Design a 10 kJ IS Mather Type Plasma Focus for Solid Target Activation to Produce Short-Lived Radioisotopes 12C(d,n)13N

NASA Astrophysics Data System (ADS)

Sadat Kiai, S. M.; Adlparvar, S.; Sheibani, S.; Elahi, M.; Safarien, A.; Farhangi, S.; Zirak, A. R.; Alhooie, S.; Mortazavi, B. N.; Khalaj, M. M.; Khanchi, A. R.; Dabirzadeh, A. A.; Kashani, A.; Zahedi, F.

2010-10-01

A 10 kJ (15 kV, 88 μF) IS (Iranian Sun) Mather type plasma focus device has been studied to determine the activity of a compound exogenous carbon solid target through 12C(d,n)13N nuclear reaction. The produced 13N is a short-lived radioisotope with a half-life of 9.97 min and threshold energy of 0.28 MeV. The results indicate that energetic deuterons impinging on the solid target can produce yield of = 6.7 × 10-5 with an activity of A = 6.8 × 104 Bq for one plasma focus shut and A ν = 4 × 105 Bq for 6 shut per mint when the projectile maximum deuterons energy is E max = 3 MeV.

The Effects of Workload Presented via Visual and Auditory Displays on Soldier Shooting and Secondary Task Performance

DTIC Science & Technology

2007-08-01

Cognitive Psychology: New Directions (pp. 112-153). London: Routledge & Kegan Paul, 1980. Allport, D. A.; Antonis, B.; Reynolds, P. On the Division of...live-fire range. The target type presentations will be an enemy targets which will consist of equal sized solid green silhouettes. Friendly targets...will consist of the solid green silhouette with a gray 6-inch disk at the center-of-mass, or a solid brown silhouette. The target exposure times will

Evaluation of Total Dissolved Solids and Specific Conductance Water Quality Targets with Paired Single-Species and Mesocosm Community Exposures

EPA Science Inventory

Isolated single-species exposures were conducted in parallel with 42 d mesocosm dosing studies that measured in-situ and whole community responses to different recipes of excess total dissolved solids (TDS). The studies were conducted with cultured species and native taxa from mo...

Surface Functionalization and Targeting Strategies of Liposomes in Solid Tumor Therapy: A Review

PubMed Central

Riaz, Muhammad Kashif; Riaz, Muhammad Adil; Zhang, Xue; Lin, Congcong; Wong, Ka Hong; Chen, Xiaoyu; Lu, Aiping

2018-01-01

Surface functionalization of liposomes can play a key role in overcoming the current limitations of nanocarriers to treat solid tumors, i.e., biological barriers and physiological factors. The phospholipid vesicles (liposomes) containing anticancer agents produce fewer side effects than non-liposomal anticancer formulations, and can effectively target the solid tumors. This article reviews information about the strategies for targeting of liposomes to solid tumors along with the possible targets in cancer cells, i.e., extracellular and intracellular targets and targets in tumor microenvironment or vasculature. Targeting ligands for functionalization of liposomes with relevant surface engineering techniques have been described. Stimuli strategies for enhanced delivery of anticancer agents at requisite location using stimuli-responsive functionalized liposomes have been discussed. Recent approaches for enhanced delivery of anticancer agents at tumor site with relevant surface functionalization techniques have been reviewed. Finally, current challenges of functionalized liposomes and future perspective of smart functionalized liposomes have been discussed. PMID:29315231

Nanoparticle-blood interactions: the implications on solid tumour targeting.

PubMed

Lazarovits, James; Chen, Yih Yang; Sykes, Edward A; Chan, Warren C W

2015-02-18

Nanoparticles are suitable platforms for cancer targeting and diagnostic applications. Typically, less than 10% of all systemically administered nanoparticles accumulate in the tumour. Here we explore the interactions of blood components with nanoparticles and describe how these interactions influence solid tumour targeting. In the blood, serum proteins adsorb onto nanoparticles to form a protein corona in a manner dependent on nanoparticle physicochemical properties. These serum proteins can block nanoparticle tumour targeting ligands from binding to tumour cell receptors. Additionally, serum proteins can also encourage nanoparticle uptake by macrophages, which decreases nanoparticle availability in the blood and limits tumour accumulation. The formation of this protein corona will also increase the nanoparticle hydrodynamic size or induce aggregation, which makes nanoparticles too large to enter into the tumour through pores of the leaky vessels, and prevents their deep penetration into tumours for cell targeting. Recent studies have focused on developing new chemical strategies to reduce or eliminate serum protein adsorption, and rescue the targeting potential of nanoparticles to tumour cells. An in-depth and complete understanding of nanoparticle-blood interactions is key to designing nanoparticles with optimal physicochemical properties with high tumour accumulation. The purpose of this review article is to describe how the protein corona alters the targeting of nanoparticles to solid tumours and explains current solutions to solve this problem.

The comparison of fossil carbon fraction and greenhouse gas emissions through an analysis of exhaust gases from urban solid waste incineration facilities.

PubMed

Kim, Seungjin; Kang, Seongmin; Lee, Jeongwoo; Lee, Seehyung; Kim, Ki-Hyun; Jeon, Eui-Chan

2016-10-01

In this study, in order to understand accurate calculation of greenhouse gas emissions of urban solid waste incineration facilities, which are major waste incineration facilities, and problems likely to occur at this time, emissions were calculated by classifying calculation methods into 3 types. For the comparison of calculation methods, the waste characteristics ratio, dry substance content by waste characteristics, carbon content in dry substance, and (12)C content were analyzed; and in particular, CO2 concentration in incineration gases and (12)C content were analyzed together. In this study, 3 types of calculation methods were made through the assay value, and by using each calculation method, emissions of urban solid waste incineration facilities were calculated then compared. As a result of comparison, with Calculation Method A, which used the default value as presented in the IPCC guidelines, greenhouse gas emissions were calculated for the urban solid waste incineration facilities A and B at 244.43 ton CO2/day and 322.09 ton CO2/day, respectively. Hence, it showed a lot of difference from Calculation Methods B and C, which used the assay value of this study. It is determined that this was because the default value as presented in IPCC, as the world average value, could not reflect the characteristics of urban solid waste incineration facilities. Calculation Method B indicated 163.31 ton CO2/day and 230.34 ton CO2/day respectively for the urban solid waste incineration facilities A and B; also, Calculation Method C indicated 151.79 ton CO2/day and 218.99 ton CO2/day, respectively. This study intends to compare greenhouse gas emissions calculated using (12)C content default value provided by the IPCC (Intergovernmental Panel on Climate Change) with greenhouse gas emissions calculated using (12)C content and waste assay value that can reflect the characteristics of the target urban solid waste incineration facilities. Also, the concentration and (12)C content were calculated by directly collecting incineration gases of the target urban solid waste incineration facilities, and greenhouse gas emissions of the target urban solid waste incineration facilities through this survey were compared with greenhouse gas emissions, which used the previously calculated assay value of solid waste.

Targeting doxorubicin encapsulated in stealth liposomes to solid tumors by non thermal diode laser.

PubMed

Ghannam, Magdy M; El Gebaly, Reem; Fadel, Maha

2016-04-05

The use of liposomes as drug delivery systems is the most promising technique for targeting drug especially for anticancer therapy. In this study sterically stabilized liposomes was prepared from DPPC/Cholesterol/PEG-PE encapsulated doxorubicin. The effect of lyophilization on liposomal stability and hence expiration date were studied. Moreover, the effect of diode laser on the drug released from liposomesin vitro and in vivo in mice carrying implanted solid tumor were also studied. The results indicated that lyophilization of the prepared liposomes encapsulating doxorubicin led to marked stability when stored at 5 °C and it is possible to use the re-hydrated lyophilized liposomes within 12 days post reconstitution. Moreover, the use of low energy diode laser for targeting anticancer drug to the tumor cells is a promising method in cancer therapy. We can conclude that lyophilization of the liposomes encapsulating doxorubicin lead to marked stability for the liposomes when stored at 5 °C. Moreover, the use of low energy diode laser for targeting anticancer drug to the tumor cells through the use of photosensitive sterically stabilized liposomes loaded with doxorubicin is a promising method. It proved to be applicable and successful for treatment of Ehrlich solid tumors implanted in mice and eliminated toxic side effects of doxorubicin.

Applications of beam-foil spectroscopy to atomic collisions in solids

NASA Technical Reports Server (NTRS)

Sellin, I. A.

1976-01-01

Some selected papers presented at the Fourth International Conference on Beam-Foil Spectroscopy, whose results are of particular pertinence to ionic collision phenomena in solids, are reviewed. The topics discussed include solid target effects and means of surmounting them in the measurement of excited projectile ion lifetimes for low-energy heavy element ions; the electron emission accompanying the passage of heavy particles through solid targets; the collision broadening of X rays emitted from 100 keV ions moving in solids; residual K-shell excitation in chlorine ions penetrating carbon; comparison between 40 MeV Si on gaseous SiH4 targets at 300 mtorr and 40 MeV Si on Al; and the emergent surface interaction in beam-foil spectroscopy. A distinct overlap of interests between the sciences of beam-foil spectroscopy and atomic collisions in solids is pointed out.

Alpha-particle radiotherapy: For large solid tumors diffusion trumps targeting.

PubMed

Zhu, Charles; Sempkowski, Michelle; Holleran, Timothy; Linz, Thomas; Bertalan, Thomas; Josefsson, Anders; Bruchertseifer, Frank; Morgenstern, Alfred; Sofou, Stavroula

2017-06-01

Diffusion limitations on the penetration of nanocarriers in solid tumors hamper their therapeutic use when labeled with α-particle emitters. This is mostly due to the α-particles' relatively short range (≤100 μm) resulting in partial tumor irradiation and limited killing. To utilize the high therapeutic potential of α-particles against solid tumors, we designed non-targeted, non-internalizing nanometer-sized tunable carriers (pH-tunable liposomes) that are triggered to release, within the slightly acidic tumor interstitium, highly-diffusive forms of the encapsulated α-particle generator Actinium-225 ( 225 Ac) resulting in more homogeneous distributions of the α-particle emitters, improving uniformity in tumor irradiation and increasing killing efficacies. On large multicellular spheroids (400 μm-in-diameter), used as surrogates of the avascular areas of solid tumors, interstitially-releasing liposomes resulted in best growth control independent of HER2 expression followed in performance by (a) the HER2-targeting radiolabeled antibody or (b) the non-responsive liposomes. In an orthotopic human HER2-negative mouse model, interstitially-releasing 225 Ac-loaded liposomes resulted in the longest overall and median survival. This study demonstrates the therapeutic potential of a general strategy to bypass the diffusion-limited transport of radionuclide carriers in solid tumors enabling interstitial release from non-internalizing nanocarriers of highly-diffusing and deeper tumor-penetrating molecular forms of α-particle emitters, independent of cell-targeting. Copyright © 2017 Elsevier Ltd. All rights reserved.

Recovery of uranium from an irradiated solid target after removal of molybdenum-99 produced from the irradiated target

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

Reilly, Sean Douglas; May, Iain; Copping, Roy

A process for minimizing waste and maximizing utilization of uranium involves recovering uranium from an irradiated solid target after separating the medical isotope product, molybdenum-99, produced from the irradiated target. The process includes irradiating a solid target comprising uranium to produce fission products comprising molybdenum-99, and thereafter dissolving the target and conditioning the solution to prepare an aqueous nitric acid solution containing irradiated uranium. The acidic solution is then contacted with a solid sorbent whereby molybdenum-99 remains adsorbed to the sorbent for subsequent recovery. The uranium passes through the sorbent. The concentrations of acid and uranium are then adjusted tomore » concentrations suitable for crystallization of uranyl nitrate hydrates. After inducing the crystallization, the uranyl nitrate hydrates are separated from a supernatant. The process results in the purification of uranyl nitrate hydrates from fission products and other contaminants. The uranium is therefore available for reuse, storage, or disposal.« less

Improvement of Characteristics of Laser Source of Ions Using Two-Element Targets

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

Khaydarov, R. T.

2006-12-04

Two-element plasma ions generated from porous (Ho2O3) and solid (PbMg) targets were studied depending on the target density {rho} and on the fraction of light (Mg) component of the target, using a mass-spectrometer. Oxygen ions with maximal charge is observed for small values of {rho}, while the heavy component of the target Ho has maximal charge for larger values of {rho}. The influence of {rho} to the energy spectra and intensity of plasma ions is also investigated. In the case of solid (PbMg) target the increase of the fraction of Mg leads to the widening of the energy spectra ofmore » Pb ions by more than a factor of two, while the intensity of Pb ions of all charge states does not depend on the Mg fraction. These effects are explained by the friction existing between light and heavy ions during their expansion away from the target.« less

A target development program for beamhole spallation neutron sources in the megawatt range

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

Bauer, G.S.; Atchison, F.

1995-10-01

Spallation sources as an alternative to fission neutron sources have been operating successfully up to 160 kW of beam power. With the next generation of these facilities aiming at the medium power range between 0.5 and 5 MW, loads on the targets will be high enough to make present experience of little relevance. With the 0.6 MW continuous facility SINQ under construction, and a 5 MW pulsed facility (ESS) under study in Europe, a research and development program is about to be started which aimes at assessing the limits of stationary and moving solid targets and the feasibility and potentialmore » benefits of flowing liquid metal targets. Apart from theoretical work and examination of existing irradiated material, including used targets from ISIS, it is intended to take advantage of the SINQ solid rod target design to improve the relevant data base by building the target in such a way that individual rods can be equipped as irradiation capsules.« less

Laser plasma cryogenic target on translating substrate for generation of continuously repetitive EUV and soft X-ray pulses

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

Amano, Sho

2014-06-15

To generate continuously repetitive EUV and soft X-ray pulses with various wavelengths from laser-produced plasmas, a one-dimensionally translating substrate system with a closed He gas cryostat that can continuously supply various cryogenic targets for ∼10 Hz laser pulses has been developed. The system was successfully operated at a lowest temperature of 15 K and at a maximum up-down speed of 12 mm/s. Solid Ar, Kr, and Xe layers were formed, and their growth rates and the laser crater sizes on them were studied. By optimization of the operational parameters in accordance with our design rule, it was shown that stablemore » output power was achieved continuously from the plasma emission at frequencies of 1–10 Hz. The average soft X-ray and EUV powers obtained were 19 mW at 3.2 nm, 33 mW at 10.0 nm, and 66 mW at 10.8 nm, with 10% bandwidths, from the Ar, Kr, and Xe solid targets, respectively, with a laser power of 1 W. We will be able to achieve higher frequencies using a high beam quality laser that produces smaller craters, and can expect higher powers. Although only Ar, Kr, and Xe gases were tested in this study, the target system achieved a temperature of 15 K and can thus solidify almost all target gases, apart from H and He, and can continuously supply the solid target. The use of various target materials will enable expansion of the EUV and soft X-ray emission wavelength range.« less

Review of hydrodynamic tunneling issues in high power particle accelerators

NASA Astrophysics Data System (ADS)

Tahir, N. A.; Burkart, F.; Schmidt, R.; Shutov, A.; Piriz, A. R.

2018-07-01

Full impact of one Large Hadron Collider (LHC) 7 TeV proton beam on solid targets made of different materials including copper and carbon, was simulated using an energy deposition code, FLUKA and a two-dimensional hydrodynamic code, BIG2, iteratively. These studies showed that the penetration depth of the entire beam comprised of 2808 proton bunches significantly increases due to a phenomenon named hydrodynamic tunneling of the protons and the shower. For example, the static range of a single 7 TeV proton and its shower is about 1 m in solid copper, but the full LHC beam will penetrate up to about 35 m in the target, if the hydrodynamic effects were included. Due to the potential implications of this result on the machine protection considerations, it was decided to have an experimental verification of the hydrodynamic tunneling effect. For this purpose, experiments were carried out at the CERN HiRadMat (High Radiation to Materials) facility in which extended solid copper cylindrical targets were irradiated with the 440 GeV proton beam generated by the Super Proton Synchrotron (SPS). Simulations of beam-target heating considering the same beam parameters that were used in the experiments, were also performed. These experiments not only confirmed the existence of the hydrodynamic tunneling, but the experimental measurements showed very good agreement with the experimental results as well. This provided confidence in the work on LHC related beam-matter heating simulations. Currently, a design study is being carried out by the international community (with CERN taking the leading role) for a post LHC collider named, the Future Circular Collider (FCC) which will accelerate two counter rotating proton beams up to a particle energy of 50 TeV. Simulations of the full impact of one FCC beam comprised of 10,600 proton bunches with a solid copper target have also been done. These simulations have shown that although the static range of a single 50 TeV proton and its shower in solid copper is around 1.8 m, the entire beam will penetrate up to about 350 m in the target. Feasibility studies of developing a water beam dump for the FCC have also been carried out. A review of this work and its implications on machine protection system are presented in this paper.

A Laboratory Impact Study of Simulated Edgeworth-Kuiper Belt Objects

NASA Astrophysics Data System (ADS)

Ryan, Eileen V.; Davis, Donald R.; Giblin, Ian

1999-11-01

This paper reports on a series of laboratory impact experiments designed to provide basic data on how simulated Edgeworth-Kuiper belt objects (EKOs) fragment in an impact event. In September-October 1997 we carried out 20 low-velocity airgun shots at the Ames Vertical Gun Range into porous and homogeneous ice spheres using aluminum, fractured ice, and solid ice projectiles. We found that the porous ice targets behaved as strongly as solid ice in collision. Energy is apparently well dissipated by the void spaces within the target, such that these fragile ice structures respond as if they were strong in impacts. Therefore, it would appear that if EKOs are porous, they are not collisionally weak. Also, our data show that collisional outcomes for low-velocity impacts into ice targets depend on the type of projectile used as well as the properties of the target. We observed that the degree of fragmentation for a given type of target increases as the strength of the projectile increases. Aluminum projectiles are far more damaging to the target at the same collisional energy than are solid ice projectiles, which, in turn, are more damaging than fractured ice projectiles. One possible explanation for this behavior is the variable depth of penetration of the projectile for the different cases—stronger projectiles penetrate more deeply and couple more energy into the target than do weak projectiles. Based on this, if we assume that there has not been significant heating or differentiation in the Edgeworth-Kuiper (E-K) belt, the most applicable impact strength for the low-velocity E-K belt collisions is likely to be that derived from similar target/projectile materials impacting each other. The laboratory data from this analysis indicate that a value for impact strength>5×10 5 erg/cm 3 is appropriate for porous ice targets impacted with solid/porous ice projectiles.

Affinity-tuned ErbB2 or EGFR chimeric antigen receptor T cells exhibit an increased therapeutic index against tumors in mice

PubMed Central

Liu, Xiaojun; Jiang, Shuguang; Fang, Chongyun; Yang, Shiyu; Olalere, Devvora; Pequignot, Edward C.; Cogdill, Alexandria P.; Li, Na; Ramones, Melissa; Granda, Brian; Zhou, Li; Loew, Andreas; Young, Regina M.; June, Carl H.; Zhao, Yangbing

2015-01-01

Target-mediated toxicity is a major limitation in the development of chimeric antigen T cell receptors (CAR) for adoptive cell therapy of solid tumors. In this study, we developed a strategy to adjust the affinities of the scFv component of CAR to discriminate tumors overexpressing the target from normal tissues which express it at physiologic levels. A CAR-expressing T cell panel was generated with target antigen affinities varying over three orders of magnitude. High-affinity cells recognized target expressed at any level, including at levels in normal cells that were undetectable by flow cytometry. Affinity-tuned cells exhibited robust antitumor efficacy similar to high-affinity cells, but spared normal cells expressing physiologic target levels. The use of affinity-tuned scFvs offers a strategy to empower wider use of CAR T cells against validated targets widely overexpressed on solid tumors, including those considered undruggable by this approach. PMID:26330166

Advances in large, transportable, highly spin-polarized, solid HD targets operable in the frozen-spin mode in a 1-4K temperature environment

NASA Astrophysics Data System (ADS)

Lewis, Aaron Paul

The development of large, portable highly spin-polarized solid HD targets has been in progress at Syracuse University for the past 5 years. These targets are scheduled for deployment at Brookhaven National Laboratory, bearing the acronym SPHICE (Spin-Polarized Hydrogen Ice), for studies of the electro-magnetic spin structure of the nucleus via scattering of polarized gammas from the HD polarized protons and deuterons. The target work has just reached the milestone demonstration of the complete system, including polarization of triple targets containing 4 moles of solid HD, aging of these targets so that they retain their polarization for months under storage at a temperature of 1.3K and in an 8 Tesla field, and for at least a week at operational conditions of 1.3K and 0.7 Tesla in an in-beam cryostat. Cold-transfers of the polarized targets to a storage cryostat have been successfully carried out, and the storage cryostat has been trucked from Syracuse to BNL with one polarized target, sufficient to test the in-beam operations there. The complete system is presented here, with emphasis on innovations for engagement and disengagement of multiple targets, a solution to the challenge of attaining sufficiently strong RF fields in the large volume probe coils at acceptable power dissipation in the cables, and the polarization production and monitoring in the highly inhomogeneous magnetic fields owing to the multiple targets and the large dimensions of the targets. In this first multiple target production and extraction-to-storage cycle, air-ice accumulation in the dilution refrigerator due to repetitive use of cold sliding o-ring seals resulted in a rupture of one of the inserted targets, and a consequent partial thermal short from a solid HD ice bridge. The o-ring fault was cured with double evacuatable o-ring seals, and the air-ice was successfully cleaned out. However, the refrigerator operating base temperature was substantially higher than that normally obtained and the proton polarizations were accordingly lower than the 48% previously obtained. Nevertheless, the targets passed all their production procedures and are still useful for a first experiment at BNL. We anticipate an era of important use of these now demonstrated specially advantageous polarized frozen-spin HD targets.

Fusion genes in solid tumors: an emerging target for cancer diagnosis and treatment.

PubMed

Parker, Brittany C; Zhang, Wei

2013-11-01

Studies over the past decades have uncovered fusion genes, a class of oncogenes that provide immense diagnostic and therapeutic advantages because of their tumor-specific expression. Originally associated with hemotologic cancers, fusion genes have recently been discovered in a wide array of solid tumors, including sarcomas, carcinomas, and tumors of the central nervous system. Fusion genes are attractive as both therapeutic targets and diagnostic tools due to their inherent expression in tumor tissue alone. Therefore, the discovery and elucidation of fusion genes in various cancer types may provide more effective therapies in the future for cancer patients.

Thin-thick hydrogen target for nuclear physics

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

Gheller, J.-M.; Juster, F.-P.; Authelet, G.

In spectroscopic studies of unstable nuclei, hydrogen targets are of key importance. The CHyMENE Project aims to provide to the nuclear physics community a thin and pure solid windowless hydrogen or deuterium target. CHyMENE project must respond to this request for the production of solid Hydrogen. The solid hydrogen target is produced in a continuous flow (1 cm/s) by an extrusion technique (developed with the PELIN laboratory) in a vacuum chamber. The shape of the target is determined by the design of the nozzle at the extrusion process. For the purpose, the choice is a rectangular shape with a widthmore » of 10 mm and a thickness in the range of 30-50 microns necessary for the physics objectives. The cryostat is equipped with a GM Cryocooler with sufficient power for the solidification of the hydrogen in the lower portion of the extruder. In the higher part of the cryostat, the hydrogen gas is first liquefied and partially solidified. It is then compressed at 100 bars in the cooled extruder before expulsion of the film through the nozzle at the center of the reaction vacuum chamber. After the previous step, the solid hydrogen ribbon falls by gravity into a dedicated chamber where it sublimes and the gas is pumped and evacuated in a exhaust line. This paper deals with the design of the cryostat with its equipment, with the sizing of the thermal bridge (Aluminum and copper), with the results regarding the contact resistance as well as with the vacuum computations of the reaction and recovery hydrogen gas chambers.« less

Effect of target composition on proton acceleration in ultraintense laser-thin foil interaction

NASA Astrophysics Data System (ADS)

Liu, Qingcao; Liu, Meng; Yu, Tongpu; Ding, Pengji; Liu, Zuoye; Sun, Shaohua; Liu, Xiaoliang; Lu, Xing; Guo, Zeqin; Hu, Bitao

2012-09-01

The interactions of ultraintense circularly polarized laser pulses with a mixed solid target and a double-layer target are studied by two-dimensional particle-in-cell simulations. Different carbon and proton compositions in the targets are used in the simulations. It is shown that the proton acceleration mechanisms in both targets are very sensitive to the ion density ratios between protons and carbon ions. For a mixed solid target, a relatively low proton density gives rise to monoenergetic peaks in the proton energy spectrum while a high proton density leads to a large cut-off energy and wide energy spread. With the increase of the ratio, the so-called directed-Coulomb-explosion becomes dominated over the radiation pressure. Surprisingly, for a double-layer target with a front proton layer and an ultrathin rear carbon layer, a highly monoenergetic proton beam with a peak energy of 1.7 GeV/u, an energy spread of ˜4%, and a divergency angle of 2° can be obtained, which might have diverse applications in medical therepy and proton imaging in future.

The future of epigenetic therapy in solid tumours--lessons from the past.

PubMed

Azad, Nilofer; Zahnow, Cynthia A; Rudin, Charles M; Baylin, Stephen B

2013-05-01

The promise of targeting epigenetic abnormalities for cancer therapy has not been realized for solid tumours, although increasing evidence is demonstrating its worth in haematological malignancies. In fact, true clinical efficacy in haematopoietic-related neoplasms has only become evident at low doses of epigenetic-targeting drugs (namely, inhibitors of histone deacetylase and DNA methyltransferases). Describing data from preclinical studies and early clinical trial results, we hypothesize that in using low-dose epigenetic-modulating agents, tumour cells can be reprogrammed, which overrides any immediate cytotoxic and off-target effect observed at high dose. We suggest that such optimization of drug dosing and scheduling of currently available agents could give these agents a prominent place in cancer management--when used alone or in combination with other therapies. If so, optimal use of these known agents might also pave the way for the introduction of other agents that target the epigenome.

LLE Review Quarterly Report (October - December 2007). Volume 113

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

Zuegel, Jonathan D.

2007-12-01

This volume of the LLE Review, covering October–December 2007, features “High-Intensity Laser–Plasma Interactions in the Refluxing Limit,” by P. M. Nilson, W. Theobald, J. Myatt, C. Stoeckl, M. Storm, O. V. Gotchev, J. D. Zuegel, R. Betti, D. D. Meyerhofer, and T. C. Sangster. In this article (p. 1), the authors report on target experiments using the Multi-Terawatt (MTW) Laser Facility to study isochoric heating of solid-density targets by fast electrons produced from intense, short-pulse laser irradiation. Electron refluxing occurs due to target-sheath field effects and contains most of the fast electrons within the target volume. This efficiently heats themore » solid-density plasma through collisions. X-ray spectroscopic measurements of absolute K α (x-radiation) photon yields and variations of the K β/K α b emission ratio both indicate that laser energy couples to fast electrons with a conversion efficiency of approximately 20%. Bulk electron temperatures of at least 200 eV are inferred for the smallest mass targets.« less

Multiple-collision analysis of characteristic X-rays from low-energy Ar 2+ travelling in solid targets

NASA Astrophysics Data System (ADS)

Cipolla, Sam J.; Mildebrath, Mark E.

1983-12-01

The density of atoms in a solid target fosters a multiple-collision mechanism that leads to the production of an equilibrium fraction of L-shell vacancies in an incident heavy ion. It is then possiblein a subsequent ion-atom collision in the solid for an L-vacancy to be transferred to the K-shell of a target atom via rotational coupling of the 2p π-2p σ molecular orbitals formed in the ion-atom quasimolecule. The vacancy-transfer cross section and the equilibrium fraction and lifetime of the vacancies can be found by using an appropriate multiple-collision analysis of the characteristic target and projectile X-rays. Results will be presented for 160-380 keV Ar 2+ incident of targets of Mg, Al, and Si.

Study of transport of laser-driven relativistic electrons in solid materials

NASA Astrophysics Data System (ADS)

Leblanc, Philippe

With the ultra intense lasers available today, it is possible to generate very hot electron beams in solid density materials. These intense laser-matter interactions result in many applications which include the generation of ultrashort secondary sources of particles and radiation such as ions, neutrons, positrons, x-rays, or even laser-driven hadron therapy. For these applications to become reality, a comprehensive understanding of laser-driven energy transport including hot electron generation through the various mechanisms of ionization, and their subsequent transport in solid density media is required. This study will focus on the characterization of electron transport effects in solid density targets using the state-of- the-art particle-in-cell code PICLS. A number of simulation results will be presented on the topics of ionization propagation in insulator glass targets, non-equilibrium ionization modeling featuring electron impact ionization, and electron beam guiding by the self-generated resistive magnetic field. An empirically derived scaling relation for the resistive magnetic in terms of the laser parameters and material properties is presented and used to derive a guiding condition. This condition may prove useful for the design of future laser-matter interaction experiments.

Ease of opening of blistered solid dosage forms in a senior citizens target group.

PubMed

Braun-Münker, Myriam; Ecker, Felix

2016-10-30

Blisters differing in design and handling are established as packaging material for solid dosage forms. The ease of opening of blisters influences application and patient's compliance. In this study the influence of visibility and movability of solid dosage forms in blister packaging on both, easy opening and patient's satisfaction, were investigated by target group testing according to ONR CEN/TS 15945. For each testing 20 participants in the age of 65-80 years were recruited randomly. They opened the blisters on realistic terms without any auxiliary devices. Video documentation of the hands' movements was recorded to analyze the opening procedure. To show the influence of visibility of the dosage form in the blister, capsules size 1 were packed in transparent and opaque blisters. A moderate influence of the visibility on both, the ease of opening and patient satisfaction, was observed. A second study dealt with the movability of solid dosage forms in blisters. Therefore, three different sizes of tablets with similar shapes were packed in identical cavities. Limited movability was found as major criterion on effectiveness and effectivity of opening as well as on satisfaction with the opening procedure. Copyright © 2015 Elsevier B.V. All rights reserved.

Long-term effects of inhaled budesonide on screening-detected lung nodules

PubMed Central

Veronesi, G.; Lazzeroni, M.; Szabo, E.; Brown, P. H.; DeCensi, A.; Guerrieri-Gonzaga, A.; Bellomi, M.; Radice, D.; Grimaldi, M. C.; Spaggiari, L.; Bonanni, B.

2015-01-01

Background A previously carried out randomized phase IIb, placebo-controlled trial of 1 year of inhaled budesonide, which was nested in a lung cancer screening study, showed that non-solid and partially solid lung nodules detected by low-dose computed tomography (LDCT), and not immediately suspicious for lung cancer, tended to regress. Because some of these nodules may be slow-growing adenocarcinoma precursors, we evaluated long-term outcomes (after stopping the 1-year intervention) by annual LDCT. Patients and methods We analyzed the evolution of target and non-target trial nodules detected by LDCT in the budesonide and placebo arms up to 5 years after randomization. The numbers and characteristics of lung cancers diagnosed during follow-up were also analyzed. Results The mean maximum diameter of non-solid nodules reduced significantly (from 5.03 mm at baseline to 2.61 mm after 5 years) in the budesonide arm; there was no significant size change in the placebo arm. The mean diameter of partially solid lesions also decreased significantly, but only by 0.69 mm. The size of solid nodules did not change. Neither the number of new lesions nor the number of lung cancers differed in the two arms. Conclusions Inhaled budesonide given for 1 year significantly decreased the size of non-solid nodules detected by screening LDCT after 5 years. This is of potential importance since some of these nodules may progress slowly to adenocarcinoma. However, further studies are required to assess clinical implications. Clinical trial number NCT01540552. PMID:25672894

Determining the Release of Radionuclides from Tank 18F Waste Residual Solids: FY2016 Report

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

King, William D.; Hobbs, David T.

Pore water leaching studies were conducted on actual Savannah River Site (SRS) Tank 18F residual waste solids to support Liquid Waste tank closure efforts. A test methodology was developed during previous simulant testing to produce slurries of tank residual solids and grout-representative solids in grout pore water solutions (based on SRS groundwater compositions) with pH and E h values expected during the aging of the closed waste tank. The target conditions are provided below where the initial pore water has a reducing potential and a relatively high pH (Reducing Region II). The pore water is expected to become increasingly oxidizingmore » with time (Oxidizing Region II) and during the latter stages of aging (Oxidizing Region III) the pH is expected to decrease. For the reducing case, tests were conducted with both unwashed and washed Tank 18F residual solids. For the oxidizing cases (Oxidizing Regions II and III), all samples were washed with simulated grout pore water solutions prior to testing, since it is expected that these conditions will occur after considerable pore water solution has passed through the system. For the reducing case, separate tests were conducted with representative ground grout solids and with calcium carbonate reagent, which is the grout phase believed to be controlling the pH. Ferrous sulfide (FeS) solids were also added to the reducing samples to lower the slurry E h value. Calcium carbonate solids were used as the grout-representative solid phase for each of the oxidizing cases. Air purge-gas with and without CO 2 removed was transferred through the oxidizing test samples and nitrogen purge-gas was transferred through the reducing test samples during leach testing. The target pH values were achieved to within 0.5 pH units for all samples. Leaching studies were conducted over an E h range of approximately 0.7 V. However, the highest and lowest E h values achieved of ~+0.5 V and ~-0.2 V were significantly less positive and less negative, respectively, than the target values. Achievement of more positive and more negative E h values is believed to require the addition of non-representative oxidants and reductants, respectively.« less

A new approach to estimate the geometrical factors, solid angle approximation, geometrical efficiency and their use in basic interaction cross section measurements

NASA Astrophysics Data System (ADS)

Rao, D. V.; Cesareo, R.; Brunetti, A.; Gigante, G. E.; Takeda, T.; Itai, Y.; Akatsuka, T.

2002-10-01

A new approach is developed to estimate the geometrical factors, solid angle approximation and geometrical efficiency for a system with experimental arrangements using X-ray tube and secondary target as an excitation source in order to produce the nearly monoenergetic Kα radiation to excite the sample. The variation of the solid angle is studied by changing the radius and length of the collimators towards and away from the source and sample. From these values the variation of the total solid angle and geometrical efficiency is deduced and the optimum value is used for the experimental work.

What is the surface temperature of a solid irradiated by a Petawatt laser?

NASA Astrophysics Data System (ADS)

Kemp, A. J.; Divol, L.

2016-09-01

When a solid target is irradiated by a Petawatt laser pulse, its surface is heated to tens of millions of degrees within a few femtoseconds, facilitating a diffusive heat wave and the acceleration of electrons to MeV energies into the target. Using numerically converged collisional particle-in-cell simulations, we observe a competition between two surface heating mechanisms-inverse bremsstrahlung in solid density on the one hand and electron scattering on turbulent electric fields on the other. Collisionless heating effectively dominates above the relativistic intensity threshold. Our numerical results show that a high-contrast 40 fs, f/5 laser pulse with 1 J energy will heat the skin layer to 5 keV, and the inside of the target over several microns deep to bulk temperatures in the range of 10-100 eV at solid density.

Antitumor Effects of Chimeric Receptor Engineered Human T Cells Directed to Tumor Stroma

PubMed Central

Kakarla, Sunitha; Chow, Kevin KH; Mata, Melinda; Shaffer, Donald R; Song, Xiao-Tong; Wu, Meng-Fen; Liu, Hao; Wang, Lisa L; Rowley, David R; Pfizenmaier, Klaus; Gottschalk, Stephen

2013-01-01

Cancer-associated fibroblasts (CAFs), the principle component of the tumor-associated stroma, form a highly protumorigenic and immunosuppressive microenvironment that mediates therapeutic resistance. Co-targeting CAFs in addition to cancer cells may therefore augment the antitumor response. Fibroblast activation protein-α (FAP), a type 2 dipeptidyl peptidase, is expressed on CAFs in a majority of solid tumors making it an attractive immunotherapeutic target. To target FAP-positive CAFs in the tumor-associated stroma, we genetically modified T cells to express a FAP-specific chimeric antigen receptor (CAR). The resulting FAP-specific T cells recognized and killed FAP-positive target cells as determined by proinflammatory cytokine release and target cell lysis. In an established A549 lung cancer model, adoptive transfer of FAP-specific T cells significantly reduced FAP-positive stromal cells, with a concomitant decrease in tumor growth. Combining these FAP-specific T cells with T cells that targeted the EphA2 antigen on the A549 cancer cells themselves significantly enhanced overall antitumor activity and conferred a survival advantage compared to either alone. Our study underscores the value of co-targeting both CAFs and cancer cells to increase the benefits of T-cell immunotherapy for solid tumors. PMID:23732988

Controllability in Multi-Stage Laser Ion Acceleration

NASA Astrophysics Data System (ADS)

Kawata, S.; Kamiyama, D.; Ohtake, Y.; Barada, D.; Ma, Y. Y.; Kong, Q.; Wang, P. X.; Gu, Y. J.; Li, X. F.; Yu, Q.

2015-11-01

The present paper shows a concept for a future laser ion accelerator, which should have an ion source, ion collimators, ion beam bunchers and ion post acceleration devices. Based on the laser ion accelerator components, the ion particle energy and the ion energy spectrum are controlled, and a future compact laser ion accelerator would be designed for ion cancer therapy or for ion material treatment. In this study each component is designed to control the ion beam quality. The energy efficiency from the laser to ions is improved by using a solid target with a fine sub-wavelength structure or a near-critical density gas plasma. The ion beam collimation is performed by holes behind the solid target or a multi-layered solid target. The control of the ion energy spectrum and the ion particle energy, and the ion beam bunching are successfully realized by a multi-stage laser-target interaction. A combination of each component provides a high controllability of the ion beam quality to meet variable requirements in various purposes in the laser ion accelerator. The work was partly supported by MEXT, JSPS, ASHULA project/ ILE, Osaka University, CORE (Center for Optical Research and Education, Utsunomiya University, Japan), Fudan University and CDI (Creative Dept. for Innovation) in CCRD, Utsunomiya University.

Observations of radiation damage and recovery in ammonia targets

NASA Astrophysics Data System (ADS)

McKee, P. M.

2004-06-01

The Polarized Target Group at the University of Virginia has conducted experiments at both the Stanford Linear Accelerator Center (SLAC) and the Thomas Jefferson National Accelerator Facility (JLab) in which a high-intensity (100 nA) electron beam was focused on a polarized target of solid ammonia and/ or solid, deuterated ammonia. Analysis of the target polarization data have revealed several unique characteristics of ammonia. Topics discussed include the rate of polarization decay with accumulated charge, methods of recovering polarization through target annealing and damage-induced shifts in the optimum microwave frequency used to drive the polarization.

Encapsulation methods for solid radionuclide production targets at a medium-energy cyclotron facility

NASA Astrophysics Data System (ADS)

Steyn, Gideon; Vermeulen, Christiaan; Isaacs, Eugene

2018-05-01

The techniques employed at iThemba LABS for the encapsulation of solid radionuclide production targets, based on cold indentation welding, electron beam welding and laser welding, are described. Some aspects of the target holders and cooling requirements to bombard targets in a tandem configuration with a 66 MeV proton beam, with intensities up to nominally 250 A, are also briefly discussed. These techniques are inter alia suitable for a production regimen compatible with the new generation of commercial, high-intensity 70 MeV cyclotrons.

First experimental evidence of hydrodynamic tunneling of ultra-relativistic protons in extended solid copper target at the CERN HiRadMat facility

NASA Astrophysics Data System (ADS)

Schmidt, R.; Blanco Sancho, J.; Burkart, F.; Grenier, D.; Wollmann, D.; Tahir, N. A.; Shutov, A.; Piriz, A. R.

2014-08-01

A novel experiment has been performed at the CERN HiRadMat test facility to study the impact of the 440 GeV proton beam generated by the Super Proton Synchrotron on extended solid copper cylindrical targets. Substantial hydrodynamic tunneling of the protons in the target material has been observed that leads to significant lengthening of the projectile range, which confirms our previous theoretical predictions [N. A. Tahir et al., Phys. Rev. Spec. Top.-Accel. Beams 15, 051003 (2012)]. Simulation results show very good agreement with the experimental measurements. These results have very important implications on the machine protection design for powerful machines like the Large Hadron Collider (LHC), the future High Luminosity LHC, and the proposed huge 80 km circumference Future Circular Collider, which is currently being discussed at CERN. Another very interesting outcome of this work is that one may also study the field of High Energy Density Physics at this test facility.

Production of Y-86 and other radiometals for research purposes using a solution target system.

PubMed

Oehlke, Elisabeth; Hoehr, Cornelia; Hou, Xinchi; Hanemaayer, Victoire; Zeisler, Stefan; Adam, Michael J; Ruth, Thomas J; Celler, Anna; Buckley, Ken; Benard, Francois; Schaffer, Paul

2015-11-01

Diagnostic radiometals are typically obtained from cyclotrons by irradiating solid targets or from radioisotope generators. These methods have the advantage of high production yields, but require additional solid target handling infrastructure that is not readily available to many cyclotron facilities. Herein, we provide an overview of our results regarding the production of various positron-emitting radiometals using a liquid target system installed on a 13 MeV cyclotron at TRIUMF. Details about the production, purification and quality control of (89)Zr, (68)Ga and for the first time (86)Y are discussed. Aqueous solutions containing 1.35-1.65 g/mL of natural-abundance zinc nitrate, yttrium nitrate, and strontium nitrate were irradiated on a 13 MeV cyclotron using a standard liquid target. Different target body and foil materials were investigated for corrosion. Production yields were calculated using theoretical cross-sections from the EMPIRE code and compared with experimental results. The radioisotopes were extracted from irradiated target material using solid phase extraction methods adapted from previously reported methods, and used for radiolabelling experiments. We demonstrated production quantities that are sufficient for chemical and biological studies for three separate radiometals, (89)Zr (Asat = 360 MBq/μA and yield = 3.17 MBq/μA), (86)Y (Asat = 31 MBq/μA and yield = 1.44 MBq/μA), and (68)Ga (Asat = 141 MBq/μA and yield = 64 MBq/μA) from one hour long irradiations on a typical medical cyclotron. (68)Ga yields were sufficient for potential clinical applications. In order to avoid corrosion of the target body and target foil, nitrate solutions were chosen as well as niobium as target-body material. An automatic loading system enabled up to three production runs per day. The separation efficiency ranged from 82 to 99%. Subsequently, (68)Ga and (86)Y were successfully used to radiolabel DOTA-based chelators while deferoxamine was used to coordinate (89)Zr. Copyright © 2015 Elsevier Inc. All rights reserved.

Diverse solid tumors expressing a restricted epitope of L1-CAM can be targeted by chimeric antigen receptor redirected T lymphocytes.

PubMed

Hong, Hao; Stastny, Michael; Brown, Christine; Chang, Wen-Chung; Ostberg, Julie R; Forman, Stephen J; Jensen, Michael C

2014-01-01

Adhesion molecule L1-CAM (CD171) was originally reported to be overexpressed on neuroblastoma and to play an important role during tumor progression. More recently, it has been shown to be overexpressed on many other solid tumors such as melanoma and carcinomas of the cervix, ovary, bladder, and others. Thus, there has been a growing interest in using this cell-surface molecule as a target for both antibody-based and cellular-based therapy-our group has previously examined the clinical utility of chimeric antigen receptor (CAR)-redirected cytolytic T cells that specifically target the CE7 epitope of L1-CAM on neuroblastoma patients. Here, we sought to determine whether this CE7 epitope is present on other recently identified L1-CAM tumors and whether it too can be targeted by CAR T cells. Our studies demonstrate that a diverse array of human tumor cell lines and primary solid tumors (ovarian, lung, and renal carcinoma, glioblastoma and neuroblastoma) do express the CE7 epitope and can efficiently stimulate CE7-specific CAR-redirected (CE7R) T-cell lytic activity and secretion of proinflamatory cytokines. L1-CAM was also detected on a limited number of normal tissues; however, L1-CAM expressed on normal human monocytes was not bound by the CE7 mAb nor was it targeted by CE7R T cells, suggesting that the CE7 epitope is more tumor restricted and not expressed on all L1-CAM tissues. Overall, the CE7 epitope of L1-CAM on a variety of tumors may be amenable to targeting by CE7R T cells, making it a promising target for adoptive immunotherapy.

Producing radiometals in liquid targets: Proof of feasibility with {sup 94m}Tc

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

Hoehr, C.; Badesso, B.; Morley, T.

2012-12-19

{sup 94m}Tc was produced in a liquid target loaded with a molybdenum-salt solution. This novel technique allows for the irradiation of metals dissolved in a liquid solution, normally only available in metal powder or foil form. By using this approach, the existing liquid targets and transfer infrastructure of many PET cyclotrons can be used to produce radiometals, avoiding the need, expense and challenges of operating solid targets. Such an approach allows for rapid testing of new isotopes for proof of feasibility studies. Different concentrations of Mo solution and their effect on the target performance were tested. Sufficient quantities to allowmore » for preclinical studies were produced.« less

Investigation of longitudinal proton acceleration in exploded targets irradiated by intense short-pulse laser

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

Gauthier, M.; CEA, DAM, DIF, 91297 Arpajon; Lévy, A.

2014-01-15

It was recently shown that a promising way to accelerate protons in the forward direction to high energies is to use under-dense or near-critical density targets instead of solids. Simulations have revealed that the acceleration process depends on the density gradients of the plasma target. Indeed, under certain conditions, the most energetic protons are predicted to be accelerated by a collisionless shock mechanism that significantly increases their energy. We report here the results of a recent experiment dedicated to the study of longitudinal ion acceleration in partially exploded foils using a high intensity (∼5 × 10{sup 18} W/cm{sup 2}) picosecond laser pulse. Wemore » show that protons accelerated using targets having moderate front and rear plasma gradients (up to ∼8 μm gradient length) exhibit similar maximum proton energy and number compared to proton beams that are produced, in similar laser conditions, from solid targets, in the well-known target normal sheath acceleration regime. Particle-In-Cell simulations, performed in the same conditions as the experiment and consistent with the measurements, allow laying a path for further improvement of this acceleration scheme.« less

Molecularly designed lipid microdomains for solid dispersions using a polymer/inorganic carrier matrix produced by hot-melt extrusion.

PubMed

Adler, Camille; Schönenberger, Monica; Teleki, Alexandra; Kuentz, Martin

2016-02-29

Amorphous solid dispersions have for many years been a focus in oral formulations, especially in combination with a hot-melt extrusion process. The present work targets a novel approach with a system based on a fatty acid, a polymer and an inorganic carrier. It was intended to adsorb the acidic lipid by specific molecular interactions onto the solid carrier to design disorder in the alkyl chains of the lipid. Such designed lipid microdomains (DLM) were created as a new microstructure to accommodate a compound in a solid dispersion. Vibrational spectroscopy, X-ray powder diffraction, atomic force microscopy as well as electron microscopic imaging were employed to study a system of stearic acid, hydroxypropylcellulose and aluminum magnesium silicate. β-carotene was used as a poorly water-soluble model substance that is difficult to formulate with conventional solid dispersion formulations. The results indicated that the targeted molecular excipient interactions indeed led to DLMs for specific compositions. The different methods provided complementary aspects and important insights into the created microstructure. The novel delivery system appeared to be especially promising for the formulation of oral compounds that exhibit both high crystal energy and lipophilicity. Copyright © 2015 Elsevier B.V. All rights reserved.

Effects of electron recirculation on a hard x-ray source observed during the interaction of a high intensity laser pulse with thin Au targets

NASA Astrophysics Data System (ADS)

Compant La Fontaine, A.; Courtois, C.; Lefebvre, E.; Bourgade, J. L.; Landoas, O.; Thorp, K.; Stoeckl, C.

2013-12-01

The interaction of a high intensity laser pulse on the preplasma of a high-Z solid target produced by the pulse's pedestal generates high-energy electrons. These electrons subsequently penetrate inside the solid target and produce bremsstrahlung photons, generating an x-ray source which can be used for photonuclear studies or to radiograph high area density objects. The source characteristics are compared for targets with thin (20 μm) and thick (100 μm) Au foils on the Omega EP laser at Laboratory for Laser Energetics. Simulations using the particle-in-cell code CALDER show that for a 20 μm thickness Au target, electrons perform multiple round-trips in the target under the effect of the laser ponderomotive potential and the target electrostatic potential. These relativistic electrons have random transverse displacements, with respect to the target normal, attributed to electrostatic fluctuation fields. As a result, the x-ray spot size is increased by a factor 2 for thin target compared to thick targets, in agreement with experimental results. In addition, the computed doses agree with the measured ones provided that electron recirculation in the thin target is taken into account. A dose increase by a factor 1.7 is then computed by allowing for recirculation. In the 100 μm target case, on the other hand, this effect is found to be negligible.

Topology of megagauss magnetic fields and of heat-carrying electrons produced in a high-power laser-solid interaction.

PubMed

Lancia, L; Albertazzi, B; Boniface, C; Grisollet, A; Riquier, R; Chaland, F; Le Thanh, K-C; Mellor, Ph; Antici, P; Buffechoux, S; Chen, S N; Doria, D; Nakatsutsumi, M; Peth, C; Swantusch, M; Stardubtsev, M; Palumbo, L; Borghesi, M; Willi, O; Pépin, H; Fuchs, J

2014-12-05

The intricate spatial and energy distribution of magnetic fields, self-generated during high power laser irradiation (at Iλ^{2}∼10^{13}-10^{14}  W.cm^{-2}.μm^{2}) of a solid target, and of the heat-carrying electron currents, is studied in inertial confinement fusion (ICF) relevant conditions. This is done by comparing proton radiography measurements of the fields to an improved magnetohydrodynamic description that fully takes into account the nonlocality of the heat transport. We show that, in these conditions, magnetic fields are rapidly advected radially along the target surface and compressed over long time scales into the dense parts of the target. As a consequence, the electrons are weakly magnetized in most parts of the plasma flow, and we observe a reemergence of nonlocality which is a crucial effect for a correct description of the energetics of ICF experiments.

X-ray tomography characterization of density gradient aerogel in laser targets

NASA Astrophysics Data System (ADS)

Borisenko, L.; Orekhov, A.; Musgrave, C.; Nazarov, W.; Merkuliev, Yu; Borisenko, N.

2016-04-01

The low-density solid laser target characterization studies begun with the SkyScan 1074 computer microtomograph (CMT) [1, 2] are now continued with higher resolution of SkyScan 1174. The research is particularly focused on the possibility to obtain, control and measure precisely the gradient density polymers for laser target production. Repeatability of the samples and possibility to obtain stable gradients are analysed. The measurements were performed on the mm-scale divinyl benzene (DVB) rods.

Cryogenci DT and D2 Targets for Inertial Confinement Fusion

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

Sangster, T.C.; Betti, R.; Craxton, R.S.

Ignition target designs for inertial confinement fusion on the National Ignition Facility (NIF) are based on a spherical ablator containing a solid, cryogenic-fuel layer of deuterium and tritium. The need for solid-fuel layers was recognized more than 30 years ago and considerable effort has resulted in the production of cryogenic targets that meet most of the critical fabrication tolerances for ignition on the NIf. Significant progress with the formation and characterization of cryogenic targets for both direct and x-ray drive will be described. Results from recent cryogenic implosions will also be presented.

Fast Electron Deposition in Laser Shock Compressed Plastic Targets

NASA Astrophysics Data System (ADS)

Hall, T. A.; Ellwi, S.; Batani, D.; Bernardinello, A.; Masella, V.; Koenig, M.; Benuzzi, A.; Krishnan, J.; Pisani, F.; Djaoui, A.; Norreys, P.; Neely, D.; Rose, S.; Key, M. H.; Fews, P.

1998-08-01

We present the first results of fast electron deposition in a laser shock compressed plasma. The interaction of a 3 ps, 15 J laser pulse with solid polyethylene targets is used to produce fast electrons on one side of foil targets and a 2 ns duration laser pulse is used to drive a shock wave into the target from the opposite side. Kα emission from chlorine fluor buried layers is used to measure the electron transport. The hot electron range in the shock compressed plastic is found to be approximately twice as large as the range in the solid density plastic.

Molecular targeted therapies for solid tumors: management of side effects.

PubMed

Grünwald, Viktor; Soltau, Jens; Ivanyi, Philipp; Rentschler, Jochen; Reuter, Christoph; Drevs, Joachim

2009-03-01

This review will provide physicians and oncologists with an overview of side effects related to targeted agents that inhibit vascular endothelial growth factor (VEGF), epidermal growth factor (EGF) and mammalian target of rapamycin (mTOR) signaling in the treatment of solid tumors. Such targeted agents can be divided into monoclonal antibodies, tyrosine kinase inhibitors, multitargeted tyrosine kinase inhibitors and serine/threonine kinase inhibitors. Molecular targeted therapies are generally well tolerated, but inhibitory effects on the biological function of the targets in healthy tissue can result in specific treatment-related side effects, particularly with multitargeted agents. We offer some guidance on how to manage adverse events in cancer patients based on the range of options currently available. Copyright 2009 S. Karger AG, Basel.

IRIS : A reaction spectroscopy facility with solid H2 /D2 target

NASA Astrophysics Data System (ADS)

Holl, Matthias; Kanungo, Ritu; Alcorta, Martin; Andreoiu, Corina; Bidaman, Harris; Burbadge, Christina; Burke, Devin; Chen, Alan; Davids, Barry; Diaz Varela, Alejandra; Garrett, Paul; Hackman, Greg; Ishimoto, Shigeru; Kaur, Satbir; Keefe, Matthew; Kruecken, Reiner; Mansour, Iymad; Randhawa, Jaspreet; Sanetullaev, Alisher; Shotter, Alan; Smith, Jenna; Tanaka, Junki; Tanihata, Isao; Turko, Joseph; Workman, Orry

2016-09-01

The charged particle reaction spectroscopy station IRIS at TRIUMF is designed to allow studies of inelastic scattering and transfer reactions for low intensity beams. To do so, a novel solid H2 /D2 target is used in combination with a low pressure ionization chamber for the identification of incoming beam particles. The light ejectiles are measured using a ΔE - E telescope consisting of an annular silicon detector followed by CsI(Tl) array. Another ΔE - E telescope, consisting of two segmented silicon detectors, is used to identify the heavy outgoing particles. An overview of the faciltity will be given and examples from recent experiments that illustrate that facility's capability for reaction studies of exotic nuclei will be shown. Support from Canada Foundation for Innovation, Nova Scotia Research and Innovation Trust and NSERC.

Milatuzumab-SN-38 conjugates for the treatment of CD74+ cancers.

PubMed

Govindan, Serengulam V; Cardillo, Thomas M; Sharkey, Robert M; Tat, Fatma; Gold, David V; Goldenberg, David M

2013-06-01

CD74 is an attractive target for antibody-drug conjugates (ADC), because it internalizes and recycles after antibody binding. CD74 mostly is associated with hematologic tumors but is expressed also in solid cancers. Therefore, ADCs of the humanized anti-CD74 antibody, milatuzumab, were examined for the therapy of CD74-expressing solid tumors. Milatuzumab-doxorubicin and two milatuzumab-SN-38 conjugates with cleavable linkers, differing in their stability in serum and how they release SN-38 in the lysosome, were prepared. CD74 expression was determined by flow cytometry and immunohistology. In vitro cytotoxicity and in vivo therapeutic studies were conducted in the human cancer cell lines A-375 (melanoma), HuH-7 and Hep-G2 (hepatoma), Capan-1 (pancreatic), NCI-N87 (gastric), and Raji Burkitt lymphoma. The milatuzumab-SN-38 ADC was compared with SN-38 ADCs prepared with anti-Trop-2 and anti-CEACAM6 antibodies in xenografts expressing their target antigens. Milatuzumab-doxorubicin was most effective in the lymphoma model, whereas in A-375 and Capan-1 solid tumors, only milatuzumab-SN-38 showed a therapeutic benefit. Despite much lower surface expression of CD74 than Trop-2 or CEACAM6, milatuzumab-SN-38 had similar efficacy in Capan-1 as anti-Trop-2-SN-38, but in NCI-N87, anti-CEACAM6 and anti-Trop-2 conjugates were superior. Studies in two hepatoma lines at a single dose level showed significant benefit over saline controls but not against an irrelevant immunoglobulin G conjugate. CD74 is a suitable target for ADCs in some solid tumor xenografts, with efficacy largely influenced by uniformity of CD74 expression and with SN-38 conjugates providing the best therapeutic responses; SN-38 conjugates were preferable in solid cancers, whereas doxorubicin ADC was better in lymphoma tested. ©2013 AACR

Evaluation of target efficiencies for solid-liquid separation steps in biofuels production.

PubMed

Kochergin, Vadim; Miller, Keith

2011-01-01

Development of liquid biofuels has entered a new phase of large scale pilot demonstration. A number of plants that are in operation or under construction face the task of addressing the engineering challenges of creating a viable plant design, scaling up and optimizing various unit operations. It is well-known that separation technologies account for 50-70% of both capital and operating cost. Additionally, reduction of environmental impact creates technological challenges that increase project cost without adding to the bottom line. Different technologies vary in terms of selection of unit operations; however, solid-liquid separations are likely to be a major contributor to the overall project cost. Despite the differences in pretreatment approaches, similar challenges arise for solid-liquid separation unit operations. A typical process for ethanol production from biomass includes several solid-liquid separation steps, depending on which particular stream is targeted for downstream processing. The nature of biomass-derived materials makes it either difficult or uneconomical to accomplish complete separation in a single step. Therefore, setting realistic efficiency targets for solid-liquid separations is an important task that influences overall process recovery and economics. Experimental data will be presented showing typical characteristics for pretreated cane bagasse at various stages of processing into cellulosic ethanol. Results of generic material balance calculations will be presented to illustrate the influence of separation target efficiencies on overall process recoveries and characteristics of waste streams.

Long-term effects of inhaled budesonide on screening-detected lung nodules.

PubMed

Veronesi, G; Lazzeroni, M; Szabo, E; Brown, P H; DeCensi, A; Guerrieri-Gonzaga, A; Bellomi, M; Radice, D; Grimaldi, M C; Spaggiari, L; Bonanni, B

2015-05-01

A previously carried out randomized phase IIb, placebo-controlled trial of 1 year of inhaled budesonide, which was nested in a lung cancer screening study, showed that non-solid and partially solid lung nodules detected by low-dose computed tomography (LDCT), and not immediately suspicious for lung cancer, tended to regress. Because some of these nodules may be slow-growing adenocarcinoma precursors, we evaluated long-term outcomes (after stopping the 1-year intervention) by annual LDCT. We analyzed the evolution of target and non-target trial nodules detected by LDCT in the budesonide and placebo arms up to 5 years after randomization. The numbers and characteristics of lung cancers diagnosed during follow-up were also analyzed. The mean maximum diameter of non-solid nodules reduced significantly (from 5.03 mm at baseline to 2.61 mm after 5 years) in the budesonide arm; there was no significant size change in the placebo arm. The mean diameter of partially solid lesions also decreased significantly, but only by 0.69 mm. The size of solid nodules did not change. Neither the number of new lesions nor the number of lung cancers differed in the two arms. Inhaled budesonide given for 1 year significantly decreased the size of non-solid nodules detected by screening LDCT after 5 years. This is of potential importance since some of these nodules may progress slowly to adenocarcinoma. However, further studies are required to assess clinical implications. NCT01540552. © The Author 2015. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: journals.permissions@oup.com.

Unveiling the nucleon tensor charge at Jefferson Lab: A study of the SoLID case

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

Ye, Zhihong; Sato, Nobuo; Allada, Kalyan

© 2017 The Authors Future experiments at the Jefferson Lab 12 GeV upgrade, in particular, the Solenoidal Large Intensity Device (SoLID), aim at a very precise data set in the region where the partonic structure of the nucleon is dominated by the valence quarks. One of the main goals is to constrain the quark transversity distributions. We apply recent theoretical advances of the global QCD extraction of the transversity distributions to study the impact of future experimental data from the SoLID experiments. Especially, we develop a simple strategy based on the Hessian matrix analysis that allows one to estimate themore » uncertainties of the transversity quark distributions and their tensor charges extracted from SoLID data simulation. We find that the SoLID measurements with the proton and the effective neutron targets can improve the precision of the u- and d-quark transversity distributions up to one order of magnitude in the range 0.05 < x < 0.6.« less

Unveiling the nucleon tensor charge at Jefferson Lab: A study of the SoLID case

NASA Astrophysics Data System (ADS)

Ye, Zhihong; Sato, Nobuo; Allada, Kalyan; Liu, Tianbo; Chen, Jian-Ping; Gao, Haiyan; Kang, Zhong-Bo; Prokudin, Alexei; Sun, Peng; Yuan, Feng

2017-04-01

Future experiments at the Jefferson Lab 12 GeV upgrade, in particular, the Solenoidal Large Intensity Device (SoLID), aim at a very precise data set in the region where the partonic structure of the nucleon is dominated by the valence quarks. One of the main goals is to constrain the quark transversity distributions. We apply recent theoretical advances of the global QCD extraction of the transversity distributions to study the impact of future experimental data from the SoLID experiments. Especially, we develop a simple strategy based on the Hessian matrix analysis that allows one to estimate the uncertainties of the transversity quark distributions and their tensor charges extracted from SoLID data simulation. We find that the SoLID measurements with the proton and the effective neutron targets can improve the precision of the u- and d-quark transversity distributions up to one order of magnitude in the range 0.05 < x < 0.6.

Laser opacity in underdense preplasma of solid targets due to quantum electrodynamics effects

NASA Astrophysics Data System (ADS)

Wang, W.-M.; Gibbon, P.; Sheng, Z.-M.; Li, Y.-T.; Zhang, J.

2017-07-01

We investigate how next-generation laser pulses at 10 -200 PW interact with a solid target in the presence of a relativistically underdense preplasma produced by amplified spontaneous emission (ASE). Laser hole boring and relativistic transparency are strongly restrained due to the generation of electron-positron pairs and γ -ray photons via quantum electrodynamics (QED) processes. A pair plasma with a density above the initial preplasma density is formed, counteracting the electron-free channel produced by hole boring. This pair-dominated plasma can block laser transport and trigger an avalanchelike QED cascade, efficiently transferring the laser energy to the photons. This renders a 1 -μ m scale-length, underdense preplasma completely opaque to laser pulses at this power level. The QED-induced opacity therefore sets much higher contrast requirements for such a pulse in solid-target experiments than expected by classical plasma physics. Our simulations show, for example, that proton acceleration from the rear of a solid with a preplasma would be strongly impaired.

Dynamics of Laser-Driven Shock Waves in Solid Targets

NASA Astrophysics Data System (ADS)

Aglitskiy, Y.; Karasik, M.; Velikovich, A. L.; Serlin, V.; Weaver, J.; Schmitt, A. J.; Obenschain, S. P.; Grun, J.; Metzler, N.; Zalesak, S. T.; Gardner, J. H.; Oh, J.; Harding, E. C.

2009-11-01

Accurate shock timing is a key issue of both indirect- and direct-drive laser fusions. The experiments on the Nike laser at NRL presented here were made possible by improvements in the imaging capability of our monochromatic x-ray diagnostics based on Bragg reflection from spherically curved crystals. Side-on imaging implemented on Nike makes it possible to observe dynamics of the shock wave and ablation front in laser-driven solid targets. We can choose to observe a sequence of 2D images or a continuous time evolution of an image resolved in one spatial dimension. A sequence of 300 ps snapshots taken using vanadium backlighter at 5.2 keV reveals propagation of a shock wave in a solid plastic target. The shape of the shock wave reflects the intensity distribution in the Nike beam. The streak records with continuous time resolution show the x-t trajectory of a laser-driven shock wave in a 10% solid density DVB foam.

What is the surface temperature of a solid irradiated by a Petawatt laser?

NASA Astrophysics Data System (ADS)

Kemp, Andreas; Divol, Laurent

2016-10-01

When a solid target is irradiated by a Petawatt laser pulse, its surface is heated to tens of millions of degrees within a few femtoseconds, facilitating a diffusive heat wave and the acceleration of electrons to MeV energies into the target. Using numerically converged collisional particle-in-cell simulations, we observe a competition between two surface heating mechanisms - inverse bremsstrahlung in solid density on one hand, and electrons scattering on turbulent electric fields on the other. Collision-less heating effectively dominates above the relativistic intensity threshold. Our numerical results show that a high-contrast 40fs, f/5 laser pulse with 1J energy will heat the skin layer to 5keV, and the inside of the target over several microns deep to a bulk temperature of 100s eV at solid density. Work performed under the auspices of the U.S. Department of Energy by the Lawrence Livermore National Laboratory under Contract DE-AC52-07NA27344.

Dental ablation with 1064 nm, 500 ps, Diode pumped solid state laser: A preliminary study.

PubMed

Sozzi, Michele; Fornaini, Carlo; Cucinotta, Annamaria; Merigo, Elisabetta; Vescovi, Paolo; Selleri, Stefano

2013-01-01

The Er:YAG laser in conservative dentistry is. good alternative to conventional instruments. Though several studies show the advantages of these devices, some drawbacks and unsolved problems are still present, such as the cost of the device and the large dimensions of the equipment. In the present study, the effectiveness of dental surface ablation with a picosecond infrared diode-pumped solid-state (DPSS) laser was investigated. In vitro tests on extracted human teeth were carried out, with assessment of the ablation quality in the tooth and thermal increase inside the pulp chamber. A solid-state picosecond laser was used for the experiments. The samples were exposed to laser energy at 1064 nm at a frequency of 30 kHz and a 500 ps pulse width. The target teeth were cooled during exposures. The internal temperature of the pulp chamber was monitored with. thermocouple. Optical microscope images showed effective ablation with the absence of carbonisation and micro-cracks. The cooling maintained the temperature rise in the pulp chamber below the permitted 5.5°C. The main problem with the use of lasers in dentistry when teeth are the target is the heat generated in the pulp chamber of the target teeth. With lasers operating in the femtosecond mode, a better management of the internal temperature is possible, but is offset by the high cost of such devices. With the ps domain system used in the present study together with cooling using chilled water, effective and clean ablation could be achieved with a controlled thermal effect in the pulp chamber. In this preliminary study with a picosecond domain DPSS laser using water cooling for the target, effective hard tissue ablation was achieved keeping the thermal increase in the pulp within the permitted range. The results suggest that this system could be used in clinical practice with appropriate modifications.

[Pharmacotherapy of solid tumors. New hopes and frustrations].

PubMed

Grünwald, V; Rickmann, M

2014-10-01

Recent years have seen dramatic changes in the biological understanding and treatment of solid tumors. Based on the tumor biology, targeting agents have been developed which directly affect the underlying genetic or immunological changes found in specific tumor entities. Significant increases in survival have delivered the functional proof of the concept of targeted and immunological tumor therapy. The management and adherence of the patient as well as optimized cooperation with clinicians are decisive for the results of therapy and disease control.Several solid tumors are currently under investigation in clinical studies evaluating the (sequential) therapy with targeting and immunologically active agents, e.g. tyrosine kinase and mTOR inhibitors, targeting antibodies, such as bevacizumab, specific antagonists, such as enzalutamide and immunological checkpoint inhibitors via PD(L)1 and/or CTLA 4 antibodies.Currently approved agents have dramatically changed the landscape of treatment options especially for prostate cancer. Such agents include hormone therapy with enzalutamide and abiraterone, radiotherapy with cabazitaxel and xofigo (radium 223), metastatic breast cancer (eribulin and everolimus), renal cell carcinoma (sunitinib, sorafenib, axitinib, everolimus and temsirolimus), non-small cell lung cancer (crizotinib and afatinib), colorectal cancer and gastrointestinal stromal tumor (regorafenib) and melanoma (ipilimumab and vemurafenib). The treatment of rarer tumors, such as pancreatic and hepatocellular cancer and soft tissue sarcoma has entered the stage of targeted therapy with the approval of nanoparticle albumin-bound (nab)-paclitaxel, sorafenib, and eribulin/pazopanib. Current clinical trials are focusing on the best time point and sequence of therapy and also improvement in the management of these promising agents.

Catalysis of Nuclear Reactions by Electrons

NASA Astrophysics Data System (ADS)

Lipoglavšek, Matej

2018-01-01

Electron screening enhances nuclear reaction cross sections at low energies. We studied the nuclear reaction 1H(19F,αγ)16O in inverse kinematics in different solid hydrogen targets. Measured resonance strengths differed by up to a factor of 10 in different targets. We also studied the 2H(p,γ)3He fusion reaction and observed electrons emitted as reaction products instead of γ rays. In this case electron screening greatly enhances internal conversion probability.

Large Hadron Collider at CERN: Beams generating high-energy-density matter.

PubMed

Tahir, N A; Schmidt, R; Shutov, A; Lomonosov, I V; Piriz, A R; Hoffmann, D H H; Deutsch, C; Fortov, V E

2009-04-01

This paper presents numerical simulations that have been carried out to study the thermodynamic and hydrodynamic responses of a solid copper cylindrical target that is facially irradiated along the axis by one of the two Large Hadron Collider (LHC) 7 TeV/ c proton beams. The energy deposition by protons in solid copper has been calculated using an established particle interaction and Monte Carlo code, FLUKA, which is capable of simulating all components of the particle cascades in matter, up to multi-TeV energies. These data have been used as input to a sophisticated two-dimensional hydrodynamic computer code BIG2 that has been employed to study this problem. The prime purpose of these investigations was to assess the damage caused to the equipment if the entire LHC beam is lost at a single place. The FLUKA calculations show that the energy of protons will be deposited in solid copper within about 1 m assuming constant material parameters. Nevertheless, our hydrodynamic simulations have shown that the energy deposition region will extend to a length of about 35 m over the beam duration. This is due to the fact that first few tens of bunches deposit sufficient energy that leads to high pressure that generates an outgoing radial shock wave. Shock propagation leads to continuous reduction in the density at the target center that allows the protons delivered in subsequent bunches to penetrate deeper and deeper into the target. This phenomenon has also been seen in case of heavy-ion heated targets [N. A. Tahir, A. Kozyreva, P. Spiller, D. H. H. Hoffmann, and A. Shutov, Phys. Rev. E 63, 036407 (2001)]. This effect needs to be considered in the design of a sacrificial beam stopper. These simulations have also shown that the target is severely damaged and is converted into a huge sample of high-energy density (HED) matter. In fact, the inner part of the target is transformed into a strongly coupled plasma with fairly uniform physical conditions. This work, therefore, has suggested an additional very important application of the LHC, namely, studies of HED states in matter.

Isochoric heating of solid gold targets with the PW-laser-driven ion beams

NASA Astrophysics Data System (ADS)

Steinke, Sven; Ji, Qing; Bulanov, Stepan; Barnard, John; Schenkel, Thomas; Esarey, Eric; Leemans, Wim

2016-10-01

We present an end-to-end simulation for isochoric heating of solid gold targets using ion beams produced with the BELLA PW laser at LBNL: (i) 2D Particle-In-Cell (PIC) simulations are applied to study the ion source characteristics of the PW laser-target interaction at the long focal length (f/#65) beamline at laser intensities of 5x1019W/cm2 at spot size of ω0 = 52 μm on a CH target. (ii) In order to transport the ion beams to an EMP-free environment, an active plasma lens will be used. This was modeled by calculating the Twiss parameters of the ion beam from the appropriate transport matrixes using the source parameters obtained from the PIC simulation. Space charge effects were considered as well. (iii) Hydrodynamic simulations indicate that these ion beams can isochorically heat a 1 mm3 gold target to the Warm Dense Matter state. This work was supported by Fusion Energy Science, and LDRD funding from Lawrence Berkeley National Laboratory, provided by the Director, Office of Science, of the U.S. Department of Energy under Contract No. DE-AC02-05CH11231.

First experimental evidence of hydrodynamic tunneling of ultra–relativistic protons in extended solid copper target at the CERN HiRadMat facility

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

Schmidt, R.; Grenier, D.; Wollmann, D.

2014-08-15

A novel experiment has been performed at the CERN HiRadMat test facility to study the impact of the 440 GeV proton beam generated by the Super Proton Synchrotron on extended solid copper cylindrical targets. Substantial hydrodynamic tunneling of the protons in the target material has been observed that leads to significant lengthening of the projectile range, which confirms our previous theoretical predictions [N. A. Tahir et al., Phys. Rev. Spec. Top.-Accel. Beams 15, 051003 (2012)]. Simulation results show very good agreement with the experimental measurements. These results have very important implications on the machine protection design for powerful machines like themore » Large Hadron Collider (LHC), the future High Luminosity LHC, and the proposed huge 80 km circumference Future Circular Collider, which is currently being discussed at CERN. Another very interesting outcome of this work is that one may also study the field of High Energy Density Physics at this test facility.« less

Femtosecond dynamics of energetic electrons in high intensity laser-matter interactions

NASA Astrophysics Data System (ADS)

Pompili, R.; Anania, M. P.; Bisesto, F.; Botton, M.; Castellano, M.; Chiadroni, E.; Cianchi, A.; Curcio, A.; Ferrario, M.; Galletti, M.; Henis, Z.; Petrarca, M.; Schleifer, E.; Zigler, A.

