (mzML for raw data storage and TraML encoding the hierarchical relationships between transitions, peptides and proteins). TAPIR is scalable to proteome-wide targeted proteomics studies (as enabled by SWATH-MS), allowing researchers to visualize high-throughput datasets. The framework integrates well with existing automated analysis pipelines and can be extended beyond targeted proteomics to other types of analyses. TAPIR is available for all computing platforms under the 3-clause BSD license at https://github.com/msproteomicstools/msproteomicstools. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Preparation of thermosensitive magnetic liposome encapsulated recombinant tissue plasminogen activator for targeted thrombolysis

Energy Technology Data Exchange (ETDEWEB)

Hsu, Hao-Lung [Department of Chemical and Materials Engineering, Chang Gung University, Kwei-San, Taoyuan 33302, Taiwan, ROC (China); Chen, Jyh-Ping, E-mail: jpchen@mail.cgu.edu.tw [Department of Chemical and Materials Engineering, Chang Gung University, Kwei-San, Taoyuan 33302, Taiwan, ROC (China); Department of Plastic and Reconstructive Surgery and Craniofacial Research Center, Chang Gung Memorial Hospital, Kwei-San, Taoyuan 33305, Taiwan, ROC (China); Graduate Institute of Health Industry and Technology, Research Center for Industry of Human Ecology, Chang Gung University of Science and Technology, Kwei-San, Taoyuan 33302, Taiwan, ROC (China); Department of Materials Engineering, Ming Chi University of Technology, Tai-Shan, New Taipei City 24301, Taiwan, ROC (China)

2017-04-01

Recombinant tissue plasminogen activator (rtPA) was encapsulated in thermosensitive magnetic liposome (TML) prepared from 1,2-dipalmitoyl-sn-glycero-3-phosphocholine, distearolyphosphatidyl ethanolamine-N-poly(ethylene glycol) 2000, cholesterol and Fe{sub 3}O{sub 4} magnetic nanoparticles by solvent evaporation/sonication and freeze-thaw cycles method. Response surface methodology was proved to be a powerful tool to predict the drug encapsulation efficiency and temperature-sensitive drug release. Validation experiments verified the accuracy of the model that provides a simple and effective method for fabricating TML with controllable encapsulation efficiency and predictable temperature-sensitive drug release behavior. The prepared samples were characterized for physico-chemical properties by dynamic light scattering, transmission electron microscopy, X-ray diffraction and differential scanning calorimetry. Temperature-sensitive release of rtPA could be confirmed from in vitro thrombolysis experiments. A thrombolytic drug delivery system using TML could be proposed for magnetic targeted delivery of rtPA to the site of thrombus followed by temperature-triggered controlled drug release in an alternating magnetic field. - Highlights: • rtPA and Fe{sub 3}O{sub 4} MNP were encapsulated in thermosensitive magnetic liposome (TML). • RSM could predict the drug encapsulation efficiency and temperature-sensitive drug release from TML. • Temperature-sensitive release of rtPA was confirmed from in vitro thrombolysis experiments. • TML-rtPA will be useful as a magnetic targeted nanodrug to improve clinical thrombolytic therapy.

International Experience with Key Program Elements of IndustrialEnergy Efficiency or Greenhouse Gas Emissions Reduction Target-SettingPrograms

Energy Technology Data Exchange (ETDEWEB)

Price, Lynn; Galitsky, Christina; Kramer, Klaas Jan

2008-02-02

Target-setting agreements, also known as voluntary ornegotiated agreements, have been used by a number of governments as amechanism for promoting energy efficiency within the industrial sector. Arecent survey of such target-setting agreement programs identified 23energy efficiency or GHG emissions reduction voluntary agreement programsin 18 countries. International best practice related to target-settingagreement programs calls for establishment of a coordinated set ofpolicies that provide strong economic incentives as well as technical andfinancial support to participating industries. The key program elementsof a target-setting program are the target-setting process,identification of energy-saving technologies and measures usingenergy-energy efficiency guidebooks and benchmarking as well as byconducting energy-efficiency audits, development of an energy-savingsaction plan, development and implementation of energy managementprotocols, development of incentives and supporting policies, monitoringprogress toward targets, and program evaluation. This report firstprovides a description of three key target-setting agreement programs andthen describes international experience with the key program elementsthat comprise such programs using information from the three keytarget-setting programs as well as from other international programsrelated to industrial energy efficiency or GHG emissionsreductions.

Energy Efficient and Reliable Target Monitoring in the Tactical Battlefield

Science.gov (United States)

Li, Yan-Xiao; Guan, Hua; Zhang, Yue-Ling

In the tactical battlefield target monitoring it is crucial to take into account the energy efficiency and data reliability issues for the purpose of military decision making, especially in large scale sensor networks. However, due to the inherent nature of power constraint and wireless communication medium it is a challenging problem in the process of actual application. An efficient and reliable data aggregation scheme is proposed to enhance the performance of wireless sensor network used in the target monitoring. Firstly, the energy consumption model is presented and analyzed in the multihop WSNs. Then idea of mobile sinks, adaptive energy saving mechanism is introduced and the concept of multiple sinks cooperation is used to assure the reliability of the data aggregation. The simulation and the associated analysis show the improved results of the presented schema. At last the future discussion about the large scale tactical battlefield application is made to broaden the coming research scope.

Search efficiency of biased migration towards stationary or moving targets in heterogeneously structured environments

Science.gov (United States)

Azimzade, Youness; Mashaghi, Alireza

2017-12-01

Efficient search acts as a strong selective force in biological systems ranging from cellular populations to predator-prey systems. The search processes commonly involve finding a stationary or mobile target within a heterogeneously structured environment where obstacles limit migration. An open generic question is whether random or directionally biased motions or a combination of both provide an optimal search efficiency and how that depends on the motility and density of targets and obstacles. To address this question, we develop a simple model that involves a random walker searching for its targets in a heterogeneous medium of bond percolation square lattice and used mean first passage time (〈T 〉 ) as an indication of average search time. Our analysis reveals a dual effect of directional bias on the minimum value of 〈T 〉 . For a homogeneous medium, directionality always decreases 〈T 〉 and a pure directional migration (a ballistic motion) serves as the optimized strategy, while for a heterogeneous environment, we find that the optimized strategy involves a combination of directed and random migrations. The relative contribution of these modes is determined by the density of obstacles and motility of targets. Existence of randomness and motility of targets add to the efficiency of search. Our study reveals generic and simple rules that govern search efficiency. Our findings might find application in a number of areas including immunology, cell biology, ecology, and robotics.

High efficiency of targeted mutagenesis in arabidopsis via meiotic promoter-driven expression of Cas9 endonuclease

KAUST Repository

Eid, Ayman

2016-05-28

Key message: The use of a meiosis I-specific promoter increased the efficiency of targeted mutagenesis and will facilitate the manipulation of homologous recombination. Abstract: The CRISPR/Cas9 system has been harnessed for targeted engineering of eukaryotic genomes, including plants; however, CRISPR/Cas9 efficiency varies considerably in different plant tissues and species. In Arabidopsis, the generation of homozygous or bi-allelic mutants in the first (T1) generation is inefficient. Here, we used specific promoters to drive the expression of Cas9 during meiosis to maximize the efficiency of recovering heritable mutants in T1 plants. Our data reveal that the use of a promoter active in meiosis I resulted in high-efficiency (28 %) recovery of targeted mutants in the T1 generation. Moreover, this method enabled efficient simultaneous targeting of three genes for mutagenesis. Taken together, our results show that the use of meiosis-specific promoters will improve methods for functional genomic analysis and studying the molecular underpinnings of homologous recombination. © 2016, Springer-Verlag Berlin Heidelberg.

High-efficiency extracellular release of free fatty acids from Aspergillus oryzae using non-ionic surfactants.

Science.gov (United States)

Tamano, Koichi; Miura, Ai; Koike, Hideaki; Kamisaka, Yasushi; Umemura, Myco; Machida, Masayuki

2017-04-20

Free fatty acids (FFAs) are useful for generating biofuel compounds and functional lipids. Microbes are increasingly exploited to produce FFAs via metabolic engineering. However, in many microorganisms, FFAs accumulate in the cytosol, and disrupting cells to extract them is energy intensive. Thus, a simple cost-effective extraction technique must be developed to remove this drawback. We found that FFAs were released from cells of the filamentous fungus Aspergillus oryzae with high efficiency when they were cultured or incubated with non-ionic surfactants such as Triton X-100. The surfactants did not reduce hyphal growth, even at 5% (w/v). When the faaA disruptant was cultured with 1% Triton X-100, more than 80% of the FFAs synthesized de novo were released. When the disruptant cells grown without surfactants were incubated for 1h in 1% Triton X-100 solution, more than 50% of the FFAs synthesized de novo were also released. Other non-ionic surfactants in the same ether series, such as Brij 58, IGEPAL CA-630, and Tergitol NP-40, elicited a similar FFA release. The dry cell weight of total hyphae decreased when grown with 1% Triton X-100. The decrement was 4.9-fold greater than the weight of the released FFAs, implying release of other intracellular compounds. Analysis of the culture supernatant showed that intracellular lactate dehydrogenase was also released, suggesting that FFAs are not released by a specific transporter. Therefore, ether-type non-ionic surfactants probably cause non-specific release of FFAs and other intracellular compounds by increasing cell membrane permeability. Copyright © 2017 Elsevier B.V. All rights reserved.

Research and development on materials for the SPES target

Directory of Open Access Journals (Sweden)

Corradetti Stefano

2014-03-01

Full Text Available The SPES project at INFN-LNL (Istituto Nazionale di Fisica Nucleare - Laboratori Nazionali di Legnaro is focused on the production of radioactive ion beams. The core of the SPES facility is constituted by the target, which will be irradiated with a 40 MeV, 200 µA proton beam in order to produce radioactive species. In order to efficiently produce and release isotopes, the material constituting the target should be able to work under extreme conditions (high vacuum and temperatures up to 2000 °C. Both neutron-rich and proton-rich isotopes will be produced; in the first case, carbon dispersed uranium carbide (UCx will be used as a target, whereas to produce p-rich isotopes, several types of targets will have to be irradiated. The synthesis and characterization of different types of material will be reported. Moreover, the results of irradiation and isotopes release tests on different uranium carbide target prototypes will be discussed.

High neutronic efficiency, low current targets for accelerator-based BNCT applications

International Nuclear Information System (INIS)

Powell, J.R.; Ludewig, H.; Todosow, M.

1998-01-01

The neutronic efficiency of target/filters for accelerator-based BNCT applications is measured by the proton current required to achieve a desirable neutron current at the treatment port (10 9 n/cm 2 /s). In this paper the authors describe two possible targeyt/filter concepts wihch minimize the required current. Both concepts are based on the Li-7 (p,n)Be-7 reaction. Targets that operate near the threshold energy generate neutrons that are close tothe desired energy for BNCT treatment. Thus, the filter can be extremely thin (∼ 5 cm iron). However, this approach has an extremely low neutron yield (n/p ∼ 1.0(-6)), thus requiring a high proton current. The proposed solutino is to design a target consisting of multiple extremely thin targets (proton energy loss per target ∼ 10 keV), and re-accelerate the protons between each target. Targets operating at ihgher proton energies (∼ 2.5 MeV) have a much higher yield (n/p ∼ 1.0(-4)). However, at these energies the maximum neutron energy is approximately 800 keV, and thus a neutron filter is required to degrade the average neutron energy to the range of interest for BNCT (10--20 keV). A neutron filter consisting of fluorine compounds and iron has been investigated for this case. Typically a proton current of approximately 5 mA is required to generate the desired neutron current at the treatment port. The efficiency of these filter designs can be further increased by incorporating neutron reflectors that are co-axial with the neutron source. These reflectors are made of materials which have high scattering cross sections in the range 0.1--1.0 MeV

DASPfind: new efficient method to predict drug–target interactions

KAUST Repository

Ba Alawi, Wail; Soufan, Othman; Essack, Magbubah; Kalnis, Panos; Bajic, Vladimir B.

2016-01-01

DASPfind is a computational method for finding reliable new interactions between drugs and proteins. We show over six different DTI datasets that DASPfind outperforms other state-of-the-art methods when the single top-ranked predictions are considered, or when a drug with no known targets or with few known targets is considered. We illustrate the usefulness and practicality of DASPfind by predicting novel DTIs for the Ion Channel dataset. The validated predictions suggest that DASPfind can be used as an efficient method to identify correct DTIs, thus reducing the cost of necessary experimental verifications in the process of drug discovery. DASPfind can be accessed online at: http://​www.​cbrc.​kaust.​edu.​sa/​daspfind.

Release of Corrosive Species above the Grate in a Waste Boiler and the Implication for Improved Electrical Efficiency

DEFF Research Database (Denmark)

Bøjer, Martin; Jensen, Peter Arendt; Dam-Johansen, Kim

2010-01-01

A relatively low electrical efficiency of 20−25% is obtained in typical west European waste boilers. Ash species released from the grate combustion zone form boiler deposits with high concentrations of Cl, Na, K, Zn, Pb, and S that cause corrosion of superheater tubes at high temperature....... The superheater steam temperature has to be limited to around 425 °C, and thereby, the electrical efficiency remains low compared to wood or coal-fired boilers. If a separate part of the flue gas from the grate has a low content of corrosive species, it may be used to superheat steam to a higher temperature......, and thereby, the electrical efficiency of the plant can be increased. In this study, the local temperature, the gas concentrations of CO, CO2, and O2, and the release of the volatile elements Cl, S, Na, K, Pb, Zn, Cu, and Sn were measured above the grate in a waste boiler to investigate if a selected fraction...

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.

A model system for targeted drug release triggered by biomolecular signals logically processed through enzyme logic networks.

Science.gov (United States)

Mailloux, Shay; Halámek, Jan; Katz, Evgeny

2014-03-07

A new Sense-and-Act system was realized by the integration of a biocomputing system, performing analytical processes, with a signal-responsive electrode. A drug-mimicking release process was triggered by biomolecular signals processed by different logic networks, including three concatenated AND logic gates or a 3-input OR logic gate. Biocatalytically produced NADH, controlled by various combinations of input signals, was used to activate the electrochemical system. A biocatalytic electrode associated with signal-processing "biocomputing" systems was electrically connected to another electrode coated with a polymer film, which was dissolved upon the formation of negative potential releasing entrapped drug-mimicking species, an enzyme-antibody conjugate, operating as a model for targeted immune-delivery and consequent "prodrug" activation. The system offers great versatility for future applications in controlled drug release and personalized medicine.

Design of effective energy efficiency policies. An analysis in the frame of target setting, monitoring and evaluation

Energy Technology Data Exchange (ETDEWEB)

Schlomann, Barbara

2014-07-01

Energy efficiency is widely acknowledged as the most important strategy for achieving global energy and climate targets. Apart from its contribution to the reduction of energy consumption and energy-related greenhouse gas emissions (GHG), improving energy efficiency can deliver a range of co-benefits to the economy and society. There are, however, indications that energy efficiency policy is still insufficiently anchored both in the EU and many Member States as well as at an international level. This thesis focuses on the question how to create more favourable preconditions for an effective anchoring of energy efficiency policy in energy and climate policy. The design of energy efficiency policies is analyzed in the frame of the setting of energy efficiency targets and the monitoring and evaluation of their success. This provides new insights in the functioning of policies and hence their improvement in view of target achievement.

Hydrophobic Drug-Loaded PEGylated Magnetic Liposomes for Drug-Controlled Release

Science.gov (United States)

Hardiansyah, Andri; Yang, Ming-Chien; Liu, Ting-Yu; Kuo, Chih-Yu; Huang, Li-Ying; Chan, Tzu-Yi

2017-05-01

Less targeted and limited solubility of hydrophobic-based drug are one of the serious obstacles in drug delivery system. Thus, new strategies to enhance the solubility of hydrophobic drug and controlled release behaviors would be developed. Herein, curcumin, a model of hydrophobic drug, has been loaded into PEGylated magnetic liposomes as a drug carrier platform for drug controlled release system. Inductive magnetic heating (hyperthermia)-stimulated drug release, in vitro cellular cytotoxicity assay of curcumin-loaded PEGylated magnetic liposomes and cellular internalization-induced by magnetic guidance would be investigated. The resultant of drug carriers could disperse homogeneously in aqueous solution, showing a superparamagnetic characteristic and could inductive magnetic heating with external high-frequency magnetic field (HFMF). In vitro curcumin release studies confirmed that the drug carriers exhibited no significant release at 37 °C, whereas exhibited rapid releasing at 45 °C. However, it would display enormous (three times higher) curcumin releasing under the HFMF exposure, compared with that without HFMF exposure at 45 °C. In vitro cytotoxicity test shows that curcumin-loaded PEGylated magnetic liposomes could efficiently kill MCF-7 cells in parallel with increasing curcumin concentration. Fluorescence microscopy observed that these drug carriers could internalize efficiently into the cellular compartment of MCF-7 cells. Thus, it would be anticipated that the novel hydrophobic drug-loaded PEGylated magnetic liposomes in combination with inductive magnetic heating are promising to apply in the combination of chemotherapy and thermotherapy for cancer therapy.

System with embedded drug release and nanoparticle degradation sensor showing efficient rifampicin delivery into macrophages.

Science.gov (United States)

Trousil, Jiří; Filippov, Sergey K; Hrubý, Martin; Mazel, Tomáš; Syrová, Zdeňka; Cmarko, Dušan; Svidenská, Silvie; Matějková, Jana; Kováčik, Lubomír; Porsch, Bedřich; Konefał, Rafał; Lund, Reidar; Nyström, Bo; Raška, Ivan; Štěpánek, Petr

2017-01-01

We have developed a biodegradable, biocompatible system for the delivery of the antituberculotic antibiotic rifampicin with a built-in drug release and nanoparticle degradation fluorescence sensor. Polymer nanoparticles based on poly(ethylene oxide) monomethyl ether-block-poly(ε-caprolactone) were noncovalently loaded with rifampicin, a combination that, to best of our knowledge, was not previously described in the literature, which showed significant benefits. The nanoparticles contain a Förster resonance energy transfer (FRET) system that allows real-time assessment of drug release not only in vitro, but also in living macrophages where the mycobacteria typically reside as hard-to-kill intracellular parasites. The fluorophore also enables in situ monitoring of the enzymatic nanoparticle degradation in the macrophages. We show that the nanoparticles are efficiently taken up by macrophages, where they are very quickly associated with the lysosomal compartment. After drug release, the nanoparticles in the cmacrophages are enzymatically degraded, with half-life 88±11 min. Copyright © 2016 Elsevier Inc. All rights reserved.

Supplementary Material for: DASPfind: new efficient method to predict drug–target interactions

KAUST Repository

Ba Alawi, Wail; Soufan, Othman; Essack, Magbubah; Kalnis, Panos; Bajic, Vladimir B.

2016-01-01

Abstract Background Identification of novel drug–target interactions (DTIs) is important for drug discovery. Experimental determination of such DTIs is costly and time consuming, hence it necessitates the development of efficient computational

Feline Tetherin Efficiently Restricts Release of Feline Immunodeficiency Virus but Not Spreading of Infection▿

Science.gov (United States)

Dietrich, Isabelle; McMonagle, Elizabeth L.; Petit, Sarah J.; Vijayakrishnan, Swetha; Logan, Nicola; Chan, Chi N.; Towers, Greg J.; Hosie, Margaret J.; Willett, Brian J.

2011-01-01

Domestic cats endure infections by all three subfamilies of the retroviridae: lentiviruses (feline immunodeficiency virus [FIV]), gammaretroviruses (feline leukemia virus [FeLV]), and spumaretroviruses (feline foamy virus [FFV]). Thus, cats present an insight into the evolution of the host-retrovirus relationship and the development of intrinsic/innate immune mechanisms. Tetherin (BST-2) is an interferon-inducible transmembrane protein that inhibits the release of enveloped viruses from infected cells. Here, we characterize the feline homologue of tetherin and assess its effects on the replication of FIV. Tetherin was expressed in many feline cell lines, and expression was induced by interferons, including alpha interferon (IFN-α), IFN-ω, and IFN-γ. Like human tetherin, feline tetherin displayed potent inhibition of FIV and HIV-1 particle release; however, this activity resisted antagonism by either HIV-1 Vpu or the FIV Env and “OrfA” proteins. Further, as overexpression of complete FIV genomes in trans could not overcome feline tetherin, these data suggest that FIV lacks a functional tetherin antagonist. However, when expressed stably in feline cell lines, tetherin did not abrogate the replication of FIV; indeed, syncytium formation was significantly enhanced in tetherin-expressing cells infected with cell culture-adapted (CD134-independent) strains of FIV (FIV Fca-F14 and FIV Pco-CoLV). Thus, while tetherin may prevent the release of nascent viral particles, cell-to-cell spread remains efficient in the presence of abundant viral receptors and tetherin upregulation may enhance syncytium formation. Accordingly, tetherin expression in vivo may promote the selective expansion of viral variants capable of more efficient cell-to-cell spread. PMID:21490095

Feline tetherin efficiently restricts release of feline immunodeficiency virus but not spreading of infection.

Science.gov (United States)

Dietrich, Isabelle; McMonagle, Elizabeth L; Petit, Sarah J; Vijayakrishnan, Swetha; Logan, Nicola; Chan, Chi N; Towers, Greg J; Hosie, Margaret J; Willett, Brian J

2011-06-01

Domestic cats endure infections by all three subfamilies of the retroviridae: lentiviruses (feline immunodeficiency virus [FIV]), gammaretroviruses (feline leukemia virus [FeLV]), and spumaretroviruses (feline foamy virus [FFV]). Thus, cats present an insight into the evolution of the host-retrovirus relationship and the development of intrinsic/innate immune mechanisms. Tetherin (BST-2) is an interferon-inducible transmembrane protein that inhibits the release of enveloped viruses from infected cells. Here, we characterize the feline homologue of tetherin and assess its effects on the replication of FIV. Tetherin was expressed in many feline cell lines, and expression was induced by interferons, including alpha interferon (IFN-α), IFN-ω, and IFN-γ. Like human tetherin, feline tetherin displayed potent inhibition of FIV and HIV-1 particle release; however, this activity resisted antagonism by either HIV-1 Vpu or the FIV Env and "OrfA" proteins. Further, as overexpression of complete FIV genomes in trans could not overcome feline tetherin, these data suggest that FIV lacks a functional tetherin antagonist. However, when expressed stably in feline cell lines, tetherin did not abrogate the replication of FIV; indeed, syncytium formation was significantly enhanced in tetherin-expressing cells infected with cell culture-adapted (CD134-independent) strains of FIV (FIV Fca-F14 and FIV Pco-CoLV). Thus, while tetherin may prevent the release of nascent viral particles, cell-to-cell spread remains efficient in the presence of abundant viral receptors and tetherin upregulation may enhance syncytium formation. Accordingly, tetherin expression in vivo may promote the selective expansion of viral variants capable of more efficient cell-to-cell spread.

Orexin–Corticotropin-Releasing Factor Receptor Heteromers in the Ventral Tegmental Area as Targets for Cocaine

Science.gov (United States)

Navarro, Gemma; Quiroz, César; Moreno-Delgado, David; Sierakowiak, Adam; McDowell, Kimberly; Moreno, Estefanía; Rea, William; Cai, Ning-Sheng; Aguinaga, David; Howell, Lesley A.; Hausch, Felix; Cortés, Antonio; Mallol, Josefa; Casadó, Vicent; Lluís, Carme; Canela, Enric I.

2015-01-01

Release of the neuropeptides corticotropin-releasing factor (CRF) and orexin-A in the ventral tegmental area (VTA) play an important role in stress-induced cocaine-seeking behavior. We provide evidence for pharmacologically significant interactions between CRF and orexin-A that depend on oligomerization of CRF1 receptor (CRF1R) and orexin OX1 receptors (OX1R). CRF1R–OX1R heteromers are the conduits of a negative crosstalk between orexin-A and CRF as demonstrated in transfected cells and rat VTA, in which they significantly modulate dendritic dopamine release. The cocaine target σ1 receptor (σ1R) also associates with the CRF1R–OX1R heteromer. Cocaine binding to the σ1R–CRF1R–OX1R complex promotes a long-term disruption of the orexin-A–CRF negative crosstalk. Through this mechanism, cocaine sensitizes VTA cells to the excitatory effects of both CRF and orexin-A, thus providing a mechanism by which stress induces cocaine seeking. PMID:25926444

Orexin-corticotropin-releasing factor receptor heteromers in the ventral tegmental area as targets for cocaine.

Science.gov (United States)

Navarro, Gemma; Quiroz, César; Moreno-Delgado, David; Sierakowiak, Adam; McDowell, Kimberly; Moreno, Estefanía; Rea, William; Cai, Ning-Sheng; Aguinaga, David; Howell, Lesley A; Hausch, Felix; Cortés, Antonio; Mallol, Josefa; Casadó, Vicent; Lluís, Carme; Canela, Enric I; Ferré, Sergi; McCormick, Peter J

2015-04-29

Release of the neuropeptides corticotropin-releasing factor (CRF) and orexin-A in the ventral tegmental area (VTA) play an important role in stress-induced cocaine-seeking behavior. We provide evidence for pharmacologically significant interactions between CRF and orexin-A that depend on oligomerization of CRF1 receptor (CRF1R) and orexin OX1 receptors (OX1R). CRF1R-OX1R heteromers are the conduits of a negative crosstalk between orexin-A and CRF as demonstrated in transfected cells and rat VTA, in which they significantly modulate dendritic dopamine release. The cocaine target σ1 receptor (σ1R) also associates with the CRF1R-OX1R heteromer. Cocaine binding to the σ1R-CRF1R-OX1R complex promotes a long-term disruption of the orexin-A-CRF negative crosstalk. Through this mechanism, cocaine sensitizes VTA cells to the excitatory effects of both CRF and orexin-A, thus providing a mechanism by which stress induces cocaine seeking. Copyright © 2015 the authors 0270-6474/15/356639-15$15.00/0.

Optimal Control as a method for Diesel engine efficiency assessment including pressure and NO_x constraints

International Nuclear Information System (INIS)

Guardiola, Carlos; Climent, Héctor; Pla, Benjamín; Reig, Alberto

2017-01-01

Highlights: • Optimal Control is applied for heat release shaping in internal combustion engines. • Optimal Control allows to assess the engine performance with a realistic reference. • The proposed method gives a target heat release law to define control strategies. - Abstract: The present paper studies the optimal heat release law in a Diesel engine to maximise the indicated efficiency subject to different constraints, namely: maximum cylinder pressure, maximum cylinder pressure derivative, and NO_x emission restrictions. With this objective, a simple but also representative model of the combustion process has been implemented. The model consists of a 0D energy balance model aimed to provide the pressure and temperature evolutions in the high pressure loop of the engine thermodynamic cycle from the gas conditions at the intake valve closing and the heat release law. The gas pressure and temperature evolutions allow to compute the engine efficiency and NO_x emissions. The comparison between model and experimental results shows that despite the model simplicity, it is able to reproduce the engine efficiency and NO_x emissions. After the model identification and validation, the optimal control problem is posed and solved by means of Dynamic Programming (DP). Also, if only pressure constraints are considered, the paper proposes a solution that reduces the computation cost of the DP strategy in two orders of magnitude for the case being analysed. The solution provides a target heat release law to define injection strategies but also a more realistic maximum efficiency boundary than the ideal thermodynamic cycles usually employed to estimate the maximum engine efficiency.

Energy efficient hotspot-targeted embedded liquid cooling of electronics

International Nuclear Information System (INIS)

Sharma, Chander Shekhar; Tiwari, Manish K.; Zimmermann, Severin; Brunschwiler, Thomas; Schlottig, Gerd; Michel, Bruno; Poulikakos, Dimos

2015-01-01

Highlights: • We present a novel concept for hotspot-targeted, energy efficient ELC for electronic chips. • Microchannel throttling zones distribute flow optimally without any external control. • Design is optimized for highly non-uniform multicore chip heat flux maps. • Optimized design minimizes chip temperature non-uniformity. • This is achieved with pumping power consumption less than 1% of total chip power. - Abstract: Large data centers today already account for nearly 1.31% of total electricity consumption with cooling responsible for roughly 33% of that energy consumption. This energy intensive cooling problem is exacerbated by the presence of hotspots in multicore microprocessors due to excess coolant flow requirement for thermal management. Here we present a novel liquid-cooling concept, for targeted, energy efficient cooling of hotspots through passively optimized microchannel structures etched into the backside of a chip (embedded liquid cooling or ELC architecture). We adopt an experimentally validated and computationally efficient modeling approach to predict the performance of our hotspot-targeted ELC design. The design is optimized for exemplar non-uniform chip power maps using Response Surface Methodology (RSM). For industrially acceptable limits of approximately 0.4 bar (40 kPa) on pressure drop and one percent of total chip power on pumping power, the optimized designs are computationally evaluated against a base, standard ELC design with uniform channel widths and uniform flow distribution. For an average steady-state heat flux of 150 W/cm 2 in core areas (hotspots) and 20 W/cm 2 over remaining chip area (background), the optimized design reduces the maximum chip temperature non-uniformity by 61% to 3.7 °C. For a higher average, steady-state hotspot heat flux of 300 W/cm 2 , the maximum temperature non-uniformity is reduced by 54% to 8.7 °C. It is shown that the base design requires a prohibitively high level of pumping power (about

Sticking efficiency of nanoparticles in high-velocity collisions with various target materials

International Nuclear Information System (INIS)

Reissaus, Philipp; Waldemarsson, Tomas; Blum, Juergen; Clement, Dominik; Llamas, Isabel; Mutschke, Harald; Giovane, Frank

2006-01-01

In order to find reliable collector surfaces for the Mesospheric Aerosol - Genesis, Interaction and Composition (MAGIC) sounding rocket experiment, intended to collect atmospheric nanoparticles, the sticking efficiency of nanoparticles was measured on several targets of different materials. The nanoparticles were generated by a molecular beam apparatus in Jena, Germany, by laser ablation (Al 2 O 3 particles, diameter 5-50 nm) and by laser pyrolysis (carbon particles, diameter 10-20 nm). In a vacuum environment (>10 -5 mbar) the particles condensed from the gas phase, formed a particle beam, and were accelerated to ∼∼1 km/s. The sticking efficiency on the target materials carbon, gold and grease was measured by a microbalance. Results demonstrate moderate to high sticking probabilities. Thus, the capture and retrieval of atmospheric nanoparticles was found to be quantitatively feasible

THE SDSS-III BARYON OSCILLATION SPECTROSCOPIC SURVEY: QUASAR TARGET SELECTION FOR DATA RELEASE NINE

Energy Technology Data Exchange (ETDEWEB)

Ross, Nicholas P.; Kirkpatrick, Jessica A.; Carithers, William C.; Ho, Shirley [Lawrence Berkeley National Laboratory, 1 Cyclotron Road, Berkeley, CA 94720 (United States); Myers, Adam D. [Department of Astronomy, MC-221, University of Illinois, 1002 West Green Street, Urbana, IL 61801 (United States); Sheldon, Erin S. [Brookhaven National Laboratory, Blgd 510, Upton, NY 11375 (United States); Yeche, Christophe; Aubourg, Eric [CEA, Centre de Saclay, IRFU, 91191 Gif-sur-Yvette (France); Strauss, Michael A.; Lee, Khee-Gan [Department of Astrophysical Sciences, Princeton University, Princeton, NJ 08544 (United States); Bovy, Jo; Blanton, Michael R.; Hogg, David W. [Center for Cosmology and Particle Physics, New York University, 4 Washington Place, New York, NY 10003 (United States); Richards, Gordon T. [Department of Physics, Drexel University, 3141 Chestnut Street, Philadelphia, PA 19104 (United States); Brandt, W. N. [Department of Astronomy and Astrophysics, The Pennsylvania State University, 525 Davey Laboratory, University Park, PA 16802 (United States); Croft, Rupert A. C. [Bruce and Astrid McWilliams Center for Cosmology, Carnegie Mellon University, Pittsburgh, PA 15213 (United States); Da Silva, Robert [Department of Astronomy and Astrophysics, University of California, Santa Cruz, Santa Cruz, CA 95064 (United States); Dawson, Kyle [Department of Physics and Astronomy, University of Utah, UT (United States); Eisenstein, Daniel J. [Steward Observatory, 933 North Cherry Avenue, Tucson, AZ 85721 (United States); Hennawi, Joseph F., E-mail: npross@lbl.gov [Max-Planck-Institut fuer Astronomie, Konigstuhl 17, 69117 Heidelberg (Germany); and others

2012-03-01

The SDSS-III Baryon Oscillation Spectroscopic Survey (BOSS), a five-year spectroscopic survey of 10,000 deg{sup 2}, achieved first light in late 2009. One of the key goals of BOSS is to measure the signature of baryon acoustic oscillations (BAOs) in the distribution of Ly{alpha} absorption from the spectra of a sample of {approx}150,000 z > 2.2 quasars. Along with measuring the angular diameter distance at z Almost-Equal-To 2.5, BOSS will provide the first direct measurement of the expansion rate of the universe at z > 2. One of the biggest challenges in achieving this goal is an efficient target selection algorithm for quasars in the redshift range 2.2 < z < 3.5, where their colors tend to overlap those of the far more numerous stars. During the first year of the BOSS survey, quasar target selection (QTS) methods were developed and tested to meet the requirement of delivering at least 15 quasars deg{sup -2} in this redshift range, with a goal of 20 out of 40 targets deg{sup -2} allocated to the quasar survey. To achieve these surface densities, the magnitude limit of the quasar targets was set at g {<=} 22.0 or r {<=} 21.85. While detection of the BAO signature in the distribution of Ly{alpha} absorption in quasar spectra does not require a uniform target selection algorithm, many other astrophysical studies do. We have therefore defined a uniformly selected subsample of 20 targets deg{sup -2}, for which the selection efficiency is just over 50% ({approx}10 z > 2.20 quasars deg{sup -2}). This 'CORE' subsample will be fixed for Years Two through Five of the survey. For the remaining 20 targets deg{sup -2}, we will continue to develop improved selection techniques, including the use of additional data sets beyond the Sloan Digital Sky Survey (SDSS) imaging data. In this paper, we describe the evolution and implementation of the BOSS QTS algorithms during the first two years of BOSS operations (through 2011 July), in support of the science investigations

Characterization studies of prototype ISOL targets for the RIA

International Nuclear Information System (INIS)

Greene, John P.; Burtseva, Tatiana; Neubauer, Janelle; Nolen, Jerry A.; Villari, Antonio C.C.; Gomes, Itacil C.

2005-01-01

Targets employing refractory compounds are being developed for the rare isotope accelerator (RIA) facility to produce ion species far from stability. With the 100 kW beams proposed for the production targets, dissipation of heat becomes a challenging issue. In our two-step target design, neutrons are generated in a refractory primary target, inducing fission in the surrounding uranium carbide. The interplay of density, grain size, thermal conductivity and diffusion properties of the UC 2 needs to be well understood before fabrication. Thin samples of uranium carbide were prepared for thermal conductivity measurements using an electron beam to heat the sample and an optical pyrometer to observe the thermal radiation. Release efficiencies and independent thermal analysis on these samples are being undertaken at Oak Ridge National Laboratory (ORNL). An alternate target concept for RIA, the tilted slab approach promises to be simple with fast ion release and capable of withstanding high beam intensities while providing considerable yields via spallation. A proposed small business innovative research (SBIR) project will design a prototype tilted target, exploring the materials needed for fabrication and testing at an irradiation facility to address issues of heat transfer and stresses within the target

Characterization studies of prototype ISOL targets for the RIA

Science.gov (United States)

Greene, John P.; Burtseva, Tatiana; Neubauer, Janelle; Nolen, Jerry A.; Villari, Antonio C. C.; Gomes, Itacil C.

2005-12-01

Targets employing refractory compounds are being developed for the rare isotope accelerator (RIA) facility to produce ion species far from stability. With the 100 kW beams proposed for the production targets, dissipation of heat becomes a challenging issue. In our two-step target design, neutrons are generated in a refractory primary target, inducing fission in the surrounding uranium carbide. The interplay of density, grain size, thermal conductivity and diffusion properties of the UC2 needs to be well understood before fabrication. Thin samples of uranium carbide were prepared for thermal conductivity measurements using an electron beam to heat the sample and an optical pyrometer to observe the thermal radiation. Release efficiencies and independent thermal analysis on these samples are being undertaken at Oak Ridge National Laboratory (ORNL). An alternate target concept for RIA, the tilted slab approach promises to be simple with fast ion release and capable of withstanding high beam intensities while providing considerable yields via spallation. A proposed small business innovative research (SBIR) project will design a prototype tilted target, exploring the materials needed for fabrication and testing at an irradiation facility to address issues of heat transfer and stresses within the target.

Novel Dual Mitochondrial and CD44 Receptor Targeting Nanoparticles for Redox Stimuli-Triggered Release

Science.gov (United States)

Wang, Kaili; Qi, Mengjiao; Guo, Chunjing; Yu, Yueming; Wang, Bingjie; Fang, Lei; Liu, Mengna; Wang, Zhen; Fan, Xinxin; Chen, Daquan

2018-02-01

In this work, novel mitochondrial and CD44 receptor dual-targeting redox-sensitive multifunctional nanoparticles (micelles) based on oligomeric hyaluronic acid (oHA) were proposed. The amphiphilic nanocarrier was prepared by (5-carboxypentyl)triphenylphosphonium bromide (TPP), oligomeric hyaluronic acid (oHA), disulfide bond, and curcumin (Cur), named as TPP-oHA-S-S-Cur. The TPP targeted the mitochondria, the antitumor drug Cur served as a hydrophobic core, the CD44 receptor targeting oHA worked as a hydrophilic shell, and the disulfide bond acted as a connecting arm. The chemical structure of TPP-oHA-S-S-Cur was characterized by 1HNMR technology. Cur was loaded into the TPP-oHA-S-S-Cur micelles by self-assembly. Some properties, including the preparation of micelles, morphology, redox sensitivity, and mitochondrial targeting, were studied. The results showed that TPP-oHA-S-S-Cur micelles had a mean diameter of 122.4 ± 23.4 nm, zeta potential - 26.55 ± 4.99 mV. In vitro release study and cellular uptake test showed that TPP-oHA-S-S-Cur micelles had redox sensibility, dual targeting to mitochondrial and CD44 receptor. This work provided a promising smart multifunctional nanocarrier platform to enhance the solubility, decrease the side effects, and improve the therapeutic efficacy of anticancer drugs.

The efficiency of ceramic-faced metal targets at high-velocity impact

Science.gov (United States)

Tolkachev, V. F.; Konyaev, A. A.; Pakhnutova, N. V.

2017-11-01

The paper represents experimental results and engineering evaluation concerning the efficiency of composite materials to be used as an additional protection during the high- velocity interaction of a tungsten rod with a target in the velocity range of 1...5 km/s. The main parameter that characterizes the high-velocity interaction of a projectile with a layered target is the penetration depth. Experimental data, numerical simulation and engineering evaluation by modified models are used to determine the penetration depth. Boron carbide, aluminum oxide, and aluminum nickelide are applied as a front surface of targets. Based on experimental data and numerical simulation, the main characteristics of ceramics are determined, which allows composite materials to be effectively used as additional elements of protection.

pH-triggered echogenicity and contents release from liposomes.

Science.gov (United States)

Nahire, Rahul; Hossain, Rayat; Patel, Rupa; Paul, Shirshendu; Meghnani, Varsha; Ambre, Avinash H; Gange, Kara N; Katti, Kalpana S; Leclerc, Estelle; Srivastava, D K; Sarkar, Kausik; Mallik, Sanku

2014-11-03

Liposomes are representative lipid nanoparticles widely used for delivering anticancer drugs, DNA fragments, or siRNA to cancer cells. Upon targeting, various internal and external triggers have been used to increase the rate for contents release from the liposomes. Among the internal triggers, decreased pH within the cellular lysosomes has been successfully used to enhance the rate for releasing contents. However, imparting pH sensitivity to liposomes requires the synthesis of specialized lipids with structures that are substantially modified at a reduced pH. Herein, we report an alternative strategy to render liposomes pH sensitive by encapsulating a precursor which generates gas bubbles in situ in response to acidic pH. The disturbance created by the escaping gas bubbles leads to the rapid release of the encapsulated contents from the liposomes. Atomic force microscopic studies indicate that the liposomal structure is destroyed at a reduced pH. The gas bubbles also render the liposomes echogenic, allowing ultrasound imaging. To demonstrate the applicability of this strategy, we have successfully targeted doxorubicin-encapsulated liposomes to the pancreatic ductal carcinoma cells that overexpress the folate receptor on the surface. In response to the decreased pH in the lysosomes, the encapsulated anticancer drug is efficiently released. Contents released from these liposomes are further enhanced by the application of continuous wave ultrasound (1 MHz), resulting in substantially reduced viability for the pancreatic cancer cells (14%).

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

An Energy-Efficient Target-Tracking Strategy for Mobile Sensor Networks.

Science.gov (United States)

Mahboubi, Hamid; Masoudimansour, Walid; Aghdam, Amir G; Sayrafian-Pour, Kamran

2017-02-01

In this paper, an energy-efficient strategy is proposed for tracking a moving target in an environment with obstacles, using a network of mobile sensors. Typically, the most dominant sources of energy consumption in a mobile sensor network are sensing, communication, and movement. The proposed algorithm first divides the field into a grid of sufficiently small cells. The grid is then represented by a graph whose edges are properly weighted to reflect the energy consumption of sensors. The proposed technique searches for near-optimal locations for the sensors in different time instants to route information from the target to destination, using a shortest path algorithm. Simulations confirm the efficacy of the proposed algorithm.

Factors affecting the efficiency of the sterile insect release method for tsetse

International Nuclear Information System (INIS)

Curtis, C.F.

1980-01-01

Data are reviewed on the levels of sterility, survival and competitiveness of Glossina males after irradiation with various gamma-ray doses delivered in air or nitrogen. A simple population model helps in the choice of the optimum dose. Field studies of mating competitiveness require a measure of the ratio of sterile to fertile males and of sterile to fertile matings, and both ratio estimates will be subject to sampling error. Data on multiple mating of female Glossina are reviewed. There is some degree of precedence for sperm from the first mating but sterile sperm are fully competitive for fertilization and, following the early death of an embryo, the timing of the next ovulation is only advanced to a slight extent. Thus in an isolated population the occurrence or non-occurrence of female polygamy would be of almost no consequence. Where mated females were immigrating into the release area female polygamy would be advantageous. The low recovery potential of tsetse populations is the main reason for thinking them suitable for control by the introduction of sterility. In trying to measure this recovery potential it is important to distinguish it from natural seasonal increase. If natural population fluctuations are studied to detect density dependent effects it is important not to confuse cause with effect. Non-isolation of the 'target' population is almost certainly the most serious obstacle to practical application of the sterile insect release method, and a steady 'rolling forward' of the release area may be a possible solution. (author)

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

Science.gov (United States)

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

2017-04-01

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

Physically Targeted Intravenous Polyurethane Nanoparticles for Controlled Release of Atorvastatin Calcium

Science.gov (United States)

Eftekhari, Behnaz Sadat; Karkhaneh, Akbar; Alizadeh, Ali

2017-01-01

Background: Intravenous drug delivery is an advantageous choice for rapid administration, immediate drug effect, and avoidance of first-pass metabolism in oral drug delivery. In this study, the synthesis, formulation, and characterization of atorvastatin-loaded polyurethane (PU) nanoparticles were investigated for intravenous route of administration. Method: First, PU was synthesized and characterized. Second, nanoparticles were prepared in four different ratios of drug to polymer through two different techniques, including emulsion-diffusion and single-emulsion. Finally, particle size and polydispersity index, shape and surface morphology, drug entrapment efficiency (EE), drug loading, and in vitro release were evaluated by dynamics light scattering, scanning electron microscopy, and UV visible spectroscopy, respectively. Results: Within two methods, the prepared nanoparticles had a spherical shape and a smooth surface with a diversity of size ranged from 174.04 nm to 277.24 nm in emulsion-diffusion and from 306.5 nm to 393.12 in the single-emulsion method. The highest EE was 84.76%, for (1:4) sample in the emulsion-diffusion method. It has also been shown that in vitro release of nanoparticles, using the emulsion-diffusion method, was sustained up to eight days by two mechanisms: drug diffusion and polymer relaxation. Conclusion: PU nanoparticles, that were prepared by the emulsion-diffusion method, could be used as effective carriers for the controlled drug delivery of poorly water soluble drugs such as atorvastatin calcium. PMID:28532144

[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

Analytical definition of fission chain reaction parameters for cylindrical uranium bar and energy release evaluations for HIF hybrid targets

International Nuclear Information System (INIS)

Imshennik, V.S.

2006-01-01

Within the conditions of Heavy-Ion Fusion (HIF) arises a possibility to obtain the fission chain reaction for a cylindrical HIF target. The paper contains the solution interpolated with the diffusion approximation in order to receive the general approximation expressions for the bar critical radius as well as for over-critical state. The obtained critical parameters generalized for uranium envelope are used for rough evaluation of the energy release in HIF hybrid targets [ru

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.

Effect of different polyphenol sources on the efficiency of ellagic acid release by Aspergillus niger.

Science.gov (United States)

Sepúlveda, Leonardo; de la Cruz, Reynaldo; Buenrostro, José Juan; Ascacio-Valdés, Juan Alberto; Aguilera-Carbó, Antonio Francisco; Prado, Arely; Rodríguez-Herrera, Raúl; Aguilar, Cristóbal Noé

2016-01-01

Fungal hydrolysis of ellagitannins produces hexahydroxydiphenic acid, which is considered an intermediate molecule in ellagic acid release. Ellagic acid has important and desirable beneficial health properties. The aim of this work was to identify the effect of different sources of ellagitannins on the efficiency of ellagic acid release by Aspergillus niger. Three strains of A. niger (GH1, PSH and HT4) were assessed for ellagic acid release from different polyphenol sources: cranberry, creosote bush, and pomegranate used as substrate. Polyurethane foam was used as support for solid-state culture in column reactors. Ellagitannase activity was measured for each of the treatments. Ellagic acid was quantified by high performance liquid chromatography. When pomegranate polyphenols were used, a maximum value of ellagic acid (350.21 mg/g) was reached with A. niger HT4 in solid-state culture. The highest amount of ellagitannase (5176.81 U/l) was obtained at 8h of culture when cranberry polyphenols and strain A. niger PSH were used. Results demonstrated the effect of different polyphenol sources and A. niger strains on ellagic acid release. It was observed that the best source for releasing ellagic acid was pomegranate polyphenols and A. niger HT4 strain, which has the ability to degrade these compounds for obtaining a potent bioactive molecule such as ellagic acid. Copyright © 2015 Asociación Argentina de Microbiología. Publicado por Elsevier España, S.L.U. All rights reserved.

High loading efficiency and sustained release of siRNA encapsulated in PLGA nanoparticles: quality by design optimization and characterization.

Science.gov (United States)

Cun, Dongmei; Jensen, Ditte Krohn; Maltesen, Morten Jonas; Bunker, Matthew; Whiteside, Paul; Scurr, David; Foged, Camilla; Nielsen, Hanne Mørck

2011-01-01

Poly(DL-lactide-co-glycolide acid) (PLGA) is an attractive polymer for delivery of biopharmaceuticals owing to its biocompatibility, biodegradability and outstanding controlled release characteristics. The purpose of this study was to understand and define optimal parameters for preparation of small interfering RNA (siRNA)-loaded PLGA nanoparticles by the double emulsion solvent evaporation method and characterize their properties. The experiments were performed according to a 2(5-1) fractional factorial design based on five independent variables: The volume ratio between the inner water phase and the oil phase, the PLGA concentration, the sonication time, the siRNA load and the amount of acetylated bovine serum albumin (Ac-BSA) in the inner water phase added to stabilize the primary emulsion. The effects on the siRNA encapsulation efficiency and the particle size were investigated. The most important factors for obtaining an encapsulation efficiency as high as 70% were the PLGA concentration and the volume ratio whereas the size was mainly affected by the PLGA concentration. The viscosity of the oil phase was increased at high PLGA concentration, which explains the improved encapsulation by stabilization of the primary emulsion and reduction of siRNA leakage to the outer water phase. Addition of Ac-BSA increased the encapsulation efficiency at low PLGA concentrations. The PLGA matrix protected siRNA against nuclease degradation, provided a burst release of surface-localized siRNA followed by a triphasic sustained release for two months. These results enable careful understanding and definition of optimal process parameters for preparation of PLGA nanoparticles encapsulating high amounts of siRNA with immediate and long-term sustained release properties. Copyright © 2010 Elsevier B.V. All rights reserved.

An aptamer cocktail-functionalized photocatalyst with enhanced antibacterial efficiency towards target bacteria

Energy Technology Data Exchange (ETDEWEB)

Song, Min Young [Center for Environment, Health and Welfare Research, Korea Institute of Science and Technology (KIST), Hwarangno 14-gil 5, Seongbuk-gu, Seoul 02792 (Korea, Republic of); Jurng, Jongsoo [Center for Environment, Health and Welfare Research, Korea Institute of Science and Technology (KIST), Hwarangno 14-gil 5, Seongbuk-gu, Seoul 02792 (Korea, Republic of); Department of Energy and Environmental Engineering, University of Science and Technology (UST), Hwarangno 14-gil 5, Seongbuk-gu, Seoul 02792 (Korea, Republic of); Park, Young-Kwon [School of Environmental Engineering, University of Seoul, Seoulsiripdae-ro 163, Dongdaemun-gu, Seoul 02504 (Korea, Republic of); Kim, Byoung Chan, E-mail: bchankim@kist.re.kr [Center for Environment, Health and Welfare Research, Korea Institute of Science and Technology (KIST), Hwarangno 14-gil 5, Seongbuk-gu, Seoul 02792 (Korea, Republic of); Department of Energy and Environmental Engineering, University of Science and Technology (UST), Hwarangno 14-gil 5, Seongbuk-gu, Seoul 02792 (Korea, Republic of)

2016-11-15

Highlights: • Aptamer-conjugated TiO{sub 2} was developed for target-specific bacterial inactivation. • TiO{sub 2}-aptamer cocktail can enhance inactivation of target bacteria faster than TiO{sub 2}. • TiO{sub 2}-aptamer cocktail can enhance inactivation of target bacteria in mixed culture. • Efficient ROS transfer to the bacteria is caused by close contact of TiO{sub 2}-aptamer. - Abstract: We developed TiO{sub 2} particles conjugated with an Escherichia coli surface-specific ssDNA aptamer cocktail (composed of three different aptamers isolated from E. coli) for targeted and enhanced disinfection of E. coli. We examined the target-specific and enhanced inactivation of this composite (TiO{sub 2}-Apc), which were compared to those of TiO{sub 2} conjugated with a single aptamer (one of the three different aptamers, TiO{sub 2}-Aps) and non-modified TiO{sub 2}. We found that TiO{sub 2}-Apc enhanced the inactivation of targeted E. coli under UV irradiation compared to both the non-modified TiO{sub 2} and TiO{sub 2}-Aps. A higher number of TiO{sub 2}-Apc than TiO{sub 2}-Aps particles was observed on the surface of E. coli. The amount of TiO{sub 2}-Apc required to inactivate ∼99.9% of E. coli (10{sup 6} CFU/ml) was 10 times lower than that of non-modified TiO{sub 2}. The close proximity of functionalized particles with E. coli resulting from the interaction between the target surface and the aptamer induced the efficient and fast transfer of reactive oxygen species to the cells. In a mixed culture of different bacteria (E. coli and Staphylococcus epidermidis), TiO{sub 2}-Apc enhanced the inactivation of only E. coli. Taken together, these results support the use of aptamer cocktail-conjugated TiO{sub 2} for improvement of the target-specific inactivation of bacteria.

