Junction region of EWS-FLI1 fusion protein has a dominant negative effect in Ewing's sarcoma in vitro.

PubMed

Jully, Babu; Vijayalakshmi, Ramshankar; Gopal, Gopisetty; Sabitha, Kesavan; Rajkumar, Thangarajan

2012-11-12

Ewing's sarcoma is a malignancy characterized by a specific 11:22 chromosomal translocation which generates a novel EWS-FLI1 fusion protein functioning as an aberrant transcription factor. In the present study, we have further characterized the junction region of the EWS-FLI1 fusion protein. In-silico model of EWS-FLI1 fusion protein was analysed for ligand binding sites, and a putative region (amino acid (aa) 251-343 of the type 1 fusion protein) in the vicinity of the fusion junction was cloned and expressed using bacterial expression. The recombinant protein was characterized by Circular Dichroism (CD). We then expressed aa 251-280 ectopically in Ewing's sarcoma cell-line and its effect on cell proliferation, tumorigenicity and expression of EWS-FLI1 target genes were analysed. Our modelling analysis indicated that Junction region (aa 251-343) encompasses potential ligand biding sites in the EWS-FLI1 protein and when expressed in bacteria was present as soluble form. Ectopically expressing this region in Ewing's sarcoma cells inhibited tumorigenicity, and EWS-FLI1 target genes indicating a dominant negative biological effect. Junction region can be exploited further as target for drug development in future to specifically target EWS-FLI1 in Ewing's Sarcoma.

Multi-look fusion identification: a paradigm shift from quality to quantity in data samples

NASA Astrophysics Data System (ADS)

Wong, S.

2009-05-01

A multi-look identification method known as score-level fusion is found to be capable of achieving very high identification accuracy, even when low quality target signatures are used. Analysis using measured ground vehicle radar signatures has shown that a 97% correct identification rate can be achieved using this multi-look fusion method; in contrast, only a 37% accuracy rate is obtained when single target signature input is used. The results suggest that quantity can be used to replace quality of the target data in improving identification accuracy. With the advent of sensor technology, a large amount of target signatures of marginal quality can be captured routinely. This quantity over quality approach allows maximum exploitation of the available data to improve the target identification performance and this could have the potential of being developed into a disruptive technology.

Identifying transposon insertions and their effects from RNA-sequencing data.

PubMed

de Ruiter, Julian R; Kas, Sjors M; Schut, Eva; Adams, David J; Koudijs, Marco J; Wessels, Lodewyk F A; Jonkers, Jos

2017-07-07

Insertional mutagenesis using engineered transposons is a potent forward genetic screening technique used to identify cancer genes in mouse model systems. In the analysis of these screens, transposon insertion sites are typically identified by targeted DNA-sequencing and subsequently assigned to predicted target genes using heuristics. As such, these approaches provide no direct evidence that insertions actually affect their predicted targets or how transcripts of these genes are affected. To address this, we developed IM-Fusion, an approach that identifies insertion sites from gene-transposon fusions in standard single- and paired-end RNA-sequencing data. We demonstrate IM-Fusion on two separate transposon screens of 123 mammary tumors and 20 B-cell acute lymphoblastic leukemias, respectively. We show that IM-Fusion accurately identifies transposon insertions and their true target genes. Furthermore, by combining the identified insertion sites with expression quantification, we show that we can determine the effect of a transposon insertion on its target gene(s) and prioritize insertions that have a significant effect on expression. We expect that IM-Fusion will significantly enhance the accuracy of cancer gene discovery in forward genetic screens and provide initial insight into the biological effects of insertions on candidate cancer genes. © The Author(s) 2017. Published by Oxford University Press on behalf of Nucleic Acids Research.

Fusion of imaging and nonimaging data for surveillance aircraft

NASA Astrophysics Data System (ADS)

Shahbazian, Elisa; Gagnon, Langis; Duquet, Jean Remi; Macieszczak, Maciej; Valin, Pierre

1997-06-01

This paper describes a phased incremental integration approach for application of image analysis and data fusion technologies to provide automated intelligent target tracking and identification for airborne surveillance on board an Aurora Maritime Patrol Aircraft. The sensor suite of the Aurora consists of a radar, an identification friend or foe (IFF) system, an electronic support measures (ESM) system, a spotlight synthetic aperture radar (SSAR), a forward looking infra-red (FLIR) sensor and a link-11 tactical datalink system. Lockheed Martin Canada (LMCan) is developing a testbed, which will be used to analyze and evaluate approaches for combining the data provided by the existing sensors, which were initially not designed to feed a fusion system. Three concurrent research proof-of-concept activities provide techniques, algorithms and methodology into three sequential phases of integration of this testbed. These activities are: (1) analysis of the fusion architecture (track/contact/hybrid) most appropriate for the type of data available, (2) extraction and fusion of simple features from the imaging data into the fusion system performing automatic target identification, and (3) development of a unique software architecture which will permit integration and independent evolution, enhancement and optimization of various decision aid capabilities, such as multi-sensor data fusion (MSDF), situation and threat assessment (STA) and resource management (RM).

A minichaperone-based fusion system for producing insoluble proteins in soluble stable forms.

PubMed

Sharapova, Olga A; Yurkova, Maria S; Fedorov, Alexey N

2016-02-01

We have developed a fusion system for reliable production of insoluble hydrophobic proteins in soluble stable forms. A carrier is thermophilic minichaperone, GroEL apical domain (GrAD), a 15 kDa monomer able to bind diverse protein substrates. The Met-less variant of GrAD has been made for further convenient use of Met-specific CNBr chemical cleavage, if desired. The Met-less GrAD retained stability and solubility of the original protein. Target polypeptides can be fused to either C-terminus or N-terminus of GrAD. The system has been tested with two unrelated insoluble proteins fused to the C-terminus of GrAD. One of the proteins was also fused to GrAD N-terminus. The fusions formed inclusion bodies at 25°C and above and were partly soluble only at lower expression temperatures. Most importantly, however, after denaturation in urea, all fusions without exception were completely renatured in soluble stable forms that safely survived freezing-thawing as well as lyophilization. All fusions for both tested target proteins retained solubility at high concentrations for days. Functional analysis revealed that a target protein may retain functionality in the fusion. Convenience features include potential thermostability of GrAD fusions, capacity for chemical and enzymatic cleavage of a target and His6 tag for purification. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Percutaneous Thermal Ablation with Ultrasound Guidance. Fusion Imaging Guidance to Improve Conspicuity of Liver Metastasis

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

Hakime, Antoine, E-mail: thakime@yahoo.com; Yevich, Steven; Tselikas, Lambros

PurposeTo assess whether fusion imaging-guided percutaneous microwave ablation (MWA) can improve visibility and targeting of liver metastasis that were deemed inconspicuous on ultrasound (US).Materials and MethodsMWA of liver metastasis not judged conspicuous enough on US was performed under CT/US fusion imaging guidance. The conspicuity before and after the fusion imaging was graded on a five-point scale, and significance was assessed by Wilcoxon test. Technical success, procedure time, and procedure-related complications were evaluated.ResultsA total of 35 patients with 40 liver metastases (mean size 1.3 ± 0.4 cm) were enrolled. Image fusion improved conspicuity sufficiently to allow fusion-targeted MWA in 33 patients. The time requiredmore » for image fusion processing and tumors’ identification averaged 10 ± 2.1 min (range 5–14). Initial conspicuity on US by inclusion criteria was 1.2 ± 0.4 (range 0–2), while conspicuity after localization on fusion imaging was 3.5 ± 1 (range 1–5, p < 0.001). Technical success rate was 83% (33/40) in intention-to-treat analysis and 100% in analysis of treated tumors. There were no major procedure-related complications.ConclusionsFusion imaging broadens the scope of US-guided MWA to metastasis lacking adequate conspicuity on conventional US. Fusion imaging is an effective tool to increase the conspicuity of liver metastases that were initially deemed non visualizable on conventional US imaging.« less

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.

Developing the Pulsed Fission-Fusion (PuFF) Engine

NASA Technical Reports Server (NTRS)

Adams, Robert B.; Cassibry, Jason; Bradley, David; Fabisinski, Leo; Statham, Geoffrey

2014-01-01

In September 2013 the NASA Innovative Advanced Concept (NIAC) organization awarded a phase I contract to the PuFF team. Our phase 1 proposal researched a pulsed fission-fusion propulsion system that compressed a target of deuterium (D) and tritium (T) as a mixture in a column, surrounded concentrically by Uranium. The target is surrounded by liquid lithium. A high power current would flow down the liquid lithium and the resulting Lorentz force would compress the column by roughly a factor of 10. The compressed column would reach criticality and a combination of fission and fusion reactions would occur. Our Phase I results, summarized herein, review our estimates of engine and vehicle performance, our work to date to model the fission-fusion reaction, and our initial efforts in experimental analysis.

Low-energy nuclear reaction of the 14N+169Tm system: Incomplete fusion

NASA Astrophysics Data System (ADS)

Kumar, R.; Sharma, Vijay R.; Yadav, Abhishek; Singh, Pushpendra P.; Agarwal, Avinash; Appannababu, S.; Mukherjee, S.; Singh, B. P.; Ali, R.; Bhowmik, R. K.

2017-11-01

Excitation functions of reaction residues produced in the 14N+169Tm system have been measured to high precision at energies above the fusion barrier, ranging from 1.04 VB to 1.30 VB , and analyzed in the framework of the statistical model code pace4. Analysis of α -emitting channels points toward the onset of incomplete fusion even at slightly above-barrier energies where complete fusion is supposed to be one of the dominant processes. The onset and strength of incomplete fusion have been deduced and studied in terms of various entrance channel parameters. Present results together with the reanalysis of existing data for various projectile-target combinations conclusively suggest strong influence of projectile structure on the onset of incomplete fusion. Also, a strong dependence on the Coulomb effect (ZPZT) has been observed for the present system along with different projectile-target combinations available in the literature. It is concluded that the fraction of incomplete fusion linearly increases with ZPZT and is found to be more for larger ZPZT values, indicating significantly important linear systematics.

Targeted resequencing reveals ALK fusions in non-small cell lung carcinomas detected by FISH, immunohistochemistry, and real-time RT-PCR: a comparison of four methods.

PubMed

Tuononen, Katja; Sarhadi, Virinder Kaur; Wirtanen, Aino; Rönty, Mikko; Salmenkivi, Kaisa; Knuuttila, Aija; Remes, Satu; Telaranta-Keerie, Aino I; Bloor, Stuart; Ellonen, Pekka; Knuutila, Sakari

2013-01-01

Anaplastic lymphoma receptor tyrosine kinase (ALK) gene rearrangements occur in a subgroup of non-small cell lung carcinomas (NSCLCs). The identification of these rearrangements is important for guiding treatment decisions. The aim of our study was to screen ALK gene fusions in NSCLCs and to compare the results detected by targeted resequencing with results detected by commonly used methods, including fluorescence in situ hybridization (FISH), immunohistochemistry (IHC), and real-time reverse transcription-PCR (RT-PCR). Furthermore, we aimed to ascertain the potential of targeted resequencing in detection of ALK-rearranged lung carcinomas. We assessed ALK fusion status for 95 formalin-fixed paraffin-embedded tumor tissue specimens from 87 patients with NSCLC by FISH and real-time RT-PCR, for 57 specimens from 56 patients by targeted resequencing, and for 14 specimens from 14 patients by IHC. All methods were performed successfully on formalin-fixed paraffin-embedded tumor tissue material. We detected ALK fusion in 5.7% (5 out of 87) of patients examined. The results obtained from resequencing correlated significantly with those from FISH, real-time RT-PCR, and IHC. Targeted resequencing proved to be a promising method for ALK gene fusion detection in NSCLC. Means to reduce the material and turnaround time required for analysis are, however, needed.

Design of a multisensor data fusion system for target detection

NASA Astrophysics Data System (ADS)

Thomopoulos, Stelios C.; Okello, Nickens N.; Kadar, Ivan; Lovas, Louis A.

1993-09-01

The objective of this paper is to discuss the issues that are involved in the design of a multisensor fusion system and provide a systematic analysis and synthesis methodology for the design of the fusion system. The system under consideration consists of multifrequency (similar) radar sensors. However, the fusion design must be flexible to accommodate additional dissimilar sensors such as IR, EO, ESM, and Ladar. The motivation for the system design is the proof of the fusion concept for enhancing the detectability of small targets in clutter. In the context of down-selecting the proper configuration for multisensor (similar and dissimilar, and centralized vs. distributed) data fusion, the issues of data modeling, fusion approaches, and fusion architectures need to be addressed for the particular application being considered. Although the study of different approaches may proceed in parallel, the interplay among them is crucial in selecting a fusion configuration for a given application. The natural sequence for addressing the three different issues is to begin from the data modeling, in order to determine the information content of the data. This information will dictate the appropriate fusion approach. This, in turn, will lead to a global fusion architecture. Both distributed and centralized fusion architectures are used to illustrate the design issues along with Monte-Carlo simulation performance comparison of a single sensor versus a multisensor centrally fused system.

21 CFR 886.1880 - Fusion and stereoscopic target.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Fusion and stereoscopic target. 886.1880 Section... (CONTINUED) MEDICAL DEVICES OPHTHALMIC DEVICES Diagnostic Devices § 886.1880 Fusion and stereoscopic target. (a) Identification. A fusion and stereoscopic target is a device intended for use as a viewing object...

21 CFR 886.1880 - Fusion and stereoscopic target.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Fusion and stereoscopic target. 886.1880 Section... (CONTINUED) MEDICAL DEVICES OPHTHALMIC DEVICES Diagnostic Devices § 886.1880 Fusion and stereoscopic target. (a) Identification. A fusion and stereoscopic target is a device intended for use as a viewing object...

Range shortening, radiation transport, and Rayleigh-Taylor instability phenomena in ion-beam-driven inertial-fusion-reactor-size targets: Implosion, ignition, and burn phases

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

Long, K.A.; Tahir, N.A.

In this paper we present an analysis of the theory of the energy deposition of ions in cold materials and hot dense plasmas together with numerical calculations for heavy and light ions of interest to ion-beam fusion. We have used the g-smcapso-smcapsr-smcapsg-smcapso-smcapsn-smcaps computer code of Long, Moritz, and Tahir (which is an extension of the code originally written for protons by Nardi, Peleg, and Zinamon) to carry out these calculations. The energy-deposition data calculated in this manner has been used in the design of heavy-ion-beam-driven fusion targets suitable for a reactor, by its inclusion in the m-smcapse-smcapsd-smcapsu-smcapss-smcapsa-smcaps code of Christiansen,more » Ashby, and Roberts as extended by Tahir and Long. A number of other improvements have been made in this code and these are also discussed. Various aspects of the theoretical analysis of such targets are discussed including the calculation of the hydrodynamic stability, the hydrodynamic efficiency, and the gain. Various different target designs have been used, some of them new. In general these targets are driven by Bi/sup +/ ions of energy 8--12 GeV, with an input energy of 4--6.5 MJ, with output energies in the range 600--900 MJ, and with gains in the range 120--180. The peak powers are in the range of 500--750 TW. We present detailed calculations of the ablation, compression, ignition, and burn phases. By the application of a new stability analysis which includes ablation and density-gradient effects we show that these targets appear to implode in a stable manner. Thus the targets designed offer working examples suited for use in a future inertial-confinement fusion reactor.« less

A pretargeted nanoparticle system for tumor cell labeling

PubMed Central

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

2011-01-01

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

A pretargeted nanoparticle system for tumor cell labeling.

PubMed

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

2011-03-01

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

External Heat Transfer Coefficient Measurements on a Surrogate Indirect Inertial Confinement Fusion Target

DOE PAGES

Miles, Robin; Havstad, Mark; LeBlanc, Mary; ...

2015-09-15

External heat transfer coefficients were measured around a surrogate Indirect inertial confinement fusion (ICF) based on the Laser Inertial Fusion Energy (LIFE) design target to validate thermal models of the LIFE target during flight through a fusion chamber. Results indicate that heat transfer coefficients for this target 25-50 W/m 2∙K are consistent with theoretically derived heat transfer coefficients and valid for use in calculation of target heating during flight through a fusion chamber.

A color fusion method of infrared and low-light-level images based on visual perception

NASA Astrophysics Data System (ADS)

Han, Jing; Yan, Minmin; Zhang, Yi; Bai, Lianfa

2014-11-01

The color fusion images can be obtained through the fusion of infrared and low-light-level images, which will contain both the information of the two. The fusion images can help observers to understand the multichannel images comprehensively. However, simple fusion may lose the target information due to inconspicuous targets in long-distance infrared and low-light-level images; and if targets extraction is adopted blindly, the perception of the scene information will be affected seriously. To solve this problem, a new fusion method based on visual perception is proposed in this paper. The extraction of the visual targets ("what" information) and parallel processing mechanism are applied in traditional color fusion methods. The infrared and low-light-level color fusion images are achieved based on efficient typical targets learning. Experimental results show the effectiveness of the proposed method. The fusion images achieved by our algorithm can not only improve the detection rate of targets, but also get rich natural information of the scenes.

Hierarchical Multi-atlas Label Fusion with Multi-scale Feature Representation and Label-specific Patch Partition

PubMed Central

Wu, Guorong; Kim, Minjeong; Sanroma, Gerard; Wang, Qian; Munsell, Brent C.; Shen, Dinggang

2014-01-01

Multi-atlas patch-based label fusion methods have been successfully used to improve segmentation accuracy in many important medical image analysis applications. In general, to achieve label fusion a single target image is first registered to several atlas images, after registration a label is assigned to each target point in the target image by determining the similarity between the underlying target image patch (centered at the target point) and the aligned image patch in each atlas image. To achieve the highest level of accuracy during the label fusion process it’s critical the chosen patch similarity measurement accurately captures the tissue/shape appearance of the anatomical structure. One major limitation of existing state-of-the-art label fusion methods is that they often apply a fixed size image patch throughout the entire label fusion procedure. Doing so may severely affect the fidelity of the patch similarity measurement, which in turn may not adequately capture complex tissue appearance patterns expressed by the anatomical structure. To address this limitation, we advance state-of-the-art by adding three new label fusion contributions: First, each image patch now characterized by a multi-scale feature representation that encodes both local and semi-local image information. Doing so will increase the accuracy of the patch-based similarity measurement. Second, to limit the possibility of the patch-based similarity measurement being wrongly guided by the presence of multiple anatomical structures in the same image patch, each atlas image patch is further partitioned into a set of label-specific partial image patches according to the existing labels. Since image information has now been semantically divided into different patterns, these new label-specific atlas patches make the label fusion process more specific and flexible. Lastly, in order to correct target points that are mislabeled during label fusion, a hierarchically approach is used to improve the label fusion results. In particular, a coarse-to-fine iterative label fusion approach is used that gradually reduces the patch size. To evaluate the accuracy of our label fusion approach, the proposed method was used to segment the hippocampus in the ADNI dataset and 7.0 tesla MR images, sub-cortical regions in LONI LBPA40 dataset, mid-brain regions in SATA dataset from MICCAI 2013 segmentation challenge, and a set of key internal gray matter structures in IXI dataset. In all experiments, the segmentation results of the proposed hierarchical label fusion method with multi-scale feature representations and label-specific atlas patches are more accurate than several well-known state-of-the-art label fusion methods. PMID:25463474

Cloning and expression of a novel antifreeze protein AFP72 from the beetle Tenebrio molitor.

PubMed

Yan, Qing-Hua; Yang, Li; Wang, Qing; Zhang, Hui-Rong; Shao, Qiang

2012-01-01

A novel antifreeze protein AFP72 cDNA (GenBbank accession No. AY929389) was obtained by RT-PCR from Tenebrio molitor. The 216 bp fragment encodes a protein of 72 amino acid residues. Sequence analysis revealed that the cDNA displays a high degree of homology with T. molitor antifreeze proteins, ranging up to 90.78%. Recombinant plasmids pMAL-p2X-afp72 and pMAL-c2X-afp72 were transferred into E. coil TBI to induce a MBP fusion protein by IPTG. The target fusion protein was released from the periplasm and cytoplasm by the cold osmotic shock procedure and sonication respectively. The content of the fusion protein came up to 38.9 and 41.5% of the total dissolved protein, respectively. The fusion protein was purified through an amylose affinity column, and incised by factor Xa. Molecular sieve chromatography was used to achieve a high state of purity of the target protein. The purified target protein displayed a single band in SDS-PAGE. The fusion protein was shown to increase resistance to low temperatures in bacteria. This finding could help in further investigations of the properties and function of antifreeze proteins.

Premature activation of the paramyxovirus fusion protein before target cell attachment with corruption of the viral fusion machinery.

PubMed

Farzan, Shohreh F; Palermo, Laura M; Yokoyama, Christine C; Orefice, Gianmarco; Fornabaio, Micaela; Sarkar, Aurijit; Kellogg, Glen E; Greengard, Olga; Porotto, Matteo; Moscona, Anne

2011-11-04

Paramyxoviruses, including the childhood pathogen human parainfluenza virus type 3, enter host cells by fusion of the viral and target cell membranes. This fusion results from the concerted action of its two envelope glycoproteins, the hemagglutinin-neuraminidase (HN) and the fusion protein (F). The receptor-bound HN triggers F to undergo conformational changes that render it competent to mediate fusion of the viral and cellular membranes. We proposed that, if the fusion process could be activated prematurely before the virion reaches the target host cell, infection could be prevented. We identified a small molecule that inhibits paramyxovirus entry into target cells and prevents infection. We show here that this compound works by an interaction with HN that results in F-activation prior to receptor binding. The fusion process is thereby prematurely activated, preventing fusion of the viral membrane with target cells and precluding viral entry. This first evidence that activation of a paramyxovirus F can be specifically induced before the virus contacts its target cell suggests a new strategy with broad implications for the design of antiviral agents.

A novel tumor-activated ALA fusion protein for specific inhibition on the growth and invasion of breast cancer cells MDA-MB-231.

PubMed

Liu, Xiufeng; Liu, Xintong; Sunchen, Suwen; Liu, Meixia; Shen, Chen; Wu, Juanjuan; Zhao, Wanli; Yu, Boyang; Liu, Jihua

2017-11-01

The aim of this research was to develop a novel ALA fusion protein for target to the malignant cells surface with high uPAR expression and locally release of the scorpion toxin AGAP in an uPA-cleavable manner. It will provide an effective approach for controlled release of the peptide toxins to treat cancerous cells. The ALA fusion proteins were expressed in pichia pastoris, and the recombinant proteins were purified by Ni-NTA affinity chromatography. The proteins were added to human breast cancer cells (MDA-MB-231) and human embryonic kidney cells (HEK-293) in order to investigate the characteristic of selective targeting and releasing of scorpion toxin AGAP in cancer cells with high uPAR expression. The inhibitory effect of ALA on MDA-MB-231, MCF7, LO2 and HEK-293 was evaluated by MTT assay. Moreover, the antiproliferation mechanism of ALA was determined by flow cytometric and western blot analysis. The results showed that ALA could target MDA-MB-231 cells and the scorpion toxin AGAP could be released with high efficiency and selectivity. ALA inhibited the growth and invasion of breast cancer cells MDA-MB231. Also, cell apoptosis pathway was found to be associated with the inhibition mechanism of ALA according to the data of flow cytometric and western blot analysis. Therefore, ALA could be a novel antitumor candidate for targeting treatment of malignant cell. This study successfully demonstrated that fusion of biotoxins with tumor target domain could provide a simple yet effective way to delivery of peptide or protein drugs.

Flunarizine Prevents Hepatitis C Virus Membrane Fusion in a Genotype-dependent Manner by Targeting the Potential Fusion Peptide within E1

PubMed Central

Perin, Paula M.; Haid, Sibylle; Brown, Richard J. P.; Doerrbecker, Juliane; Schulze, Kai; Zeilinger, Carsten; von Schaewen, Markus; Heller, Brigitte; Vercauteren, Koen; Luxenburger, Eva; Baktash, Yasmine M.; Vondran, Florian W. R.; Speerstra, Sietkse; Awadh, Abdullah; Mukhtarov, Furkat; Schang, Luis M; Kirschning, Andreas; Müller, Rolf; Guzman, Carlos A.; Kaderali, Lars; Randall, Glenn; Meuleman, Philip; Ploss, Alexander; Pietschmann, Thomas

2015-01-01

To explore mechanisms of hepatitis C virus (HCV) replication we screened a compound library including licensed drugs. Flunarizine, a diphenylmethylpiperazine used to treat migraine, inhibited HCV cell entry in vitro and in vivo in a genotype-dependent fashion. Analysis of mosaic viruses between susceptible and resistant strains revealed that E1 and E2 glycoproteins confer susceptibility to flunarizine. Time of addition experiments and single particle tracking of HCV demonstrated that flunarizine specifically prevents membrane fusion. Related phenothiazines and pimozide also inhibited HCV infection and preferentially targeted HCV genotype 2 viruses. However, phenothiazines and pimozide exhibited improved genotype coverage including the difficult to treat genotype 3. Flunarizine-resistant HCV carried mutations within the alleged fusion peptide and displayed cross-resistance to these compounds, indicating that these drugs have a common mode of action. Conclusion: These observations reveal novel details about HCV membrane fusion. Moreover, flunarizine and related compounds represent first-in-class HCV fusion inhibitors that merit consideration for repurposing as cost-effective component of HCV combination therapies. PMID:26248546

Concordance of preclinical and clinical pharmacology and toxicology of therapeutic monoclonal antibodies and fusion proteins: cell surface targets

PubMed Central

Bugelski, Peter J; Martin, Pauline L

2012-01-01

Monoclonal antibodies (mAbs) and fusion proteins directed towards cell surface targets make an important contribution to the treatment of disease. The purpose of this review was to correlate the clinical and preclinical data on the 15 currently approved mAbs and fusion proteins targeted to the cell surface. The principal sources used to gather data were: the peer reviewed Literature; European Medicines Agency ‘Scientific Discussions’; and the US Food and Drug Administration ‘Pharmacology/Toxicology Reviews’ and package inserts (United States Prescribing Information). Data on the 15 approved biopharmaceuticals were included: abatacept; abciximab; alefacept; alemtuzumab; basiliximab; cetuximab; daclizumab; efalizumab; ipilimumab; muromonab; natalizumab; panitumumab; rituximab; tocilizumab; and trastuzumab. For statistical analysis of concordance, data from these 15 were combined with data on the approved mAbs and fusion proteins directed towards soluble targets. Good concordance with human pharmacodynamics was found for mice receiving surrogates or non-human primates (NHPs) receiving the human pharmaceutical. In contrast, there was poor concordance for human pharmacodynamics in genetically deficient mice and for human adverse effects in all three test systems. No evidence that NHPs have superior predictive value was found. PMID:22168282

Statistical sensor fusion analysis of near-IR polarimetric and thermal imagery for the detection of minelike targets

NASA Astrophysics Data System (ADS)

Weisenseel, Robert A.; Karl, William C.; Castanon, David A.; DiMarzio, Charles A.

1999-02-01

We present an analysis of statistical model based data-level fusion for near-IR polarimetric and thermal data, particularly for the detection of mines and mine-like targets. Typical detection-level data fusion methods, approaches that fuse detections from individual sensors rather than fusing at the level of the raw data, do not account rationally for the relative reliability of different sensors, nor the redundancy often inherent in multiple sensors. Representative examples of such detection-level techniques include logical AND/OR operations on detections from individual sensors and majority vote methods. In this work, we exploit a statistical data model for the detection of mines and mine-like targets to compare and fuse multiple sensor channels. Our purpose is to quantify the amount of knowledge that each polarimetric or thermal channel supplies to the detection process. With this information, we can make reasonable decisions about the usefulness of each channel. We can use this information to improve the detection process, or we can use it to reduce the number of required channels.

Heterogeneous Vision Data Fusion for Independently Moving Cameras

DTIC Science & Technology

2010-03-01

target detection , tracking , and identification over a large terrain. The goal of the project is to investigate and evaluate the existing image...fusion algorithms, develop new real-time algorithms for Category-II image fusion, and apply these algorithms in moving target detection and tracking . The...moving target detection and classification. 15. SUBJECT TERMS Image Fusion, Target Detection , Moving Cameras, IR Camera, EO Camera 16. SECURITY

Sensor fusion III: 3-D perception and recognition; Proceedings of the Meeting, Boston, MA, Nov. 5-8, 1990

NASA Technical Reports Server (NTRS)

Schenker, Paul S. (Editor)

1991-01-01

The volume on data fusion from multiple sources discusses fusing multiple views, temporal analysis and 3D motion interpretation, sensor fusion and eye-to-hand coordination, and integration in human shape perception. Attention is given to surface reconstruction, statistical methods in sensor fusion, fusing sensor data with environmental knowledge, computational models for sensor fusion, and evaluation and selection of sensor fusion techniques. Topics addressed include the structure of a scene from two and three projections, optical flow techniques for moving target detection, tactical sensor-based exploration in a robotic environment, and the fusion of human and machine skills for remote robotic operations. Also discussed are K-nearest-neighbor concepts for sensor fusion, surface reconstruction with discontinuities, a sensor-knowledge-command fusion paradigm for man-machine systems, coordinating sensing and local navigation, and terrain map matching using multisensing techniques for applications to autonomous vehicle navigation.

Eradication of Human Hepatic and Pulmonary Melanoma Metastases in SCID Mice by Antibody--Interleukin 2 Fusion Proteins

NASA Astrophysics Data System (ADS)

Becker, Jurgen C.; Pancook, James D.; Gillies, Stephen D.; Mendelsohn, John; Reisfeld, Ralph A.

1996-04-01

Antibody--cytokine fusion proteins combine the unique targeting ability of antibodies with the multifunctional activity of cytokines. Here, we demonstrate the therapeutic efficacy of such constructs for the treatment of hepatic and pulmonary metastases of different melanoma cell lines. Two antibody--interleukin 2 (IL-2) fusion proteins, ch225-IL2 and ch14.18-IL2, constructed by fusion of a synthetic sequence coding for human IL-2 to the carboxyl end of the Cγ 1 gene of the corresponding antibodies, were tested for their therapeutic efficacy against xenografted human melanoma in vivo. Tumorspecific fusion proteins completely inhibited the growth of hepatic and pulmonary metastases in C.B-17 scid/scid mice previously reconstituted with human lymphokine-activated killer cells, whereas treatment with combinations of the corresponding antibodies plus recombinant IL-2 only reduced the tumor load. Even when treatment with fusion proteins was delayed up to 8 days after inoculation of tumor cells, it still resulted in complete eradication of micrometastases that were established at that time point. Selection of tumor cell lines expressing or lacking the targeted antigen of the administered fusion protein proved the specificity of the observed antitumor effect. Biodistribution analysis demonstrated that the tumorspecific fusion protein accumulated not only in subcutaneous tumors but also in lungs and livers affected with micrometastases. Survival times of animals treated with the fusion protein were more than doubled as compared to those treated with the combination of the corresponding antibody plus IL-2. Our data demonstrate that an immunotherapeutic approach using cytokines targeted by antibodies to tumor sites has potent effects against disseminated human melanoma.

Cost Modeling and Design of Field-Reversed Configuration Fusion Power Plants

NASA Astrophysics Data System (ADS)

Kirtley, David; Slough, John; Helion Team

2017-10-01

The Inductively Driven Liner (IDL) fusion concept uses the magnetically driven implosion of thin (0.5-1 mm) Aluminum hoops to magnetically compress a merged Field-Reversed Configuration (FRC) plasma to fusion conditions. Both the driver and the target have been studied experimentally and theoretically by researchers at Helion Energy, MSNW, and the University of Washington, demonstrating compression fields greater than 100 T and suitable fusion targets. In the presented study, a notional power plant facility using this approach will be described. In addition, a full cost study based on the LLNL Z-IFE and HYLIFE-II studies, the ARIES Tokamak concept, and RAND power plant studies will be described. Finally, the expected capital costs, development requirements, and LCOE for 50 and 500 MW power plants will be given. This analysis includes core FRC plant scaling, metallic liner recycling, radiation shielding, operations, and facilities capital requirements.

Infrared and visible image fusion with the target marked based on multi-resolution visual attention mechanisms

NASA Astrophysics Data System (ADS)

Huang, Yadong; Gao, Kun; Gong, Chen; Han, Lu; Guo, Yue

2016-03-01

During traditional multi-resolution infrared and visible image fusion processing, the low contrast ratio target may be weakened and become inconspicuous because of the opposite DN values in the source images. So a novel target pseudo-color enhanced image fusion algorithm based on the modified attention model and fast discrete curvelet transformation is proposed. The interesting target regions are extracted from source images by introducing the motion features gained from the modified attention model, and source images are performed the gray fusion via the rules based on physical characteristics of sensors in curvelet domain. The final fusion image is obtained by mapping extracted targets into the gray result with the proper pseudo-color instead. The experiments show that the algorithm can highlight dim targets effectively and improve SNR of fusion image.

Alternative divertor target concepts for next step fusion devices

NASA Astrophysics Data System (ADS)

Mazul, I. V.

2016-12-01

The operational conditions of a divertor target in the next steps of fusion devices are more severe in comparison with ITER. The current divertor designs and technologies have a limited application concerning these conditions, and so new design concepts/technologies are required. The main reasons which practically prevent the use of the traditional motionless solid divertor target are analyzed. We describe several alternative divertor target concepts in this paper. The comparative analysis of these concepts (including the advantages and the drawbacks) is made and the prospects for their practical implementation are prioritized. The concept of the swept divertor target with a liquid metal interlayer between the moving armour and motionless heat-sink is presented in more detail. The critical issues of this design are listed and outlined, and the possible experiments are presented.

Fusion-based multi-target tracking and localization for intelligent surveillance systems

NASA Astrophysics Data System (ADS)

Rababaah, Haroun; Shirkhodaie, Amir

2008-04-01

In this paper, we have presented two approaches addressing visual target tracking and localization in complex urban environment. The two techniques presented in this paper are: fusion-based multi-target visual tracking, and multi-target localization via camera calibration. For multi-target tracking, the data fusion concepts of hypothesis generation/evaluation/selection, target-to-target registration, and association are employed. An association matrix is implemented using RGB histograms for associated tracking of multi-targets of interests. Motion segmentation of targets of interest (TOI) from the background was achieved by a Gaussian Mixture Model. Foreground segmentation, on other hand, was achieved by the Connected Components Analysis (CCA) technique. The tracking of individual targets was estimated by fusing two sources of information, the centroid with the spatial gating, and the RGB histogram association matrix. The localization problem is addressed through an effective camera calibration technique using edge modeling for grid mapping (EMGM). A two-stage image pixel to world coordinates mapping technique is introduced that performs coarse and fine location estimation of moving TOIs. In coarse estimation, an approximate neighborhood of the target position is estimated based on nearest 4-neighbor method, and in fine estimation, we use Euclidean interpolation to localize the position within the estimated four neighbors. Both techniques were tested and shown reliable results for tracking and localization of Targets of interests in complex urban environment.

Adaptation of Decoy Fusion Strategy for Existing Multi-Stage Search Workflows

NASA Astrophysics Data System (ADS)

Ivanov, Mark V.; Levitsky, Lev I.; Gorshkov, Mikhail V.

2016-09-01

A number of proteomic database search engines implement multi-stage strategies aiming at increasing the sensitivity of proteome analysis. These approaches often employ a subset of the original database for the secondary stage of analysis. However, if target-decoy approach (TDA) is used for false discovery rate (FDR) estimation, the multi-stage strategies may violate the underlying assumption of TDA that false matches are distributed uniformly across the target and decoy databases. This violation occurs if the numbers of target and decoy proteins selected for the second search are not equal. Here, we propose a method of decoy database generation based on the previously reported decoy fusion strategy. This method allows unbiased TDA-based FDR estimation in multi-stage searches and can be easily integrated into existing workflows utilizing popular search engines and post-search algorithms.

FusionHub: A unified web platform for annotation and visualization of gene fusion events in human cancer.

PubMed

Panigrahi, Priyabrata; Jere, Abhay; Anamika, Krishanpal

2018-01-01

Gene fusion is a chromosomal rearrangement event which plays a significant role in cancer due to the oncogenic potential of the chimeric protein generated through fusions. At present many databases are available in public domain which provides detailed information about known gene fusion events and their functional role. Existing gene fusion detection tools, based on analysis of transcriptomics data usually report a large number of fusion genes as potential candidates, which could be either known or novel or false positives. Manual annotation of these putative genes is indeed time-consuming. We have developed a web platform FusionHub, which acts as integrated search engine interfacing various fusion gene databases and simplifies large scale annotation of fusion genes in a seamless way. In addition, FusionHub provides three ways of visualizing fusion events: circular view, domain architecture view and network view. Design of potential siRNA molecules through ensemble method is another utility integrated in FusionHub that could aid in siRNA-based targeted therapy. FusionHub is freely available at https://fusionhub.persistent.co.in.

Highly specific targeting of the TMPRSS2/ERG fusion gene using liposomal nanovectors

PubMed Central

Shao, Longjiang; Tekedereli, Ibrahim; Wang, Jianghua; Yuca, Erkan; Tsang, Susan; Sood, Anil; Lopez-Berestein, Gabriel; Ozpolat, Bulent; Ittmann, Michael

2012-01-01

Purpose The TMPRSS2/ERG (T/E) fusion gene is present in half of all prostate cancer (PCa) tumors. Fusion of the oncogenic ERG gene with the androgen-regulated TMPRSS2 gene promoter results in expression of fusion mRNAs in PCa cells. The junction of theTMPRSS2 and ERG derived portions of the fusion mRNA constitutes a cancer specific target in cells containing the T/E fusion gene. Targeting the most common alternatively spliced fusion gene mRNA junctional isoforms in vivo using siRNAs in liposomal nanovectors may potentially be a novel, low toxicity treatment for PCa. Experimental Design We designed and optimized siRNAs targeting the two most common T/E fusion gene mRNA junctional isoforms (Type III or Type VI). Specificity of siRNAs was assessed by transient co-transfection in vitro. To test their ability to inhibit growth of PCa cells expressing these fusion gene isoforms in vivo, specific siRNAs in liposomal nanovectors were used to treat mice bearing orthotopic or subcutaneous xenograft tumors expressing the targeted fusion isoforms. Results The targeting siRNAs were both potent and highly specific in vitro. In vivo they significantly inhibited tumor growth. The degree of growth inhibition was variable and was correlated with the extent of fusion gene knockdown. The growth inhibition was associated with marked inhibition of angiogenesis and, to a lesser degree, proliferation and a marked increase in apoptosis of tumor cells. No toxicity was observed. Conclusions Targeting the T/E fusion junction in vivo with specific siRNAs delivered via liposomal nanovectors is a promising therapy for men with PCa. PMID:23052253

Highly specific targeting of the TMPRSS2/ERG fusion gene using liposomal nanovectors.

PubMed

Shao, Longjiang; Tekedereli, Ibrahim; Wang, Jianghua; Yuca, Erkan; Tsang, Susan; Sood, Anil; Lopez-Berestein, Gabriel; Ozpolat, Bulent; Ittmann, Michael

2012-12-15

The TMPRSS2/ERG (T/E) fusion gene is present in half of all prostate cancer tumors. Fusion of the oncogenic ERG gene with the androgen-regulated TMPRSS2 gene promoter results in expression of fusion mRNAs in prostate cancer cells. The junction of theTMPRSS2- and ERG-derived portions of the fusion mRNA constitutes a cancer-specific target in cells containing the T/E fusion gene. Targeting the most common alternatively spliced fusion gene mRNA junctional isoforms in vivo using siRNAs in liposomal nanovectors may potentially be a novel, low-toxicity treatment for prostate cancer. We designed and optimized siRNAs targeting the two most common T/E fusion gene mRNA junctional isoforms (type III or type VI). Specificity of siRNAs was assessed by transient co-transfection in vitro. To test their ability to inhibit growth of prostate cancer cells expressing these fusion gene isoforms in vivo, specific siRNAs in liposomal nanovectors were used to treat mice bearing orthotopic or subcutaneous xenograft tumors expressing the targeted fusion isoforms. The targeting siRNAs were both potent and highly specific in vitro. In vivo they significantly inhibited tumor growth. The degree of growth inhibition was variable and was correlated with the extent of fusion gene knockdown. The growth inhibition was associated with marked inhibition of angiogenesis and, to a lesser degree, proliferation and a marked increase in apoptosis of tumor cells. No toxicity was observed. Targeting the T/E fusion junction in vivo with specific siRNAs delivered via liposomal nanovectors is a promising therapy for men with prostate cancer. ©2012 AACR.

Magnetized Target Fusion Driven by Plasma Liners

NASA Technical Reports Server (NTRS)

Thio, Y. C. Francis; Kirkpatrick, Ronald C.; Knapp, Charles E.; Rodgers, Stephen L. (Technical Monitor)

2002-01-01

Magnetized target fusion is an emerging, relatively unexplored approach to fusion for electrical power and propulsion application. The physical principles of the concept are founded upon both inertial confinement fusion (ICF) and magnetic confinement fusion (MCF). It attempts to combine the favorable attributes of both these orthogonal approaches to fusion, but at the same time, avoiding the extreme technical challenges of both by exploiting a fusion regime intermediate between them. It uses a material liner to compress, heat and contain the fusion reacting plasma (the target plasma) mentally. By doing so, the fusion burn could be made to occur at plasma densities as high as six orders of magnitude higher than conventional MCF such as tokamak, thus leading to an approximately three orders of magnitude reduction in the plasma energy required for ignition. It also uses a transient magnetic field, compressed to extremely high intensity (100's T to 1000T) in the target plasma, to slow down the heat transport to the liner and to increase the energy deposition of charged-particle fusion products. This has several compounding beneficial effects. It leads to longer energy confinement time compared with conventional ICF without magnetized target, and thus permits the use of much lower plasma density to produce reasonable burn-up fraction. The compounding effects of lower plasma density and the magneto-insulation of the target lead to greatly reduced compressional heating power on the target. The increased energy deposition rate of charged-particle fusion products also helps to lower the energy threshold required for ignition and increasing the burn-up fraction. The reduction in ignition energy and the compressional power compound to lead to reduced system size, mass and R&D cost. It is a fusion approach that has an affordable R&D pathway, and appears attractive for propulsion application in the nearer term.

Novel kinase fusion transcripts found in endometrial cancer

PubMed Central

Tamura, Ryo; Yoshihara, Kosuke; Yamawaki, Kaoru; Suda, Kazuaki; Ishiguro, Tatsuya; Adachi, Sosuke; Okuda, Shujiro; Inoue, Ituro; Verhaak, Roel G. W.; Enomoto, Takayuki

2015-01-01

Recent advances in RNA-sequencing technology have enabled the discovery of gene fusion transcripts in the transcriptome of cancer cells. However, it remains difficult to differentiate the therapeutically targetable fusions from passenger events. We have analyzed RNA-sequencing data and DNA copy number data from 25 endometrial cancer cell lines to identify potential therapeutically targetable fusion transcripts, and have identified 124 high-confidence fusion transcripts, of which 69% are associated with gene amplifications. As targetable fusion candidates, we focused on three in-frame kinase fusion transcripts that retain a kinase domain (CPQ-PRKDC, CAPZA2-MET, and VGLL4-PRKG1). We detected only CPQ-PRKDC fusion transcript in three of 122 primary endometrial cancer tissues. Cell proliferation of the fusion-positive cell line was inhibited by knocking down the expression of wild-type PRKDC but not by blocking the CPQ-PRKDC fusion transcript expression. Quantitative real-time RT-PCR demonstrated that the expression of the CPQ-PRKDC fusion transcript was significantly lower than that of wild-type PRKDC, corresponding to a low transcript allele fraction of this fusion, based on RNA-sequencing read counts. In endometrial cancers, the CPQ-PRKDC fusion transcript may be a passenger aberration related to gene amplification. Our findings suggest that transcript allele fraction is a useful predictor to find bona-fide therapeutic-targetable fusion transcripts. PMID:26689674

Novel kinase fusion transcripts found in endometrial cancer.

PubMed

Tamura, Ryo; Yoshihara, Kosuke; Yamawaki, Kaoru; Suda, Kazuaki; Ishiguro, Tatsuya; Adachi, Sosuke; Okuda, Shujiro; Inoue, Ituro; Verhaak, Roel G W; Enomoto, Takayuki

2015-12-22

Recent advances in RNA-sequencing technology have enabled the discovery of gene fusion transcripts in the transcriptome of cancer cells. However, it remains difficult to differentiate the therapeutically targetable fusions from passenger events. We have analyzed RNA-sequencing data and DNA copy number data from 25 endometrial cancer cell lines to identify potential therapeutically targetable fusion transcripts, and have identified 124 high-confidence fusion transcripts, of which 69% are associated with gene amplifications. As targetable fusion candidates, we focused on three in-frame kinase fusion transcripts that retain a kinase domain (CPQ-PRKDC, CAPZA2-MET, and VGLL4-PRKG1). We detected only CPQ-PRKDC fusion transcript in three of 122 primary endometrial cancer tissues. Cell proliferation of the fusion-positive cell line was inhibited by knocking down the expression of wild-type PRKDC but not by blocking the CPQ-PRKDC fusion transcript expression. Quantitative real-time RT-PCR demonstrated that the expression of the CPQ-PRKDC fusion transcript was significantly lower than that of wild-type PRKDC, corresponding to a low transcript allele fraction of this fusion, based on RNA-sequencing read counts. In endometrial cancers, the CPQ-PRKDC fusion transcript may be a passenger aberration related to gene amplification. Our findings suggest that transcript allele fraction is a useful predictor to find bona-fide therapeutic-targetable fusion transcripts.

Cluster-impact fusion, or beam-contaminant fusion? (abstract)a),b)

NASA Astrophysics Data System (ADS)

Lo, Daniel H.; Petrasso, Richard D.; Wenzel, Kevin W.

1992-10-01

Beuhler, Friedlander, and Friedman (BFF) reported anomalously huge D-D fusion rates while bombarding deuterated targets with (D2O)N+ clusters (N˜25-1000) accelerated to ≊325 keV [R. J. Beuhler et al., Phys. Rev. Lett. 63, 1292 (1989); R. J. Beuhler et al., J. Phys. Chem. 94, 7665 (1990)] [i.e., ≊0.3 keV lab energy for D in (D2O)100+]. However, from our analysis of BFF's fusion product spectra, we conclude that their D lab energy was ˜50 keV. Therefore, no gross anomalies exist. Also, from our analysis of the BFF beam-ranging experiments through 500 μg/cm2 of Au, we conclude that light-ion-beam contaminants (e.g., D+ of order 100 keV) have not been ruled out, and are the probable cause of their fusion reactions. This work was supported by LLNL Subcontract B116798, Department of Energy (DOE) Grant No. DE-FG02-91ER54109, DOE Magnetic Fusion Energy Technology Fellowship Program (D. H. Lo), and DOE Fusion Energy Postdoctoral Research Program (Kevin W. Wenzel).

ChimerDB 3.0: an enhanced database for fusion genes from cancer transcriptome and literature data mining.

PubMed

Lee, Myunggyo; Lee, Kyubum; Yu, Namhee; Jang, Insu; Choi, Ikjung; Kim, Pora; Jang, Ye Eun; Kim, Byounggun; Kim, Sunkyu; Lee, Byungwook; Kang, Jaewoo; Lee, Sanghyuk

2017-01-04

Fusion gene is an important class of therapeutic targets and prognostic markers in cancer. ChimerDB is a comprehensive database of fusion genes encompassing analysis of deep sequencing data and manual curations. In this update, the database coverage was enhanced considerably by adding two new modules of The Cancer Genome Atlas (TCGA) RNA-Seq analysis and PubMed abstract mining. ChimerDB 3.0 is composed of three modules of ChimerKB, ChimerPub and ChimerSeq. ChimerKB represents a knowledgebase including 1066 fusion genes with manual curation that were compiled from public resources of fusion genes with experimental evidences. ChimerPub includes 2767 fusion genes obtained from text mining of PubMed abstracts. ChimerSeq module is designed to archive the fusion candidates from deep sequencing data. Importantly, we have analyzed RNA-Seq data of the TCGA project covering 4569 patients in 23 cancer types using two reliable programs of FusionScan and TopHat-Fusion. The new user interface supports diverse search options and graphic representation of fusion gene structure. ChimerDB 3.0 is available at http://ercsb.ewha.ac.kr/fusiongene/. © The Author(s) 2016. Published by Oxford University Press on behalf of Nucleic Acids Research.