2016-10-01

Highly energetic electrons are generated at the early phases of the interaction of short-pulse high-intensity lasers with solid targets. These escaping particles are identified as the essential core of picosecond-scale phenomena such as laser-based acceleration, surface manipulation, generation of intense magnetic fields and electromagnetic pulses. Increasing the number of the escaping electrons facilitate the late time processes in all cases. Up to now only indirect evidences of these important forerunners have been recorded, thus no detailed study of the governing mechanisms was possible. Here we report, for the first time, direct time-dependent measurements of energetic electrons ejected from solid targets by the interaction with a short-pulse high-intensity laser. We measured electron bunches up to 7 nanocoulombs charge, picosecond duration and 12 megaelectronvolts energy. Our ’snapshots’ capture their evolution with an unprecedented temporal resolution, demonstrat- ing a significant boost in charge and energy of escaping electrons when increasing the geometrical target curvature. These results pave the way toward significant improvement in laser acceleration of ions using shaped targets allowing the future development of small scale laser-ion accelerators.

Generation of shock waves and formation of craters in a solid material irradiated by a short laser pulse

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

Gus'kov, Sergei Yu; Borodziuk, S; Kasperczuk, A

2004-11-30

The results of investigations are presented which are concerned with laser radiation absorption in a target, the plasma state of its ablated material, the energy transfer to the solid target material, the characteristics of the shock wave and craters on the target surface. The investigation involved irradiation of a planar target by a subnanosecond plasma-producing laser pulse. The experiments were carried out with massive aluminium targets using the PALS iodine laser, whose pulse duration (0.4 ns) was much shorter than the shock wave attenuation and on-target crater formation times (50-200 ns). The investigations were conducted for a laser radiation energymore » of 100 J at two wavelengths of 0.438 and 1.315 {mu}m. For a given pulse energy, the irradiation intensity was varied in a broad range (10{sup 13}-10{sup 16} W cm{sup -2}) by varying the radius of the laser beam. The efficiency of laser radiation-to-shock energy transfer was determined as a function of the intensity and wavelength of laser radiation; also determined were the characteristics of the plasma plume and the shock wave propagating in the solid target, including the experimental conditions under which two-dimensional effects are highly significant. (invited paper)« less

Fusion energy with lasers, direct drive targets, and dry wall chambers

NASA Astrophysics Data System (ADS)

Sethian, J. D.; Friedman, M.; Lehmberg, R. H.; Myers, M.; Obenschain, S. P.; Giuliani, J.; Kepple, P.; Schmitt, A. J.; Colombant, D.; Gardner, J.; Hegeler, F.; Wolford, M.; Swanekamp, S. B.; Weidenheimer, D.; Welch, D.; Rose, D.; Payne, S.; Bibeau, C.; Baraymian, A.; Beach, R.; Schaffers, K.; Freitas, B.; Skulina, K.; Meier, W.; Latkowski, J.; Perkins, L. J.; Goodin, D.; Petzoldt, R.; Stephens, E.; Najmabadi, F.; Tillack, M.; Raffray, R.; Dragojlovic, Z.; Haynes, D.; Peterson, R.; Kulcinski, G.; Hoffer, J.; Geller, D.; Schroen, D.; Streit, J.; Olson, C.; Tanaka, T.; Renk, T.; Rochau, G.; Snead, L.; Ghoneim, N.; Lucas, G.

2003-12-01

A coordinated, focused effort is underway to develop Laser Inertial Fusion Energy. The key components are developed in concert with one another and the science and engineering issues are addressed concurrently. Recent advances include: target designs have been evaluated that show it could be possible to achieve the high gains (>100) needed for a practical fusion system.These designs feature a low-density CH foam that is wicked with solid DT and over-coated with a thin high-Z layer. These results have been verified with three independent one-dimensional codes, and are now being evaluated with two- and three-dimensional codes. Two types of lasers are under development: Krypton Fluoride (KrF) gas lasers and Diode Pumped Solid State Lasers (DPSSL). Both have recently achieved repetitive 'first light', and both have made progress in meeting the fusion energy requirements for durability, efficiency, and cost. This paper also presents the advances in development of chamber operating windows (target survival plus no wall erosion), final optics (aluminium at grazing incidence has high reflectivity and exceeds the required laser damage threshold), target fabrication (demonstration of smooth DT ice layers grown over foams, batch production of foam shells, and appropriate high-Z overcoats), and target injection (new facility for target injection and tracking studies).

Shock-induced perturbation evolution in planar laser targets

NASA Astrophysics Data System (ADS)

Aglitskiy, Y.; Karasik, M.; Velikovich, A. L.; Serlin, V.; Weaver, J. L.; Kessler, T. J.; Schmitt, A. J.; Obenschain, S. P.; Metzler, N.; Oh, J.

2013-10-01

Experimental studies of hydrodynamic perturbation evolution triggered by a laser-driven shock wave in a planar target done on the KrF Nike laser facility are reported. The targets were made of solid plastic and/or plastic foam with single mode sinusoidal perturbation on the front or back surface or plastic/foam interface. Two specific cases are discussed. When a planar solid plastic target rippled at the front side is irradiated with a 350 ps long laser pulse, ablative Richtmyer-Meshkov (RM) oscillation of its areal mass modulation amplitude is detected while the laser is on, followed by observed strong oscillations of the areal mass in the unsupported shock flow after the laser pulse ends. When the target is rippled at the rear side, the nature of the perturbation evolution after the shock breakout is determined by the strength of the laser-driven shock wave. At pressure below 1 Mbar shock interaction with rear-surface ripples produces planar collimated jets manifesting the development of a classical RM instability in a weakly compressible shocked fluid. At shock pressure ~ 8 Mbar sufficient for vaporizing the shocked target material we observed instead the strong areal mass oscillations characteristic of a rippled centered rarefaction wave. Work supported by US DOE, Defense Programs.

Integrated modeling/analyses of thermal-shock effects in SNS targets

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

Taleyarkhan, R.P.; Haines, J.

1996-06-01

In a spallation neutron source (SNS), extremely rapid energy pulses are introduced in target materials such as mercury, lead, tungsten, uranium, etc. Shock phenomena in such systems may possibly lead to structural material damage beyond the design basis. As expected, the progression of shock waves and interaction with surrounding materials for liquid targets can be quite different from that in solid targets. The purpose of this paper is to describe ORNL`s modeling framework for `integrated` assessment of thermal-shock issues in liquid and solid target designs. This modeling framework is being developed based upon expertise developed from past reactor safety studies,more » especially those related to the Advanced Neutron Source (ANS) Project. Unlike previous separate-effects modeling approaches employed (for evaluating target behavior when subjected to thermal shocks), the present approach treats the overall problem in a coupled manner using state-of-the-art equations of state for materials of interest (viz., mercury, tungsten and uranium). That is, the modeling framework simultaneously accounts for localized (and distributed) compression pressure pulse generation due to transient heat deposition, the transport of this shock wave outwards, interaction with surrounding boundaries, feedback to mercury from structures, multi-dimensional reflection patterns & stress induced (possible) breakup or fracture.« less

Targeting epigenetics for the treatment of prostate cancer: recent progress and future directions.

PubMed

Lin, Jianqing; Wang, Chenguang; Kelly, Wm Kevin

2013-06-01

Epigenetic aberrations contribute to prostate cancer carcinogenesis and disease progression. Efforts have been made to target DNA methyltransferase and histone deacetylases (HDACs) in prostate cancer and other solid tumors but have not had the success that was seen in the hematologic malignancies. Oral, less toxic, and more specific agents are being developed in solid tumors including prostate cancer. Combinations of epigenetic agents alone or with a targeted agent such as androgen receptor signaling inhibitors are promising approaches and will be discussed further. Copyright © 2013 Elsevier Inc. All rights reserved.

Development of qualitative and quantitative analysis methods in pharmaceutical application with new selective signal excitation methods for 13 C solid-state nuclear magnetic resonance using 1 H T1rho relaxation time.

PubMed

Nasu, Mamiko; Nemoto, Takayuki; Mimura, Hisashi; Sako, Kazuhiro

2013-01-01

Most pharmaceutical drug substances and excipients in formulations exist in a crystalline or amorphous form, and an understanding of their state during manufacture and storage is critically important, particularly in formulated products. Carbon 13 solid-state nuclear magnetic resonance (NMR) spectroscopy is useful for studying the chemical and physical state of pharmaceutical solids in a formulated product. We developed two new selective signal excitation methods in (13) C solid-state NMR to extract the spectrum of a target component from such a mixture. These methods were based on equalization of the proton relaxation time in a single domain via rapid intraproton spin diffusion and the difference in proton spin-lattice relaxation time in the rotating frame ((1) H T1rho) of individual components in the mixture. Introduction of simple pulse sequences to one-dimensional experiments reduced data acquisition time and increased flexibility. We then demonstrated these methods in a commercially available drug and in a mixture of two saccharides, in which the (13) C signals of the target components were selectively excited, and showed them to be applicable to the quantitative analysis of individual components in solid mixtures, such as formulated products, polymorphic mixtures, or mixtures of crystalline and amorphous phases. Copyright © 2012 Wiley Periodicals, Inc.

Inertial confinement fusion and fast ignitor studies

NASA Astrophysics Data System (ADS)

Willi, O.; Barringer, L.; Bell, A.; Borghesi, M.; Davies, J.; Gaillard, R.; Iwase, A.; MacKinnon, A.; Malka, G.; Meyer, C.; Nuruzzaman, S.; Taylor, R.; Vickers, C.; Hoarty, D.; Gobby, P.; Johnson, R.; Watt, R. G.; Blanchot, N.; Canaud, B.; Croso, H.; Meyer, B.; Miquel, J. L.; Reverdin, C.; Pukhov, A.; Meyer-ter-Vehn, J.

2000-03-01

Laser imprinting has been studied and, in particular, saturation of areal density perturbations induced by near single mode laser imprinting was observed. Several issues important for the foam buffered direct drive scheme have been investigated. These studies included measurements of the absolute levels of stimulated Brillouin and Raman scattering observed from laser irradiated low density foam targets, either bare or overcoated with a thin layer of gold. A novel scheme is proposed to increase the pressure in indirectly driven targets. By heating a foam supersonically that is attached to a solid target the pressure generated is not only the ablation pressure but also the combined pressure due to ablation at the foam-foil interface and the heated foam material. Planar brominated plastic foil targets overcoated with a low density foam were irradiated by a soft X ray pulse. The pressure was obtained by comparing the rear side trajectory of the driven target observed by soft X ray radiography with one dimensional radiation hydrodynamic simulations. Observations were also carried out of the transition from supersonic to subsonic propagation of an ionization front in low density chlorinated foam targets irradiated by an intense soft X ray pulse. The diagnostic for these measurements was K shell point projection absorption spectroscopy. In the fast ignitor area the channelling and guiding of picosecond laser pulses through underdense plasmas, preformed density channels and microtubes were investigated. It was observed that a large fraction of the incident laser energy can be propagated. Megagauss magnetic fields were measured, with a polarimetric technique, during and after propagation of intense picosecond pulses in preionized plasmas. Two types of toroidal fields, of opposite orientation, were detected. In addition, the production and propagation of an electron beam through solid glass targets irradiated at intensities above 1019W/cm2 were observed using optical probing techniques.

Summary of the XIII International Workshop on Polarized Sources, Targets and Polarimetry

NASA Astrophysics Data System (ADS)

Rathmann, F.

2011-01-01

The workshops on polarized sources, targets, and polarimetry are held every two years. The present meeting took place in Ferrara, Italy, and was organized by the University of Ferrara. Sessions on Polarized Proton and Deuterium Sources, Polarized Electron Sources, Polarimetry, Polarized Solid Targets, and Polarized Internal Targets, highlighted topics, recent developments, and progress in the field. A session decicated to Future Facilities provided an overview of a number of new activities in the spin-physics sector at facilities that are currently in the planning stage. Besides presenting a broad overview of polarized ion sources, electron sources, solid and gaseous targets, and their neighboring fields, the workshop also addressed the application of polarized atoms in applied sciences and medicine that is becoming increasingly important.

Intranasal agomelatine solid lipid nanoparticles to enhance brain delivery: formulation, optimization and in vivo pharmacokinetics

PubMed Central

Fatouh, Ahmed M; Elshafeey, Ahmed H; Abdelbary, Ahmed

2017-01-01

Purpose Agomelatine is a novel antidepressant drug suffering from an extensive first-pass metabolism leading to a diminished absolute bioavailability. The aim of the study is: first to enhance its absolute bioavailability, and second to increase its brain delivery. Methods To achieve these aims, the nasal route was adopted to exploit first its avoidance of the hepatic first-pass metabolism to increase the absolute bioavailability, and second the direct nose-to-brain pathway to enhance the brain drug delivery. Solid lipid nanoparticles were selected as a drug delivery system to enhance agomelatine permeability across the blood–brain barrier and therefore its brain delivery. Results The optimum solid lipid nanoparticles have a particle size of 167.70 nm ±0.42, zeta potential of −17.90 mV ±2.70, polydispersity index of 0.12±0.10, entrapment efficiency % of 91.25%±1.70%, the percentage released after 1 h of 35.40%±1.13% and the percentage released after 8 h of 80.87%±5.16%. The pharmacokinetic study of the optimized solid lipid nanoparticles revealed a significant increase in each of the plasma peak concentration, the AUC(0–360 min) and the absolute bioavailability compared to that of the oral suspension of Valdoxan® with the values of 759.00 ng/mL, 7,805.69 ng⋅min/mL and 44.44%, respectively. The optimized solid lipid nanoparticles gave a drug-targeting efficiency of 190.02, which revealed more successful brain targeting by the intranasal route compared with the intravenous route. The optimized solid lipid nanoparticles had a direct transport percentage of 47.37, which indicates a significant contribution of the direct nose-to-brain pathway in the brain drug delivery. Conclusion The intranasal administration of agomelatine solid lipid nanoparticles has effectively enhanced both the absolute bioavailability and the brain delivery of agomelatine. PMID:28684900

Global capacity, potentials and trends of solid waste research and management.

PubMed

Nwachukwu, Michael A; Ronald, Mersky; Feng, Huan

2017-09-01

In this study, United States, China, India, United Kingdom, Nigeria, Egypt, Brazil, Italy, Germany, Taiwan, Australia, Canada and Mexico were selected to represent the global community. This enabled an overview of solid waste management worldwide and between developed and developing countries. These are countries that feature most in the International Conference on Solid Waste Technology and Management (ICSW) over the past 20 years. A total of 1452 articles directly on solid waste management and technology were reviewed and credited to their original country of research. Results show significant solid waste research potentials globally, with the United States leading by 373 articles, followed by India with 230 articles. The rest of the countries are ranked in the order of: UK > Taiwan > Brazil > Nigeria > Italy > Japan > China > Canada > Germany >Mexico > Egypt > Australia. Global capacity in solid waste management options is in the order of: Waste characterisation-management > waste biotech/composting > waste to landfill > waste recovery/reduction > waste in construction > waste recycling > waste treatment-reuse-storage > waste to energy > waste dumping > waste education/public participation/policy. It is observed that the solid waste research potential is not a measure of solid waste management capacity. The results show more significant research impacts on solid waste management in developed countries than in developing countries where economy, technology and society factors are not strong. This article is targeted to motivate similar study in each country, using solid waste research articles from other streamed databases to measure research impacts on solid waste management.

Two-dimensional studies of relativistic electron beam plasma instabilities in an inhomogeneous plasma

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

Shukla, Chandrasekhar; Das, Amita, E-mail: amita@ipr.res.in; Patel, Kartik

Relativistic electron beam propagation in plasma is fraught with several micro instabilities like two stream, filamentation, etc., in plasma. This results in severe limitation of the electron transport through a plasma medium. Recently, however, there has been an experimental demonstration of improved transport of Mega Ampere of electron currents (generated by the interaction of intense laser with solid target) in a carbon nanotube structured solid target [G. Chatterjee et al., Phys. Rev. Lett. 108, 235005 (2012)]. This then suggests that the inhomogeneous plasma (created by the ionization of carbon nanotube structured target) helps in containing the growth of the beammore » plasma instabilities. This manuscript addresses this issue with the help of a detailed analytical study and 2-D Particle-In-Cell simulations. The study conclusively demonstrates that the growth rate of the dominant instability in the 2-D geometry decreases when the plasma density is chosen to be inhomogeneous, provided the scale length 1/k{sub s} of the inhomogeneous plasma is less than the typical plasma skin depth (c/ω{sub 0}) scale. At such small scale lengths channelization of currents is also observed in simulation.« less

Laser-driven proton acceleration with nanostructured targets

NASA Astrophysics Data System (ADS)

Vallières, Simon; Morabito, Antonia; Veltri, Simona; Scisciò, Massimiliano; Barberio, Marianna; Antici, Patrizio

2017-05-01

Laser-driven particle acceleration has become a growing field of research, in particular for its numerous interesting applications. One of the most common proton acceleration mechanism that is obtained on typically available multi-hundred TW laser systems is based on the irradiation of thin solid metal foils by the intense laser, generating the proton acceleration on its rear target surface. The efficiency of this acceleration scheme strongly depends on the type of target used. Improving the acceleration mechanism, i.e. enhancing parameters such as maximum proton energy, laminarity, efficiency, monocromaticy, and number of accelerated particles, is heavily depending on the laser-to-target absorption, where obviously cheap and easy to implement targets are best candidates. In this work, we present nanostructured targets that are able to increase the absorption of light compared to what can be achieved with a classical solid (non-nanostructured) target and are produced with a method that is much simpler and cheaper than conventional lithographic processes. Several layers of gold nanoparticles were deposited on solid targets (aluminum, Mylar and multiwalled carbon nanotube buckypaper) and allow for an increased photon absorption. This ultimately permits to increase the laser-to-particle energy transfer, and thus to enhance the yield in proton production. Experimental characterization results on the nanostructured films are presented (UV-Vis spectroscopy and AFM), along with preliminary experimental proton spectra obtained at the JLF-TITAN laser facility at LLNL.

Experimental evidence of beam-foil plasma creation during ion-solid interaction

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

Sharma, Prashant, E-mail: prashant@iuac.res.in; Nandi, Tapan

2016-08-15

Charge state evolution of the energetic projectile ions during the passage through thin carbon foils has been revisited using the X-ray spectroscopy technique. Contributions from the bulk and the solid surface in the charge changing processes have been segregated by measuring the charge state distribution of the projectile ions in the bulk of the target during the ion–solid interaction. Interestingly, the charge state distribution measured in the bulk exhibits Lorentzian profile in contrast to the well-known Gaussian structure observed using the electromagnetic methods and the theoretical predictions. The occurrence of such behavior is a direct consequence of the imbalance betweenmore » charge changing processes, which has been seen in various cases of the laboratory plasma. It suggests that the ion-solid collisions constitute high-density, localized plasma in the bulk of the solid target, called the beam-foil plasma. This condensed beam-foil plasma is similar to the high-density solar and stellar plasma which may have practical implementations in various fields, in particular, plasma physics and nuclear astrophysics. The present work suggests further modification in the theoretical charge state distribution calculations by incorporating the plasma coupling effects during the ion–solid interactions. Moreover, the multi-electron capture from the target exit surface has been confirmed through comparison between experimentally measured and theoretically predicted values of the mean charge state of the projectile ions.« less

Pharmaceutical development and optimization of azithromycin suppository for paediatric use.

PubMed

Kauss, Tina; Gaubert, Alexandra; Boyer, Chantal; Ba, Boubakar B; Manse, Muriel; Massip, Stephane; Léger, Jean-Michel; Fawaz, Fawaz; Lembege, Martine; Boiron, Jean-Michel; Lafarge, Xavier; Lindegardh, Niklas; White, Nicholas J; Olliaro, Piero; Millet, Pascal; Gaudin, Karen

2013-01-30

Pharmaceutical development and manufacturing process optimization work was undertaken in order to propose a potential paediatric rectal formulation of azithromycin as an alternative to existing oral or injectable formulations. The target product profile was to be easy-to-use, cheap and stable in tropical conditions, with bioavailability comparable to oral forms, rapidly achieving and maintaining bactericidal concentrations. PEG solid solution suppositories were characterized in vitro using visual, HPLC, DSC, FTIR and XRD analyses. In vitro drug release and in vivo bioavailability were assessed; a study in rabbits compared the bioavailability of the optimized solid solution suppository to rectal solution and intra-venous product (as reference) and to the previous, non-optimized formulation (suspended azithromycin suppository). The bioavailability of azithromycin administered as solid solution suppositories relative to intra-venous was 43%, which compared well to the target of 38% (oral product in humans). The results of 3-month preliminary stability and feasibility studies were consistent with industrial production scale-up. This product has potential both as a classical antibiotic and as a product for use in severely ill children in rural areas. Industrial partners for further development are being sought. Copyright © 2012 Elsevier B.V. All rights reserved.

Pharmaceutical development and optimization of azithromycin suppository for paediatric use

PubMed Central

Kauss, Tina; Gaubert, Alexandra; Boyer, Chantal; Ba, Boubakar B.; Manse, Muriel; Massip, Stephane; Léger, Jean-Michel; Fawaz, Fawaz; Lembege, Martine; Boiron, Jean-Michel; Lafarge, Xavier; Lindegardh, Niklas; White, Nicholas J.; Olliaro, Piero; Millet, Pascal; Gaudin, Karen

2013-01-01

Pharmaceutical development and manufacturing process optimization work was undertaken in order to propose a potential paediatric rectal formulation of azithromycin as an alternative to existing oral or injectable formulations. The target product profile was to be easy-to-use, cheap and stable in tropical conditions, with bioavailability comparable to oral forms, rapidly achieving and maintaining bactericidal concentrations. PEG solid solution suppositories were characterized in vitro using visual, HPLC, DSC, FTIR and XRD analyses. In vitro drug release and in vivo bioavailability were assessed; a study in rabbits compared the bioavailability of the optimized solid solution suppository to rectal solution and intra-venous product (as reference) and to the previous, non-optimized formulation (suspended azithromycin suppository). The bioavailability of azithromycin administered as solid solution suppositories relative to intra-venous was 43%, which compared well to the target of 38% (oral product in humans). The results of 3-month preliminary stability and feasibility studies were consistent with industrial production scale-up. This product has potential both as a classical antibiotic and as a product for use in severely ill children in rural areas. Industrial partners for further development are being sought. PMID:23220079

Solid-Phase Biological Assays for Drug Discovery

NASA Astrophysics Data System (ADS)

Forsberg, Erica M.; Sicard, Clémence; Brennan, John D.

2014-06-01

In the past 30 years, there has been a significant growth in the use of solid-phase assays in the area of drug discovery, with a range of new assays being used for both soluble and membrane-bound targets. In this review, we provide some basic background to typical drug targets and immobilization protocols used in solid-phase biological assays (SPBAs) for drug discovery, with emphasis on particularly labile biomolecular targets such as kinases and membrane-bound receptors, and highlight some of the more recent approaches for producing protein microarrays, bioaffinity columns, and other devices that are central to small molecule screening by SPBA. We then discuss key applications of such assays to identify drug leads, with an emphasis on the screening of mixtures. We conclude by highlighting specific advantages and potential disadvantages of SPBAs, particularly as they relate to particular assay formats.

Targeting solid tumors with non-pathogenic obligate anaerobic bacteria.

PubMed

Taniguchi, Shun'ichiro; Fujimori, Minoru; Sasaki, Takayuki; Tsutsui, Hiroko; Shimatani, Yuko; Seki, Keiichi; Amano, Jun

2010-09-01

Molecular-targeting drugs with fewer severe adverse effects are attracting great attention as the next wave of cancer treatment. There exist, however, populations of cancer cells resistant to these drugs that stem from the instability of tumor cells and/or the existence of cancer stem cells, and thus specific toxicity is required to destroy them. If such selectivity is not available, these targets may be sought out not by the cancer cell types themselves, but rather in their adjacent cancer microenvironments by means of hypoxia, low pH, and so on. The anaerobic conditions present in malignant tumor tissues have previously been regarded as a source of resistance in cancer cells against conventional therapy. However, there now appears to be a way to make use of these limiting factors as a selective target. In this review, we will refer to several trials, including our own, to direct attention to the utilizable anaerobic conditions present in malignant tumor tissues and the use of bacteria as carriers to target them. Specifically, we have been developing a method to attack solid cancers using the non-pathogenic obligate anaerobic bacterium Bifidobacterium longum as a vehicle to selectively recognize and target the anaerobic conditions in solid cancer tissues. We will also discuss the existence of low oxygen pressure in tumor masses in spite of generally enhanced angiogenesis, overview current cancer therapies, especially the history and present situation of bacterial utility to treat solid tumors, and discuss the rationality and future possibilities of this novel mode of cancer treatment. © 2010 Japanese Cancer Association.

High e+/e– ratio dense pair creation with 10 21W.cm –2 laser irradiating solid targets

DOE PAGES

Liang, E.; Clarke, T.; Henderson, A.; ...

2015-09-14

In this study, we report results of new pair creation experiments using ~100 Joule pulses of the Texas Petawatt Laser to irradiate solid gold and platinum targets, with intensities up to ~1.9 × 10 21 W.cm –2 and pulse durations as short as ~130 fs. Positron to electron (e+/e–) ratios >15% were observed for many thick disk and rod targets, with the highest e+/e– ratio reaching ~50% for a Pt rod. The inferred pair yield was ~ few ×10 10 with emerging pair density reaching ~10 15/cm 3 so that the pair skin depth becomes < pair jet transverse size.more » These results represent major milestones towards the goal of creating a significant quantity of dense pair-dominated plasmas with e+/e– approaching 100% and pair skin depth << pair plasma size, which will have wide-ranging applications to astrophysics and fundamental physics.« less

Chimeric antigen receptor T cells: a novel therapy for solid tumors.

PubMed

Yu, Shengnan; Li, Anping; Liu, Qian; Li, Tengfei; Yuan, Xun; Han, Xinwei; Wu, Kongming

2017-03-29

The chimeric antigen receptor T (CAR-T) cell therapy is a newly developed adoptive antitumor treatment. Theoretically, CAR-T cells can specifically localize and eliminate tumor cells by interacting with the tumor-associated antigens (TAAs) expressing on tumor cell surface. Current studies demonstrated that various TAAs could act as target antigens for CAR-T cells, for instance, the type III variant epidermal growth factor receptor (EGFRvIII) was considered as an ideal target for its aberrant expression on the cell surface of several tumor types. CAR-T cell therapy has achieved gratifying breakthrough in hematological malignancies and promising outcome in solid tumor as showed in various clinical trials. The third generation of CAR-T demonstrates increased antitumor cytotoxicity and persistence through modification of CAR structure. In this review, we summarized the preclinical and clinical progress of CAR-T cells targeting EGFR, human epidermal growth factor receptor 2 (HER2), and mesothelin (MSLN), as well as the challenges for CAR-T cell therapy.

Pointing and Jitter Control for the USNA Multi-Beam Combining System

DTIC Science & Technology

2013-05-10

previous work, an adaptive H-infinity optimal controller has been developed to control a single beam using a beam position detector for feedback... turbulence and airborne particles, platform jitter, lack of feedback from the target , and current laser technology represent just a few of these...lasers. Solid state lasers, however, cannot currently provide high enough power levels to destroy a target using a single beam. On solid-state

Split Flow Online Solid-Phase Extraction Coupled with Inductively Coupled Plasma Mass Spectrometry System for One-Shot Data Acquisition of Quantification and Recovery Efficiency.

PubMed

Furukawa, Makoto; Takagai, Yoshitaka

2016-10-04

Online solid-phase extraction (SPE) coupled with inductively coupled plasma mass spectrometry (ICPMS) is a useful tool in automatic sequential analysis. However, it cannot simultaneously quantify the analytical targets and their recovery percentages (R%) in one-shot samples. We propose a system that simultaneously acquires both data in a single sample injection. The main flowline of the online solid-phase extraction is divided into main and split flows. The split flow line (i.e., bypass line), which circumvents the SPE column, was placed on the main flow line. Under program-controlled switching of the automatic valve, the ICPMS sequentially measures the targets in a sample before and after column preconcentration and determines the target concentrations and the R% on the SPE column. This paper describes the system development and two demonstrations to exhibit the analytical significance, i.e., the ultratrace amounts of radioactive strontium ( 90 Sr) using commercial Sr-trap resin and multielement adsorbability on the SPE column. This system is applicable to other flow analyses and detectors in online solid phase extraction.

PST 2009: XIII International Workshop on Polarized Sources Targets and Polarimetry

NASA Astrophysics Data System (ADS)

Lenisa, Paolo

2011-05-01

The workshops on polarized sources, targets, and polarimetry are held every two years. In 2009 the meeting took place in Ferrara, Italy, and was organized by the University of Ferrara and INFN. Sessions on Polarized Proton and Deuterium Sources, Polarized Electron Sources, Polarimetry, Polarized Solid Targets, and Polarized Internal Targets, highlighted topics, recent developments, and progress in the field. A session dedicated to Future Facilities provided an overview of a number of new activities in the spin-physics sector at facilities that are currently in the planning stage. Besides presenting a broad overview of polarized ion sources, electron sources, solid and gaseous targets, and their neighbouring fields, the workshop also addressed the application of polarized atoms in applied sciences and medicine that is becoming increasingly important.

Biopolymers codelivering engineered T cells and STING agonists can eliminate heterogeneous tumors

PubMed Central

Smith, Tyrel T.; Moffett, Howell F.; Stephan, Sirkka B.; Opel, Cary F.; Dumigan, Amy G.; Jiang, Xiuyun; Pillarisetty, Venu G.; Pillai, Smitha P. S.; Wittrup, K. Dane; Stephan, Matthias T.

2017-01-01

Therapies using T cells that are programmed to express chimeric antigen receptors (CAR T cells) consistently produce positive results in patients with hematologic malignancies. However, CAR T cell treatments are less effective in solid tumors for several reasons. First, lymphocytes do not efficiently target CAR T cells; second, solid tumors create an immunosuppressive microenvironment that inactivates T cell responses; and third, solid cancers are typified by phenotypic diversity and thus include cells that do not express proteins targeted by the engineered receptors, enabling the formation of escape variants that elude CAR T cell targeting. Here, we have tested implantable biopolymer devices that deliver CAR T cells directly to the surfaces of solid tumors, thereby exposing them to high concentrations of immune cells for a substantial time period. In immunocompetent orthotopic mouse models of pancreatic cancer and melanoma, we found that CAR T cells can migrate from biopolymer scaffolds and eradicate tumors more effectively than does systemic delivery of the same cells. We have also demonstrated that codelivery of stimulator of IFN genes (STING) agonists stimulates immune responses to eliminate tumor cells that are not recognized by the adoptively transferred lymphocytes. Thus, these devices may improve the effectiveness of CAR T cell therapy in solid tumors and help protect against the emergence of escape variants. PMID:28436934

Biopolymers codelivering engineered T cells and STING agonists can eliminate heterogeneous tumors.

PubMed

Smith, Tyrel T; Moffett, Howell F; Stephan, Sirkka B; Opel, Cary F; Dumigan, Amy G; Jiang, Xiuyun; Pillarisetty, Venu G; Pillai, Smitha P S; Wittrup, K Dane; Stephan, Matthias T

2017-06-01

Therapies using T cells that are programmed to express chimeric antigen receptors (CAR T cells) consistently produce positive results in patients with hematologic malignancies. However, CAR T cell treatments are less effective in solid tumors for several reasons. First, lymphocytes do not efficiently target CAR T cells; second, solid tumors create an immunosuppressive microenvironment that inactivates T cell responses; and third, solid cancers are typified by phenotypic diversity and thus include cells that do not express proteins targeted by the engineered receptors, enabling the formation of escape variants that elude CAR T cell targeting. Here, we have tested implantable biopolymer devices that deliver CAR T cells directly to the surfaces of solid tumors, thereby exposing them to high concentrations of immune cells for a substantial time period. In immunocompetent orthotopic mouse models of pancreatic cancer and melanoma, we found that CAR T cells can migrate from biopolymer scaffolds and eradicate tumors more effectively than does systemic delivery of the same cells. We have also demonstrated that codelivery of stimulator of IFN genes (STING) agonists stimulates immune responses to eliminate tumor cells that are not recognized by the adoptively transferred lymphocytes. Thus, these devices may improve the effectiveness of CAR T cell therapy in solid tumors and help protect against the emergence of escape variants.

Solid-phase synthesis of molecularly imprinted nanoparticles.

PubMed

Canfarotta, Francesco; Poma, Alessandro; Guerreiro, Antonio; Piletsky, Sergey

2016-03-01

Molecularly imprinted polymers (MIPs) are synthetic materials, generally based on acrylic or methacrylic monomers, that are polymerized in the presence of a specific target molecule called the 'template' and capable of rebinding selectively to this target molecule. They have the potential to be low-cost and robust alternatives to biomolecules such as antibodies and receptors. When prepared by traditional synthetic methods (i.e., with free template in solution), their usefulness has been limited by high binding site heterogeneity, the presence of residual template and the fact that the production methods are complex and difficult to standardize. To overcome some of these limitations, we developed a method for the synthesis of MIP nanoparticles (nanoMIPs) using an innovative solid-phase approach, which relies on the covalent immobilization of the template molecules onto the surface of a solid support (glass beads). The obtained nanoMIPs are virtually free of template and demonstrate high affinity for the target molecule (e.g., melamine and trypsin in our published work). Because of an affinity separation step performed on the solid phase after polymerization, poor binders and unproductive polymer are removed, so the final product has more uniform binding characteristics. The overall protocol, starting from the immobilization of the template onto the solid phase and including the purification and characterization of the nanoparticles, takes up to 1 week.

Damage of target edges in brush-like geometry in the course of ELM-like plasma pulses in QSPA Kh-50

NASA Astrophysics Data System (ADS)

Makhlaj, V. A.; Garkusha, I. E.; Aksenov, N. N.; Bazylev, B.; Byrka, O. V.; Chebotarev, V. V.; Landman, I.; Herashchenko, S. S.; Staltsov, V. V.

2015-08-01

Castellated edges of macro-brush armour elements of ITER divertor can be a source of molten/solid dust particles which are injected into the plasma. The targets that combined in brush-like geometry have been irradiated under different inclination angles in QSPA Kh-50. The cubic brushes element has typical size of 1 cm. The titanium was used to investigate dynamics of mountains' formation. The onset of dust particles ejection from the exposed castellated targets has been studied. Formation of resolidified bridges through the gaps of brush-like targets due to the melt motion is studied in dynamics. With following plasma impacts such resolidified bridges became additional source of dust.

Large Area Solid Radiochemistry (LASR) collector at the National Ignition Facility

NASA Astrophysics Data System (ADS)

Waltz, Cory; Gharibyan, Narek; Hardy, Mike; Shaughnessy, Dawn; Jedlovec, Don; Smith, Cal

2017-08-01

The flux of neutrons and charged particles produced from inertial confinement fusion experiments at the National Ignition Facility (NIF) induces measurable concentrations of nuclear reaction products in various target materials. The collection and radiochemical analysis of the post-shot debris can be utilized as an implosion diagnostic to obtain information regarding fuel areal density and ablator-fuel mixing. Furthermore, assessment of the debris from specially designed targets, material doped in capsules or mounted on the external surface of the target assembly, can support experiments relevant to nuclear forensic research. To collect the shot debris, we have deployed the Large Area Solid Radiochemistry Collector (LASR) at NIF. LASR uses a main collector plate that contains a large collection foil with an exposed 20 cm diameter surface located ˜50 cm from the NIF target. This covers ˜0.12 steradians, or about 1% of the total solid angle. We will describe the design, analysis, and operation of this experimental platform as well as the initial results. To speed up the design process 3-dimensional printing was utilized. Design analysis includes the dynamic loading of the NIF target vaporized mass, which was modeled using LS-DYNA.

KENNEDY SPACE CENTER, FLA. - Workers in KSC's Vertical Processing Facility prepare a solid state recorder for installation in a protective enclosure as part of the prelaunch preparations for STS-82, the second Hubble Space Telescope servicing mission. The digital solid state recorder will replace one of three engineering/science tape recorders on Hubble. The solid state recorder has no moving parts to wear out. It also is more flexible than a reel-to-reel recorder and can store 10 times as much data. Liftoff aboard Discovery is targeted Feb. 11 with a crew of seven.

NASA Image and Video Library

1997-01-16

KENNEDY SPACE CENTER, FLA. - Workers in KSC's Vertical Processing Facility prepare a solid state recorder for installation in a protective enclosure as part of the prelaunch preparations for STS-82, the second Hubble Space Telescope servicing mission. The digital solid state recorder will replace one of three engineering/science tape recorders on Hubble. The solid state recorder has no moving parts to wear out. It also is more flexible than a reel-to-reel recorder and can store 10 times as much data. Liftoff aboard Discovery is targeted Feb. 11 with a crew of seven.

KENNEDY SPACE CENTER, FLA. - Workers in KSC's Vertical Processing Facility install a solid state recorder into a transport assembly in its protective enclosure as part of the prelaunch preparations for STS-82, the second Hubble Space Telescope servicing mission. The digital solid state recorder will replace one of three engineering/science tape recorders on Hubble. The solid state recorder has no moving parts to wear out. It also is more flexible than a reel-to-reel recorder and can store 10 times as much data. Liftoff aboard Discovery is targeted Feb. 11 with a crew of seven.

NASA Image and Video Library

1997-01-16

KENNEDY SPACE CENTER, FLA. - Workers in KSC's Vertical Processing Facility install a solid state recorder into a transport assembly in its protective enclosure as part of the prelaunch preparations for STS-82, the second Hubble Space Telescope servicing mission. The digital solid state recorder will replace one of three engineering/science tape recorders on Hubble. The solid state recorder has no moving parts to wear out. It also is more flexible than a reel-to-reel recorder and can store 10 times as much data. Liftoff aboard Discovery is targeted Feb. 11 with a crew of seven.

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

NASA Astrophysics Data System (ADS)

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

2003-05-01

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

The EphA2 Receptor and EphrinA1 Ligand in Solid Tumors: Function and Therapeutic Targeting

PubMed Central

Wykosky, Jill; Debinski, Waldemar

2013-01-01

The Eph receptor tyrosine kinases and ephrin ligands have been studied extensively for their roles in developmental processes. In recent years, Eph receptors and ephrins have been found to be integral players in cancer formation and progression. Among these are EphA2 and ephrinA1, which are involved in the development and maintenance of many different types of solid tumors. The function of EphA2 and ephrinA1 in tumorigenesis and tumor progression is complex and seems to be dependent on cell type and microenvironment. These variables affect the expression of the EphA2 and ephrinA1 proteins, the pathways through which they induce signaling, and the functional consequences of that signaling on the behavior of tumor cells and tumor-associated cells. This review will specifically focus on the roles that EphA2 and ephrinA1 play in the different cell types that contribute to the malignancy of solid tumors, with emphasis on the opportunities for therapeutic targeting. PMID:19074825

Thermal analysis of combinatorial solid geometry models using SINDA

NASA Technical Reports Server (NTRS)

Gerencser, Diane; Radke, George; Introne, Rob; Klosterman, John; Miklosovic, Dave

1993-01-01

Algorithms have been developed using Monte Carlo techniques to determine the thermal network parameters necessary to perform a finite difference analysis on Combinatorial Solid Geometry (CSG) models. Orbital and laser fluxes as well as internal heat generation are modeled to facilitate satellite modeling. The results of the thermal calculations are used to model the infrared (IR) images of targets and assess target vulnerability. Sample analyses and validation are presented which demonstrate code products.

Preparation of Conjugates of Cytotoxic Lupane Triterpenes with Biotin.

PubMed

Soural, Miroslav; Hodon, Jiri; Dickinson, Niall J; Sidova, Veronika; Gurska, Sona; Dzubak, Petr; Hajduch, Marian; Sarek, Jan; Urban, Milan

2015-12-16

To better understand the mechanism of action of antitumor triterpenes, we are developing methods to identify their molecular targets. A promising method is based on combination of quantitative proteomics with SILAC and uses active compounds anchored to magnetic beads via biotin-streptavidin interaction. We developed a simple and fast solid-phase synthetic technique to connect terpenes to biotin through a linker. Betulinic acid was biotinylated from three different conjugation sites for use as a standard validation tool since many molecular targets of this triterpene are already known. Then, a set of four other cytotoxic triterpenoids was biotinylated. Biotinylated terpenes were similarly cytotoxic to their nonbiotinylated parents, which suggests that the target identification should not be influenced by linker or biotin. The developed solid-phase synthetic approach is the first attempt to use solid-phase synthesis to connect active triterpenes to biotin and is applicable as a general procedure for routine conjugation of triterpenes with other molecules of choice.

Interactions between Impacting Particles and Target in Two-Phase Flow

NASA Astrophysics Data System (ADS)

Kang, Sang-Wook; Chow, Tze-Show

1996-11-01

The time-dependent interaction phenomena between a target and the incident solid particles borne by supersonic gas-jet stream have been numerically analyzed. In particular, the analysis dealt with particles such as aluminum, copper, and uranium ipinging on aluminum, copper, or uranium targets at various impact velocities ranging from 200 m/s to 1,000 m/s. Typical particle sizes were 50 to 100 micrometers. Results show considerable deformation of both the incident particles and the target when the velocity is greater than 500 m/s. Experiments performed on copper particles impacting an aluminum target demonstrate that under certain conditions (such as a supersonic gas jet issuing from a nozzle carrying solid particles) the impacts not only deform but also cause deposition of the particles on the surface. The present analysis shows the plausibility of such behavior when the particles impact the target at high velocities.

Distribution of Dechlorinating Bacteria between the Aqueous and Solid Phases

NASA Astrophysics Data System (ADS)

Cápiro, N. L.; Hatt, J. K.; Wang, Y.; Loeffler, F. E.; Pennell, K. D.

2010-12-01

Microbial monitoring of aquifers relies on nucleic acid biomarker analysis, which is typically performed with biomass recovered from groundwater samples; however, it is unclear what fraction of the target population(s) is associated with groundwater (i.e., planktonic cells) or is attached to solid phases (i.e., biofilms). Understanding how the titer of target organism(s) in groundwater correlates with the true cell titers of the target organism in the aquifer (i.e., planktonic plus attached cells) is critical for a meaningful interpretation of the data, the prediction of bioremediation performance, and the implementation of site management strategies. To evaluate the distribution of active cells between resident solid phase and the aqueous phase, one-dimensional columns were packed under water-saturated conditions with Bio-Dechlor INOCULUM, a PCE-to ethene-dechlorinating bacterial consortium containing both multiple Dehalococcoides (Dhc) strains and Geobacter lovleyi strain SZ (GeoSZ). The columns were packed with two distinct solid matrices: a low organic content sandy Federal Fine Ottawa soil or Appling soil with higher organic matter content. Influent reduced mineral salts medium supplied at a groundwater pore-water velocity of 0.3 m/day contained both 10 mM lactate as electron donor and 0.33 mM PCE as electron acceptor. Routine collection of biomass from column side ports and effluent samples measured the titers of target cells in the aqueous phase and determined when steady state conditions had been reached. A second set of column experiments evaluated delivery and filtration effects by the solid matrix (i.e., Federal Fine Ottawa sand versus Appling soil) under the same conditions except that electron donor or acceptor were omitted (no growth conditions). Quantitative real-time PCR (qPCR) analysis using Dhc and GeoSZ 16S rRNA gene-targeted primer and probe sets determined the planktonic cell counts, and destructive sampling of the columns allowed measurement of the total cell titer (i.e., attached plus planktonic cells). The results indicate that within the higher organic matter Appling soil, the fraction of target cells associated with the solid phase was nearly 2-orders of magnitude higher compared to the fraction attached to the aqueous phase. In the sandy soil, differences were approximately 1-order of magnitude. Ongoing efforts use dynamic light scattering and electrophoretic mobility measurements over a range of ionic strengths and pH values to shed light on the parameters that control microbial attachment behavior. Knowledge of factors that affect microbial distribution between aqueous and solid phases is essential for interpreting qPCR data obtained from site groundwater where biological remedies are implemented.

Treating cancer stem cells and cancer metastasis using glucose-coated gold nanoparticles

PubMed Central

Hu, Chenxia; Niestroj, Martin; Yuan, Daniel; Chang, Steven; Chen, Jie

2015-01-01

Cancer ranks among the leading causes of human mortality. Cancer becomes intractable when it spreads from the primary tumor site to various organs (such as bone, lung, liver, and then brain). Unlike solid tumor cells, cancer stem cells and metastatic cancer cells grow in a non-attached (suspension) form when moving from their source to other locations in the body. Due to the non-attached growth nature, metastasis is often first detected in the circulatory systems, for instance in a lymph node near the primary tumor. Cancer research over the past several decades has primarily focused on treating solid tumors, but targeted therapy to treat cancer stem cells and cancer metastasis has yet to be developed. Because cancers undergo faster metabolism and consume more glucose than normal cells, glucose was chosen in this study as a reagent to target cancer cells. In particular, by covalently binding gold nanoparticles (GNPs) with thio-PEG (polyethylene glycol) and thio-glucose, the resulting functionalized GNPs (Glu-GNPs) were created for targeted treatment of cancer metastasis and cancer stem cells. Suspension cancer cell THP-1 (human monocytic cell line derived from acute monocytic leukemia patients) was selected because it has properties similar to cancer stem cells and has been used as a metastatic cancer cell model for in vitro studies. To take advantage of cancer cells’ elevated glucose consumption over normal cells, different starvation periods were screened in order to achieve optimal treatment effects. Cancer cells were then fed using Glu-GNPs followed by X-ray irradiation treatment. For comparison, solid tumor MCF-7 cells (breast cancer cell line) were studied as well. Our irradiation experimental results show that Glu-GNPs are better irradiation sensitizers to treat THP-1 cells than MCF-7 cells, or Glu-GNPs enhance the cancer killing of THP-1 cells 20% more than X-ray irradiation alone and GNP treatment alone. This finding can help oncologists to design therapeutic strategies to target cancer stem cells and cancer metastasis. PMID:25844037

Tailored semiconductors for high-harmonic optoelectronics

NASA Astrophysics Data System (ADS)

Sivis, Murat; Taucer, Marco; Vampa, Giulio; Johnston, Kyle; Staudte, André; Naumov, Andrei Yu.; Villeneuve, D. M.; Ropers, Claus; Corkum, P. B.

2017-07-01

The advent of high-harmonic generation in gases 30 years ago set the foundation for attosecond science and facilitated ultrafast spectroscopy in atoms, molecules, and solids. We explore high-harmonic generation in the solid state by means of nanostructured and ion-implanted semiconductors. We use wavelength-selective microscopic imaging to map enhanced harmonic emission and show that the generation medium and the driving field can be locally tailored in solids by modifying the chemical composition and morphology. This enables the control of high-harmonic technology within precisely engineered solid targets. We demonstrate customized high-harmonic wave fields with wavelengths down to 225 nanometers (ninth-harmonic order of 2-micrometer laser pulses) and present an integrated Fresnel zone plate target in silicon, which leads to diffraction-limited self-focusing of the generated harmonics down to 1-micrometer spot sizes.

Isochoric heating of solid gold targets with the PW-laser-driven ion beams (Conference Presentation)

NASA Astrophysics Data System (ADS)

Steinke, Sven; Ji, Qing; Bulanov, Stepan S.; Barnard, John; Vincenti, Henri; Schenkel, Thomas; Esarey, Eric H.; Leemans, Wim P.

2017-05-01

We present first results on ion acceleration with the BELLA PW laser as well as end-to-end simulation for isochoric heating of solid gold targets using PW-laser generated ion beams: (i) 2D Particle-In-Cell (PIC) simulations are applied to study the ion source characteristics of the PW laser-target interaction at the long focal length (f/65) beamline at laser intensities of ˜[5×10]^19 Wcm-2 at spot size of 0=53 μm on a CH target. (ii) In order to transport the ion beams to an EMP-free environment, an active plasma lens will be used. This was modeled [1] by calculating the Twiss parameters of the ion beam from the appropriate transport matrixes taking the source parameters obtained from the PIC simulation. (iii) Hydrodynamic simulations indicate that these ion beams can isochorically heat a 1 mm3 gold target to the Warm Dense Matter state. Reference: J. van Tilborg et al, Phys. Rev. Lett. 115, 184802 (2015). This work was supported by Laboratory Directed Research and Development (LDRD) funding from Lawrence Berkeley National Laboratory, provided by the Director, Office of Science, of the U.S. Department of Energy under Contract No. DE-AC02-05CH11231.

Preparation and characterisation of isotopically enriched Ta2O5 targets for nuclear astrophysics studies

NASA Astrophysics Data System (ADS)

Caciolli, A.; Scott, D. A.; Di Leva, A.; Formicola, A.; Aliotta, M.; Anders, M.; Bellini, A.; Bemmerer, D.; Broggini, C.; Campeggio, M.; Corvisiero, P.; Depalo, R.; Elekes, Z.; Fülöp, Zs.; Gervino, G.; Guglielmetti, A.; Gustavino, C.; Gyürky, Gy.; Imbriani, G.; Junker, M.; Marta, M.; Menegazzo, R.; Napolitani, E.; Prati, P.; Rigato, V.; Roca, V.; Rolfs, C.; Rossi Alvarez, C.; Somorjai, E.; Salvo, C.; Straniero, O.; Strieder, F.; Szücs, T.; Terrasi, F.; Trautvetter, H. P.; Trezzi, D.

2012-10-01

The direct measurement of reaction cross-sections at astrophysical energies often requires the use of solid targets of known thickness, isotopic composition, and stoichiometry that are able to withstand high beam currents for extended periods of time. Here, we report on the production and characterisation of isotopically enriched Ta2O5 targets for the study of proton-induced reactions at the Laboratory for Underground Nuclear Astrophysics facility of the Laboratori Nazionali del Gran Sasso. The targets were prepared by anodisation of tantalum backings in enriched water (up to 66% in 17O and up to 96% in 18O. Special care was devoted to minimising the presence of any contaminants that could induce unwanted background reactions with the beam in the energy region of astrophysical interest. Results from target characterisation measurements are reported, and the conclusions for proton capture measurements with these targets are drawn.

Quantitative analysis of impact of awareness-raising activities on organic solid waste separation behaviour in Balikpapan City, Indonesia.

PubMed

Murase, Noriaki; Murayama, Takehiko; Nishikizawa, Shigeo; Sato, Yuriko

2017-10-01

Many cities in Indonesia are under pressure to reduce solid waste and dispose of it properly. In response to this pressure, the Japan International Cooperation Agency and the Indonesian Government have implemented a solid waste separation and collection project to reduce solid waste in the target area (810 households) of Balikpapan City. We used a cluster randomised controlled trial method to measure the impact of awareness-raising activities that were introduced by the project on residents' organic solid waste separation behaviour. The level of properly separated organic solid waste increased by 6.0% in areas that conducted awareness-raising activities. Meanwhile, the level decreased by 3.6% in areas that did not conduct similar activities. Therefore, in relative comparison, awareness-raising increased the level by 9.6%. A comparison among small communities in the target area confirmed that awareness-raising activities had a significant impact on organic solid waste separation. High frequencies of monitoring at waste stations and door-to-door visits by community members had a positive impact on organic solid waste separation. A correlation between the proximity of environmental volunteers' houses to waste stations and a high level of separation was also confirmed. The awareness-raising activities introduced by the project led to a significant increase in the separation of organic solid waste.

A phase 1 dose-escalation study of the oral histone deacetylase inhibitor abexinostat in combination with standard hypofractionated radiotherapy in advanced solid tumors

PubMed Central

Deutsch, Eric; Moyal, Elizabeth Cohen-Jonathan; Gregorc, Vanesa; Zucali, Paolo Andrea; Menard, Jean; Soria, Jean-Charles; Kloos, Ioana; Hsu, Jeff; Luan, Ying; Liu, Emily; Vezan, Remus; Graef, Thorsten; Rivera, Sofia

2017-01-01

Current treatments for advanced solid tumors tend to be only palliative. Although radiotherapy is administered with a curative intent, radioresistance and dose-limiting toxicities pose limitations to treatment. Abexinostat, an oral pan-histone deacetylase inhibitor, demonstrated enhanced sensitivity to radiation in various solid tumor cell lines. We conducted an exploratory, phase 1, dose-escalation study of abexinostat in combination with standard hypofractionated radiotherapy in patients with advanced solid tumors treated in a palliative setting. Among 58 treated patients, the median age was 61.5 years (range, 20-82); 47% of the patients had M1 stage disease, and 95% had received previous chemotherapy alone or chemotherapy in combination with surgery and/or radiotherapy. The recommended phase 2 dose was determined to be 90 mg/m2 (140 mg). Of the 51 patients evaluable for response, best overall response was 8% (1 complete response [CR], 3 partial responses [PRs]), and best loco-regional response was 12% (1 CR and 5 PRs) at a median follow-up of 16 weeks. Of note, patients with target or non-target brain lesions showed encouraging responses, with 1 patient achieving a best loco-regional response of CR. Treatment-emergent grade ≥3 adverse events (AEs) were few, with most common being thrombocytopenia (17%), lymphopenia (12%), and hypokalemia (7%). Six patients (10%) discontinued treatment due to AEs. No grade ≥3 prolongation of the QTc interval was observed, with no treatment discontinuations due to this AE. Oral abexinostat combined with radiotherapy was well tolerated in patients with advanced solid tumors. The combination may have potential for treatment of patients with brain lesions. PMID:28915584

Coherent Doppler lidar for automated space vehicle, rendezvous, station-keeping and capture

NASA Technical Reports Server (NTRS)

Dunkin, James A.

1991-01-01

Recent advances in eye-safe, short wavelength solid-state lasers offer real potential for the development of compact, reliable, light-weight, efficient coherent lidar. Laser diode pumping of these devices has been demonstrated, thereby eliminating the need for flash lamp pumping, which has been a major drawback to the use of these lasers in space based applications. Also these lasers now have the frequency stability required to make them useful in coherent lidar, which offers all of the advantages of non-coherent lidar, but with the additional advantage that direct determination of target velocity is possible by measurement of the Doppler shift. By combining the Doppler velocity measurement capability with the inherent high angular resolution and range accuracy of lidar it is possible to construct Doppler images of targets for target motion assessment. A coherent lidar based on a Tm,Ho:YAG 2-micrometer wavelength laser was constructed and successfully field tested on atmospheric targets in 1990. This lidar incorporated an all solid state (laser diode pumped) master oscillator, in conjunction with a flash lamp pumped slave oscillator. Solid-state laser technology is rapidly advancing, and with the advent of high efficiency, high power, semiconductor laser diodes as pump sources, all-solid-state, coherent lidars are a real possibility in the near future. MSFC currently has a feasibility demonstration effort under way which will involve component testing, and preliminary design of an all-solid-state, coherent lidar for automatic rendezvous, and capture. This two year effort, funded by the Director's Discretionary Fund is due for completion in 1992.

A holistic approach for food waste management towards zero-solid disposal and energy/resource recovery.

PubMed

Ma, Yingqun; Yin, Yao; Liu, Yu

2017-03-01

This study developed a holistic approach which was based on the ultra-fast hydrolysis of food waste with the fungal mash rich in various hydrolytic enzymes produced in situ from food waste as well. After the 8-h hydrolytic treatment, the solid residue and liquor were separated. It was found that the produced solid residue can meet all the requirements for biofertilizer in terms of NPK and heavy metal contents, while the separated liquor with high soluble organics concentration was further subject to anaerobic digestion for enhanced biomethane production. The results showed that 0.41kg of biofertilizer with a moisture content of 76.9% and 54.4L of biomethane could be produced from 1kg of food waste. As such, it is expected that this study may lead to the paradigm shift in food waste management with the ultimate target of zero-solid discharge. Copyright © 2016 Elsevier Ltd. All rights reserved.

Unveiling the nucleon tensor charge at Jefferson Lab: A study of the SoLID case

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

Ye, Zhihong; Sato, Nobuo; Allada, Kalyan

2017-01-27

Here, future experiments at the Jefferson Lab 12 GeV upgrade, in particular, the Solenoidal Large Intensity Device (SoLID), aim at a very precise data set in the region where the partonic structure of the nucleon is dominated by the valence quarks. One of the main goals is to constrain the transversity quark distributions. We apply recent theoretical advances of the global QCD extraction of the transversity distributions to study the impact of future experimental data from the SoLID. Especially, we develop a model-independent method based on the hessian matrix analysis that allows to estimate the uncertainties of the transversity quarkmore » distributions and their tensor charge contributions extracted from the pseudo-data for the SoLID. Both u and d-quark transversity distributions are shown to be very well constrained in the kinematical region of the future experiments with the proton and the effective neutron targets.« less

Occurrence of naproxen, ibuprofen, and diclofenac residues in wastewater and river water of KwaZulu-Natal Province in South Africa.

PubMed

Madikizela, Lawrence Mzukisi; Chimuka, Luke

2017-07-01

The present paper reports a detailed study that is based on the monitoring of naproxen, ibuprofen, and diclofenac in Mbokodweni River and wastewater treatment plants (WWTPs) located around the city of Durban in KwaZulu-Natal Province of South Africa. Target compounds were extracted from water samples using a multi-template molecularly imprinted solid-phase extraction prior to separation and quantification on a high-performance liquid chromatography equipped with photo diode array detector. The analytical method yielded the detection limits of 0.15, 1.00, and 0.63 μg/L for naproxen, ibuprofen, and diclofenac, respectively. Solid-phase extraction method was evaluated for its performance using deionized water samples that were spiked with 5 and 50 μg/L of target compounds. Recoveries were greater than 80% for all target compounds with RSD values in the range of 4.1 to 10%. Target compounds were detected in most wastewater and river water samples with ibuprofen being the most frequently detected pharmaceutical. Maximum concentrations detected in river water for naproxen, ibuprofen, and diclofenac were 6.84, 19.2, and 9.69 μg/L, respectively. The concentrations of target compounds found in effluent and river water samples compared well with some studies. The analytical method employed in this work is fast, selective, sensitive, and affordable; therefore, it can be used routinely to evaluate the occurrence of acidic pharmaceuticals in South African water resources.

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

PubMed

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.

Analytical strategies for organic food packaging contaminants.

PubMed

Sanchis, Yovana; Yusà, Vicent; Coscollà, Clara

2017-03-24

In this review, we present current approaches in the analysis of food-packaging contaminants. Gas and liquid chromatography coupled to mass spectrometry detection have been widely used in the analysis of some relevant families of these compounds such as primary aromatic amines, bisphenol A, bisphenol A diglycidyl ether and related compounds, UV-ink photoinitiators, perfluorinated compounds, phthalates and non-intentionally added substances. Main applications for sample treatment and different types of food-contact material migration studies have been also discussed. Pressurized Liquid Extraction, Solid-Phase Microextraction, Focused Ultrasound Solid-Liquid Extraction and Quechers have been mainly used in the extraction of food contact material (FCM) contaminants, due to the trend of minimising solvent consumption, automatization of sample preparation and integration of extraction and clean-up steps. Recent advances in analytical methodologies have allowed unequivocal identification and confirmation of these contaminants using Liquid Chromatography coupled to High Resolution Mass Spectrometry (LC-HRMS) through mass accuracy and isotopic pattern applying. LC-HRMS has been used in the target analysis of primary aromatic amines in different plastic materials, but few studies have been carried out applying this technique in post-target and non-target analysis of FCM contaminants. Copyright © 2017 Elsevier B.V. All rights reserved.

Relative Advantages of Direct and Indirect Drive for an Inertial Fusion Energy Power Plant Driven by a Diode-Pumped Solid-State Laser

NASA Astrophysics Data System (ADS)

Orth, C. D.

2001-03-01

This paper reviews our current understanding of the relative advantages of direct drive (DD) and indirect drive (ID) for a 1 GWe inertial fusion energy (IFE) power plant driven by a diode-pumped solid-state laser (DPSSL). This comparison is motivated by a recent study (1) that shows that the projected cost of electricity (COE) for DD is actually about the same as that for ID even though the target gain for DD can be much larger. We can therefore no longer assume that DD is the ultimate targeting scenario for IFE, and must begin a more rigorous comparison of these two drive options. The comparison begun here shows that ID may actually end up being preferred, but the uncertainties are still rather large.

Observation of LPI Thresholds for the Nike Laser

NASA Astrophysics Data System (ADS)

Weaver, J. L.; Oh, J.; Afeyan, B.; Charbonneau-Lefort, M.; Phillips, L.; Seely, J.; Kehne, D.; Brown, C.; Obenschain, S.; Schmitt, A. J.; Feldman, U.; Holland, G.; Lehmberg, R. H.; McLean, E.; Manka, C.

2008-11-01

The Nike laser is being used to study thresholds for laser plasma instabilities (LPI) at intensities (10^15-10^16 W/cm^2) relevant to advanced implosion designs for direct drive inertial confinement fusion. The combination of short wavelength (248 nm), large bandwidth (1-2 THz), and beam smoothing by induced spatial incoherence available with this krypton-fluoride laser make these experiments unique among current facilities. This talk will present an overview of results with an emphasis on the two-plasmon decay instability (2φp). Measurements of x-rays and emission near ^1/2φo and ^3/2 φo harmonics of the laser wavelength have been collected over a wide range of intensities for both solid and foam targets. Data indicate collective multiple-angle driven excitation compatible with previous observations using solid planar targets.

Immunotherapy Targets in Pediatric Cancer

PubMed Central

Orentas, Rimas J.; Lee, Daniel W.; Mackall, Crystal

2011-01-01

Immunotherapy for cancer has shown increasing success and there is ample evidence to expect that progress gleaned in immune targeting of adult cancers can be translated to pediatric oncology. This manuscript reviews principles that guide selection of targets for immunotherapy of cancer, emphasizing the similarities and distinctions between oncogene-inhibition targets and immune targets. It follows with a detailed review of molecules expressed by pediatric tumors that are already under study as immune targets or are good candidates for future studies of immune targeting. Distinctions are made between cell surface antigens that can be targeted in an MHC independent manner using antibodies, antibody derivatives, or chimeric antigen receptors versus intracellular antigens which must be targeted with MHC restricted T cell therapies. Among the most advanced immune targets for childhood cancer are CD19 and CD22 on hematologic malignancies, GD2 on solid tumors, and NY-ESO-1 expressed by a majority of synovial sarcomas, but several other molecules reviewed here also have properties which suggest that they too could serve as effective targets for immunotherapy of childhood cancer. PMID:22645714

Adoptive therapy with CAR redirected T cells: the challenges in targeting solid tumors.

PubMed

Abken, Hinrich

2015-01-01

Recent spectacular success in the adoptive cell therapy of leukemia and lymphoma with chimeric antigen receptor (CAR)-modified T cells raised the expectations that this therapy may be efficacious in a wide range of cancer entities. The expectations are based on the predefined specificity of CAR T cells by an antibody-derived binding domain that acts independently of the natural T-cell receptor, recognizes targets independently of presentation by the major histocompatibility complex and allows targeting toward virtually any cell surface antigen. We here discuss that targeting CAR T cells toward solid tumors faces certain circumstances critical for the therapeutic success. Targeting tumor stroma and taking advantage of TRUCK cells, in other words, CAR T cells with inducible release of a transgenic payload, are some strategies envisaged to overcome current limitations in the near future.

PREFACE: 1st Tensor Polarized Solid Target Workshop

NASA Astrophysics Data System (ADS)

2014-10-01

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

High energy density physics effects predicted in simulations of the CERN HiRadMat beam-target interaction experiments

NASA Astrophysics Data System (ADS)

Tahir, N. A.; Burkart, F.; Schmidt, R.; Shutov, A.; Wollmann, D.; Piriz, A. R.

2016-12-01

Experiments have been done at the CERN HiRadMat (High Radiation to Materials) facility in which large cylindrical copper targets were irradiated with 440 GeV proton beam generated by the Super Proton Synchrotron (SPS). The primary purpose of these experiments was to confirm the existence of hydrodynamic tunneling of ultra-relativistic protons and their hadronic shower in solid materials, that was predicted by previous numerical simulations. The experimental measurements have shown very good agreement with the simulation results. This provides confidence in our simulations of the interaction of the 7 TeV LHC (Large Hadron Collider) protons and the 50 TeV Future Circular Collider (FCC) protons with solid materials, respectively. This work is important from the machine protection point of view. The numerical simulations have also shown that in the HiRadMat experiments, a significant part of thetarget material is be converted into different phases of High Energy Density (HED) matter, including two-phase solid-liquid mixture, expanded as well as compressed hot liquid phases, two-phase liquid-gas mixture and gaseous state. The HiRadMat facility is therefore a unique ion beam facility worldwide that is currently available for studying the thermophysical properties of HED matter. In the present paper we discuss the numerical simulation results and present a comparison with the experimental measurements.

The new solid target system at UNAM in a self-shielded 11 MeV cyclotron

NASA Astrophysics Data System (ADS)

Zarate-Morales, A.; Gaspar-Carcamo, R. E.; Lopez-Rodriguez, V.; Flores-Moreno, A.; Trejo-Ballado, F.; Avila-Rodriguez, Miguel A.

2012-12-01

A dual beam line (BL) self-shielded RDS 111 cyclotron for radionuclide production was installed at the School of Medicine of the National Autonomous University of Mexico in 2001. One of the BL's was upgraded to Eclipse HP (Siemens) in 2008 and the second BL was recently upgraded (June 2011) to the same version with the option for the irradiation of solid targets for the production of metallic radioisotopes.

The new solid target system at UNAM in a self-shielded 11 MeV cyclotron

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

Zarate-Morales, A.; Gaspar-Carcamo, R. E.; Lopez-Rodriguez, V.

2012-12-19

A dual beam line (BL) self-shielded RDS 111 cyclotron for radionuclide production was installed at the School of Medicine of the National Autonomous University of Mexico in 2001. One of the BL's was upgraded to Eclipse HP (Siemens) in 2008 and the second BL was recently upgraded (June 2011) to the same version with the option for the irradiation of solid targets for the production of metallic radioisotopes.

System study of a diode-pumped solid-state-laser driver for inertial fusion energy

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

Orth, C.D.; Payne, S.A.

The present a conceptual design of a diode-pumped solid-state-laser (DPSSL) driver for an inertial fusion energy (IFE) power plant based on the maximized cost of electricity (COE) as determined in a comprehensive systems study. This study contained extensive detail for all significant DPSSL physics and costs, plus published scaling relationships for the costs of the target chamber and the balance of plant (BOP). Our DPSSL design offers low development cost because it is modular, can be fully tested functionally at reduced scale, and is based on mature solid-state-laser technology. Most of the parameter values that we used are being verifiedmore » by experiments now in progress. Future experiments will address the few issues that remain. As a consequence, the economic and technical risk of our DPSSL driver concept is becoming rather low. Baseline performance at 1 GW{sub e} using a new gain medium [Yb{sup 3+}-doped Sr{sub 5}(PO{sub 4}){sub 3}F or Yb:S-FAP] includes a product of laser efficiency and target gain of {eta}G = 7, and a COE of 8.6 cents/kW{center_dot}h, although values of {eta}G {ge} 11 and COEs {le}6.6 cents/kW{center_dot}h are possible at double the assumed target gain of 76 at 3.7 MJ. We present a summary of our results, discuss why other more-common types of laser media do not perform as well as Yb:S-FAP, and present a simple model that shows where DPSSL development should proceed to reduce projected COEs.« less

Pair production by high intensity picosecond laser interacting with thick solid target at XingGuangIII

NASA Astrophysics Data System (ADS)

Wu, Yuchi; Dong, Kegong; Yan, Yonghong; Zhu, Bin; Zhang, Tiankui; Chen, Jia; Yu, Minghai; Tan, Fang; Wang, Shaoyi; Han, Dan; Lu, Feng; Gu, Yuqiu

2017-06-01

An experiment for pair production by high intensity laser irradiating thick solid targets is present. The experiment used picosecond beam of the XingGuangIII laser facility, with intensities up to several 1019 W/cm2, pulse durations about 0.8 ps and laser energies around 120 J. Pairs were generated from 1 mm-thick tantalum disk targets with different diameters from 1 mm to 10 mm. Energy spectra of hot electron from targetrear surface represent a Maxwellian distribution and obey a scaling of ∼(Iλ2)0.5. Large quantity of positrons were observed at the target rear normal direction with a yield up to 2.8 × 109 e+/sr. Owing to the target rear surface sheath field, the positrons behave as a quasi-monoenergetic beam with peak energy of several MeV. Our experiment shows that the peak energy of positron beam is inversely proportional to the target diameter.

The use of a proteinaceous "cushion" with a polystyrene-binding peptide tag to control the orientation and function of a target peptide adsorbed to a hydrophilic polystyrene surface.

PubMed

Imanaka, Hiroyuki; Yamadzumi, Daisuke; Yanagita, Keisuke; Ishida, Naoyuki; Nakanishi, Kazuhiro; Imamura, Koreyoshi

2016-03-01

In immobilizing target biomolecules on a solid surface, it is essential (i) to orient the target moiety in a preferred direction and (ii) to avoid unwanted interactions of the target moiety including with the solid surface. The preferred orientation of the target moiety can be achieved by genetic conjugation of an affinity peptide tag specific to the immobilization surface. Herein, we report on a strategy for reducing the extent of direct interaction between the target moiety and surface in the immobilization of hexahistidine peptide (6His) and green fluorescent protein (GFP) on a hydrophilic polystyrene (PS) surface: Ribonuclease HII from Thermococcus kodakaraensis (cHII) was genetically inserted as a "cushion" between the PS-affinity peptide tag and target moiety. The insertion of a cushion protein resulted in a considerably stronger immobilization of target biomolecules compared to conjugation with only a PS affinity peptide tag, resulting in a substantially enhanced accessibility of the detection antibody to the target 6His peptide. The fluorescent intensity of the GFP moiety was decreased by approximately 30% as the result of fusion with cHII and the PS-affinity peptide tag but was fully retained in the immobilization on the PS surface irrespective of the increased binding force. Furthermore, the fusion of cHII did not impair the stability of the target GFP moiety. Accordingly, the use of a proteinaceous cushion appears to be promising for the immobilization of functional biomolecules on a solid surface. © 2016 American Institute of Chemical Engineers Biotechnol. Prog., 32:527-534, 2016. © 2016 American Institute of Chemical Engineers.

Systematic Approach for the Formulation and Optimization of Solid Lipid Nanoparticles of Efavirenz by High Pressure Homogenization Using Design of Experiments for Brain Targeting and Enhanced Bioavailability

PubMed Central

Gupta, Shweta; Kesarla, Rajesh; Chotai, Narendra; Misra, Ambikanandan

2017-01-01

The nonnucleoside reverse transcriptase inhibitors, used for the treatment of HIV infections, are reported to have low bioavailability pertaining to high first-pass metabolism, high protein binding, and enzymatic metabolism. They also show low permeability across blood brain barrier. The CNS is reported to be the most important HIV reservoir site. In the present study, solid lipid nanoparticles of efavirenz were prepared with the objective of providing increased permeability and protection of drug due to biocompatible lipidic content and nanoscale size and thus developing formulation having potential for enhanced bioavailability and brain targeting. Solid lipid nanoparticles were prepared by high pressure homogenization technique using a systematic approach of design of experiments (DoE) and evaluated for particle size, polydispersity index, zeta potential, and entrapment efficiency. Particles of average size 108.5 nm having PDI of 0.172 with 64.9% entrapment efficiency were produced. Zeta potential was found to be −21.2 mV and the formulation was found stable. The in-vivo pharmacokinetic studies revealed increased concentration of the drug in brain, as desired, when administered through intranasal route indicating its potential for an attempt towards complete eradication of HIV and cure of HIV-infected patients. PMID:28243600

Safety and Efficacy in Advanced Solid Tumors of a Targeted Nanocomplex Carrying the p53 Gene Used in Combination with Docetaxel: A Phase 1b Study

PubMed Central

Pirollo, Kathleen F; Nemunaitis, John; Leung, Po Ki; Nunan, Robert; Adams, Jana; Chang, Esther H

2016-01-01

Loss of p53 suppressor function, through mutations or inactivation of the p53 pathway, occurs in most human cancers. SGT-53 is a liposomal nanocomplex designed for systemic, tumor-targeting delivery of the wt p53 gene. In this nanodelivery system, an anti-transferrin receptor single-chain antibody fragment serves as the targeting moiety. In an initial phase 1 trial in patients with advanced solid tumors, SGT-53 demonstrated tumor-specific targeting, was shown to be well tolerated, and was associated with an antitumor effect in several patients. Our preclinical studies have also demonstrated enhanced antitumor activity with the combination of SGT-53 and docetaxel. Thus, this dose-escalation trial was undertaken to assess the combination of SGT-53 and docetaxel for safety and potential efficacy in 14 advanced cancer patients. Results reveal that the combination of SGT-53 (maximum dose, 3.6 mg DNA/infusion) and docetaxel (75 mg/m2/infusion) was well tolerated. Moreover, clinical activity involving 12 evaluable patients was observed. Three of these patients achieved RECIST-verified partial responses with tumor reductions of −47%, −51%, and −79%. Two others had stable disease with significant shrinkage (−25% and −16%). These results support phase 2 testing of SGT-53 in combination with docetaxel. PMID:27357628

Targeted drug delivery to circulating tumor cells via platelet membrane-functionalized particles

PubMed Central

Li, Jiahe; Ai, Yiwei; Wang, Lihua; Bu, Pengcheng; Sharkey, Charles C.; Wu, Qianhui; Wun, Brittany; Roy, Sweta; Shen, Xiling; King, Michael R.