Biofortified varieties released under HarvestPlus

African Journals Online (AJOL)

Chapter 5: Annex 1 - Biofortified varieties released under HarvestPlus (as of December 2016). Crop. Micronutrient. Country. Variety. Year of Release. Origin. Type. Baseline. (ppm). Target increment. (ppm). Increment. (ppm). % Target. Increment. (ppm). Micronutrient. Content. (ppm). 11940. BRRI dhan64. 2014. BRRI. Boro.

Learning networks as an enabler for informed decisions to target energy-efficiency potentials in companies

NARCIS (Netherlands)

Wohlfarth, Katharina; Eichhammer, W.A.; Schlomann, Barbara; Mielicke, Ursula

2017-01-01

his paper deals with possibilities of targeting energy efficiency potentials in German companies by delivering information and support within a cooperative management system “Learning Energy Efficiency Networks” (LEEN). Information deficits are pointed out as a relevant barrier to implementing

Efficient immunoglobulin gene disruption and targeted replacement in rabbit using zinc finger nucleases.

Directory of Open Access Journals (Sweden)

Tatiana Flisikowska

Full Text Available Rabbits are widely used in biomedical research, yet techniques for their precise genetic modification are lacking. We demonstrate that zinc finger nucleases (ZFNs introduced into fertilized oocytes can inactivate a chosen gene by mutagenesis and also mediate precise homologous recombination with a DNA gene-targeting vector to achieve the first gene knockout and targeted sequence replacement in rabbits. Two ZFN pairs were designed that target the rabbit immunoglobulin M (IgM locus within exons 1 and 2. ZFN mRNAs were microinjected into pronuclear stage fertilized oocytes. Founder animals carrying distinct mutated IgM alleles were identified and bred to produce offspring. Functional knockout of the immunoglobulin heavy chain locus was confirmed by serum IgM and IgG deficiency and lack of IgM(+ and IgG(+ B lymphocytes. We then tested whether ZFN expression would enable efficient targeted sequence replacement in rabbit oocytes. ZFN mRNA was co-injected with a linear DNA vector designed to replace exon 1 of the IgM locus with ∼1.9 kb of novel sequence. Double strand break induced targeted replacement occurred in up to 17% of embryos and in 18% of fetuses analyzed. Two major goals have been achieved. First, inactivation of the endogenous IgM locus, which is an essential step for the production of therapeutic human polyclonal antibodies in the rabbit. Second, establishing efficient targeted gene manipulation and homologous recombination in a refractory animal species. ZFN mediated genetic engineering in the rabbit and other mammals opens new avenues of experimentation in immunology and many other research fields.

CRISPRscan: designing highly efficient sgRNAs for CRISPR/Cas9 targeting in vivo

Science.gov (United States)

Moreno-Mateos, Miguel A.; Vejnar, Charles E.; Beaudoin, Jean-Denis; Fernandez, Juan P.; Mis, Emily K.; Khokha, Mustafa K.; Giraldez, Antonio J.

2015-01-01

CRISPR/Cas9 technology provides a powerful system for genome engineering. However, variable activity across different single guide RNAs (sgRNAs) remains a significant limitation. We have analyzed the molecular features that influence sgRNA stability, activity and loading into Cas9 in vivo. We observe that guanine enrichment and adenine depletion increase sgRNA stability and activity, while loading, nucleosome positioning and Cas9 off-target binding are not major determinants. We additionally identified truncated and 5′ mismatch-containing sgRNAs as efficient alternatives to canonical sgRNAs. Based on these results, we created a predictive sgRNA-scoring algorithm (CRISPRscan.org) that effectively captures the sequence features affecting Cas9/sgRNA activity in vivo. Finally, we show that targeting Cas9 to the germ line using a Cas9-nanos-3′-UTR fusion can generate maternal-zygotic mutants, increase viability and reduce somatic mutations. Together, these results provide novel insights into the determinants that influence Cas9 activity and a framework to identify highly efficient sgRNAs for genome targeting in vivo. PMID:26322839

Chitosan-based DNA delivery vector targeted to gonadotropin-releasing hormone (GnRH) receptor.

Science.gov (United States)

Boonthum, Chatwalee; Namdee, Katawut; Boonrungsiman, Suwimon; Chatdarong, Kaywalee; Saengkrit, Nattika; Sajomsang, Warayuth; Ponglowhapan, Suppawiwat; Yata, Teerapong

2017-02-10

The main purpose of this study was to investigate the application of modified chitosan as a potential vector for gene delivery to gonadotropin-releasing hormone receptor (GnRHR)-expressing cells. Such design of gene carrier could be useful in particular for gene therapy for cancers related to the reproductive system, gene disorders of sexual development, and contraception and fertility control. In this study, a decapeptide GnRH was successfully conjugated to chitosan (CS) as confirmed by proton nuclear magnetic resonance spectroscopy ( 1 H NMR) and Attenuated total reflectance Fourier transform infrared spectroscopy (ATR-FTIR). The synthesized GnRH-conjugated chitosan (GnRH-CS) was able to condense DNA to form positively charged nanoparticles and specifically deliver plasmid DNA to targeted cells in both two-dimensional (2D) and three-dimensional (3D) cell cultures systems. Importantly, GnRH-CS exhibited higher transfection activity compared to unmodified CS. In conclusion, GnRH-conjugated chitosan can be a promising carrier for targeted DNA delivery to GnRHR-expressing cells. Copyright © 2016 Elsevier Ltd. All rights reserved.

Supplementary Material for: DASPfind: new efficient method to predict drug–target interactions

KAUST Repository

Ba Alawi, Wail

2016-01-01

Abstract Background Identification of novel drug–target interactions (DTIs) is important for drug discovery. Experimental determination of such DTIs is costly and time consuming, hence it necessitates the development of efficient computational methods for the accurate prediction of potential DTIs. To-date, many computational methods have been proposed for this purpose, but they suffer the drawback of a high rate of false positive predictions. Results Here, we developed a novel computational DTI prediction method, DASPfind. DASPfind uses simple paths of particular lengths inferred from a graph that describes DTIs, similarities between drugs, and similarities between the protein targets of drugs. We show that on average, over the four gold standard DTI datasets, DASPfind significantly outperforms other existing methods when the single top-ranked predictions are considered, resulting in 46.17 % of these predictions being correct, and it achieves 49.22 % correct single top ranked predictions when the set of all DTIs for a single drug is tested. Furthermore, we demonstrate that our method is best suited for predicting DTIs in cases of drugs with no known targets or with few known targets. We also show the practical use of DASPfind by generating novel predictions for the Ion Channel dataset and validating them manually. Conclusions DASPfind is a computational method for finding reliable new interactions between drugs and proteins. We show over six different DTI datasets that DASPfind outperforms other state-of-the-art methods when the single top-ranked predictions are considered, or when a drug with no known targets or with few known targets is considered. We illustrate the usefulness and practicality of DASPfind by predicting novel DTIs for the Ion Channel dataset. The validated predictions suggest that DASPfind can be used as an efficient method to identify correct DTIs, thus reducing the cost of necessary experimental verifications in the process of drug discovery

HER2 Targeted Breast Cancer Therapy with Switchable "Off/On" Multifunctional "Smart" Magnetic Polymer Core-Shell Nanocomposites.

Science.gov (United States)

Vivek, Raju; Thangam, Ramar; Kumar, Selvaraj Rajesh; Rejeeth, Chandrababu; Kumar, Gopal Senthil; Sivasubramanian, Srinivasan; Vincent, Savariar; Gopi, Dhanaraj; Kannan, Soundarapandian

2016-01-27

Multifunctional magnetic polymer nanocombinations are gaining importance in cancer nanotheranostics due to their safety and their potential in delivering targeted functions. Herein, we report a novel multifunctional core-shell magnetic polymer therapeutic nanocomposites (NCs) exhibiting pH dependent "Off-On" release of drug against breast cancer cells. The NCs are intact in blood circulation ("Off" state), i.e., at physiological pH, whereas activated ("On" state) at intracellular acidic pH environment of the targeted breast cancer cells. The NCs are prepared by coating the cannonball (iron nanocore) with hydrophobic nanopockets of pH-responsive poly(d,l-lactic-co-glycolic acid) (PLGA) polymer nanoshell that allows efficient loading of therapeutics. Further, the nanocore-polymer shell is stabilized by poly(vinylpyrrolidone) (PVP) and functionalized with a targeting HER2 ligand. The prepared Her-Fe3O4@PLGA-PVP nanocomposites facilitate packing of anticancer drug (Tamoxifen) without premature release in the bloodstream, recognizing the target cells through binding of Herceptin antibody to HER2, a cell surface receptor expressed by breast cancer cells to promote HER2 receptor mediated endocytosis and finally releasing the drug at the intracellular site of tumor cells ("On" state) to induce apoptosis. The therapeutic efficiency of hemo/cytocompatible NCs drug delivery system (DDS) in terms of targeted delivery and sustained release of therapeutic agent against breast cancer cells was substantiated by in vitro and in vivo studies. The multifunctional properties of Her-Tam-Fe3O4@PLGA-PVP NCs may open up new avenues in cancer therapy through overcoming the limitations of conventional cancer therapy.

Efficient gene targeting by homology-directed repair in rat zygotes using TALE nucleases.

Science.gov (United States)

Remy, Séverine; Tesson, Laurent; Menoret, Séverine; Usal, Claire; De Cian, Anne; Thepenier, Virginie; Thinard, Reynald; Baron, Daniel; Charpentier, Marine; Renaud, Jean-Baptiste; Buelow, Roland; Cost, Gregory J; Giovannangeli, Carine; Fraichard, Alexandre; Concordet, Jean-Paul; Anegon, Ignacio

2014-08-01

The generation of genetically modified animals is important for both research and commercial purposes. The rat is an important model organism that until recently lacked efficient genetic engineering tools. Sequence-specific nucleases, such as ZFNs, TALE nucleases, and CRISPR/Cas9 have allowed the creation of rat knockout models. Genetic engineering by homology-directed repair (HDR) is utilized to create animals expressing transgenes in a controlled way and to introduce precise genetic modifications. We applied TALE nucleases and donor DNA microinjection into zygotes to generate HDR-modified rats with large new sequences introduced into three different loci with high efficiency (0.62%-5.13% of microinjected zygotes). Two of these loci (Rosa26 and Hprt1) are known to allow robust and reproducible transgene expression and were targeted for integration of a GFP expression cassette driven by the CAG promoter. GFP-expressing embryos and four Rosa26 GFP rat lines analyzed showed strong and widespread GFP expression in most cells of all analyzed tissues. The third targeted locus was Ighm, where we performed successful exon exchange of rat exon 2 for the human one. At all three loci we observed HDR only when using linear and not circular donor DNA. Mild hypothermic (30°C) culture of zygotes after microinjection increased HDR efficiency for some loci. Our study demonstrates that TALE nuclease and donor DNA microinjection into rat zygotes results in efficient and reproducible targeted donor integration by HDR. This allowed creation of genetically modified rats in a work-, cost-, and time-effective manner. © 2014 Remy et al.; Published by Cold Spring Harbor Laboratory Press.

Carnauba wax as a promising excipient in melt granulation targeting the preparation of mini-tablets for sustained release of highly soluble drugs.

Science.gov (United States)

Nart, Viviane; Beringhs, André O'Reilly; França, Maria Terezinha; de Espíndola, Brenda; Pezzini, Bianca Ramos; Stulzer, Hellen Karine

2017-01-01

Mini-tablets are a new tendency in solid dosage form design for overcoming therapeutic obstacles such as impaired swallowing and polypharmacy therapy. Among their advantages, these systems offer therapeutic benefits such as dose flexibility and combined drug release patterns. The use of lipids in the formulation has also drawn considerable interest as means to modify the drug release from the dosage form. Therefore, this paper aimed at developing sustained release mini-tablets containing the highly soluble drugs captopril and metformin hydrochloride. Carnauba wax was used as a lipid component in melt granulation, targeting the improvement of the drugs poor flowability and tabletability, as well as to sustain the drug release profiles in association with other excipients. To assist sustaining the drug release, Ethocel™ (EC) and Kollicoat® SR 30D associated with Opadry® II were employed as matrix-forming and reservoir-forming materials, respectively. The neat drugs, granules and the bulk formulations were evaluated for their angle of repose, compressibility index, Hausner ratio and tabletability. Mini-tablets were evaluated for their weight variation, hardness, friability, drug content and in-vitro drug release. The results indicated that melt granulation with carnauba wax improved the flow and the tabletability of the drugs, allowing the preparation of mini-tablets with adequate tensile strength under reduced compaction pressures. All mini-tablet formulations showed acceptable hardness (within the range of 1.16 to 3.93Kp) and friability (carnauba wax proved to be a promising excipient in melt granulation targeting the preparation of mini-tablets for sustained release of soluble drugs. Copyright © 2016 Elsevier B.V. All rights reserved.

Impact of the recession on the realization of the Kyoto target and the 2011 target of the working programme 'Clean and Efficient'. Memo

International Nuclear Information System (INIS)

2009-01-01

By request of the Dutch Ministry of Housing, Spatial Planning and the Environment the Environmental Assessment Agency (PBL) drew up this memo on the impact of the recession on the realization of the Kyoto target and the intermediate target for 2011 from the working programme Clean and Efficient. The main conclusion of this memo is that both with and without the recession the Kyoto target will probably be realized. The main difference lies in the volume of emission allowances deployed by the government to realize the target [mk] [nl

In Vitro Transduction and Target-Mutagenesis Efficiency of HIV-1 pol Gene Targeting ZFN and CRISPR/Cas9 Delivered by Various Plasmids and/or Vectors: Toward an HIV Cure.

Science.gov (United States)

Okee, Moses; Bayiyana, Alice; Musubika, Carol; Joloba, Moses L; Ashaba-Katabazi, Fred; Bagaya, Bernard; Wayengera, Misaki

2018-01-01

Efficiency of artificial restriction enzymes toward curing HIV has only been separately examined, using differing delivery vehicles. We compared the in vitro transduction and target-mutagenesis efficiency of consortium plasmid and adenoviral vector delivered HIV-1 pol gene targeting zinc finger nuclease (ZFN) with CRISPR/Cas, Custom-ZFN, CRISPR-Cas-9, and plasmids and vectors (murCTSD_pZFN, pGS-U-gRNA, pCMV-Cas-D01A, Ad5-RGD); cell lines (TZM-bl and ACH-2/J-Lat cells); and the latency reversing agents prostratin, suberoylanilide hydroxamic acid, and phorbol myristate acetate. Cell lines were grown in either Dulbecco's modified Eagle's medium or Roswell Park Memorial Institute with the antibiotics kanamycin, zeocin, and efavirenz. Efficiency was assayed by GFP/luciferase activity and/or validated by yeast MEL1 reporter assay, CEL1 restriction fragment assay, and quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR). Ad5-RGD vectors had better transduction efficiency than murCTSD and pGS-U-gRNA/pCMV-Cas-D01A plasmids. CRISPR/Cas9 exhibited better target-mutagenesis efficiency relative to ZFN (delivered by either plasmid or Ad5 vector) based on gel electrophoresis of pol gene amplicons within ACH-2 and J-Lat cells. Ad-5-RGD vectors enhanced target mutagenesis of ZFN, relative to murCTSD_pZFN plasmids, to levels of CRISPR/Cas9 plasmids. Similar reduction of luciferase activity among TZM-bl treated with Ad5-ZFN vectors relative to CRISPR/Cas-9 and murCTSD_pZFN plasmids was observed on challenge with HIV-1. qRT-PCR of HIV-1 pol gene transcripts affirmed that Ad5 (RGD) vectors enhanced target mutagenesis of ZFN. Whereas CRISPR/Cas-9 may possess inherent superior target-mutagenesis efficiency; the efficiency of ZFN (off-target toxicity withstanding) can be enhanced by altering delivery vehicle from plasmid to Ad5 (RGD) vectors.

Enhanced solubility and targeted delivery of curcumin by lipopeptide micelles.

Science.gov (United States)

Liang, Ju; Wu, Wenlan; Lai, Danyu; Li, Junbo; Fang, Cailin

2015-01-01

A lipopeptide (LP)-containing KKGRGDS as the hydrophilic heads and lauric acid (C12) as the hydrophobic tails has been designed and prepared by standard solid-phase peptide synthesis technique. LP can self-assemble into spherical micelles with the size of ~30 nm in PBS (phosphate buffer saline) (pH 7.4). Curcumin-loaded LP micelles were prepared in order to increase the water solubility, sustain the releasing rate, and improve the tumor targeted delivery of curcumin. Water solubility, cytotoxicity, in vitro release behavior, and intracellular uptake of curcumin-loaded LP micelles were investigated. The results showed that LP micelles can increase the water solubility of curcumin 1.1 × 10(3) times and sustain the release of curcumin in a low rate. Curcumin-loaded LP micelles showed much higher cell inhibition than free curcumin on human cervix carcinoma (HeLa) and HepG2 cells. When incubating these curcumin-loaded micelles with HeLa and COS7 cells, due to the over-expression of integrins on cancer cells, the micelles can efficiently use the tumor-targeting function of RGD (functionalized peptide sequences: Arg-Gly-Asp) sequence to deliver the drug into HeLa cells, and better efficiency of the self-assembled LP micelles for curcumin delivery than crude curcumin was also confirmed by LCSM (laser confocal scanning microscope) assays. Combined with the enhanced solubility and higher cell inhibition, LP micelles reported in this study may be promising in clinical application for targeted curcumin delivery.

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.

Beam transmission efficiency between injector and target in the GANIL complex

International Nuclear Information System (INIS)

Beck, R.; Bru, B.; Ricaud, C.

1984-06-01

In order to achieve a maximum transmission efficiency, efforts have been made in three directions: beam measurements, understanding of the physical phenomenon, tuning method. The characteristics of the beam extracted from the three cyclotrons have been measured. The ensuing optical effects are analysed. The tuning of the transport-lines, depending on the characteristics of the extracted beams and the required beam properties on the target, is described

Target-nontarget similarity decreases search efficiency and increases stimulus-driven control in visual search.

Science.gov (United States)

Barras, Caroline; Kerzel, Dirk

2017-10-01

Some points of criticism against the idea that attentional selection is controlled by bottom-up processing were dispelled by the attentional window account. The attentional window account claims that saliency computations during visual search are only performed for stimuli inside the attentional window. Therefore, a small attentional window may avoid attentional capture by salient distractors because it is likely that the salient distractor is located outside the window. In contrast, a large attentional window increases the chances of attentional capture by a salient distractor. Large and small attentional windows have been associated with efficient (parallel) and inefficient (serial) search, respectively. We compared the effect of a salient color singleton on visual search for a shape singleton during efficient and inefficient search. To vary search efficiency, the nontarget shapes were either similar or dissimilar with respect to the shape singleton. We found that interference from the color singleton was larger with inefficient than efficient search, which contradicts the attentional window account. While inconsistent with the attentional window account, our results are predicted by computational models of visual search. Because of target-nontarget similarity, the target was less salient with inefficient than efficient search. Consequently, the relative saliency of the color distractor was higher with inefficient than with efficient search. Accordingly, stronger attentional capture resulted. Overall, the present results show that bottom-up control by stimulus saliency is stronger when search is difficult, which is inconsistent with the attentional window account.

Real-time observation of DNA target interrogation and product release by the RNA-guided endonuclease CRISPR Cpf1 (Cas12a).

Science.gov (United States)

Singh, Digvijay; Mallon, John; Poddar, Anustup; Wang, Yanbo; Tippana, Ramreddy; Yang, Olivia; Bailey, Scott; Ha, Taekjip

2018-05-22

CRISPR-Cas9, which imparts adaptive immunity against foreign genomic invaders in certain prokaryotes, has been repurposed for genome-engineering applications. More recently, another RNA-guided CRISPR endonuclease called Cpf1 (also known as Cas12a) was identified and is also being repurposed. Little is known about the kinetics and mechanism of Cpf1 DNA interaction and how sequence mismatches between the DNA target and guide-RNA influence this interaction. We used single-molecule fluorescence analysis and biochemical assays to characterize DNA interrogation, cleavage, and product release by three Cpf1 orthologs. Our Cpf1 data are consistent with the DNA interrogation mechanism proposed for Cas9. They both bind any DNA in search of protospacer-adjacent motif (PAM) sequences, verify the target sequence directionally from the PAM-proximal end, and rapidly reject any targets that lack a PAM or that are poorly matched with the guide-RNA. Unlike Cas9, which requires 9 bp for stable binding and ∼16 bp for cleavage, Cpf1 requires an ∼17-bp sequence match for both stable binding and cleavage. Unlike Cas9, which does not release the DNA cleavage products, Cpf1 rapidly releases the PAM-distal cleavage product, but not the PAM-proximal product. Solution pH, reducing conditions, and 5' guanine in guide-RNA differentially affected different Cpf1 orthologs. Our findings have important implications on Cpf1-based genome engineering and manipulation applications.

Evaluation of Efficiency Activities in the Industrial Sector Undertaken in Response to Greenhouse Gas Emission Reduction Targets

Energy Technology Data Exchange (ETDEWEB)

Price, Lynn; de la Rue du Can, Stephane; Lu, Hongyou; Horvath, Arpad

2010-05-21

The 2006 California Global Warming Solutions Act calls for reducing greenhouse gas (GHG) emissions to 1990 levels by 2020. Meeting this target will require action from all sectors of the California economy, including industry. The industrial sector consumes 25% of the energy used and emits 28% of the carbon dioxide (CO{sub 2}) produced in the state. Many countries around the world have national-level GHG reduction or energy-efficiency targets, and comprehensive programs focused on implementation of energy efficiency and GHG emissions mitigation measures in the industrial sector are essential for achieving their goals. A combination of targets and industry-focused supporting programs has led to significant investments in energy efficiency as well as reductions in GHG emissions within the industrial sectors in these countries. This project has identified program and policies that have effectively targeted the industrial sector in other countries to achieve real energy and CO{sub 2} savings. Programs in Ireland, France, The Netherlands, Denmark, and the UK were chosen for detailed review. Based on the international experience documented in this report, it is recommended that companies in California's industrial sector be engaged in a program to provide them with support to meet the requirements of AB32, The Global Warming Solution Act. As shown in this review, structured programs that engage industry, require members to evaluate their potential efficiency measures, plan how to meet efficiency or emissions reduction goals, and provide support in achieving the goals, can be quite effective at assisting companies to achieve energy efficiency levels beyond those that can be expected to be achieved autonomously.

Targeting energy justice: Exploring spatial, racial/ethnic and socioeconomic disparities in urban residential heating energy efficiency

International Nuclear Information System (INIS)

Reames, Tony Gerard

2016-01-01

Fuel poverty, the inability of households to afford adequate energy services, such as heating, is a major energy justice concern. Increasing residential energy efficiency is a strategic fuel poverty intervention. However, the absence of easily accessible household energy data impedes effective targeting of energy efficiency programs. This paper uses publicly available data, bottom-up modeling and small-area estimation techniques to predict the mean census block group residential heating energy use intensity (EUI), an energy efficiency proxy, in Kansas City, Missouri. Results mapped using geographic information systems (GIS) and statistical analysis, show disparities in the relationship between heating EUI and spatial, racial/ethnic, and socioeconomic block group characteristics. Block groups with lower median incomes, a greater percentage of households below poverty, a greater percentage of racial/ethnic minority headed-households, and a larger percentage of adults with less than a high school education were, on average, less energy efficient (higher EUIs). Results also imply that racial segregation, which continues to influence urban housing choices, exposes Black and Hispanic households to increased fuel poverty vulnerability. Lastly, the spatial concentration and demographics of vulnerable block groups suggest proactive, area- and community-based targeting of energy efficiency assistance programs may be more effective than existing self-referral approaches. - Highlights: • Develops statistical model to predict block group (BG) residential heating energy use intensity (EUI), an energy efficiency proxy. • Bivariate and multivariate analyses explore racial/ethnic and socioeconomic relationships with heating EUI. • BGs with more racial/ethnic minority households had higher heating EUI. • BGs with lower socioeconomics had higher heating EUI. • Mapping heating EUI can facilitate effective energy efficiency intervention targeting.

Enhanced Anti-Tumoral Activity of Methotrexate-Human Serum Albumin Conjugated Nanoparticles by Targeting with Luteinizing Hormone-Releasing Hormone (LHRH) Peptide

Science.gov (United States)

Taheri, Azade; Dinarvand, Rassoul; Atyabi, Fatemeh; Ahadi, Fatemeh; Nouri, Farank Salman; Ghahremani, Mohammad Hossein; Ostad, Seyed Nasser; Borougeni, Atefeh Taheri; Mansoori, Pooria

2011-01-01

Active targeting could increase the efficacy of anticancer drugs. Methotrexate-human serum albumin (MTX-HSA) conjugates, functionalized by luteinizing hormone-releasing hormone (LHRH) as targeting moieties, with the aim of specifically targeting the cancer cells, were prepared. Owing to the high expression of LHRH receptors in many cancer cells as compared to normal cells, LHRH was used as the targeting ligand in this study. LHRH was conjugated to MTX-HSA nanoparticles via a cross-linker. Three types of LHRH targeted nanoparticles with a mean particle size between 120–138 nm were prepared. The cytotoxicity of LHRH targeted and non-targeted nanoparticles were determined on the LHRH positive and negative cell lines. The internalization of the targeted and non-targeted nanoparticles in LHRH receptor positive and negative cells was investigated using flow cytometry analysis and fluorescence microscopy. The cytotoxicity of the LHRH targeted nanoparticles on the LHRH receptor positive cells were significantly more than non-targeted nanoparticles. LHRH targeted nanoparticles were also internalized by LHRH receptor positive cells significantly more than non-targeted nanoparticles. There were no significant differences between the uptake of targeted and non-targeted nanoparticles to the LHRH receptor negative cells. The active targeting procedure using LHRH targeted MTX-HSA nanoparticles could increase the anti-tumoral activity of MTX. PMID:21845098

Galactosylated DNA lipid nanocapsules for efficient hepatocyte targeting.

Science.gov (United States)

Morille, M; Passirani, C; Letrou-Bonneval, E; Benoit, J-P; Pitard, B

2009-09-11

The main objective of gene therapy via a systemic pathway is the development of a stable and non-toxic gene vector that can encapsulate and deliver foreign genetic materials into specific cell types with the transfection efficiency of viral vectors. With this objective, DNA complexed with cationic lipids of DOTAP/DOPE was encapsulated into lipid nanocapsules (LNCs) forming nanocarriers (DNA LNCs) with a size suitable for systemic injection (109+/-6 nm). With the goal of increasing systemic delivery, LNCs were stabilised with long chains of poly(ethylene glycol) (PEG), either from a PEG lipid derivative (DSPE-mPEG(2000)) or from an amphiphilic block copolymer (F108). In order to overcome internalisation difficulties encountered with PEG shield, a specific ligand (galactose) was covalently added at the distal end of the PEG chains, in order to provide active targeting of the asialoglycoprotein-receptor present on hepatocytes. This study showed that DNA LNCs were as efficient as positively charged DOTAP/DOPE lipoplexes for transfection. In primary hepatocytes, when non-galactosylated, the two polymers significantly decreased the transfection, probably by creating a barrier around the DNA LNCs. Interestingly, galactosylated F108 coated DNA LNCs led to a 18-fold increase in luciferase expression compared to non-galactosylated ones.

A targeted liposome delivery system for combretastatin A4: formulation optimization through drug loading and in vitro release studies.

Science.gov (United States)

Nallamothu, Ramakrishna; Wood, George C; Kiani, Mohammad F; Moore, Bob M; Horton, Frank P; Thoma, Laura A

2006-01-01

Efficient liposomal therapeutics require high drug loading and low leakage. The objective of this study is to develop a targeted liposome delivery system for combretastatin A4 (CA4), a novel antivascular agent, with high loading and stable drug encapsulation. Liposomes composed of hydrogenated soybean phosphatidylcholine (HSPC), cholesterol, and distearoyl phosphoethanolamine-PEG-2000 conjugate (DSPE-PEG) were prepared by the lipid film hydration and extrusion process. Cyclic arginine-glycine-aspartic acid (RGD) peptides with affinity for alphav beta3-integrins overexpressed on tumor vascular endothelial cells were coupled to the distal end of polyethylene glycol (PEG) on the liposomes sterically stabilized with PEG (non-targeted liposomes; LCLs). Effect of lipid concentration, drug-to-lipid ratio, cholesterol, and DSPE-PEG content in the formulation on CA4 loading and its release from the liposomes was studied. Total liposomal CA4 levels obtained increased with increasing lipid concentration in the formulation. As the drug-to-lipid ratio increased from 10:100 to 20:100, total drug in the liposome formulation increased from 1.05+/-0.11 mg/mL to 1.55+/-0.13 mg/mL, respectively. When the drug-to-lipid ratio was further raised to 40:100, the total drug in liposome formulation did not increase, but the amount of free drug increased significantly, thereby decreasing the percent of entrapped drug. Increasing cholesterol content in the formulation decreased drug loading. In vitro drug leakage from the liposomes increased with increase in drug-to-lipid ratio or DSPE-PEG content in the formulation; whereas increasing cholesterol content of the formulation up to 30 mol-percent, decreased CA4 leakage from the liposomes. Ligand coupling to the liposome surface increased drug leakage as a function of ligand density. Optimized liposome formulation with 100 mM lipid concentration, 20:100 drug-to-lipid ratio, 30 mol-percent cholesterol, 4 mol-percent DSPE-PEG, and 1 mol

Hierarchical mesosilicalite nanoformulation integrated with cisplatin exhibits target-specific efficient anticancer activity

Science.gov (United States)

Jermy, B. Rabindran; Acharya, Sadananda; Ravinayagam, Vijaya; Alghamdi, Hajer Saleh; Akhtar, Sultan; Basuwaidan, Rehab S.

2018-04-01

Hierarchically structured zeolitic ZSM-5 and meso MCM-41 interlinked domain had an impeccable use as catalysis in many applications. The aim of the study was to develop a new drug delivery nanoformulation, specifically, cisplatin/mesosilicalite using top-down approach for cancer therapy. Hierarchical mesosilicalite with variable porosity was synthesized using alkaline molar solution (0.2 and 0.7 M NaOH) and was loaded with cisplatin through equilibrium adsorption technique. Physico-chemical properties of the nanoformulation (IAUM-56—Imam Abdulrahman Bin Faisal University Mesosilicalite-56) were characterized using X-ray diffraction, surface area analysis (BET), Fourier transformed infrared spectroscopy (FT-IR), diffuse reflectance UV-Vis spectroscopy, and transmission electron microscopy. Drug release study and anticancer activity were assayed on HeLa and MCF7 cancer cells using MTT assay. X-ray diffraction pattern showed interrelated meso- and microphases, while BET analysis revealed considerable mesoporosity formation with a remodulation of isotherm hysteresis indicating the presence of hierarchical pores. FT-IR showed the presence of nanozeolitic subunits into mesostructure with a band at about 550 cm-1. IAUM-56 demonstrated high cytotoxic activity against HeLa cancer cells with an LC50 of 0.02 mg/ml, MCF7 cancer cells with an LC50 of 0.05 mg/ml, and less toxic to normal fibroblast cells with an LC50 of approximately ten times higher at 0.5 mg/ml. Overall, IAUM-56 showed a high rate of sustained release of cisplatin imparting target specific cytotoxic effect against tumor cells with at least tenfold lower toxicity on normal fibroblast cells. Our nanoformulation has the potential use in cancer therapy as a targeted drug delivery system.

Human lactoferrin efficiently targeted into caprine beta-lactoglobulin locus with transcription activator-like effector nucleases

Directory of Open Access Journals (Sweden)

Yu-Guo Yuan

2017-08-01

Full Text Available Objective To create genetically modified goat as a biopharming source of recombinant human lacotoferrin (hLF with transcription activator-like effector nucleases. Methods TALENs and targeting vector were transferred into cultured fibroblasts to insert hLF cDNA in the goat beta-lactoglobulin (BLG locus with homology-directed repair. The gene targeted efficiency was checked using sequencing and TE7I assay. The bi-allelic gene targeted colonies were isolated and confirmed with polymerase chain reaction, and used as donor cells for somatic cell nuclear transfer (SCNT. Results The targeted efficiency for BLG gene was approximately 10%. Among 12 Bi-allelic gene targeted colonies, five were used in first round SCNT and 4 recipients (23% were confirmed pregnant at 30 d. In second round SCNT, 7 (53%, 4 (31%, and 3 (23% recipients were confirmed to be pregnant by ultrasound on 30 d, 60 d, and 90 d. Conclusion This finding signifies the combined use of TALENs and SCNT can generate bi-allelic knock-in fibroblasts that can be cloned in a fetus. Therefore, it might lay the foundation for transgenic hLF goat generation and possible use of their mammary gland as a bioreactor for large-scale production of recombinant hLF.

Whole genome analysis of CRISPR Cas9 sgRNA off-target homologies via an efficient computational algorithm.

Science.gov (United States)

Zhou, Hong; Zhou, Michael; Li, Daisy; Manthey, Joseph; Lioutikova, Ekaterina; Wang, Hong; Zeng, Xiao

2017-11-17

The beauty and power of the genome editing mechanism, CRISPR Cas9 endonuclease system, lies in the fact that it is RNA-programmable such that Cas9 can be guided to any genomic loci complementary to a 20-nt RNA, single guide RNA (sgRNA), to cleave double stranded DNA, allowing the introduction of wanted mutations. Unfortunately, it has been reported repeatedly that the sgRNA can also guide Cas9 to off-target sites where the DNA sequence is homologous to sgRNA. Using human genome and Streptococcus pyogenes Cas9 (SpCas9) as an example, this article mathematically analyzed the probabilities of off-target homologies of sgRNAs and discovered that for large genome size such as human genome, potential off-target homologies are inevitable for sgRNA selection. A highly efficient computationl algorithm was developed for whole genome sgRNA design and off-target homology searches. By means of a dynamically constructed sequence-indexed database and a simplified sequence alignment method, this algorithm achieves very high efficiency while guaranteeing the identification of all existing potential off-target homologies. Via this algorithm, 1,876,775 sgRNAs were designed for the 19,153 human mRNA genes and only two sgRNAs were found to be free of off-target homology. By means of the novel and efficient sgRNA homology search algorithm introduced in this article, genome wide sgRNA design and off-target analysis were conducted and the results confirmed the mathematical analysis that for a sgRNA sequence, it is almost impossible to escape potential off-target homologies. Future innovations on the CRISPR Cas9 gene editing technology need to focus on how to eliminate the Cas9 off-target activity.

An efficient method of fuel ice formation in moving free-standing ICF/IFE targets

Science.gov (United States)

Aleksandrova, I. V.; Bazdenkov, S. V.; Chtcherbakov, V. I.; Gromov, A. I.; Koresheva, E. R.; Koshelev, E. A.; Osipov, I. E.; Yaguzinskiy, L. S.

2004-04-01

Currently, research fields related to the elaboration of efficient layering methods for ICF/IFE applications are rapidly expanding. Significant progress has been made in the technology development based on rapid fuel layering inside moving free-standing targets (FST) which is referred to as the FST layering method. This paper presents our new results obtained in this area and describes technologically elegant solutions towards demonstrating a credible pathway for mass production of IFE cryogenic targets.

An efficient method of fuel ice formation in moving free-standing ICF/IFE targets

International Nuclear Information System (INIS)

Aleksandrova, I V; Bazdenkov, S V; Chtcherbakov, V I; Gromov, A I; Koresheva, E R; Koshelev, E A; Osipov, I E; Yaguzinskiy, L S

2004-01-01

Currently, research fields related to the elaboration of efficient layering methods for ICF/IFE applications are rapidly expanding. Significant progress has been made in the technology development based on rapid fuel layering inside moving free-standing targets (FST) which is referred to as the FST layering method. This paper presents our new results obtained in this area and describes technologically elegant solutions towards demonstrating a credible pathway for mass production of IFE cryogenic targets

Preparation and quality evaluation of LHRHa-targeted Brucea javanica oil liposomes

Directory of Open Access Journals (Sweden)

Xiao-juan LIU

2013-07-01

Full Text Available Objective　To prepare luteinizing hormone-releasing hormone a (LHRHa targeted Bruceajavanicaliposomes and evaluate its quality. Methods　The LHRHa-targeted Bruceajavanicaliposome was prepared by thin layer dispersion together with biotin¬streptavidin bridge method. The optimum formation was selected by means of orthogonal design of experiment. The morphology of liposome was observed with transmission electron microscope. Zetasizer Nano ZS analyzer was used to measure the particle size and zeta potential. The entrapment efficiency was determined by ultra-violet spectroscopy and column chromatography. Centrifugal acceleration experiment and determination of leak rate were performed to prove the liposome stability. The targeting ability of liposome was appraised by cell experiment in vitro. Results　The formed optimum formula was as follows: the ratio of lecithin to cholesterol was 4:1, Brucea javanicaoil:lipid was 3:10, DSPE-PEG (2000-Biotin:lecithin content was 3%, ultrasonic-homogenized for 8 minutes. Liposomes were round in shape, the average diameter and zeta potential of liposome were 155.1±14.5mm and –(24.1±0.54 mV, respectively. The average entrapment efficiency was 92.2%. Binding capacity with the A2780/DDP cell line in the LHRHa-targeted liposomes was 2.7 times higher than that in the non-targeting liposomes. Conclusion　The technique of preparing LHRHa-targeted Bruceajavanicaliposome is suitable, and high in entrapment efficiency, with good stability and targeting ability.

Formulation and Characterization of Pyrazinamide Polymeric Nanoparticles for Pulmonary Tuberculosis: Efficiency for Alveolar Macrophage Targeting

OpenAIRE

Varma, J. N. Ravi; Kumar, T. Santosh; Prasanthi, B.; Ratna, J. Vijaya

2015-01-01

Pyrazinamide, a highly specific agent against Mycobacterium tuberculosis is used as first-line drug to treat tuberculosis. The current work aims to formulate polymeric nanoparticles based drug delivery system to sustain the release profile and reduce the dosing frequency of pyrazinamide. Further aim was to target the macrophages within body fluid. These polymeric nanoparticles were prepared by simultaneous double-emulsion (W/O/W) solvent evaporation/diffusion technique. The prepared dispersio...

On the efficiency calibration of Si(Li) detector in the low-energy region using thick-target bremsstrahlung

Energy Technology Data Exchange (ETDEWEB)

An, Z. E-mail: anzhu@scu.edu.cn; Liu, M.T

2002-10-01

In this paper, the efficiency calibration of a Si(Li) detector in the low-energy region down to 0.58 keV has been performed using thick-carbon-target bremsstrahlung by 19 keV electron impact. The shape of the efficiency calibration curve was determined from the thick-carbon-target bremsstrahlung spectrum, and the absolute value for the efficiency calibration was obtained from the use of {sup 241}Am radioactive standard source. The modified Wentzel's formula for thick-target bremsstrahlung was employed and it was also compared with the most recently developed theoretical model based upon the doubly differential cross-sections for bremsstrahlung of Kissel, Quarles and Pratt. In the present calculation of theoretical bremsstrahlung, the self-absorption correction and the convolution of detector's response function with the bremsstrahlung spectrum have simultaneously been taken into account. The accuracy for the efficiency calibration in the low-energy region with the method described here was estimated to be about 6%. Moreover, the self-absorption correction calculation based upon the prescription of Wolters et al. has also been presented as an analytical factor with the accuracy of {approx}1%.

Progress in transmutation targets from Efttra

International Nuclear Information System (INIS)

Haas, D.; Fernandez, A.; Warin, D.; Bonnerot, J.M.; Garzenne, C.; Scaffidi-Argentina, F.; Maschek, W.; Schram, R.; Klaassen, F.

2007-01-01

Since 15 years, the EFTTRA partners have organised programmes to demonstrate the feasibility of the transmutation of americium in uranium-free targets. In the related transmutation scenario, the targets are introduced in a thermal neutron zone of a fast reactor, to maximize the efficiency of transmutation. Amongst these programmes, those carried out in the HFR reactor in Petten have led to important conclusions and are still at the core of the research in that field. The analysis of the EFTTRA T4 and T4bis irradiation experiments, carried out with targets of MgAl 2 O 4 +11 wt% 241 Am, showed that the release/trapping of helium is the key issue for target design, and also demonstrated a lack of technical benefits of this material, due to a unsatisfactory in-pile behaviour in terms of irradiation damage and chemical stability. A new irradiation experiment called HELIOS is currently under fabrication and will be carried out in HFR. The in-pile behaviour of U-free fuels and targets such as (Am,Zr)O 2 , (Pu,Am,Zr)O 2 , CERCER (MgO) or CERMET (Mo) will be examined. The irradiation temperature will be high enough in some of the pins to be able to tune the release of a significant fraction of helium produced so that the material swelling can be minimized as much as reasonably possible. The HELIOS irradiation experiment is planned to be carried out in the HFR core and shall last 300 full power days starting in 2007. (authors)

Test of a High Power Target Design

CERN Multimedia

2002-01-01

%IS343 :\\\\ \\\\ A high power tantalum disc-foil target (RIST) has been developed for the proposed radioactive beam facility, SIRIUS, at the Rutherford Appleton Laboratory. The yield and release characteristics of the RIST target design have been measured at ISOLDE. The results indicate that the yields are at least as good as the best ISOLDE roll-foil targets and that the release curves are significantly faster in most cases. Both targets use 20 -25 $\\mu$m thick foils, but in a different internal geometry.\\\\ \\\\Investigations have continued at ISOLDE with targets having different foil thickness and internal geometries in an attempt to understand the release mechanisms and in particular to maximise the yield of short lived isotopes. A theoretical model has been developed which fits the release curves and gives physical values of the diffusion constants.\\\\ \\\\The latest target is constructed from 2 $\\mu$m thick tantalum foils (mass only 10 mg) and shows very short release times. The yield of $^{11}$Li (half-life of ...

Efficient in planta gene targeting in tomato using geminiviral replicons and the CRISPR/Cas9 system.

Science.gov (United States)

Dahan-Meir, Tal; Filler-Hayut, Shdema; Melamed-Bessudo, Cathy; Bocobza, Samuel; Czosnek, Henryk; Aharoni, Asaph; Levy, Avraham A

2018-04-18

Current breeding relies mostly on random mutagenesis and recombination to generate novel genetic variation. However, targeted genome editing is becoming an increasingly important tool for precise plant breeding. Using the CRISPR-Cas system combined with the bean yellow dwarf virus rolling circle replicon we optimized a method for targeted mutagenesis and gene replacement in tomato. The carotenoid isomerase (CRTISO) and phytoene synthase 1 (PSY1) genes from the carotenoid biosynthesis pathway were chosen as targets due to their easily detectable change of phenotype. We took advantage of the geminiviral replicon amplification as a mean to provide a large amount of donor template for the repair of a CRISPR-Cas-induced DNA double strand break (DSB) in the target gene, via homologous recombination. Mutagenesis experiments, performed in the Micro-Tom variety achieved precise modification of the CRTISO and PSY1 loci at an efficiency of up to 90%. In the gene targeting experiments, our target was a fast-neutron-induced crtiso allele that contained a 281bp deletion. This deletion was repaired with the wildtype sequence through homologous recombination between the CRISPR-Cas-induced DSB in the crtiso target and the amplified donor in 25% of the plants transformed. This shows that efficient gene targeting can be achieved in the absence of selection markers or reporters using a single and modular construct that is adaptable to other tomato targets and other crops. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

[Nutrient use efficiency and yield-increasing effect of single basal application of rice specific controlled release fertilizer].

Science.gov (United States)

Chen, Jiansheng; Xu, Peizhi; Tang, Shuanhu; Zhang, Fabao; Xie, Chunsheng

2005-10-01

A series of pot and field experiments and field demonstrations showed that in comparing with the commonly used specific-fertilizers containing same amounts of nutrients, single basal application of rice-specific controlled release fertilizer could increase the use efficiency of N and P by 12.2% - 22.7% and 7.0% - 35.0%, respectively in pot experiment, and the use efficiency of N by 17.1% in field experiment. In 167 field demonstrations successively conducted for 3 years in various rice production areas of Guangdong Province, single basal application of the fertilizer saved the application rate of N and P by 22.1% and 21.8%, respectively, and increased the yield by 8.2%, compared with normal split fertilization.

Impact of controlled release urea on maize yield and nitrogen use efficiency under different water conditions.

Directory of Open Access Journals (Sweden)

Guanghao Li

Full Text Available Controlled release urea (CRU has been widely adopted to increase nitrogen (N use efficiency and maize production, but the impacts can range widely depending on water availability in the soil. In an experiment using Zhengdan 958 (a popular summer maize hybrid, three levels of water treatments (adequate water condition [W3], which maintained soil moisture at about 75% ± 5% of the soil's field capacity; mild water stress [W2], which maintained moisture content at 55% ± 5% of field capacity; and severe water stress [W1], which had a moisture content of 35% ± 5% of field capacity and four levels of controlled release urea fertilizer (N0, N1, N2 and N3 were 0, 105, 210 and 315 kg N ha-1, respectively were compared in a rainout shelter system with soil. The results revealed that CRU had significant effects on maize yields and N use efficiencies under different water conditions. The mean yields increased with increasing water levels and showed significant differences. Under W1, the accumulation of dry matter and N were limited, and N internal efficiency (NIE and the apparent recovery efficiency of applied N (REN decreased with N increases; yields of N1, N2, and N3 were similar. Under W2, the dry matter and N accumulation, as well as the yield, showed an increasing trend with an increase in N application, and the NIE and REN of N3 showed no difference from N2. Under W3, yields of N2 and N3 were similar and they were significantly higher than that of N1, but the agronomic N use efficiency (ANUE, REN, and the physiological NUE (PNUE of N2 were 54.2, 34.9, and 14.4% higher, respectively, than those of N3. N application beyond the optimal N rate did not consistently increase maize yield, and caused a decrease in N use efficiencies. Highest overall dry matter, N accumulation, and yields were observed with N3 under W2, and those showed no differences with N2 and N3 under W3. Under this experimental condition, the CRU of 210 kg ha-1 was optimized when soil

A highly efficient targeted recombination system for engineering linear chromosomes of industrial bacteria Streptomyces.

Science.gov (United States)

Pan, Hung-Yin; Chen, Carton W; Huang, Chih-Hung

2018-04-17

Soil bacteria Streptomyces are the most important producers of secondary metabolites, including most known antibiotics. These bacteria and their close relatives are unique in possessing linear chromosomes, which typically harbor 20 to 30 biosynthetic gene clusters of tens to hundreds of kb in length. Many Streptomyces chromosomes are accompanied by linear plasmids with sizes ranging from several to several hundred kb. The large linear plasmids also often contain biosynthetic gene clusters. We have developed a targeted recombination procedure for arm exchanges between a linear plasmid and a linear chromosome. A chromosomal segment inserted in an artificially constructed plasmid allows homologous recombination between the two replicons at the homology. Depending on the design, the recombination may result in two recombinant replicons or a single recombinant chromosome with the loss of the recombinant plasmid that lacks a replication origin. The efficiency of such targeted recombination ranges from 9 to 83% depending on the locations of the homology (and thus the size of the chromosomal arm exchanged), essentially eliminating the necessity of selection. The targeted recombination is useful for the efficient engineering of the Streptomyces genome for large-scale deletion, addition, and shuffling.

Design of Effective Energy Efficiency Policies : An analysis in the frame of target setting, monitoring and evaluation

NARCIS (Netherlands)

Schlomann, B.

2014-01-01

Energy efficiency (EE) is widely acknowledged as the most important strategy for achieving global energy and climate targets. Apart from its contribution to the reduction of energy consumption and energy-related greenhouse gas emissions (GHG), improving energy efficiency can deliver a range of

Efficient and Heritable Gene Targeting in Tilapia by CRISPR/Cas9

Science.gov (United States)

Li, Minghui; Yang, Huihui; Zhao, Jiue; Fang, Lingling; Shi, Hongjuan; Li, Mengru; Sun, Yunlv; Zhang, Xianbo; Jiang, Dongneng; Zhou, Linyan; Wang, Deshou

2014-01-01

Studies of gene function in non-model animals have been limited by the approaches available for eliminating gene function. The CRISPR/Cas9 (clustered regularly interspaced short palindromic repeats/CRISPR associated) system has recently become a powerful tool for targeted genome editing. Here, we report the use of the CRISPR/Cas9 system to disrupt selected genes, including nanos2, nanos3, dmrt1, and foxl2, with efficiencies as high as 95%. In addition, mutations in dmrt1 and foxl2 induced by CRISPR/Cas9 were efficiently transmitted through the germline to F1. Obvious phenotypes were observed in the G0 generation after mutation of germ cell or somatic cell-specific genes. For example, loss of Nanos2 and Nanos3 in XY and XX fish resulted in germ cell-deficient gonads as demonstrated by GFP labeling and Vasa staining, respectively, while masculinization of somatic cells in both XY and XX gonads was demonstrated by Dmrt1 and Cyp11b2 immunohistochemistry and by up-regulation of serum androgen levels. Our data demonstrate that targeted, heritable gene editing can be achieved in tilapia, providing a convenient and effective approach for generating loss-of-function mutants. Furthermore, our study shows the utility of the CRISPR/Cas9 system for genetic engineering in non-model species like tilapia and potentially in many other teleost species. PMID:24709635

Better Targeting, Better Efficiency for Wide-scale Neuronal Transduction with the Synapsin Promoter and AAV-PHP.B

Directory of Open Access Journals (Sweden)

Kasey L Jackson

2016-11-01

Full Text Available Widespread genetic modification of cells in the central nervous system (CNS with a viral vector has become possible and increasingly more efficient. We previously applied an AAV9 vector with the cytomegalovirus/chicken beta-actin hybrid (CBA promoter and achieved wide-scale CNS transduction in neonatal and adult rats. However, this method transduces a variety of tissues in addition to the CNS. Thus we studied intravenous AAV9 gene transfer with a synapsin promoter to better target the neurons. We noted in systematic comparisons that the synapsin promoter drives lower level expression than does the CBA promoter. The engineered AAV-PHP.B serotype was compared with AAV9, and AAV-PHP.B did enhance the efficiency of expression. Combining the synapsin promoter with AAV-PHP.B could therefore be advantageous in terms of combining two refinements of targeting and efficiency. Wide-scale expression was used to model a disease with widespread pathology. Vectors encoding the amyotrophic lateral sclerosis (ALS-related protein TDP-43 with the synapsin promoter and AAV-PHP.B were used for efficient CNS-targeted TDP-43 expression. Intracerebroventricular injections were also explored to limit TDP-43 expression to the CNS. The neuron-selective promoter and the AAV-PHP.B enhanced gene transfer and ALS disease modeling in adult rats.

Efficient and Adaptive Node Selection for Target Tracking in Wireless Sensor Network

Directory of Open Access Journals (Sweden)

Juan Feng

2016-01-01

Full Text Available In target tracking wireless sensor network, choosing the proper working nodes can not only minimize the number of active nodes, but also satisfy the tracking reliability requirement. However, most existing works focus on selecting sensor nodes which are the nearest to the target for tracking missions and they did not consider the correlation of the location of the sensor nodes so that these approaches can not meet all the goals of the network. This work proposes an efficient and adaptive node selection approach for tracking a target in a distributed wireless sensor network. The proposed approach combines the distance-based node selection strategy and particle filter prediction considering the spatial correlation of the different sensing nodes. Moreover, a joint distance weighted measurement is proposed to estimate the information utility of sensing nodes. Experimental results show that EANS outperformed the state-of-the-art approaches by reducing the energy cost and computational complexity as well as guaranteeing the tracking accuracy.

Receptor-targeted liposome-peptide-siRNA nanoparticles represent an efficient delivery system for MRTF silencing in conjunctival fibrosis.