Fusion Energy and Stopping Power in a Degenerate DT Pellet Driven by a Laser-Accelerated Proton Beam

NASA Astrophysics Data System (ADS)

Mehrangiz, M.; Ghasemizad, A.; Jafari, S.; Khanbabaei, B.

2016-06-01

In this paper, we have improved the fast ignition scheme in order to have more authority needed for high-energy-gain. Due to the more penetrability and energy deposition of the particle beams in fusion targets, we employ a laser-to-ion converter foil as a scheme for generating energetic ion beams to ignite the fusion fuel. We find the favorable intensity and wavelength of incident laser by evaluating the laser-proton conversion gain. By calculating the source-target distance, proton beam power and energy are estimated. Our analysis is generalized to the plasma degeneracy effects which can increase the fusion gain several orders of magnitude by decreasing the ion-electron collisions in the plasma. It is found that the wavelength of 0.53 μm and the intensity of about 1020 W/cm2, by saving about 10% conversion coefficient, are the suitable measured values for converting a laser into protons. Besides, stopping power and fusion burn calculations have been done in degenerate and non-degenerate plasma mediums. The results indicate that in the presence of degeneracy, the rate of fusion enhances. Supported by the Research Council of University of Guilan

Pharmacokinetics and safety in rhesus monkeys of a monoclonal antibody-GDNF fusion protein for targeted blood-brain barrier delivery.

PubMed

Pardridge, William M; Boado, Ruben J

2009-10-01

Glial-derived neurotrophic factor (GDNF) is a potential therapy for stroke, Parkinson's disease, or drug addiction. However, GDNF does not cross the blood-brain barrier (BBB). GDNF is re-engineered as a fusion protein with a chimeric monoclonal antibody (MAb) to the human insulin receptor (HIR), which acts as a molecular Trojan horse to deliver the GDNF across the BBB. The pharmacokinetics (PK), toxicology, and safety pharmacology of the HIRMAb-GDNF fusion protein were investigated in Rhesus monkeys. The fusion protein was administered as an intravenous injection at doses up to 50 mg/kg over a 60 h period to 56 Rhesus monkeys. The plasma concentration of the HIRMAb-GDNF fusion protein was measured with a 2-site sandwich ELISA. No adverse events were observed in a 2-week terminal toxicology study, and no neuropathologic changes were observed. The PK analysis showed a linear relationship between plasma AUC and dose, a large systemic volume of distribution, as well as high clearance rates of 8-10 mL/kg/min. A no-observable-adverse-effect level is established in the Rhesus monkey for the acute administration of the HIRMAb-GDNF fusion protein. The fusion protein targeting the insulin receptor has a PK profile similar to a classical small molecule.

Magnetized Target Fusion Driven by Plasma Liners

NASA Technical Reports Server (NTRS)

Thio, Y. C. Francis; Cassibry, Jason; Eskridge, Richard; Kirkpatrick, Ronald C.; Knapp, Charles E.; Lee, Michael; Martin, Adam; Smith, James; Wu, S. T.; Rodgers, Stephen L. (Technical Monitor)

2001-01-01

For practical applications of magnetized target fusion, standoff drivers to deliver the imploding momentum flux to the target plasma remotely are required. Quasi-spherically converging plasma jets have been proposed as standoff drivers for this purpose. The concept involves the dynamic formation of a quasi-spherical plasma liner by the merging of plasma jets, and the use of the liner so formed to compress a spheromak or a field reversed configuration (FRC). Theoretical analysis and computer modeling of the concept are presented. It is shown that, with the appropriate choice of the flow parameters in the liner and the target, the impact between the liner and the target plasma can be made to be shockless in the liner or to generate at most a very weak shock in the liner. Additional information is contained in the original extended abstract.

New High Gain Target Design for a Laser Fusion Power Plant

DTIC Science & Technology

2000-06-07

target with a minimum energy gain, about 100. Demonstration of ignition or low gain is only important for fusion energy if it leads into a target concept...nonlinear saturation of these instabilities. Our approach is to try to avoid them. 4. A Development Path to Fusion Energy The laser and target concept...on the exact date required to develop fusion energy , it would be worthwhile for a power plant development program to provide enough time and funds

Expression and activity analysis of a new fusion protein targeting ovarian cancer cells.

PubMed

Su, Manman; Chang, Weiqin; Wang, Dingding; Cui, Manhua; Lin, Yang; Wu, Shuying; Xu, Tianmin

2015-09-01

The aim of the present study was to develop a new therapeutic drug to improve the prognosis of ovarian cancer patients. Human urokinase-type plasminogen activator (uPA)17-34-kunitz-type protease inhibitor (KPI) eukaryotic expression vector was constructed and recombinant human uPA17-34-KPI (rhuPA17-34-KPI) in P. pastoris was expressed. In the present study, the DNA sequences that encode uPA 17-34 amino acids were created according to the native amino acids sequence and inserted into the KPI-pPICZαC vector, which was constructed. Then, uPA17‑34-KPI-pPICZαC was transformed into P. pastoris X-33, and rhuPA17-34-KPI was expressed by induction of methanol. The bioactivities of a recombinant fusion protein were detected with trypsin inhibition analysis, and the inhibitory effects on the growth of ovarian cancer cells were identified using the TUNEL assay, in vitro wound‑healing assay and Matrigel model analysis. The results of the DNA sequence analysis of the recombinant vector uPA17-34-KPI‑pPICZα demonstrated that the DNA‑encoding human uPA 17-34 amino acids, 285-288 amino acids of amyloid precursor protein (APP) and 1-57 amino acids of KPI were correctly inserted into the pPICZαC vector. Following induction by methonal, the fusion protein with a molecular weight of 8.8 kDa was observed using SDS-PAGE and western blot analysis. RhuPA17-34-KPI was expressed in P. pastoris with a yield of 50 mg/l in a 50-ml tube. The recombinant fusion protein was able to inhibit the activity of trypsin, inhibit growth and induce apoptosis of SKOV3 cells, and inhibit the invasion and metastasis of ovarian cancer cells. By considering uPA17-34 amino acid specific binding uPAR as the targeted part of fusion protein and utilizing the serine protease inhibitor activity of KPI, it was found that the recombinant fusion protein uPA17-34-KPI inhibited the invasion and metastasis of ovarian tumors, and may therefore be regarded as effective in targeted treatment.

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

Kirkpatrick, R. C.

Nuclear fusion was discovered experimentally in 1933-34 and other charged particle nuclear reactions were documented shortly thereafter. Work in earnest on the fusion ignition problem began with Edward Teller's group at Los Alamos during the war years. His group quantified all the important basic atomic and nuclear processes and summarized their interactions. A few years later, the success of the early theory developed at Los Alamos led to very successful thermonuclear weapons, but also to decades of unsuccessful attempts to harness fusion as an energy source of the future. The reasons for this history are many, but it seems appropriatemore » to review some of the basics with the objective of identifying what is essential for success and what is not. This tutorial discusses only the conditions required for ignition in small fusion targets and how the target design impacts driver requirements. Generally speaking, the driver must meet the energy, power and power density requirements needed by the fusion target. The most relevant parameters for ignition of the fusion fuel are the minimum temperature and areal density (rhoR), but these parameters set secondary conditions that must be achieved, namely an implosion velocity, target size and pressure, which are interrelated. Despite the apparent simplicity of inertial fusion targets, there is not a single mode of fusion ignition, and the necessary combination of minimum temperature and areal density depends on the mode of ignition. However, by providing a magnetic field of sufficient strength, the conditions needed for fusion ignition can be drastically altered. Magnetized target fusion potentially opens up a vast parameter space between the extremes of magnetic and inertial fusion.« less

Airborne Infrared and Visible Image Fusion Combined with Region Segmentation

PubMed Central

Zuo, Yujia; Liu, Jinghong; Bai, Guanbing; Wang, Xuan; Sun, Mingchao

2017-01-01

This paper proposes an infrared (IR) and visible image fusion method introducing region segmentation into the dual-tree complex wavelet transform (DTCWT) region. This method should effectively improve both the target indication and scene spectrum features of fusion images, and the target identification and tracking reliability of fusion system, on an airborne photoelectric platform. The method involves segmenting the region in an IR image by significance, and identifying the target region and the background region; then, fusing the low-frequency components in the DTCWT region according to the region segmentation result. For high-frequency components, the region weights need to be assigned by the information richness of region details to conduct fusion based on both weights and adaptive phases, and then introducing a shrinkage function to suppress noise; Finally, the fused low-frequency and high-frequency components are reconstructed to obtain the fusion image. The experimental results show that the proposed method can fully extract complementary information from the source images to obtain a fusion image with good target indication and rich information on scene details. They also give a fusion result superior to existing popular fusion methods, based on eithers subjective or objective evaluation. With good stability and high fusion accuracy, this method can meet the fusion requirements of IR-visible image fusion systems. PMID:28505137

Airborne Infrared and Visible Image Fusion Combined with Region Segmentation.

PubMed

Zuo, Yujia; Liu, Jinghong; Bai, Guanbing; Wang, Xuan; Sun, Mingchao

2017-05-15

This paper proposes an infrared (IR) and visible image fusion method introducing region segmentation into the dual-tree complex wavelet transform (DTCWT) region. This method should effectively improve both the target indication and scene spectrum features of fusion images, and the target identification and tracking reliability of fusion system, on an airborne photoelectric platform. The method involves segmenting the region in an IR image by significance, and identifying the target region and the background region; then, fusing the low-frequency components in the DTCWT region according to the region segmentation result. For high-frequency components, the region weights need to be assigned by the information richness of region details to conduct fusion based on both weights and adaptive phases, and then introducing a shrinkage function to suppress noise; Finally, the fused low-frequency and high-frequency components are reconstructed to obtain the fusion image. The experimental results show that the proposed method can fully extract complementary information from the source images to obtain a fusion image with good target indication and rich information on scene details. They also give a fusion result superior to existing popular fusion methods, based on eithers subjective or objective evaluation. With good stability and high fusion accuracy, this method can meet the fusion requirements of IR-visible image fusion systems.

Challenges Surrounding the Injection and Arrival of Targets at LIFE Fusion Chamber Center

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

Miles, R; Spaeth, M; Manes, K

2010-12-01

IFE target designers must consider several engineering requirements in addition to the physics requirements for successful target implosion. These considerations include low target cost, high manufacturing throughput, the ability of the target to survive the injection into the fusion chamber and arrive in a condition and physical position consistent with proper laser-target interaction and ease of post-implosion debris removal. This article briefly describes these considerations for the Laser Inertial Fusion-based Energy (LIFE) targets currently being designed.

Inertial Fusion Power Plant Concept of Operations and Maintenance

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

Anklam, T.; Knutson, B.; Dunne, A. M.

2015-01-15

Parsons and LLNL scientists and engineers performed design and engineering work for power plant pre-conceptual designs based on the anticipated laser fusion demonstrations at the National Ignition Facility (NIF). Work included identifying concepts of operations and maintenance (O&M) and associated requirements relevant to fusion power plant systems analysis. A laser fusion power plant would incorporate a large process and power conversion facility with a laser system and fusion engine serving as the heat source, based in part on some of the systems and technologies advanced at NIF. Process operations would be similar in scope to those used in chemical, oilmore » refinery, and nuclear waste processing facilities, while power conversion operations would be similar to those used in commercial thermal power plants. While some aspects of the tritium fuel cycle can be based on existing technologies, many aspects of a laser fusion power plant presents several important and unique O&M requirements that demand new solutions. For example, onsite recovery of tritium; unique remote material handling systems for use in areas with high radiation, radioactive materials, or high temperatures; a five-year fusion engine target chamber replacement cycle with other annual and multi-year cycles anticipated for major maintenance of other systems, structures, and components (SSC); and unique SSC for fusion target waste recycling streams. This paper describes fusion power plant O&M concepts and requirements, how O&M requirements could be met in design, and how basic organizational and planning issues can be addressed for a safe, reliable, economic, and feasible fusion power plant.« less

Inertial fusion power plant concept of operations and maintenance

NASA Astrophysics Data System (ADS)

Knutson, Brad; Dunne, Mike; Kasper, Jack; Sheehan, Timothy; Lang, Dwight; Anklam, Tom; Roberts, Valerie; Mau, Derek

2015-02-01

Parsons and LLNL scientists and engineers performed design and engineering work for power plant pre-conceptual designs based on the anticipated laser fusion demonstrations at the National Ignition Facility (NIF). Work included identifying concepts of operations and maintenance (O&M) and associated requirements relevant to fusion power plant systems analysis. A laser fusion power plant would incorporate a large process and power conversion facility with a laser system and fusion engine serving as the heat source, based in part on some of the systems and technologies advanced at NIF. Process operations would be similar in scope to those used in chemical, oil refinery, and nuclear waste processing facilities, while power conversion operations would be similar to those used in commercial thermal power plants. While some aspects of the tritium fuel cycle can be based on existing technologies, many aspects of a laser fusion power plant presents several important and unique O&M requirements that demand new solutions. For example, onsite recovery of tritium; unique remote material handling systems for use in areas with high radiation, radioactive materials, or high temperatures; a five-year fusion engine target chamber replacement cycle with other annual and multi-year cycles anticipated for major maintenance of other systems, structures, and components (SSC); and unique SSC for fusion target waste recycling streams. This paper describes fusion power plant O&M concepts and requirements, how O&M requirements could be met in design, and how basic organizational and planning issues can be addressed for a safe, reliable, economic, and feasible fusion power plant.

RNA sequencing of esophageal adenocarcinomas identifies novel fusion transcripts, including NPC1-MELK, arising from a complex chromosomal rearrangement.

PubMed

Wang, Zhixiong; Cheng, Yulan; Abraham, John M; Yan, Rong; Liu, Xi; Chen, Wei; Ibrahim, Sariat; Schroth, Gary P; Ke, Xiquan; He, Yulong; Meltzer, Stephen J

2017-10-15

Studies of chromosomal rearrangements and fusion transcripts have elucidated mechanisms of tumorigenesis and led to targeted cancer therapies. This study was aimed at identifying novel fusion transcripts in esophageal adenocarcinoma (EAC). To identify new fusion transcripts associated with EAC, targeted RNA sequencing and polymerase chain reaction (PCR) verification were performed in 40 EACs and matched nonmalignant specimens from the same patients. Genomic PCR and Sanger sequencing were performed to find the breakpoint of fusion genes. Five novel in-frame fusion transcripts were identified and verified in 40 EACs and in a validation cohort of 15 additional EACs (55 patients in all): fibroblast growth factor receptor 2 (FGFR2)-GRB2-associated binding protein 2 (GAB2) in 2 of 55 or 3.6%, Niemann-Pick C1 (NPC1)-maternal embryonic leucine zipper kinase (MELK) in 2 of 55 or 3.6%, ubiquitin-specific peptidase 54 (USP54)-calcium/calmodulin dependent protein kinase II γ (CAMK2G) in 2 of 55 or 3.6%, megakaryoblastic leukemia (translocation) 1 (MKL1)-fibulin 1 (FBLN1) in 1 of 55 or 1.8%, and CCR4-NOT transcription complex subunit 2 (CNOT2)-chromosome 12 open reading frame 49 (C12orf49) in 1 of 55 or 1.8%. A genomic analysis indicated that NPC1-MELK arose from a complex interchromosomal translocation event involving chromosomes 18, 3, and 9 with 3 rearrangement points, and this was consistent with chromoplexy. These data indicate that fusion transcripts occur at a stable frequency in EAC. Furthermore, our results indicate that chromoplexy is an underlying mechanism that generates fusion transcripts in EAC. These and other fusion transcripts merit further study as diagnostic markers and potential therapeutic targets in EAC. Cancer 2017;123:3916-24. © 2017 American Cancer Society. © 2017 American Cancer Society.

A tri-modality image fusion method for target delineation of brain tumors in radiotherapy.

PubMed

Guo, Lu; Shen, Shuming; Harris, Eleanor; Wang, Zheng; Jiang, Wei; Guo, Yu; Feng, Yuanming

2014-01-01

To develop a tri-modality image fusion method for better target delineation in image-guided radiotherapy for patients with brain tumors. A new method of tri-modality image fusion was developed, which can fuse and display all image sets in one panel and one operation. And a feasibility study in gross tumor volume (GTV) delineation using data from three patients with brain tumors was conducted, which included images of simulation CT, MRI, and 18F-fluorodeoxyglucose positron emission tomography (18F-FDG PET) examinations before radiotherapy. Tri-modality image fusion was implemented after image registrations of CT+PET and CT+MRI, and the transparency weight of each modality could be adjusted and set by users. Three radiation oncologists delineated GTVs for all patients using dual-modality (MRI/CT) and tri-modality (MRI/CT/PET) image fusion respectively. Inter-observer variation was assessed by the coefficient of variation (COV), the average distance between surface and centroid (ADSC), and the local standard deviation (SDlocal). Analysis of COV was also performed to evaluate intra-observer volume variation. The inter-observer variation analysis showed that, the mean COV was 0.14(± 0.09) and 0.07(± 0.01) for dual-modality and tri-modality respectively; the standard deviation of ADSC was significantly reduced (p<0.05) with tri-modality; SDlocal averaged over median GTV surface was reduced in patient 2 (from 0.57 cm to 0.39 cm) and patient 3 (from 0.42 cm to 0.36 cm) with the new method. The intra-observer volume variation was also significantly reduced (p = 0.00) with the tri-modality method as compared with using the dual-modality method. With the new tri-modality image fusion method smaller inter- and intra-observer variation in GTV definition for the brain tumors can be achieved, which improves the consistency and accuracy for target delineation in individualized radiotherapy.

Information theoretic partitioning and confidence based weight assignment for multi-classifier decision level fusion in hyperspectral target recognition applications

NASA Astrophysics Data System (ADS)

Prasad, S.; Bruce, L. M.

2007-04-01

There is a growing interest in using multiple sources for automatic target recognition (ATR) applications. One approach is to take multiple, independent observations of a phenomenon and perform a feature level or a decision level fusion for ATR. This paper proposes a method to utilize these types of multi-source fusion techniques to exploit hyperspectral data when only a small number of training pixels are available. Conventional hyperspectral image based ATR techniques project the high dimensional reflectance signature onto a lower dimensional subspace using techniques such as Principal Components Analysis (PCA), Fisher's linear discriminant analysis (LDA), subspace LDA and stepwise LDA. While some of these techniques attempt to solve the curse of dimensionality, or small sample size problem, these are not necessarily optimal projections. In this paper, we present a divide and conquer approach to address the small sample size problem. The hyperspectral space is partitioned into contiguous subspaces such that the discriminative information within each subspace is maximized, and the statistical dependence between subspaces is minimized. We then treat each subspace as a separate source in a multi-source multi-classifier setup and test various decision fusion schemes to determine their efficacy. Unlike previous approaches which use correlation between variables for band grouping, we study the efficacy of higher order statistical information (using average mutual information) for a bottom up band grouping. We also propose a confidence measure based decision fusion technique, where the weights associated with various classifiers are based on their confidence in recognizing the training data. To this end, training accuracies of all classifiers are used for weight assignment in the fusion process of test pixels. The proposed methods are tested using hyperspectral data with known ground truth, such that the efficacy can be quantitatively measured in terms of target recognition accuracies.

Fusion barrier characteristics of actinides

NASA Astrophysics Data System (ADS)

Manjunatha, H. C.; Sridhar, K. N.

2018-03-01

We have studied fusion barrier characteristics of actinide compound nuclei with atomic number range 89 ≤ Z ≤ 103 for all projectile target combinations. After the calculation of fusion barrier heights and positions, we have searched for their parameterization. We have achieved the empirical formula for fusion barrier heights (VB), positions (RB), curvature of the inverted parabola (ħω) of actinide compound nuclei with atomic number range 89 ≤ Z ≤ 103 for all projectile target combinations (6

The Physics of Advanced High-Gain Targets for Inertial Fusion Energy

NASA Astrophysics Data System (ADS)

Perkins, L. John

2010-11-01

In ca. 2011-2012, the National Ignition Facility is poised to demonstrate fusion ignition and gain in the laboratory for the first time. This key milestone in the development of inertial confinement fusion (ICF) can be expected to engender interest in the development of inertial fusion energy (IFE) and expanded efforts on a number of advanced targets that may achieve high fusion energy gain at lower driver energies. In this tutorial talk, we will discuss the physics underlying ICF ignition and thermonuclear burn, examine the requirements for high gain, and outline candidate R&D programs that will be required to assess the performance of these target concepts under various driver systems including lasers, heavy-ions and pulsed power. Such target concepts include those operating by fast ignition, shock ignition, impact ignition, dual-density, magnetically-insulated, one- and two-sided drive, etc., some of which may have potential to burn advanced, non-DT fusion fuels. We will then delineate the role of such targets in their application to the production of high average fusion power. Here, systems studies of IFE economics suggest that we should strive for target fusion gains of around 100 at drive energies of 1MJ, together with corresponding rep-rates of up to 10Hz and driver electrical efficiencies around 15%. In future years, there may be exciting opportunities to study such ``innovative confinement concepts'' with prospects of fielding them on facilities such as NIF to obtain high fusion energy gains on a single shot basis.

Comparative Effectiveness of Targeted Prostate Biopsy Using Magnetic Resonance Imaging Ultrasound Fusion Software and Visual Targeting: a Prospective Study.

PubMed

Lee, Daniel J; Recabal, Pedro; Sjoberg, Daniel D; Thong, Alan; Lee, Justin K; Eastham, James A; Scardino, Peter T; Vargas, Hebert Alberto; Coleman, Jonathan; Ehdaie, Behfar

2016-09-01

We compared the diagnostic outcomes of magnetic resonance-ultrasound fusion and visually targeted biopsy for targeting regions of interest on prostate multiparametric magnetic resonance imaging. Patients presenting for prostate biopsy with regions of interest on multiparametric magnetic resonance imaging underwent magnetic resonance imaging targeted biopsy. For each region of interest 2 visually targeted cores were obtained, followed by 2 cores using a magnetic resonance-ultrasound fusion device. Our primary end point was the difference in the detection of high grade (Gleason 7 or greater) and any grade cancer between visually targeted and magnetic resonance-ultrasound fusion, investigated using McNemar's method. Secondary end points were the difference in detection rate by biopsy location using a logistic regression model and the difference in median cancer length using the Wilcoxon signed rank test. We identified 396 regions of interest in 286 men. The difference in the detection of high grade cancer between magnetic resonance-ultrasound fusion biopsy and visually targeted biopsy was -1.4% (95% CI -6.4 to 3.6, p=0.6) and for any grade cancer the difference was 3.5% (95% CI -1.9 to 8.9, p=0.2). Median cancer length detected by magnetic resonance-ultrasound fusion and visually targeted biopsy was 5.5 vs 5.8 mm, respectively (p=0.8). Magnetic resonance-ultrasound fusion biopsy detected 15% more cancers in the transition zone (p=0.046) and visually targeted biopsy detected 11% more high grade cancer at the prostate base (p=0.005). Only 52% of all high grade cancers were detected by both techniques. We found no evidence of a significant difference in the detection of high grade or any grade cancer between visually targeted and magnetic resonance-ultrasound fusion biopsy. However, the performance of each technique varied in specific biopsy locations and the outcomes of both techniques were complementary. Combining visually targeted biopsy and magnetic resonance-ultrasound fusion biopsy may optimize the detection of prostate cancer. Copyright © 2016 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

Multisensor fusion for 3D target tracking using track-before-detect particle filter

NASA Astrophysics Data System (ADS)

Moshtagh, Nima; Romberg, Paul M.; Chan, Moses W.

2015-05-01

This work presents a novel fusion mechanism for estimating the three-dimensional trajectory of a moving target using images collected by multiple imaging sensors. The proposed projective particle filter avoids the explicit target detection prior to fusion. In projective particle filter, particles that represent the posterior density (of target state in a high-dimensional space) are projected onto the lower-dimensional observation space. Measurements are generated directly in the observation space (image plane) and a marginal (sensor) likelihood is computed. The particles states and their weights are updated using the joint likelihood computed from all the sensors. The 3D state estimate of target (system track) is then generated from the states of the particles. This approach is similar to track-before-detect particle filters that are known to perform well in tracking dim and stealthy targets in image collections. Our approach extends the track-before-detect approach to 3D tracking using the projective particle filter. The performance of this measurement-level fusion method is compared with that of a track-level fusion algorithm using the projective particle filter. In the track-level fusion algorithm, the 2D sensor tracks are generated separately and transmitted to a fusion center, where they are treated as measurements to the state estimator. The 2D sensor tracks are then fused to reconstruct the system track. A realistic synthetic scenario with a boosting target was generated, and used to study the performance of the fusion mechanisms.

Infrared and visible image fusion based on robust principal component analysis and compressed sensing

NASA Astrophysics Data System (ADS)

Li, Jun; Song, Minghui; Peng, Yuanxi

2018-03-01

Current infrared and visible image fusion methods do not achieve adequate information extraction, i.e., they cannot extract the target information from infrared images while retaining the background information from visible images. Moreover, most of them have high complexity and are time-consuming. This paper proposes an efficient image fusion framework for infrared and visible images on the basis of robust principal component analysis (RPCA) and compressed sensing (CS). The novel framework consists of three phases. First, RPCA decomposition is applied to the infrared and visible images to obtain their sparse and low-rank components, which represent the salient features and background information of the images, respectively. Second, the sparse and low-rank coefficients are fused by different strategies. On the one hand, the measurements of the sparse coefficients are obtained by the random Gaussian matrix, and they are then fused by the standard deviation (SD) based fusion rule. Next, the fused sparse component is obtained by reconstructing the result of the fused measurement using the fast continuous linearized augmented Lagrangian algorithm (FCLALM). On the other hand, the low-rank coefficients are fused using the max-absolute rule. Subsequently, the fused image is superposed by the fused sparse and low-rank components. For comparison, several popular fusion algorithms are tested experimentally. By comparing the fused results subjectively and objectively, we find that the proposed framework can extract the infrared targets while retaining the background information in the visible images. Thus, it exhibits state-of-the-art performance in terms of both fusion effects and timeliness.

Transcriptome Meta-Analysis of Lung Cancer Reveals Recurrent Aberrations in NRG1 and Hippo Pathway Genes

PubMed Central

Dhanasekaran, Saravana M.; Balbin, O. Alejandro; Chen, Guoan; Nadal, Ernest; Kalyana-Sundaram, Shanker; Pan, Jincheng; Veeneman, Brendan; Cao, Xuhong; Malik, Rohit; Vats, Pankaj; Wang, Rui; Huang, Stephanie; Zhong, Jinjie; Jing, Xiaojun; Iyer, Matthew; Wu, Yi-Mi; Harms, Paul W.; Lin, Jules; Reddy, Rishindra; Brennan, Christine; Palanisamy, Nallasivam; Chang, Andrew C.; Truini, Anna; Truini, Mauro; Robinson, Dan R.; Beer, David G.; Chinnaiyan, Arul M.

2014-01-01

Lung cancer is emerging as a paradigm for disease molecular subtyping, facilitating targeted therapy based on driving somatic alterations. Here, we perform transcriptome analysis of 153 samples representing lung adenocarcinomas, squamous cell carcinomas, large cell lung cancer, adenoid cystic carcinomas and cell lines. By integrating our data with The Cancer Genome Atlas and published sources, we analyze 753 lung cancer samples for gene fusions and other transcriptomic alterations. We show that higher numbers of gene fusions is an independent prognostic factor for poor survival in lung cancer. Our analysis confirms the recently reported CD74-NRG1 fusion and suggests that NRG1, NF1 and Hippo pathway fusions may play important roles in tumors without known driver mutations. In addition, we observe exon skipping events in c-MET, which are attributable to splice site mutations. These classes of genetic aberrations may play a significant role in the genesis of lung cancers lacking known driver mutations. PMID:25531467

The choice of the energy embedding law in the design of heavy ionic fusion cylindrical targets

NASA Astrophysics Data System (ADS)

Dolgoleva, GV; Zykova, A. I.

2017-10-01

The paper considers the numerical design of heavy ion fusion (FIHIF) targets, which is one of the branches of controlled thermonuclear fusion (CTF). One of the important tasks in the targets design for controlled thermonuclear fusion is the energy embedding selection whereby it is possible to obtain “burning” (the presence of thermonuclear reactions) of the working DT region. The work is devoted to the rapid ignition of FIHIF targets by means of an additional short-term energy contribution to the DT substance already compressed by massively more longer by energy embedding. This problem has been fairly well studied for laser targets, but this problem is new for heavy ion fusion targets. Maximum momentum increasing is very technically difficult and expensive on modern FIHIF installations. The work shows that the additional energy embedding (“igniting” impulse) reduces the requirements to the maximum impulse. The purpose of this work is to research the ignition impulse effect on the FIHIF target parameters.

Shock Ignition Target Design for Inertial Fusion Energy

DTIC Science & Technology

2010-01-01

Shock ignition target design for inertial fusion energy Andrew J. Schmitt,1, a) Jason W. Bates,1 Steven P. Obenschain,1 Steven T. Zalesak,2 and David...2010 to 00-00-2010 4. TITLE AND SUBTITLE Shock ignition target design for inertial fusion energy 5a. CONTRACT NUMBER 5b. GRANT NUMBER 5c. PROGRAM

Electrochemical branched-DNA assay for polymerase chain reaction-free detection and quantification of oncogenes in messenger RNA.

PubMed

Lee, Ai-Cheng; Dai, Ziyu; Chen, Baowei; Wu, Hong; Wang, Jun; Zhang, Aiguo; Zhang, Lurong; Lim, Tit-Meng; Lin, Yuehe

2008-12-15

We describe a novel electrochemical branched-DNA (bDNA) assay for polymerase chain reaction (PCR)-free detection and quantification of p185 BCR-ABL leukemia fusion transcripts in the population of messenger ribonucleic acid (mRNA) extracted from cell lines. The bDNA amplifier carrying high loading of alkaline phosphatase (ALP) tracers was used to amplify the target signal. The targets were captured on microplate well surfaces through cooperative sandwich hybridization prior to the labeling of bDNA. The activity of captured ALP was monitored by square-wave voltammetric (SWV) analysis of the electroactive enzymatic product in the presence of 1-naphthyl phosphate. The voltammetric characteristics of substrate and enzymatic product as well as the parameters of SWV analysis were systematically optimized. A detection limit of 1 fM (1 x 10(-19) mol of target transcripts in 100 microL) and a 3-order-wide dynamic range of target concentration were achieved by the electrochemical bDNA assay. Such limit corresponded to approximately 17 fg of the p185 BCR-ABL fusion transcripts. The specificity and sensitivity of assay enabled direct detection of target transcripts in as little as 4.6 ng of mRNA population without PCR amplification. In combination with the use of a well-quantified standard, the electrochemical bDNA assay was capable of direct use for a PCR-free quantitative analysis of target transcripts in mRNA population. A mean transcript copy number of 62,900/ng of mRNA was determined, which was at least 50-fold higher than that of real-time quantitative PCR (qPCR). The finding was consistent with the underestimation of targets by qPCR reported earlier. In addition, the unique design based on bDNA technology increases the assay specificity as only the p185 BCR-ABL fusion transcripts will respond to the detection. The approach thus provides a simple, sensitive, accurate, and quantitative tool alternative to the qPCR for early disease diagnosis.

The addition of a sagittal image fusion improves the prostate cancer detection in a sensor-based MRI /ultrasound fusion guided targeted biopsy.

PubMed

Günzel, Karsten; Cash, Hannes; Buckendahl, John; Königbauer, Maximilian; Asbach, Patrick; Haas, Matthias; Neymeyer, Jörg; Hinz, Stefan; Miller, Kurt; Kempkensteffen, Carsten

2017-01-13

To explore the diagnostic benefit of an additional image fusion of the sagittal plane in addition to the standard axial image fusion, using a sensor-based MRI/US fusion platform. During July 2013 and September 2015, 251 patients with at least one suspicious lesion on mpMRI (rated by PI-RADS) were included into the analysis. All patients underwent MRI/US targeted biopsy (TB) in combination with a 10 core systematic prostate biopsy (SB). All biopsies were performed on a sensor-based fusion system. Group A included 162 men who received TB by an axial MRI/US image fusion. Group B comprised 89 men in whom the TB was performed with an additional sagittal image fusion. The median age in group A was 67 years (IQR 61-72) and in group B 68 years (IQR 60-71). The median PSA level in group A was 8.10 ng/ml (IQR 6.05-14) and in group B 8.59 ng/ml (IQR 5.65-12.32). In group A the proportion of patients with a suspicious digital rectal examination (DRE) (14 vs. 29%, p = 0.007) and the proportion of primary biopsies (33 vs 46%, p = 0.046) were significantly lower. The rate of PI-RADS 3 lesions were overrepresented in group A compared to group B (19 vs. 9%; p = 0.044). Classified according to PI-RADS 3, 4 and 5, the detection rates of TB were 42, 48, 75% in group A and 25, 74, 90% in group B. The rate of PCa with a Gleason score ≥7 missed by TB was 33% (18 cases) in group A and 9% (5 cases) in group B; p-value 0.072. An explorative multivariate binary logistic regression analysis revealed that PI-RADS, a suspicious DRE and performing an additional sagittal image fusion were significant predictors for PCa detection in TB. 9 PCa were only detected by TB with sagittal fusion (sTB) and sTB identified 10 additional clinically significant PCa (Gleason ≥7). Performing an additional sagittal image fusion besides the standard axial fusion appears to improve the accuracy of the sensor-based MRI/US fusion platform.

Comparison of conventional ultrasonography and ultrasonography-computed tomography fusion imaging for target identification using digital/real hybrid phantoms: a preliminary study.

PubMed

Soyama, Takeshi; Sakuhara, Yusuke; Kudo, Kohsuke; Abo, Daisuke; Wang, Jeff; Ito, Yoichi M; Hasegawa, Yu; Shirato, Hiroki

2016-07-01

This preliminary study compared ultrasonography-computed tomography (US-CT) fusion imaging and conventional ultrasonography (US) for accuracy and time required for target identification using a combination of real phantoms and sets of digitally modified computed tomography (CT) images (digital/real hybrid phantoms). In this randomized prospective study, 27 spheres visible on B-mode US were placed at depths of 3.5, 8.5, and 13.5 cm (nine spheres each). All 27 spheres were digitally erased from the CT images, and a radiopaque sphere was digitally placed at each of the 27 locations to create 27 different sets of CT images. Twenty clinicians were instructed to identify the sphere target using US alone and fusion imaging. The accuracy of target identification of the two methods was compared using McNemar's test. The mean time required for target identification and error distances were compared using paired t tests. At all three depths, target identification was more accurate and the mean time required for target identification was significantly less with US-CT fusion imaging than with US alone, and the mean error distances were also shorter with US-CT fusion imaging. US-CT fusion imaging was superior to US alone in terms of accurate and rapid identification of target lesions.

Massive NGS Data Analysis Reveals Hundreds Of Potential Novel Gene Fusions in Human Cell Lines.

PubMed

Gioiosa, Silvia; Bolis, Marco; Flati, Tiziano; Massini, Annalisa; Garattini, Enrico; Chillemi, Giovanni; Fratelli, Maddalena; Castrignanò, Tiziana

2018-06-01

Gene fusions derive from chromosomal rearrangements and the resulting chimeric transcripts are often endowed with oncogenic potential. Furthermore, they serve as diagnostic tools for the clinical classification of cancer subgroups with different prognosis and, in some cases, they can provide specific drug targets. So far, many efforts have been carried out to study gene fusion events occurring in tumor samples. In recent years, the availability of a comprehensive Next Generation Sequencing dataset for all the existing human tumor cell lines has provided the opportunity to further investigate these data in order to identify novel and still uncharacterized gene fusion events. In our work, we have extensively reanalyzed 935 paired-end RNA-seq experiments downloaded from "The Cancer Cell Line Encyclopedia" repository, aiming at addressing novel putative cell-line specific gene fusion events in human malignancies. The bioinformatics analysis has been performed by the execution of four different gene fusion detection algorithms. The results have been further prioritized by running a bayesian classifier which makes an in silico validation. The collection of fusion events supported by all of the predictive softwares results in a robust set of ∼ 1,700 in-silico predicted novel candidates suitable for downstream analyses. Given the huge amount of data and information produced, computational results have been systematized in a database named LiGeA. The database can be browsed through a dynamical and interactive web portal, further integrated with validated data from other well known repositories. Taking advantage of the intuitive query forms, the users can easily access, navigate, filter and select the putative gene fusions for further validations and studies. They can also find suitable experimental models for a given fusion of interest. We believe that the LiGeA resource can represent not only the first compendium of both known and putative novel gene fusion events in the catalog of all of the human malignant cell lines, but it can also become a handy starting point for wet-lab biologists who wish to investigate novel cancer biomarkers and specific drug targets.

Directed Energy HPM, PP, & PPS Efforts: Magnetized Target Fusion - Field Reversed Configuration

DTIC Science & Technology

2006-08-04

interior. 15. SUBJECT TERMS Magnetized Target Fusion (MTF), Field-Reversed Configuration (FRC), Alternative Confinement Concepts, Fusion Energy 16...research, the Department of Energy’s Office of Fusion Energy Studies (DOE OFES). Sections 2 through 4, which follow, describe in detail SAIC’s, FabTek’s...the plasma physics areas (FRCs and fusion energy ) in which we are working. The conference paper was submitted at this time, as well, and will

Dim target detection method based on salient graph fusion

NASA Astrophysics Data System (ADS)

Hu, Ruo-lan; Shen, Yi-yan; Jiang, Jun

2018-02-01

Dim target detection is one key problem in digital image processing field. With development of multi-spectrum imaging sensor, it becomes a trend to improve the performance of dim target detection by fusing the information from different spectral images. In this paper, one dim target detection method based on salient graph fusion was proposed. In the method, Gabor filter with multi-direction and contrast filter with multi-scale were combined to construct salient graph from digital image. And then, the maximum salience fusion strategy was designed to fuse the salient graph from different spectral images. Top-hat filter was used to detect dim target from the fusion salient graph. Experimental results show that proposal method improved the probability of target detection and reduced the probability of false alarm on clutter background images.

Target Fabrication Technology and New Functional Materials for Laser Fusion and Laser-Plasma Experiment

NASA Astrophysics Data System (ADS)

Nagai, Keiji; Norimatsu, Takayoshi; Izawa, Yasukazu

Target fabrication technique is a key issue of laser fusion. We present a comprehensive, up-to-data compilation of laser fusion target fabrication and relating new materials. To achieve highly efficient laser implosion, organic and inorganic highly spherical millimeter-sized capsules and cryogenic hydrogen layers inside should be uniform in diameter and thickness within sub-micrometer ˜ nanometer error. Porous structured targets and molecular cluster targets are required for laser-plasma experiments and applications. Various technologies and new materials concerning above purposes are summarized including fast-ignition targets, equation-of-state measurement targets, high energy ion generation targets, etc.

Radiotherapy treatment planning: benefits of CT-MR image registration and fusion in tumor volume delineation.

PubMed

Djan, Igor; Petrović, Borislava; Erak, Marko; Nikolić, Ivan; Lucić, Silvija

2013-08-01

Development of imaging techniques, computed tomography (CT), magnetic resonance imaging (MRI), and positron emission tomography (PET), made great impact on radiotherapy treatment planning by improving the localization of target volumes. Improved localization allows better local control of tumor volumes, but also minimizes geographical misses. Mutual information is obtained by registration and fusion of images achieved manually or automatically. The aim of this study was to validate the CT-MRI image fusion method and compare delineation obtained by CT versus CT-MRI image fusion. The image fusion software (XIO CMS 4.50.0) was applied to delineate 16 patients. The patients were scanned on CT and MRI in the treatment position within an immobilization device before the initial treatment. The gross tumor volume (GTV) and clinical target volume (CTV) were delineated on CT alone and on CT+MRI images consecutively and image fusion was obtained. Image fusion showed that CTV delineated on a CT image study set is mainly inadequate for treatment planning, in comparison with CTV delineated on CT-MRI fused image study set. Fusion of different modalities enables the most accurate target volume delineation. This study shows that registration and image fusion allows precise target localization in terms of GTV and CTV and local disease control.

Flexible Fusion Structure-Based Performance Optimization Learning for Multisensor Target Tracking

PubMed Central

Ge, Quanbo; Wei, Zhongliang; Cheng, Tianfa; Chen, Shaodong; Wang, Xiangfeng

2017-01-01

Compared with the fixed fusion structure, the flexible fusion structure with mixed fusion methods has better adjustment performance for the complex air task network systems, and it can effectively help the system to achieve the goal under the given constraints. Because of the time-varying situation of the task network system induced by moving nodes and non-cooperative target, and limitations such as communication bandwidth and measurement distance, it is necessary to dynamically adjust the system fusion structure including sensors and fusion methods in a given adjustment period. Aiming at this, this paper studies the design of a flexible fusion algorithm by using an optimization learning technology. The purpose is to dynamically determine the sensors’ numbers and the associated sensors to take part in the centralized and distributed fusion processes, respectively, herein termed sensor subsets selection. Firstly, two system performance indexes are introduced. Especially, the survivability index is presented and defined. Secondly, based on the two indexes and considering other conditions such as communication bandwidth and measurement distance, optimization models for both single target tracking and multi-target tracking are established. Correspondingly, solution steps are given for the two optimization models in detail. Simulation examples are demonstrated to validate the proposed algorithms. PMID:28481243

Mass Producing Targets for Nuclear Fusion

NASA Technical Reports Server (NTRS)

Wang, T. G.; Elleman, D. D.; Kendall, J. M.

1983-01-01

Metal-encapsulating technique advances prospects of controlling nuclear fusion. Prefilled fusion targets form at nozzle as molten metal such as tin flows through outer channel and pressurized deuterium/tritium gas flows through inner channel. Molten metal completely encloses gas charge as it drops off nozzle.

Sensor Fusion of Gaussian Mixtures for Ballistic Target Tracking in the Re-Entry Phase

PubMed Central

Lu, Kelin; Zhou, Rui

2016-01-01

A sensor fusion methodology for the Gaussian mixtures model is proposed for ballistic target tracking with unknown ballistic coefficients. To improve the estimation accuracy, a track-to-track fusion architecture is proposed to fuse tracks provided by the local interacting multiple model filters. During the fusion process, the duplicate information is removed by considering the first order redundant information between the local tracks. With extensive simulations, we show that the proposed algorithm improves the tracking accuracy in ballistic target tracking in the re-entry phase applications. PMID:27537883

Sensor Fusion of Gaussian Mixtures for Ballistic Target Tracking in the Re-Entry Phase.

PubMed

Lu, Kelin; Zhou, Rui

2016-08-15

A sensor fusion methodology for the Gaussian mixtures model is proposed for ballistic target tracking with unknown ballistic coefficients. To improve the estimation accuracy, a track-to-track fusion architecture is proposed to fuse tracks provided by the local interacting multiple model filters. During the fusion process, the duplicate information is removed by considering the first order redundant information between the local tracks. With extensive simulations, we show that the proposed algorithm improves the tracking accuracy in ballistic target tracking in the re-entry phase applications.

Laser program annual report, 1980

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

Coleman, L.W.; Krupke, W.F.; Strack, J.R.

1981-06-01

Volume 2 contains five sections that cover the areas of target design, target fabrication, diagnostics, and fusion experiments. Section 3 reports on target design activities, plasma theory and simulation, code development, and atomic theory. Section 4 presents the accomplishments of the Target Fabrication Group, Section 5 contains the results of our diagnostics development, and Section 6 describes advances made in the management and analysis of experimental data. Finally, Section 7 in Volume 2 reports the results of laser target experiments conducted during the year.

Fast retrieval and autonomous regulation of single spontaneously recycling synaptic vesicles

PubMed Central

Leitz, Jeremy; Kavalali, Ege T

2014-01-01

Presynaptic terminals release neurotransmitters spontaneously in a manner that can be regulated by Ca2+. However, the mechanisms underlying this regulation are poorly understood because the inherent stochasticity and low probability of spontaneous fusion events has curtailed their visualization at individual release sites. Here, using pH-sensitive optical probes targeted to synaptic vesicles, we visualized single spontaneous fusion events and found that they are retrieved extremely rapidly with faster re-acidification kinetics than their action potential-evoked counterparts. These fusion events were coupled to postsynaptic NMDA receptor-driven Ca2+ signals, and at elevated Ca2+ concentrations there was an increase in the number of vesicles that would undergo fusion. Furthermore, spontaneous vesicle fusion propensity in a synapse was Ca2+-dependent but regulated autonomously: independent of evoked fusion probability at the same synapse. Taken together, these results expand classical quantal analysis to incorporate endocytic and exocytic phases of single fusion events and uncover autonomous regulation of spontaneous fusion. DOI: http://dx.doi.org/10.7554/eLife.03658.001 PMID:25415052

Domain retention in transcription factor fusion genes and its biological and clinical implications: a pan-cancer study

PubMed Central

Kim, Pora; Ballester, Leomar Y.; Zhao, Zhongming

2017-01-01

Genomic rearrangements involving transcription factors (TFs) can form fusion proteins resulting in either enhanced, weakened, or even loss of TF activity. Functional domain (FD) retention is a critical factor in the activity of transcription factor fusion genes (TFFGs). A systematic investigation of FD retention in TFFGs and their outcome (e.g. expression changes) in a pan-cancer study has not yet been completed. Here, we examined the FD retention status in 386 TFFGs across 13 major cancer types and identified 83 TFFGs involving 67 TFs that retained FDs. To measure the potential biological relevance of TFs in TFFGs, we introduced a Major Active Isofusion Index (MAII) and built a prioritized TFFG network using MAII scores and the observed frequency of fusion positive samples. Interestingly, the four TFFGs (PML-RARA, RUNX1-RUNX1T1, TMPRSS2-ERG, and SFPQ-TFE3) with the highest MAII scores showed 50 differentially expressed target genes (DETGs) in fusion-positive versus fusion-negative cancer samples. DETG analysis revealed that they were involved in tumorigenesis-related processes in each cancer type. PLAU, which encodes plasminogen activator urokinase and serves as a biomarker for tumor invasion, was found to be consistently activated in the samples with the highest MAII scores. Among the 50 DETGs, 21 were drug targetable genes. Fourteen of these 21 DETGs were expressed in acute myeloid leukemia (AML) samples. Accordingly, we constructed an AML-specific TFFG network, which included 38 DETGs in RUNX1-RUNX1T1 or PML-RARA positive samples. In summary, this study revealed several TFFGs and their potential target genes, and provided insights into the clinical implications of TFFGs. PMID:29299133

Clinicopathological Characteristics of Patients with Non-Small-Cell Lung Cancer Who Harbor EML4-ALK Fusion Gene: A Meta-Analysis

PubMed Central

Zhao, Fengzhi; Xu, Meng; Lei, Honcho; Zhou, Ziqi; Wang, Liang; Li, Ping; Zhao, Jianfu; Hu, Penghui

2015-01-01

Background A novel fusion gene of echinoderm microtubule-associated protein-like 4 (EML4) and anaplastic lymphoma kinase (ALK) has been recently identified in non-small-cell lung cancers (NSCLCs). Patients with the EML4-ALK fusion gene demonstrate unique clinicopathological and physiological characteristics. Here we present a meta-analysis of large-scale studies to evaluate the clinicopathological characteristics of NSCLC patients harboring the EML4-ALK fusion gene. Methods Both English and Chinese databases were systematically used to search the materials of the clinicopathological characteristics of patients with NSCLC harboring the EML4-ALK fusion gene. Pooled relative risk (RR) estimates and the 95% confidence intervals (95% CI) were calculated with the fixed or random effect model. Publication bias and chi-square test were also calculated. Results 27 retrospective studies were included in our meta-analysis. These studies included a total of 6950 patients. The incidence rate of EML4-ALK fusion in NSCLC patients was found to be 6.8% (472/6950). The correlation of the EML4-ALK fusion gene and clinicopathological characteristics of NSCLC patients demonstrated a significant difference in smoking status, histological types, stage, and ethnic characteristics. The positive rate of the EML4-ALK fusion gene expression in females were slightly higher than that in males, but not significantly (P = 0.52). In addition, the EML4-ALK fusion gene was mutually exclusive of the EGFR and KRAS mutation genes (P = 0.00). Conclusion Our pooled analysis revealed that the EML4-ALK fusion gene was observed predominantly in adenocarcinoma, non-smoking and NSCLC patients, especially those diagnosed in the advanced clinical stage of NSCLC. Additionally, the EML4-ALK fusion gene was exclusive of the EGFR and KRAS mutation genes. We surmise that IHC assay is a valuable tool for the prescreening of patients with ALK fusion gene in clinical practice, and FISH assay can be performed as a confirmation method. These insights might be helpful in guiding the appropriate molecular target therapy for NSCLC. PMID:25706305

Clinicopathological characteristics of patients with non-small-cell lung cancer who harbor EML4-ALK fusion gene: a meta-analysis.