2015-01-01

Circulating tumor cells (CTCs) are responsible for metastases in distant organs via hematogenous dissemination. Fundamental studies in the past decade have suggested that neutralization of CTCs in circulation could represent an effective strategy to prevent metastasis. Current paradigms of targeted drug delivery into a solid tumor largely fall into two main categories: unique cancer markers (e.g. overexpression of surface receptors) and tumor-specific microenvironment (e.g. low pH, hypoxia, etc.). While relying on a surface receptor to target CTCs can be greatly challenged by cancer heterogeneity, targeting of tumor microenvironments has the advantage of recognizing a broader spectrum of cancer cells regardless of genetic differences or tumor types. The blood circulation, however, where CTCs transit through, lacks the same tumor microenvironment as that found in a solid tumor. In this study, a unique “microenvironment” was confirmed upon introduction of cancer cells of different types into circulation where activated platelets and fibrin were physically associated with blood-borne cancer cells. Inspired by this observation, synthetic silica particles were functionalized with activated platelet membrane along with surface conjugation of tumor-specific apoptosis-inducing ligand cytokine, TRAIL. Biomimetic synthetic particles incorporated into CTC-associated micro-thrombi in lung vasculature and dramatically decreased lung metastases in a mouse breast cancer metastasis model. Our results demonstrate a “Trojan Horse” strategy of neutralizing CTCs to attenuate metastasis. PMID:26519648

Adoptive transfer of autologous, HER2-specific, cytotoxic T lymphocytes for the treatment of HER2-overexpressing breast cancer.

PubMed

Bernhard, Helga; Neudorfer, Julia; Gebhard, Kerstin; Conrad, Heinke; Hermann, Christine; Nährig, Jörg; Fend, Falko; Weber, Wolfgang; Busch, Dirk H; Peschel, Christian

2008-02-01

The human epidermal growth factor receptor 2 (HER2) has been targeted as a breast cancer-associated antigen by immunotherapeutical approaches based on HER2-directed monoclonal antibodies and cancer vaccines. We describe the adoptive transfer of autologous HER2-specific T-lymphocyte clones to a patient with metastatic HER2-overexpressing breast cancer. The HLA/multimer-based monitoring of the transferred T lymphocytes revealed that the T cells rapidly disappeared from the peripheral blood. The imaging studies indicated that the T cells accumulated in the bone marrow (BM) and migrated to the liver, but were unable to penetrate into the solid metastases. The disseminated tumor cells in the BM disappeared after the completion of adoptive T-cell therapy. This study suggests the therapeutic potential for HER2-specific T cells for eliminating disseminated HER2-positive tumor cells and proposes the combination of T cell-based therapies with strategies targeting the tumor stroma to improve T-cell infiltration into solid tumors.

MACC1 - a novel target for solid cancers.

PubMed

Stein, Ulrike

2013-09-01

The metastatic dissemination of primary tumors is directly linked to patient survival in many tumor entities. The previously undescribed gene metastasis-associated in colon cancer 1 (MACC1) was discovered by genome-wide analyses in colorectal cancer (CRC) tissues. MACC1 is a tumor stage-independent predictor for CRC metastasis linked to metastasis-free survival. In this review, the discovery of MACC1 is briefly presented. In the following, the overwhelming confirmation of these data is provided supporting MACC1 as a new remarkable biomarker for disease prognosis and prediction of therapy response for CRC and also for a variety of additional forms of solid cancers. Lastly, the potential clinical utility of MACC1 as a target for prevention or restriction of tumor progression and metastasis is envisioned. MACC1 has been identified as a prognostic biomarker in a variety of solid cancers. MACC1 correlated with tumor formation and progression, development of metastases and patient survival representing a decisive driver for tumorigenesis and metastasis. MACC1 was also demonstrated to be of predictive value for therapy response. MACC1 is a promising therapeutic target for anti-tumor and anti-metastatic intervention strategies of solid cancers. Its clinical utility, however, must be demonstrated in clinical trials.

Off-target Effects in CRISPR/Cas9-mediated Genome Engineering

PubMed Central

Zhang, Xiao-Hui; Tee, Louis Y; Wang, Xiao-Gang; Huang, Qun-Shan; Yang, Shi-Hua

2015-01-01

CRISPR/Cas9 is a versatile genome-editing technology that is widely used for studying the functionality of genetic elements, creating genetically modified organisms as well as preclinical research of genetic disorders. However, the high frequency of off-target activity (≥50%)—RGEN (RNA-guided endonuclease)-induced mutations at sites other than the intended on-target site—is one major concern, especially for therapeutic and clinical applications. Here, we review the basic mechanisms underlying off-target cutting in the CRISPR/Cas9 system, methods for detecting off-target mutations, and strategies for minimizing off-target cleavage. The improvement off-target specificity in the CRISPR/Cas9 system will provide solid genotype–phenotype correlations, and thus enable faithful interpretation of genome-editing data, which will certainly facilitate the basic and clinical application of this technology. PMID:26575098

Laser ablated hydantoin: A high resolution rotational study.

PubMed

Alonso, Elena R; Kolesniková, Lucie; Alonso, José L

2017-09-28

Laser ablation techniques coupled with broadband and narrowband Fourier transform microwave spectroscopies have allowed the high resolution rotational study of solid hydantoin, an important target in astrochemistry as a possible precursor of glycine. The complicated hyperfine structure arising from the presence of two 14 N nuclei in non-equivalent positions has been resolved and interpreted in terms of the nuclear quadrupole coupling interactions. The results reported in this work provide a solid base for the interstellar searches of hydantoin in the astrophysical surveys. The values of the nuclear quadrupole coupling constants have been also discussed in terms of the electronic environment around the respective nitrogen atom.

Influence of Solid Target Reflectivity and Incident Angle on Depolarization Ratio and Reflected Energy from Polarized Lights: Experimental Results of the May 2008 Field Trial

DTIC Science & Technology

2009-11-01

enviromental targets . . . . . . . . . . . . 45 Figure 25: Relative reectivity of environmental targets . . . . . . . . . . . . 46 Figure 26: Relationship...Environmental targets and position of the center . . . . . . . . . . 41 Table 11: Depolarization ratio of enviromental targets...42 Table 12: Relative reectivity results of enviromental targets . . . . . . . . . 42 Table 13: Sand papers and position of the center

Construction of ultrasonic nanobubbles carrying CAIX polypeptides to target carcinoma cells derived from various organs.

PubMed

Zhu, Lianhua; Guo, Yanli; Wang, Luofu; Fan, Xiaozhou; Xiong, Xingyu; Fang, Kejing; Xu, Dan

2017-09-29

Ultrasound molecular imaging is a novel diagnostic approach for tumors, whose key link is the construction of targeted ultrasound contrast agents. However, available targeted ultrasound contrast agents for molecular imaging of tumors are only achieving imaging in blood pool or one type tumor. No targeted ultrasound contrast agents have realized targeted ultrasound molecular imaging of tumor parenchymal cells in a variety of solid tumors so far. Carbonic anhydrase IX (CAIX) is highly expressed on cell membranes of various malignant solid tumors, so it's a good target for ultrasound molecular imaging. Here, targeted nanobubbles carrying CAIX polypeptides for targeted binding to a variety of malignant tumors were constructed, and targeted binding ability and ultrasound imaging effect in different types of tumors were evaluated. The mean diameter of lipid targeted nanobubbles was (503.7 ± 78.47) nm, and the polypeptides evenly distributed on the surfaces of targeted nanobubbles, which possessed the advantages of homogenous particle size, high stability, and good safety. Targeted nanobubbles could gather around CAIX-positive cells (786-O and Hela cells), while they cannot gather around CAIX-negative cells (BxPC-3 cells) in vitro, and the affinity of targeted nanobubbles to CAIX-positive cells were significantly higher than that to CAIX-negative cells (P < 0.05). Peak intensity and duration time of targeted nanobubbles and blank nanobubbles were different in CAIX-positive transplanted tumor tissues in vivo (P < 0.05). Moreover, targeted nanobubbles in CAIX-positive transplanted tumor tissues produced higher peak intensity and longer duration time than those in CAIX-negative transplanted tumor tissues (P < 0.05). Finally, immunofluorescence not only confirmed targeted nanobubbles could pass through blood vessels to enter in tumor tissue spaces, but also clarified imaging differences of targeted nanobubbles in different types of transplanted tumor tissues. Targeted nanobubbles carrying CAIX polypeptides can specifically enhance ultrasound imaging in CAIX-positive transplanted tumor tissues and could potentially be used in early diagnosis of a variety of solid tumors derived from various organs.

Calculations of high-power production target and beamdump for the GSI future Super-FRS for a fast extraction scheme at the FAIR Facility

NASA Astrophysics Data System (ADS)

Tahir, N. A.; Weick, H.; Iwase, H.; Geissel, H.; Hoffmann, D. H. H.; Kindler, B.; Lommel, B.; Radon, T.; Münzenberg, G.; Shutov, A.; Sümmerer, K.; Winkler, M.

2005-06-01

A superconducting fragment separator (Super-FRS) is being designed for the production and separation of radioactive isotopes at the future FAIR (Facility for Antiprotons and Ion Research) facility at Darmstadt. This paper discusses various aspects and requirements for the high-power production target that will be used in the Super-FRS experiments. The production target must survive over an extended period of time as it will be used during the course of many experiments. The specific power deposited by the high intensity beam that will be generated at the future FAIR facility will be high enough to destroy the target in most of the cases as a result of a single shot from the new heavy ion synchrotrons SIS100/300. By using an appropriate beam intensity and focal spot parameters, the target would survive after being irradiated once. However, the heat should be dissipated efficiently before the same target area is irradiated again. We have considered a wheel shaped solid carbon target that rotates around its axis so that different areas of the target are irradiated successively. This allows for cooling of the beam heated region by thermal conduction before the same part of the target is irradiated a second time. Another attractive option is to use a liquid jet target at the Super-FRS. First calculations of a possible liquid lithium target are also presented in this paper. One of the advantages of using lithium as a target is that it will survive even if one uses a smaller focal spot, which has half the area of that used for a solid carbon target. This will significantly improve the isotope resolution. A similar problem associated with these experiments will be safe deposition of the beam energy in a beamdump after its interaction with the production target. We also present calculations to study the suitability of a proposed beamdump.

Implementation of a solid target production facility

NASA Astrophysics Data System (ADS)

Tochon-Danguy, H. J.; Poniger, S. S.; Sachinidis, J. I.; Panopoulos, H. P.; Scott, A. M.

2012-12-01

The desire to utilize long-lived PET isotopes in Australia has significantly increased over the years and several research projects for labelling of peptides, proteins and biomolecules, including labelling of recombinant antibodies has been restricted due to the limited availability of suitable isotopes. This need has led to the recent installation and commissioning of a new facility dedicated to fully automated solid target isotope production, including 24I, 64Cu, 89Zr and 86Y at the Austin Health Centre for PET.

Ultra-intense laser interaction with specially-designed targets as a source of energetic protons

NASA Astrophysics Data System (ADS)

Psikal, J.; Matys, M.

2017-05-01

In this contribution, we discuss the optimization of laser driven proton acceleration efficiency by nanostructured targets, interpret the experimental results showing the manipulation of proton beam profiles by nanosctructured rear surface of the targets and investigate the acceleration of protons from hydrogen solid ribbon by PW-class lasers, with the help of multidimensional particle-in-cell simulations. Microstructured hollow targets are proposed to enhance the absorption of the laser pulse energy while keeping the target thickness to minimum, which is both favorable for enhanced efficiency of the acceleration of protons. Thin targets with grating structures of various configurations on their rear sides stretch the proton beams in the perpendicular direction to the grating orientation due to transverse electric fields generated inside the target grooves and can reduce the proton beam divergence in the parallel direction to the grating due to a lower density of the stretched beam compared with flat foils. Finally, it is shown that when multiPW laser pulse interacts with hydrogen solid ribbon, hole boring radiation pressure acceleration (RPA) dominates over the target normal sheath acceleration (TNSA).

Simultaneous Determination of Perfluorinated Compounds in Edible Oil by Gel-Permeation Chromatography Combined with Dispersive Solid-Phase Extraction and Liquid Chromatography-Tandem Mass Spectrometry.

PubMed

Yang, Lili; Jin, Fen; Zhang, Peng; Zhang, Yanxin; Wang, Jian; Shao, Hua; Jin, Maojun; Wang, Shanshan; Zheng, Lufei; Wang, Jing

2015-09-30

A simple analytical method was developed for the simultaneous analysis of 18 perfluorinated compounds (PFCs) in edible oil. The target compounds were extracted by acetonitrile, purified by gel permeation chromatography (GPC) and dispersive solid-phase extraction (DSPE) using graphitized carbon black (GCB) and octadecyl (C18), and analyzed by liquid chromatography-electrospray ionization tandem mass spectrometry (LC-ES-MS/MS) in negative ion mode. Recovery studies were performed at three fortification levels. The average recoveries of all target PFCs ranged from 60 to 129%, with an acceptable relative standard deviation (RSD) (1-20%, n = 3). The method detection limits (MDLs) ranged from 0.004 to 0.4 μg/kg, which was significantly improved compared with the existing liquid-liquid extraction and cleanup method. The method was successfully applied for the analysis of all target PFCs in edible oil samples collected from markets in Beijing, China, and the results revealed that C6-C10 perfluorocarboxylic acid (PFCAs) and C7 perfluorosulfonic acid PFSAs were the major PFCs detected in oil samples.

Solid-phase-assisted synthesis of targeting peptide-PEG-oligo(ethane amino)amides for receptor-mediated gene delivery.

PubMed

Martin, Irene; Dohmen, Christian; Mas-Moruno, Carlos; Troiber, Christina; Kos, Petra; Schaffert, David; Lächelt, Ulrich; Teixidó, Meritxell; Günther, Michael; Kessler, Horst; Giralt, Ernest; Wagner, Ernst

2012-04-28

In the forthcoming era of cancer gene therapy, efforts will be devoted to the development of new efficient and non-toxic gene delivery vectors. In this regard, the use of Fmoc/Boc-protected oligo(ethane amino)acids as building blocks for solid-phase-supported assembly represents a novel promising approach towards fully controlled syntheses of effective gene vectors. Here we report on the synthesis of defined polymers containing the following: (i) a plasmid DNA (pDNA) binding domain of eight succinoyl-tetraethylenpentamine (Stp) units and two terminal cysteine residues; (ii) a central polyethylene glycol (PEG) chain (with twenty-four oxyethylene units) for shielding; and (iii) specific peptides for targeting towards cancer cells. Peptides B6 and c(RGDfK), which bind transferrin receptor and α(v)β(3) integrin, respectively, were chosen because of the high expression of these receptors in many tumoral cells. This study shows the feasibility of designing these kinds of fully controlled vectors and their success for targeted pDNA-based gene transfer. This journal is © The Royal Society of Chemistry 2012

JAERI R & D on accelerator-based transmutation under OMEGA program

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

Takizuka, T.; Nishida, T.; Mizumoto, M.

1995-10-01

The overview of the Japanese long-term research and development program on nuclide partitioning and transmutation, called {open_quotes}OMEGA,{close_quotes} is presented. Under this national program, major R&D activities are being carried out at JAERI, PNC, and CRIEPI. Accelerator-based transmutation study at JAERI is focused on a dedicated transmutor with a subcritical actinide-fueled subcritical core coupled with a spallation target driven by a high intensity proton accelerator. Two types of system concept, solid system and molten-salt system, are discussed. The solid system consists of sodium-cooled tungsten target and metallic actinide fuel. The molten-salt system is fueled with molten actinide chloride that acts alsomore » as a target material. The proposed plant transmutes about 250 kg of minor actinide per year, and generates enough electricity to power its own accelerator. JAERI is proposing the development of an intense proton linear accelerator ETA with 1.5 GeV-10 mA beam for engineering tests of accelerator-based transmutation. Recent achievements in the accelerator development are described.« less

The use of real-time PCR to study Penicillium chrysogenum growth kinetics on solid food at different water activities.

PubMed

Arquiza, J M R Apollo; Hunter, Jean

2014-09-18

Fungal growth on solid foods can make them unfit for human consumption, but certain specialty foods require fungi to produce their characteristic properties. In either case, a reliable way of measuring biomass is needed to study how various factors (e.g. water activity) affect fungal growth rates on these substrates. Biochemical markers such as chitin, glucosamine or ergosterol have been used to estimate fungal growth, but they cannot distinguish between individual species in mixed culture. In this study, a real-time polymerase chain reaction (rt-PCR) protocol specific for a target fungal species was used to quantify its DNA while growing on solid food. The measured amount of DNA was then related to the biomass present using an experimentally determined DNA-to-biomass ratio. The highly sensitive rt-PCR biomass assay was found to have a wide range, able to quantify the target DNA within a six orders-of-magnitude difference. The method was used to monitor germination and growth of Penicillium chrysogenum spores on a model porous food (cooked wheat flour) at 25°C and different water activities of 0.973, 0.936, and 0.843. No growth was observed at 0.843, but lag, exponential and stationary phases were identified in the growth curves for the higher water activities. The calculated specific growth rates (μ) during the exponential phase were almost identical, at 0.075/h and 0.076/h for aw=0.973 and 0.936, respectively. The specificity of the method was demonstrated by measuring the biomass of P. chrysogenum while growing together with Aspergillus niger on solid media at aw=0.973. Copyright © 2014 Elsevier B.V. All rights reserved.

Novel cryogenic sources for liquid droplet and solid filament beams

NASA Astrophysics Data System (ADS)

Grams, Michael P.

Two novel atomic and molecular beam sources have been created and tested consisting first of a superfluid helium liquid jet, and secondly a solid filament of argon. The superfluid helium apparatus is the second of its kind in the world and uses a modified liquid helium cryostat to inject a cylindrical stream of superfluid helium into vacuum through glass capillary nozzles with diameters on the order of one micron created on-site at Arizona State University. The superfluid beam is an entirely new way to study superfluid behavior, and has many new applications such as superfluid beam-surface scattering, beam-beam scattering, and boundary-free study of superfluidity. The solid beam of argon is another novel beam source created by flowing argon gas through a capillary 50 microns in diameter which is clamped by a small copper plate to a copper block kept at liquid nitrogen temperature. The gas subsequently cools and solidifies plugging the capillary. Upon heating, the solid plug melts and liquid argon exits the capillary and immediately freezes by evaporative cooling. The solid filaments may find application as wall-less cryogenic matrices, or targets for laser plasma sources of extreme UV and soft x-ray sources.

A First-Time-In-Human Phase I Clinical Trial of Bispecific Antibody-Targeted, Paclitaxel-Packaged Bacterial Minicells

PubMed Central

Rosenthal, Mark; McArthur, Grant A.; Pattison, Scott T.; Pattison, Stacey L.; MacDiarmid, Jennifer; Brahmbhatt, Himanshu; Scott, Andrew M.

2015-01-01

Background We have harnessed a novel biological system, the bacterial minicell, to deliver cancer therapeutics to cancer cells. Preclinical studies showed that epidermal growth factor receptor (EGFR)-targeted, paclitaxel-loaded minicells (EGFRminicellsPac) have antitumor effects in xenograft models. To examine the safety of the minicell delivery system, we initiated a first-time-in-human, open-label, phase I clinical study of EGFRminicellsPac in patients with advanced solid tumors. Methodology Patients received 5 weekly infusions followed by a treatment free week. Seven dose levels (1x108, 1x109, 3x109, 1x1010, 1.5x1010, 2x1010, 5x1010) were evaluated using a 3+3 dose-escalation design. Primary objectives were safety, tolerability and determination of the maximum tolerated dose. Secondary objectives were assessment of immune/inflammatory responses and antitumor activity. Principal Findings Twenty eight patients were enrolled, 22 patients completed at least one cycle of EGFRminicellsPac; 6 patients did not complete a cycle due to rapidly progressive disease. A total of 236 doses was delivered over 42 cycles, with a maximum of 45 doses administered to a single patient. Most common treatment-related adverse events were rigors and pyrexia. No deaths resulted from treatment-related adverse events and the maximum tolerated dose was defined as 1x1010 EGFRminicellsPac. Surprisingly, only a mild self-limiting elevation in the inflammatory cytokines IL-6, IL-8 and TNFα and anti-inflammatory IL-10 was observed. Anti-LPS antibody titers peaked by dose 3 and were maintained at that level despite repeat dosing with the bacterially derived minicells. Ten patients (45%; n = 22) achieved stable disease as their best response. Conclusions/Significance This is the first study in humans of a novel biological system that can provide targeted delivery of a range of chemotherapeutic drugs to solid tumor cells. Bispecific antibody-targeted minicells, packaged with the chemotherapeutic paclitaxel, were shown to be safe in patients with advanced solid tumors with modest clinical efficacy observed. Further study in Phase II trials is planned. Trial Registration Australian New Zealand Clinical Trials Registry ACTRN12609000672257 PMID:26659127

Thermal hydraulic design and decay heat removal of a solid target for a spallation neutron source

NASA Astrophysics Data System (ADS)

Takenaka, N.; Nio, D.; Kiyanagi, Y.; Mishima, K.; Kawai, M.; Furusaka, M.

2005-08-01

Thermal hydraulic design and thermal stress calculations were conducted for a water-cooled solid target irradiated by a MW-class proton beam for a spallation neutron source. Plate type and rod bundle type targets were examined. The thickness of the plate and the diameter of the rod were determined based on the maximum and the wall surface temperature. The thermal stress distributions were calculated by a finite element method (FEM). The neutronics performance of the target is roughly proportional to its average density. The averaged densities of the designed targets were calculated for tungsten plates, tantalum clad tungsten plates, tungsten rods sheathed by tantalum and Zircaloy and they were compared with mercury density. It was shown that the averaged density was highest for the tungsten plates and was high for the tantalum cladding tungsten plates, the tungsten rods sheathed by tantalum and Zircaloy in order. They were higher than or equal to that of mercury for the 1 2 MW proton beams. Tungsten target without the cladding or the sheath is not practical due to corrosion by water under irradiation condition. Therefore, the tantalum cladding tungsten plate already made successfully by HIP and the sheathed tungsten rod are the candidate of high performance solid targets. The decay heat of each target was calculated. It was low enough low compared to that of ISIS for the target without tantalum but was about four times as high as that of ISIS when the thickness of the tantalum cladding was 0.5 mm. Heat removal methods of the decay heat with tantalum were examined. It was shown that a special cooling system was required for the target exchange when tantalum was used for the target. It was concluded that the tungsten rod target sheathed with stainless steel or Zircaloy was the most reliable from the safety considerations and had similar neutronics performance to that of mercury.

The use of solid lipid nanoparticles to target a lipophilic molecule to the liver after intravenous administration to mice.

PubMed

Lu, Wen; He, Lang Chong; Wang, Chang He; Li, Yan Hua; Zhang, San Qi

2008-10-01

Taspine solid lipid nanoparticles (Ta-SLN) and taspine solid lipid nanoparticles modified by galactoside (Ta-G2SLN) were prepared by the film evaporation-extrusion method. The nanoparticles were spherical or near-spherical particles with smooth surface, small size and high encapsulation efficiency. Ta-G2SLN and Ta-SLN showed significant inhibition on 7721 cell growth. Intravenous injection of either Ta-SLN or Ta-G2SLN resulted in a higher plasma and liver concentration and a longer retention time in mice compared with the administration of Ta. These results suggested that SLN tended to be preferentially delivered to the liver and Ta-G2SLN may further enhance liver targeting.

Detection and isolation of nucleic acid sequences using competitive hybridization probes

DOEpatents

Lucas, Joe N.; Straume, Tore; Bogen, Kenneth T.

1997-01-01

A method for detecting a target nucleic acid sequence in a sample is provided using hybridization probes which competitively hybridize to a target nucleic acid. According to the method, a target nucleic acid sequence is hybridized to first and second hybridization probes which are complementary to overlapping portions of the target nucleic acid sequence, the first hybridization probe including a first complexing agent capable of forming a binding pair with a second complexing agent and the second hybridization probe including a detectable marker. The first complexing agent attached to the first hybridization probe is contacted with a second complexing agent, the second complexing agent being attached to a solid support such that when the first and second complexing agents are attached, target nucleic acid sequences hybridized to the first hybridization probe become immobilized on to the solid support. The immobilized target nucleic acids are then separated and detected by detecting the detectable marker attached to the second hybridization probe. A kit for performing the method is also provided.

Nucleic Acid Detection Methods

DOEpatents

Smith, Cassandra L.; Yaar, Ron; Szafranski, Przemyslaw; Cantor, Charles R.

1998-05-19

The invention relates to methods for rapidly determining the sequence and/or length a target sequence. The target sequence may be a series of known or unknown repeat sequences which are hybridized to an array of probes. The hybridized array is digested with a single-strand nuclease and free 3'-hydroxyl groups extended with a nucleic acid polymerase. Nuclease cleaved heteroduplexes can be easily distinguish from nuclease uncleaved heteroduplexes by differential labeling. Probes and target can be differentially labeled with detectable labels. Matched target can be detected by cleaving resulting loops from the hybridized target and creating free 3-hydroxyl groups. These groups are recognized and extended by polymerases added into the reaction system which also adds or releases one label into solution. Analysis of the resulting products using either solid phase or solution. These methods can be used to detect characteristic nucleic acid sequences, to determine target sequence and to screen for genetic defects and disorders. Assays can be conducted on solid surfaces allowing for multiple reactions to be conducted in parallel and, if desired, automated.

Detection and isolation of nucleic acid sequences using competitive hybridization probes

DOEpatents

Lucas, J.N.; Straume, T.; Bogen, K.T.

1997-04-01

A method for detecting a target nucleic acid sequence in a sample is provided using hybridization probes which competitively hybridize to a target nucleic acid. According to the method, a target nucleic acid sequence is hybridized to first and second hybridization probes which are complementary to overlapping portions of the target nucleic acid sequence, the first hybridization probe including a first complexing agent capable of forming a binding pair with a second complexing agent and the second hybridization probe including a detectable marker. The first complexing agent attached to the first hybridization probe is contacted with a second complexing agent, the second complexing agent being attached to a solid support such that when the first and second complexing agents are attached, target nucleic acid sequences hybridized to the first hybridization probe become immobilized on to the solid support. The immobilized target nucleic acids are then separated and detected by detecting the detectable marker attached to the second hybridization probe. A kit for performing the method is also provided. 7 figs.

Design of a liquid membrane target for high repetition rate neutron generation

NASA Astrophysics Data System (ADS)

Poole, Patrick; Andereck, C. David; Storm, Mike; Schumacher, Douglass

2013-10-01

Ultra-bright, pulsed, spatially-small sources of energetic neutrons have applications in radiography and non-destructive remote sensing. Neutrons can be generated by a process wherein ions accelerated from a laser-irradiated primary target subsequently bombard a converter material, causing neutron-producing nuclear reactions, such as 7Li(d,n)8Be. Deuterons from this process are suppressed by contamination that builds up on the rear of the solid primary target. To eliminate this issue we propose a self-replenishing liquid membrane target consisting of heavy water and deuterated surfactant, formed in-vacuum within a moveable wire frame. In addition to removing issues associated with solid target positioning and collateral damage, this apparatus provides flow rate and target thickness control, and allows for the high repetition rates required to generate desired neutron fluxes with a portable laser-based system. The apparatus design will be presented, as well as a novel interferometric method that measures the membrane thickness using tightly-focused light. This work was performed with support from DARPA.

Solid-state Marx based two-switch voltage modulator for the On-Line Isotope Mass Separator accelerator at the European Organization for Nuclear Research

NASA Astrophysics Data System (ADS)

Redondo, L. M.; Silva, J. Fernando; Canacsinh, H.; Ferrão, N.; Mendes, C.; Soares, R.; Schipper, J.; Fowler, A.

2010-07-01

A new circuit topology is proposed to replace the actual pulse transformer and thyratron based resonant modulator that supplies the 60 kV target potential for the ion acceleration of the On-Line Isotope Mass Separator accelerator, the stability of which is critical for the mass resolution downstream separator, at the European Organization for Nuclear Research. The improved modulator uses two solid-state switches working together, each one based on the Marx generator concept, operating as series and parallel switches, reducing the stress on the series stacked semiconductors, and also as auxiliary pulse generator in order to fulfill the target requirements. Preliminary results of a 10 kV prototype, using 1200 V insulated gate bipolar transistors and capacitors in the solid-state Marx circuits, ten stages each, with an electrical equivalent circuit of the target, are presented, demonstrating both the improved voltage stability and pulse flexibility potential wanted for this new modulator.

Co-Targeting HER2 and EphB4 Pathways

DTIC Science & Technology

2013-09-01

soluble EphB4 decoy receptor that efficiently blocks EphB4/EphB2 signaling. A phase I study for solid tumors using this agent given intravenously...June 2013 3 . DATES COVERED 4. TITLE AND SUBTITLE Co-Targeting HER2 and EphB4 Pathways 5a. CONTRACT NUMBER W81XWH-11-1-0471 5b. GRANT...13. SUPPLEMENTARY NOTES 14. ABSTRACT Multiple receptor pathways allow for redundancy in growth pathways that are dysregulated in cancer and lead to

Taking aim at Mer and Axl receptor tyrosine kinases as novel therapeutic targets in solid tumors

PubMed Central

Linger, Rachel M.A.; Keating, Amy K.; Earp, H. Shelton

2010-01-01

Importance of the field Axl and/or Mer expression correlates with poor prognosis in several cancers. Until recently, the specific role of these receptor tyrosine kinases (RTKs) in the development and progression of cancer remained unexplained. Studies demonstrating that Axl and Mer contribute to mechanisms of cell survival, migration, invasion, metastasis, and chemosensitivity justify further investigation of Axl and Mer as novel therapeutic targets in cancer. Areas covered in this review Axl and Mer signaling pathways in cancer cells are summarized and evidence validating these RTKs as therapeutic targets in glioblastoma multiforme, non-small cell lung cancer, and breast cancer is examined. A comprehensive discussion of Axl and/or Mer inhibitors in development is also provided. What the reader will gain Potential toxicities associated with Axl or Mer inhibition are addressed. We hypothesize that the probable action of Mer and Axl inhibitors on cells within the tumor microenvironment will provide a unique therapeutic opportunity to target both tumor cells and the stromal components which facilitate disease progression. Take home message Axl and Mer mediate multiple oncogenic phenotypes and activation of these RTKs constitutes a mechanism of chemoresistance in a variety of solid tumors. Targeted inhibition of these RTKs may be effective as anti-tumor and/or anti-metastatic therapy, particularly if combined with standard cytotoxic therapies. PMID:20809868

Apatinib: A novel receptor tyrosine kinase inhibitor for the treatment of gastric cancer.

PubMed

Roviello, Giandomenico; Ravelli, Andrea; Polom, Karol; Petrioli, Roberto; Marano, Luigi; Marrelli, Daniele; Roviello, Franco; Generali, Daniele

2016-03-28

Metastatic gastric cancer is a lethal disease characterized by a very short overall survival, underlining a critical need of new therapeutic options. Unfortunately, although several molecular targets have been investigated, only very few recently approved agents, such as trastuzumab in the HER2-positive setting and ramucirumab, led to a clinical improvement in the outcome of metastatic gastric cancer patients. VEGF (vascular endothelial growth factor) is one of the most potent angiogenic factors and is a signalling molecule secreted by many solid tumours. Since high VEGF expression is one of the characteristic features of gastric carcinomas, targeting VEGF is therefore considered as a promising therapeutic strategy for gastric cancer. In the scenario of possible new target therapies with particular regard to angiogenesis, apatinib is a novel receptor tyrosine kinase inhibitor selectively targeting VEGFR-2. It is an orally-bioavailable agent currently being studied in several solid tumour types showing a promising activity in gastric cancer. Due to the recent positive results as a third line of treatment for metastatic gastric cancer patients, apatinib may be an interesting and novel type of targeted treatment for metastatic gastric cancer in several lines of therapy. In this review, we summarize the available data of apatinib, mainly focused on the clinical aspect, in advanced/metastatic gastric cancer. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Experimental study of the dynamics of penetration of a solid body into a soil medium

NASA Astrophysics Data System (ADS)

Balandin, Vl. V.; Balandin, Vl. Vl.; Bragov, A. M.; Kotov, V. L.

2016-06-01

An experimental system is developed to determine the main parameters of the impact and penetration of a solid deformable body into a soft soil medium. This system is based on the technique of an inverse experiment with a measuring rod and the technique of a direct experiment with photo recording and the application of a shadow picture of the interaction of a striker with a soil target. To verify these techniques, the collision of a solid body with soil is studied by a numerical calculation and the time intervals in which the change of the resistance force is proportional to the penetration velocity squared are determined. The penetration resistance coefficients determined in direct and inverse experiments are shown to agree with each other in the collision velocity range 80-400 m/s, which supports the validity of the techniques and the reliability of measuring the total load.

Convergent solid-phase and solution approaches in the synthesis of the cysteine-rich Mdm2 RING finger domain.

PubMed

Vasileiou, Zoe; Barlos, Kostas; Gatos, Dimitrios

2009-12-01

The RING finger domain of the Mdm2, located at the C-terminus of the protein, is necessary for regulation of p53, a tumor suppressor protein. The 48-residues long Mdm2 peptide is an important target for studying its interaction with small anticancer drug candidates. For the chemical synthesis of the Mdm2 RING finger domain, the fragment condensation on solid-phase and the fragment condensation in solution were studied. The latter method was performed using either protected or free peptides at the C-terminus as the amino component. Best results were achieved using solution condensation where the N-component was applied with the C-terminal carboxyl group left unprotected. The developed method is well suited for large-scale synthesis of Mdm2 RING finger domain, combining the advantages of both solid-phase and solution synthesis. (c) 2009 European Peptide Society and John Wiley & Sons, Ltd.

Experimental Investigation of the Properties of an Acoustic Wave Induced by Laser Ablation of a Solid Target in Water-Confined Plasma Propulsion

NASA Astrophysics Data System (ADS)

Zheng, Zhiyuan; Gao, Hua; Gao, Lu; Xing, Jie

2014-11-01

Acoustic waves generated in nanosecond pulsed-laser ablation of a solid target in both air and water-confined environments were measured experimentally. It was found that the amplitude of the acoustic wave tended to decrease with an increase in water thickness. The waves were analyzed by means of fast Fourier transform. It was shown that there are several frequency components in the acoustic waves with the dominant frequency shifting from high frequency to low frequency as the thickness of the water layer increases. Furthermore, strong acoustic pressure led to enhancement of the coupling of the laser energy to the target in laser plasma propulsion.

Impact of high energy high intensity proton beams on targets: Case studies for Super Proton Synchrotron and Large Hadron Collider

NASA Astrophysics Data System (ADS)

Tahir, N. A.; Sancho, J. Blanco; Shutov, A.; Schmidt, R.; Piriz, A. R.

2012-05-01

The Large Hadron Collider (LHC) is designed to collide two proton beams with unprecedented particle energy of 7 TeV. Each beam comprises 2808 bunches and the separation between two neighboring bunches is 25 ns. The energy stored in each beam is 362 MJ, sufficient to melt 500 kg copper. Safety of operation is very important when working with such powerful beams. An accidental release of even a very small fraction of the beam energy can result in severe damage to the equipment. The machine protection system is essential to handle all types of possible accidental hazards; however, it is important to know about possible consequences of failures. One of the critical failure scenarios is when the entire beam is lost at a single point. In this paper we present detailed numerical simulations of the full impact of one LHC beam on a cylindrical solid carbon target. First, the energy deposition by the protons is calculated with the FLUKA code and this energy deposition is used in the BIG2 code to study the corresponding thermodynamic and the hydrodynamic response of the target that leads to a reduction in the density. The modified density distribution is used in FLUKA to calculate new energy loss distribution and the two codes are thus run iteratively. A suitable iteration step is considered to be the time interval during which the target density along the axis decreases by 15%-20%. Our simulations suggest that the full LHC proton beam penetrates up to 25 m in solid carbon whereas the range of the shower from a single proton in solid carbon is just about 3 m (hydrodynamic tunneling effect). It is planned to perform experiments at the experimental facility HiRadMat (High Radiation Materials) at CERN using the proton beam from the Super Proton Synchrotron (SPS), to compare experimental results with the theoretical predictions. Therefore simulations of the response of a solid copper cylindrical target hit by the SPS beam were performed. The particle energy in the SPS beam is 440 GeV while it has the same bunch structure as the LHC beam, except that it has only up to 288 bunches. Beam focal spot sizes of σ=0.1, 0.2, and 0.5 mm have been considered. The phenomenon of significant hydrodynamic tunneling due to the hydrodynamic effects is also expected for the experiments.

Synergistic retention strategy of RGD active targeting and radiofrequency-enhanced permeability for intensified RF & chemotherapy synergistic tumor treatment.

PubMed

Zhang, Kun; Li, Pei; He, Yaping; Bo, Xiaowan; Li, Xiaolong; Li, Dandan; Chen, Hangrong; Xu, Huixiong

2016-08-01

Despite gaining increasing attention, chelation of multiple active targeting ligands greatly increase the formation probability of protein corona, disabling active targeting. To overcome it, a synergistic retention strategy of RGD-mediated active targeting and radiofrequency (RF) electromagnetic field-enhanced permeability has been proposed here. It is validated that such a special synergistic retention strategy can promote more poly lactic-co-glycolic acid (PLGA)-based capsules encapsulating camptothecin (CPT) and solid DL-menthol (DLM) to enter and retain in tumor in vitro and in vivo upon exposure to RF irradiation, receiving an above 8 fold enhancement in HeLa retention. Moreover, the PLGA-based capsules can respond RF field to trigger the entrapped DLM to generate solid-liquid-gas (SLG) tri-phase transformation for enhancing RF ablation and CPT release. Therefore, depending on the enhanced RF ablation and released CPT and the validated synergistic retention effect, the inhibitory outcome for tumor growth has gained an over 10-fold improvement, realizing RF ablation & chemotherapy synergistic treatment against HeLa solid tumor, which indicates a significant promise in clinical RF ablation. Copyright © 2016 Elsevier Ltd. All rights reserved.

Method and apparatus for electrokinetic co-generation of hydrogen and electric power from liquid water microjets

DOEpatents

Saykally, Richard J; Duffin, Andrew M; Wilson, Kevin R; Rude, Bruce S

2013-02-12

A method and apparatus for producing both a gas and electrical power from a flowing liquid, the method comprising: a) providing a source liquid containing ions that when neutralized form a gas; b) providing a velocity to the source liquid relative to a solid material to form a charged liquid microjet, which subsequently breaks up into a droplet spay, the solid material forming a liquid-solid interface; and c) supplying electrons to the charged liquid by contacting a spray stream of the charged liquid with an electron source. In one embodiment, where the liquid is water, hydrogen gas is formed and a streaming current is generated. The apparatus comprises a source of pressurized liquid, a microjet nozzle, a conduit for delivering said liquid to said microjet nozzle, and a conductive metal target sufficiently spaced from said nozzle such that the jet stream produced by said microjet is discontinuous at said target. In one arrangement, with the metal nozzle and target electrically connected to ground, both hydrogen gas and a streaming current are generated at the target as it is impinged by the streaming, liquid spray microjet.

Particle production of a graphite target system for the intensity frontier

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

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

2015-05-03

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

Analysis of rumen microbial populations in lactating dairy cattle fed diets varying in carbohydrate profiles and Saccharomyces cerevisiae fermentation product.

PubMed

Mullins, C R; Mamedova, L K; Carpenter, A J; Ying, Y; Allen, M S; Yoon, I; Bradford, B J

2013-09-01

The rumen microbial ecosystem is a critical factor that links diets to bovine physiology and productivity; however, information about dietary effects on microbial populations has generally been limited to small numbers of samples and qualitative assessment. To assess whether consistent shifts in microbial populations occur in response to common dietary manipulations in dairy cattle, samples of rumen contents were collected from 2 studies for analysis by quantitative real-time PCR (qPCR). In one study, lactating Holstein cows (n=8) were fed diets in which a nonforage fiber source replaced an increasing proportion of forages and concentrates in a 4×4 Latin square design, and samples of ruminal digesta were collected at 9-h intervals over 3 d at the end of each period. In the second study, lactating Holstein cows (n=15) were fed diets with or without the inclusion of a Saccharomyces cerevisiae fermentation product (SCFP) in a crossover design. In this study, rumen liquid and solid samples were collected during total rumen evacuations before and after feeding in a 42-h period. In total, 146 samples of ruminal digesta were used for microbial DNA isolation and analysis by qPCR. Validated primer sets were used to quantify total bacterial and anaerobic fungal populations as well as 12 well-studied bacterial taxa. The relative abundance of the target populations was similar to those previously reported. No significant treatment effects were observed for any target population. A significant interaction of treatment and dry matter intake was observed, however, for the abundance of Eubacterium ruminantium. Increasing dry matter intake was associated with a quadratic decrease in E. ruminantium populations in control animals but with a quadratic increase in E.ruminantium populations in cows fed SCFP. Analysis of sample time effects revealed that Fibrobacter succinogenes and fungal populations were more abundant postfeeding, whereas Ruminococcus albus tended to be more abundant prefeeding. Seven of the target taxa were more abundant in either the liquid or solid fractions of ruminal digesta. By accounting for the total mass of liquid and solid fractions in the rumen and the relative abundance of total bacteria in each fraction, it was estimated that 92% of total bacteria were found in the solid digesta fraction. Copyright © 2013 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

To be targeted: is the magic bullet concept a viable option for synthetic nucleic acid therapeutics?

PubMed

Ogris, Manfred; Wagner, Ernst

2011-07-01

Nucleic acids offer the possibility of tailor-made, individualized treatments for genetic disorders, infectious diseases, and cancer. As an alternative to viral vectors, synthetic delivery systems have a potentially improved safety profile, but often lack sufficient efficiency especially when applied in vivo. Receptor targeting of synthetic vectors can improve the specificity of the vector and increase the efficiency of nucleic acid delivery to the target site. This review covers recent concepts for targeted DNA and RNA delivery to organs like liver and lung, and also to solid cancers. Syntheses and applications of delivery systems targeted with proteins, peptides, and small molecules as ligands coupled to polymeric or lipidic nucleic acid carriers are reviewed. Therapeutic concepts for treatment of genetic and infectious diseases are explained. Systemic treatment regimens of metastasized malignancies in combination with chemotherapy and radiation have already been successfully applied in preclinical studies. In addition, a first clinical study in the human application of a targeted synthetic carrier has been performed.

The evaluation of the average energy parameters for spectra of quasimonoenergetic neutrons produced in (p,n)-reactions on solid tritium targets

NASA Astrophysics Data System (ADS)

Sosnin, A. N.; Shorin, V. S.

1989-10-01

Fast neutron cross-section measurements using quasimonoenergetic (p,n) neutron sources require the determination of the average neutron spectrum parameters such as the mean energy < E> and the variance D. In this paper a simple model has been considered for determining the < E>- andD-values. The approach takes into account the actual layout of the solid tritium target and the irradiated sample. It is valid for targets with a thickness of less than 1 mg/cm 2. It has been shown that the first and the second tritium distribution function moments < x> and < x2> are connected by simple analytical expressions with average characteristics of the neutron yield measured above the (p,n) reaction threshold energy. Our results are compared with accurate calculations for Sc-T targets.

Integrated simulation of magnetic-field-assist fast ignition laser fusion

NASA Astrophysics Data System (ADS)

Johzaki, T.; Nagatomo, H.; Sunahara, A.; Sentoku, Y.; Sakagami, H.; Hata, M.; Taguchi, T.; Mima, K.; Kai, Y.; Ajimi, D.; Isoda, T.; Endo, T.; Yogo, A.; Arikawa, Y.; Fujioka, S.; Shiraga, H.; Azechi, H.

2017-01-01

To enhance the core heating efficiency in fast ignition laser fusion, the concept of relativistic electron beam guiding by external magnetic fields was evaluated by integrated simulations for FIREX class targets. For the cone-attached shell target case, the core heating performance deteriorates by applying magnetic fields since the core is considerably deformed and most of the fast electrons are reflected due to the magnetic mirror formed through the implosion. On the other hand, in the case of a cone-attached solid ball target, the implosion is more stable under the kilo-tesla-class magnetic field. In addition, feasible magnetic field configuration is formed through the implosion. As a result, the core heating efficiency doubles by magnetic guiding. The dependence of core heating properties on the heating pulse shot timing was also investigated for the solid ball target.

Method and apparatus for optimized sampling of volatilizable target substances

DOEpatents

Lindgren, Eric R.; Phelan, James M.

2002-01-01

An apparatus for capturing, from gases such as soil gas, target analytes. Target analytes may include emanations from explosive materials or from residues of explosive materials. The apparatus employs principles of sorption common to solid phase microextraction, and is best used in conjunction with analysis means such as a gas chromatograph. To sorb target analytes, the apparatus functions using various sorptive structures to capture target analyte. Depending upon the embodiment, those structures may include 1) a conventional solid-phase microextraction (SPME) fiber, 2) a SPME fiber suspended in a capillary tube (with means provided for moving gases through the capillary tube so that the gases come into close proximity to the suspended fiber), and 3) a capillary tube including an interior surface on which sorptive material (similar to that on the surface of a SPME fiber) is supported (along with means for moving gases through the capillary tube so that the gases come into close proximity to the sorptive material). In one disclosed embodiment, at least one such sorptive structure is associated with an enclosure including an opening in communication with the surface of a soil region potentially contaminated with buried explosive material such as unexploded ordnance. Emanations from explosive materials can pass into and accumulate in the enclosure where they are sorbed by the sorptive structures. Also disclosed is the use of heating means such as microwave horns to drive target analytes into the soil gas from solid and liquid phase components of the soil.

Effect of liquid-to-solid ratio on semi-solid Fenton process in hazardous solid waste detoxication.

PubMed

Hu, Li-Fang; Feng, Hua-Jun; Long, Yu-Yang; Zheng, Yuan-Ge; Fang, Cheng-Ran; Shen, Dong-Sheng

2011-01-01

The liquid-to-solid ratio (L/S) of semi-solid Fenton process (SSFP) designated for hazardous solid waste detoxication was investigated. The removal and minimization effects of o-nitroaniline (ONA) in simulate solid waste residue (SSWR) from organic arsenic industry was evaluated by total organic carbon (TOC) and ONA removal efficiency, respectively. Initially, Box-Behnken design (BBD) and response surface methodology (RSM) were used to optimize the key factors of SSFP. Results showed that the removal rates of TOC and ONA decreased as L/S increased. Subsequently, four target initial ONA concentrations including 100 mg kg(-1), 1 g kg(-1), 10 g kg(-1), and 100 gk g(-1) on a dry basis were evaluated for the effect of L/S. A significant cubic empirical model between the initial ONA concentration and L/S was successfully developed to predict the optimal L/S for given initial ONA concentration for SSFP. Moreover, an optimized operation strategy of multi-SSFP for different cases was determined based on the residual target pollutant concentration and the corresponding environmental conditions. It showed that the total L/S of multi-SSFP in all tested scenarios was no greater than 3.8, which is lower than the conventional slurry systems (L/S ≥ 5). The multi-SSFP is environment-friendly when it used for detoxication of hazardous solid waste contaminated by ONA and provides a potential method for the detoxication of hazardous solid waste contaminated by organics. Copyright © 2010 Elsevier Ltd. All rights reserved.

Selective extraction and separation of oxymatrine from Sophora flavescens Ait. extract by silica-confined ionic liquid.

PubMed

Bi, Wentao; Tian, Minglei; Row, Kyung Ho

2012-01-01

This study highlighted the application of a two-stepped extraction method for extraction and separation of oxymatrine from Sophora flavescens Ait. extract by utilizing silica-confined ionic liquids as sorbent. The optimized silica-confined ionic liquid was firstly mixed with plant extract to adsorb oxymatrine. Simultaneously, some interference, such as matrine, was removed. The obtained suspension was then added to a cartridge for solid phase extraction. Through these two steps, target compound was adequately separated from interferences with 93.4% recovery. In comparison with traditional solid phase extraction, this method accelerates loading and reduces the use of organic solvents during washing. Moreover, the optimization of loading volume was simplified as optimization of solid/liquid ratio. Copyright © 2011 Elsevier B.V. All rights reserved.

Ultrafast electron radiography of magnetic fields in high-intensity laser-solid interactions.

PubMed

Schumaker, W; Nakanii, N; McGuffey, C; Zulick, C; Chyvkov, V; Dollar, F; Habara, H; Kalintchenko, G; Maksimchuk, A; Tanaka, K A; Thomas, A G R; Yanovsky, V; Krushelnick, K

2013-01-04

Using electron bunches generated by laser wakefield acceleration as a probe, the temporal evolution of magnetic fields generated by a 4 × 10(19) W/cm(2) ultrashort (30 fs) laser pulse focused on solid density targets is studied experimentally. Magnetic field strengths of order B(0) ~ 10(4) T are observed expanding at close to the speed of light from the interaction point of a high-contrast laser pulse with a 10-μm-thick aluminum foil to a maximum diameter of ~1 mm. The field dynamics are shown to agree with particle-in-cell simulations.

Electron transport in solid targets and in the active mixture of a CO2 laser amplifier

NASA Astrophysics Data System (ADS)

Galkowski, A.

The paper examines the use of the NIKE code for the Monte Carlo computation of the deposited energy profile and other characteristics of the absorption process of an electron beam in a solid target and the spatial distribution of primary ionization in the active mixture of a CO2 laser amplifier. The problem is considered in connection with the generation of intense electron beams and the acceleration of thin metal foils, as well as in connection with the electric discharge pumping of a CO2 laser amplifier.

Targeting solid tumours with potassium channel activators. A return to fundamentals?

PubMed

Trechot, Philippe

2014-01-01

From a pharmacological point of view nicotinamide and minoxidil are potassium channel activators. Nicotinamide is used as a radiosensitizer in ARCON (accelerated radiotherapy combined with carbogen breathing and nicotinamide) therapeutic strategy with promising results but not confirmed so far. Minoxidil has never been considered by radiotherapists. Based from recent pathophysiological considerations we suggest a new perspective for the use of these two "old" molecules in order to target solid tumours. © 2014 Société Française de Pharmacologie et de Thérapeutique.

Mechanism of equivalent electric dipole oscillation for high-order harmonic generation from grating-structured solid-surface by femtosecond laser pulse

NASA Astrophysics Data System (ADS)

Wang, Yang; Song, Hai-Ying; Liu, H. Y.; Liu, Shi-Bing

2017-07-01

We theoretically study high-order harmonic generation (HHG) from relativistically driven overdense plasma targets with rectangularly grating-structured surfaces by femtosecond laser pulses. Our particle-in-cell (PIC) simulations show that, under the conditions of low laser intensity and plasma density, the harmonics emit principally along small angles deviating from the target surface. Further investigation of the surface electron dynamics reveals that the electron bunches are formed by the interaction between the laser field and the target surface, giving rise to the oscillation of equivalent electric-dipole (OEED), which enhances specific harmonic orders. Our work helps understand the mechanism of harmonic emissions from grating targets and the distinction from the planar harmonic scheme.

A study of H+ production using metal hydride and other compounds by means of laser ion source

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

Sekine M.; Kondo K.; Okamura, M.

2012-02-22

A laser ion source can provide wide variety of ion beams from solid target materials, however, it has been difficult to create proton beam efficiently. We examined capability of proton production using beeswax, polyethylene, and metal hydrides (MgH2 and ZrH2) as target materials. The results showed that beeswax and polyethylene could not be used to produce protons because these targets are transparent to the laser wavelength of 1064 nm. On the other hand, the metal hydrides could supply protons. Although the obtained particle numbers of protons were less than those of the metal ions, the metal hydrides could be usedmore » as a target for proton laser ion source.« less

Actively targeted delivery of anticancer drug to tumor cells by redox-responsive star-shaped micelles.

PubMed

Shi, Chunli; Guo, Xing; Qu, Qianqian; Tang, Zhaomin; Wang, Yi; Zhou, Shaobing

2014-10-01

In cancer therapy nanocargos based on star-shaped polymer exhibit unique features such as better stability, smaller size distribution and higher drug capacity in comparison to linear polymeric micelles. In this study, we developed a multifunctional star-shaped micellar system by combination of active targeting ability and redox-responsive behavior. The star-shaped micelles with good stability were self-assembled from four-arm poly(ε-caprolactone)-poly(ethylene glycol) copolymer. The redox-responsive behaviors of these micelles triggered by glutathione were evaluated from the changes of micellar size, morphology and molecular weight. In vitro drug release profiles exhibited that in a stimulated normal physiological environment, the redox-responsive star-shaped micelles could maintain good stability, whereas in a reducing and acid environment similar with that of tumor cells, the encapsulated agent was promptly released. In vitro cellular uptake and subcellular localization of these micelles were further studied with confocal laser scanning microscopy and flow cytometry against the human cervical cancer cell line HeLa. In vivo and ex vivo DOX fluorescence imaging displayed that these FA-functionalized star-shaped micelles possessed much better specificity to target solid tumor. Both the qualitative and quantitative results of the antitumor effect in 4T1 tumor-bearing BALB/c mice demonstrated that these redox-responsive star-shaped micelles have a high therapeutic efficiency to artificial solid tumor. Therefore, the multifunctional star-shaped micelles are a potential platform for targeted anticancer drug delivery. Copyright © 2014 Elsevier Ltd. All rights reserved.

Landing response of Aedes (Stegomyia) polynesiensis mosquitoes to coloured targets.

PubMed

Chambers, E W; Bossin, H C; Ritchie, S A; Russell, R C; Dobson, S L

2013-09-01

Aedes polynesiensis Marks (Diptera: Culicidae) is the primary vector of lymphatic filariasis (LF) in the island countries and territories of the South Pacific. In the development of a novel control tool, the response of Ae. polynesiensis to six different colours (three solid fabrics, two patterned fabrics and a plastic tarp) was measured using a digital photographic system. Adult mosquitoes were placed into an environmental chamber and allowed to choose between a white target and one of six experimental targets. Mosquito landing frequency and landing duration were calculated. Adult female Ae. polynesiensis preferred all of the experimental targets to the white control target. Mosquito landing frequency was highest for the solid targets (black, navy blue and red) followed in turn by the two colour pattern targets and the polyethylene target. Mosquito landing duration was greater for experimental targets when compared with white control targets. Mosquito landing frequencies did not change over time during the course of the assay. The response of male Ae. polynesiensis was also measured when exposed to a 100% cotton black target. Male mosquitoes preferred the black target to the white control target, although at levels lower than that observed in female mosquitoes. The results suggest that future investigations evaluating the visual responses of Ae. polynesiensis mosquitoes are warranted, with a special emphasis on semi-field and field-based experiments. © 2013 The Royal Entomological Society.

Tailored semiconductors for high-harmonic optoelectronics.

PubMed

Sivis, Murat; Taucer, Marco; Vampa, Giulio; Johnston, Kyle; Staudte, André; Naumov, Andrei Yu; Villeneuve, D M; Ropers, Claus; Corkum, P B

2017-07-21

The advent of high-harmonic generation in gases 30 years ago set the foundation for attosecond science and facilitated ultrafast spectroscopy in atoms, molecules, and solids. We explore high-harmonic generation in the solid state by means of nanostructured and ion-implanted semiconductors. We use wavelength-selective microscopic imaging to map enhanced harmonic emission and show that the generation medium and the driving field can be locally tailored in solids by modifying the chemical composition and morphology. This enables the control of high-harmonic technology within precisely engineered solid targets. We demonstrate customized high-harmonic wave fields with wavelengths down to 225 nanometers (ninth-harmonic order of 2-micrometer laser pulses) and present an integrated Fresnel zone plate target in silicon, which leads to diffraction-limited self-focusing of the generated harmonics down to 1-micrometer spot sizes. Copyright © 2017 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.

Research challenges in municipal solid waste logistics management.

PubMed

Bing, Xiaoyun; Bloemhof, Jacqueline M; Ramos, Tania Rodrigues Pereira; Barbosa-Povoa, Ana Paula; Wong, Chee Yew; van der Vorst, Jack G A J

2016-02-01

During the last two decades, EU legislation has put increasing pressure on member countries to achieve specified recycling targets for municipal household waste. These targets can be obtained in various ways choosing collection methods, separation methods, decentral or central logistic systems, etc. This paper compares municipal solid waste (MSW) management practices in various EU countries to identify the characteristics and key issues from a waste management and reverse logistics point of view. Further, we investigate literature on modelling municipal solid waste logistics in general. Comparing issues addressed in literature with the identified issues in practice result in a research agenda for modelling municipal solid waste logistics in Europe. We conclude that waste recycling is a multi-disciplinary problem that needs to be considered at different decision levels simultaneously. A holistic view and taking into account the characteristics of different waste types are necessary when modelling a reverse supply chain for MSW recycling. Copyright © 2015 Elsevier Ltd. All rights reserved.

Treatment of biomass to obtain a target chemical

DOEpatents

Dunson, Jr., James B.; Tucker, III, Melvin P.; Elander, Richard T.; Hennessey, Susan Marie

2010-08-24

Target chemicals were produced using biocatalysts that are able to ferment sugars derived from treated biomass. Sugars were obtained by pretreating biomass under conditions of high solids and low ammonia concentration, followed by saccharification.

Lightweight Target Generates Bright, Energetic X-Rays

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

Hazi, A

Radiography with x rays is a long-established method to see inside objects, from human limbs to weapon parts. Livermore scientists have a continuing need for powerful x rays for such applications as backlighting, or illuminating, inertial confinement fusion (ICF) experiments and imaging still or exploding materials for the nation's Stockpile Stewardship Program. X-radiography is one of the prime diagnostics for ICF experiments because it captures the fine detail needed to determine what happens to nearly microscopic targets when they are compressed by laser light. For example, Livermore scientists participating in the National Ignition Facility's (NIF's) 18-month-long Early Light experimental campaign,more » which ended in 2004, used x rays to examine hydrodynamic instabilities in jets of plasma. In these experiments, one laser beam irradiated a solid target of titanium, causing it to form a high-temperature plasma that generated x rays of about 4.65 kiloelectronvolts (keV). These x rays backlit a jet of plasma formed when two other laser beams hit a plastic ablator and sent a shock to an aluminum washer. Livermore physicist Kevin Fournier of the Physics and Advanced Technologies Directorate leads a team that is working to increase the efficiency of converting laser energy into x rays so the resulting images provide more information about the object being illuminated. The main characteristics of x-ray sources are energy and brightness. ''As experimental targets get larger and as compression of the targets increases, the backlighter sources must be brighter and more energetic'', says Fournier. The more energetic the x rays, the further they penetrate an object. The brighter the source--that is, the more photons it has--the clearer the image. historically, researchers have used solid targets such as thin metal foils to generate x rays. however, when photon energies are greater than a few kiloelectronvolts, the conversion efficiency of solid targets is only a fraction of 1 percent. Solid targets have low efficiencies because much of the laser energy is deposited far from the target's x-ray emitting region, and the energy is carried by the relatively slow process of thermal conduction. ''The laser beam ablates material from the massive target, and that material moves away from the target's surface'', says Fournier. With a nanosecond pulse or longer, the laser interacts with the blow-off plasma rather than the remaining bulk sample. As a result, much of the laser's energy goes into the kinetic energy of the blow-off material, not into heating the bulk of the foil.« less

Dominance of hole-boring radiation pressure acceleration regime with thin ribbon of ionized solid hydrogen

NASA Astrophysics Data System (ADS)

Psikal, J.; Matys, M.

2018-04-01

Laser-driven proton acceleration from novel cryogenic hydrogen target of the thickness of tens of microns irradiated by multiPW laser pulse is investigated here for relevant laser parameters accessible in near future. It is demonstrated that the efficiency of proton acceleration from relatively thick hydrogen solid ribbon largely exceeds the acceleration efficiency for a thinner ionized plastic foil, which can be explained by enhanced hole boring (HB) driven by laser ponderomotive force in the case of light ions and lower target density. Three-dimensional particle-in-cell (PIC) simulations of laser pulse interaction with relatively thick hydrogen target show larger energies of protons accelerated in the target interior during the HB phase and reduced energies of protons accelerated from the rear side of the target by quasistatic electric field compared with the results obtained from two-dimensional PIC calculations. Linearly and circularly polarized multiPW laser pulses of duration exceeding 100 fs show similar performance in terms of proton acceleration from both the target interior as well as from the rear side of the target. When ultrashort pulse (∼30 fs) is assumed, the number of accelerated protons from the target interior is substantially reduced.

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

PubMed

Berger, Michael; VON Schweinitz, Dietrich

2017-11-01

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

From targeting the tumor to targeting the immune system: Transversal challenges in oncology with the inhibition of the PD-1/PD-L1 axis

PubMed Central

Bersanelli, Melissa; Buti, Sebastiano

2017-01-01

After that the era of chemotherapy in the treatment of solid tumors have been overcome by the “translational era”, with the innovation introduced by targeted therapies, medical oncology is currently looking at the dawn of a new “immunotherapy era” with the advent of immune checkpoint inhibitors (CKI) antibodies. The onset of PD-1/PD-L1 targeted therapy has demonstrated the importance of this axis in the immune escape across almost all human cancers. The new CKI allowed to significantly prolong survival and to generate durable response, demonstrating remarkable efficacy in a wide range of cancer types. The aim of this article is to review the most up to date literature about the clinical effectiveness of CKI antibodies targeting PD-1/PD-L1 axis for the treatment of advanced solid tumors and to explore transversal challenges in the immune checkpoint blockade. PMID:28246584

Electromagnetic pulse (EMP) radiation by laser interaction with a solid H2 ribbon

NASA Astrophysics Data System (ADS)

De Marco, M.; Krása, J.; Cikhardt, J.; Velyhan, A.; Pfeifer, M.; Dudžák, R.; Dostál, J.; Krouský, E.; Limpouch, J.; Pisarczyk, T.; Kalinowska, Z.; Chodukowski, T.; Ullschmied, J.; Giuffrida, L.; Chatain, D.; Perin, J.-P.; Margarone, D.

2017-08-01

The electromagnetic pulses (EMPs) generated during the interaction of a focused 1.315-μm sub-nanosecond laser pulse with a solid hydrogen ribbon were measured. The strength and temporal characteristics of EMPs were found to be dependent on the target density. If a low density target is ionized during the interaction with the laser, and the plasma does not physically touch the target holder, the EMP is weaker in strength and shorter in time duration. It is shown that during the H2 target experiment, the EMP does not strongly affect the response of fast electronic devices. The measurements of the EMP were carried out by Rohde&Schwarz B-Probes, particularly sensitive in the frequency range from 30 MHz and 1 GHz. Numerical simulations of resonant frequencies of the target chamber used in the experiment at the Prague Asterix Laser System kJ-class laser facility elucidate the peaked structure of EMP frequency spectra in the GHz domain.

New trial engineers immune cells to treat solid tumors | Center for Cancer Research

Cancer.gov

No existing systemic treatments can currently eradicate the great majority of metastatic solid cancers. To meet that need, Steve Rosenberg, M.D., Ph.D., is testing a new immunotherapy that targets each tumor’s unique genetic mutations in a clinical trial.

Generation of sub-gigabar-pressure shocks by a hyper-velocity impact in the collider driven by laser-induced cavity pressure

NASA Astrophysics Data System (ADS)

Badziak, J.; Kucharik, M.; Liska, R.

2018-02-01

The generation of high-pressure shocks in the newly proposed collider in which the projectile impacting a solid target is driven by the laser-induced cavity pressure acceleration (LICPA) mechanism is investigated using two-dimensional hydrodynamic simulations. The dependence of parameters of the shock generated in the target by the impact of a gold projectile on the impacted target material and the laser driver energy is examined. It is found that both in case of low-density (CH, Al) and high-density (Au, Cu) solid targets the shock pressures in the sub-Gbar range can be produced in the LICPA-driven collider with the laser energy of only a few hundreds of joules, and the laser-to-shock energy conversion efficiency can reach values of 10 - 20 %, by an order of magnitude higher than the conversion efficiencies achieved with other laser-based methods used so far.

Production and characterization of pure cryogenic inertial fusion targets

NASA Astrophysics Data System (ADS)

Boyd, B. A.; Kamerman, G. W.

An experimental cryogenic inertial fusion target generator and two optical techniques for automated target inspection are described. The generator produces 100 microns diameter solid hydrogen spheres at a rate compatible with fueling requirements of conceptual inertial fusion power plants. A jet of liquified hydrogen is disrupted into droplets by an ultrasonically excited nozzle. The droplets solidify into microspheres while falling through a chamber maintained below the hydrogen triple point pressure. Stable operation of the generator has been demonstrated for up to three hours. The optical inspection techniques are computer aided photomicrography and coarse diffraction pattern analysis (CDPA). The photomicrography system uses a conventional microscope coupled to a computer by a solid state camera and digital image memory. The computer enhances the stored image and performs feature extraction to determine pellet parameters. The CDPA technique uses Fourier transform optics and a special detector array to perform optical processing of a target image.

Solid phase sequencing of biopolymers

DOEpatents

Cantor, Charles; Koster, Hubert

2010-09-28

This invention relates to methods for detecting and sequencing target nucleic acid sequences, to mass modified nucleic acid probes and arrays of probes useful in these methods, and to kits and systems which contain these probes. Useful methods involve hybridizing the nucleic acids or nucleic acids which represent complementary or homologous sequences of the target to an array of nucleic acid probes. These probes comprise a single-stranded portion, an optional double-stranded portion and a variable sequence within the single-stranded portion. The molecular weights of the hybridized nucleic acids of the set can be determined by mass spectroscopy, and the sequence of the target determined from the molecular weights of the fragments. Nucleic acids whose sequences can be determined include DNA or RNA in biological samples such as patient biopsies and environmental samples. Probes may be fixed to a solid support such as a hybridization chip to facilitate automated molecular weight analysis and identification of the target sequence.

Solid-phase single molecule biosensing using dual-color colocalization of fluorescent quantum dot nanoprobes

NASA Astrophysics Data System (ADS)

Liu, Jianbo; Yang, Xiaohai; Wang, Kemin; Wang, Qing; Liu, Wei; Wang, Dong

2013-10-01

The development of solid-phase surface-based single molecule imaging technology has attracted significant interest during the past decades. Here we demonstrate a sandwich hybridization method for highly sensitive detection of a single thrombin protein at a solid-phase surface based on the use of dual-color colocalization of fluorescent quantum dot (QD) nanoprobes. Green QD560-modified thrombin binding aptamer I (QD560-TBA I) were deposited on a positive poly(l-lysine) assembled layer, followed by bovine serum albumin blocking. It allowed the thrombin protein to mediate the binding of the easily detectable red QD650-modified thrombin binding aptamer II (QD650-TBA II) to the QD560-TBA I substrate. Thus, the presence of the target thrombin can be determined based on fluorescent colocalization measurements of the nanoassemblies, without target amplification or probe separation. The detection limit of this assay reached 0.8 pM. This fluorescent colocalization assay has enabled single molecule recognition in a separation-free detection format, and can serve as a sensitive biosensing platform that greatly suppresses the nonspecific adsorption false-positive signal. This method can be extended to other areas such as multiplexed immunoassay, single cell analysis, and real time biomolecule interaction studies.The development of solid-phase surface-based single molecule imaging technology has attracted significant interest during the past decades. Here we demonstrate a sandwich hybridization method for highly sensitive detection of a single thrombin protein at a solid-phase surface based on the use of dual-color colocalization of fluorescent quantum dot (QD) nanoprobes. Green QD560-modified thrombin binding aptamer I (QD560-TBA I) were deposited on a positive poly(l-lysine) assembled layer, followed by bovine serum albumin blocking. It allowed the thrombin protein to mediate the binding of the easily detectable red QD650-modified thrombin binding aptamer II (QD650-TBA II) to the QD560-TBA I substrate. Thus, the presence of the target thrombin can be determined based on fluorescent colocalization measurements of the nanoassemblies, without target amplification or probe separation. The detection limit of this assay reached 0.8 pM. This fluorescent colocalization assay has enabled single molecule recognition in a separation-free detection format, and can serve as a sensitive biosensing platform that greatly suppresses the nonspecific adsorption false-positive signal. This method can be extended to other areas such as multiplexed immunoassay, single cell analysis, and real time biomolecule interaction studies. Electronic supplementary information (ESI) available: Absorbance and fluorescence spectra of quantum dot nanoprobes, electrophoresis analysis, and experimental setup for fluorescence imaging with dual channels. See DOI: 10.1039/c3nr03291d

Physics of giant electromagnetic pulse generation in short-pulse laser experiments.

PubMed

Poyé, A; Hulin, S; Bailly-Grandvaux, M; Dubois, J-L; Ribolzi, J; Raffestin, D; Bardon, M; Lubrano-Lavaderci, F; D'Humières, E; Santos, J J; Nicolaï, Ph; Tikhonchuk, V

2015-04-01

In this paper we describe the physical processes that lead to the generation of giant electromagnetic pulses (GEMPs) at powerful laser facilities. Our study is based on experimental measurements of both the charging of a solid target irradiated by an ultra-short, ultra-intense laser and the detection of the electromagnetic emission in the GHz domain. An unambiguous correlation between the neutralization current in the target holder and the electromagnetic emission shows that the source of the GEMP is the remaining positive charge inside the target after the escape of fast electrons accelerated by the ultra-intense laser. A simple model for calculating this charge in the thick target case is presented. From this model and knowing the geometry of the target holder, it becomes possible to estimate the intensity and the dominant frequencies of the GEMP at any facility.

Neutron measurements from beam-target reactions at the ELISE neutral beam test facility

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

Xufei, X., E-mail: xiexufei@pku.edu.cn; Fan, T.; Nocente, M.

2014-11-15

Measurements of 2.5 MeV neutron emission from beam-target reactions performed at the ELISE neutral beam test facility are presented in this paper. The measurements are used to study the penetration of a deuterium beam in a copper dump, based on the observation of the time evolution of the neutron counting rate from beam-target reactions with a liquid scintillation detector. A calculation based on a local mixing model of deuterium deposition in the target up to a concentration of 20% at saturation is used to evaluate the expected neutron yield for comparison with data. The results are of relevance to understandmore » neutron emission associated to beam penetration in a solid target, with applications to diagnostic systems for the SPIDER and MITICA Neutral Beam Injection prototypes.« less

Nucleic acid detection methods

DOEpatents

Smith, C.L.; Yaar, R.; Szafranski, P.; Cantor, C.R.

1998-05-19

The invention relates to methods for rapidly determining the sequence and/or length a target sequence. The target sequence may be a series of known or unknown repeat sequences which are hybridized to an array of probes. The hybridized array is digested with a single-strand nuclease and free 3{prime}-hydroxyl groups extended with a nucleic acid polymerase. Nuclease cleaved heteroduplexes can be easily distinguish from nuclease uncleaved heteroduplexes by differential labeling. Probes and target can be differentially labeled with detectable labels. Matched target can be detected by cleaving resulting loops from the hybridized target and creating free 3-hydroxyl groups. These groups are recognized and extended by polymerases added into the reaction system which also adds or releases one label into solution. Analysis of the resulting products using either solid phase or solution. These methods can be used to detect characteristic nucleic acid sequences, to determine target sequence and to screen for genetic defects and disorders. Assays can be conducted on solid surfaces allowing for multiple reactions to be conducted in parallel and, if desired, automated. 18 figs.