Science.gov (United States)

Yu-Wai-Man, Cynthia; Tagalakis, Aristides D; Manunta, Maria D; Hart, Stephen L; Khaw, Peng T

2016-02-24

There is increasing evidence that the Myocardin-related transcription factor/Serum response factor (MRTF/SRF) pathway plays a key role in fibroblast activation and that knocking down MRTF can lead to reduced scarring and fibrosis. Here, we have developed a receptor-targeted liposome-peptide-siRNA nanoparticle as a non-viral delivery system for MRTF-B siRNA in conjunctival fibrosis. Using 50 nM siRNA, the MRTF-B gene was efficiently silenced by 76% and 72% with LYR and LER nanoparticles, respectively. The silencing efficiency was low when non-targeting peptides or siRNA alone or liposome-siRNA alone were used. LYR and LER nanoparticles also showed higher silencing efficiency than PEGylated LYR-P and LER-P nanoparticles. The nanoparticles were not cytotoxic using different liposomes, targeting peptides, and 50 nM siRNA. Three-dimensional fibroblast-populated collagen matrices were also used as a functional assay to measure contraction in vitro, and showed that MRTF-B LYR nanoparticles completely blocked matrix contraction after a single transfection treatment. In conclusion, this is the first study to develop and show that receptor-targeted liposome-peptide-siRNA nanoparticles represent an efficient and safe non-viral siRNA delivery system that could be used to prevent fibrosis after glaucoma filtration surgery and other contractile scarring conditions in the eye.

Efficient reconstruction of contaminant release history

Energy Technology Data Exchange (ETDEWEB)

Alezander, Francis [Los Alamos National Laboratory; Anghel, Marian [Los Alamos National Laboratory; Gulbahce, Natali [NON LANL; Tartakovsky, Daniel [NON LANL

2009-01-01

We present a generalized hybrid Monte Carlo (GHMC) method for fast, statistically optimal reconstruction of release histories of reactive contaminants. The approach is applicable to large-scale, strongly nonlinear systems with parametric uncertainties and data corrupted by measurement errors. The use of discrete adjoint equations facilitates numerical implementation of GHMC, without putting any restrictions on the degree of nonlinearity of advection-dispersion-reaction equations that are used to described contaminant transport in the subsurface. To demonstrate the salient features of the proposed algorithm, we identify the spatial extent of a distributed source of contamination from concentration measurements of a reactive solute.

Fabrication and Evaluation of Tinidazole Microbeads for Colon Targeting

Directory of Open Access Journals (Sweden)

Amit K. Pandey

2012-05-01

Full Text Available Objective: The purpose of present investigation was to develop and evaluate multiparticulate system exploiting pH-sensitive property and specific biodegradability of calcium alginate microbeads, for colon- targeted delivery of Tinidazole for the treatment of amoebic colitis. Methods: Calcium alginate beads containing Tinidazole were prepared by ionotropic gelation technique followed by coating with Eudragit S100 using solvent evaporation method to obtain pH sensitive microbeads. Various formulation parameters were optimized which included concentration of sodium alginate (2% w/v, curing time (20 min and concentration of pectin (1% w/ v. All the formulations were evaluated for surface morphology, particle size analysis, entrapment efficiency and in-vitro drug release in conditions simulating colonic fluid in the presence of rat caecal (2% w/v content. Results: The average size of beads of optimized formulation (FT4 was found to be 998.73依5.12 毺 m with entrapment efficiency of 87.28依2.19 %. The invitro release of Eudragit S100 coated beads in presence of rat caecal content was found to be 70.73%依1.91% in 24 hours. Data of in-vitro release was fitted into Higuchi kinetics and Korsmeyer Peppas equation to explain release profile. The optimized formulation (FT4 showed zero order release. Conclusions: It is concluded that calcium alginate microbeads are the potential system for colon delivery of Tinidazole for chemotherapy of amoebic infection.

Optimization of LDL targeted nanostructured lipid carriers of 5-FU by a full factorial design.

Science.gov (United States)

Andalib, Sare; Varshosaz, Jaleh; Hassanzadeh, Farshid; Sadeghi, Hojjat

2012-01-01

Nanostructured lipid carriers (NLC) are a mixture of solid and liquid lipids or oils as colloidal carrier systems that lead to an imperfect matrix structure with high ability for loading water soluble drugs. The aim of this study was to find the best proportion of liquid and solid lipids of different types for optimization of the production of LDL targeted NLCs used in carrying 5-Fu by the emulsification-solvent evaporation method. The influence of the lipid type, cholesterol or cholesteryl stearate for targeting LDL receptors, oil type (oleic acid or octanol), lipid and oil% on particle size, surface charge, drug loading efficiency, and drug released percent from the NLCs were studied by a full factorial design. The NLCs prepared by 54.5% cholesterol and 25% of oleic acid, showed optimum results with particle size of 105.8 nm, relatively high zeta potential of -25 mV, drug loading efficiency of 38% and release efficiency of about 40%. Scanning electron microscopy of nanoparticles confirmed the results of dynamic light scattering method used in measuring the particle size of NLCs. The optimization method by a full factorial statistical design is a useful optimization method for production of nanostructured lipid carriers.

Efficient VEGF targeting delivery of DOX using Bevacizumab conjugated SiO2@LDH for anti-neuroblastoma therapy.

Science.gov (United States)

Zhu, Rongrong; Wang, Zhaoqi; Liang, Peng; He, Xiaolie; Zhuang, Xizhen; Huang, Ruiqi; Wang, Mei; Wang, Qigang; Qian, Yechang; Wang, Shilong

2017-11-01

Vascular endothelial growth factor (VEGF) plays an important role in angiogenesis and is highly expressed in carcinoma, which make it an important target for tumor targeting therapy. Neuroblastoma is the main cause for cancer-related death in children. Like most solid tumors, it is also accompanied with the overexpression of VEGF. Doxorubicin Hydrochloride (DOX), a typical chemotherapeutic agent, exhibits efficient anticancer activities for various cancers. However, DOX, without targeting ability, usually causes severe damage to normal tissues. To overcome the shortages, we designed a novel nano-composite, which is Bevacizumab (Bev) modified SiO 2 @LDH nanoparticles (SiO 2 @LDH-Bev), loading with DOX to achieve targeting ability and curative efficiency. SiO 2 @LDH-DOX and SiO 2 @LDH-Bev-DOX nanoparticles were synthesized and the physicochemical properties were characterized by TEM detection, Zeta potential analysis, FTIR, Raman and XPS analysis. Then in vitro and in vivo anti-neuroblastoma efficiency, targeting ability and mechanisms of anti-carcinoma and anti-angiogenesis of SiO 2 @LDH-Bev-DOX were explored. Our results indicated that we obtained the core-shell structure SiO 2 @LDH-Bev with an average diameter of 253±10nm and the amount of conjugated Bev was 4.59±0.38μg/mg SiO 2 @LDH-Bev. SiO 2 @LDH-Bev-DOX could improve the cellular uptake and the targeting effect of DOX to brain and tumor, enhance the anti-neuroblastoma and anti-angiogenesis efficiency both in vitro and in vivo, and alleviate side effects of DOX sharply, especially hepatic injury. In addition, we also demonstrated that angiogenesis inhibitory effect was mediated by DOX and VEGF triggered signal pathways, including PI3K/Akt, Raf/MEK/ERK, and adhesion related pathways. In summary, SiO 2 @LDH-Bev could be a potential VEGF targeting nanocarrier applied in VEGF positive cancer therapy. This paper explored that a novel core-shell structure nanomaterial SiO 2 @LDH and modified SiO 2 @LDH with

The critical role of the industrial sector in reaching long-term emission reduction, energy efficiency and renewable targets

International Nuclear Information System (INIS)

Fais, Birgit; Sabio, Nagore; Strachan, Neil

2016-01-01

Highlights: • A new industrial modelling approach in a whole energy systems model is developed. • The contribution of UK industry to long-term energy policy targets is analysed. • Emission reductions of up to 77% can be achieved in the UK industry until 2050. • The UK industry sector is essential for achieving the overall efficiency commitments. • UK industry can make a moderate contribution to the expansion of renewable energies. - Abstract: This paper evaluates the critical contribution of the industry sector to long-term decarbonisation, efficiency and renewable energy policy targets. Its methodological novelty is the incorporation of a process-oriented modelling approach based on a comprehensive technology database for the industry sector in a national energy system model for the UK (UKTM), allowing quantification of the role of both decarbonisation of upstream energy vectors and of mitigation options in the industrial sub-categories. This enhanced model is then applied in a comparative policy scenario analysis that explores various target dimensions on emission mitigation, renewable energy and energy efficiency at both a national and European level. The results show that ambitious emission cuts in the industry sector of up to 77% until 2050 compared to 2010 can be achieved. Moreover, with a reduction in industrial energy demand of up to 31% between 2010 and 2050, the sector is essential for achieving the overall efficiency commitments. The industry sector also makes a moderate contribution to the expansion of renewable energies mostly through the use of biomass for low-temperature heating services. However, additional sub-targets on renewable sources and energy efficiency need to be assessed critically, as they can significantly distort the cost-efficiency of the long-term mitigation pathway.

Cancer Nanomedicine: From Targeted Delivery to Combination Therapy

Science.gov (United States)

Xu, Xiaoyang; Ho, William; Zhang, Xueqing; Bertrand, Nicolas; Farokhzad, Omid

2015-01-01

The advent of nanomedicine marks an unparalleled opportunity to advance the treatment of a variety of diseases, including cancer. The unique properties of nanoparticles, such as large surface-to volume ratio, small size, the ability to encapsulate a variety of drugs, and tunable surface chemistry, gives them many advantages over their bulk counterparts. This includes multivalent surface modification with targeting ligands, efficient navigation of the complex in vivo environment, increased intracellular trafficking, and sustained release of drug payload. These advantages make nanoparticles a mode of treatment potentially superior to conventional cancer therapies. This article highlights the most recent developments in cancer treatment using nanoparticles as drug-delivery vehicles, including promising opportunities in targeted and combination therapy. PMID:25656384

Efficient and robust identification of cortical targets in concurrent TMS-fMRI experiments

Science.gov (United States)

Yau, Jeffrey M.; Hua, Jun; Liao, Diana A.; Desmond, John E.

2014-01-01

Transcranial magnetic stimulation (TMS) can be delivered during fMRI scans to evoke BOLD responses in distributed brain networks. While concurrent TMS-fMRI offers a potentially powerful tool for non-invasively investigating functional human neuroanatomy, the technique is currently limited by the lack of methods to rapidly and precisely localize targeted brain regions – a reliable procedure is necessary for validly relating stimulation targets to BOLD activation patterns, especially for cortical targets outside of motor and visual regions. Here we describe a convenient and practical method for visualizing coil position (in the scanner) and identifying the cortical location of TMS targets without requiring any calibration or any particular coil-mounting device. We quantified the precision and reliability of the target position estimates by testing the marker processing procedure on data from 9 scan sessions: Rigorous testing of the localization procedure revealed minimal variability in coil and target position estimates. We validated the marker processing procedure in concurrent TMS-fMRI experiments characterizing motor network connectivity. Together, these results indicate that our efficient method accurately and reliably identifies TMS targets in the MR scanner, which can be useful during scan sessions for optimizing coil placement and also for post-scan outlier identification. Notably, this method can be used generally to identify the position and orientation of MR-compatible hardware placed near the head in the MR scanner. PMID:23507384

Paclitaxel molecularly imprinted polymer-PEG-folate nanoparticles for targeting anticancer delivery: Characterization and cellular cytotoxicity

International Nuclear Information System (INIS)

Esfandyari-Manesh, Mehdi; Darvishi, Behrad; Ishkuh, Fatemeh Azizi; Shahmoradi, Elnaz; Mohammadi, Ali; Javanbakht, Mehran; Dinarvand, Rassoul; Atyabi, Fatemeh

2016-01-01

The aim of this work was to synthesize molecularly imprinted polymer-poly ethylene glycol-folic acid (MIP-PEG-FA) nanoparticles for use as a controlled release carrier for targeting delivery of paclitaxel (PTX) to cancer cells. MIP nanoparticles were synthesized by a mini-emulsion polymerization technique and then PEG-FA was conjugated to the surface of nanoparticles. Nanoparticles showed high drug loading and encapsulation efficiency, 15.6 ± 0.8 and 100%, respectively. The imprinting efficiency of MIPs was evaluated by binding experiments in human serum. Good selective binding and recognition were found in MIP nanoparticles. In vitro drug release studies showed that MIP-PEG-FA have a controlled release of PTX, because of the presence of imprinted sites in the polymeric structure, which makes it is suitable for sustained drug delivery. The drug release from polymeric nanoparticles was indeed higher at acidic pH. The molecular structure of MIP-PEG-FA was confirmed by Hydrogen-Nuclear Magnetic Resonance (H NMR), Fourier Transform InfraRed (FT-IR), and Attenuated Total Reflection (ATR) spectroscopy, and their thermal behaviors by Differential Scanning Calorimetry (DSC) and Thermogravimetric Analysis (TGA). Scanning Electron Microscopy (SEM) and Photon Correlation Spectroscopy (PCS) results showed that nanoparticles have a smooth surface and spherical shape with an average size of 181 nm. MIP-PEG-FA nanoparticles showed a greater amount of intracellular uptake in folate receptor-positive cancer cells (MDA-MB-231 cells) in comparison with the non-folate nanoparticles and free PTX, with half maximal inhibitory concentrations (IC_5_0) of 4.9 ± 0.9, 7.4 ± 0.5 and 32.8 ± 3.8 nM, respectively. These results suggest that MIP-PEG-FA nanoparticles could be a potentially useful drug carrier for targeting drug delivery to cancer cells. - Highlights: • MIP-PEG-FA was synthesized as a controlled release carrier for targeting delivery to cancerous cells. • Nanoparticles

Paclitaxel molecularly imprinted polymer-PEG-folate nanoparticles for targeting anticancer delivery: Characterization and cellular cytotoxicity

Energy Technology Data Exchange (ETDEWEB)

Esfandyari-Manesh, Mehdi [Nanotechnology Research Center,Tehran University of Medical Sciences, Tehran (Iran, Islamic Republic of); Department of Chemistry, Amirkabir University of Technology, Tehran (Iran, Islamic Republic of); Darvishi, Behrad [Nanotechnology Research Center,Tehran University of Medical Sciences, Tehran (Iran, Islamic Republic of); Ishkuh, Fatemeh Azizi [Department of Chemistry, Amirkabir University of Technology, Tehran (Iran, Islamic Republic of); Shahmoradi, Elnaz [Department of Chemical Engineering, Sharif University of Technology, Tehran (Iran, Islamic Republic of); Mohammadi, Ali [Nanotechnology Research Center,Tehran University of Medical Sciences, Tehran (Iran, Islamic Republic of); Department of Drug and Food Control, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran (Iran, Islamic Republic of); Javanbakht, Mehran [Department of Chemistry, Amirkabir University of Technology, Tehran (Iran, Islamic Republic of); Dinarvand, Rassoul [Nanotechnology Research Center,Tehran University of Medical Sciences, Tehran (Iran, Islamic Republic of); Atyabi, Fatemeh, E-mail: atyabifa@tums.ac.ir [Nanotechnology Research Center,Tehran University of Medical Sciences, Tehran (Iran, Islamic Republic of)

2016-05-01

The aim of this work was to synthesize molecularly imprinted polymer-poly ethylene glycol-folic acid (MIP-PEG-FA) nanoparticles for use as a controlled release carrier for targeting delivery of paclitaxel (PTX) to cancer cells. MIP nanoparticles were synthesized by a mini-emulsion polymerization technique and then PEG-FA was conjugated to the surface of nanoparticles. Nanoparticles showed high drug loading and encapsulation efficiency, 15.6 ± 0.8 and 100%, respectively. The imprinting efficiency of MIPs was evaluated by binding experiments in human serum. Good selective binding and recognition were found in MIP nanoparticles. In vitro drug release studies showed that MIP-PEG-FA have a controlled release of PTX, because of the presence of imprinted sites in the polymeric structure, which makes it is suitable for sustained drug delivery. The drug release from polymeric nanoparticles was indeed higher at acidic pH. The molecular structure of MIP-PEG-FA was confirmed by Hydrogen-Nuclear Magnetic Resonance (H NMR), Fourier Transform InfraRed (FT-IR), and Attenuated Total Reflection (ATR) spectroscopy, and their thermal behaviors by Differential Scanning Calorimetry (DSC) and Thermogravimetric Analysis (TGA). Scanning Electron Microscopy (SEM) and Photon Correlation Spectroscopy (PCS) results showed that nanoparticles have a smooth surface and spherical shape with an average size of 181 nm. MIP-PEG-FA nanoparticles showed a greater amount of intracellular uptake in folate receptor-positive cancer cells (MDA-MB-231 cells) in comparison with the non-folate nanoparticles and free PTX, with half maximal inhibitory concentrations (IC{sub 50}) of 4.9 ± 0.9, 7.4 ± 0.5 and 32.8 ± 3.8 nM, respectively. These results suggest that MIP-PEG-FA nanoparticles could be a potentially useful drug carrier for targeting drug delivery to cancer cells. - Highlights: • MIP-PEG-FA was synthesized as a controlled release carrier for targeting delivery to cancerous cells. • Nanoparticles

The gas release programs to increase competition in the European gas market

International Nuclear Information System (INIS)

Clastres, Cedric

2005-01-01

Regulators have implemented asymmetric regulation measures, such as gas release programs and market share targets, because of European gas supply features and gas market specificities. Empirical experiences show in line with economic theory that these regulation measures favour entry and competition without deterring investments. If we look at impacts on competition, they are mitigated. Some positive effects result from the increase in consumption or in importation and transportation infrastructure developments. But these regulations can also encourage anti-competitive behaviours like collusion, cream-skimming, reverse cherry picking or inefficient entries. Gas release measures establish a link between the incumbent and its competitors. A system of constraints on operators capacities can also appear. Thus, pricing or quantity strategies are more complex. Equilibrium prices are more volatile and very different of competition mark-up. The incumbent, for high gas release quantities and low supplies, can increase its costs to make more profit. This Raising Rivals' Costs strategy often occur if the gas release price is closer to supply costs. This strategy does not impact on consumers surplus but decreases welfare. The regulator can restore incentives to efficiency by setting gas release proportion function of incumbent's supplies. This proportion must be high enough to have a positive impact on the market because of incumbent's incentives to efficiency and greater total quantities sold by the two operators. But, on another way, it must not be too high as it could, thus, increase the probability of Raising Rivals' Costs or favour collusive strategies. (author) [fr

TALE nickase mediates high efficient targeted transgene integration at the human multi-copy ribosomal DNA locus.

Science.gov (United States)

Wu, Yong; Gao, Tieli; Wang, Xiaolin; Hu, Youjin; Hu, Xuyun; Hu, Zhiqing; Pang, Jialun; Li, Zhuo; Xue, Jinfeng; Feng, Mai; Wu, Lingqian; Liang, Desheng

2014-03-28

Although targeted gene addition could be stimulated strikingly by a DNA double strand break (DSB) created by either zinc finger nucleases (ZFNs) or TALE nucleases (TALENs), the DSBs are really mutagenic and toxic to human cells. As a compromised solution, DNA single-strand break (SSB) or nick has been reported to mediate high efficient gene addition but with marked reduction of random mutagenesis. We previously demonstrated effective targeted gene addition at the human multicopy ribosomal DNA (rDNA) locus, a genomic safe harbor for the transgene with therapeutic potential. To improve the transgene integration efficiency by using TALENs while lowering the cytotoxicity of DSBs, we created both TALENs and TALE nickases (TALENickases) targeting this multicopy locus. A targeting vector which could integrate a GFP cassette at the rDNA locus was constructed and co-transfected with TALENs or TALENickases. Although the fraction of GFP positive cells using TALENs was greater than that using TALENickases during the first few days after transfection, it reduced to a level less than that using TALENickases after continuous culture. Our findings showed that the TALENickases were more effective than their TALEN counterparts at the multi-copy rDNA locus, though earlier studies using ZFNs and ZFNickases targeting the single-copy loci showed the reverse. Besides, TALENickases mediated the targeted integration of a 5.4 kb fragment at a frequency of up to 0.62% in HT1080 cells after drug selection, suggesting their potential application in targeted gene modification not being limited at the rDNA locus. Copyright © 2014 Elsevier Inc. All rights reserved.

Efficient Subcellular Targeting to the Cell Nucleus of Quantum Dots Densely Decorated with a Nuclear Localization Sequence Peptide.

Science.gov (United States)

Maity, Amit Ranjan; Stepensky, David

2016-01-27

Organelle-targeted drug delivery can enhance the efficiency of the intracellularly acting drugs and reduce their toxicity. We generated core-shell type CdSe-ZnS quantum dots (QDs) densely decorated with NLS peptidic targeting residues using a 3-stage decoration approach and investigated their endocytosis and nuclear targeting efficiencies. The diameter of the generated QDs increased following the individual decoration stages (16.3, 18.9, and 21.9 nm), the ζ-potential became less negative (-33.2, -17.5, and -11.9 mV), and characteristic changes appeared in the FTIR spectra following decoration with the linker and NLS peptides. Quantitative analysis of the last decoration stage revealed that 37.9% and 33.2% of the alkyne-modified NLS groups that were added to the reaction mix became covalently attached or adsorbed to the QDs surface, respectively. These numbers correspond to 63.6 and 55.7 peptides conjugated or adsorbed to a single QD (the surface density of 42 and 37 conjugated and adsorbed peptides per 1000 nm(2) of the QDs surface), which is higher than in the majority of previous studies that reported decoration efficiencies of formulations intended for nuclear-targeted drug delivery. QDs decorated with NLS peptides undergo more efficient endocytosis, as compared to other investigated QDs formulations, and accumulated to a higher extent in the cell nucleus or in close vicinity to it (11.9%, 14.6%, and 56.1% of the QDs endocytosed by an average cell for the QD-COOH, QD-azide, and QD-NLS formulations, respectively). We conclude that dense decoration of QDs with NLS residues increased their endocytosis and led to their nuclear targeting (preferential accumulation in the cells nuclei or in close vicinity to them). The experimental system and research tools that were used in this study allow quantitative investigation of the mechanisms that govern the QDs nuclear targeting and their dependence on the formulation properties. These findings will contribute to the

Better Targeting, Better Efficiency for Wide-Scale Neuronal Transduction with the Synapsin Promoter and AAV-PHP.B.

Science.gov (United States)

Jackson, Kasey L; Dayton, Robert D; Deverman, Benjamin E; Klein, Ronald L

2016-01-01

Widespread genetic modification of cells in the central nervous system (CNS) with a viral vector has become possible and increasingly more efficient. We previously applied an AAV9 vector with the cytomegalovirus/chicken beta-actin (CBA) hybrid promoter and achieved wide-scale CNS transduction in neonatal and adult rats. However, this method transduces a variety of tissues in addition to the CNS. Thus we studied intravenous AAV9 gene transfer with a synapsin promoter to better target the neurons. We noted in systematic comparisons that the synapsin promoter drives lower level expression than does the CBA promoter. The engineered adeno-associated virus (AAV)-PHP.B serotype was compared with AAV9, and AAV-PHP.B did enhance the efficiency of expression. Combining the synapsin promoter with AAV-PHP.B could therefore be advantageous in terms of combining two refinements of targeting and efficiency. Wide-scale expression was used to model a disease with widespread pathology. Vectors encoding the amyotrophic lateral sclerosis (ALS)-related protein transactive response DNA-binding protein, 43 kDa (TDP-43) with the synapsin promoter and AAV-PHP.B were used for efficient CNS-targeted TDP-43 expression. Intracerebroventricular injections were also explored to limit TDP-43 expression to the CNS. The neuron-selective promoter and the AAV-PHP.B enhanced gene transfer and ALS disease modeling in adult rats.

Controlled Release Urea as a Nitrogen Source for Spring Wheat in Western Canada: Yield, Grain N Content, and N Use Efficiency

Directory of Open Access Journals (Sweden)

Lenz Haderlein

2001-01-01

Full Text Available Controlled release nitrogen (N fertilizers have been commonly used in horticultural applications such as turf grasses and container-grown woody perennials. Agrium, a major N manufacturer in North and South America, is developing a low-cost controlled release urea (CRU product for use in field crops such as grain corn, canola, wheat, and other small grain cereals. From 1998 to 2000, 11 field trials were conducted across western Canada to determine if seed-placed CRU could maintain crop yields and increase grain N and N use efficiency when compared to the practice of side-banding of urea N fertilizer. CRU was designed to release timely and adequate, but not excessive, amounts of N to the crop. Crop uptake of N from seed-placed CRU was sufficient to provide yields similar to those of side-banded urea N. Grain N concentrations of the CRU treatments were higher, on average, than those from side-banded urea, resulting in 4.2% higher N use efficiency across the entire N application range from 25 to 100 kg ha-1. Higher levels of removal of N in grain from CRU compared to side-banded urea can result in less residual N remaining in the soil, and limit the possibility of N losses due to denitrification and leaching.

Magnetic graphene oxide as a carrier for targeted delivery of chemotherapy drugs in cancer therapy

Energy Technology Data Exchange (ETDEWEB)

Huang, Ya-Shu [Department of Chemical and Materials Engineering, Chang Gung University, Kwei-San, Taoyuan 33302, Taiwan, ROC (China); Lu, Yu-Jen [Department of Neurosurgery, Chang Gung Memorial Hospital, Kwei-San, Taoyuan 33305, Taiwan, ROC (China); Chen, Jyh-Ping, E-mail: jpchen@mail.cgu.edu.tw [Department of Chemical and Materials Engineering, Chang Gung University, Kwei-San, Taoyuan 33302, Taiwan, ROC (China); Department of Plastic and Reconstructive Surgery and Craniofacial Research Center, Chang Gung Memorial Hospital, Kwei-San, Taoyuan 33305, Taiwan, ROC (China); Graduate Institute of Health Industry and Technology, Research Center for Industry of Human Ecology, Chang Gung University of Science and Technology, Kwei-San, Taoyuan 33302, Taiwan, ROC (China); Department of Materials Engineering, Ming Chi University of Technology, Tai-Shan, New Taipei City 24301, Taiwan, ROC (China)

2017-04-01

A magnetic targeted functionalized graphene oxide (GO) complex is constituted as a nanocarrier for targeted delivery and pH-responsive controlled release of chemotherapy drugs to cancer cells. Magnetic graphene oxide (mGO) was prepared by chemical co-precipitation of Fe{sub 3}O{sub 4} magnetic nanoparticles on GO nano-platelets. The mGO was successively modified by chitosan and mPEG-NHS through covalent bindings to synthesize mGOC-PEG. The polyethylene glycol (PEG) moiety is expected to prolong the circulation time of mGO by reducing the reticuloendothelial system clearance. Irinotecan (CPT-11) or doxorubicin (DOX) was loaded to mGOC-PEG through π-π stacking interactions for magnetic targeted delivery of the cancer chemotherapy drug. The best values of loading efficiency and loading content of CPT-11 were 54% and 2.7% respectively; whereas for DOX, they were 65% and 393% The pH-dependent drug release profile was further experimented at different pHs, in which ~60% of DOX was released at pH 5.4 and ~10% was released at pH 7.4. In contrast, ~90% CPT-11 was released at pH 5.4 and ~70% at pH 7.4. Based on the drug loading and release characteristics, mGOC-PEG/DOX was further chosen for in vitro cytotoxicity tests against U87 human glioblastoma cell line. The IC50 value of mGOC-PEG/DOX was found to be similar to that of free DOX but was reduced dramatically when subject to magnetic targeting. It is concluded that with the high drug loading and pH-dependent drug release properties, mGOC-PEG will be a promising drug carrier for targeted delivery of chemotherapy drugs in cancer therapy. - Highlights: • mGO was prepared by chemical co-precipitation of Fe{sub 3}O{sub 4} MNP on GO nano-platelets. • mGO was further modified by chitosan and mPEG-NHS to synthesize mGOC-PEG. • mGOC-PEG showed higher drug loading of doxorubicin (DOX) than irinotecan. • mGOC-PEG showed pH-responsive controlled release of chemotherapy drugs. • Magnetic targeting enhanced cytotoxicity of

Magnetic graphene oxide as a carrier for targeted delivery of chemotherapy drugs in cancer therapy

International Nuclear Information System (INIS)

Huang, Ya-Shu; Lu, Yu-Jen; Chen, Jyh-Ping

2017-01-01

A magnetic targeted functionalized graphene oxide (GO) complex is constituted as a nanocarrier for targeted delivery and pH-responsive controlled release of chemotherapy drugs to cancer cells. Magnetic graphene oxide (mGO) was prepared by chemical co-precipitation of Fe 3 O 4 magnetic nanoparticles on GO nano-platelets. The mGO was successively modified by chitosan and mPEG-NHS through covalent bindings to synthesize mGOC-PEG. The polyethylene glycol (PEG) moiety is expected to prolong the circulation time of mGO by reducing the reticuloendothelial system clearance. Irinotecan (CPT-11) or doxorubicin (DOX) was loaded to mGOC-PEG through π-π stacking interactions for magnetic targeted delivery of the cancer chemotherapy drug. The best values of loading efficiency and loading content of CPT-11 were 54% and 2.7% respectively; whereas for DOX, they were 65% and 393% The pH-dependent drug release profile was further experimented at different pHs, in which ~60% of DOX was released at pH 5.4 and ~10% was released at pH 7.4. In contrast, ~90% CPT-11 was released at pH 5.4 and ~70% at pH 7.4. Based on the drug loading and release characteristics, mGOC-PEG/DOX was further chosen for in vitro cytotoxicity tests against U87 human glioblastoma cell line. The IC50 value of mGOC-PEG/DOX was found to be similar to that of free DOX but was reduced dramatically when subject to magnetic targeting. It is concluded that with the high drug loading and pH-dependent drug release properties, mGOC-PEG will be a promising drug carrier for targeted delivery of chemotherapy drugs in cancer therapy. - Highlights: • mGO was prepared by chemical co-precipitation of Fe 3 O 4 MNP on GO nano-platelets. • mGO was further modified by chitosan and mPEG-NHS to synthesize mGOC-PEG. • mGOC-PEG showed higher drug loading of doxorubicin (DOX) than irinotecan. • mGOC-PEG showed pH-responsive controlled release of chemotherapy drugs. • Magnetic targeting enhanced cytotoxicity of m

Nitrogen release, tree uptake, and ecosystem retention in a mid-rotation loblolly pine plantation following fertilization with 15N-enriched enhanced efficiency fertilizers.

OpenAIRE

Werner, Amy

2013-01-01

Nitrogen is the most frequently limiting nutrient in southern pine plantations.  Previous studies found that only 10 to 25% of applied urea fertilizer N is taken up by trees.  Enhanced efficiency fertilizers could increase tree uptake efficiency by controlling the release of N and/or stabilize N.  Three enhanced efficiency fertilizers were selected as a representation of fertilizers that could be used in forestry: 1) NBPT treated urea (NBPT urea), 2) polymer coated urea (PC urea), and 3) mono...

Fast and efficient three-step target-specific curing of a virulence plasmid in Salmonella enterica.

Science.gov (United States)

de Moraes, Marcos H; Teplitski, Max

2015-12-01

Virulence plasmids borne by serovars of Salmonella enterica carry genes involved in its pathogenicity, as well as other functions. Characterization of phenotypes associated with virulence plasmids requires a system for efficiently curing strains of their virulence plasmids. Here, we developed a 3-step protocol for targeted curing of virulence plasmids. The protocol involves insertion of an I-SecI restriction site linked to an antibiotic resistance gene into the target plasmid using λ-Red mutagenesis, followed by the transformation with a temperature-sensitive auxiliary plasmid which carries I-SecI nuclease expressed from a tetracycline-inducible promoter. Finally, the auxiliary plasmid is removed by incubation at 42 °C and the plasmid-less strains are verified on antibiotic-containing media. This method is fast and very efficient: over 90 % of recovered colonies lacked their virulence plasmid.

Pathways for the release of polonium from a lead-bismuth spallation target (thermochemical calculation); Verfluechtigungspfade des Poloniums aus einem Pb-Bi-Spallationstarget (Thermochemische Kalkulation)

Energy Technology Data Exchange (ETDEWEB)

Eichler, B.; Neuhausen, J

2004-06-01

An analysis of literature data for the thermochemical constants of polonium reveals considerable discrepancies in the relations of these data among each other as well as in their expected trends within the chalcogen group. This fact hinders a reliable assessment of possible reaction paths for the release of polonium from a liquid lead-bismuth spallation target. In this work an attempt is made to construct a coherent data set for the thermochemical properties of polonium and some of its compounds that are of particular importance with respect to the behaviour of polonium in a liquid Pb-Bi target. This data set is based on extrapolations using general trends throughout the periodic table and, in particular, within the chalcogen group. Consequently, no high accuracy should be attributed to the derived data set. However, the data set derived in this work is consistent with definitely known experimental data. Furthermore, it complies with the general trends of physicochemical properties within the chalcogen group. Finally, well known relations between thermochemical quantities are fulfilled by the data derived in this work. Thus, given the lack of accurate experimental data it can be regarded as best available data. Thermochemical constants of polonium hydride, lead polonide and polonium dioxide are derived based on extrapolative procedures. Furthermore, the possibility of formation of the gaseous intermetallic molecule BiPo, which has been omitted from discussion up to now, is investigated. From the derived thermochemical data the equilibrium constants of formation, release and dissociation reactions are calculated for different polonium containing species. Furthermore equilibrium constants are determined for the reaction of lead polonide and polonium dioxide with hydrogen, water vapour and the target components lead and bismuth. The most probable release pathways are discussed. From thermochemical evaluations polonium is expected to be released from liquid lead

pH responsive controlled release of anti-cancer hydrophobic drugs from sodium alginate and hydroxyapatite bi-coated iron oxide nanoparticles.

Science.gov (United States)

Manatunga, Danushika C; de Silva, Rohini M; de Silva, K M Nalin; de Silva, Nuwan; Bhandari, Shiva; Yap, Yoke Khin; Costha, N Pabakara

2017-08-01

Developing a drug carrier system which could perform targeted and controlled release over a period of time is utmost concern in the pharmaceutical industry. This is more relevant when designing drug carriers for poorly water soluble drug molecules such as curcumin and 6-gingerol. Development of a drug carrier system which could overcome these limitations and perform controlled and targeted drug delivery is beneficial. This study describes a promising approach for the design of novel pH sensitive sodium alginate, hydroxyapatite bilayer coated iron oxide nanoparticle composite (IONP/HAp-NaAlg) via the co-precipitation approach. This system consists of a magnetic core for targeting and a NaAlg/HAp coating on the surface to accommodate the drug molecules. The nanocomposite was characterized using FT-IR spectroscopy, X-ray diffraction, scanning electron microscopy, transmission electron microscopy and thermogravimetric analysis. The loading efficiency and loading capacity of curcumin and 6-gingerol were examined. In vitro drug releasing behavior of curcumin and 6-gingerol was studied at pH 7.4 and pH 5.3 over a period of seven days at 37°C. The mechanism of drug release from the nanocomposite of each situation was studied using kinetic models and the results implied that, the release is typically via diffusion and a higher release was observed at pH 5.3. This bilayer coated system can be recognized as a potential drug delivery system for the purpose of curcumin and 6-gingerol release in targeted and controlled manner to treat diseases such as cancer. Copyright © 2017 Elsevier B.V. All rights reserved.

Selection of targets and ion sources for RIB generation at the Holifield Radioactive Ion Beam Facility

International Nuclear Information System (INIS)

Alton, G.D.

1995-01-01

In this report, the authors describe the performance characteristics for a selected number of target ion sources that will be employed for initial use at the Holifield Radioactive Ion Beam Facility (HRIBF) as well as prototype ion sources that show promise for future use for RIB applications. A brief review of present efforts to select target materials and to design composite target matrix/heat-sink systems that simultaneously incorporate the short diffusion lengths, high permeabilities, and controllable temperatures required to effect fast and efficient diffusion release of the short-lived species is also given

Development of new target concepts for proton beams at CERN/ISOLDE

CERN Document Server

Delonca, Melanie; Montavon, Ghislain; Peyraut, Francois

More and more, the power of primary beam sent onto targets increases until reaching several kiloWatts of magnitude, inducing new problematic and challenges. Consequently, the need of new target design arises and leads to new conceptual design proposal. Amongst them, a concept of Lead Bismuth Eutectic (LBE) loop target making use of an heat exchanger (HEX) and a pump has been proposed during the European project EURISOL Design Study. This concept proposed an improvement in terms of release efficiency of short-lived species by transforming the irradiated liquid into droplets shape. This thesis presents the development of this target design proposal. A prototype target has been developed and will be tested under proton beam at ISOLDE at Cern, Geneva. Several analytical tools for the study of this kind of targets are proposed, taking into account different design parameters. These tools can be applied for other high power target concept and allow an easy dimensioning of this kind of targets. As well, an innovativ...

Dominant dwarfism in transgenic rats by targeting human growth hormone (GH) expression to hypothalamic GH-releasing factor neurons.

OpenAIRE

Flavell, D M; Wells, T; Wells, S E; Carmignac, D F; Thomas, G B; Robinson, I C

1996-01-01

Expression of human growth hormone (hGH) was targeted to growth hormone-releasing (GRF) neurons in the hypothalamus of transgenic rats. This induced dominant dwarfism by local feedback inhibition of GRF. One line, bearing a single copy of a GRF-hGH transgene, has been characterized in detail, and has been termed Tgr (for Transgenic growth-retarded). hGH was detected by immunocytochemistry in the brain, restricted to the median eminence of the hypothalamus. Low levels were also detected in the...

Polymer Coated Echogenic Lipid Nanoparticles with Dual Release Triggers

Science.gov (United States)

Nahire, Rahul; Haldar, Manas K.; Paul, Shirshendu; Mergoum, Anaas; Ambre, Avinash H.; Katti, Kalpana S.; Gange, Kara N.; Srivastava, D. K.; Sarkar, Kausik; Mallik, Sanku

2013-01-01

Although lipid nanoparticles are promising drug delivery vehicles, passive release of encapsulated contents at the target site is often slow. Herein, we report contents release from targeted, polymer coated, echogenic lipid nanoparticles in the cell cytoplasm by redox trigger and simultaneously enhanced by diagnostic frequency ultrasound. The lipid nanoparticles were polymerized on the external leaflet using a disulfide cross-linker. In the presence of cytosolic concentrations of glutathione, the lipid nanoparticles released 76% of encapsulated contents. Plasma concentrations of glutathione failed to release the encapsulated contents. Application of 3 MHz ultrasound for 2 minutes simultaneously with the reducing agent enhanced the release to 96%. Folic acid conjugated, doxorubicin loaded nanoparticles showed enhanced uptake and higher cytotoxicity in cancer cells overexpressing the folate receptor (compared to the control). With further developments, these lipid nanoparticles have the potential to be used as multimodal nanocarriers for simultaneous targeted drug delivery and ultrasound imaging. PMID:23394107

Targeted Delivery of Toxoplasma gondii Antigens to Dendritic Cells Promote Immunogenicity and Protective Efficiency against Toxoplasmosis

Directory of Open Access Journals (Sweden)

Zineb Lakhrif

2018-02-01

Full Text Available Toxoplasmosis is a major public health problem and the development of a human vaccine is of high priority. Efficient vaccination against Toxoplasma gondii requires both a mucosal and systemic Th1 immune response. Moreover, dendritic cells play a critical role in orchestrating the innate immune functions and driving specific adaptive immunity to T. gondii. In this study, we explore an original vaccination strategy that combines administration via mucosal and systemic routes of fusion proteins able to target the major T. gondii surface antigen SAG1 to DCs using an antibody fragment single-chain fragment variable (scFv directed against DEC205 endocytic receptor. Our results show that SAG1 targeting to DCs by scFv via intranasal and subcutaneous administration improved protection against chronic T. gondii infection. A marked reduction in brain parasite burden is observed when compared with the intranasal or the subcutaneous route alone. DC targeting improved both local and systemic humoral and cellular immune responses and potentiated more specifically the Th1 response profile by more efficient production of IFN-γ, interleukin-2, IgG2a, and nasal IgA. This study provides evidence of the potential of DC targeting for the development of new vaccines against a range of Apicomplexa parasites.

Productivity, utilization efficiency and sward targets for mixed pastures of marandugrass, forage peanut and tropical kudzu

Directory of Open Access Journals (Sweden)

Carlos Mauricio Soares de Andrade

2012-03-01

Full Text Available This study was carried out to evaluate the productivity and utilization efficiency of a mixed marandugrass (Brachiaria brizantha cv. Marandu, forage peanut (Arachis pintoi cv. Mandobi and tropical kudzu (Pueraria phaseoloides pasture, rotationally stocked at four daily forage allowance levels (6.6, 10.3, 14.3 and 17.9% of live weight, in order to define sward management targets for these mixtures. In each stocking cycle, dry matter (DM accumulation rates, defoliation intensity (%, grazing depth (% and grazed horizon (cm were evaluated. Sward targets were defined according to the sward condition that best conciliated the grass-legume balance and the equilibrium between forage production and utilization. Pastures submitted to higher forage allowance levels showed higher productivity, but were less efficiently utilized. It was not possible to establish sward management targets for marandugrass-tropical kudzu pastures. For marandugrass-forage peanut pastures the best sward state was set with forage allowance of 10.3% of live weight. Under rotational stocking, the following sward targets were suggested for these pastures in the Western Amazon: pre-grazing height of 30-35 cm (June to September or 45-50 cm (October to May and post-grazing sward height of 20-25 cm (June to September or 25-30 cm (October to May.

Features of target cell lysis by class I and class II MHC restricted cytolytic T lymphocytes

International Nuclear Information System (INIS)

Maimone, M.M.; Morrison, L.A.; Braciale, V.L.; Braciale, T.J.

1986-01-01

The lytic activity of influenza virus-specific muvine cytolytic T lymphocyte (CTL) clones that are restricted by either H-2K/D (class I) or H-2I (class II) major histocompatibility (MHC) locus products was compared on an influenza virus-infected target cell expressing both K/D and I locus products. With the use of two in vitro measurements of cytotoxicity, conventional 51 Cr release, and detergent-releasable radiolabeled DNA (as a measure of nuclear disintegration in the early post-lethal hit period), the authors found no difference between class I and class II MHC-restricted CTL in the kinetics of target cell destruction. In addition, class II MHC-restricted antiviral CTL failed to show any lysis of radiolabeled bystander cells. Killing of labeled specific targets by these class II MHC-restricted CTL was also efficiently inhibited by unlabeled specific competitor cells in a cold target inhibition assay. In sum, these data suggest that class I and class II MHC-restricted CTL mediate target cell destruction by an essentially similar direct mechanism

Development of a liquid tin microjet target for an efficient laser-produced plasma extreme ultraviolet source

Science.gov (United States)

Higashiguchi, Takeshi; Hamada, Masaya; Kubodera, Shoichi

2007-03-01

A regenerative tin liquid microjet target was developed for a high average power extreme ultraviolet (EUV) source. The diameter of the target was smaller than 160 μm and good vacuum lower than 0.5 Pa was maintained during the operation. A maximum EUV conversion efficiency of 1.8% at the Nd:yttrium-aluminum-garnet laser intensity of around 2×1011 W/cm2 with a spot diameter of 175 μm (full width at half maximum) was observed. The angular distribution of the EUV emission remained almost isotropic, whereas suprathermal ions mainly emerged toward the target normal.

Development of a liquid tin microjet target for an efficient laser-produced plasma extreme ultraviolet source

International Nuclear Information System (INIS)

Higashiguchi, Takeshi; Hamada, Masaya; Kubodera, Shoichi

2007-01-01

A regenerative tin liquid microjet target was developed for a high average power extreme ultraviolet (EUV) source. The diameter of the target was smaller than 160 μm and good vacuum lower than 0.5 Pa was maintained during the operation. A maximum EUV conversion efficiency of 1.8% at the Nd:yttrium-aluminum-garnet laser intensity of around 2x10 11 W/cm 2 with a spot diameter of 175 μm (full width at half maximum) was observed. The angular distribution of the EUV emission remained almost isotropic, whereas suprathermal ions mainly emerged toward the target normal

Development of a liquid tin microjet target for an efficient laser-produced plasma extreme ultraviolet source.

Science.gov (United States)

Higashiguchi, Takeshi; Hamada, Masaya; Kubodera, Shoichi

2007-03-01

A regenerative tin liquid microjet target was developed for a high average power extreme ultraviolet (EUV) source. The diameter of the target was smaller than 160 microm and good vacuum lower than 0.5 Pa was maintained during the operation. A maximum EUV conversion efficiency of 1.8% at the Nd:yttrium-aluminum-garnet laser intensity of around 2 x 10(11) Wcm(2) with a spot diameter of 175 microm (full width at half maximum) was observed. The angular distribution of the EUV emission remained almost isotropic, whereas suprathermal ions mainly emerged toward the target normal.

Preparation and characterization of vinculin-targeted polymer-lipid nanoparticle as intracellular delivery vehicle.

Science.gov (United States)

Wang, Junping; Ornek-Ballanco, Ceren; Xu, Jiahua; Yang, Weiguo; Yu, Xiaojun

2013-01-01

Intracellular delivery vehicles have been extensively investigated as these can serve as an effective tool in studying the cellular mechanism, by delivering functional protein to specific locations of the cells. In the current study, a polymer-lipid nanoparticle (PLN) system was developed as an intracellular delivery vehicle specifically targeting vinculin, a focal adhesion protein associated with cellular adhesive structures, such as focal adhesions and adherens junctions. The PLNs possessed an average size of 106 nm and had a positively charged surface. With a lower encapsulation efficiency 32% compared with poly(lactic-co-glycolic) acid (PLGA) nanoparticles (46%), the PLNs showed the sustained release profile of model drug BSA, while PLGA nanoparticles demonstrated an initial burst-release property. Cell-uptake experiments using mouse embryonic fibroblasts cultured in fibrin-fibronectin gels observed, under confocal microscope, that the anti-vinculin conjugated PLNs could successfully ship the cargo to the cytoplasm of fibroblasts, adhered to fibronectin-fibrin. With the use of cationic lipid, the unconjugated PLNs were shown to have high gene transfection efficiency. Furthermore, the unconjugated PLNs had nuclear-targeting capability in the absence of nuclear-localization signals. Therefore, the PLNs could be manipulated easily via different type of targeting ligands and could potentially be used as a powerful tool for cellular mechanism study, by delivering drugs to specific cellular organelles.

Highly Efficient Release of Glycopeptides from Hydrazide Beads by Hydroxylamine Assisted PNGase F Deglycosylation for N-Glycoproteome Analysis.

Science.gov (United States)

Huang, Junfeng; Wan, Hao; Yao, Yating; Li, Jinan; Cheng, Kai; Mao, Jiawei; Chen, Jin; Wang, Yan; Qin, Hongqiang; Zhang, Weibing; Ye, Mingliang; Zou, Hanfa

2015-10-20

Selective enrichment of glycopeptides from complex sample followed by cleavage of N-glycans by PNGase F to expose an easily detectable mark on the former glycosylation sites has become the popular protocol for comprehensive glycoproteome analysis. On account of the high enrichment specificity, hydrazide chemistry based solid-phase extraction of N-linked glycopeptides technique has sparked numerous interests. However, the enzymatic release of glycopeptides captured by hydrazide beads through direct incubation of the beads with PNGase F is not efficient due to the inherent steric hindrance effect. In this study, we developed a hydroxylamine assisted PNGase F deglycosylation (HAPD) method using the hydroxylamine to release glycopeptides captured on the hydrazide beads through the cleavage of hydrazone bonds by transamination followed with the PNGase F deglycosylation of the released glycopeptides in the free solution. Because of the homogeneous condition for the deglycosylation, the recovery of deglycosylated peptides (deglycopeptides) was improved significantly. It was found that 27% more N-glycosylation sites were identified by the HAPD strategy compared with the conventional method. Moreover, the ratio of identified N-terminal glycosylated peptides was improved over 5-fold.

Reactive oxygen species responsive drug releasing nanoparticle based on chondroitin sulfate-anthocyanin nanocomplex for efficient tumor therapy.

Science.gov (United States)

Jeong, Dooyong; Bae, Byoung-Chan; Park, Sin-Jung; Na, Kun

2016-01-28

To develop a reactive oxygen species (ROS) sensitive drug carrier, a chondroitin sulfate (CS)-anthocyanin (ATC) based nanocomplex was developed. Doxorubicin hydrochloride (DOX) was loaded in the CS-ATC nanocomplex (CS-ATC-DOX) via intermolecular stacking interaction. The nanocomplex was fabricated by a simple mixing method in the aqueous phase. The morphology and size of CS-ATC-DOX were determined by ATC content. In the group with 1.5mg/ml of ATC loaded CS-ATC-DOX (CS-ATC2-DOX), the drug content and loading efficiency were 8.5% and 99.1%, respectively. The ROS sensitive drug release of CS-ATC2-DOX was confirmed under in vitro physiological conditions. The results demonstrated that 1.67 times higher DOX release occurred in CS-ATC2-DOX for 48h compared to CS-DOX (ATC absent sample). Drug release and nanocomplex destruction were induced by ROS mediated ATC degradation. We determined that 66.7% of ROS was scavenged by CS-ATC2-DOX. Additionally, an HCT-116 tumor bearing animal model was used to confirm ROS sensitive therapeutic effects of CS-ATC2-DOX. The results indicate that DOX was released from the intravenously injected CS-ATC2-DOX in the tumor tissue. Thus, nuclei shrinkage and dead cells were observed in H&E staining and TUNEL assay, respectively. These data suggest that the tumor growth was effectively inhibited. This study means that CS-ATC2-DOX has potential in improving tumor therapy. Copyright © 2015 Elsevier B.V. All rights reserved.

Novel targeted siRNA-loaded hybrid nanoparticles: preparation, characterization and in vitro evaluation.

Science.gov (United States)

Dim, Nneka; Perepelyuk, Maryna; Gomes, Olukayode; Thangavel, Chellappagounder; Liu, Yi; Den, Robert; Lakshmikuttyamma, Ashakumary; Shoyele, Sunday A

2015-09-26

siRNAs have a high potential for silencing critical molecular pathways that are pathogenic. Nevertheless, their clinical application has been limited by a lack of effective and safe nanotechnology-based delivery system that allows a controlled and safe transfection to cytosol of targeted cells without the associated adverse effects. Our group recently reported a very effective and safe hybrid nanoparticle delivery system composing human IgG and poloxamer-188 for siRNA delivery to cancer cells. However, these nanoparticles need to be optimized in terms of particle size, loading capacity and encapsulation efficiency. In the present study, we explored the effects of certain production parameters on particle size, loading capacity and encapsulation efficiency. Further, to make these nanoparticles more specific in their delivery of siRNA, we conjugated anti-NTSR1-mAb to the surface of these nanoparticles to target NTSR1-overexpressing cancer cells. The mechanism of siRNA release from these antiNTSR1-mAb functionalized nanoparticles was also elucidated. It was demonstrated that the concentration of human IgG in the starting nanoprecipitation medium and the rotation speed of the magnetic stirrer influenced the encapsulation efficiency, loading capacity and the size of the nanoparticles produced. We also successfully transformed these nanoparticles into actively targeted nanoparticles by functionalizing with anti-NTSR1-mAb to specifically target NTSR1-overexpressing cancer cells, hence able to avoid undesired accumulation in normal cells. The mechanism of siRNA release from these nanoparticles was elucidated to be by Fickian diffusion. Using flow cytometry and fluorescence microscopy, we were able to confirm the active involvement of NTSR1 in the uptake of these anti-NTSR1-mAb functionalized hybrid nanoparticles by lung adenocarcinoma cells. This hybrid nanoparticle delivery system can be used as a platform technology for intracellular delivery of siRNAs to NTSR1

Optimization of LDL targeted nanostructured lipid carriers of 5-FU by a full factorial design

Directory of Open Access Journals (Sweden)

Sare Andalib

2012-01-01

Full Text Available Background: Nanostructured lipid carriers (NLC are a mixture of solid and liquid lipids or oils as colloidal carrier systems that lead to an imperfect matrix structure with high ability for loading water soluble drugs. The aim of this study was to find the best proportion of liquid and solid lipids of different types for optimization of the production of LDL targeted NLCs used in carrying 5-Fu by the emulsification-solvent evaporation method. Materials and Methods: The influence of the lipid type, cholesterol or cholesteryl stearate for targeting LDL receptors, oil type (oleic acid or octanol, lipid and oil% on particle size, surface charge, drug loading efficiency, and drug released percent from the NLCs were studied by a full factorial design. Results: The NLCs prepared by 54.5% cholesterol and 25% of oleic acid, showed optimum results with particle size of 105.8 nm, relatively high zeta potential of −25 mV, drug loading efficiency of 38% and release efficiency of about 40%. Scanning electron microscopy of nanoparticles confirmed the results of dynamic light scattering method used in measuring the particle size of NLCs. Conclusions: The optimization method by a full factorial statistical design is a useful optimization method for production of nanostructured lipid carriers.