PubMed

Zhao, Fengzhi; Xu, Meng; Lei, Honcho; Zhou, Ziqi; Wang, Liang; Li, Ping; Zhao, Jianfu; Hu, Penghui

2015-01-01

A novel fusion gene of echinoderm microtubule-associated protein-like 4 (EML4) and anaplastic lymphoma kinase (ALK) has been recently identified in non-small-cell lung cancers (NSCLCs). Patients with the EML4-ALK fusion gene demonstrate unique clinicopathological and physiological characteristics. Here we present a meta-analysis of large-scale studies to evaluate the clinicopathological characteristics of NSCLC patients harboring the EML4-ALK fusion gene. Both English and Chinese databases were systematically used to search the materials of the clinicopathological characteristics of patients with NSCLC harboring the EML4-ALK fusion gene. Pooled relative risk (RR) estimates and the 95% confidence intervals (95% CI) were calculated with the fixed or random effect model. Publication bias and chi-square test were also calculated. 27 retrospective studies were included in our meta-analysis. These studies included a total of 6950 patients. The incidence rate of EML4-ALK fusion in NSCLC patients was found to be 6.8% (472/6950). The correlation of the EML4-ALK fusion gene and clinicopathological characteristics of NSCLC patients demonstrated a significant difference in smoking status, histological types, stage, and ethnic characteristics. The positive rate of the EML4-ALK fusion gene expression in females were slightly higher than that in males, but not significantly (P = 0.52). In addition, the EML4-ALK fusion gene was mutually exclusive of the EGFR and KRAS mutation genes (P = 0.00). Our pooled analysis revealed that the EML4-ALK fusion gene was observed predominantly in adenocarcinoma, non-smoking and NSCLC patients, especially those diagnosed in the advanced clinical stage of NSCLC. Additionally, the EML4-ALK fusion gene was exclusive of the EGFR and KRAS mutation genes. We surmise that IHC assay is a valuable tool for the prescreening of patients with ALK fusion gene in clinical practice, and FISH assay can be performed as a confirmation method. These insights might be helpful in guiding the appropriate molecular target therapy for NSCLC.

Spin distribution of evaporation residues formed in complete and incomplete fusion in 16O+154Sm system

NASA Astrophysics Data System (ADS)

Singh, D.; Linda, Sneha B.; Giri, Pankaj K.; Mahato, Amritraj; Tripathi, R.; Kumar, Harish; Afzal Ansari, M.; Sathik, N. P. M.; Ali, Rahbar; Kumar, Rakesh; Muralithar, S.; Singh, R. P.

2017-11-01

Spin distributions for several evaporation residues populated in the 16O+154Sm system have been measured at projectile energy ≈ 6.2 MeV/A by using the charged particle-γ-coincidence technique. The measured spin distributions of the evaporation residues populated through incomplete fusion associated with 'fast' α and 2α-emission channels are found to be entirely different from fusion-evaporation channels. It is observed that the mean input angular momentum for the evaporation residues formed in incomplete fusion channel is relatively higher than that observed for evaporation residues in complete fusion channels. The feeding intensity profile of evaporation residues populated through complete fusion and incomplete fusion have also been studied. The incomplete fusion channels are found to have narrow range feeding only for high spin states, while complete fusion channels are strongly fed over a broad spin range and widely populated. Comparison of present results with earlier data suggests that the mean input angular momentum values are relatively smaller for spherical target than that of deformed target using the same projectile and incident energy highlighting the role of target deformation in incomplete fusion dynamics.

In-beam Fission Study at JAEA

NASA Astrophysics Data System (ADS)

Nishio, Katsuhisa

2013-12-01

Fission fragment mass distributions were measured in heavy-ion induced fissions using 238U target nucleus. The measured mass distributions changed drastically with incident energy. The results are explained by a change of the ratio between fusion and quasifission with nuclear orientation. A calculation based on a fluctuation dissipation model reproduced the mass distributions and their incident energy dependence. Fusion probability was determined in the analysis. Evaporation residue cross sections were calculated with a statistical model in the reactions of 30Si + 238U and 34S + 238U using the obtained fusion probability in the entrance channel. The results agree with the measured cross sections for seaborgium and hassium isotopes.

In-beam fission study for Heavy Element Synthesis

NASA Astrophysics Data System (ADS)

Nishio, Katsuhisa

2013-12-01

Fission fragment mass distributions were measured in heavy-ion induced fissions using 238U target nucleus. The measured mass distributions changed drastically with incident energy. The results are explained by a change of the ratio between fusion and qasifission with nuclear orientation. A calculation based on a fluctuation dissipation model reproduced the mass distributions and their incident energy dependence. Fusion probability was determined in the analysis. Evaporation residue cross sections were calculated with a statistical model in the reactions of 30Si + 238U and 34S + 238U using the obtained fusion probability in the entrance channel. The results agree with the measured cross sections for seaborgium and hassium isotopes.

Tracking fusion of human mesenchymal stem cells after transplantation to the heart.

PubMed

Freeman, Brian T; Kouris, Nicholas A; Ogle, Brenda M

2015-06-01

Evidence suggests that transplanted mesenchymal stem cells (MSCs) can aid recovery of damaged myocardium caused by myocardial infarction. One possible mechanism for MSC-mediated recovery is reprogramming after cell fusion between transplanted MSCs and recipient cardiac cells. We used a Cre/LoxP-based luciferase reporter system coupled to biophotonic imaging to detect fusion of transplanted human pluripotent stem cell-derived MSCs to cells of organs of living mice. Human MSCs, with transient expression of a viral fusogen, were delivered to the murine heart via a collagen patch. At 2 days and 1 week later, living mice were probed for bioluminescence indicative of cell fusion. Cell fusion was detected at the site of delivery (heart) and in distal tissues (i.e., stomach, small intestine, liver). Fusion was confirmed at the cellular scale via fluorescence in situ hybridization for human-specific and mouse-specific centromeres. Human cells in organs distal to the heart were typically located near the vasculature, suggesting MSCs and perhaps MSC fusion products have the ability to migrate via the circulatory system to distal organs and engraft with local cells. The present study reveals previously unknown migratory patterns of delivered human MSCs and associated fusion products in the healthy murine heart. The study also sets the stage for follow-on studies to determine the functional effects of cell fusion in a model of myocardial damage or disease. Mesenchymal stem cells (MSCs) are transplanted to the heart, cartilage, and other tissues to recover lost function or at least limit overactive immune responses. Analysis of tissues after MSC transplantation shows evidence of fusion between MSCs and the cells of the recipient. To date, the biologic implications of cell fusion remain unclear. A newly developed in vivo tracking system was used to identify MSC fusion products in living mice. The migratory patterns of fusion products were determined both in the target organ (i.e., the heart) and in distal organs. This study shows, for the first time, evidence of fusion products at sites distal from the target organ and data to suggest that migration occurs via the vasculature. These results will inform and improve future, MSC-based therapeutics. ©AlphaMed Press.

Method for mounting laser fusion targets for irradiation

DOEpatents

Fries, R. Jay; Farnum, Eugene H.; McCall, Gene H.

1977-07-26

Methods for preparing laser fusion targets of the ball-and-disk type are disclosed. Such targets are suitable for irradiation with one or two laser beams to produce the requisite uniform compression of the fuel material.

Computational modeling of joint U.S.-Russian experiments relevant to magnetic compression/magnetized target fusion (MAGO/MTF)

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

Sheehey, P.T.; Faehl, R.J.; Kirkpatrick, R.C.

1997-12-31

Magnetized Target Fusion (MTF) experiments, in which a preheated and magnetized target plasma is hydrodynamically compressed to fusion conditions, present some challenging computational modeling problems. Recently, joint experiments relevant to MTF (Russian acronym MAGO, for Magnitnoye Obzhatiye, or magnetic compression) have been performed by Los Alamos National Laboratory and the All-Russian Scientific Research Institute of Experimental Physics (VNIIEF). Modeling of target plasmas must accurately predict plasma densities, temperatures, fields, and lifetime; dense plasma interactions with wall materials must be characterized. Modeling of magnetically driven imploding solid liners, for compression of target plasmas, must address issues such as Rayleigh-Taylor instability growthmore » in the presence of material strength, and glide plane-liner interactions. Proposed experiments involving liner-on-plasma compressions to fusion conditions will require integrated target plasma and liner calculations. Detailed comparison of the modeling results with experiment will be presented.« less

Detecting protein-protein interactions using Renilla luciferase fusion proteins.

PubMed

Burbelo, Peter D; Kisailus, Adam E; Peck, Jeremy W

2002-11-01

We have developed a novel system designated the luciferase assay for protein detection (LAPD) to study protein-protein interactions. This method involves two protein fusions, a soluble reporter fusion and a fusion for immobilizing the target protein. The soluble reporter is an N-terminal Renilla luciferase fusion protein that exhibits high Renilla luciferase activity. Crude cleared lysates from transfected Cos1 cells that express the Renilla luciferase fusion protein can be used in binding assays with immobilized target proteins. Following incubation and washing, target-bound Renilla luciferase fusion proteins produce light from the coelenterazine substrate, indicating an interaction between the two proteins of interest. As proof of the principle, we reproduced known, transient protein-protein interactions between the Cdc42 GTPase and its effector proteins. GTPase Renilla fusion proteins produced in Cos1 cells were tested with immobilized recombinant GST-N-WASP and CEP5 effector proteins. Using this assay, we could detect specific interactions of Cdc42 with these effector proteins in approximately 50 min. The specificity of these interactions was demonstrated by showing that they were GTPase-specific and GTP-dependent and not seen with other unrelated target proteins. These results suggest that the LAPD method, which is both rapid and sensitive, may have research and practical applications.

FOXO1 is a direct target of EWS-Fli1 oncogenic fusion protein in Ewing's sarcoma cells

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

Yang, Liu, E-mail: lyang@u.washington.edu; Medical Research Service, VA Puget Sound Health Care System, Seattle, WA 98108; Hu, Hsien-Ming

2010-11-05

Research highlights: {yields} Inducible and reversible siRNA knockdown of an oncogenic fusion protein such as EWS-Fli1 is feasible and more advantageous than other siRNA methods. {yields} The tumor suppressor gene FOXO1 is a new EWS-Fli1 target. {yields} While trans-activators are known for the FOXO1 gene, there has been no report on negative regulators of FOXO1 transcription. {yields} This study provides first evidence that the EWS-Fli1 oncogenic fusion protein can function as a transcriptional repressor of the FOXO1 gene. -- Abstract: Ewing's family tumors are characterized by a specific t(11;22) chromosomal translocation that results in the formation of EWS-Fli1 oncogenic fusionmore » protein. To investigate the effects of EWS-Fli1 on gene expression, we carried out DNA microarray analysis after specific knockdown of EWS-Fli1 through transfection of synthetic siRNAs. EWS-Fli1 knockdown increased expression of genes such as DKK1 and p57 that are known to be repressed by EWS-Fli1 fusion protein. Among other potential EWS-Fli1 targets identified by our microarray analysis, we have focused on the FOXO1 gene since it encodes a potential tumor suppressor and has not been previously reported in Ewing's cells. To better understand how EWS-Fli1 affects FOXO1 expression, we have established a doxycycline-inducible siRNA system to achieve stable and reversible knockdown of EWS-Fli1 in Ewing's sarcoma cells. Here we show that FOXO1 expression in Ewing's cells has an inverse relationship with EWS-Fli1 protein level, and FOXO1 promoter activity is increased after doxycycline-induced EWS-Fli1 knockdown. In addition, we have found that direct binding of EWS-Fli1 to FOXO1 promoter is attenuated after doxycycline-induced siRNA knockdown of the fusion protein. Together, these results suggest that suppression of FOXO1 function by EWS-Fli1 fusion protein may contribute to cellular transformation in Ewing's family tumors.« less

Possible application of electromagnetic guns to impact fusion

NASA Astrophysics Data System (ADS)

Kostoff, R. N.; Peaslee, A. T., Jr.; Ribe, F. L.

1982-01-01

The possible application of electromagnetic guns to impact fusion for the generation of electric power is discussed, and advantages of impact fusion over the more conventional inertial confinement fusion concepts are examined. It is shown that impact fusion can achieve the necessary high yields, of the order of a few gigajoules, which are difficult to achieve with lasers except at unrealistically high target gains. The rail gun accelerator is well adapted to the delivery of some 10-100 megajoules of energy to the fusion target, and the electrical technology involved is relatively simple: inductive storage or rotating machinery and capacitors. It is concluded that the rail gun has the potential of developing into an impact fusion macroparticle accelerator.

Radiographic detection of 100 A thickness variations in 1-. mu. m-thick coatings applied to submillimeter-diameter laser fusion targets

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

Stupin, D.M.

1986-01-01

We have developed x-ray radiography to measure thickness variations of coatings on laser fusion targets. Our technique is based on measuring the variation in x-ray transmission through the targets. The simplest targets are hollow glass microshells or microballoons 100 to 500 ..mu..m in diameter, that have several layers of metals or plastics, 1 to 100 ..mu..m thick. Our goal is to examine these opaque coatings for thickness variations as small as 1% or 0.1%, depending on the type of defect. Using contact radiography we have obtained the desired sensitivity for concentric and elliptical defects of 1%. This percentage corresponds tomore » thickness variations as small as 100 A in a 1-..mu..m-thick coating. For warts and dimples, the desired sensitivity is a function of the area of the defect, and we are developing a system to detect 0.1% thickness variations that cover an area 10 ..mu..m by 10 ..mu..m. We must use computer analysis of contact radiographs to measure 1% thickness variations in either concentricity or ellipticity. Because this analysis takes so long on our minicomputer, we preselect the radiographs by looking for defects at the 10% level on a video image analysis system.« less

Sub-barrier quasifission in heavy element formation reactions with deformed actinide target nuclei

NASA Astrophysics Data System (ADS)

Hinde, D. J.; Jeung, D. Y.; Prasad, E.; Wakhle, A.; Dasgupta, M.; Evers, M.; Luong, D. H.; du Rietz, R.; Simenel, C.; Simpson, E. C.; Williams, E.

2018-02-01

Background: The formation of superheavy elements (SHEs) by fusion of two massive nuclei is severely inhibited by the competing quasifission process. Low excitation energies favor SHE survival against fusion-fission competition. In "cold" fusion with spherical target nuclei near 208Pb, SHE yields are largest at beam energies significantly below the average capture barrier. In "hot" fusion with statically deformed actinide nuclei, this is not the case. Here the elongated deformation-aligned configurations in sub-barrier capture reactions inhibits fusion (formation of a compact compound nucleus), instead favoring rapid reseparation through quasifission. Purpose: To determine the probabilities of fast and slow quasifission in reactions with prolate statically deformed actinide nuclei, through measurement and quantitative analysis of the dependence of quasifission characteristics at beam energies spanning the average capture barrier energy. Methods: The Australian National University Heavy Ion Accelerator Facility and CUBE fission spectrometer have been used to measure fission and quasifission mass and angle distributions for reactions with projectiles from C to S, bombarding Th and U target nuclei. Results: Mass-asymmetric quasifission occurring on a fast time scale, associated with collisions with the tips of the prolate actinide nuclei, shows a rapid increase in probability with increasing projectile charge, the transition being centered around projectile atomic number ZP=14 . For mass-symmetric fission events, deviations of angular anisotropies from expectations for fusion fission, indicating a component of slower quasifission, suggest a similar transition, but centered around ZP˜8 . Conclusions: Collisions with the tips of statically deformed prolate actinide nuclei show evidence for two distinct quasifission processes of different time scales. Their probabilities both increase rapidly with the projectile charge. The probability of fusion can be severely suppressed by these two quasifission processes, since the sub-barrier heavy element yield is likely to be determined by the product of the probabilities of surviving each quasifission process.

A flexible data fusion architecture for persistent surveillance using ultra-low-power wireless sensor networks

NASA Astrophysics Data System (ADS)

Hanson, Jeffrey A.; McLaughlin, Keith L.; Sereno, Thomas J.

2011-06-01

We have developed a flexible, target-driven, multi-modal, physics-based fusion architecture that efficiently searches sensor detections for targets and rejects clutter while controlling the combinatoric problems that commonly arise in datadriven fusion systems. The informational constraints imposed by long lifetime requirements make systems vulnerable to false alarms. We demonstrate that our data fusion system significantly reduces false alarms while maintaining high sensitivity to threats. In addition, mission goals can vary substantially in terms of targets-of-interest, required characterization, acceptable latency, and false alarm rates. Our fusion architecture provides the flexibility to match these trade-offs with mission requirements unlike many conventional systems that require significant modifications for each new mission. We illustrate our data fusion performance with case studies that span many of the potential mission scenarios including border surveillance, base security, and infrastructure protection. In these studies, we deployed multi-modal sensor nodes - including geophones, magnetometers, accelerometers and PIR sensors - with low-power processing algorithms and low-bandwidth wireless mesh networking to create networks capable of multi-year operation. The results show our data fusion architecture maintains high sensitivities while suppressing most false alarms for a variety of environments and targets.

Fusion yield rate recovery by escaping hot-spot fast ions in the neighboring fuel layer

NASA Astrophysics Data System (ADS)

Tang, Xian-Zhu; McDevitt, C. J.; Guo, Zehua; Berk, H. L.

2014-02-01

Free-streaming loss by fast ions can deplete the tail population in the hot spot of an inertial confinement fusion (ICF) target. Escaping fast ions in the neighboring fuel layer of a cryogenic target can produce a surplus of fast ions locally. In contrast to the Knudsen layer effect that reduces hot-spot fusion reactivity due to tail ion depletion, the inverse Knudsen layer effect increases fusion reactivity in the neighboring fuel layer. In the case of a burning ICF target in the presence of significant hydrodynamic mix which aggravates the Knudsen layer effect, the yield recovery largely compensates for the yield reduction. For mix-dominated sub-ignition targets, the yield reduction is the dominant process.

Robust Ground Target Detection by SAR and IR Sensor Fusion Using Adaboost-Based Feature Selection

PubMed Central

Kim, Sungho; Song, Woo-Jin; Kim, So-Hyun

2016-01-01

Long-range ground targets are difficult to detect in a noisy cluttered environment using either synthetic aperture radar (SAR) images or infrared (IR) images. SAR-based detectors can provide a high detection rate with a high false alarm rate to background scatter noise. IR-based approaches can detect hot targets but are affected strongly by the weather conditions. This paper proposes a novel target detection method by decision-level SAR and IR fusion using an Adaboost-based machine learning scheme to achieve a high detection rate and low false alarm rate. The proposed method consists of individual detection, registration, and fusion architecture. This paper presents a single framework of a SAR and IR target detection method using modified Boolean map visual theory (modBMVT) and feature-selection based fusion. Previous methods applied different algorithms to detect SAR and IR targets because of the different physical image characteristics. One method that is optimized for IR target detection produces unsuccessful results in SAR target detection. This study examined the image characteristics and proposed a unified SAR and IR target detection method by inserting a median local average filter (MLAF, pre-filter) and an asymmetric morphological closing filter (AMCF, post-filter) into the BMVT. The original BMVT was optimized to detect small infrared targets. The proposed modBMVT can remove the thermal and scatter noise by the MLAF and detect extended targets by attaching the AMCF after the BMVT. Heterogeneous SAR and IR images were registered automatically using the proposed RANdom SAmple Region Consensus (RANSARC)-based homography optimization after a brute-force correspondence search using the detected target centers and regions. The final targets were detected by feature-selection based sensor fusion using Adaboost. The proposed method showed good SAR and IR target detection performance through feature selection-based decision fusion on a synthetic database generated by OKTAL-SE. PMID:27447635

Robust Ground Target Detection by SAR and IR Sensor Fusion Using Adaboost-Based Feature Selection.

PubMed

Kim, Sungho; Song, Woo-Jin; Kim, So-Hyun

2016-07-19

Long-range ground targets are difficult to detect in a noisy cluttered environment using either synthetic aperture radar (SAR) images or infrared (IR) images. SAR-based detectors can provide a high detection rate with a high false alarm rate to background scatter noise. IR-based approaches can detect hot targets but are affected strongly by the weather conditions. This paper proposes a novel target detection method by decision-level SAR and IR fusion using an Adaboost-based machine learning scheme to achieve a high detection rate and low false alarm rate. The proposed method consists of individual detection, registration, and fusion architecture. This paper presents a single framework of a SAR and IR target detection method using modified Boolean map visual theory (modBMVT) and feature-selection based fusion. Previous methods applied different algorithms to detect SAR and IR targets because of the different physical image characteristics. One method that is optimized for IR target detection produces unsuccessful results in SAR target detection. This study examined the image characteristics and proposed a unified SAR and IR target detection method by inserting a median local average filter (MLAF, pre-filter) and an asymmetric morphological closing filter (AMCF, post-filter) into the BMVT. The original BMVT was optimized to detect small infrared targets. The proposed modBMVT can remove the thermal and scatter noise by the MLAF and detect extended targets by attaching the AMCF after the BMVT. Heterogeneous SAR and IR images were registered automatically using the proposed RANdom SAmple Region Consensus (RANSARC)-based homography optimization after a brute-force correspondence search using the detected target centers and regions. The final targets were detected by feature-selection based sensor fusion using Adaboost. The proposed method showed good SAR and IR target detection performance through feature selection-based decision fusion on a synthetic database generated by OKTAL-SE.

Assessment of Prospectively Assigned Likert Scores for Targeted Magnetic Resonance Imaging-Transrectal Ultrasound Fusion Biopsies in Patients with Suspected Prostate Cancer.

PubMed

Costa, Daniel N; Lotan, Yair; Rofsky, Neil M; Roehrborn, Claus; Liu, Alexander; Hornberger, Brad; Xi, Yin; Francis, Franto; Pedrosa, Ivan

2016-01-01

We assess the performance of prospectively assigned magnetic resonance imaging based Likert scale scores for the detection of clinically significant prostate cancer, and analyze the pre-biopsy imaging variables associated with increased cancer detection using targeted magnetic resonance imaging-transrectal ultrasound fusion biopsy. In this retrospective review of prospectively generated data including men with abnormal multiparametric prostate magnetic resonance imaging (at least 1 Likert score 3 or greater lesion) who underwent subsequent targeted magnetic resonance imaging-transrectal ultrasound fusion biopsy, we determined the association between different imaging variables (Likert score, lesion size, lesion location, prostate volume, radiologist experience) and targeted biopsy positivity rate. We also compared the detection of clinically significant cancer according to Likert scale scores. Tumors with high volume (50% or more of any core) Gleason score 3+4 or any tumor with greater Gleason score were considered clinically significant. Each lesion served as the elementary unit for analysis. We used logistic regression for univariate and multivariate (stepwise selection) analysis to assess for an association between targeted biopsy positivity rate and each tested variable. The relationship between Likert scale and Gleason score was evaluated using the Spearman correlation coefficient. A total of 161 men with 244 lesions met the study eligibility criteria. Targeted biopsies diagnosed cancer in 41% (66 of 161) of the men and 41% (99 of 244) of the lesions. The Likert score was the strongest predictor of targeted biopsy positivity (OR 3.7, p <0.0001). Other imaging findings associated with a higher targeted biopsy positivity rate included smaller prostate volume (OR 0.7, p <0.01), larger lesion size (OR 2.2, p <0.001) and anterior location (OR 2.0, p=0.01). On multiple logistic regression analysis Likert score, lesion size and prostate volume were significant predictors of targeted biopsy positivity. Higher Likert scores were also associated with increased detection of clinically significant tumors (p <0.0001). The Likert scale score used to convey the degree of suspicion on multiparametric magnetic resonance imaging is the strongest predictor of targeted biopsy positivity and of the presence of clinically significant tumor. Copyright © 2016 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

Role of input angular momentum and target deformation on the incomplete-fusion dynamics in the 16O+154Sm system at ELab=6.1 MeV/nucleon

NASA Astrophysics Data System (ADS)

Singh, D.; Linda, Sneha B.; Giri, Pankaj K.; Mahato, Amritraj; Tripathi, R.; Kumar, Harish; Ansari, M. Afzal; Sathik, N. P. M.; Ali, Rahbar; Kumar, R.; Muralithar, S.; Singh, R. P.

2018-06-01

Spin distributions of nine evaporation residues 164Yb(x n ) , 163Tm(p x n ) , Er,167168(2 p x n ) , Ho-161163(α p x n ) , 164Dy(α 2 p x n ) , and 160Dy(2 α x n ) produced through complete- and incomplete-fusion reactions have been measured in the system 16O+154Sm at projectile energy =6.1 MeV /nucleon using the in-beam charged-particle (Z =1 ,2 )-γ-ray coincidence technique. The results indicate the occurrence of incomplete fusion involving the breakup of 16O into 4He+12C and/or 8Be+8Be followed by fusion of one of the fragments with target nucleus 154Sm. The pattern of measured spin distributions of the evaporation residues produced through complete and incomplete fusion are found to be entirely different from each other. It has been observed from these present results that the mean input angular momentum for the evaporation residues produced through complete fusion is relatively lower than that of evaporation residues produced through incomplete-fusion reactions. The pattern of feeding intensity of evaporation residues populated through complete- and incomplete-fusion reactions has also been studied. The evaporation residues populated through complete-fusion channels are strongly fed over a broad spin range and widely populated, while evaporation residues populated through incomplete-fusion reactions are found to have narrow range feeding only for high spin states. Comparison of present results with earlier data suggests that the value of mean input angular momentum is relatively higher for a deformed target and more mass asymmetric system than that of a spherical target and less mass asymmetric system by using the same projectile and the same energy. Thus, present results indicate that the incomplete-fusion reactions not only depend on the mass asymmetry of the system, but also depend on the deformation of the target.

Successful construction and stable expression of an anti-CD45RA scFv-EGFP fusion protein in Chinese hamster ovary cells.

PubMed

Wang, Zhujun; Chen, Yuanyuan; Li, Sisi; Cheng, Yuping; Zhao, Haizhao; Jia, Ming; Luo, Zebin; Tang, Yongmin

2014-02-01

CD45RA has been found highly expressed on leukemia cells and may be a potential target of the disease. In this study, an anti-CD45RA single-chain antibody fragment (scFv3A4) was genetically linked to the N terminus of the enhanced green fluorescent protein (EGFP) to generate a scFv3A4-EGFP fusion protein. The scFv3A4-EGFP with a molecular weight of 57kDa was stably expressed and secreted from the transfected CHO cells through the ER/Golgi-dependent pathway. The fusion protein was soluble in the culture supernatant and the yield was 1350μg/L. Flow cytometry analysis showed that the scFv3A4-EGFP had the same binding site and a very similar reactivity pattern with its parental murine monoclonal antibody (mAb) 3A4. Furthermore, comparing to conventional labeled 3A4-FITC antibody, the scFv3A4-EGFP was more resistant to illumination and more suitable for immunofluorescence histology (IFH) detection. Therefore, the scFv3A4-EGFP fusion protein can be a powerful tool to investigate the targeting of CD45RA on leukemia cells, biological activity of the target and possibly for the genetic manipulation of the antibody. Copyright © 2013 Elsevier Inc. All rights reserved.

A Cell-Cell Fusion Assay to Assess Arenavirus Envelope Glycoprotein Membrane-Fusion Activity.

PubMed

York, Joanne; Nunberg, Jack H

2018-01-01

For many viruses that enter their target cells through pH-dependent fusion of the viral and endosomal membranes, cell-cell fusion assays can provide an experimental platform for investigating the structure-function relationships that promote envelope glycoprotein membrane-fusion activity. Typically, these assays employ effector cells expressing the recombinant envelope glycoprotein on the cell surface and target cells engineered to quantitatively report fusion with the effector cell. In the protocol described here, Vero cells are transfected with a plasmid encoding the arenavirus envelope glycoprotein complex GPC and infected with the vTF7-3 vaccinia virus expressing the bacteriophage T7 RNA polymerase. These effector cells are mixed with target cells infected with the vCB21R-lacZ vaccinia virus encoding a β-galactosidase reporter under the control of the T7 promoter. Cell-cell fusion is induced upon exposure to low-pH medium (pH 5.0), and the resultant expression of the β-galactosidase reporter is quantitated using a chemiluminescent substrate. We have utilized this robust microplate cell-cell fusion assay extensively to study arenavirus entry and its inhibition by small-molecule fusion inhibitors.

Multifunctional cellulase catalysis targeted by fusion to different carbohydrate-binding modules

DOE PAGES

Walker, Johnnie A.; Takasuka, Taichi E.; Deng, Kai; ...

2015-12-21

Carbohydrate binding modules (CBMs) bind polysaccharides and help target glycoside hydrolases catalytic domains to their appropriate carbohydrate substrates. To better understand how CBMs can improve cellulolytic enzyme reactivity, representatives from each of the 18 families of CBM found in Ruminoclostridium thermocellum were fused to the multifunctional GH5 catalytic domain of CelE (Cthe_0797, CelEcc), which can hydrolyze numerous types of polysaccharides including cellulose, mannan, and xylan. Since CelE is a cellulosomal enzyme, none of these fusions to a CBM previously existed. CelEcc_CBM fusions were assayed for their ability to hydrolyze cellulose, lichenan, xylan, and mannan. Several CelEcc_CBM fusions showed enhanced hydrolyticmore » activity with different substrates relative to the fusion to CBM3a from the cellulosome scaffoldin, which has high affinity for binding to crystalline cellulose. Additional binding studies and quantitative catalysis studies using nanostructure-initiator mass spectrometry (NIMS) were carried out with the CBM3a, CBM6, CBM30, and CBM44 fusion enzymes. In general, and consistent with observations of others, enhanced enzyme reactivity was correlated with moderate binding affinity of the CBM. Numerical analysis of reaction time courses showed that CelEcc_CBM44, a combination of a multifunctional enzyme domain with a CBM having broad binding specificity, gave the fastest rates for hydrolysis of both the hexose and pentose fractions of ionic-liquid pretreated switchgrass. In conclusion, we have shown that fusions of different CBMs to a single multifunctional GH5 catalytic domain can increase its rate of reaction with different pure polysaccharides and with pretreated biomass. This fusion approach, incorporating domains with broad specificity for binding and catalysis, provides a new avenue to improve reactivity of simple combinations of enzymes within the complexity of plant biomass.« less

Comprehensive analysis of the MYB-NFIB gene fusion in salivary adenoid cystic carcinoma: Incidence, variability, and clinicopathologic significance.

PubMed

Mitani, Yoshitsugu; Li, Jie; Rao, Pulivarthi H; Zhao, Yi-Jue; Bell, Diana; Lippman, Scott M; Weber, Randal S; Caulin, Carlos; El-Naggar, Adel K

2010-10-01

The objectives of this study were to determine the incidence of the MYB-NFIB fusion in salivary adenoid cystic carcinoma (ACC), to establish the clinicopathologic significance of the fusion, and to analyze the expression of MYB in ACCs in the context of the MYB-NFIB fusion. We did an extensive analysis involving 123 cancers of the salivary gland, including primary and metastatic ACCs, and non-ACC salivary carcinomas. MYB-NFIB fusions were identified by reverse transcriptase-PCR (RT-PCR) and sequencing of the RT-PCR products, and confirmed by fluorescence in situ hybridization. MYB RNA expression was determined by quantitative RT-PCR and protein expression was analyzed by immunohistochemistry. The MYB-NFIB fusion was detected in 28% primary and 35% metastatic ACCs, but not in any of the non-ACC salivary carcinomas analyzed. Different exons in both the MYB and NFIB genes were involved in the fusions, resulting in expression of multiple chimeric variants. Notably, MYB was overexpressed in the vast majority of the ACCs, although MYB expression was significantly higher in tumors carrying the MYB-NFIB fusion. The presence of the MYB-NFIB fusion was significantly associated (P = 0.03) with patients older than 50 years of age. No correlation with other clinicopathologic markers, factors, and survival was found. We conclude that the MYB-NFIB fusion characterizes a subset of ACCs and contributes to MYB overexpression. Additional mechanisms may be involved in MYB overexpression in ACCs lacking the MYB-NFIB fusion. These findings suggest that MYB may be a specific novel target for tumor intervention in patients with ACC. ©2010 AACR.

Celastrol suppresses tumor cell growth through targeting an AR-ERG-NF-κB pathway in TMPRSS2/ERG fusion gene expressing prostate cancer.

PubMed

Shao, Longjiang; Zhou, Zhansong; Cai, Yi; Castro, Patricia; Dakhov, Olga; Shi, Ping; Bai, Yaoxia; Ji, Huixiang; Shen, Wenhao; Wang, Jianghua

2013-01-01

The TMPRSS2/ERG (T/E) fusion gene is present in the majority of all prostate cancers (PCa). We have shown previously that NF-kB signaling is highly activated in these T/E fusion expressing cells via phosphorylation of NF-kB p65 Ser536 (p536). We therefore hypothesize that targeting NF-kB signaling may be an efficacious approach for the subgroup of PCas that carry T/E fusions. Celastrol is a well known NF-kB inhibitor, and thus may inhibit T/E fusion expressing PCa cell growth. We therefore evaluated Celastrol's effects in vitro and in vivo in VCaP cells, which express the T/E fusion gene. VCaP cells were treated with different concentrations of Celastrol and growth inhibition and target expression were evaluated. To test its ability to inhibit growth in vivo, 0.5 mg/kg Celastrol was used to treat mice bearing subcutaneous VCaP xenograft tumors. Our results show Celastrol can significantly inhibit the growth of T/E fusion expressing PCa cells both in vitro and in vivo through targeting three critical signaling pathways: AR, ERG and NF-kB in these cells. When mice received 0.5 mg/kg Celastrol for 4 times/week, significant growth inhibition was seen with no obvious toxicity or significant weight loss. Therefore, Celastrol is a promising candidate drug for T/E fusion expressing PCa. Our findings provide a novel strategy for the targeted therapy which may benefit the more than half of PCa patients who have T/E fusion expressing PCas.

Prostate cancer risk regions at 8q24 and 17q24 are differentially associated with somatic TMPRSS2:ERG fusion status

PubMed Central

Luedeke, Manuel; Rinckleb, Antje E.; FitzGerald, Liesel M.; Geybels, Milan S.; Schleutker, Johanna; Eeles, Rosalind A.; Teixeira, Manuel R.; Cannon-Albright, Lisa; Ostrander, Elaine A.; Weikert, Steffen; Herkommer, Kathleen; Wahlfors, Tiina; Visakorpi, Tapio; Leinonen, Katri A.; Tammela, Teuvo L.J.; Cooper, Colin S.; Kote-Jarai, Zsofia; Edwards, Sandra; Goh, Chee L.; McCarthy, Frank; Parker, Chris; Flohr, Penny; Paulo, Paula; Jerónimo, Carmen; Henrique, Rui; Krause, Hans; Wach, Sven; Lieb, Verena; Rau, Tilman T.; Vogel, Walther; Kuefer, Rainer; Hofer, Matthias D.; Perner, Sven; Rubin, Mark A.; Agarwal, Archana M.; Easton, Doug F.; Al Olama, Ali Amin; Benlloch, Sara; Hoegel, Josef; Stanford, Janet L.

2016-01-01

Abstract Molecular and epidemiological differences have been described between TMPRSS2:ERG fusion-positive and fusion-negative prostate cancer (PrCa). Assuming two molecularly distinct subtypes, we have examined 27 common PrCa risk variants, previously identified in genome-wide association studies, for subtype specific associations in a total of 1221 TMPRSS2:ERG phenotyped PrCa cases. In meta-analyses of a discovery set of 552 cases with TMPRSS2:ERG data and 7650 unaffected men from five centers we have found support for the hypothesis that several common risk variants are associated with one particular subtype rather than with PrCa in general. Risk variants were analyzed in case-case comparisons (296 TMPRSS2:ERG fusion-positive versus 256 fusion-negative cases) and an independent set of 669 cases with TMPRSS2:ERG data was established to replicate the top five candidates. Significant differences (P < 0.00185) between the two subtypes were observed for rs16901979 (8q24) and rs1859962 (17q24), which were enriched in TMPRSS2:ERG fusion-negative (OR = 0.53, P = 0.0007) and TMPRSS2:ERG fusion-positive PrCa (OR = 1.30, P = 0.0016), respectively. Expression quantitative trait locus analysis was performed to investigate mechanistic links between risk variants, fusion status and target gene mRNA levels. For rs1859962 at 17q24, genotype dependent expression was observed for the candidate target gene SOX9 in TMPRSS2:ERG fusion-positive PrCa, which was not evident in TMPRSS2:ERG negative tumors. The present study established evidence for the first two common PrCa risk variants differentially associated with TMPRSS2:ERG fusion status. TMPRSS2:ERG phenotyping of larger studies is required to determine comprehensive sets of variants with subtype-specific roles in PrCa. PMID:27798103

Study of heavy-ion induced fission for heavy-element synthesis

NASA Astrophysics Data System (ADS)

Nishio, K.; Ikezoe, H.; Hofmann, S.; Heßberger, F. P.; Ackermann, D.; Antalic, S.; Aritomo, Y.; Comas, V. F.; Düllman, Ch. E.; Gorshkov, A.; Graeger, R.; Heinz, S.; Heredia, J. A.; Hirose, K.; Khuyagbaatar, J.; Kindler, B.; Kojouharov, I.; Lommel, B.; Makii, H.; Mann, R.; Mitsuoka, S.; Nagame, Y.; Nishinaka, I.; Ohtsuki, T.; Popeko, A. G.; Saro, S.; Schädel, M.; Türler, A.; Wakabayashi, Y.; Watanabe, Y.; Yakushev, A.; Yeremin, A. V.

2014-03-01

Fission fragment mass distributions were measured in heavy-ion induced fissions using 238U target nucleus. The measured mass distributions changed drastically with incident energy. The results are explained by a change of the ratio between fusion and qasifission with nuclear orientation. A calculation based on a fluctuation dissipation model reproduced the mass distributions and their incident energy dependence. Fusion probability was determined in the analysis, and the values were consistent with those determined from the evaporation residue cross sections.

EFFECTS OF LASER RADIATION ON MATTER. LASER PLASMA: Physics of the plasma corona in the problem of laser controlled thermonuclear fusion

NASA Astrophysics Data System (ADS)

Andreev, N. E.; Gorbunov, Leonid M.; Tikhonchuk, Vladimir T.

1994-09-01

A brief analysis is made of the most important nonlinear processes which result from the interaction of laser radiation with thermonuclear targets. lt is shown that problems in the physics of the plasma corona should be an essential part of any programme of research on laser controlled thermonuclear fusion. A list is given of the problems that have to be solved first before going to the next level of laser energies.

A transversal approach for patch-based label fusion via matrix completion

PubMed Central

Sanroma, Gerard; Wu, Guorong; Gao, Yaozong; Thung, Kim-Han; Guo, Yanrong; Shen, Dinggang

2015-01-01

Recently, multi-atlas patch-based label fusion has received an increasing interest in the medical image segmentation field. After warping the anatomical labels from the atlas images to the target image by registration, label fusion is the key step to determine the latent label for each target image point. Two popular types of patch-based label fusion approaches are (1) reconstruction-based approaches that compute the target labels as a weighted average of atlas labels, where the weights are derived by reconstructing the target image patch using the atlas image patches; and (2) classification-based approaches that determine the target label as a mapping of the target image patch, where the mapping function is often learned using the atlas image patches and their corresponding labels. Both approaches have their advantages and limitations. In this paper, we propose a novel patch-based label fusion method to combine the above two types of approaches via matrix completion (and hence, we call it transversal). As we will show, our method overcomes the individual limitations of both reconstruction-based and classification-based approaches. Since the labeling confidences may vary across the target image points, we further propose a sequential labeling framework that first labels the highly confident points and then gradually labels more challenging points in an iterative manner, guided by the label information determined in the previous iterations. We demonstrate the performance of our novel label fusion method in segmenting the hippocampus in the ADNI dataset, subcortical and limbic structures in the LONI dataset, and mid-brain structures in the SATA dataset. We achieve more accurate segmentation results than both reconstruction-based and classification-based approaches. Our label fusion method is also ranked 1st in the online SATA Multi-Atlas Segmentation Challenge. PMID:26160394

Diagnostic Accuracy of Multiparametric Magnetic Resonance Imaging and Fusion Guided Targeted Biopsy Evaluated by Transperineal Template Saturation Prostate Biopsy for the Detection and Characterization of Prostate Cancer.

PubMed

Mortezavi, Ashkan; Märzendorfer, Olivia; Donati, Olivio F; Rizzi, Gianluca; Rupp, Niels J; Wettstein, Marian S; Gross, Oliver; Sulser, Tullio; Hermanns, Thomas; Eberli, Daniel

2018-02-21

We evaluated the diagnostic accuracy of multiparametric magnetic resonance imaging and multiparametric magnetic resonance imaging/transrectal ultrasound fusion guided targeted biopsy against that of transperineal template saturation prostate biopsy to detect prostate cancer. We retrospectively analyzed the records of 415 men who consecutively presented for prostate biopsy between November 2014 and September 2016 at our tertiary care center. Multiparametric magnetic resonance imaging was performed using a 3 Tesla device without an endorectal coil, followed by transperineal template saturation prostate biopsy with the BiopSee® fusion system. Additional fusion guided targeted biopsy was done in men with a suspicious lesion on multiparametric magnetic resonance imaging, defined as Likert score 3 to 5. Any Gleason pattern 4 or greater was defined as clinically significant prostate cancer. The detection rates of multiparametric magnetic resonance imaging and fusion guided targeted biopsy were compared with the detection rate of transperineal template saturation prostate biopsy using the McNemar test. We obtained a median of 40 (range 30 to 55) and 3 (range 2 to 4) transperineal template saturation prostate biopsy and fusion guided targeted biopsy cores, respectively. Of the 124 patients (29.9%) without a suspicious lesion on multiparametric magnetic resonance imaging 32 (25.8%) were found to have clinically significant prostate cancer on transperineal template saturation prostate biopsy. Of the 291 patients (70.1%) with a Likert score of 3 to 5 clinically significant prostate cancer was detected in 129 (44.3%) by multiparametric magnetic resonance imaging fusion guided targeted biopsy, in 176 (60.5%) by transperineal template saturation prostate biopsy and in 187 (64.3%) by the combined approach. Overall 58 cases (19.9%) of clinically significant prostate cancer would have been missed if fusion guided targeted biopsy had been performed exclusively. The sensitivity of multiparametric magnetic resonance imaging and fusion guided targeted biopsy for clinically significant prostate cancer was 84.6% and 56.7% with a negative likelihood ratio of 0.35 and 0.46, respectively. Multiparametric magnetic resonance imaging alone should not be performed as a triage test due to a substantial number of false-negative cases with clinically significant prostate cancer. Systematic biopsy outperformed fusion guided targeted biopsy. Therefore, it will remain crucial in the diagnostic pathway of prostate cancer. Copyright © 2018 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

[Construction and expression of the targeting super-antigen EGF-SEA fusion gene].

PubMed

Xie, Yang; Peng, Shaoping; Liao, Zhiying; Liu, Jiafeng; Liu, Xuemei; Chen, Weifeng

2014-05-01

To construct expression vector for the SEA-EGF fusion gene. Clone the SEA gene and the EGF gene segment with PCR and RT-PCR independently, and connect this two genes by the bridge PCR. Insert the fusion gene EGF-SEA into the expression vector PET-44. Induced the secretion of the fusion protein SEA-EGF by the antileptic. The gene fragment encoding EGF and SEA mature peptide was successfully cloned. The fusion gene EGF-SEA was successfully constructed and was inserted into expression vector. The new recombinant expression vector for fusion gene EGF-SEA is specific for head and neck cancer, laid the foundation for the further study of fusion protein SEA-EGF targeting immune therapy in head and neck tumors.

Recurrent R-spondin fusions in colon cancer.

PubMed

Seshagiri, Somasekar; Stawiski, Eric W; Durinck, Steffen; Modrusan, Zora; Storm, Elaine E; Conboy, Caitlin B; Chaudhuri, Subhra; Guan, Yinghui; Janakiraman, Vasantharajan; Jaiswal, Bijay S; Guillory, Joseph; Ha, Connie; Dijkgraaf, Gerrit J P; Stinson, Jeremy; Gnad, Florian; Huntley, Melanie A; Degenhardt, Jeremiah D; Haverty, Peter M; Bourgon, Richard; Wang, Weiru; Koeppen, Hartmut; Gentleman, Robert; Starr, Timothy K; Zhang, Zemin; Largaespada, David A; Wu, Thomas D; de Sauvage, Frederic J

2012-08-30

Identifying and understanding changes in cancer genomes is essential for the development of targeted therapeutics. Here we analyse systematically more than 70 pairs of primary human colon tumours by applying next-generation sequencing to characterize their exomes, transcriptomes and copy-number alterations. We have identified 36,303 protein-altering somatic changes that include several new recurrent mutations in the Wnt pathway gene TCF7L2, chromatin-remodelling genes such as TET2 and TET3 and receptor tyrosine kinases including ERBB3. Our analysis for significantly mutated cancer genes identified 23 candidates, including the cell cycle checkpoint kinase ATM. Copy-number and RNA-seq data analysis identified amplifications and corresponding overexpression of IGF2 in a subset of colon tumours. Furthermore, using RNA-seq data we identified multiple fusion transcripts including recurrent gene fusions involving R-spondin family members RSPO2 and RSPO3 that together occur in 10% of colon tumours. The RSPO fusions were mutually exclusive with APC mutations, indicating that they probably have a role in the activation of Wnt signalling and tumorigenesis. Consistent with this we show that the RSPO fusion proteins were capable of potentiating Wnt signalling. The R-spondin gene fusions and several other gene mutations identified in this study provide new potential opportunities for therapeutic intervention in colon cancer.