Micro versus macro solid phase extraction for monitoring water contaminants: a preliminary study using trihalomethanes.

PubMed

Alexandrou, Lydon D; Spencer, Michelle J S; Morrison, Paul D; Meehan, Barry J; Jones, Oliver A H

2015-04-15

Solid phase extraction is one of the most commonly used pre-concentration and cleanup steps in environmental science. However, traditional methods need electrically powered pumps, can use large volumes of solvent (if multiple samples are run), and require several hours to filter a sample. Additionally, if the cartridge is open to the air volatile compounds may be lost and sample integrity compromised. In contrast, micro cartridge based solid phase extraction can be completed in less than 2 min by hand, uses only microlitres of solvent and provides comparable concentration factors to established methods. It is also an enclosed system so volatile components are not lost. The sample can also be eluted directly into a detector (e.g. a mass spectrometer) if required. However, the technology is new and has not been much used for environmental analysis. In this study we compare traditional (macro) and the new micro solid phase extraction for the analysis of four common volatile trihalomethanes (trichloromethane, bromodichloromethane, dibromochloromethane and tribromomethane). The results demonstrate that micro solid phase extraction is faster and cheaper than traditional methods with similar recovery rates for the target compounds. This method shows potential for further development in a range of applications. Copyright © 2015 Elsevier B.V. All rights reserved.

Experimental Study of Proton Acceleration from Ultra Intense Laser Matter Interactions

NASA Astrophysics Data System (ADS)

Paudel, Yadab Kumar

This dissertation describes proton and ion acceleration measurements from high intensity (˜ 1019 Wcm-2) laser interactions with thin foil targets. Protons and ions accelerated from the back surface of a target driven by a high intensity laser are detected using solid-state nuclear track detector CR39. A simple digital imaging technique, with an adjustable halogen light source shined on CR39 and use of a digital camera with suitable f-number and exposure time, is used to detect particles tracks. This new technique improves the quality 2D image with vivid track patterns in CR39. Our technique allows us to quickly record and sort CR39 pieces for further analysis. This is followed by detailed quantitative information on the protons and ions. Protons and multicharged ions generated from high-intensity laser interactions with thin foil targets have been studied with a 100 TW laser system. Protons/ions with energies up to 10 MeV are accelerated either from the front or the rear surface of the target material. We have observed for the first time a self-radiograph of the target with a glass stalk holding the target itself in the stacked radiochromic films (RCF) placed behind the target. The self-radiography indicates that the fast ions accelerated backward, in a direction opposite to the laser propagation, are turning around in strong magnetic fields. This unique result is a signature of long-living (ns time scale) magnetic fields in the expanding plasma, which are important in energy transport during the intense laser irradiation and have never been considered in the previous studies. The magnetic fields induced by the main pulse near the absorption point expand rapidly with the backward accelerated protons in the pre-formed plasma. The protons are rotated by these magnetic fields and they are recorded in the RCF, making the self-radiography. Angular profiles of protons and multicharged ions accelerated from the target rear surface have been studied with the subpicosecond laser pulse produced by the 100 TW laser system. The protons/ions beam features recorded on CR39 show the hollow beam structure at the center of the beam pattern. This hollow structure in the proton/ion beam pattern associates to the electron transport inside the solid target, which affects the target's rear-surface emission or the electrostatic profile on the target rear-surface. The proton/ion beam filamentation has been seen clearly outside the hollow beam pattern in the CR39 images processed by the new digital imaging technique.

Energy deposition and neutron flux study in a gravity-driven dense granular target (DGT) with GEANT4 toolkit

NASA Astrophysics Data System (ADS)

Zhao, Qiang; Cui, Wenjuan; He, Zhiyong; Zhang, Xueying; Ma, Wenjing

2018-07-01

China initiative Accelerator Driven System (CiADS) has been approved as a strategic plan to build an ADS demonstration facility in the next few years. It proposed a new concept for a high-power spallation target: the gravity-driven dense granular target (DGT). As the same with a monolithic target (MT), both solid and liquid target, energy deposition and neutron flux are two critical issues. In this paper, we focus on these two issues and long for some valuable results for the project. Unlike a solid target, the internal geometry structure of a DGT is very complicated. To be as much as closer with the reality, we designed an algorithm and firstly packed the grains randomly in a cylindrical container in GEANT4 software. The packing result was in great agreement with the experimentally measured results. It shows that the algorithm is practicable. In the next step, all the simulations about energy deposition and neutron flux of a DGT were performed with the GEANT4 codes, and the results were compared with the data of a MT. Compared to a MT, a DGT has inarguable advantages in both terms of energy deposition and neutron flux. In addition, the simulations with different radius of grains were also performed. Finally, we found that both the energy deposition and neutron flux are nearly irrelevant to the radius of the grains in the range of 0.5 mm-5 mm when the packing density is same by analyzing the results meticulously.

Solid tumor therapy by selectively targeting stromal endothelial cells

PubMed Central

Liu, Shihui; Liu, Jie; Ma, Qian; Cao, Liu; Fattah, Rasem J.; Yu, Zuxi; Bugge, Thomas H.; Finkel, Toren; Leppla, Stephen H.

2016-01-01

Engineered tumor-targeted anthrax lethal toxin proteins have been shown to strongly suppress growth of solid tumors in mice. These toxins work through the native toxin receptors tumor endothelium marker-8 and capillary morphogenesis protein-2 (CMG2), which, in other contexts, have been described as markers of tumor endothelium. We found that neither receptor is required for tumor growth. We further demonstrate that tumor cells, which are resistant to the toxin when grown in vitro, become highly sensitive when implanted in mice. Using a range of tissue-specific loss-of-function and gain-of-function genetic models, we determined that this in vivo toxin sensitivity requires CMG2 expression on host-derived tumor endothelial cells. Notably, engineered toxins were shown to suppress the proliferation of isolated tumor endothelial cells. Finally, we demonstrate that administering an immunosuppressive regimen allows animals to receive multiple toxin dosages and thereby produces a strong and durable antitumor effect. The ability to give repeated doses of toxins, coupled with the specific targeting of tumor endothelial cells, suggests that our strategy should be efficacious for a wide range of solid tumors. PMID:27357689

Target design for materials processing very far from equilibrium

NASA Astrophysics Data System (ADS)

Barnard, John J.; Schenkel, Thomas

2016-10-01

Local heating and electronic excitations can trigger phase transitions or novel material states that can be stabilized by rapid quenching. An example on the few nanometer scale are phase transitions induced by the passage of swift heavy ions in solids where nitrogen-vacancy color centers form locally in diamonds when ions heat the diamond matrix to warm dense matter conditions at 0.5 eV. We optimize mask geometries for target materials such as silicon and diamond to induce phase transitions by intense ion pulses (e. g. from NDCX-II or from laser-plasma acceleration). The goal is to rapidly heat a solid target volumetrically and to trigger a phase transition or local lattice reconstruction followed by rapid cooling. The stabilized phase can then be studied ex situ. We performed HYDRA simulations that calculate peak temperatures for a series of excitation conditions and cooling rates of crystal targets with micro-structured masks. A simple analytical model, that includes ion heating and radial, diffusive cooling, was developed that agrees closely with the HYDRA simulations. The model gives scaling laws that can guide the design of targets over a wide range of parameters including those for NDCX-II and the proposed BELLA-i. This work was performed under the auspices of the U.S. DOE under contracts DE-AC52-07NA27344 (LLNL), DE-AC02-05CH11231 (LBNL) and was supported by the US DOE Office of Science, Fusion Energy Sciences. LLNL-ABS-697271.

Effect of microbubble ligation to cells on ultrasound signal enhancement: implications for targeted imaging.

PubMed

Lankford, Miles; Behm, Carolyn Z; Yeh, James; Klibanov, Alexander L; Robinson, Peter; Lindner, Jonathan R

2006-10-01

Molecular imaging with contrast-enhanced ultrasound (CEU) relies on the detection of microbubbles retained in regions of disease. The aim of this study was to determine whether microbubble attachment to cells influences their acoustic signal generation and stability. Biotinylated microbubbles were attached to streptavidin-coated plates to derive density versus intensity relations during low- and high-power imaging. To assess damping from microbubble attachment to solid or cell surfaces, in vitro imaging was performed for microbubbles charge-coupled to methacrylate spheres and for vascular cell adhesion molecule-1-targeted microbubbles attached to endothelial cells. Signal enhancement on plates increased according to acoustic power and microbubble site density up to 300 mm. Microbubble signal was reduced by attachment to solid spheres during high- and low-power imaging but was minimally reduced by attachment to endothelial cells and only at low power. Attachment of targeted microbubbles to rigid surfaces results in damping and a reduction of their acoustic signal, which is not seen when microbubbles are attached to cells. A reliable concentration versus intensity relationship can be expected from microbubble attachment to 2-dimensional surfaces until a very high site density is reached.

A new method for spray deposit assessment

Treesearch

Chester M. Himel; Leland Vaughn; Raymond P. Miskus; Arthur D. Moore

1965-01-01

Solid fluorescent particles suspended in a spray liquid are distributed in direct proportion to the size of the spray droplets. Use of solid fluorescent particles is the basis of a new method for visual recognition of the size and number of droplets impinging on target and nontarget portions of sprayed areas.

Solid-phase assays for small molecule screening using sol-gel entrapped proteins.

PubMed

Lebert, Julie M; Forsberg, Erica M; Brennan, John D

2008-04-01

With compound libraries exceeding one million compounds, the ability to quickly and effectively screen these compounds against relevant pharmaceutical targets has become crucial. Solid-phase assays present several advantages over solution-based methods. For example, a higher degree of miniaturization can be achieved, functional- and affinity-based studies are possible, and a variety of detection methods can be used. Unfortunately, most protein immobilization methods are either too harsh or require recombinant proteins and thus are not amenable to delicate proteins such as kinases and membrane-bound receptors. Sol-gel encapsulation of proteins in an inorganic silica matrix has emerged as a novel solid-phase assay platform. In this minireview, we discuss the development of sol-gel derived protein microarrays and sol-gel based monolithic bioaffinity columns for the high-throughput screening of small molecule libraries and mixtures.

Buparvaquone loaded solid lipid nanoparticles for targeted delivery in theleriosis

PubMed Central

Soni, Maheshkumar P.; Shelkar, Nilakash; Gaikwad, Rajiv V.; Vanage, Geeta R.; Samad, Abdul; Devarajan, Padma V.

2014-01-01

Background: Buparvaquone (BPQ), a hydroxynaphthoquinone derivative, has been investigated for the treatment of many infections and is recommended as the gold standard for the treatment of theileriosis. Theileriosis, an intramacrophage infection is localized mainly in reticuloendotheileial system (RES) organs. The present study investigates development of solid lipid nanoparticles (SLN) of BPQ for targeted delivery to the RES. Materials and Methods: BPQ SLN was prepared using melt method by adding a molten mixture into aqueous Lutrol F68 solution (80°C). Larger batches were prepared up to 6 g of BPQ with GMS: BPQ, 2:1. SLN of designed size were obtained using ultraturrax and high pressure homogenizer. A freeze and thaw study was used to optimize type and concentration of cryoprotectant with Sf: Mean particle size, Si: Initial particle size <1.3. Differential scanning calorimetry (DSC), powder X-ray diffraction (XRD) and scanning electron microscope (SEM) study was performed on optimized formulation. Formulation was investigated for in vitro serum stability, hemolysis and cell uptake study. Pharmacokinetic and biodistribution study was performed in Holtzman rat. Results: Based on solubility in lipid; glyceryl monostearate (GMS) was selected for preparation of BPQ SLN. Batches of BPQ SLN were optimized for average particle size and entrapment efficiency at <100 mg solid content. A combination of Solutol HS-15 and Lutrol F68 at 2% w/v and greater enabled the desired Sf/Si < 1.3. Differential scanning calorimetry and powder X-ray diffraction revealed decrease in crystallinity of BPQ in BPQ SLN while, scanning electron microscope revealed spherical morphology. BPQ SLN revealed good stability at 4°C and 25°C. Low hemolytic potential (<8%) and in vitro serum stability up to 5 h was observed. Cytotoxicity of SLN to the U937 cell was low. The macrophage cell line revealed high (52%) uptake of BPQ SLN in 1 h suggesting the potential to RES uptake. SLN revealed longer circulation and biodistrbution study confirmed high RES uptake (75%) in RES organs like liver lung spleen etc. Conclusion: The high RES uptake suggests BPQ SLN as a promising approach for targeted and improved delivery in theileriosis. PMID:24459400

Cell-based immunotherapy in gynecologic malignancies.

PubMed

Schaar, Bruce; Krishnan, Venkatesh; Tallapragada, Supreeti; Dorigo, Oliver

2018-02-01

To provide an overview of the principles, safety and efficacy of adoptive cell therapy (ACT) in solid tumors particularly in gynecological cancers. Efforts to target solid tumors using tumor-infiltrating lymphocytes and genetically modified T cells have shown promising efficacy in some patients. Two food and drug administration approvals for the treatment of leukemia are the first gene therapies available for cancer treatment in the United States. Genetic engineering of antitumor immunity using T cells has the potential to target specific tumor-associated antigens and overcome obstacles to successful immunotherapy like immune-suppressive factors in the tumor microenvironment.

Immunoaffinity centrifugal precipitation chromatography.

PubMed

Qi, Lin; Ito, Yoichiro

2007-06-01

Purification of proteins based on immunoaffinity has been performed using a solid support coated with antibody against the target proteins. The method requires immobilizing the antibody onto the solid support using protein A or G, and has a risk of adsorptive loss of target proteins onto the solid support. Centrifugal precipitation chromatography has been successfully used to purify enzymes, such as ketosteroid isomerase and hyaluronidase without the use of solid support. The purpose of this study is to demonstrate that immunoaffinity centrifugal precipitation chromatography is capable of isolating an antigen by exploiting antigen-antibody binding. The separation was initiated by filling both channels with 40% saturated ammonium sulfate (AS) of pH 4-4.5 followed by loading 20 microl of human plasma (National Institutes of Health blood bank) mixed with 2 mg of rabbit anti-HSA (human serum protein) antibody (Sigma). Then, the sample channel was eluted with water at 0.03 ml/min and AS channel with 40% AS solution of pH 4-4.5 at 1 ml/min until all non-binding components were eluted. Then, the releasing reagent (50% AS solution containing 0.5 M glycine and 10% ammonium hydroxide at pH 10) was introduced through the AS channel to release the target protein (HSA). The retained antibody was recovered by eluting the sample channel with water at 1 ml/min. A hollow fiber membrane device at the outlet (MicroKros, Spectrum, New Brunswick, NJ, USA) was provided on-line dialysis of the eluent before fractions were collected, so that the fractions could be analyzed by SDS-PAGE (sodium dodecyl sulfate - polyacrylamide gel electrophoresis) without further dialysis. The current method does not require immobilizing the antibody onto a matrix, which is used by the conventional immunoaffinity chromatography. This method ensures full recovery of the antigen and antibody, and it may be applied to purification of other proteins.

Numerical Simulation of Ballistic Impact on Particulate Composite Target using Discrete Element Method: 1-D and 2-D Models

NASA Astrophysics Data System (ADS)

Nair, Rajesh P.; Lakshmana Rao, C.

2014-01-01

Ballistic impact (BI) is a study that deals with a projectile hitting a target and observing its effects in terms of deformation and fragmentation of the target. The Discrete Element Method (DEM) is a powerful numerical technique used to model solid and particulate media. Here, an attempt is made to simulate the BI process using DEM. 1-D DEM for BI is developed and depth of penetration (DOP) is obtained. The DOP is compared with results obtained from 2-D DEM. DEM results are found to match empirical results. Effects of strain rate sensitivity of the material response on DOP are also simulated.

Simultaneous Determination of Parathion, Malathion, Diazinon, and Pirimiphos Methyl in Dried Medicinal Plants Using Solid-Phase Microextraction Fibre Coated with Single-Walled Carbon Nanotubes

PubMed Central

Ahmadkhaniha, Reza; Samadi, Nasrin; Salimi, Mona; Sarkhail, Parisa; Rastkari, Noushin

2012-01-01

A reliable and sensitive headspace solid-phase microextraction gas chromatography-mass spectrometry method for simultaneous determination of different organophosphorus pesticides in dried medicinal plant samples is described. The analytes were extracted by single-walled carbon nanotubes as a new solid-phase microextraction adsorbent. The developed method showed good performance. For diazinon and pirimiphos methyl calibration, curves were linear (r 2 ≥ 0.993) over the concentration ranges from 1.5 to 300 ng g−1, and the limit of detection at signal-to-noise ratio of 3 was 0.3 ng g−1. For parathion and malathion, the linear range and limit of detection were 2.5–300 (r 2 ≥ 0.991) and 0.5 ng g−1, respectively. In addition, a comparative study between the single-walled carbon nanotubes and a commercial polydimethylsiloxane fibre for the determination of target analytes was carried out. Single-walled carbon nanotubes fibre showed higher extraction capacity, better thermal stability (over 350°C), and longer lifespan (over 250 times) than the commercial polydimethylsiloxane fibre. The developed method was successfully applied to determine target organophosphorus pesticides in real samples. PMID:22645439

Thermal decomposition of solid phase nitromethane under various heating rates and target temperatures based on ab initio molecular dynamics simulations.

PubMed

Xu, Kai; Wei, Dong-Qing; Chen, Xiang-Rong; Ji, Guang-Fu

2014-10-01

The Car-Parrinello molecular dynamics simulation was applied to study the thermal decomposition of solid phase nitromethane under gradual heating and fast annealing conditions. In gradual heating simulations, we found that, rather than C-N bond cleavage, intermolecular proton transfer is more likely to be the first reaction in the decomposition process. At high temperature, the first reaction in fast annealing simulation is intermolecular proton transfer leading to CH3NOOH and CH2NO2, whereas the initial chemical event at low temperature tends to be a unimolecular C-N bond cleavage, producing CH3 and NO2 fragments. It is the first time to date that the direct rupture of a C-N bond has been reported as the first reaction in solid phase nitromethane. In addition, the fast annealing simulations on a supercell at different temperatures are conducted to validate the effect of simulation cell size on initial reaction mechanisms. The results are in qualitative agreement with the simulations on a unit cell. By analyzing the time evolution of some molecules, we also found that the time of first water molecule formation is clearly sensitive to heating rates and target temperatures when the first reaction is an intermolecular proton transfer.

Tumor control by hypoxia-specific chemotargeting of iron-oxide nanoparticle - Berberine complexes in a mouse model.

PubMed

Sreeja, S; Krishnan Nair, C K

2018-02-15

To evaluate the therapeutic efficacy of hypoxic cell-sensitizer Sanazole (SAN) -directed targeting of cytotoxic drug Berberine (BBN) and Iron-oxide nanoparticle (NP) complexes, to solid tumor in Swiss albino mice. NP-BBN-SAN complexes were characterized by FTIR, XRD, TEM and Nano-size analyzer. This complex was orally administered to mice-bearing solid tumor in hind limb. Tumor regression was analysed by measuring tumor volume. Cellular DNA damages were assessed by comet assay. Transcriptional expression of genes related to tumor hypoxia and apoptosis was evaluated by quantitative real-time PCR and morphological changes in tissues were analysed by histopathology. Also levels of antioxidants and tumor markers in tissues and serum biochemical parameters were analysed. Administration of NP-BBN-SAN complexes reduced tumor volume and studies were focussed on the underlying mechanisms. Extensive damage to cellular-DNA; down-regulated transcription of hif-1α, vegf, akt and bcl2; and up-regulated expression of bax and caspases, were observed in tumor. Results on tumor markers, antioxidant-status and serum parameters corroborated the molecular findings. Histopathology of tumor, liver and kidney revealed the therapeutic specificity of NP-BBN-SAN. Thus SAN and NP can be used for specific targeting of drugs, to hypoxic solid tumor, to improve therapeutic efficacy. Copyright © 2017. Published by Elsevier Inc.

An empirical approach to the stopping power of solids and gases for ions from 3Li to 18Ar

NASA Astrophysics Data System (ADS)

Paul, Helmut; Schinner, Andreas

2001-08-01

A large collection of stopping power data for projectiles from 3Li to 18Ar is investigated as a possible basis for producing a table of stopping powers. We divide the experimental stopping powers for a particular projectile (nuclear charge Z1) by those for alpha particles in the same element, as given in ICRU Report 49. With proper normalization, we then obtain experimental stopping power ratios Srel that lie approximately on a single curve, provided we treat solid and gaseous targets separately, and provided we exclude H 2 and He targets. For every projectile, this curve is then fitted by a 3-parameter sigmoid function Srel= Srel( a, b, c). We find that the three parameters a, b and c depend smoothly on Z1 and can themselves be fitted by suitable functions af, bf and cf of Z1, separately for solid and gaseous targets. The low energy limit (coefficient a) for solids agrees approximately with the prediction by Lindhard and Scharff. We find that agas< asol in almost all cases. Introducing the coefficients af , bf and cf in Srel, we can calculate the stopping power for any ion (3⩽ Z1⩽18), and for any element (except H 2 and He) and any mixture or compound contained in the ICRU table.

Targeted next-generation sequencing at copy-number breakpoints for personalized analysis of rearranged ends in solid tumors.

PubMed

Kim, Hyun-Kyoung; Park, Won Cheol; Lee, Kwang Man; Hwang, Hai-Li; Park, Seong-Yeol; Sorn, Sungbin; Chandra, Vishal; Kim, Kwang Gi; Yoon, Woong-Bae; Bae, Joon Seol; Shin, Hyoung Doo; Shin, Jong-Yeon; Seoh, Ju-Young; Kim, Jong-Il; Hong, Kyeong-Man

2014-01-01

The concept of the utilization of rearranged ends for development of personalized biomarkers has attracted much attention owing to its clinical applicability. Although targeted next-generation sequencing (NGS) for recurrent rearrangements has been successful in hematologic malignancies, its application to solid tumors is problematic due to the paucity of recurrent translocations. However, copy-number breakpoints (CNBs), which are abundant in solid tumors, can be utilized for identification of rearranged ends. As a proof of concept, we performed targeted next-generation sequencing at copy-number breakpoints (TNGS-CNB) in nine colon cancer cases including seven primary cancers and two cell lines, COLO205 and SW620. For deduction of CNBs, we developed a novel competitive single-nucleotide polymorphism (cSNP) microarray method entailing CNB-region refinement by competitor DNA. Using TNGS-CNB, 19 specific rearrangements out of 91 CNBs (20.9%) were identified, and two polymerase chain reaction (PCR)-amplifiable rearrangements were obtained in six cases (66.7%). And significantly, TNGS-CNB, with its high positive identification rate (82.6%) of PCR-amplifiable rearrangements at candidate sites (19/23), just from filtering of aligned sequences, requires little effort for validation. Our results indicate that TNGS-CNB, with its utility for identification of rearrangements in solid tumors, can be successfully applied in the clinical laboratory for cancer-relapse and therapy-response monitoring.

Development of a high-power neutron-producing lithium target for boron neutron capture therapy

NASA Astrophysics Data System (ADS)

Brown, Adam V.; Scott, Malcolm C.

2000-12-01

A neutron producing lithium target for a novel, accelerator based cancer treatment requires the removal of up to 6kW of heat produced by 1-2mA beam of 2.3-3.0MeV protons. This paper presents the results form computer simulations which show that, using submerged jet cooling, a solid lithium target can be maintained up to 1.6mA, and a liquid target up to 2.6mA, assuming a 3.0MeV proton beam. The predictions from the simulations are verified through the use of an experimental heat transfer test-rig and the result form a number of metallurgical studies made to select a compatible substrate material for the lithium are reported.

A chimeric switch-receptor targeting PD1 augments the efficacy of second generation CAR T-Cells in advanced solid tumors

PubMed Central

Liu, Xiaojun; Ranganathan, Raghuveer; Jiang, Shuguang; Fang, Chongyun; Sun, Jing; Kim, Soyeon; Newick, Kheng; Lo, Albert; June, Carl H.; Zhao, Yangbing; Moon, Edmund K.

2015-01-01

Chimeric antigen receptor (CAR)-modified adoptive T-cell therapy (ATC) has been successfully applied to the treatment of hematologic malignancies, but faces many challenges in solid tumors. One major obstacle is the immune-suppressive effects induced in both naturally-occurring and genetically-modified tumor infiltrating lymphocytes (TILs) by inhibitory receptors (IRs), namely PD1. We hypothesized that interfering with PD1 signaling would augment CAR T cell activity against solid tumors. To address this possibility, we introduced a genetically-engineered switch receptor construct, comprising the truncated extracellular domain of PD1 and the transmembrane and cytoplasmic signaling domains of CD28, into CAR T-cells. We tested the effect of this supplement, “PD1CD28”, on human CAR T-cells targeting aggressive models of human solid tumors expressing relevant tumor antigens. Treatment of mice bearing large, established solid tumors with PD1CD28 CAR T-cells led to significant regression in tumor volume due to enhanced CAR TIL infiltrate, decreased susceptibility to tumor-induced hypofunction, and attenuation of IR expression compared to treatments with CAR T-cells alone or PD1 antibodies. Taken together, our findings suggest that the application of PD1CD28 to boost CAR T-cell activity is efficacious against solid tumors via a variety of mechanisms, prompting clinical investigation of this potentially promising treatment modality. PMID:26979791

Study of the {sup 15}N(p,gamma){sup 16}O Reaction at LUNA with a Solid Target

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

Capogrosso, Valentina

2010-03-01

The case of the most recent measurement performed at LUNA, the {sup 15}N(p,gamma){sup 16}O reaction, is presented. This reaction, together with the {sup 15}N(p,alpha){sup 12}C, forms the branching point from the first to the second CNO cycle and the ratio of their respective reaction rates influences the nucleosynthesis yields of {sup 16}O, {sup 17}O e {sup 17}F. In particular, one of the three different campaigns performed by the LUNA collaboration to measure the cross section of this reaction will be discussed. This experiment was performed by impinging a proton beam from the LUNA accelerator with energies ranging from 77 tomore » 350 keV in the centre-of-mass reference frame on a TiN solid target, enriched in {sup 15}N to 98%. The gamma-rays following the (p, gamma) reaction were detected by means of an high-efficiency BGO detector.« less

High frequency of loss of PTEN expression in human solid salivary adenoid cystic carcinoma and its implication for targeted therapy.

PubMed

Liu, Han; Du, Li; Wang, Ru; Wei, Chao; Liu, Bo; Zhu, Lei; Liu, Pixu; Liu, Qiang; Li, Jiang; Lu, Shi-Long; Xiao, Jing

2015-05-10

Salivary gland tumor (SGT) is one of the least studied cancers due to its rarity and heterogeneous histological types. Here, we reported that loss of PTEN expression was most frequently found in the poorly differentiated, high grade solid adenoid cystic carcinomas. Loss of PTEN expression correlated with activation of mTOR by increased phosphorylated S6 ribosome protein. We further functionally studied the role of PTEN in a pair of human SACC cell lines, SACC-83 and SACC-LM. Reduced PTEN level was correlated with the metastasis potential. When we knocked down PTEN in the SACC-83 cell line, we observed increased proliferation and enhanced migration/invasion in vitro, and increased tumor size in vivo. We further tested the therapeutical effect by applying a PI3K/mTOR inhibitor NVP-BEZ235 to both SACC cell lines. Decreased cell proliferation, increased apoptosis, as well as reduced cell migration/invasion were observed in both cell lines upon the NVP-BEZ235 treatment. Moreover, the NVP-BEZ235 treatment in a SGT xenograft mouse model significantly reduced primary tumor size and lung metastasis. Taken together, our results demonstrated that PTEN is a potent tumor suppressor in human SGTs, and targeting PI3K/mTOR pathway may be effective in the targeted therapy for human SGT patients with loss of PTEN expression.

Influence of the laser pulse repetition rate and scanning speed on the morphology of Ag nanostructures fabricated by pulsed laser ablation of solid target in water

NASA Astrophysics Data System (ADS)

Nikolov, A. S.; Balchev, I. I.; Nedyalkov, N. N.; Kostadinov, I. K.; Karashanova, D. B.; Atanasova, G. B.

2017-11-01

Nanostructures of noble metal were produced by pulsed laser ablation in liquid. A solid Ag target was immersed in double distilled water and a CuBr laser in a master oscillator—power amplifier configuration oscillating at 511 nm and emitting pulses with duration of 30 ns at a repetition rate of up to 20 kHz was employed to produce different colloids. The impact was studied of the laser pulse repetition rate and the beam scanning speed on the morphology of the nanostructures formed. Further, the optical extinction spectra of the colloids in the UV/VIS range were measured and used to make an indirect assessment of the changes in the shape and size distribution of the nanostructures. The transmission values in the near UV range were used to estimate the efficiency of the ablation process under the different experimental conditions implemented. A visualization of the nanostructures was made possible by transmission electron microscopy (TEM). The structure and phase composition of the nanoparticles were studied by high-resolution transmission electron microscopy (HRTEM) and selected area electron diffraction (SAED), while the alteration of the target surface caused by the impact of the high-repetition-rate laser illumination was investigated by X-ray photoelectron spectroscopy (XPS). The optimal conditions were determined yielding the highest efficiency in terms of amount of ablated material.

Determination of alkylphenols and 17beta-estradiol in fish homogenate. Extraction and clean-up strategies.

PubMed

Navarro, P; Bustamante, J; Vallejo, A; Prieto, A; Usobiaga, A; Arrasate, S; Anakabe, E; Puy-Azurmendi, E; Zuloaga, O

2010-09-17

The determination of target analytes such as nonyl- and octylphenols and 17beta-estradiol in fish homogenate require of solid-liquid extraction step. In this work microwave-assisted extraction (MAE) and focused-ultrasound liquid extraction (FUSLE) were studied as two different alternatives for extraction of the target compounds in zebrafish (Danio rerio) homogenate. In this work solid phase extraction (SPE) using 5-g and 10-g Florisil cartridges and gel permeation chromatography (GPC) were studied for the clean-up of the MAE and FUSLE extracts due to the non-selective extraction step. Although good recoveries were obtained both for SPE (106% and 126% range) and GPC (79% and 100% range) clean-up procedures, cleaner chromatograms were obtained after SPE and finally 5-g Florisil cartridges were tested since no improvement was observed when 10-g Florisil cartridges were used. Under optimized clean-up conditions, MAE and FUSLE provided comparable results for 4nOP and NP, while more accurate results were obtained for 4tOP and E2 after FUSLE. Finally, the method was applied to the determination of alkylphenols and 17beta-estradiol in zebrafish homogenate that had been exposed to known concentrations of the target analytes. In the case of alkylphenols two different isomers of nonyl- and octylphenol (4-(3',6'-dimethyl-3'-hepthyl)phenol, 363-NP, and 4-(3'-methyl-3'-hepthyl)phenol, 33-OP) were studied. 2010 Elsevier B.V. All rights reserved.

A study to evaluate STS heads-up ascent trajectory performance employing a minimum-Hamiltonian optimization strategy

NASA Technical Reports Server (NTRS)

Sinha, Sujit

1988-01-01

A study was conducted to evaluate the performance implications of a heads-up ascent flight design for the Space Transportation System, as compared to the current heads-down flight mode. The procedure involved the use of the Minimum Hamiltonian Ascent Shuttle Trajectory Evaluation Program, which is a three-degree-of-freedom moment balance simulation of shuttle ascent. A minimum-Hamiltonian optimization strategy was employed to maximize injection weight as a function of maximum dynamic pressure constraint and Solid Rocket Motor burnrate. Performance Reference Mission Four trajectory groundrules were used for consistency. The major conclusions are that for heads-up ascent and a mission nominal design maximum dynamic pressure value of 680 psf, the optimum solid motor burnrate is 0.394 ips, which produces a performance enhancement of 4293 lbm relative to the baseline heads-down ascent, with 0.368 ips burnrate solid motors and a 680 psf dynamic pressure constraint. However, no performance advantage exists for heads-up flight if the current Solid Rocket Motor target burnrate of 0.368 ips is used. The advantage of heads-up ascent flight employing the current burnrate is that Space Shuttle Main Engine throttling for dynamic pressure control is not necessary.

Who owns urban waste? Appropriation conflicts in emerging countries.

PubMed

Cavé, Jérémie

2014-09-01

Managing solid waste in developing cities is not an easy task and many public policies have failed to bring the expected results. It is here argued that comprehending the solid waste handling in the South implies reconsidering the proper definition of waste. Where does the product end and where does rubbish begin? The answer to this question is far from being obvious. Solid waste appears as a blurred concept. Such a thorny issue is all the more relevant today, as municipal solid waste management approaches in the developing world are being reformulated: dumping sites are banned, sanitary landfills are imposed, and separate collection is being introduced. The current sector transformations are here analysed through a novel theoretical analysis combined with an original qualitative and quantitative empirical work. Through two case-studies of one-million inhabitant cities from emerging countries, it is shown that if appropriation conflicts arise that is because the urban solid waste deposit in Southern countries can be defined as an impure public good. This issue does not only involve private service operators and informal wastepickers; several other actors covet the urban solid waste deposit's cream, that is, recyclable items. In emerging countries, huge industrial groups are starting to target domestic recyclable waste as an alternative for raw materials, which costs are increasing ever more. © The Author(s) 2014.

Carbon capture test unit design and development using amine-based solid sorbent

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

Breault, Ronald W.; Spenik, James L.; Shadle, Lawrence J.

This study presents the design and development of a reactor system and the subsequent modifications to evaluate an integrated process to scrub carbon dioxide (CO 2) from synthetic flue gas using amine based solid sorbents. The paper presents the initial system design and then discusses the various changes implemented to address the change in sorbent from a 180 μm Geldart group B material to a 115 μm Geldart group A material as well as issues discovered during experimental trials where the major obstacle in system operation was the ability to maintain a constant circulation of a solid sorbent stemming frommore » this change in sorbent material. The system primarily consisted of four fluid beds, through which an amine impregnated solid sorbent was circulated and adsorption, pre-heat, regeneration, and cooling processes occurred. Instrumentation was assembled to characterize thermal, hydrodynamic, and gas adsorption performance in this integrated unit. A series of shakedown tests were performed and the configuration altered to meet the needs of the sorbent performance and achieve desired target capture efficiencies. Finally, methods were identified, tested, and applied to continuously monitor critical operating parameters including solids circulation rate, adsorbed and desorbed CO 2, solids inventories, and pressures.« less

The Solid State Image Sensor's Contribution To The Development Of Silicon Technology

NASA Astrophysics Data System (ADS)

Weckler, Gene P.

1985-12-01

Until recently, a solid-state image sensor with full television resolution was a dream. However, the dream of a solid state image sensor has been a driving force in the development of silicon technology for more than twenty-five years. There are probably many in the main stream of semiconductor technology who would argue with this; however, the solid state image sensor was conceived years before the invention of the semi conductor RAM or the microprocessor (i.e., even before the invention of the integrated circuit). No other potential application envisioned at that time required such complexity. How could anyone have ever hoped in 1960 to make a semi conductor chip containing half-a-million picture elements, capable of resolving eight to twelve bits of infornation, and each capable of readout rates in the tens of mega-pixels per second? As early as 1960 arrays of p-n junctions were being investigated as the optical targets in vidicon tubes, replacing the photoconductive targets. It took silicon technology several years to catch up with these dreamers.

Directional enhancement of selected high-order-harmonics from intense laser irradiated blazed grating targets.

PubMed

Zhang, Guobo; Chen, Min; Liu, Feng; Yuan, Xiaohui; Weng, Suming; Zheng, Jun; Ma, Yanyun; Shao, Fuqiu; Sheng, Zhengming; Zhang, Jie

2017-10-02

Relativistically intense laser solid target interaction has been proved to be a promising way to generate high-order harmonics, which can be used to diagnose ultrafast phenomena. However, their emission direction and spectra still lack tunability. Based upon two-dimensional particle-in-cell simulations, we show that directional enhancement of selected high-order-harmonics can be realized using blazed grating targets. Such targets can select harmonics with frequencies being integer times of the grating frequency. Meanwhile, the radiation intensity and emission area of the harmonics are increased. The emission direction is controlled by tailoring the local blazed structure. Theoretical and electron dynamics analysis for harmonics generation, selection and directional enhancement from the interaction between multi-cycle laser and grating target are carried out. These studies will benefit the generation and application of laser plasma-based high order harmonics.

Recent advances and results from the solid radiochemistry nuclear diagnostic at the National Ignition Facility

DOE PAGES

Gharibyan, N.; Shaughnessy, D. A.; Moody, K. J.; ...

2016-08-05

The solid debris collection capability at the National Ignition Facility has been expanded to include a third line-of-sight assembly. The solid radiochemistry nuclear diagnostic measurement of the ratio of gold isotopes is dependent on the efficient collection of neutron-activated hohlraum debris by passive metal disks. As a result, the collection of target debris at this new location is more reliable in comparison to the historic locations, and it appears to be independent of collector surface ablation.

Recent advances and results from the solid radiochemistry nuclear diagnostic at the National Ignition Facility.

PubMed

Gharibyan, N; Shaughnessy, D A; Moody, K J; Grant, P M; Despotopulos, J D; Faye, S A; Jedlovec, D R; Yeamans, C B

2016-11-01

The solid debris collection capability at the National Ignition Facility has been expanded to include a third line-of-sight assembly. The solid radiochemistry nuclear diagnostic measurement of the ratio of gold isotopes is dependent on the efficient collection of neutron-activated hohlraum debris by passive metal disks. The collection of target debris at this new location is more reliable in comparison to the historic locations, and it appears to be independent of collector surface ablation.

ACCELERATED SOLVENT EXTRACTION COMBINED WITH ...

EPA Pesticide Factsheets

A research project was initiated to address a recurring problem of elevated detection limits above required risk-based concentrations for the determination of semivolatile organic compounds in high moisture content solid samples. This project was initiated, in cooperation with the EPA Region 1 Laboratory, under the Regional Methods Program administered through the ORD Office of Science Policy. The aim of the project was to develop an approach for the rapid removal of water in high moisture content solids (e.g., wetland sediments) in preparation for analysis via Method 8270. Alternative methods for water removal have been investigated to enhance compound solid concentrations and improve extraction efficiency, with the use of pressure filtration providing a high-throughput alternative for removal of the majority of free water in sediments and sludges. In order to eliminate problems with phase separation during extraction of solids using Accelerated Solvent Extraction, a variation of a water-isopropanol extraction method developed at the USGS National Water Quality Laboratory in Denver, CO is being employed. The concentrations of target compounds in water-isopropanol extraction fluids are subsequently analyzed using an automated Solid Phase Extraction (SPE)-GC/MS method developed in our laboratory. The coupled approaches for dewatering, extraction, and target compound identification-quantitation provide a useful alternative to enhance sample throughput for Me

An update on anticancer drug development and delivery targeting carbonic anhydrase IX

PubMed Central

Parkkila, Seppo

2017-01-01

The expression of carbonic anhydrase (CA) IX is up-regulated in many types of solid tumors in humans under hypoxic and acidic microenvironment. Inhibition of CA IX enzymatic activity with selective inhibitors, antibodies or labeled probes has been shown to reverse the acidic environment of solid tumors and reduce the tumor growth establishing the significant role of CA IX in tumorigenesis. Thus, the development of potent antitumor drugs targeting CA IX with minimal toxic effects is important for the target-specific tumor therapy. Recently, several promising antitumor agents against CA IX have been developed to treat certain types of cancers in combination with radiation and chemotherapy. Here we review the inhibition of CA IX by small molecule compounds and monoclonal antibodies. The methods of enzymatic assays, biophysical methods, animal models including zebrafish and Xenopus oocytes, and techniques of diagnostic imaging to detect hypoxic tumors using CA IX-targeted conjugates are discussed with the aim to overview the recent progress related to novel therapeutic agents that target CA IX in hypoxic tumors. PMID:29181278

Relativistic-electron-beam/target interaction in plasma channels

NASA Astrophysics Data System (ADS)

Halbleib, J. A., Sr.; Wright, T. P.

1980-08-01

A model describing the transport of relativistic electron beams in plasma channels and their subsequent interaction with solid targets is developed and applied to single-beam and multiple-beam configurations. For single beams the targets consist of planar tantalum foils and, in some cases, cusp fields on the transmission side of the foils are employed to improve beam/target coupling efficiency. In the multi-beam configurations, several beams are arranged in wagon-wheel fashion so as to converge upon cylindrical targets, consisting of either hollow tantalum or solid graphite cylinders, located at the hub. For 0.3-cm beam radii that are less than or equal to the channel radii, mean specific power depositions up to about 17 TW/g per MA of injected beam current are obtained for single beams; 12-beam results are typically an order-of-magnitude less. The corresponding enhancements are up to five times the collisional stopping power for either single or multiple beams. Substantial improvement is predicted for the multi-beam interaction should future channel technology permit transport at higher current densities in smaller channels.

Solid-Phase Synthesis of Difficult Purine-Rich PNAs through Selective Hmb Incorporation: Application to the Total Synthesis of Cell Penetrating Peptide-PNAs

PubMed Central

Tailhades, Julien; Takizawa, Hotake; Gait, Michael J.; Wellings, Don A.; Wade, John D.; Aoki, Yoshitsugu; Shabanpoor, Fazel

2017-01-01

Antisense oligonucleotide (ASO)-based drug development is gaining significant momentum following the recent FDA approval of Eteplirsen (an ASO based on phosphorodiamidate morpholino) and Spinraza (2′-O-methoxyethyl-phosphorothioate) in late 2016. Their attractiveness is mainly due to the backbone modifications which have improved the in vivo characteristics of oligonucleotide drugs. Another class of ASO, based on peptide nucleic acid (PNA) chemistry, is also gaining popularity as a platform for development of gene-specific therapy for various disorders. However, the chemical synthesis of long PNAs, which are more target-specific, remains an ongoing challenge. Most of the reported methodology for the solid-phase synthesis of PNA suffer from poor coupling efficiency which limits production to short PNA sequences of less than 15 residues. Here, we have studied the effect of backbone modifications with Hmb (2-hydroxy-4-methoxybenzyl) and Dmb (2,4-dimethoxybenzyl) to ameliorate difficult couplings and reduce “on-resin” aggregation. We firstly synthesized a library of PNA dimers incorporating either Hmb or Dmb and identified that Hmb is superior to Dmb in terms of its ease of removal. Subsequently, we used Hmb backbone modification to synthesize a 22-mer purine-rich PNA, targeting dystrophin RNA splicing, which could not be synthesized by standard coupling methodology. Hmb backbone modification allowed this difficult PNA to be synthesized as well as to be continued to include a cell-penetrating peptide on the same solid support. This approach provides a novel and straightforward strategy for facile solid-phase synthesis of difficult purine-rich PNA sequences. PMID:29094037

Solid-Phase Synthesis of Difficult Purine-Rich PNAs through Selective Hmb Incorporation: Application to the Total Synthesis of Cell Penetrating Peptide-PNAs.

PubMed

Tailhades, Julien; Takizawa, Hotake; Gait, Michael J; Wellings, Don A; Wade, John D; Aoki, Yoshitsugu; Shabanpoor, Fazel

2017-01-01

Antisense oligonucleotide (ASO)-based drug development is gaining significant momentum following the recent FDA approval of Eteplirsen (an ASO based on phosphorodiamidate morpholino) and Spinraza (2'- O -methoxyethyl-phosphorothioate) in late 2016. Their attractiveness is mainly due to the backbone modifications which have improved the in vivo characteristics of oligonucleotide drugs. Another class of ASO, based on peptide nucleic acid (PNA) chemistry, is also gaining popularity as a platform for development of gene-specific therapy for various disorders. However, the chemical synthesis of long PNAs, which are more target-specific, remains an ongoing challenge. Most of the reported methodology for the solid-phase synthesis of PNA suffer from poor coupling efficiency which limits production to short PNA sequences of less than 15 residues. Here, we have studied the effect of backbone modifications with Hmb (2-hydroxy-4-methoxybenzyl) and Dmb (2,4-dimethoxybenzyl) to ameliorate difficult couplings and reduce "on-resin" aggregation. We firstly synthesized a library of PNA dimers incorporating either Hmb or Dmb and identified that Hmb is superior to Dmb in terms of its ease of removal. Subsequently, we used Hmb backbone modification to synthesize a 22-mer purine-rich PNA, targeting dystrophin RNA splicing, which could not be synthesized by standard coupling methodology. Hmb backbone modification allowed this difficult PNA to be synthesized as well as to be continued to include a cell-penetrating peptide on the same solid support. This approach provides a novel and straightforward strategy for facile solid-phase synthesis of difficult purine-rich PNA sequences.

Solid-phase synthesis of difficult purine-rich PNAs through selective Hmb incorporation: Application to the total synthesis of cell penetrating peptide-PNAs

NASA Astrophysics Data System (ADS)

Tailhades, Julien; Takizawa, Hotake; Gait, Michael J.; Wellings, Don A.; Wade, John D.; Aoki, Yoshitsugu; Shabanpoor, Fazel

2017-10-01

Antisense oligonucleotide (ASO)-based drug development is gaining significant momentum following the recent FDA approval of Eteplirsen (an ASO based on phosphorodiamidate morpholino) and Spinraza (2’-O-methoxyethyl-phosphorothioate) in late 2016. Their attractiveness is mainly due to the backbone modifications which have improved the in vivo characteristics of oligonucleotide drugs. Another class of ASO, based on peptide nucleic acid (PNA) chemistry, is also gaining popularity as a platform for development of gene-specific therapy for various disorders. However, the chemical synthesis of long PNAs, which are more target-specific, remains an ongoing challenge. Most of the reported methodology for the solid-phase synthesis of PNA suffer from poor coupling efficiency which limits production to short PNA sequences of less than 15 residues. Here we have studied the effect of backbone modifications with Hmb (2-hydroxy-4-methoxybenzyl) and Dmb (2,4-dimethoxybenzyl) to ameliorate difficult couplings and reduce “on-resin” aggregation. We firstly synthesized a library of PNA dimers incorporating either Hmb or Dmb and identified that Hmb is superior to Dmb in terms of its ease of removal. Subsequently, we used Hmb backbone modification to synthesize a 22-mer purine-rich PNA, targeting dystrophin RNA splicing, which could not be synthesized by standard coupling methodology. Hmb backbone modification allowed this difficult PNA to be synthesized as well as to be continued to include a cell-penetrating peptide on the same solid support. This approach provides a novel and straightforward strategy for facile solid-phase synthesis of difficult purine-rich PNA sequences.

Method and apparatus for optimized sampling of volatilizable target substances

DOEpatents

Lindgren, Eric R.; Phelan, James M.

2004-10-12

An apparatus for capturing, from gases such as soil gas, target analytes. Target analytes may include emanations from explosive materials or from residues of explosive materials. The apparatus employs principles of sorption common to solid phase microextraction, and is best used in conjunction with analysis means such as a gas chromatograph. To sorb target analytes, the apparatus functions using various sorptive structures to capture target analyte. Depending upon the embodiment, those structures may include a capillary tube including an interior surface on which sorptive material (similar to that on the surface of a SPME fiber) is supported (along with means for moving gases through the capillary tube so that the gases come into close proximity to the sorptive material). In one disclosed embodiment, at least one such sorptive structure is associated with an enclosure including an opening in communication with the surface of a soil region potentially contaminated with buried explosive material such as unexploded ordnance. Emanations from explosive materials can pass into and accumulate in the enclosure where they are sorbed by the sorptive structures. Also disclosed is the use of heating means such as microwave horns to drive target analytes into the soil gas from solid and liquid phase components of the soil.

Progress on CBET Platform at the Nike Laser

NASA Astrophysics Data System (ADS)

Weaver, J. L.; McKenty, P.; Oh, J.; Kehne, D.; Schmitt, A. J.; Obenschain, S.; Serlin, V.; Lehmberg, R.; Tsung, F.

2015-11-01

Cross-beam energy transport (CBET) studies are underway at the Nike krypton-fluoride (KrF) laser at NRL. This facility has unique characteristics that provide an excellent platform for CBET work - including short wavelength (248 nm), large bandwidth (1-3 THz), beam smoothing by induced spatial incoherence (ISI), and full aperture focal spot zooming. Nike's two beam arrays are widely separated (135° in azimuth) which facilitates CBET studies in a nearly opposing geometry, relevant to Polar Direct Drive implosions. Various target types are planned: planar slabs, cylindrical and spherical shells, and low-density targets. The solid targets will be used to examine gradient geometries and the latter will access larger volume, more uniform plasmas. The initial campaign is exploring changes observed by scattered light diagnostics for both beam arrays as the probe laser spectrum is modified. Work supported by DoE/NNSA.

A simplified radiometabolite analysis procedure for PET radioligands using a solid phase extraction with micellar medium.

PubMed

Nakao, Ryuji; Halldin, Christer

2013-07-01

A solid phase extraction method has been developed for simple and high-speed direct determination of PET radioligands in plasma. This methodology makes use of a micellar medium and a solid-phase extraction cartridge for displacement of plasma protein bound radioligand and separation of PET radioligands from their radiometabolites without significant preparation. The plasma samples taken from monkey or human during PET measurements were mixed with a micellar eluent containing an anionic surfactant sodium dodecyl sulphate and loaded onto SPE cartridges. The amount of radioactivity corresponding to parent radioligand (retained on the cartridge) and its radioactive metabolites (eluted with micellar eluent) was measured. Under the optimized conditions, excellent separation of target PET radioligands from their radiometabolites was achieved with a single elution and short run-time of 1 min. This method was successfully applied to study the metabolism for (11)C-labelled radioligands in human or monkey plasma. The amount of parent PET radioligands estimated by micellar solid phase extraction strongly corresponded with that determined by radio-LC. The improved throughput permitted the analysis of a large number of plasma samples (up to 13 samples per one PET study) for accurate estimation of metabolite-corrected input function during quantitative PET imaging studies. Solid phase extraction together with micellar medium is fast, sensitive and easy to use, and therefore it is an attractive alternative method to determine relative composition of PET radioligands in plasma. Copyright © 2013 Elsevier Inc. All rights reserved.

Pharmaceutical Applications of Relaxation Filter-Selective Signal Excitation Methods for ¹⁹F Solid-State Nuclear Magnetic Resonance: Case Study With Atorvastatin in Dosage Formulation.

PubMed

Asada, Mamiko Nasu; Nemoto, Takayuki; Mimura, Hisashi

2016-03-01

We recently developed several new relaxation filter-selective signal excitation (RFS) methods for (13)C solid-state nuclear magnetic resonance (NMR) that allow (13)C signal extraction of the target components from pharmaceuticals. These methods were successful in not only qualification but also quantitation over the wide range of 5% to 100%. Here, we aimed to improve the sensitivity of these methods and initially applied them to (19)F solid-state NMR, on the basis that the fluorine atom is one of the most sensitive NMR-active nuclei. For testing, we selected atorvastatin calcium (ATC), an antilipid BCS class II drug that inhibits 3-hydroxy-3-methylglutaryl-coenzyme A reductase and is marketed in crystalline and amorphous forms. Tablets were obtained from 2 generic drug suppliers, and the ATC content occurred mainly as an amorphous form. Using the RFS method with (19)F solid-state NMR, we succeeded in qualifying trace amounts (less than 0.5% w/w level) of crystalline phase (Form I) of ATC in the tablets. RFS methods with (19)F solid-state NMR are practical and time efficient and can contribute not only to the study of pharmaceutical drugs, including those with small amounts of a highly potent active ingredient within a formulated product, but also to the study of fluoropolymers in material sciences. Copyright © 2016 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.

Investigation of automotive primer and basecoat paint surface's adhesion by solid particle erosion

NASA Astrophysics Data System (ADS)

Demirci, M.; Baǧcı, M.

2018-05-01

Millions of cars are sold around the world and tons of paint are used for these cars. Since the car paint industry is alive in this way, new developments in the paint sector have been taking place every day. It is important to determine how these developments affect paint erosion. Solid particle erosion wear is a subject that keeps its update for car paints and it always needs to be investigated in detail. The target of this experimental study is to investigate solid particle erosion behavior of a commercial acrylic/melamine primer surface and basecoat of automotive paint. As a erodent, silica particles having a weight of 1 to 5 kg were used. Tests were performed at 30° and 90° impact angle and particle velocity 23 m s-1. With this work, an idea about the adhesion of the car paint coatings to the material surface was obtained.

Accelerated exploration of multi-principal element alloys with solid solution phases

PubMed Central

Senkov, O.N.; Miller, J.D.; Miracle, D.B.; Woodward, C.

2015-01-01

Recent multi-principal element, high entropy alloy (HEA) development strategies vastly expand the number of candidate alloy systems, but also pose a new challenge—how to rapidly screen thousands of candidate alloy systems for targeted properties. Here we develop a new approach to rapidly assess structural metals by combining calculated phase diagrams with simple rules based on the phases present, their transformation temperatures and useful microstructures. We evaluate over 130,000 alloy systems, identifying promising compositions for more time-intensive experimental studies. We find the surprising result that solid solution alloys become less likely as the number of alloy elements increases. This contradicts the major premise of HEAs—that increased configurational entropy increases the stability of disordered solid solution phases. As the number of elements increases, the configurational entropy rises slowly while the probability of at least one pair of elements favouring formation of intermetallic compounds increases more rapidly, explaining this apparent contradiction. PMID:25739749

Developing a vacuum cooking equipment prototype to produce strawberry jam and optimization of vacuum cooking conditions.

PubMed

Okut, Dilara; Devseren, Esra; Koç, Mehmet; Ocak, Özgül Özdestan; Karataş, Haluk; Kaymak-Ertekin, Figen

2018-01-01

Purpose of this study was to develop prototype cooking equipment that can work at reduced pressure and to evaluate its performance for production of strawberry jam. The effect of vacuum cooking conditions on color soluble solid content, reducing sugars total sugars HMF and sensory properties were investigated. Also, the optimum vacuum cooking conditions for strawberry jam were optimized for Composite Rotatable Design. The optimum cooking temperature and time were determined targeting maximum soluble solid content and sensory attributes (consistency) and minimum Hue value and HMF content. The optimum vacuum cooking conditions determined were 74.4 °C temperature and 19.8 time. The soluble solid content strawberry jam made by vacuum process were similar to those prepared by traditional method. HMF contents of jams produced with vacuum cooking method were well within limit of standards.

Delivery of kinesin spindle protein targeting siRNA in solid lipid nanoparticles to cellular models of tumor vasculature

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

Ying, Bo; Campbell, Robert B., E-mail: robert.campbell@mcphs.edu

2014-04-04

Highlights: • siRNA-lipid nanoparticles are solid particles not lipid bilayers with aqueous core. • High, but not low, PEG content can prevent nanoparticle encapsulation of siRNA. • PEG reduces cellular toxicity of cationic nanoparticles in vitro. • PEG reduces zeta potential while improving gene silencing of siRNA nanoparticles. • Kinesin spindle protein can be an effective target for tumor vascular targeting. - Abstract: The ideal siRNA delivery system should selectively deliver the construct to the target cell, avoid enzymatic degradation, and evade uptake by phagocytes. In the present study, we evaluated the importance of polyethylene glycol (PEG) on lipid-based carriermore » systems for encapsulating, and delivering, siRNA to tumor vessels using cellular models. Lipid nanoparticles containing different percentage of PEG were evaluated based on their physical chemical properties, density compared to water, siRNA encapsulation, toxicity, targeting efficiency and gene silencing in vitro. siRNA can be efficiently loaded into lipid nanoparticles (LNPs) when DOTAP is included in the formulation mixture. However, the total amount encapsulated decreased with increase in PEG content. In the presence of siRNA, the final formulations contained a mixed population of particles based on density. The major population which contains the majority of siRNA exhibited a density of 4% glucose, and the minor fraction associated with a decreased amount of siRNA had a density less than PBS. The inclusion of 10 mol% PEG resulted in a greater amount of siRNA associated with the minor fraction. Finally, when kinesin spindle protein (KSP) siRNA was encapsulated in lipid nanoparticles containing a modest amount of PEG, the proliferation of endothelial cells was inhibited due to the efficient knock down of KSP mRNA. The presence of siRNA resulted in the formation of solid lipid nanoparticles when prepared using the thin film and hydration method. LNPs with a relatively modest amount of PEG can sufficiently encapsulate siRNA, improve cellular uptake and the efficiency of gene silencing.« less

ErbB-targeted CAR T-cell immunotherapy of cancer.

PubMed

Whilding, Lynsey M; Maher, John

2015-01-01

Chimeric antigen receptor (CAR) based immunotherapy has been under development for the last 25 years and is now a promising new treatment modality in the field of cancer immunotherapy. The approach involves genetically engineering T cells to target malignant cells through expression of a bespoke fusion receptor that couples an HLA-independent antigen recognition domain to one or more intracellular T-cell activating modules. Multiple clinical trials are now underway in several centers to investigate CAR T-cell immunotherapy of diverse hematologic and solid tumor types. The most successful results have been achieved in the treatment of patients with B-cell malignancies, in whom several complete and durable responses have been achieved. This review focuses on the preclinical and clinical development of CAR T-cell immunotherapy of solid cancers, targeted against members of the ErbB family.

The SeaQuest Spectrometer at Fermilab

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

Aidala, C.A.; et al.

The SeaQuest spectrometer at Fermilab was designed to detect oppositely-charged pairs of muons (dimuons) produced by interactions between a 120 GeV proton beam and liquid hydrogen, liquid deuterium and solid nuclear targets. The primary physics program uses the Drell-Yan process to probe antiquark distributions in the target nucleon. The spectrometer consists of a target system, two dipole magnets and four detector stations. The upstream magnet is a closed-aperture solid iron magnet which also serves as the beam dump, while the second magnet is an open aperture magnet. Each of the detector stations consists of scintillator hodoscopes and a high-resolution trackingmore » device. The FPGA-based trigger compares the hodoscope signals to a set of pre-programmed roads to determine if the event contains oppositely-signed, high-mass muon pairs.« less

Using response evaluation criteria in solid tumors in real-world evidence cancer research.

PubMed

Feinberg, Bruce A; Bharmal, Murtuza; Klink, Andrew J; Nabhan, Chadi; Phatak, Hemant

2018-05-31

Real-world evidence of charted treatment responses to cancer drug therapy was compared with medical record derived radiographic measurements of target lesions per Response Evaluation Criteria in Solid Tumors (RECIST). 15 physicians treating 59 metastatic Merkel cell cancer (mMCC) patients contributed patient-level data. A comparison of medical record reported best response with radiographic measurements per RECIST of pre- and post-treatment target lesions. RECIST response rates were significantly lower compared with medical record reported with a concordance of 43.2% (95% CI: 28.0-58.4%). Subjective assessment of tumor response collected via traditional chart abstraction may overestimate benefit and limit the potential role of real-world evidence in value-based care research. The use of target lesion measurements presents an attractive alternative that better aligns with trial results.

Measuring the radiation force of megahertz ultrasound acting on a solid spherical scatterer

NASA Astrophysics Data System (ADS)

Nikolaeva, A. V.; Tsysar, S. A.; Sapozhnikov, O. A.

2016-01-01

The paper considers the problem of precise measurement of the acoustic radiation force of an ultrasonic beam on targets in the form of solid spherical scatterers. Using known analytic relations, a numerical model is developed to perform calculations for different sizes of spherical scatterers and arbitrary frequencies of the incident acoustic wave. A novel method is proposed for measuring the radiation force, which is based on the principle of acoustic echolocation. The radiation force is measured experimentally in a wide range of incident wave intensities using two chosen methods differing in the way the location of the target is controlled.

Automated production of 124I and 64Cu using IBA Terimo and Pinctada metal electroplating and processing modules

NASA Astrophysics Data System (ADS)

Poniger, S. S.; Tochon-Danguy, H. J.; Panopoulos, H. P.; O'Keefe, G. J.; Peake, D.; Rasool, R.; Scott, A. M.

2012-12-01

There is worldwide growing interest for the production of long-lived positron emitters for molecular imaging and the development of novel immuno-PET techniques for drugs discovery. The desire to produce solid target isotopes in Australia has significantly increased over the years and several research projects for labelling of peptides, proteins and biomolecules, including labelling of recombinant antibodies has been limited due to the availability of suitable isotopes. This has led to the recent installation and commissioning of a new lab dedicated to fully automated solid target isotope production, including 124I, 64Cu, 89Zr and 86Y.

Solid phase sequencing of double-stranded nucleic acids

DOEpatents

Fu, Dong-Jing; Cantor, Charles R.; Koster, Hubert; Smith, Cassandra L.

2002-01-01

This invention relates to methods for detecting and sequencing of target double-stranded nucleic acid sequences, to nucleic acid probes and arrays of probes useful in these methods, and to kits and systems which contain these probes. Useful methods involve hybridizing the nucleic acids or nucleic acids which represent complementary or homologous sequences of the target to an array of nucleic acid probes. These probe comprise a single-stranded portion, an optional double-stranded portion and a variable sequence within the single-stranded portion. The molecular weights of the hybridized nucleic acids of the set can be determined by mass spectroscopy, and the sequence of the target determined from the molecular weights of the fragments. Nucleic acids whose sequences can be determined include nucleic acids in biological samples such as patient biopsies and environmental samples. Probes may be fixed to a solid support such as a hybridization chip to facilitate automated determination of molecular weights and identification of the target sequence.

Long Scalelength Plasmas for LPI Studies at the Nike Laser

NASA Astrophysics Data System (ADS)

Weaver, J. L.; Oh, J.; Bates, J. W.; Schmitt, A. J.; Kehne, D. M.; Wolford, M. F.; Obenschain, S. P.; Serlin, V.; Lehmberg, R. H.; Follett, R. K.; Shaw, J. G.; Myatt, J. F.; McKenty, P. W.; Wei, M. S.; Reynolds, H.; Williams, J.; Tsung, F.

2017-10-01

Studies of laser plasma instabilities (LPI) at the Nike laser have mainly used short pulses, small focal spots, and solid plastic (CH) targets that have yielded maximum gradient scalelengths below 200 microns. The current experimental effort aims to produce larger volume plasmas with 5-10x reduction in the density and velocity gradients as a platform for SBS, SRS, and TPD studies. The next campaign will concentrate on the effects of wavelength shifting and bandwidth changes on CBET in low density (5-10 mg/cm3) CH foam targets. This poster will discuss the development of this new LPI target platform based on modelling with the LPSE code developed at LLE. The presentation will also discuss alternative target schemes (e.g. exploding foils) and improvements to the LPI diagnostic suite and laser operations; for example, a new set of etalons will be available for the next campaign that should double the range of available wavelength shifting. Upgrades to the scattered light spectrometers in general use for LPI studies will also be presented. Work supported by DoE/NNSA.

Visualization of nanoconstructions with DNA-Aptamers for targeted molecules binding on the surface of screen-printed electrodes

NASA Astrophysics Data System (ADS)

Lapin, Ivan N.; Shabalina, Anastasiia V.; Svetlichyi, Valery A.; Kolovskaya, Olga S.

2018-04-01

Nanoconstructions of gold nanoparticles (NPs) obtained via pulsed laser ablation in liquid with DNA-aptamer specific to protein tumor marker were visualized on the surface of screen-printed electrode using scanning electron microscopy (SEM) and confocal laser scanning microscopy (CLSM). AuNPs/aptamer nanoconstuctions distribution on the solid surface was studied. More uniform coverage of the carbon electrode surface with the nanoconstuctions was showed in comparison with DNA-aptamer alone on the golden electrode surface. Targeted binding of the tumor marker molecules with the AuNPs/DNA-aptamer nanoconstuctions was approved.

Isochoric heating and strong blast wave formation driven by fast electrons in solid-density targets

NASA Astrophysics Data System (ADS)

Santos, J. J.; Vauzour, B.; Touati, M.; Gremillet, L.; Feugeas, J.-L.; Ceccotti, T.; Bouillaud, R.; Deneuville, F.; Floquet, V.; Fourment, C.; Hadj-Bachir, M.; Hulin, S.; Morace, A.; Nicolaï, Ph; d'Oliveira, P.; Reau, F.; Samaké, A.; Tcherbakoff, O.; Tikhonchuk, V. T.; Veltcheva, M.; Batani, D.

2017-10-01

We experimentally investigate the fast (< 1 {ps}) isochoric heating of multi-layer metallic foils and subsequent high-pressure hydrodynamics induced by energetic electrons driven by high-intensity, high-contrast laser pulses. The early-time temperature profile inside the target is measured from the streaked optical pyrometry of the target rear side. This is further characterized from benchmarked simulations of the laser-target interaction and the fast electron transport. Despite a modest laser energy (< 1 {{J}}), the early-time high pressures and associated gradients launch inwards a strong compression wave developing over ≳ 10 ps into a ≈ 140 {Mbar} blast wave, according to hydrodynamic simulations, consistent with our measurements. These experimental and numerical findings pave the way to a short-pulse-laser-based platform dedicated to high-energy-density physics studies.

Deploying Solid Targets in Dense Plasma Focus Devices for Improved Neutron Yields

NASA Astrophysics Data System (ADS)

Podpaly, Y. A.; Chapman, S.; Povilus, A.; Falabella, S.; Link, A.; Shaw, B. H.; Cooper, C. M.; Higginson, D.; Holod, I.; Sipe, N.; Gall, B.; Schmidt, A. E.

2017-10-01

We report on recent progress in using solid targets in dense plasma focus (DPF) devices. DPFs have been observed to generate energetic ion beams during the pinch phase; these beams interact with the dense plasma in the pinch region as well as the background gas and are believed to be the primary neutron generation mechanism for a D2 gas fill. Targets can be placed in the beam path to enhance neutron yield and to shorten the neutron pulse if desired. In this work, we measure yields from placing titanium deuteride foils, deuterated polyethylene, and non-deuterated control targets in deuterium filled DPFs at both megajoule and kilojoule scales. Furthermore, we have deployed beryllium targets in a helium gas-filled, kilojoule scale DPF for use as a potential AmBe radiological source replacement. Neutron yield, neutron time of flight, and optical images are used to diagnose the effectiveness of target deployments relative to particle-in-cell simulation predictions. A discussion of target holder engineering for material compatibility and damage control will be shown as well. Prepared by LLNL under Contract DE-AC52-07NA27344. Supported by the Office of Defense Nuclear Nonproliferation Research and Development within U.S. DOE's National Nuclear Security Administration and the LLNL Institutional Computing Grand Challenge program.

Developing vascular and hypoxia based theranostics in solid tumors

NASA Astrophysics Data System (ADS)

Koonce, Nathan A.

Tissue hypoxia was recognized for its biological attenuating effects on ionizing radiation over a century ago and is a characteristic feature of many solid tumors. Clinical and experimental evidence indicates tumor hypoxia plays diverse and key roles in tumor progression, angiogenesis, and resistance to chemotherapy/radiotherapy. Hypoxia has known effects on progression and resistance to several standard treatment approaches and the significant history of study might suggest diagnostic imaging and therapeutic interventions would be routine in oncological practice. Curiously, this is not the case and the research results involved in this report will attempt to better understand and contribute to why this gap in knowledge exists and a rationale for harnessing the potential of detecting and targeting hypoxia. Despite the addition of oxygen and reversal of hypoxia being known as the best radiosensitizer, hypoxia remains unexploited in clinical cancer therapy. The studies reported herein detail development of a novel imaging technique to detect a subtype of tumor hypoxia, vascular hypoxia or hypoxemia, with a 17-fold increase (p<0.05) in uptake of pimonidazole targeted microbubbles observed compared to controls. This technique creates the potential to study the role of hypoxemia in progression and therapeutic response. Additionally, description of a nanoparticle-based therapy that targets tumor areas associated with tumor hypoxia and the tumor microenvironment in general is reported. TNF-loaded nanoparticles combined with radiotherapy resulted in a 5.25-fold growth delay that was found to be synergistic (p<0.05) and suggests clinical evaluation is warranted. An additional study to evaluate an approach to use thermal ablation of intratumoral hypoxia by an image-guided technique developed in our group is described along with a sequence dependence of radiation preceding ablation. A final study on the use of galectin-1 antagonist to significantly decrease (p<0.05) hypoxia in the tumor microenvironment by altering tumor vessel characteristics is illustrated in Chapter 5. Overall, this thesis details imaging approaches of tumor hypoxia and its detection, quantification and targeting in therapeutic approaches.

Ab Initio Simulation Beryllium in Solid Molecular Hydrogen: Elastic Constant

NASA Astrophysics Data System (ADS)

Guerrero, Carlo L.; Perlado, Jose M.

2016-03-01

In systems of inertial confinement fusion targets Deuterium-Tritium are manufactured with a solid layer, it must have specific properties to increase the efficiency of ignition. Currently there have been some proposals to model the phases of hydrogen isotopes and hence their high pressure, but these works do not allow explaining some of the structures present at the solid phase change effect of increased pressure. By means of simulation with first principles methods and Quantum Molecular Dynamics, we compare the structural difference of solid molecular hydrogen pure and solid molecular hydrogen with beryllium, watching beryllium inclusion in solid hydrogen matrix, we obtain several differences in mechanical properties, in particular elastic constants. For C11 the difference between hydrogen and hydrogen with beryllium is 37.56%. This may produce a non-uniform initial compression and decreased efficiency of ignition.

Transient changes in electric fields induced by interaction of ultraintense laser pulses with insulator and metal foils: Sustainable fields spanning several millimeters

NASA Astrophysics Data System (ADS)

Inoue, Shunsuke; Tokita, Shigeki; Hashida, Masaki; Sakabe, Shuji

2015-04-01

The temporal evolutions of electromagnetic fields generated by the interaction between ultraintense lasers (1.3 ×1018 and 8.2 ×1018W /c m2 ) and solid targets at a distance of several millimeters from the laser-irradiated region have been investigated by electron deflectometry. For three types of foil targets (insulating foil, conductive foil, and insulating foil onto which a metal disk was deposited), transient changes in the fields were observed. We found that the direction, strength, and temporal evolution of the generated fields differ markedly for these three types of targets. The results provide an insight for studying the emission dynamics of laser-accelerated fast electrons.

Automatic target validation based on neuroscientific literature mining for tractography

PubMed Central

Vasques, Xavier; Richardet, Renaud; Hill, Sean L.; Slater, David; Chappelier, Jean-Cedric; Pralong, Etienne; Bloch, Jocelyne; Draganski, Bogdan; Cif, Laura

2015-01-01

Target identification for tractography studies requires solid anatomical knowledge validated by an extensive literature review across species for each seed structure to be studied. Manual literature review to identify targets for a given seed region is tedious and potentially subjective. Therefore, complementary approaches would be useful. We propose to use text-mining models to automatically suggest potential targets from the neuroscientific literature, full-text articles and abstracts, so that they can be used for anatomical connection studies and more specifically for tractography. We applied text-mining models to three structures: two well-studied structures, since validated deep brain stimulation targets, the internal globus pallidus and the subthalamic nucleus and, the nucleus accumbens, an exploratory target for treating psychiatric disorders. We performed a systematic review of the literature to document the projections of the three selected structures and compared it with the targets proposed by text-mining models, both in rat and primate (including human). We ran probabilistic tractography on the nucleus accumbens and compared the output with the results of the text-mining models and literature review. Overall, text-mining the literature could find three times as many targets as two man-weeks of curation could. The overall efficiency of the text-mining against literature review in our study was 98% recall (at 36% precision), meaning that over all the targets for the three selected seeds, only one target has been missed by text-mining. We demonstrate that connectivity for a structure of interest can be extracted from a very large amount of publications and abstracts. We believe this tool will be useful in helping the neuroscience community to facilitate connectivity studies of particular brain regions. The text mining tools used for the study are part of the HBP Neuroinformatics Platform, publicly available at http://connectivity-brainer.rhcloud.com/. PMID:26074781

A novel approach to the simultaneous extraction and non-targeted analysis of the small molecules metabolome and lipidome using 96-well solid phase extraction plates with column-switching technology.