Chlorogenic acid loaded chitosan nanoparticles with sustained release property, retained antioxidant activity and enhanced bioavailability

Directory of Open Access Journals (Sweden)

Ilaiyaraja Nallamuthu

2015-06-01

Full Text Available In this study, chlorogenic acid (CGA, a phenolic compound widely distributed in fruits and vegetables, was encapsulated into chitosan nanoparticles by ionic gelation method. The particles exhibited the size and zeta potential of 210 nm and 33 mV respectively. A regular, spherical shaped distribution of nanoparticles was observed through scanning electron microscopy (SEM and the success of entrapment was confirmed by FTIR analysis. The encapsulation efficiency of CGA was at about 59% with the loading efficiency of 5.2%. In vitro ABTS assay indicated that the radical scavenging activity of CAG was retained in the nanostructure and further, the release kinetics study revealed the burst release of 69% CGA from nanoparticles at the end of 100th hours. Pharmacokinetic analysis in rats showed a lower level of Cmax, longer Tmax, longer MRT, larger AUC0–t and AUC0–∞ for the CGA nanoparticles compared to free CGA. Collectively, these results suggest that the synthesised nanoparticle with sustained release property can therefore ease the fortification of food-matrices targeted for health benefits through effective delivery of CGA in body.

Techniques for Reaeration of Hydropower Releases.

Science.gov (United States)

1983-02-01

release improvement. However, selected reservoir aeration studies not conducted primarily for improving hydroturbine releases but which have application...for hydroturbine release reaeration were also reviewed. Because oxygen transfer mechanisms are vitally important to the development of more efficient...the key words turbine aeration, turbine vent, turbine I’ aspiration, hydroturbine aeration, tailrace aeration, draft tube vent, and vacuum breaker. A

Nifedipine-loaded polymeric nanocapsules: validation of a stability-indicating HPLC method to evaluate the drug entrapment efficiency and in vitro release profiles.

Science.gov (United States)

Granada, Andréa; Tagliari, Monika Piazzon; Soldi, Valdir; Silva, Marcos António Segatto; Zanetti-Ramos, Betina Ghiel; Fernandes, Daniel; Stulzer, Hellen Karine

2013-01-01

A simple stability-indicating analytical method was developed and validated to quantify nifedipine in polymeric nanocapsule suspensions; an in vitro drug release study was then carried out. The analysis was performed using an RP C18 column, UV-Vis detection at 262 nm, and methanol-water (70 + 30, v/v) mobile phase at a flow rate of 1.2 mL/min. The method was validated in terms of specificity, linearity and range, LOQ, accuracy, precision, and robustness. The results obtained were within the acceptable ranges. The nanocapsules, made of poly(epsilon-caprolactone), were prepared by the solvent displacement technique and showed high entrapment efficiency. The entrapment efficiency was 97.6 and 98.2% for the nifedipine-loaded polymeric nanocapsules prepared from polyvinyl alcohol (PVA) and Pluronic F68 (PF68), respectively. The particle size and zeta potential of nanocapsules were found to be influenced by the nature of the stabilizer used. The mean diameter and zeta potential for nanocapsules with PVA and PF68 were 290.9 and 179.9 nm, and -17.7 mV and -32.7 mV, respectively. The two formulations prepared showed a drug release of up to 70% over 4 days. This behavior indicates the viability of this drug delivery system for use as a controlled-release system.

Galaxy And Mass Assembly (GAMA): the G02 field, Herschel-ATLAS target selection and Data Release 3 arXiv

CERN Document Server

Baldry, I.K.; Brown, M.J.I.; Robotham, A.S.G.; Driver, S.P.; Dunne, L.; Alpaslan, M.; Brough, S.; Cluver, M.E.; Eardley, E.; Farrow, D.J.; Heymans, C.; Hildebrandt, H.; Hopkins, A.M.; Kelvin, L.S.; Loveday, J.; Moffett, A.J.; Norberg, P.; Owers, M.S.; Taylor, E.N.; Wright, A.H.; Bamford, S.P.; Bland-Hawthorn, J.; Bourne, N.; Bremer, M.N.; Colless, M.; Conselice, C.J.; Croom, S.M.; Davies, L.J.M.; Foster, C.; Grootes, M.W.; Holwerda, B.W.; Jones, D.H.; Kafle, P.R.; Kuijken, K.; Lara-Lopez, M.A.; Lopez-Sanchez, A.R.; Meyer, M.J.; Phillipps, S.; Sutherland, W.J.; van Kampen, E.; Wilkins, S.M.

We describe data release 3 (DR3) of the Galaxy And Mass Assembly (GAMA) survey. The GAMA survey is a spectroscopic redshift and multi-wavelength photometric survey in three equatorial regions each of 60.0 deg^2 (G09, G12, G15), and two southern regions of 55.7 deg^2 (G02) and 50.6 deg^2 (G23). DR3 consists of: the first release of data covering the G02 region and of data on H-ATLAS sources in the equatorial regions; and updates to data on sources released in DR2. DR3 includes 154809 sources with secure redshifts across four regions. A subset of the G02 region is 95.5% redshift complete to r<19.8 over an area of 19.5 deg^2, with 20086 galaxy redshifts, that overlaps substantially with the XXL survey (X-ray) and VIPERS (redshift survey). In the equatorial regions, the main survey has even higher completeness (98.5%), and spectra for about 75% of H-ATLAS filler targets were also obtained. This filler sample extends spectroscopic redshifts, for probable optical counterparts to H-ATLAS sub-mm sources, to 0.8 ma...

Host-Guest Recognition-Assisted Electrochemical Release: Its Reusable Sensing Application Based on DNA Cross Configuration-Fueled Target Cycling and Strand Displacement Reaction Amplification.

Science.gov (United States)

Chang, Yuanyuan; Zhuo, Ying; Chai, Yaqin; Yuan, Ruo

2017-08-15

In this work, an elegantly designed host-guest recognition-assisted electrochemical release was established and applied in a reusable electrochemical biosensor for the detection of microRNA-182-5p (miRNA-182-5p), a prostate cancer biomarker in prostate cancer, based on the DNA cross configuration-fueled target cycling and strand displacement reaction (SDR) amplification. With such a design, the single target miRNA input could be converted to large numbers of single-stranded DNA (S1-Trp and S2-Trp) output, which could be trapped by cucurbit[8]uril methyl viologen (CB-8-MV 2+ ) based on the host-guest recognition, significantly enhancing the sensitivity for miRNA detection. Moreover, the nucleic acids products obtained from the process of cycling amplification could be utilized sufficiently, avoiding the waste and saving the experiment cost. Impressively, by resetting a settled voltage, the proposed biosensor could release S1-Trp and S2-Trp from the electrode surface, attributing that the guest ion methyl viologen (MV 2+ ) was reduced to MV +· under this settled voltage and formed a more-stable CB-8-MV +· -MV +· complex. Once O 2 was introduced in this system, MV +· could be oxidized to MV 2+ , generating the complex of CB-8-MV 2+ for capturing S1-Trp and S2-Trp again in only 5 min. As a result, the simple and fast regeneration of biosensor for target detection was realized on the base of electrochemical redox-driven assembly and release, overcoming the challenges of time-consuming, burdensome operations and expensive experimental cost in traditional reusable biosensors and updating the construction method for a reusable bisensor. Furthermore, the biosensor could be reused for more than 10 times with a regeneration rate of 93.20%-102.24%. After all, the conception of this work provides a novel thought for the construction of effective reusable biosensor to detect miRNA and other biomarkers and has great potential application in the area requiring the release of

Anti-inflammatory drugs for Duchenne muscular dystrophy: focus on skeletal muscle-releasing factors.

Science.gov (United States)

Miyatake, Shouta; Shimizu-Motohashi, Yuko; Takeda, Shin'ichi; Aoki, Yoshitsugu

2016-01-01

Duchenne muscular dystrophy (DMD), an incurable and a progressive muscle wasting disease, is caused by the absence of dystrophin protein, leading to recurrent muscle fiber damage during contraction. The inflammatory response to fiber damage is a compelling candidate mechanism for disease exacerbation. The only established pharmacological treatment for DMD is corticosteroids to suppress muscle inflammation, however this treatment is limited by its insufficient therapeutic efficacy and considerable side effects. Recent reports show the therapeutic potential of inhibiting or enhancing pro- or anti-inflammatory factors released from DMD skeletal muscles, resulting in significant recovery from muscle atrophy and dysfunction. We discuss and review the recent findings of DMD inflammation and opportunities for drug development targeting specific releasing factors from skeletal muscles. It has been speculated that nonsteroidal anti-inflammatory drugs targeting specific inflammatory factors are more effective and have less side effects for DMD compared with steroidal drugs. For example, calcium channels, reactive oxygen species, and nuclear factor-κB signaling factors are the most promising targets as master regulators of inflammatory response in DMD skeletal muscles. If they are combined with an oligonucleotide-based exon skipping therapy to restore dystrophin expression, the anti-inflammatory drug therapies may address the present therapeutic limitation of low efficiency for DMD.

Comparison of CRISPR/Cas9 expression constructs for efficient targeted mutagenesis in rice.

Science.gov (United States)

Mikami, Masafumi; Toki, Seiichi; Endo, Masaki

2015-08-01

The CRISPR/Cas9 system is an efficient tool used for genome editing in a variety of organisms. Despite several recent reports of successful targeted mutagenesis using the CRISPR/Cas9 system in plants, in each case the target gene of interest, the Cas9 expression system and guide-RNA (gRNA) used, and the tissues used for transformation and subsequent mutagenesis differed, hence the reported frequencies of targeted mutagenesis cannot be compared directly. Here, we evaluated mutation frequency in rice using different Cas9 and/or gRNA expression cassettes under standardized experimental conditions. We introduced Cas9 and gRNA expression cassettes separately or sequentially into rice calli, and assessed the frequency of mutagenesis at the same endogenous targeted sequences. Mutation frequencies differed significantly depending on the Cas9 expression cassette used. In addition, a gRNA driven by the OsU6 promoter was superior to one driven by the OsU3 promoter. Using an all-in-one expression vector harboring the best combined Cas9/gRNA expression cassette resulted in a much improved frequency of targeted mutagenesis in rice calli, and bi-allelic mutant plants were produced in the T0 generation. The approach presented here could be adapted to optimize the construction of Cas9/gRNA cassettes for genome editing in a variety of plants.

Release-ability of nano fillers from different nanomaterials (toward the acceptability of nanoproduct)

International Nuclear Information System (INIS)

Golanski, L.; Guiot, A.; Pras, M.; Malarde, M.; Tardif, F.

2012-01-01

It is of great interest to set up a reproducible and sensitive method able to qualify nanomaterials before their market introduction in terms of their constitutive nanoparticle release-ability in usage. Abrasion was performed on polycarbonate, epoxy, and PA11 polymers containing carbone nanotubes (CNT) up to 4 %wt. Using Taber linear standard tool and standard abrasion conditions no release from polymer coatings containing CNT was measured. In this study, new practical tools inducing non-standardized stresses able to compete with van der Waals forces were developed and tested on model polymers, showing controlled CNT dispersion. These stresses are still realistic, corresponding to scratching, instantaneous mechanical shocks, and abrasion of the surface. They offer an efficient way to quantify if release is possible from nanomaterials under different mechanical stresses and therefore give an idea about the mechanisms that favors it. Release under mechanical shocks and hard abrasion was obtained using these tools but only when nanomaterials present a bad dispersion of CNT within the epoxy matrix. Under the same conditions no release was obtained from the same material presenting a good dispersion. The CNT used in this study showed an external diameter Dext = 12 nm, an internal diameter Din = 5 nm, and a mean length of 1 μm. Release from paints under hard abrasion using a standard rotative Taber tool was obtained from a intentionaly non-optimized paint containing SiO 2 nanoparticles up to 35 %wt. The primary diameter of the SiO 2 was estimated to be around 12 nm. A metallic rake was efficient to remove nanoparticles from a non-woven fabric nanomaterial.

Nonmyopic Sensor Scheduling and its Efficient Implementation for Target Tracking Applications

Directory of Open Access Journals (Sweden)

Morrell Darryl

2006-01-01

Full Text Available We propose two nonmyopic sensor scheduling algorithms for target tracking applications. We consider a scenario where a bearing-only sensor is constrained to move in a finite number of directions to track a target in a two-dimensional plane. Both algorithms provide the best sensor sequence by minimizing a predicted expected scheduler cost over a finite time-horizon. The first algorithm approximately computes the scheduler costs based on the predicted covariance matrix of the tracker error. The second algorithm uses the unscented transform in conjunction with a particle filter to approximate covariance-based costs or information-theoretic costs. We also propose the use of two branch-and-bound-based optimal pruning algorithms for efficient implementation of the scheduling algorithms. We design the first pruning algorithm by combining branch-and-bound with a breadth-first search and a greedy-search; the second pruning algorithm combines branch-and-bound with a uniform-cost search. Simulation results demonstrate the advantage of nonmyopic scheduling over myopic scheduling and the significant savings in computational and memory resources when using the pruning algorithms.

Measuring the Acoustic Release of a Chemotherapeutic Agent from Folate-Targeted Polymeric Micelles.

Science.gov (United States)

Abusara, Ayah; Abdel-Hafez, Mamoun; Husseini, Ghaleb

2018-08-01

In this paper, we compare the use of Bayesian filters for the estimation of release and re-encapsulation rates of a chemotherapeutic agent (namely Doxorubicin) from nanocarriers in an acoustically activated drug release system. The study is implemented using an advanced kinetic model that takes into account cavitation events causing the antineoplastic agent's release from polymeric micelles upon exposure to ultrasound. This model is an improvement over the previous representations of acoustic release that used simple zero-, first- and second-order release and re-encapsulation kinetics to study acoustically triggered drug release from polymeric micelles. The new model incorporates drug release and micellar reassembly events caused by cavitation allowing for the controlled release of chemotherapeutics specially and temporally. Different Bayesian estimators are tested for this purpose including Kalman filters (KF), Extended Kalman filters (EKF), Particle filters (PF), and multi-model KF and EKF. Simulated and experimental results are used to verify the performance of the above-mentioned estimators. The proposed methods demonstrate the utility and high-accuracy of using estimation methods in modeling this drug delivery technique. The results show that, in both cases (linear and non-linear dynamics), the modeling errors are expensive but can be minimized using a multi-model approach. In addition, particle filters are more flexible filters that perform reasonably well compared to the other two filters. The study improved the accuracy of the kinetic models used to capture acoustically activated drug release from polymeric micelles, which may in turn help in designing hardware and software capable of precisely controlling the delivered amount of chemotherapeutics to cancerous tissue.

Release of dissolved 85Kr by standing

International Nuclear Information System (INIS)

Ootsuka, Norikatsu; Yamamoto, Tadatoshi; Tsukui, Kohei

1986-01-01

The experiments on the release of dissolved 85 Kr by standing at room temperature were carried out to examine the influence of liquid level in a sampler and properties of solvent on the release efficiency. Six kinds of organic solvents as well as water were taken as solvents. The half-life period in case of the decrease in concentration of the dissolved 85 Kr which was used as an index of release efficiency, was proportional to the liquid level in the sampler and was inversely proportional to the diffusion coefficient of Kr gas in solvent. For organic solvents belonging to homologous series, the half-life period became longer with increasing the carbon number of solvent molecule. From the relationship between the half-life period and the carbon number, the release efficiency in the dissolved 85 Kr can be predicted for any commonly used solvent as a practical application. This method was found to be an effective means of removing the dissolved 85 Kr of low level though it takes rather long time. (author)

Nerve growth factor alters microtubule targeting agent-induced neurotransmitter release but not MTA-induced neurite retraction in sensory neurons.

Science.gov (United States)

Pittman, Sherry K; Gracias, Neilia G; Fehrenbacher, Jill C

2016-05-01

Peripheral neuropathy is a dose-limiting side effect of anticancer treatment with the microtubule-targeted agents (MTAs), paclitaxel and epothilone B (EpoB); however, the mechanisms by which the MTAs alter neuronal function and morphology are unknown. We previously demonstrated that paclitaxel alters neuronal sensitivity, in vitro, in the presence of nerve growth factor (NGF). Evidence in the literature suggests that NGF may modulate the neurotoxic effects of paclitaxel. Here, we examine whether NGF modulates changes in neuronal sensitivity and morphology induced by paclitaxel and EpoB. Neuronal sensitivity was assessed using the stimulated release of calcitonin gene-related peptide (CGRP), whereas morphology of established neurites was evaluated using a high content screening system. Dorsal root ganglion cultures, maintained in the absence or presence of NGF, were treated from day 7 to day 12 in culture with paclitaxel (300nM) or EpoB (30nM). Following treatment, the release of CGRP was stimulated using capsaicin or high extracellular potassium. In the presence of NGF, EpoB mimicked the effects of paclitaxel: capsaicin-stimulated release was attenuated, potassium-stimulated release was slightly enhanced and the total peptide content was unchanged. In the absence of NGF, both paclitaxel and EpoB decreased capsaicin- and potassium-stimulated release and the total peptide content, suggesting that NGF may reverse MTA-induced hyposensitivity. Paclitaxel and EpoB both decreased neurite length and branching, and this attenuation was unaffected by NGF in the growth media. These differential effects of NGF on neuronal sensitivity and morphology suggest that neurite retraction is not a causative factor to alter neuronal sensitivity. Copyright © 2016 Elsevier Inc. All rights reserved.

Efficient Solar-Thermal Energy Harvest Driven by Interfacial Plasmonic Heating-Assisted Evaporation.

Science.gov (United States)

Chang, Chao; Yang, Chao; Liu, Yanming; Tao, Peng; Song, Chengyi; Shang, Wen; Wu, Jianbo; Deng, Tao

2016-09-07

The plasmonic heating effect of noble nanoparticles has recently received tremendous attention for various important applications. Herein, we report the utilization of interfacial plasmonic heating-assisted evaporation for efficient and facile solar-thermal energy harvest. An airlaid paper-supported gold nanoparticle thin film was placed at the thermal energy conversion region within a sealed chamber to convert solar energy into thermal energy. The generated thermal energy instantly vaporizes the water underneath into hot vapors that quickly diffuse to the thermal energy release region of the chamber to condense into liquids and release the collected thermal energy. The condensed water automatically flows back to the thermal energy conversion region under the capillary force from the hydrophilic copper mesh. Such an approach simultaneously realizes efficient solar-to-thermal energy conversion and rapid transportation of converted thermal energy to target application terminals. Compared to conventional external photothermal conversion design, the solar-thermal harvesting device driven by the internal plasmonic heating effect has reduced the overall thermal resistance by more than 50% and has demonstrated more than 25% improvement of solar water heating efficiency.

Targeted therapy of hepatocellular carcinoma with aptamer-functionalized biodegradable nanoparticles

Energy Technology Data Exchange (ETDEWEB)

Weigum, Shannon, E-mail: sweigum@txstate.edu [Texas State University, Department of Biology (United States); McIvor, Elizabeth; Munoz, Christopher; Feng, Richard [Texas State University, Department of Chemistry and Biochemistry (United States); Cantu, Travis [Texas State University, Materials Science, Engineering, and Commercialization Program (United States); Walsh, Kyle [Texas State University, Department of Chemistry and Biochemistry (United States); Betancourt, Tania, E-mail: tania.betancourt@txstate.edu [Texas State University, Materials Science, Engineering, and Commercialization Program (United States)

2016-11-15

Hepatocellular carcinoma (HCC) is the most common form of liver cancer, occurring primarily in regions where viral hepatitis infections are common. Unfortunately, most HCC cases remain undiagnosed until late stages of the disease when patient outcome is poor, typically limiting survival from a few months to a year after initial diagnosis. In order to better care for HCC patients, new target-specific approaches are needed to improve early detection and therapeutic intervention. In this work, polymeric nanoparticles functionalized with a HCC-specific aptamer were examined as potential targeted drug delivery vehicles. Specifically, doxorubicin-loaded nanoparticles were prepared via nanoprecipitation of blends of poly(lactic-co-glycolic acid)-b-poly(ethylene glycol). These particles were further functionalized with the HCC-specific TLS11a aptamer. The in vitro interaction and therapeutic efficacy of the aptamer and aptamer-functionalized nanoparticles were characterized in a hepatoma cell line. Nanoparticles were found to be spherical in shape, roughly 100–125 nm in diameter, with a low polydispersity (≤0.2) and slightly negative surface potential. Doxorubicin was encapsulated within the particles at ~40 % efficiency. Drug release was found to occur through anomalous transport influenced by diffusion and polymer relaxation, releasing ~50 % doxorubicin in the first 10 h and full release occurring within 36 h. Confocal microscopy confirmed binding and attachment of aptamer-targeted nanoparticles to the cell surface of cultured HCC cells. Efficacy studies demonstrated a significant improvement in doxorubicin delivery and cell-killing capacity using the aptamer-functionalized, drug-loaded nanoparticles versus controls further supporting use of aptamer nanoparticles as a targeted drug delivery system for HCC tumors.

Performance and efficiency evaluation and heat release study of a direct-injection stratified-charge rotary engine

Science.gov (United States)

Nguyen, H. L.; Addy, H. E.; Bond, T. H.; Lee, C. M.; Chun, K. S.

1987-01-01

A computer simulation which models engine performance of the Direct Injection Stratified Charge (DISC) rotary engines was used to study the effect of variations in engine design and operating parameters on engine performance and efficiency of an Outboard Marine Corporation (OMC) experimental rotary combustion engine. Engine pressure data were used in a heat release analysis to study the effects of heat transfer, leakage, and crevice flows. Predicted engine data were compared with experimental test data over a range of engine speeds and loads. An examination of methods to improve the performance of the rotary engine using advanced heat engine concepts such as faster combustion, reduced leakage, and turbocharging is also presented.

Efficient Nonlocal M-Control and N-Target Controlled Unitary Gate Using Non-symmetric GHZ States

Science.gov (United States)

Chen, Li-Bing; Lu, Hong

2018-03-01

Efficient local implementation of a nonlocal M-control and N-target controlled unitary gate is considered. We first show that with the assistance of two non-symmetric qubit(1)-qutrit(N) Greenberger-Horne-Zeilinger (GHZ) states, a nonlocal 2-control and N-target controlled unitary gate can be constructed from 2 local two-qubit CNOT gates, 2 N local two-qutrit conditional SWAP gates, N local qutrit-qubit controlled unitary gates, and 2 N single-qutrit gates. At each target node, the two third levels of the two GHZ target qutrits are used to expose one and only one initial computational state to the local qutrit-qubit controlled unitary gate, instead of being used to hide certain states from the conditional dynamics. This scheme can be generalized straightforwardly to implement a higher-order nonlocal M-control and N-target controlled unitary gate by using M non-symmetric qubit(1)-qutrit(N) GHZ states as quantum channels. Neither the number of the additional levels of each GHZ target particle nor that of single-qutrit gates needs to increase with M. For certain realistic physical systems, the total gate time may be reduced compared with that required in previous schemes.

Graphite target for the spiral project

International Nuclear Information System (INIS)

Putaux, J.C.; Ducourtieux, M.; Ferro, A.; Foury, P.; Kotfila, L.; Mueller, A.C.; Obert, J.; Pauwels, N.; Potier, J.C.; Proust, J.; Loiselet, M.

1996-01-01

A study of the thermal and physical properties of graphite targets for the SPIRAL project is presented. The main objective is to develop an optimized set-up both mechanically and thermally resistant, presenting good release properties (hot targets with thin slices). The results of irradiation tests concerning the mechanical and thermal resistance of the first prototype of SPIRAL target with conical geometry are presented. The micro-structural properties of the graphite target is also studied, in order to check that the release properties are not deteriorated by the irradiation. Finally, the results concerning the latest pilot target internally heated by an electrical current are shown. (author)

Ultramild protein-mediated click chemistry creates efficient oligonucleotide probes for targeting and detecting nucleic acids

DEFF Research Database (Denmark)

Nåbo, Lina J.; Madsen, Charlotte S.; Jensen, Knud J.

2015-01-01

Functionalized synthetic oligonucleotides are finding growing applications in research, clinical studies, and therapy. However, it is not easy to prepare them in a biocompatible and highly efficient manner. We report a new strategy to synthesize oligonucleotides with promising nucleic acid...... targeting and detection properties. We focus in particular on the pH sensitivity of these new probes and their high target specificity. For the first time, human copper(I)-binding chaperon Cox17 was applied to effectively catalyze click labeling of oligonucleotides. This was performed under ultramild...... conditions with fluorophore, peptide, and carbohydrate azide derivatives. In thermal denaturation studies, the modified probes showed specific binding to complementary DNA and RNA targets. Finally, we demonstrated the pH sensitivity of the new rhodamine-based fluorescent probes in vitro and rationalize our...

Control of laser absorbing efficiency and proton quality by a specific double target

Czech Academy of Sciences Publication Activity Database

Yu, Q.; Gu, Yanjun; Li, X.F.; Qu, J.F.; Kong, Q.; Kawata, S.

2016-01-01

Roč. 18, č. 8 (2016), 1-9, č. článku 083024. ISSN 1367-2630 R&D Projects: GA MŠk LQ1606; GA MŠk EF15_008/0000162 Grant - others:ELI Beamlines(XE) CZ.02.1.01/0.0/0.0/15_008/0000162 Institutional support: RVO:68378271 Keywords : improved proton beam quality * increased laser absorption efficiency * specific double-layer target Subject RIV: BL - Plasma and Gas Discharge Physics Impact factor: 3.786, year: 2016

High efficiency dry coating of non-subcoated pellets for sustained drug release formulations using amino methacrylate copolymers.

Science.gov (United States)

Klar, Fabian; Urbanetz, Nora Anne

2017-12-12

Dry coating utilizing a fluidized bed was evaluated in order to produce films with sustained drug release using amino methacrylate copolymers as film former. In contrast to other dry coating procedures using amino methacrylate copolymers, the described method enables an appropriate polymer adhesion by the selection of a plasticizer additive mixture in combination with the use of a three-way nozzle for simultaneous application. Well spreading fatty acid esters were found to increase the coating efficiency from 73% to approximately 86%, when they were used in conjunction with the plasticizer. Pellets were used as drug cores without previous treatment. After a curing step at 55 °C, the pellets exhibited a prolongation of the drug release over a period of about 6 h. Mainly the three parameters, coating level, composition of the polymers in the coating mixture, and the type of plasticizer, were found to exert distinct influence on the dissolution profile. Despite the differences in the coating procedure, the dissolution profiles of the coated pellets as well as the influencing parameters were similar to those known from conventional coating techniques.

Efficient four fragment cloning for the construction of vectors for targeted gene replacement in filamentous fungi

DEFF Research Database (Denmark)

Frandsen, Rasmus John Normand; Andersson, Jens A.; Kristensen, Matilde Bylov

2008-01-01

Background: The rapid increase in whole genome fungal sequence information allows large scale functional analyses of target genes. Efficient transformation methods to obtain site-directed gene replacement, targeted over-expression by promoter replacement, in-frame epitope tagging or fusion...... of coding sequences with fluorescent markers such as GFP are essential for this process. Construction of vectors for these experiments depends on the directional cloning of two homologous recombination sequences on each side of a selection marker gene. Results: Here, we present a USER Friendly cloning based...

An efficient and accurate method for computation of energy release rates in beam structures with longitudinal cracks

DEFF Research Database (Denmark)

Blasques, José Pedro Albergaria Amaral; Bitsche, Robert

2015-01-01

This paper proposes a novel, efficient, and accurate framework for fracture analysis of beam structures with longitudinal cracks. The three-dimensional local stress field is determined using a high-fidelity beam model incorporating a finite element based cross section analysis tool. The Virtual...... Crack Closure Technique is used for computation of strain energy release rates. The devised framework was employed for analysis of cracks in beams with different cross section geometries. The results show that the accuracy of the proposed method is comparable to that of conventional three......-dimensional solid finite element models while using only a fraction of the computation time....

Can we improve the identification of cold homes for targeted home energy-efficiency improvements?

International Nuclear Information System (INIS)

Hutchinson, Emma J.; Wilkinson, Paul; Hong, Sung H.; Oreszczyn, Tadj

2006-01-01

Objective: To investigate the extent to which homes with low indoor-temperatures can be identified from dwelling and household characteristics. Design: Analysis of data from a national survey of dwellings, occupied by low-income households, scheduled for home energy-efficiency improvements. Setting: Five urban areas of England: Birmingham, Liverpool, Manchester, Newcastle and Southampton. Methods: Half-hourly living-room temperatures were recorded for two to four weeks in dwellings over the winter periods November to April 2001-2002 and 2002-2003. Regression of indoor on outdoor temperatures was used to identify cold-homes in which standardized daytime living-room and/or nighttime bedroom-temperatures were o C (when the outdoor temperature was 5 o C). Tabulation and logistic regression were used to examine the extent to which these cold-homes can be identified from dwelling and household characteristics. Results: Overall, 21.0% of dwellings had standardized daytime living-room temperatures o C, and 46.4% had standardized nighttime bedroom-temperatures below the same temperature. Standardized indoor-temperatures were influenced by a wide range of household and dwelling characteristics, but most strongly by the energy efficiency (SAP) rating and by standardized heating costs. However, even using these variables, along with other dwelling and household characteristics in a multi-variable prediction model, it would be necessary to target more than half of all dwellings in our sample to ensure at least 80% sensitivity for identifying dwellings with cold living-room temperatures. An even higher proportion would have to be targeted to ensure 80% sensitivity for identifying dwellings with cold-bedroom temperatures. Conclusion: Property and household characteristics provide only limited potential for identifying dwellings where winter indoor temperatures are likely to be low, presumably because of the multiple influences on home heating, including personal choice and

Investigating the in vitro drug release kinetics from controlled release diclofenac potassium-ethocel matrix tablets and the influence of co-excipients on drug release patterns.

Science.gov (United States)

Shah, Shefaat Ullah; Shah, Kifayat Ullah; Rehman, Asimur; Khan, Gul Majid

2011-04-01

The objective of the study was to formulate and evaluate controlled release polymeric tablets of Diclofenac Potassium for the release rate, release patterns and the mechanism involved in the release process of the drug. Formulations with different types and grades of Ethyl Cellulose Ether derivatives in several drug-to-polymer ratios (D:P) were compressed into tablets using the direct compression method. In vitro drug release studies were performed in phosphate buffer (pH 7.4) as dissolution medium by using USP Method-1 (Rotating Basket Method). Similarity factor f2 and dissimilarity factor f1 were applied for checking the similarities and dissimilarities of the release profiles of different formulations. For the determination of the release mechanism and drug release kinetics various mathematical/kinetic models were employed. It was found that all of the Ethocel polymers could significantly slow down the drug release rate with Ethocel FP polymers being the most efficient, especially at D:P ratios of 10:03 which lead towards the achievement of zero or near zero order release kinetics.

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

Science.gov (United States)

Sellers, Eric W.; Wang, Xingyu

2013-01-01

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

Distributed Bees Algorithm Parameters Optimization for a Cost Efficient Target Allocation in Swarms of Robots

Directory of Open Access Journals (Sweden)

Álvaro Gutiérrez

2011-11-01

Full Text Available Swarms of robots can use their sensing abilities to explore unknown environments and deploy on sites of interest. In this task, a large number of robots is more effective than a single unit because of their ability to quickly cover the area. However, the coordination of large teams of robots is not an easy problem, especially when the resources for the deployment are limited. In this paper, the Distributed Bees Algorithm (DBA, previously proposed by the authors, is optimized and applied to distributed target allocation in swarms of robots. Improved target allocation in terms of deployment cost efficiency is achieved through optimization of the DBA’s control parameters by means of a Genetic Algorithm. Experimental results show that with the optimized set of parameters, the deployment cost measured as the average distance traveled by the robots is reduced. The cost-efficient deployment is in some cases achieved at the expense of increased robots’ distribution error. Nevertheless, the proposed approach allows the swarm to adapt to the operating conditions when available resources are scarce.

Effect of firing conditions & release height on terminal performance of submunitions and conditions for optimum height of release

Directory of Open Access Journals (Sweden)

L.K. Gite

2017-06-01

Full Text Available Submunitions should exhibit optimum terminal performance at target end when released from certain pre-determined height. Selection of an optimum height of release of the submunitions depends on the terminal parameters like forward throw, remaining velocity, impact angle and flight time. In this paper, the effects of initial firing conditions and height of release on terminal performance of submunitions discussed in detail. For different height of release, the relation between range and forward throw is also established & validated for a number of firing altitude and rocket configurations.

Mechanisms and biomaterials in pH-responsive tumour targeted drug delivery: A review.

Science.gov (United States)

Kanamala, Manju; Wilson, William R; Yang, Mimi; Palmer, Brian D; Wu, Zimei

2016-04-01

As the mainstay in the treatment of various cancers, chemotherapy plays a vital role, but still faces many challenges, such as poor tumour selectivity and multidrug resistance (MDR). Targeted drug delivery using nanotechnology has provided a new strategy for addressing the limitations of the conventional chemotherapy. In the last decade, the volume of research published in this area has increased tremendously, especially with functional nano drug delivery systems (nanocarriers). Coupling a specific stimuli-triggered drug release mechanism with these delivery systems is one of the most prevalent approaches for improving therapeutic outcomes. Among the various stimuli, pH triggered delivery is regarded as the most general strategy, targeting the acidic extracellular microenvironment and intracellular organelles of solid tumours. In this review, we discuss recent advances in the development of pH-sensitive nanocarriers for tumour-targeted drug delivery. The review focuses on the chemical design of pH-sensitive biomaterials, which are used to fabricate nanocarriers for extracellular and/or intracellular tumour site-specific drug release. The pH-responsive biomaterials bring forth conformational changes in these nanocarriers through various mechanisms such as protonation, charge reversal or cleavage of a chemical bond, facilitating tumour specific cell uptake or drug release. A greater understanding of these mechanisms will help to design more efficient drug delivery systems to address the challenges encountered in conventional chemotherapy. Copyright © 2016 Elsevier Ltd. All rights reserved.

Adaptive Energy-Efficient Target Detection Based on Mobile Wireless Sensor Networks

Directory of Open Access Journals (Sweden)

Tengyue Zou

2017-05-01

Full Text Available Target detection is a widely used application for area surveillance, elder care, and fire alarms; its purpose is to find a particular object or event in a region of interest. Usually, fixed observing stations or static sensor nodes are arranged uniformly in the field. However, each part of the field has a different probability of being intruded upon; if an object suddenly enters an area with few guardian devices, a loss of detection will occur, and the stations in the safe areas will waste their energy for a long time without any discovery. Thus, mobile wireless sensor networks may benefit from adaptation and pertinence in detection. Sensor nodes equipped with wheels are able to move towards the risk area via an adaptive learning procedure based on Bayesian networks. Furthermore, a clustering algorithm based on k-means++ and an energy control mechanism is used to reduce the energy consumption of nodes. The extended Kalman filter and a voting data fusion method are employed to raise the localization accuracy of the target. The simulation and experimental results indicate that this new system with adaptive energy-efficient methods is able to achieve better performance than the traditional ones.

Adaptive Energy-Efficient Target Detection Based on Mobile Wireless Sensor Networks.

Science.gov (United States)

Zou, Tengyue; Li, Zhenjia; Li, Shuyuan; Lin, Shouying

2017-05-04

Target detection is a widely used application for area surveillance, elder care, and fire alarms; its purpose is to find a particular object or event in a region of interest. Usually, fixed observing stations or static sensor nodes are arranged uniformly in the field. However, each part of the field has a different probability of being intruded upon; if an object suddenly enters an area with few guardian devices, a loss of detection will occur, and the stations in the safe areas will waste their energy for a long time without any discovery. Thus, mobile wireless sensor networks may benefit from adaptation and pertinence in detection. Sensor nodes equipped with wheels are able to move towards the risk area via an adaptive learning procedure based on Bayesian networks. Furthermore, a clustering algorithm based on k -means++ and an energy control mechanism is used to reduce the energy consumption of nodes. The extended Kalman filter and a voting data fusion method are employed to raise the localization accuracy of the target. The simulation and experimental results indicate that this new system with adaptive energy-efficient methods is able to achieve better performance than the traditional ones.

Efficient inhibition of heavy metal release from mine tailings against acid rain exposure by triethylenetetramine intercalated montmorillonite (TETA-Mt).

Science.gov (United States)

Gong, Beini; Wu, Pingxiao; Huang, Zhujian; Li, Yuanyuan; Yang, Shanshan; Dang, Zhi; Ruan, Bo; Kang, Chunxi

2016-11-15

The potential application of triethylenetetramine intercalated montmorillonite (TETA-Mt) in mine tailings treatment and AMD (acid mine drainage) remediation was investigated with batch experiments. The structural and morphological characteristics of TETA-Mt were analyzed with XRD, FTIR, DTG-TG and SEM. The inhibition efficiencies of TETA-Mt against heavy metal release from mine tailings when exposed to acid rain leaching was examined and compared with that of triethylenetetramine (TETA) and Mt. Results showed that the overall inhibition by TETA-Mt surpassed that by TETA or Mt for various heavy metal ions over an acid rain pH range of 3-5.6 and a temperature range of 25-40°C. When mine tailings were exposed to acid rain of pH 4.8 (the average rain pH of the mining site where the mine tailings were from), TETA-Mt achieved an inhibition efficiency of over 90% for Cu(2+), Zn(2+), Cd(2+) and Mn(2+) release, and 70% for Pb(2+) at 25°C. It was shown that TETA-Mt has a strong buffering capacity. Moreover, TETA-Mt was able to adsorb heavy metal ions and the adsorption process was fast, suggesting that coordination was mainly responsible. These results showed the potential of TETA-Mt in AMD mitigation, especially in acid rain affected mining area. Copyright © 2016 Elsevier B.V. All rights reserved.

Mannan-Modified PLGA Nanoparticles for Targeted Gene Delivery

Directory of Open Access Journals (Sweden)

Fansheng Kong

2012-01-01

Full Text Available The studies of targeted gene delivery nanocarriers have gained increasing attention during the past decades. In this study, mannan modified DNA loaded bioadhesive PLGA nanoparticles (MAN-DNA-NPs were investigated for targeted gene delivery to the Kupffer cells (KCs. Bioadhesive PLGA nanoparticles were prepared and subsequently bound with pEGFP. Following the coupling of the mannan-based PE-grafted ligands (MAN-PE with the DNA-NPs, the MAN-DNA-NPs were delivered intravenously to rats. The transfection efficiency was determined from the isolated KCs and flow cytometry was applied for the quantitation of gene expression after 48 h post transfection. The size of the MAN-DNA-NPs was found to be around 190 nm and the Zeta potential was determined to be −15.46mV. The pEGFP binding capacity of MAN-DNA-NPs was (88.9±5.8% and the in vitro release profiles of the MAN-DNA-NPs follow the Higuchi model. When compared with non-modified DNA-NPs and Lipofectamine 2000-DNA, MAN-DNA-NPs produced the highest gene expressions, especially in vivo. The in vivo data from flow cytometry analysis showed that MAN-DNA-NPs displayed a remarkably higher transfection efficiency (39% than non-modified DNA-NPs (25% and Lipofectamine 2000-DNA (23% in KCs. The results illustrate that MAN-DNA-NPs have the ability to target liver KCs and could function as promising active targeting drug delivery vectors.

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.

Folate-conjugated polymeric micelle HB-loaded on targeting effect by intraperitoneal to ovarian cancer in vitro and in vivo.

Science.gov (United States)

Li, Jie; Yao, Shu; Wang, Kai; Lu, Zaijun; Su, Xuantao; Li, Li; Yuan, Cunzhong; Feng, Jinbo; Yan, Shi; Kong, Beihua; Song, Kun

2018-04-04

Photodynamic therapy (PDT) is considered as an innovative and attractive modality to treat ovarian cancer. In this study, a biodegradable polymer poly (ethylene glycol)-poly (lactic acid)(PLA)-folate (FA-PEG-PLA) was prepared in order to synthesize an active targeting, water soluble and pharmacomodulated photosensitizer nano-carriers. The drug loading content, encapsulation efficiency, in vitro and in vivo release were characterized, in which HB/FA-PEG-PLA micelles had a high encapsulation efficiency and much slower control release for drugs compared to free drugs (pHB/FA-PEG-PLA micelles, the cellular uptake study in vitro were tested, which owned significantly enhanced uptake of HB/FA-PEG-PLA micelles in SKOV3 (FR+) compared to A2780 cancer cells (FR-). The enhanced uptake of HB/FA-PEG-PLA micelles to cancer cells resulted in a more effective post-PDT killing of SKOV3 cells compared to plain micelles and free drugs. Binding and uptake of HB/FA-PEG-PLA micelles by SKOV3 cells were also observed in vivo after intraperitoneal injection of folate targeted micelles in tumor-bearing ascitic ovarian cancer animals. The drug levels in ascitic tumor tissues were increased by 20-fold (pHB-loaded micelles were mainly distributed in kidney and liver (the main clearance organs) in biodistribution. These results demonstrated that our new developed PDT photosensitizer HB/FA-PEG-PLA micelles has a high drug-loading capacity, good biocompatibility, control drug release, and enhanced targeting and antitumor effect, which is a potential approach to future targeting ovarian cancer therapy. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

The roles of energy and material efficiency in meeting steel industry CO2 targets.

Science.gov (United States)

Milford, Rachel L; Pauliuk, Stefan; Allwood, Julian M; Müller, Daniel B

2013-04-02

Identifying strategies for reducing greenhouse gas emissions from steel production requires a comprehensive model of the sector but previous work has either failed to consider the whole supply chain or considered only a subset of possible abatement options. In this work, a global mass flow analysis is combined with process emissions intensities to allow forecasts of future steel sector emissions under all abatement options. Scenario analysis shows that global capacity for primary steel production is already near to a peak and that if sectoral emissions are to be reduced by 50% by 2050, the last required blast furnace will be built by 2020. Emissions reduction targets cannot be met by energy and emissions efficiency alone, but deploying material efficiency provides sufficient extra abatement potential.

Production of Cs and Fr isotopes from a high-density UC targets with different grain dimensions

Energy Technology Data Exchange (ETDEWEB)

Panteleev, V.N.; Barzakh, A.E.; Fedorov, D.V.; Ivanov, V.S.; Mezilev, K.A.; Molkanov, P.L.; Moroz, F.V.; Orlov, S.Yu.; Volkov, Yu.M. [Petersburg Nuclear Physics Institute RAS, Gatchina (Russian Federation); Alyakrinskiy, O.; Barbui, M.; Stroe, L.; Tecchio, L.B.; Tonezzer, M. [Laboratori Nationali di Legnaro, Legnaro (Padova) (Italy); Lhersonneau, G. [GANIL, Caen Cedex 5 (France)

2009-12-15

A UC target material of 11.3{+-}0.5 g/cm{sup 3} uranium density with the grain size of 20 and 5{mu}m manufactured in a form of pills by the method of powder metallurgy has been tested on-line within the temperature range of 1800-2100 C. The mass of uranium exposed to the beam was 4-7g. The yields and release rates of Cs and Fr isotopes produced by fission and spallation reactions of {sup 238}U by 1GeV protons have been measured. The yields of Cs and Fr isotopes obtained from the tested target materials have been compared, including yields of very short-lived Fr isotopes with half-lives down to 1ms. Temperature-resistant materials (porous graphite and tantalum foil) have been used for the internal-container construction, which holds the UC target pills inside a tungsten external container heated by the resistant heating. The fastest release and the highest efficiency for short-lived isotopes have been obtained for the targets with the internal container manufactured from the tantalum foil. Results of on-line tests of a big mass target (730g of 5{mu}m grain UC target material) have been discussed. (orig.)

Production of Cs and Fr isotopes from a high-density UC targets with different grain dimensions

International Nuclear Information System (INIS)

Panteleev, V.N.; Barzakh, A.E.; Fedorov, D.V.; Ivanov, V.S.; Mezilev, K.A.; Molkanov, P.L.; Moroz, F.V.; Orlov, S.Yu.; Volkov, Yu.M.; Alyakrinskiy, O.; Barbui, M.; Stroe, L.; Tecchio, L.B.; Tonezzer, M.; Lhersonneau, G.

2009-01-01

A UC target material of 11.3±0.5 g/cm 3 uranium density with the grain size of 20 and 5μm manufactured in a form of pills by the method of powder metallurgy has been tested on-line within the temperature range of 1800-2100 C. The mass of uranium exposed to the beam was 4-7g. The yields and release rates of Cs and Fr isotopes produced by fission and spallation reactions of 238 U by 1GeV protons have been measured. The yields of Cs and Fr isotopes obtained from the tested target materials have been compared, including yields of very short-lived Fr isotopes with half-lives down to 1ms. Temperature-resistant materials (porous graphite and tantalum foil) have been used for the internal-container construction, which holds the UC target pills inside a tungsten external container heated by the resistant heating. The fastest release and the highest efficiency for short-lived isotopes have been obtained for the targets with the internal container manufactured from the tantalum foil. Results of on-line tests of a big mass target (730g of 5μm grain UC target material) have been discussed. (orig.)

Targeted delivery and pH-responsive release of stereoisomeric anti-cancer drugs using β-cyclodextrin assemblied Fe{sub 3}O{sub 4} nanoparticles

Energy Technology Data Exchange (ETDEWEB)

Wang, Congli; Huang, Lizhen; Song, Shengmei; Saif, Bassam; Zhou, Yehong; Dong, Chuan; Shuang, Shaomin, E-mail: smshuang@sxu.edu.cn

2015-12-01

Graphical abstract: - Highlights: • β-Cyclodextrin assemblied magnetic Fe{sub 3}O{sub 4} nanoparticles (β-CD-MNPs) with good stability were successfully fabricated. • Stereoisomeric doxorubicin (DOX) and epirubicin (EPI) were used to explore the loading and release performance. • The loading properties of β-CD-MNPs were investigated using the Langmuir and Freundlich adsorption equilibrium models. • {sup 1}H NMR and the computer simulation were used to demonstrate the inclusion position between drug molecules and β-CD. - Abstract: The β-cyclodextrin assemblied magnetic Fe{sub 3}O{sub 4} nanoparticles (β-CD-MNPs) were successfully fabricated via a layer-by-layer method. Possessing an average size 14 nm, good stability and super-paramagnetic response (Ms 64 emu/g), the resultant nanocomposites could be served as a versatile biocompatible platform for selective loading, targeted delivery and pH-responsive release of stereoisomeric doxorubicin (DOX) and epirubicin (EPI). {sup 1}H-nuclear magnetic resonance ({sup 1}H NMR) and the computer simulation further give the evidence that partial anthracene ring of drug molecule is included by β-CD. In addition, non-toxic β-CD-MNPs have excellent biocompatibility on MCF-7 cells, and cellular uptake indicate that different amounts of DOX or EPI can be transported to targeting site and released from the internalized carriers. The results demonstrate that as-prepared β-CD-MNPs could be a very promising vehicle for DOX and EPI.

Theranostic pH-sensitive nanoparticles for highly efficient targeted delivery of doxorubicin for breast tumor treatment.

Science.gov (United States)

Pan, Changqie; Liu, Yuqing; Zhou, Minyu; Wang, Wensheng; Shi, Min; Xing, Malcolm; Liao, Wangjun

2018-01-01

A multifunctional theranostic nanoplatform integrated with environmental responses has been developed rapidly over the past few years as a novel treatment strategy for several solid tumors. We synthesized pH-sensitive poly(β-thiopropionate) nanoparticles with a supermagnetic core and folic acid (FA) conjugation (FA-doxorubicin-iron oxide nanoparticles [FA-DOX@ IONPs]) to deliver an antineoplastic drug, DOX, for the treatment of folate receptor (FR)-overexpressed breast cancer. In addition to an imaging function, the nanoparticles can release their payloads in response to an environment of pH 5, such as the acidic environment found in tumors. After chemical ( 1 H nuclear magnetic resonance) and physical (morphology and super-magnetic) characterization, FA-DOX@IONPs were shown to demonstrate pH-dependent drug release profiles. Western blotting analysis revealed the expression of FRs in three breast cancer cell lines, MCF-7, BT549, and MD-MBA-231. The cell counting kit-8 assay and transmission electron microscopy showed that FA-DOX@IONPs had the strongest cytotoxicity against breast cancer cells, compared with free DOX and non-FR targeted nanoparticles (DOX@IONPs), and caused cellular apoptosis. The FA-DOX@IONP-mediated cellular uptake and intracellular internalization were clarified by fluorescence microscopy. FA-DOX@IONPs plus magnetic field treatment suppressed in vivo tumor growth in mice to a greater extent than either treatment alone; furthermore, the nanoparticles exerted no toxicity against healthy organs. Magnetic resonance imaging was successfully applied to monitor the nanoparticle accumulation. Our results suggest that theranostic pH-sensitive nanoparticles with dual targeting could enhance the available therapies for cancer.

Efficient interruption of infection chains by targeted removal of central holdings in an animal trade network.

Science.gov (United States)

Büttner, Kathrin; Krieter, Joachim; Traulsen, Arne; Traulsen, Imke

2013-01-01

Centrality parameters in animal trade networks typically have right-skewed distributions, implying that these networks are highly resistant against the random removal of holdings, but vulnerable to the targeted removal of the most central holdings. In the present study, we analysed the structural changes of an animal trade network topology based on the targeted removal of holdings using specific centrality parameters in comparison to the random removal of holdings. Three different time periods were analysed: the three-year network, the yearly and the monthly networks. The aim of this study was to identify appropriate measures for the targeted removal, which lead to a rapid fragmentation of the network. Furthermore, the optimal combination of the removal of three holdings regardless of their centrality was identified. The results showed that centrality parameters based on ingoing trade contacts, e.g. in-degree, ingoing infection chain and ingoing closeness, were not suitable for a rapid fragmentation in all three time periods. More efficient was the removal based on parameters considering the outgoing trade contacts. In all networks, a maximum percentage of 7.0% (on average 5.2%) of the holdings had to be removed to reduce the size of the largest component by more than 75%. The smallest difference from the optimal combination for all three time periods was obtained by the removal based on out-degree with on average 1.4% removed holdings, followed by outgoing infection chain and outgoing closeness. The targeted removal using the betweenness centrality differed the most from the optimal combination in comparison to the other parameters which consider the outgoing trade contacts. Due to the pyramidal structure and the directed nature of the pork supply chain the most efficient interruption of the infection chain for all three time periods was obtained by using the targeted removal based on out-degree.

Caffeine Modulates Vesicle Release and Recovery at Cerebellar Parallel Fibre Terminals, Independently of Calcium and Cyclic AMP Signalling

Science.gov (United States)

Dobson, Katharine L.; Jackson, Claire; Balakrishnan, Saju; Bellamy, Tomas C.