Recurrent R-spondin fusions in colon cancer

PubMed Central

Seshagiri, Somasekar; Stawiski, Eric W.; Durinck, Steffen; Modrusan, Zora; Storm, Elaine E.; Conboy, Caitlin B.; Chaudhuri, Subhra; Guan, Yinghui; Janakiraman, Vasantharajan; Jaiswal, Bijay S.; Guillory, Joseph; Ha, Connie; Dijkgraaf, Gerrit J. P.; Stinson, Jeremy; Gnad, Florian; Huntley, Melanie A.; Degenhardt, Jeremiah D.; Haverty, Peter M.; Bourgon, Richard; Wang, Weiru; Koeppen, Hartmut; Gentleman, Robert; Starr, Timothy K.; Zhang, Zemin; Largaespada, David A.; Wu, Thomas D.; de Sauvage, Frederic J

2013-01-01

Identifying and understanding changes in cancer genomes is essential for the development of targeted therapeutics1. Here we analyse systematically more than 70 pairs of primary human colon tumours by applying next-generation sequencing to characterize their exomes, transcriptomes and copy-number alterations. We have identified 36,303 protein-altering somatic changes that include several new recurrent mutations in the Wnt pathway gene TCF7L2, chromatin-remodelling genes such as TET2 and TET3 and receptor tyrosine kinases including ERBB3. Our analysis for significantly mutated cancer genes identified 23 candidates, including the cell cycle checkpoint kinase ATM. Copy-number and RNA-seq data analysis identified amplifications and corresponding overexpression of IGF2 in a subset of colon tumours. Furthermore, using RNA-seq data we identified multiple fusion transcripts including recurrent gene fusions involving R-spondin family members RSPO2 and RSPO3 that together occur in 10% of colon tumours. The RSPO fusions were mutually exclusive with APC mutations, indicating that they probably have a role in the activation of Wnt signalling and tumorigenesis. Consistent with this we show that the RSPO fusion proteins were capable of potentiating Wnt signalling. The R-spondin gene fusions and several other gene mutations identified in this study provide new potential opportunities for therapeutic intervention in colon cancer. PMID:22895193

Universal antibodies against the highly conserved influenza fusion peptide cross-neutralize several subtypes of influenza A virus

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

Hashem, Anwar M.; Department of Microbiology, Faculty of Medicine, King Abdulaziz University, Jeddah; Department of Biochemistry, Microbiology and Immunology, University of Ottawa, Ottawa, ON

Research highlights: {yields} The fusion peptide is the only universally conserved epitope in all influenza viral hemagglutinins. {yields} Anti-fusion peptide antibodies are universal antibodies that cross-react with all influenza HA subtypes. {yields} The universal antibodies cross-neutralize different influenza A subtypes. {yields} The universal antibodies inhibit the fusion process between the viruses and the target cells. -- Abstract: The fusion peptide of influenza viral hemagglutinin plays a critical role in virus entry by facilitating membrane fusion between the virus and target cells. As the fusion peptide is the only universally conserved epitope in all influenza A and B viruses, it couldmore » be an attractive target for vaccine-induced immune responses. We previously reported that antibodies targeting the first 14 amino acids of the N-terminus of the fusion peptide could bind to virtually all influenza virus strains and quantify hemagglutinins in vaccines produced in embryonated eggs. Here we demonstrate that these universal antibodies bind to the viral hemagglutinins in native conformation presented in infected mammalian cell cultures and neutralize multiple subtypes of virus by inhibiting the pH-dependant fusion of viral and cellular membranes. These results suggest that this unique, highly-conserved linear sequence in viral hemagglutinin is exposed sufficiently to be attacked by the antibodies during the course of infection and merits further investigation because of potential importance in the protection against diverse strains of influenza viruses.« less

Laser or charged-particle-beam fusion reactor with direct electric generation by magnetic flux compression

DOEpatents

Lasche, George P.

1988-01-01

A high-power-density laser or charged-particle-beam fusion reactor system maximizes the directed kinetic energy imparted to a large mass of liquid lithium by a centrally located fusion target. A fusion target is embedded in a large mass of lithium, of sufficient radius to act as a tritium breeding blanket, and provided with ports for the access of beam energy to implode the target. The directed kinetic energy is converted directly to electricity with high efficiency by work done against a pulsed magnetic field applied exterior to the lithium. Because the system maximizes the blanket thickness per unit volume of lithium, neutron-induced radioactivities in the reaction chamber wall are several orders of magnitude less than is typical of other fusion reactor systems.

Laser or charged-particle-beam fusion reactor with direct electric generation by magnetic flux compression

DOEpatents

Lasche, G.P.

1987-02-20

A high-power-density-laser or charged-particle-beam fusion reactor system maximizes the directed kinetic energy imparted to a large mass of liquid lithium by a centrally located fusion target. A fusion target is embedded in a large mass of lithium, of sufficient radius to act as a tritium breeding blanket, and provided with ports for the access of beam energy to implode the target. The directed kinetic energy is converted directly to electricity with high efficiency by work done against a pulsed magnetic field applied exterior to the lithium. Because the system maximizes the blanket thickness per unit volume of lithium, neutron-induced radioactivities in the reaction chamber wall are several orders of magnitude less than is typical of other fusion reactor systems. 25 figs.

Magnetized target fusion: An ultra high energy approach in an unexplored parameter space

NASA Astrophysics Data System (ADS)

Lindemuth, I. R.

Magnetized target fusion is a concept that may lead to practical fusion applications in a variety of settings. However, the crucial first step is to demonstrate that it works as advertised. Among the possibilities for doing this is an ultrahigh energy approach to magnetized target fusion, one powered by explosive pulsed power generators that have become available for application to thermonuclear fusion research. In a collaborative effort between Los Alamos and the All-Russian Scientific Institute for Experimental Physics (VNIIEF) a very powerful helical generator with explosive power switching has been used to produce an energetic magnetized plasma. Several diagnostics have been fielded to ascertain the properties of this plasma. We are intensively studying the results of the experiments and calculationally analyzing the performance of this experiment.

Influence of incomplete fusion on complete fusion at energies above the Coulomb barrier

NASA Astrophysics Data System (ADS)

Shuaib, Mohd; Sharma, Vijay R.; Yadav, Abhishek; Sharma, Manoj Kumar; Singh, Pushpendra P.; Singh, Devendra P.; Kumar, R.; Singh, R. P.; Muralithar, S.; Singh, B. P.; Prasad, R.

2017-10-01

In the present work, excitation functions of several reaction residues in the system 19F+169Tm, populated via the complete and incomplete fusion processes, have been measured using off-line γ-ray spectroscopy. The analysis of excitation functions has been done within the framework of statistical model code pace4. The excitation functions of residues populated via xn and pxn channels are found to be in good agreement with those estimated by the theoretical model code, which confirms the production of these residues solely via complete fusion process. However, a significant enhancement has been observed in the cross-sections of residues involving α-emitting channels as compared to the theoretical predictions. The observed enhancement in the cross-sections has been attributed to the incomplete fusion processes. In order to have a better insight into the onset and strength of incomplete fusion, the incomplete fusion strength function has been deduced. At present, there is no theoretical model available which can satisfactorily explain the incomplete fusion reaction data at energies ≈4-6 MeV/nucleon. In the present work, the influence of incomplete fusion on complete fusion in the 19F+169Tm system has also been studied. The measured cross-section data may be important for the development of reactor technology as well. It has been found that the incomplete fusion strength function strongly depends on the α-Q value of the projectile, which is found to be in good agreement with the existing literature data. The analysis strongly supports the projectile-dependent mass-asymmetry systematics. In order to study the influence of Coulomb effect ({Z}{{P}}{Z}{{T}}) on incomplete fusion, the deduced strength function for the present work is compared with the nearby projectile-target combinations. The incomplete fusion strength function is found to increase linearly with {Z}{{P}}{Z}{{T}}, indicating a strong influence of Coulomb effect in the incomplete fusion reactions.

Non-ad-hoc decision rule for the Dempster-Shafer method of evidential reasoning

NASA Astrophysics Data System (ADS)

Cheaito, Ali; Lecours, Michael; Bosse, Eloi

1998-03-01

This paper is concerned with the fusion of identity information through the use of statistical analysis rooted in Dempster-Shafer theory of evidence to provide automatic identification aboard a platform. An identity information process for a baseline Multi-Source Data Fusion (MSDF) system is defined. The MSDF system is applied to information sources which include a number of radars, IFF systems, an ESM system, and a remote track source. We use a comprehensive Platform Data Base (PDB) containing all the possible identity values that the potential target may take, and we use the fuzzy logic strategies which enable the fusion of subjective attribute information from sensor and the PDB to make the derivation of target identity more quickly, more precisely, and with statistically quantifiable measures of confidence. The conventional Dempster-Shafer lacks a formal basis upon which decision can be made in the face of ambiguity. We define a non-ad hoc decision rule based on the expected utility interval for pruning the `unessential' propositions which would otherwise overload the real-time data fusion systems. An example has been selected to demonstrate the implementation of our modified Dempster-Shafer method of evidential reasoning.

Recurrent LRP1-SNRNP25 and KCNMB4-CCND3 fusion genes promote tumor cell motility in human osteosarcoma.

PubMed

Yang, Jilong; Annala, Matti; Ji, Ping; Wang, Guowen; Zheng, Hong; Codgell, David; Du, Xiaoling; Fang, Zhiwei; Sun, Baocun; Nykter, Matti; Chen, Kexin; Zhang, Wei

2014-10-10

The identification of fusion genes such as SYT-SSX1/SSX2, PAX3-FOXO1, TPM3/TPM4-ALK and EWS-FLI1 in human sarcomas has provided important insight into the diagnosis and targeted therapy of sarcomas. No recurrent fusion has been reported in human osteosarcoma. Transcriptome sequencing was used to characterize the gene fusions and mutations in 11 human osteosarcomas. Nine of 11 samples were found to harbor genetic inactivating alterations in the TP53 pathway. Two recurrent fusion genes associated with the 12q locus, LRP1-SNRNP25 and KCNMB4-CCND3, were identified and validated by RT-PCR, Sanger sequencing and fluorescence in situ hybridization, and were found to be osteosarcoma specific in a validation cohort of 240 other sarcomas. Expression of LRP1-SNRNP25 fusion gene promoted SAOS-2 osteosarcoma cell migration and invasion. Expression of KCNMB4-CCND3 fusion gene promoted SAOS-2 cell migration. Our study represents the first whole transcriptome analysis of untreated human osteosarcoma. Our discovery of two osteosarcoma specific fusion genes associated with osteosarcoma cellular motility highlights the heterogeneity of osteosarcoma and provides opportunities for new treatment modalities.

PAX3-FOXO1: Zooming in on an "undruggable" target.

PubMed

Wachtel, Marco; Schäfer, Beat W

2018-06-01

Driver oncogenes are prime targets for therapy in tumors many of which, including leukemias and sarcomas, express recurrent fusion transcription factors. One specific example for such a cancer type is alveolar rhabdomyosarcoma, which is associated in the majority of cases with the fusion protein PAX3-FOXO1. Since fusion transcription factors are challenging targets for development of small molecule inhibitors, indirect inhibitory strategies for this type of oncogenes represent a more promising approach. One can envision strategies at different molecular levels including upstream modifiers and activators, epigenetic and transcriptional co-regulators, and downstream effector targets. In this review, we will discuss the current knowledge regarding potential therapeutic targets that might contribute to indirect interference with PAX3-FOXO1 activity in alveolar rhabdomyosarcoma at the different molecular levels and extrapolate these findings to fusion transcription factors in general. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

Magnetic resonance/transrectal ultrasound fusion biopsy of the prostate compared to systematic 12-core biopsy for the diagnosis and characterization of prostate cancer: multi-institutional retrospective analysis of 389 patients.

PubMed

Mariotti, Guilherme C; Costa, Daniel N; Pedrosa, Ivan; Falsarella, Priscila M; Martins, Tatiana; Roehrborn, Claus G; Rofsky, Neil M; Xi, Yin; M Andrade, Thais C; Queiroz, Marcos R; Lotan, Yair; Garcia, Rodrigo G; Lemos, Gustavo C; Baroni, Ronaldo H

2016-09-01

To determine the incremental diagnostic value of targeted biopsies added to an extended sextant biopsy scheme on a per-patient, risk-stratified basis in 2 academic centers using different multiparametric magnetic resonance imaging (MRI) protocols, a large group of radiologists, multiple biopsy systems, and different biopsy operators. All patients with suspected prostate cancer (PCa) who underwent multiparametric MRI of the prostate in 2 academic centers between February 2013 and January 2015 followed by systematic and targeted MRI-transrectal ultrasound fusion biopsy were reviewed. Risk-stratified detection rate using systematic biopsies was compared with targeted biopsies on a per-patient basis. The McNemar test was used to compare diagnostic performance of the 2 approaches. A total of 389 men met eligibility criteria. PCa was diagnosed in 47% (182/389), 52%(202/389), and 60%(235/389) of patients using the targeted, systematic, and combined (targeted plus systematic) approach, respectively. Compared with systematic biopsy, targeted biopsy diagnosed 11% (37 vs. 26) more intermediate-to-high risk (P<0.0001) and 16% (10 vs. 16) fewer low-risk tumors (P<0.0001). These results were replicated when data from each center, biopsy-naïve patients, and men with previous negative biopsies were analyzed separately. Targeted MRI-transrectal ultrasound fusion biopsy consistently improved the detection of clinically significant PCa in a large patient cohort with diverse equipment, protocols, radiologists, and biopsy operators as can be encountered in clinical practice. Copyright © 2016 Elsevier Inc. All rights reserved.

Covariance descriptor fusion for target detection

NASA Astrophysics Data System (ADS)

Cukur, Huseyin; Binol, Hamidullah; Bal, Abdullah; Yavuz, Fatih

2016-05-01

Target detection is one of the most important topics for military or civilian applications. In order to address such detection tasks, hyperspectral imaging sensors provide useful images data containing both spatial and spectral information. Target detection has various challenging scenarios for hyperspectral images. To overcome these challenges, covariance descriptor presents many advantages. Detection capability of the conventional covariance descriptor technique can be improved by fusion methods. In this paper, hyperspectral bands are clustered according to inter-bands correlation. Target detection is then realized by fusion of covariance descriptor results based on the band clusters. The proposed combination technique is denoted Covariance Descriptor Fusion (CDF). The efficiency of the CDF is evaluated by applying to hyperspectral imagery to detect man-made objects. The obtained results show that the CDF presents better performance than the conventional covariance descriptor.

Understanding fuel magnetization and mix using secondary nuclear reactions in magneto-inertial fusion.

PubMed

Schmit, P F; Knapp, P F; Hansen, S B; Gomez, M R; Hahn, K D; Sinars, D B; Peterson, K J; Slutz, S A; Sefkow, A B; Awe, T J; Harding, E; Jennings, C A; Chandler, G A; Cooper, G W; Cuneo, M E; Geissel, M; Harvey-Thompson, A J; Herrmann, M C; Hess, M H; Johns, O; Lamppa, D C; Martin, M R; McBride, R D; Porter, J L; Robertson, G K; Rochau, G A; Rovang, D C; Ruiz, C L; Savage, M E; Smith, I C; Stygar, W A; Vesey, R A

2014-10-10

Magnetizing the fuel in inertial confinement fusion relaxes ignition requirements by reducing thermal conductivity and changing the physics of burn product confinement. Diagnosing the level of fuel magnetization during burn is critical to understanding target performance in magneto-inertial fusion (MIF) implosions. In pure deuterium fusion plasma, 1.01 MeV tritons are emitted during deuterium-deuterium fusion and can undergo secondary deuterium-tritium reactions before exiting the fuel. Increasing the fuel magnetization elongates the path lengths through the fuel of some of the tritons, enhancing their probability of reaction. Based on this feature, a method to diagnose fuel magnetization using the ratio of overall deuterium-tritium to deuterium-deuterium neutron yields is developed. Analysis of anisotropies in the secondary neutron energy spectra further constrain the measurement. Secondary reactions also are shown to provide an upper bound for the volumetric fuel-pusher mix in MIF. The analysis is applied to recent MIF experiments [M. R. Gomez et al., Phys. Rev. Lett. 113, 155003 (2014)] on the Z Pulsed Power Facility, indicating that significant magnetic confinement of charged burn products was achieved and suggesting a relatively low-mix environment. Both of these are essential features of future ignition-scale MIF designs.

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.

Hybrid Capture-Based Tumor Sequencing and Copy Number Analysis to Confirm Origin of Metachronous Metastases in BRCA1-Mutant Cholangiocarcinoma Harboring a Novel YWHAZ-BRAF Fusion.

PubMed

Lim, Huat C; Montesion, Meagan; Botton, Thomas; Collisson, Eric A; Umetsu, Sarah E; Behr, Spencer C; Gordan, John D; Stephens, Phil J; Kelley, Robin K

2018-04-05

Biliary tract cancers such as cholangiocarcinoma represent a heterogeneous group of cancers that can be difficult to diagnose. Recent comprehensive genomic analyses in large cholangiocarcinoma cohorts have defined important molecular subgroups within cholangiocarcinoma that may relate to anatomic location and etiology [1-4] and may predict responsiveness to targeted therapies in development [5-7]. These emerging data highlight the potential for tumor genomics to inform diagnosis and treatment options in this challenging tumor type. We report the case of a patient with a germline BRCA1 mutation who presented with a cholangiocarcinoma driven by the novel YWHAZ-BRAF fusion. Hybrid capture-based DNA sequencing and copy number analysis performed as part of clinical care demonstrated that two later-occurring tumors were clonally derived from the primary cholangiocarcinoma rather than distinct new primaries, revealing an unusual pattern of late metachronous metastasis. We discuss the clinical significance of these genetic alterations and their relevance to therapeutic strategies. Hybrid capture-based next-generation DNA sequencing assays can provide diagnostic clarity in patients with unusual patterns of metastasis and recurrence in which the pathologic diagnosis is ambiguous.To our knowledge, this is the first reported case of a YWHAZ-BRAF fusion in pancreaticobiliary cancer, and a very rare case of cholangiocarcinoma in the setting of a germline BRCA1 mutation.The patient's BRCA1 mutation and YWHAZ-BRAF fusion constitute potential targets for future therapy. © AlphaMed Press 2018.

Progress In Magnetized Target Fusion Driven by Plasma Liners

NASA Technical Reports Server (NTRS)

Thio, Francis Y. C.; Kirkpatrick, Ronald C.; Knapp, Charles E.; Cassibry, Jason; Eskridge, Richard; Lee, Michael; Smith, James; Martin, Adam; Wu, S. T.; Schmidt, George;

[Targeted detecting HER2 expression with recombinant anti HER2 ScFv-GFP fusion antibody].

PubMed

Gao, Guohui; Chen, Chong; Yang, Yanmei; Yang, Han; Wang, Jindan; Zheng, Yi; Huang, Qidi; Hu, Xiaoqu

2012-08-01

To verify the reliability of targeted detecting HER2 positive cancer cells and clinical pathological tissue specimens with a recombinant anti HER2 single chain antibody in single chain Fv fragment (scFv) format, we have constructed the fusion variable regions of the ScFv specific for HER2/neu. labeled a green-fluorescent protein(GFP). The humanized recombinant Anti HER2 ScFv-GFP gene was inserted into pFast Bac HT A, and expressed in insect cells sf9. Then the recombinant fusion protein Anti HER2 ScFv-GFP was properly purified with Ni2+-NTA affinity chromatography from the infected sf9 cells used to test the specificity of the fusion antibody for HER2 positive cancer cells. Firstly, the purified antibody incubated with HER2 positive breast cancer cells SKBR3, BT474 and HER2 negative breast cancer cells MCF7 for 12 h/24 h/48 h at 37 degrees C, in order to confirm targeted detecting HER2 positive breast cancer cells by Laser Confocal Microscopy. Furthermore, the same clinical pathological tissue samples were assessed by immunohistochemistry (IHC) and the fusion antibody Anti HER2 ScFv-GFP in the meanwhile. The data obtained indicated that the recombinant eukaryotic expression plasmid pFast Bac HT A/Anti HER2 ScFv-GFP was constructed successfully In addition, obvious green fluorescent was observed in insect cells sf9. When the purified fusion antibody was incubated with different cancer cells, much more green fluorescent was observed on the surface of the HER2 positive cancer cells SKBR3 and BT474. In contrast, no green fluorescent on the surface of the HER2 negative cancer cells MCF7 was detected. The concentration of the purified fusion antibody was 115.5 microg/mL, of which protein relative molecular weight was 60 kDa. The analysis showed the purity was about 97% and the titer was about 1:64. The detection results of IHC and fusion antibody testing indicated the conformity. In summary, the study showed that the new fusion antibody Anti HER2 ScFv-GFP can test HER2 positive cancer cells, indicating a potential candidate method for clinical HER2 positive specimens detection.

Activity of foreign proteins targeted within the bacteriophage T4 head and prohead: implications for packaged DNA structure.

PubMed

Mullaney, J M; Black, L W

1998-11-13

The phage-derived expression, packaging, and processing (PEPP) system was used to target foreign proteins into the bacteriophage capsid to probe the intracapsid environment and the structure of packaged DNA. Small proteins with minimal requirements for activity were selected, staphylococcal nuclease (SN) and green fluorescent protein (GFP). These proteins were targeted into the T4 head by means of IPIII (internal protein III) fusions or CTS (capsid targeting sequence) fusions. Additional evidence is provided that foreign proteins are targeted into T4 by the N-terminal ten amino acid residue consensus CTS of IPIII identified in previous work. Fusion proteins were produced within host bacteria by expression from plasmids or by produc tion from recombinant phage carrying the fusion genes. Packaged fusion proteins CTS IPIII SN, CTS IPIII TSN, CTS IPIII GFP, CTS IPIII TGFP, and CTS GFP, where [symbol: see text] indicates a linkage peptide sequence Leu(Ile)-N-Glu cleaved by the T4 head morphogenetic proteinase gp21 during head maturation, are observed to exhibit intracapsid activity. SN activity within the head is demonstrated by loss of phage viability and by digested genomic DNA patterns visualized by gel electrophoresis when viable phage are incubated in Ca2+. Green fluorescent phage result immediately after packaging GFP produced at 30 degreesC and below, and continue to give green fluorescence under 470 nm light after CsCl purification. Non-fluorescent GFP-fusions are produced in bacteria at 37 degreesC, and phage packaged with these proteins achieve a fluorescent state after incubation for several months at 4 degreesC. GFP-packaged phage and proheads analyzed by fluorescence spectroscopy show that the mature head and the DNA-empty prohead package identical numbers of GFP-fusion proteins. Encapsidated GFP and SN can be injected into bacteria and rapidly exhibit intracellular activity. In vivo SN digestion of encapsidated DNA gives an intriguing pattern of DNA fragments by gel analysis, predominantly a repeat pattern of 160 bp multiples, reminiscent of a nucleosome digestion ladder, This quasi-limit DNA digestion pattern, reached >100-fold more slowly than the loss of titer, is invariant over a range

Target detection method by airborne and spaceborne images fusion based on past images

NASA Astrophysics Data System (ADS)

Chen, Shanjing; Kang, Qing; Wang, Zhenggang; Shen, ZhiQiang; Pu, Huan; Han, Hao; Gu, Zhongzheng

2017-11-01

To solve the problem that remote sensing target detection method has low utilization rate of past remote sensing data on target area, and can not recognize camouflage target accurately, a target detection method by airborne and spaceborne images fusion based on past images is proposed in this paper. The target area's past of space remote sensing image is taken as background. The airborne and spaceborne remote sensing data is fused and target feature is extracted by the means of airborne and spaceborne images registration, target change feature extraction, background noise suppression and artificial target feature extraction based on real-time aerial optical remote sensing image. Finally, the support vector machine is used to detect and recognize the target on feature fusion data. The experimental results have established that the proposed method combines the target area change feature of airborne and spaceborne remote sensing images with target detection algorithm, and obtains fine detection and recognition effect on camouflage and non-camouflage targets.

Pretargeting with bispecific fusion proteins facilitates delivery of nanoparticles to tumor cells with distinct surface antigens.

PubMed

Yang, Qi; Parker, Christina L; Lin, Yukang; Press, Oliver W; Park, Steven I; Lai, Samuel K

2017-06-10

Tumor heterogeneity, which describes the genetically and phenotypically distinct subpopulations of tumor cells present within the same tumor or patient, presents a major challenge to targeted delivery of diagnostic and/or therapeutic agents. An ideal targeting strategy should deliver a given nanocarrier to the full diversity of cancer cells, which is difficult to achieve with conventional ligand-conjugated nanoparticles. We evaluated pretargeting (i.e., multistep targeting) as a strategy to facilitate nanoparticle delivery to multiple target cells by measuring the uptake of biotinylated nanoparticles by lymphoma cells with distinct surface antigens pretreated with different bispecific streptavidin-scFv fusion proteins. Fusion proteins targeting CD20 or tumor-associated glycoprotein 72 (TAG-72) mediated the specific in vitro uptake of 100nm biotin-functionalized nanoparticles by Raji and Jurkat lymphoma cells (CD20-positive and TAG-72-positive cells, respectively). Greater uptake was observed for pretargeted nanoparticles with increasing amounts of surface biotin, with 6- to 18-fold higher uptake vs. non-biotinylated nanoparticle and fusion protein controls. Fully biotin-modified particles remained resistant to cultured macrophage cell uptake, although they were still quickly cleared from systemic circulation in vivo (t 1/2 <1h). For single Raji tumor-bearing mice, pretargeting with CD20-specific FP significantly increased nanoparticle tumor targeting. In mice bearing both Raji and Jurkat tumors, pretargeting with both fusion proteins markedly increased nanoparticle targeting to both tumor types, compared to animals dosed with nanoparticles alone. These in vitro and in vivo observations support further evaluations of pretargeting fusion protein cocktails as a strategy to enhance nanoparticle delivery to a diverse array of molecularly distinct target cells. Copyright © 2017 Elsevier B.V. All rights reserved.

Influence of hydrophobic and electrostatic residues on SARS-coronavirus S2 protein stability: Insights into mechanisms of general viral fusion and inhibitor design

PubMed Central

Aydin, Halil; Al-Khooly, Dina; Lee, Jeffrey E

2014-01-01

Severe acute respiratory syndrome (SARS) is an acute respiratory disease caused by the SARS-coronavirus (SARS-CoV). SARS-CoV entry is facilitated by the spike protein (S), which consists of an N-terminal domain (S1) responsible for cellular attachment and a C-terminal domain (S2) that mediates viral and host cell membrane fusion. The SARS-CoV S2 is a potential drug target, as peptidomimetics against S2 act as potent fusion inhibitors. In this study, site-directed mutagenesis and thermal stability experiments on electrostatic, hydrophobic, and polar residues to dissect their roles in stabilizing the S2 postfusion conformation was performed. It was shown that unlike the pH-independent retroviral fusion proteins, SARS-CoV S2 is stable over a wide pH range, supporting its ability to fuse at both the plasma membrane and endosome. A comprehensive SARS-CoV S2 analysis showed that specific hydrophobic positions at the C-terminal end of the HR2, rather than electrostatics are critical for fusion protein stabilization. Disruption of the conserved C-terminal hydrophobic residues destabilized the fusion core and reduced the melting temperature by 30°C. The importance of the C-terminal hydrophobic residues led us to identify a 42-residue substructure on the central core that is structurally conserved in all existing CoV S2 fusion proteins (root mean squared deviation = 0.4 Å). This is the first study to identify such a conserved substructure and likely represents a common foundation to facilitate viral fusion. We have discussed the role of key residues in the design of fusion inhibitors and the potential of the substructure as a general target for the development of novel therapeutics against CoV infections. PMID:24519901

Influence of hydrophobic and electrostatic residues on SARS-coronavirus S2 protein stability: insights into mechanisms of general viral fusion and inhibitor design.

PubMed

Aydin, Halil; Al-Khooly, Dina; Lee, Jeffrey E

2014-05-01

Severe acute respiratory syndrome (SARS) is an acute respiratory disease caused by the SARS-coronavirus (SARS-CoV). SARS-CoV entry is facilitated by the spike protein (S), which consists of an N-terminal domain (S1) responsible for cellular attachment and a C-terminal domain (S2) that mediates viral and host cell membrane fusion. The SARS-CoV S2 is a potential drug target, as peptidomimetics against S2 act as potent fusion inhibitors. In this study, site-directed mutagenesis and thermal stability experiments on electrostatic, hydrophobic, and polar residues to dissect their roles in stabilizing the S2 postfusion conformation was performed. It was shown that unlike the pH-independent retroviral fusion proteins, SARS-CoV S2 is stable over a wide pH range, supporting its ability to fuse at both the plasma membrane and endosome. A comprehensive SARS-CoV S2 analysis showed that specific hydrophobic positions at the C-terminal end of the HR2, rather than electrostatics are critical for fusion protein stabilization. Disruption of the conserved C-terminal hydrophobic residues destabilized the fusion core and reduced the melting temperature by 30°C. The importance of the C-terminal hydrophobic residues led us to identify a 42-residue substructure on the central core that is structurally conserved in all existing CoV S2 fusion proteins (root mean squared deviation=0.4 Å). This is the first study to identify such a conserved substructure and likely represents a common foundation to facilitate viral fusion. We have discussed the role of key residues in the design of fusion inhibitors and the potential of the substructure as a general target for the development of novel therapeutics against CoV infections. © 2014 The Protein Society.

[Binocular fusion method for prevention of myopia].

PubMed

Xu, G D

1989-03-01

When looking at a far object with two eyes, relaxation of convergence and accommodation occurred and accompanied by binocular fusion. Using this phenomenon a method of binocular fusion of targets was designed, that is the distance between two targets are just the same as the distance between two visual lines, while looking at a far object. During the images of the targets are fused, the accommodation and convergence are relaxed concomitantly; thus a result of correction of pseudomyopia and prevention of myopia is achieved. By means of binocular fusion, the eye muscle exercises were conducted and resulted in not only the far point further but also the near point closer. The skiascopic examination carried out at the same time of binocular fusion showed that the degrees of relaxed accommodation was 97.9% that of looking at an object in far distance. The above results indicated that the binocular fusion method had excellent effect on the prevention of myopia. This method is simple and feasible, conforms to the visual physiology, and thus can be widely adopted.

One-Dimensional Burn Dynamics of Plasma-Jet Magneto-Inertial Fusion

NASA Astrophysics Data System (ADS)

Santarius, John

2009-11-01

This poster will discuss several issues related to using plasma jets to implode a Magneto-Inertial Fusion (MIF) liner onto a magnetized plasmoid and compress it to fusion-relevant temperatures [1]. The problem of pure plasma jet convergence and compression without a target present will be investigated. Cases with a target present will explore how well the liner's inertia provides transient plasma stability and confinement. The investigation uses UW's 1-D Lagrangian radiation-hydrodynamics code, BUCKY, which solves single-fluid equations of motion with ion-electron interactions, PdV work, table-lookup equations of state, fast-ion energy deposition, and pressure contributions from all species. Extensions to the code include magnetic field evolution as the plasmoid compresses plus dependence of the thermal conductivity and fusion product energy deposition on the magnetic field.[4pt] [1] Y.C. F. Thio, et al.,``Magnetized Target Fusion in a Spheroidal Geometry with Standoff Drivers,'' in Current Trends in International Fusion Research, E. Panarella, ed. (National Research Council of Canada, Ottawa, Canada, 1999), p. 113.

Image fusion pitfalls for cranial radiosurgery.

PubMed

Jonker, Benjamin P

2013-01-01

Stereotactic radiosurgery requires imaging to define both the stereotactic space in which the treatment is delivered and the target itself. Image fusion is the process of using rotation and translation to bring a second image set into alignment with the first image set. This allows the potential concurrent use of multiple image sets to define the target and stereotactic space. While a single magnetic resonance imaging (MRI) sequence alone can be used for delineation of the target and fiducials, there may be significant advantages to using additional imaging sets including other MRI sequences, computed tomography (CT) scans, and advanced imaging sets such as catheter-based angiography, diffusor tension imaging-based fiber tracking and positon emission tomography in order to more accurately define the target and surrounding critical structures. Stereotactic space is usually defined by detection of fiducials on the stereotactic head frame or mask system. Unfortunately MRI sequences are susceptible to geometric distortion, whereas CT scans do not face this problem (although they have poorer resolution of the target in most cases). Thus image fusion can allow the definition of stereotactic space to proceed from the geometrically accurate CT images at the same time as using MRI to define the target. The use of image fusion is associated with risk of error introduced by inaccuracies of the fusion process, as well as workflow changes that if not properly accounted for can mislead the treating clinician. The purpose of this review is to describe the uses of image fusion in stereotactic radiosurgery as well as its potential pitfalls.

Paramyxovirus Glycoproteins and the Membrane Fusion Process.

PubMed

Aguilar, Hector C; Henderson, Bryce A; Zamora, J Lizbeth; Johnston, Gunner P

2016-09-01

The family Paramyxoviridae includes many viruses that significantly affect human and animal health. An essential step in the paramyxovirus life cycle is viral entry into host cells, mediated by virus-cell membrane fusion. Upon viral entry, infection results in expression of the paramyxoviral glycoproteins on the infected cell surface. This can lead to cell-cell fusion (syncytia formation), often linked to pathogenesis. Thus membrane fusion is essential for both viral entry and cell-cell fusion and an attractive target for therapeutic development. While there are important differences between viral-cell and cell-cell membrane fusion, many aspects are conserved. The paramyxoviruses generally utilize two envelope glycoproteins to orchestrate membrane fusion. Here, we discuss the roles of these glycoproteins in distinct steps of the membrane fusion process. These findings can offer insights into evolutionary relationships among Paramyxoviridae genera and offer future targets for prophylactic and therapeutic development.

Paramyxovirus Glycoproteins and the Membrane Fusion Process

PubMed Central

Aguilar, Hector C.; Henderson, Bryce A.; Zamora, J. Lizbeth; Johnston, Gunner P.

2016-01-01

The family Paramyxoviridae includes many viruses that significantly affect human and animal health. An essential step in the paramyxovirus life cycle is viral entry into host cells, mediated by virus-cell membrane fusion. Upon viral entry, infection results in expression of the paramyxoviral glycoproteins on the infected cell surface. This can lead to cell-cell fusion (syncytia formation), often linked to pathogenesis. Thus membrane fusion is essential for both viral entry and cell-cell fusion and an attractive target for therapeutic development. While there are important differences between viral-cell and cell-cell membrane fusion, many aspects are conserved. The paramyxoviruses generally utilize two envelope glycoproteins to orchestrate membrane fusion. Here, we discuss the roles of these glycoproteins in distinct steps of the membrane fusion process. These findings can offer insights into evolutionary relationships among Paramyxoviridae genera and offer future targets for prophylactic and therapeutic development. PMID:28138419

Generation and validation of homozygous fluorescent knock-in cells using CRISPR-Cas9 genome editing.

PubMed

Koch, Birgit; Nijmeijer, Bianca; Kueblbeck, Moritz; Cai, Yin; Walther, Nike; Ellenberg, Jan

2018-06-01

Gene tagging with fluorescent proteins is essential for investigations of the dynamic properties of cellular proteins. CRISPR-Cas9 technology is a powerful tool for inserting fluorescent markers into all alleles of the gene of interest (GOI) and allows functionality and physiological expression of the fusion protein. It is essential to evaluate such genome-edited cell lines carefully in order to preclude off-target effects caused by (i) incorrect insertion of the fluorescent protein, (ii) perturbation of the fusion protein by the fluorescent proteins or (iii) nonspecific genomic DNA damage by CRISPR-Cas9. In this protocol, we provide a step-by-step description of our systematic pipeline to generate and validate homozygous fluorescent knock-in cell lines.We have used the paired Cas9D10A nickase approach to efficiently insert tags into specific genomic loci via homology-directed repair (HDR) with minimal off-target effects. It is time-consuming and costly to perform whole-genome sequencing of each cell clone to check for spontaneous genetic variations occurring in mammalian cell lines. Therefore, we have developed an efficient validation pipeline of the generated cell lines consisting of junction PCR, Southern blotting analysis, Sanger sequencing, microscopy, western blotting analysis and live-cell imaging for cell-cycle dynamics. This protocol takes between 6 and 9 weeks. With this protocol, up to 70% of the targeted genes can be tagged homozygously with fluorescent proteins, thus resulting in physiological levels and phenotypically functional expression of the fusion proteins.

Production and characterization of in planta transiently produced polygalacturanase from Aspergillus niger and its fusions with hydrophobin or ELP tags.

PubMed

Pereira, Eridan Orlando; Kolotilin, Igor; Conley, Andrew Jonathan; Menassa, Rima

2014-06-27

Pectinases play an important role in plant cell wall deconstruction and have potential in diverse industries such as food, wine, animal feed, textile, paper, fuel, and others. The demand for such enzymes is increasing exponentially, as are the efforts to improve their production and to implement their use in several industrial processes. The goal of this study was to examine the potential of producing polygalacturonase I from Aspergillus niger in plants and to investigate the effects of subcellular compartmentalization and protein fusions on its accumulation and activity. Polygalacturonase I from Aspergillus niger (AnPGI) was transiently produced in Nicotiana benthamiana by targeting it to five different cellular compartments: apoplast, endoplasmic reticulum (ER), vacuole, chloroplast and cytosol. Accumulation levels of 2.5%, 3.0%, and 1.9% of total soluble protein (TSP) were observed in the apoplast, ER, and vacuole, respectively, and specific activity was significantly higher in vacuole-targeted AnPGI compared to the same enzyme targeted to the ER or apoplast. No accumulation was found for AnPGI when targeted to the chloroplast or cytosol. Analysis of AnPGI fused with elastin-like polypeptide (ELP) revealed a significant increase in the protein accumulation level, especially when targeted to the vacuole where the protein doubles its accumulation to 3.6% of TSP, while the hydrophobin (HFBI) fusion impaired AnPGI accumulation and both tags impaired activity, albeit to different extents. The recombinant protein showed activity against polygalacturonic acid with optimum conditions at pH 5.0 and temperature from 30 to 50°C, depending on its fusion. In vivo analysis of reducing sugar content revealed a higher release of reducing sugars in plant tissue expressing recombinant AnPGI compared to wild type N. benthamiana leaves. Our results demonstrate that subcellular compartmentalization of enzymes has an impact on both the target protein accumulation and its activity, especially in the case of proteins that undergo post-translational modifications, and should be taken into consideration when protein production strategies are designed. Using plants to produce heterologous enzymes for the degradation of a key component of the plant cell wall could reduce the cost of biomass pretreatment for the production of cellulosic biofuels.

Production and characterization of in planta transiently produced polygalacturanase from Aspergillus niger and its fusions with hydrophobin or ELP tags

PubMed Central

2014-01-01

Background Pectinases play an important role in plant cell wall deconstruction and have potential in diverse industries such as food, wine, animal feed, textile, paper, fuel, and others. The demand for such enzymes is increasing exponentially, as are the efforts to improve their production and to implement their use in several industrial processes. The goal of this study was to examine the potential of producing polygalacturonase I from Aspergillus niger in plants and to investigate the effects of subcellular compartmentalization and protein fusions on its accumulation and activity. Results Polygalacturonase I from Aspergillus niger (AnPGI) was transiently produced in Nicotiana benthamiana by targeting it to five different cellular compartments: apoplast, endoplasmic reticulum (ER), vacuole, chloroplast and cytosol. Accumulation levels of 2.5%, 3.0%, and 1.9% of total soluble protein (TSP) were observed in the apoplast, ER, and vacuole, respectively, and specific activity was significantly higher in vacuole-targeted AnPGI compared to the same enzyme targeted to the ER or apoplast. No accumulation was found for AnPGI when targeted to the chloroplast or cytosol. Analysis of AnPGI fused with elastin-like polypeptide (ELP) revealed a significant increase in the protein accumulation level, especially when targeted to the vacuole where the protein doubles its accumulation to 3.6% of TSP, while the hydrophobin (HFBI) fusion impaired AnPGI accumulation and both tags impaired activity, albeit to different extents. The recombinant protein showed activity against polygalacturonic acid with optimum conditions at pH 5.0 and temperature from 30 to 50°C, depending on its fusion. In vivo analysis of reducing sugar content revealed a higher release of reducing sugars in plant tissue expressing recombinant AnPGI compared to wild type N. benthamiana leaves. Conclusion Our results demonstrate that subcellular compartmentalization of enzymes has an impact on both the target protein accumulation and its activity, especially in the case of proteins that undergo post-translational modifications, and should be taken into consideration when protein production strategies are designed. Using plants to produce heterologous enzymes for the degradation of a key component of the plant cell wall could reduce the cost of biomass pretreatment for the production of cellulosic biofuels. PMID:24970673

Developments for Personalized Medicine of Lung Cancer Subtypes: Mass Spectrometry-Based Clinical Proteogenomic Analysis of Oncogenic Mutations.

PubMed

Nishimura, Toshihide; Nakamura, Haruhiko

2016-01-01

Molecular therapies targeting lung cancers with mutated epidermal growth factor receptor (EGFR) by EGFR-tyrosin kinase inhibitors (EGFR-TKIs), gefitinib and erlotinib, changed the treatment system of lung cancer. It was revealed that drug efficacy differs by race (e.g., Caucasians vs. Asians) due to oncogenic driver mutations specific to each race, exemplified by gefitinib / erlotinib. The molecular target drugs for lung cancer with anaplastic lymphoma kinase (ALK) gene translocation (the fusion gene, EML4-ALK) was approved, and those targeting lung cancers addicted ROS1, RET, and HER2 have been under development. Both identification and quantification of gatekeeper mutations need to be performed using lung cancer tissue specimens obtained from patients to improve the treatment for lung cancer patients: (1) identification and quantitation data of targeted mutated proteins, including investigation of mutation heterogeneity within a tissue; (2) exploratory mass spectrometry (MS)-based clinical proteogenomic analysis of mutated proteins; and also importantly (3) analysis of dynamic protein-protein interaction (PPI) networks of proteins significantly related to a subgroup of patients with lung cancer not only with good efficacy but also with acquired resistance. MS-based proteogenomics is a promising approach to directly capture mutated and fusion proteins expressed in a clinical sample. Technological developments are further expected, which will provide a powerful solution for the stratification of patients and drug discovery (Precision Medicine).

A comparative study on generating simulated Landsat NDVI images using data fusion and regression method-the case of the Korean Peninsula.

PubMed

Lee, Mi Hee; Lee, Soo Bong; Eo, Yang Dam; Kim, Sun Woong; Woo, Jung-Hun; Han, Soo Hee

2017-07-01

Landsat optical images have enough spatial and spectral resolution to analyze vegetation growth characteristics. But, the clouds and water vapor degrade the image quality quite often, which limits the availability of usable images for the time series vegetation vitality measurement. To overcome this shortcoming, simulated images are used as an alternative. In this study, weighted average method, spatial and temporal adaptive reflectance fusion model (STARFM) method, and multilinear regression analysis method have been tested to produce simulated Landsat normalized difference vegetation index (NDVI) images of the Korean Peninsula. The test results showed that the weighted average method produced the images most similar to the actual images, provided that the images were available within 1 month before and after the target date. The STARFM method gives good results when the input image date is close to the target date. Careful regional and seasonal consideration is required in selecting input images. During summer season, due to clouds, it is very difficult to get the images close enough to the target date. Multilinear regression analysis gives meaningful results even when the input image date is not so close to the target date. Average R 2 values for weighted average method, STARFM, and multilinear regression analysis were 0.741, 0.70, and 0.61, respectively.

Expression and purification of chimeric peptide comprising EGFR B-cell epitope and measles virus fusion protein T-cell epitope in Escherichia coli.

PubMed

Wu, Meizhi; Zhao, Lin; Zhu, Lei; Chen, Zhange; Li, Huangjin

2013-03-01

Chimeric peptide MVF-EGFR(237-267), comprising a B-cell epitope from the dimerization interface of human epidermal growth factor receptor (EGFR) and a promiscuous T-cell epitope from measles virus fusion protein (MVF), is a promising candidate antigen peptide for therapeutic vaccine. To establish a high-efficiency preparation process of this small peptide, the coding sequence was cloned into pET-21b and pET-32a respectively, to be expressed alone or in the form of fusion protein with thioredoxin (Trx) and His(6)-tag in Escherichia coli BL21 (DE3). The chimeric peptide failed to be expressed alone, but over-expressed in the fusion form, which presented as soluble protein and took up more than 30% of total proteins of host cells. The fusion protein was seriously degraded during the cell disruption, in which endogenous metalloproteinase played a key role. Degradation of target peptide was inhibited by combined application of EDTA in the cell disruption buffer and a step of Source 30Q anion exchange chromatography (AEC) before metal-chelating chromatography (MCAC) for purifying His(6)-tagged fusion protein. The chimeric peptide was recovered from the purified fusion protein by enterokinase digestion at a yield of 3.0 mg/L bacteria culture with a purity of more than 95%. Immunogenicity analysis showed that the recombinant chimeric peptide was able to arouse more than 1×10(4) titers of specific antibody in BALB/c mice. Present work laid a solid foundation for the development of therapeutic peptide vaccine targeting EGFR dimerization and provided a convenient and low-cost preparation method for small peptides. Copyright © 2012 Elsevier Inc. All rights reserved.

PD Trafficking of Potato Leaf Roll Virus Movement Protein in Arabidopsis Depends on Site-specific Protein Phosphorylation

PubMed Central

Sonnewald, Uwe

2011-01-01

Many plant viruses encode for specialized movement proteins (MP) to facilitate passage of viral material to and through plasmodesmata (PD). To analyze intracellular trafficking of potato leaf roll virus (PLRV) movement protein (MP17) we performed GFP fusion experiments with distinct deletion variants of MP17. These studies revealed that the C-terminus of MP17 is essential but not sufficient for PD targeting. Interestingly, fusion of GFP to three C-terminal MP17 deletion variants resulted in the accumulation of GFP in chloroplasts. This indicates that MP17 harbors hidden plastid targeting sequences. Previous studies showed that posttranslational protein phosphorylation influences PD targeting of MP and virus spread. Analysis of MP17-derived phospho-peptides by mass spectrometry revealed four phosphorylated serine residues (S71, S79, S137, and S140). Site-directed mutagenesis of S71/S79 and S137/S140 showed that the C-terminal serine residues S137/S140 are dispensable for PD targeting. However, exchange of S71/S79 to A71/A79 abolished PD targeting of the mutated MP17 protein. To mimic phosphorylation of S71/S79 both amino acids were substituted by aspartic acid. The resulting D71/D79 variant of MP17 was efficiently targeted to PD. Further deletion analysis showed that PD targeting of MP17 is dependent on the C-terminus, phosphorylation of S71 and/or S79 and a N-terminal domain. PMID:22645527

The new approach for infrared target tracking based on the particle filter algorithm

NASA Astrophysics Data System (ADS)

Sun, Hang; Han, Hong-xia

2011-08-01

Target tracking on the complex background in the infrared image sequence is hot research field. It provides the important basis in some fields such as video monitoring, precision, and video compression human-computer interaction. As a typical algorithms in the target tracking framework based on filtering and data connection, the particle filter with non-parameter estimation characteristic have ability to deal with nonlinear and non-Gaussian problems so it were widely used. There are various forms of density in the particle filter algorithm to make it valid when target occlusion occurred or recover tracking back from failure in track procedure, but in order to capture the change of the state space, it need a certain amount of particles to ensure samples is enough, and this number will increase in accompany with dimension and increase exponentially, this led to the increased amount of calculation is presented. In this paper particle filter algorithm and the Mean shift will be combined. Aiming at deficiencies of the classic mean shift Tracking algorithm easily trapped into local minima and Unable to get global optimal under the complex background. From these two perspectives that "adaptive multiple information fusion" and "with particle filter framework combining", we expand the classic Mean Shift tracking framework .Based on the previous perspective, we proposed an improved Mean Shift infrared target tracking algorithm based on multiple information fusion. In the analysis of the infrared characteristics of target basis, Algorithm firstly extracted target gray and edge character and Proposed to guide the above two characteristics by the moving of the target information thus we can get new sports guide grayscale characteristics and motion guide border feature. Then proposes a new adaptive fusion mechanism, used these two new information adaptive to integrate into the Mean Shift tracking framework. Finally we designed a kind of automatic target model updating strategy to further improve tracking performance. Experimental results show that this algorithm can compensate shortcoming of the particle filter has too much computation, and can effectively overcome the fault that mean shift is easy to fall into local extreme value instead of global maximum value .Last because of the gray and fusion target motion information, this approach also inhibit interference from the background, ultimately improve the stability and the real-time of the target track.

Antitumor effect of FGFR inhibitors on a novel cholangiocarcinoma patient derived xenograft mouse model endogenously expressing an FGFR2-CCDC6 fusion protein.