PubMed

Li, Yubo; Zhang, Zhenzhu; Liu, Xinyu; Li, Aizhu; Hou, Zhiguo; Wang, Yuming; Zhang, Yanjun

2015-08-28

This study combines solid phase extraction (SPE) using 96-well plates with column-switching technology to construct a rapid and high-throughput method for the simultaneous extraction and non-targeted analysis of small molecules metabolome and lipidome based on ultra-performance liquid chromatography quadrupole time-of-flight mass spectrometry. This study first investigated the columns and analytical conditions for small molecules metabolome and lipidome, separated by an HSS T3 and BEH C18 columns, respectively. Next, the loading capacity and actuation duration of SPE were further optimized. Subsequently, SPE and column switching were used together to rapidly and comprehensively analyze the biological samples. The experimental results showed that the new analytical procedure had good precision and maintained sample stability (RSD<15%). The method was then satisfactorily applied to more widely analyze the small molecules metabolome and lipidome to test the throughput. The resulting method represents a new analytical approach for biological samples, and a highly useful tool for researches in metabolomics and lipidomics. Copyright © 2015 Elsevier B.V. All rights reserved.

Influence of food intrinsic complexity on Listeria monocytogenes growth in/on vacuum-packed model systems at suboptimal temperatures.

PubMed

Baka, Maria; Noriega, Estefanía; Van Langendonck, Kristof; Van Impe, Jan F

2016-10-17

Food intrinsic factors e.g., food (micro)structure, compositional and physicochemical aspects, which are mutually dependent, influence microbial growth. While the effect of composition and physicochemical properties on microbial growth has been thoroughly assessed and characterised, the role of food (micro)structure still remains unravelled. Most studies on food (micro)structure focus on comparing planktonic growth in liquid (microbiological) media with colonial growth in/on solid-like systems or on real food surfaces. However, foods are not only liquids or solids; they can also be emulsions or gelled emulsions and have complex compositions. In this study, Listeria monocytogenes growth was studied on the whole spectrum of (micro)structure, in terms of food (model) systems. The model systems varied not only in (micro)structure, which was the target of the study, but also in compositional and physicochemical characteristics, which was an inevitable consequence of the (micro)structural variability. The compositional and physicochemical differences were mainly due to the presence or absence of fat and gelling agents. The targeted (micro)structures were: i) liquids, ii) aqueous gels, iii) emulsions and iv) gelled emulsions. Furthermore, the microbial dynamics were studied and compared in/on all these model systems, as well as on a compositionally predefined canned meat, developed in order to have equal compositional level to the gelled emulsion model system and represent a real food system. Frankfurter sausages were the targeted real foods, selected as a case study, to which the canned meat had similar compositional characteristics. All systems were vacuum packed and incubated at 4, 8 and 12°C. The most appropriate protocol for the preparation of the model systems was developed. The pH, water activity and resistance to penetration of the model systems were characterised. Results indicated that low temperature contributes to growth variations among the model systems. Additionally, the firmer the solid system, the faster L. monocytogenes grew on it. Finally, it was found that L. monocytogenes grows faster on canned meat and real Frankfurters, as found in a previous study, followed by liquids, aqueous gels, emulsions and gelled emulsions. This observation indicates that all model systems, developed in this study, underestimated L. monocytogenes growth. Despite some limitations, model systems are overall advantageous and therefore, their validation is always recommended prior to further use. Copyright © 2016. Published by Elsevier B.V.

Preclinical efficacy of maternal embryonic leucine-zipper kinase (MELK) inhibition in acute myeloid leukemia.

PubMed

Alachkar, Houda; Mutonga, Martin B G; Metzeler, Klaus H; Fulton, Noreen; Malnassy, Gregory; Herold, Tobias; Spiekermann, Karsten; Bohlander, Stefan K; Hiddemann, Wolfgang; Matsuo, Yo; Stock, Wendy; Nakamura, Yusuke

2014-12-15

Maternal embryonic leucine-zipper kinase (MELK), which was reported to be frequently up-regulated in various types of solid cancer, plays critical roles in formation and maintenance of cancer stem cells. However, little is known about the relevance of this kinase in hematologic malignancies. Here we report characterization of possible roles of MELK in acute myeloid leukemia (AML). MELK is expressed in AML cell lines and AML blasts with higher levels in less differentiated cells. MELK is frequently upregulated in AML with complex karyotypes and is associated with worse clinical outcome. MELK knockdown resulted in growth inhibition and apoptosis of leukemic cells. Hence, we investigated the potent anti-leukemia activity of OTS167, a small molecule MELK kinase inhibitor, in AML, and found that the compound induced cell differentiation and apoptosis as well as decreased migration of AML cells. MELK expression was positively correlated with the expression of FOXM1 as well as its downstream target genes. Furthermore, MELK inhibition resulted in downregulation of FOXM1 activity and the expression of its downstream targets. Taken together, and given that OTS167 is undergoing a phase I clinical trial in solid cancer, our study warrants clinical evaluation of this compound as a novel targeted therapy for AML patients.

Preclinical efficacy of maternal embryonic leucine-zipper kinase (MELK) inhibition in acute myeloid leukemia

PubMed Central

Alachkar, Houda; Mutonga, Martin B.G.; Metzeler, Klaus H.; Fulton, Noreen; Malnassy, Gregory; Herold, Tobias; Spiekermann, Karsten; Bohlander, Stefan K.; Hiddemann, Wolfgang; Matsuo, Yo; Stock, Wendy; Nakamura, Yusuke

2014-01-01

Maternal embryonic leucine-zipper kinase (MELK), which was reported to be frequently up-regulated in various types of solid cancer, plays critical roles in formation and maintenance of cancer stem cells. However, little is known about the relevance of this kinase in hematologic malignancies. Here we report characterization of possible roles of MELK in acute myeloid leukemia (AML). MELK is expressed in AML cell lines and AML blasts with higher levels in less differentiated cells. MELK is frequently upregulated in AML with complex karyotypes and is associated with worse clinical outcome. MELK knockdown resulted in growth inhibition and apoptosis of leukemic cells. Hence, we investigated the potent anti-leukemia activity of OTS167, a small molecule MELK kinase inhibitor, in AML, and found that the compound induced cell differentiation and apoptosis as well as decreased migration of AML cells. MELK expression was positively correlated with the expression of FOXM1 as well as its downstream target genes. Furthermore, MELK inhibition resulted in downregulation of FOXM1 activity and the expression of its downstream targets. Taken together, and given that OTS167 is undergoing a phase I clinical trial in solid cancer, our study warrants clinical evaluation of this compound as a novel targeted therapy for AML patients. PMID:25365263

Ultrafast Kα x-ray Thomson scattering from shock compressed lithium hydride

DOE PAGES

Kritcher, A. L.; Neumayer, P.; Castor, J.; ...

2009-04-13

Spectrally and temporally resolved x-ray Thomson scattering using ultrafast Ti Kα x rays has provided experimental validation for modeling of the compression and heating of shocked matter. The coalescence of two shocks launched into a solid density LiH target by a shaped 6 ns heater beam was observed from rapid heating to temperatures of 2.2 eV, enabling tests of shock timing models. Here, the temperature evolution of the target at various times during shock progression was characterized from the intensity of the elastic scattering component. The observation of scattering from plasmons, electron plasma oscillations, at shock coalescence indicates a transitionmore » to a dense metallic plasma state in LiH. From the frequency shift of the measured plasmon feature the electron density was directly determined with high accuracy, providing a material compression of a factor of 3 times solid density. The quality of data achieved in these experiments demonstrates the capability for single shot dynamic characterization of dense shock compressed matter. Here, the conditions probed in this experiment are relevant for the study of the physics of planetary formation and to characterize inertial confinement fusion targets for experiments such as on the National Ignition Facility, Lawrence Livermore National Laboratory.« less

Upgrades toward high-heat flux, liquid lithium plasma-facing components in the NSTX-U

DOE PAGES

Jaworski, M. A.; Brooks, A.; Kaita, R.; ...

2016-08-08

Liquid metal plasma-facing components (PFCs) provide numerous potential advantages over solid-material components. One critique of the approach is the relatively less developed technologies associated with deploying these components in a fusion plasma-experiment. Exploration of the temperature limits of liquid lithium PFCs in a tokamak divertor and the corresponding consequences on core operation are a high priority informing the possibilities for future liquid lithium PFCs. An all-metal NSTX-U is envisioned to make direct comparison between all high-Z wall operation and liquid lithium PFCs in a single device. By executing the all-metal upgrades incrementally, scientific productivity will be maintained while enabling physicsmore » and engineering-science studies to further develop the solid- and liquid-metal components. Six major elements of a flowing liquid-metal divertor system are described and a three-step program for implementing this system is laid out. The upgrade steps involve the first high-Z divertor target upgrade in NSTX-U, pre-filled liquid metal targets and finally, an integrated, flowing liquid metal divertor target. As a result, two example issues are described where the engineering and physics experiments are shown to be closely related in examining the prospects for future liquid metal PFCs.« less

miR-139-5p Modulates Radiotherapy Resistance in Breast Cancer by Repressing Multiple Gene Networks of DNA Repair and ROS Defense.

PubMed

Pajic, Marina; Froio, Danielle; Daly, Sheridan; Doculara, Louise; Millar, Ewan; Graham, Peter H; Drury, Alison; Steinmann, Angela; de Bock, Charles E; Boulghourjian, Alice; Zaratzian, Anaiis; Carroll, Susan; Toohey, Joanne; O'Toole, Sandra A; Harris, Adrian L; Buffa, Francesca M; Gee, Harriet E; Hollway, Georgina E; Molloy, Timothy J

2018-01-15

Radiotherapy is essential to the treatment of most solid tumors and acquired or innate resistance to this therapeutic modality is a major clinical problem. Here we show that miR-139-5p is a potent modulator of radiotherapy response in breast cancer via its regulation of genes involved in multiple DNA repair and reactive oxygen species defense pathways. Treatment of breast cancer cells with a miR-139-5p mimic strongly synergized with radiation both in vitro and in vivo , resulting in significantly increased oxidative stress, accumulation of unrepaired DNA damage, and induction of apoptosis. Several miR-139-5p target genes were also strongly predictive of outcome in radiotherapy-treated patients across multiple independent breast cancer cohorts. These prognostically relevant miR-139-5p target genes were used as companion biomarkers to identify radioresistant breast cancer xenografts highly amenable to sensitization by cotreatment with a miR-139-5p mimetic. Significance: The microRNA described in this study offers a potentially useful predictive biomarker of radiosensitivity in solid tumors and a generally applicable druggable target for tumor radiosensitization. Cancer Res; 78(2); 501-15. ©2017 AACR . ©2017 American Association for Cancer Research.

Report: new guidelines for characterization of municipal solid waste: the Portuguese case.

PubMed

da Graça Madeira Martinho, Maria; Silveira, Ana Isabel; Fernandes Duarte Branco, Elsa Maria

2008-10-01

This report proposes a new set of guidelines for the characterization of municipal solid waste. It is based on an analysis of reference methodologies, used internationally, and a case study of Valorsul (a company that handles recovery and treatment of solid waste in the North Lisbon Metropolitan Area). In particular, the suggested guidelines present a new definition of the waste to be analysed, change the sampling unit and establish statistical standards for the results obtained. In these new guidelines, the sampling level is the waste collection vehicle and contamination and moisture are taken into consideration. Finally, focus is on the quality of the resulting data, which is essential for comparability of data between countries. These new guidelines may also be applicable outside Portugal because the methodology includes, besides municipal mixed waste, separately collected fractions of municipal waste. They are a response to the need for information concerning Portugal (e.g. Eurostat or OECD inquiries) and follow European Union municipal solid waste management policies (e.g. packaging waste recovery and recycling targets and the reduction of biodegradable waste going to landfill).

Aerosol-Assisted Solid Debris Collection for the National Ignition Facility

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

Nelson, S L; Shaughnessy, D A; Moody, K J

2010-05-21

The National Ignition Facility (NIF) has been completed and has made its first shots on-target. While upcoming experiments will be focused on achieving ignition, a variety of subsequent experiments are planned for the facility, including measurement of cross sections, astrophysical measurements, and investigation of hydrodynamic instability in the target capsule. In order to successfully execute several of these planned experiments, the ability to collect solid debris following a NIF capsule shot will be required. The ability to collect and analyze solid debris generated in a shot at the National Ignition Facility (NIF) will greatly expand the number of nuclear reactionsmore » studied for diagnostic purposes. Currently, reactions are limited to only those producing noble gases for cryogenic collection and counting with the Radchem Apparatus for Gas Sampling (RAGS). The radchem solid collection diagnostic has already been identified by NIF to be valuable for the determination and understanding of mix generated in the target capsule's ablation. LLNL is currently developing this solid debris collection capability at NIF, and is in the stage of testing credible designs. Some of these designs explore the use of x-ray generated aerosols to assist in collection of solid debris. However, the variety of harsh experimental conditions this solid collection device will encounter in NIF are challenging to replicate. Experiments performed by Gary Grim et al. at Sandia National Laboratory's RHEPP1 facility have shown that ablation causes a cloud of material removed from an exposed surface to move normal to and away from the surface. This ablation is certain to be a concern in the NIF target chamber from the prompt x-rays, gamma rays, etc. generated in the shot. The cloud of ablated material could interfere with the collection of the desired reaction debris by slowing down the debris so that the kinetic energy is too low to allow implantation, or by stopping the debris from reaching the collection device entirely. Our goal is to use this primary ablation wave to our advantage, by the creation of ionized alkali metal halide salt aerosols. This technique is similar to that used by many particle accelerator groups for gas-jet transport. Ideally the salt would be ablated from a substrate, encounter the reaction debris, agglomerate, and be collected for further study. We have done studies at laser and pulsed-power facilities (Titan laser at LLNL, Trident laser at LANL, Zebra z-pinch at Nevada Terawatt Facility) evaluating the hardiness of materials for placement in the NIF target chamber, as well as testing aerosol generation by the incident x-rays generated in device shots. To test this method's potential success in the NIF environment, we have tested KCl, KI, RbI, and CsI films of 1 and 2 um linear thickness on aluminum and silicon wafer substrates in these aforementioned facilities, at varied distances. These salts do ablate in the presence of sufficient x-ray fluence. Further analysis to quantify the final ablation depth as a function of x-ray fluence is ongoing. Half of each sample was masked with a thick tungsten foil for photon opacity. KCl was the most difficult salt to ablate, from comparing the tungsten-masked side of the samples to the unmasked side of the samples. This is likely due to KCl's absorbance peak being at lower wavelengths than that of KI, {approx}160 nm vs. {approx}220 nm, respectively. Samples with and without collimation were tested to identify if any condensation of these ablated salts occurred after ablation. Visual inspection of the silicon wafer witness plates placed parallel to the direction of the incident photons showed that a vapor was deposited on the wafers next to the collimators. Further analysis with EDS in the case of the collimated samples conclusively identified the vapor as CsI. We also intend to examine samples of bare substrate exposed to the same experimental conditions for post-shot change via SEM images, optical microscopy, and atomic force microscopy (AFM). Furthermore, tests with separated isotopes may be done to reduce background contamination. When sample optimization is complete, we plan to develop a 'catcher' device for these desorbed aerosols. Current ideas include biased grids to either attract the ionized particles to the grid, or repel them towards a collection device.« less

CRISPR screen identifies the NCOR/HDAC3 complex as a major suppressor of differentiation in rhabdomyosarcoma

PubMed Central

Phelps, Michael P.; Bailey, Jenna N.; Vleeshouwer-Neumann, Terra

2016-01-01

Dysregulated gene expression resulting from abnormal epigenetic alterations including histone acetylation and deacetylation has been demonstrated to play an important role in driving tumor growth and progression. However, the mechanisms by which specific histone deacetylases (HDACs) regulate differentiation in solid tumors remains unclear. Using pediatric rhabdomyosarcoma (RMS) as a paradigm to elucidate the mechanism blocking differentiation in solid tumors, we identified HDAC3 as a major suppressor of myogenic differentiation from a high-efficiency Clustered regularly interspaced short palindromic repeats (CRISPR)-based phenotypic screen of class I and II HDAC genes. Detailed characterization of the HDAC3-knockout phenotype in vitro and in vivo using a tamoxifen-inducible CRISPR targeting strategy demonstrated that HDAC3 deacetylase activity and the formation of a functional complex with nuclear receptor corepressors (NCORs) were critical in restricting differentiation in RMS. The NCOR/HDAC3 complex specifically functions by blocking myoblast determination protein 1 (MYOD1)-mediated activation of myogenic differentiation. Interestingly, there was also a transient up-regulation of growth-promoting genes upon initial HDAC3 targeting, revealing a unique cancer-specific response to the forced transition from a neoplastic state to terminal differentiation. Our study applied modifications of CRISPR/CRISPR-associated endonuclease 9 (Cas9) technology to interrogate the function of essential cancer genes and pathways and has provided insights into cancer cell adaptation in response to altered differentiation status. Because current pan-HDAC inhibitors have shown disappointing results in clinical trials of solid tumors, therapeutic targets specific to HDAC3 function represent a promising option for differentiation therapy in malignant tumors with dysregulated HDAC3 activity. PMID:27956629

CRISPR screen identifies the NCOR/HDAC3 complex as a major suppressor of differentiation in rhabdomyosarcoma.

PubMed

Phelps, Michael P; Bailey, Jenna N; Vleeshouwer-Neumann, Terra; Chen, Eleanor Y

2016-12-27

Dysregulated gene expression resulting from abnormal epigenetic alterations including histone acetylation and deacetylation has been demonstrated to play an important role in driving tumor growth and progression. However, the mechanisms by which specific histone deacetylases (HDACs) regulate differentiation in solid tumors remains unclear. Using pediatric rhabdomyosarcoma (RMS) as a paradigm to elucidate the mechanism blocking differentiation in solid tumors, we identified HDAC3 as a major suppressor of myogenic differentiation from a high-efficiency Clustered regularly interspaced short palindromic repeats (CRISPR)-based phenotypic screen of class I and II HDAC genes. Detailed characterization of the HDAC3-knockout phenotype in vitro and in vivo using a tamoxifen-inducible CRISPR targeting strategy demonstrated that HDAC3 deacetylase activity and the formation of a functional complex with nuclear receptor corepressors (NCORs) were critical in restricting differentiation in RMS. The NCOR/HDAC3 complex specifically functions by blocking myoblast determination protein 1 (MYOD1)-mediated activation of myogenic differentiation. Interestingly, there was also a transient up-regulation of growth-promoting genes upon initial HDAC3 targeting, revealing a unique cancer-specific response to the forced transition from a neoplastic state to terminal differentiation. Our study applied modifications of CRISPR/CRISPR-associated endonuclease 9 (Cas9) technology to interrogate the function of essential cancer genes and pathways and has provided insights into cancer cell adaptation in response to altered differentiation status. Because current pan-HDAC inhibitors have shown disappointing results in clinical trials of solid tumors, therapeutic targets specific to HDAC3 function represent a promising option for differentiation therapy in malignant tumors with dysregulated HDAC3 activity.

Targeting Alpha-Fetoprotein (AFP)-MHC Complex with CAR T-Cell Therapy for Liver Cancer.

PubMed

Liu, Hong; Xu, Yiyang; Xiang, Jingyi; Long, Li; Green, Shon; Yang, Zhiyuan; Zimdahl, Bryan; Lu, Jingwei; Cheng, Neal; Horan, Lucas H; Liu, Bin; Yan, Su; Wang, Pei; Diaz, Juan; Jin, Lu; Nakano, Yoko; Morales, Javier F; Zhang, Pengbo; Liu, Lian-Xing; Staley, Binnaz K; Priceman, Saul J; Brown, Christine E; Forman, Stephen J; Chan, Vivien W; Liu, Cheng

2017-01-15

The majority of tumor-specific antigens are intracellular and/or secreted and therefore inaccessible by conventional chimeric antigen receptor (CAR) T-cell therapy. Given that all intracellular/secreted proteins are processed into peptides and presented by class I MHC on the surface of tumor cells, we used alpha-fetoprotein (AFP), a specific liver cancer marker, as an example to determine whether peptide-MHC complexes can be targets for CAR T-cell therapy against solid tumors. We generated a fully human chimeric antigen receptor, ET1402L1-CAR (AFP-CAR), with exquisite selectivity and specificity for the AFP 158-166 peptide complexed with human leukocyte antigen (HLA)-A*02:01. We report that T cells expressing AFP-CAR selectively degranulated, released cytokines, and lysed liver cancer cells that were HLA-A*02:01 + /AFP + while sparing cells from multiple tissue types that were negative for either expressed proteins. In vivo, intratumoral injection of AFP-CAR T cells significantly regressed both Hep G2 and AFP 158 -expressing SK-HEP-1 tumors in SCID-Beige mice (n = 8 for each). Moreover, intravenous administration of AFP-CAR T cells in Hep G2 tumor-bearing NSG mice lead to rapid and profound tumor growth inhibition (n = 6). Finally, in an established intraperitoneal liver cancer xenograft model, AFP-CAR T cells showed robust antitumor activity (n = 6). This study demonstrates that CAR T-cell immunotherapy targeting intracellular/secreted solid tumor antigens can elicit a potent antitumor response. Our approach expands the spectrum of antigens available for redirected T-cell therapy against solid malignancies and offers a promising new avenue for liver cancer immunotherapy. Clin Cancer Res; 23(2); 478-88. ©2016 AACR. ©2016 American Association for Cancer Research.

Inertial Confinement fusion targets

NASA Technical Reports Server (NTRS)

Hendricks, C. D.

1982-01-01

Inertial confinement fusion (ICF) targets are made as simple flat discs, as hollow shells or as complicated multilayer structures. Many techniques were devised for producing the targets. Glass and metal shells are made by using drop and bubble techniques. Solid hydrogen shells are also produced by adapting old methods to the solution of modern problems. Some of these techniques, problems, and solutions are discussed. In addition, the applications of many of the techniques to fabrication of ICF targets is presented.

Method and apparatus for staining immobilized nucleic acids

DOEpatents

Ramsey, J. Michael; Foote, Robert S.; Jacobson, Stephen C.

2000-01-01

A method for staining immobilized nucleic acids includes the steps of affixing DNA probes to a solid substrate, moving target DNA material into proximity with the DNA probes, whereby the target DNA hybridized with specific ones of the DNA probes, and moving a fluorescent dye into proximity with the hybridized target DNA, whereby the fluorescent dye binds to the hybridized DNA to enable subsequent detection of fluorescence.

GEANT4 simulation of cyclotron radioisotope production in a solid target.

PubMed

Poignant, F; Penfold, S; Asp, J; Takhar, P; Jackson, P

2016-05-01

The use of radioisotopes in nuclear medicine is essential for diagnosing and treating cancer. The optimization of their production is a key factor in maximizing the production yield and minimizing the associated costs. An efficient approach to this problem is the use of Monte Carlo simulations prior to experimentation. By predicting isotopes yields, one can study the isotope of interest expected activity for different energy ranges. One can also study the target contamination with other radioisotopes, especially undesired radioisotopes of the wanted chemical element which are difficult to separate from the irradiated target and might result in increasing the dose when delivering the radiopharmaceutical product to the patient. The aim of this work is to build and validate a Monte Carlo simulation platform using the GEANT4 toolkit to model the solid target system of the South Australian Health and Medical Research Institute (SAHMRI) GE Healthcare PETtrace cyclotron. It includes a GEANT4 Graphical User Interface (GUI) where the user can modify simulation parameters such as the energy, shape and current of the proton beam, the target geometry and material, the foil geometry and material and the time of irradiation. The paper describes the simulation and presents a comparison of simulated and experimental/theoretical yields for various nuclear reactions on an enriched nickel 64 target using the GEANT4 physics model QGSP_BIC_AllHP, a model recently developed to evaluate with high precision the interaction of protons with energies below 200MeV available in Geant4 version 10.1. The simulation yield of the (64)Ni(p,n)(64)Cu reaction was found to be 7.67±0.074 mCi·μA(-1) for a target energy range of 9-12MeV. Szelecsenyi et al. (1993) gives a theoretical yield of 6.71mCi·μA(-1) and an experimental yield of 6.38mCi·μA(-1). The (64)Ni(p,n)(64)Cu cross section obtained with the simulation was also verified against the yield predicted from the nuclear database TENDL and compared to experimental yield obtained from literature. Copyright © 2016 Associazione Italiana di Fisica Medica. All rights reserved.

Development of a solid surface fluorescence-based sensing system for aluminium monitoring in drinking water.

PubMed

Reyes, J F García; Barrales, P Ortega; Díaz, A Molina

2005-03-15

A novel, single and robust solid surface fluorescence-based sensing device assembled in a continuous flow system has been developed for the determination of trace amounts of aluminium in water samples. The proposed method is based on the transient immobilization of the target species on an appropriate active solid sensing zone (C(18) silica gel). The target species was the fluorogenic chelate, formed as a result of the on-line complexation of Al(III) with chromotropic acid (CA) at pH 4.1. The fluorescence of the complex is continuously monitored at an emission wavelength of 390nm upon excitation at 361nm. The instrumental, chemical and flow-injection variables affecting the fluorescence signal were carefully investigated and optimized. After selecting the most suitable conditions, the sensing system was calibrated in the range 10-500mugl(-1), obtaining a detection limit of 2.6mugl(-1), and a R.S.D. of 2.2%, with a sampling frequency of 24h(-1). In addition, the selectivity of the proposed methodology was evaluated by performing interference studies with different cations and anions which could affect the analytical response. Finally, the proposed method, which meets the EU regulations regarding the aluminium content in drinking waters, was satisfactorily applied to different water samples, with recoveries between 97 and 105%. The simplicity, low cost and easy operation are the main advantages of the present procedure.

Development of sensitive determination method for fungicides from environmental water samples with Titanate nanotube array micro-solid phase extraction prior to high performance liquid chromatography.

PubMed

Huang, Yunrui; Zhou, Qingxiang; Xie, Guohong

2013-01-01

Fungicides have been widely used throughout the world, and the resulted pollution has absorbed great attention in recent years. Present study described an effective measurement technique for fungicides including thiram, metalaxyl, diethofencarb, myclobutanil and tebuconazole in environmental water samples. A micro-solid phase extraction (μSPE) was developed utilizing ordered TiO(2) nanotube array for determination of target fungicides prior to a high performance liquid chromatography (HPLC). The experimental results indicated that TiO(2) nanotube arrays demonstrated excellent merits on the preconcentration of fungicides, and excellent linear relationship between peak area and the concentration of fungicides was obtained in the range of 0.1-50 μg L(-1). The detection limits for the targeted fungicides were in the range of 0.016-0.086 μg L(-1) (S/N=3). Four real environmental water samples were used to validate the applicability of the proposed method, and good spiked recoveries in the range of 73.9-114% were achieved. A comparison of present method with conventional solid phase extraction was made and the results exhibited that proposed method resulted in better recoveries. The results demonstrated that this μ-SPE technique was a viable alternative for the analysis of fungicides in complex samples. Copyright © 2012 Elsevier Ltd. All rights reserved.

Directional Track Selection Technique in CR39 SSNTD for lowyield reaction experiments

NASA Astrophysics Data System (ADS)

Ingenito, Francesco; Andreoli, Pierluigi; Batani, Dimitri; Bonasera, Aldo; Boutoux, Guillaume; Burgy, Frederic; Cipriani, Mattia; Consoli, Fabrizio; Cristofari, Giuseppe; De Angelis, Riccardo; Di Giorgio, Giorgio; Ducret, Jean Eric; Giulietti, Danilo; Jakubowska, Katarzyna

2018-01-01

There is a great interest in the study of p-11B aneutronic nuclear fusion reactions, both for energy production and for determination of fusion cross-sections at low energies. In this context we performed experiments at CELIA in which energetic protons, accelerated by the laser ECLIPSE, were directed toward a solid Boron target. Because of the small cross-sections at these energies the number of expected reactions is low. CR39 Solid-State Nuclear Track Detectors (SSNTD) were used to detect the alpha particles produced. Because of the low expected yield, it is difficult to discriminate the tracks due to true fusion products from those due to natural background in the CR39. To this purpose we developed a methodology of particle recognition according to their direction with respect to the detector normal, able to determine the position of their source. We applied this to the specific experiment geometry, so to select from all the tracks those due to particles coming from the region of interaction between accelerated protons and solid boron target. This technique can be of great help on the analysis of SSNTD in experiments with low yield reactions, but can be also generally applied to any experiment where particles reach the track detector with known directions, and for example to improve the detection limit of particle spectrometers using CR39.

Co-stimulatory signaling determines tumor antigen sensitivity and persistence of CAR T cells targeting PSCA+ metastatic prostate cancer

PubMed Central

Priceman, Saul J.; Gerdts, Ethan A.; Tilakawardane, Dileshni; Kennewick, Kelly T.; Murad, John P.; Park, Anthony K.; Jeang, Brook; Yamaguchi, Yukiko; Urak, Ryan; Weng, Lihong; Chang, Wen-Chung; Wright, Sarah; Pal, Sumanta; Reiter, Robert E.; Brown, Christine E.; Forman, Stephen J.

2018-01-01

ABSTRACT Advancing chimeric antigen receptor (CAR)-engineered adoptive T cells for the treatment of solid cancers is a major focus in the field of immunotherapy, given impressive recent clinical responses in hematological malignancies. Prostate cancer may be amenable to T cell-based immunotherapy since several tumor antigens, including prostate stem-cell antigen (PSCA), are widely over-expressed in metastatic disease. While antigen selectivity of CARs for solid cancers is crucial, it is problematic due to the absence of truly restricted tumor antigen expression and potential safety concerns with “on-target off-tumor” activity. Here, we show that the intracellular co-stimulatory signaling domain can determine a CAR's sensitivity for tumor antigen expression. A 4-1BB intracellular co-stimulatory signaling domain in PSCA-CARs confers improved selectivity for higher tumor antigen density, reduced T cell exhaustion phenotype, and equivalent tumor killing ability compared to PSCA-CARs containing the CD28 co-stimulatory signaling domain. PSCA-CARs exhibit robust in vivo anti-tumor activity in patient-derived bone-metastatic prostate cancer xenograft models, and 4-1BB-containing CARs show superior T cell persistence and control of disease compared with CD28-containing CARs. Our study demonstrates the importance of co-stimulation in defining an optimal CAR T cell, and also highlights the significance of clinically relevant models in developing solid cancer CAR T cell therapies. PMID:29308300

Low-dose decitabine-based chemoimmunotherapy for patients with refractory advanced solid tumors: a phase I/II report.

PubMed

Fan, Hui; Lu, Xuechun; Wang, Xiaohui; Liu, Yang; Guo, Bo; Zhang, Yan; Zhang, Wenying; Nie, Jing; Feng, Kaichao; Chen, Meixia; Zhang, Yajing; Wang, Yao; Shi, Fengxia; Fu, Xiaobing; Zhu, Hongli; Han, Weidong

2014-01-01

Aberrant DNA methylation is one of the main drivers of tumor initiation and progression. The reversibility of methylation modulation makes it an attractive target for novel anticancer therapies. Clinical studies have demonstrated that high-dose decitabine, a hypomethylating agent, results in some clinical benefits in patients with refractory advanced tumors; however, they are extremely toxic. Low doses of decitabine minimize toxicity while potentially improving the targeted effects of DNA hypomethylation. Based on these mechanisms, low-dose decitabine combined with chemoimmunotherapy may be a new treatment option for patients with refractory advanced tumors. We proposed the regimen of low-dose decitabine-based chemoimmunotherapy for patients with refractory advanced solid tumors. A favorable adverse event profile was observed in our trial that was highlighted by the finding that most of these adverse events were grades 1-2. Besides, the activity of our cohort was optimistic and the clinical benefit rate was up to 60%, and the median PFS was prolonged compared with PFS to previous treatment. We also identified a significant correlation between the PFS to previous treatment and clinical response. The low-dose DAC decitabine-based chemoimmunotherapy might be a promising protocol for improving the specificity and efficiency of patients with refractory advanced solid tumors. This trial is registered in the ClinicalTrials.gov database (identifier NCT01799083).

Foam shell cryogenic ICF target

DOEpatents

Darling, Dale H.

1987-01-01

A uniform cryogenic layer of DT fuel is maintained in a fusion target having a low density, small pore size, low Z rigid foam shell saturated with liquid DT fuel. Capillary action prevents gravitational slumping of the fuel layer. The saturated shell may be cooled to produce a solid fuel layer.

Ultrashort pulse high intensity laser illumination of a simple metal

NASA Astrophysics Data System (ADS)

Milchberg, H. M.; Freeman, R. R.; Davey, S. C.

1988-10-01

We have observed the self-reflection of intense, sub-picosecond 308 nm light pulse incident on a planar Al target and have inferred the electrical conductivity of solid density Al. The pulse lengths were sufficiently short that no significant expansion of the target occurred during the measurement.

Behavior Of A Simple Metal Under Ultrashort Pulse High Intensity Laser Illumination

NASA Astrophysics Data System (ADS)

Milchberg, H. M.; Freeman, R. R.; Davey, S. C.

1988-07-01

We have observed the self-reflection of intense, sub-picosecond 308 nm light pulse incident on a planar AI target and have inferred the electrical conductivity of solid density AI. The pulse lengths were sufficiently short that no significant expansion of the target occurred during the measurement.

Continuous low-level aquatic monitoring (CLAM) samplers for pesticide contaminant screening in urban runoff: Analytical approach and a field test case.

PubMed

Ensminger, Michael P; Vasquez, Martice; Tsai, Hsing-Ju; Mohammed, Sarah; Van Scoy, A; Goodell, Korena; Cho, Gail; Goh, Kean S

2017-10-01

Monitoring of surface waters for organic contaminants is costly. Grab water sampling often results in non-detects for organic contaminants due to missing a pulse event or analytical instrumentation limitations with a small sample size. Continuous Low-Level Aquatic Monitoring (CLAM) samplers (C.I.Agent ® Solutions) continually extract and concentrate organic contaminants in surface water onto a solid phase extraction disk. Utilizing CLAM samplers, we developed a broad spectrum analytical screen for monitoring organic contaminants in urban runoff. An intermediate polarity solid phase, hydrophobic/lipophilic balance (HLB), was chosen as the sorbent for the CLAM to target a broad range of compounds. Eighteen urban-use pesticides and pesticide degradates were targeted for analysis by LC/MS/MS, with recoveries between 59 and 135% in laboratory studies. In field studies, CLAM samplers were deployed at discrete time points from February 2015 to March 2016. Half of the targeted chemicals were detected with reporting limits up to 90 times lower than routine 1-L grab samples with good precision between field replicates. In a final deployment, CLAM samplers were compared to 1-L water samples. In this side-by-side comparison, imidacloprid, fipronil, and three fipronil degradates were detected by the CLAM sampler but only imidacloprid and fipronil sulfone were detected in the water samples. However, concentrations of fipronil sulfone and imidacloprid were significantly lower with the CLAM and a transient spike of diuron was not detected. Although the CLAM sampler has limitations, it can be a powerful tool for development of more focused and informed monitoring efforts based on pre-identified targets in the field. Copyright © 2017 Elsevier Ltd. All rights reserved.

Target micro-displacement measurement by a "comb" structure of intensity distribution in laser plasma propulsion

NASA Astrophysics Data System (ADS)

Zheng, Z. Y.; Zhang, S. Q.; Gao, L.; Gao, H.

2015-05-01

A "comb" structure of beam intensity distribution is designed and achieved to measure a target displacement of micrometer level in laser plasma propulsion. Base on the "comb" structure, the target displacement generated by nanosecond laser ablation solid target is measured and discussed. It is found that the "comb" structure is more suitable for a thin film target with a velocity lower than tens of millimeters per second. Combing with a light-electric monitor, the `comb' structure can be used to measure a large range velocity.

9-Fluorenylmethyloxycarbonyl/ tbutyl-based convergent protein synthesis.

PubMed

Barlos, K; Gatos, D

1999-01-01

Besides linear solid phase peptide synthesis, segment condensation in solution and chemical ligation, convergent peptide synthesis (CPS) was developed in order to enable the efficient preparation of complex peptides and small proteins. According to this synthetic strategy, solid phase synthesized and suitably protected peptide fragments corresponding to the entire peptide/protein-sequence are condensed on a solid support or in solution, to the target protein. This review summarizes CPS performed utilizing the mild 9-fluorenylmethyloxycarbonyl/tbutyloxycarbonyl-based protecting scheme for the amino acids. Copyright 1999 John Wiley & Sons, Inc.

How many genomics targets can a portfolio afford?

PubMed

Betz, Ulrich A K

2005-08-01

The pharmaceutical industry can look back at a history of successful innovations. Although genomics technologies have provided drug discovery pipelines with a plethora of new potential drug targets, solid target validation is crucial to avoiding high attrition rates. Biomarkers for patient stratification and approaches for personalized medicine will further help to reduce the risk associated with new targets. To achieve an overall risk balance, portfolios have to be supplemented with precedented targets, me-too approaches and line extensions of existing drugs. However, capitalizing on genomics investments and working on unprecedented targets is essential for a continuous stream of innovative drugs.

Implementing Material Surfaces with an Adhesive Switch

DTIC Science & Technology

2014-02-28

squares), M15 (solid triangles), M13 (open circles), M11 (solid circles), or NC14 (open triangles) DNA primary targets. Error bars indicating...5’–ATCAGGCGCAA–3’ M13 = 5’–ATCAGCGGCAATC–3’ M15 = 5’–ATCAGCCCCAATCCA–3’ L3M9 = 5’–ATLCACLCCGLC–3’ L3M11 = 5

Parity Violation in DIS region with SoLID at the upgraded 12 GeV JLab

NASA Astrophysics Data System (ADS)

Tian, Ye; SoLID Collaboration

2017-09-01

In this talk, an overview of PVDIS future experiment by using a Solenoidal Large Intensity Device (SoLID) at Jefferson Lab (JLab) Hall A with the 12 GeV upgrade, along with a brief description of the proposed SoLID spectrometer is discussed. We will obtain data with high statistic and large kinematic coverage for Bjorken 0.3 < x < 0.7 and in the momentum transfer Q2 range 2 - 10 GeV2 by a polarized electron beam scattering on unpolarized deuteron and proton targets. A measurement of PVDIS in deuteron aims to extract fundamental coupling constants C1 q ,C2 q as well as the weak mixing angle sin2θw with a high precision. This measurement can also access QCD physics of searching for charge asymmetry violation in PDF's and higher-twist effects with quark-quark correlations. In addition, the proton target experiment can be a powerful probe of the d / u ratio at high x without any nuclear correction. The designed SoLID spectrometer with its unique feature of high luminosity and large acceptance provides an opportunity to probe physics beyond the Standard Model.

Technique for Forming Solid D2 and D-T Layers for Shock Timing Experiments at the National Ignition Facility

DOE PAGES

Sater, J. D.; Espinosa-Loza, F.; Kozioziemski, B.; ...

2016-07-11

Capsule implosion experiments on the National Ignition Facility (NIF) are driven with a carefully tailored laser pulse that delivers a sequence of shocks to the ablator and fuel. In order to ensure the shocks converge at the desired position, the shock strength and velocity are measured in experimental platforms referred to as keyhole targets. We made shock measurements on capsules completely filled with liquid deuterium for the solid deuterium tritide (D-T) layer campaigns. Modeling has been used to extend these results to form an estimate of the shock properties in solid D-T layers. Furthermore, to verify and improve the surrogacymore » of the liquid-filled keyhole measurements, we have developed a technique to form a solid layer inside the keyhole capsule. The layer is typically uniform over a 400-μm-diameter area. This is sufficient to allow direct measurement of the shock velocity. This layering technique has been successfully applied to 13 experiments on the NIF. The technique may also be applicable to fast-igniter experiments since some proposed designs resemble keyhole targets. We discuss our method in detail and give representative results.« less

Solid hydrogen target for laser driven proton acceleration

NASA Astrophysics Data System (ADS)

Perin, J. P.; Garcia, S.; Chatain, D.; Margarone, D.

2015-05-01

The development of very high power lasers opens up new horizons in various fields, such as laser plasma acceleration in Physics and innovative approaches for proton therapy in Medicine. Laser driven proton acceleration is commonly based on the so-called Target Normal Sheath Acceleration (TNSA) mechanisms: a high power laser is focused onto a solid target (thin metallic or plastic foil) and interact with matter at very high intensity, thus generating a plasma; as a consequence "hot" electrons are produced and move into the forward direction through the target. Protons are generated at the target rear side, electrons try to escape from the target and an ultra-strong quasi-electrostatic field (~1TV/m) is generated. Such a field can accelerate protons with a wide energy spectrum (1-200 MeV) in a few tens of micrometers. The proton beam characteristics depend on the laser parameters and on the target geometry and nature. This technique has been validated experimentally in several high power laser facilities by accelerating protons coming from hydrogenated contaminant (mainly water) at the rear of metallic target, however, several research groups are investigating the possibility to perform experiments by using "pure" hydrogen targets. In this context, the low temperature laboratory at CEA-Grenoble has developed a cryostat able to continuously produce a thin hydrogen ribbon (from 40 to 100 microns thick). A new extrusion concept, without any moving part has been carried out, using only the thermodynamic properties of the fluid. First results and perspectives are presented in this paper.

Investigation into the electromagnetic impulses from long-pulse laser illuminating solid targets inside a laser facility

NASA Astrophysics Data System (ADS)

Yi, Tao; Yang, Jinwen; Yang, Ming; Wang, Chuanke; Yang, Weiming; Li, Tingshuai; Liu, Shenye; Jiang, Shaoen; Ding, Yongkun; Xiao, Shaoqiu

2016-09-01

Emission of the electromagnetic pulses (EMP) due to laser-target interaction in laser facility had been evaluated using a cone antenna in this work. The microwave in frequencies ranging from several hundreds of MHz to 2 GHz was recorded when long-pulse lasers with several thousands of joules illuminated the solid targets, meanwhile the voltage signals from 1 V to 4 V were captured as functions of laser energy and backlight laser, where the corresponding electric field strengths were obtained by simulating the cone antenna in combination with conducting a mathematical process (Tiknohov Regularization with L curve). All the typical coupled voltage oscillations displayed multiple peaks and had duration of up to 80 ns before decaying into noise and mechanisms of the EMP generation was schematically interpreted in basis of the practical measuring environments. The resultant data were expected to offer basic know-how to achieve inertial confinement fusion.

Laser-driven proton and deuteron acceleration from a pure solid-density H2/D2 cryogenic jet

NASA Astrophysics Data System (ADS)

Kim, Jongjin; Gauthier, Maxence; Aurand, Bastian; Curry, Chandra; Goede, Sebastian; Goyon, Clement; Williams, Jackson; Kerr, Shaun; Ruby, John; Propp, Adrienne; Ramakrishna, Bhuvanesh; Pak, Art; Hazi, Andy; Glenzer, Siegfried; Roedel, Christian

2015-11-01

Laser-driven proton acceleration has become of tremendous interest for the fundamental science and the potential applications in tumor therapy and proton radiography. We have developed a cryogenic liquid hydrogen jet, which can deliver a self-replenishing target of pure solid-density hydrogen or deuterium. This allows for a target compatible with high-repetition-rate experiments and results in a pure hydrogen plasma, facilitating comparison with simulations. A new modification has allowed for the formation of jets with rectangular profiles, facilitating comparison with foil targets. This jet was installed at the Titan laser and driven by laser pulses of 40-60 J of 527 nm laser light in 1 ps. The resulting proton and deuteron spectra were measured in multiple directions with Thomson parabola spectrometers and RCF stacks. The spectral and angular information suggest contribution from both the TNSA and RPA acceleration mechanisms.

1 Hz fast-heating fusion driver HAMA pumped by a 10 J green diode-pumped solid-state laser

NASA Astrophysics Data System (ADS)

Mori, Y.; Sekine, T.; Komeda, O.; Nakayama, S.; Ishii, K.; Hanayama, R.; Fujita, K.; Okihara, S.; Satoh, N.; Kurita, T.; Kawashima, T.; Kan, H.; Nakamura, N.; Kondo, T.; Fujine, M.; Azuma, H.; Hioki, T.; Kakeno, M.; Motohiro, T.; Nishimura, Y.; Sunahara, A.; Sentoku, Y.; Kitagawa, Y.

2013-07-01

A Ti : sapphire laser HAMA pumped by a diode-pumped solid-state laser (DPSSL) is developed to enable a high-repetitive inertial confinement fusion (ICF) experiment to be conducted. To demonstrate a counter-irradiation fast-heating fusion scheme, a 3.8 J, 0.4 ns amplified chirped pulse is divided into four beams: two counter-irradiate a target with intensities of 6 × 1013 W cm-2, and the remaining two are pulse-compressed to 110 fs for heating the imploded target with intensities of 2 × 1017 W cm-2. HAMA contributed to the first demonstration by showing that a 10 J class DPSSL is adaptable to ICF experiments and succeeded in DD neutron generation in the repetition mode. Based on HAMA, we can design and develop an integrated repetitive ICF experiment machine by including target injection and tracking.

Targeting Tumor-Associated Macrophages as a Potential Strategy to Enhance the Response to Immune Checkpoint Inhibitors.

PubMed

Cassetta, Luca; Kitamura, Takanori

2018-01-01

Inhibition of immune checkpoint pathways in CD8 + T cell is a promising therapeutic strategy for the treatment of solid tumors that has shown significant anti-tumor effects and is now approved by the FDA to treat patients with melanoma and lung cancer. However the response to this therapy is limited to a certain fraction of patients and tumor types, for reasons still unknown. To ensure success of this treatment, CD8 + T cells, the main target of the checkpoint inhibitors, should exert full cytotoxicity against tumor cells. However recent studies show that tumor-associated macrophages (TAM) can impede this process by different mechanisms. In this mini-review we will summarize recent studies showing the effect of TAM targeting on immune checkpoint inhibitors efficacy. We will also discuss on the limitations of the current strategies as well on the future scientific challenges for the progress of the tumor immunology field.

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

PubMed

Farghali, Hassan; Kameníková, Ludmila

2017-01-01

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

Carbodiimide versus click chemistry for nanoparticle surface functionalization: a comparative study for the elaboration of multimodal superparamagnetic nanoparticles targeting αvβ3 integrins.

PubMed

Bolley, Julie; Guenin, Erwann; Lievre, Nicole; Lecouvey, Marc; Soussan, Michael; Lalatonne, Yoann; Motte, Laurence

2013-11-26

Superparamagnetic fluorescent nanoparticles targeting αvβ3 integrins were elaborated using two methodologies: carbodiimide coupling and click chemistries (CuACC and thiol-yne). The nanoparticles are first functionalized with hydroxymethylenebisphonates (HMBP) bearing carboxylic acid or alkyne functions. Then, a large number of these reactives functions were used for the covalent coupling of dyes, poly(ethylene glycol) (PEG), and cyclic RGD. Several methods were used to characterize the nanoparticle surface functionalization, and the magnetic properties of these contrast agents were studied using a 1.5 T clinical MRI. The affinity toward integrins was evidenced by solid-phase receptor-binding assay. In addition to their chemoselective natures, click reactions were shown to be far more efficient than the carbodiimide coupling. The grafting increase was shown to enhance targeting affinity to integrin without imparing MRI and fluorescent properties.

Simulations of bremsstrahlung emission in ultra-intense laser interactions with foil targets

NASA Astrophysics Data System (ADS)

Vyskočil, Jiří; Klimo, Ondřej; Weber, Stefan

2018-05-01

Bremsstrahlung emission from interactions of short ultra-intense laser pulses with solid foils is studied using particle-in-cell (PIC) simulations. A module for simulating bremsstrahlung has been implemented in the PIC loop to self-consistently account for the dynamics of the laser–plasma interaction, plasma expansion, and the emission of gamma ray photons. This module made it possible to study emission from thin targets, where refluxing of hot electrons plays an important role. It is shown that the angular distribution of the emitted photons exhibits a four-directional structure with the angle of emission decreasing with the increase of the width of the target. Additionally, a collimated forward flash consisting of high energy photons has been identified in thin targets. The conversion efficiency of the energy of the laser pulse to the energy of the gamma rays rises with both the driving pulse intensity, and the thickness of the target. The amount of gamma rays also increases with the atomic number of the target material, despite a lower absorption of the driving laser pulse. The angular spectrum of the emitted gamma rays is directly related to the increase of hot electron divergence during their refluxing and its measurement can be used in experiments to study this process.

Bacteria-mediated in vivo delivery of quantum dots into solid tumor

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

Liu, Ying; Zhou, Mei; Luo, Dan

Highlights: Black-Right-Pointing-Pointer New approach using the probiotic Bifidobacterium bifidum as a vehicle to deliver QDs into the deep tissue of solid tumors in vivo was achieved. Black-Right-Pointing-Pointer Bifidobacterium bifidum delivery system has intrinsic biocompatibility. Black-Right-Pointing-Pointer The targeting efficacy was improved by folic acids. -- Abstract: Semiconductor nanocrystals, so-called quantum dots (QDs), promise potential application in bioimaging and diagnosis in vitro and in vivo owing to their high-quality photoluminescence and excellent photostability as well as size-tunable spectra. Here, we describe a biocompatible, comparatively safe bacteria-based system that can deliver QDs specifically into solid tumor of living animals. In our strategy, anaerobicmore » bacterium Bifidobacterium bifidum (B. bifidum) that colonizes selectively in hypoxic regions of animal body was successfully used as a vehicle to load with QDs and transported into the deep tissue of solid tumors. The internalization of lipid-encapsuled QDs into B. bifidum was conveniently carried by electroporation. To improve the efficacy and specificity of tumor targeting, the QDs-carrying bacterium surface was further conjugated with folic acids (FAs) that can bind to the folic acid receptor overexpressed tumor cells. This new approach opens a pathway for delivering different types of functional cargos such as nanoparticles and drugs into solid tumor of live animals for imaging, diagnosis and therapy.« less

Fabrication of high-k dielectric Calcium Copper Titanate (CCTO) target by solid state route

NASA Astrophysics Data System (ADS)

Tripathy, N.; Das, K. C.; Ghosh, S. P.; Bose, G.; Kar, J. P.

2016-02-01

CaCu3Ti4O12 (CCTO) ceramic pellet of 10mm diameter has been synthesized by adopting solid state route. The structural and morphological characterization of the ceramics sample was carried out by X-ray diffraction (XRD) and scanning electron microscope (SEM), respectively. XRD pattern revealed the CCTO phase formation, where as SEM micrograph shows the sample consisting of well defined grain and grain boundaries. The room temperature dielectric constant of the sample was found to be ∼ 5000 at 1kHz. After successful preparation of CCTO pellet, a 2 inch diameter CCTO sputtering target is also fabricated in order to deposit CCTO thin films for microelectronic applications.

Preliminary Results of IS Plasma Focus as a Breeder of Short-Lived Radioisotopes 12C(d,n)13N

NASA Astrophysics Data System (ADS)

Sadat Kiai, S. M.; Elahi, M.; Adlparvar, S.; Shahhoseini, E.; Sheibani, S.; Ranjber akivaj, H.; Alhooie, S.; Safarien, A.; Farhangi, S.; Aghaei, N.; Amini, S.; Khalaj, M. M.; Zirak, A. R.; Dabirzadeh, A. A.; Soleimani, J.; Torkzadeh, F.; Mousazadeh, M. M.; Moradi, K.; Abdollahzadeh, M.; Talaei, A.; Zaeem, A. A.; Moslehi, A.; Kashani, A.; Babazadeh, A. R.; Bagiyan, F.; Ardestani, M.; Roozbahani, A.; Pourbeigi, H.; Tajik Ahmadi, H.; Ahmadifaghih, M. A.; Mahlooji, M. S.; Mortazavi, B. N.; Zahedi, F.

2011-04-01

Modified IS (Iranian Sun) plasma focus (10 kJ,15 kV, 94 μF, 0.1 Hz) has been used to produce the short-lived radioisotope 13N (half-life of 9.97 min) through 12C(d,n)13N nuclear reaction. The filling gas was 1.5-3 torr of hydrogen (60%) deuterium (40%) mixture. The target was solid nuclear grade graphite with 5 mm thick, 9 cm width and 13 in length. The activations of the exogenous target on average of 20 shots (only one-third acceptable) through 10-13 kV produced the 511 keV gamma rays. Another peak found at the 570 keV gamma of which both was measured by a NaI portable gamma spectrometer calibrated by a 137Cs 0.25 μCi sealed reference source with its single line at 661.65 keV and 22Na 0.1 μCi at 511 keV. To measure the gamma rays, the graphite target converts to three different phases; solid graphite, powder graphite, and powder graphite in water solution. The later phase approximately has a doubled activity with respect to the solid graphite target up to 0.5 μCi of 511 keV and 1.1 μCi of 570 keV gamma lines were produced. This increment in activity was perhaps due to structural transformation of graphite powder to nano-particles characteristic in liquid water.

Antibody-Drug Conjugates (ADCs) for Personalized Treatment of Solid Tumors: A Review.

PubMed

Lambert, John M; Morris, Charles Q

2017-05-01

Attaching a cytotoxic "payload" to an antibody to form an antibody-drug conjugate (ADC) provides a mechanism for selective delivery of the cytotoxic agent to cancer cells via the specific binding of the antibody to cancer-selective cell surface molecules. The first ADC to receive marketing authorization was gemtuzumab ozogamicin, which comprises an anti-CD33 antibody conjugated to a highly potent DNA-targeting antibiotic, calicheamicin, approved in 2000 for treating acute myeloid leukemia. It was withdrawn from the US market in 2010 following an unsuccessful confirmatory trial. The development of two classes of highly potent microtubule-disrupting agents, maytansinoids and auristatins, as payloads for ADCs resulted in approval of brentuximab vedotin in 2011 for treating Hodgkin lymphoma and anaplastic large cell lymphoma, and approval of ado-trastuzumab emtansine in 2013 for treating HER2-positive breast cancer. Their success stimulated much research into the ADC approach, with >60 ADCs currently in clinical evaluation, mostly targeting solid tumors. Five ADCs have advanced into pivotal clinical trials for treating various solid tumors-platinum-resistant ovarian cancer, mesothelioma, triple-negative breast cancer, glioblastoma, and small cell lung cancer. The level of target expression is a key parameter in predicting the likelihood of patient benefit for all these ADCs, as well as for the approved compound, ado-trastuzumab emtansine. The development of a patient selection strategy linked to target expression on the tumor is thus critically important for identifying the population appropriate for receiving treatment.

Automation of (64)Cu production at Turku PET Centre.

PubMed

Elomaa, Viki-Veikko; Jurttila, Jori; Rajander, Johan; Solin, Olof

2014-07-01

At Turku PET Centre automation for handling solid targets for the production of (64)Cu has been built. The system consists of a module for moving the target from the irradiation position into a lead transport shield and a robotic-arm assisted setup for moving the target within radiochemistry laboratory. The main motivation for designing automation arises from radiation hygiene. Copyright © 2014 Elsevier Ltd. All rights reserved.

Targeting the Notch signaling pathway in autoimmune diseases.

PubMed

Ma, Daoxin; Zhu, Yuanchao; Ji, Chunyan; Hou, Ming

2010-05-01

The Notch signaling pathway regulates a variety of processes and has been linked to diverse effects. Aberrant Notch function is important in several disorders. Pre-clinical studies have suggested that inhibition of Notch is an attractive approach to treat hematologic and solid malignancies. Many patients with refractory autoimmune diseases respond poorly to therapy and have significant morbidity and the treatment is highly toxic, so more effective therapies for autoimmune diseases are being examined. The role of the Notch pathway and therapeutic strategies targeting it in many illnesses, especially autoimmune diseases. The Notch pathway has unique and attractive advantages for targeting. Targeting it has already been trialed in many experiments, which may show better efficacy and fewer side effects compared with classical drugs for the treatment. Targeting Notch might provide etiological rather than symptomatic treatment. Various methods targeting the Notch pathway have been under investigation. Rational targeting of the Notch signaling pathway in cancer and some autoimmune diseases has proven to be successful. Classical drugs for the treatment of autoimmune diseases are inefficient and toxic to some extent, and targeting the Notch pathway is a promising therapeutic concept. However, there are still many questions about targeting Notch in autoimmune diseases, and further investigation will be needed.

Combined-modality treatment of solid tumors using radiotherapy and molecular targeted agents.

PubMed

Ma, Brigette B Y; Bristow, Robert G; Kim, John; Siu, Lillian L

2003-07-15

Molecular targeted agents have been combined with radiotherapy (RT) in recent clinical trials in an effort to optimize the therapeutic index of RT. The appeal of this strategy lies in their potential target specificity and clinically acceptable toxicity. This article integrates the salient, published research findings into the underlying molecular mechanisms, preclinical efficacy, and clinical applicability of combining RT with molecular targeted agents. These agents include inhibitors of intracellular signal transduction molecules, modulators of apoptosis, inhibitors of cell cycle checkpoints control, antiangiogenic agents, and cyclo-oxygenase-2 inhibitors. Molecular targeted agents can have direct effects on the cytoprotective and cytotoxic pathways implicated in the cellular response to ionizing radiation (IR). These pathways involve cellular proliferation, DNA repair, cell cycle progression, nuclear transcription, tumor angiogenesis, and prostanoid-associated inflammation. These pathways can also converge to alter RT-induced apoptosis, terminal growth arrest, and reproductive cell death. Pharmacologic modulation of these pathways may potentially enhance tumor response to RT though inhibition of tumor repopulation, improvement of tumor oxygenation, redistribution during the cell cycle, and alteration of intrinsic tumor radiosensitivity. Combining RT and molecular targeted agents is a rational approach in the treatment of solid tumors. Translation of this approach from promising preclinical data to clinical trials is actively underway.

Novel apparatus and methods for performing remotely controlled particle-solid interaction experiments at CERN

NASA Astrophysics Data System (ADS)

Krause, H. F.; Deveney, E. F.; Jones, N. L.; Vane, C. R.; Datz, S.; Knudsen, H.; Grafström, P.; Schuch, R.

1997-04-01

Recent atomic physics studies involving ultrarelativistic Pb ions required solid target positioners, scintillators, and a sophisticated data acquisition and control system placed in a remote location at the CERN Super Proton Synchrotron near Geneva, Switzerland. The apparatus, installed in a high-radiation zone underground, had to (i) function for months, (ii) automatically respond to failures such as power outages and particle-induced computer upsets, and (iii) communicate with the outside world via a telephone line. The heart of the apparatus developed was an Apple Macintosh-based CAMAC system that answered the telephone and interpreted and executed remote control commands that (i) sensed and set targets, (ii) controlled voltages and discriminator levels for scintillators, (iii) modified data acquisition hardware logic, (iv) reported control information, and (v) automatically synchronized data acquisition to the CERN spill cycle via a modem signal and transmitted experimental data to a remote computer. No problems were experienced using intercontinental telephone connections at 1200 baud. Our successful "virtual laboratory" approach that uses off-the-shelf electronics is generally adaptable to more conventional bench-type experiments.

A visual LISP program for voxelizing AutoCAD solid models

NASA Astrophysics Data System (ADS)

Marschallinger, Robert; Jandrisevits, Carmen; Zobl, Fritz

2015-01-01

AutoCAD solid models are increasingly recognized in geological and geotechnical 3D modeling. In order to bridge the currently existing gap between AutoCAD solid models and the grid modeling realm, a Visual LISP program is presented that converts AutoCAD solid models into voxel arrays. Acad2Vox voxelizer works on a 3D-model that is made up of arbitrary non-overlapping 3D-solids. After definition of the target voxel array geometry, 3D-solids are scanned at grid positions and properties are streamed to an ASCII output file. Acad2Vox has a novel voxelization strategy that combines a hierarchical reduction of sampling dimensionality with an innovative use of AutoCAD-specific methods for a fast and memory-saving operation. Acad2Vox provides georeferenced, voxelized analogs of 3D design data that can act as regions-of-interest in later geostatistical modeling and simulation. The Supplement includes sample geological solid models with instructions for practical work with Acad2Vox.

Specular Reflectivity and Hot-Electron Generation in High-Contrast Relativistic Laser-Plasma Interactions

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

Kemp, Gregory Elijah

2013-01-01

Ultra-intense laser (> 1018 W/cm2) interactions with matter are capable of producing relativistic electrons which have a variety of applications in state-of-the-art scientific and medical research conducted at universities and national laboratories across the world. Control of various aspects of these hot-electron distributions is highly desired to optimize a particular outcome. Hot-electron generation in low-contrast interactions, where significant amounts of under-dense pre-plasma are present, can be plagued by highly non-linear relativistic laser-plasma instabilities and quasi-static magnetic field generation, often resulting in less than desirable and predictable electron source characteristics. High-contrast interactions offer more controlled interactions but often at the costmore » of overall lower coupling and increased sensitivity to initial target conditions. An experiment studying the differences in hot-electron generation between high and low-contrast pulse interactions with solid density targets was performed on the Titan laser platform at the Jupiter Laser Facility at Lawrence Livermore National Laboratory in Livermore, CA. To date, these hot-electrons generated in the laboratory are not directly observable at the source of the interaction. Instead, indirect studies are performed using state-of-the-art simulations, constrained by the various experimental measurements. These measurements, more-often-than-not, rely on secondary processes generated by the transport of these electrons through the solid density materials which can susceptible to a variety instabilities and target material/geometry effects. Although often neglected in these types of studies, the specularly reflected light can provide invaluable insight as it is directly influenced by the interaction. In this thesis, I address the use of (personally obtained) experimental specular reflectivity measurements to indirectly study hot-electron generation in the context of high-contrast, relativistic laser-plasma interactions.« less

Malachite green interferes with postantibiotic recovery of mycobacteria.

PubMed

Gelman, Ekaterina; McKinney, John D; Dhar, Neeraj

2012-07-01

The genus Mycobacterium comprises slow-growing species with generation times ranging from hours to weeks. The protracted incubation time before colonies appear on solid culture medium can result in overgrowth by faster-growing microorganisms. To prevent contamination, the solid media used in laboratories and clinics for cultivation of mycobacteria contain the arylmethane compound malachite green, which has broad-spectrum antimicrobial activity. Malachite green has no impact on the plating efficiency of mycobacteria when cells are grown under normal conditions. However, we found that malachite green interfered with colony formation when bacteria were preexposed to antibiotics targeting cell wall biogenesis (isoniazid, ethionamide, ethambutol). This inhibitory effect of malachite green was not observed when bacteria were preexposed to antibiotics targeting cellular processes other than cell wall biogenesis (rifampin, moxifloxacin, streptomycin). Sputum specimens from tuberculosis patients are routinely evaluated on solid culture medium containing high concentrations of malachite green. This practice could lead to underestimation of bacterial loads and overestimation of chemotherapeutic efficacy.

Malachite Green Interferes with Postantibiotic Recovery of Mycobacteria

PubMed Central

Gelman, Ekaterina; McKinney, John D.

2012-01-01

The genus Mycobacterium comprises slow-growing species with generation times ranging from hours to weeks. The protracted incubation time before colonies appear on solid culture medium can result in overgrowth by faster-growing microorganisms. To prevent contamination, the solid media used in laboratories and clinics for cultivation of mycobacteria contain the arylmethane compound malachite green, which has broad-spectrum antimicrobial activity. Malachite green has no impact on the plating efficiency of mycobacteria when cells are grown under normal conditions. However, we found that malachite green interfered with colony formation when bacteria were preexposed to antibiotics targeting cell wall biogenesis (isoniazid, ethionamide, ethambutol). This inhibitory effect of malachite green was not observed when bacteria were preexposed to antibiotics targeting cellular processes other than cell wall biogenesis (rifampin, moxifloxacin, streptomycin). Sputum specimens from tuberculosis patients are routinely evaluated on solid culture medium containing high concentrations of malachite green. This practice could lead to underestimation of bacterial loads and overestimation of chemotherapeutic efficacy. PMID:22526306

Challenges in realizing selectivity for nanoparticle biodistribution and clearance: lessons from gold nanoparticles.

PubMed

Haute, Desiree Van; Berlin, Jacob M

2017-08-01

The field of nanomedicine has received much attention for its potential to allow for targeted identification and treatment of tumors, while sparing healthy tissue. This promise has yet to be clinically realized; instead nanomedicine has translated into clinical benefit via formulations that improve the pharmacokinetics and toxicity profiles of toxic chemotherapeutic agents. In this perspective, we highlight that several of the defining strategies for using nanoparticles intravenously to target solid tumors have limited supporting data in animal studies. Namely, it does not appear that reducing macrophage (and other cell type) uptake in vitro leads to better biodistribution in vivo, nor does increasing blood circulation time nor active targeting. We suggest instead that the coming decade will primarily see nanoparticles impact immunotherapy and local/pseudolocal cancer therapy.

Stopping power in D6Li plasmas for target ignition studies

NASA Astrophysics Data System (ADS)

Cortez, Ross J.; Cassibry, Jason T.

2018-02-01

The ability to calculate the range of charged fusion products in a target is critical when estimating driver requirements. Additionally, charged particle ranges are a determining factor in the possibility that a burn front will propagate through the surrounding cold fuel layer, igniting the plasma. Performance parameters of the plasma, such as yield, gain, etc therefore rely on accurate knowledge of particle ranges and stopping power over a wide range of densities and temperatures. Further, this knowledge is essential in calculating ignition conditions for a given target design. In this paper, stopping power is calculated for DD and D6Li plasmas using a molecular dynamics based model. Emphasis is placed on solid D6Li which has been recently considered as a fuel option for fusion propulsion systems.

Screening possible solid electrolytes by calculating the conduction pathways using Bond Valence method

NASA Astrophysics Data System (ADS)

Gao, Jian; Chu, Geng; He, Meng; Zhang, Shu; Xiao, RuiJuan; Li, Hong; Chen, LiQuan

2014-08-01

Inorganic solid electrolytes have distinguished advantages in terms of safety and stability, and are promising to substitute for conventional organic liquid electrolytes. However, low ionic conductivity of typical candidates is the key problem. As connective diffusion path is the prerequisite for high performance, we screen for possible solid electrolytes from the 2004 International Centre for Diffraction Data (ICDD) database by calculating conduction pathways using Bond Valence (BV) method. There are 109846 inorganic crystals in the 2004 ICDD database, and 5295 of them contain lithium. Except for those with toxic, radioactive, rare, or variable valence elements, 1380 materials are candidates for solid electrolytes. The rationality of the BV method is approved by comparing the existing solid electrolytes' conduction pathways we had calculated with those from experiments or first principle calculations. The implication for doping and substitution, two important ways to improve the conductivity, is also discussed. Among them Li2CO3 is selected for a detailed comparison, and the pathway is reproduced well with that based on the density functional studies. To reveal the correlation between connectivity of pathways and conductivity, α/ γ-LiAlO2 and Li2CO3 are investigated by the impedance spectrum as an example, and many experimental and theoretical studies are in process to indicate the relationship between property and structure. The BV method can calculate one material within a few minutes, providing an efficient way to lock onto targets from abundant data, and to investigate the structure-property relationship systematically.

Measurements of cross-section of charge current inclusive of antineutrino scattering off nucleons using carbon, iron, lead and scintillator at MINER$$\

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

Rakotondravohitra, Laza

2015-08-18

Neutrino physics is one of the most active fields in the domaine of high energy physics during the last century. The need of precise measurement of neutrino-nucleus interactions required by the neutrino oscillation experiments is a an exiting step. These measurements of cross-section are more than essential for neutrino oscillation experiment. Over the year, many measurements from varieties of experiments have been presented. MINERνA is one of the world leaders in measuring cross-section of neutrino and antineutrino -nucleus interactions. MINERνA is a neutrino-nucleus scattering experiment installed in the few-GeV NuMI beam line at Fermilab. In order to study nuclear dependence,more » MINERνA is endowed with different types of solid nuclear targets as well are liquid targets such as helium and water. This thesis presents measurements of cross-section of antineutrino scattering off nucleons using a variety of solid nuclear targets, carbon, iron, lead and also polystyrene scintillator (CH). The data set of antineutrino used for this analysis was taken between March and July 2010 with a total of 1.60X10 20 protons on target. Charged current inclusive interactions were selected by requiring a positive muon and kinematics limitation of acceptance of the muon spectrometer are applied. The analysis requires neutrino energy between 2GeV et 20GeV and the angle of muon θ mu < 17degree . The absolute cross-section # as function of neutrino energy and the differential cross-section dσ/ dx bj measured and shown the corresponding systematics for each nuclear targets. Data results are compared with prediction of the models implemented in the neutrino events generators GENIE 2.6.2 used by the experiment.« less

A sensitive EUV Schwarzschild microscope for plasma studies with sub-micrometer resolution

DOE PAGES

Zastrau, U.; Rodel, C.; Nakatsutsumi, M.; ...

2018-02-05

We present an extreme ultraviolet (EUV) microscope using a Schwarzschild objective which is optimized for single-shot sub-micrometer imaging of laser-plasma targets. The microscope has been designed and constructed for imaging the scattering from an EUV-heated solid-density hydrogen jet. Here, imaging of a cryogenic hydrogen target was demonstrated using single pulses of the free-electron laser in Hamburg (FLASH) free-electron laser at a wavelength of 13.5 nm. In a single exposure, we observe a hydrogen jet with ice fragments with a spatial resolution in the sub-micrometer range. In situ EUV imaging is expected to enable novel experimental capabilities for warm dense mattermore » studies of micrometer-sized samples in laser-plasma experiments.« less

A sensitive EUV Schwarzschild microscope for plasma studies with sub-micrometer resolution

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

Zastrau, U.; Rodel, C.; Nakatsutsumi, M.

We present an extreme ultraviolet (EUV) microscope using a Schwarzschild objective which is optimized for single-shot sub-micrometer imaging of laser-plasma targets. The microscope has been designed and constructed for imaging the scattering from an EUV-heated solid-density hydrogen jet. Here, imaging of a cryogenic hydrogen target was demonstrated using single pulses of the free-electron laser in Hamburg (FLASH) free-electron laser at a wavelength of 13.5 nm. In a single exposure, we observe a hydrogen jet with ice fragments with a spatial resolution in the sub-micrometer range. In situ EUV imaging is expected to enable novel experimental capabilities for warm dense mattermore » studies of micrometer-sized samples in laser-plasma experiments.« less

Laser comminution of submerged samples

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

Mariella, R. Jr.; Rubenchik, A.; Norton, M.

With the long-term goal in mind of investigating possible designs for a 'universal, solid-sample comminution technique' for elemental analysis of debris and rubble, we have studied pulsed-laser ablation of solid samples that were submerged in water. Using 351-nm, 15-ns laser pulses with energy between 1 J and 0.35 J, intensities between 500 MW/cm{sup 2} and 30 MW/cm{sup 2}, and samples of broken rock [quartzite] and concrete debris, we have observed conditions in which the laser-driven process can remove material from the solid target substrate, dissolving it and/or converting it into ultrafine particles in a controlled manner. Our study used impure,more » non-metallic substrates and investigated both the rate of material removal as well as the size distribution of particles that were ablated from the process. We studied ablation at lower regimes of intensity and fluence [below 100 MW/cm{sup 2} and 0.4 J/cm{sup 2}, respectively] than has previously attracted attention and discovered that there appears to be a new regime for energy-efficient material removal [Q* < 4000 J/g, for quartzite and <2000 J/g for concrete] and for the generation of ultrafine particles.« less

Development of a sensitive methodology for the analysis of chlorobenzenes in air by combination of solid-phase extraction and headspace solid-phase microextraction.

PubMed

Barro, Ruth; Ares, Sergio; Garcia-Jares, Carmen; Llompart, Maria; Cela, Rafael

2004-08-06

In this study, a combination of solid-phase extraction (SPE) and solid-phase microextraction (SPME) has been used to determine chlorobenzenes in air. Analytes were sampled by pumping a known volume of air through a porous polymer (Tenax TA). Then, the adsorbent was transferred into a glass vial and SPME was performed. The quantification was carried out using gas chromatography (GC)-electron-capture detection or GC-MS. Several SPME coatings (100 microm poly(dimethylsiloxane) (PDMS), 75 microm Carboxen (CAR)-PDMS, 65 microm PDMS-divinylbenzene (DVB), 65 microm PDMS-DVB and 85 microm polyacrylate (PA) were evaluated, obtaining the highest responses with Carbowax (CW)- PDMS for the most volatile chlorobenzenes, and with PDMS-DVB or CW-DVB fibers for the semivolatile compounds. To optimize some other factors that could affect the SPME step, a factorial design was used. Kinetic studies of the SPME process were also performed. Concerning the SPE step, breakthrough was studied, showing that 2.5 m3 of air could be processed without losses of the most volatile compounds. The performance of the method was evaluated. External calibration, which does not require the complete sampling process, demonstrated to be suitable, obtaining good linearity (R2 > 0.99) for all chlorobenzenes. Recovery studies were performed at two concentration levels (4 and 40 ng/m3), obtaining quantitative recoveries (>80%). Limits of detection at the sub ng/m3 were achieved for all the target compounds.