2015-01-01

Background Cerebellar parallel fibres release glutamate at both the synaptic active zone and at extrasynaptic sites—a process known as ectopic release. These sites exhibit different short-term and long-term plasticity, the basis of which is incompletely understood but depends on the efficiency of vesicle release and recycling. To investigate whether release of calcium from internal stores contributes to these differences in plasticity, we tested the effects of the ryanodine receptor agonist caffeine on both synaptic and ectopic transmission. Methods Whole cell patch clamp recordings from Purkinje neurons and Bergmann glia were carried out in transverse cerebellar slices from juvenile (P16-20) Wistar rats. Key Results Caffeine caused complex changes in transmission at both synaptic and ectopic sites. The amplitude of postsynaptic currents in Purkinje neurons and extrasynaptic currents in Bergmann glia were increased 2-fold and 4-fold respectively, but paired pulse ratio was substantially reduced, reversing the short-term facilitation observed under control conditions. Caffeine treatment also caused synaptic sites to depress during 1 Hz stimulation, consistent with inhibition of the usual mechanisms for replenishing vesicles at the active zone. Unexpectedly, pharmacological intervention at known targets for caffeine—intracellular calcium release, and cAMP signalling—had no impact on these effects. Conclusions We conclude that caffeine increases release probability and inhibits vesicle recovery at parallel fibre synapses, independently of known pharmacological targets. This complex effect would lead to potentiation of transmission at fibres firing at low frequencies, but depression of transmission at high frequency connections. PMID:25933382

Surface-modified CMOS IC electrochemical sensor array targeting single chromaffin cells for highly parallel amperometry measurements.

Science.gov (United States)

Huang, Meng; Delacruz, Joannalyn B; Ruelas, John C; Rathore, Shailendra S; Lindau, Manfred

2018-01-01

Amperometry is a powerful method to record quantal release events from chromaffin cells and is widely used to assess how specific drugs modify quantal size, kinetics of release, and early fusion pore properties. Surface-modified CMOS-based electrochemical sensor arrays allow simultaneous recordings from multiple cells. A reliable, low-cost technique is presented here for efficient targeting of single cells specifically to the electrode sites. An SU-8 microwell structure is patterned on the chip surface to provide insulation for the circuitry as well as cell trapping at the electrode sites. A shifted electrode design is also incorporated to increase the flexibility of the dimension and shape of the microwells. The sensitivity of the electrodes is validated by a dopamine injection experiment. Microwells with dimensions slightly larger than the cells to be trapped ensure excellent single-cell targeting efficiency, increasing the reliability and efficiency for on-chip single-cell amperometry measurements. The surface-modified device was validated with parallel recordings of live chromaffin cells trapped in the microwells. Rapid amperometric spikes with no diffusional broadening were observed, indicating that the trapped and recorded cells were in very close contact with the electrodes. The live cell recording confirms in a single experiment that spike parameters vary significantly from cell to cell but the large number of cells recorded simultaneously provides the statistical significance.

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

Science.gov (United States)

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

2012-01-01

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

Highly efficient targeted mutagenesis in axolotl using Cas9 RNA-guided nuclease

Science.gov (United States)

Flowers, G. Parker; Timberlake, Andrew T.; Mclean, Kaitlin C.; Monaghan, James R.; Crews, Craig M.

2014-01-01

Among tetrapods, only urodele salamanders, such as the axolotl Ambystoma mexicanum, can completely regenerate limbs as adults. The mystery of why salamanders, but not other animals, possess this ability has for generations captivated scientists seeking to induce this phenomenon in other vertebrates. Although many recent advances in molecular biology have allowed limb regeneration and tissue repair in the axolotl to be investigated in increasing detail, the molecular toolkit for the study of this process has been limited. Here, we report that the CRISPR-Cas9 RNA-guided nuclease system can efficiently create mutations at targeted sites within the axolotl genome. We identify individual animals treated with RNA-guided nucleases that have mutation frequencies close to 100% at targeted sites. We employ this technique to completely functionally ablate EGFP expression in transgenic animals and recapitulate developmental phenotypes produced by loss of the conserved gene brachyury. Thus, this advance allows a reverse genetic approach in the axolotl and will undoubtedly provide invaluable insight into the mechanisms of salamanders' unique regenerative ability. PMID:24764077

The impact of preparation parameters on typical attributes of chitosan-heparin nanohydrogels: particle size, loading efficiency, and drug release.

Science.gov (United States)

Shahbazi, Mohammad-Ali; Hamidi, Mehrdad

2013-11-01

Today, developing an optimized nanoparticle (NP) preparation procedure is of paramount importance in all nanoparticulate drug delivery researches, leading to expanding more operative and clinically validated nanomedicines. In this study, a one-at-a-time experimental approach was used for evaluating the effect of various preparation factors on size, loading, and drug release of hydrogel NPs prepared with ionotropic gelation between heparin and chitosan. The size, loading efficiency (LE) and drug release profile of the NPs were evaluated when the chitosan molecular weight, chitosan concentration, heparin addition time to chitosan solution, heparin concentration, pH value of chitosan solution, temperature, and mixing rate were changed separately while other factors were in optimum condition. The results displayed that size and LE are highly influenced by chitosan concentration, getting an optimum of 63 ± 0.57 and 75.19 ± 2.65, respectively, when chitosan concentration was 0.75 mg/ml. Besides, heparin addition time of 3 min leaded to 74.1 ± 0.79 % LE with no sensible effect on size and release profile. In addition, pH 5.5 showed a minimum size of 63 ± 1.87, maximum LE of 73.81 ± 3.13 and the slowest drug release with 63.71 ± 3.84 % during one week. Although LE was not affected by temperature, size and release reduced to 63 ± 0 and 74.21 ± 1.99% when temperature increased from 25°C to 55°C. Also, continuous increase of mixer rate from 500 to 3500 rpm resulted in constant enhancement of LE from 58.3 ± 3.6 to 74.4 ± 2.59 as well as remarkable decrease in size from 148 ± 4.88 to 63 ± 2.64.

Intracellular siRNA delivery dynamics of integrin-targeted, PEGylated chitosan-poly(ethylene imine) hybrid nanoparticles

DEFF Research Database (Denmark)

Ragelle, Héloïse; Colombo, Stefano; Pourcelle, Vincent

2015-01-01

chitosan-poly(ethylene imine) hybrid nanoparticles. The amount of intracellular siRNA delivered by αvβ3-targeted versus non-targeted nanoparticles was quantified in the human non-small cell lung carcinoma cell line H1299 expressing enhanced green fluorescent protein (EGFP) using a stem-loop reverse...... that these nanoparticles might end up in late endosomes or lysosomes without releasing their cargo to the cell cytoplasm. Thus, the silencing efficiency of the chitosan-based nanoparticles is strongly dependent on the uptake and the intracellular trafficking in H1299 EGFP cells, which is critical information towards...

Increased efficiency of targeted mutagenesis by CRISPR/Cas9 in plants using heat stress.

Science.gov (United States)

LeBlanc, Chantal; Zhang, Fei; Mendez, Josefina; Lozano, Yamile; Chatpar, Krishna; Irish, Vivian F; Jacob, Yannick

2018-01-01

The CRISPR/Cas9 system has greatly improved our ability to engineer targeted mutations in eukaryotic genomes. While CRISPR/Cas9 appears to work universally, the efficiency of targeted mutagenesis and the adverse generation of off-target mutations vary greatly between different organisms. In this study, we report that Arabidopsis plants subjected to heat stress at 37°C show much higher frequencies of CRISPR-induced mutations compared to plants grown continuously at the standard temperature (22°C). Using quantitative assays relying on green fluorescent protein (GFP) reporter genes, we found that targeted mutagenesis by CRISPR/Cas9 in Arabidopsis is increased by approximately 5-fold in somatic tissues and up to 100-fold in the germline upon heat treatment. This effect of temperature on the mutation rate is not limited to Arabidopsis, as we observed a similar increase in targeted mutations by CRISPR/Cas9 in Citrus plants exposed to heat stress at 37°C. In vitro assays demonstrate that Cas9 from Streptococcus pyogenes (SpCas9) is more active in creating double-stranded DNA breaks at 37°C than at 22°C, thus indicating a potential contributing mechanism for the in vivo effect of temperature on CRISPR/Cas9. This study reveals the importance of temperature in modulating SpCas9 activity in eukaryotes, and provides a simple method to increase on-target mutagenesis in plants using CRISPR/Cas9. © 2017 The Authors The Plant Journal © 2017 John Wiley & Sons Ltd.

Altered Elementary Calcium Release Events and Enhanced Calcium Release by Thymol in Rat Skeletal Muscle

OpenAIRE

Szentesi, Péter; Szappanos, Henrietta; Szegedi, Csaba; Gönczi, Monika; Jona, István; Cseri, Julianna; Kovács, László; Csernoch, László

2004-01-01

The effects of thymol on steps of excitation-contraction coupling were studied on fast-twitch muscles of rodents. Thymol was found to increase the depolarization-induced release of calcium from the sarcoplasmic reticulum, which could not be attributed to a decreased calcium-dependent inactivation of calcium release channels/ryanodine receptors or altered intramembrane charge movement, but rather to a more efficient coupling of depolarization to channel opening. Thymol increased ryanodine bind...

Suppress orthotopic colon cancer and its metastasis through exact targeting and highly selective drug release by a smart nanomicelle.

Science.gov (United States)

Zhu, Chunqi; Zhang, Hanbo; Li, Wei; Luo, Lihua; Guo, Xiaomeng; Wang, Zuhua; Kong, Fenfen; Li, Qingpo; Yang, Jie; Du, Yongzhong; You, Jian

2018-04-01

The treatment of metastatic cancer is a huge challenge at the moment. Highly precise targeting delivery and drug release in tumor have always been our pursuit in cancer therapy, especially to advance cancer with metastasis, for increasing the efficacy and biosafety. We established a smart nanosized micelle, formed by tocopherol succinate (TOS) conjugated hyaluronic acid (HA) using a disulfide bond linker. The micelle (HA-SS-TOS, HSST) can highly specifically bind with CD44 receptor over-expressed tumor, and response selectively to high GSH level in the cells, inducing disulfide bond breakage and the release of the payload (paclitaxel, PTX). To predict the antitumor efficacy of the micelles more clinically, we established an orthotopic colon cancer model with high metastasis rate, which could be visualized by the luciferase bioluminescence. Our data confirmed CD44 high expression in the colon cancer cells. Highly matching between the micellar fluorescence and bioluminescence of cancer cells in intestines demonstrated an exact recognition of our micelles to orthotopic colon tumor and its metastatic cells, attributing to the mediation of CD44 receptors. Furthermore, the fluorescence of the released Nile Red from the micelles was found only in the tumor and its metastatic cells, and almost completely overlapped with the bioluminescence of the cancer cells, indicating a highly selective drug release. Our micelles presented an excellent therapeutic effect against metastatic colon cancer, and induced significantly prolonged survival time for the mice, which might become a promising nanomedicine platform for the future clinical application against advanced cancers with high CD44 receptor expression. Copyright © 2018 Elsevier Ltd. All rights reserved.

Preparation of magnetic polylactic acid microspheres and investigation of its releasing property for loading curcumin

Energy Technology Data Exchange (ETDEWEB)

Li Fengxia [Heilongjiang Key Laboratory of Molecular Design and Preparation of Flame Retarded Materials, College of Science, Northeast Forestry University, Harbin 150040 (China); Li Xiaoli, E-mail: lixiaoli0903@163.com [Heilongjiang Key Laboratory of Molecular Design and Preparation of Flame Retarded Materials, College of Science, Northeast Forestry University, Harbin 150040 (China); Li Bin, E-mail: libinzh62@163.com [Heilongjiang Key Laboratory of Molecular Design and Preparation of Flame Retarded Materials, College of Science, Northeast Forestry University, Harbin 150040 (China)

2011-11-15

In order to obtain a targeting drug carrier system, magnetic polylactic acid (PLA) microspheres loading curcumin were synthesized by the classical oil-in-water emulsion solvent-evaporation method. In the Fourier transform infrared spectra of microspheres, the present functional groups of PLA were all kept invariably. The morphology and size distribution of magnetic microspheres were observed with scanning electron microscopy and dynamic light scattering, respectively. The results showed that the microspheres were regularly spherical and the surface was smooth with a diameter of 0.55-0.75 {mu}m. Magnetic Fe{sub 3}O{sub 4} was loaded in PLA microspheres and the content of magnetic particles was 12 wt% through thermogravimetric analysis. The magnetic property of prepared microspheres was measured by vibrating sample magnetometer. The results showed that the magnetic microspheres exhibited typical superparamagnetic behavior and the saturated magnetization was 14.38 emu/g. Through analysis of differential scanning calorimetry, the curcumin was in an amorphous state in the magnetic microspheres. The drug loading, encapsulation efficiency and releasing properties of curcumin in vitro were also investigated by ultraviolet-visible spectrum analysis. The results showed that the drug loading and encapsulation efficiency were 8.0% and 24.2%, respectively. And curcumin was obviously slowly released because the cumulative release percentage of magnetic microspheres in the phosphate buffer (pH=7.4) solution was only 49.01% in 72 h, and the basic release of curcumin finished in 120 h. - Highlights: > We prepare magnetic polylactic acid microspheres loading curcumin. > The classical oil-in-water emulsion solvent-evaporation method is used. > The magnetic microspheres are regularly spherical with a diameter of 0.55-0.75 {mu}m. > They show a certain sustained release effect on in vitro drug releasing.

Preparation of magnetic polylactic acid microspheres and investigation of its releasing property for loading curcumin

International Nuclear Information System (INIS)

Li Fengxia; Li Xiaoli; Li Bin

2011-01-01

In order to obtain a targeting drug carrier system, magnetic polylactic acid (PLA) microspheres loading curcumin were synthesized by the classical oil-in-water emulsion solvent-evaporation method. In the Fourier transform infrared spectra of microspheres, the present functional groups of PLA were all kept invariably. The morphology and size distribution of magnetic microspheres were observed with scanning electron microscopy and dynamic light scattering, respectively. The results showed that the microspheres were regularly spherical and the surface was smooth with a diameter of 0.55-0.75 μm. Magnetic Fe 3 O 4 was loaded in PLA microspheres and the content of magnetic particles was 12 wt% through thermogravimetric analysis. The magnetic property of prepared microspheres was measured by vibrating sample magnetometer. The results showed that the magnetic microspheres exhibited typical superparamagnetic behavior and the saturated magnetization was 14.38 emu/g. Through analysis of differential scanning calorimetry, the curcumin was in an amorphous state in the magnetic microspheres. The drug loading, encapsulation efficiency and releasing properties of curcumin in vitro were also investigated by ultraviolet-visible spectrum analysis. The results showed that the drug loading and encapsulation efficiency were 8.0% and 24.2%, respectively. And curcumin was obviously slowly released because the cumulative release percentage of magnetic microspheres in the phosphate buffer (pH=7.4) solution was only 49.01% in 72 h, and the basic release of curcumin finished in 120 h. - Highlights: → We prepare magnetic polylactic acid microspheres loading curcumin. → The classical oil-in-water emulsion solvent-evaporation method is used. → The magnetic microspheres are regularly spherical with a diameter of 0.55-0.75 μm. → They show a certain sustained release effect on in vitro drug releasing.

Nanoparticle-neural stem cells for targeted ovarian cancer treatment: optimization of silica nanoparticles for efficient drug loading

Science.gov (United States)

Patel, Z.; Berlin, J.; Abidi, W.

2018-02-01

One of the drugs used to treat ovarian cancer is cisplatin. However, cisplatin kills normal surrounding tissue in addition to cancer cells. To improve tumor targeting efficiency, our lab uses neural stem cells (NSCs), which migrate directly to ovarian tumors. If free cisplatin is loaded into NSCs for targeted drug delivery, it will kill the NSCs. To prevent the drug cisplatin from killing both the NSCs and normal surrounding tissue, our lab synthesizes silica nanoparticles (SiNPs) that act as a protective carrier. The big picture here is to maximize efficiency of tumor targeting using NSCs and minimize toxicity to these NSCs using SiNPs. The goal of this project is to optimize the stability of SiNPs, which is important for efficient drug loading. To do this, the concentration of tetraethyl orthosilicate (TEOS), one of the main components of SiNPs, was varied. We hypothesized that more TEOS equates to more stable SiNPs because TEOS contributes carbon to SiNPs, and thus a tightly-packed chemical structure results in a stable particle. Then, the stability of the SiNPs were checked in cell media and phosphate buffered saline (PBS). Lastly, the SiNPs were analyzed for their porosity using the transmission electron microscope (TEM). TEM imaging showed white spots in the 200-800 μL TEOS batches and no white spots in the 1000-1800 μL TEOS batches. The white spots were pores, which indicate instability. We concluded that the ultimate factor that determines the stability of SiNPs (100 nm) is the concentration of organic substance.

Gene-carried hepatoma targeting complex induced high gene transfection efficiency with low toxicity and significant antitumor activity

Directory of Open Access Journals (Sweden)

Zhao QQ

2012-06-01

Full Text Available Qing-Qing Zhao,1,2 Yu-Lan Hu,1 Yang Zhou,3 Ni Li,1 Min Han,1 Gu-Ping Tang,4 Feng Qiu,2 Yasuhiko Tabata,5 Jian-Qing Gao,11Institute of Pharmaceutics, Zhejiang University, Hangzhou, China; 2Department of Pharmacy, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China; 3Institute of Biochemistry, Iowa State University, Ames, IA, USA; 4Institute of Chemical Biology and Pharmaceutical Chemistry, Zhejiang University, Hangzhou, China; 5Institute for Frontier Medical Sciences, Kyoto University, Kyoto, JapanBackground: The success of gene transfection is largely dependent on the development of a vehicle or vector that can efficiently deliver a gene to cells with minimal toxicity.Methods: A liver cancer-targeted specific peptide (FQHPSF sequence was successfully synthesized and linked with chitosan-linked polyethylenimine (CP to form a new targeted gene delivery vector called CPT (CP/peptide. The structure of CPT was confirmed by 1H nuclear magnetic resonance spectroscopy and ultraviolet spectrophotometry. The particle size of CPT/DNA complexes was measured using laser diffraction spectrometry and the cytotoxicity of the copolymer was evaluated by methylthiazol tetrazolium method. The transfection efficiency evaluation of the CP copolymer was performed using luciferase activity assay. Cellular internalization of the CP/DNA complex was observed under confocal laser scanning microscopy. The targeting specificity of the polymer coupled to peptide was measured by competitive inhibition transfection study. The liver targeting specificity of the CPT copolymer in vivo was demonstrated by combining the copolymer with a therapeutic gene, interleukin-12, and assessed by its abilities in suppressing the growth of ascites tumor in mouse model.Results: The results showed that the liver cancer-targeted specific peptide was successfully synthesized and linked with CP to form a new targeted gene delivery vector called CPT. The composition of CPT

Functional single-walled carbon nanotubes based on an integrin αvβ3 monoclonal antibody for highly efficient cancer cell targeting

International Nuclear Information System (INIS)

Ou Zhongmin; Wu Baoyan; Xing Da; Zhou Feifan; Wang Huiying; Tang Yonghong

2009-01-01

The application of single-walled carbon nanotubes (SWNTs) in the field of biomedicine is becoming an entirely new and exciting topic. In this study, a novel functional SWNT based on an integrin α v β 3 monoclonal antibody was developed and was used for cancer cell targeting in vitro. SWNTs were first modified by phospholipid-bearing polyethylene glycol (PL-PEG). The PL-PEG functionalized SWNTs were then conjugated with protein A. A SWNT-integrin α v β 3 monoclonal antibody system (SWNT-PEG-mAb) was thus constructed by conjugating protein A with the fluorescein labeled integrin α v β 3 monoclonal antibody. In vitro study revealed that SWNT-PEG-mAb presented a high targeting efficiency on integrin α v β 3 -positive U87MG cells with low cellular toxicity, while for integrin α v β 3 -negative MCF-7 cells, the system had a low targeting efficiency, indicating that the high targeting to U87MG cells was due to the specific integrin targeting of the monoclonal antibody. In conclusion, SWNT-PEG-mAb developed in this research is a potential candidate for cancer imaging and drug delivery in cancer targeting therapy.

Transient overexpression of DNA adenine methylase enables efficient and mobile genome engineering with reduced off-target effects

DEFF Research Database (Denmark)

Lennen, Rebecca; Nilsson Wallin, Annika; Pedersen, Margit

2016-01-01

Homologous recombination of single-stranded oligonucleotides is a highly efficient process for introducing precise mutations into the genome of E. coli and other organisms when mismatch repair (MMR) is disabled. This can result in the rapid accumulation of off-target mutations that can mask desir...

Specific and Efficient Regression of Cancers Harboring KRAS Mutation by Targeted RNA Replacement.

Science.gov (United States)

Kim, Sung Jin; Kim, Ju Hyun; Yang, Bitna; Jeong, Jin-Sook; Lee, Seong-Wook

2017-02-01

Mutations in the KRAS gene, which persistently activate RAS function, are most frequently found in many types of human cancers. Here, we proposed and verified a new approach against cancers harboring the KRAS mutation with high cancer selectivity and efficient anti-cancer effects based on targeted RNA replacement. To this end, trans-splicing ribozymes from Tetrahymena group I intron were developed, which can specifically target and reprogram the mutant KRAS G12V transcript to induce therapeutic gene activity in cells. Adenoviral vectors containing the specific ribozymes with downstream suicide gene were constructed and then infection with the adenoviruses specifically downregulated KRAS G12V expression and killed KRAS G12V-harboring cancer cells additively upon pro-drug treatment, but it did not affect the growth of wild-type KRAS-expressing cells. Minimal liver toxicity was noted when the adenoviruses were administered systemically in vivo. Importantly, intratumoral injection of the adenoviruses with pro-drug treatment specifically and significantly impeded the growth of xenografted tumors harboring KRAS G12V through a trans-splicing reaction with the target RNA. In contrast, xenografted tumors harboring wild-type KRAS were not affected by the adenoviruses. Therefore, RNA replacement with a mutant KRAS-targeting trans-splicing ribozyme is a potentially useful therapeutic strategy to combat tumors harboring KRAS mutation. Copyright © 2017 The American Society of Gene and Cell Therapy. Published by Elsevier Inc. All rights reserved.

Efficient laser-induced 6-8 keV x-ray production from iron oxide aerogel and foil-lined cavity targets

Energy Technology Data Exchange (ETDEWEB)

Pérez, F.; Kay, J. J.; Patterson, J. R.; Kane, J.; Villette, B.; Girard, F.; Reverdin, C.; May, M.; Emig, J.; Sorce, C.; Colvin, J.; Gammon, S.; Jaquez, J.; Satcher, J. H.; Fournier, K. B.

2012-08-01

The performance of new iron-based laser-driven x-ray sources has been tested at the OMEGA laser facility for production of x rays in the 6.5–8.5 keV range. Two types of targets were experimentally investigated: low-density iron oxide aerogels (density 6-16 mg/cm36-16 mg/cm3) and stainless steel foil-lined cavity targets (steel thickness 1-5 μm1-5 μm). The targets were irradiated by 40 beams of the OMEGA laser (500 J/beam, 1 ns pulse, wavelength 351 nm). All targets showed good coupling with the laser, with <5%<5% of the incident laser light backscattered by the resulting plasma in all cases (typically <2.5%<2.5%). The aerogel targets produced Te=2Te=2 to 3 keV, ne=0.12-0.2ne=0.12-0.2 critical density plasmas yielding a 40%–60% laser-to-x-ray total conversion efficiency (CE) (1.2%–3% in the Fe K-shell range). The foil cavity targets produced Te~2 keV, T_e~2 keV, n_e~0.15ne~0.15 critical density plasmas yielding a 60%–75% conversion efficiency (1.6%–2.2% in the Fe K-shell range). Time-resolved images illustrate that the volumetric heating of low-density aerogels allow them to emit a higher K-shell x-ray yield even though they contain fewer Fe atoms. However, their challenging fabrication process leads to a larger shot-to-shot variation than cavity targets.

Stimuli responsive nanomaterials for controlled release applications

KAUST Repository

Li, Song

2012-01-01

The controlled release of therapeutics has been one of the major challenges for scientists and engineers during the past three decades. Coupled with excellent biocompatibility profiles, various nanomaterials have showed great promise for biomedical applications. Stimuli-responsive nanomaterials guarantee the controlled release of cargo to a given location, at a specific time, and with an accurate amount. In this review, we have combined the major stimuli that are currently used to achieve the ultimate goal of controlled and targeted release by "smart" nanomaterials. The most heavily explored strategies include (1) pH, (2) enzymes, (3) redox, (4) magnetic, and (5) light-triggered release.

Correction of acid beta-galactosidase deficiency in GM1 gangliosidosis human fibroblasts by retrovirus vector-mediated gene transfer: higher efficiency of release and cross-correction by the murine enzyme.

Science.gov (United States)

Sena-Esteves, M; Camp, S M; Alroy, J; Breakefield, X O; Kaye, E M

2000-03-20

Mutations in the lysosomal acid beta-galactosidase (EC 3.2.1.23) underlie two different disorders: GM1 gangliosidosis, which involves the nervous system and visceral organs to varying extents, and Morquio's syndrome type B (Morquio B disease), which is a skeletal-connective tissue disease without any CNS symptoms. This article shows that transduction of human GM1 gangliosidosis fibroblasts with retrovirus vectors encoding the human acid beta-galactosidase cDNA leads to complete correction of the enzymatic deficiency. The newly synthesized enzyme is correctly processed and targeted to the lysosomes in transduced cells. Cross-correction experiments using retrovirus-modified cells as enzyme donors showed, however, that the human enzyme is transferred at low efficiencies. Experiments using a different retrovirus vector carrying the human cDNA confirmed this observation. Transduction of human GM1 fibroblasts and mouse NIH 3T3 cells with a retrovirus vector encoding the mouse beta-galactosidase cDNA resulted in high levels of enzymatic activity. Furthermore, the mouse enzyme was found to be transferred to human cells at high efficiency. Enzyme activity measurements in medium conditioned by genetically modified cells suggest that the human beta-galactosidase enzyme is less efficiently released to the extracellular space than its mouse counterpart. This study suggests that lysosomal enzymes, contrary to the generalized perception in the field of gene therapy, may differ significantly in their properties and provides insights for design of future gene therapy interventions in acid beta-galactosidase deficiency.

Isotope release cytotoxicity assay applicable to human tumors: the use of 111-indium

Energy Technology Data Exchange (ETDEWEB)

Frost, P; Wiltrout, R; Maciorowski, Z; Rose, N R

1977-01-01

We have demonstrated that human tumors can be labelled efficiently with the 111indium-oxine chelate. Subsequently, this isotope can be released by cytotoxic lymphoid cells. Both natural and induced cytotoxicity can be demonstrated utilizing this isotope release method. Because of the slow spontaneous release of 111indium and its efficient labelling of human tumor cells, this isotope release assay can be utilized in long-term cytotoxic assays in the study of human tumor immunology.

Efficient energy absorption of intense ps-laser pulse into nanowire target

Energy Technology Data Exchange (ETDEWEB)

Habara, H.; Honda, S.; Katayama, M.; Tanaka, K. A. [Graduate School of Engineering, Osaka University, 2-1 Suita, Osaka 565-0871 (Japan); Sakagami, H. [National Institute for Fusion Science, Toki, Gifu 509-5292 (Japan); Nagai, K. [Laboratory for Chemistry and Life Science, Institute of Innovative Research, Tokyo Institute of Technology, Nagatsuda 4259, Midori-ku, Yokohama 226-8503, Kanagawa (Japan)

2016-06-15

The interaction between ultra-intense laser light and vertically aligned carbon nanotubes is investigated to demonstrate efficient laser-energy absorption in the ps laser-pulse regime. Results indicate a clear enhancement of the energy conversion from laser to energetic electrons and a simultaneously small plasma expansion on the surface of the target. A two-dimensional plasma particle calculation exhibits a high absorption through laser propagation deep into the nanotube array, even for a dense array whose structure is much smaller than the laser wavelength. The propagation leads to the radial expansion of plasma perpendicular to the nanotubes rather than to the front side. These features may contribute to fast ignition in inertial confinement fusion and laser particle acceleration, both of which require high current and small surface plasma simultaneously.

Encapsulation of naproxen in lipid-based matrix microspheres: characterization and release kinetics.

Science.gov (United States)

Bhoyar, P K; Morani, D O; Biyani, D M; Umekar, M J; Mahure, J G; Amgaonkar, Y M

2011-04-01

The objective of this study was to microencapsulate the anti-inflammatory drug (naproxen) to provide controlled release and minimizing or eliminating local side effect by avoiding the drug release in the upper gastrointestinal track. Naproxen was microencapsulated with lipid-like carnauba wax, hydrogenated castor oil using modified melt dispersion (modified congealable disperse phase encapsulation) technique. Effect of various formulation and process variables such as drug-lipid ratio, concentration of modifier, concentration of dispersant, stirring speed, stirring time, temperature of external phase, on evaluatory parameters such as size, entrapment efficiency, and in vitro release of naproxen were studied. The microspheres were characterized for particle size, scanning electron microscopy (SEM), FT-IR spectroscopy, drug entrapment efficiency, in vitro release studies, for in vitro release kinetics. The shape of microspheres was found to be spherical by SEM. The drug entrapment efficiency of various batches of microspheres was found to be ranging from 60 to 90 %w/w. In vitro drug release studies were carried out up to 24 h in pH 7.4 phosphate buffer showing 50-65% drug release. In vitro drug release from all the batches showed better fitting with the Korsmeyer-Peppas model, indicating the possible mechanism of drug release to be by diffusion and erosion of the lipid matrix.

Effect of linkers on the αvβ3 integrin targeting efficiency of cyclic RGD-conjugates

Science.gov (United States)

Karmakar, Partha; Grabowska, Dorota; Sudlow, Gail; Ziabrev, Kostiantyn; Sanyal, Nibedita; Achilefu, Samuel

2018-02-01

Cyclic arginine-glycine-aspartic acid (cRGD) peptides are well known to target ανβ3 integrin expressed on cancer cells and neovasculature. Conjugation of these peptides with dyes, drugs, antibodies and other biomolecules through covalent linkers provides a facile way to deliver these products to tumor cells for targeted cancer therapy and diagnosis. Click chemistry and acid-amine couplings are widely used conjugation strategies. However, the effects of different linkers and the distance between the cRGD and the conjugates on the binding of cRGD ligand with ανβ3 has been underexplored. In this present study, we prepared cRGD-conjugates using different linkers and determined how they altered the tumor targeting efficiency in vitro and in vivo. The results demonstrate that different linkers significantly altered the pharmacokinetics of the cRGD conjugates and the tumor uptake kinetics. Unlike large antibodies, this preliminary finding shows that linkers used to attach drugs and fluorescent molecular probes to small peptides play a major role in the accuracy of tumor targeting and treatment outcomes. As a result, considerable attention should be paid to the nature of linkers used in the design of molecular probes and targeted therapeutics.

A novel folate-modified self-microemulsifying drug delivery system of curcumin for colon targeting

Directory of Open Access Journals (Sweden)

Zhang L

2012-01-01

Full Text Available Lin Zhang1*, Weiwei Zhu2*, Chunfen Yang1, Hongxia Guo1, Aihua Yu1, Jianbo Ji3, Yan Gao1, Min Sun1, Guangxi Zhai11Department of Pharmaceutical Engineering, College of Pharmacy, Shandong University, Jinan; 2Department of Pharmacy, Yantai Yuhuangding Hospital, Yantai; 3Department of Pharmacology, College of Pharmacy, Shandong University, Jinan, China*These authors contributed equally to the workBackground: The objective of this study was to prepare, characterize, and evaluate a folate-modified self-microemulsifying drug delivery system (FSMEDDS with the aim to improve the solubility of curcumin and its delivery to the colon, facilitating endocytosis of FSMEDDS mediated by folate receptors on colon cancer cells.Methods: Ternary phase diagrams were constructed in order to obtain the most efficient self-emulsification region, and the formulation of curcumin-loaded SMEDDS was optimized by a simplex lattice experiment design. Then, three lipophilic folate derivatives (folate-polyethylene glycol-distearoylphosphatidylethanolamine, folate-polyethylene glycol-cholesteryl hemisuccinate, and folate-polyethylene glycol-cholesterol used as a surfactant were added to curcumin-loaded SMEDDS formulations. An in situ colon perfusion method in rats was used to optimize the formulation of FSMEDDS. Curcumin-loaded FSMEDDS was then filled into colon-targeted capsules and the in vitro release was investigated. Cytotoxicity studies and cellular uptake studies was used in this research.Results: The optimal formulation of FSMEDDS obtained with the established in situ colon perfusion method in rats was comprised of 57.5% Cremophor® EL, 32.5% Transcutol® HP, 10% Capryol™ 90, and a small amount of folate-polyethylene glycol-cholesteryl hemisuccinate (the weight ratio of folate materials to Cremophor EL was 1:100. The in vitro release results indicated that the obtained formulation of curcumin could reach the colon efficiently and release the drug immediately. Cellular

Clickable and imageable multiblock polymer micelles with magnetically guided and PEG-switched targeting and release property for precise tumor theranosis.

Science.gov (United States)

Wei, Jing; Shuai, Xiaoyu; Wang, Rui; He, Xueling; Li, Yiwen; Ding, Mingming; Li, Jiehua; Tan, Hong; Fu, Qiang

2017-11-01

Targeted delivery of therapeutics and diagnostics using nanotechnology holds great promise to minimize the side effects of conventional chemotherapy and enable specific and real-time detection of diseases. To realize this goal, we report a clickable and imageable nanovehicle assembled from multiblock polyurethanes (MPUs). The soft segments of the polymers are based on detachable poly(ethylene glycol) (PEG) and degradable poly(ε-caprolactone) (PCL), and the hard segments are constructed from lysine- and cystine-derivatives bearing reduction-responsive disulfide linkages and click-active alkynyl moieties, allowing for post-conjugation of targeting ligands via a click chemistry. It was found that the cleavage of PEG corona bearing a pH-sensitive benzoic-imine linkage (BPEG) could act as an on-off switch, which is capable of activating the clicked targeting ligands under extracellular acidic condition, followed by triggering the core degradation and payload release within tumor cells. In combination with superparamagnetic iron oxide nanoparticles (SPION) clustered within the micellar core, the MPUs exhibit excellent magnetic resonance imaging (MRI) contrast effects and T 2 relaxation in vitro, as well as magnetically guided MR imaging and multimodal targeting of therapeutics to tumor precisely, leading to significant inhibition of cancer with minimal side effect. This work provides a safe and versatile platform for the further development of smart theranostic systems for potential magnetically-targeted and imaging-guided personalized medicine. Copyright © 2017 Elsevier Ltd. All rights reserved.

A mRNA-Responsive G-Quadruplex-Based Drug Release System

Directory of Open Access Journals (Sweden)

Hidenobu Yaku

2015-04-01

Full Text Available G-quadruplex-based drug delivery carriers (GDDCs were designed to capture and release a telomerase inhibitor in response to a target mRNA. Hybridization between a loop on the GDDC structure and the mRNA should cause the G-quadruplex structure of the GDDC to unfold and release the bound inhibitor, anionic copper(II phthalocyanine (CuAPC. As a proof of concept, GDDCs were designed with a 10-30-mer loop, which can hybridize with a target sequence in epidermal growth factor receptor (EGFR mRNA. Structural analysis using circular dichroism (CD spectroscopy showed that the GDDCs form a (3 + 1 type G-quadruplex structure in 100 mM KCl and 10 mM MgCl2 in the absence of the target RNA. Visible absorbance titration experiments showed that the GDDCs bind to CuAPC with Ka values of 1.5 × 105 to 5.9 × 105 M−1 (Kd values of 6.7 to 1.7 μM at 25 °C, depending on the loop length. Fluorescence titration further showed that the G-quadruplex structure unfolds upon binding to the target RNA with Ka values above 1.0 × 108 M−1 (Kd values below 0.01 μM at 25 °C. These results suggest the carrier can sense and bind to the target RNA, which should result in release of the bound drug. Finally, visible absorbance titration experiments demonstrated that the GDDC release CuAPC in response to the target RNA.

Development and evaluation of intestinal targeted mucoadhesive microspheres of Bacillus coagulans.

Science.gov (United States)

Alli, Sk Md Athar; Ali, Sk Md Ajhar; Samanta, Amalesh

2011-11-01

Intestinal targeted mucoadhesive microsphere of probiotics may provide numerous associated health benefits. To develop mucoadhesive microspheres that will deliver viable probiotic cells into gut protectively against harsh environmental conditions of stomach for extended period. Core mucoadhesive microspheres of Bacillus coagulans were prepared using hypromellose, following coacervation and phase separation technique and were then coated with hypromellose phthalate to achieve their site-specific release. Microspheres were evaluated for percent yield, entrapment efficiency, surface morphology, particle size and size distribution, flow property, swelling property, mucoadhesion property by the in vitro wash-off and the ex vivo mucoadhesive strength tests, in vitro release profile and release kinetic, in vivo probiotic activity, and stability. The values for kinetic constant and regression coefficient of model-dependent approaches and the difference factor, the similarity factor, and the Rescigno index of model-independent approaches were determined for accessing and comparing in vitro performance. Microsphere formulation batches have percent yield value between 56.26% and 69.13% and entrapment efficiency value between 66.95% and 77.89%. Microspheres were coarser with spherical shape having mean particle size from 28.03 to 48.31 μm. In vitro B. coagulans release profile follows zero-order kinetics and depends on the grade of hypromellose and the B. coagulans-to-hypromellose ratio. Experimental microspheres rendered adequate stability to B. coagulans at room temperature. Microspheres had delivered B. coagulans in simulated intestinal condition following zero-order kinetics, protectively in simulated gastric condition, exhibiting appreciable mucoadhesion in intestinal condition, which could be useful to achieve site-specific delivery for extended period.

Metering Best Practices, A Guide to Achieving Utility Resource Efficiency, Release 2.0

Energy Technology Data Exchange (ETDEWEB)

Sullivan, Greg; Hunt, W. D.; Pugh, Ray; Sandusky, William F.; Koehler, Theresa M.; Boyd, Brian K.

2011-08-31

This release is an update and expansion of the information provided in Release 1.0 of the Metering Best Practice Guide that was issued in October 2007. This release, as was the previous release, was developed under the direction of the U.S. Department of Energy's Federal Energy Management Program (FEMP). The mission of FEMP is to facilitate the Federal Government's implementation of sound cost-effective energy management and investment practices to enhance the nation's energy security and environmental stewardship. Each of these activities is directly related to achieving requirements set forth in the Energy Policy Acts of 1992 and 2005, the Energy Independence and Security Act (EISA) of 2007, and the goals that have been established in Executive Orders 13423 and 13514 - and also those practices that are inherent in sound management of Federal financial and personnel resources.

Electrosprayed nanoparticle delivery system for controlled release

Energy Technology Data Exchange (ETDEWEB)

Eltayeb, Megdi, E-mail: megdi.eltayeb@sustech.edu [Department of Biomedical Engineering, Sudan University of Science and Technology, PO Box 407, Khartoum (Sudan); Stride, Eleanor, E-mail: eleanor.stride@eng.ox.ac.uk [Institute of Biomedical Engineering, Department of Engineering Science, University of Oxford, Old Road Campus Research Building, Headington OX3 7DQ (United Kingdom); Edirisinghe, Mohan, E-mail: m.edirisinghe@ucl.ac.uk [Department of Mechanical Engineering, University College London, Torrington Place, London WC1E 7JE (United Kingdom); Harker, Anthony, E-mail: a.harker@ucl.ac.uk [London Centre for Nanotechnology, Gordon Street, London WC1H 0AH (United Kingdom); Department of Physics & Astronomy, University College London, Gower Street, London WC1E 6BT (United Kingdom)

2016-09-01

This study utilises an electrohydrodynamic technique to prepare core-shell lipid nanoparticles with a tunable size and high active ingredient loading capacity, encapsulation efficiency and controlled release. Using stearic acid and ethylvanillin as model shell and active ingredients respectively, we identify the processing conditions and ratios of lipid:ethylvanillin required to form nanoparticles. Nanoparticles with a mean size ranging from 60 to 70 nm at the rate of 1.37 × 10{sup 9} nanoparticles per minute were prepared with different lipid:ethylvanillin ratios. The polydispersity index was ≈ 21% and the encapsulation efficiency ≈ 70%. It was found that the rate of ethylvanillin release was a function of the nanoparticle size, and lipid:ethylvanillin ratio. The internal structure of the lipid nanoparticles was studied by transmission electron microscopy which confirmed that the ethylvanillin was encapsulated within a stearic acid shell. Fourier transform infrared spectroscopy analysis indicated that the ethylvanillin had not been affected. Extensive analysis of the release of ethylvanillin was performed using several existing models and a new diffusive release model incorporating a tanh function. The results were consistent with a core-shell structure. - Highlights: • Electrohydrodynamic spraying is used to produce lipid-coated nanoparticles. • A new model is proposed for the release rates of active components from nanoparticles. • The technique has potential applications in food science and medicine. • Electrohydrodynamic processing controlled release lipid nanoparticles.

Release of the radioactive patient following radiation therapy

International Nuclear Information System (INIS)

Powers, J.; Cancer Board, A.

2004-01-01

Patients walk out of medical facilities containing as much as a complete therapeutic dose of radiation on a daily basis. This presents a significant challenge to the radiation protection community, as most patients have no prior education related to radiation and may not have the aptitude to assimilate such knowledge. In the case of targeted radiation therapy in which radionuclides are used to selectively target the cancer, patients are typically released only after adequate elimination and decay of the radionuclide administered. Established modalities of targeted radiotherapy include the use of iodine for thyroid cancer, strontium for bone pain, phosphorous for haematological diseases, 131I-mIBG for neuroblastoma, and most recently Y-90 labelled monoclonal antibodies for lymphoma. In the case of permanent implants, implants of encapsulated radioactive sources are left permanently in the tissues, thus patients are released containing their complete therapeutic dose. Isotopes used in permanent implants include I-125, Pd-103 and Au-198. Radiation safety considerations for both cases, the release of a patient who has received targeted radiotherapy, and the release of a patient who has received a permanent implant, will be discussed. A summary of applicable regulations will serve as a starting point for each of the following considerations; i) Security and source control ii) Instructions to patient and family members iii) Risk to the public As the incidence of cancer increases, and the popularity of targeted radiotherapy and permanent seed implants grows, the event of having an untrained person in possession of a therapeutic dose of radiation becomes more and more common. It is essential to stop and examine the risk of this practice, whether current strategies to reduce the risk to an acceptable level are indeed effective, and whether control over these sources is even feasible. (Author)

Release of the radioactive patient following radiation therapy

Energy Technology Data Exchange (ETDEWEB)

Powers, J.; Cancer Board, A.

2004-07-01

Patients walk out of medical facilities containing as much as a complete therapeutic dose of radiation on a daily basis. This presents a significant challenge to the radiation protection community, as most patients have no prior education related to radiation and may not have the aptitude to assimilate such knowledge. In the case of targeted radiation therapy in which radionuclides are used to selectively target the cancer, patients are typically released only after adequate elimination and decay of the radionuclide administered. Established modalities of targeted radiotherapy include the use of iodine for thyroid cancer, strontium for bone pain, phosphorous for haematological diseases, 131I-mIBG for neuroblastoma, and most recently Y-90 labelled monoclonal antibodies for lymphoma. In the case of permanent implants, implants of encapsulated radioactive sources are left permanently in the tissues, thus patients are released containing their complete therapeutic dose. Isotopes used in permanent implants include I-125, Pd-103 and Au-198. Radiation safety considerations for both cases, the release of a patient who has received targeted radiotherapy, and the release of a patient who has received a permanent implant, will be discussed. A summary of applicable regulations will serve as a starting point for each of the following considerations; i) Security and source control ii) Instructions to patient and family members iii) Risk to the public As the incidence of cancer increases, and the popularity of targeted radiotherapy and permanent seed implants grows, the event of having an untrained person in possession of a therapeutic dose of radiation becomes more and more common. It is essential to stop and examine the risk of this practice, whether current strategies to reduce the risk to an acceptable level are indeed effective, and whether control over these sources is even feasible. (Author)

Human endogenous retrovirus K Gag coassembles with HIV-1 Gag and reduces the release efficiency and infectivity of HIV-1.

Science.gov (United States)

Monde, Kazuaki; Contreras-Galindo, Rafael; Kaplan, Mark H; Markovitz, David M; Ono, Akira

2012-10-01

Human endogenous retroviruses (HERVs), which are remnants of ancestral retroviruses integrated into the human genome, are defective in viral replication. Because activation of HERV-K and coexpression of this virus with HIV-1 have been observed during HIV-1 infection, it is conceivable that HERV-K could affect HIV-1 replication, either by competition or by cooperation, in cells expressing both viruses. In this study, we found that the release efficiency of HIV-1 Gag was 3-fold reduced upon overexpression of HERV-K(CON) Gag. In addition, we observed that in cells expressing Gag proteins of both viruses, HERV-K(CON) Gag colocalized with HIV-1 Gag at the plasma membrane. Furthermore, HERV-K(CON) Gag was found to coassemble with HIV-1 Gag, as demonstrated by (i) processing of HERV-K(CON) Gag by HIV-1 protease in virions, (ii) coimmunoprecipitation of virion-associated HERV-K(CON) Gag with HIV-1 Gag, and (iii) rescue of a late-domain-defective HERV-K(CON) Gag by wild-type (WT) HIV-1 Gag. Myristylation-deficient HERV-K(CON) Gag localized to nuclei, suggesting cryptic nuclear trafficking of HERV-K Gag. Notably, unlike WT HERV-K(CON) Gag, HIV-1 Gag failed to rescue myristylation-deficient HERV-K(CON) Gag to the plasma membrane. Efficient colocalization and coassembly of HIV-1 Gag and HERV-K Gag also required nucleocapsid (NC). These results provide evidence that HIV-1 Gag heteromultimerizes with HERV-K Gag at the plasma membrane, presumably through NC-RNA interaction. Intriguingly, HERV-K Gag overexpression reduced not only HIV-1 release efficiency but also HIV-1 infectivity in a myristylation- and NC-dependent manner. Altogether, these results indicate that Gag proteins of endogenous retroviruses can coassemble with HIV-1 Gag and modulate the late phase of HIV-1 replication.

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.

Effective genetic modification and differentiation of hMSCs upon controlled release of rAAV vectors using alginate/poloxamer composite systems.

Science.gov (United States)

Díaz-Rodríguez, P; Rey-Rico, A; Madry, H; Landin, M; Cucchiarini, M

2015-12-30

Viral vectors are common tools in gene therapy to deliver foreign therapeutic sequences in a specific target population via their natural cellular entry mechanisms. Incorporating such vectors in implantable systems may provide strong alternatives to conventional gene transfer procedures. The goal of the present study was to generate different hydrogel structures based on alginate (AlgPH155) and poloxamer PF127 as new systems to encapsulate and release recombinant adeno-associated viral (rAAV) vectors. Inclusion of rAAV in such polymeric capsules revealed an influence of the hydrogel composition and crosslinking temperature upon the vector release profiles, with alginate (AlgPH155) structures showing the fastest release profiles early on while over time vector release was more effective from AlgPH155+PF127 [H] capsules crosslinked at a high temperature (50°C). Systems prepared at room temperature (AlgPH155+PF127 [C]) allowed instead to achieve a more controlled release profile. When tested for their ability to target human mesenchymal stem cells, the different systems led to high transduction efficiencies over time and to gene expression levels in the range of those achieved upon direct vector application, especially when using AlgPH155+PF127 [H]. No detrimental effects were reported on either cell viability or on the potential for chondrogenic differentiation. Inclusion of PF127 in the capsules was also capable of delaying undesirable hypertrophic cell differentiation. These findings are of promising value for the further development of viral vector controlled release strategies. Copyright © 2015 Elsevier B.V. All rights reserved.

Development of fast-release solid catchers for rare isotopes

Science.gov (United States)

Nolen, Jerry; Greene, John; Elam, Jeffrey; Mane, Anil; Sampathkumaran, Uma; Winter, Raymond; Hess, David; Mushfiq, Mohammad; Stracener, Daniel; Wiendenhoever, Ingo

2015-04-01

Porous solid catchers of rare isotopes are being developed for use at high power heavy ion accelerator facilities such as RIKEN, FRIB, and RISP. Compact solid catchers are complementary to helium gas catchers for parasitic harvesting of rare isotopes in the in-flight separators. They are useful for short lived isotopes for basic nuclear physics research and longer-lived isotopes for off-line applications. Solid catchers can operate effectively with high intensity secondary beams, e.g. >> 1E10 atoms/s with release times as short as 10-100 milliseconds. A new method using a very sensitive and efficient RGA has been commissioned off-line at Argonne and is currently being shipped to Florida State University for in-beam measurements of the release curves using stable beams. The same porous solid catcher technology is also being evaluated for use in targets for the production of medical isotopes such as 211-At. Research supported by the U.S. DOE Office of Nuclear Physics under the SBIR Program and Contract # DE-AC02-06CH11357 and a University of Chicago Comprehensive Cancer Center/ANL Pilot Project.

Sustained release nimesulide microparticles: evaluation of release modifying property of ethy

International Nuclear Information System (INIS)

Khan, S.A.; Ahmed, M.; Nisar-ur-Rehman; Madni, A.U.; Aamir, M.N.; Murtaza, G.

2011-01-01

Microencapsulated controlled-release preparations of nimesulide were formulated. Microparticles were prepared by modified phase separation (non-solvent addition) technique using different ratios of ethylcellulose. The microparticles (M/sub 1/, M/sub 2/, and M/sub 3/) were yellow, free flowing and spherical in shape with the particle size varying from 93.62 +- 14.15 to 104.19 +- 18.15 mu m. The t/sub 60%/of nimesulide release from microparticles was found to be 3 +- 0.6, 5 +- 0.6 and 8 +- 0.8 h for formulations M/sub 1/, M/sub 2/, and M/sub 3/, respectively. FT-IR, XRD, and thermal analysis were done which showed that there is no interaction between the polymer and drug. The mechanism of drug release from nimesulide microparticles was studied by using Higuchi and Korsmeyer-Peppas models. The value of coefficient of determination (R/sup 2/) for M/sub 1/, M/sub 2/, and M/sub 3/ indicates anomalous and case-II transport release mechanism. The dissolution data of designed system verified its ability to maintain plasma concentration without the need of frequent dosing. The Nimesulide microparticles prolonged drug release for 12 hours or longer. Based on the results of release studies, M/sub 3/ was opted as a suitable microparticulate formulation allowing the controlled release of nimesulide over a prolonged period of time. Moreover, its encapsulation efficiency was also comparable to the other two formulations (M/sub 1/ and M/sub 2/). In conclusion, the influence of polymer concentration should be considered during formulation development. (author)

Directional R-Loop Formation by the CRISPR-Cas Surveillance Complex Cascade Provides Efficient Off-Target Site Rejection

Directory of Open Access Journals (Sweden)

Marius Rutkauskas

2015-03-01

Full Text Available CRISPR-Cas systems provide bacteria and archaea with adaptive immunity against foreign nucleic acids. In type I CRISPR-Cas systems, invading DNA is detected by a large ribonucleoprotein surveillance complex called Cascade. The crRNA component of Cascade is used to recognize target sites in foreign DNA (protospacers by formation of an R-loop driven by base-pairing complementarity. Using single-molecule supercoiling experiments with near base-pair resolution, we probe here the mechanism of R-loop formation and detect short-lived R-loop intermediates on off-target sites bearing single mismatches. We show that R-loops propagate directionally starting from the protospacer-adjacent motif (PAM. Upon reaching a mismatch, R-loop propagation stalls and collapses in a length-dependent manner. This unambiguously demonstrates that directional zipping of the R-loop accomplishes efficient target recognition by rapidly rejecting binding to off-target sites with PAM-proximal mutations. R-loops that reach the protospacer end become locked to license DNA degradation by the auxiliary Cas3 nuclease/helicase without further target verification.

Operations & Maintenance Best Practices - A Guide to Achieving Operational Efficiency (Release 3)

Energy Technology Data Exchange (ETDEWEB)

Sullivan, Greg; Pugh, Ray; Melendez, Aldo P.; Hunt, W. D.