PubMed

Wang, Yu; Ding, Xiwei; Wang, Shaoqing; Moser, Catherine D; Shaleh, Hassan M; Mohamed, Essa A; Chaiteerakij, Roongruedee; Allotey, Loretta K; Chen, Gang; Miyabe, Katsuyuki; McNulty, Melissa S; Ndzengue, Albert; Barr Fritcher, Emily G; Knudson, Ryan A; Greipp, Patricia T; Clark, Karl J; Torbenson, Michael S; Kipp, Benjamin R; Zhou, Jie; Barrett, Michael T; Gustafson, Michael P; Alberts, Steven R; Borad, Mitesh J; Roberts, Lewis R

2016-09-28

Cholangiocarcinoma is a highly lethal cancer with limited therapeutic options. Recent genomic analysis of cholangiocarcinoma has revealed the presence of fibroblast growth factor receptor 2 (FGFR2) fusion proteins in up to 13% of intrahepatic cholangiocarcinoma (iCCA). FGFR fusions have been identified as a novel oncogenic and druggable target in a number of cancers. In this study, we established a novel cholangiocarcinoma patient derived xenograft (PDX) mouse model bearing an FGFR2-CCDC6 fusion protein from a metastatic lung nodule of an iCCA patient. Using this PDX model, we confirmed the ability of the FGFR inhibitors, ponatinib, dovitinib and BGJ398, to modulate FGFR signaling, inhibit cell proliferation and induce cell apoptosis in cholangiocarcinoma tumors harboring FGFR2 fusions. In addition, BGJ398 appeared to be superior in potency to ponatinib and dovitinib in this model. Our findings provide a strong rationale for the investigation of FGFR inhibitors, particularly BGJ398, as a therapeutic option for cholangiocarcinoma patients harboring FGFR2 fusions. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Ribozyme Targeting the Novel Fusion Junction of EGFRvIII in Breast Cancer

DTIC Science & Technology

2003-07-01

targeting the novel junction of EGFRvyII. * Demonstrate the therapeutic efficacy of an anti-EGFRvIll hammerhead ribozyme targeting the endogenous...first demonstration of the therapeutic efficacy of an anti-EGFRvlII hammerhead ribozyme targeting the endogenous EGFRvAII expression against human...202-687-7505.designed and generated a tumor specific hammerhead ribozyme E-mail: Tangc@georgetown.edu targeted to the novel fusion junction of

Fusion of single proteoliposomes with planar, cushioned bilayers in microfluidic flow cells

PubMed Central

Karatekin, Erdem; Rothman, James E.

2013-01-01

Many biological processes rely on membrane fusion, therefore assays to study its mechanisms are necessary. Here we report an assay with sensitivity to single-vesicle, even to single-molecule events using fluorescently labeled vesicle-associated v-SNARE liposomes and target-membrane-associated t-SNARE-reconstituted planar, supported bilayers (SBLs). Docking and fusion events can be detected using conventional far-field epifluorescence or total internal reflection fluorsecence microscopy. Unlike most previous attempts, fusion here is dependent on SNAP25, one of the t-SNARE subunits that is required for fusion in vivo. The success of the assay is due to the use of (i) bilayers covered with a thin layer of poly(ethylene glycol) to control bilayer-bilayer and bilayer-substrate interactions, (ii) microfluidic flow channels which presents many advantages such as the removal of non-specifically bound liposomes by flow. The protocol takes 6–8 days to complete. Analysis can take up to two weeks. PMID:22517259

MicroRNA Detection by DNA-Mediated Liposome Fusion.

PubMed

Jumeaux, Coline; Wahlsten, Olov; Block, Stephan; Kim, Eunjung; Chandrawati, Rona; Howes, Philip D; Höök, Fredrik; Stevens, Molly M

2018-03-02

Membrane fusion is a process of fundamental importance in biological systems that involves highly selective recognition mechanisms for the trafficking of molecular and ionic cargos. Mimicking natural membrane fusion mechanisms for the purpose of biosensor development holds great potential for amplified detection because relatively few highly discriminating targets lead to fusion and an accompanied engagement of a large payload of signal-generating molecules. In this work, sequence-specific DNA-mediated liposome fusion is used for the highly selective detection of microRNA. The detection of miR-29a, a known flu biomarker, is demonstrated down to 18 nm within 30 min with high specificity by using a standard laboratory microplate reader. Furthermore, one order of magnitude improvement in the limit of detection is demonstrated by using a novel imaging technique combined with an intensity fluctuation analysis, which is coined two-color fluorescence correlation microscopy. © 2018 The Authors. Published by Wiley-VCH Verlag GmbH & Co. KGaA.

Magnetic Inertial Confinement Fusion (MICF)

NASA Astrophysics Data System (ADS)

Miao, Feng; Zheng, Xianjun; Deng, Baiquan; Liu, Wei; Ou, Wei; Huang, Yi

2016-11-01

Based on the similarity in models of the early Sun and the 3-D common focal region of the micro-pinch in X-pinch experiments, a novel hybrid fusion configuration by continuous focusing of multiple Z-pinched plasma beams on spatially symmetric plasma is proposed. By replacing gravity with Lorentz force with subsequent centripetal spherical pinch, the beam-target fusion reactivity is enhanced in a quasi-spherical converging region, thus achieving MICF. An assessment, presented here, suggests that a practical fusion power source could be achieved using deuterium alone. Plasma instabilities can be suppressed by fast rotation resulting from an asymmetric tangential torsion in the spherical focal region of this configuration. Mathematical equivalence with the Sun allows the development of appropriate equations for the focal region of MICF, which are solved numerically to provide density, temperature and pressure distributions that produce net fusion energy output. An analysis of MICF physics and a preliminary experimental demonstration of a single beam are also carried out. supported by National Natural Science Foundation of China (Nos. 11374217 and 11176020)

A testbed for architecture and fidelity trade studies in the Bayesian decision-level fusion of ATR products

NASA Astrophysics Data System (ADS)

Erickson, Kyle J.; Ross, Timothy D.

2007-04-01

Decision-level fusion is an appealing extension to automatic/assisted target recognition (ATR) as it is a low-bandwidth technique bolstered by a strong theoretical foundation that requires no modification of the source algorithms. Despite the relative simplicity of decision-level fusion, there are many options for fusion application and fusion algorithm specifications. This paper describes a tool that allows trade studies and optimizations across these many options, by feeding an actual fusion algorithm via models of the system environment. Models and fusion algorithms can be specified and then exercised many times, with accumulated results used to compute performance metrics such as probability of correct identification. Performance differences between the best of the contributing sources and the fused result constitute examples of "gain." The tool, constructed as part of the Fusion for Identifying Targets Experiment (FITE) within the Air Force Research Laboratory (AFRL) Sensors Directorate ATR Thrust, finds its main use in examining the relationships among conditions affecting the target, prior information, fusion algorithm complexity, and fusion gain. ATR as an unsolved problem provides the main challenges to fusion in its high cost and relative scarcity of training data, its variability in application, the inability to produce truly random samples, and its sensitivity to context. This paper summarizes the mathematics underlying decision-level fusion in the ATR domain and describes a MATLAB-based architecture for exploring the trade space thus defined. Specific dimensions within this trade space are delineated, providing the raw material necessary to define experiments suitable for multi-look and multi-sensor ATR systems.

A high density field reversed configuration (FRC) target for magnetized target fusion: First internal profile measurements of a high density FRC

NASA Astrophysics Data System (ADS)

Intrator, T.; Zhang, S. Y.; Degnan, J. H.; Furno, I.; Grabowski, C.; Hsu, S. C.; Ruden, E. L.; Sanchez, P. G.; Taccetti, J. M.; Tuszewski, M.; Waganaar, W. J.; Wurden, G. A.

2004-05-01

Magnetized target fusion (MTF) is a potentially low cost path to fusion, intermediate in plasma regime between magnetic and inertial fusion energy. It requires compression of a magnetized target plasma and consequent heating to fusion relevant conditions inside a converging flux conserver. To demonstrate the physics basis for MTF, a field reversed configuration (FRC) target plasma has been chosen that will ultimately be compressed within an imploding metal liner. The required FRC will need large density, and this regime is being explored by the FRX-L (FRC-Liner) experiment. All theta pinch formed FRCs have some shock heating during formation, but FRX-L depends further on large ohmic heating from magnetic flux annihilation to heat the high density (2-5×1022m-3), plasma to a temperature of Te+Ti≈500 eV. At the field null, anomalous resistivity is typically invoked to characterize the resistive like flux dissipation process. The first resistivity estimate for a high density collisional FRC is shown here. The flux dissipation process is both a key issue for MTF and an important underlying physics question.

Magnetized Target Fusion At General Fusion: An Overview

NASA Astrophysics Data System (ADS)

Laberge, Michel; O'Shea, Peter; Donaldson, Mike; Delage, Michael; Fusion Team, General

2017-10-01

Magnetized Target Fusion (MTF) involves compressing an initial magnetically confined plasma on a timescale faster than the thermal confinement time of the plasma. If near adiabatic compression is achieved, volumetric compression of 350X or more of a 500 eV target plasma would achieve a final plasma temperature exceeding 10 keV. Interesting fusion gains could be achieved provided the compressed plasma has sufficient density and dwell time. General Fusion (GF) is developing a compression system using pneumatic pistons to collapse a cavity formed in liquid metal containing a magnetized plasma target. Low cost driver, straightforward heat extraction, good tritium breeding ratio and excellent neutron protection could lead to a practical power plant. GF (65 employees) has an active plasma R&D program including both full scale and reduced scale plasma experiments and simulation of both. Although pneumatic driven compression of full scale plasmas is the end goal, present compression studies use reduced scale plasmas and chemically accelerated aluminum liners. We will review results from our plasma target development, motivate and review the results of dynamic compression field tests and briefly describe the work to date on the pneumatic driver front.

[The poster as a communication medium].

PubMed

Tovar Samanez, C

1987-01-01

The poster as a medium of communication serves to transmit a message by means of a graphical synthesis. It elicits attention by its originality, contrast, and focus on the center of interest. The poster is effective if the images and slogans can be identified easily. Its visual attractiveness is also essential. The understanding of the message is the function of the cultural characteristics of the public with symbols, metaphors, gestures, and detailed description. The appeal of the message allows the public to accept it on sensorial, emotional, social, intellectual, and economical levels. Adverse motivations should not be confused with the positive appeal (prejudice, preconceived ideas, and bias). Confusion and ambiguity can carry conflicting messages, therefore negative examples should be avoided. The force of the message targets the memory carrying conviction and calling to action. The target group and objective must be defined as to age, occupation, location, and sex. The message also has to be defined precisely for the target audience. It is in the analysis of the context whereby the poster is received as to notions of the target topic, alternative attitudes relative to the promotion of the message, obstacles that are encountered in the mentality of the target, and cultural characteristics of the target audience. The text of the slogan must be given before drawing the poster. The designing of the poster should be creative with association of ideas, metaphors and symbols, descriptive images, fusion of symbolic and descriptive forms, humor, the fusion of graphics with letters, and the fusion of letters with images. Completed forms of the poster use illustration, photography, typography, calligraphy, and photo montage.

Generation of fusion protein EGFRvIII-HBcAg and its anti-tumor effect in vivo

PubMed Central

Duan, Xiao-yi; Han, Dong-gang; Zhang, Ming-xin; Wang, Jian-sheng

2009-01-01

The epidermal growth factor receptor variant III (EGFRvIII) is the most common variation of EGFR. Because it shows a high frequency in several different types of tumor and has not been detected in normal tissues, it is an ideal target for tumor specific therapy. In this study, we prepared EGFRvIII-HBcAg fusion protein. After immunization with fusion protein, HBcAg or PBS, the titers of antibody in BALB/c mice immunized with fusion protein reached 2.75 × 105. Western blot analysis demonstrated that the fusion protein had specific antigenicity against anti-EGFRvIII antibody. Further observation showed fusion protein induced a high frequency of IFN-γ-secreting lymphocytes. CD4+T cells rather than CD8+T cells were associated with the production of IFN-γ. Using Renca-vIII(+) cell as specific stimulator, we observed remarkable cytotoxic activity in splenocytes from mice immunized with fusion protein. Mice were challenged with Renca-vIII(+) cells after five times immunization. In fusion protein group, three of ten mice failed to develop tumor and all survived at the end of the research. The weight of tumors in fusion protein were obviously lighter than that in other two groups (t = 4.73, P = 0.044;t = 6.89, P = 0.040). These findings demonstrated that EGFRvIII-HBcAg fusion protein triggered protective responses against tumor expressing EGFRvIII. PMID:19788747

Magnetized Target Fusion in Advanced Propulsion Research

NASA Technical Reports Server (NTRS)

Cylar, Rashad

2003-01-01

The Magnetized Target Fusion (MTF) Propulsion lab at NASA Marshall Space Flight Center in Huntsville, Alabama has a program in place that has adopted to attempt to create a faster, lower cost and more reliable deep space transportation system. In this deep space travel the physics and development of high velocity plasma jets must be understood. The MTF Propulsion lab is also in attempt to open up the solar system for human exploration and commercial use. Fusion, as compared to fission, is just the opposite. Fusion involves the light atomic nuclei combination to produce denser nuclei. In the process, the energy is created by destroying the mass according to the distinguished equation: E = mc2 . Fusion energy development is being pursued worldwide as a very sustainable form of energy that is environmentally friendly. For the purposes of space exploration fusion reactions considered include the isotopes of hydrogen-deuterium (D2) and tritium (T3). Nuclei have an electrostatic repulsion between them and in order for the nuclei to fuse this repulsion must be overcome. One technique to bypass repulsion is to heat the nuclei to very high temperatures. The temperatures vary according to the type of reactions. For D-D reactions, one billion degrees Celsius is required, and for D-T reactions, one hundred million degrees is sufficient. There has to be energy input for useful output to be obtained form the fusion To make fusion propulsion practical, the mass, the volume, and the cost of the equipment to produce the reactions (generally called the reactor) need to be reduced by an order of magnitude or two from the state-of-the-art fusion machines. Innovations in fusion schemes are therefore required, especially for obtaining thrust for propulsive applications. Magnetized target fusion (MTF) is one of the innovative fusion concepts that have emerged over the last several years. MSFC is working with Los Alamos National Laboratory and other research groups in studying the underlying principles involved in MTF. Magnetized Target Fusion is an attempt to combine MCF (magnetic confinement fusion) for energy confinement and ICF (inertial confinement fusion) for efficient compression heating and wall free containment of the fusing plasma. It also seeks to combine the best features to these two main commonplace approaches to fusion.

The Progress of Research Project for Magnetized Target Fusion in China

NASA Astrophysics Data System (ADS)

Yang, Xian-Jun

2015-11-01

The fusion of magnetized plasma called Magnetized Target Fusion (MTF) is a hot research area recently. It may significantly reduce the cost and size. Great progress has been achieved in past decades around the world. Five years ago, China initiated the MTF project and has gotten some progress as follows: 1. Verifying the feasibility of ignition of MTF by means of first principle and MHD simulation; 2. Generating the magnetic field over 1400 Tesla, which can be suppress the heat conduction from charged particles, deposit the energy of alpha particle to promote the ignition process, and produce the stable magnetized plasma for the target of ignition; 3. The imploding facility of FP-1 can put several Mega Joule energy to the solid liner of about ten gram in the range of microsecond risen time, while the simulating tool has been developed for design and analysis of the process; 4. The target of FRC can be generated by ``YG 1 facility'' while some simulating tools have be developed. Next five years, the above theoretical work and the experiments of MTF may be integrated to step up as the National project, which may make my term play an important lead role and be supposed to achieve farther progress in China. Supported by the National Natural Science Foundation of China under Grant No 11175028.

Breakup and fusion cross sections of the 6Li nucleus with targets of mass A = 58, 144 and 208

NASA Astrophysics Data System (ADS)

Mukeru, B.; Rampho, G. J.; Lekala, M. L.

2018-04-01

We use the continuum discretized coupled channels method to investigate the effects of continuum-continuum coupling on the breakup and fusion cross sections of the weakly bound 6Li nucleus with the 58Ni, 144Sm and 208Pb nuclear targets. The cross sections were analyzed at incident energies E cm below, close to and above the Coulomb barrier V B. We found that for the medium and heavy targets, the breakup cross sections are enhanced at energies below the Coulomb barrier (E cm/V B ≤ 0.8) owing to these couplings. For the lighter target, relatively small enhancement of the breakup cross sections appear at energies well below the barrier (E cm/V B ≤ 0.6). At energies E cm/V B > 0.8 for medium and heavy targets, and E cm/V B > 0.6 for the light target, the continuum-continuum couplings substantially suppress the breakup cross sections. On the other hand, the fusion cross sections are enhanced at energies E cm/V B < 1.4, E cm/V B < 1.2 and E cm/V B < 0.8 for the light, medium and heavy target, respectively. The enhancement decreases as the target mass increases. Above the indicated respective energies, these couplings suppress the fusion cross sections. We also compared the breakup and fusion cross sections, and found that below the barrier, the breakup cross sections are more dominant regardless of whether continuum-continuum couplings are included.

Targeting of a Nuclease to Murine Leukemia Virus Capsids Inhibits Viral Multiplication

NASA Astrophysics Data System (ADS)

Natsoulis, Georges; Seshaiah, Partha; Federspiel, Mark J.; Rein, Alan; Hughes, Stephen H.; Boeke, Jef D.

1995-01-01

Capsid-targeted viral inactivation is an antiviral strategy in which toxic fusion proteins are targeted to virions, where they inhibit viral multiplication by destroying viral components. These fusion proteins consist of a virion structural protein moiety and an enzymatic moiety such as a nuclease. Such fusion proteins can severely inhibit transposition of yeast retrotransposon Ty1, an element whose transposition mechanistically resembles retroviral multiplication. We demonstrate that expression of a murine retrovirus capsid-staphylococcal nuclease fusion protein inhibits multiplication of the corresponding murine leukemia virus by 30- to 100-fold. Staphylococcal nuclease is apparently inactive intracellularly and hence nontoxic to the host cell, but it is active extracellularly because of its requirement for high concentrations of Ca2+ ions. Virions assembled in and shed from cells expressing the fusion protein contain very small amounts of intact viral RNA, as would be predicted for nuclease-mediated inhibition of viral multiplication.

Multisensor data fusion for integrated maritime surveillance

NASA Astrophysics Data System (ADS)

Premji, A.; Ponsford, A. M.

1995-01-01

A prototype Integrated Coastal Surveillance system has been developed on Canada's East Coast to provide effective surveillance out to and beyond the 200 nautical mile Exclusive Economic Zone. The system has been designed to protect Canada's natural resources, and to monitor and control the coastline for smuggling, drug trafficking, and similar illegal activity. This paper describes the Multiple Sensor - Multiple Target data fusion system that has been developed. The fusion processor has been developed around the celebrated Multiple Hypothesis Tracking algorithm which accommodates multiple targets, new targets, false alarms, and missed detections. This processor performs four major functions: plot-to-track association to form individual radar tracks; fusion of radar tracks with secondary sensor reports; track identification and tagging using secondary reports; and track level fusion to form common tracks. Radar data from coherent and non-coherent radars has been used to evaluate the performance of the processor. This paper presents preliminary results.

An unusual dependence of human herpesvirus-8 glycoproteins-induced cell-to-cell fusion on heparan sulfate

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

Tiwari, Vaibhav; Department of Microbiology and Immunology, University of Illinois at Chicago, Chicago, IL 60612; Department of Basic Medical Sciences, College of Osteopathic Medicine of the Pacific and College of Optometry, Western University of Health Sciences, Pomona, CA 91766

2009-12-18

Human herpesvirus-8 (HHV-8) is known to interact with cell surface heparan sulfate (HS) for entry into a target cell. Here we investigated the role of HS during HHV-8 glycoproteins-induced cell fusion. Interestingly, the observed fusion demonstrated an unusual dependence on HS as evident from following lines of evidence: (1) a significant reduction in cell-to-cell fusion occurred when target cells were treated with heparinase; (2) in a competition assay, when the effector cells expressing HHV-8 glycoproteins were challenged with soluble HS, cell-to-cell fusion was reduced; and, (3) co-expression of HHV-8 glycoproteins gH-gL on target cells resulted in inhibition of cell surfacemore » HS expression. Taken together, our results indicate that cell surface HS can play an additional role during HHV-8 pathogenesis.« less

The cytoplasmic domain of the gamete membrane fusion protein HAP2 targets the protein to the fusion site in Chlamydomonas and regulates the fusion reaction.

PubMed

Liu, Yanjie; Pei, Jimin; Grishin, Nick; Snell, William J

2015-03-01

Cell-cell fusion between gametes is a defining step during development of eukaryotes, yet we know little about the cellular and molecular mechanisms of the gamete membrane fusion reaction. HAP2 is the sole gamete-specific protein in any system that is broadly conserved and shown by gene disruption to be essential for gamete fusion. The wide evolutionary distribution of HAP2 (also known as GCS1) indicates it was present in the last eukaryotic common ancestor and, therefore, dissecting its molecular properties should provide new insights into fundamental features of fertilization. HAP2 acts at a step after membrane adhesion, presumably directly in the merger of the lipid bilayers. Here, we use the unicellular alga Chlamydomonas to characterize contributions of key regions of HAP2 to protein location and function. We report that mutation of three strongly conserved residues in the ectodomain has no effect on targeting or fusion, although short deletions that include those residues block surface expression and fusion. Furthermore, HAP2 lacking a 237-residue segment of the cytoplasmic region is expressed at the cell surface, but fails to localize at the apical membrane patch specialized for fusion and fails to rescue fusion. Finally, we provide evidence that the ancient HAP2 contained a juxta-membrane, multi-cysteine motif in its cytoplasmic region, and that mutation of a cysteine dyad in this motif preserves protein localization, but substantially impairs HAP2 fusion activity. Thus, the ectodomain of HAP2 is essential for its surface expression, and the cytoplasmic region targets HAP2 to the site of fusion and regulates the fusion reaction. © 2015. Published by The Company of Biologists Ltd.

HIP1-ALK, a novel fusion protein identified in lung adenocarcinoma.

PubMed

Hong, Mineui; Kim, Ryong Nam; Song, Ji-Young; Choi, So-Jung; Oh, Ensel; Lira, Maruja E; Mao, Mao; Takeuchi, Kengo; Han, Joungho; Kim, Jhingook; Choi, Yoon-La

2014-03-01

The most common mechanism underlying overexpression and activation of anaplastic lymphoma kinase (ALK) in non-small-cell lung carcinoma could be attributed to the formation of a fusion protein. To date, five fusion partners of ALK have been reported, namely, echinoderm microtubule associated protein like 4, tropomyosin-related kinase-fused gene, kinesin family member 5B, kinesin light chain 1, and protein tyrosine phosphatase, nonreceptor type 3. In this article, we report a novel fusion gene huntingtin interacting protein 1 (HIP1)-ALK, which is conjoined between the huntingtin-interacting protein 1 gene HIP1 and ALK. Reverse-transcriptase polymerase chain reaction and immunohistochemical analysis were used to detect this fusion gene's transcript and protein expression, respectively. We had amplified the full-length cDNA sequence of this novel fusion gene by using 5'-rapid amplification of cDNA ends. The causative genomic translocation t(2;7)(p23;q11.23) for generating this novel fusion gene was verified by using genomic sequencing. The examined adenocarcinoma showed predominant acinar pattern, and ALK immunostaining was localized to the cytoplasm, with intense staining in the submembrane region. In break-apart, fluorescence in situ hybridization analysis for ALK, split of the 5' and 3' probe signals, and isolated 3' signals were observed. Reverse-transcriptase polymerase chain reaction revealed that the tumor harbored a novel fusion transcript in which exon 21 of HIP1 was fused to exon 20 of ALK in-frame. The novel fusion gene and its protein HIP1-ALK harboring epsin N-terminal homology, coiled-coil, juxtamembrane, and kinase domains, which could play a role in carcinogenesis, could become diagnostic and therapeutic target of the lung adenocarcinoma and deserve a further study in the future.

Fusion Protein Vaccines Targeting Two Tumor Antigens Generate Synergistic Anti-Tumor Effects

PubMed Central

Cheng, Wen-Fang; Chang, Ming-Cheng; Sun, Wei-Zen; Jen, Yu-Wei; Liao, Chao-Wei; Chen, Yun-Yuan; Chen, Chi-An

2013-01-01

Introduction Human papillomavirus (HPV) has been consistently implicated in causing several kinds of malignancies, and two HPV oncogenes, E6 and E7, represent two potential target antigens for cancer vaccines. We developed two fusion protein vaccines, PE(ΔIII)/E6 and PE(ΔIII)/E7 by targeting these two tumor antigens to test whether a combination of two fusion proteins can generate more potent anti-tumor effects than a single fusion protein. Materials and Methods In vivo antitumor effects including preventive, therapeutic, and antibody depletion experiments were performed. In vitro assays including intracellular cytokine staining and ELISA for Ab responses were also performed. Results PE(ΔIII)/E6+PE(ΔIII)/E7 generated both stronger E6 and E7-specific immunity. Only 60% of the tumor protective effect was observed in the PE(ΔIII)/E6 group compared to 100% in the PE(ΔIII)/E7 and PE(ΔIII)/E6+PE(ΔIII)/E7 groups. Mice vaccinated with the PE(ΔIII)/E6+PE(ΔIII)/E7 fusion proteins had a smaller subcutaneous tumor size than those vaccinated with PE(ΔIII)/E6 or PE(ΔIII)/E7 fusion proteins alone. Conclusion Fusion protein vaccines targeting both E6 and E7 tumor antigens generated more potent immunotherapeutic effects than E6 or E7 tumor antigens alone. This novel strategy of targeting two tumor antigens together can promote the development of cancer vaccines and immunotherapy in HPV-related malignancies. PMID:24058440

A fungal biofilm reactor based on metal structured packing improves the quality of a Gla::GFP fusion protein produced by Aspergillus oryzae.

PubMed

Zune, Q; Delepierre, A; Gofflot, S; Bauwens, J; Twizere, J C; Punt, P J; Francis, F; Toye, D; Bawin, T; Delvigne, F

2015-08-01

Fungal biofilm is known to promote the excretion of secondary metabolites in accordance with solid-state-related physiological mechanisms. This work is based on the comparative analysis of classical submerged fermentation with a fungal biofilm reactor for the production of a Gla::green fluorescent protein (GFP) fusion protein by Aspergillus oryzae. The biofilm reactor comprises a metal structured packing allowing the attachment of the fungal biomass. Since the production of the target protein is under the control of the promoter glaB, specifically induced in solid-state fermentation, the biofilm mode of culture is expected to enhance the global productivity. Although production of the target protein was enhanced by using the biofilm mode of culture, we also found that fusion protein production is also significant when the submerged mode of culture is used. This result is related to high shear stress leading to biomass autolysis and leakage of intracellular fusion protein into the extracellular medium. Moreover, 2-D gel electrophoresis highlights the preservation of fusion protein integrity produced in biofilm conditions. Two fungal biofilm reactor designs were then investigated further, i.e. with full immersion of the packing or with medium recirculation on the packing, and the scale-up potentialities were evaluated. In this context, it has been shown that full immersion of the metal packing in the liquid medium during cultivation allows for a uniform colonization of the packing by the fungal biomass and leads to a better quality of the fusion protein.

A novel anti-CD22 scFv-apoptin fusion protein induces apoptosis in malignant B-cells.

PubMed

Agha Amiri, Solmaz; Shahhosseini, Soraya; Zarei, Najmeh; Khorasanizadeh, Dorsa; Aminollahi, Elahe; Rezaie, Faegheh; Zargari, Mehryar; Azizi, Mohammad; Khalaj, Vahid

2017-12-01

CD22 marker is a highly internalizing antigen which is located on the surface of B-cells and is being used as a promising target for treatment of B cell malignancies. Monoclonal antibodies targeting CD22 have been introduced and some are currently under investigation in clinical trials. Building on the success of antibody drug conjugates, we developed a fusion protein consisting of a novel anti-CD22 scFv and apoptin and tested binding and therapeutic effects in lymphoma cells. The recombinant protein was expressed in E. coli and successfully purified and refolded. In vitro binding analysis by immunofluorescence and flow cytometry demonstrated that the recombinant protein specifically binds to CD22 positive Raji cells but not to CD22 negative Jurkat cells. The cytotoxic properties of scFv-apoptin were assessed by an MTT assay and Annexin V/PI flow cytometry analysis and showed that the recombinant protein induced apoptosis preferentially in Raji cells with no detectable effects in Jurkat cells. Our findings indicated that the recombinant anti-CD22 scFv-apoptin fusion protein could successfully cross the cell membrane and induce apoptosis with high specificity, make it as a promising molecule for immunotherapy of B-cell malignancies.

RNA-seq of 272 gliomas revealed a novel, recurrent PTPRZ1-MET fusion transcript in secondary glioblastomas.

PubMed

Bao, Zhao-Shi; Chen, Hui-Min; Yang, Ming-Yu; Zhang, Chuan-Bao; Yu, Kai; Ye, Wan-Lu; Hu, Bo-Qiang; Yan, Wei; Zhang, Wei; Akers, Johnny; Ramakrishnan, Valya; Li, Jie; Carter, Bob; Liu, Yan-Wei; Hu, Hui-Min; Wang, Zheng; Li, Ming-Yang; Yao, Kun; Qiu, Xiao-Guang; Kang, Chun-Sheng; You, Yong-Ping; Fan, Xiao-Long; Song, Wei Sonya; Li, Rui-Qiang; Su, Xiao-Dong; Chen, Clark C; Jiang, Tao

2014-11-01

Studies of gene rearrangements and the consequent oncogenic fusion proteins have laid the foundation for targeted cancer therapy. To identify oncogenic fusions associated with glioma progression, we catalogued fusion transcripts by RNA-seq of 272 gliomas. Fusion transcripts were more frequently found in high-grade gliomas, in the classical subtype of gliomas, and in gliomas treated with radiation/temozolomide. Sixty-seven in-frame fusion transcripts were identified, including three recurrent fusion transcripts: FGFR3-TACC3, RNF213-SLC26A11, and PTPRZ1-MET (ZM). Interestingly, the ZM fusion was found only in grade III astrocytomas (1/13; 7.7%) or secondary GBMs (sGBMs, 3/20; 15.0%). In an independent cohort of sGBMs, the ZM fusion was found in three of 20 (15%) specimens. Genomic analysis revealed that the fusion arose from translocation events involving introns 3 or 8 of PTPRZ and intron 1 of MET. ZM fusion transcripts were found in GBMs irrespective of isocitrate dehydrogenase 1 (IDH1) mutation status. sGBMs harboring ZM fusion showed higher expression of genes required for PIK3CA signaling and lowered expression of genes that suppressed RB1 or TP53 function. Expression of the ZM fusion was mutually exclusive with EGFR overexpression in sGBMs. Exogenous expression of the ZM fusion in the U87MG glioblastoma line enhanced cell migration and invasion. Clinically, patients afflicted with ZM fusion harboring glioblastomas survived poorly relative to those afflicted with non-ZM-harboring sGBMs (P < 0.001). Our study profiles the shifting RNA landscape of gliomas during progression and reveled ZM as a novel, recurrent fusion transcript in sGBMs. © 2014 Bao et al.; Published by Cold Spring Harbor Laboratory Press.

RNA-seq of 272 gliomas revealed a novel, recurrent PTPRZ1-MET fusion transcript in secondary glioblastomas

PubMed Central

Bao, Zhao-Shi; Yang, Ming-Yu; Zhang, Chuan-Bao; Yu, Kai; Ye, Wan-Lu; Hu, Bo-Qiang; Yan, Wei; Zhang, Wei; Akers, Johnny; Ramakrishnan, Valya; Li, Jie; Carter, Bob; Liu, Yan-Wei; Hu, Hui-Min; Wang, Zheng; Li, Ming-Yang; Yao, Kun; Qiu, Xiao-Guang; Kang, Chun-Sheng; You, Yong-Ping; Fan, Xiao-Long; Song, Wei Sonya; Li, Rui-Qiang

2014-01-01

Studies of gene rearrangements and the consequent oncogenic fusion proteins have laid the foundation for targeted cancer therapy. To identify oncogenic fusions associated with glioma progression, we catalogued fusion transcripts by RNA-seq of 272 gliomas. Fusion transcripts were more frequently found in high-grade gliomas, in the classical subtype of gliomas, and in gliomas treated with radiation/temozolomide. Sixty-seven in-frame fusion transcripts were identified, including three recurrent fusion transcripts: FGFR3-TACC3, RNF213-SLC26A11, and PTPRZ1-MET (ZM). Interestingly, the ZM fusion was found only in grade III astrocytomas (1/13; 7.7%) or secondary GBMs (sGBMs, 3/20; 15.0%). In an independent cohort of sGBMs, the ZM fusion was found in three of 20 (15%) specimens. Genomic analysis revealed that the fusion arose from translocation events involving introns 3 or 8 of PTPRZ and intron 1 of MET. ZM fusion transcripts were found in GBMs irrespective of isocitrate dehydrogenase 1 (IDH1) mutation status. sGBMs harboring ZM fusion showed higher expression of genes required for PIK3CA signaling and lowered expression of genes that suppressed RB1 or TP53 function. Expression of the ZM fusion was mutually exclusive with EGFR overexpression in sGBMs. Exogenous expression of the ZM fusion in the U87MG glioblastoma line enhanced cell migration and invasion. Clinically, patients afflicted with ZM fusion harboring glioblastomas survived poorly relative to those afflicted with non-ZM-harboring sGBMs (P < 0.001). Our study profiles the shifting RNA landscape of gliomas during progression and reveled ZM as a novel, recurrent fusion transcript in sGBMs. PMID:25135958

Detection of 22 common leukemic fusion genes using a single-step multiplex qRT-PCR-based assay.

PubMed

Lyu, Xiaodong; Wang, Xianwei; Zhang, Lina; Chen, Zhenzhu; Zhao, Yu; Hu, Jieying; Fan, Ruihua; Song, Yongping

2017-07-25

Fusion genes generated from chromosomal translocation play an important role in hematological malignancies. Detection of fusion genes currently employ use of either conventional RT-PCR methods or fluorescent in situ hybridization (FISH), where both methods involve tedious methodologies and require prior characterization of chromosomal translocation events as determined by cytogenetic analysis. In this study, we describe a real-time quantitative reverse transcription PCR (qRT-PCR)-based multi-fusion gene screening method with the capacity to detect 22 fusion genes commonly found in leukemia. This method does not require pre-characterization of gene translocation events, thereby facilitating immediate diagnosis and therapeutic management. We performed fluorescent qRT-PCR (F-qRT-PCR) using a commercially-available multi-fusion gene detection kit on a patient cohort of 345 individuals comprising 108 cases diagnosed with acute myeloid leukemia (AML) for initial evaluation; remaining patients within the cohort were assayed for confirmatory diagnosis. Results obtained by F-qRT-PCR were compared alongside patient analysis by cytogenetic characterization. Gene translocations detected by F-qRT-PCR in AML cases were diagnosed in 69.4% of the patient cohort, which was comparatively similar to 68.5% as diagnosed by cytogenetic analysis, thereby demonstrating 99.1% concordance. Overall gene fusion was detected in 53.7% of the overall patient population by F-qRT-PCR, 52.9% by cytogenetic prediction in leukemia, and 9.1% in non-leukemia patients by both methods. The overall concordance rate was calculated to be 99.0%. Fusion genes were detected by F-qRT-PCR in 97.3% of patients with CML, followed by 69.4% with AML, 33.3% with acute lymphoblastic leukemia (ALL), 9.1% with myelodysplastic syndromes (MDS), and 0% with chronic lymphocytic leukemia (CLL). We describe the use of a F-qRT-PCR-based multi-fusion gene screening method as an efficient one-step diagnostic procedure as an effective alternative to lengthy conventional diagnostic procedures requiring both cytogenetic analysis followed by targeted quantitative reverse transcription (qRT-PCR) methods, thus allowing timely patient management.

Fusion-fission Study at JAEA for Heavy-element Synthesis

NASA Astrophysics Data System (ADS)

Nishio, K.

Fission fragment mass distributions were measured in the heavy-ion induced fission using 238U target nucleus. The mass distribu- tions changed drastically with incident energy. The results are explained by a change of the ratio between fusion and qasifission with nuclear orientation. A calculation based on a fluctuation dissipation model reproduced the mass distributions and their inci- dent energy dependence. Fusion probability was determined in the analysis. Evaporation residue cross sections were calculated with a statistical model in the reactions of 30Si+238U and 34S+238U using the obtained fusion probability in the entrance channel. The results agree with the measured cross sections of 263,264Sg and 267,268Hs, produced by 30Si+238U and 34S+238U, respectively. It is also suggested that the sub-barrier energies can be used for heavy element synthesis.

RET fusion as a novel driver of medullary thyroid carcinoma.

PubMed

Grubbs, Elizabeth G; Ng, Patrick Kwok-Shing; Bui, Jacquelin; Busaidy, Naifa L; Chen, Ken; Lee, Jeffrey E; Lu, Xinyan; Lu, Hengyu; Meric-Bernstam, Funda; Mills, Gordon B; Palmer, Gary; Perrier, Nancy D; Scott, Kenneth L; Shaw, Kenna R; Waguespack, Steven G; Williams, Michelle D; Yelensky, Roman; Cote, Gilbert J

2015-03-01

Oncogenic RET tyrosine kinase gene fusions and activating mutations have recently been identified in lung cancers, prompting initiation of targeted therapy trials in this disease. Although RET point mutation has been identified as a driver of tumorigenesis in medullary thyroid carcinoma (MTC), no fusions have been described to date. We evaluated the role of RET fusion as an oncogenic driver in MTC. We describe a patient who died from aggressive sporadic MTC < 10 months after diagnosis. Her tumor was evaluated by means of next-generation sequencing, including an intronic capture strategy. A reciprocal translocation involving RET intron 12 was identified. The fusion was validated using a targeted break apart fluorescence in situ hybridization probe, and RNA sequencing confirmed the existence of an in-frame fusion transcript joining MYH13 exon 35 with RET exon 12. Ectopic expression of fusion product in a murine Ba/F3 cell reporter model established strong oncogenicity. Three tyrosine kinase inhibitors currently used to treat MTC in clinical practice blocked tumorigenic cell growth. This finding represents the report of a novel RET fusion, the first of its kind described in MTC. The finding of this potential novel oncogenic mechanism has clear implications for sporadic MTC, which in the majority of cases has no driver mutation identified. The presence of a RET fusion also provides a plausible target for RET tyrosine kinase inhibitor therapies.

Laser targets compensate for limitations in inertial confinement fusion drivers

NASA Astrophysics Data System (ADS)

Kilkenny, J. D.; Alexander, N. B.; Nikroo, A.; Steinman, D. A.; Nobile, A.; Bernat, T.; Cook, R.; Letts, S.; Takagi, M.; Harding, D.

2005-10-01

Success in inertial confinement fusion (ICF) requires sophisticated, characterized targets. The increasing fidelity of three-dimensional (3D), radiation hydrodynamic computer codes has made it possible to design targets for ICF which can compensate for limitations in the existing single shot laser and Z pinch ICF drivers. Developments in ICF target fabrication technology allow more esoteric target designs to be fabricated. At present, requirements require new deterministic nano-material fabrication on micro scale.

Non-Canonical Thinking for Targeting ALK-Fusion Onco-Proteins in Lung Cancer

PubMed Central

Wu, Wei; Haderk, Franziska; Bivona, Trever G.

2017-01-01

Anaplastic lymphoma kinase (ALK) gene rearrangements have been identified in lung cancer at 3–7% frequency, thus representing an important subset of genetic lesions that drive oncogenesis in this disease. Despite the availability of multiple FDA-approved small molecule inhibitors targeting ALK fusion proteins, drug resistance to ALK kinase inhibitors is a common problem in clinic. Thus, there is an unmet need to deepen the current understanding of genomic characteristics of ALK rearrangements and to develop novel therapeutic strategies that can overcome ALK inhibitor resistance. In this review, we present the genomic landscape of ALK fusions in the context of co-occurring mutations with other cancer-related genes, pointing to the central role of genetic epistasis (gene-gene interactions) in ALK-driven advanced-stage lung cancer. We discuss the possibility of targeting druggable domains within ALK fusion partners in addition to available strategies inhibiting the ALK kinase domain directly. Finally, we examine the potential of targeting ALK fusion-specific neoantigens in combination with other treatments, a strategy that could open a new avenue for the improved treatment of ALK positive lung cancer patients. PMID:29189709

Understanding the fusion cross section among light nuclei around the Coulomb barrier

NASA Astrophysics Data System (ADS)

Del Zoppo, Antonio; La Cognata, Marco

2017-11-01

In this work we investigate fusion induced by a radioactive 8Li projectile on a 4He gas target, at center-of-mass energies between 0.6 and 5 MeV. The main result is the tendency of the dimensionless fusion cross section to form well visible plateaus alternated to steep rises. This is likely to be the most genuine consequence of the discrete nature of the intervening angular momenta observed so far in fusion reactions right above the Coulomb barrier. A partial-wave analysis, exclusively based on a pure quantal penetration fusion model, identifies a remarkably low-height barrier. Indeed, these plateaus allow enhanced experimental sensitivity to the fusion barrier given that the most barrier-sensitive lowest partial waves are well separated. We expect that the present results for 8Li+4He will promote further investigations of the fusion reaction mechanism between very light ions at energies much below the interaction barrier. For the moment, we believe that understanding the plateau origin in the cross section above the barrier will almost certainly be useful to corroborate the extrapolation to the important astrophysical region below the Coulomb barrier, not only in the case of the 8Li+4He fusion but also for other systems, such as the 12C+12C.

Project Icarus: Analysis of Plasma jet driven Magneto-Inertial Fusion as potential primary propulsion driver for the Icarus probe

NASA Astrophysics Data System (ADS)

Stanic, M.; Cassibry, J. T.; Adams, R. B.

2013-05-01

Hopes of sending probes to another star other than the Sun are currently limited by the maturity of advanced propulsion technologies. One of the few candidate propulsion systems for providing interstellar flight capabilities is nuclear fusion. In the past many fusion propulsion concepts have been proposed and some of them have even been explored in detail, Project Daedalus for example. However, as scientific progress in this field has advanced, new fusion concepts have emerged that merit evaluation as potential drivers for interstellar missions. Plasma jet driven Magneto-Inertial Fusion (PJMIF) is one of those concepts. PJMIF involves a salvo of converging plasma jets that form a uniform liner, which compresses a magnetized target to fusion conditions. It is an Inertial Confinement Fusion (ICF)-Magnetic Confinement Fusion (MCF) hybrid approach that has the potential for a multitude of benefits over both ICF and MCF, such as lower system mass and significantly lower cost. This paper concentrates on a thermodynamic assessment of basic performance parameters necessary for utilization of PJMIF as a candidate propulsion system for the Project Icarus mission. These parameters include: specific impulse, thrust, exhaust velocity, mass of the engine system, mass of the fuel required etc. This is a submission of the Project Icarus Study Group.

Image Fusion for Radiosurgery, Neurosurgery and Hypofractionated Radiotherapy.

PubMed

Inoue, Hiroshi K; Nakajima, Atsushi; Sato, Hiro; Noda, Shin-Ei; Saitoh, Jun-Ichi; Suzuki, Yoshiyuki

2015-03-01

Precise target detection is essential for radiosurgery, neurosurgery and hypofractionated radiotherapy because treatment results and complication rates are related to accuracy of the target definition. In skull base tumors and tumors around the optic pathways, exact anatomical evaluation of cranial nerves are important to avoid adverse effects on these structures close to lesions. Three-dimensional analyses of structures obtained with MR heavy T2-images and image fusion with CT thin-sliced sections are desirable to evaluate fine structures during radiosurgery and microsurgery. In vascular lesions, angiography is most important for evaluations of whole structures from feeder to drainer, shunt, blood flow and risk factors of bleeding. However, exact sites and surrounding structures in the brain are not shown on angiography. True image fusions of angiography, MR images and CT on axial planes are ideal for precise target definition. In malignant tumors, especially recurrent head and neck tumors, biologically active areas of recurrent tumors are main targets of radiosurgery. PET scan is useful for quantitative evaluation of recurrences. However, the examination is not always available at the time of radiosurgery. Image fusion of MR diffusion images with CT is always available during radiosurgery and useful for the detection of recurrent lesions. All images are fused and registered on thin sliced CT sections and exactly demarcated targets are planned for treatment. Follow-up images are also able to register on this CT. Exact target changes, including volume, are possible in this fusion system. The purpose of this review is to describe the usefulness of image fusion for 1) skull base, 2) vascular, 3) recurrent target detection, and 4) follow-up analyses in radiosurgery, neurosurgery and hypofractionated radiotherapy.

Image Fusion for Radiosurgery, Neurosurgery and Hypofractionated Radiotherapy

PubMed Central

Nakajima, Atsushi; Sato, Hiro; Noda, Shin-ei; Saitoh, Jun-ichi; Suzuki, Yoshiyuki

2015-01-01

Precise target detection is essential for radiosurgery, neurosurgery and hypofractionated radiotherapy because treatment results and complication rates are related to accuracy of the target definition. In skull base tumors and tumors around the optic pathways, exact anatomical evaluation of cranial nerves are important to avoid adverse effects on these structures close to lesions. Three-dimensional analyses of structures obtained with MR heavy T2-images and image fusion with CT thin-sliced sections are desirable to evaluate fine structures during radiosurgery and microsurgery. In vascular lesions, angiography is most important for evaluations of whole structures from feeder to drainer, shunt, blood flow and risk factors of bleeding. However, exact sites and surrounding structures in the brain are not shown on angiography. True image fusions of angiography, MR images and CT on axial planes are ideal for precise target definition. In malignant tumors, especially recurrent head and neck tumors, biologically active areas of recurrent tumors are main targets of radiosurgery. PET scan is useful for quantitative evaluation of recurrences. However, the examination is not always available at the time of radiosurgery. Image fusion of MR diffusion images with CT is always available during radiosurgery and useful for the detection of recurrent lesions. All images are fused and registered on thin sliced CT sections and exactly demarcated targets are planned for treatment. Follow-up images are also able to register on this CT. Exact target changes, including volume, are possible in this fusion system. The purpose of this review is to describe the usefulness of image fusion for 1) skull base, 2) vascular, 3) recurrent target detection, and 4) follow-up analyses in radiosurgery, neurosurgery and hypofractionated radiotherapy. PMID:26180676

Gene array analysis reveals a common Runx transcriptional program controlling cell adhesion and survival

PubMed Central

Wotton, Sandy; Terry, Anne; Kilbey, Anna; Jenkins, Alma; Herzyk, Pawel; Cameron, Ewan; Neil, James C.

2008-01-01

The Runx genes play divergent roles in development and cancer, where they can act either as oncogenes or tumour suppressors. We compared the effects of ectopic Runx expression in established fibroblasts, where all three genes produce an indistinguishable phenotype entailing epithelioid morphology and increased cell survival under stress conditions. Gene array analysis revealed a strongly overlapping transcriptional signature, with no examples of opposing regulation of the same target gene. A common set of 50 highly regulated genes was identified after further filtering on regulation by inducible RUNX1-ER. This set revealed a strong bias towards genes with annotated roles in cancer and development, and a preponderance of targets encoding extracellular or surface proteins, reflecting the marked effects of Runx on cell adhesion. Furthermore, in silico prediction of resistance to glucocorticoid growth inhibition was confirmed in fibroblasts and lymphoid cells expressing ectopic Runx. The effects of fibroblast expression of common RUNX1 fusion oncoproteins (RUNX1-ETO, TEL-RUNX1, CBFB-MYH11) were also tested. While two direct Runx activation target genes were repressed (Ncam1, Rgc32), the fusion proteins appeared to disrupt regulation of down-regulated targets (Cebpd, Id2, Rgs2) rather than impose constitutive repression. These results elucidate the oncogenic potential of the Runx family and reveal novel targets for therapeutic inhibition. PMID:18560354

Fusion proteins in head and neck neoplasms: Clinical implications, genetics, and future directions for targeting

PubMed Central

Escalante, Derek A.; Wang, He; Fundakowski, Christopher E.