Detection of Human Neutrophil Elastase with Fluorescent Peptide Sensors Conjugated to Nanocellulosic Solid Supports Targeting Wound Care Diagnostics

USDA-ARS?s Scientific Manuscript database

Human neutrophil elastase (HNE) is a biomarker for chronic wounds and a therapeutic target for certain diseases. An unchecked influx of neutrophils, which contain about one pictogram of elastase per neutrophil, is responsible for degrading growth factors and collagen formation, indefinitely delaying...

Flexible Solar Cells Using Doped Crystalline Si Film Prepared by Self-Biased Sputtering Solid Doping Source in SiCl4/H2 Microwave Plasma.

PubMed

Hsieh, Ping-Yen; Lee, Chi-Young; Tai, Nyan-Hwa

2016-02-01

We developed an innovative approach of self-biased sputtering solid doping source process to synthesize doped crystalline Si film on flexible polyimide (PI) substrate via microwave-plasma-enhanced chemical vapor deposition (MWPECVD) using SiCl4/H2 mixture. In this process, P dopants or B dopants were introduced by sputtering the solid doping target through charged-ion bombardment in situ during high-density microwave plasma deposition. A strong correlation between the number of solid doping targets and the characteristics of doped Si films was investigated in detail. The results show that both P- and B-doped crystalline Si films possessed a dense columnar structure, and the crystallinity of these structures decreased with increasing the number of solid doping targets. The films also exhibited a high growth rate (>4.0 nm/s). Under optimal conditions, the maximum conductivity and corresponding carrier concentration were, respectively, 9.48 S/cm and 1.2 × 10(20) cm(-3) for P-doped Si film and 7.83 S/cm and 1.5 × 10(20) cm(-3) for B-doped Si film. Such high values indicate that the incorporation of dopant with high doping efficiency (around 40%) into the Si films was achieved regardless of solid doping sources used. Furthermore, a flexible crystalline Si film solar cell with substrate configuration was fabricated by using the structure of PI/Mo film/n-type Si film/i-type Si film/p-type Si film/ITO film/Al grid film. The best solar cell performance was obtained with an open-circuit voltage of 0.54 V, short-circuit current density of 19.18 mA/cm(2), fill factor of 0.65, and high energy conversion of 6.75%. According to the results of bending tests, the critical radius of curvature (RC) was 12.4 mm, and the loss of efficiency was less than 1% after the cyclic bending test for 100 cycles at RC, indicating superior flexibility and bending durability. These results represent important steps toward a low-cost approach to high-performance flexible crystalline Si film-based photovoltaic devices.

Isochoric heating of low Z solid targets with sub 10 fs laser pulses

NASA Astrophysics Data System (ADS)

Osterholz, Jens

2004-11-01

The investigation of high density plasmas plays an important role for astrophysics, inertial confinement fusion and x-ray lasers. Therefore the generation of dense plasmas with ultra-intense laser pulses is a field of enormous topical interest. An upper limit of the maximum plasma density that can be achieved with this method, however, occurs due to the formation of a preplasma and the expansion of the plasma during the interaction [1,2]. Here we describe a novel approach that is based on a laser system that generates sub 10 fs pulses with a low prepulse energy. Isochoric heating is demonstrated with small Z solid targets. Time integrated XUV spectroscopy is used to investigate K-shell emission from the plasma. In the spectra, only the Ly α and He α lines are observed, whereas transitions from orbitals with principal quantum numbers n > 2 are not present. This series limit is explained by pressure ionisation in the dense plasma. The XUV spectra were simulated by two different models [3]. The first calculates the effect of pressure ionisation and the second calculates the line intensity ratios. Preliminary calculations suggest that the plasma density of the emitting region is close to solid density with an electron temperature of about 100eV. We conclude that our laser system is well suited for isochoric heating of solid targets and an efficient transfer of the laser energy to the dense region of the target is possible. In cooperation with: T. Fischer, F. Brandl, G. Pretzler and O. Willi, Heinrich-Heine-University Duesseldorf, Germany, S. J. Rose, University of Oxford, United Kingdom [1] D. Riley et al., PRL 69, 3739 (1992). [2] A. Saemann et al., PRL 82, 4843 (1999). [3] S. J. Rose, J Phys B: Atom Molec Opt Phys, 25, 1667 (1992), 31, 2129 (1998).

Colorectal cancer chemoprevention: the potential of a selective approach.

PubMed

Ben-Amotz, Oded; Arber, Nadir; Kraus, Sarah

2010-10-01

Colorectal cancer (CRC) is a leading cause of cancer death, and therefore demands special attention. Novel recent approaches for the chemoprevention of CRC focus on selective targeting of key pathways. We review the study by Zhang and colleagues, evaluating a selective approach targeting APC-deficient premalignant cells using retinoid-based therapy and TNF-related apoptosis-inducing ligand (TRAIL). This study demonstrates that induction of TRAIL-mediated death signaling contributes to the chemopreventive value of all-trans-retinyl acetate (RAc) by sensitizing premalignant adenoma cells for apoptosis without affecting normal cells. We discuss these important findings, raise few points that deserve consideration, and may further contribute to the development of RAc-based combination therapies with improved efficacy. The authors clearly demonstrate a synergistic interaction between TRAIL, RAc and APC, which leads to the specific cell death of premalignant target cells. The study adds to the growing body of literature related to CRC chemoprevention, and provides solid data supporting a potentially selective approach for preventing CRC using RAc and TRAIL.

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

PubMed Central

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

2017-01-01

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

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

PubMed

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

2014-10-01

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

A smart telerobotic system driven by monocular vision

NASA Technical Reports Server (NTRS)

Defigueiredo, R. J. P.; Maccato, A.; Wlczek, P.; Denney, B.; Scheerer, J.

1994-01-01

A robotic system that accepts autonomously generated motion and control commands is described. The system provides images from the monocular vision of a camera mounted on a robot's end effector, eliminating the need for traditional guidance targets that must be predetermined and specifically identified. The telerobotic vision system presents different views of the targeted object relative to the camera, based on a single camera image and knowledge of the target's solid geometry.

Ion acceleration in electrostatic field of charged cavity created by ultra-short laser pulses of 1020-1021 W/cm2

NASA Astrophysics Data System (ADS)

Bychenkov, V. Yu.; Singh, P. K.; Ahmed, H.; Kakolee, K. F.; Scullion, C.; Jeong, T. W.; Hadjisolomou, P.; Alejo, A.; Kar, S.; Borghesi, M.; Ter-Avetisyan, S.

2017-01-01

Ion acceleration resulting from the interaction of ultra-high intensity and ultra-high contrast (˜10-10) laser pulses with thin A l foil targets at 30° angle of laser incidence is studied. Proton maximum energies of 30 and 18 MeV are measured along the target normal rear and front sides, respectively, showing intensity scaling as Ib . For the target front bf r o n t= 0.5-0.6 and for the target rear br e a r= 0.7-0.8 is observed in the intensity range 1020-1021 W/cm2. The fast scaling from the target rear ˜I0.75 can be attributed enhancement of laser energy absorption as already observed at relatively low intensities. The backward acceleration of the front side protons with intensity scaling as ˜I0.5 can be attributed to the to the formation of a positively charged cavity at the target front via ponderomotive displacement of the target electrons at the interaction of relativistic intense laser pulses with a solid target. The experimental results are in a good agreement with theoretical predictions.

Multi-layer solid-phase extraction and evaporation-enrichment methods for polar organic chemicals from aqueous matrices.

PubMed

Köke, Niklas; Zahn, Daniel; Knepper, Thomas P; Frömel, Tobias

2018-03-01

Analysis of polar organic chemicals in the aquatic environment is exacerbated by the lack of suitable and widely applicable enrichment methods. In this work, we assessed the suitability of a novel combination of well-known solid-phase extraction (SPE) materials in one cartridge as well as an evaporation method and for the enrichment of 26 polar model substances (predominantly log D < 0) covering a broad range of physico-chemical properties in three different aqueous matrices. The multi-layer solid-phase extraction (mlSPE) and evaporation method were investigated for the recovery and matrix effects of the model substances and analyzed with hydrophilic interaction liquid chromatography-tandem mass spectrometry (HILIC-MS/MS). In total, 65% of the model substances were amenable (> 10% recovery) to the mlSPE method with a mean recovery of 76% while 73% of the model substances were enriched with the evaporation method achieving a mean recovery of 78%. Target and non-target screening comparison of both methods with a frequently used reversed-phase SPE method utilizing "hydrophilic and lipophilic balanced" (HLB) material was performed. Target analysis showed that the mlSPE and evaporation method have pronounced advantages over the HLB method since the HLB material retained only 30% of the model substances. Non-target screening of a ground water sample with the investigated enrichment methods showed that the median retention time of all detected features on a HILIC system decreased in the order mlSPE (3641 features, median t R 9.7 min), evaporation (1391, 9.3 min), HLB (4414, 7.2 min), indicating a higher potential of the described methods to enrich polar analytes from water compared with HLB-SPE. Graphical abstract Schematic of the method evaluation (recovery and matrix effects) and method comparison (target and non-target analysis) of the two investigated enrichment methods for very polar chemicals in aqueousmatrices.

On the feasibility of increasing the energy of laser-accelerated protons by using low-density targets

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

Brantov, A. V., E-mail: brantov@lebedev.ru; Bychenkov, V. Yu., E-mail: bychenk@lebedev.ru

2015-06-15

Optimal regimes of proton acceleration in the interaction of short high-power laser pulses with thin foils and low-density targets are determined by means of 3D numerical simulation. It is demonstrated that the maximum proton energy can be increased by using low-density targets in which ions from the front surface of the target are accelerated most efficiently. It is shown using a particular example that, for the same laser pulse, the energy of protons accelerated from a low-density target can be increased by one-third as compared to a solid-state target.

Design and in vivo evaluation of solid lipid nanoparticulate systems of Olanzapine for acute phase schizophrenia treatment: Investigations on antipsychotic potential and adverse effects.

PubMed

Joseph, Emil; Reddi, Satish; Rinwa, Vibhu; Balwani, Garima; Saha, Ranendra

2017-06-15

The present paper discusses the design, characterization and in vivo evaluation of glyceryl monostearate nanoparticles of Olanzapine, an atypical antipsychotic drug for acute schizophrenia treatment, during which hospitalization is mandatory and adverse effects are at its peak. The solid lipid nanoparticulate system was obtained by emulsification-ultra sonication technique wherein three factors such as solid lipid content, concentration of surfactant and drug: solid lipid ratio were selected at three different levels in order to study their influence on significant characteristic responses such as particle size, encapsulation efficiency and drug content. A Box Behnken design with 17 runs involving whole factors at three levels was employed for the study. The optimized formulation was further coated with Polysorbate 80 in order to enhance its brain targeting potential through endocytosis transport process via blood brain barrier. The designed formulations were pre-clinically tested successfully in Wistar rat model for in vivo antipsychotic efficacy (apomorphine induced psychosis) and adverse effects (weight gain study for 28days). The results obtained indicated that solid lipid nanoparticles had very narrow size distribution (151.29±3.36nm) with very high encapsulation efficiency (74.51±1.75%). Morphological studies by SEM have shown that solid lipid nanoparticles were spherical in shape with smooth surface. Olanzapine-loaded nanoparticles prepared from solid lipid, extended the release of drug for 48h, as found by the in vitro release studies. The formulations also exhibited high redispersibility after freeze-drying and stability study results demonstrated good stability, with no significant change for a period of 6months. In vivo evaluation and adverse effects studies of Olanzapine-loaded nanoparticulate systems in animal model have demonstrated an improved therapeutic efficacy than pure Olanzapine. The antipsychotic effect of drug loaded nanoparticulate systems was maintained for 48h as compared to 8h antipsychotic action of pure Olanzapine solution. The weight gain studies for 28days demonstrated a significant inhibition in weight gain for Olanzapine-loaded nanoparticulate systems as compared to the pure Olanzapine. The present research findings indicate that OLN-loaded nanoparticulate systems may be highly promising for effective delivery of Olanzapine with better efficacy and minimum adverse effects. Copyright © 2017 Elsevier B.V. All rights reserved.

Fluidics platform and method for sample preparation

DOEpatents

Benner, Henry W.; Dzenitis, John M.

2016-06-21

Provided herein are fluidics platforms and related methods for performing integrated sample collection and solid-phase extraction of a target component of the sample all in one tube. The fluidics platform comprises a pump, particles for solid-phase extraction and a particle-holding means. The method comprises contacting the sample with one or more reagents in a pump, coupling a particle-holding means to the pump and expelling the waste out of the pump while the particle-holding means retains the particles inside the pump. The fluidics platform and methods herein described allow solid-phase extraction without pipetting and centrifugation.

A novel superparamagnetic surface molecularly imprinted nanoparticle adopting dummy template: an efficient solid-phase extraction adsorbent for bisphenol A.

PubMed

Lin, Zhenkun; Cheng, Wenjing; Li, Yanyan; Liu, Zhiren; Chen, Xiangping; Huang, Changjiang

2012-03-30

Leakage of the residual template molecules is one of the biggest challenges for application of molecularly imprinted polymer (MIP) in solid-phase extraction (SPE). In this study, bisphenol F (BPF) was adopted as a dummy template to prepare MIP of bisphenol A (BPA) with a superparamagnetic core-shell nanoparticle as the supporter, aiming to avoid residual template leakage and to increase the efficiency of SPE. Characterization and test of the obtained products (called mag-DMIP beads) revealed that these novel nanoparticles not only had excellent magnetic property but also displayed high selectivity to the target molecule BPA. As mag-DMIP beads were adopted as the adsorbents of solid-phase extraction for detecting BPA in real water samples, the recoveries of spiked samples ranged from 84.7% to 93.8% with the limit of detection of 2.50 pg mL(-1), revealing that mag-DMIP beads were efficient SPE adsorbents. Copyright © 2012 Elsevier B.V. All rights reserved.

Second-harmonic generation of ZnO nanoparticles synthesized by laser ablation of solids in liquids

NASA Astrophysics Data System (ADS)

Rocha-Mendoza, Israel; Camacho-López, Santiago; Luna-Palacios, Yryx Y.; Esqueda-Barrón, Yasmín; Camacho-López, Miguel A.; Camacho-López, Marco; Aguilar, Guillermo

2018-02-01

We report the synthesis of small zinc oxide nanoparticles (ZnO NPs) based colloidal suspensions and the study of second-harmonic generation from aggregated ZnO NPs deposited on glass substrates. The colloidal suspensions were obtained using the laser ablation of solids in liquids technique, ablating a Zn solid target immersed in acetone as the liquid medium, with ns-laser pulses (1064 nm) of a Nd-YAG laser. The per pulse laser fluence, the laser repetition rate frequency and the ablation time were kept constant. The absorption evolution of the obtained suspensions was optically characterized through absorption spectroscopy until stabilization. Raman spectroscopy, SEM and HRTEM were used to provide evidence of the ZnO NPs structure. HRTEM results showed that 5-8 nm spheroids ZnO NPs were obtained. Strong second-harmonic signal is obtained from random ZnO monocrystalline NPs and from aggregated ZnO NPs, suggesting that the high efficiency of the nonlinear process may not depend on the NPs size or aggregation state.

Solid supports for extraction and preconcentration of proteins and peptides in microfluidic devices: A review.

PubMed

Dziomba, Szymon; Araya-Farias, Monica; Smadja, Claire; Taverna, Myriam; Carbonnier, Benjamin; Tran, N Thuy

2017-02-22

Determination of proteins and peptides is among the main challenges of today's bioanalytical chemistry. The application of microchip technology in this field is an exhaustively developed concept that aims to create integrated and fully automated analytical devices able to quantify or detect one or several proteins from a complex matrix. Selective extraction and preconcentration of targeted proteins and peptides especially from biological fluids is of the highest importance for a successful realization of these microsystems. Incorporation of solid structures or supports is a convenient solution employed to face these demands. This review presents a critical view on the latest achievements in sample processing techniques for protein determination using solid supports in microfluidics. The study covers the period from 2006 to 2015 and focuses mainly on the strategies based on microbeads, monolithic materials and membranes. Less common approaches are also briefly discussed. The reviewed literature suggests future trends which are discussed in the concluding remarks. Copyright © 2016 Elsevier B.V. All rights reserved.

Combining targeted drugs to overcome and prevent resistance of solid cancers with some stem-like cell features

PubMed Central

Koivunen, Peppi; Koivunen, Jussi P.

2014-01-01

Treatment resistance significantly inhibits the efficiency of targeted cancer therapies in drug-sensitive genotypes. In the current work, we studied mechanisms for rapidly occurring, adaptive resistance in targeted therapy-sensitive lung, breast, and melanoma cancer cell lines. The results show that in ALK translocated lung cancer lines H3122 and H2228, cells with cancer stem-like cell features characterized by high expression of cancer stem cell markers and/or in vivo tumorigenesis can mediate adaptive resistance to oncogene ablative therapy. When pharmacological ablation of ALK oncogene was accompanied with PI3K inhibitor or salinomycin therapy, cancer stem-like cell features were reversed which was accompanied with decreased colony formation. Furthermore, co-targeting was able to block the formation of acquired resistance in H3122 line. The results suggest that cells with cancer stem-like cell features can mediate adaptive resistance to targeted therapies. Since these cells follow the stochastic model, concurrent therapy with an oncogene ablating agent and a stem-like cell-targeting drug is needed for maximal therapeutic efficiency. PMID:25238228

Slow-proton reemission from noble-gas solids

NASA Astrophysics Data System (ADS)

Mills, A. P., Jr.; Leventhal, M.; Lanzerotti, M. Y.; Zuckerman, D. M.; Gullikson, E. M.; Brandes, G. R.

1990-10-01

A 1-μsec pulsed proton beam is being used to study H+ thermalization and reemission from solid target surfaces in ultrahigh vacuum in order to help clarify analogous experiments using muon beams. Using a solid Ar target, vapor deposited on an ~=6-K Cu substrate, the reemission probability Y is 6×10-4 at a proton implantation energy E+H=1.4 keV and falls with increasing energy to 3×10-4 at E+H=5 keV and 2×10-4 at E+H=15 keV. Ne exhibits a 25% larger yield, while the yield for Kr is a factor of 4 lower. The reemitted protons are slow, with kinetic energies of order 1 eV. The reemitted proton yield Y decreases with an ~=100-m time constant, presumably due to deposition of neutral contaminants associated with the incoming beam, and thus ruling out the possibility that the slow protons originate from surface contaminants. For Ar, the observed variation of Y with E+H is interpreted with the help of a Monte Carlo calculation of the stopping and backscattering of the incident protons. The observed magnitude of Y is significantly greater than the calculated backscattering yield at the higher values of E+H. We therefore hypothesize that few-eV protons in the solid, which are considered ``stopped'' by the simulation, can diffuse a significant distance and escape into the vacuum. In our model, the diffusion length for few-eV protons in pristine solid Ar, λ0, is found to be λ0=(50+70-20) Å. However, the diffusion length we deduce from our measurements and simulations varies with E+H, possibly because of the interaction of the slow proton with its implantation trail. The vacancy density is computed to be too low for few-eV protons near the surface to be trapped at defects created by the energetic incoming particle. On the other hand, the proton neutralization probability could be dependent on the availability of free electrons in the ion trail of the implanted particle [O. E. Mogensen, J. Chem. Phys. 60, 998 (1974)]. Extension of our model to the case of positive muons suggests that an experiment to moderate 4-MeV μ+ with a solid Ar target [Harshman et al., Phys. Rev. B 36, 8850 (1987)] may have underestimated λ0 for μ+ due to sample impurities. It appears that the prospects for making a slow μ+ beam are better than we thought, but that remoderation of a few-keV μ+ beam using an Ar surface might have an efficiency less than 1% due to the high muonium-formation probability.

Isotope labeling for studying RNA by solid-state NMR spectroscopy.

PubMed

Marchanka, Alexander; Kreutz, Christoph; Carlomagno, Teresa

2018-04-12

Nucleic acids play key roles in most biological processes, either in isolation or in complex with proteins. Often they are difficult targets for structural studies, due to their dynamic behavior and high molecular weight. Solid-state nuclear magnetic resonance spectroscopy (ssNMR) provides a unique opportunity to study large biomolecules in a non-crystalline state at atomic resolution. Application of ssNMR to RNA, however, is still at an early stage of development and presents considerable challenges due to broad resonances and poor dispersion. Isotope labeling, either as nucleotide-specific, atom-specific or segmental labeling, can resolve resonance overlaps and reduce the line width, thus allowing ssNMR studies of RNA domains as part of large biomolecules or complexes. In this review we discuss the methods for RNA production and purification as well as numerous approaches for isotope labeling of RNA. Furthermore, we give a few examples that emphasize the instrumental role of isotope labeling and ssNMR for studying RNA as part of large ribonucleoprotein complexes.

Lesion detectability in 2D-mammography and digital breast tomosynthesis using different targets and observers

NASA Astrophysics Data System (ADS)

Elangovan, Premkumar; Mackenzie, Alistair; Dance, David R.; Young, Kenneth C.; Wells, Kevin

2018-05-01

This work investigates the detection performance of specialist and non-specialist observers for different targets in 2D-mammography and digital breast tomosynthesis (DBT) using the OPTIMAM virtual clinical trials (VCT) Toolbox and a 4-alternative forced choice (4AFC) assessment paradigm. Using 2D-mammography and DBT images of virtual breast phantoms, we compare the detection limits of simple uniform spherical targets and irregular solid masses. Target diameters of 4 mm and 6 mm have been chosen to represent target sizes close to the minimum detectable size found in breast screening, across a range of controlled contrast levels. The images were viewed by a set of specialist observers (five medical physicists and six experienced clinical readers) and five non-specialists. Combined results from both observer groups indicate that DBT has a significantly lower detectable threshold contrast than 2D-mammography for small masses (4 mm: 2.1% [DBT] versus 6.9% [2D]; 6 mm: 0.7% [DBT] versus 3.9% [2D]) and spheres (4 mm: 2.9% [DBT] versus 5.3% [2D]; 6 mm: 0.3% [DBT] versus 2.2% [2D]) (p  <  0.0001). Both observer groups found spheres significantly easier to detect than irregular solid masses for both sizes and modalities (p  <  0.0001) (except 4 mm DBT). The detection performances of specialist and non-specialist observers were generally found to be comparable, where each group marginally outperformed the other in particular detection tasks. Within the specialist group, the clinical readers performed better than the medical physicists with irregular masses (p  <  0.0001). The results indicate that using spherical targets in such studies may produce over-optimistic detection thresholds compared to more complex masses, and that the superiority of DBT for detecting masses over 2D-mammography has been quantified. The results also suggest specialist observers may be supplemented by non-specialist observers (with training) in some types of 4AFC studies.

Trispecific antibodies for CD16A-directed NK cell engagement and dual-targeting of tumor cells.

PubMed

Gantke, Thorsten; Weichel, Michael; Herbrecht, Carmen; Reusch, Uwe; Ellwanger, Kristina; Fucek, Ivica; Eser, Markus; Müller, Thomas; Griep, Remko; Molkenthin, Vera; Zhukovsky, Eugene A; Treder, Martin

2017-09-01

Bispecific antibodies that redirect the lytic activity of cytotoxic immune effector cells, such as T- and NK cells, onto tumor cells have emerged as a highly attractive and clinically validated treatment modality for hematological malignancies. Advancement of this therapeutic concept into solid tumor indications, however, is hampered by the scarcity of targetable antigens that are surface-expressed on tumor cells but demonstrate only limited expression on healthy tissues. To overcome this limitation, the concept of dual-targeting, i.e. the simultaneous targeting of two tumor-expressed surface antigens with limited co-expression on non-malignant cells, with multispecific antibodies has been proposed to increase tumor selectivity of antibody-induced effector cell cytotoxicity. Here, a novel CD16A (FcγRIIIa)-directed trispecific, tetravalent antibody format, termed aTriFlex, is described, that is capable of redirecting NK cell cytotoxicity to two surface-expressed antigens. Using a BCMA/CD200-based in vitro model system, the potential use of aTriFlex antibodies for dual-targeting and selective induction of NK cell-mediated target cell lysis was investigated. Bivalent bispecific target cell binding was found to result in significant avidity gains and up to 17-fold increased in vitro potency. These data suggest trispecific aTriFlex antibodies may support dual-targeting strategies to redirect NK cell cytotoxicity with increased selectivity to enable targeting of solid tumor antigens. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Analytical methodologies based on LC-MS/MS for monitoring selected emerging compounds in liquid and solid phases of the sewage sludge.

PubMed

Boix, C; Ibáñez, M; Fabregat-Safont, D; Morales, E; Pastor, L; Sancho, J V; Sánchez-Ramírez, J E; Hernández, F

2016-01-01

In this work, two analytical methodologies based on liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS) were developed for quantification of emerging pollutants identified in sewage sludge after a previous wide-scope screening. The target list included 13 emerging contaminants (EC): thiabendazole, acesulfame, fenofibric acid, valsartan, irbesartan, salicylic acid, diclofenac, carbamazepine, 4-aminoantipyrine (4-AA), 4-acetyl aminoantipyrine (4-AAA), 4-formyl aminoantipyrine (4-FAA), venlafaxine and benzoylecgonine. The aqueous and solid phases of the sewage sludge were analyzed making use of Solid-Phase Extraction (SPE) and UltraSonic Extraction (USE) for sample treatment, respectively. The methods were validated at three concentration levels: 0.2, 2 and 20 μg L(-1) for the aqueous phase, and 50, 500 and 2000 μg kg(-1) for the solid phase of the sludge. In general, the method was satisfactorily validated, showing good recoveries (70-120%) and precision (RSD < 20%). Regarding the limit of quantification (LOQ), it was below 0.1 μg L(-1) in the aqueous phase and below 50 μg kg(-1) in the solid phase for the majority of the analytes. The method applicability was tested by analysis of samples from a wider study on degradation of emerging pollutants in sewage sludge under anaerobic digestion. The key benefits of these methodologies are: • SPE and USE are appropriate sample procedures to extract selected emerging contaminants from the aqueous phase of the sewage sludge and the solid residue. • LC-MS/MS is highly suitable for determining emerging contaminants in both sludge phases. • Up to our knowledge, the main metabolites of dipyrone had not been studied before in sewage sludge.

Radiogenetic therapy: strategies to overcome tumor resistance.

PubMed

Marples, B; Greco, O; Joiner, M C; Scott, S D

2003-01-01

The aim of cancer gene therapy is to selectively kill malignant cells at the tumor site, by exploiting traits specific to cancer cells and/or solid tumors. Strategies that take advantage of biological features common to different tumor types are particularly promising, since they have wide clinical applicability. Much attention has focused on genetic methods that complement radiotherapy, the principal treatment modality, or that exploit hypoxia, the most ubiquitous characteristic of most solid cancers. The goal of this review is to highlight two promising gene therapy methods developed specifically to target the tumor volume that can be readily used in combination with radiotherapy. The first approach uses radiation-responsive gene promoters to control the selective expression of a suicide gene (e.g., herpes simplex virus thymidine kinase) to irradiated tissue only, leading to targeted cell killing in the presence of a prodrug (e.g., ganciclovir). The second method utilizes oxygen-dependent promoters to produce selective therapeutic gene expression and prodrug activation in hypoxic cells, which are refractive to conventional radiotherapy. Further refining of tumor targeting can be achieved by combining radiation and hypoxia responsive elements in chimeric promoters activated by either and dual stimuli. The in vitro and in vivo studies described in this review suggest that the combination of gene therapy and radiotherapy protocols has potential for use in cancer care, particularly in cases currently refractory to treatment as a result of inherent or hypoxia-mediated radioresistance.

Notch Signaling and Alloreactivity.

PubMed

Radojcic, Vedran; Maillard, Ivan

2016-12-01

Solid organ and allogeneic hematopoietic cell transplantation have become standard therapeutic interventions that save patient lives and improve quality of life. Our enhanced understanding of transplantation immunobiology has refined clinical management and improved outcomes. However, organ rejection and graft-versus-host disease remain major obstacles to the broader successful application of these therapeutic procedures. Notch signaling regulates multiple aspects of adaptive and innate immunity. Preclinical studies identified Notch signaling as a promising target in autoimmune diseases, as well as after allogeneic hematopoietic cell and solid organ transplantation. Notch was found to be a central regulator of alloreactivity across clinically relevant models of transplantation. Notch inhibition in T cells prevented graft-versus-host disease and organ rejection, establishing organ tolerance by skewing CD4 T helper polarization away from a proinflammatory response toward suppressive regulatory T cells. Notch ligand blockade also dampened alloantibody deposition and prevented chronic rejection through humoral mechanisms. Toxicities of systemic Notch blockade were observed with γ-secretase inhibitors in preclinical and early clinical trials across different indications, but they did not arise upon preclinical targeting of Delta-like Notch ligands, a strategy sufficient to confer full benefits of Notch ablation in T cell alloimmunity. Because multiple clinical grade reagents have been developed to target individual Notch ligands and receptors, the benefits of Notch blockade in transplantation are calling for translation of preclinical findings into human transplantation medicine.

Targeting the adenosine 2A receptor enhances chimeric antigen receptor T cell efficacy

PubMed Central

Beavis, Paul A.; Henderson, Melissa A.; Giuffrida, Lauren; Mills, Jane K.; Sek, Kevin; Cross, Ryan S.; Davenport, Alexander J.; John, Liza B.; Mardiana, Sherly; Slaney, Clare Y.; Johnstone, Ricky W.; Trapani, Joseph A.; Stagg, John; Loi, Sherene; Kats, Lev; Gyorki, David; Kershaw, Michael H.; Darcy, Phillip K.

2017-01-01

Chimeric antigen receptor (CAR) T cells have been highly successful in treating hematological malignancies, including acute and chronic lymphoblastic leukemia. However, treatment of solid tumors using CAR T cells has been largely unsuccessful to date, partly because of tumor-induced immunosuppressive mechanisms, including adenosine production. Previous studies have shown that adenosine generated by tumor cells potently inhibits endogenous antitumor T cell responses through activation of adenosine 2A receptors (A2ARs). Herein, we have observed that CAR activation resulted in increased A2AR expression and suppression of both murine and human CAR T cells. This was reversible using either A2AR antagonists or genetic targeting of A2AR using shRNA. In 2 syngeneic HER2+ self-antigen tumor models, we found that either genetic or pharmacological targeting of the A2AR profoundly increased CAR T cell efficacy, particularly when combined with PD-1 blockade. Mechanistically, this was associated with increased cytokine production of CD8+ CAR T cells and increased activation of both CD8+ and CD4+ CAR T cells. Given the known clinical relevance of the CD73/adenosine pathway in several solid tumor types, and the initiation of phase I trials for A2AR antagonists in oncology, this approach has high translational potential to enhance CAR T cell efficacy in several cancer types. PMID:28165340

Target development for diversified irradiations at a medical cyclotron.

PubMed

Spellerberg, S; Scholten, B; Spahn, I; Bolten, W; Holzgreve, M; Coenen, H H; Qaim, S M

2015-10-01

The irradiation facility at an old medical cyclotron (Ep=17 MeV; Ed=10 MeV) was upgraded by extending the beam line and incorporation of solid state targetry. Tests performed to check the quality of the available beam are outlined. Results on nuclear data measurements and improvement of radiochemical separations are described. Using solid targets, with the proton beam falling at a slanting angle of 20°, a few radionuclides, e.g. (75)Se, (120)I, (124)I, etc. were produced with medium currents (up to 20 µA) in no-carrier-added form in quantities sufficient for local use. The extended irradiation facility has considerably enhanced the utility of the medical cyclotron. Copyright © 2015 Elsevier Ltd. All rights reserved.

Role of the kinematics of probing electrons in electron energy-loss spectroscopy of solid surfaces

NASA Astrophysics Data System (ADS)

Nazarov, V. U.; Silkin, V. M.; Krasovskii, E. E.

2016-01-01

Inelastic scattering of electrons incident on a solid surface is determined by two properties: (i) electronic response of the target system and (ii) the detailed quantum-mechanical motion of the projectile electron inside and in the vicinity of the target. We emphasize the equal importance of the second ingredient, pointing out the fundamental limitations of the conventionally used theoretical description of the electron energy-loss spectroscopy (EELS) in terms of the "energy-loss functions." Our approach encompasses the dipole and impact scattering as specific cases, with the emphasis on the quantum-mechanical treatment of the probe electron. Applied to the high-resolution EELS of Ag surface, our theory largely agrees with recent experiments, while some instructive exceptions are rationalized.

A modular solid state detector for measuring high energy heavy ion fragmentation near the beam axis

NASA Technical Reports Server (NTRS)

Zeitlin, C. J.; Frankel, K. A.; Gong, W.; Heilbronn, L.; Lampo, E. J.; Leres, R.; Miller, J.; Schimmerling, W.

1994-01-01

A multi-element solid state detector has been designed to measure fluences of fragments produced near the beam axis by high energy heavy ion beams in thick targets. The detector is compact and modular, so as to be readily reconfigured according to the range of fragment charges and energies to be measured. Preamplifier gain settings and detector calibrations are adjustable remotely under computer control. We describe the central detector, its associated detectors and electronics, triggering scheme, data acquisition and particle identification techniques, illustrated by data taken with 600 MeV/u 56Fe beams and thick polyethylene targets at the LBL Bevalac. The applications of this work to space radiation protection are discussed.

(Updated) Targeted T-Cell Therapy Shows Promise Against Triple-Negative Breast Cancer | Poster

Cancer.gov

(Updated May 8) A study led by the Baylor College of Medicine and supported by NCI’s Center for Cancer Research (CCR) has demonstrated that chimeric antigen receptor (CAR) T-cell therapy can be used to treat solid triple-negative breast cancer (TNBC) tumors. The investigation is the first work using CAR T-cell therapy against TEM8, a cell surface protein that is frequently

A spring system method for a mesh generation problem

NASA Astrophysics Data System (ADS)

Romanov, A.

2018-04-01

A new direct method for the 2d-mesh generation for a simply-connected domain using a spring system is observed. The method can be used with other methods to modify a mesh for growing solid problems. Advantages and disadvantages of the method are shown. Different types of boundary conditions are explored. The results of modelling for different target domains are given. Some applications for composite materials are studied.

R&D 100, 2016: Ultrafast X-ray Imager

ScienceCinema

Porter, John; Claus, Liam; Sanchez, Marcos; Robertson, Gideon; Riley, Nathan; Rochau, Greg

2018-06-13

The Ultrafast X-ray Imager is a solid-state camera capable of capturing a sequence of images with user-selectable exposure times as short as 2 billionths of a second. Using 3D semiconductor integration techniques to form a hybrid chip, this camera was developed to enable scientists to study the heating and compression of fusion targets in the quest to harness the energy process that powers the stars.

R&D 100, 2016: Ultrafast X-ray Imager

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

Porter, John; Claus, Liam; Sanchez, Marcos

The Ultrafast X-ray Imager is a solid-state camera capable of capturing a sequence of images with user-selectable exposure times as short as 2 billionths of a second. Using 3D semiconductor integration techniques to form a hybrid chip, this camera was developed to enable scientists to study the heating and compression of fusion targets in the quest to harness the energy process that powers the stars.

Gold Nanoparticle Contrast Agents in Mammography: A Feasibility Study

DTIC Science & Technology

2008-08-01

grid and allowed to dry for 6 hours prior to imaging. The grid was then imaged using a high-resolution transmission electron microscopy, and the...9. Lasfargues EY , Coutinho WG, Redfield ES. Isolation of two human tumor epithelial cell lines from solid breast carcinomas. Journal of National...tissue [14]. These probes have also been used to track immune-stimulating cells implanted into cancer patients for treatment purposes. Targeted contrast

Impact of 7-TeV/c large hadron collider proton beam on a copper target

NASA Astrophysics Data System (ADS)

Tahir, N. A.; Goddard, B.; Kain, V.; Schmidt, R.; Shutov, A.; Lomonosov, I. V.; Piriz, A. R.; Temporal, M.; Hoffmann, D. H. H.; Fortov, V. E.

2005-04-01

The large hadron collider (LHC) will allow for collision between two 7TeV/c proton beams, each comprising 2808 bunches with 1.1×1011 protons per bunch, traveling in opposite direction. The bunch length is 0.5ns and two neighboring bunches are separated by 25ns so that the duration of the entire beam is about 89μs. The beam power profile in the transverse direction is a Gaussian with a standard deviation of 0.2mm. The energy stored in each beam is about 350MJ that is sufficient to melt 500kg of copper. In case of a failure in the machine protection systems, the entire beam could impact directly onto an accelerator equipment. A first estimate of the scale of damage resulting from such a failure has been assessed for a solid copper target hit by the beam by carrying out three-dimensional energy deposition calculations and two-dimensional numerical simulations of the hydrodynamic and thermodynamic response of the target. This work has shown that the penetration depth of the LHC protons will be between 10 and 40m in solid copper. These calculations show that material conditions obtained in the target are similar to those planned for beam impact at dedicated accelerators designed to study the physics of high-energy-density states of matter, for example, the Facility for Antiprotons and Ion Research at the Gesellschaft für Schwerionenforschung, Darmstadt [W. F. Henning, Nucl. Instrum Methods Phys. Res. B 214, 211 (2004)].

In vivo Biocompatibility, Biodistribution and Therapeutic Efficiency of Titania Coated Upconversion Nanoparticles for Photodynamic Therapy of Solid Oral Cancers

PubMed Central

Lucky, Sasidharan Swarnalatha; Idris, Niagara Muhammad; Huang, Kai; Kim, Jaejung; Li, Zhengquan; Thong, Patricia Soo Ping; Xu, Rong; Soo, Khee Chee; Zhang, Yong

2016-01-01

Despite the advantages of using photodynamic therapy (PDT) for the treatment of head and neck tumors, it can only be used to treat early stage flat lesions due to the limited tissue penetration ability of the visible light. Here, we developed near-infrared (NIR) excitable upconversion nanoparticle (UCN) based PDT agent that can specifically target epithelial growth factor receptor (EGFR) overexpressing oral cancer cells, in a bid to widen the application of PDT against thick and solid advanced or recurrent head and neck cancers. In vivo studies using the synthesized anti-EGFR-PEG-TiO2-UCNs following systemic administration displayed no major sub-acute or long term toxic effects in terms of blood biochemical, hematological or histopathological changes at a concentration of 50 mg/kg. NIR-PDT even in the presence of a 10 mm tissue phantom placed over the xenograft tumor, showed significant delay in tumor growth and improved survival rate compared to conventional chlorin-e6 (Ce6) PDT using 665 nm red light. Our work, one of the longest study till date in terms of safety (120 d), PDT efficacy (35 d) and survival (60 d), demonstrates the usefulness of UCN based PDT technology for targeted treatment of thick and bulky head and neck tumors. PMID:27570555

Preparation and evaluation of miconazole nitrate-loaded solid lipid nanoparticles for topical delivery.

PubMed

Bhalekar, Mangesh R; Pokharkar, Varsha; Madgulkar, Ashwini; Patil, Nilam; Patil, Nilkanth

2009-01-01

The purpose of this study was to prepare miconazole nitrate (MN) loaded solid lipid nanoparticles (MN-SLN) effective for topical delivery of miconazole nitrate. Compritol 888 ATO as lipid, propylene glycol (PG) to increase drug solubility in lipid, tween 80, and glyceryl monostearate were used as the surfactants to stabilize SLN dispersion in the SLN preparation using hot homogenization method. SLN dispersions exhibited average size between 244 and 766 nm. All the dispersions had high entrapment efficiency ranging from 80% to 100%. The MN-SLN dispersion which showed good stability for a period of 1 month was selected. This MN-SLN was characterized for particle size, entrapment efficiency, and X-ray diffraction. The penetration of miconazole nitrate from the gel formulated using selected MN-SLN dispersion as into cadaver skins was evaluated ex-vivo using franz diffusion cell. The results of differential scanning calorimetry (DSC) showed that MN was dispersed in SLN in an amorphous state. The MN-SLN formulations could significantly increase the accumulative uptake of MN in skin over the marketed gel and showed a significantly enhanced skin targeting effect. These results indicate that the studied MN-SLN formulation with skin targeting may be a promising carrier for topical delivery of miconazole nitrate.

Social network profiles as information sources for adolescents' offline relations.

PubMed

Courtois, Cédric; All, Anissa; Vanwynsberghe, Hadewijch

2012-06-01

This article presents the results of a study concerning the use of online profile pages by adolescents to know more about "offline" friends and acquaintances. Previous research has indicated that social networking sites (SNSs) are used to gather information on new online contacts. However, several studies have demonstrated a substantial overlap between offline and online social networks. Hence, we question whether online connections are meaningful in gathering information on offline friends and acquaintances. First, the results indicate that a combination of passive uncertainty reduction (monitoring a target's profile) and interactive uncertainty reduction (communication through the target's profile) explains a considerable amount of variance in the level of uncertainty about both friends and acquaintances. More specifically, adolescents generally get to know much more about their acquaintances. Second, the results of online uncertainty reduction positively affect the degree of self-disclosure, which is imperative in building a solid friend relation. Further, we find that uncertainty reduction strategies positively mediate the effect of social anxiety on the level of certainty about friends. This implies that socially anxious teenagers benefit from SNSs by getting the conditions right to build a more solid relation with their friends. Hence, we conclude that SNSs play a substantial role in today's adolescents' everyday interpersonal communication.

Bacteriophage-Derived Vectors for Targeted Cancer Gene Therapy

PubMed Central

Pranjol, Md Zahidul Islam; Hajitou, Amin

2015-01-01

Cancer gene therapy expanded and reached its pinnacle in research in the last decade. Both viral and non-viral vectors have entered clinical trials, and significant successes have been achieved. However, a systemic administration of a vector, illustrating safe, efficient, and targeted gene delivery to solid tumors has proven to be a major challenge. In this review, we summarize the current progress and challenges in the targeted gene therapy of cancer. Moreover, we highlight the recent developments of bacteriophage-derived vectors and their contributions in targeting cancer with therapeutic genes following systemic administration. PMID:25606974

Bacteriophage-derived vectors for targeted cancer gene therapy.

PubMed

Pranjol, Md Zahidul Islam; Hajitou, Amin

2015-01-19

Cancer gene therapy expanded and reached its pinnacle in research in the last decade. Both viral and non-viral vectors have entered clinical trials, and significant successes have been achieved. However, a systemic administration of a vector, illustrating safe, efficient, and targeted gene delivery to solid tumors has proven to be a major challenge. In this review, we summarize the current progress and challenges in the targeted gene therapy of cancer. Moreover, we highlight the recent developments of bacteriophage-derived vectors and their contributions in targeting cancer with therapeutic genes following systemic administration.

Nail-like targets for laser plasma interaction experiments

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

Pasley, J; Wei, M; Shipton, E

2007-12-18

The interaction of ultra-high power picosecond laser pulses with solid targets is of interest both for benchmarking the results of hybrid particle in cell (PIC) codes and also for applications to re-entrant cone guided fast ignition. We describe the construction of novel targets in which copper/titanium wires are formed into 'nail-like' objects by a process of melting and micromachining, so that energy can be reliably coupled to a 24 {micro}m diameter wire. An extreme-ultraviolet image of the interaction of the Titan laser with such a target is shown.

Matrix solid-phase dispersion coupled with homogeneous ionic liquid microextraction for the determination of sulfonamides in animal tissues using high-performance liquid chromatography.

PubMed

Wang, Zhibing; He, Mengyu; Jiang, Chunzhu; Zhang, Fengqing; Du, Shanshan; Feng, Wennan; Zhang, Hanqi

2015-12-01

Matrix solid-phase dispersion coupled with homogeneous ionic liquid microextraction was developed and applied to the extraction of some sulfonamides, including sulfamerazine, sulfamethazine, sulfathiazole, sulfachloropyridazine, sulfadoxine, sulfisoxazole, and sulfaphenazole, in animal tissues. High-performance liquid chromatography was applied to the separation and determination of the target analytes. The solid sample was directly treated by matrix solid-phase dispersion and the eluate obtained was treated by homogeneous ionic liquid microextraction. The ionic liquid was used as the extraction solvent in this method, which may result in the improvement of the recoveries of the target analytes. To avoid using organic solvent and reduce environmental pollution, water was used as the elution solvent of matrix solid-phase dispersion. The effects of the experimental parameters on recoveries, including the type and volume of ionic liquid, type of dispersant, ratio of sample to dispersant, pH value of elution solvent, volume of elution solvent, amount of salt in eluate, amount of ion-pairing agent (NH4 PF6 ), and centrifuging time, were evaluated. When the present method was applied to the analysis of animal tissues, the recoveries of the analytes ranged from 85.4 to 118.0%, and the relative standard deviations were lower than 9.30%. The detection limits for the analytes were 4.3-13.4 μg/kg. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Identification of unwanted photoproducts of cosmetic preservatives in personal care products under ultraviolet-light using solid-phase microextraction and micro-matrix solid-phase dispersion.

PubMed

Alvarez-Rivera, Gerardo; Llompart, Maria; Garcia-Jares, Carmen; Lores, Marta

2015-04-17

The photochemical transformation of widely used cosmetic preservatives including benzoates, parabens, BHA, BHT and triclosan has been investigated in this work applying an innovative double-approach strategy: identification of transformation products in aqueous photodegradation experiments (UV-light, 254nm), followed by targeted screening analysis of such photoproducts in UV-irradiated cosmetic samples. Solid-phase microextraction (SPME) was applied, using different fiber coatings, in order to widen the range of detectable photoproducts in water, whereas UV-irradiated personal care products (PCPs) containing the target preservatives were extracted by micro-matrix solid-phase dispersion (micro-MSPD). Both SPME and micro-MSPD-based methodologies were successfully optimized and validated. Degradation kinetics of parent species, and photoformation of their transformation by-products were monitored by gas chromatography coupled to mass spectrometry (GC-MS). Thirty nine photoproducts were detected in aqueous photodegradation experiments, being tentatively identified based on their mass spectra. Transformation pathways between structurally related by-products, consistent with their kinetic behavior were postulated. The photoformation of unexpected photoproducts such as 2- and 4-hydroxybenzophenones, and 2,8-dichlorodibenzo-p-dioxin in PCPs are reported in this work for the first time. Copyright © 2015 Elsevier B.V. All rights reserved.

Developing Strategies for Waste Reduction by Means of Tailored Interventions in Santiago De Cuba

ERIC Educational Resources Information Center

Tobias, Robert; Brugger, Adrian; Mosler, Hans-Joachim

2009-01-01

This article introduces an approach to tailoring behavior-change campaigns to target populations using the example of solid waste reduction in Santiago de Cuba. Tailoring is performed in the following steps: (1) Psychological constructs are selected to detect problems in performing the target behavior, and data are gathered on these constructs.…

Backscattering of electrons from solid targets

NASA Astrophysics Data System (ADS)

Dapor, Maurizio

1990-11-01

A simple equation is derived which describes the electron backscattering coefficient as a function of the target atomic number in the primary energy range 2-45 KeV. Such an equation, very useful for practical purposes, is in better agreement with the experimental data of Palluel and of Cosslett and Thomas than both the treatments of Everhart and of Archard.

Interaction of the high energy deuterons with the graphite target in the plasma focus devices based on Lee model

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

Akel, M., E-mail: pscientific2@aec.org.sy; Alsheikh Salo, S.; Ismael, Sh.

2014-07-15

Numerical experiments are systematically carried out using the Lee model code extended to compute the ion beams on various plasma focus devices operated with Deuterium gas. The deuteron beam properties of the plasma focus are studied for low and high energy plasma focus device. The energy spectral distribution for deuteron ions ejected from the pinch plasma is calculated and the ion numbers with energy around 1 MeV is then determined. The deuteron–graphite target interaction is studied for different conditions. The yield of the reaction {sup 12}C(d,n){sup 13}N and the induced radioactivity for one and multi shots plasma focus devices in themore » graphite solid target is investigated. Our results present the optimized high energy repetitive plasma focus devices as an alternative to accelerators for the production of {sup 13}N short lived radioisotopes. However, technical challenges await solutions on two fronts: (a) operation of plasma focus machines at high rep rates for a sufficient period of time (b) design of durable targets that can take the thermal load.« less

A qualitative study of the infant feeding beliefs and behaviours of mothers with low educational attainment.

PubMed

Russell, Catherine Georgina; Taki, Sarah; Azadi, Leva; Campbell, Karen J; Laws, Rachel; Elliott, Rosalind; Denney-Wilson, Elizabeth

2016-05-21

Infancy is an important period for the promotion of healthy eating, diet and weight. However little is known about how best to engage caregivers of infants in healthy eating programs. This is particularly true for caregivers, infants and children from socioeconomically disadvantaged backgrounds who experience greater rates of overweight and obesity yet are more challenging to reach in health programs. Behaviour change interventions targeting parent-infant feeding interactions are more likely to be effective if assumptions about what needs to change for the target behaviours to occur are identified. As such we explored the precursors of key obesity promoting infant feeding practices in mothers with low educational attainment. One-on-one semi-structured telephone interviews were developed around the Capability Opportunity Motivation Behaviour (COM-B) framework and applied to parental feeding practices associated with infant excess or healthy weight gain. The target behaviours and their competing alternatives were (a) initiating breastfeeding/formula feeding, (b) prolonging breastfeeding/replacing breast milk with formula, (c) best practice formula preparation/sub-optimal formula preparation, (d) delaying the introduction of solid foods until around six months of age/introducing solids earlier than four months of age, and (e) introducing healthy first foods/introducing unhealthy first foods, and (f) feeding to appetite/use of non-nutritive (i.e., feeding for reasons other than hunger) feeding. The participants' education level was used as the indicator of socioeconomic disadvantage. Two researchers independently undertook thematic analysis. Participants were 29 mothers of infants aged 2-11 months. The COM-B elements of Social and Environmental Opportunity, Psychological Capability, and Reflective Motivation were the key elements identified as determinants of a mother's likelihood to adopt the healthy target behaviours although the relative importance of each of the COM-B factors varied with each of the target feeding behaviours. Interventions targeting healthy infant feeding practices should be tailored to the unique factors that may influence mothers' various feeding practices, taking into account motivational and social influences.

Size dependence of the disruption threshold: laboratory examination of millimeter-centimeter porous targets

NASA Astrophysics Data System (ADS)

Nakamura, Akiko M.; Yamane, Fumiya; Okamoto, Takaya; Takasawa, Susumu

2015-03-01

The outcome of collision between small solid bodies is characterized by the threshold energy density Q*s, the specific energy to shatter, that is defined as the ratio of projectile kinetic energy to the target mass (or the sum of target and projectile) needed to produce the largest intact fragment that contains one half the target mass. It is indicated theoretically and by numerical simulations that the disruption threshold Q*s decreases with target size in strength-dominated regime. The tendency was confirmed by laboratory impact experiments using non-porous rock targets (Housen and Holsapple, 1999; Nagaoka et al., 2014). In this study, we performed low-velocity impact disruption experiments on porous gypsum targets with porosity of 65-69% and of three different sizes to examine the size dependence of the disruption threshold for porous material. The gypsum specimens were shown to have a weaker volume dependence on static tensile strength than do the non-porous rocks. The disruption threshold had also a weaker dependence on size scale as Q*s ∝D-γ , γ ≤ 0.25 - 0.26, while the previous laboratory studies showed γ=0.40 for the non-porous rocks. The measurements at low-velocity lead to a value of about 100 J kg-1 for Q*s which is roughly one order of magnitude lower than the value of Q*s for the gypsum targets of 65% porosity but impacted by projectiles with higher velocities. Such a clear dependence on the impact velocity was also shown by previous studies of gypsum targets with porosity of 50%.

Optimization of a sensitive method for the determination of nitro musk fragrances in waters by solid-phase microextraction and gas chromatography with micro electron capture detection using factorial experimental design.

PubMed

Polo, Maria; Garcia-Jares, Carmen; Llompart, Maria; Cela, Rafael

2007-08-01

A solid-phase microextraction method (SPME) followed by gas chromatography with micro electron capture detection for determining trace levels of nitro musk fragrances in residual waters was optimized. Four nitro musks, musk xylene, musk moskene, musk tibetene and musk ketone, were selected for the optimization of the method. Factors affecting the extraction process were studied using a multivariate approach. Two extraction modes (direct SPME and headspace SPME) were tried at different extraction temperatures using two fiber coatings [Carboxen-polydimethylsiloxane (CAR/PDMS) and polydimethylsiloxane-divinylbenzene (PDMS/DVB)] selected among five commercial tested fibers. Sample agitation and the salting-out effect were also factors studied. The main effects and interactions between the factors were studied for all the target compounds. An extraction temperature of 100 degrees C and sampling the headspace over the sample, using either CAR/PDMS or PDMS/DVB as fiber coatings, were found to be the experimental conditions that led to a more effective extraction. High sensitivity, with detection limits in the low nanogram per liter range, and good linearity and repeatability were achieved for all nitro musks. Since the method proposed performed well for real samples, it was applied to different water samples, including wastewater and sewage, in which some of the target compounds (musk xylene and musk ketone) were detected and quantified.

Development of solid tunable optics for ultra-miniature imaging systems

NASA Astrophysics Data System (ADS)

Yongchao, Zou

This thesis focuses on the optimal design, fabrication and testing of solid tunable optics and exploring their applications in miniature imaging systems. It starts with the numerical modelling of such lenses, followed by the optimum design method and alignment tolerance analysis. A miniature solid tunable lens driven by a piezo actuator is then developed. To solve the problem of limited maximum optical power and tuning range in conventional lens designs, a novel multi-element solid tunable lens is proposed and developed. Inspired by the Alvarez principle, a novel miniature solid tunable dual-focus lens, which is designed using freeform surfaces and driven by one micro-electro-mechanical-systems (MEMS) rotary actuator, is demonstrated. To explore the applications of these miniature solid tunable lenses, a miniature adjustable-focus endoscope and one compact adjustable-focus camera module are developed. The adjustable-focus capability of these two miniature imaging systems is fully proved by electrically focusing targets placed at different positions.

Beam Induced Hydrodynamic Tunneling in the Future Circular Collider Components

NASA Astrophysics Data System (ADS)

Tahir, N. A.; Burkart, F.; Schmidt, R.; Shutov, A.; Wollmann, D.; Piriz, A. R.

2016-08-01

A future circular collider (FCC) has been proposed as a post-Large Hadron Collider accelerator, to explore particle physics in unprecedented energy ranges. The FCC is a circular collider in a tunnel with a circumference of 80-100 km. The FCC study puts an emphasis on proton-proton high-energy and electron-positron high-intensity frontier machines. A proton-electron interaction scenario is also examined. According to the nominal FCC parameters, each of the 50 TeV proton beams will carry an amount of 8.5 GJ energy that is equivalent to the kinetic energy of an Airbus A380 (560 t) at a typical speed of 850 km /h . Safety of operation with such extremely energetic beams is an important issue, as off-nominal beam loss can cause serious damage to the accelerator and detector components with a severe impact on the accelerator environment. In order to estimate the consequences of an accident with the full beam accidently deflected into equipment, we have carried out numerical simulations of interaction of a FCC beam with a solid copper target using an energy-deposition code (fluka) and a 2D hydrodynamic code (big2) iteratively. These simulations show that, although the penetration length of a single FCC proton and its shower in solid copper is about 1.5 m, the full FCC beam will penetrate up to about 350 m into the target because of the "hydrodynamic tunneling." These simulations also show that a significant part of the target is converted into high-energy-density matter. We also discuss this interesting aspect of this study.

Micron-scale mapping of megagauss magnetic fields using optical polarimetry to probe hot electron transport in petawatt-class laser-solid interactions.

PubMed

Chatterjee, Gourab; Singh, Prashant Kumar; Robinson, A P L; Blackman, D; Booth, N; Culfa, O; Dance, R J; Gizzi, L A; Gray, R J; Green, J S; Koester, P; Kumar, G Ravindra; Labate, L; Lad, Amit D; Lancaster, K L; Pasley, J; Woolsey, N C; Rajeev, P P

2017-08-21

The transport of hot, relativistic electrons produced by the interaction of an intense petawatt laser pulse with a solid has garnered interest due to its potential application in the development of innovative x-ray sources and ion-acceleration schemes. We report on spatially and temporally resolved measurements of megagauss magnetic fields at the rear of a 50-μm thick plastic target, irradiated by a multi-picosecond petawatt laser pulse at an incident intensity of ~10 20 W/cm 2 . The pump-probe polarimetric measurements with micron-scale spatial resolution reveal the dynamics of the magnetic fields generated by the hot electron distribution at the target rear. An annular magnetic field profile was observed ~5 ps after the interaction, indicating a relatively smooth hot electron distribution at the rear-side of the plastic target. This is contrary to previous time-integrated measurements, which infer that such targets will produce highly structured hot electron transport. We measured large-scale filamentation of the hot electron distribution at the target rear only at later time-scales of ~10 ps, resulting in a commensurate large-scale filamentation of the magnetic field profile. Three-dimensional hybrid simulations corroborate our experimental observations and demonstrate a beam-like hot electron transport at initial time-scales that may be attributed to the local resistivity profile at the target rear.

Targeting tissue factor as a novel therapeutic oncotarget for eradication of cancer stem cells isolated from tumor cell lines, tumor xenografts and patients of breast, lung and ovarian cancer.

PubMed

Hu, Zhiwei; Xu, Jie; Cheng, Jijun; McMichael, Elizabeth; Yu, Lianbo; Carson, William E

2017-01-03

Targeting cancer stem cell (CSC) represents a promising therapeutic approach as it can potentially fight cancer at its root. The challenge is to identify a surface therapeutic oncotarget on CSC. Tissue factor (TF) is known as a common yet specific surface target for cancer cells and tumor neovasculature in several solid cancers. However, it is unknown if TF is expressed by CSCs. Here we demonstrate that TF is constitutively expressed on CD133 positive (CD133+) or CD24-CD44+ CSCs isolated from human cancer cell lines, tumor xenografts from mice and breast tumor tissues from patients. TF-targeted agents, i.e., a factor VII (fVII)-conjugated photosensitizer (fVII-PS for targeted photodynamic therapy) and fVII-IgG1Fc (Immunoconjugate or ICON for immunotherapy), can eradicate CSC via the induction of apoptosis and necrosis and via antibody-dependent cellular cytotoxicity and complement-dependent cytotoxicity, respectively. In conclusion, these results demonstrate that TF is a novel surface therapeutic oncotarget for CSC, in addition to cancer cell TF and tumor angiogenic vascular endothelial TF. Moreover, this research highlights that TF-targeting therapeutics can effectively eradicate CSCs, without drug resistance, isolated from breast, lung and ovarian cancer with potential to translate into other most commonly diagnosed solid cancer, in which TF is also highly expressed.

Studies of Ion Acceleration from Thin Solid-Density Targets on High-Intensity Lasers

NASA Astrophysics Data System (ADS)

Willis, Christopher R.

Over the past two decades, a number of experiments have been performed demonstrating the acceleration of ions from the interaction of an intense laser pulse with a thin, solid density target. These ions are accelerated by quasi-static electric fields generated by energetic electrons produced at the front of the target, resulting in ion energies up to tens of MeV. These ions have been widely studied for a variety of potential applications ranging from treatment of cancer to the production of neutrons for advanced radiography techniques. However, realization of these applications will require further optimization of the maximum energy, spectrum, or species of the accelerated ions, which has been a primary focus of research to date. This thesis presents two experiments designed to optimize several characteristics of the accelerated ion beam. The first of these experiments took place on the GHOST laser system at the University of Texas at Austin, and was designed to demonstrate reliable acceleration of deuterium ions, as needed for the most efficient methods of neutron generation from accelerated ions. This experiment leveraged cryogenically cooled targets coated in D2 O ice to suppress the protons which typically dominate the accelerated ions, producing as many as 2 x 1010 deuterium ions per 1 J laser shot, exceeding the proton yield by an average ratio of 5:1. The second major experiment in this work was performed on the Scarlet laser system at The Ohio State University, and studied the accelerated ion energy, yield, and spatial distribution as a function of the target thickness. In principle, the peak energy increases with decreasing target thickness, with the thinnest targets accessing additional acceleration mechanisms which provide favorable scaling with the laser intensity. However, laser prepulse characteristics provide a lower bound for the target thickness, yielding an optimum target thickness for ion acceleration which is dependent on the laser system. This experiment utilized new liquid crystal film targets developed at OSU, which may be formed at variable thicknesses from tens of nanometers to several microns. On this experiment, an optimum ion energy and flux was reached for targets of 600-900 nm, providing a peak proton energy of 24 MeV, and total ion flux of > 109 protons over 3.4 MeV from 5.5 J of laser energy at an intensity of 1 x 1020 W cm -2. The primary ion diagnostics for these two experiments are described in detail, including the analysis techniques needed to extract absolutely calibrated spatial and spectral distributions of the accelerated ions. Additionally, a new technique for target alignment is presented, providing repeatable target alignment on the micron scale. This allows for a repeatable laser intensity on target, allowing improved shot to shot consistency on high intensity experiments. In addition to these two experiments, work on the upgrade and characterization of the 400 TW Scarlet laser is discussed, including several calculations critical to the design and upgrade of the laser system, as well as prepulse characterization needed for experiments on thin targets.

Overview on the target fabrication facilities at ELI-NP and ongoing strategies

NASA Astrophysics Data System (ADS)

Gheorghiu, C. C.; Leca, V.; Popa, D.; Cernaianu, M. O.; Stutman, D.

2016-10-01

Along with the development of petawatt class laser systems, the interaction between high power lasers and matter flourished an extensive research, with high-interest applications like: laser nuclear physics, proton radiography or cancer therapy. The new ELI-NP (Extreme Light Infrastructure - Nuclear Physics) petawatt laser facility, with 10PW and ~ 1023W/cm2 beam intensity, is one of the innovative projects that will provide novel research of fundamental processes during light-matter interaction. As part of the ELI-NP facility, Targets Laboratory will provide the means for in-house manufacturing and characterization of the required targets (mainly solid ones) for the experiments, in addition to the research activity carried out in order to develop novel target designs with improved performances. A description of the Targets Laboratory with the main pieces of equipment and their specifications are presented. Moreover, in view of the latest progress in the target design, one of the proposed strategies for the forthcoming experiments at ELI-NP is also described, namely: ultra-thin patterned foil of diamond-like carbon (DLC) coated with a carbon-based ultra-low density layer. The carbon foam which behaves as a near-critical density plasma, will allow the controlled-shaping of the laser pulse before the main interaction with the solid foil. Particular emphasis will be directed towards the target's design optimization, by simulation tests and tuning the key-properties (thickness/length, spacing, density foam, depth, periodicity etc.) which are expected to have a crucial effect on the laser-matter interaction process.

Numerical modeling of laser-driven ion acceleration from near-critical gas targets

NASA Astrophysics Data System (ADS)

Tatomirescu, Dragos; Vizman, Daniel; d’Humières, Emmanuel

2018-06-01

In the past two decades, laser-accelerated ion sources and their applications have been intensely researched. Recently, it has been shown through experiments that proton beams with characteristics comparable to those obtained with solid targets can be obtained from gaseous targets. By means of particle-in-cell simulations, this paper studies in detail the effects of a near-critical density gradient on ion and electron acceleration after the interaction with ultra high intensity lasers. We can observe that the peak density of the gas jet has a significant influence on the spectrum features. As the gas jet density increases, so does the peak energy of the central quasi-monoenergetic ion bunch due to the increase in laser absorption while at the same time having a broadening effect on the electron angular distribution.

On-line solid-phase microextraction of triclosan, bisphenol A, chlorophenols, and selected pharmaceuticals in environmental water samples by high-performance liquid chromatography-ultraviolet detection.

PubMed

Kim, Dalho; Han, Jungho; Choi, Yongwook

2013-01-01

A method using on-line solid-phase microextraction (SPME) on a carbowax-templated fiber followed by liquid chromatography (LC) with ultraviolet (UV) detection was developed for the determination of triclosan in environmental water samples. Along with triclosan, other selected phenolic compounds, bisphenol A, and acidic pharmaceuticals were studied. Previous SPME/LC or stir-bar sorptive extraction/LC-UV for polar analytes showed lack of sensitivity. In this study, the calculated octanol-water distribution coefficient (log D) values of the target analytes at different pH values were used to estimate polarity of the analytes. The lack of sensitivity observed in earlier studies is identified as a lack of desorption by strong polar-polar interactions between analyte and solid-phase. Calculated log D values were useful to understand or predict the interaction between analyte and solid phase. Under the optimized conditions, the method detection limit of selected analytes by using on-line SPME-LC-UV method ranged from 5 to 33 ng L(-1), except for very polar 3-chlorophenol and 2,4-dichlorophenol which was obscured in wastewater samples by an interfering substance. This level of detection represented a remarkable improvement over the conventional existing methods. The on-line SPME-LC-UV method, which did not require derivatization of analytes, was applied to the determination of TCS including phenolic compounds and acidic pharmaceuticals in tap water and river water and municipal wastewater samples.

Improving CART-Cell Therapy of Solid Tumors with Oncolytic Virus-Driven Production of a Bispecific T-cell Engager.

PubMed

Wing, Anna; Fajardo, Carlos Alberto; Posey, Avery D; Shaw, Carolyn; Da, Tong; Young, Regina M; Alemany, Ramon; June, Carl H; Guedan, Sonia

2018-05-01

T cells expressing chimeric antigen receptors (CART) have shown significant promise in clinical trials to treat hematologic malignancies, but their efficacy in solid tumors has been limited. Oncolytic viruses have the potential to act in synergy with immunotherapies due to their immunogenic oncolytic properties and the opportunity of incorporating therapeutic transgenes in their genomes. Here, we hypothesized that an oncolytic adenovirus armed with an EGFR-targeting, bispecific T-cell engager (OAd-BiTE) would improve the outcome of CART-cell therapy in solid tumors. We report that CART cells targeting the folate receptor alpha (FR-α) successfully infiltrated preestablished xenograft tumors but failed to induce complete responses, presumably due to the presence of antigen-negative cancer cells. We demonstrated that OAd-BiTE-mediated oncolysis significantly improved CART-cell activation and proliferation, while increasing cytokine production and cytotoxicity, and showed an in vitro favorable safety profile compared with EGFR-targeting CARTs. BiTEs secreted from infected cells redirected CART cells toward EGFR in the absence of FR-α, thereby addressing tumor heterogeneity. BiTE secretion also redirected CAR-negative, nonspecific T cells found in CART-cell preparations toward tumor cells. The combinatorial approach improved antitumor efficacy and prolonged survival in mouse models of cancer when compared with the monotherapies, and this was the result of an increased BiTE-mediated T-cell activation in tumors. Overall, these results demonstrated that the combination of a BiTE-expressing oncolytic virus with adoptive CART-cell therapy overcomes key limitations of CART cells and BiTEs as monotherapies in solid tumors and encourage its further evaluation in human trials. Cancer Immunol Res; 6(5); 605-16. ©2018 AACR . ©2018 American Association for Cancer Research.

Plasma Immersion Ion Implantation with Solid Targets for Space and Aerospace Applications

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

Oliveira, R. M.; Goncalves, J. A. N.; Ueda, M.

2009-01-05

This paper describes successful results obtained by a new type of plasma source, named as Vaporization of Solid Targets (VAST), for treatment of materials for space and aerospace applications, by means of plasma immersion ion implantation and deposition (PIII and D). Here, the solid element is vaporized in a high pressure glow discharge, being further ionized and implanted/deposited in a low pressure cycle, with the aid of an extra electrode. First experiments in VAST were run using lithium as the solid target. Samples of silicon and aluminum alloy (2024) were immersed into highly ionized lithium plasma, whose density was measuredmore » by a double Langmuir probe. Measurements performed with scanning electron microscopy (SEM) showed clear modification of the cross-sectioned treated silicon samples. X-ray photoelectron spectroscopy (XPS) analysis revealed that lithium was implanted/deposited into/onto the surface of the silicon. Implantation depth profiles may vary according to the condition of operation of VAST. One direct application of this treatment concerns the protection against radiation damage for silicon solar cells. For the case of the aluminum alloy, X-ray diffraction analysis indicated the appearance of prominent new peaks. Surface modification of A12024 by lithium implantation/deposition can lower the coefficient of friction and improve the resistance to fatigue of this alloy. Recently, cadmium was vaporized and ionized in VAST. The main benefit of this element is associated with the improvement of corrosion resistance of metallic substrates. Besides lithium and cadmium, VAST allows to performing PIII and D with other species, leading to the modification of the near-surface of materials for distinct purposes, including applications in the space and aerospace areas.« less

Simultaneous determination of the endocrine disrupting compounds nonylphenol, nonylphenol ethoxylates, triclosan and bisphenol A in wastewater and sewage sludge by gas chromatography-mass spectrometry.

PubMed

Gatidou, Georgia; Thomaidis, Nikolaos S; Stasinakis, Athanasios S; Lekkas, Themistokles D

2007-01-05

An integrated analytical method for the simultaneous determination of 4-n-nonylphenol (4-n-NP), nonylphenol monoethoxylate (NP1EO), nonylphenol diethoxylate (NP2EO), bisphenol A (BPA) and triclosan (TCS) in wastewater (dissolved and particulate phase) and sewage sludge was developed based on gas chromatography-mass spectrometry. Chromatographic analysis was achieved after derivatization with bis(trimethylsilyl)trifluoroacetamide (BSTFA). Extraction from water samples was performed by solid-phase extraction (SPE). The optimization of SPE procedure included the type of sorbent and the type of the organic solvent used for the elution. Referred to solid samples, the target compounds were extracted by sonication. In this case the optimization of the extraction procedure included the variation of the amount of the extracted biomass, the duration and the temperature of sonication and the type of the extraction organic solvent. The developed extraction procedures resulted in good repeatability and reproducibility with relative standard deviations (RSDs) less than 13% for all the tested compounds for both types of samples. Satisfactory recoveries were obtained (>60%) for all the compounds in both liquid and solid samples, except for 4-n-NP, which gave recoveries up to 35% in wastewater samples and up to 63% in sludge samples. The limits of detection (LODs) of the target compounds varied from 0.03 (4-n-NP) to 0.41 microg l(-1) (NP2EO) and from 0.04 (4-n-NP) to 0.96 microg kg(-1) (NP2EO) for liquid and solid samples, respectively. The developed methods were successfully applied to the analysis of the target compounds in real samples.

Recurrently Mutated Genes Differ between Leptomeningeal and Solid Lung Cancer Brain Metastases.

PubMed

Li, Yingmei; Liu, Boxiang; Connolly, Ian David; Kakusa, Bina Wasunga; Pan, Wenying; Nagpal, Seema; Montgomery, Stephen B; Hayden Gephart, Melanie

2018-03-29

When compared with solid brain metastases from NSCLC, leptomeningeal disease (LMD) has unique growth patterns and is rapidly fatal. Patients with LMD do not undergo surgical resection, limiting the tissue available for scientific research. In this study we performed whole exome sequencing on eight samples of LMD to identify somatic mutations and compared the results with those for 26 solid brain metastases. We found that taste 2 receptor member 31 gene (TAS2R31) and phosphodiesterase 4D interacting protein gene (PDE4DIP) were recurrently mutated among LMD samples, suggesting involvement in LMD progression. Together with a retrospective review of the charts of an additional 44 patients with NSCLC LMD, we discovered a surprisingly low number of KRAS mutations (n = 4 [7.7%]) but a high number of EGFR mutations (n = 33 [63.5%]). The median interval for development of LMD from NSCLC was shorter in patients with mutant EGFR (16.3 months) than in patients with wild-type EGFR (23.9 months) (p = 0.017). Targeted analysis of recurrent mutations thus presents a useful complement to the existing diagnostic tool kit, and correlations of EGFR in LMD and KRAS in solid metastases suggest that molecular distinctions or systemic treatment pressure underpin the differences in growth patterns within the brain. Copyright © 2018 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved.

Design and operation of an anaerobic digester for waste management and fuel generation during long term lunar mission

NASA Astrophysics Data System (ADS)

Dhoble, Abhishek S.; Pullammanappallil, Pratap C.

2014-10-01

Waste treatment and management for manned long term exploratory missions to moon will be a challenge due to longer mission duration. The present study investigated appropriate digester technologies that could be used on the base. The effect of stirring, operation temperature, organic loading rate and reactor design on the methane production rate and methane yield was studied. For the same duration of digestion, the unmixed digester produced 20-50% more methane than mixed system. Two-stage design which separated the soluble components from the solids and treated them separately had more rapid kinetics than one stage system, producing the target methane potential in one-half the retention time than the one stage system. The two stage system degraded 6% more solids than the single stage system. The two stage design formed the basis of a prototype digester sized for a four-person crew during one year exploratory lunar mission.