2010-08-04

This guide highlights operations and maintenance programs targeting energy and water efficiency that are estimated to save 5% to 20% on energy bills without a significant capital investment. The purpose of this guide is to provide you, the Operations and Maintenance (O&M)/Energy manager and practitioner, with useful information about O&M management, technologies, energy and water efficiency, and cost-reduction approaches. To make this guide useful and to reflect your needs and concerns, the authors met with O&M and Energy managers via Federal Energy Management Program (FEMP) workshops. In addition, the authors conducted extensive literature searches and contacted numerous vendors and industry experts. The information and case studies that appear in this guide resulted from these activities. It needs to be stated at the outset that this guide is designed to provide information on effective O&M as it applies to systems and equipment typically found at Federal facilities. This guide is not designed to provide the reader with step-by-step procedures for performing O&M on any specific piece of equipment. Rather, this guide first directs the user to the manufacturer's specifications and recommendations. In no way should the recommendations in this guide be used in place of manufacturer's recommendations. The recommendations in this guide are designed to supplement those of the manufacturer, or, as is all too often the case, provide guidance for systems and equipment for which all technical documentation has been lost. As a rule, this guide will first defer to the manufacturer's recommendations on equipment operation and maintenance.

Spatial Cytoskeleton Organization Supports Targeted Intracellular Transport

Science.gov (United States)

Hafner, Anne E.; Rieger, Heiko

2018-03-01

The efficiency of intracellular cargo transport from specific source to target locations is strongly dependent upon molecular motor-assisted motion along the cytoskeleton. Radial transport along microtubules and lateral transport along the filaments of the actin cortex underneath the cell membrane are characteristic for cells with a centrosome. The interplay between the specific cytoskeleton organization and the motor performance realizes a spatially inhomogeneous intermittent search strategy. In order to analyze the efficiency of such intracellular search strategies we formulate a random velocity model with intermittent arrest states. We evaluate efficiency in terms of mean first passage times for three different, frequently encountered intracellular transport tasks: i) the narrow escape problem, which emerges during cargo transport to a synapse or other specific region of the cell membrane, ii) the reaction problem, which considers the binding time of two particles within the cell, and iii) the reaction-escape problem, which arises when cargo must be released at a synapse only after pairing with another particle. Our results indicate that cells are able to realize efficient search strategies for various intracellular transport tasks economically through a spatial cytoskeleton organization that involves only a narrow actin cortex rather than a cell body filled with randomly oriented actin filaments.

Lipoprotein-biomimetic nanostructure enables efficient targeting delivery of siRNA to Ras-activated glioblastoma cells via macropinocytosis

Science.gov (United States)

Huang, Jia-Lin; Jiang, Gan; Song, Qing-Xiang; Gu, Xiao; Hu, Meng; Wang, Xiao-Lin; Song, Hua-Hua; Chen, Le-Pei; Lin, Ying-Ying; Jiang, Di; Chen, Jun; Feng, Jun-Feng; Qiu, Yong-Ming; Jiang, Ji-Yao; Jiang, Xin-Guo; Chen, Hong-Zhuan; Gao, Xiao-Ling

2017-05-01

Hyperactivated Ras regulates many oncogenic pathways in several malignant human cancers including glioblastoma and it is an attractive target for cancer therapies. Ras activation in cancer cells drives protein internalization via macropinocytosis as a key nutrient-gaining process. By utilizing this unique endocytosis pathway, here we create a biologically inspired nanostructure that can induce cancer cells to `drink drugs' for targeting activating transcription factor-5 (ATF5), an overexpressed anti-apoptotic transcription factor in glioblastoma. Apolipoprotein E3-reconstituted high-density lipoprotein is used to encapsulate the siRNA-loaded calcium phosphate core and facilitate it to penetrate the blood-brain barrier, thus targeting the glioblastoma cells in a macropinocytosis-dependent manner. The nanostructure carrying ATF5 siRNA exerts remarkable RNA-interfering efficiency, increases glioblastoma cell apoptosis and inhibits tumour cell growth both in vitro and in xenograft tumour models. This strategy of targeting the macropinocytosis caused by Ras activation provides a nanoparticle-based approach for precision therapy in glioblastoma and other Ras-activated cancers.

Orally Targeted Delivery of Tripeptide KPV via Hyaluronic Acid-Functionalized Nanoparticles Efficiently Alleviates Ulcerative Colitis.

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Xiao, Bo; Xu, Zhigang; Viennois, Emilie; Zhang, Yuchen; Zhang, Zhan; Zhang, Mingzhen; Han, Moon Kwon; Kang, Yuejun; Merlin, Didier

2017-07-05

Overcoming adverse effects and selectively delivering drug to target cells are two major challenges in the treatment of ulcerative colitis (UC). Lysine-proline-valine (KPV), a naturally occurring tripeptide, has been shown to attenuate the inflammatory responses of colonic cells. Here, we loaded KPV into hyaluronic acid (HA)-functionalized polymeric nanoparticles (NPs). The resultant HA-KPV-NPs had a desirable particle size (∼272.3 nm) and a slightly negative zeta potential (∼-5.3 mV). These NPs successfully mediated the targeted delivery of KPV to key UC therapy-related cells (colonic epithelial cells and macrophages). In addition, these KPV-loaded NPs appear to be nontoxic and biocompatible with intestinal cells. Intriguingly, we found that HA-KPV-NPs exert combined effects against UC by both accelerating mucosal healing and alleviating inflammation. Oral administration of HA-KPV-NPs encapsulated in a hydrogel (chitosan/alginate) exhibited a much stronger capacity to prevent mucosa damage and downregulate TNF-α, thus they showed a much better therapeutic efficacy against UC in a mouse model, compared with a KPV-NP/hydrogel system. These results collectively demonstrate that our HA-KPV-NP/hydrogel system has the capacity to release HA-KPV-NPs in the colonic lumen and that these NPs subsequently penetrate into colitis tissues and enable KPV to be internalized into target cells, thereby alleviating UC. Copyright © 2016 The American Society of Gene and Cell Therapy. Published by Elsevier Inc. All rights reserved.

Simple and Efficient Targeting of Multiple Genes Through CRISPR-Cas9 in Physcomitrella patens

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Mauricio Lopez-Obando

2016-11-01

Full Text Available Powerful genome editing technologies are needed for efficient gene function analysis. The CRISPR-Cas9 system has been adapted as an efficient gene-knock-out technology in a variety of species. However, in a number of situations, knocking out or modifying a single gene is not sufficient; this is particularly true for genes belonging to a common family, or for genes showing redundant functions. Like many plants, the model organism Physcomitrella patens has experienced multiple events of polyploidization during evolution that has resulted in a number of families of duplicated genes. Here, we report a robust CRISPR-Cas9 system, based on the codelivery of a CAS9 expressing cassette, multiple sgRNA vectors, and a cassette for transient transformation selection, for gene knock-out in multiple gene families. We demonstrate that CRISPR-Cas9-mediated targeting of five different genes allows the selection of a quintuple mutant, and all possible subcombinations of mutants, in one experiment, with no mutations detected in potential off-target sequences. Furthermore, we confirmed the observation that the presence of repeats in the vicinity of the cutting region favors deletion due to the alternative end joining pathway, for which induced frameshift mutations can be potentially predicted. Because the number of multiple gene families in Physcomitrella is substantial, this tool opens new perspectives to study the role of expanded gene families in the colonization of land by plants.

Gastrin-releasing peptide receptor-targeted gadolinium oxide-based multifunctional nanoparticles for dual magnetic resonance/fluorescent molecular imaging of prostate cancer

Directory of Open Access Journals (Sweden)

Cui DT

2017-09-01

Full Text Available Danting Cui,1 Xiaodan Lu,1 Chenggong Yan,1 Xiang Liu,1 Meirong Hou,1 Qi Xia,2 Yikai Xu,1 Ruiyuan Liu2,3 1Department of Medical Imaging Center, Nanfang Hospital, Southern Medical University, Guangzhou, People’s Republic of China; 2School of Pharmaceutical Sciences, Southern Medical University, Guangzhou, People’s Republic of China; 3School of Biomedical Engineering, Southern Medical University, Guangzhou, People’s Republic of China Abstract: Bombesin (BBN, an analog of gastrin-releasing peptide (GRP, specifically binds to GRP receptors, which are overexpressed in human prostate cancer (PC. Here, we synthesized a BBN-modified gadolinium oxide (Gd2O3 nanoprobe containing fluorescein (Gd2O3-5(6-carboxyfluorescein [FI]-polyethylene glycol [PEG]-BBN for targeted magnetic resonance (MR/optical dual-modality imaging of PC. The Gd2O3-FI-PEG-BBN nanoparticles exhibited a relatively uniform particle size with an average diameter of 52.3 nm and spherical morphology as depicted by transmission electron microscopy. The longitudinal relaxivity (r1 of Gd2O3-FI-PEG-BBN (r1 =4.23 mM–1s–1 is comparable to that of clinically used Magnevist (Gd-DTPA. Fluorescence microscopy and in vitro cellular MRI demonstrated GRP receptor-specific and enhanced cellular uptake of the Gd2O3-FI-PEG-BBN in PC-3 tumor cells. Moreover, Gd2O3-FI-PEG-BBN showed more remarkable contrast enhancement than the corresponding nontargeted Gd2O3-FI-PEG according to in vivo MRI and fluorescent imaging. Tumor immunohistochemical analysis further demonstrated improved accumulation of the targeted nanoprobe in tumors. BBN-conjugated Gd2O3 may be a promising nanoplatform for simultaneous GRP receptor-targeted molecular cancer diagnosis and antitumor drug delivery in future clinical applications. Keywords: magnetic resonance imaging, gadolinium oxide, bombesin, gastrin-releasing peptide receptor, molecular imaging

Release from proactive interference in rat spatial working memory.

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Roberts, William A; MacDonald, Hayden; Brown, Lyn; Macpherson, Krista

2017-09-01

A three-phase procedure was used to produce proactive interference (PI) in one trial on an eight-arm radial maze. Rats were forced to enter four arms for reward on an initial interference phase, to then enter the four remaining arms on a target phase, and to then choose among all eight arms on a retention test, with only the arms not visited in the target phase containing reward. Control trials involved only the target phase and the retention test. Lower accuracy was found on PI trials than on control trials, but performance on PI trials significantly exceeded chance, showing some retention of target memories. Changes in temporal and reward variables between the interference, target, and retention test phases showed release from PI, but changes in context and pattern of arm entry did not. It is suggested that the release from PI paradigm can be used to understand spatial memory encoding in rats and other species.

Enhanced cellular transport and drug targeting using dendritic nanostructures

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Kannan, R. M.; Kolhe, Parag; Kannan, Sujatha; Lieh-Lai, Mary

2003-03-01

Dendrimers and hyperbranched polymers possess highly branched architectures, with a large number of controllable, tailorable, peripheral' functionalities. Since the surface chemistry of these materials can be modified with relative ease, these materials have tremendous potential in targeted drug delivery. The large density of end groups can also be tailored to create enhanced affinity to targeted cells, and can also encapsulate drugs and deliver them in a controlled manner. We are developing tailor-modified dendritic systems for drug delivery. Synthesis, drug/ligand conjugation, in vitro cellular and in vivo drug delivery, and the targeting efficiency to the cell are being studied systematically using a wide variety of experimental tools. Results on PAMAM dendrimers and polyol hyperbranched polymers suggest that: (1) These materials complex/encapsulate a large number of drug molecules and release them at tailorable rates; (2) The drug-dendrimer complex is transported very rapidly through a A549 lung epithelial cancel cell line, compared to free drug, perhaps by endocytosis. The ability of the drug-dendrimer-ligand complexes to target specific asthma and cancer cells is currently being explored using in vitro and in vivo animal models.

New mechanism for enhancing ash removal efficiency and reducing tritium inventory

International Nuclear Information System (INIS)

Li Chengyue; Deng Baiquan; Yan Jiancheng

2007-01-01

A new mechanism is suggested to suppress ash particle back streams in the divertor region of our fusion experimental breeder (FEB) reactor for enhancing the ash removal efficiency and reducing the tritium inventory by applications of the nonlinear effect of high power rf ponderomotive force potential which reflects the plate-released and re-ionized He + back to the plate. Meanwhile, the potential does not hinder α particles, which are coming from scraping of the layer, flowing to the target plate. However, it does stop tritium ions flowing to the target. Based on the FEB design parameters, our calculations have shown that the ash removal efficiency can be improved by as much as 40% if the parallel component of rf field 150-200 V/cm is applied to the location at a perpendicular distance L=20 cm apart from the plate and the plate-recycling neutral helium atom energy is about 0.75 eV, at the same time, the tritium inventory can be reduced to some extent. (authors)

Sustained release of verapamil hydrochloride from sodium alginate microcapsules.

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Farhana, S Ayesha; Shantakumar, S M; Shyale, Somashekar; Shalam, Md; Narasu, Laxmi

2010-04-01

The objective of the present study was to develop sustained release microcapsules of verapamil hydrochloride (VH) using biodegradable polymers. For this purpose microcapsules embedded verapamil hydrochloride were prepared using sodium alginate alone and also by incorporating some co polymers like methyl cellulose (MC), sodium carboxy methyl cellulose (SCMC) , poly vinyl pyrollidone (PVP) and xanthan gum by employing complex emulsion method of microencapsulation. Microcapsules were prepared in various core: coat ratios to know the effect of polymer and co polymers on drug release. Overall ten formulations were prepared and evaluated for flow behaviour, sieve analysis, drug entrapment efficiency, in vitro dissolution studies, stability studies, including scanning electron microscopy and DSC. The resulting microcapsules were discrete, large, spherical and also free flowing. The drug content in all the batches of microcapsules was found to be uniform. The release was depended on core: coat ratio and nature of the polymers. FTIR analysis revealed chemical integrity between Verapamil hydrochloride (VH), sodium alginate and between the copolymers. Among the four copolymers used methyl cellulose retarded the drug release more than the other three, hence the same formulation was subjected for in vivo studies. The drug release from the microcapsules was found to be following non fickian diffusion. Mechanism of drug release was diffusion controlled first order kinetics. Drug diffusion co efficient and correlation co efficient were also assessed by using various mathematical models. In vivo result analysis of pharmacokinetic parameters revealed that t max of reference and test formulations were almost same. From the study it was concluded that, sustained release Verapamil hydro chloride microcapsules could be achieved with success using sodium alginate alone and also in combination with other biodegradable polymers.

Detection of glutathione based on MnO2 nanosheet-gated mesoporous silica nanoparticles and target induced release of glucose measured with a portable glucose meter.

Science.gov (United States)

Tan, Qingqing; Zhang, Ruirui; Kong, Rongmei; Kong, Weisu; Zhao, Wenzhi; Qu, Fengli

2017-12-08

The authors describe a novel method for the determination of glutathione (GSH). Detection is based on target induced release of glucose from MnO 2 nanosheet-gated aminated mesoporous silica nanoparticles (MSNs). In detail, glucose is loaded into the pores of MSNs. Negatively charged MnO 2 nanosheets are assembled on the MSNs through electrostatic interactions. The nanosheets are reduced by GSH, and this results in the release of glucose which is quantified by using a commercial electrochemical glucose meter. GSH can be quantified by this method in the 100 nM to 10 μM concentration range, with a 34 nM limit of detection. Graphical abstract Glucose is loaded into the pores of mesoporous silica nanoparticles (MSNs). MnO 2 nanosheets are assembled on MSNs through electrostatic interactions. Glutathione (GSH) can reduce the nanosheets, and this results in the release of glucose which is quantified by using a commercial glucose meter.

Impact of target mRNA structure on siRNA silencing efficiency: A large-scale study.

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Gredell, Joseph A; Berger, Angela K; Walton, S Patrick

2008-07-01

The selection of active siRNAs is generally based on identifying siRNAs with certain sequence and structural properties. However, the efficiency of RNA interference has also been shown to depend on the structure of the target mRNA, primarily through studies using exogenous transcripts with well-defined secondary structures in the vicinity of the target sequence. While these studies provide a means for examining the impact of target sequence and structure independently, the predicted secondary structures for these transcripts are often not reflective of structures that form in full-length, native mRNAs where interactions can occur between relatively remote segments of the mRNAs. Here, using a combination of experimental results and analysis of a large dataset, we demonstrate that the accessibility of certain local target structures on the mRNA is an important determinant in the gene silencing ability of siRNAs. siRNAs targeting the enhanced green fluorescent protein were chosen using a minimal siRNA selection algorithm followed by classification based on the predicted minimum free energy structures of the target transcripts. Transfection into HeLa and HepG2 cells revealed that siRNAs targeting regions of the mRNA predicted to have unpaired 5'- and 3'-ends resulted in greater gene silencing than regions predicted to have other types of secondary structure. These results were confirmed by analysis of gene silencing data from previously published siRNAs, which showed that mRNA target regions unpaired at either the 5'-end or 3'-end were silenced, on average, approximately 10% more strongly than target regions unpaired in the center or primarily paired throughout. We found this effect to be independent of the structure of the siRNA guide strand. Taken together, these results suggest minimal requirements for nucleation of hybridization between the siRNA guide strand and mRNA and that both mRNA and guide strand structure should be considered when choosing candidate si

Controlled Release Formulations of Auxinic Herbicides

Science.gov (United States)

Kowalski, Witold J.; Siłowiecki, Andrzej.; Romanowska, Iwona; Glazek, Mariola; Bajor, Justyna; Cieciwa, Katarzyna; Rychter, Piotr

2013-04-01

Controlled release formulations are applied extensively for the release of active ingredients such as plant protection agents and fertilizers in response to growing concern for ecological problems associated with increased use of plant protection chemicals required for intensive agricultural practices [1]. We synthesized oligomeric mixtures of (R,S)-3-hydroxy butyric acid chemically bonded with 2,4-D, Dicamba and MCPA herbicides (HBA) respectively, and determined their molecular structure and molecular weight dispersion by the size exclusion chromatography, proton magnetic resonance spectrometry and electro-spray ionization mass spectrometry. Further we carried out bioassays of herbicidal effectiveness of the HBA herbicides vs. series of dicotyledonous weeds and crop injury tests [2, 3, 4]. Field bioassays were accomplished according to the EPPO standards [5]. Groups of representative weeds (the development stages in the BCCH scale: 10 - 30) were selected as targets. Statistical variabilities were assessed by the Fisher LSD test for plants treated with the studied herbicides in form of HBA oligomers, the reference herbicides in form of dimethyl ammonium salts (DMA), and untreated plants. No statistically significant differences in the crop injuries caused by the HBA vs. the DMA reference formulation were observed. The effectiveness of the HBA herbicides was lower through the initial period (ca. 2 weeks) relative to the DMA salts, but a significant increase in the effectiveness of the HBA systems followed during the remaining fraction of each assay. After 6 weeks all observed efficiencies approached 100%. The death of weeds treated with the HBA herbicides was delayed when compared with the DMA reference herbicides. The delayed uptake observed for the HBA oligomers relative to the DMA salts was due to controlled release phenomena. In case of the DMA salts the total amount of active ingredients was available at the target site. By contrast, the amount of an active

Efficient methods for targeted mutagenesis in zebrafish using zinc-finger nucleases: data from targeting of nine genes using CompoZr or CoDA ZFNs.

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Raman Sood

Full Text Available Recently, it has been shown that targeted mutagenesis using zinc-finger nucleases (ZFNs and transcription activator-like effector nucleases (TALENs can be used to generate knockout zebrafish lines for analysis of their function and/or developing disease models. A number of different methods have been developed for the design and assembly of gene-specific ZFNs and TALENs, making them easily available to most zebrafish researchers. Regardless of the choice of targeting nuclease, the process of generating mutant fish is similar. It is a time-consuming and multi-step process that can benefit significantly from development of efficient high throughput methods. In this study, we used ZFNs assembled through either the CompoZr (Sigma-Aldrich or the CoDA (context-dependent assembly platforms to generate mutant zebrafish for nine genes. We report our improved high throughput methods for 1 evaluation of ZFNs activity by somatic lesion analysis using colony PCR, eliminating the need for plasmid DNA extractions from a large number of clones, and 2 a sensitive founder screening strategy using fluorescent PCR with PIG-tailed primers that eliminates the stutter bands and accurately identifies even single nucleotide insertions and deletions. Using these protocols, we have generated multiple mutant alleles for seven genes, five of which were targeted with CompoZr ZFNs and two with CoDA ZFNs. Our data also revealed that at least five-fold higher mRNA dose was required to achieve mutagenesis with CoDA ZFNs than with CompoZr ZFNs, and their somatic lesion frequency was lower (<5% when compared to CopmoZr ZFNs (9-98%. This work provides high throughput protocols for efficient generation of zebrafish mutants using ZFNs and TALENs.

Enhancement of conversion efficiency of extreme ultraviolet radiation from a liquid aqueous solution microjet target by use of dual laser pulses

Science.gov (United States)

Higashiguchi, Takeshi; Dojyo, Naoto; Hamada, Masaya; Kawasaki, Keita; Sasaki, Wataru; Kubodera, Shoichi

2006-03-01

We demonstrated a debris-free, efficient laser-produced plasma extreme ultraviolet (EUV) source by use of a regenerative liquid microjet target containing tin-dioxide (SnO II) nano-particles. By using a low SnO II concentration (6%) solution and dual laser pulses for the plasma control, we observed the EUV conversion efficiency of 1.2% with undetectable debris.

Air-Stimulated ATP Release from Keratinocytes Occurs through Connexin Hemichannels

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Barr, Travis P.; Albrecht, Phillip J.; Hou, Quanzhi; Mongin, Alexander A.; Strichartz, Gary R.; Rice, Frank L.

2013-01-01

Cutaneous ATP release plays an important role in both epidermal stratification and chronic pain, but little is known about ATP release mechanisms in keratinocytes that comprise the epidermis. In this study, we analyzed ATP release from cultured human neonatal keratinocytes briefly exposed to air, a process previously demonstrated to trigger ATP release from these cells. We show that exposing keratinocytes to air by removing media for 15 seconds causes a robust, long-lasting ATP release. This air-stimulated ATP release was increased in calcium differentiated cultures which showed a corresponding increase in connexin 43 mRNA, a major component of keratinocyte hemichannels. The known connexin hemichannel inhibitors 1-octanol and carbenoxolone both significantly reduced air-stimulated ATP release, as did two drugs traditionally used as ABC transporter inhibitors (glibenclamide and verapamil). These same 4 inhibitors also prevented an increase in the uptake of a connexin permeable dye induced by air exposure, confirming that connexin hemichannels are open during air-stimulated ATP release. In contrast, activity of the MDR1 ABC transporter was reduced by air exposure and the drugs that inhibited air-stimulated ATP release had differential effects on this transporter. These results indicate that air exposure elicits non-vesicular release of ATP from keratinocytes through connexin hemichannels and that drugs used to target connexin hemichannels and ABC transporters may cross-inhibit. Connexins represent a novel, peripheral target for the treatment of chronic pain and dermatological disease. PMID:23457608

A simple fluorescence based assay for quantification of human immunodeficiency virus particle release

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Heuser Anke-Mareil

2010-04-01

Full Text Available Abstract Background The assembly and release of human immunodeficiency virus (HIV particles from infected cells represent attractive, but not yet exploited targets for antiretroviral therapy. The availability of simple methods to measure the efficiency of these replication steps in tissue culture would facilitate the identification of host factors essential for these processes as well as the screening for lead compounds acting as specific inhibitors of particle formation. We describe here the development of a rapid cell based assay for quantification of human immunodeficiency virus type 1 (HIV-1 particle assembly and/or release. Results Using a fluorescently labelled HIV-derivative, which carries an eYFP domain within the main viral structural protein Gag in the complete viral protein context, the release of virus like particles could be monitored by directly measuring the fluorescence intensity of the tissue culture supernatant. Intracellular Gag was quantitated in parallel by direct fluorescence analysis of cell lysates, allowing us to normalize for Gag expression efficiency. The assay was validated by comparison with p24 capsid ELISA measurements, a standard method for quantifying HIV-1 particles. Optimization of conditions allowed the robust detection of particle amounts corresponding to 50 ng p24/ml in medium by fluorescence spectroscopy. Further adaptation to a multi-well format rendered the assay suitable for medium or high throughput screening of siRNA libraries to identify host cell factors involved in late stages of HIV replication, as well as for random screening approaches to search for potential inhibitors of HIV-1 assembly or release. Conclusions The fast and simple fluorescence based quantification of HIV particle release yielded reproducible results which were comparable to the well established ELISA measurements, while in addition allowing the parallel determination of intracellular Gag expression. The protocols described here

Cratering efficiency on coarse-grain targets: Implications for the dynamical evolution of asteroid 25143 Itokawa

Science.gov (United States)

Tatsumi, Eri; Sugita, Seiji

2018-01-01

Remote sensing observations made by the spacecraft Hayabusa provided the first direct evidence of a rubble-pile asteroid: 25143 Itokawa. Itokawa was found to have a surface structure very different from other explored asteroids; covered with coarse pebbles and boulders ranging at least from cm to meter size. The cumulative size distribution of small circular depressions on Itokawa, most of which may be of impact origin, has a significantly shallower slope than that on the Moon; small craters are highly depleted on Itokawa compared to the Moon. This deficiency of small circular depressions and other features, such as clustered fragments and pits on boulders, suggest that the boulders on Itokawa might behave like armor, preventing crater formation: the ;armoring effect;. This might contribute to the low number density of small crater candidates. In this study, the cratering efficiency reduction due to coarse-grained targets was investigated based on impact experiments at velocities ranging from ∼ 70 m/s to ∼ 6 km/s using two vertical gas gun ranges. We propose a scaling law extended for cratering on coarse-grained targets (i.e., target grain size ≳ projectile size). We have found that the crater efficiency reduction is caused by energy dissipation at the collision site where momentum is transferred from the impactor to the first-contact target grain, and that the armoring effect can be classified into three regimes: (1) gravity scaled regime, (2) reduced size crater regime, or (3) no apparent crater regime, depending on the ratio of the impactor size to the target grain size and the ratio of the impactor kinetic energy to the disruption energy of a target grain. We found that the shallow slope of the circular depressions on Itokawa cannot be accounted for by this new scaling law, suggesting that obliteration processes, such as regolith convection and migration, play a greater role in the depletion of circular depressions on Itokawa. Based on the new extended

Ultrasound stimulated release of gallic acid from chitin hydrogel matrix

Energy Technology Data Exchange (ETDEWEB)

Jiang, Huixin; Kobayashi, Takaomi, E-mail: takaomi@nagaokaut.ac.jp

2017-06-01

Ultrasound (US) stimulated drug release was examined in this study using a chitin hydrogel matrix loaded with gallic acid (GA), a drug used for wound healing and anticancer. Using phase inversion, GA-chitin hydrogels were prepared from chitin-dimethylacetamide (DMAc)/lithium chloride (LiCl) solution in the presence of GA, with 24 h exposure of the solution to water vapor. The GA release from the GA-chitin hydrogel was examined under different US powers of 0–30 W at 43 kHz. The effects of GA loading amounts in the hydrogels (0.54, 0.43, and 0.25 mg/cm{sup 3}) and chitin concentrations (0.1, 0.5, and 1 wt%) on the release behaviors were recorded under 43 kHz US exposure at 30 W. Results show that US accelerated the release efficiencies for all samples. Furthermore, the release efficiency increased concomitantly with increasing US power, GA loading amount, and decrease of the chitin concentration. The highest release rate of 0.74 μg/mL·min was obtained from 0.54 mg/cm{sup 3} of GA-loaded hydrogel fabricated from a 0.1 wt% chitin mixture solution under 43 kHz US exposure at 30 W: nine times higher than that of the sample without US exposure. The hydrogel viscoelasticity demonstrated that the US irradiation rigidified the material. FT-IR showed that US can break the hydrogen bonds in the GA-chitin hydrogels. - Highlights: • Ultrasound (US) stimulated Gallic acid (GA) release from chitin hydrogel was studied. • The release efficiency of GA from chitin hydrogel increased nine times when irradiated by 43 kHz US compared with the sample without US. • Generalized 2D correlation and deconvolution study of FT-IR showed that US could promote the GA release by breaking hydrogen bonds.

Ultrasound stimulated release of gallic acid from chitin hydrogel matrix

International Nuclear Information System (INIS)

Jiang, Huixin; Kobayashi, Takaomi

2017-01-01

Ultrasound (US) stimulated drug release was examined in this study using a chitin hydrogel matrix loaded with gallic acid (GA), a drug used for wound healing and anticancer. Using phase inversion, GA-chitin hydrogels were prepared from chitin-dimethylacetamide (DMAc)/lithium chloride (LiCl) solution in the presence of GA, with 24 h exposure of the solution to water vapor. The GA release from the GA-chitin hydrogel was examined under different US powers of 0–30 W at 43 kHz. The effects of GA loading amounts in the hydrogels (0.54, 0.43, and 0.25 mg/cm 3 ) and chitin concentrations (0.1, 0.5, and 1 wt%) on the release behaviors were recorded under 43 kHz US exposure at 30 W. Results show that US accelerated the release efficiencies for all samples. Furthermore, the release efficiency increased concomitantly with increasing US power, GA loading amount, and decrease of the chitin concentration. The highest release rate of 0.74 μg/mL·min was obtained from 0.54 mg/cm 3 of GA-loaded hydrogel fabricated from a 0.1 wt% chitin mixture solution under 43 kHz US exposure at 30 W: nine times higher than that of the sample without US exposure. The hydrogel viscoelasticity demonstrated that the US irradiation rigidified the material. FT-IR showed that US can break the hydrogen bonds in the GA-chitin hydrogels. - Highlights: • Ultrasound (US) stimulated Gallic acid (GA) release from chitin hydrogel was studied. • The release efficiency of GA from chitin hydrogel increased nine times when irradiated by 43 kHz US compared with the sample without US. • Generalized 2D correlation and deconvolution study of FT-IR showed that US could promote the GA release by breaking hydrogen bonds.

Target Improves Efficiency in New Construction

Energy Technology Data Exchange (ETDEWEB)

None

2013-03-01

Target Corporation partnered with the U.S. Department of Energy (DOE) to develop and implement solutions to reduce annual energy consumption in new stores by at least 50% versus requirements set by ASHRAE/ANSI/IESNA Standard 90.1-20041 as part of DOE’s Commercial Building Partnership (CBP) program.

Smart IR780 Theranostic Nanocarrier for Tumor-Specific Therapy: Hyperthermia-Mediated Bubble-Generating and Folate-Targeted Liposomes.

Science.gov (United States)

Guo, Fang; Yu, Meng; Wang, Jinping; Tan, Fengping; Li, Nan

2015-09-23

The therapeutic effectiveness of chemotherapy was hampered by dose-limiting toxicity and was optimal only when tumor cells were subjected to a maximum drug exposure. The purpose of this work was to design a dual-functional thermosensitive bubble-generating liposome (BTSL) combined with conjugated targeted ligand (folate, FA) and photothermal agent (IR780), to realize enhanced therapeutic and diagnostic functions. This drug carrier was proposed to target tumor cells owing to FA-specific binding, followed by triggering drug release due to the decomposition of encapsulated ammonium bicarbonate (NH4HCO3) (generated CO2 bubbles) by being subjected to near-infrared (near-IR) laser irradiation, creating permeable defects in the lipid bilayer that rapidly release drug. In vitro temperature-triggered release study indicated the BTSL system was sensitive to heat triggering, resulting in rapid drug release under hyperthermia. For in vitro cellular uptake experiments, different results were observed on human epidermoid carcinoma cells (KB cells) and human lung cancer cells (A549 cells) due to their different (positive or negative) response to FA receptor. Furthermore, in vivo biodistribution analysis and antitumor study indicated IR780-BTSL-FA could specifically target KB tumor cells, exhibiting longer circulation time than free drug. In the pharmacodynamics experiments, IR780-BTSL-FA efficiently inhibited tumor growth in nude mice with no evident side effect to normal tissues and organs. Results of this study demonstrated that the constructed smart theranostic nanocarrier IR780-BTSL-FA might contribute to establishment of tumor-selective and effective chemotherapy.

In vitro atrazine-exposure inhibits human natural killer cell lytic granule release

International Nuclear Information System (INIS)

Rowe, Alexander M.; Brundage, Kathleen M.; Barnett, John B.

2007-01-01

The herbicide atrazine is a known immunotoxicant and an inhibitor of human natural killer (NK) cell lytic function. The precise changes in NK cell lytic function following atrazine exposure have not been fully elucidated. The current study identifies the point at which atrazine exerts its affect on the stepwise process of human NK cell-mediated lyses of the K562 target cell line. Using intracellular staining of human peripheral blood lymphocytes, it was determined that a 24-h in vitro exposure to atrazine did not decrease the level of NK cell lytic proteins granzyme A, granzyme B or perforin. Thus, it was hypothesized that atrazine exposure was inhibiting the ability of the NK cells to bind to the target cell and subsequently inhibit the release of lytic protein from the NK cell. To test this hypothesis, flow cytometry and fluorescent microscopy were employed to analyze NK cell-target cell co-cultures following atrazine exposure. These assays demonstrated no significant decrease in the level of target cell binding. However, the levels of NK intracellular lytic protein retained and the amount of lytic protein released were assessed following a 4-h incubation with K562 target cells. The relative level of intracellular lytic protein was 25-50% higher, and the amount of lytic protein released was 55-65% less in atrazine-treated cells than vehicle-treated cells following incubation with the target cells. These results indicate that ATR exposure inhibits the ability of NK cells to lyse target cells by blocking lytic granule release without affecting the ability of the NK cell to form stable conjugates with target cells

Dual drug delivery using "smart" liposomes for triggered release of anticancer agents

Science.gov (United States)

Jain, Ankit; Gulbake, Arvind; Jain, Ashish; Shilpi, Satish; Hurkat, Pooja; Jain, Sanjay K.

2013-07-01

Ovarian cancer is one of the most fatal gynecologic cancers. In this debut study, dual approach using synergistically active combination of paclitaxel-topotecan (Pac-Top; 20:1, w/w) is investigated with utilization of characteristic features of tumor micro-environment and additionally overexpressed folate receptors (FR-α) to achieve targeting to tumor site. Various liposomes namely liposomes, PEGylated liposomes, and FR-targeted PEGylated liposomes with lipid compositions viz. DPPC:DMPG (85.5:9.5), DPPC:DMPG:mPEG2000-DSPE (85.5:9.5:5), and DPPC:DMPG:mPEG2000-DSPE:DSPE-PEG-folate (85.5:9.5:4.5:0.5), respectively, were developed using thin film casting method. These were nanometric in size around 200 nm. In vitro drug release study showed initial burst release followed by sustained release for more than 72 h at physiological milieu (37 ± 0.5 °C, pH 7.4) while burst release (i.e., more than 90 %) within 5 min at simulated tumor milieu (41 ± 1 °C, pH 4). SRB cytotoxicity assay in OVCAR-3 cell line revealed Pac-Top free (20:1, w/w) to be more toxic (GI50 = 6.5 μg/ml) than positive control (Adriamycin, GI50 = 9.1 μg/ml) and FR-targeted PEGylated liposomes GI50 (14.7 μg/ml). Moreover, florescence microscopy showed the highest cell uptake of FR-targeted PEGylated liposomes so called "smart liposomes" which has not only mediated effective targeting to FR-α but also triggered release of drugs upon hyperthermia.

Integrin-mediated targeting of protein polymer nanoparticles carrying a cytostatic macrolide

Science.gov (United States)

Shi, Pu

nanoparticulate drug delivery. To explore this approach, genetically engineered diblock copolymers were constructed from elastin-like polypeptides (ELPs) that assemble small nanoparticles. ELPs are protein polymers of the sequence (Val-Pro-Gly-Xaa-Gly)n, where the identity of Xaa and n determine their assembly properties. Initially, a screening assay for model drug encapsulation in ELP nanoparticles was developed, which showed that Rose Bengal and Rapa have high non-specific encapsulation in the core of ELP nanoparticles with a sequence where Xaa = Ile or Phe. While excellent at entrapping these drugs, their release was relatively fast compared to their intended mean residence time in the human body. Having determined that Rapa can be non-specifically entrapped in the core of ELP nanoparticles, FK506 binding protein 12 (FKBP), which is the cognate protein target of Rapa, was genetically fused to the surface of these nanoparticles (FSI) to enhance their avidity towards Rapa. The fusion of FKBP to these nanoparticles slowed the terminal half-life of drug release to 57.8 h. To determine if this class of drug carriers has potential applications in vivo, FSI/Rapa was administered to mice carrying a human breast cancer model (MDA-MB-468). Compared to free drug, FSI encapsulation significantly decreased gross toxicity and enhanced the anti-cancer activity. In conclusion, protein polymer nanoparticles decorated with the cognate receptor of a high potency, low solubility drug (Rapa) efficiently improved drug loading capacity and its release. This approach has applications to the delivery of Rapa and its analogs; furthermore, this strategy has broader applications in the encapsulation, targeting, and release of other potent small molecules. Elastin-like polypeptides (ELPs) are genetically encoded protein polymers that reversibly phase separate in response to stimuli. They respond sharply to small shifts in temperature and form dense microdomains in the living eukaryotic cytosol. This

Scheduling with target start times

NARCIS (Netherlands)

Hoogeveen, J.A.; Velde, van de S.L.; Klein Haneveld, W.K.; Vrieze, O.J.; Kallenberg, L.C.M.

1997-01-01

We address the single-machine problem of scheduling n independent jobs subject to target start times. Target start times are essentially release times that may be violated at a certain cost. The goal is to minimize an objective function that is composed of total completion time and maximum

Materials considerations in accelerator targets

International Nuclear Information System (INIS)

Peacock, H.B. Jr.; Iyer, N.C.; Louthan, M.R. Jr.

1994-01-01

Future nuclear materials production and/or the burn-up of long lived radioisotopes may be accomplished through the capture of spallation produced neutrons in accelerators. Aluminum clad-lead and/or lead alloys has been proposed as a spallation target. Aluminum was the cladding choice because of the low neutron absorption cross section, fast radioactivity decay, high thermal conductivity, and excellent fabricability. Metallic lead and lead oxide powders were considered for the target core with the fabrication options being casting or powder metallurgy (PM). Scoping tests to evaluate gravity casting, squeeze casting, and casting and swaging processes showed that, based on fabricability and heat transfer considerations, squeeze casting was the preferred option for manufacture of targets with initial core cladding contact. Thousands of aluminum clad aluminum-lithium alloy core targets and control rods for tritium production have been fabricated by coextrusion processes and successfully irradiated in the SRS reactors. Tritium retention in, and release from the coextruded product was modeled from experimental and operational data. Newly produced tritium atoms were trapped by lithium atoms to form a lithium tritide. The effective tritium pressure required for trap or tritide stability was the equilibrium decomposition pressure of tritium over a lithium tritide-aluminum mixture. The temperature dependence of tritium release was determined by the permeability of the cladding to tritium and the local equilibrium at the trap sites. The model can be used to calculate tritium release from aluminum clad, aluminum-lithium alloy targets during postulated accelerator operational and accident conditions. This paper describes the manufacturing technologies evaluated and presents the model for tritium retention in aluminum clad, aluminum-lithium alloy tritium production targets

Theranostic gas-generating nanoparticles for targeted ultrasound imaging and treatment of neuroblastoma.

Science.gov (United States)

Lee, Jangwook; Min, Hyun-Su; You, Dong Gil; Kim, Kwangmeyung; Kwon, Ick Chan; Rhim, Taiyoun; Lee, Kuen Yong

2016-02-10

The development of safe and efficient diagnostic/therapeutic agents for treating cancer in clinics remains challenging due to the potential toxicity of conventional agents. Although the annual incidence of neuroblastoma is not that high, the disease mainly occurs in children, a population vulnerable to toxic contrast agents and therapeutics. We demonstrate here that cancer-targeting, gas-generating polymeric nanoparticles are useful as a theranostic tool for ultrasound (US) imaging and treating neuroblastoma. We encapsulated calcium carbonate using poly(d,l-lactide-co-glycolide) and created gas-generating polymer nanoparticles (GNPs). These nanoparticles release carbon dioxide bubbles under acidic conditions and enhance US signals. When GNPs are modified using rabies virus glycoprotein (RVG) peptide, a targeting moiety to neuroblastoma, RVG-GNPs effectively accumulate at the tumor site and substantially enhance US signals in a tumor-bearing mouse model. Intravenous administration of RVG-GNPs also reduces tumor growth in the mouse model without the use of conventional therapeutic agents. This approach to developing theranostic agents with disease-targeting ability may provide useful strategy for the detection and treatment of cancers, allowing safe and efficient clinical applications with fewer side effects than may occur with conventional agents. Copyright © 2015 Elsevier B.V. All rights reserved.

Natural Resource Management Index (NRMI), 2011 Release

Data.gov (United States)

National Aeronautics and Space Administration — The Natural Resource Management Index (NRMI), 2011 Release is a composite index for 174 countries derived from the average of four proximity-to-target indicators for...

Natural Resource Management Index (NRMI), 2010 Release

Data.gov (United States)

National Aeronautics and Space Administration — The Natural Resource Management Index (NRMI), 2010 Release is a composite index for 157 countries derived from the average of four proximity-to-target indicators for...

EPA Releases Neonicotinoid Assessments for Public Comment

Science.gov (United States)

Release of preliminary ecological and human health risk assessments for the neonicotinoid insecticides clothianidin, thiamethoxam, and dinotefuran, and a preliminary ecological risk assessment for imidacloprid, assessing risks to birds,mammals, non-target

Natural Resource Management Index (NRMI), 2010 Release

Data.gov (United States)

National Aeronautics and Space Administration — The Natural Resource Management Index (NRMI), 2011 Release is a composite index for 174 countries derived from the average of four proximity-to-target indicators for...

Natural Resource Management Index (NRMI), 2009 Release

Data.gov (United States)

National Aeronautics and Space Administration — The Natural Resource Management Index (NRMI), 2009 Release is a composite index for 171 countries derived from the average of four proximity-to-target indicators for...

Self-Assembled Smart Nanocarriers for Targeted Drug Delivery.

Science.gov (United States)

Cui, Wei; Li, Junbai; Decher, Gero

2016-02-10

Nanostructured drug-carrier systems promise numerous benefits for drug delivery. They can be engineered to precisely control drug-release rates or to target specific sites within the body with a specific amount of therapeutic agent. However, to achieve the best therapeutic effects, the systems should be designed for carrying the optimum amount of a drug to the desired target where it should be released at the optimum rate for a specified time. Despite numerous attempts, fulfilling all of these requirements in a synergistic way remains a huge challenge. The trend in drug delivery is consequently directed toward integrated multifunctional carrier systems, providing selective recognition in combination with sustained or triggered release. Capsules as vesicular systems enable drugs to be confined for controlled release. Furthermore, carriers modified with recognition groups can enhance the capability of encapsulated drug efficacy. Here, recent advances are reviewed regarding designing and preparing assembled capsules with targeting ligands or size controllable for selective recognition in drug delivery. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Efficient CRISPR-Cas9-mediated generation of knockin human pluripotent stem cells lacking undesired mutations at the targeted locus.

Science.gov (United States)

Merkle, Florian T; Neuhausser, Werner M; Santos, David; Valen, Eivind; Gagnon, James A; Maas, Kristi; Sandoe, Jackson; Schier, Alexander F; Eggan, Kevin

2015-05-12

The CRISPR-Cas9 system has the potential to revolutionize genome editing in human pluripotent stem cells (hPSCs), but its advantages and pitfalls are still poorly understood. We systematically tested the ability of CRISPR-Cas9 to mediate reporter gene knockin at 16 distinct genomic sites in hPSCs. We observed efficient gene targeting but found that targeted clones carried an unexpectedly high frequency of insertion and deletion (indel) mutations at both alleles of the targeted gene. These indels were induced by Cas9 nuclease, as well as Cas9-D10A single or dual nickases, and often disrupted gene function. To overcome this problem, we designed strategies to physically destroy or separate CRISPR target sites at the targeted allele and developed a bioinformatic pipeline to identify and eliminate clones harboring deleterious indels at the other allele. This two-pronged approach enables the reliable generation of knockin hPSC reporter cell lines free of unwanted mutations at the targeted locus. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

Protein Nanocage-Based Photo-Controlled Nitric Oxide Releasing Platform.

Science.gov (United States)

Li, Xiao; Zhang, Yajie; Sun, Jian; Chen, Weijian; Wang, Xuewei; Shao, Fenli; Zhu, Yuyu; Feng, Fude; Sun, Yang

2017-06-14

A photoactive NO releasing system was constructed by incorporation of NO-bound Fe-S clusters into horse spleen apoferritin cavities with high loading efficacy. The composites retained intact core-shell structure and indicated advantages such as enhanced stability, reduced cytotoxicity, efficient cellular uptake, and photocontrolled NO releasing property.

A Graphene-Based Biosensing Platform Based on Regulated Release of an Aptameric DNA Biosensor.

Science.gov (United States)

Mao, Yu; Chen, Yongli; Li, Song; Lin, Shuo; Jiang, Yuyang

2015-11-09

A novel biosensing platform was developed by integrating an aptamer-based DNA biosensor with graphene oxide (GO) for rapid and facile detection of adenosine triphosphate (ATP, as a model target). The DNA biosensor, which is locked by GO, is designed to contain two sensing modules that include recognition site for ATP and self-replication track that yields the nicking domain for Nt.BbvCI. By taking advantage of the different binding affinity of single-stranded DNA, double-stranded DNA and aptamer-target complex toward GO, the DNA biosensor could be efficiently released from GO in the presence of target with the help of a complementary DNA strand (CPDNA) that partially hybridizes to the DNA biosensor. Then, the polymerization/nicking enzyme synergetic isothermal amplification could be triggered, leading to the synthesis of massive DNA amplicons, thus achieving an enhanced sensitivity with a wide linear dynamic response range of four orders of magnitude and good selectivity. This biosensing strategy expands the applications of GO-DNA nanobiointerfaces in biological sensing, showing great potential in fundamental research and biomedical diagnosis.

Kepler Planet Detection Metrics: Pixel-Level Transit Injection Tests of Pipeline Detection Efficiency for Data Release 25

Science.gov (United States)

Christiansen, Jessie L.

2017-01-01

This document describes the results of the fourth pixel-level transit injection experiment, which was designed to measure the detection efficiency of both the Kepler pipeline (Jenkins 2002, 2010; Jenkins et al. 2017) and the Robovetter (Coughlin 2017). Previous transit injection experiments are described in Christiansen et al. (2013, 2015a,b, 2016).In order to calculate planet occurrence rates using a given Kepler planet catalogue, produced with a given version of the Kepler pipeline, we need to know the detection efficiency of that pipeline. This can be empirically determined by injecting a suite of simulated transit signals into the Kepler data, processing the data through the pipeline, and examining the distribution of successfully recovered transits. This document describes the results for the pixel-level transit injection experiment performed to accompany the final Q1-Q17 Data Release 25 (DR25) catalogue (Thompson et al. 2017)of the Kepler Objects of Interest. The catalogue was generated using the SOC pipeline version 9.3 and the DR25 Robovetter acting on the uniformly processed Q1-Q17 DR25 light curves (Thompson et al. 2016a) and assuming the Q1-Q17 DR25 Kepler stellar properties (Mathur et al. 2017).

Prostate stem cell antigen-targeted nanoparticles with dual functional properties: in vivo imaging and cancer chemotherapy

Directory of Open Access Journals (Sweden)

Gao X

2012-07-01

Full Text Available Xin Gao,1,* Yun Luo,1,* Yuanyuan Wang,1,* Jun Pang,1 Chengde Liao,2 Hanlun Lu,3 Youqiang Fang11Department of Urology, The Third Affiliated Hospital, 2Department of Radiology, The Second Affiliated Hospital, Sun Yat-Sen University, 3Materials Science Institute of Zhongshan University, Guangzhou, China*These authors contributed equally to this workBackground: We designed dual-functional nanoparticles for in vivo application using a modified electrostatic and covalent layer-by-layer assembly strategy to address the challenge of assessment and treatment of hormone-refractory prostate cancer.Methods: Core-shell nanoparticles were formulated by integrating three distinct functional components, ie, a core constituted by poly(D,L-lactic-co-glycolic acid, docetaxel, and hydrophobic superparamagnetic iron oxide nanocrystals (SPIONs, a multilayer shell formed by poly(allylamine hydrochloride and two different sized poly(ethylene glycol molecules, and a single-chain prostate stem cell antigen antibody conjugated to the nanoparticle surface for targeted delivery.Results: Drug release profiles indicated that the dual-function nanoparticles had a sustained release pattern over 764 hours, and SPIONs could facilitate the controlled release of the drug in vitro. The nanoparticles showed increased antitumor efficiency and enhanced magnetic resonance imaging in vitro through targeted delivery of docetaxel and SPIONs to PC3M cells. Moreover, in nude mice bearing PC3M xenografts, the nanoparticles provided MRI negative contrast enhancement, as well as halting and even reversing tumor growth during the 76-day study duration, and without significant systemic toxicity. The lifespan of the mice treated with these targeted dual-function nanoparticles was significantly increased (Chi-square = 22.514, P < 0.0001.Conclusion: This dual-function nanomedical platform may be a promising candidate for tumor imaging and targeted delivery of chemotherapeutic agents in vivo

The Resolved Stellar Populations Early Release Science Program

Science.gov (United States)

Gilbert, Karoline; Weisz, Daniel; Resolved Stellar Populations ERS Program Team

2018-06-01

The Resolved Stellar Populations Early Release Science Program (PI D. Weisz) will observe Local Group targets covering a range of stellar density and star formation histories, including a globular cluster, and ultra-faint dwarf galaxy, and a star-forming dwarf galaxy. Using observations of these diverse targets we will explore a broad science program: we will measure star formation histories, the sub-solar stellar initial mass function, and proper motions, perform studies of evolved stars, and map extinction in the target fields. Our observations will be of high archival value for other science such as calibrating stellar evolution models, studying variable stars, and searching for metal-poor stars. We will determine optimal observational setups and develop data reduction techniques that will be common to JWST studies of resolved stellar populations. We will also design, test, and release point spread function (PSF) fitting software specific to NIRCam and NIRISS, required for the crowded stellar regime. Prior to the Cycle 2 Call for Proposals, we will release PSF fitting software, matched HST and JWST catalogs, and clear documentation and step-by-step tutorials (such as Jupyter notebooks) for reducing crowded stellar field data and producing resolved stellar photometry catalogs, as well as for specific resolved stellar photometry science applications.

Sterile insect supply, emergence, and release

International Nuclear Information System (INIS)

Dowell, R.V.; Worley, J.; Gomes, P.J.

2005-01-01

Insect mass-rearing for a sterile insect technique (SIT) programme is designed to move beyond the large-scale rearing of insects in a laboratory to the industrial production of consistently high-quality insects for sterilization and release. Each facility reflects the unique biology of the insect reared within it, but there are some generalities for all rearing facilities. Rearing insects in self-contained modules offers flexibility, and increased safety from catastrophic occurrences, compared with using a single building which houses all facets of the rearing process. Although mechanizing certain aspects of the rearing steps helps provide a consistently high-quality insect, successful mass-rearing and delivery depends largely upon the human component. Besides production in centralized facilities, insects can be produced from purchased eggs, or nowadays, adult insects are often obtained from specialized satellite emergence/collection facilities. Interest in commercializing insect production and release is increasing. Shipping sterile insects, sometimes over long distances, is now common practice. Procedures for handling and chilling adult insects, and providing food and water prior to release, are continually being improved. Sterile insects are released via static-release receptacles, ground-release systems, or most commonly from the air. The aerial release of chilled sterile insects is the most efficient method of release, especially when aircraft flight paths are guided by a Global Positioning System (GPS) linked to a computer-controlled release mechanism. (author)

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

Recent developments and on-line tests of uranium carbide targets for production of nuclides far from

CERN Document Server

V.N. Panteleev et al.

The capacity of uranium carbide target materials of different structure and density for production of neutron-rich and heavy neutron-deficient isotopes have been investigated at the IRIS facility (PNPI) in the collaboration with Legnaro – GANIL – Orsay laboratories. The yields and release times of the species produced in the targets by the reactions induced by a 1 GeV proton beam of the PNPI synchrocyclotron have been measured. For the purpose to elaborate the most efficient and fast uranium carbide target prototype three kinds of the target materials were studied: a) a high density UC target material having ceramic-like structure with the density of 11 g/cm3 and the grain dimensions of about 200 microns; b) a high density UC target material with the density of 12 g/cm3 and the grain dimensions of about 20 microns prepared by the method of the powder metallurgy; c) a low density UCx target material with the density 3g/cm3 and the grain dimensions of about 20 microns prepared by the ISOLDE method. The comp...