2016-01-01

ABSTRACT Fusion proteins resulting from chromosomal rearrangements are known to drive the pathogenesis of a variety of hematological and solid neoplasms such as chronic myeloid leukemia and non-small-cell lung cancer. Efforts to elucidate the role they play in these malignancies have led to important diagnostic and therapeutic triumphs, including the famous development of the tyrosine kinase inhibitor dasatinib targeting the BCR-ABL fusion. Until recently, there has been a paucity of research investigating fusion proteins harbored by head and neck neoplasms. The discovery and characterization of novel fusion proteins in neoplasms originating from the thyroid, nasopharynx, salivary glands, and midline head and neck structures offer substantial contributions to our understanding of the pathogenesis and biological behavior of these neoplasms, while raising new therapeutic and diagnostic opportunities. Further characterization of these fusion proteins promises to facilitate advances on par with those already achieved with regard to hematologic malignancies in the precise, molecularly guided diagnosis and treatment of head and neck neoplasms. The following is a subsite specific review of the clinical implications of fusion proteins in head and neck neoplasms and the future potential for diagnostic targeting. PMID:27636353

Multi-atlas label fusion using hybrid of discriminative and generative classifiers for segmentation of cardiac MR images.

PubMed

Sedai, Suman; Garnavi, Rahil; Roy, Pallab; Xi Liang

2015-08-01

Multi-atlas segmentation first registers each atlas image to the target image and transfers the label of atlas image to the coordinate system of the target image. The transferred labels are then combined, using a label fusion algorithm. In this paper, we propose a novel label fusion method which aggregates discriminative learning and generative modeling for segmentation of cardiac MR images. First, a probabilistic Random Forest classifier is trained as a discriminative model to obtain the prior probability of a label at the given voxel of the target image. Then, a probability distribution of image patches is modeled using Gaussian Mixture Model for each label, providing the likelihood of the voxel belonging to the label. The final label posterior is obtained by combining the classification score and the likelihood score under Bayesian rule. Comparative study performed on MICCAI 2013 SATA Segmentation Challenge demonstrates that our proposed hybrid label fusion algorithm is accurate than other five state-of-the-art label fusion methods. The proposed method obtains dice similarity coefficient of 0.94 and 0.92 in segmenting epicardium and endocardium respectively. Moreover, our label fusion method achieves more accurate segmentation results compared to four other label fusion methods.

Image fusion pitfalls for cranial radiosurgery

PubMed Central

Jonker, Benjamin P.

2013-01-01

Stereotactic radiosurgery requires imaging to define both the stereotactic space in which the treatment is delivered and the target itself. Image fusion is the process of using rotation and translation to bring a second image set into alignment with the first image set. This allows the potential concurrent use of multiple image sets to define the target and stereotactic space. While a single magnetic resonance imaging (MRI) sequence alone can be used for delineation of the target and fiducials, there may be significant advantages to using additional imaging sets including other MRI sequences, computed tomography (CT) scans, and advanced imaging sets such as catheter-based angiography, diffusor tension imaging-based fiber tracking and positon emission tomography in order to more accurately define the target and surrounding critical structures. Stereotactic space is usually defined by detection of fiducials on the stereotactic head frame or mask system. Unfortunately MRI sequences are susceptible to geometric distortion, whereas CT scans do not face this problem (although they have poorer resolution of the target in most cases). Thus image fusion can allow the definition of stereotactic space to proceed from the geometrically accurate CT images at the same time as using MRI to define the target. The use of image fusion is associated with risk of error introduced by inaccuracies of the fusion process, as well as workflow changes that if not properly accounted for can mislead the treating clinician. The purpose of this review is to describe the uses of image fusion in stereotactic radiosurgery as well as its potential pitfalls. PMID:23682338

Binding and Fusion of Extracellular Vesicles to the Plasma Membrane of Their Cell Targets.

PubMed

Prada, Ilaria; Meldolesi, Jacopo

2016-08-09

Exosomes and ectosomes, extracellular vesicles of two types generated by all cells at multivesicular bodies and the plasma membrane, respectively, play critical roles in physiology and pathology. A key mechanism of their function, analogous for both types of vesicles, is the fusion of their membrane to the plasma membrane of specific target cells, followed by discharge to the cytoplasm of their luminal cargo containing proteins, RNAs, and DNA. Here we summarize the present knowledge about the interactions, binding and fusions of vesicles with the cell plasma membrane. The sequence initiates with dynamic interactions, during which vesicles roll over the plasma membrane, followed by the binding of specific membrane proteins to their cell receptors. Membrane binding is then converted rapidly into fusion by mechanisms analogous to those of retroviruses. Specifically, proteins of the extracellular vesicle membranes are structurally rearranged, and their hydrophobic sequences insert into the target cell plasma membrane which undergoes lipid reorganization, protein restructuring and membrane dimpling. Single fusions are not the only process of vesicle/cell interactions. Upon intracellular reassembly of their luminal cargoes, vesicles can be regenerated, released and fused horizontally to other target cells. Fusions of extracellular vesicles are relevant also for specific therapy processes, now intensely investigated.

Design of multivalent complexes using the barnase*barstar module.

PubMed

Deyev, Sergey M; Waibel, Robert; Lebedenko, Ekaterina N; Schubiger, August P; Plückthun, Andreas

2003-12-01

The ribonuclease barnase (12 kDa) and its inhibitor barstar (10 kDa) form a very tight complex in which all N and C termini are accessible for fusion. Here we exploit this system to create modular targeting molecules based on antibody scFv fragment fusions to barnase, to two barnase molecules in series and to barstar. We describe the construction, production and purification of defined dimeric and trimeric complexes. Immobilized barnase fusions are used to capture barstar fusions from crude extracts to yield homogeneous, heterodimeric fusion proteins. These proteins are stable, soluble and resistant to proteolysis. Using fusions with anti-p185(HER2-ECD) 4D5 scFv, we show that the anticipated gain in avidity from monomer to dimer to trimer is obtained and that favorable tumor targeting properties are achieved. Many permutations of engineered multispecific fusion proteins become accessible with this technology of quasi-covalent heterodimers.

Decision-level fusion of SAR and IR sensor information for automatic target detection

NASA Astrophysics Data System (ADS)

Cho, Young-Rae; Yim, Sung-Hyuk; Cho, Hyun-Woong; Won, Jin-Ju; Song, Woo-Jin; Kim, So-Hyeon

2017-05-01

We propose a decision-level architecture that combines synthetic aperture radar (SAR) and an infrared (IR) sensor for automatic target detection. We present a new size-based feature, called target-silhouette to reduce the number of false alarms produced by the conventional target-detection algorithm. Boolean Map Visual Theory is used to combine a pair of SAR and IR images to generate the target-enhanced map. Then basic belief assignment is used to transform this map into a belief map. The detection results of sensors are combined to build the target-silhouette map. We integrate the fusion mass and the target-silhouette map on the decision level to exclude false alarms. The proposed algorithm is evaluated using a SAR and IR synthetic database generated by SE-WORKBENCH simulator, and compared with conventional algorithms. The proposed fusion scheme achieves higher detection rate and lower false alarm rate than the conventional algorithms.

Conceptual design of fast-ignition laser fusion reactor FALCON-D

NASA Astrophysics Data System (ADS)

Goto, T.; Someya, Y.; Ogawa, Y.; Hiwatari, R.; Asaoka, Y.; Okano, K.; Sunahara, A.; Johzaki, T.

2009-07-01

A new conceptual design of the laser fusion power plant FALCON-D (Fast-ignition Advanced Laser fusion reactor CONcept with a Dry wall chamber) has been proposed. The fast-ignition method can achieve sufficient fusion gain for a commercial operation (~100) with about 10 times smaller fusion yield than the conventional central ignition method. FALCON-D makes full use of this property and aims at designing with a compact dry wall chamber (5-6 m radius). 1D/2D simulations by hydrodynamic codes showed a possibility of achieving sufficient gain with a laser energy of 400 kJ, i.e. a 40 MJ target yield. The design feasibility of the compact dry wall chamber and the solid breeder blanket system was shown through thermomechanical analysis of the dry wall and neutronics analysis of the blanket system. Moderate electric output (~400 MWe) can be achieved with a high repetition (30 Hz) laser. This dry wall reactor concept not only reduces several difficulties associated with a liquid wall system but also enables a simple cask maintenance method for the replacement of the blanket system, which can shorten the maintenance period. The basic idea of the maintenance method for the final optics system has also been proposed. Some critical R&D issues required for this design are also discussed.

Differential pH-dependent cellular uptake pathways among foamy viruses elucidated using dual-colored fluorescent particles

PubMed Central

2012-01-01

Background It is thought that foamy viruses (FVs) enter host cells via endocytosis because all FV glycoproteins examined display pH-dependent fusion activities. Only the prototype FV (PFV) glycoprotein has also significant fusion activity at neutral pH, suggesting that its uptake mechanism may deviate from other FVs. To gain new insights into the uptake processes of FV in individual live host cells, we developed fluorescently labeled infectious FVs. Results N-terminal tagging of the FV envelope leader peptide domain with a fluorescent protein resulted in efficient incorporation of the fluorescently labeled glycoprotein into secreted virions without interfering with their infectivity. Double-tagged viruses consisting of an eGFP-tagged PFV capsid (Gag-eGFP) and mCherry-tagged Env (Ch-Env) from either PFV or macaque simian FV (SFVmac) were observed during early stages of the infection pathway. PFV Env, but not SFVmac Env, containing particles induced strong syncytia formation on target cells. Both virus types showed trafficking of double-tagged virions towards the cell center. Upon fusion and subsequent capsid release into the cytosol, accumulation of naked capsid proteins was observed within four hours in the perinuclear region, presumably representing the centrosomes. Interestingly, virions harboring fusion-defective glycoproteins still promoted virus attachment and uptake, but failed to show syncytia formation and perinuclear capsid accumulation. Biochemical and initial imaging analysis indicated that productive fusion events occur predominantly within 4–6 h after virus attachment. Non-fused or non-fusogenic viruses are rapidly cleared from the cells by putative lysosomal degradation. Quantitative monitoring of the fraction of individual viruses containing both Env and capsid signals as a function of time demonstrated that PFV virions fused within the first few minutes, whereas fusion of SFVmac virions was less pronounced and observed over the entire 90 minutes measured. Conclusions The characterized double-labeled FVs described here provide new mechanistic insights into FV early entry steps, demonstrating that productive viral fusion occurs early after target cell attachment and uptake. The analysis highlights apparent differences in the uptake pathways of individual FV species. Furthermore, the infectious double-labeled FVs promise to provide important tools for future detailed analyses on individual FV fusion events in real time using advanced imaging techniques. PMID:22935135

Pre-fusion RSV F strongly boosts pre-fusion specific neutralizing responses in cattle pre-exposed to bovine RSV.

PubMed

Steff, Ann-Muriel; Monroe, James; Friedrich, Kristian; Chandramouli, Sumana; Nguyen, Thi Lien-Anh; Tian, Sai; Vandepaer, Sarah; Toussaint, Jean-François; Carfi, Andrea

2017-10-20

Human respiratory syncytial virus (hRSV) is responsible for serious lower respiratory tract disease in infants and in older adults, and remains an important vaccine need. RSV fusion (F) glycoprotein is a key target for neutralizing antibodies. RSV F stabilized in its pre-fusion conformation (DS-Cav1 F) induces high neutralizing antibody titers in naïve animals, but it remains unknown to what extent pre-fusion F can boost pre-existing neutralizing responses in RSV seropositive adults. We here assess DS-Cav1 F immunogenicity in seropositive cattle pre-exposed to bovine RSV, a virus closely related to hRSV. A single immunization with non-adjuvanted DS-Cav1 F strongly boosts RSV neutralizing responses, directed towards pre-fusion F-specific epitopes, whereas a post-fusion F is unable to do so. Vaccination with pre-fusion F thus represents a promising strategy for maternal immunization and for other RSV vaccine target populations such as older adults.

A sensitive HIV-1 envelope induced fusion assay identifies fusion enhancement of thrombin

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

Cheng, De-Chun; Zhong, Guo-Cai; Su, Ju-Xiang

2010-01-22

To evaluate the interaction between HIV-1 envelope glycoprotein (Env) and target cell receptors, various cell-cell-fusion assays have been developed. In the present study, we established a novel fusion system. In this system, the expression of the sensitive reporter gene, firefly luciferase (FL) gene, in the target cells was used to evaluate cell fusion event. Simultaneously, constitutively expressed Renilla luciferase (RL) gene was used to monitor effector cell number and viability. FL gave a wider dynamic range than other known reporters and the introduction of RL made the assay accurate and reproducible. This system is especially beneficial for investigation of potentialmore » entry-influencing agents, for its power of ruling out the false inhibition or enhancement caused by the artificial cell-number variation. As a case study, we applied this fusion system to observe the effect of a serine protease, thrombin, on HIV Env-mediated cell-cell fusion and have found the fusion enhancement activity of thrombin over two R5-tropic HIV strains.« less

Robust fusion-based processing for military polarimetric imaging systems

NASA Astrophysics Data System (ADS)

Hickman, Duncan L.; Smith, Moira I.; Kim, Kyung Su; Choi, Hyun-Jin

2017-05-01

Polarisation information within a scene can be exploited in military systems to give enhanced automatic target detection and recognition (ATD/R) performance. However, the performance gain achieved is highly dependent on factors such as the geometry, viewing conditions, and the surface finish of the target. Such performance sensitivities are highly undesirable in many tactical military systems where operational conditions can vary significantly and rapidly during a mission. Within this paper, a range of processing architectures and fusion methods is considered in terms of their practical viability and operational robustness for systems requiring ATD/R. It is shown that polarisation information can give useful performance gains but, to retained system robustness, the introduction of polarimetric processing should be done in such a way as to not compromise other discriminatory scene information in the spectral and spatial domains. The analysis concludes that polarimetric data can be effectively integrated with conventional intensity-based ATD/R by either adapting the ATD/R processing function based on the scene polarisation or else by detection-level fusion. Both of these approaches avoid the introduction of processing bottlenecks and limit the impact of processing on system latency.

[Construction, expression and characterization of the fusion gene of super-antigen SEA and single chain Fv of the ND-1 monoclonal antibody against human colorectal cancer].

PubMed

Chen, Hang; Li, Li; Fang, Jin

2012-04-01

To construct and express the recombinant ND-1-scFv/SEA, a fusion protein of superantigen (staphylococcal enterotoxinA, SEA) and single-chain variable fragment of monoclonal antibody ND-1 against human clolorectal carcinoma, and to enhance the targeted killing effect of SEA. The expression of the fusion protein was induced in E.coli M15 by IPTG. Ni-NTA resin affinity chromatography was used to separate and purify the expressed product. The specific binding activity of the purified ND-1-scFv/SEA protein was examined by indirect immunofluorescence assay and the targeted-cytotoxicity was determined using MTT assay. The expressing vector of fusion gene ND-1scFv/SEA was constructed successfully. ND-1-scFv/SEA protein retained a high binding affinity to antigen-positive human colorectal cancer cell CCL-187 and had a stronger capability to activate PBMC and kill the target cells compared to SEA alone, with a killing rate of 91% at 4 μg/mL. ND-1-scFv/SEA fusion protein could specifically target colorectal cancer cell, enhance the activity of kill tumor cell and has potential applications in the targeted therapy of colorectal cancer.

Deuteron Beam Driven Fast Ignition of a Pre-Compressed Inertial Confinement Fusion (ICF) Fuel Capsule

NASA Astrophysics Data System (ADS)

Yang, Xiaoling; Miley, George; Flippo, Kirk; Hora, Heinrich; Gaillard, Sandrine; Offermann, Dustin

2012-10-01

We proposed to utilize a new ``Deuterium Cluster'' type structure for the laser interaction foil to generate an energetic deuteron beam as the fast igniter to ignite inertial confinement fusion fuel capsule. The benefit of deuteron beam driven fast ignition is that its deposition in the target fuel will not only provide heating but also fuse with fuel as they slow down in the target. The preliminary results from recent laser-deuteron acceleration experiment at LANL were encouraging. Also, in most recent calculations, we found that a 12.73% extra energy gain from deuteron beam-target fusion could be achieved when quasi-Maxwellian deuteron beam was assumed, and when a ρrb = 4.5 g/cm2 was considered, where ρ is the fuel density, and rb is the ion beam focusing radius on the target. These results provide some insight into the contribution of the extra heat produced by deuteron beam-target fusion to the hot spot ignition process. If the physics works as anticipated, this novel type of interaction foil can efficiently generate energetic deuterons during intense laser pulses. The massive yield of deuterons should turn out to be the most efficient way of igniting the DT fuel, making the dream of near-term commercialization of FI fusion more achievable.

Species separation and modification of neutron diagnostics in inertial-confinement fusion

NASA Astrophysics Data System (ADS)

Inglebert, A.; Canaud, B.; Larroche, O.

2014-09-01

The different behaviours of deuterium (D) and tritium (T) in the hot spot of marginally igniting cryogenic DT inertial-confinement fusion (ICF) targets are investigated with an ion Fokker-Planck model. With respect to an equivalent single-species model, a higher density and a higher temperature are found for T in the stagnation phase of the target implosion. In addition, the stagnating hot spot is found to be less dense but hotter than in the single-species case. As a result, the fusion reaction yield in the hot spot is significantly increased. Fusion neutron diagnostics of the implosion find a larger ion temperature as deduced from DT reactions than from DD reactions, in good agreement with NIF experimental results. ICF target designs should thus definitely take ion-kinetic effects into account.

Sequential CD4-Coreceptor Interactions in Human Immunodeficiency Virus Type 1 Env Function: Soluble CD4 Activates Env for Coreceptor-Dependent Fusion and Reveals Blocking Activities of Antibodies against Cryptic Conserved Epitopes on gp120

PubMed Central

Salzwedel, Karl; Smith, Erica D.; Dey, Barna; Berger, Edward A.

2000-01-01

We devised an experimental system to examine sequential events by which the human immunodeficiency virus type 1 (HIV-1) envelope glycoprotein (Env) interacts with CD4 and coreceptor to induce membrane fusion. Recombinant soluble CD4 (sCD4) activated fusion between effector cells expressing Env and target cells expressing coreceptor (CCR5 or CXCR4) but lacking CD4. sCD4-activated fusion was dose dependent, occurred comparably with two- and four-domain proteins, and demonstrated Env-coreceptor specificities parallel to those reported in conventional fusion and infectivity systems. Fusion activation occurred upon sCD4 preincubation and washing of the Env-expressing effector cells but not the coreceptor-bearing target cells, thereby demonstrating that sCD4 exerts its effects by acting on Env. These findings provide direct functional evidence for a sequential two-step model of Env-receptor interactions, whereby gp120 binds first to CD4 and becomes activated for subsequent functional interaction with coreceptor, leading to membrane fusion. We used the sCD4-activated system to explore neutralization by the anti-gp120 human monoclonal antibodies 17b and 48d. These antibodies reportedly bind conserved CD4-induced epitopes involved in coreceptor interactions but neutralize HIV-1 infection only weakly. We found that 17b and 48d had minimal effects in the standard cell fusion system using target cells expressing both CD4 and coreceptor but potently blocked sCD4-activated fusion with target cells expressing coreceptor alone. Both antibodies strongly inhibited sCD4-activated fusion by Envs from genetically diverse HIV-1 isolates. Thus, the sCD4-activated system reveals conserved Env-blocking epitopes that are masked in native Env and hence not readily detected by conventional systems. PMID:10590121

Hendra virus fusion protein transmembrane domain contributes to pre-fusion protein stability

PubMed Central

Webb, Stacy; Nagy, Tamas; Moseley, Hunter; Fried, Michael; Dutch, Rebecca

2017-01-01

Enveloped viruses utilize fusion (F) proteins studding the surface of the virus to facilitate membrane fusion with a target cell membrane. Fusion of the viral envelope with a cellular membrane is required for release of viral genomic material, so the virus can ultimately reproduce and spread. To drive fusion, the F protein undergoes an irreversible conformational change, transitioning from a metastable pre-fusion conformation to a more thermodynamically stable post-fusion structure. Understanding the elements that control stability of the pre-fusion state and triggering to the post-fusion conformation is important for understanding F protein function. Mutations in F protein transmembrane (TM) domains implicated the TM domain in the fusion process, but the structural and molecular details in fusion remain unclear. Previously, analytical ultracentrifugation was utilized to demonstrate that isolated TM domains of Hendra virus F protein associate in a monomer-trimer equilibrium (Smith, E. C., Smith, S. E., Carter, J. R., Webb, S. R., Gibson, K. M., Hellman, L. M., Fried, M. G., and Dutch, R. E. (2013) J. Biol. Chem. 288, 35726–35735). To determine factors driving this association, 140 paramyxovirus F protein TM domain sequences were analyzed. A heptad repeat of β-branched residues was found, and analysis of the Hendra virus F TM domain revealed a heptad repeat leucine-isoleucine zipper motif (LIZ). Replacement of the LIZ with alanine resulted in dramatically reduced TM-TM association. Mutation of the LIZ in the whole protein resulted in decreased protein stability, including pre-fusion conformation stability. Together, our data suggest that the heptad repeat LIZ contributed to TM-TM association and is important for F protein function and pre-fusion stability. PMID:28213515

Hendra virus fusion protein transmembrane domain contributes to pre-fusion protein stability.

PubMed

Webb, Stacy; Nagy, Tamas; Moseley, Hunter; Fried, Michael; Dutch, Rebecca

2017-04-07

Enveloped viruses utilize fusion (F) proteins studding the surface of the virus to facilitate membrane fusion with a target cell membrane. Fusion of the viral envelope with a cellular membrane is required for release of viral genomic material, so the virus can ultimately reproduce and spread. To drive fusion, the F protein undergoes an irreversible conformational change, transitioning from a metastable pre-fusion conformation to a more thermodynamically stable post-fusion structure. Understanding the elements that control stability of the pre-fusion state and triggering to the post-fusion conformation is important for understanding F protein function. Mutations in F protein transmembrane (TM) domains implicated the TM domain in the fusion process, but the structural and molecular details in fusion remain unclear. Previously, analytical ultracentrifugation was utilized to demonstrate that isolated TM domains of Hendra virus F protein associate in a monomer-trimer equilibrium (Smith, E. C., Smith, S. E., Carter, J. R., Webb, S. R., Gibson, K. M., Hellman, L. M., Fried, M. G., and Dutch, R. E. (2013) J. Biol. Chem. 288, 35726-35735). To determine factors driving this association, 140 paramyxovirus F protein TM domain sequences were analyzed. A heptad repeat of β-branched residues was found, and analysis of the Hendra virus F TM domain revealed a heptad repeat leucine-isoleucine zipper motif (LIZ). Replacement of the LIZ with alanine resulted in dramatically reduced TM-TM association. Mutation of the LIZ in the whole protein resulted in decreased protein stability, including pre-fusion conformation stability. Together, our data suggest that the heptad repeat LIZ contributed to TM-TM association and is important for F protein function and pre-fusion stability. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

Analysis of histological findings obtained combining US/mp-MRI fusion-guided biopsies with systematic US biopsies: mp-MRI role in prostate cancer detection and false negative.

PubMed

Faiella, Eliodoro; Santucci, Domiziana; Greco, Federico; Frauenfelder, Giulia; Giacobbe, Viola; Muto, Giovanni; Zobel, Bruno Beomonte; Grasso, Rosario Francesco

2018-02-01

To evaluate the diagnostic accuracy of mp-MRI correlating US/mp-MRI fusion-guided biopsy with systematic random US-guided biopsy in prostate cancer diagnosis. 137 suspected prostatic abnormalities were identified on mp-MRI (1.5T) in 96 patients and classified according to PI-RADS score v2. All target lesions underwent US/mp-MRI fusion biopsy and prostatic sampling was completed by US-guided systematic random 12-core biopsies. Histological analysis and Gleason score were established for all the samples, both target lesions defined by mp-MRI, and random biopsies. PI-RADS score was correlated with the histological results, divided in three groups (benign tissue, atypia and carcinoma) and with Gleason groups, divided in four categories considering the new Grading system of the ISUP 2014, using t test. Multivariate analysis was used to correlate PI-RADS and Gleason categories to PSA level and abnormalities axial diameter. When the random core biopsies showed carcinoma (mp-MRI false-negatives), PSA value and lesions Gleason median value were compared with those of carcinomas identified by mp-MRI (true-positives), using t test. There was statistically significant difference between PI-RADS score in carcinoma, atypia and benign lesions groups (4.41, 3.61 and 3.24, respectively) and between PI-RADS score in Gleason < 7 group and Gleason > 7 group (4.14 and 4.79, respectively). mp-MRI performance was more accurate for lesions > 15 mm and in patients with PSA > 6 ng/ml. In systematic sampling, 130 (11.25%) mp-MRI false-negative were identified. There was no statistic difference in Gleason median value (7.0 vs 7.06) between this group and the mp-MRI true-positives, but a significant lower PSA median value was demonstrated (7.08 vs 7.53 ng/ml). mp-MRI remains the imaging modality of choice to identify PCa lesions. Integrating US-guided random sampling with US/mp-MRI fusion target lesions sampling, 3.49% of false-negative were identified.

Accuracy of flat panel detector CT with integrated navigational software with and without MR fusion for single-pass needle placement.

PubMed

Mabray, Marc C; Datta, Sanjit; Lillaney, Prasheel V; Moore, Teri; Gehrisch, Sonja; Talbott, Jason F; Levitt, Michael R; Ghodke, Basavaraj V; Larson, Paul S; Cooke, Daniel L

2016-07-01

Fluoroscopic systems in modern interventional suites have the ability to perform flat panel detector CT (FDCT) with navigational guidance. Fusion with MR allows navigational guidance towards FDCT occult targets. We aim to evaluate the accuracy of this system using single-pass needle placement in a deep brain stimulation (DBS) phantom. MR was performed on a head phantom with DBS lead targets. The head phantom was placed into fixation and FDCT was performed. FDCT and MR datasets were automatically fused using the integrated guidance system (iGuide, Siemens). A DBS target was selected on the MR dataset. A 10 cm, 19 G needle was advanced by hand in a single pass using laser crosshair guidance. Radial error was visually assessed against measurement markers on the target and by a second FDCT. Ten needles were placed using CT-MR fusion and 10 needles were placed without MR fusion, with targeting based solely on FDCT and fusion steps repeated for every pass. Mean radial error was 2.75±1.39 mm as defined by visual assessment to the centre of the DBS target and 2.80±1.43 mm as defined by FDCT to the centre of the selected target point. There were no statistically significant differences in error between MR fusion and non-MR guided series. Single pass needle placement in a DBS phantom using FDCT guidance is associated with a radial error of approximately 2.5-3.0 mm at a depth of approximately 80 mm. This system could accurately target sub-centimetre intracranial lesions defined on MR. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

Analysis of Yersinia enterocolitica Effector Translocation into Host Cells Using Beta-lactamase Effector Fusions.

PubMed

Wolters, Manuel; Zobiak, Bernd; Nauth, Theresa; Aepfelbacher, Martin

2015-10-13

Many gram-negative bacteria including pathogenic Yersinia spp. employ type III secretion systems to translocate effector proteins into eukaryotic target cells. Inside the host cell the effector proteins manipulate cellular functions to the benefit of the bacteria. To better understand the control of type III secretion during host cell interaction, sensitive and accurate assays to measure translocation are required. We here describe the application of an assay based on the fusion of a Yersinia enterocolitica effector protein fragment (Yersinia outer protein; YopE) with TEM-1 beta-lactamase for quantitative analysis of translocation. The assay relies on cleavage of a cell permeant FRET dye (CCF4/AM) by translocated beta-lactamase fusion. After cleavage of the cephalosporin core of CCF4 by the beta-lactamase, FRET from coumarin to fluorescein is disrupted and excitation of the coumarin moiety leads to blue fluorescence emission. Different applications of this method have been described in the literature highlighting its versatility. The method allows for analysis of translocation in vitro and also in in vivo, e.g., in a mouse model. Detection of the fluorescence signals can be performed using plate readers, FACS analysis or fluorescence microscopy. In the setup described here, in vitro translocation of effector fusions into HeLa cells by different Yersinia mutants is monitored by laser scanning microscopy. Recording intracellular conversion of the FRET reporter by the beta-lactamase effector fusion in real-time provides robust quantitative results. We here show exemplary data, demonstrating increased translocation by a Y. enterocolitica YopE mutant compared to the wild type strain.

Selective targeting of a TNFR decoy receptor pharmaceutical to the primate brain as a receptor-specific IgG fusion protein.

PubMed

Boado, Ruben J; Hui, Eric Ka-Wai; Lu, Jeff Zhiqiang; Zhou, Qing-Hui; Pardridge, William M

2010-03-01

Decoy receptors, such as the human tumor necrosis factor receptor (TNFR), are potential new therapies for brain disorders. However, decoy receptors are large molecule drugs that are not transported across the blood-brain barrier (BBB). To enable BBB transport of a TNFR decoy receptor, the human TNFR-II extracellular domain was re-engineered as a fusion protein with a chimeric monoclonal antibody (MAb) against the human insulin receptor (HIR). The HIRMAb acts as a molecular Trojan horse to ferry the TNFR therapeutic decoy receptor across the BBB. The HIRMAb-TNFR fusion protein was expressed in stably transfected CHO cells, and was analyzed with electrophoresis, Western blotting, size exclusion chromatography, and binding assays for the HIR and TNFalpha. The HIRMAb-TNFR fusion protein was radio-labeled by trititation, in parallel with the radio-iodination of recombinant TNFR:Fc fusion protein, and the proteins were co-injected in the adult Rhesus monkey. The TNFR:Fc fusion protein did not cross the primate BBB in vivo, but the uptake of the HIRMAb-TNFR fusion protein was high and 3% of the injected dose was taken up by the primate brain. The TNFR was selectively targeted to brain, relative to peripheral organs, following fusion to the HIRMAb. This study demonstrates that decoy receptors may be re-engineered as IgG fusion proteins with a BBB molecular Trojan horse that selectively targets the brain, and enables penetration of the BBB in vivo. IgG-decoy receptor fusion proteins represent a new class of human neurotherapeutics. Copyright 2010 Elsevier B.V. All rights reserved.

Multispectral image fusion based on fractal features

NASA Astrophysics Data System (ADS)

Tian, Jie; Chen, Jie; Zhang, Chunhua

2004-01-01

Imagery sensors have been one indispensable part of the detection and recognition systems. They are widely used to the field of surveillance, navigation, control and guide, et. However, different imagery sensors depend on diverse imaging mechanisms, and work within diverse range of spectrum. They also perform diverse functions and have diverse circumstance requires. So it is unpractical to accomplish the task of detection or recognition with a single imagery sensor under the conditions of different circumstances, different backgrounds and different targets. Fortunately, the multi-sensor image fusion technique emerged as important route to solve this problem. So image fusion has been one of the main technical routines used to detect and recognize objects from images. While, loss of information is unavoidable during fusion process, so it is always a very important content of image fusion how to preserve the useful information to the utmost. That is to say, it should be taken into account before designing the fusion schemes how to avoid the loss of useful information or how to preserve the features helpful to the detection. In consideration of these issues and the fact that most detection problems are actually to distinguish man-made objects from natural background, a fractal-based multi-spectral fusion algorithm has been proposed in this paper aiming at the recognition of battlefield targets in the complicated backgrounds. According to this algorithm, source images are firstly orthogonally decomposed according to wavelet transform theories, and then fractal-based detection is held to each decomposed image. At this step, natural background and man-made targets are distinguished by use of fractal models that can well imitate natural objects. Special fusion operators are employed during the fusion of area that contains man-made targets so that useful information could be preserved and features of targets could be extruded. The final fused image is reconstructed from the composition of source pyramid images. So this fusion scheme is a multi-resolution analysis. The wavelet decomposition of image can be actually considered as special pyramid decomposition. According to wavelet decomposition theories, the approximation of image (formula available in paper) at resolution 2j+1 equal to its orthogonal projection in space , that is, where Ajf is the low-frequency approximation of image f(x, y) at resolution 2j and , , represent the vertical, horizontal and diagonal wavelet coefficients respectively at resolution 2j. These coefficients describe the high-frequency information of image at direction of vertical, horizontal and diagonal respectively. Ajf, , and are independent and can be considered as images. In this paper J is set to be 1, so the source image is decomposed to produce the son-images Af, D1f, D2f and D3f. To solve the problem of detecting artifacts, the concepts of vertical fractal dimension FD1, horizontal fractal dimension FD2 and diagonal fractal dimension FD3 are proposed in this paper. The vertical fractal dimension FD1 corresponds to the vertical wavelet coefficients image after the wavelet decomposition of source image, the horizontal fractal dimension FD2 corresponds to the horizontal wavelet coefficients and the diagonal fractal dimension FD3 the diagonal one. These definitions enrich the illustration of source images. Therefore they are helpful to classify the targets. Then the detection of artifacts in the decomposed images is a problem of pattern recognition in 4-D space. The combination of FD0, FD1, FD2 and FD3 make a vector of (FD0, FD1, FD2, FD3), which can be considered as a united feature vector of the studied image. All the parts of the images are classified in the 4-D pattern space created by the vector of (FD0, FD1, FD2, FD3) so that the area that contains man-made objects could be detected. This detection can be considered as a coarse recognition, and then the significant areas in each son-images are signed so that they can be dealt with special rules. There has been various fusion rules developed with each one aiming at a special problem. These rules have different performance, so it is very important to select an appropriate rule during the design of an image fusion system. Recent research denotes that the rule should be adjustable so that it is always suitable to extrude the features of targets and to preserve the pixels of useful information. In this paper, owing to the consideration that fractal dimension is one of the main features to distinguish man-made targets from natural objects, the fusion rule was defined that if the studied region of image contains man-made target, the pixels of the source image whose fractal dimension is minimal are saved to be the pixels of the fused image, otherwise, a weighted average operator is adopted to avoid loss of information. The main idea of this rule is to store the pixels with low fractal dimensions, so it can be named Minimal Fractal dimensions (MFD) fusion rule. This fractal-based algorithm is compared with a common weighted average fusion algorithm. An objective assessment is taken to the two fusion results. The criteria of Entropy, Cross-Entropy, Peak Signal-to-Noise Ratio (PSNR) and Standard Gray Scale Difference are defined in this paper. Reversely to the idea of constructing an ideal image as the assessing reference, the source images are selected to be the reference in this paper. It can be deemed that this assessment is to calculate how much the image quality has been enhanced and the quantity of information has been increased when the fused image is compared with the source images. The experimental results imply that the fractal-based multi-spectral fusion algorithm can effectively preserve the information of man-made objects with a high contrast. It is proved that this algorithm could well preserve features of military targets because that battlefield targets are most man-made objects and in common their images differ from fractal models obviously. Furthermore, the fractal features are not sensitive to the imaging conditions and the movement of targets, so this fractal-based algorithm may be very practical.

[Optimization of expression conditions and activity identification of hepatocyte-targeting peptide-human endostatin].

PubMed

Ma, Yan; Li, Wei; Li, Xiaobo; Bao, Dongmei; Lu, Jianpei

2016-12-25

To obtain sufficient purified and active fusion protein-hepatocyte-targeting peptide-human endostatin (HTP-rES), we studied the growth curve and the optimal induction timing of BL21/pET21b-HTP-rES. Different conditions of pH value, induction time, induction concentration and induction temperature were optimized by univariate analysis. After washing, refolding and purifying, the activity of fusion protein was identified by flow cytometry and 3-(4,5)-dimethylthiahiazo (-z-y1)-3,5-di-phenytetrazoliumromide (MTT). Results show that the logarithmic growth phase of BL21/pET21b-HTP-rES was from 1.5 h to 3.5 h, the optimum expression conditions were pH 8.0, 0.06 mmol/L IPTG, at 42 ℃ for 5 h. The purity of inclusion bodies was up to 60% after washing. The purity of target protein was more than 95% after refolding and purification. Our findings provide the foundation for further biological activity and drug development.

Expression of 16 Nitrogenase Proteins within the Plant Mitochondrial Matrix

PubMed Central

Allen, Robert S.; Tilbrook, Kimberley; Warden, Andrew C.; Campbell, Peter C.; Rolland, Vivien; Singh, Surinder P.; Wood, Craig C.

2017-01-01

The industrial production and use of nitrogenous fertilizer involves significant environmental and economic costs. Strategies to reduce fertilizer dependency are required to address the world's increasing demand for sustainable food, fibers, and biofuels. Biological nitrogen fixation, a process unique to diazatrophic bacteria, is catalyzed by the nitrogenase complex, and reconstituting this function in plant cells is an ambitious biotechnological strategy to reduce fertilizer use. Here we establish that the full array of biosynthetic and catalytic nitrogenase (Nif) proteins from the diazotroph Klebsiella pneumoniae can be individually expressed as mitochondrial targeting peptide (MTP)-Nif fusions in Nicotiana benthamiana. We show that these are correctly targeted to the plant mitochondrial matrix, a subcellular location with biochemical and genetic characteristics potentially supportive of nitrogenase function. Although Nif proteins B, D, E, F, H, J, K, M, N, Q, S, U, V, X, Y, and Z were all detectable by Western blot analysis, the NifD catalytic component was the least abundant. To address this problem, a translational fusion between NifD and NifK was designed based on the crystal structure of the nitrogenase MoFe protein heterodimer. This fusion protein enabled equimolar NifD:NifK stoichiometry and improved NifD expression levels in plants. Finally, four MTP-Nif fusion proteins (B, S, H, Y) were successfully co-expressed, demonstrating that multiple components of nitrogenase can be targeted to plant mitochondria. These results establish the feasibility of reconstituting the complete componentry for nitrogenase in plant cells, within an intracellular environment that could support the conversion of nitrogen gas into ammonia. PMID:28316608

Cost effectiveness of EML4-ALK fusion testing and first-line crizotinib treatment for patients with advanced ALK-positive non-small-cell lung cancer.

PubMed

Djalalov, Sandjar; Beca, Jaclyn; Hoch, Jeffrey S; Krahn, Murray; Tsao, Ming-Sound; Cutz, Jean-Claude; Leighl, Natasha B

2014-04-01

ALK-targeted therapy with crizotinib offers significant improvement in clinical outcomes for the treatment of EML4-ALK fusion-positive non-small-cell lung cancer (NSCLC). We estimated the cost effectiveness of EML4-ALK fusion testing in combination with targeted first-line crizotinib treatment in Ontario. A cost-effectiveness analysis was conducted using a Markov model from the Canadian Public health (Ontario) perspective and a lifetime horizon in patients with stage IV NSCLC with nonsquamous histology. Transition probabilities and mortality rates were calculated from the Ontario Cancer Registry and Cancer Care Ontario New Drug Funding Program (CCO NDFP). Costs were obtained from the Ontario Case Costing Initiative, CCO NDFP, University Health Network, and literature. Molecular testing with first-line targeted crizotinib treatment in the population with advanced nonsquamous NSCLC resulted in a gain of 0.011 quality-adjusted life-years (QALYs) compared with standard care. The incremental cost was Canadian $2,725 per patient, and the incremental cost-effectiveness ratio (ICER) was $255,970 per QALY gained. Among patients with known EML4-ALK-positive advanced NSCLC, first-line crizotinib therapy provided 0.379 additional QALYs, cost an additional $95,043 compared with standard care, and produced an ICER of $250,632 per QALY gained. The major driver of cost effectiveness was drug price. EML4-ALK fusion testing in stage IV nonsquamous NSCLC with crizotinib treatment for ALK-positive patients is not cost effective in the setting of high drug costs and a low biomarker frequency in the population.

Study of Cold Fusion Reactions Using Collective Clusterization Approach

NASA Astrophysics Data System (ADS)

Kaur, Gurjit; Sandhu, Kirandeep; Sharma, Manoj K.

2017-10-01

Within the framework of the dynamical cluster decay model (DCM), the 1n evaporation cross-sections ({σ }1n) of cold fusion reactions (Pb and Bi targets) are calculated for {Z}{CN}=104-113 superheavy nuclei. The calculations are carried out in the fixed range of excitation energy {E}{CN}* =15+/- 1 {MeV}, so that the comparative analysis of reaction dynamics can be worked out. First of all, the fission barriers (B f ) and neutron separation energies ({S}1n) are estimated to account the decreasing cross-sections of cold fusion reactions. In addition to this, the importance of hot optimum orientations of β 2i-deformed nuclei over cold one is explored at fixed angular momentum and neck-length parameters. The hot optimum orientations support all the target-projectile (t,p) combinations, which are explored experimentally in the cold fusion reactions. Some new target-projectile combinations are also predicted for future exploration. Further, the 1n cross-sections are addressed for {Z}{CN}=104-113 superheavy nuclei at comparable excitation energies which show the decent agrement with experimental data upto {Z}{CN}=109 nuclei. Finally, to understand the dynamics of higher-Z superheavy nuclei, the cross-sections are also calculated at maximum available energies around the Coulomb barrier and the effect of non-sticking moment of inertia ({I}{NS}) is also investigated at these energies. Supported by the Council of Scientific and Industrial Research (CSIR), in the Form of Research Project Grant No. 03(1341)/15/EMR-II, and to DST, New Delhi, for INSPIRE-Fellowship Grant No. DST/INSPIRE/03/2015/000199

Cryogenic hydrogen fuel for controlled inertial confinement fusion (formation of reactor-scale cryogenic targets)

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

Aleksandrova, I. V.; Koresheva, E. R., E-mail: elena.koresheva@gmail.com; Krokhin, O. N.

2016-12-15

In inertial fusion energy research, considerable attention has recently been focused on low-cost fabrication of a large number of targets by developing a specialized layering module of repeatable operation. The targets must be free-standing, or unmounted. Therefore, the development of a target factory for inertial confinement fusion (ICF) is based on methods that can ensure a cost-effective target production with high repeatability. Minimization of the amount of tritium (i.e., minimization of time and space at all production stages) is a necessary condition as well. Additionally, the cryogenic hydrogen fuel inside the targets must have a structure (ultrafine layers—the grain sizemore » should be scaled back to the nanometer range) that supports the fuel layer survivability under target injection and transport through the reactor chamber. To meet the above requirements, significant progress has been made at the Lebedev Physical Institute (LPI) in the technology developed on the basis of rapid fuel layering inside moving free-standing targets (FST), also referred to as the FST layering method. Owing to the research carried out at LPI, unique experience has been gained in the development of the FST-layering module for target fabrication with an ultrafine fuel layer, including a reactor- scale target design. This experience can be used for the development of the next-generation FST-layering module for construction of a prototype of a target factory for power laser facilities and inertial fusion power plants.« less

Antibody-targeted interleukin 2 stimulates T-cell killing of autologous tumor cells.

PubMed Central

Gillies, S D; Reilly, E B; Lo, K M; Reisfeld, R A

1992-01-01

A genetically engineered fusion protein consisting of a chimeric anti-ganglioside GD2 antibody (ch14.18) and interleukin 2 (IL2) was tested for its ability to enhance the killing of autologous GD2-expressing melanoma target cells by a tumor-infiltrating lymphocyte line (660 TIL). The fusion of IL2 to the carboxyl terminus of the immunoglobulin heavy chain did not reduce IL2 activity as measured in a standard proliferation assay using either mouse or human T-cell lines. Antigen-binding activity was greater than that of the native chimeric antibody. The ability of resting 660 TIL cells to kill their autologous GD2-positive target cells was enhanced if the target cells were first coated with the fusion protein. This stimulation of killing was greater than that of uncoated cells in the presence of equivalent or higher concentrations of free IL2. Such antibody-cytokine fusion proteins may prove useful in targeting the biological effect of IL2 and other cytokines to tumor cells and in this way stimulate their immune destruction. Images PMID:1741398

Investigating inertial confinement fusion target fuel conditions through x-ray spectroscopya)

NASA Astrophysics Data System (ADS)

Hansen, Stephanie B.

2012-05-01

Inertial confinement fusion (ICF) targets are designed to produce hot, dense fuel in a neutron-producing core that is surrounded by a shell of compressing material. The x-rays emitted from ICF plasmas can be analyzed to reveal details of the temperatures, densities, gradients, velocities, and mix characteristics of ICF targets. Such diagnostics are critical to understand the target performance and to improve the predictive power of simulation codes.

Energy and Technology Review

NASA Astrophysics Data System (ADS)

Poggio, Andrew J.

1988-10-01

This issue of Energy and Technology Review contains: Neutron Penumbral Imaging of Laser-Fusion Targets--using our new penumbral-imaging diagnostic, we have obtained the first images that can be used to measure directly the deuterium-tritium burn region in laser-driven fusion targets; Computed Tomography for Nondestructive Evaluation--various computed tomography systems and computational techniques are used in nondestructive evaluation; Three-Dimensional Image Analysis for Studying Nuclear Chromatin Structure--we have developed an optic-electronic system for acquiring cross-sectional views of cell nuclei, and computer codes to analyze these images and reconstruct the three-dimensional structures they represent; Imaging in the Nuclear Test Program--advanced techniques produce images of unprecedented detail and resolution from Nevada Test Site data; and Computational X-Ray Holography--visible-light experiments and numerically simulated holograms test our ideas about an X-ray microscope for biological research.

Improved detection probability of low level light and infrared image fusion system

NASA Astrophysics Data System (ADS)

Luo, Yuxiang; Fu, Rongguo; Zhang, Junju; Wang, Wencong; Chang, Benkang

2018-02-01

Low level light(LLL) image contains rich information on environment details, but is easily affected by the weather. In the case of smoke, rain, cloud or fog, much target information will lose. Infrared image, which is from the radiation produced by the object itself, can be "active" to obtain the target information in the scene. However, the image contrast and resolution is bad, the ability of the acquisition of target details is very poor, and the imaging mode does not conform to the human visual habit. The fusion of LLL and infrared image can make up for the deficiency of each sensor and give play to the advantages of single sensor. At first, we show the hardware design of fusion circuit. Then, through the recognition probability calculation of the target(one person) and the background image(trees), we find that the trees detection probability of LLL image is higher than that of the infrared image, and the person detection probability of the infrared image is obviously higher than that of LLL image. The detection probability of fusion image for one person and trees is higher than that of single detector. Therefore, image fusion can significantly enlarge recognition probability and improve detection efficiency.

Image fusion and navigation platforms for percutaneous image-guided interventions.

PubMed

Rajagopal, Manoj; Venkatesan, Aradhana M

2016-04-01

Image-guided interventional procedures, particularly image guided biopsy and ablation, serve an important role in the care of the oncology patient. The need for tumor genomic and proteomic profiling, early tumor response assessment and confirmation of early recurrence are common scenarios that may necessitate successful biopsies of targets, including those that are small, anatomically unfavorable or inconspicuous. As image-guided ablation is increasingly incorporated into interventional oncology practice, similar obstacles are posed for the ablation of technically challenging tumor targets. Navigation tools, including image fusion and device tracking, can enable abdominal interventionalists to more accurately target challenging biopsy and ablation targets. Image fusion technologies enable multimodality fusion and real-time co-displays of US, CT, MRI, and PET/CT data, with navigational technologies including electromagnetic tracking, robotic, cone beam CT, optical, and laser guidance of interventional devices. Image fusion and navigational platform technology is reviewed in this article, including the results of studies implementing their use for interventional procedures. Pre-clinical and clinical experiences to date suggest these technologies have the potential to reduce procedure risk, time, and radiation dose to both the patient and the operator, with a valuable role to play for complex image-guided interventions.

Early and late HIV-1 membrane fusion events are impaired by sphinganine lipidated peptides that target the fusion site.

PubMed

Klug, Yoel A; Ashkenazi, Avraham; Viard, Mathias; Porat, Ziv; Blumenthal, Robert; Shai, Yechiel

2014-07-15

Lipid-conjugated peptides have advanced the understanding of membrane protein functions and the roles of lipids in the membrane milieu. These lipopeptides modulate various biological systems such as viral fusion. A single function has been suggested for the lipid, binding to the membrane and thus elevating the local concentration of the peptide at the target site. In the present paper, we challenged this argument by exploring in-depth the antiviral mechanism of lipopeptides, which comprise sphinganine, the lipid backbone of DHSM (dihydrosphingomyelin), and an HIV-1 envelope-derived peptide. Surprisingly, we discovered a partnership between the lipid and the peptide that impaired early membrane fusion events by reducing CD4 receptor lateral diffusion and HIV-1 fusion peptide-mediated lipid mixing. Moreover, only the joint function of sphinganine and its conjugate peptide disrupted HIV-1 fusion protein assembly and folding at the later fusion steps. Via imaging techniques we revealed for the first time the direct localization of these lipopeptides to the virus-cell and cell-cell contact sites. Overall, the findings of the present study may suggest lipid-protein interactions in various biological systems and may help uncover a role for elevated DHSM in HIV-1 and its target cell membranes.