Current and Future Clinical Applications of High-Intensity Focused Ultrasound (HIFU) for Pancreatic Cancer.

PubMed

Jang, Hyun Joo; Lee, Jae-Young; Lee, Don-Haeng; Kim, Won-Hong; Hwang, Joo Ha

2010-09-01

High-intensity focused ultrasound (HIFU) is a novel therapeutic modality that permits noninvasive treatment of various benign and malignant solid tumors, including prostatic cancer, uterine fibroids, hepatic tumors, renal tumors, breast cancers, and pancreatic cancers. Several preclinical and clinical studies have investigated the safety and efficacy of HIFU for treating solid tumors, including pancreatic cancer. The results of nonrandomized studies of HIFU therapy in patients with pancreatic cancer have suggested that HIFU treatment can effectively alleviate cancer-related pain without any significant complications. This noninvasive method of delivering ultrasound energy into the body has recently been evolving from a method for purely thermal ablation to harnessing the mechanical effects of HIFU to induce a systemic immune response and to enhance targeted drug delivery. This review provides a brief overview of HIFU, describes current clinical applications of HIFU for pancreatic cancer, and discusses future applications and challenges.

Current and Future Clinical Applications of High-Intensity Focused Ultrasound (HIFU) for Pancreatic Cancer

PubMed Central

Jang, Hyun Joo; Lee, Jae-Young; Lee, Don-Haeng; Kim, Won-Hong

2010-01-01

High-intensity focused ultrasound (HIFU) is a novel therapeutic modality that permits noninvasive treatment of various benign and malignant solid tumors, including prostatic cancer, uterine fibroids, hepatic tumors, renal tumors, breast cancers, and pancreatic cancers. Several preclinical and clinical studies have investigated the safety and efficacy of HIFU for treating solid tumors, including pancreatic cancer. The results of nonrandomized studies of HIFU therapy in patients with pancreatic cancer have suggested that HIFU treatment can effectively alleviate cancer-related pain without any significant complications. This noninvasive method of delivering ultrasound energy into the body has recently been evolving from a method for purely thermal ablation to harnessing the mechanical effects of HIFU to induce a systemic immune response and to enhance targeted drug delivery. This review provides a brief overview of HIFU, describes current clinical applications of HIFU for pancreatic cancer, and discusses future applications and challenges. PMID:21103296

Research pressure instrumentation for NASA Space Shuttle main engine, modification no. 5

NASA Technical Reports Server (NTRS)

Anderson, P. J.; Nussbaum, P.; Gustafson, G.

1984-01-01

The purpose of Modification No. 5 of this contract is to expand the scope of work (Task C) of this research study effort to develop pressure instrumentation for the SSME. The objective of this contract (Task C) is to direct Honeywell's Solid State Electronics Division's (SSED) extensive experience and expertise in solid state sensor technology to develop prototype pressure transducers which are targeted to meet the SSME performance design goals and to fabricate, test and deliver a total of 10 prototype units. SSED's basic approach is to effectively utilize the many advantages of silicon piezoresistive strain sensing technology to achieve the objectives of advanced state-of-the-art pressure sensors in terms of reliability, accuracy and ease of manufacture. More specifically, integration of multiple functions on a single chip is the key attribute of this technology which will be exploited during this research study.

Simulation and Automation of Microwave Frequency Control in Dynamic Nuclear Polarization for Solid Polarized Targets

NASA Astrophysics Data System (ADS)

Perera, Gonaduwage; Johnson, Ian; Keller, Dustin

2017-09-01

Dynamic Nuclear Polarization (DNP) is used in most of the solid polarized target scattering experiments. Those target materials must be irradiated using microwaves at a frequency determined by the difference in the nuclear Larmor and electron paramagnetic resonance (EPR) frequencies. But the resonance frequency changes with time as a result of radiation damage. Hence the microwave frequency should be adjusted accordingly. Manually adjusting the frequency can be difficult, and improper adjustments negatively impact the polarization. In order to overcome these difficulties, two controllers were developed which automate the process of seeking and maintaining the optimal frequency: one being a standalone controller for a traditional DC motor and the other a LabVIEW VI for a stepper motor configuration. Further a Monte-Carlo simulation was developed which can accurately model the polarization over time as a function of microwave frequency. In this talk, analysis of the simulated data and recent improvements to the automated system will be presented. DOE.

Drug Target Interference in Immunogenicity Assays: Recommendations and Mitigation Strategies.

PubMed

Zhong, Zhandong Don; Clements-Egan, Adrienne; Gorovits, Boris; Maia, Mauricio; Sumner, Giane; Theobald, Valerie; Wu, Yuling; Rajadhyaksha, Manoj

2017-11-01

Sensitive and specific methodology is required for the detection and characterization of anti-drug antibodies (ADAs). High-quality ADA data enables the evaluation of potential impact of ADAs on the drug pharmacokinetic profile, patient safety, and efficacious response to the drug. Immunogenicity assessments are typically initiated at early stages in preclinical studies and continue throughout the drug development program. One of the potential bioanalytical challenges encountered with ADA testing is the need to identify and mitigate the interference mediated by the presence of soluble drug target. A drug target, when present at sufficiently high circulating concentrations, can potentially interfere with the performance of ADA and neutralizing antibody (NAb) assays, leading to either false-positive or, in some cases, false-negative ADA and NAb assay results. This publication describes various mechanisms of assay interference by soluble drug target, as well as strategies to recognize and mitigate such target interference. Pertinent examples are presented to illustrate the impact of target interference on ADA and NAb assays as well as several mitigation strategies, including the use of anti-target antibodies, soluble versions of the receptors, target-binding proteins, lectins, and solid-phase removal of targets. Furthermore, recommendations for detection and mitigation of such interference in different formats of ADA and NAb assays are provided.

Rexin-G, a targeted genetic medicine for cancer.

PubMed

Gordon, Erlinda M; Hall, Frederick L

2010-05-01

Rexin-G, a tumor-targeted retrovector bearing a cytocidal cyclin G1 construct, is the first targeted gene therapy vector to gain fast track designation and orphan drug priorities for multiple cancer indications in the US. This review describes the major milestones in the clinical development of Rexin-G: from the molecular cloning and characterization of the human cyclin G1 proto-oncogene in 1994, to the design of the first knockout constructs and genetic engineering of the targeted delivery system from 1995 to 1997, through the initial proofs-of-concept, molecular pharmacology and toxicology studies of Rexin-G in preclinical cancer models from 1997 to 2001, to the pioneering clinical studies in humans from 2002 to 2004, which--together with the advancements in bioprocess development of high-potency clinical grade vectors circa 2005 - 2006--led to the accelerated approval of Rexin-G for all solid tumors by the Philippine FDA in 2007 and the rapid progression of clinical studies from 2007 to 2009 to the cusp of pivotal Phase III trials in the US. In recording the development of Rexin-G as a novel form of targeted biological therapy, this review also highlights important aspects of vector design engineering which served to overcome the physiological barriers to gene delivery as it addresses the key regulatory issues involved in the development of a targeted gene therapy product. Progressive clinical development of Rexin-G demonstrates the potential safety and efficacy of targeted genetic medicine, while validating the design engineering of the molecular biotechnology platform.

Numerical study of impact erosion of multiple solid particle

NASA Astrophysics Data System (ADS)

Zheng, Chao; Liu, Yonghong; Chen, Cheng; Qin, Jie; Ji, Renjie; Cai, Baoping

2017-11-01

Material erosion caused by continuous particle impingement during hydraulic fracturing results in significant economic loss and increased production risks. The erosion process is complex and has not been clearly explained through physical experiments. To address this problem, a multiple particle model in a 3D configuration was proposed to investigate the dynamic erosion process. This approach can significantly reduce experiment costs. The numerical model considered material damping and elastic-plastic material behavior of target material. The effects of impact parameters on erosion characteristics, such as plastic deformation, contact time, and energy loss rate, were investigated. Based on comprehensive studies, the dynamic erosion mechanism and geometry evolution of eroded crater was obtained. These findings can provide a detailed erosion process of target material and insights into the material erosion caused by multiple particle impingement.

Molecular Analyses Reveal Inflammatory Mediators in the Solid Component and Cyst Fluid of Human Adamantinomatous Craniopharyngioma.

PubMed

Donson, Andrew M; Apps, John; Griesinger, Andrea M; Amani, Vladimir; Witt, Davis A; Anderson, Richard C E; Niazi, Toba N; Grant, Gerald; Souweidane, Mark; Johnston, James M; Jackson, Eric M; Kleinschmidt-DeMasters, Bette K; Handler, Michael H; Tan, Aik-Choon; Gore, Lia; Virasami, Alex; Gonzalez-Meljem, Jose Mario; Jacques, Thomas S; Martinez-Barbera, Juan Pedro; Foreman, Nicholas K; Hankinson, Todd C

2017-09-01

Pediatric adamantinomatous craniopharyngioma (ACP) is a highly solid and cystic tumor, often causing substantial damage to critical neuroendocrine structures such as the hypothalamus, pituitary gland, and optic apparatus. Paracrine signaling mechanisms driving tumor behavior have been hypothesized, with IL-6R overexpression identified as a potential therapeutic target. To identify potential novel therapies, we characterized inflammatory and immunomodulatory factors in ACP cyst fluid and solid tumor components. Cytometric bead analysis revealed a highly pro-inflammatory cytokine pattern in fluid from ACP compared to fluids from another cystic pediatric brain tumor, pilocytic astrocytoma. Cytokines and chemokines with particularly elevated concentrations in ACPs were IL-6, CXCL1 (GRO), CXCL8 (IL-8) and the immunosuppressive cytokine IL-10. These data were concordant with solid tumor compartment transcriptomic data from a larger cohort of ACPs, other pediatric brain tumors and normal brain. The majority of receptors for these cytokines and chemokines were also over-expressed in ACPs. In addition to IL-10, the established immunosuppressive factor IDO-1 was overexpressed by ACPs at the mRNA and protein levels. These data indicate that ACP cyst fluids and solid tumor components are characterized by an inflammatory cytokine and chemokine expression pattern. Further study regarding selective cytokine blockade may inform novel therapeutic interventions. © 2017 American Association of Neuropathologists, Inc. All rights reserved.

A Population Pharmacokinetic Model for a Solid Oral Tablet Formulation of Posaconazole.

PubMed

van Iersel, Marlou L P S; Rossenu, Stefaan; de Greef, Rik; Waskin, Hetty

2018-04-30

A delayed-release solid tablet formulation that releases posaconazole in the small intestine was developed to maximize systemic absorption. This study aimed to characterize the pharmacokinetics of the posaconazole solid tablet formulation in adult subjects and to investigate the potential impact of demographic and clinical factors on posaconazole exposure through a population pharmacokinetic approach. Nonlinear mixed-effects modeling was performed using data from several studies conducted in healthy volunteers and patients. The influence of demographic and clinical factors on pharmacokinetic parameters was evaluated using a stepwise forward inclusion/backward exclusion procedure. The final pharmacokinetic model was used to simulate posaconazole exposure in patients at high risk for invasive fungal diseases treated with the proposed posaconazole dose of 300 mg twice daily on day 1, followed by 300 mg daily for 27 days. A one-compartment pharmacokinetic model with sequential zero-order and first-order absorption and a first-order disposition from the central compartment adequately described the pharmacokinetic profile of the posaconazole solid tablet formulation. Significant covariates included disease state (acute myeloid leukemia/myelodysplasia vs allogeneic hematopoietic stem cell transplantation), body weight, and formulation on bioavailability; food status on first-order absorption rate; and dosing regimen (single dose vs multiple doses) on clearance. Except for body weight, the impact of these covariates on posaconazole exposure was considered clinically irrelevant. This population pharmacokinetic analysis confirmed that the proposed dose of the posaconazole solid tablet formulation provides adequate target therapeutic exposure (>0.5 mg/l) to a broad range of patients at high risk for invasive fungal disease. Copyright © 2018 American Society for Microbiology.

Experimental evidence for short-pulse laser heating of solid-density target to high bulk temperatures.

PubMed

Soloviev, A; Burdonov, K; Chen, S N; Eremeev, A; Korzhimanov, A; Pokrovskiy, G V; Pikuz, T A; Revet, G; Sladkov, A; Ginzburg, V; Khazanov, E; Kuzmin, A; Osmanov, R; Shaikin, I; Shaykin, A; Yakovlev, I; Pikuz, S; Starodubtsev, M; Fuchs, J

2017-09-22

Heating efficiently solid-density, or even compressed, matter has been a long-sought goal in order to allow investigation of the properties of such state of matter of interest for various domains, e.g. astrophysics. High-power lasers, pinches, and more recently Free-Electron-Lasers (FELs) have been used in this respect. Here we show that by using the high-power, high-contrast "PEARL" laser (Institute of Applied Physics-Russian Academy of Science, Nizhny Novgorod, Russia) delivering 7.5 J in a 60 fs laser pulse, such coupling can be efficiently obtained, resulting in heating of a slab of solid-density Al of 0.8 µm thickness at a temperature of 300 eV, and with minimal density gradients. The characterization of the target heating is achieved combining X-ray spectrometry and measurement of the protons accelerated from the Al slab. The measured heating conditions are consistent with a three-temperatures model that simulates resistive and collisional heating of the bulk induced by the hot electrons. Such effective laser energy deposition is achieved owing to the intrinsic high contrast of the laser which results from the Optical Parametric Chirped Pulse Amplification technology it is based on, allowing to attain high target temperatures in a very compact manner, e.g. in comparison with large-scale FEL facilities.

Transition of Femtosecond-Filament-Solid Interactions from Single to Multiple Filament Regime

DOE PAGES

Skrodzki, P. J.; Burger, M.; Jovanovic, I.

2017-10-06

High-peak-power fs-laser filaments offer unique characteristics attractive to remote sensing via techniques such as remote laser-induced breakdown spectroscopy (R-LIBS). The dynamics of several ablation mechanisms following the interaction between a filament and a solid determines the emission strength and reproducibility of target plasma, which is of relevance for R-LIBS applications. Here, we investigate the space- and time-resolved dynamics of ionic and atomic emission from copper as well as the surrounding atmosphere in order to understand limitations of fs-filament-ablation for standoff energy delivery. Furthermore, we probe the shock front produced from filament-target interaction using time-resolved shadowgraphy and infer laser-material coupling efficienciesmore » for both single and multiple filament regimes through analysis of shock expansion with the Sedov model for point detonation. The results provide insight into plasma structure for the range of peak powers up to 30 times the critical power for filamentation P cr. Despite the stochastic nucleation of multiple filaments at peak-powers greater than 16 P cr, emission of ionic and neutral species increases with pump beam intensity, and short-lived nitrogen emission originating from the ambient is consistently observed. Ultimately, results suggest favorable scaling of emission intensity from target species on the laser pump energy, furthering the prospects for use of filament-solid interactions for remote sensing.« less

Transition of Femtosecond-Filament-Solid Interactions from Single to Multiple Filament Regime

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

Skrodzki, P. J.; Burger, M.; Jovanovic, I.

High-peak-power fs-laser filaments offer unique characteristics attractive to remote sensing via techniques such as remote laser-induced breakdown spectroscopy (R-LIBS). The dynamics of several ablation mechanisms following the interaction between a filament and a solid determines the emission strength and reproducibility of target plasma, which is of relevance for R-LIBS applications. Here, we investigate the space- and time-resolved dynamics of ionic and atomic emission from copper as well as the surrounding atmosphere in order to understand limitations of fs-filament-ablation for standoff energy delivery. Furthermore, we probe the shock front produced from filament-target interaction using time-resolved shadowgraphy and infer laser-material coupling efficienciesmore » for both single and multiple filament regimes through analysis of shock expansion with the Sedov model for point detonation. The results provide insight into plasma structure for the range of peak powers up to 30 times the critical power for filamentation P cr. Despite the stochastic nucleation of multiple filaments at peak-powers greater than 16 P cr, emission of ionic and neutral species increases with pump beam intensity, and short-lived nitrogen emission originating from the ambient is consistently observed. Ultimately, results suggest favorable scaling of emission intensity from target species on the laser pump energy, furthering the prospects for use of filament-solid interactions for remote sensing.« less

Analysis of isothiazolinones in environmental waters by gas chromatography-mass spectrometry.

PubMed

Rafoth, Astrid; Gabriel, Sabine; Sacher, Frank; Brauch, Heinz-Jürgen

2007-09-14

This paper describes an analytical method for the determination of five biocides of isothiazolinone type (2-methyl-3-isothiazolinone (MI), 5-chloro-2-methyl-3-isothiazolinone (CMI), 1,2-benzisothiazolinone (BIT), 2-octyl-3-isothiazolinone (OI), 4,5-dichloro-2-octyl-3-isothiazolinone (DCOI)) in environmental waters. The method is based on pre-concentration of the analytes by solid-phase extraction onto a mixture of a polymeric material and RP-C18 material and subsequent determination by gas chromatography-mass spectrometry (GC-MS). One of the target compounds (BIT) is derivatised with diazomethane after pre-concentration to improve its chromatographic performance. The method was optimised with respect to pre-concentration conditions (liquid-liquid extraction versus solid-phase extraction, solid-phase material, elution solvent and volume) and extensively validated. Applying the method to surface waters, groundwaters, and drinking waters, limits of detection between 0.01 and 0.1 microg/l could be achieved and the repeatability was below 10% for all compounds except for MI. Additional investigations showed that the stability of the isothiazolinones in environmental waters is limited and sample storage at 4 degrees C is mandatory to preserve the target biocides. First investigations of influents and effluents of a wastewater treatment plant showed that conventional wastewater treatment exhibits a high efficiency for removal of the isothiazolinones. In river waters, the target isothiazolinones could not be detected.

Environmental exposure of road borders to zinc.

PubMed

Blok, J

2005-09-15

The emissions of zinc along roads originating from tyre wear, corrosion of safety fence and other traffic-related sources have been quantified and validated by measured long-term loads in road run-off and airborne solids (drift) for 29 published case studies. The distribution pattern over the road border at various distances from the edge of the paved surface is assessed on the basis of 38 published case studies with measured concentrations in soil. For the impact assessment, the road border is differentiated into a zone that is part of the "technosphere" and the "target zone" beyond that technosphere that can be considered as part of the receiving environment. The "technosphere" of the road includes the central reservation, the hard and the soft shoulder or, if one or both shoulders are not present, the so-called obstacle "free zone" that is defined by road engineers. Pollution within the technosphere may require appropriate management of solid disposal and isolation from groundwater to prevent further distribution of pollutants to the environment. In the target zone along regional roads, the zinc load is about 4 mg/m(2) year and this is of the same order of magnitude as that of atmospheric deposition in areas beyond the influence of roads (background). In the target zone along highways, the zinc load is increased in comparison to the background deposition. The average load of about 38 mg/m(2) year is similar to that in fertilised agricultural land. Because most of the emitted zinc stays in the technosphere, the total amount entering this target zone along highways is limited. From the 140 tons of zinc per year that is released from tyre wear in The Netherlands, 64 tons is emitted in the urban area, 6.5 tons reaches to the target zones of all roads and only 1.1 tons of zinc will enter the target zone along highways. This amount will be further decreased by the application of porous asphalt in the near future. The emission from safety fence corrosion does not enter the target zone. Only in special cases, such as bridges, crossings and squares the release of zinc from these sources may enter the aquatic environment by the discharge of run-off.

Nanocarrier possibilities for functional targeting of bioactive peptides and proteins: state-of-the-art.

PubMed

Moutinho, Carla G; Matos, Carla M; Teixeira, José A; Balcão, Victor M

2012-02-01

This review attempts to provide an updated compilation of studies reported in the literature pertaining to production of nanocarriers encasing peptides and/or proteins, in a way that helps the reader direct a bibliographic search and develop an integrated perspective of the subject. Highlights are given to bioactive proteins and peptides, with a special focus on those from dairy sources (including physicochemical characteristics and properties, and biopharmaceutical application possibilities of e.g. lactoferrin and glycomacropeptide), as well as to nanocarrier functional targeting. Features associated with micro- and (multiple) nanoemulsions, micellar systems, liposomes and solid lipid nanoparticles, together with biopharmaceutical considerations, are presented in the text in a systematic fashion.

Experimental demonstration of laser to x-ray conversion enhancements with low density gold targets

DOE PAGES

Shang, Wanli; Yang, Jiamin; Zhang, Wenhai; ...

2016-02-12

The enhancement of laser to x-ray conversion efficiencies using low density gold targets [W. L. Shang, J. M. Yang, and Y. S. Dong, Appl. Phys. Lett. 102, 094105 (2013)] is demonstrated. Laser to x-ray conversion efficiencies with 6.3% and 12% increases are achieved with target densities of 1 and 0.25 g/cm 3, when compared with that of a solid gold target (19.3 g/cm 3). Experimental data and numerical simulations are in good agreement. Lastly, the enhancement is caused by larger x-ray emission zone lengths formed in low density targets, which is in agreement with the simulation results.

Experimental demonstration of laser to x-ray conversion enhancements with low density gold targets

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

Shang, Wanli; Yang, Jiamin; Zhang, Wenhai

The enhancement of laser to x-ray conversion efficiencies using low density gold targets [W. L. Shang, J. M. Yang, and Y. S. Dong, Appl. Phys. Lett. 102, 094105 (2013)] is demonstrated. Laser to x-ray conversion efficiencies with 6.3% and 12% increases are achieved with target densities of 1 and 0.25 g/cm 3, when compared with that of a solid gold target (19.3 g/cm 3). Experimental data and numerical simulations are in good agreement. Lastly, the enhancement is caused by larger x-ray emission zone lengths formed in low density targets, which is in agreement with the simulation results.

Polarized targets in high energy physics

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

Cates, G.D. Jr.

1994-12-01

Various approaches are discussed for producing polarized nuclear targets for high energy physics experiments. As a unifying theme, examples are drawn from experiments to measure spin dependent structure functions of nucleons in deep inelastic scattering. This single physics goal has, over roughly two decades, been a driving force in advances in target technology. Actual or planned approaches have included solid targets polarized by dynamic nuclear polarization (DNP), several types of internal targets for use in storage rings, and gaseous {sup 3}He targets polarized by spin-exchange optical pumping. This last approach is the type of target adopted for SLAC E-142, anmore » experiment to measure the spin structure function of the neutron, and is described in detail.« less

Solid Lipid Nanoparticle-Based Calix[n]arenes and Calix-Resorcinarenes as Building Blocks: Synthesis, Formulation and Characterization

PubMed Central

Montasser, Imed; Shahgaldian, Patrick; Perret, Florent; Coleman, Anthony W.

2013-01-01

Solid lipid nanoparticles (SLNs) have attracted increasing attention during recent years. This paper presents an overview about the use of calix[n]arenes and calix-resorcinarenes in the formulation of SLNs. Because of their specific inclusion capability both in the intraparticle spaces and in the host cavities as well as their capacity for functionalization, these colloidal nanostructures represent excellent tools for the encapsulation of different active pharmaceutical ingredients (APIs) in the area of drug targeting, cosmetic additives, contrast agents, etc. Various synthetic routes to the supramolecular structures will be given. These various routes lead to the formulation of the corresponding SLNs. Characterization, properties, toxicological considerations as well as numerous corresponding experimental studies and analytical methods will be also exposed and discussed. PMID:24196356

Systems and methods for the combinatorial synthesis of novel materials

DOEpatents

Wu, Xin Di; Wang, Youqi; Goldwasser, Isy

2000-01-01

Methods and apparatus for the preparation of a substrate having an array of diverse materials in predefined regions thereon. A substrate having an array of diverse materials thereon is generally prepared by depositing components of target materials to predefined regions on the substrate, and, in some embodiments, simultaneously reacting the components to form at least two resulting materials. In particular, the present invention provides novel masking systems and methods for applying components of target materials onto a substrate in a combinatorial fashion, thus creating arrays of resulting materials that differ slightly in composition, stoichiometry, and/or thickness. Using the novel masking systems of the present invention, components can be delivered to each site in a uniform distribution, or in a gradient of stoichiometries, thicknesses, compositions, etc. Resulting materials which can be prepared using the methods and apparatus of the present invention include, for example, covalent network solids, ionic solids and molecular solids. Once prepared, these resulting materials can be screened sequentially, or in parallel, for useful properties including, for example, electrical, thermal, mechanical, morphological, optical, magnetic, chemical and other properties.

Solid-State Nuclear Power

NASA Technical Reports Server (NTRS)

George, Jeffrey A.

2012-01-01

A strategy for "Solid-State" Nuclear Power is proposed to guide development of technologies and systems into the second 50 years of nuclear spaceflight. The strategy emphasizes a simple and highly integrated system architecture with few moving parts or fluid loops; the leverage of modern advances in materials, manufacturing, semiconductors, microelectromechanical and nanotechnology devices; and the targeted advancement of high temperature nuclear fuels, materials and static power conversion to enable high performance from simple system topologies.

Antiperovskite Li 3 OCl superionic conductor films for solid-state Li-ion batteries

DOE PAGES

Lü, Xujie; Howard, John W.; Chen, Aiping; ...

2016-02-02

We prepared antiperovskite Li 3OCl superionic conductor films via pulsed laser deposition using a composite target. A significantly enhanced ionic conductivity of 2.0 × 10 -4 S cm -1 at room temperature is achieved, and this value is more than two orders of magnitude higher than that of its bulk counterpart. Moreover, the applicability of Li 3OCl as a solid electrolyte for Li-ion batteries is demonstrated.

A cellular automata model for avascular solid tumor growth under the effect of therapy

NASA Astrophysics Data System (ADS)

Reis, E. A.; Santos, L. B. L.; Pinho, S. T. R.

2009-04-01

Tumor growth has long been a target of investigation within the context of mathematical and computer modeling. The objective of this study is to propose and analyze a two-dimensional stochastic cellular automata model to describe avascular solid tumor growth, taking into account both the competition between cancer cells and normal cells for nutrients and/or space and a time-dependent proliferation of cancer cells. Gompertzian growth, characteristic of some tumors, is described and some of the features of the time-spatial pattern of solid tumors, such as compact morphology with irregular borders, are captured. The parameter space is studied in order to analyze the occurrence of necrosis and the response to therapy. Our findings suggest that transitions exist between necrotic and non-necrotic phases (no-therapy cases), and between the states of cure and non-cure (therapy cases). To analyze cure, the control and order parameters are, respectively, the highest probability of cancer cell proliferation and the probability of the therapeutic effect on cancer cells. With respect to patterns, it is possible to observe the inner necrotic core and the effect of the therapy destroying the tumor from its outer borders inwards.

In vivo growth of 60 non-screening detected lung cancers: a computed tomography study.

PubMed

Mets, Onno M; Chung, Kaman; Zanen, Pieter; Scholten, Ernst T; Veldhuis, Wouter B; van Ginneken, Bram; Prokop, Mathias; Schaefer-Prokop, Cornelia M; de Jong, Pim A

2018-04-01

Current pulmonary nodule management guidelines are based on nodule volume doubling time, which assumes exponential growth behaviour. However, this is a theory that has never been validated in vivo in the routine-care target population. This study evaluates growth patterns of untreated solid and subsolid lung cancers of various histologies in a non-screening setting.Growth behaviour of pathology-proven lung cancers from two academic centres that were imaged at least three times before diagnosis (n=60) was analysed using dedicated software. Random-intercept random-slope mixed-models analysis was applied to test which growth pattern most accurately described lung cancer growth. Individual growth curves were plotted per pathology subgroup and nodule type.We confirmed that growth in both subsolid and solid lung cancers is best explained by an exponential model. However, subsolid lesions generally progress slower than solid ones. Baseline lesion volume was not related to growth, indicating that smaller lesions do not grow slower compared to larger ones.By showing that lung cancer conforms to exponential growth we provide the first experimental basis in the routine-care setting for the assumption made in volume doubling time analysis. Copyright ©ERS 2018.

Efficient neutron generation from solid-nanoparticle explosions driven by DPSSL-pumped high-repetition rate femtosecond laser pulse

NASA Astrophysics Data System (ADS)

Watari, T.; Matsukado, K.; Sekine, T.; Takeuchi, Y.; Hatano, Y.; Yoshimura, R.; Satoh, N.; Nishihara, K.; Takagi, M.; Kawashima, T.

2016-03-01

We propose novel neutron source using high-intensity laser based on the cluster fusion scheme. We developed DPSSL-pumped high-repetition-rate 20-TW laser system and solid nanoparticle target for neutron generation demonstration. In our neutron generation experiment, high-energy deuterons were generated from coulomb explosion of CD solid- nanoparticles and neutrons were generated by DD fusion reaction. Efficient and stable neutron generation was obtained by irradiating an intense femtosecond laser pulse of >2×1018 W/cm2. A yield of ∼105 neutrons per shot was stably observed during 0.1-1 Hz continuous operation.

A Novel Soluble Peptide with pH-Responsive Membrane Insertion.

PubMed

Nguyen, Vanessa P; Alves, Daiane S; Scott, Haden L; Davis, Forrest L; Barrera, Francisco N

2015-11-03

Several diseases, such as cancer, are characterized by acidification of the extracellular environment. Acidosis can be employed as a target to specifically direct therapies to the diseased tissue. We have used first principles to design an acidity-triggered rational membrane (ATRAM) peptide with high solubility in solution that is able to interact with lipid membranes in a pH-dependent fashion. Biophysical studies show that the ATRAM peptide binds to the surface of lipid membranes at pH 8.0. However, acidification leads to the peptide inserting into the lipid bilayer as a transmembrane α-helix. The insertion of ATRAM into membranes occurs at a moderately acidic pH (with a pK of 6.5), similar to the extracellular pH found in solid tumors. Studies with human cell lines showed a highly efficient pH-dependent membrane targeting, without causing toxicity. Here we show that it is possible to rationally design a soluble peptide that selectively targets cell membranes in acidic environments.

Electromagnetic Pulses Generated From Laser Target Interactions at Shenguang II Laser Facility

NASA Astrophysics Data System (ADS)

Yang, Jinwen; Li, Tingshuai; Yi, Tao; Wang, Chuanke; Yang, Ming; Yang, Weiming; Liu, Shenye; Jiang, Shaoen; Ding, Yongkun

2016-10-01

Significant electromagnetic pulses (EMP) can be generated by the intensive laser irradiating solid targets in inertial confinement fusion (ICF). To evaluate the EMP intensity and distribution in and outside the laser chamber, we designed and fabricated a discone antenna with ultra-wide bands of over 10 GHz. The return loss (S11 parameter) of this antenna was below -10 dB and could even achieve under -30 dB at 3.1 GHz. The EMP intensity in this study at 80 cm and 40 cm away from the target chamber center (TCC) reached 400 kV/m and 2000 kV/m. The current results are expected to offer preliminary information to study physics regarding laser plasma interactions and will also lay experimental foundation for EMI shielding design to protect various diagnostics. supported by the Fundamental Research Funds for the Central Universities of China (No. ZYGX2015J108) and National Natural Science Foundation of China (Nos. 11575166 and 51581140)

Foldable polymers as probes

DOEpatents

Li, Alexander D. Q. [Pullman, WA; Wang, Wei [Pullman, WA

2007-07-03

Disclosed herein are novel probes, which can be used to detect and identify target molecules of interest in a sample. The disclosed probes can be used to monitor conformational changes induced by molecular recognition events in addition to providing signaling the presence and/or identity of a target molecule. Methods, including solid phase synthesis techniques, for making probe molecules that exhibit changes in their optical properties upon target molecule binding are described in the disclosure. Also disclosed herein are novel chromophore moieties, which have tailored fluorescent emission spectra.

Foldable polymers as probes

DOEpatents

Li, Alexander D. Q. [Pullman, WA; Wang, Wei [Pullman, WA

2009-07-07

Disclosed herein are novel probes, which can be used to detect and identify target molecules of interest in a sample. The disclosed probes can be used to monitor conformational changes induced by molecular recognition events in addition to providing signaling the presence and/or identity of a target molecule. Methods, including solid phase synthesis techniques, for making probe molecules that exhibit changes in their optical properties upon target molecule binding are described in the disclosure. Also disclosed herein are novel chromophore moieties, which have tailored fluorescent emission spectra.

45th Annual Targets, UAVs and Range Operations Symposium and Exhibition - Tools and Technologies for the Warfighter. Volume 2. Wednesday

DTIC Science & Technology

2007-10-31

ENGINEER Ms. Jo-An Williams FINANCE Ms. Leanne Green CONTRACTING Mr. Ken Hislop QF-16 Ms. Lee Neugin QF-4 Mr. Jim Cornwell AFSAT Ms. Audrea Feist DEPUTY...Target Program Manager: Mr. Ken Hislop Description Fullscale Target for Threat-Representative Weapon System Evaluation Meets USAF, Army, Navy, Allied Test...1940 1950 1960 1970 1980 1990 2000 2010 Approved for Public Release: Control No. UMS-2007-927, October 2007 6 A Solid Future for Unmanned Missions

Apparatus for producing laser targets

DOEpatents

Jarboe, T.R.; Baker, W.R.

1975-09-23

This patent relates to an apparatus and method for producing deuterium targets or pellets of 25u to 75u diameter. The pellets are sliced from a continuously spun solid deuterium thread at a rate of up to 10 pellets/second. The pellets after being sliced from the continuous thread of deuterium are collimated and directed to a point of use, such as a laser activated combustion or explosion chamber wherein the pellets are imploded by laser energy or laser produced target plasmas for neutral beam injection. (auth)

Molecules that target nucleophosmin for cancer treatment: an update

PubMed Central

Di Matteo, Adele; Franceschini, Mimma; Chiarella, Sara; Rocchio, Serena; Travaglini-Allocatelli, Carlo; Federici, Luca

2016-01-01

Nucleophosmin is a highly and ubiquitously expressed protein, mainly localized in nucleoli but able to shuttle between nucleus and cytoplasm. Nucleophosmin plays crucial roles in ribosome maturation and export, centrosome duplication, cell cycle progression, histone assembly and response to a variety of stress stimuli. Much interest in this protein has arisen in the past ten years, since the discovery of heterozygous mutations in the terminal exon of the NPM1 gene, which are the most frequent genetic alteration in acute myeloid leukemia. Nucleophosmin is also frequently overexpressed in solid tumours and, in many cases, its overexpression correlates with mitotic index and metastatization. Therefore it is considered as a promising target for the treatment of both haematologic and solid malignancies. NPM1 targeting molecules may suppress different functions of the protein, interfere with its subcellular localization, with its oligomerization properties or drive its degradation. In the recent years, several such molecules have been described and here we review what is currently known about them, their interaction with nucleophosmin and the mechanistic basis of their toxicity. Collectively, these molecules exemplify a number of different strategies that can be adopted to target nucleophosmin and we summarize them at the end of the review. PMID:27058426

Matrix solid phase dispersion assisted enzymatic hydrolysis as a novel approach for cocaine and opiates isolation from human hair.

PubMed

Míguez-Framil, Martha; Cabarcos, Pamela; Tabernero, María Jesús; Bermejo, Ana María; Bermejo-Barrera, Pilar; Moreda-Piñeiro, Antonio

2013-11-05

The possibility of assisting enzymatic hydrolysis (EH) procedures by sample disruption mechanisms inherent to matrix solid phase dispersion (MSPD) has been explored in the current study. EH of hair specimens from poly-drug abusers was assisted by dispersing/blending the sample (0.05 g) with alumina (2.25 g) before loading the dissolved enzyme (6 mL of 1 mg mL(-1) Pronase E in 1.4 M/1.4 M Tris/HCl, pH 7.3) through the hair-alumina solid phase packaged inside a disposable MSPD syringe. The MSPD-EH method was developed, and it proved to offer quantitative results when isolating cocaine, benzoylecgonine (BZE), codeine, morphine and 6-monoacethylmorphine (6-MAM) from human hair samples. The procedure allows an on column clean-up/pre-concentration procedure of the isolated targets by attaching a previously conditioned Oasis HLB cartridge to the end of the MSPD syringe. The EH procedure of human hair with Pronase E can therefore be shortened to approximately 30 min. Within this time, sample blending/dispersion, MSPD syringe package, elution (EH when dissolved Pronase E is passing through the sample-dispersant bed), and extract clean-up and target pre-concentration stages are achieved. Gas chromatography-mass spectrometry (GC-MS) was used for determining each target after elution from the Oasis HLB cartridges with 2 mL of 2% (v/v) acetic acid in methanol, concentration by N2 stream evaporation, and dried extract derivatization with N-methyl-tert-butylsilyltrifluoroacetamide (BSTFA) and chlorotrimethylsilane (TMCS). The method was validated according to the guidance for bioanalytical method validation of the US Department of Health and Human Services, Food and Drug Administration. The simplicity of the proposed approach makes it a useful procedure for screening/quantifying drugs of abuse in hair specimens from poly-drug abusers. Copyright © 2013 Elsevier B.V. All rights reserved.

Novel Culturing Techniques Select for Heterotrophs and Hydrocarbon Degraders in a Subantarctic Soil

PubMed Central

van Dorst, J. M.; Hince, G.; Snape, I.; Ferrari, B. C.

2016-01-01

The soil substrate membrane system (SSMS) is a novel micro-culturing technique targeted at terrestrial soil systems. We applied the SSMS to pristine and diesel fuel spiked polar soils, along with traditional solid media culturing and culture independent 454 tag pyrosequencing to elucidate the effects of diesel fuel on the soil community. The SSMS enriched for up to 76% of the total soil diversity within high diesel fuel concentration soils, in contrast to only 26% of the total diversity for the control soils. The majority of organisms originally recovered with the SSMS were lost in the transfer to solid media, with all 300 isolates belonging to Proteobacteria, Firmicutes, Actinobacteria or Bacteroidetes, the four phyla most frequently associated with soil culturing efforts. The soils spiked with high diesel fuel concentrations exhibited reduced species richness, diversity and a selection towards heterotrophs and hydrocarbon degraders in comparison to the control soils. Based on these observations and the unusually high level of overlap in microbial taxa observed between methods, we suggest the SSMS holds potential to exploit hydrocarbon degraders and other targets within simplified bacterial systems, yet is inadequate for soil ecology and ecotoxicology studies where identifying rare oligotrophic species is paramount. PMID:27827405

Time-resolved K α spectroscopy measurements of hot-electron equilibration dynamics in thin-foil solid targets: collisional and collective effects

NASA Astrophysics Data System (ADS)

Nilson, P. M.; Solodov, A. A.; Davies, J. R.; Theobald, W.; Mileham, C.; Stoeckl, C.; Begishev, I. A.; Zuegel, J. D.; Froula, D. H.; Betti, R.; Meyerhofer, D. D.

2015-11-01

Time-resolved K α spectroscopy measurements from high-intensity laser interactions with thin-foil solid targets are reviewed. Thin Cu foils were irradiated with 1-10 J, 1 ps pulses at focused intensities from 1018 to 1019 W cm-2. The experimental data show K α -emission pulse widths from 3 to 6 ps, increasing with laser intensity. The time-resolved K α -emission data are compared to a hot-electron transport and K α -production model that includes collisional electron-energy coupling, resistive heating, and electromagnetic field effects. The experimental data show good agreement with the model when a reduced ponderomotive scaling is used to describe the initial mean hot-electron energy over the relevant intensity range.

New Chimeric Antigen Receptor Design for Solid Tumors

PubMed Central

Wang, Yuedi; Luo, Feifei; Yang, Jiao; Zhao, Chujun; Chu, Yiwei

2017-01-01

In recent years, chimeric antigen receptor (CAR) T-cell therapy has become popular in immunotherapy, particularly after its tremendous success in the treatment of lineage-restricted hematologic cancers. However, the application of CAR T-cell therapy for solid tumors has not reached its full potential because of the lack of specific tumor antigens and inhibitory factors in suppressive tumor microenvironment (TME) (e.g., programmed death ligand-1, myeloid-derived suppressor cells, and transforming growth factor-β). In this review, we include some limitations in CAR design, such as tumor heterogeneity, indefinite spatial distance between CAR T-cell and its target cell, and suppressive TME. We also summarize some new approaches to overcome these hurdles, including targeting neoantigens and/or multiple antigens at once and depleting some inhibitory factors. PMID:29312360

Solid-phase organic synthesis of difluoroalkyl entities using a novel fluorinating cleavage strategy: part 1. Linker development: scope and limitations.

PubMed

Wiehn, Matthias S; Lindell, Stephen D; Bräse, Stefan

2009-01-01

An efficient method to synthesize gem-difluorinated compounds on solid supports is described. The strategy is based on the design of a novel sulfur linker system that enables, to the best of our knowledge for the first time, the release of target structures from the resin under simultaneous fluorination. Starting from an immobilized dithiol, coupling with an excess of aldehyde or ketone furnished dithianes. These can be further functionalized prior to release from the resin using our newly developed fluorinating cleavage conditions. Amide forming reactions, palladium-catalyzed reactions (Heck, Suzuki, and Sonogashira couplings), reductions, alkylations, and olefinations were successfully explored on the linker. The difluorinated target substances were obtained in modest to excellent yields and in high purities.

Guiding of relativistic electron beams in solid targets by resistively controlled magnetic fields.

PubMed

Kar, S; Robinson, A P L; Carroll, D C; Lundh, O; Markey, K; McKenna, P; Norreys, P; Zepf, M

2009-02-06

Guided transport of a relativistic electron beam in solid is achieved experimentally by exploiting the strong magnetic fields created at the interface of two metals of different electrical resistivities. This is of substantial relevance to the Fast Ignitor approach to fusion energy production [M. Tabak, Phys. Plasmas 12, 057305 (2005)10.1063/1.1871246], since it allows the electron deposition to be spatially tailored-thus adding substantial design flexibility and preventing inefficiencies due to electron beam spreading. In the experiment, optical transition radiation and thermal emission from the target rear surface provide a clear signature of the electron confinement within a high resistivity tin layer sandwiched transversely between two low resistivity aluminum slabs. The experimental data are found to agree well with numerical simulations.

Multicenter Feasibility Study of Tumor Molecular Profiling to Inform Therapeutic Decisions in Advanced Pediatric Solid Tumors: The Individualized Cancer Therapy (iCat) Study.

PubMed

Harris, Marian H; DuBois, Steven G; Glade Bender, Julia L; Kim, AeRang; Crompton, Brian D; Parker, Erin; Dumont, Ian P; Hong, Andrew L; Guo, Dongjing; Church, Alanna; Stegmaier, Kimberly; Roberts, Charles W M; Shusterman, Suzanne; London, Wendy B; MacConaill, Laura E; Lindeman, Neal I; Diller, Lisa; Rodriguez-Galindo, Carlos; Janeway, Katherine A

2016-01-28

Pediatric cancers represent a unique case with respect to cancer genomics and precision medicine, as the mutation frequency is low, and targeted therapies are less available. Consequently, it is unknown whether clinical sequencing can be of benefit. To assess the feasibility of identifying actionable alterations and making individualized cancer therapy (iCat) recommendations in pediatric patients with extracranial solid tumors. Clinical sequencing study at 4 academic medical centers enrolling patients between September 5, 2012, and November 19, 2013, with 1 year of clinical follow-up. Participants were 30 years or younger with high-risk, recurrent, or refractory extracranial solid tumors. The data analysis was performed October 28, 2014. Tumor profiling performed on archived clinically acquired specimens consisted of mutation detection by a Sequenom assay or targeted next-generation sequencing and copy number assessment by array comparative genomic hybridization. Results were reviewed by a multidisciplinary expert panel, and iCat recommendations were made if an actionable alteration was present, and an appropriate drug was available. Feasibility was assessed using a 2-stage design based on the proportion of patients with recommendations. Of 100 participants (60 male; median [range] age, 13.4 [0.8-29.8] years), profiling was technically successful in 89 (89% [95% CI, 83%-95%]). Median (range) follow-up was 6.8 (2.0-23.6) months. Overall, 31 (31% [95% CI, 23%-41%]) patients received an iCat recommendation and 3 received matched therapy. The most common actionable alterations leading to an iCat recommendation were cancer-associated signaling pathway gene mutations (n = 10) and copy number alterations in MYC/MYCN (n = 6) and cell cycle genes (n = 11). Additional alterations with implications for clinical care but not resulting in iCat recommendations were identified, including mutations indicating the possible presence of a cancer predisposition syndrome and translocations suggesting a change in diagnosis. In total, 43 (43% [95% CI, 33%-53%]) participants had results with potential clinical significance. A multi-institution clinical genomics study in pediatric oncology is feasible and a substantial proportion of relapsed or refractory pediatric solid tumors have actionable alterations. clinicaltrials.gov Identifier: NCT01853345.

Hot atoms in cosmic chemistry.

PubMed

Rossler, K; Jung, H J; Nebeling, B

1984-01-01

High energy chemical reactions and atom molecule interactions might be important for cosmic chemistry with respect to the accelerated species in solar wind, cosmic rays, colliding gas and dust clouds and secondary knock-on particles in solids. "Hot" atoms with energies ranging from a few eV to some MeV can be generated via nuclear reactions and consequent recoil processes. The chemical fate of the radioactive atoms can be followed by radiochemical methods (radio GC or HPLC). Hot atom chemistry may serve for laboratory simulation of the reactions of energetic species with gaseous or solid interstellar matter. Due to the effective measurement of 10(8)-10(10) atoms only it covers a low to medium dose regime and may add to the studies of ion implantation which due to the optical methods applied are necessarily in the high dose regime. Experimental results are given for the systems: C/H2O (gas), C/H2O (solid, 77 K), N/CH4 (solid, 77K) and C/NH3 (solid, 77 K). Nuclear reactions used for the generation of 2 to 3 MeV atoms are: N(p,alpha) 11C, 16O(p,alpha pn) 11C and 12C(d,n) 13N with 8 to 45 MeV protons or deuterons from a cyclotron. Typical reactions products are: CO, CO2, CH4, CH2O, CH3OH, HCOOH, NH3, CH3NH2, cyanamide, formamidine, guanidine etc. Products of hot reactions in solids are more complex than in corresponding gaseous systems, which underlines the importance of solid state reactions for the build-up of precursors for biomolecules in space. As one of the major mechanisms for product formation, the simultaneous or fast consecutive reactions of a hot carbon with two target molecules (reaction complex) is discussed.

Effects of hyperthermia and calcium channel blocker co-therapy on mice injected with Meth A solid of Meth A ascites tumors

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

Prince, R.N.

1986-01-01

A study was made to determine the effectiveness of treating tumor-injected mice with verapamil, a calcium antagonist, and hyperthermia. The co-treatment reduced the incidence of tumors in animals injected with Meth A solid cells. It was shown that the decrease in tumors corresponded to increases in natural killer (NK) cell activity measured in a /sup 51/Cr release assay, in the amount of anti-Meth A antibody measured in an immunofluorescence assay, and a decrease in the amount of intra-tumor cyclic AMP measured by radioimmunoassay in co-treated compared to untreated sarcoma-injected animals. A role of the immune system for mediating the preventionmore » of sarcoma growth was indicated by Winn assays. Splenocytes sensitized in vivo against Meth A solid cells for 14 days exhibited an enhanced cytotoxic activity against syngeneic target cells compared to untreated tumor-sensitized splenocytes following heat-drug co-treatment. It was established that the stimulation of cytotoxic T cells against a histocompatibility antigen (H-2/sup d/) present on Meth A sarcoma cells resulted in tumor cell lysis. Animals bearing established Meth A solid sarcomas did not manifest tumor regressions following the administration of co-treatment alone or the adoptive transfer of co-treated tumor-sensitized splenocytes. The growth of Meth A ascites and Meth A ascites-derived solid sarcomas, unlike Meth A solid cell tumors, were not prevented in Winn assays. Additionally, the lifespan of animals injected with Meth A ascites cells was reduced by 50% compared to animals injected with Meth A solid sarcoma cells.« less

Target Z dependence of Xe L x-ray emission in heavy ion-atom collision near the Bohr velocity: influence of level matching

NASA Astrophysics Data System (ADS)

Ren, Jieru; Zhao, Yongtao; Zhou, Xianming; Cheng, Rui; Lei, Yu; Sun, Yuanbo; Wang, Xing; Xu, Ge; Wang, Yuyu; Liu, Shidong; Yu, Yang; Li, Yongfeng; Zhang, Xiaoan; Xu, Zhongfeng; Xiao, Guoqing

2013-09-01

X-ray yields for the projectile L-shell have been measured for collisions between Xe20+ and thick solid targets throughout the periodic table with incident energies near the Bohr velocity. The yields show a very pronounced cyclic dependence on the target atomic number. This result indicates that Xe L x-ray emission intensity is greatly enhanced either in near-symmetric collisions or if the binding energy of the Xe M-shell matches the L- or N-shell binding energy of the target.

Nanoparticles that reshape the tumor milieu create a therapeutic window for effective T cell therapy in solid malignancies.

PubMed

Zhang, Fan; Stephan, Sirkka B; Ene, Chibawanye I; Smith, Tyrel T; Holland, Eric C; Stephan, Matthias T

2018-05-14

A major obstacle to the success rate of chimeric antigen receptor (CAR-) T cell therapy against solid tumors is the microenvironment antagonistic to T cells that solid tumors create. Conventional checkpoint blockade can silence lymphocyte anti-survival pathways activated by tumors, but because they are systemic, these treatments disrupt immune homeostasis and induce autoimmune side effects. Thus, new technologies are required to remodel the tumor milieu without causing systemic toxicities. Here we demonstrate that targeted nanocarriers that deliver a combination of immune-modulatory agents can remove pro-tumor cell populations and simultaneously stimulate anti-tumor effector cells. We administered repeated infusions of lipid nanoparticles coated with the tumor-targeting peptide iRGD and loaded with a combination of a PI3K inhibitor to inhibit immune-suppressive tumor cells and an alpha-GalCer agonist of therapeutic T cells to synergistically sway the tumor microenvironment of solid tumors from suppressive to stimulatory. This treatment created a therapeutic window of two weeks, enabling tumor-specific CAR-T cells to home to the lesion, undergo robust expansion, and trigger tumor regression. CAR-T cells administered outside this therapeutic window had no curative effect. The lipid nanoparticles we used are easy to manufacture in substantial amounts, and we demonstrate that repeated infusions of them are safe. Our technology may therefore provide a practical and low-cost strategy to potentiate many cancer immunotherapies used to treat solid tumors, including T cell therapy, vaccines, and BITE platforms. Copyright ©2018, American Association for Cancer Research.

Computational selection of antibody-drug conjugate targets for breast cancer

PubMed Central

Fauteux, François; Hill, Jennifer J.; Jaramillo, Maria L.; Pan, Youlian; Phan, Sieu; Famili, Fazel; O'Connor-McCourt, Maureen

2016-01-01

The selection of therapeutic targets is a critical aspect of antibody-drug conjugate research and development. In this study, we applied computational methods to select candidate targets overexpressed in three major breast cancer subtypes as compared with a range of vital organs and tissues. Microarray data corresponding to over 8,000 tissue samples were collected from the public domain. Breast cancer samples were classified into molecular subtypes using an iterative ensemble approach combining six classification algorithms and three feature selection techniques, including a novel kernel density-based method. This feature selection method was used in conjunction with differential expression and subcellular localization information to assemble a primary list of targets. A total of 50 cell membrane targets were identified, including one target for which an antibody-drug conjugate is in clinical use, and six targets for which antibody-drug conjugates are in clinical trials for the treatment of breast cancer and other solid tumors. In addition, 50 extracellular proteins were identified as potential targets for non-internalizing strategies and alternative modalities. Candidate targets linked with the epithelial-to-mesenchymal transition were identified by analyzing differential gene expression in epithelial and mesenchymal tumor-derived cell lines. Overall, these results show that mining human gene expression data has the power to select and prioritize breast cancer antibody-drug conjugate targets, and the potential to lead to new and more effective cancer therapeutics. PMID:26700623

Eradication of Large Solid Tumors by Gene Therapy with a T-Cell Receptor Targeting a Single Cancer-Specific Point Mutation.

PubMed

Leisegang, Matthias; Engels, Boris; Schreiber, Karin; Yew, Poh Yin; Kiyotani, Kazuma; Idel, Christian; Arina, Ainhoa; Duraiswamy, Jaikumar; Weichselbaum, Ralph R; Uckert, Wolfgang; Nakamura, Yusuke; Schreiber, Hans

2016-06-01

Cancers usually contain multiple unique tumor-specific antigens produced by single amino acid substitutions (AAS) and encoded by somatic nonsynonymous single nucleotide substitutions. We determined whether adoptively transferred T cells can reject large, well-established solid tumors when engineered to express a single type of T-cell receptor (TCR) that is specific for a single AAS. By exome and RNA sequencing of an UV-induced tumor, we identified an AAS in p68 (mp68), a co-activator of p53. This AAS seemed to be an ideal tumor-specific neoepitope because it is encoded by a trunk mutation in the primary autochthonous cancer and binds with highest affinity to the MHC. A high-avidity mp68-specific TCR was used to genetically engineer T cells as well as to generate TCR-transgenic mice for adoptive therapy. When the neoepitope was expressed at high levels and by all cancer cells, their direct recognition sufficed to destroy intratumor vessels and eradicate large, long-established solid tumors. When the neoepitope was targeted as autochthonous antigen, T cells caused cancer regression followed by escape of antigen-negative variants. Escape could be thwarted by expressing the antigen at increased levels in all cancer cells or by combining T-cell therapy with local irradiation. Therapeutic efficacies of TCR-transduced and TCR-transgenic T cells were similar. Gene therapy with a single TCR targeting a single AAS can eradicate large established cancer, but a uniform expression and/or sufficient levels of the targeted neoepitope or additional therapy are required to overcome tumor escape. Clin Cancer Res; 22(11); 2734-43. ©2015 AACRSee related commentary by Liu, p. 2602. ©2015 American Association for Cancer Research.

LRRC15 is a novel mesenchymal protein and stromal target for antibody-drug conjugates.

PubMed

Purcell, James W; Tanlimco, Sonia G; Hickson, Jonathan A; Fox, Melvin; Sho, Mien; Durkin, Lisa; Uziel, Tamar; Powers, Rick; Foster-Duke, Kelly D; McGonigal, Thomas; Kumar, Subashri; Samayoa, Josue; Zhang, Dong; Palma, Joann P; Mishra, Sasmita; Hollenbaugh, Diane; Gish, Kurt; Morgan-Lappe, Susan E; Hsi, Eric D; Chao, Debra T

2018-05-15

Progress in understanding tumor stromal biology has been constrained in part because cancer-associated fibroblasts (CAF) are a heterogeneous population with limited cell type-specific protein markers. Using RNA expression profiling, we identified the membrane protein leucine rich repeat containing 15 (LRRC15) as highly expressed in multiple solid tumor indications with limited normal tissue expression. LRRC15 was expressed on stromal fibroblasts in many solid tumors (e.g., breast, head and neck, lung, pancreatic) as well as directly on a subset of cancer cells of mesenchymal origin (e.g., sarcoma, melanoma, glioblastoma). LRRC15 expression was induced by TGFβ on activated fibroblasts (αSMA+) as well as on mesenchymal stem cells (MSC). These collective findings suggested LRRC15 as a novel CAF and mesenchymal marker with utility as a therapeutic target for the treatment of cancers with LRRC15-positive stromal desmoplasia or cancers of mesenchymal origin. ABBV-085 is a monomethyl auristatin E (MMAE)-containing antibody-drug conjugate (ADC) directed against LRRC15 and it demonstrated robust preclinical efficacy against LRRC15 stromal-positive/cancer-negative, and LRRC15 cancer-positive models as a monotherapy, or in combination with standard of care therapies. ABBV-085's unique mechanism of action relied upon the cell-permeable properties of MMAE to preferentially kill cancer cells over LRRC15-positive CAF while also increasing immune infiltrate (e.g., F4/80+ macrophages) in the tumor microenvironment. In summary, these findings validate LRRC15 as a novel therapeutic target in multiple solid tumor indications and support the ongoing clinical development of the LRRC15-targeted ADC ABBV-085. Copyright ©2018, American Association for Cancer Research.

Antitumor and radiosensitizing synergistic effects of apigenin and cryptotanshinone against solid Ehrlich carcinoma in female mice.

PubMed

Medhat, Amina M; Azab, Khaled Sh; Said, Mahmoud M; El Fatih, Neama M; El Bakary, Nermeen M

2017-10-01

Considerable attention has been paid to the introduction of novel naturally occurring plant-derived radiosensitizer compounds in order to augment the radiation efficacy and improve the treatment outcome of different tumors. This study was therefore undertaken to evaluate the antitumor, antiangiogeneic, and synergistic radiosensitizing effects of apigenin, a dietary flavonoid, and/or cryptotanshinone, a terpenoid isolated from the roots of Salvia miltiorrhiza, against the growth of solid Ehrlich carcinoma in female mice. Apigenin (50 mg/kg body weight) and/or cryptotanshinone (40 mg/kg body weight) was intraperitoneally (i.p.) injected into non-irradiated or γ-irradiated (6.5 Gy whole-body γ-irradiation) solid Ehrlich carcinoma-bearing mice for 30 consecutive days. Investigations included molecular targets involved in proliferation, inflammation, angiogenesis, and tumor invasiveness. Treatment with apigenin and/or cryptotanshinone significantly suppressed the growth of solid Ehrlich carcinoma tumors and demonstrated a synergistic radiosensitizing efficacy together with γ-irradiation. These effects were achieved through downregulating the expression of angiogenic and lymphangiogenic regulators, including signal transducer and activator of transcription 3, vascular endothelial growth factor C, and tumor necrosis factor alpha, suppressing matrix metalloproteinase-2 and -9 activities, which play a key role in tumor invasion and metastasis, and enhancing apoptosis via inducing cleaved caspase-3 and granzyme B levels. Histological findings of solid Ehrlich carcinoma tumors verified the recorded data. In conclusion, a synergistic radiosensitizing efficacy for apigenin and cryptotanshinone was demonstrated against Ehrlich carcinoma in the current in vivo murine model, representing therefore a potential therapeutic strategy for increasing the radiation response of solid tumors.

Performance evaluation of laser induced breakdown spectroscopy in the measurement of liquid and solid samples

NASA Astrophysics Data System (ADS)

Bilge, Gonca; Sezer, Banu; Boyaci, Ismail Hakki; Eseller, Kemal Efe; Berberoglu, Halil

2018-07-01

Liquid analysis by using LIBS is a complicated process due to difficulties encountered during the collection of light and formation of plasma in liquid. To avoid these, some applications are performed such as aerosol formation and transforming liquid into solid state. However, performance of LIBS in liquid samples still remains a challenging issue. In this study, performance evaluation of LIBS and parameter optimizations in liquid and solid phase samples were performed. For this purpose, milk was chosen as model sample; milk powder was used as solid sample, and milk was used as liquid sample in the experiments. Different experimental setups have been constructed for each sampling technique, and optimizations were performed to determine suitable parameters such as delay time, laser energy, repetition rate and speed of rotary table for solid sampling technique, and flow rate of carrier gas for liquid sampling technique. Target element was determined as Ca, which is a critically important element in milk for determining its nutritional value and Ca addition. In optimum parameters, limit of detection (LOD), limit of quantification (LOQ) and relative standard deviation (RSD) values were calculated as 0.11%, 0.36% and 8.29% respectively for milk powders samples; while LOD, LOQ and RSD values were calculated as 0.24%, 0.81%, and 10.93% respectively for milk samples. It can be said that LIBS is an applicable method in both liquid and solid samples with suitable systems and parameters. However, liquid analysis requires much more developed systems for more accurate results.

Pharmacokinetics and metabolism of benzene in Zymbal gland and other key target tissues after oral administration in rats.

PubMed Central

Low, L K; Meeks, J R; Norris, K J; Mehlman, M A; Mackerer, C R

1989-01-01

Solid tumors have been reported in the Zymbal gland, oral and nasal cavities, and mammary gland of Sprague-Dawley rats following chronic oral administration of benzene. The cause for the specificity of such lesions remains unclear, but it is possible that tissue-specific metabolism or pharmacokinetics of benzene is responsible. Metabolism and pharmacokinetic studies were carried out in our laboratory with 14C-benzene at oral doses of 0.15 to 500 mg/kg to ascertain tissue retention, metabolite profile, and elimination kinetics in target and nontarget organs and in blood. Findings from those studies indicate the following: a) the Zymbal gland is not a sink or a site of accumulation for benzene or its metabolites even after a single high dose (500 mg/kg) or after repeated oral administration; b) the metabolite profile is quantitatively different in target tissues (e.g., Zymbal gland, nasal cavity), nontarget tissues and blood; and (c) pharmacokinetic studies show that the elimination of radioactivity from the Zymbal gland is biphasic. PMID:2792043

Evaluation of the adverse event profile and pharmacodynamics of toceranib phosphate administered to dogs with solid tumors at doses below the maximum tolerated dose

PubMed Central

2013-01-01

Background The receptor kinase inhibitor toceranib phosphate (Palladia) was approved for use in dogs in 2009 using a dose of 3.25 mg/kg administered every other day. Preliminary data suggests that lower doses of toeceranib may be associated with a reduced adverse event profile while maintaining sufficient drug exposure to provide biologic activity. The purpose of this study was to determine the Cmax of toceranib in dogs with solid tumors receiving 2.5-2.75 mg/kg every other day and to document the adverse events associated with this dose rate. Secondary objectives included determination of plasma VEGF concentrations in treated dogs and response to therapy. Results Dogs with solid tumors were administered toceranib at an intended target dose ranging from 2.5-2.75 mg/kg every other day and plasma samples were obtained for analysis of toceranib and VEGF plasma concentrations on days 0, 7, 14 and 30 of the study at 6 and 8 hours post drug administration. Additionally, plasma samples were obtained at 0, 1, 2, 6, 8, and 12 hours from dogs on day 30 for confirmation of Cmax. Response to therapy was assessed using standard RECIST criteria and adverse events were characterized using the VCOG-CTCAE. Toceranib administered at doses between 2.4-2.9 mg/kg every other day resulted in an average 6–8 hr plasma concentration ranging from 100–120 ng/ml, well above the 40 ng/ml concentration associated with target inhibition. Plasma VEGF concentrations increased significantly over the 30 day treatment period indicating that VEGFR2 inhibition was likely achieved in the majority of dogs. The lower doses of toceranib used in this study were associated with a substantially reduced adverse event profile compared to the established label dose of 3.25 mg/kg EOD. Conclusions Doses of toceranib ranging from 2.4-2.9 mg/kg every other day provide drug exposure considered sufficient for target inhibition while resulting in an adverse event profile substantially reduced from that associated with the label dose of toceranib. This lower dose range of toceranib should be considered for future use in dogs with cancer. PMID:24079884

Rapid targeted somatic mutation analysis of solid tumors in routine clinical diagnostics.

PubMed

Magliacane, Gilda; Grassini, Greta; Bartocci, Paola; Francaviglia, Ilaria; Dal Cin, Elena; Barbieri, Gianluca; Arrigoni, Gianluigi; Pecciarini, Lorenza; Doglioni, Claudio; Cangi, Maria Giulia

2015-10-13

Tumor genotyping is an essential step in routine clinical practice and pathology laboratories face a major challenge in being able to provide rapid, sensitive and updated molecular tests. We developed a novel mass spectrometry multiplexed genotyping platform named PentaPanel to concurrently assess single nucleotide polymorphisms in 56 hotspots of the 5 most clinically relevant cancer genes, KRAS, NRAS, BRAF, EGFR and PIK3CA for a total of 221 detectable mutations. To both evaluate and validate the PentaPanel performance, we investigated 1025 tumor specimens of 6 different cancer types (carcinomas of colon, lung, breast, pancreas, and biliary tract, and melanomas), systematically addressing sensitivity, specificity, and reproducibility of our platform. Sanger sequencing was also performed for all the study samples. Our data showed that PentaPanel is a high throughput and robust tool, allowing genotyping for targeted therapy selection of 10 patients in the same run, with a practical turnaround time of 2 working days. Importantly, it was successfully used to interrogate different DNAs isolated from routinely processed specimens (formalin-fixed paraffin embedded, frozen, and cytological samples), covering all the requirements of clinical tests. In conclusion, the PentaPanel platform can provide an immediate, accurate and cost effective multiplex approach for clinically relevant gene mutation analysis in many solid tumors and its utility across many diseases can be particularly relevant in multiple clinical trials, including the new basket trial approach, aiming to identify appropriate targeted drug combination strategies.

Too many targets, not enough patients: rethinking neuroblastoma clinical trials.

PubMed

Fletcher, Jamie I; Ziegler, David S; Trahair, Toby N; Marshall, Glenn M; Haber, Michelle; Norris, Murray D

2018-06-01

Neuroblastoma is a rare solid tumour of infancy and early childhood with a disproportionate contribution to paediatric cancer mortality and morbidity. Combination chemotherapy, radiation therapy and immunotherapy remains the standard approach to treat high-risk disease, with few recurrent, actionable genetic aberrations identified at diagnosis. However, recent studies indicate that actionable aberrations are far more common in relapsed neuroblastoma, possibly as a result of clonal expansion. In addition, although the major validated disease driver, MYCN, is not currently directly targetable, multiple promising approaches to target MYCN indirectly are in development. We propose that clinical trial design needs to be rethought in order to meet the challenge of providing rigorous, evidence-based assessment of these new approaches within a fairly small patient population and that experimental therapies need to be assessed at diagnosis in very-high-risk patients rather than in relapsed and refractory patients.

Evidence of locally enhanced target heating due to instabilities of counter-streaming fast electron beams

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

Koester, Petra; Cecchetti, Carlo A.; Booth, Nicola

2015-02-15

The high-current fast electron beams generated in high-intensity laser-solid interactions require the onset of a balancing return current in order to propagate in the target material. Such a system of counter-streaming electron currents is unstable to a variety of instabilities such as the current-filamentation instability and the two-stream instability. An experimental study aimed at investigating the role of instabilities in a system of symmetrical counter-propagating fast electron beams is presented here for the first time. The fast electron beams are generated by double-sided laser-irradiation of a layered target foil at laser intensities above 10{sup 19 }W/cm{sup 2}. High-resolution X-ray spectroscopy ofmore » the emission from the central Ti layer shows that locally enhanced energy deposition is indeed achieved in the case of counter-propagating fast electron beams.« less

Aluminum Target Dissolution in Support of the Pu-238 Program

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

McFarlane, Joanna; Benker, Dennis; DePaoli, David W

2014-09-01

Selection of an aluminum alloy for target cladding affects post-irradiation target dissolution and separations. Recent tests with aluminum alloy 6061 yielded greater than expected precipitation in the caustic dissolution step, forming up to 10 wt.% solids of aluminum hydroxides and aluminosilicates. We present a study to maximize dissolution of aluminum metal alloy, along with silicon, magnesium, and copper impurities, through control of temperature, the rate of reagent addition, and incubation time. Aluminum phase transformations have been identified as a function of time and temperature, using X-ray diffraction. Solutions have been analyzed using wet chemical methods and X-ray fluorescence. These datamore » have been compared with published calculations of aluminum phase diagrams. Temperature logging during the transients has been investigated as a means to generate kinetic and mass transport data on the dissolution process. Approaches are given to enhance the dissolution of aluminum and aluminosilicate phases in caustic solution.« less

Liquid crystals as on-demand, variable thickness targets for intense laser applications

NASA Astrophysics Data System (ADS)

Poole, Patrick L.; Andereck, C. David; Schumacher, Douglass W.

2014-10-01

Laser-based ion acceleration is currently studied for its applications to advanced imaging and cancer therapy, among others. Targets for these and other high-intensity laser experiments are often small metallic foils with few to sub-micron thicknesses, where the thickness determines the physics of the dominant acceleration mechanism. We have developed liquid crystal films that preserve the planar target geometry advantageous to ion acceleration schemes while providing on-demand thickness variation between 50 and 5000 nm. This thickness control is obtained in part by varying the temperature at which films are formed, which governs the phase (and hence molecular ordering) of the liquid crystal material. Liquid crystals typically have vapor pressures well below the 10-6 Torr operating pressures of intense laser target chambers, and films formed in air maintain their thickness during chamber evacuation. Additionally, the minute volume that comprises each film makes the cost of each target well below one cent, in stark contrast to many standard solid targets. We will discuss the details of liquid crystal film control and formation, as well as characterization experiments performed at the Scarlet laser facility. This work was performed with support from DARPA and NNSA.

Analytical model for release calculations in solid thin-foils ISOL targets

NASA Astrophysics Data System (ADS)

Egoriti, L.; Boeckx, S.; Ghys, L.; Houngbo, D.; Popescu, L.

2016-10-01

A detailed analytical model has been developed to simulate isotope-release curves from thin-foils ISOL targets. It involves the separate modeling of diffusion and effusion inside the target. The former has been modeled using both first and second Fick's law. The latter, effusion from the surface of the target material to the end of the ionizer, was simulated with the Monte Carlo code MolFlow+. The calculated delay-time distribution for this process was then fitted using a double-exponential function. The release curve obtained from the convolution of diffusion and effusion shows good agreement with experimental data from two different target geometries used at ISOLDE. Moreover, the experimental yields are well reproduced when combining the release fraction with calculated in-target production.

Laser Irradiated Foam Targets: Absorption and Radiative Properties

NASA Astrophysics Data System (ADS)

Salvadori, Martina; Luigi Andreoli, Pier; Cipriani, Mattia; Consoli, Fabrizio; Cristofari, Giuseppe; De Angelis, Riccardo; di Giorgio, Giorgio; Giulietti, Danilo; Ingenito, Francesco; Gus'kov, Sergey Yu.; Rupasov, Alexander A.

2018-01-01

An experimental campaign to characterize the laser radiation absorption of foam targets and the subsequent emission of radiation from the produced plasma was carried out in the ABC facility of the ENEA Research Center in Frascati (Rome). Different targets have been used: plastic in solid or foam state and aluminum targets. The activated different diagnostics allowed to evaluate the plasma temperature, the density distribution, the fast particle spectrum and the yield of the X-Ray radiation emitted by the plasma for the different targets. These results confirm the foam homogenization action on laser-plasma interaction, mainly attributable to the volume absorption of the laser radiation propagating in such structured materials. These results were compared with simulation absorption models of the laser propagating into a foam target.

Formulation and validation of a computational model for a dilute biomass slurry undergoing rotational mixing

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

Sprague, Michael A.; Stickel, Jonathan J.; Sitaraman, Hariswaran

In this paper we develop a computational model for the mixing and transport of a dilute biomass slurry. The objective was to create a sufficiently simple and efficient model for biomass transport that can be coupled with reaction models for the study of conversion of cellulosic biomass into fermentable sugars. Our target system is 5%-by-mass ..alpha..-cellulose, which is our proxy for more complex lignocellulosic biomass. In the authors' previous work, an experimental investigation with ..alpha..-cellulose under two vane-mixer configurations showed a bifurcation between a settling regime, for which settling effects dominate, and a suspended regime, for which solids are mostlymore » suspended. Here, a mixed-fluid model was chosen, for which the model for the mixture-velocity field is the incompressible Navier-Stokes equations under the Boussinesq approximation for buoyancy. Solids transport includes solids motion due to diffusion, settling, advection, and shear. Comparison of simulated and experimental results show good agreement in the suspended regime, and in capturing the bifurcation rate. While the model captured well the distribution of solids in the settling regime, the model was incapable of capturing the high torque values seen in experiments with vanishing mixer rotation rate.« less

Formulation and validation of a computational model for a dilute biomass slurry undergoing rotational mixing

DOE PAGES

Sprague, Michael A.; Stickel, Jonathan J.; Sitaraman, Hariswaran; ...

2018-02-17

In this paper we develop a computational model for the mixing and transport of a dilute biomass slurry. The objective was to create a sufficiently simple and efficient model for biomass transport that can be coupled with reaction models for the study of conversion of cellulosic biomass into fermentable sugars. Our target system is 5%-by-mass ..alpha..-cellulose, which is our proxy for more complex lignocellulosic biomass. In the authors' previous work, an experimental investigation with ..alpha..-cellulose under two vane-mixer configurations showed a bifurcation between a settling regime, for which settling effects dominate, and a suspended regime, for which solids are mostlymore » suspended. Here, a mixed-fluid model was chosen, for which the model for the mixture-velocity field is the incompressible Navier-Stokes equations under the Boussinesq approximation for buoyancy. Solids transport includes solids motion due to diffusion, settling, advection, and shear. Comparison of simulated and experimental results show good agreement in the suspended regime, and in capturing the bifurcation rate. While the model captured well the distribution of solids in the settling regime, the model was incapable of capturing the high torque values seen in experiments with vanishing mixer rotation rate.« less

Behaviour of emerging contaminants in sewage sludge after anaerobic digestion.