Fluid mechanics aspects of magnetic drug targeting.

Science.gov (United States)

Odenbach, Stefan

2015-10-01

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

Cancer Patient T Cells Genetically Targeted to Prostate-Specific Membrane Antigen Specifically Lyse Prostate Cancer Cells and Release Cytokines in Response to Prostate-Specific Membrane Antigen

Directory of Open Access Journals (Sweden)

Michael C. Gong

1999-06-01

Full Text Available The expression of immunoglobulin-based artificial receptors in normal T lymphocytes provides a means to target lymphocytes to cell surface antigens independently of major histocompatibility complex restriction. Such artificial receptors have been previously shown to confer antigen-specific tumoricidal properties in murine T cells. We constructed a novel ζ chain fusion receptor specific for prostate-specific membrane antigen (PSMA termed Pz-1. PSMA is a cell-surface glycoprotein expressed on prostate cancer cells and the neovascular endothelium of multiple carcinomas. We show that primary T cells harvested from five of five patients with different stages of prostate cancer and transduced with the Pz-1 receptor readily lyse prostate cancer cells. Having established a culture system using fibroblasts that express PSMA, we next show that T cells expressing the Pz-1 receptor release cytokines in response to cell-bound PSMA. Furthermore, we show that the cytokine release is greatly augmented by B7.1-mediated costimulation. Thus, our findings support the feasibility of adoptive cell therapy by using genetically engineered T cells in prostate cancer patients and suggest that both CD4+ and CD8+ T lymphocyte functions can be synergistically targeted against tumor cells.

Dual drug delivery using “smart” liposomes for triggered release of anticancer agents

International Nuclear Information System (INIS)

Jain, Ankit; Gulbake, Arvind; Jain, Ashish; Shilpi, Satish; Hurkat, Pooja; Jain, Sanjay K.

2013-01-01

Ovarian cancer is one of the most fatal gynecologic cancers. In this debut study, dual approach using synergistically active combination of paclitaxel–topotecan (Pac–Top; 20:1, w/w) is investigated with utilization of characteristic features of tumor micro-environment and additionally overexpressed folate receptors (FR-α) to achieve targeting to tumor site. Various liposomes namely liposomes, PEGylated liposomes, and FR-targeted PEGylated liposomes with lipid compositions viz. DPPC:DMPG (85.5:9.5), DPPC:DMPG:mPEG 2000 –DSPE (85.5:9.5:5), and DPPC:DMPG:mPEG 2000 –DSPE:DSPE–PEG–folate (85.5:9.5:4.5:0.5), respectively, were developed using thin film casting method. These were nanometric in size around 200 nm. In vitro drug release study showed initial burst release followed by sustained release for more than 72 h at physiological milieu (37 ± 0.5 °C, pH 7.4) while burst release (i.e., more than 90 %) within 5 min at simulated tumor milieu (41 ± 1 °C, pH 4). SRB cytotoxicity assay in OVCAR-3 cell line revealed Pac–Top free (20:1, w/w) to be more toxic (GI 50 = 6.5 μg/ml) than positive control (Adriamycin, GI 50 = 9.1 μg/ml) and FR-targeted PEGylated liposomes GI 50 (14.7 μg/ml). Moreover, florescence microscopy showed the highest cell uptake of FR-targeted PEGylated liposomes so called “smart liposomes” which has not only mediated effective targeting to FR-α but also triggered release of drugs upon hyperthermia

An Efficient Method for Identifying Gene Fusions by Targeted RNA Sequencing from Fresh Frozen and FFPE Samples.

Directory of Open Access Journals (Sweden)

Jonathan A Scolnick

Full Text Available Fusion genes are known to be key drivers of tumor growth in several types of cancer. Traditionally, detecting fusion genes has been a difficult task based on fluorescent in situ hybridization to detect chromosomal abnormalities. More recently, RNA sequencing has enabled an increased pace of fusion gene identification. However, RNA-Seq is inefficient for the identification of fusion genes due to the high number of sequencing reads needed to detect the small number of fusion transcripts present in cells of interest. Here we describe a method, Single Primer Enrichment Technology (SPET, for targeted RNA sequencing that is customizable to any target genes, is simple to use, and efficiently detects gene fusions. Using SPET to target 5701 exons of 401 known cancer fusion genes for sequencing, we were able to identify known and previously unreported gene fusions from both fresh-frozen and formalin-fixed paraffin-embedded (FFPE tissue RNA in both normal tissue and cancer cells.

Two-step membrane binding by the bacterial SRP receptor enable efficient and accurate Co-translational protein targeting.

Science.gov (United States)

Hwang Fu, Yu-Hsien; Huang, William Y C; Shen, Kuang; Groves, Jay T; Miller, Thomas; Shan, Shu-Ou

2017-07-28

The signal recognition particle (SRP) delivers ~30% of the proteome to the eukaryotic endoplasmic reticulum, or the bacterial plasma membrane. The precise mechanism by which the bacterial SRP receptor, FtsY, interacts with and is regulated at the target membrane remain unclear. Here, quantitative analysis of FtsY-lipid interactions at single-molecule resolution revealed a two-step mechanism in which FtsY initially contacts membrane via a Dynamic mode, followed by an SRP-induced conformational transition to a Stable mode that activates FtsY for downstream steps. Importantly, mutational analyses revealed extensive auto-inhibitory mechanisms that prevent free FtsY from engaging membrane in the Stable mode; an engineered FtsY pre-organized into the Stable mode led to indiscriminate targeting in vitro and disrupted FtsY function in vivo. Our results show that the two-step lipid-binding mechanism uncouples the membrane association of FtsY from its conformational activation, thus optimizing the balance between the efficiency and fidelity of co-translational protein targeting.

Novel apigenin-loaded sodium hyaluronate nano-assemblies for targeting tumor cells.

Science.gov (United States)

Zhao, Ting; He, Yue; Chen, Huali; Bai, Yan; Hu, Wenjing; Zhang, Liangke

2017-12-01

We aimed to construct a novel nano-assembly carrying apigenin (APG), a hydrophobic drug, and to evaluate its in vitro targeting ability for A549 cells overexpressing CD44 receptors. The apigenin-loaded sodium hyaluronate nano-assemblies (APG/SH-NAs) were assembled by multiple non-covalent interactions between sodium hyaluronate (SH) and APG. The prepared APG/SH-NAs exhibited a small average size and narrow particle size distribution. In addition, satisfactory encapsulation efficiency and drug loading were obtained. The drug release curves indicated that APG/SH-NAs achieved a sustainable drug-release effect due to the presence of hydrophilic materials. The in vitro cytotoxicity of APG/SH-NAs against A549 cells and HepG2 cells was evaluated, and the results indicated that the prepared APG/SH-NA showed higher cytotoxicity compared to apigenin suspensions. When CD44 receptors on the surface of A549 cells were blocked by the addition of excess SH, the cytotoxicity of APG/SH-NA was significantly reduced. However, similar phenomena were not observed in HepG2 cells with relatively low CD44 receptor expression. The resulting APG/SH-NAs could efficiently facilitate the internalization of APG into A549 cells, which might be due to their high affinity for CD44 receptors. Moreover, the apoptotic rate of APG/SH-NAs through receptor-mediated endocytosis mechanism was higher than that of the other groups in A549 cells. Thus, such nano-assemblies were considered to be an effective transport system with excellent affinity for CD44 receptors to allow the SH-mediated targeted delivery of APG. Copyright © 2017. Published by Elsevier Ltd.

Production and Release of ISOL Beams from Molten Fluoride Salt Targets

CERN Document Server

Mendonca, T M; Ghetta, V; Alibert, M; Heuer, D; Noah, E; Cimmino, S; Delonca, M; Gottberg, A; Kronberger, M; Ramos, J; Seiffert, C; Stora, T; CERN. Geneva. ATS Department

2014-01-01

In the framework of the Beta Beams study, a molten fluoride target has been proposed for the production of the required 1013 18Ne/s. The production and extraction of such rates are obtained on a circulating molten salt with proton beam energy beams at close to 1 MW power. As a most important step to validate the concept, a prototype has been designed and investigated at CERN-ISOLDE using a static target unit. The target material consisted of a binary fluoride system, NaF:LiF (39:61 % mol.), with melting point at 649ºC. The production of Ne beams has been monitored as a function of the target temperature and proton beam intensity. The prototype development and the results of the first online tests with 1.4 GeV proton beam are presented in this paper.

Preparation and characterization of glycidyl methacrylate organo bridges grafted mesoporous silica SBA-15 as ibuprofen and mesalamine carrier for controlled release

Energy Technology Data Exchange (ETDEWEB)

Rehman, Fozia, E-mail: fozia@iqm.unicamp.br [Institute of Chemistry, University of Campinas, UNICAMP, P.O. Box 6154, 13084-971 Campinas, SP (Brazil); Interdisciplinary Research Centre in Biomedical Materials (IRCBM), COMSATS Institute of Information Technology, Lahore (Pakistan); Rahim, Abdur [Interdisciplinary Research Centre in Biomedical Materials (IRCBM), COMSATS Institute of Information Technology, Lahore (Pakistan); Airoldi, Claudio; Volpe, Pedro L.O. [Institute of Chemistry, University of Campinas, UNICAMP, P.O. Box 6154, 13084-971 Campinas, SP (Brazil)

2016-02-01

Mesoporous silica SBA-15 was synthesized and functionalized with bridged polysilsesquioxane monomers obtained by the reaction of 3-aminopropyltriethoxy silane with glycidyl methacrylate in 2:1 ratio. The synthesized mesoporous silica materials were characterized by elemental analysis, infrared spectroscopy, nuclear magnetic resonance spectroscopy, nitrogen adsorption, X-ray diffraction, thermogravimetry and scanning electron microscopy. The nuclear magnetic resonance in the solid state is in agreement with the sequence of carbon distributed in the attached organic chains, as expected for organically functionalized mesoporous silica. After functionalization with organic bridges the BET surface area was reduced from 1311.80 to 494.2 m{sup 2} g{sup −1} and pore volume was reduced from 1.98 to 0.89 cm{sup 3} g{sup −1}, when compared to original precursor silica. Modification of the silica surface with organic bridges resulted in high loading capacity and controlled release of ibuprofen and mesalamine in biological fluids. The Korsmeyer–Peppas model better fits the release data indicating Fickian diffusion and zero order kinetics for synthesized mesoporous silica. The drug release rate from the modified silica was slow in simulated gastric fluid, (pH 1.2) where less than 10% of mesalamine and ibuprofen were released in initial 8 h, while comparatively high release rates were observed in simulated intestinal (pH 6.8) and simulated body fluids (pH 7.2). The preferential release of mesalamine at intestinal pH suggests that the modified silica could be a simple, efficient, inexpensive and convenient carrier for colon targeted drugs, such a mesalamine and also as a controlled drug release system. - Highlights: • Modified SBA-15 silica with long hydrophobic chains was evaluated as drug carrier. • This silica showed improved loading capacity and controlled release of ibuprofen. • Compared to gastric pH high release rate of mesalamine was observed at colonic pH. �

Preparation and characterization of glycidyl methacrylate organo bridges grafted mesoporous silica SBA-15 as ibuprofen and mesalamine carrier for controlled release

International Nuclear Information System (INIS)

Rehman, Fozia; Rahim, Abdur; Airoldi, Claudio; Volpe, Pedro L.O.

2016-01-01

Mesoporous silica SBA-15 was synthesized and functionalized with bridged polysilsesquioxane monomers obtained by the reaction of 3-aminopropyltriethoxy silane with glycidyl methacrylate in 2:1 ratio. The synthesized mesoporous silica materials were characterized by elemental analysis, infrared spectroscopy, nuclear magnetic resonance spectroscopy, nitrogen adsorption, X-ray diffraction, thermogravimetry and scanning electron microscopy. The nuclear magnetic resonance in the solid state is in agreement with the sequence of carbon distributed in the attached organic chains, as expected for organically functionalized mesoporous silica. After functionalization with organic bridges the BET surface area was reduced from 1311.80 to 494.2 m 2 g −1 and pore volume was reduced from 1.98 to 0.89 cm 3 g −1 , when compared to original precursor silica. Modification of the silica surface with organic bridges resulted in high loading capacity and controlled release of ibuprofen and mesalamine in biological fluids. The Korsmeyer–Peppas model better fits the release data indicating Fickian diffusion and zero order kinetics for synthesized mesoporous silica. The drug release rate from the modified silica was slow in simulated gastric fluid, (pH 1.2) where less than 10% of mesalamine and ibuprofen were released in initial 8 h, while comparatively high release rates were observed in simulated intestinal (pH 6.8) and simulated body fluids (pH 7.2). The preferential release of mesalamine at intestinal pH suggests that the modified silica could be a simple, efficient, inexpensive and convenient carrier for colon targeted drugs, such a mesalamine and also as a controlled drug release system. - Highlights: • Modified SBA-15 silica with long hydrophobic chains was evaluated as drug carrier. • This silica showed improved loading capacity and controlled release of ibuprofen. • Compared to gastric pH high release rate of mesalamine was observed at colonic pH. • Modified silica

Evaluation of sodium diclofenac release using natural rubber latex as carrier

International Nuclear Information System (INIS)

Aielo, Patricia B.; Borges, Felipe A.; Romeira, Karoline M.; Herculano, Rondinelli D.; Miranda, Matheus Carlos Romeiro; Arruda, Larisa B. de; Lisboa Filho, Paulo Noronha; Drago, Bruno de C.

2014-01-01

Sodium Diclofenac is a non-steroidal anti-inflammatory drug (NSAID) taken to reduce inflammation and, as an analgesic, reduce pain. Although this drug is widely used in the general population, properties such as the short half-time and some side effects restrict its clinical use. The most common side effects are: gastric irritation, gastritis, peptic ulcer and bleeding. Studies involving biomaterials as carrier for drug release have been proving their efficiency in overcoming those problems and better controlling the release rate and targeting of the drug. Natural rubber latex (NRL) has been proven excellent for its biocompatibility and ability to stimulate angiogenesis, cellular adhesion and the formation of extracellular matrix, promoting the replacement and regeneration of tissue. In this work, a NRL membrane is used to deliver sodium diclofenac. Sodium diclofenac (NaDic) was found to be adsorbed on the NRL membrane, with little or no incorporation into the membrane bulk, according to energy dispersive Scanning Electron Microscopy with X-Ray microanalysis (SEM-EDS) spectroscopy. In addition, FT-IR shows that there is no molecular-level interaction between drug and NRL. Already, the X-Ray Diffraction (XRD) of NaDic-NRL shows a broader one spectrum than the sharper halo (amorphous characteristic XRD spectrum) of pure NRL. More importantly, the release time of diclofenac in a NRL membrane in vitro was increased from the typical 2-3 h for oral tablets to ca. 74 h. The kinetics of the drug release could be fitted with a double exponential function, with two characteristic times of 0.899 and 32.102 h. In this study, we demonstrated that the interesting properties provided by NRL membranes combined with a controlled release of drug is relevant for biomedical applications.(author)

Evaluation of sodium diclofenac release using natural rubber latex as carrier

Energy Technology Data Exchange (ETDEWEB)

Aielo, Patricia B.; Borges, Felipe A.; Romeira, Karoline M.; Herculano, Rondinelli D., E-mail: rond@assis.unesp.br [Universidade Estadual Paulista Julio de Mesquita Filho (UNESP), Assis, SP (Brazil). Fac. de Ciencias e Letras. Dept. de Ciencias Biologicas; Miranda, Matheus Carlos Romeiro [Universidade Estadual Paulista Julio de Mesquita Filho (UNESP), Araraquara, SP (Brazil). Inst. de Quimica; Arruda, Larisa B. de; Lisboa Filho, Paulo Noronha; Drago, Bruno de C. [Universidade Estadual Paulista Julio de Mesquita Filho (UNESP), Bauru, SP (Brazil). Fac. de Ciencias. Dept. de Fisica

2014-08-15

Sodium Diclofenac is a non-steroidal anti-inflammatory drug (NSAID) taken to reduce inflammation and, as an analgesic, reduce pain. Although this drug is widely used in the general population, properties such as the short half-time and some side effects restrict its clinical use. The most common side effects are: gastric irritation, gastritis, peptic ulcer and bleeding. Studies involving biomaterials as carrier for drug release have been proving their efficiency in overcoming those problems and better controlling the release rate and targeting of the drug. Natural rubber latex (NRL) has been proven excellent for its biocompatibility and ability to stimulate angiogenesis, cellular adhesion and the formation of extracellular matrix, promoting the replacement and regeneration of tissue. In this work, a NRL membrane is used to deliver sodium diclofenac. Sodium diclofenac (NaDic) was found to be adsorbed on the NRL membrane, with little or no incorporation into the membrane bulk, according to energy dispersive Scanning Electron Microscopy with X-Ray microanalysis (SEM-EDS) spectroscopy. In addition, FT-IR shows that there is no molecular-level interaction between drug and NRL. Already, the X-Ray Diffraction (XRD) of NaDic-NRL shows a broader one spectrum than the sharper halo (amorphous characteristic XRD spectrum) of pure NRL. More importantly, the release time of diclofenac in a NRL membrane in vitro was increased from the typical 2-3 h for oral tablets to ca. 74 h. The kinetics of the drug release could be fitted with a double exponential function, with two characteristic times of 0.899 and 32.102 h. In this study, we demonstrated that the interesting properties provided by NRL membranes combined with a controlled release of drug is relevant for biomedical applications.(author)

Development and Targeting Efficiency of Irinotecan Engineered ...

African Journals Online (AJOL)

Erah

Conclusion: Proniosomes offer a suitable alternative colloidal carrier approach to achieving drug ... for the treatment of localized disease in the body ... analogue of the natural alkaloid, campto- ..... vasculature targeted tumor necrosis factor-α.

Experimental methods in radioactive ion-beam target/ion source development and characterization

International Nuclear Information System (INIS)

Welton, R.F.; Alton, G.D.; Cui, B.; Murray, S.N.

1998-01-01

We have developed off-line experimental techniques and apparatuses that permit direct measurement of effusive-flow delay times and ionization efficiencies for nearly any chemically reactive element in high-temperature target/ion sources (TIS) commonly used for on-line radioactive ion-beam (RIB) generation. The apparatuses include a hot Ta valve for effusive-flow delay-time measurements, a cooled molecular injection system for determination of ionization efficiencies, and a gas flow measurement/control system for introducing very low, well-defined molecular flows into the TIS. Measurements are performed on a test stand using molecular feed compounds containing stable complements of the radioactive nuclei of interest delivered to the TIS at flow rates commensurate with on-line RIB generation. In this article, the general techniques are described and effusive-flow delay times and ionization efficiency measurements are reported for fluorine in an electron-beam plasma target/ion source developed for RIB generation and operated in both positive- and negative-ion extraction modes. copyright 1998 American Institute of Physics

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

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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

Specific and efficient targeting of cyanobacterial bicarbonate transporters to the inner envelope membrane of chloroplasts in Arabidopsis

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Susumu eUehara

2016-02-01

Full Text Available Installation of cyanobacterial bicarbonate transporters to the inner envelope membrane (IEM of chloroplasts in C3 plants has been thought to improve photosynthetic performance. However, the method to deliver cyanobacterial bicarbonate transporters to the chloroplast IEM remains to be established. In this study, we provide evidence that the cyanobacterial bicarbonate transporters, BicA and SbtA, can be specifically installed into the chloroplast IEM using the chloroplast IEM targeting signal in conjunction with the transit peptide. We fused the transit peptide and the mature portion of Cor413im1, whose targeting mechanism to the IEM has been characterized in detail, to either BicA or SbtA isolated from Synechocystis sp. PCC6803. Among the seven chimeric constructs tested, we confirmed that four chimeric bicarbonate transporters, designated as BicAI, BicAII, SbtAII, and SbtAIII, were expressed in Arabidopsis. Furthermore, these chimeric transporters were specifically targeted to the chloroplast IEM. They were also resistant to alkaline extraction but can be solubilized by Triton X-100, indicating that they are integral membrane proteins in the chloroplast IEM. One of the transporters, BicA, could reside in the chloroplast IEM even after removal of the IEM targeting signal. Taken together, our results indicate that the addition of IEM targeting signal, as well as the transit peptide, to bicarbonate transporters allows us to efficiently target nuclear-encoded chimeric bicarbonate transporters to the chloroplast IEM.

Oxaliplatin loaded PLAGA microspheres: design of specific release profiles.

Science.gov (United States)

Lagarce, F; Cruaud, O; Deuschel, C; Bayssas, M; Griffon-Etienne, G; Benoit, J

2002-08-21

Oxaliplatin loaded PLAGA microspheres have been prepared by solvent extraction process. Parameters affecting the release kinetics in vitro have been studied in order to design specific release profiles suitable for direct intra-tumoral injection. By varying the nature and the relative proportions of different polymers we managed to prepare microspheres with good encapsulation efficiency (75-90%) and four different release profiles: zero order kinetics (type II) and the classical sigmoïd release profile with three different sizes of plateau and burst. These results, if correlated with in vivo activity, are promising to enhance effectiveness of local tumor treatment.

Laser-accelerated proton conversion efficiency thickness scaling

International Nuclear Information System (INIS)

Hey, D. S.; Foord, M. E.; Key, M. H.; LePape, S. L.; Mackinnon, A. J.; Patel, P. K.; Ping, Y.; Akli, K. U.; Stephens, R. B.; Bartal, T.; Beg, F. N.; Fedosejevs, R.; Friesen, H.; Tiedje, H. F.; Tsui, Y. Y.

2009-01-01

The conversion efficiency from laser energy into proton kinetic energy is measured with the 0.6 ps, 9x10 19 W/cm 2 Titan laser at the Jupiter Laser Facility as a function of target thickness in Au foils. For targets thicker than 20 μm, the conversion efficiency scales approximately as 1/L, where L is the target thickness. This is explained by the domination of hot electron collisional losses over adiabatic cooling. In thinner targets, the two effects become comparable, causing the conversion efficiency to scale weaker than 1/L; the measured conversion efficiency is constant within the scatter in the data for targets between 5 and 15 μm, with a peak conversion efficiency of 4% into protons with energy greater than 3 MeV. Depletion of the hydrocarbon contaminant layer is eliminated as an explanation for this plateau by using targets coated with 200 nm of ErH 3 on the rear surface. The proton acceleration is modeled with the hybrid-particle in cell code LSP, which reproduced the conversion efficiency scaling observed in the data.

Anti-inflammatory drugs for Duchenne muscular dystrophy: focus on skeletal muscle-releasing factors

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Miyatake S

2016-08-01

Full Text Available Shouta Miyatake,1 Yuko Shimizu-Motohashi,2 Shin’ichi Takeda,1 Yoshitsugu Aoki1 1Department of Molecular Therapy, National Institute of Neuroscience, National Center of Neurology and Psychiatry, Kodaira, Tokyo, Japan; 2Department of Child Neurology, National Center Hospital, National Center of Neurology and Psychiatry, Kodaira, Tokyo, Japan Abstract: Duchenne muscular dystrophy (DMD, an incurable and a progressive muscle wasting disease, is caused by the absence of dystrophin protein, leading to recurrent muscle fiber damage during contraction. The inflammatory response to fiber damage is a compelling candidate mechanism for disease exacerbation. The only established pharmacological treatment for DMD is corticosteroids to suppress muscle inflammation, however this treatment is limited by its insufficient therapeutic efficacy and considerable side effects. Recent reports show the therapeutic potential of inhibiting or enhancing pro- or anti-inflammatory factors released from DMD skeletal muscles, resulting in significant recovery from muscle atrophy and dysfunction. We discuss and review the recent findings of DMD inflammation and opportunities for drug development targeting specific releasing factors from skeletal muscles. It has been speculated that nonsteroidal anti-inflammatory drugs targeting specific inflammatory factors are more effective and have less side effects for DMD compared with steroidal drugs. For example, calcium channels, reactive oxygen species, and nuclear factor-κB signaling factors are the most promising targets as master regulators of inflammatory response in DMD skeletal muscles. If they are combined with an oligonucleotide-based exon skipping therapy to restore dystrophin expression, the anti-inflammatory drug therapies may address the present therapeutic limitation of low efficiency for DMD. Keywords: calcium channels, ryanodine receptor 1, exon skipping, NF-κB, myokine, ROS

A review on target drug delivery: magnetic microspheres

Directory of Open Access Journals (Sweden)

Amit Chandna

2013-01-01

Magnetic microsphere is newer approach in pharmaceutical field. Magnetic microspheres as an alternative to traditional radiation methods which use highly penetrating radiation that is absorbed throughout the body. Its use is limited by toxicity and side effects. The aim of the specific targeting is to enhance the efficiency of drug delivery & at the same time to reduce the toxicity & side effects. This kind of delivery system is very much important which localises the drug to the disease site. In this larger amount of freely circulating drug can be replaced by smaller amount of magnetically targeted drug. Magnetic carriers receive magnetic responses to a magnetic field from incorporated materials that are used for magnetic microspheres are chitosan, dextran etc. magnetic microspheres can be prepared from a variety of carrier material. One of the most utilized is serum albumin from human or other appropriate species. Drug release from albumin microspheres can be sustained or controlled by various stabilization procedures generally involving heat or chemical cross-linking of the protein carrier matrix.

Development of Houttuynia cordata Extract-Loaded Solid Lipid Nanoparticles for Oral Delivery: High Drug Loading Efficiency and Controlled Release

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Ju-Heon Kim

2017-12-01

Full Text Available Houttuynia cordata (H. cordata has been used for diuresis and detoxification in folk medicine as well as a herbal medicine with antiviral and antibacterial activities. H. cordata extract-loaded solid lipid nanoparticles (H-SLNs were prepared with various concentration of poloxamer 188 or poloxamer 407 by a hot homogenization and ultrasonication method. H-SLNs dispersion was freeze-dried with or without trehalose as a cryoprotectant. The physicochemical characteristics of H-SLNs were evaluated by dynamic laser scattering (DLS, differential scanning calorimetry (DSC, Fourier transform infrared spectroscopy (FT-IR, and scanning electron microscopy (SEM. Additionally, the in vitro release and in vitro cytotoxicity of H-SLNs were measured. Encapsulation efficiencies of H-SLNs (as quercitrin were 92.9–95.9%. The SEM images of H-SLNs showed that H-SLNs have a spherical morphology. DSC and FT-IR showed that there were no interactions between ingredients. The increased extent of particle size of freeze-dried H-SLNs with trehalose was significantly lower than that of H-SLNs without trehalose. H-SLNs provided sustained release of quercitrin from H. cordata extracts. Cell viability of Caco-2 cells was over 70% according to the concentration of various formulation. Therefore, it was suggested that SLNs could be good carrier for administering H. cordata extracts.

Efficient regeneration of partially spent ammonia borane fuel

International Nuclear Information System (INIS)

Davis, Benjamin Lee; Gordon, John C.; Stephens, Frances; Dixon, David A.; Matus, Myrna H.

2008-01-01

A necessary target in realizing a hydrogen (H 2 ) economy, especially for the transportation sector, is its storage for controlled delivery, presumably to an energy producing fuel cell. In this vein, the U.S. Department of Energy's (DOE) Centers of Excellence (CoE) in Hydrogen Storage have pursued different methodologies, including metal hydrides, chemical hydrides, and sorbents, for the expressed purpose of supplanting gasoline's current > 300 mile driving range. Chemical hydrogen storage has been dominated by one appealing material, ammonia borane (H 3 B-NH 3 , AB), due to its high gravimetric capacity of hydrogen (19.6 wt %) and low molecular weight (30.7 g mol -1 ). In addition, AB has both hydridic and protic moieties, yielding a material from which H2 can be readily released. As such, a number of publications have described H 2 release from amine boranes, yielding various rates depending on the method applied. Even though the viability of any chemical hydrogen storage system is critically dependent on efficient recyclability, reports on the latter subject are sparse, invoke the use of high energy reducing agents, and suffer from low yields. For example, the DOE recently decided to no longer pursue the use of NaBH 4 as a H 2 storage material, in part because of inefficient regeneration. We thus endeavored to find an energy efficient regeneration process for the spent fuel from H 2 depleted AB with a minimum number of steps.

Report on the R&D of Uranium Carbide targets by the PLOG collaboration at PNPI-Gatchina

CERN Document Server

A.E. Barzakh, D.V. Fedorov, A.M. Ionan, V.S. Ivanov, M.P. Levchenko, K.A. Mezilev, F.V. Moroz, S.Yu. Orlov, V.N. Panteleev, Yu.M. Volkov,O. Alyakrinskiy, A. Andrighetto, A. Lanchais, G. Lhersonneau*, V. Rizzi, L. Stroe#, L.B. Tecchio,O. Bajeat, M. Cheikh Mhamed, S. Essabaa, C. Lau, B. Roussière,M. Dubois, C. Eléon, G. Gaubert, P. Jardin, N. Lecesne, R. Leroy, J.Y. Pacquet, M. -G. Saint Laurent, A.C.C. Villari.

The aim of this report is to summarize the experimental results of the R&D program on Uranium Carbide targets for Radioactive Ion Beam (RIB) production performed at the Petersburg Nuclear Physics Institute (PNPI) of Gatchina (Russia). The targets have been irradiated with 1 GeV protons delivered by the Synchrocyclotron and the measurements were carried out at the IRIS isotope separator on-line. Different compositions of Uranium Carbide targets as well as different kinds of ion sources have been tested in order to evaluate efficiency and release times of the reaction products. The report includes the results of experiments performed in the period of time going from November 2001 up to March 2006. This R&D program was performed in the framework of the collaboration with the EURISOL, SPES and SPIRAL-2 projects and ISTC program.

An efficient hybrid technique in RCS predictions of complex targets at high frequencies

Science.gov (United States)

Algar, María-Jesús; Lozano, Lorena; Moreno, Javier; González, Iván; Cátedra, Felipe

2017-09-01

Most computer codes in Radar Cross Section (RCS) prediction use Physical Optics (PO) and Physical theory of Diffraction (PTD) combined with Geometrical Optics (GO) and Geometrical Theory of Diffraction (GTD). The latter approaches are computationally cheaper and much more accurate for curved surfaces, but not applicable for the computation of the RCS of all surfaces of a complex object due to the presence of caustic problems in the analysis of concave surfaces or flat surfaces in the far field. The main contribution of this paper is the development of a hybrid method based on a new combination of two asymptotic techniques: GTD and PO, considering the advantages and avoiding the disadvantages of each of them. A very efficient and accurate method to analyze the RCS of complex structures at high frequencies is obtained with the new combination. The proposed new method has been validated comparing RCS results obtained for some simple cases using the proposed approach and RCS using the rigorous technique of Method of Moments (MoM). Some complex cases have been examined at high frequencies contrasting the results with PO. This study shows the accuracy and the efficiency of the hybrid method and its suitability for the computation of the RCS at really large and complex targets at high frequencies.

Coaxial Electrospinning with Mixed Solvents: From Flat to Round Eudragit L100 Nanofibers for Better Colon-Targeted Sustained Drug Release Profiles

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Deng-Guang Yu

2014-01-01

Full Text Available A modified coaxial electrospinning process was developed for creating drug-loaded composite nanofibers. Using a mixed solvent of ethanol and N,N-dimethylacetamide as a sheath fluid, the electrospinning of a codissolving solution of diclofenac sodium (DS and Eudragit L100 (EL100 could run smoothly and continuously without any clogging. A series of analyses were undertaken to characterize the resultant nanofibers from both the modified coaxial process and a one-fluid electrospinning in terms of their morphology, physical form of the components, and their functional performance. Compared with those from the one-fluid electrospinning, the DS-loaded EL100 fibers from the modified coaxial process were rounder and smoother and possessed higher quality in terms of diameter and distribution with the DS existing in the EL100 matrix in an amorphous state; they also provided a better colon-targeted sustained drug release profile with a longer release time period. The modified coaxial process not only can smooth the electrospinning process to prevent clogging of spinneret, but also is a useful tool to tailor the shape of electrospun nanofibers and thus endow them improved functions.

Gastrin-releasing peptide receptor-based targeting using bombesin analogues is superior to metabolism-based targeting using choline for in vivo imaging of human prostate cancer xenografts

Energy Technology Data Exchange (ETDEWEB)

Schroeder, Rogier P.J. [Erasmus MC, Department of Nuclear Medicine, Rotterdam (Netherlands); Erasmus MC, Department of Urology, Rotterdam (Netherlands); Weerden, W.M. van; Bangma, C.H.; Reneman, S. [Erasmus MC, Department of Urology, Rotterdam (Netherlands); Krenning, E.P.; Berndsen, S.; Grievink-de Ligt, C.H.; Groen, H.C.; Blois, E. de; Breeman, W.A.P.; Jong, M. de [Erasmus MC, Department of Nuclear Medicine, Rotterdam (Netherlands)

2011-07-15

Prostate cancer (PC) is a major health problem. Overexpression of the gastrin-releasing peptide receptor (GRPR) in PC, but not in the hyperplastic prostate, provides a promising target for staging and monitoring of PC. Based on the assumption that cancer cells have increased metabolic activity, metabolism-based tracers are also being used for PC imaging. We compared GRPR-based targeting using the {sup 68}Ga-labelled bombesin analogue AMBA with metabolism-based targeting using {sup 18}F-methylcholine ({sup 18}F-FCH) in nude mice bearing human prostate VCaP xenografts. PET and biodistribution studies were performed with both {sup 68}Ga-AMBA and {sup 18}F-FCH in all VCaP tumour-bearing mice, with PC-3 tumour-bearing mice as reference. Scanning started immediately after injection. Dynamic PET scans were reconstructed and analysed quantitatively. Biodistribution of tracers and tissue uptake was expressed as percent of injected dose per gram tissue (%ID/g). All tumours were clearly visualized using {sup 68}Ga-AMBA. {sup 18}F-FCH showed significantly less contrast due to poor tumour-to-background ratios. Quantitative PET analyses showed fast tumour uptake and high retention for both tracers. VCaP tumour uptake values determined from PET at steady-state were 6.7 {+-} 1.4%ID/g (20-30 min after injection, N = 8) for {sup 68}Ga-AMBA and 1.6 {+-} 0.5%ID/g (10-20 min after injection, N = 8) for {sup 18}F-FCH, which were significantly different (p <0.001). The results in PC-3 tumour-bearing mice were comparable. Biodistribution data were in accordance with the PET results showing VCaP tumour uptake values of 9.5 {+-} 4.8%ID/g (N = 8) for {sup 68}Ga-AMBA and 2.1 {+-} 0.4%ID/g (N = 8) for {sup 18}F-FCH. Apart from the GRPR-expressing organs, uptake in all organs was lower for {sup 68}Ga-AMBA than for {sup 18}F-FCH. Tumour uptake of {sup 68}Ga-AMBA was higher while overall background activity was lower than observed for {sup 18}F-FCH in the same PC-bearing mice. These results

α-Imaging Confirmed Efficient Targeting of CD₄₅-Positive Cells After ²¹¹At-Radioimmunotherapy for Hematopoietic Cell Transplantation

Energy Technology Data Exchange (ETDEWEB)

Frost, Sophia; Miller, Brian W.; Back, Tom; Santos, E. B.; Hamlin, Donald K.; Knoblaugh, E.; Frayo, Shani; Kenoyer, Aimee L.; Storb, Rainer; Press, O. W.; Wilbur, D. Scott; Pagel, John M.; Sandmaier, B. M.

2015-09-03

Alpha-radioimmunotherapy (α-RIT) targeting CD45 may substitute for total body irradiation in hematopoietic cell transplantation (HCT) preparative regimens for lymphoma. Our goal was to optimize the anti-CD45 monoclonal antibody (MAb; CA12.10C12) protein dose for astatine-²¹¹(²¹¹At)-RIT, extending the analysis to include intra-organ ²¹¹At activity distribution and α-imaging-based small-scale dosimetry, along with imunohistochemical staining. Methods: Eight normal dogs were injected with either 0.75 (n=5) or 1.00 mg/kg (n=3) of ²¹¹At-B10-CA12.10C12 (11.5–27.6 MBq/kg). Two were euthanized and necropsied 19–22 hours postinjection (p.i.), and six received autologous HCT three days after ²¹¹At-RIT, following lymph node and bone marrow biopsies at 2–4 and/or 19 hours p.i. Blood was sampled to study toxicity and clearance; CD45 targeting was evaluated by flow cytometry. ²¹¹At localization and small scale dosimetry were assessed using two α-imaging : α-camera and iQID. Results: Uptake of ²¹¹At was highest in spleen (0.31–0.61 %IA/g), lymph nodes (0.02–0.16 %IA/g), liver (0.11–0.12 %IA/g), and marrow (0.06–0.08 %IA/g). Lymphocytes in blood and marrow were efficiently targeted using either MAb dose. Lymph nodes remained unsaturated, but displayed targeted ²¹¹At localization in T lymphocyte-rich areas. Absorbed doses to blood, marrow, and lymph nodes were estimated at 3.9, 3.0, and 4.2 Gy/210 MBq, respectively. All transplanted dogs experienced transient hepatic toxicity. Liver enzyme levels were temporarily elevated in 5 of 6 dogs; 1 treated with 1.00 mg MAb/kg developed ascites and was euthanized 136 days after HCT. Conclusion: ²¹¹At-anti-CD45 RIT with 0.75 mg MAb/kg efficiently targeted blood and marrow without severe toxicity. Dosimetry calculations and observed radiation-induced effects indicated that sufficient ²¹¹At-B10-CA12.10C12 localization was achieved for efficient conditioning for HCT.

pH responsive N-succinyl chitosan/Poly (acrylamide-co-acrylic acid hydrogels and in vitro release of 5-fluorouracil.

Directory of Open Access Journals (Sweden)

Shahid Bashir

Full Text Available There has been significant progress in the last few decades in addressing the biomedical applications of polymer hydrogels. Particularly, stimuli responsive hydrogels have been inspected as elegant drug delivery systems capable to deliver at the appropriate site of action within the specific time. The present work describes the synthesis of pH responsive semi-interpenetrating network (semi-IPN hydrogels of N-succinyl-chitosan (NSC via Schiff base mechanism using glutaraldehyde as a crosslinking agent and Poly (acrylamide-co-acrylic acid(Poly (AAm-co-AA was embedded within the N-succinyl chitosan network. The physico-chemical interactions were characterized by Fourier transform infrared (FTIR, X-ray diffraction (XRD, thermogravimetric analysis (TGA, and field emission scanning electron microscope (FESEM. The synthesized hydrogels constitute porous structure. The swelling ability was analyzed in physiological mediums of pH 7.4 and pH 1.2 at 37°C. Swelling properties of formulations with various amounts of NSC/ Poly (AAm-co-AA and crosslinking agent at pH 7.4 and pH 1.2 were investigated. Hydrogels showed higher swelling ratios at pH 7.4 while lower at pH 1.2. Swelling kinetics and diffusion parameters were also determined. Drug loading, encapsulation efficiency, and in vitro release of 5-fluorouracil (5-FU from the synthesized hydrogels were observed. In vitro release profile revealed the significant influence of pH, amount of NSC, Poly (AAm-co-AA, and crosslinking agent on the release of 5-FU. Accordingly, rapid and large release of drug was observed at pH 7.4 than at pH 1.2. The maximum encapsulation efficiency and release of 5-FU from SP2 were found to be 72.45% and 85.99%, respectively. Kinetics of drug release suggested controlled release mechanism of 5-FU is according to trend of non-Fickian. From the above results, it can be concluded that the synthesized hydrogels have capability to adapt their potential exploitation as targeted oral drug

Colloid electrochemistry of conducting polymer: towards potential-induced in-situ drug release

International Nuclear Information System (INIS)

Sankoh, Supannee; Vagin, Mikhail Yu.; Sekretaryova, Alina N.; Thavarungkul, Panote; Kanatharana, Proespichaya; Mak, Wing Cheung

2017-01-01

Highlights: • Pulsed electrode potential induced an in-situ drug release from dispersion of conducting polymer microcapsules. • Fast detection of the released drug within the colloid microenvironment. • Improved the efficiency of localized drug release at the electrode interface. - Abstract: Over the past decades, controlled drug delivery system remains as one of the most important area in medicine for various diseases. We have developed a new electrochemically controlled drug release system by combining colloid electrochemistry and electro-responsive microcapsules. The pulsed electrode potential modulation led to the appearance of two processes available for the time-resolved registration in colloid microenvironment: change of the electronic charge of microparticles (from 0.5 ms to 0.1 s) followed by the drug release associated with ionic equilibration (1–10 s). The dynamic electrochemical measurements allow the distinction of drug release associated with ionic relaxation and the change of electronic charge of conducting polymer colloid microparticles. The amount of released drug (methylene blue) could be controlled by modulating the applied potential. Our study demonstrated a surface-potential driven controlled drug release of dispersion of conducting polymer carrier at the electrode interfaces, while the bulk colloids dispersion away from the electrode remains as a reservoir to improve the efficiency of localized drug release. The developed new methodology creates a model platform for the investigations of surface potential-induced in-situ electrochemical drug release mechanism.

Alkali reversal of psoralen cross-link for the targeted delivery of psoralen monoadduct lesion

International Nuclear Information System (INIS)

Yeung, A.T.; Dinehart, W.J.; Jones, B.K.

1988-01-01

Psoralen intercalates into double-stranded DNA and photoreacts mainly with thymines to form monoadducts and interstrand cross-links. The authors used an oligonucleotide model to demonstrate a novel mechanism: the reversal of psoralen cross-links by base-catalyzed rearrangement at 90 0 C (BCR). The BCR reaction is more efficient than the photoreversal reaction. They show that the BCR occurs predominantly on the furan side of a psoralen cross-link. The cleavage does not result in the breaking of the DNA backbone, and the thymine based freed from the cross-link by the cleavage reaction appears to be unmodified. Similarly, BCR of the furan-side monoadduct of psoralen removed the psoralen molecule and regenerated the unaltered native oligonucleotide. The pyrone-side psoralen monoadduct is relatively resistant to BCR. One can use BCR to perform efficient oligonucleotide-directed, site-specific delivery of a psoralen monoadduct. As a demonstration of this approach, they have hybridized a 19 base long oligonucleotide vehicle containing a furan-side psoralen monoadduct to a 56 base long complementary oligonucleotide target strand and formed a specific cross-link at the target site with 365-nm UV. Subsequent BCR released the oligonucleotide vehicle and deposited the psoralen at the target site

Drug delivery systems with modified release for systemic and biophase bioavailability.

Science.gov (United States)

Leucuta, Sorin E

2012-11-01

This review describes the most important new generations of pharmaceutical systems: medicines with extended release, controlled release pharmaceutical systems, pharmaceutical systems for the targeted delivery of drug substances. The latest advances and approaches for delivering small molecular weight drugs and other biologically active agents such as proteins and nucleic acids require novel delivery technologies, the success of a drug being many times dependent on the delivery method. All these dosage forms are qualitatively superior to medicines with immediate release, in that they ensure optimal drug concentrations depending on specific demands of different disease particularities of the body. Drug delivery of these pharmaceutical formulations has the benefit of improving product efficacy and safety, as well as patient convenience and compliance. This paper describes the biopharmaceutical, pharmacokinetic, pharmacologic and technological principles in the design of drug delivery systems with modified release as well as the formulation criteria of prolonged and controlled release drug delivery systems. The paper presents pharmaceutical prolonged and controlled release dosage forms intended for different routes of administration: oral, ocular, transdermal, parenteral, pulmonary, mucoadhesive, but also orally fast dissolving tablets, gastroretentive drug delivery systems, colon-specific drug delivery systems, pulsatile drug delivery systems and carrier or ligand mediated transport for site specific or receptor drug targeting. Specific technologies are given on the dosage forms with modified release as well as examples of marketed products, and current research in these areas.

Differential Impact of Plasma Proteins on the Adhesion Efficiency of Vascular-Targeted Carriers (VTCs) in Blood of Common Laboratory Animals.

Science.gov (United States)

Namdee, Katawut; Sobczynski, Daniel J; Onyskiw, Peter J; Eniola-Adefeso, Omolola

2015-12-16

Vascular-targeted carrier (VTC) interaction with human plasma is known to reduce targeted adhesion efficiency in vitro. However, the role of plasma proteins on the adhesion efficiency of VTCs in laboratory animals remains unknown. Here, in vitro blood flow assays are used to explore the effects of plasma from mouse, rabbit, and porcine on VTC adhesion. Porcine blood exhibited a strong negative plasma effect on VTC adhesion while no significant plasma effect was found with rabbit and mouse blood. A brush density poly(ethylene glycol) (PEG) on VTCs was effective at improving adhesion of microsized, but not nanosized, VTCs in porcine blood. Overall, the results suggest that porcine models, as opposed to mouse, can serve as better models in preclinical research for predicting the in vivo functionality of VTCs for use in humans. These considerations hold great importance for the design of various pharmaceutical products and development of reliable drug delivery systems.

Overall effect of carbon production and nutrient release in sludge holding tank on mainstream biological nutrient removal efficiency.

Science.gov (United States)

Jabari, Pouria; Yuan, Qiuyan; Oleszkiewicz, Jan A

2017-09-11

The potential of hydrolysis/fermentation of activated sludge in sludge holding tank (SHT) to produce additional carbon for the biological nutrient removal (BNR) process was investigated. The study was conducted in anaerobic batch tests using the BNR sludge (from a full-scale Westside process) and the mixture of BNR sludge with conventional non-BNR activated sludge (to have higher biodegradable particulate chemical oxygen demand (bpCOD) in sludge). The BioWin 4.1 was used to simulate the anaerobic batch test of the BNR sludge. Also, the overall effect of FCOD production and nutrient release on BNR efficiency of the Westside process was estimated. The experimental results showed that the phosphorous uptake of sludge increased during hydrolysis/ fermentation condition up to the point when poly-P was completely utilized; afterwards, it decreased significantly. The BioWin simulation could not predict the loss of aerobic phosphorous uptake after poly-P was depleted. The results showed that in the case of activated sludge with relatively higher bpCOD (originating from plants with short sludge retention time or without primary sedimentation), beneficial effect of SHT on BNR performance is feasible. In order to increase the potential of SHT to enhance BNR efficiency, a relatively low retention time and high sludge load is recommended.

Efficient characterization of labeling uncertainty in closely-spaced targets tracking

NARCIS (Netherlands)

Moreno Leon, Carlos; Moreno Leon, Carlos; Driessen, Hans; Mandal, Pranab K.

2016-01-01

In this paper we propose a novel solution to the labeled multi-target tracking problem. The method presented is specially effective in scenarios where the targets have once moved in close proximity. When this is the case, disregarding the labeling uncertainty present in a solution (after the targets

Targeting brain cells with glutathione-modulated nanoliposomes: in vitro and in vivo study

Directory of Open Access Journals (Sweden)

Salem HF

2015-07-01

Full Text Available Heba F Salem,1 Sayed M Ahmed,2 Ashraf E Hassaballah,3 Mahmoud M Omar1,4 1Department of Pharmaceutics and Industrial Pharmacy, Beni-suef University, 2Department of Industrial Pharmacy, Assiut University, 3Department of Clinical Pathology, Faculty of Medicine, Assiut University, Assuit, 4Department of Pharmaceutics and Industrial Pharmacy, Deraya University, Egypt Background: The blood–brain barrier prevents many drug moieties from reaching the central nervous system. Therefore, glutathione-modulated nanoliposomes have been engineered to enhance the targeting of flucytosine to the brain. Methods: Glutathione-modulated nanoliposomes were prepared by thin-film hydration technique and evaluated in the primary brain cells of rats. Lecithin, cholesterol, and span 65 were mixed at 1:1:1 molar ratio. The molar percentage of PEGylated glutathione varied from 0 mol% to 0.75 mol%. The cellular binding and the uptake of the targeted liposomes were both monitored by epifluorescent microscope and flow cytometry techniques. A biodistribution and a pharmacokinetic study of flucytosine and flucytosine-loaded glutathione–modulated liposomes was carried out to evaluate the in vivo brain-targeting efficiency. Results: The size of glutathione-modulated nanoliposomes was <100 nm and the zeta potential was more than -65 mV. The cumulative release reached 70% for certain formulations. The cellular uptake increased as molar percent of glutathione increased to reach the maximum at 0.75 mol%. The uptake of the targeted liposomes by brain cells of the rats was three times greater than that of the nontargeted liposomes. An in vivo study showed that the relative efficiency was 2.632±0.089 and the concentration efficiency was 1.590±0.049, and also, the drug-targeting index was 3.670±0.824. Conclusion: Overall, these results revealed that glutathione-PEGylated nanoliposomes enhance the effective delivery of flucytosine to brain and could become a promising new

Octadecylamine-Mediated Versatile Coating of CoFe2O4 NPs for the Sustained Release of Anti-Inflammatory Drug Naproxen and in Vivo Target Selectivity.

Science.gov (United States)

Georgiadou, Violetta; Makris, George; Papagiannopoulou, Dionysia; Vourlias, Georgios; Dendrinou-Samara, Catherine

2016-04-13

Magnetic nanoparticles (MNPs) can play a distinct role in magnetic drug delivery via their distribution to the targeted area. The preparation of such MNPs is a challenging multiplex task that requires the optimization of size, magnetic, and surface properties for the achievement of desirable target selectivity, along with the sustained drug release as a prerequisite. In that context, CoFe2O4 MNPs with a small size of ∼7 nm and moderate saturation magnetization of ∼60 emu g(-1) were solvothermally synthesized in the presence of octadecylamine (ODA) with a view to investigate the functionalization route effect on the drug release. Synthetic regulations allowed us to prepare MNPs with aminated (AmMNPs) and amine-free (FAmMNPs) surface. The addition of the nonsteroidal anti-inflammatory drug with a carboxylate donor, Naproxen (NAP), was achieved by direct coupling with the NH2 groups, rendered by ODA, through the formation of an amide bond in the case of AmMNPs. In the case of FAmMNPs, indirect coupling of NAP was performed through an intermediate linker (polyethylenimine) and on PEG-ylated MNPs. FT-IR, (1)H NMR, (13)C NMR, and UV-vis data confirmed the addition of NAP, whereas diverse drug-release behavior was observed for the different functionalization approaches. The biological behavior of the MNPs@NAP was evaluated in vitro in rat serum and in vivo in mice, after radiolabeling with a γ-emitting radionuclide, (99m)Tc. The in vivo fate of MNPs@NAP carriers was in straightforward relation with the direct or indirect coupling of NAP. Furthermore, an inflammation was induced intramuscularly, where the directly coupled (99m)Tc-MNPs@NAP carriers showed increased accumulation at the inflammation site.

Nuclear energy release in hadron-nucleus collisions

International Nuclear Information System (INIS)

Strugalski, Z.; Strugalska-Gola, E.

1998-01-01

Energy release process in nuclear reactions induced by fast hadrons in hadron-nucleus collisions is discussed. Some portion of the internal nuclear energy is released when the locally damaged in a collision, and instable therefore, residual target nucleus transits itself into light nuclear fragments (nucleons, D, T) and a stable lighter final nucleus or some number of stable lighter nuclei. It is not excluded that in some of the collisions the induced intranuclear nuclear reactions may be energy overcompensating. Corresponding reconnaissance should be made - in analysing the nuclear reactions induced in hadron-nucleus collisions

Magnetic Nanoparticle Facilitated Drug Delivery for Cancer Therapy with Targeted and Image-Guided Approaches.