Fusion of radar and satellite target measurements

NASA Astrophysics Data System (ADS)

Moy, Gabriel; Blaty, Donald; Farber, Morton; Nealy, Carlton

2011-06-01

A potentially high payoff for the ballistic missile defense system (BMDS) is the ability to fuse the information gathered by various sensor systems. In particular, it may be valuable in the future to fuse measurements made using ground based radars with passive measurements obtained from satellite-based EO/IR sensors. This task can be challenging in a multitarget environment in view of the widely differing resolution between active ground-based radar and an observation made by a sensor at long range from a satellite platform. Additionally, each sensor system could have a residual pointing bias which has not been calibrated out. The problem is further compounded by the possibility that an EO/IR sensor may not see exactly the same set of targets as a microwave radar. In order to better understand the problems involved in performing the fusion of metric information from EO/IR satellite measurements with active microwave radar measurements, we have undertaken a study of this data fusion issue and of the associated data processing techniques. To carry out this analysis, we have made use of high fidelity simulations to model the radar observations from a missile target and the observations of the same simulated target, as gathered by a constellation of satellites. In the paper, we discuss the improvements seen in our tests when fusing the state vectors, along with the improvements in sensor bias estimation. The limitations in performance due to the differing phenomenology between IR and microwave radar are discussed as well.

Genetic analysis of heptad-repeat regions in the G2 fusion subunit of the Junin arenavirus envelope glycoprotein

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

York, Joanne; Agnihothram, Sudhakar S.; Romanowski, Victor

2005-12-20

The G2 fusion subunit of the Junin virus envelope glycoprotein GP-C contains two hydrophobic heptad-repeat regions that are postulated to form a six-helix bundle structure required for the membrane fusion activity of Class I viral fusion proteins. We have investigated the role of these heptad-repeat regions and, specifically, the importance of the putative interhelical a and d position sidechains by using alanine-scanning mutagenesis. All the mutant glycoproteins were expressed and transported to the cell surface. Proteolytic maturation at the subtilisin kexin isozyme-1/site-1-protease (SKI-1/S1P) cleavage site was observed in all but two of the mutants. Among the adequately cleaved mutant glycoproteins,more » four positions in the N-terminal region (I333, L336, L347 and L350) and two positions in the C-terminal region (R392 and W395) were shown to be important determinants of cell-cell fusion. Taken together, our results indicate that {alpha}-helical coiled-coil structures are likely critical in promoting arenavirus membrane fusion. These findings support the inclusion of the arenavirus GP-C among the Class I viral fusion proteins and suggest pharmacologic and immunologic strategies for targeting arenavirus infection and hemorrhagic fever.« less

Flight data results of estimate fusion for spacecraft rendezvous navigation from shuttle mission STS-69

NASA Technical Reports Server (NTRS)

Carpenter, J. Russell; Bishop, Robert H.

1996-01-01

A recently developed rendezvous navigation fusion filter that optimally exploits existing distributed filters for rendezvous and GPS navigation to achieve the relative and inertial state accuracies of both in a global solution is utilized here to process actual flight data. Space Shuttle Mission STS-69 was the first mission to date which gathered data from both the rendezvous and Global Positioning System filters allowing, for the first time, a test of the fusion algorithm with real flight data. Furthermore, a precise best estimate of trajectory is available for portions of STS-69, making possible a check on the performance of the fusion filter. In order to successfully carry out this experiment with flight data, two extensions to the existing scheme were necessary: a fusion edit test based on differences between the filter state vectors, and an underweighting scheme to accommodate the suboptimal perfect target assumption made by the Shuttle rendezvous filter. With these innovations, the flight data was successfully fused from playbacks of downlinked and/or recorded measurement data through ground analysis versions of the Shuttle rendezvous filter and a GPS filter developed for another experiment. The fusion results agree with the best estimate of trajectory at approximately the levels of uncertainty expected from the fusion filter's covariance matrix.

Detection of early stage atherosclerotic plaques using PET and CT fusion imaging targeting P-selectin in low density lipoprotein receptor-deficient mice

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

Nakamura, Ikuko, E-mail: nakamuri@riken.jp; Department of Cardiovascular Medicine, Saga University, Saga; Hasegawa, Koki

2013-03-29

Highlights: ► P-selectin regulates leukocyte recruitment as an early stage event of atherogenesis. ► We developed an antibody-based molecular imaging probe targeting P-selectin for PET. ► This is the first report on successful PET imaging for delineation of P-selectin. ► P-selectin is a candidate target for atherosclerotic plaque imaging by clinical PET. -- Abstract: Background: Sensitive detection and qualitative analysis of atherosclerotic plaques are in high demand in cardiovascular clinical settings. The leukocyte–endothelial interaction mediated by an adhesion molecule P-selectin participates in arterial wall inflammation and atherosclerosis. Methods and results: A {sup 64}Cu-1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid conjugated anti-P-selectin monoclonal antibody ({sup 64}Cu-DOTA-anti-P-selectinmore » mAb) probe was prepared by conjugating an anti-P-selectin monoclonal antibody with DOTA followed by {sup 64}Cu labeling. Thirty-six hours prior to PET and CT fusion imaging, 3 MBq of {sup 64}Cu-DOTA-anti-P-selectin mAb was intravenously injected into low density lipoprotein receptor-deficient Ldlr-/- mice. After a 180 min PET scan, autoradiography and biodistribution of {sup 64}Cu-DOTA-anti-P-selectin monoclonal antibody was examined using excised aortas. In Ldlr-/- mice fed with a high cholesterol diet for promotion of atherosclerotic plaque development, PET and CT fusion imaging revealed selective and prominent accumulation of the probe in the aortic root. Autoradiography of aortas that demonstrated probe uptake into atherosclerotic plaques was confirmed by Oil red O staining for lipid droplets. In Ldlr-/- mice fed with a chow diet to develop mild atherosclerotic plaques, probe accumulation was barely detectable in the aortic root on PET and CT fusion imaging. Probe biodistribution in aortas was 6.6-fold higher in Ldlr-/- mice fed with a high cholesterol diet than in those fed with a normal chow diet. {sup 64}Cu-DOTA-anti-P-selectin mAb accumulated selectively in aortic atherosclerotic plaques and was detectable by PET and CT fusion imaging in Ldlr-/- mice. Conclusions: P-selectin is a candidate target molecule for early-phase detection by PET and CT fusion imaging of atherosclerotic plaques.« less

Z-Pinch Pulsed Plasma Propulsion Technology Development

NASA Technical Reports Server (NTRS)

Polsgrove, Tara; Adams, Robert B.; Fabisinski, Leo; Fincher, Sharon; Maples, C. Dauphne; Miernik, Janie; Percy, Tom; Statham, Geoff; Turner, Matt; Cassibry, Jason;

Engineering of the Magnetized Target Fusion Propulsion System

NASA Technical Reports Server (NTRS)

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

2003-01-01

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

Ion kinetic effects on the ignition and burn of inertial confinement fusion targets: A multi-scale approach

NASA Astrophysics Data System (ADS)

Peigney, B. E.; Larroche, O.; Tikhonchuk, V.

2014-12-01

In this article, we study the hydrodynamics and burn of the thermonuclear fuel in inertial confinement fusion pellets at the ion kinetic level. The analysis is based on a two-velocity-scale Vlasov-Fokker-Planck kinetic model that is specially tailored to treat fusion products (suprathermal α-particles) in a self-consistent manner with the thermal bulk. The model assumes spherical symmetry in configuration space and axial symmetry in velocity space around the mean flow velocity. A typical hot-spot ignition design is considered. Compared with fluid simulations where a multi-group diffusion scheme is applied to model α transport, the full ion-kinetic approach reveals significant non-local effects on the transport of energetic α-particles. This has a direct impact on hydrodynamic spatial profiles during combustion: the hot spot reactivity is reduced, while the inner dense fuel layers are pre-heated by the escaping α-suprathermal particles, which are transported farther out of the hot spot. We show how the kinetic transport enhancement of fusion products leads to a significant reduction of the fusion yield.

MLL-ENL cooperates with SCF to transform primary avian multipotent cells.

PubMed

Schulte, Cathleen E; von Lindern, Marieke; Steinlein, Peter; Beug, Hartmut; Wiedemann, Leanne M

2002-08-15

The MLL gene is targeted by chromosomal translocations, which give rise to heterologous MLL fusion proteins and are associated with distinct types of acute lymphoid and myeloid leukaemia. To determine how MLL fusion proteins alter the proliferation and/or differentiation of primary haematopoietic progenitors, we introduced the MLL-AF9 and MLL-ENL fusion proteins into primary chicken bone marrow cells. Both fusion proteins caused the sustained outgrowth of immature haematopoietic cells, which was strictly dependent on stem cell factor (SCF). The renewing cells have a long in vitro lifespan exceeding the Hayflick limit of avian cells. Analysis of clonal cultures identified the renewing cells as immature, multipotent progenitors, expressing erythroid, myeloid, lymphoid and stem cell surface markers. Employing a two-step commitment/differentiation protocol involving the controlled withdrawal of SCF, the MLL-ENL-transformed progenitors could be induced to terminal erythroid or myeloid differentiation. Finally, in cooperation with the weakly leukaemogenic receptor tyrosine kinase v-Sea, the MLL-ENL fusion protein gave rise to multilineage leukaemia in chicks, suggesting that other activated, receptor tyrosine kinases can substitute for ligand-activated c-Kit in vivo.

Ion kinetic effects on the ignition and burn of inertial confinement fusion targets: A multi-scale approach

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

Peigney, B. E.; Larroche, O.; Tikhonchuk, V.

2014-12-15

In this article, we study the hydrodynamics and burn of the thermonuclear fuel in inertial confinement fusion pellets at the ion kinetic level. The analysis is based on a two-velocity-scale Vlasov-Fokker-Planck kinetic model that is specially tailored to treat fusion products (suprathermal α-particles) in a self-consistent manner with the thermal bulk. The model assumes spherical symmetry in configuration space and axial symmetry in velocity space around the mean flow velocity. A typical hot-spot ignition design is considered. Compared with fluid simulations where a multi-group diffusion scheme is applied to model α transport, the full ion-kinetic approach reveals significant non-local effectsmore » on the transport of energetic α-particles. This has a direct impact on hydrodynamic spatial profiles during combustion: the hot spot reactivity is reduced, while the inner dense fuel layers are pre-heated by the escaping α-suprathermal particles, which are transported farther out of the hot spot. We show how the kinetic transport enhancement of fusion products leads to a significant reduction of the fusion yield.« less

Prolate-Spheroid (``Rugby-Shaped'') Hohlraum for Inertial Confinement Fusion

NASA Astrophysics Data System (ADS)

Vandenboomgaerde, M.; Bastian, J.; Casner, A.; Galmiche, D.; Jadaud, J.-P.; Laffite, S.; Liberatore, S.; Malinie, G.; Philippe, F.

2007-08-01

A novel rugby-ball shaped hohlraum is designed in the context of the indirect-drive scheme of inertial-confinement fusion (ICF). Experiments were performed on the OMEGA laser and are the first use of rugby hohlraums for ICF studies. Analysis of experimental data shows that the hohlraum energetics is well understood. We show that the rugby-ball shape exhibits advantages over cylinder, in terms of temperature and of symmetry control of the capsule implosion. Simulations indicate that rugby hohlraum driven targets may be candidates for ignition in a context of early Laser MegaJoule experiments with reduced laser energy.

Combining multiple ChIP-seq peak detection systems using combinatorial fusion.

PubMed

Schweikert, Christina; Brown, Stuart; Tang, Zuojian; Smith, Phillip R; Hsu, D Frank

2012-01-01

Due to the recent rapid development in ChIP-seq technologies, which uses high-throughput next-generation DNA sequencing to identify the targets of Chromatin Immunoprecipitation, there is an increasing amount of sequencing data being generated that provides us with greater opportunity to analyze genome-wide protein-DNA interactions. In particular, we are interested in evaluating and enhancing computational and statistical techniques for locating protein binding sites. Many peak detection systems have been developed; in this study, we utilize the following six: CisGenome, MACS, PeakSeq, QuEST, SISSRs, and TRLocator. We define two methods to merge and rescore the regions of two peak detection systems and analyze the performance based on average precision and coverage of transcription start sites. The results indicate that ChIP-seq peak detection can be improved by fusion using score or rank combination. Our method of combination and fusion analysis would provide a means for generic assessment of available technologies and systems and assist researchers in choosing an appropriate system (or fusion method) for analyzing ChIP-seq data. This analysis offers an alternate approach for increasing true positive rates, while decreasing false positive rates and hence improving the ChIP-seq peak identification process.

Personalized oncogenomic analysis of metastatic adenoid cystic carcinoma: using whole-genome sequencing to inform clinical decision-making

PubMed Central

Chahal, Manik; Pleasance, Erin; Grewal, Jasleen; Zhao, Eric; Ng, Tony; Chapman, Erin; Jones, Martin R.; Shen, Yaoqing; Mungall, Karen L.; Bonakdar, Melika; Taylor, Gregory A.; Ma, Yussanne; Mungall, Andrew J.; Moore, Richard A.; Lim, Howard; Renouf, Daniel; Yip, Stephen; Jones, Steven J.M.; Marra, Marco A.; Laskin, Janessa

2018-01-01

Metastatic adenoid cystic carcinomas (ACCs) can cause significant morbidity and mortality. Because of their slow growth and relative rarity, there is limited evidence for systemic therapy regimens. Recently, molecular profiling studies have begun to reveal the genetic landscape of these poorly understood cancers, and new treatment possibilities are beginning to emerge. The objective is to use whole-genome and transcriptome sequencing and analysis to better understand the genetic alterations underlying the pathology of metastatic and rare ACCs and determine potentially actionable therapeutic targets. We report five cases of metastatic ACC, not originating in the salivary glands, in patients enrolled in the Personalized Oncogenomics (POG) Program at the BC Cancer Agency. Genomic workup included whole-genome and transcriptome sequencing, detailed analysis of tumor alterations, and integration with existing knowledge of drug–target combinations to identify potential therapeutic targets. Analysis reveals low mutational burden in these five ACC cases, and mutation signatures that are commonly observed in multiple cancer types. Notably, the only recurrent structural aberration identified was the well-described MYB-NFIB fusion that was present in four of five cases, and one case exhibited a closely related MYBL1-NFIB fusion. Recurrent mutations were also identified in BAP1 and BCOR, with additional mutations in individual samples affecting NOTCH1 and the epigenetic regulators ARID2, SMARCA2, and SMARCB1. Copy changes were rare, and they included amplification of MYC and homozygous loss of CDKN2A in individual samples. Genomic analysis revealed therapeutic targets in all five cases and served to inform a therapeutic choice in three of the cases to date. PMID:29610392

Drosophila and mammalian models uncover a role for the myoblast fusion gene TANC1 in rhabdomyosarcoma.

PubMed

Avirneni-Vadlamudi, Usha; Galindo, Kathleen A; Endicott, Tiana R; Paulson, Vera; Cameron, Scott; Galindo, Rene L

2012-01-01

Rhabdomyosarcoma (RMS) is a malignancy of muscle myoblasts, which fail to exit the cell cycle, resist terminal differentiation, and are blocked from fusing into syncytial skeletal muscle. In some patients, RMS is caused by a translocation that generates the fusion oncoprotein PAX-FOXO1, but the underlying RMS pathogenetic mechanisms that impede differentiation and promote neoplastic transformation remain unclear. Using a Drosophila model of PAX-FOXO1-mediated transformation, we show here that mutation in the myoblast fusion gene rolling pebbles (rols) dominantly suppresses PAX-FOXO1 lethality. Further analysis indicated that PAX-FOXO1 expression caused upregulation of rols, which suggests that Rols acts downstream of PAX-FOXO1. In mammalian myoblasts, gene silencing of Tanc1, an ortholog of rols, revealed that it is essential for myoblast fusion, but is dispensable for terminal differentiation. Misexpression of PAX-FOXO1 in myoblasts upregulated Tanc1 and blocked differentiation, whereas subsequent reduction of Tanc1 expression to native levels by RNAi restored both fusion and differentiation. Furthermore, decreasing human TANC1 gene expression caused RMS cancer cells to lose their neoplastic state, undergo fusion, and form differentiated syncytial muscle. Taken together, these findings identify misregulated myoblast fusion caused by ectopic TANC1 expression as a RMS neoplasia mechanism and suggest fusion molecules as candidates for targeted RMS therapy.

Joint sparsity based heterogeneous data-level fusion for target detection and estimation

NASA Astrophysics Data System (ADS)

Niu, Ruixin; Zulch, Peter; Distasio, Marcello; Blasch, Erik; Shen, Dan; Chen, Genshe

2017-05-01

Typical surveillance systems employ decision- or feature-level fusion approaches to integrate heterogeneous sensor data, which are sub-optimal and incur information loss. In this paper, we investigate data-level heterogeneous sensor fusion. Since the sensors monitor the common targets of interest, whose states can be determined by only a few parameters, it is reasonable to assume that the measurement domain has a low intrinsic dimensionality. For heterogeneous sensor data, we develop a joint-sparse data-level fusion (JSDLF) approach based on the emerging joint sparse signal recovery techniques by discretizing the target state space. This approach is applied to fuse signals from multiple distributed radio frequency (RF) signal sensors and a video camera for joint target detection and state estimation. The JSDLF approach is data-driven and requires minimum prior information, since there is no need to know the time-varying RF signal amplitudes, or the image intensity of the targets. It can handle non-linearity in the sensor data due to state space discretization and the use of frequency/pixel selection matrices. Furthermore, for a multi-target case with J targets, the JSDLF approach only requires discretization in a single-target state space, instead of discretization in a J-target state space, as in the case of the generalized likelihood ratio test (GLRT) or the maximum likelihood estimator (MLE). Numerical examples are provided to demonstrate that the proposed JSDLF approach achieves excellent performance with near real-time accurate target position and velocity estimates.

A fusion approach for coarse-to-fine target recognition

NASA Astrophysics Data System (ADS)

Folkesson, Martin; Grönwall, Christina; Jungert, Erland

2006-04-01

A fusion approach in a query based information system is presented. The system is designed for querying multimedia data bases, and here applied to target recognition using heterogeneous data sources. The recognition process is coarse-to-fine, with an initial attribute estimation step and a following matching step. Several sensor types and algorithms are involved in each of these two steps. An independence of the matching results, on the origin of the estimation results, is observed. It allows for distribution of data between algorithms in an intermediate fusion step, without risk of data incest. This increases the overall chance of recognising the target. An implementation of the system is described.

[Value of Immunohistochemical Methods in Detecting EML4-ALK Fusion Mutations: A Meta-analysis].

PubMed

Liu, Chang; Cai, Lu; Zhong, Diansheng; Wang, Jing

2016-01-01

The fusion between echinoderm microtubule-associated protein 4 (EML4) and anaplastic lymphatic tumor kinase (ALK) rearrangement is present in approximately 5% of non-small cell lung cancer (NSCLC) patients. It has been regarded as another new target gene after epidermal growth factor receptor (EGFR) and K-ras. Figures showed that the disease control rate could reach up to 80% in NSCLC patients with EML4-ALK fusion gene after treated with ALK inhibitors. Thus, exploring an accurate and rapid detecting method is the key in screening NSCLC patients with EML4-ALK expressions. The aim of this study is to analyze the specificity and sensitivity of IHC in detecting EML4-ALK fusion mutations. To evaluate the accuracy and clinical value of this method, and then provide basis for individual molecular therapy of NSCLC patients. Using Pubmed database to search all documents required. The deadline of retrieval was February 25, 2015. Then further screening the articles according to the inclusion and exclusion criteria. Using diagnostic test meta-analysis methods to analyze the sensitivity and specificity of the immunohistochemistry (IHC) method compared with fluorescence in situ hybridization (FISH) method. Eleven literatures were added into the meta analysis, there were 3,234 of total cases. The diagnostic odds ratio (DOR) was 1,135.00 (95%CI: 337.10-3,821.46); the area under curve (AUC) of summary receiver operating characteristic curve (SROC) curve was 0.992,3 (SEAUC=0.003,2), the Q* was 0.964,4 (SEQ*=0.008,7). Immunohistochemical detection of EML4-ALK fusion gene mutation with specific antibody is feasible. It has high sensitivity and specificity. IHC can be a simple and rapid way in screening EML4-ALK fusion gene mutation and exhibits important clinical values.

Fusion peptide of HIV-1 as a site of vulnerability to neutralizing antibody

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

Kong, Rui; Xu, Kai; Zhou, Tongqing

The HIV-1 fusion peptide, comprising 15 to 20 hydrophobic residues at the N terminus of the Env-gp41 subunit, is a critical component of the virus-cell entry machinery. In this paper, we report the identification of a neutralizing antibody, N123-VRC34.01, which targets the fusion peptide and blocks viral entry by inhibiting conformational changes in gp120 and gp41 subunits of Env required for entry. Crystal structures of N123-VRC34.01 liganded to the fusion peptide, and to the full Env trimer, revealed an epitope consisting of the N-terminal eight residues of the gp41 fusion peptide and glycan N88 of gp120, and molecular dynamics showedmore » that the N-terminal portion of the fusion peptide can be solvent-exposed. Finally, these results reveal the fusion peptide to be a neutralizing antibody epitope and thus a target for vaccine design.« less

Fusion peptide of HIV-1 as a site of vulnerability to neutralizing antibody

DOE PAGES

Kong, Rui; Xu, Kai; Zhou, Tongqing; ...

2016-05-13

The HIV-1 fusion peptide, comprising 15 to 20 hydrophobic residues at the N terminus of the Env-gp41 subunit, is a critical component of the virus-cell entry machinery. In this paper, we report the identification of a neutralizing antibody, N123-VRC34.01, which targets the fusion peptide and blocks viral entry by inhibiting conformational changes in gp120 and gp41 subunits of Env required for entry. Crystal structures of N123-VRC34.01 liganded to the fusion peptide, and to the full Env trimer, revealed an epitope consisting of the N-terminal eight residues of the gp41 fusion peptide and glycan N88 of gp120, and molecular dynamics showedmore » that the N-terminal portion of the fusion peptide can be solvent-exposed. Finally, these results reveal the fusion peptide to be a neutralizing antibody epitope and thus a target for vaccine design.« less

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.

Engineering of the Magnetized Target Fusion Propulsion System

NASA Technical Reports Server (NTRS)

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

2002-01-01

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

Method and apparatus for producing cryogenic targets

DOEpatents

Murphy, James T.; Miller, John R.

1984-01-01

An improved method and apparatus are given for producing cryogenic inertially driven fusion targets in the fast isothermal freezing (FIF) method. Improved coupling efficiency and greater availability of volume near the target for diagnostic purposes and for fusion driver beam propagation result. Other embodiments include a new electrical switch and a new explosive detonator, all embodiments making use of a purposeful heating by means of optical fibers.

Beyond ALK-RET, ROS1 and other oncogene fusions in lung cancer

PubMed Central

Nakaoku, Takashi; Tsuta, Koji; Tsuchihara, Katsuya; Matsumoto, Shingo; Yoh, Kiyotaka; Goto, Koichi

2015-01-01

Fusions of the RET and ROS1 protein tyrosine kinase oncogenes with several partner genes were recently identified as new targetable genetic aberrations in cases of non-small cell lung cancer (NSCLC) lacking activating EGFR, KRAS, ALK, BRAF, or HER2 oncogene aberrations. RET and ROS1 fusion-positive tumors are mainly observed in young, female, and/or never smoking patients. Studies based on in vitro and in vivo (i.e., mouse) models and studies of several fusion-positive patients indicate that inhibiting the kinase activity of the RET and ROS1 fusion proteins is a promising therapeutic strategy. Accordingly, there are several ongoing clinical trials aimed at examining the efficacy of tyrosine kinase inhibitors (TKIs) against RET and ROS1 proteins in patients with fusion-positive lung cancer. Other gene fusions (NTRK1, NRG1, and FGFR1/2/3) that are targetable by existing TKIs have also been identified in NSCLCs. Options for personalized lung cancer therapy will be increased with the help of multiplex diagnosis systems able to detect multiple druggable gene fusions. PMID:25870798

Z-Pinch fusion-based nuclear propulsion

NASA Astrophysics Data System (ADS)

Miernik, J.; Statham, G.; Fabisinski, L.; Maples, C. D.; Adams, R.; Polsgrove, T.; Fincher, S.; Cassibry, J.; Cortez, R.; Turner, M.; Percy, T.

2013-02-01

Fusion-based nuclear propulsion has the potential to enable fast interplanetary transportation. Due to the great distances between the planets of our solar system and the harmful radiation environment of interplanetary space, high specific impulse (Isp) propulsion in vehicles with high payload mass fractions must be developed to provide practical and safe vehicles for human space flight missions. The Z-Pinch dense plasma focus method is a Magneto-Inertial Fusion (MIF) approach that may potentially lead to a small, low cost fusion reactor/engine assembly [1]. Recent advancements in experimental and theoretical understanding of this concept suggest favorable scaling of fusion power output yield [2]. The magnetic field resulting from the large current compresses the plasma to fusion conditions, and this process can be pulsed over short timescales (10-6 s). This type of plasma formation is widely used in the field of Nuclear Weapons Effects testing in the defense industry, as well as in fusion energy research. A Z-Pinch propulsion concept was designed for a vehicle based on a previous fusion vehicle study called "Human Outer Planet Exploration" (HOPE), which used Magnetized Target Fusion (MTF) [3] propulsion. The reference mission is the transport of crew and cargo to Mars and back, with a reusable vehicle. The analysis of the Z-Pinch MIF propulsion system concludes that a 40-fold increase of Isp over chemical propulsion is predicted. An Isp of 19,436 s and thrust of 3812 N s/pulse, along with nearly doubling the predicted payload mass fraction, warrants further development of enabling technologies.

Genomic analysis of fibrolamellar hepatocellular carcinoma.

PubMed

Xu, Lei; Hazard, Florette K; Zmoos, Anne-Flore; Jahchan, Nadine; Chaib, Hassan; Garfin, Phillip M; Rangaswami, Arun; Snyder, Michael P; Sage, Julien

2015-01-01

Pediatric tumors are relatively infrequent, but are often associated with significant lethality and lifelong morbidity. A major goal of pediatric cancer research has been to identify key drivers of tumorigenesis to eventually develop targeted therapies to enhance cure rate and minimize acute and long-term toxic effects. Here, we used genomic approaches to identify biomarkers and candidate drivers for fibrolamellar hepatocellular carcinoma (FL-HCC), a very rare subtype of pediatric liver cancer for which limited therapeutic options exist. In-depth genomic analyses of one tumor followed by immunohistochemistry validation on seven other tumors showed expression of neuroendocrine markers in FL-HCC. DNA and RNA sequencing data further showed that common cancer pathways are not visibly altered in FL-HCC but identified two novel structural variants, both resulting in fusion transcripts. The first, a 400 kb deletion, results in a DNAJB1-PRKCA fusion transcript, which leads to increased cAMP-dependent protein kinase (PKA) activity in the index tumor case and other FL-HCC cases compared with normal liver. This PKA fusion protein is oncogenic in HCC cells. The second gene fusion event, a translocation between the CLPTM1L and GLIS3 genes, generates a transcript whose product also promotes cancer phenotypes in HCC cell lines. These experiments further highlight the tumorigenic role of gene fusions in the etiology of pediatric solid tumors and identify both candidate biomarkers and possible therapeutic targets for this lethal pediatric disease. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Visualization and Sequencing of Membrane Remodeling Leading to Influenza Virus Fusion

PubMed Central

Gui, Long; Ebner, Jamie L.; Mileant, Alexander; Williams, James A.

2016-01-01

ABSTRACT Protein-mediated membrane fusion is an essential step in many fundamental biological events, including enveloped virus infection. The nature of protein and membrane intermediates and the sequence of membrane remodeling during these essential processes remain poorly understood. Here we used cryo-electron tomography (cryo-ET) to image the interplay between influenza virus and vesicles with a range of lipid compositions. By following the population kinetics of membrane fusion intermediates imaged by cryo-ET, we found that membrane remodeling commenced with the hemagglutinin fusion protein spikes grappling onto the target membrane, followed by localized target membrane dimpling as local clusters of hemagglutinin started to undergo conformational refolding. The local dimples then transitioned to extended, tightly apposed contact zones where the two proximal membrane leaflets were in most cases indistinguishable from each other, suggesting significant dehydration and possible intermingling of the lipid head groups. Increasing the content of fusion-enhancing cholesterol or bis-monoacylglycerophosphate in the target membrane led to an increase in extended contact zone formation. Interestingly, hemifused intermediates were found to be extremely rare in the influenza virus fusion system studied here, most likely reflecting the instability of this state and its rapid conversion to postfusion complexes, which increased in population over time. By tracking the populations of fusion complexes over time, the architecture and sequence of membrane reorganization leading to efficient enveloped virus fusion were thus resolved. IMPORTANCE Enveloped viruses employ specialized surface proteins to mediate fusion of cellular and viral membranes that results in the formation of pores through which the viral genetic material is delivered to the cell. For influenza virus, the trimeric hemagglutinin (HA) glycoprotein spike mediates host cell attachment and membrane fusion. While structures of a subset of conformations and parts of the fusion machinery have been characterized, the nature and sequence of membrane deformations during fusion have largely eluded characterization. Building upon studies that focused on early stages of HA-mediated membrane remodeling, here cryo-electron tomography (cryo-ET) was used to image the three-dimensional organization of intact influenza virions at different stages of fusion with liposomes, leading all the way to completion of the fusion reaction. By monitoring the evolution of fusion intermediate populations over the course of acid-induced fusion, we identified the progression of membrane reorganization that leads to efficient fusion by an enveloped virus. PMID:27226364

Repetition rates in heavy ion beam driven fusion reactors

NASA Astrophysics Data System (ADS)

Peterson, Robert R.

1986-01-01

The limits on the cavity gas density required for beam propagation and condensation times for material vaporized by target explosions can determine the maximum repetition rate of Heavy Ion Beam (HIB) driven fusion reactors. If the ions are ballistically focused onto the target, the cavity gas must have a density below roughly 10-4 torr (3×1012 cm-3) at the time of propagation; other propagation schemes may allow densities as high as 1 torr or more. In some reactor designs, several kilograms of material may be vaporized off of the target chamber walls by the target generated x-rays, raising the average density in the cavity to 100 tor or more. A one-dimensional combined radiation hydrodynamics and vaporization and condensation computer code has been used to simulate the behavior of the vaporized material in the target chambers of HIB fusion reactors.

VEGFR2-targeted fusion antibody improved NK cell-mediated immunosurveillance against K562 cells.

PubMed

Ren, Xueyan; Xie, Wei; Wang, Youfu; Xu, Menghuai; Liu, Fang; Tang, Mingying; Li, Chenchen; Wang, Min; Zhang, Juan

2016-08-01

MHC class I polypeptide-related sequence A (MICA), which is normally expressed on cancer cells, activates NK cells via NK group 2-member D pathway. However, some cancer cells escape NK-mediated immune surveillance by shedding membrane MICA causing immune suppression. To address this issue, we designed an antibody-MICA fusion targeting tumor-specific antigen (vascular endothelial growth factor receptor 2, VEGFR2) based on our patented antibody (mAb04) against VEGFR2. In vitro results demonstrate that the fusion antibody retains both the antineoplastic and the immunomodulatory activity of mAb04. Further, we revealed that it enhanced NK-mediated immunosurveillance against K562 cells through increasing degranulation and cytokine production of NK cells. The overall data suggest our new fusion protein provides a promising approach for cancer-targeted immunotherapy and has prospects for potential application of chronic myeloid leukemia.

Estimation and Fusion for Tracking Over Long-Haul Links Using Artificial Neural Networks

DOE PAGES

Liu, Qiang; Brigham, Katharine; Rao, Nageswara S. V.

2017-02-01

In a long-haul sensor network, sensors are remotely deployed over a large geographical area to perform certain tasks, such as tracking and/or monitoring of one or more dynamic targets. A remote fusion center fuses the information provided by these sensors so that a final estimate of certain target characteristics – such as the position – is expected to possess much improved quality. In this paper, we pursue learning-based approaches for estimation and fusion of target states in longhaul sensor networks. In particular, we consider learning based on various implementations of artificial neural networks (ANNs). Finally, the joint effect of (i)more » imperfect communication condition, namely, link-level loss and delay, and (ii) computation constraints, in the form of low-quality sensor estimates, on ANN-based estimation and fusion, is investigated by means of analytical and simulation studies.« less

Estimation and Fusion for Tracking Over Long-Haul Links Using Artificial Neural Networks

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

Liu, Qiang; Brigham, Katharine; Rao, Nageswara S. V.

In a long-haul sensor network, sensors are remotely deployed over a large geographical area to perform certain tasks, such as tracking and/or monitoring of one or more dynamic targets. A remote fusion center fuses the information provided by these sensors so that a final estimate of certain target characteristics – such as the position – is expected to possess much improved quality. In this paper, we pursue learning-based approaches for estimation and fusion of target states in longhaul sensor networks. In particular, we consider learning based on various implementations of artificial neural networks (ANNs). Finally, the joint effect of (i)more » imperfect communication condition, namely, link-level loss and delay, and (ii) computation constraints, in the form of low-quality sensor estimates, on ANN-based estimation and fusion, is investigated by means of analytical and simulation studies.« less

Targeted entry of enveloped viruses: measles and herpes simplex virus I.

PubMed

Navaratnarajah, Chanakha K; Miest, Tanner S; Carfi, Andrea; Cattaneo, Roberto

2012-02-01

We compare the receptor-based mechanisms that a small RNA virus and a larger DNA virus have evolved to drive the fusion of viral and cellular membranes. Both systems rely on tight control over triggering the concerted refolding of a trimeric fusion protein. While measles virus entry depends on a receptor-binding protein and a fusion protein only, the herpes simplex virus (HSV) is more complex and requires four viral proteins. Nevertheless, in both viruses a receptor-binding protein is required for triggering the membrane fusion process. Moreover, specificity domains can be appended to these receptor-binding proteins to target virus entry to cells expressing a designated receptor. We discuss how principles established with measles and HSV can be applied to targeting other enveloped viruses, and alternatively how retargeted envelopes can be fitted on foreign capsids. Copyright © 2011 Elsevier B.V. All rights reserved.

Antitumor activity of a dual cytokine/single-chain antibody fusion protein for simultaneous delivery of GM-CSF and IL-2 to Ep-CAM expressing tumor cells.

PubMed

Schanzer, Juergen M; Fichtner, Iduna; Baeuerle, Patrick A; Kufer, Peter

2006-01-01

Cytokine targeting to tumor-associated antigens via antibody cytokine fusion proteins has demonstrated potent antitumor activity in numerous animal models and has led to the clinical development of 2 antibody-interleukin-2 (IL-2) fusion proteins. We previously reported on the construction and in vitro properties of a "dual" cytokine fusion protein for simultaneous targeted delivery of human granulocyte macrophage-colony stimulating factor (GM-CSF) and IL-2 to human tumors. The fusion protein is based on a heterodimerized core structure formed by human CH1 and Ckappa domains (heterominibody) with C-terminally fused human cytokines and N-terminally fused single-chain antibody fragments specific for the tumor-associated surface antigen epithelial cell adhesion molecule (Ep-CAM). For testing the antitumor activity in syngeneic mouse xenograft models, we developed "dual cytokine heterominibodies" with murine cytokines (mDCH). mDCH fusion proteins and, as controls, "single cytokine heterominibodies" (SCH) carrying either murine GM-CSF (mGM-CSF) or murine IL-2 (mIL-2) were constructed, of which all retained the specific activities of cytokines and binding to the Ep-CAM antigen on human Ep-CAM transfected mouse colon carcinoma CT26-KSA cells. Over a 5-day treatment course, DCH fusion proteins induced significant inhibition of established pulmonary CT26-KSA metastases in immune-competent Balb/c mice at low daily doses of 1 mug of fusion protein per mouse. However, with the tested dosing schemes, antitumor activity of mDCH was largely independent of cytokine targeting to tumors as demonstrated by a control protein with mutated Ep-CAM binding sites. Single cytokine fusion proteins mSCH-GM-CSF and mSCH-IL-2 showed similar antitumor activity as the dual cytokine fusion protein mDCH, indicating that GM-CSF and IL-2 in one molecule did not significantly synergize in tumor rejection under our experimental conditions. Our results seem to contradict the notion that IL-2 and GM-CSF can synergize in antitumor activity and that with conventional dose regimens, their specific targeting to tumors, as tested here with 2 antibodies of different affinities, enhances their antitumor activity.

Method and apparatus for producing cryogenic targets

DOEpatents

Murphy, J.T.; Miller, J.R.

1984-08-07

An improved method and apparatus are given for producing cryogenic inertially driven fusion targets in the fast isothermal freezing (FIF) method. Improved coupling efficiency and greater availability of volume near the target for diagnostic purposes and for fusion driver beam propagation result. Other embodiments include a new electrical switch and a new explosive detonator, all embodiments making use of a purposeful heating by means of optical fibers. 6 figs.

Optimal Path to a Laser Fusion Energy Power Plant

NASA Astrophysics Data System (ADS)

Bodner, Stephen

2013-10-01

There was a decision in the mid 1990s to attempt ignition using indirect-drive targets. It is now obvious that this decision was unjustified. The target design was too geometrically complex, too inefficient, and too far above plasma instability thresholds. By that same time, the mid 1990s, there had also been major advances in the direct-drive target concept. It also was not yet ready for a major test. Now, finally, because of significant advances in target designs, laser-target experiments, and laser development, the direct-drive fusion concept is ready for significant enhancements in funding, on the path to commercial fusion energy. There are two laser contenders. A KrF laser is attractive because of its shortest wavelength, broad bandwidth, and superb beam uniformity. A frequency-converted DPSSL has the disadvantage of inherently narrow bandwidth and longer wavelength, but by combining many beams in parallel one might be able to produce at the target the equivalent of an ultra-broad bandwidth. One or both of these lasers may also meet all of the engineering and economic requirements for a reactor. It is time to further develop and evaluate these two lasers as rep-rate systems, in preparation for a future high-gain fusion test.

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).

Overcoming resistance to single-agent therapy for oncogenic BRAF gene fusions via combinatorial targeting of MAPK and PI3K/mTOR signaling pathways

PubMed Central

Jain, Payal; Silva, Amanda; Han, Harry J.; Lang, Shih-Shan; Zhu, Yuankun; Boucher, Katie; Smith, Tiffany E.; Vakil, Aesha; Diviney, Patrick; Choudhari, Namrata; Raman, Pichai; Busch, Christine M.; Delaney, Tim; Yang, Xiaodong; Olow, Aleksandra K.; Mueller, Sabine; Haas-Kogan, Daphne; Fox, Elizabeth; Storm, Phillip B.; Resnick, Adam C.; Waanders, Angela J.

2017-01-01

Pediatric low-grade gliomas (PLGGs) are frequently associated with activating BRAF gene fusions, such as KIAA1549-BRAF, that aberrantly drive the mitogen activated protein kinase (MAPK) pathway. Although RAF inhibitors (RAFi) have been proven effective in BRAF-V600E mutant tumors, we have previously shown how the KIAA1549-BRAF fusion can be paradoxically activated by RAFi. While newer classes of RAFi, such as PLX8394, have now been shown to inhibit MAPK activation by KIAA1549-BRAF, we sought to identify alternative MAPK pathway targeting strategies using clinically relevant MEK inhibitors (MEKi), along with potential escape mechanisms of acquired resistance to single-agent MAPK pathway therapies. We demonstrate effectiveness of multiple MEKi against diverse BRAF-fusions with novel N-terminal partners, with trametinib being the most potent. However, resistance to MEKi or PLX8394 develops via increased RTK expression causing activation of PI3K/mTOR pathway in BRAF-fusion expressing resistant clones. To circumvent acquired resistance, we show potency of combinatorial targeting with trametinib and everolimus, an mTOR inhibitor (mTORi) against multiple BRAF-fusions. While single-agent mTORi and MEKi PLGG clinical trials are underway, our study provides preclinical rationales for using MEKi and mTORi combinatorial therapy to stave off or prevent emergent drug-resistance in BRAF-fusion driven PLGGs. PMID:29156677

Hybrid-drive implosion system for ICF targets

DOEpatents

Mark, James W.

1988-08-02

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

Hybrid-drive implosion system for ICF targets

DOEpatents

Mark, James W.

1988-01-01

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

Hybrid-drive implosion system for ICF targets

DOEpatents

Mark, J.W.K.

1987-10-14

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

Membrane Topology Mapping of the Na+-Pumping NADH: Quinone Oxidoreductase from Vibrio cholerae by PhoA- Green Fluorescent Protein Fusion Analysis▿

PubMed Central

Duffy, Ellen B.; Barquera, Blanca

2006-01-01

The membrane topologies of the six subunits of Na+-translocating NADH:quinone oxidoreductase (Na+-NQR) from Vibrio cholerae were determined by a combination of topology prediction algorithms and the construction of C-terminal fusions. Fusion expression vectors contained either bacterial alkaline phosphatase (phoA) or green fluorescent protein (gfp) genes as reporters of periplasmic and cytoplasmic localization, respectively. A majority of the topology prediction algorithms did not predict any transmembrane helices for NqrA. A lack of PhoA activity when fused to the C terminus of NqrA and the observed fluorescence of the green fluorescent protein C-terminal fusion confirm that this subunit is localized to the cytoplasmic side of the membrane. Analysis of four PhoA fusions for NqrB indicates that this subunit has nine transmembrane helices and that residue T236, the binding site for flavin mononucleotide (FMN), resides in the cytoplasm. Three fusions confirm that the topology of NqrC consists of two transmembrane helices with the FMN binding site at residue T225 on the cytoplasmic side. Fusion analysis of NqrD and NqrE showed almost mirror image topologies, each consisting of six transmembrane helices; the results for NqrD and NqrE are consistent with the topologies of Escherichia coli homologs YdgQ and YdgL, respectively. The NADH, flavin adenine dinucleotide, and Fe-S center binding sites of NqrF were localized to the cytoplasm. The determination of the topologies of the subunits of Na+-NQR provides valuable insights into the location of cofactors and identifies targets for mutagenesis to characterize this enzyme in more detail. The finding that all the redox cofactors are localized to the cytoplasmic side of the membrane is discussed. PMID:17041063

A robust color image fusion for low light level and infrared images

NASA Astrophysics Data System (ADS)

Liu, Chao; Zhang, Xiao-hui; Hu, Qing-ping; Chen, Yong-kang

2016-09-01

The low light level and infrared color fusion technology has achieved great success in the field of night vision, the technology is designed to make the hot target of fused image pop out with intenser colors, represent the background details with a nearest color appearance to nature, and improve the ability in target discovery, detection and identification. The low light level images have great noise under low illumination, and that the existing color fusion methods are easily to be influenced by low light level channel noise. To be explicit, when the low light level image noise is very large, the quality of the fused image decreases significantly, and even targets in infrared image would be submerged by the noise. This paper proposes an adaptive color night vision technology, the noise evaluation parameters of low light level image is introduced into fusion process, which improve the robustness of the color fusion. The color fuse results are still very good in low-light situations, which shows that this method can effectively improve the quality of low light level and infrared fused image under low illumination conditions.

COREnet: The Fusion of Social Network Analysis and Target Audience Analysis

DTIC Science & Technology

2014-12-01

misunderstanding of MISO (PSYOP) not only in doctrine, but also in practice, is easily understood. MISO has a long history of name changes starting ...TAA does not strictly adhere to any particular theory; studying dynamics is a valid starting point for analysis, and is naturally congruent with the...provides a starting point for further analysis. The PO is a pre-approved objective by the Office of the Secretary of Defense (OSD) (JP 3–53, 2003, V-1

Evidence that TMPRSS2 Activates the Severe Acute Respiratory Syndrome Coronavirus Spike Protein for Membrane Fusion and Reduces Viral Control by the Humoral Immune Response▿

PubMed Central

Glowacka, Ilona; Bertram, Stephanie; Müller, Marcel A.; Allen, Paul; Soilleux, Elizabeth; Pfefferle, Susanne; Steffen, Imke; Tsegaye, Theodros Solomon; He, Yuxian; Gnirss, Kerstin; Niemeyer, Daniela; Schneider, Heike; Drosten, Christian; Pöhlmann, Stefan

2011-01-01

The spike (S) protein of the severe acute respiratory syndrome coronavirus (SARS-CoV) can be proteolytically activated by cathepsins B and L upon viral uptake into target cell endosomes. In contrast, it is largely unknown whether host cell proteases located in the secretory pathway of infected cells and/or on the surface of target cells can cleave SARS S. We along with others could previously show that the type II transmembrane protease TMPRSS2 activates the influenza virus hemagglutinin and the human metapneumovirus F protein by cleavage. Here, we assessed whether SARS S is proteolytically processed by TMPRSS2. Western blot analysis revealed that SARS S was cleaved into several fragments upon coexpression of TMPRSS2 (cis-cleavage) and upon contact between SARS S-expressing cells and TMPRSS2-positive cells (trans-cleavage). cis-cleavage resulted in release of SARS S fragments into the cellular supernatant and in inhibition of antibody-mediated neutralization, most likely because SARS S fragments function as antibody decoys. trans-cleavage activated SARS S on effector cells for fusion with target cells and allowed efficient SARS S-driven viral entry into targets treated with a lysosomotropic agent or a cathepsin inhibitor. Finally, ACE2, the cellular receptor for SARS-CoV, and TMPRSS2 were found to be coexpressed by type II pneumocytes, which represent important viral target cells, suggesting that SARS S is cleaved by TMPRSS2 in the lung of SARS-CoV-infected individuals. In summary, we show that TMPRSS2 might promote viral spread and pathogenesis by diminishing viral recognition by neutralizing antibodies and by activating SARS S for cell-cell and virus-cell fusion. PMID:21325420

Cryo-EM structures of MERS-CoV and SARS-CoV spike glycoproteins reveal the dynamic receptor binding domains.

PubMed

Yuan, Yuan; Cao, Duanfang; Zhang, Yanfang; Ma, Jun; Qi, Jianxun; Wang, Qihui; Lu, Guangwen; Wu, Ying; Yan, Jinghua; Shi, Yi; Zhang, Xinzheng; Gao, George F

2017-04-10

The envelope spike (S) proteins of MERS-CoV and SARS-CoV determine the virus host tropism and entry into host cells, and constitute a promising target for the development of prophylactics and therapeutics. Here, we present high-resolution structures of the trimeric MERS-CoV and SARS-CoV S proteins in its pre-fusion conformation by single particle cryo-electron microscopy. The overall structures resemble that from other coronaviruses including HKU1, MHV and NL63 reported recently, with the exception of the receptor binding domain (RBD). We captured two states of the RBD with receptor binding region either buried (lying state) or exposed (standing state), demonstrating an inherently flexible RBD readily recognized by the receptor. Further sequence conservation analysis of six human-infecting coronaviruses revealed that the fusion peptide, HR1 region and the central helix are potential targets for eliciting broadly neutralizing antibodies.

Method for selecting hollow microspheres for use in laser fusion targets

DOEpatents

Farnum, Eugene H.; Fries, R. Jay; Havenhill, Jerry W.; Smith, Maurice Lee; Stoltz, Daniel L.

1976-01-01

Hollow microspheres having thin and very uniform wall thickness are useful as containers for the deuterium and tritium gas mixture used as a fuel in laser fusion targets. Hollow microspheres are commercially available; however, in commercial lots only a very small number meet the rigid requirements for use in laser fusion targets. Those meeting these requirements may be separated from the unsuitable ones by subjecting the commercial lot to size and density separations and then by subjecting those hollow microspheres thus separated to an external pressurization at which those which are aspherical or which have nonuniform walls are broken and separating the sound hollow microspheres from the broken ones.

Measurement of the beryllium-7 plus proton fusion cross section

NASA Astrophysics Data System (ADS)

Fitzgerald, Ryan P.