PubMed

Boix, C; Ibáñez, M; Fabregat-Safont, D; Morales, E; Pastor, L; Sancho, J V; Sánchez-Ramírez, J E; Hernández, F

2016-11-01

Nowadays, there is an increasing concern over the presence of contaminants in the aquatic environment, where they can be introduced from wastewater after their incomplete removal in the treatment plants. In this work, degradation of selected emerging pollutants in the aqueous and solid phases of sewage sludge has been investigated after anaerobic digestion using two different digesters: mesophilic and thermophilic. Initially, sludge samples were screened by ultra-high-performance liquid chromatography coupled to quadrupole time-of-flight mass spectrometry (UHPLC-QTOF MS) for identification of emerging contaminants in the samples. In a second step, a target quantitative method based on LC coupled to tandem MS was applied for selected pollutants identified in the previous screening. The behaviour of the compounds under anaerobic conditions was studied estimating the degradation efficiency and distribution of compounds between both sludge phases. Irbesartan and benzoylecgonine seemed to be notably degraded in both phases of the sludge. Venlafaxine showed a significant concentration decrease in the aqueous phase in parallel to an increase in the solid phase. The majority of the compounds showed an increase of their concentrations in both phases after the digestion. Concentrations in the solid phase were commonly higher than in the aqueous for most contaminants, indicating that they were preferentially adsorbed onto the solid particles. Copyright © 2016 Elsevier Ltd. All rights reserved.

Micro-matrix solid-phase dispersion coupled with MEEKC for quantitative analysis of lignans in Schisandrae Chinensis Fructus using molecular sieve TS-1 as a sorbent.

PubMed

Chu, Chu; Wei, Mengmeng; Wang, Shan; Zheng, Liqiong; He, Zheng; Cao, Jun; Yan, Jizhong

2017-09-15

A simple and effective method was developed for determining lignans in Schisandrae Chinensis Fructus by using a micro-matrix solid phase dispersion (MSPD) technique coupled with microemulsion electrokinetic chromatography (MEEKC). Molecular sieve, TS-1, was applied as a solid supporting material in micro MSPD extraction for the first time. Parameters that affect extraction efficiency, such as type of dispersant, mass ratio of the sample to the dispersant, grinding time, elution solvent and volume were optimized. The optimal extraction conditions involve dispersing 25mg of powdered Schisandrae samples with 50mg of TS-1 by a mortar and pestle. A grinding time of 150s was adopted. The blend was then transferred to a solid-phase extraction cartridge and the target analytes were eluted with 500μL of methanol. Moreover, several parameters affecting MEEKC separation were studied, including the type of oil, SDS concentration, type and concentration of cosurfactant, and concentration of organic modifier. A satisfactory linearity (R>0.9998) was obtained, and the calculated limits of quantitation were less than 2.77μg/mL. Finally, the micro MSPD-MEEKC method was successfully applied to the analysis of lignans in complex Schisandrae fructus samples. Copyright © 2017 Elsevier B.V. All rights reserved.

Blue and Black Cloth Targets: Effects of Size, Shape, and Color on Stable Fly (Diptera: Muscidae) Attraction.

PubMed

Hogsette, Jerome A; Foil, Lane D

2018-04-02

Stable fly management is challenging because of the fly's dispersal behavior and its tendency to remain on the host only while feeding. Optically attractive traps have been used to survey and sometimes reduce adult populations. Insecticide-treated blue and black cloth targets developed for tsetse fly management in Africa were found to be attractive to stable flies in the United States, and various evaluations were conducted in Louisiana and Florida. Tests using untreated targets were designed to answer questions about configuration, size, and color relative to efficacy and stability in high winds. Studies with electric grid targets and with targets paired with Olson traps showed cloth target color attraction in the following decreasing order: black > blue-black > blue. A solid black target is easier to make than a blue-black target because no sewing is involved. Attraction was not affected when flat 1-m2 targets were formed into cylinders, despite the limited view of the blue and black colors together. There was no reduction in attraction when the 1-m2 cylindrical targets were compared with smaller (63 × 30 cm high) cylindrical targets. In addition, there was no difference in attraction between the small blue-black, blue, and black targets. Significance of findings and implications of potential uses for treated targets are discussed. Target attraction was indicated by the numbers of stable flies captured on an Olson sticky trap placed 30 cm from the target. Although this system is adequate for field research, it greatly underestimates the actual numbers of stable flies attracted to treated targets.

Modulation of butyrate anticancer activity by solid lipid nanoparticle delivery: an in vitro investigation on human breast cancer and leukemia cell lines.

PubMed

Foglietta, Federica; Serpe, Loredana; Canaparo, Roberto; Vivenza, Nicoletta; Riccio, Giovanna; Imbalzano, Erica; Gasco, Paolo; Zara, Gian Paolo

2014-01-01

Histone modification has emerged as a promising approach to cancer therapy. The short-chain fatty acid, butyric acid, a histone deacetylase (HD) inhibitor, has shown anticancer activity. Butyrate transcriptional activation is indeed able to withdraw cancer cells from the cell cycle, leading to programmed cell death. Since butyrate's clinical use is hampered by unfavorable pharmacokinetic and pharmacodynamic properties, delivery systems, such as solid lipid nanoparticles (SLN), have been developed to overcome these constraints. In order to outline the influence of butyrate delivery on its anticancer activity, the effects of butyrate as a free (sodium butyrate, NB) or nanoparticle (cholesteryl butyrate solid lipid nanoparticles, CBSLN) formulation on the growth of different human cancer cell lines, such as the promyelocytic leukemia, HL-60, and the breast cancer, MCF-7 was investigated. A detailed investigation into the mechanism of the induced cytotoxicity was also carried out, with a special focus on the modulation of HD and cyclin-dependent kinase (CDK) mRNA gene expression by real time PCR analysis. In HL-60 cells, CBSLN induced a higher and prolonged expression level of the butyrate target genes at lower concentrations than NB. This led to a significant decrease in cell proliferation, along with considerable apoptosis, cell cycle block in the G0/G1 phase, significant inhibition of total HD activity and overexpression of the p21 protein. Conversely, in MCF-7 cells, CBSLN did not enhance the level of expression of the butyrate target genes, leading to the same anticancer activity as that of NB. Solid lipid nanoparticles were able to improve butyrate anticancer activity in HL-60, but not in MCF-7 cells. This is consistent with difference in properties of the cells under study, such as expression of the TP53 tumor suppressor, or the transporter for short-chain fatty acids, SLC5A8.

Comparative evaluation of liquid-liquid extraction, solid-phase extraction and solid-phase microextraction for the gas chromatography-mass spectrometry determination of multiclass priority organic contaminants in wastewater.

PubMed

Robles-Molina, José; Gilbert-López, Bienvenida; García-Reyes, Juan F; Molina-Díaz, Antonio

2013-12-15

The European Water Framework Directive (WFD) 2000/60/EC establishes guidelines to control the pollution of surface water by sorting out a list of priority substances that involves a significant risk to or via the aquatic systems. In this article, the analytical performance of three different sample preparation methodologies for the GC-MS/MS determination of multiclass organic contaminants-including priority comprounds from the WFD-in wastewater samples using gas chromatography-mass spectrometry was evaluated. The methodologies tested were: (a) liquid-liquid extraction (LLE) with n-hexane; (b) solid-phase extraction (SPE) with C18 cartridges and elution with ethyl acetate:dichloromethane (1:1 (v/v)), and (c) headspace solid-phase microextraction (HS-SPME) using two different fibers: polyacrylate and polydimethylsiloxane/carboxen/divinilbenzene. Identification and confirmation of the selected 57 compounds included in the study (comprising polycyclic aromatic hydrocarbons (PAHs), pesticides and other contaminants) were accomplished using gas chromatography tandem mass spectrometry (GC-MS/MS) with a triple quadrupole instrument operated in the multiple reaction monitoring (MRM) mode. Three MS/MS transitions were selected for unambiguous confirmation of the target chemicals. The different advantages and pitfalls of each method were discussed. In the case of both LLE and SPE procedures, the method was validated at two different concentration levels (15 and 150 ng L(-1)) obtaining recovery rates in the range 70-120% for most of the target compounds. In terms of analyte coverage, results with HS-SPME were not satisfactory, since 14 of the compounds tested were not properly recovered and the overall performance was worse than the other two methods tested. LLE, SPE and HS-SPME (using polyacrylate fiber) procedures also showed good linearity and precision. Using any of the three methodologies tested, limits of quantitation obtained for most of the detected compounds were in the low nanogram per liter range. © 2013 Elsevier B.V. All rights reserved.

The appropriate use of technology (particularly in medical problems of the elderly).

PubMed

Gilbert, F I

1990-09-01

Technology, particularly "high" technology, with little solid data, is often blamed for much of our increasing cost of health care. Politics and emotions are poor substitutes for accurate information needed for rational solutions. By targeting the desired outcome and studying the process needed to reach the outcome, we can make better decisions. The methods of designing, conducting and funding the studies needed to answer the difficult questions posed by the use of high technology in the elderly are available. Do we have the wisdom to use them?

Preparative isolation of flavonoid glycosides from Sphaerophysa salsula using hydrophilic interaction solid-phase extraction coupled with two-dimensional preparative liquid chromatography.

PubMed

Jiao, Lijin; Tao, Yanduo; Wang, Weidong; Shao, Yun; Mei, Lijuan; Wang, Qilan; Dang, Jun

2017-10-01

An offline preparative two-dimensional reversed-phase liquid chromatography/hydrophilic interaction liquid chromatography coupled with hydrophilic interaction solid-phase extraction method was developed for the preparative isolation of flavonoid glycosides from a crude sample of Sphaerophysa salsula. First, the non-flavonoids were removed using an XAmide solid-phase extraction cartridge. Based on the separation results of three different chromatographic stationary phases, the first-dimensional preparation was performed on an XAqua C18 prep column, and 15 fractions were obtained from the 5.2 g target sample. Then, three representative fractions were selected for additional purification on an XAmide preparative column to further isolate the flavonoid glycosides. In all, eight flavonoid glycosides were isolated in purities over 97%. The results demonstrated that the two-dimensional liquid chromatography method used in this study was effective for the preparative separation of flavonoid glycosides from Sphaerophysa salsula. Additionally, this method showed great potential for the separation of flavonoid glycosides from other plant materials. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Targeting constitutively-activated STAT3 in hypoxic ovarian cancer, using a novel STAT3 inhibitor

PubMed Central

McCann, Georgia A.; Naidu, Shan; Rath, Kellie S.; Bid, Hemant K.; Tierney, Brent J.; Suarez, Adrian; Varadharaj, Saradhadevi; Zhang, Jianying; Hideg, Kálmán; Houghton, Peter; Kuppusamy, Periannan; Cohn, David E.; Selvendiran, Karuppaiyah

2014-01-01

Tumor hypoxia, a feature of many solid tumors including ovarian cancer, is associated with resistance to therapies. We previously demonstrated that hypoxic exposure results in increased expression of phosphorylated signal transducer and activator of transcription 3 (pSTAT3). We hypothesized the activation of STAT3 could lead to chemotherapeutic resistance in ovarian cancer cells in hypoxic conditions. In this study, we demonstrate the level of pSTAT3 Tyr705 is increased in the hypoxic regions of human epithelial ovarian cancer (EOC) specimens, as determined by HIF-1α and CD-31 staining. In vitro mutagenesis studies proved that pSTAT3 Tyr705 is necessary for cell survival and proliferation under hypoxic conditions. In addition, we show that S1PR1, a regulator of STAT3 transcription via the JAK/STAT pathway, is highly expressed in hypoxic ovarian cancer cells (HOCCs). Knock down of S1PR1 in HOCCs reduced pSTAT3 Tyr705 levels and was associated with decreased cell survival. Treatment of HOCCs with the STAT3 inhibitor HO-3867 resulted in a rapid and dramatic decrease in pSTAT3 Tyr705 levels as a result of ubiquitin proteasome degradation. STAT3-target proteins Bcl-xL, cyclin D2 and VEGF showed similar decreases in HO-3867 treated cells. Taken together, these findings suggest that activation of STAT3 Tyr705 promotes cell survival and proliferation in HOCCs, and that S1PR1 is involved in the initiation of STAT3 activation. Targeting hypoxia-mediated STAT3 activation represents a therapeutic option for ovarian cancer and other solid tumors. PMID:25594014

Anti-tumor effects and apoptosis induction by Realgar bioleaching solution in Sarcoma-180 cells in vitro and transplanted tumors in mice in vivo.

PubMed

Xie, Qin-Jian; Cao, Xin-Li; Bai, Lu; Wu, Zheng-Rong; Ma, Ying-Ping; Li, Hong-Yu

2014-01-01

Realgar which contains arsenic components has been used in traditional Chinese medicine (TCM) as an anticancer drug. However, neither Realgar nor its formula are soluble in water. As a result, high dose of Realgar has to be administered to achieve an effective blood medicine concentration, and this is associated with adverse side effects. The objective of the present study was to increase the solubility of a formula using hydrometallurgy technology as well as investigating its effects on in vitro and in vivo cell proliferation and apoptosis in Sarcoma-180 cell line. Antiproliferative activity of Realgar Bioleaching Solution (RBS) was evaluated by MTT assay. Further, effects of RBS on cell proliferation and apoptosis were studied using flow cytometry and transmission electron microscopy. Kunming mice were administered RBS in vivo, where arsenic specifically targeted solid tumors. The results indicated that RBS extract potently inhibited the tumor growth of Sarcoma-180 cell line in a dose-dependent manner. Flow cytometry and transmission electron microscopy further indicated that RBS significantly induced cell apoptosis through the inhibition of cell cycle pathway in a dose-dependent manner. Further, on RBS administration to mice, arsenic was specifically targeted to solid tumors RBS could substitute for traditional Realgar or its formula to work as a potent tool in cancer treatment.

Clinical Development of VEGF Signaling Pathway Inhibitors in Childhood Solid Tumors

PubMed Central

Yamashiro, Darrell J.; Fox, Elizabeth

2011-01-01

Angiogenesis is a target shared by both adult epithelial cancers and the mesenchymal or embryonal tumors of childhood. Development of antiangiogenic agents for the pediatric population has been complicated by largely theoretical concern for toxicities specific to the growing child and prioritization among the many antiangiogenic agents being developed for adults. This review summarizes the mechanism of action and preclinical data relevant to childhood cancers and early-phase clinical trials in childhood solid tumors. Single-agent adverse event profiles in adults and children are reviewed with emphasis on cardiovascular, bone health, and endocrine side effects. In addition, pharmacological factors that may be relevant for prioritizing clinical trials of these agents in children are reviewed. Considerations for further clinical evaluation should include preclinical data, relative potency, efficacy in adults, and the current U.S. Food and Drug Administration approval status. Toxicity profiles of vascular endothelial growth factor (VEGF) signaling pathway inhibitors may be age dependent and ultimately, their utility in the treatment of childhood cancer will require combination with standard cytotoxic drugs or other molecularly targeted agents. In combination studies, toxicity profiles, potential drug interactions, and late effects must be considered. Studies to assess the long-term impact of VEGF signaling pathway inhibitors on cardiovascular, endocrine, and bone health in children with cancer are imperative if these agents are to be administered to growing children and adolescents with newly diagnosed cancers. PMID:22042784

Preheating study by reflectivity measurements in laser-driven shocks

NASA Astrophysics Data System (ADS)

Benuzzi, A.; Koenig, M.; Faral, B.; Krishnan, J.; Pisani, F.; Batani, D.; Bossi, S.; Beretta, D.; Hall, T.; Ellwi, S.; Hüller, S.; Honrubia, J.; Grandjouan, N.

1998-06-01

A study on preheating effects in laser-driven shock waves is presented. Two different diagnostics were used: the color temperature measurement deduced by recording the target rear side emissivity in two spectral bands, and the rear surface reflectivity measurement by using a probe beam. In order to test the response of the two diagnostics to the preheating, three types of targets characterized by different radiative properties were used. The greater sensitivity of the second diagnostic compared with the first was demonstrated. A model which calculates the reflectivity using a one-dimensional hydrodynamic code data was developed. In this model, the wave propagation equations in the expanding plasma using an appropriate model for the electron-ion collision frequency applicable to the cold solid-hot plasma transition were solved. The comparison between the calculated and measured reflectivities allows us to estimate the preheating process.

Soft x-ray generation by a tabletop Nd:YAG/glass laser system

NASA Astrophysics Data System (ADS)

Martellucci, S.; Bellecci, C.; Francucci, M.; Gaudio, P.; Richetta, M.; Toscano, D.; Rydzy, A.; Gelfusa, M.; Ciuffa, P.

2006-08-01

The advent and development of ultra-intense tabletop laser systems has played a significant role in recent decades thanks to the wide number of applications and studies in which these systems were demonstrated to be appropriate. Among these, one of the main applications of ultra-intense radiation is generation of plasma by solid, liquid or gaseous targets. The by-product of x-radiation found many different applications such as spectroscopy, imaging, microlithography, microscopy, radiographies (in particular of biological samples), radiation-matter interaction, fundamental plasma parameter determination, astrophysics, inertial confinement fusion, high energy physics, quantum electrodynamics, and many others. In the following a brief description of our tabletop Nd:YAG/glass apparatus (facility of the Quantum Electronic and Plasma Laboratory of the University of Rome 'Tor Vergata'), together with x-ray conversion efficiency studies for different targets, are reported.

Ignition of deuterium-trtium fuel targets

DOEpatents

Musinski, Donald L.; Mruzek, Michael T.

1991-01-01

A method of igniting a deuterium-tritium ICF fuel target to obtain fuel burn in which the fuel target initially includes a hollow spherical shell having a frozen layer of DT material at substantially uniform thickness and cryogenic temperature around the interior surface of the shell. The target is permitted to free-fall through a target chamber having walls heated by successive target ignitions, so that the target is uniformly heated during free-fall to at least partially melt the frozen fuel layer and form a liquid single-phase layer or a mixed liquid/solid bi-phase layer of substantially uniform thickness around the interior shell surface. The falling target is then illuminated from exteriorly of the chamber while the fuel layer is at substantially uniformly single or bi-phase so as to ignite the fuel layer and release energy therefrom.

Ignition of deuterium-tritium fuel targets

DOEpatents

Musinski, D.L.; Mruzek, M.T.

1991-08-27

Disclosed is a method of igniting a deuterium-tritium ICF fuel target to obtain fuel burn in which the fuel target initially includes a hollow spherical shell having a frozen layer of DT material at substantially uniform thickness and cryogenic temperature around the interior surface of the shell. The target is permitted to free-fall through a target chamber having walls heated by successive target ignitions, so that the target is uniformly heated during free-fall to at least partially melt the frozen fuel layer and form a liquid single-phase layer or a mixed liquid/solid bi-phase layer of substantially uniform thickness around the interior shell surface. The falling target is then illuminated from exteriorly of the chamber while the fuel layer is at substantially uniformly single or bi-phase so as to ignite the fuel layer and release energy therefrom. 5 figures.

Multi probes measurements at the PALS Facility Research Centre during high intense laser pulse interactions with various target materials

NASA Astrophysics Data System (ADS)

De Marco, Massimo; Krása, Josef; Cikhardt, Jakub; Consoli, Fabrizio; De Angelis, Riccardo; Pfeifer, Miroslav; Krůs, Miroslav; Dostál, Jan; Margarone, Daniele; Picciotto, Antonino; Velyhan, Andriy; Klír, Daniel; Dudžák, Roman; Limpouch, Jiří; Korn, Georg

2018-01-01

During the interaction of high intense laser pulse with solid target, a large amount of hot electrons is produced and a giant Electromagnetic Pulse (EMP) is generated due to the current flowing into the system target-target holder, as well as due to the escaping charged particles in vacuum. EMP production for different target materials is investigated inside and outside the target chamber, using monopole antenna, super wide-band microstrip antenna and Moebius antenna. The EMP consists in a fast transient magnetic field lasting hundreds of nanosecond with frequencies ranging from MHz to tens of GHz. Measurements of magnetic field and return target current in the range of kA were carried out by an inductive target probe (Cikhardt J. et al. Rev. Sci. Instrum. 85 (2014) 103507).

Translating genomic discoveries to the clinic in pediatric oncology.

PubMed

Glade Bender, Julia; Verma, Anupam; Schiffman, Joshua D

2015-02-01

The present study describes the recent advances in the identification of targetable genomic alterations in pediatric cancers, along with the progress and associated challenges in translating these findings into therapeutic benefit. Each field within pediatric cancer has rapidly and comprehensively begun to define genomic targets in tumors that potentially can improve the clinical outcome of patients, including hematologic malignancies (leukemia and lymphoma), solid malignancies (neuroblastoma, rhabdomyosarcoma, Ewing sarcoma, and osteosarcoma), and brain tumors (gliomas, ependymomas, and medulloblastomas). Although each tumor has specific and sometimes overlapping genomic targets, the translation to the clinic of new targeted trials and precision medicine protocols is still in its infancy. The first clinical tumor profiling studies in pediatric oncology have demonstrated feasibility and patient enthusiasm for the personalized medicine paradigm, but have yet to demonstrate clinical utility. Complexities influencing implementation include rapidly evolving sequencing technologies, tumor heterogeneity, and lack of access to targeted therapies. The return of incidental findings from the germline also remains a challenge, with evolving policy statements and accepted standards. The translation of genomic discoveries to the clinic in pediatric oncology continues to move forward at a brisk pace. Early adoption of genomics for tumor classification, risk stratification, and initial trials of targeted therapeutic agents has led to powerful results. As our experience grows in the integration of genomic and clinical medicine, the outcome for children with cancer should continue to improve.

Solid-phase microextraction gas chromatography-mass spectrometry determination of fragrance allergens in baby bathwater.

PubMed

Lamas, J Pablo; Sanchez-Prado, Lucia; Garcia-Jares, Carmen; Llompart, Maria

2009-07-01

A method based on solid-phase microextraction (SPME) and gas chromatography-mass spectrometry (GC-MS) has been optimized for the determination of fragrance allergens in water samples. This is the first study devoted to this family of cosmetic ingredients performed by SPME. The influence of parameters such as fibre coating, extraction and desorption temperatures, salting-out effect and sampling mode on the extraction efficiency has been studied by means of a mixed-level factorial design, which allowed the study of the main effects as well as two-factor interactions. Excluding desorption temperature, the other parameters were, in general, very important for the achievement of high response. The final procedure was based on headspace sampling at 100 degrees C, using polydimethylsiloxane/divinylbenzene fibres. The method showed good linearity and precision for all compounds, with detection limits ranging from 0.001 to 0.3 ng mL(-1). Reliability was demonstrated through the evaluation of the recoveries in different real water samples, including baby bathwater and swimming pool water. The absence of matrix effects allowed the use of external standard calibration to quantify the target compounds in the samples. The proposed procedure was applied to the determination of allergens in several real samples. All the target compounds were found in the samples, and, in some cases, at quite high concentrations. The presence and the levels of these chemicals in baby bathwater should be a matter of concern.

Hydrodynamic Tunneling of 440 GeV SPS protons in Solid Material: Production of Warm Dense Matter at CERN HiRadMat Facility

NASA Astrophysics Data System (ADS)

Tahir, Naeem Ahmad; Blanco Sancho, Juan; Schmidt, Ruediger; Shutov, Alaxander; Burkart, Florian; Wollmann, Daniel; Piriz, Antonio Roberto

2013-10-01

Numerical simulations have shown that the range of 7 TeV LHC protons in solid matter will be significantly increased due to hydrodynamic tunneling. For example, in solid copper and solid carbon, these protons and the shower can penetrate up to 35 m and 25 m, respectively. However, their corresponding static range in the two materials is 1 m and 3 m, respectively. This will have important implications on machine protection design. In order to validate these simulation results, experiments have been performed at the CERN HiRadMat facility using the 440 GeV SPS proton beam irradiating solid copper cylindrical target. The phenomenon of hydrodynamic tunneling has been experimentally confirmed and good agreement has been found between the simulations and the experimental results. A very interesting outcome of this work is that the HiRadMat facility can be used to generate High Energy Density matter including Warm Dense Matter and strongly coupled plasmas in the laboratory.

Strong terahertz radiation from relativistic laser interaction with solid density plasmas

NASA Astrophysics Data System (ADS)

Li, Y. T.; Li, C.; Zhou, M. L.; Wang, W. M.; Du, F.; Ding, W. J.; Lin, X. X.; Liu, F.; Sheng, Z. M.; Peng, X. Y.; Chen, L. M.; Ma, J. L.; Lu, X.; Wang, Z. H.; Wei, Z. Y.; Zhang, J.

2012-06-01

We report a plasma-based strong THz source generated in intense laser-solid interactions at relativistic intensities >1018 W/cm2. Energies up to 50 μJ/sr per THz pulse is observed when the laser pulses are incident onto a copper foil at 67.5°. The temporal properties of the THz radiation are measured by a single shot, electro-optic sampling method with a chirped laser pulse. The THz radiation is attributed to the self-organized transient fast electron currents formed along the target surface. Such a source allows potential applications in THz nonlinear physics and provides a diagnostic of transient currents generated in intense laser-solid interactions.

Solid-state coherent laser radar wind shear measuring systems

NASA Technical Reports Server (NTRS)

Huffaker, R. Milton

1992-01-01

Coherent Technologies, Inc. (CTI) was established in 1984 to engage in the development of coherent laser radar systems and subsystems with applications in atmospheric remote sensing, and in target tracking, ranging and imaging. CTI focuses its capabilities in three major areas: (1) theoretical performance and design of coherent laser radar system; (2) development of coherent laser radar systems for government agencies such as DoD and NASA; and (3) development of coherent laser radar systems for commercial markets. The topics addressed are: (1) 1.06 micron solid-state coherent laser radar system; (2) wind measurement using 1.06 micron system; and flashlamp-pumped 2.09 micron solid-state coherent laser radar system.

The power of combining adoptive cell therapy (ACT) and pathogen-boosted vaccination to treat solid tumors.

PubMed

Zander, Ryan; Cui, Weiguo

2017-10-03

Recent advancements in adoptive cell therapy (ACT) are opening up new frontiers for cancer immunotherapy. CAR T cells targeting CD19 have emerged as a remarkable T cell-based therapy for the successful treatment of certain types of leukemia and lymphomas. Despite these clinical successes, as well as significant breakthroughs in T cell engineering, the treatment of solid tumors with ACT remains a relentless challenge. Thus, the current consensus of the field is that an urgent need exists for the design of innovative approaches that can improve the efficacy of ACT in treating solid cancers while maintaining a high degree of reliability and safety.

Recent advances and challenges for diode-pumped solid-state lasers as an inertial fusion energy driver candidate

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

Payne, S.A.; Beach, R.J.; Bibeau, C.

We discuss how solid-state laser technology can serve in the interests of fusion energy beyond the goals of the National Ignition Facility (NIF), which is now being constructed to ignite a deuterium-tritium target to fusion conditions in the laboratory for the first time. We think that advanced solid-state laser technology can offer the repetition-rate and efficiency needed to drive a fusion power plant, in contrast to the single-shot character of NIF. As discuss below, we propose that a gas-cooled, diode-pumped Yb:S-FAP laser can provide a new paradigm for fusion laser technology leading into the next century.

Optimization of biological and instrumental detection of explosives and ignitable liquid residues including canines, SPME/ITMS and GC/MSn

NASA Astrophysics Data System (ADS)

Furton, Kenneth G.; Harper, Ross J.; Perr, Jeannette M.; Almirall, Jose R.

2003-09-01

A comprehensive study and comparison is underway using biological detectors and instrumental methods for the rapid detection of ignitable liquid residues (ILR) and high explosives. Headspace solid phase microextraction (SPME) has been demonstrated to be an effective sampling method helping to identify active odor signature chemicals used by detector dogs to locate forensic specimens as well as a rapid pre-concentration technique prior to instrumental detection. Common ignitable liquids and common military and industrial explosives have been studied including trinitrotoluene, tetryl, RDX, HMX, EGDN, PETN and nitroglycerine. This study focuses on identifying volatile odor signature chemicals present, which can be used to enhance the level and reliability of detection of ILR and explosives by canines and instrumental methods. While most instrumental methods currently in use focus on particles and on parent organic compounds, which are often involatile, characteristic volatile organics are generally also present and can be exploited to enhance detection particularly for well-concealed devices. Specific examples include the volatile odor chemicals 2-ethyl-1-hexanol and cyclohexanone, which are readily available in the headspace of the high explosive composition C-4; whereas, the active chemical cyclo-1,3,5-trimethylene-2,4,6-trinitramine (RDX) is not. The analysis and identification of these headspace 'fingerprint' organics is followed by double-blind dog trials of the individual components using certified teams in an attempt to isolate and understand the target compounds to which dogs are sensitive. Studies to compare commonly used training aids with the actual target explosive have also been undertaken to determine their suitability and effectiveness. The optimization of solid phase microextraction (SPME) combined with ion trap mobility spectrometry (ITMS) and gas chromatography/mass spectrometry/mass spectrometry (GC/MSn) is detailed including interface development and comparisons of limits of detection. These instrumental methods are being optimized in order to detect the same target odor chemicals used by detector dogs to reliably locate explosives and ignitable liquids.

Synergistic co-digestion of solid-organic-waste and municipal-sewage-sludge: 1 plus 1 equals more than 2 in terms of biogas production and solids reduction.

PubMed

Aichinger, Peter; Wadhawan, Tanush; Kuprian, Martin; Higgins, Matthew; Ebner, Christian; Fimml, Christian; Murthy, Sudhir; Wett, Bernhard

2015-12-15

Making good use of existing water infrastructure by adding organic wastes to anaerobic digesters improves the energy balance of a wastewater treatment plant (WWTP) substantially. This paper explores co-digestion load limits targeting a good trade-off for boosting methane production, and limiting process-drawbacks on nitrogen-return loads, cake-production, solids-viscosity and polymer demand. Bio-methane potential tests using whey as a model co-substrate showed diversification and intensification of the anaerobic digestion process resulting in a synergistical enhancement in sewage sludge methanization. Full-scale case-studies demonstrate organic co-substrate addition of up to 94% of the organic sludge load resulted in tripling of the biogas production. At organic co-substrate addition of up to 25% no significant increase in cake production and only a minor increase in ammonia release of ca. 20% have been observed. Similar impacts were measured at a high-solids digester pilot with up-stream thermal hydrolyses where the organic loading rate was increased by 25% using co-substrate. Dynamic simulations were used to validate the synergistic impact of co-substrate addition on sludge methanization, and an increase in hydrolysis rate from 1.5 d(-1) to 2.5 d(-1) was identified for simulating measured gas production rate. This study demonstrates co-digestion for maximizing synergy as a step towards energy efficiency and ultimately towards carbon neutrality. Copyright © 2015 Elsevier Ltd. All rights reserved.

Time-resolved K α spectroscopy measurements of hot-electron equilibration dynamics in thin-foil solid targets: Collisional and collective effects

DOE PAGES

Nilson, P. M.; Solodov, A. A.; Davies, J. R.; ...

2015-09-25

Time-resolved K α spectroscopy measurements from high-intensity laser interactions with thin-foil solid targets are reviewed. Thin Cu foils were irradiated with 1- to 10-J, 1-ps pulses at focused intensities from 10 18 to 10 19 W/cm 2. The experimental data show K α-emission pulse widths from 3 to 6 ps, increasing with laser intensity. The time-resolved K α-emission data are compared to a hot-electron transport and K α-production model that includes collisional electron-energy coupling, resistive heating, and electromagnetic field effects. The experimental data show good agreement with the model when a reduced ponderomotive scaling is used to describe the initialmore » mean hot-electron energy over the relevant intensity range.« less

Megagauss magnetic fields in ultra-intense laser generated dense plasmas

NASA Astrophysics Data System (ADS)

Shaikh, Moniruzzaman; Lad, Amit D.; Jana, Kamalesh; Sarkar, Deep; Dey, Indranuj; Kumar, G. Ravindra

2017-01-01

Table-top terawatt lasers can create relativistic light intensities and launch megaampere electron pulses in a solid. These pulses induce megagauss (MG) magnetic pulses, which in turn strongly affect the hot electron transport via electromagnetic instabilities. It is therefore crucial to characterize the MG magnetic fields in great detail. Here, we present measurements of the spatio-temporal evolution of MG magnetic fields produced by a high contrast (picosecond intensity contrast 10-9) laser in a dense plasma on a solid target. The MG magnetic field is measured using the magneto-optic Cotton-Mouton effect, with a time delayed second harmonic (400 nm) probe. The magnetic pulse created by the high contrast laser in a glass target peaks much faster and has a more rapid fall than that induced by a low contrast (10-6) laser.

Generation of ultra-high-pressure shocks by collision of a fast plasma projectile driven in the laser-induced cavity pressure acceleration scheme with a solid target

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

Badziak, J.; Rosiński, M.; Krousky, E.

2015-03-15

A novel, efficient method of generating ultra-high-pressure shocks is proposed and investigated. In this method, the shock is generated by collision of a fast plasma projectile (a macro-particle) driven by laser-induced cavity pressure acceleration (LICPA) with a solid target placed at the LICPA accelerator channel exit. Using the measurements performed at the kilojoule PALS laser facility and two-dimensional hydrodynamic simulations, it is shown that the shock pressure ∼ Gbar can be produced with this method at the laser driver energy of only a few hundred joules, by an order of magnitude lower than the energy needed for production of suchmore » pressure with other laser-based methods known so far.« less

Theoretic criteria for antibody penetration into solid tumors and micrometastases.

PubMed

Thurber, Greg M; Zajic, Stefan C; Wittrup, K Dane

2007-06-01

Targeting tumors with antibody-based therapeutics is a complex task presenting multiple kinetic barriers. Antibody internalization and clearance inhibit uptake both in solid tumors, limited by tumor vascular permeability, and in micrometastases, limited by diffusion. A modeling exercise is used to introduce 2 simple criteria that must be less than unity for saturation of both tumors and micrometastases. The clearance modulus and the Thiele modulus are ratios of the plasma clearance rate and antibody catabolism, respectively, to the tumor tissue penetration rate. Even low rates of antigen internalization from constitutive membrane turnover can significantly retard antibody penetration. Rapid clearance of single-chain variable fragments also hinders uptake, often more than counterbalancing their more rapid extravasation and diffusion. The model illustrates that with the large resistance from the tumor capillary, antibodies may be more suitable for targeting micrometastases than vascularized tumors.

Petawatt laser absorption bounded

PubMed Central

Levy, Matthew C.; Wilks, Scott C.; Tabak, Max; Libby, Stephen B.; Baring, Matthew G.

2014-01-01

The interaction of petawatt (1015 W) lasers with solid matter forms the basis for advanced scientific applications such as table-top particle accelerators, ultrafast imaging systems and laser fusion. Key metrics for these applications relate to absorption, yet conditions in this regime are so nonlinear that it is often impossible to know the fraction of absorbed light f, and even the range of f is unknown. Here using a relativistic Rankine-Hugoniot-like analysis, we show for the first time that f exhibits a theoretical maximum and minimum. These bounds constrain nonlinear absorption mechanisms across the petawatt regime, forbidding high absorption values at low laser power and low absorption values at high laser power. For applications needing to circumvent the absorption bounds, these results will accelerate a shift from solid targets, towards structured and multilayer targets, and lead the development of new materials. PMID:24938656

Investigation of Surface Phenomena in Shocked Tin in Converging Geometry

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

Rousculp, Christopher L.; Oro, David Michael; Griego, Jeffrey Randall

2016-03-21

There is great interest in the behavior of the free surface of tin under shock loading. While it is known that meso-scale surface imperfections can seed the Richtmyer- Meshkov Instability (RMI) for a surface that is melted on release, much less is known about a tin surface that is solid, but plastically deforming. Here material properties such as shear and yield strength come into play especially in converging geometry. Previous experiments have been driven by direct contact HE. Usually a thin, flat target coupon is fielded with various single-mode, sinusoidal, machined, profiles on the free surface. The free surface ismore » adjacent to either vacuum or an inert receiver gas. Most of these previous driver/target configurations have been nominal planer geometry. With modern HE it has been straightforward to shock tin into melt on release. However it has been challenging to achieve a low enough pressure for solid state on release. Here we propose to extend the existing base of knowledge to include the behavior of the free surface of tin in cylindrical converging geometry. By shock loading a cylindrical tin shell with a magnetically driven cylindrical liner impactor, the free surface evolution can be diagnosed with proton radiography. With the PHELIX capacitor bank, the drive can easily be varied to span the pressure range to achieve solid, mixed, and liquid states on release. A conceptual cylindrical liner and target is shown in Figure 1.« less

Driving gene-engineered T cell immunotherapy of cancer

PubMed Central

Johnson, Laura A; June, Carl H

2017-01-01

Chimeric antigen receptor (CAR) gene-engineered T cell therapy holds the potential to make a meaningful difference in the lives of patients with terminal cancers. For decades, cancer therapy was based on biophysical parameters, with surgical resection to debulk, followed by radiation and chemotherapy to target the rapidly growing tumor cells, while mostly sparing quiescent normal tissues. One breakthrough occurred with allogeneic bone-marrow transplant for patients with leukemia, which provided a sometimes curative therapy. The field of adoptive cell therapy for solid tumors was established with the discovery that tumor-infiltrating lymphocytes could be expanded and used to treat and even cure patients with metastatic melanoma. Tumor-specific T-cell receptors (TCRs) were identified and engineered into patient peripheral blood lymphocytes, which were also found to treat tumors. However, these were limited by patient HLA-restriction. Close behind came generation of CAR, combining the exquisite recognition of an antibody with the effector function of a T cell. The advent of CD19-targeted CARs for treating patients with multiple forms of advanced B-cell malignancies met with great success, with up to 95% response rates. Applying CAR treatment to solid tumors, however, has just begun, but already certain factors have been made clear: the tumor target is of utmost importance for clinicians to do no harm; and solid tumors respond differently to CAR therapy compared with hematologic ones. Here we review the state of clinical gene-engineered T cell immunotherapy, its successes, challenges, and future. PMID:28025979

New target and detection methods: active detectors

NASA Astrophysics Data System (ADS)

Mittig, W.; Savajols, H.; Demonchy, C. E.; Giot, L.; Roussel-Chomaz, P.; Wang, H.; Ter-Akopian, G.; Fomichev, A.; Golovkov, M. S.; Stepansov, S.; Wolski, R.; Alamanos, N.; Drouart, A.; Gillibert, A.; Lapoux, V.; Pollacco, E.

2003-07-01

The study of nuclei far from stability interacting with simple target nuclei, such as protons, deuterons, 3He and 4He implies the use of inverse kinematics. The very special kinematics, together with the low intensities of the beams calls for special techniques. In july 2002 we tested a new detector, in which the detector gas is the target. This allows in principle a 4π solid angle of the detection, and a big effective target thickness without loss of resolution. The detector developped, called Maya, used isobuthane C4H10 as gas in present tests, and other gases are possible. The multiplexed electronics of more than 1000channels allows the reconstruction of the events occuring between the incoming particle and the detector gas atoms in 3D. Here we were interested in the elastic scattering of 8He on protons for the study of the isobaric analogue states (IAS) of 9He. The beam, in this case, is stopped in the detector. The resonance energy is determined by the place of interaction and the energy of the recoiling proton. The design of the detector is shown, together with some preliminary results are discussed.

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

Li, Li; Gu, Chun; Xu, Lixin, E-mail: xulixin@ustc.edu.cn

The self-adapting algorithms are improved to optimize a beam configuration in the direct drive laser fusion system with the solid state lasers. A configuration of 32 laser beams is proposed for achieving a high uniformity illumination, with a root-mean-square deviation at 10{sup −4} level. In our optimization, the parameters such as beam number, beam arrangement, and beam intensity profile are taken into account. The illumination uniformity robustness versus the parameters such as intensity profile deviations, power imbalance, intensity profile noise, the pointing error, and the target position error is also discussed. In this study, the model is assumed a solid-spheremore » illumination, and refraction effects of incident light on the corona are not considered. Our results may have a potential application in the design of the direct-drive laser fusion of the Shen Guang-II Upgrading facility (SG-II-U, China).« less

Atomic-level structure characterization of biomass pre- and post-lignin treatment by dynamic nuclear polarization-enhanced solid-state NMR

DOE PAGES

Perras, Frederic A.; Luo, Hao; Zhang, Ximing; ...

2016-12-27

Here, lignocellulosic biomass is a promising sustainable feedstock for the production of biofuels, biomaterials, and biospecialty chemicals. However, efficient utilization of biomass has been limited by our poor understanding of its molecular structure. Here, we report a dynamic nuclear polarization (DNP)-enhanced solid-state (SS)NMR study of the molecular structure of biomass, both pre- and postcatalytic treatment. This technique enables the measurement of 2D homonuclear 13C– 13C correlation SSNMR spectra under natural abundance, yielding, for the first time, an atomic-level picture of the structure of raw and catalytically treated biomass samples. We foresee that further such experiments could be used to determinemore » structure–function relationships and facilitate the development of more efficient, and chemically targeted, biomass-conversion technologies.« less

Atomic-level structure characterization of biomass pre- and post-lignin treatment by dynamic nuclear polarization-enhanced solid-state NMR

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

Perras, Frederic A.; Luo, Hao; Zhang, Ximing

Here, lignocellulosic biomass is a promising sustainable feedstock for the production of biofuels, biomaterials, and biospecialty chemicals. However, efficient utilization of biomass has been limited by our poor understanding of its molecular structure. Here, we report a dynamic nuclear polarization (DNP)-enhanced solid-state (SS)NMR study of the molecular structure of biomass, both pre- and postcatalytic treatment. This technique enables the measurement of 2D homonuclear 13C– 13C correlation SSNMR spectra under natural abundance, yielding, for the first time, an atomic-level picture of the structure of raw and catalytically treated biomass samples. We foresee that further such experiments could be used to determinemore » structure–function relationships and facilitate the development of more efficient, and chemically targeted, biomass-conversion technologies.« less

Dense gamma-ray and pair creation using ultra-intense lasers

NASA Astrophysics Data System (ADS)

Liang, Edison; Lo, Willie; Hasson, Hannah; Dyer, Gilliss; Clarke, Taylor; Fasanelli, Fabio; Yao, Kelly; Marchenka, Ilija; Henderson, Alexander; Dashko, Andriy; Zhang, Yuling; Ditmire, Todd

2016-10-01

We report recent results of gamma-ray and e +e- pair creation experiments using the Texas Petawatt laser (TPW) in Austin and the Trident laser at LANL irradiating solid high-Z targets. In addition to achieving record high densities of emerging gamma-rays and pairs at TPW, we measured in detail the spectra of hot electrons, positrons, and gamma-rays, and studied their spectral variation with laser and target parameters. A new type of gamma-ray spectrometer, called the scintillator attenuation spectrometer (SAS), was successfully demonstrated in Trident experiments in 2015. We will discuss the design and results of the SAS. Preliminary results of new experiments at TPW carried out in the summer of 2016 will also be presented.

SEPARATION AND PURIFICATION OF TWO MINOR COMPOUNDS FROM RADIX ISATIDIS BY INTEGRATIVE MPLC AND HSCCC WITH PREPARATIVE HPLC.

PubMed

Liang, Zhenjie; Li, Bin; Liang, Yong; Su, Yaping; Ito, Yoichiro

2015-01-01

Radix isatidis has been widely used as a Chinese traditional medicine for its anti-virus and anticancer activities where the minor components may contribute to these beneficial pharmaceutical effects. In order to enrich the target minor compounds effectively and rapidly, extraction, medium-pressure liquid chromatography (MPLC), high-speed countercurrent chromatography (HSCCC) and preparative high-performance liquid chromatography (pre-HPLC) were integratively used for separation and purification of two target minor compounds indole-3-acetonitrile-6-O-β-D-glucopyranoside (target 1) and clemastanin B (target 2) in the present study. Radix isatidis was dried, pulverized and extracted with 50% methanol at room temperature, then concentrated and subjected to pretreatment with D-101 macroporous resin chromatography and extraction by MPLC. The first target compound was separated by MPLC at the purity raised to 70-80%, but without the second minor compounds which were irreversibly adsorbed by C18 solid support. Therefore, the second target compound in the crude extract was directly separated by HSCCC at purity of 80-90%. Finally these refined samples were further separated by pre-HPLC to obtain a high purity at 98-99%. The chemical structure identification of each target compound was carried out by IR, ESI-MS and 1 H NMR.

Hydrogen isotope and light element profiling in solid tritium targets used for neutron production

NASA Astrophysics Data System (ADS)

Earwaker, L. G.; England, J. B. A.; Goldie, D. J.

1987-04-01

Five targets consisting of titanium tritide layers on copper backings have been investigated using nuclear reaction analysis. As these targets are commonly used to produce monoenergetic neutrons via the T(p, n) 3 He and T(d, n) 4 He reactions, it is important to know of the presence of other elements which may produce neutrons at different energies. The thicknesses of the titanium tritide layers were measured by observing the T(p, n) 3 He threshold yield curve and also the energy spread of the neutrons using a 3He-filled gridded ion chamber. Elastic recoil analysis with a particle identifying system was used to measure the hydrogen, deuterium, tritium and 3He content, and elastic scattering was used to study the carbon and oxygen. Surprisingly high concentrations of both hydrogen and oxygen were found on all targets, including the three which had never been used. Also surprising was the 3He content which was approximately the same for targets of all ages and conditions of use. As expected, the carbon content increased strongly with use, originating no doubt, from vacuum pump oil. Up to 3% deuterium atoms were observed in unused targets with much higher contents being recorded in used targets.

Galectin-9 Expression Predicts Favorable Clinical Outcome in Solid Tumors: A Systematic Review and Meta-Analysis

PubMed Central

Zhou, Xiaoxiang; Sun, Lejia; Jing, Dan; Xu, Gang; Zhang, Jinmei; Lin, Li; Zhao, Jingjing; Yao, Zhuoran; Lin, Hongfeng

2018-01-01

Background and Objective: Galectin-9 (Gal-9) is one of the galectin family members which are known as proteins with β-galactoside-binding affinity. Accumulative evidence suggest that Gal-9 plays multifaceted roles in tumor biology. However, the prognostic significance of Gal-9 in solid cancer patients remains controversial. The objective of the study was to clarify the prognostic significance of Gal-9 in solid tumors via meta-analysis. Methods: We searched PubMed, Embase and the Cochrane library for studies that report the correlation between Gal-9 expression and prognosis or clinicopathological parameters in solid cancer patients from inception to October 2017, with no language restriction. We calculated pooled hazard ratio (HR) and 95% confidence interval (CI) to investigate the prognostic significance of Gal-9 expression in solid tumors. We also calculated Odds ratio (OR) to explore the association between Gal-9 expression and clinicopathological features. Results: We included Fourteen studies with 2326 patients in our meta-analysis. The synthetic results revealed that high Gal-9 expression indicated improved overall survival (OS; HR = 0.70, 95% CI = 0.51–0.71, P = 0.006) but had no correlation with disease-free survival (DFS)/recurrence-free survival (RFS) (HR = 0.85, 95% CI = 0.51–1.41, P = 0.527) in solid tumors. In stratified analyses, high Gal-9 expression was significantly correlated with improved OS in hepatocellular carcinoma and colon cancer and with improved DFS/RFS in gastric cancer and non-small cell lung cancer. In addition, ethnicity and the method of data extraction didn’t affect the positive prognostic values of high Gal-9 expression. Moreover, high Gal-9 expression was significantly correlated with a smaller depth of invasion (TI/TII vs. TIII/TIV, OR = 2.80, 95% CI = 1.97–3.96, P < 0.001), an earlier histopathological stage (I/II vs. III/IV, OR = 3.00, 95% CI = 2.04–4.42, P < 0.001), negative lymph node metastasis (Presence vs. Absence, OR = 0.47, 95% CI = 0.25–0.89, P = 0.020) and negative distal tumor metastasis (Presence vs. Absence, OR = 13.85, 95% CI = 3.50–54.76, P < 0.001). Conclusion: Gal-9 expression indicates beneficial outcome in patients with solid tumors and is correlated with the pathogenesis of solid tumors. Gal-9 may serve as a prognostic biomarker and an emerging therapeutic target against solid tumors. PMID:29765332

Galectin-9 Expression Predicts Favorable Clinical Outcome in Solid Tumors: A Systematic Review and Meta-Analysis.

PubMed

Zhou, Xiaoxiang; Sun, Lejia; Jing, Dan; Xu, Gang; Zhang, Jinmei; Lin, Li; Zhao, Jingjing; Yao, Zhuoran; Lin, Hongfeng

2018-01-01

Background and Objective: Galectin-9 (Gal-9) is one of the galectin family members which are known as proteins with β-galactoside-binding affinity. Accumulative evidence suggest that Gal-9 plays multifaceted roles in tumor biology. However, the prognostic significance of Gal-9 in solid cancer patients remains controversial. The objective of the study was to clarify the prognostic significance of Gal-9 in solid tumors via meta-analysis. Methods: We searched PubMed, Embase and the Cochrane library for studies that report the correlation between Gal-9 expression and prognosis or clinicopathological parameters in solid cancer patients from inception to October 2017, with no language restriction. We calculated pooled hazard ratio (HR) and 95% confidence interval (CI) to investigate the prognostic significance of Gal-9 expression in solid tumors. We also calculated Odds ratio (OR) to explore the association between Gal-9 expression and clinicopathological features. Results: We included Fourteen studies with 2326 patients in our meta-analysis. The synthetic results revealed that high Gal-9 expression indicated improved overall survival (OS; HR = 0.70, 95% CI = 0.51-0.71, P = 0.006) but had no correlation with disease-free survival (DFS)/recurrence-free survival (RFS) (HR = 0.85, 95% CI = 0.51-1.41, P = 0.527) in solid tumors. In stratified analyses, high Gal-9 expression was significantly correlated with improved OS in hepatocellular carcinoma and colon cancer and with improved DFS/RFS in gastric cancer and non-small cell lung cancer. In addition, ethnicity and the method of data extraction didn't affect the positive prognostic values of high Gal-9 expression. Moreover, high Gal-9 expression was significantly correlated with a smaller depth of invasion (TI/TII vs. TIII/TIV, OR = 2.80, 95% CI = 1.97-3.96, P < 0.001), an earlier histopathological stage (I/II vs. III/IV, OR = 3.00, 95% CI = 2.04-4.42, P < 0.001), negative lymph node metastasis (Presence vs. Absence, OR = 0.47, 95% CI = 0.25-0.89, P = 0.020) and negative distal tumor metastasis (Presence vs. Absence, OR = 13.85, 95% CI = 3.50-54.76, P < 0.001). Conclusion: Gal-9 expression indicates beneficial outcome in patients with solid tumors and is correlated with the pathogenesis of solid tumors. Gal-9 may serve as a prognostic biomarker and an emerging therapeutic target against solid tumors.

Tunable mega-ampere electron current propagation in solids by dynamic control of lattice melt

DOE PAGES

MacLellan, D.  A.; Carroll, D.  C.; Gray, R.  J.; ...

2014-10-31

The influence of lattice-melt-induced resistivity gradients on the transport of mega-ampere currents of fast electrons in solids is investigated numerically and experimentally using laser-accelerated protons to induce isochoric heating. Tailoring the heating profile enables the resistive magnetic fields which strongly influence the current propagation to be manipulated. This tunable laser-driven process enables important fast electron beam properties, including the beam divergence, profile, and symmetry to be actively tailored, and without recourse to complex target manufacture.

Solid-phase Extraction Using Hierarchical Organosilicates for Enhanced Detection of Nitroenergetic Targets

DTIC Science & Technology

2011-01-01

THIS PAGE unclassified Standard Form 298 (Rev. 8-98) Prescribed by ANSI Std Z39-18 liquid or gas chromatography and do not Icnd themselves well...typically compatible with gas or liquid chromatography , and equilibration times can be lengthy. Other solid-phase extraction pTOtoools have utilized a...aniH M"X vr sat,~rat io~ of> an ~quifer o.r. soi ~. Surface water often contains from sea water was similar to recovery from deionized waier for ,:’ a

Quantitative Determination of Wax Contamination in Polystyrene HIPE Foam Using Solid-State NMR

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

Cluff, Kyle James; Goodwin, Lynne Alese; Hamilton, Christopher Eric

Differences in molecular mobility between polystyrene foam and Brij-78 wax results in vast differences in the 1H nuclear magnetic resonance (NMR) linewidth. This allows for the convenient determination of wax content in the polystyrene foam components of inertial confinement fusion targets via solid-state NMR. Lastly, contamination levels as low as 0.1% are easily recognized and quantified, and the detection limit is calculated to be 0.02% even when only 32 transients are recorded.

Cell and molecular mechanisms of pathogenesis and treatment of cancer.

PubMed Central

Rew, D. A.

1998-01-01

Surgery remains the mainstay of treatment for most classes of human solid tumours, with the principal exception of lymphomas, but it is insufficient in many cases to guarantee cure. With few exceptions, recurrent and metastatic solid tumours continue to defy attempts to develop effective adjuvant therapies. Recent insights into tumour biology reveal an increasingly complex picture of cell and molecular processes which confer heterogeneity and resistance to treatment upon tumours. These insights may also yield new targets for more effective adjuvant therapies. PMID:9616488

Quantitative Determination of Wax Contamination in Polystyrene HIPE Foam Using Solid-State NMR

DOE PAGES

Cluff, Kyle James; Goodwin, Lynne Alese; Hamilton, Christopher Eric; ...

2017-11-29

Differences in molecular mobility between polystyrene foam and Brij-78 wax results in vast differences in the 1H nuclear magnetic resonance (NMR) linewidth. This allows for the convenient determination of wax content in the polystyrene foam components of inertial confinement fusion targets via solid-state NMR. Lastly, contamination levels as low as 0.1% are easily recognized and quantified, and the detection limit is calculated to be 0.02% even when only 32 transients are recorded.

Shock wave as a probe of flux-dimited thermal transport in laser-heated solids

NASA Astrophysics Data System (ADS)

Smith, K.; Forsman, A.; Chiu, G.

1996-11-01

Laser-generated shock waves in solids result from the ablation of the target material. Where radiation transport is negligible, the ablation process is dominated by electron thermal conduction. This offers an opportunity to probe the degree of transport inhibition (compared with classical heat flow) for steep temperature gradients in a dense plasma. Using a 1-dimensional hydrodynamic code, we have examined the effect of flux-limited thermal conduction on the amplitude of the resulting shock wave.

Aural Discrimination of Targets by Human Subjects Using Broadband Sonar Pulses

DTIC Science & Technology

1982-10-01

in;’ Animal Sonai Systems: Biology and Bionics. RE Busnell. ed. Laboratoire de Physiologic.I Jouy-en-Josas 78. France, 1967. 6. Au. WW and KJ Snyder...1970. 11. Welton, PJ, Mde Billy. A Hayman and G Quentin, Backscattering of Short Ultrasonic Pulses by Solid Eastic Cylinders at Large /a, J Acoust Soc... G Quentin, Backscattering of Short Ultrasonic Pulses by Solid Elastic Cylinders at Large ka, J Acoust Soc Amer, 67, p 470-476, 1980. 12. Small, AM and

All optical electron injector using an intense ultrashort pulse laser and a solid wire target

NASA Astrophysics Data System (ADS)

Palchan, T.; Eisenmann, S.; Zigler, A.; Kaganovich, D.; Hubbard, R. F.; Fraenkel, M.; Fisher, D.; Henis, Z.

2006-05-01

Energetic electron bunches were generated by irradiating a solid tungsten wire 13 μm wide with 50 femtosecond pulses at an intensity of ˜3×1018 W/cm2. The electron yield, energy spectrum and angular distribution were measured. These energetic electron bunches are suitable for injection into a laser driven plasma accelerator. An all-optical electron injector based on this approach could simplify timing and alignment in future laser-plasma accelerator experiments.

Hypoxia regulates alternative splicing of HIF and non-HIF target genes.

PubMed

Sena, Johnny A; Wang, Liyi; Heasley, Lynn E; Hu, Cheng-Jun

2014-09-01

Hypoxia is a common characteristic of many solid tumors. The hypoxic microenvironment stabilizes hypoxia-inducible transcription factor 1α (HIF1α) and 2α (HIF2α/EPAS1) to activate gene transcription, which promotes tumor cell survival. The majority of human genes are alternatively spliced, producing RNA isoforms that code for functionally distinct proteins. Thus, an effective hypoxia response requires increased HIF target gene expression as well as proper RNA splicing of these HIF-dependent transcripts. However, it is unclear if and how hypoxia regulates RNA splicing of HIF targets. This study determined the effects of hypoxia on alternative splicing (AS) of HIF and non-HIF target genes in hepatocellular carcinoma cells and characterized the role of HIF in regulating AS of HIF-induced genes. The results indicate that hypoxia generally promotes exon inclusion for hypoxia-induced, but reduces exon inclusion for hypoxia-reduced genes. Mechanistically, HIF activity, but not hypoxia per se is found to be necessary and sufficient to increase exon inclusion of several HIF targets, including pyruvate dehydrogenase kinase 1 (PDK1). PDK1 splicing reporters confirm that transcriptional activation by HIF is sufficient to increase exon inclusion of PDK1 splicing reporter. In contrast, transcriptional activation of a PDK1 minigene by other transcription factors in the absence of endogenous HIF target gene activation fails to alter PDK1 RNA splicing. This study demonstrates a novel function of HIF in regulating RNA splicing of HIF target genes. ©2014 American Association for Cancer Research.

Rapid screening of selective serotonin re-uptake inhibitors in urine samples using solid-phase microextraction gas chromatography-mass spectrometry.

PubMed

Salgado-Petinal, Carmen; Lamas, J Pablo; Garcia-Jares, Carmen; Llompart, Maria; Cela, Rafael

2005-07-01

In this paper a solid-phase microextraction-gas chromatography-mass spectrometry (SPME-GC-MS) method is proposed for a rapid analysis of some frequently prescribed selective serotonin re-uptake inhibitors (SSRI)-venlafaxine, fluvoxamine, mirtazapine, fluoxetine, citalopram, and sertraline-in urine samples. The SPME-based method enables simultaneous determination of the target SSRI after simple in-situ derivatization of some of the target compounds. Calibration curves in water and in urine were validated and statistically compared. This revealed the absence of matrix effect and, in consequence, the possibility of quantifying SSRI in urine samples by external water calibration. Intra-day and inter-day precision was satisfactory for all the target compounds (relative standard deviation, RSD, <14%) and the detection limits achieved were <0.4 ng mL(-1) urine. The time required for the SPME step and for GC analysis (30 min each) enables high throughput. The method was applied to real urine samples from different patients being treated with some of these pharmaceuticals. Some SSRI metabolites were also detected and tentatively identified.

The Potential Role of Aerobic Exercise to Modulate Cardiotoxicity of Molecularly Targeted Cancer Therapeutics

PubMed Central

Lakoski, Susan; Mackey, John R.; Douglas, Pamela S.; Haykowsky, Mark J.; Jones, Lee W.

2013-01-01

Molecularly targeted therapeutics (MTT) are the future of cancer systemic therapy. They have already moved from palliative therapy for advanced solid malignancies into the setting of curative-intent treatment for early-stage disease. Cardiotoxicity is a frequent and potentially serious adverse complication of some targeted therapies, leading to a broad range of potentially life-threatening complications, therapy discontinuation, and poor quality of life. Low-cost pleiotropic interventions are therefore urgently required to effectively prevent and/or treat MTT-induced cardiotoxicity. Aerobic exercise therapy has the unique capacity to modulate, without toxicity, multiple gene expression pathways in several organ systems, including a plethora of cardiac-specific molecular and cell-signaling pathways implicated in MTT-induced cardiac toxicity. In this review, we examine the molecular signaling of antiangiogenic and HER2-directed therapies that may underpin cardiac toxicity and the hypothesized molecular mechanisms underlying the cardioprotective properties of aerobic exercise. It is hoped that this knowledge can be used to maximize the benefits of small molecule inhibitors, while minimizing cardiac damage in patients with solid malignancies. PMID:23335619

A novel solid lipid nanoparticle formulation for active targeting to tumor α(v) β(3) integrin receptors reveals cyclic RGD as a double-edged sword.

PubMed

Shuhendler, Adam J; Prasad, Preethy; Leung, Michael; Rauth, Andrew M; Dacosta, Ralph S; Wu, Xiao Yu

2012-09-01

The overexpression of α(v) β(3) integrin receptors on tumor cells and tumor vascular endothelium makes it a useful target for imaging, chemotherapy and anti-angiogenic therapy. However integrin-targeted delivery of therapeutics by nanoparticles have provided only marginal, if any, enhancement of therapeutic effect. This work was thus focused on the development of novel α(v) β(3) -targeted near infrared light-emitting solid lipid nanoparticles (SLN) through conjugation to the α(v) β(3) integrin-specific ligand cyclic Arg-Gly-Asp (cRGD), and the assessment of the effects of α(v) β(3) targeting on nanoparticle biodistribution. Since our previously developed non-targeted "stealth" SLN showed little hepatic accumulation, unlike most reported liposomes and micelles, they served as a reference for quantifying the effects of cRGD-conjugation on tumor uptake and whole animal biodistribution of SLN. Non-targeted SLN, actively targeted (RGD-SLN) and blocked RGD-SLN were prepared to contain near infrared quantum dots for live animal imaging. They were injected intravenously to nude mice bearing xenograft orthotopic human breast tumors or dorsal window chamber breast tumors. Tumor micropharmacokinetics of various SLN formulations were determined using intravital microscopy, and whole animal biodistribution was followed over time by optical imaging. The active tumor targeting with cRGD was found to be a "double-edged sword": while the specificity of RGD-SLN accumulation in tumor blood vessels and their tumor residence time increased, their distribution in the liver, spleen, and kidneys was significantly greater than the non-targeted SLN, leaving a smaller amount of nanoparticles in the tumor tissue. Nevertheless the enhanced specificity and retention of RGD-SLN in tumor neovasculature could make this novel formulation useful for tumor neovascular-specific therapies and imaging applications. Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Device and method for enhanced collection and assay of chemicals with high surface area ceramic

DOEpatents

Addleman, Raymond S.; Li, Xiaohong Shari; Chouyyok, Wilaiwan; Cinson, Anthony D.; Bays, John T.; Wallace, Krys

2016-02-16

A method and device for enhanced capture of target analytes is disclosed. This invention relates to collection of chemicals for separations and analysis. More specifically, this invention relates to a solid phase microextraction (SPME) device having better capability for chemical collection and analysis. This includes better physical stability, capacity for chemical collection, flexible surface chemistry and high affinity for target analyte.

Methods and apparatus for producing cryogenic inertially driven fusion targets

DOEpatents

Miller, John R.

1981-01-01

A new technique for producing uniform layers of solid DT on microballoon surfaces. Local heating of the target, typically by means of a focused laser, within an isothermal freezing cell containing a low pressure cryogenic exchange gas such as helium, vaporizes the DT fuel. Removal of the laser heating source causes the DT gas to rapidly condense and freeze in a layer which exhibits a good degree of uniformity.

Advancing cancer drug discovery towards more agile development of targeted combination therapies.

PubMed

Carragher, Neil O; Unciti-Broceta, Asier; Cameron, David A

2012-01-01

Current drug-discovery strategies are typically 'target-centric' and are based upon high-throughput screening of large chemical libraries against nominated targets and a selection of lead compounds with optimized 'on-target' potency and selectivity profiles. However, high attrition of targeted agents in clinical development suggest that combinations of targeted agents will be most effective in treating solid tumors if the biological networks that permit cancer cells to subvert monotherapies are identified and retargeted. Conventional drug-discovery and development strategies are suboptimal for the rational design and development of novel drug combinations. In this article, we highlight a series of emerging technologies supporting a less reductionist, more agile, drug-discovery and development approach for the rational design, validation, prioritization and clinical development of novel drug combinations.

Novel high-energy physics studies using intense lasers and plasmas

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

Leemans, Wim P.; Bulanov, Stepan; Esarey, Eric

2015-06-29

In the framework of the project “Novel high-energy physics studies using intense lasers and plasmas” we conducted the study of ion acceleration and “flying mirrors” with high intensity lasers in order to develop sources of ion beams and high frequency radiation for different applications. Since some schemes of laser ion acceleration are also considered a good source of “flying mirrors”, we proposed to investigate the mechanisms of “mirror” formation. As a result we were able to study the laser ion acceleration from thin foils and near critical density targets. We identified several fundamental factors limiting the acceleration in the RPAmore » regime and proposed the target design to compensate these limitations. In the case of near critical density targets, we developed a concept for the laser driven ion source for the hadron therapy. Also we studied the mechanism of “flying mirror” generation during the intense laser interaction with thin solid density targets. As for the laser-based positron creation and capture we initially proposed to study different regimes of positron beam generation and positron beam cooling. Since the for some of these schemes a good quality electron beam is required, we studied the generation of ultra-low emittance electron beams. In order to understand the fundamental physics of high energy electron beam interaction with high intensity laser pulses, which may affect the efficient generation of positron beams, we studied the radiation reaction effects.« less

Bremsstrahlung Dose Yield for High-Intensity Short-Pulse Laser–Solid Experiments

DOE PAGES

Liang, Taiee; Bauer, Johannes M.; Liu, James C.; ...

2016-12-01

A bremsstrahlung source term has been developed by the Radiation Protection (RP) group at SLAC National Accelerator Laboratory for high-intensity short-pulse laser–solid experiments between 10 17 and 10 22 W cm –2. This source term couples the particle-in-cell plasma code EPOCH and the radiation transport code FLUKA to estimate the bremsstrahlung dose yield from laser–solid interactions. EPOCH characterizes the energy distribution, angular distribution, and laser-to-electron conversion efficiency of the hot electrons from laser–solid interactions, and FLUKA utilizes this hot electron source term to calculate a bremsstrahlung dose yield (mSv per J of laser energy on target). The goal of thismore » paper is to provide RP guidelines and hazard analysis for high-intensity laser facilities. In conclusion, a comparison of the calculated bremsstrahlung dose yields to radiation measurement data is also made.« less

Targeted Therapy Directed by Genetic Testing in Treating Patients With Advanced Refractory Solid Tumors, Lymphomas, or Multiple Myeloma (The MATCH Screening Trial)

ClinicalTrials.gov

2018-06-25

Advanced Malignant Solid Neoplasm; Bladder Carcinoma; Breast Carcinoma; Cervical Carcinoma; Colon Carcinoma; Colorectal Carcinoma; Endometrial Carcinoma; Esophageal Carcinoma; Gastric Carcinoma; Glioma; Head and Neck Carcinoma; Kidney Carcinoma; Liver and Intrahepatic Bile Duct Carcinoma; Lung Carcinoma; Lymphoma; Malignant Uterine Neoplasm; Melanoma; Ovarian Carcinoma; Pancreatic Carcinoma; Plasma Cell Myeloma; Prostate Carcinoma; Rectal Carcinoma; Recurrent Bladder Carcinoma; Recurrent Breast Carcinoma; Recurrent Cervical Carcinoma; Recurrent Colon Carcinoma; Recurrent Colorectal Carcinoma; Recurrent Esophageal Carcinoma; Recurrent Gastric Carcinoma; Recurrent Glioma; Recurrent Head and Neck Carcinoma; Recurrent Liver Carcinoma; Recurrent Lung Carcinoma; Recurrent Lymphoma; Recurrent Malignant Solid Neoplasm; Recurrent Melanoma; Recurrent Ovarian Carcinoma; Recurrent Pancreatic Carcinoma; Recurrent Plasma Cell Myeloma; Recurrent Prostate Carcinoma; Recurrent Rectal Carcinoma; Recurrent Skin Carcinoma; Recurrent Thyroid Gland Carcinoma; Recurrent Uterine Corpus Carcinoma; Refractory Lymphoma; Refractory Malignant Solid Neoplasm; Refractory Plasma Cell Myeloma; Skin Carcinoma; Thyroid Gland Carcinoma; Uterine Corpus Cancer

Bremsstrahlung Dose Yield for High-Intensity Short-Pulse Laser–Solid Experiments

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

Liang, Taiee; Bauer, Johannes M.; Liu, James C.

A bremsstrahlung source term has been developed by the Radiation Protection (RP) group at SLAC National Accelerator Laboratory for high-intensity short-pulse laser–solid experiments between 10 17 and 10 22 W cm –2. This source term couples the particle-in-cell plasma code EPOCH and the radiation transport code FLUKA to estimate the bremsstrahlung dose yield from laser–solid interactions. EPOCH characterizes the energy distribution, angular distribution, and laser-to-electron conversion efficiency of the hot electrons from laser–solid interactions, and FLUKA utilizes this hot electron source term to calculate a bremsstrahlung dose yield (mSv per J of laser energy on target). The goal of thismore » paper is to provide RP guidelines and hazard analysis for high-intensity laser facilities. In conclusion, a comparison of the calculated bremsstrahlung dose yields to radiation measurement data is also made.« less

Pediatric Sarcomas Are Targetable by MR-Guided High Intensity Focused Ultrasound (MR-HIFU): Anatomical Distribution and Radiological Characteristics.

PubMed

Shim, Jenny; Staruch, Robert M; Koral, Korgun; Xie, Xian-Jin; Chopra, Rajiv; Laetsch, Theodore W

2016-10-01

Despite intensive therapy, children with metastatic and recurrent sarcoma or neuroblastoma have a poor prognosis. Magnetic resonance guided high intensity focused ultrasound (MR-HIFU) is a noninvasive technique allowing the delivery of targeted ultrasound energy under MR imaging guidance. MR-HIFU may be used to ablate tumors without ionizing radiation or target chemotherapy using hyperthermia. Here, we evaluated the anatomic locations of tumors to assess the technical feasibility of MR-HIFU therapy for children with solid tumors. Patients with sarcoma or neuroblastoma with available cross-sectional imaging were studied. Tumors were classified based on the location and surrounding structures within the ultrasound beam path as (i) not targetable, (ii) completely or partially targetable with the currently available MR-HIFU system, and (iii) potentially targetable if a respiratory motion compensation technique was used. Of the 121 patients with sarcoma and 61 patients with neuroblastoma, 64% and 25% of primary tumors were targetable at diagnosis, respectively. Less than 20% of metastases at diagnosis or relapse were targetable for both sarcoma and neuroblastoma. Most targetable lesions were located in extremities or in the pelvis. Respiratory motion compensation may increase the percentage of targetable tumors by 4% for sarcomas and 10% for neuroblastoma. Many pediatric sarcomas are localized at diagnosis and are targetable by current MR-HIFU technology. Some children with neuroblastoma have bony tumors targetable by MR-HIFU at relapse, but few newly diagnosed children with neuroblastoma have tumors amenable to MR-HIFU therapy. Clinical trials of MR-HIFU should focus on patients with anatomically targetable tumors. © 2016 Wiley Periodicals, Inc.

Hydrogen-deuterium substitution in solid ethanol by surface reactions at low temperatures

NASA Astrophysics Data System (ADS)

Oba, Yasuhiro; Osaka, Kazuya; Chigai, Takeshi; Kouchi, Akira; Watanabe, Naoki

2016-10-01

Ethanol (CH3CH2OH) is one of the most abundant complex organic molecules in star-forming regions. Despite its detection in the gas phase only, ethanol is believed to be formed by low-temperature grain-surface reactions. Methanol, the simplest alcohol, has been a target for observational, experimental, and theoretical studies in view of its deuterium enrichment in the interstellar medium; however, the deuterium chemistry of ethanol has not yet been an area of focus. Recently, deuterated dimethyl ether, a structural isomer of ethanol, was found in star-forming regions, indicating that deuterated ethanol can also be present in those environments. In this study, we performed laboratory experiments on the deuterium fractionation of solid ethanol at low temperatures through a reaction with deuterium (D) atoms at 10 K. Hydrogen (H)-D substitution, which increases the deuteration level, was found to occur on the ethyl group but not on the hydroxyl group. In addition, when deuterated ethanol (e.g. CD3CD2OD) solid was exposed to H atoms at 10 K, D-H substitution that reduced the deuteration level occurred on the ethyl group. Based on the results, it is likely that deuterated ethanol is present even under H-atom-dominant conditions in the interstellar medium.