Science.gov (United States)

Huang, Jing; Li, Yuancheng; Orza, Anamaria; Lu, Qiong; Guo, Peng; Wang, Liya; Yang, Lily; Mao, Hui

2016-06-14

With rapid advances in nanomedicine, magnetic nanoparticles (MNPs) have emerged as a promising theranostic tool in biomedical applications, including diagnostic imaging, drug delivery and novel therapeutics. Significant preclinical and clinical research has explored their functionalization, targeted delivery, controllable drug release and image-guided capabilities. To further develop MNPs for theranostic applications and clinical translation in the future, we attempt to provide an overview of the recent advances in the development and application of MNPs for drug delivery, specifically focusing on the topics concerning the importance of biomarker targeting for personalized therapy and the unique magnetic and contrast-enhancing properties of theranostic MNPs that enable image-guided delivery. The common strategies and considerations to produce theranostic MNPs and incorporate payload drugs into MNP carriers are described. The notable examples are presented to demonstrate the advantages of MNPs in specific targeting and delivering under image guidance. Furthermore, current understanding of delivery mechanisms and challenges to achieve efficient therapeutic efficacy or diagnostic capability using MNP-based nanomedicine are discussed.

A study of the 51Cr release assay system in micro-method

International Nuclear Information System (INIS)

Kiya, Katsuzo; Harada, Kiyoshi; Uozumi, Tohru; Toge, Tetsuya; Hattori, Takao.

1981-01-01

Conditions of 51 Cr release assay in microculture were investigated to measure the natural cytotoxic (NC) activity of mouse spleen cells. Malignant glioma (MG) cells of C57BL/6 mouse, induced by 20-methylcholanthrene, were labeled with Na 2 51 CrO 4 . Spleen cells collected from the same mouse strain were suspended in Eagle's MEM. Labeled MG cells and spleen cells were incubated for several hours in a CO 2 incubator. Then the activity of the supernatant was measured by an automatic gamma counter. The optimum conditions of 51 Cr release assay in micro-culture were, (1) number of the target cells: 5 x 10 3 / well (2) FCS concentration: 10% (3) E/T ratio: less than 100 : 1, 50 : 1 was possible (4) incubation time: 15 hours. The number of the target cells at labeling incubation was set to 2 x 10 6 /ml. Though the natural release of 51 Cr was not effected by the viability of the target cells, it was suggested that the NC activity was dependent on the viability of both cells, target and effector cells. (Tsunoda, M.)

Study of the /sup 51/Cr release assay system in micro-method

Energy Technology Data Exchange (ETDEWEB)

Kiya, K.; Harada, K.; Uozumi, T. (Hiroshima Univ. (Japan). School of Medicine); Toge, T.; Hattori, T.

1981-05-01

Conditions of /sup 51/Cr release assay in microculture were investigated to measure the natural cytotoxic (NC) activity of mouse spleen cells. Malignant glioma (MG) cells of C57BL/6 mouse, induced by 20-methylcholanthrene, were labeled with Na/sub 2//sup 51/CrO/sub 4/. Spleen cells collected from the same mouse strain were suspended in Eagle's MEM. Labeled MG cells and spleen cells were incubated for several hours in a CO/sub 2/ incubator. Then the activity of the supernatant was measured by an automatic gamma counter. The optimum conditions of /sup 51/Cr release assay in micro-culture were, (1) number of the target cells: 5 x 10/sup 3// well (2) FCS concentration: 10% (3) E/T ratio: less than 100 : 1, 50 : 1 was possible (4) incubation time: 15 hours. The number of the target cells at labeling incubation was set to 2 x 10/sup 6//ml. Though the natural release of /sup 51/Cr was not effected by the viability of the target cells, it was suggested that the NC activity was dependent on the viability of both cells, target and effector cells.

Materials considerations in accelerator targets

International Nuclear Information System (INIS)

Peacock, H. B. Jr.; Iyer, N. C.; Louthan, M. R. Jr.

1995-01-01

Future nuclear materials production and/or the burn-up of long lived radioisotopes may be accomplished through the capture of spallation produced neutrons in accelerators. Aluminum clad-lead and/or lead alloys has been proposed as a spallation target. Aluminum was the cladding choice because of the low neutron absorption cross section, fast radioactivity decay, high thermal conductivity, and excellent fabricability. Metallic lead and lead oxide powders were considered for the target core with the fabrication options being casting or powder metallurgy (PM). Scoping tests to evaluate gravity casting, squeeze casting, and casting and swaging processes showed that, based on fabricability and heat transfer considerations, squeeze casting was the preferred option for manufacture of targets with initial core cladding contact. Thousands of aluminum clad aluminum-lithium alloy core targets and control rods for tritium production have been fabricated by coextrusion processes and successfully irradiated in the SRS reactors. Tritium retention in, and release from, the coextruded product was modeled from experimental and operational data. The model assumed that tritium atoms, formed by the 6Li(n,a)3He reaction, were produced in solid solution in the Al-Li alloy. Because of the low solubility of hydrogen isotopes in aluminum alloys, the irradiated Al-Li rapidly became supersaturated in tritium. Newly produced tritium atoms were trapped by lithium atoms to form a lithium tritide. The effective tritium pressure required for trap or tritide stability was the equilibrium decomposition pressure of tritium over a lithium tritide-aluminum mixture. The temperature dependence of tritium release was determined by the permeability of the cladding to tritium and the local equilibrium at the trap sites. The model can be used to calculate tritium release from aluminum clad, aluminum-lithium alloy targets during postulated accelerator operational and accident conditions. This paper describes

Microgels produced using microfluidic on-chip polymer blending for controlled released of VEGF encoding lentivectors.

Science.gov (United States)

Madrigal, Justin L; Sharma, Shonit N; Campbell, Kevin T; Stilhano, Roberta S; Gijsbers, Rik; Silva, Eduardo A

2018-03-15

Alginate hydrogels are widely used as delivery vehicles due to their ability to encapsulate and release a wide range of cargos in a gentle and biocompatible manner. The release of encapsulated therapeutic cargos can be promoted or stunted by adjusting the hydrogel physiochemical properties. However, the release from such systems is often skewed towards burst-release or lengthy retention. To address this, we hypothesized that the overall magnitude of burst release could be adjusted by combining microgels with distinct properties and release behavior. Microgel suspensions were generated using a process we have termed on-chip polymer blending to yield composite suspensions of a range of microgel formulations. In this manner, we studied how alginate percentage and degradation relate to the release of lentivectors. Whereas changes in alginate percentage had a minimal impact on lentivector release, microgel degradation led to a 3-fold increase, and near complete release, over 10 days. Furthermore, by controlling the amount of degradable alginate present within microgels the relative rate of release can be adjusted. A degradable formulation of microgels was used to deliver vascular endothelial growth factor (VEGF)-encoding lentivectors in the chick chorioallantoic membrane (CAM) assay and yielded a proangiogenic response in comparison to the same lentivectors delivered in suspension. The utility of blended microgel suspensions may provide an especially appealing platform for the delivery of lentivectors or similarly sized therapeutics. Genetic therapeutics hold considerable potential for the treatment of diseases and disorders including ischemic cardiovascular diseases. To realize this potential, genetic vectors must be precisely and efficiently delivered to targeted regions of the body. However, conventional methods of delivery do not provide sufficient spatial and temporal control. Here, we demonstrate how alginate microgels provide a basis for developing systems for

Methane release

International Nuclear Information System (INIS)

Seifert, M.

1999-01-01

The Swiss Gas Industry has carried out a systematic, technical estimate of methane release from the complete supply chain from production to consumption for the years 1992/1993. The result of this survey provided a conservative value, amounting to 0.9% of the Swiss domestic output. A continuation of the study taking into account new findings with regard to emission factors and the effect of the climate is now available, which provides a value of 0.8% for the target year of 1996. These results show that the renovation of the network has brought about lower losses in the local gas supplies, particularly for the grey cast iron pipelines. (author)

Development and evaluation of camptothecin loaded polymer stabilized nanoemulsion: Targeting potential in 4T1-breast tumour xenograft model.

Science.gov (United States)

Sugumaran, Abimanyu; Ponnusamy, Chandrasekar; Kandasamy, Palanivel; Krishnaswami, Venkateshwaran; Palanichamy, Rajaguru; Kandasamy, Ruckmani; Lakshmanan, Manikandan; Natesan, Subramanian

2018-04-30

Targeted delivery of anticancer agents is poised to improve cancer therapy, for which polymers can serve as targeting ligands or nanocarriers for chemotherapeutic agents. In this study, we have developed and evaluated the efficacy of a camptothecin (CPT)-loaded polymer stabilized nanoemulsion (PSNE) for the passive targeted delivery to breast cancer. Based on the pseudo-ternary phase diagrams, PSNEs were developed using capmul MCM:poloxamer 407 (4:1), solutol HS 15:simulsol P23 (1:2) and water. CPT polymer mixture was developed by solvent evaporation technique. The PSNEs were characterized for droplet size distribution, plasma protein adsorption, drug release, in-vivo targeting potential, hemolytic potential, cytotoxicity, genotoxicity, in-vivo biodistribution and CPT lactone ring stability. The developed PSNEs showed uniform droplet distribution, extended drug release (76.59±6.12% at 24h), acceptable hemolytic potential, significant cytotoxicity (IC 50 =176±4.3ng/mL) and genotoxicity against MCF-7 cancer cells but low DNA damage potential in human peripheral blood lymphocytes. The efficiency of PSNEs for the targeted delivery of CPT into the tumour regions was documented in 4T1-breast tumour xenografted BALB/c mice. In-vivo biodistribution study shows that 7105.84±568.46ng/g of CPT was passively targeted from PSNE to breast cancer tissue. About 80% of the lactone form was stable for 24h. Taken together, our study provides a promising strategy for developing PSNE-targeted drug delivery system for the breast cancer therapy. Copyright © 2017 Elsevier B.V. All rights reserved.

DDR: Efficient computational method to predict drug–target interactions using graph mining and machine learning approaches

KAUST Repository

Olayan, Rawan S.

2017-11-23

Motivation Finding computationally drug-target interactions (DTIs) is a convenient strategy to identify new DTIs at low cost with reasonable accuracy. However, the current DTI prediction methods suffer the high false positive prediction rate. Results We developed DDR, a novel method that improves the DTI prediction accuracy. DDR is based on the use of a heterogeneous graph that contains known DTIs with multiple similarities between drugs and multiple similarities between target proteins. DDR applies non-linear similarity fusion method to combine different similarities. Before fusion, DDR performs a pre-processing step where a subset of similarities is selected in a heuristic process to obtain an optimized combination of similarities. Then, DDR applies a random forest model using different graph-based features extracted from the DTI heterogeneous graph. Using five repeats of 10-fold cross-validation, three testing setups, and the weighted average of area under the precision-recall curve (AUPR) scores, we show that DDR significantly reduces the AUPR score error relative to the next best start-of-the-art method for predicting DTIs by 34% when the drugs are new, by 23% when targets are new, and by 34% when the drugs and the targets are known but not all DTIs between them are not known. Using independent sources of evidence, we verify as correct 22 out of the top 25 DDR novel predictions. This suggests that DDR can be used as an efficient method to identify correct DTIs.

Fission gas release behaviour in MOX fuels

International Nuclear Information System (INIS)

Viswanathan, U.K.; Anantharaman, S.; Sahoo, K.C.

2002-01-01

As a part of plutonium recycling programme MOX (U,Pu)O 2 fuels will be used in Indian boiling water reactors (BWR) and pressurised heavy water reactors (PHWR). Based on successful test irradiation of MOX fuel in CIRUS reactor, 10 MOX fuel assemblies have been loaded in the BWR of Tarapur Atomic Power Station (TAPS). Some of these MOX fuel assemblies have successfully completed the initial target average burnup of ∼16,000 MWD/T. Enhancing the burnup target of the MOX fuels and increasing loading of MOX fuels in TAPS core will depend on the feedback information generated from the measurement of released fission gases. Fission gas release behaviour has been studied in the experimental MOX fuel elements (UO 2 - 4% PuO 2 ) irradiated in pressurised water loop (PWL) of CIRUS. Eight (8) MOX fuel elements irradiated to an average burnup of ∼16,000 MWD/T have been examined. Some of these fuel elements contained controlled porosity pellets and chamfered pellets. This paper presents the design details of the experimental set up for studying fission gas release behaviour including measurement of gas pressure, void volume and gas composition. The experimental data generated is compared with the prediction of fuel performance modeling codes of PROFESS and GAPCON THERMAL-3. (author)

Platelet microparticle-inspired clot-responsive nanomedicine for targeted fibrinolysis.

Science.gov (United States)

Pawlowski, Christa L; Li, Wei; Sun, Michael; Ravichandran, Kavya; Hickman, DaShawn; Kos, Clarissa; Kaur, Gurbani; Sen Gupta, Anirban

2017-06-01

Intravascular administration of plasminogen activators is a clinically important thrombolytic strategy to treat occlusive vascular conditions. A major issue with this strategy is the systemic off-target drug action, which affects hemostatic capabilities and causes substantial hemorrhagic risks. This issue can be potentially resolved by designing technologies that allow thrombus-targeted delivery and site-specific action of thrombolytic drugs. To this end, leveraging a liposomal platform, we have developed platelet microparticle (PMP)-inspired nanovesicles (PMINs), that can protect encapsulated thrombolytic drugs in circulation to prevent off-target uptake and action, anchor actively onto thrombus via PMP-relevant molecular mechanisms and allow drug release via thrombus-relevant enzymatic trigger. Specifically, the PMINs can anchor onto thrombus via heteromultivalent ligand-mediated binding to active platelet integrin GPIIb-IIIa and P-selectin, and release the thrombolytic payload due to vesicle destabilization triggered by clot-relevant enzyme phospholipase-A 2 . Here we report on the evaluation of clot-targeting efficacy, lipase-triggered drug release and resultant thrombolytic capability of the PMINs in vitro, and subsequently demonstrate that intravenous delivery of thrombolytic-loaded PMINs can render targeted fibrinolysis without affecting systemic hemostasis, in vivo, in a carotid artery thrombosis model in mice. Our studies establish significant promise of the PMIN technology for safe and site-targeted nanomedicine therapies in the vascular compartment. Copyright © 2017. Published by Elsevier Ltd.

Dual drug delivery using 'smart' liposomes for triggered release of anticancer agents

Energy Technology Data Exchange (ETDEWEB)

Jain, Ankit; Gulbake, Arvind; Jain, Ashish; Shilpi, Satish; Hurkat, Pooja; Jain, Sanjay K., E-mail: drskjainin@yahoo.com [Dr. Hari Singh Gour Vishwavidyalaya, Pharmaceutics Research Projects Laboratory, Department of Pharmaceutical Sciences (India)

2013-07-15

Ovarian cancer is one of the most fatal gynecologic cancers. In this debut study, dual approach using synergistically active combination of paclitaxel-topotecan (Pac-Top; 20:1, w/w) is investigated with utilization of characteristic features of tumor micro-environment and additionally overexpressed folate receptors (FR-{alpha}) to achieve targeting to tumor site. Various liposomes namely liposomes, PEGylated liposomes, and FR-targeted PEGylated liposomes with lipid compositions viz. DPPC:DMPG (85.5:9.5), DPPC:DMPG:mPEG{sub 2000}-DSPE (85.5:9.5:5), and DPPC:DMPG:mPEG{sub 2000}-DSPE:DSPE-PEG-folate (85.5:9.5:4.5:0.5), respectively, were developed using thin film casting method. These were nanometric in size around 200 nm. In vitro drug release study showed initial burst release followed by sustained release for more than 72 h at physiological milieu (37 {+-} 0.5 Degree-Sign C, pH 7.4) while burst release (i.e., more than 90 %) within 5 min at simulated tumor milieu (41 {+-} 1 Degree-Sign C, pH 4). SRB cytotoxicity assay in OVCAR-3 cell line revealed Pac-Top free (20:1, w/w) to be more toxic (GI{sub 50} = 6.5 {mu}g/ml) than positive control (Adriamycin, GI{sub 50} = 9.1 {mu}g/ml) and FR-targeted PEGylated liposomes GI{sub 50} (14.7 {mu}g/ml). Moreover, florescence microscopy showed the highest cell uptake of FR-targeted PEGylated liposomes so called 'smart liposomes' which has not only mediated effective targeting to FR-{alpha} but also triggered release of drugs upon hyperthermia.

INITIAL DATA RELEASE OF THE KEPLER-INT SURVEY

Energy Technology Data Exchange (ETDEWEB)

Greiss, S.; Steeghs, D.; Gaensicke, B. T. [Department of Physics, Astronomy and Astrophysics group, University of Warwick, CV4 7AL Coventry (United Kingdom); Martin, E. L. [INTA-CSIC Centro de Astrobiologia, Carretera de Ajalvir km 4, 28550 Torrejon de Ardoz (Spain); Groot, P. J.; Verbeek, K.; Jonker, P. G.; Scaringi, S. [Department of Astrophysics/IMAPP, Radboud University Nijmegen, P.O. Box 9010, 6500 GL Nijmegen (Netherlands); Irwin, M. J.; Gonzalez-Solares, E. [Cambridge Astronomy Survey Unit, Institute of Astronomy, University of Cambridge, Madingley Road, CB3 0HA Cambridge (United Kingdom); Greimel, R. [Institut fuer Physik, Karl-Franzen Universitaet Graz, Universitaetsplatz 5, 8010 Graz (Austria); Knigge, C. [School of Physics and Astronomy, University of Southampton, Southampton, Hampshire SO17 1BJ (United Kingdom); Ostensen, R. H. [Instituut voor Sterrenkunde, KU Leuven, Celestijnenlaan 200D, 3001 Leuven (Belgium); Drew, J. E.; Farnhill, H. [Centre for Astrophysics Research, University of Hertfordshire, College Lane, Hatfield AL10 9AB (United Kingdom); Drake, J.; Wright, N. J. [Harvard-Smithsonian Center for Astrophysics, 60 Garden Street, Cambridge, MA 02138 (United States); Ripepi, V. [INAF-Osservatorio Astronomico di Capodimonte, via Moiariello 16, Naples I-80131 (Italy); Southworth, J. [Astrophysics Group, Keele University, Newcastle-under-Lyme ST5 5BG (United Kingdom); Still, M., E-mail: s.greiss@warwick.ac.uk [NASA Ames Research Center, M/S 244-40, Moffett Field, CA 94035 (United States); and others

2012-07-15

This paper describes the first data release of the Kepler-INT Survey (KIS) that covers a 116 deg{sup 2} region of the Cygnus and Lyra constellations. The Kepler field is the target of the most intensive search for transiting planets to date. Despite the fact that the Kepler mission provides superior time-series photometry, with an enormous impact on all areas of stellar variability, its field lacks optical photometry complete to the confusion limit of the Kepler instrument necessary for selecting various classes of targets. For this reason, we follow the observing strategy and data reduction method used in the IPHAS and UVEX galactic plane surveys in order to produce a deep optical survey of the Kepler field. This initial release concerns data taken between 2011 May and August, using the Isaac Newton Telescope on the island of La Palma. Four broadband filters were used, U, g, r, i, as well as one narrowband one, H{alpha}, reaching down to a 10{sigma} limit of {approx}20th mag in the Vega system. Observations covering {approx}50 deg{sup 2}, thus about half of the field, passed our quality control thresholds and constitute this first data release. We derive a global photometric calibration by placing the KIS magnitudes as close as possible to the Kepler Input Catalog (KIC) photometry. The initial data release catalog containing around 6 million sources from all the good photometric fields is available for download from the KIS Web site (www.astro.warwick.ac.uk/research/kis/) as well as via MAST (KIS magnitudes can be retrieved using the MAST enhanced target search page http://archive.stsci.edu/kepler/kepler{sub f}ov/search.php and also via Casjobs at MAST Web site http://mastweb.stsci.edu/kplrcasjobs/).

INITIAL DATA RELEASE OF THE KEPLER-INT SURVEY

International Nuclear Information System (INIS)

Greiss, S.; Steeghs, D.; Gänsicke, B. T.; Martín, E. L.; Groot, P. J.; Verbeek, K.; Jonker, P. G.; Scaringi, S.; Irwin, M. J.; González-Solares, E.; Greimel, R.; Knigge, C.; Østensen, R. H.; Drew, J. E.; Farnhill, H.; Drake, J.; Wright, N. J.; Ripepi, V.; Southworth, J.; Still, M.

2012-01-01

This paper describes the first data release of the Kepler-INT Survey (KIS) that covers a 116 deg 2 region of the Cygnus and Lyra constellations. The Kepler field is the target of the most intensive search for transiting planets to date. Despite the fact that the Kepler mission provides superior time-series photometry, with an enormous impact on all areas of stellar variability, its field lacks optical photometry complete to the confusion limit of the Kepler instrument necessary for selecting various classes of targets. For this reason, we follow the observing strategy and data reduction method used in the IPHAS and UVEX galactic plane surveys in order to produce a deep optical survey of the Kepler field. This initial release concerns data taken between 2011 May and August, using the Isaac Newton Telescope on the island of La Palma. Four broadband filters were used, U, g, r, i, as well as one narrowband one, Hα, reaching down to a 10σ limit of ∼20th mag in the Vega system. Observations covering ∼50 deg 2 , thus about half of the field, passed our quality control thresholds and constitute this first data release. We derive a global photometric calibration by placing the KIS magnitudes as close as possible to the Kepler Input Catalog (KIC) photometry. The initial data release catalog containing around 6 million sources from all the good photometric fields is available for download from the KIS Web site (www.astro.warwick.ac.uk/research/kis/) as well as via MAST (KIS magnitudes can be retrieved using the MAST enhanced target search page http://archive.stsci.edu/kepler/kepler_fov/search.php and also via Casjobs at MAST Web site http://mastweb.stsci.edu/kplrcasjobs/).

Controlled release system for ametryn using polymer microspheres: Preparation, characterization and release kinetics in water

International Nuclear Information System (INIS)

Grillo, Renato; Pereira, Anderson do Espirito Santo; Ferreira Silva de Melo, Nathalie; Porto, Raquel Martins; Feitosa, Leandro Oliveira; Tonello, Paulo Sergio; Dias Filho, Newton L.; Rosa, Andre Henrique; Lima, Renata; Fraceto, Leonardo Fernandes

2011-01-01

The purpose of this work was to develop a modified release system for the herbicide ametryn by encapsulating the active substance in biodegradable polymer microparticles produced using the polymers poly(hydroxybutyrate) (PHB) or poly(hydroxybutyrate-valerate) (PHBV), in order to both improve the herbicidal action and reduce environmental toxicity. PHB or PHBV microparticles containing ametryn were prepared and the efficiencies of herbicide association and loading were evaluated, presenting similar values of approximately 40%. The microparticles were characterized by scanning electron microscopy (SEM), which showed that the average sizes of the PHB and PHBV microparticles were 5.92 ± 0.74 μm and 5.63 ± 0.68 μm, respectively. The ametryn release profile was modified when it was encapsulated in the microparticles, with slower and more sustained release compared to the release profile of pure ametryn. When ametryn was associated with the PHB and PHBV microparticles, the amount of herbicide released in the same period of time was significantly reduced, declining to 75% and 87%, respectively. For both types of microparticle (PHB and PHBV) the release of ametryn was by diffusion processes due to anomalous transport (governed by diffusion and relaxation of the polymer chains), which did not follow Fick's laws of diffusion. The results presented in this paper are promising, in view of the successful encapsulation of ametryn in PHB or PHBV polymer microparticles, and indications that this system may help reduce the impacts caused by the herbicide, making it an environmentally safer alternative.

Investigations on ideal mode of cell disruption in extremely halophilic Actinopolyspora halophila (MTCC 263 for efficient release of glycine betaine and trehalose

Directory of Open Access Journals (Sweden)

Jayaranjan R. Kar

2015-03-01

Full Text Available Actinopolyspora halophila produces glycine betaine and trehalose intracellularly in considerable quantities. These biomolecules are commercially important as they have applications in food, pharmaceuticals, and agricultural sector. Development of an efficient cell disruption technique is an important step for the release of these biomolecules. In this study, various cell disruption methods such as chemical, enzymatic, physico-mechanical and physical methods were evaluated. Cell disruption by osmotic shock was found to be the best suited method for A. halophila which also has a potential to be industrially scaled up. Cell bursting pressure that is generated during osmotic shock in A. halophila was computed using Morse equation and was found to be π = 238.37 ± 29.54 atm or 2.35 ± 0.29 kPa. In addition, it was found that osmotic shock followed a first order release rate kinetics in A. halophila. The findings can be used for commercially important biomolecules from other halophilic and/or halotolerant microbes.

Low-debris, efficient laser-produced plasma extreme ultraviolet source by use of a regenerative liquid microjet target containing tin dioxide (SnO2) nanoparticles

Science.gov (United States)

Higashiguchi, Takeshi; Dojyo, Naoto; Hamada, Masaya; Sasaki, Wataru; Kubodera, Shoichi

2006-05-01

We demonstrated a low-debris, efficient laser-produced plasma extreme ultraviolet (EUV) source by use of a regenerative liquid microjet target containing tin-dioxide (SnO2) nanoparticles. By using a low SnO2 concentration (6%) solution and dual laser pulses for the plasma control, we observed the EUV conversion efficiency of 1.2% with undetectable debris.

Low-debris, efficient laser-produced plasma extreme ultraviolet source by use of a regenerative liquid microjet target containing tin dioxide (SnO2) nanoparticles

International Nuclear Information System (INIS)

Higashiguchi, Takeshi; Dojyo, Naoto; Hamada, Masaya; Sasaki, Wataru; Kubodera, Shoichi

2006-01-01

We demonstrated a low-debris, efficient laser-produced plasma extreme ultraviolet (EUV) source by use of a regenerative liquid microjet target containing tin-dioxide (SnO 2 ) nanoparticles. By using a low SnO 2 concentration (6%) solution and dual laser pulses for the plasma control, we observed the EUV conversion efficiency of 1.2% with undetectable debris

Synthesis, characterization, and in vitro release of diclofenac sodium from hybrid nanostructured magnetite–calcium pectinate

International Nuclear Information System (INIS)

Dutta, Raj Kumar; Sahu, Saurabh; Reddy, V. R.

2012-01-01

A stable spherical nanostructured calcium pectinate loaded with diclofenac sodium (DS) and functionalized by superparamagnetic iron oxide nanoparticles, referred as MCPDS, was developed as a potential magnetically targeted drug delivery system. The sizes of the MCPDS were in the range of 100–200 nm in dried condition, confirmed by scanning electron microscopy and transmission electron microscopy. In the aqueous medium, the sizes of MCPDS were in the range 300 ± 50 nm, measured by dynamic light scattering technique. The X-ray diffraction and 57 Fe Mössbauer spectroscopy confirmed magnetite phase in MCPDS. The magnetic property of the MCPDS nanostructures was confirmed from high saturation magnetization (44.05 emu/g), measured using a vibrating sample magnetometer. The superparamagnetic property of MCPDS was characterized by superconducting quantum unit interference device magnetometry and corroborated by Mössbauer spectroscopy. The loading efficiency of DS in MCPDS was measured by UV–Vis spectrophotometry and corroborated by thermal analysis. The in vitro release of the drug from MCPDS in simulated gastrointestinal fluids and in phosphate buffer solution was found to be pH sensitive and exhibited sustained release property. The cumulative drug release agreed well with that of swelling controlled diffusion mechanism, given by the Korsemeyer Peppas model.

Synthesis, characterization, and in vitro release of diclofenac sodium from hybrid nanostructured magnetite-calcium pectinate

Energy Technology Data Exchange (ETDEWEB)

Dutta, Raj Kumar, E-mail: duttafcy@iitr.ernet.in; Sahu, Saurabh, E-mail: saurabhsahu12@gmail.com [Indian Institute of Technology Roorkee, Analytical Chemistry Laboratory, Department of Chemistry (India); Reddy, V. R., E-mail: vrreddy@csr.res.in [UGC-DAE Consortium for Scientific Research (India)

2012-08-15

A stable spherical nanostructured calcium pectinate loaded with diclofenac sodium (DS) and functionalized by superparamagnetic iron oxide nanoparticles, referred as MCPDS, was developed as a potential magnetically targeted drug delivery system. The sizes of the MCPDS were in the range of 100-200 nm in dried condition, confirmed by scanning electron microscopy and transmission electron microscopy. In the aqueous medium, the sizes of MCPDS were in the range 300 {+-} 50 nm, measured by dynamic light scattering technique. The X-ray diffraction and {sup 57}Fe Moessbauer spectroscopy confirmed magnetite phase in MCPDS. The magnetic property of the MCPDS nanostructures was confirmed from high saturation magnetization (44.05 emu/g), measured using a vibrating sample magnetometer. The superparamagnetic property of MCPDS was characterized by superconducting quantum unit interference device magnetometry and corroborated by Moessbauer spectroscopy. The loading efficiency of DS in MCPDS was measured by UV-Vis spectrophotometry and corroborated by thermal analysis. The in vitro release of the drug from MCPDS in simulated gastrointestinal fluids and in phosphate buffer solution was found to be pH sensitive and exhibited sustained release property. The cumulative drug release agreed well with that of swelling controlled diffusion mechanism, given by the Korsemeyer Peppas model.

Synthesis, characterization, and in vitro release of diclofenac sodium from hybrid nanostructured magnetite-calcium pectinate

Science.gov (United States)

Dutta, Raj Kumar; Sahu, Saurabh; Reddy, V. R.

2012-08-01

A stable spherical nanostructured calcium pectinate loaded with diclofenac sodium (DS) and functionalized by superparamagnetic iron oxide nanoparticles, referred as MCPDS, was developed as a potential magnetically targeted drug delivery system. The sizes of the MCPDS were in the range of 100-200 nm in dried condition, confirmed by scanning electron microscopy and transmission electron microscopy. In the aqueous medium, the sizes of MCPDS were in the range 300 ± 50 nm, measured by dynamic light scattering technique. The X-ray diffraction and 57Fe Mössbauer spectroscopy confirmed magnetite phase in MCPDS. The magnetic property of the MCPDS nanostructures was confirmed from high saturation magnetization (44.05 emu/g), measured using a vibrating sample magnetometer. The superparamagnetic property of MCPDS was characterized by superconducting quantum unit interference device magnetometry and corroborated by Mössbauer spectroscopy. The loading efficiency of DS in MCPDS was measured by UV-Vis spectrophotometry and corroborated by thermal analysis. The in vitro release of the drug from MCPDS in simulated gastrointestinal fluids and in phosphate buffer solution was found to be pH sensitive and exhibited sustained release property. The cumulative drug release agreed well with that of swelling controlled diffusion mechanism, given by the Korsemeyer Peppas model.

Dual-controlled release system of drugs for bone regeneration.

Science.gov (United States)

Kim, Yang-Hee; Tabata, Yasuhiko

2015-11-01

Controlled release systems have been noted to allow drugs to enhance their ability for bone regeneration. To this end, various biomaterials have been used as the release carriers of drugs, such as low-molecular-weight drugs, growth factors, and others. The drugs are released from the release carriers in a controlled fashion to maintain their actions for a long time period. Most research has been focused on the controlled release of single drugs to demonstrate the therapeutic feasibility. Controlled release of two combined drugs, so-called dual release systems, are promising and important for tissue regeneration. This is because the tissue regeneration process of bone formation is generally achieved by multiple bioactive molecules, which are produced from cells by other molecules. If two types of bioactive molecules, (i.e., drugs), are supplied in an appropriate fashion, the regeneration process of living bodies will be efficiently promoted. This review focuses on the bone regeneration induced by dual-controlled release of drugs. In this paper, various dual-controlled release systems of drugs aiming at bone regeneration are overviewed explaining the type of drugs and their release materials. Copyright © 2015 Elsevier B.V. All rights reserved.

Kepler Data Release 25 Notes (Q0-Q17)

Science.gov (United States)

Mullally, Susan E.; Caldwell, Douglas A.; Barclay, Thomas Stewart; Barentsen, Geert; Clarke, Bruce Donald; Bryson, Stephen T.; Burke, Christopher James; Campbell, Jennifer Roseanna; Catanzarite, Joseph H.; Christiansen, Jessie;

Emergency response capability for pollutant releases to streams and rivers

International Nuclear Information System (INIS)

Buckner, M.R.; Hayes, D.W.; Watts, J.R.

1975-01-01

Stream-river models have been developed which provide an accurate prediction of normal and accidental pollutant releases to streams and rivers. Stream parameters are being developed for the Savannah River Plant streams and the Savannah River to allow quick response in case of an accidental release of radioactive material. These data are stored on permanent disk storage for quick access via the JOSHUA operating system. This system provides an efficient and flexible emergency response capability for pollutant releases to streams and rivers

Radiation curing of intelligent coating for controlled release and permeation

International Nuclear Information System (INIS)

Nakayama, Hiroshi; Kaetsu, Isao; Uchida, Kumao; Sakata, Shoei; Tougou, Kazuhide; Hara, Takamichi; Matsubara, Yoshio

2002-01-01

Intelligent membranes for pH and temperature-responsive drug releases were developed by coating and curing of polymer-drug composite film with electrolyte or N-isopropyl acrylamide curable mixture. It was proved that those intelligent membranes showed the stimule-sensitive and responsive release functions and could be produced efficiently by radiation curing processing with a conveyer system

Field experiments with subsurface releases of oil and and dyed water

International Nuclear Information System (INIS)

Rye, H.; Brandvik, P.J.; Strom, T.

1998-01-01

A field experiment with a subsurface release of oil and air was carried out in June 1996 close to the Frigg Field in the North Sea area. One of the purposes of this sea trial was to increase the knowledge concerning the behaviour of the oil and gas during a subsurface blowout. This was done by releasing oil and air at 106 meters depth with a realistic gas oil ratio (GOR=67) and release velocity of the oil. In addition to the oil release, several releases with dyed water and gas (GOR=7 - 65) were performed. Important and unique data were collected during these subsurface releases. In particular, the experiments with the dyed water releases combined with air turned out to be an efficient way of obtaining field data for the behaviour of subsurface plumes. The main conclusions from analysis for the data collected are: the field methodology used to study blowout releases in the field appears to be appropriate. The use of dyed water to determine the performance of the subsurface plume proved out to be an efficient way to obtain reliable and useful data. The behaviour of the subsurface plume is very sensitive to gas flow rates. For low gas flow rates, the plume did not reach the sea surface at all due to the presence of stratification in the ambient water. Some discrepancies were found between a numerical model for subsurface releases and field results. These discrepancies are pointed out, and recommendations for possible model improvements are given. (author)

Targeting BRCAness in Gastric Cancer

Science.gov (United States)

2017-10-01

Award Number: W81XWH-16-1-0472 TITLE: Targeting BRCAness in Gastric Cancer PRINCIPAL INVESTIGATOR: Lawrence Fong CONTRACTING ORGANIZATION...Targeting BRCAness in Gastric Cancer 5b. GRANT NUMBER W81XWH-16-1-0473 (Ashworth) 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) Eric Collisson, David Quigley...for Public Release; Distribution Unlimited 13. SUPPLEMENTARY NOTES 14. ABSTRACT We performed the screen of gastric cancer cell lines for their

Mechanical efficiency of the energy release during a steam explosion

International Nuclear Information System (INIS)

Krieg, R.

1997-01-01

The mechanical processes during the expansion phase of a steam explosion with intimately fragmented liquid particles is investigated based on elementary principles and analytical solutions. During a short load pulse, the different densities of the water and the melted particles lead to different velocities. After the load pulse, viscosity effects lead to a slow down of the higher velocities and to a corresponding reconversion of the kinetic energy of the mixture into thermal energy. It is shown that both effects are proportional to each other. The ratio between the residual and the applied mechanical energy is defined as the mechanical efficiency of the steam explosion. Using data typical for a steam explosion in a pressurized water reactor, mechanical efficiencies of <50% are estimated. Considering that the thermodynamic efficiencies are quite limited, the very low conversion rates from thermal energy into mechanical energy observed during steam explosion experiments can be more easily understood

Chemical Characterization and Release Efficiency of Defatted Mustard Meals: 2000-2002

Energy Technology Data Exchange (ETDEWEB)

Morra, M. J.

2005-07-01

Glucosinolates, compounds that occur in agronomically important crops, may represent a viable source of allelochemic control for various soil-borne plant pests. Toxicity is not attributed to intact glucosinolates, but instead to biologically active products such as isothiocyanates (ITCs), organic cyanides, oxazolidinethiones, and ionic thiocyanate (SCN-) released upon enzymatic degradation by myrosinase (thioglucoside glucohydrolase, EC 3.2.3.1) in the presence of water.

Conditional Probability Modulates Visual Search Efficiency

Directory of Open Access Journals (Sweden)

Bryan eCort

2013-10-01

Full Text Available We investigated the effects of probability on visual search. Previous work has shown that people can utilize spatial and sequential probability information to improve target detection. We hypothesized that performance improvements from probability information would extend to the efficiency of visual search. Our task was a simple visual search in which the target was always present among a field of distractors, and could take one of two colors. The absolute probability of the target being either color was 0.5; however, the conditional probability – the likelihood of a particular color given a particular combination of two cues – varied from 0.1 to 0.9. We found that participants searched more efficiently for high conditional probability targets and less efficiently for low conditional probability targets, but only when they were explicitly informed of the probability relationship between cues and target color.

Slow release coating remedy for nitrogen loss from conventional urea: a review.

Science.gov (United States)

Naz, Muhammad Yasin; Sulaiman, Shaharin Anwar

2016-03-10

Developing countries are consuming major part of the global urea production with an anticipated nitrogen use efficiency of 20 to 35%. The release of excess nitrogen in the soil is not only detrimental to the environment but also lessens the efficiency of the conventional urea. The urea performance can be enhanced by encapsulating it with slow release coating materials and synchronizing the nutrients' release with the plant up-taking. However, the present cost of most of the coated fertilizers is considerably higher than the conventional fertilizers. The high cost factor prevents their widespread use in mainstream agriculture. This paper documents a review of literature related to the global urea market, issues pertaining to the conventional urea use, natural and synthetic materials for slow release urea and fluidized bed spray coating process. The aim of the current review is to develop technical understanding of the conventional and non-conventional coating materials and associated spray coating mechanism for slow release urea production. The study also investigated the potential of starch as the coating material in relation to the coatings tested previously for controlled release fertilizers. Copyright © 2016 Elsevier B.V. All rights reserved.

Preparation, characterization, and in vitro release study of albendazole-encapsulated nanosize liposomes

Science.gov (United States)

Panwar, Preety; Pandey, Bhumika; Lakhera, P C; Singh, K P

2010-01-01

The purpose of the present study was to formulate effective and controlled release albendazole liposomal formulations. Albendazole, a hydrophobic drug used for the treatment of hydatid cysts, was encapsulated in nanosize liposomes. Rapid evaporation method was used for the preparation of albendazole-encapsulated conventional and PEGylated liposomes consisting of egg phosphatidylcholine (PC) and cholesterol (CH) in the molar ratios of (6:4) and PC:CH: polyethylene glycol (PEG) (5:4:1), respectively. In this study, PEGylated and conventional liposomes containing albendazole were prepared and their characteristics, such as particle size, encapsulation efficiency, and in vitro drug release were investigated. The drug encapsulation efficiency of PEGylated and conventional liposomes was 81% and 72%, respectively. The biophysical characterization of both conventional and PEG-coated liposomes were done by transmission electron microscopy and UV-vis spectrophotometry. Efforts were made to study in vitro release of albendazole. The drug release rate showed decrease in albendazole release in descending order: free albendazole, albendazole-loaded conventional liposomes, and least with albendazole-loaded PEG-liposomes. Biologically relevant vesicles were prepared and in vitro release of liposome-entrapped albendazole was determined. PMID:20309396

Rhamnogalacturonan-I based microcapsules for targeted drug release

DEFF Research Database (Denmark)

Svagan, Anna J.; Kusic, Anja; De Gobba, Cristian

2016-01-01

Drug targeting to the colon via the oral administration route for local treatment of e.g. inflammatory bowel disease and colonic cancer has several advantages such as needle-free administration and low infection risk. A new source for delivery is plant-polysaccharide based delivery platforms...... such as Rhamnogalacturonan-I (RG-I). In the gastro-intestinal tract the RG-I is only degraded by the action of the colonic microflora. For assessment of potential drug delivery properties, RG-I based microcapsules (~1 μm in diameter) were prepared by an interfacial poly-addition reaction. The cross-linked capsules were...

HSA-based multi-target combination therapy: regulating drugs' release from HSA and overcoming single drug resistance in a breast cancer model.

Science.gov (United States)

Gou, Yi; Zhang, Zhenlei; Li, Dongyang; Zhao, Lei; Cai, Meiling; Sun, Zhewen; Li, Yongping; Zhang, Yao; Khan, Hamid; Sun, Hongbing; Wang, Tao; Liang, Hong; Yang, Feng

2018-11-01

Multi-drug delivery systems, which may be promising solution to overcome obstacles, have limited the clinical success of multi-drug combination therapies to treat cancer. To this end, we used three different anticancer agents, Cu(BpT)Br, NAMI-A, and doxorubicin (DOX), to build human serum albumin (HSA)-based multi-drug delivery systems in a breast cancer model to investigate the therapeutic efficacy of overcoming single drug (DOX) resistance to cancer cells in vivo, and to regulate the drugs' release from HSA. The HSA complex structure revealed that NAMI-A and Cu(BpT)Br bind to the IB and IIA sub-domain of HSA by N-donor residue replacing a leaving group and coordinating to their metal centers, respectively. The MALDI-TOF mass spectra demonstrated that one DOX molecule is conjugated with lysine of HSA by a pH-sensitive linker. Furthermore, the release behavior of three agents form HSA can be regulated at different pH levels. Importantly, in vivo results revealed that the HSA-NAMI-A-Cu(BpT)Br-DOX complex not only increases the targeting ability compared with a combination of the three agents (the NAMI-A/Cu(BpT)Br/DOX mixture), but it also overcomes DOX resistance to drug-resistant breast cancer cell lines.

Lactoferrin modified graphene oxide iron oxide nanocomposite for glioma-targeted drug delivery.

Science.gov (United States)

Song, Meng-Meng; Xu, Huai-Liang; Liang, Jun-Xing; Xiang, Hui-Hui; Liu, Rui; Shen, Yu-Xian

2017-08-01

Targeting delivery of drugs in a specific manner represents a potential powerful technology in gliomas. Herein, we prepared a multifunctional targeted delivery system based on graphene oxide (GO) that contains a molecular bio-targeting ligand and superparamagnetic iron oxide nanoparticles on the surface of GO for magnetic targeting. Superparamagnetic Fe 3 O 4 nanoparticles was loaded on the surface of GO via chemical precipitation method to form GO@Fe 3 O 4 nanocomposites. Lactoferrin (Lf), an iron-transporting serum glycoprotein that binds to receptors overexpressed at the surface of glioma cells and vascular endothelial cell of the blood brain barrier, was chosen as the targeted ligand to construct the targeted delivery system Lf@GO@Fe 3 O 4 through EDC/NHS chemistry. With the confirmation of TEM, DLS and VSM, the resulting Lf@GO@Fe 3 O 4 had a size distribution of 200-1000nm and exhibited a superparamagnetic behavior. The nano delivery system had a high loading capacity and exhibited a pH-dependent release behavior. Compared with free DOX and DOX@GO@Fe 3 O 4 , Lf@GO@Fe 3 O 4 @DOX displayed greater intracellular delivery efficiency and stronger cytotoxicity against C6 glioma cells. The results demonstrated the potential utility of Lf conjugated GO@Fe 3 O 4 nanocomposites for therapeutic application in the treatment of gliomas. Copyright © 2017. Published by Elsevier B.V.

The Impact of Pollution Prevention on Toxic Environmental Releases from U.S. Manufacturing Facilities.

Science.gov (United States)

Ranson, Matthew; Cox, Brendan; Keenan, Cheryl; Teitelbaum, Daniel

2015-11-03

Between 1991 and 2012, the facilities that reported to the U.S. Environmental Protection Agency's Toxic Release Inventory (TRI) Program conducted 370,000 source reduction projects. We use this data set to conduct the first quasi-experimental retrospective evaluation of how implementing a source reduction (pollution prevention) project affects the quantity of toxic chemicals released to the environment by an average industrial facility. We use a differences-in-differences methodology, which measures how implementing a source reduction project affects a facility's releases of targeted chemicals, relative to releases of (a) other untargeted chemicals from the same facility, or (b) the same chemical from other facilities in the same industry. We find that the average source reduction project causes a 9-16% decrease in releases of targeted chemicals in the year of implementation. Source reduction techniques vary in effectiveness: for example, raw material modification causes a large decrease in releases, while inventory control has no detectable effect. Our analysis suggests that in aggregate, the source reduction projects carried out in the U.S. since 1991 have prevented between 5 and 14 billion pounds of toxic releases.

A comparative study of matrix metalloproteinase and aggrecanase mediated release of latent cytokines at arthritic joints.

Science.gov (United States)

Mullen, Lisa; Adams, Gill; Foster, Julie; Vessillier, Sandrine; Köster, Mario; Hauser, Hansjörg; Layward, Lorna; Gould, David; Chernajovsky, Yuti

2014-09-01

Latent cytokines are engineered by fusing the latency associated peptide (LAP) derived from transforming growth factor-β (TGF-β) with the therapeutic cytokine, in this case interferon-β (IFN-β), via an inflammation-specific matrix metalloproteinase (MMP) cleavage site. To demonstrate latency and specific delivery in vivo and to compare therapeutic efficacy of aggrecanase-mediated release of latent IFN-β in arthritic joints to the original MMP-specific release. Recombinant fusion proteins with MMP, aggrecanase or devoid of cleavage site were expressed in CHO cells, purified and characterised in vitro by Western blotting and anti-viral protection assays. Therapeutic efficacy and half-life were assessed in vivo using the mouse collagen-induced arthritis model (CIA) of rheumatoid arthritis and a model of acute paw inflammation, respectively. Transgenic mice with an IFN-regulated luciferase gene were used to assess latency in vivo and targeted delivery to sites of disease. Efficient localised delivery of IFN-β to inflamed paws, with low levels of systemic delivery, was demonstrated in transgenic mice using latent IFN-β. Engineering of latent IFN-β with an aggrecanase-sensitive cleavage site resulted in efficient cleavage by ADAMTS-4, ADAMTS-5 and synovial fluid from arthritic patients, with an extended half-life similar to the MMP-specific molecule and greater therapeutic efficacy in the CIA model. Latent cytokines require cleavage in vivo for therapeutic efficacy, and they are delivered in a dose dependent fashion only to arthritic joints. The aggrecanase-specific cleavage site is a viable alternative to the MMP cleavage site for the targeting of latent cytokines to arthritic joints. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Internal targets for LEAR

International Nuclear Information System (INIS)

Kilian, K.; Gspann, J.; Mohl, D.; Poth, H.

1984-01-01

This chapter considers the use of thin internal targets in conjunction with phase-space cooling at the Low-Energy Antiproton Ring (LEAR). Topics considered include the merits of internal target operation; the most efficient use of antiprotons and of proton synchrotron (PS) protons, highest center-of-mass (c.m.) energy resolution; highest angular resolution and access to extreme angles; the transparent environment for all reaction products; a windowless source and pure targets; highest luminosity and count rates; access to lowest energies with increasing resolution; internal target thickness and vacuum requirements; required cooling performance; and modes of operation. It is demonstrated that an internal target in conjunction with phase-space cooling has the potential of better performance in terms of the economic use of antiprotons and consequently of PS protons; energy resolution; angular resolution; maximum reaction rate capability (statistical precision); efficient parasitic operation; transparency of the target for reaction products; access to low energies; and the ease of polarized target experiments. It is concluded that all p - experiments which need high statistics and high p - flux, such as studies of rare channels or broad, weak resonance structures, would profit from internal targets

Cargo Release from Polymeric Vesicles under Shear

Directory of Open Access Journals (Sweden)

Yingying Guo

2018-03-01

Full Text Available In this paper we study the release of cargo from polymeric nano-carriers under shear. Vesicles formed by two star block polymers— A 12 B 6 C 2 ( A B C and A 12 B 6 A 2 ( A B A —and one linear block copolymer— A 14 B 6 ( A B , are investigated using dissipative particle dynamics (DPD simulations. A - and C -blocks are solvophobic and B -block is solvophilic. The three polymers form vesicles of different structures. The vesicles are subjected to shear both in bulk and between solvophobic walls. In bulk shear, the mechanisms of cargo release are similar for all vesicles, with cargo travelling through vesicle membrane with no preferential release location. When sheared between walls, high cargo release rate is only observed with A B C vesicle after it touches the wall. For A B C vesicle, the critical condition for high cargo release rate is the formation of wall-polymersome interface after which the effect of shear rate in promoting cargo release is secondary. High release rate is achieved by the formation of solvophilic pathway allowing cargo to travel from the vesicle cavity to the vesicle exterior. The results in this paper show that well controlled target cargo release using polymersomes can be achieved with polymers of suitable design and can potentially be very useful for engineering applications. As an example, polymersomes can be used as carriers for surface active friction reducing additives which are only released at rubbing surfaces where the additives are needed most.

An efficient enzyme-powered micromotor device fabricated by cyclic alternate hybridization assembly for DNA detection.

Science.gov (United States)

Fu, Shizhe; Zhang, Xueqing; Xie, Yuzhe; Wu, Jie; Ju, Huangxian

2017-07-06

An efficient enzyme-powered micromotor device was fabricated by assembling multiple layers of catalase on the inner surface of a poly(3,4-ethylenedioxythiophene and sodium 4-styrenesulfonate)/Au microtube (PEDOT-PSS/Au). The catalase assembly was achieved by programmed DNA hybridization, which was performed by immobilizing a designed sandwich DNA structure as the sensing unit on the PEDOT-PSS/Au, and then alternately hybridizing with two assisting DNA to bind the enzyme for efficient motor motion. The micromotor device showed unique features of good reproducibility, stability and motion performance. Under optimal conditions, it showed a speed of 420 μm s -1 in 2% H 2 O 2 and even 51 μm s -1 in 0.25% H 2 O 2 . In the presence of target DNA, the sensing unit hybridized with target DNA to release the multi-layer DNA as well as the multi-catalase, resulting in a decrease of the motion speed. By using the speed as a signal, the micromotor device could detect DNA from 10 nM to 1 μM. The proposed micromotor device along with the cyclic alternate DNA hybridization assembly technique provided a new path to fabricate efficient and versatile micromotors, which would be an exceptional tool for rapid and simple detection of biomolecules.

psRNATarget: a plant small RNA target analysis server (2017 release).

Science.gov (United States)

Dai, Xinbin; Zhuang, Zhaohong; Zhao, Patrick Xuechun

2018-04-30

Plant regulatory small RNAs (sRNAs), which include most microRNAs (miRNAs) and a subset of small interfering RNAs (siRNAs), such as the phased siRNAs (phasiRNAs), play important roles in regulating gene expression. Although generated from genetically distinct biogenesis pathways, these regulatory sRNAs share the same mechanisms for post-translational gene silencing and translational inhibition. psRNATarget was developed to identify plant sRNA targets by (i) analyzing complementary matching between the sRNA sequence and target mRNA sequence using a predefined scoring schema and (ii) by evaluating target site accessibility. This update enhances its analytical performance by developing a new scoring schema that is capable of discovering miRNA-mRNA interactions at higher 'recall rates' without significantly increasing total prediction output. The scoring procedure is customizable for the users to search both canonical and non-canonical targets. This update also enables transmitting and analyzing 'big' data empowered by (a) the implementation of multi-threading chunked file uploading, which can be paused and resumed, using HTML5 APIs and (b) the allocation of significantly more computing nodes to its back-end Linux cluster. The updated psRNATarget server has clear, compelling and user-friendly interfaces that enhance user experiences and present data clearly and concisely. The psRNATarget is freely available at http://plantgrn.noble.org/psRNATarget/.

Listeners Experience Linguistic Masking Release in Noise-Vocoded Speech-in-Speech Recognition

Science.gov (United States)

Viswanathan, Navin; Kokkinakis, Kostas; Williams, Brittany T.

2018-01-01

Purpose: The purpose of this study was to evaluate whether listeners with normal hearing perceiving noise-vocoded speech-in-speech demonstrate better intelligibility of target speech when the background speech was mismatched in language (linguistic release from masking [LRM]) and/or location (spatial release from masking [SRM]) relative to the…