2005-11-01

The fusion of protons with radioactive nuclei plays an important role in a wide variety of astrophysical scenarios ranging from high-temperature environments like novae and X-ray bursts to the production of neutrinos in the sun. For example, the 8 B neutrino flux measured in neutrino detectors on earth is directly proportional to the cross section for the fusion of protons with radioactive 7 Be. An experimental program has been established to study proton-fusion experiments in inverse kinematics at the Holifield Radioactive Ion Beam Facility (HRIBF) at Oak Ridge National Laboratory (ORNL) using a windowless gas target and the Daresbury Recoil Separator (DRS). The performance of the target and separator have been well characterized using a variety of experiments with stable beams including 12 C, 19 F, and 24 Mg. For instance, the areal density of hydrogen in the target was determined to 3% accuracy. This well-characterized system was used to measure accurate stopping powers for many elements in hydrogen gas for the first time. The first measurement of a proton-fusion cross section with a radioactive ion beam at ORNL, the fusion of protons with 7 Be, was performed using the hydrogen gas target and the DRS. The 7 Be was produced at the Triangle Universities Nuclear Laboratory (TUNL) and chemically isolated at ORNL. An average 7 Be beam current of 2.5 ppA bombarded the windowless gas target for a period of 3 days. Recoiling B-8 nuclei were efficiently collected using the DRS and were clearly identified in a gas-filled ion detector. The cross section at a center-of-mass energy of 1.502 MeV was determined to be 1.12 mb with 24% uncertainty. The zero-energy S-factor was determined to be 26.8 eV-b with 25% uncertainty. The technique has been clearly demonstrated, and a precise measurement of the fusion cross section will be possible with the development of a somewhat more intense 7 Be radioactive ion beam.

Integrative epigenomic analysis identifies biomarkers and therapeutic targets in adult B-acute lymphoblastic leukemia

PubMed Central

Geng, Huimin; Brennan, Sarah; Milne, Thomas A.; Chen, Wei-Yi; Li, Yushan; Hurtz, Christian; Kweon, Soo-Mi; Zickl, Lynette; Shojaee, Seyedmehdi; Neuberg, Donna; Huang, Chuanxin; Biswas, Debabrata; Xin, Yuan; Racevskis, Janis; Ketterling, Rhett P.; Luger, Selina M.; Lazarus, Hillard; Tallman, Martin S.; Rowe, Jacob M.; Litzow, Mark R.; Guzman, Monica L.; Allis, C. David; Roeder, Robert G.; Müschen, Markus; Paietta, Elisabeth; Elemento, Olivier; Melnick, Ari M.

2012-01-01

Genetic lesions such as BCR-ABL1, E2A-PBX1 and MLL rearrangements (MLLr) are associated with unfavorable outcomes in adult B-acute lymphoblastic leukemia (B-ALL). Leukemia oncoproteins may directly or indirectly disrupt cytosine methylation patterning to mediate the malignant phenotype. We postulated that DNA methylation signatures in these aggressive B-ALLs would point towards disease mechanisms and useful biomarkers and therapeutic targets. We therefore performed DNA methylation and gene expression profiling on a cohort of 215 adult B-ALL patients enrolled in a single phase III clinical trial (ECOG E2993) and normal control B-cells. In BCR-ABL1-positive B-ALL, aberrant cytosine methylation patterning centered around a cytokine network defined by hypomethylation and overexpression of IL2RA(CD25). The E2993 trial clinical data showed that CD25 expression was strongly associated with a poor outcome in ALL patients regardless of BCR-ABL1 status, suggesting CD25 as a novel prognostic biomarker for risk stratification in B-ALL. In E2A-PBX1-positive B-ALL, aberrant DNA methylation patterning was strongly associated with direct fusion protein binding as shown by the E2A-PBX1 ChIP sequencing (ChIP-seq), suggesting that E2A-PBX1 fusion protein directly remodels the epigenome to impose an aggressive B-ALL phenotype. MLLr B-ALL featured prominent cytosine hypomethylation, which was linked with MLL fusion protein binding, H3K79 dimethylation and transcriptional upregulation, affecting a set of known and newly identified MLL fusion direct targets with oncogenic activity such as FLT3 and BCL6. Notably, BCL6 blockade or loss of function suppressed proliferation and survival of MLLr leukemia cells, suggesting BCL6 targeted therapy as a new therapeutic strategy for MLLr B-ALL. PMID:23107779

Recurrent EML4-NTRK3 fusions in infantile fibrosarcoma and congenital mesoblastic nephroma suggest a revised testing strategy.

PubMed

Church, Alanna J; Calicchio, Monica L; Nardi, Valentina; Skalova, Alena; Pinto, Andre; Dillon, Deborah A; Gomez-Fernandez, Carmen R; Manoj, Namitha; Haimes, Josh D; Stahl, Joshua A; Dela Cruz, Filemon S; Tannenbaum-Dvir, Sarah; Glade-Bender, Julia L; Kung, Andrew L; DuBois, Steven G; Kozakewich, Harry P; Janeway, Katherine A; Perez-Atayde, Antonio R; Harris, Marian H

2018-03-01

Infantile fibrosarcoma and congenital mesoblastic nephroma are tumors of infancy traditionally associated with the ETV6-NTRK3 gene fusion. However, a number of case reports have identified variant fusions in these tumors. In order to assess the frequency of variant NTRK3 fusions, and in particular whether the recently identified EML4-NTRK3 fusion is recurrent, 63 archival cases of infantile fibrosarcoma, congenital mesoblastic nephroma, mammary analog secretory carcinoma and secretory breast carcinoma (tumor types that are known to carry recurrent ETV6-NTRK3 fusions) were tested with NTRK3 break-apart FISH, EML4-NTRK3 dual fusion FISH, and targeted RNA sequencing. The EML4-NTRK3 fusion was identified in two cases of infantile fibrosarcoma (one of which was previously described), and in one case of congenital mesoblastic nephroma, demonstrating that the EML4-NTRK3 fusion is a recurrent genetic event in these related tumors. The growing spectrum of gene fusions associated with infantile fibrosarcoma and congenital mesoblastic nephroma along with the recent availability of targeted therapies directed toward inhibition of NTRK signaling argue for alternate testing strategies beyond ETV6 break-apart FISH. The use of either NTRK3 FISH or next-generation sequencing will expand the number of cases in which an oncogenic fusion is identified and facilitate optimal diagnosis and treatment for patients.

Shock ignition: a new approach to high gain inertial confinement fusion on the national ignition facility.

PubMed

Perkins, L J; Betti, R; LaFortune, K N; Williams, W H

2009-07-24

Shock ignition, an alternative concept for igniting thermonuclear fuel, is explored as a new approach to high gain, inertial confinement fusion targets for the National Ignition Facility (NIF). Results indicate thermonuclear yields of approximately 120-250 MJ may be possible with laser drive energies of 1-1.6 MJ, while gains of approximately 50 may still be achievable at only approximately 0.2 MJ drive energy. The scaling of NIF energy gain with laser energy is found to be G approximately 126E (MJ);{0.510}. This offers the potential for high-gain targets that may lead to smaller, more economic fusion power reactors and a cheaper fusion energy development path.

Research on multi-source image fusion technology in haze environment

NASA Astrophysics Data System (ADS)

Ma, GuoDong; Piao, Yan; Li, Bing

2017-11-01

In the haze environment, the visible image collected by a single sensor can express the details of the shape, color and texture of the target very well, but because of the haze, the sharpness is low and some of the target subjects are lost; Because of the expression of thermal radiation and strong penetration ability, infrared image collected by a single sensor can clearly express the target subject, but it will lose detail information. Therefore, the multi-source image fusion method is proposed to exploit their respective advantages. Firstly, the improved Dark Channel Prior algorithm is used to preprocess the visible haze image. Secondly, the improved SURF algorithm is used to register the infrared image and the haze-free visible image. Finally, the weighted fusion algorithm based on information complementary is used to fuse the image. Experiments show that the proposed method can improve the clarity of the visible target and highlight the occluded infrared target for target recognition.

Osiris and SOMBRERO inertial confinement fusion power plant designs. Volume 2, Designs, assessments, and comparisons, Final report

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

Meier, W.R.; Bieri, R.L.; Monsler, M.J.

1992-03-01

The primary objective of the of the IFE Reactor Design Studies was to provide the Office of Fusion Energy with an evaluation of the potential of inertial fusion for electric power production. The term reactor studies is somewhat of a misnomer since these studies included the conceptual design and analysis of all aspects of the IFE power plants: the chambers, heat transport and power conversion systems, other balance of plant facilities, target systems (including the target production, injection, and tracking systems), and the two drivers. The scope of the IFE Reactor Design Studies was quite ambitious. The majority of ourmore » effort was spent on the conceptual design of two IFE electric power plants, one using an induction linac heavy ion beam (HIB) driver and the other using a Krypton Fluoride (KrF) laser driver. After the two point designs were developed, they were assessed in terms of their (1) environmental and safety aspects; (2) reliability, availability, and maintainability; (3) technical issues and technology development requirements; and (4) economics. Finally, we compared the design features and the results of the assessments for the two designs.« less

Audio Visual Integration with Competing Sources in the Framework of Audio Visual Speech Scene Analysis.

PubMed

Ganesh, Attigodu Chandrashekara; Berthommier, Frédéric; Schwartz, Jean-Luc

2016-01-01

We introduce "Audio-Visual Speech Scene Analysis" (AVSSA) as an extension of the two-stage Auditory Scene Analysis model towards audiovisual scenes made of mixtures of speakers. AVSSA assumes that a coherence index between the auditory and the visual input is computed prior to audiovisual fusion, enabling to determine whether the sensory inputs should be bound together. Previous experiments on the modulation of the McGurk effect by audiovisual coherent vs. incoherent contexts presented before the McGurk target have provided experimental evidence supporting AVSSA. Indeed, incoherent contexts appear to decrease the McGurk effect, suggesting that they produce lower audiovisual coherence hence less audiovisual fusion. The present experiments extend the AVSSA paradigm by creating contexts made of competing audiovisual sources and measuring their effect on McGurk targets. The competing audiovisual sources have respectively a high and a low audiovisual coherence (that is, large vs. small audiovisual comodulations in time). The first experiment involves contexts made of two auditory sources and one video source associated to either the first or the second audio source. It appears that the McGurk effect is smaller after the context made of the visual source associated to the auditory source with less audiovisual coherence. In the second experiment with the same stimuli, the participants are asked to attend to either one or the other source. The data show that the modulation of fusion depends on the attentional focus. Altogether, these two experiments shed light on audiovisual binding, the AVSSA process and the role of attention.

In Vivo Efficacy of Measles Virus Fusion Protein-Derived Peptides Is Modulated by the Properties of Self-Assembly and Membrane Residence

PubMed Central

Figueira, T. N.; Palermo, L. M.; Veiga, A. S.; Huey, D.; Alabi, C. A.; Santos, N. C.; Welsch, J. C.; Mathieu, C.; Niewiesk, S.; Moscona, A.

2016-01-01

ABSTRACT Measles virus (MV) infection is undergoing resurgence and remains one of the leading causes of death among young children worldwide despite the availability of an effective measles vaccine. MV infects its target cells by coordinated action of the MV hemagglutinin (H) and fusion (F) envelope glycoproteins; upon receptor engagement by H, the prefusion F undergoes a structural transition, extending and inserting into the target cell membrane and then refolding into a postfusion structure that fuses the viral and cell membranes. By interfering with this structural transition of F, peptides derived from the heptad repeat (HR) regions of F can inhibit MV infection at the entry stage. In previous work, we have generated potent MV fusion inhibitors by dimerizing the F-derived peptides and conjugating them to cholesterol. We have shown that prophylactic intranasal administration of our lead fusion inhibitor efficiently protects from MV infection in vivo. We show here that peptides tagged with lipophilic moieties self-assemble into nanoparticles until they reach the target cells, where they are integrated into cell membranes. The self-assembly feature enhances biodistribution and the half-life of the peptides, while integration into the target cell membrane increases fusion inhibitor potency. These factors together modulate in vivo efficacy. The results suggest a new framework for developing effective fusion inhibitory peptides. IMPORTANCE Measles virus (MV) infection causes an acute illness that may be associated with infection of the central nervous system (CNS) and severe neurological disease. No specific treatment is available. We have shown that fusion-inhibitory peptides delivered intranasally provide effective prophylaxis against MV infection. We show here that specific biophysical properties regulate the in vivo efficacy of MV F-derived peptides. PMID:27733647

In Vivo Efficacy of Measles Virus Fusion Protein-Derived Peptides Is Modulated by the Properties of Self-Assembly and Membrane Residence.

PubMed

Figueira, T N; Palermo, L M; Veiga, A S; Huey, D; Alabi, C A; Santos, N C; Welsch, J C; Mathieu, C; Horvat, B; Niewiesk, S; Moscona, A; Castanho, M A R B; Porotto, M

2017-01-01

Measles virus (MV) infection is undergoing resurgence and remains one of the leading causes of death among young children worldwide despite the availability of an effective measles vaccine. MV infects its target cells by coordinated action of the MV hemagglutinin (H) and fusion (F) envelope glycoproteins; upon receptor engagement by H, the prefusion F undergoes a structural transition, extending and inserting into the target cell membrane and then refolding into a postfusion structure that fuses the viral and cell membranes. By interfering with this structural transition of F, peptides derived from the heptad repeat (HR) regions of F can inhibit MV infection at the entry stage. In previous work, we have generated potent MV fusion inhibitors by dimerizing the F-derived peptides and conjugating them to cholesterol. We have shown that prophylactic intranasal administration of our lead fusion inhibitor efficiently protects from MV infection in vivo We show here that peptides tagged with lipophilic moieties self-assemble into nanoparticles until they reach the target cells, where they are integrated into cell membranes. The self-assembly feature enhances biodistribution and the half-life of the peptides, while integration into the target cell membrane increases fusion inhibitor potency. These factors together modulate in vivo efficacy. The results suggest a new framework for developing effective fusion inhibitory peptides. Measles virus (MV) infection causes an acute illness that may be associated with infection of the central nervous system (CNS) and severe neurological disease. No specific treatment is available. We have shown that fusion-inhibitory peptides delivered intranasally provide effective prophylaxis against MV infection. We show here that specific biophysical properties regulate the in vivo efficacy of MV F-derived peptides. Copyright © 2016 American Society for Microbiology.

Final report on the Magnetized Target Fusion Collaboration

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

John Slough

Nuclear fusion has the potential to satisfy the prodigious power that the world will demand in the future, but it has yet to be harnessed as a practical energy source. The entry of fusion as a viable, competitive source of power has been stymied by the challenge of finding an economical way to provide for the confinement and heating of the plasma fuel. It is the contention here that a simpler path to fusion can be achieved by creating fusion conditions in a different regime at small scale (~ a few cm). One such program now under study, referred tomore » as Magnetized Target Fusion (MTF), is directed at obtaining fusion in this high energy density regime by rapidly compressing a compact toroidal plasmoid commonly referred to as a Field Reversed Configuration (FRC). To make fusion practical at this smaller scale, an efficient method for compressing the FRC to fusion gain conditions is required. In one variant of MTF a conducting metal shell is imploded electrically. This radially compresses and heats the FRC plasmoid to fusion conditions. The closed magnetic field in the target plasmoid suppresses the thermal transport to the confining shell, thus lowering the imploding power needed to compress the target. The undertaking to be described in this proposal is to provide a suitable target FRC, as well as a simple and robust method for inserting and stopping the FRC within the imploding liner. The timescale for testing and development can be rapidly accelerated by taking advantage of a new facility funded by the Department of Energy. At this facility, two inductive plasma accelerators (IPA) were constructed and tested. Recent experiments with these IPAs have demonstrated the ability to rapidly form, accelerate and merge two hypervelocity FRCs into a compression chamber. The resultant FRC that was formed was hot (T&ion ~ 400 eV), stationary, and stable with a configuration lifetime several times that necessary for the MTF liner experiments. The accelerator length was less than 1 meter, and the time from the initiation of formation to the establishment of the final equilibrium was less than 10 microseconds. With some modification, each accelerator was made capable of producing FRCs suitable for the production of the target plasma for the MTF liner experiment. Based on the initial FRC merging/compression results, the design and methodology for an experimental realization of the target plasma for the MTF liner experiment can now be defined. A high density FRC plasmoid is to be formed and accelerated out of each IPA into a merging/compression chamber similar to the imploding liner at AFRL. The properties of the resultant FRC plasma (size, temperature, density, flux, lifetime) are obtained in the reevant regime of interest. The process still needs to be optimized, and a final design for implementation at AFRL must now be carried out. When implemented at AFRL it is anticipated that the colliding/merging FRCs will then be compressed by the liner. In this manner it is hoped that ultimately a plasma with ion temperatures reaching the 10 keV range and fusion gain near unity can be obtained.« less

High-Speed Incoming Infrared Target Detection by Fusion of Spatial and Temporal Detectors

PubMed Central

Kim, Sungho

2015-01-01

This paper presents a method for detecting high-speed incoming targets by the fusion of spatial and temporal detectors to achieve a high detection rate for an active protection system (APS). The incoming targets have different image velocities according to the target-camera geometry. Therefore, single-target detector-based approaches, such as a 1D temporal filter, 2D spatial filter and 3D matched filter, cannot provide a high detection rate with moderate false alarms. The target speed variation was analyzed according to the incoming angle and target velocity. The speed of the distant target at the firing time is almost stationary and increases slowly. The speed varying targets are detected stably by fusing the spatial and temporal filters. The stationary target detector is activated by an almost zero temporal contrast filter (TCF) and identifies targets using a spatial filter called the modified mean subtraction filter (M-MSF). A small motion (sub-pixel velocity) target detector is activated by a small TCF value and finds targets using the same spatial filter. A large motion (pixel-velocity) target detector works when the TCF value is high. The final target detection is terminated by fusing the three detectors based on the threat priority. The experimental results of the various target sequences show that the proposed fusion-based target detector produces the highest detection rate with an acceptable false alarm rate. PMID:25815448

Inhibition of Nipah virus infection in vivo: targeting an early stage of paramyxovirus fusion activation during viral entry.

PubMed

Porotto, Matteo; Rockx, Barry; Yokoyama, Christine C; Talekar, Aparna; Devito, Ilaria; Palermo, Laura M; Liu, Jie; Cortese, Riccardo; Lu, Min; Feldmann, Heinz; Pessi, Antonello; Moscona, Anne

2010-10-28

In the paramyxovirus cell entry process, receptor binding triggers conformational changes in the fusion protein (F) leading to viral and cellular membrane fusion. Peptides derived from C-terminal heptad repeat (HRC) regions in F have been shown to inhibit fusion by preventing formation of the fusogenic six-helix bundle. We recently showed that the addition of a cholesterol group to HRC peptides active against Nipah virus targets these peptides to the membrane where fusion occurs, dramatically increasing their antiviral effect. In this work, we report that unlike the untagged HRC peptides, which bind to the postulated extended intermediate state bridging the viral and cell membranes, the cholesterol tagged HRC-derived peptides interact with F before the fusion peptide inserts into the target cell membrane, thus capturing an earlier stage in the F-activation process. Furthermore, we show that cholesterol tagging renders these peptides active in vivo: the cholesterol-tagged peptides cross the blood brain barrier, and effectively prevent and treat in an established animal model what would otherwise be fatal Nipah virus encephalitis. The in vivo efficacy of cholesterol-tagged peptides, and in particular their ability to penetrate the CNS, suggests that they are promising candidates for the prevention or therapy of infection by Nipah and other lethal paramyxoviruses.

Conceptual design considerations and neutronics of lithium fall laser fusion target chambers

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

Meier, W.R.; Thomson, W.B.

1978-05-31

Atomics International and Lawrence Livermore Laboratory are involved in the conceptual design of a laser fusion power plant incorporating the lithium fall target chamber. In this paper we discuss some of the more important design considerations for the target chamber and evaluate its nuclear performance. Sizing and configuration of the fall, hydraulic effects, and mechanical design considerations are addressed. The nuclear aspects examined include tritium breeding, energy deposition, and radiation damage.

Transcription factor mutations in myelodysplastic/myeloproliferative neoplasms

PubMed Central

Ernst, Thomas; Chase, Andrew; Zoi, Katerina; Waghorn, Katherine; Hidalgo-Curtis, Claire; Score, Joannah; Jones, Amy; Grand, Francis; Reiter, Andreas; Hochhaus, Andreas; Cross, Nicholas C.P.

2010-01-01

Background Aberrant activation of tyrosine kinases, caused by either mutation or gene fusion, is of major importance for the development of many hematologic malignancies, particularly myeloproliferative neoplasms. We hypothesized that hitherto unrecognized, cytogenetically cryptic tyrosine kinase fusions may be common in non-classical or atypical myeloproliferative neoplasms and related myelodysplastic/myeloproliferative neoplasms. Design and Methods To detect genomic copy number changes associated with such fusions, we performed a systematic search in 68 patients using custom designed, targeted, high-resolution array comparative genomic hybridization. Arrays contained 44,000 oligonucleotide probes that targeted 500 genes including all 90 tyrosine kinases plus downstream tyrosine kinase signaling components, other translocation targets, transcription factors, and other factors known to be important for myelopoiesis. Results No abnormalities involving tyrosine kinases were detected; however, nine cytogenetically cryptic copy number imbalances were detected in seven patients, including hemizygous deletions of RUNX1 or CEBPA in two cases with atypical chronic myeloid leukemia. Mutation analysis of the remaining alleles revealed non-mutated RUNX1 and a frameshift insertion within CEBPA. A further mutation screen of 187 patients with myelodysplastic/myeloproliferative neoplasms identified RUNX1 mutations in 27 (14%) and CEBPA mutations in seven (4%) patients. Analysis of other transcription factors known to be frequently mutated in acute myeloid leukemia revealed NPM1 mutations in six (3%) and WT1 mutations in two (1%) patients with myelodysplastic/myeloproliferative neoplasms. Univariate analysis indicated that patients with mutations had a shorter overall survival (28 versus 44 months, P=0.019) compared with patients without mutations, with the prognosis for cases with CEBPA, NPM1 or WT1 mutations being particularly poor. Conclusions We conclude that mutations of transcription and other nuclear factors are frequent in myelodysplastic/myeloproliferative neoplasms and are generally mutually exclusive. CEBPA, NPM1 or WT1 mutations may be associated with a poor prognosis, an observation that will need to be confirmed by detailed prospective studies. PMID:20421268

Mildly Acidic pH Triggers an Irreversible Conformational Change in the Fusion Domain of Herpes Simplex Virus 1 Glycoprotein B and Inactivation of Viral Entry.

PubMed

Weed, Darin J; Pritchard, Suzanne M; Gonzalez, Floricel; Aguilar, Hector C; Nicola, Anthony V

2017-03-01

Herpes simplex virus (HSV) entry into a subset of cells requires endocytosis and endosomal low pH. Preexposure of isolated virions to mildly acidic pH of 5 to 6 partially inactivates HSV infectivity in an irreversible manner. Acid inactivation is a hallmark of viruses that enter via low-pH pathways; this occurs by pretriggering conformational changes essential for fusion. The target and mechanism(s) of low-pH inactivation of HSV are unclear. Here, low-pH-treated HSV-1 was defective in fusion activity and yet retained normal levels of attachment to cell surface heparan sulfate and binding to nectin-1 receptor. Low-pH-triggered conformational changes in gB reported to date are reversible, despite irreversible low-pH inactivation. gB conformational changes and their reversibility were measured by antigenic analysis with a panel of monoclonal antibodies and by detecting changes in oligomeric conformation. Three-hour treatment of HSV-1 virions with pH 5 or multiple sequential treatments at pH 5 followed by neutral pH caused an irreversible >2.5 log infectivity reduction. While changes in several gB antigenic sites were reversible, alteration of the H126 epitope was irreversible. gB oligomeric conformational change remained reversible under all conditions tested. Altogether, our results reveal that oligomeric alterations and fusion domain changes represent distinct conformational changes in gB, and the latter correlates with irreversible low-pH inactivation of HSV. We propose that conformational change in the gB fusion domain is important for activation of membrane fusion during viral entry and that in the absence of a host target membrane, this change results in irreversible inactivation of virions. IMPORTANCE HSV-1 is an important pathogen with a high seroprevalence throughout the human population. HSV infects cells via multiple pathways, including a low-pH route into epithelial cells, the primary portal into the host. HSV is inactivated by low-pH preexposure, and gB, a class III fusion protein, undergoes reversible conformational changes in response to low-pH exposure. Here, we show that low-pH inactivation of HSV is irreversible and due to a defect in virion fusion activity. We identified an irreversible change in the fusion domain of gB following multiple sequential low-pH exposures or following prolonged low-pH treatment. This change appears to be separable from the alteration in gB quaternary structure. Together, the results are consistent with a model by which low pH can have an activating or inactivating effect on HSV depending on the presence of a target membrane. Copyright © 2017 American Society for Microbiology.

Formation of Neutron-Enriched Heavy and Superheavy Nuclei in Fusion Reactions

NASA Astrophysics Data System (ADS)

Karpov, A. V.; Rachkov, V. A.; Saiko, V. V.

2018-05-01

The formation of new isotopes of heavy and superheavy elements in the fusion of neutron-enriched projectiles with actinide targets is discussed. Cross sections for the formation of evaporation residues in fusion reactions is predicted for several combinations of colliding nuclei.

Calcium-dependent regulation of SNARE-mediated membrane fusion by calmodulin.

PubMed

Di Giovanni, Jerome; Iborra, Cécile; Maulet, Yves; Lévêque, Christian; El Far, Oussama; Seagar, Michael

2010-07-30

Neuroexocytosis requires SNARE proteins, which assemble into trans complexes at the synaptic vesicle/plasma membrane interface and mediate bilayer fusion. Ca(2+) sensitivity is thought to be conferred by synaptotagmin, although the ubiquitous Ca(2+)-effector calmodulin has also been implicated in SNARE-dependent membrane fusion. To examine the molecular mechanisms involved, we examined the direct action of calmodulin and synaptotagmin in vitro, using fluorescence resonance energy transfer to assay lipid mixing between target- and vesicle-SNARE liposomes. Ca(2+)/calmodulin inhibited SNARE assembly and membrane fusion by binding to two distinct motifs located in the membrane-proximal regions of VAMP2 (K(D) = 500 nm) and syntaxin 1 (K(D) = 2 microm). In contrast, fusion was increased by full-length synaptotagmin 1 anchored in vesicle-SNARE liposomes. When synaptotagmin and calmodulin were combined, synaptotagmin overcame the inhibitory effects of calmodulin. Furthermore, synaptotagmin displaced calmodulin binding to target-SNAREs. These findings suggest that two distinct Ca(2+) sensors act antagonistically in SNARE-mediated fusion.

Knudsen and inverse Knudsen layer effect on tail ion distribution and fusion reactivity in inertial confinement fusion targets

NASA Astrophysics Data System (ADS)

McDevitt, C. J.; Tang, X.-Z.; Guo, Z.; Berk, H. L.

2014-10-01

A series of reduced models are used to study the fast ion tail in the vicinity of a transition layer between plasmas at disparate temperatures and densities, which is typical of the gas-pusher interface in inertial confinement fusion targets. Emphasis is placed on utilizing progressively more comprehensive models in order to identify the essential physics for computing the fast ion tail at energies comparable to the Gamow peak. The resulting fast ion tail distribution is subsequently used to compute the fusion reactivity as a function of collisionality and temperature. It is found that while the fast ion distribution can be significantly depleted in the hot spot, leading to a reduction of the fusion reactivity in this region, a surplus of fast ions is present in the neighboring cold region. The presence of this fast ion surplus in the neighboring cold region is shown to lead to a partial recovery of the fusion yield lost in the hot spot.

Simulation of the target creation through FRC merging for a magneto-inertial fusion concept

NASA Astrophysics Data System (ADS)

Li, Chenguang; Yang, Xianjun

2017-04-01

A two-dimensional magnetohydrodynamics model has been used to simulate the target creation process in a magneto-inertial fusion concept named Magnetized Plasma Fusion Reactor (MPFR) [C. Li and X. Yang, Phys. Plasmas 23, 102702 (2016)], where the target plasma created through Field reversed configuration (FRC) merging was compressed by an imploding liner driven by the pulsed-power driver. In the scheme, two initial FRCs (Field reversed configurations) are translated into the region where FRC merging occurs, bringing out the target plasma ready for compression. The simulations cover the three stages of the target creation process: formation, translation, and merging. The factors affecting the achieved target are analyzed numerically. The magnetic field gradient produced by the conical coils is found to determine how fast the FRC is accelerated to peak velocity and the collision merging occurs. Moreover, it is demonstrated that FRC merging can be realized by real coils with gaps showing nearly identical performance, and the optimized target by FRC merging shows larger internal energy and retained flux, which is more suitable for the MPFR concept.

Deep RNA sequencing analysis of readthrough gene fusions in human prostate adenocarcinoma and reference samples

PubMed Central

2011-01-01

Background Readthrough fusions across adjacent genes in the genome, or transcription-induced chimeras (TICs), have been estimated using expressed sequence tag (EST) libraries to involve 4-6% of all genes. Deep transcriptional sequencing (RNA-Seq) now makes it possible to study the occurrence and expression levels of TICs in individual samples across the genome. Methods We performed single-end RNA-Seq on three human prostate adenocarcinoma samples and their corresponding normal tissues, as well as brain and universal reference samples. We developed two bioinformatics methods to specifically identify TIC events: a targeted alignment method using artificial exon-exon junctions within 200,000 bp from adjacent genes, and genomic alignment allowing splicing within individual reads. We performed further experimental verification and characterization of selected TIC and fusion events using quantitative RT-PCR and comparative genomic hybridization microarrays. Results Targeted alignment against artificial exon-exon junctions yielded 339 distinct TIC events, including 32 gene pairs with multiple isoforms. The false discovery rate was estimated to be 1.5%. Spliced alignment to the genome was less sensitive, finding only 18% of those found by targeted alignment in 33-nt reads and 59% of those in 50-nt reads. However, spliced alignment revealed 30 cases of TICs with intervening exons, in addition to distant inversions, scrambled genes, and translocations. Our findings increase the catalog of observed TIC gene pairs by 66%. We verified 6 of 6 predicted TICs in all prostate samples, and 2 of 5 predicted novel distant gene fusions, both private events among 54 prostate tumor samples tested. Expression of TICs correlates with that of the upstream gene, which can explain the prostate-specific pattern of some TIC events and the restriction of the SLC45A3-ELK4 e4-e2 TIC to ERG-negative prostate samples, as confirmed in 20 matched prostate tumor and normal samples and 9 lung cancer cell lines. Conclusions Deep transcriptional sequencing and analysis with targeted and spliced alignment methods can effectively identify TIC events across the genome in individual tissues. Prostate and reference samples exhibit a wide range of TIC events, involving more genes than estimated previously using ESTs. Tissue specificity of TIC events is correlated with expression patterns of the upstream gene. Some TIC events, such as MSMB-NCOA4, may play functional roles in cancer. PMID:21261984

Studies of Ebola Virus Glycoprotein-Mediated Entry and Fusion by Using Pseudotyped Human Immunodeficiency Virus Type 1 Virions: Involvement of Cytoskeletal Proteins and Enhancement by Tumor Necrosis Factor Alpha

PubMed Central

Yonezawa, Akihito; Cavrois, Marielle; Greene, Warner C.

2005-01-01

The Ebola filoviruses are aggressive pathogens that cause severe and often lethal hemorrhagic fever syndromes in humans and nonhuman primates. To date, no effective therapies have been identified. To analyze the entry and fusion properties of Ebola virus, we adapted a human immunodeficiency virus type 1 (HIV-1) virion-based fusion assay by substituting Ebola virus glycoprotein (GP) for the HIV-1 envelope. Fusion was detected by cleavage of the fluorogenic substrate CCF2 by β-lactamase-Vpr incorporated into virions and released as a result of virion fusion. Entry and fusion induced by the Ebola virus GP occurred with much slower kinetics than with vesicular stomatitis virus G protein (VSV-G) and were blocked by depletion of membrane cholesterol and by inhibition of vesicular acidification with bafilomycin A1. These properties confirmed earlier studies and validated the assay for exploring other properties of Ebola virus GP-mediated entry and fusion. Entry and fusion of Ebola virus GP pseudotypes, but not VSV-G or HIV-1 Env pseudotypes, were impaired in the presence of the microtubule-disrupting agent nocodazole but were enhanced in the presence of the microtubule-stabilizing agent paclitaxel (Taxol). Agents that impaired microfilament function, including cytochalasin B, cytochalasin D, latrunculin A, and jasplakinolide, also inhibited Ebola virus GP-mediated entry and fusion. Together, these findings suggest that both microtubules and microfilaments may play a role in the effective trafficking of vesicles containing Ebola virions from the cell surface to the appropriate acidified vesicular compartment where fusion occurs. In terms of Ebola virus GP-mediated entry and fusion to various target cells, primary macrophages proved highly sensitive, while monocytes from the same donors displayed greatly reduced levels of entry and fusion. We further observed that tumor necrosis factor alpha, which is released by Ebola virus-infected monocytes/macrophages, enhanced Ebola virus GP-mediated entry and fusion to human umbilical vein endothelial cells. Thus, Ebola virus infection of one target cell may induce biological changes that facilitate infection of secondary target cells that play a key role in filovirus pathogenesis. Finally, these studies indicate that pseudotyping in the HIV-1 virion-based fusion assay may be a valuable approach to the study of entry and fusion properties mediated through the envelopes of other viral pathogens. PMID:15613320

Simulation studies of hydrodynamic aspects of magneto-inertial fusion and high order adaptive algorithms for Maxwell equations

NASA Astrophysics Data System (ADS)

Wu, Lingling

Three-dimensional simulations of the formation and implosion of plasma liners for the Plasma Jet Induced Magneto Inertial Fusion (PJMIF) have been performed using multiscale simulation technique based on the FronTier code. In the PJMIF concept, a plasma liner, formed by merging of a large number of radial, highly supersonic plasma jets, implodes on the target in the form of two compact plasma toroids, and compresses it to conditions of the nuclear fusion ignition. The propagation of a single jet with Mach number 60 from the plasma gun to the merging point was studied using the FronTier code. The simulation result was used as input to the 3D jet merger problem. The merger of 144, 125, and 625 jets and the formation and heating of plasma liner by compression waves have been studied and compared with recent theoretical predictions. The main result of the study is the prediction of the average Mach number reduction and the description of the liner structure and properties. We have also compared the effect of different merging radii. Spherically symmetric simulations of the implosion of plasma liners and compression of plasma targets have also been performed using the method of front tracking. The cases of single deuterium and xenon liners and double layer deuterium - xenon liners compressing various deuterium-tritium targets have been investigated, optimized for maximum fusion energy gains, and compared with theoretical predictions and scaling laws of [P. Parks, On the efficacy of imploding plasma liners for magnetized fusion target compression, Phys. Plasmas 15, 062506 (2008)]. In agreement with the theory, the fusion gain was significantly below unity for deuterium - tritium targets compressed by Mach 60 deuterium liners. In the most optimal setup for a given chamber size that contained a target with the initial radius of 20 cm compressed by 10 cm thick, Mach 60 xenon liner, the target ignition and fusion energy gain of 10 was achieved. Simulations also showed that composite deuterium - xenon liners reduce the energy gain due to lower target compression rates. The effect of heating of targets by alpha particles on the fusion energy gain has also been investigated. The study of the dependence of the ram pressure amplification on radial compressibility showed a good agreement with the theory. The study concludes that a liner with higher Mach number and lower adiabatic index gamma (the radio of specific heats) will generate higher ram pressure amplification and higher fusion energy gain. We implemented a second order embedded boundary method for the Maxwell equations in geometrically complex domains. The numerical scheme is second order in both space and time. Comparing to the first order stair-step approximation of complex geometries within the FDTD method, this method can avoid spurious solution introduced by the stair step approximation. Unlike the finite element method and the FE-FD hybrid method, no triangulation is needed for this scheme. This method preserves the simplicity of the embedded boundary method and it is easy to implement. We will also propose a conservative (symplectic) fourth order scheme for uniform geometry boundary.

Research on HDR image fusion algorithm based on Laplace pyramid weight transform with extreme low-light CMOS

NASA Astrophysics Data System (ADS)

Guan, Wen; Li, Li; Jin, Weiqi; Qiu, Su; Zou, Yan

2015-10-01

Extreme-Low-Light CMOS has been widely applied in the field of night-vision as a new type of solid image sensor. But if the illumination in the scene has drastic changes or the illumination is too strong, Extreme-Low-Light CMOS can't both clearly present the high-light scene and low-light region. According to the partial saturation problem in the field of night-vision, a HDR image fusion algorithm based on the Laplace Pyramid was researched. The overall gray value and the contrast of the low light image is very low. We choose the fusion strategy based on regional average gradient for the top layer of the long exposure image and short exposure image, which has rich brightness and textural features. The remained layers which represent the edge feature information of the target are based on the fusion strategy based on regional energy. In the process of source image reconstruction with Laplacian pyramid image, we compare the fusion results with four kinds of basal images. The algorithm is tested using Matlab and compared with the different fusion strategies. We use information entropy, average gradient and standard deviation these three objective evaluation parameters for the further analysis of the fusion result. Different low illumination environment experiments show that the algorithm in this paper can rapidly get wide dynamic range while keeping high entropy. Through the verification of this algorithm features, there is a further application prospect of the optimized algorithm. Keywords: high dynamic range imaging, image fusion, multi-exposure image, weight coefficient, information fusion, Laplacian pyramid transform.

Improved prediction of drug-target interactions using regularized least squares integrating with kernel fusion technique.

PubMed

Hao, Ming; Wang, Yanli; Bryant, Stephen H

2016-02-25

Identification of drug-target interactions (DTI) is a central task in drug discovery processes. In this work, a simple but effective regularized least squares integrating with nonlinear kernel fusion (RLS-KF) algorithm is proposed to perform DTI predictions. Using benchmark DTI datasets, our proposed algorithm achieves the state-of-the-art results with area under precision-recall curve (AUPR) of 0.915, 0.925, 0.853 and 0.909 for enzymes, ion channels (IC), G protein-coupled receptors (GPCR) and nuclear receptors (NR) based on 10 fold cross-validation. The performance can further be improved by using a recalculated kernel matrix, especially for the small set of nuclear receptors with AUPR of 0.945. Importantly, most of the top ranked interaction predictions can be validated by experimental data reported in the literature, bioassay results in the PubChem BioAssay database, as well as other previous studies. Our analysis suggests that the proposed RLS-KF is helpful for studying DTI, drug repositioning as well as polypharmacology, and may help to accelerate drug discovery by identifying novel drug targets. Published by Elsevier B.V.

Science of Land Target Spectral Signatures

DTIC Science & Technology

2013-04-03

F. Meriaudeau, T. Downey , A. Wig , A. Passian, M. Buncick, T.L. Ferrell, Fiber optic sensor based on gold island plasmon resonance , Sensors and...processing, detection algorithms, sensor fusion, spectral signature modeling Dr. J. Michael Cathcart Georgia Tech Research Corporation Office of...target detection and sensor fusion. The phenomenology research continued to focus on spectroscopic soil measurements, optical property analyses, field

Magnetized Target Fusion

NASA Technical Reports Server (NTRS)

Griffin, Steven T.

2002-01-01

Magnetized target fusion (MTF) is under consideration as a means of building a low mass, high specific impulse, and high thrust propulsion system for interplanetary travel. This unique combination is the result of the generation of a high temperature plasma by the nuclear fusion process. This plasma can then be deflected by magnetic fields to provide thrust. Fusion is initiated by a small traction of the energy generated in the magnetic coils due to the plasma's compression of the magnetic field. The power gain from a fusion reaction is such that inefficiencies due to thermal neutrons and coil losses can be overcome. Since the fusion reaction products are directly used for propulsion and the power to initiate the reaction is directly obtained from the thrust generation, no massive power supply for energy conversion is required. The result should be a low engine mass, high specific impulse and high thrust system. The key is to successfully initiate fusion as a proof-of-principle for this application. Currently MSFC is implementing MTF proof-of-principle experiments. This involves many technical details and ancillary investigations. Of these, selected pertinent issues include the properties, orientation and timing of the plasma guns and the convergence and interface development of the "pusher" plasma. Computer simulations of the target plasma's behavior under compression and the convergence and mixing of the gun plasma are under investigation. This work is to focus on the gun characterization and development as it relates to plasma initiation and repeatability.

Broad-spectrum antivirals against viral fusion

PubMed Central

Vigant, Frederic; Santos, Nuno C.; Lee, Benhur

2015-01-01

Effective antivirals have been developed against specific viruses, such as HIV, Hepatitis C virus and influenza virus. This ‘one bug–one drug’ approach to antiviral drug development can be successful, but it may be inadequate for responding to an increasing diversity of viruses that cause significant diseases in humans. The majority of viral pathogens that cause emerging and re-emerging infectious diseases are membrane-enveloped viruses, which require the fusion of viral and cell membranes for virus entry. Therefore, antivirals that target the membrane fusion process represent new paradigms for broad-spectrum antiviral discovery. In this Review, we discuss the mechanisms responsible for the fusion between virus and cell membranes and explore how broad-spectrum antivirals target this process to prevent virus entry. PMID:26075364

Sub-barrier radioactive ion beam investigations using a new methodology and analysis for the stacked target technique

NASA Astrophysics Data System (ADS)

Fisichella, M.; Shotter, A. C.; Di Pietro, A.; Figuera, P.; Lattuada, M.; Marchetta, C.; Privitera, V.; Romano, L.; Ruiz, C.; Zadro, M.

2015-12-01

For low energy reaction studies involving radioactive ion beams, the experimental reaction yields are generally small due to the low intensity of the beams. For this reason, the stacked target technique has been often used to measure excitation functions. This technique offers considerable advantages since the reaction cross-section at several energies can be simultaneously measured. In a further effort to increase yields, thick targets are also employed. The main disadvantage of the method is the degradation of the beam quality as it passes through the stack due to the statistical nature of energy loss processes and any nonuniformity of the stacked targets. This degradation can lead to ambiguities of associating effective beam energies to reaction product yields for the targets within the stack and, as a consequence, to an error in the determination of the excitation function for the reaction under study. A thorough investigation of these ambiguities is reported, and a best practice procedure of analyzing data obtained using the stacked target technique with radioactive ion beams is recommended. Using this procedure a re-evaluation is reported of some previously published sub-barrier fusion data in order to demonstrate the possibility of misinterpretations of derived excitation functions. In addition, this best practice procedure has been used to evaluate, from a new data set, the sub-barrier fusion excitation function for the reaction 6Li+120Sn .

Novel cancer gene variants and gene fusions of triple-negative breast cancers (TNBCs) reveal their molecular diversity conserved in the patient-derived xenograft (PDX) model.

PubMed

Jung, Jaeyun; Jang, Kiwon; Ju, Jung Min; Lee, Eunji; Lee, Jong Won; Kim, Hee Jung; Kim, Jisun; Lee, Sae Byul; Ko, Beom Seok; Son, Byung Ho; Lee, Hee Jin; Gong, Gyungyup; Ahn, Sei Yeon; Choi, Jung Kyoon; Singh, Shree Ram; Chang, Suhwan

2018-08-01

Despite the improved 5-year survival rate of breast cancer, triple-negative breast cancer (TNBC) remains a challenge due to lack of effective targeted therapy and higher recurrence and metastasis than other subtypes. To identify novel druggable targets and to understand its unique biology, we tried to implement 24 patient-derived xenografts (PDXs) of TNBC. The overall success rate of PDX implantation was 45%, much higher than estrogen receptor (ER)-positive cases. Immunohistochemical analysis revealed conserved ER/PR/Her2 negativity (with two exceptions) between the original and PDX tumors. Genomic analysis of 10 primary tumor-PDX pairs with Ion AmpliSeq CCP revealed high degree of variant conservation (85.0%-96.9%) between primary and PDXs. Further analysis showed 44 rare variants with a predicted high impact in 36 genes including Trp53, Pten, Notch1, and Col1a1. Among them, we confirmed frequent Notch1 variant. Furthermore, RNA-seq analysis of 24 PDXs revealed 594 gene fusions, of which 163 were in-frame, including AZGP1-GJC3 and NF1-AARSD1. Finally, western blot analysis of oncogenic signaling proteins supporting molecular diversity of TNBC PDXs. Overall, our report provides a molecular basis for the usefulness of the TNBC PDX model in preclinical study. Published by Elsevier B.V.

An Il12-Il2-Antibody Fusion Protein Targeting Hodgkin's Lymphoma Cells Potentiates Activation Of Nk And T Cells For An Anti-Tumor Attack

PubMed Central

Friedrichs, Björn; Heuser, Claudia; Guhlke, Stefan; Abken, Hinrich; Hombach, Andreas A.

2012-01-01

Successful immunotherapy of Hodgkin's disease is so far hampered by the striking unresponsiveness of lymphoma infiltrating immune cells. To mobilize both adoptive and innate immune cells for an anti-tumor attack we fused the pro-inflammatory cytokines IL2 and IL12 to an anti-CD30 scFv antibody in a dual cytokine fusion protein to accumulate both cytokines at the malignant CD30+ Hodgkin/Reed-Sternberg cells in the lymphoma lesion. The tumor-targeted IL12-IL2 fusion protein was superior in activating resting T cells to amplify and secrete pro-inflammatory cytokines compared to targeted IL2 or IL12 alone. NK cells were also activated by the dual cytokine protein to secrete IFN-γ and to lyse target cells. The tumor-targeted IL12-IL2, when applied by i.v. injection to immune-competent mice with established antigen-positive tumors, accumulated at the tumor site and induced tumor regression. Data demonstrate that simultaneous targeting of two cytokines in a spatial and temporal simultaneous fashion to pre-defined tissues is feasible by a dual-cytokine antibody fusion protein. In the case of IL12 and IL2, this produced superior anti-tumor efficacy implying the strategy to muster a broader immune cell response in the combat against cancer. PMID:23028547

Continuous and scalable polymer capsule processing for inertial fusion energy target shell fabrication using droplet microfluidics.

PubMed

Li, Jin; Lindley-Start, Jack; Porch, Adrian; Barrow, David

2017-07-24

High specification, polymer capsules, to produce inertial fusion energy targets, were continuously fabricated using surfactant-free, inertial centralisation, and ultrafast polymerisation, in a scalable flow reactor. Laser-driven, inertial confinement fusion depends upon the interaction of high-energy lasers and hydrogen isotopes, contained within small, spherical and concentric target shells, causing a nuclear fusion reaction at ~150 M°C. Potentially, targets will be consumed at ~1 M per day per reactor, demanding a 5000x unit cost reduction to ~$0.20, and is a critical, key challenge. Experimentally, double emulsions were used as templates for capsule-shells, and were formed at 20 Hz, on a fluidic chip. Droplets were centralised in a dynamic flow, and their shapes both evaluated, and mathematically modeled, before subsequent shell solidification. The shells were photo-cured individually, on-the-fly, with precisely-actuated, millisecond-length (70 ms), uniform-intensity UV pulses, delivered through eight, radially orchestrated light-pipes. The near 100% yield rate of uniform shells had a minimum 99.0% concentricity and sphericity, and the solidification processing period was significantly reduced, over conventional batch methods. The data suggest the new possibility of a continuous, on-the-fly, IFE target fabrication process, employing sequential processing operations within a continuous enclosed duct system, which may include cryogenic fuel-filling, and shell curing, to produce ready-to-use IFE targets.

Airborne net-centric multi-INT sensor control, display, fusion, and exploitation systems

NASA Astrophysics Data System (ADS)

Linne von Berg, Dale C.; Lee, John N.; Kruer, Melvin R.; Duncan, Michael D.; Olchowski, Fred M.; Allman, Eric; Howard, Grant

2004-08-01

The NRL Optical Sciences Division has initiated a multi-year effort to develop and demonstrate an airborne net-centric suite of multi-intelligence (multi-INT) sensors and exploitation systems for real-time target detection and targeting product dissemination. The goal of this Net-centric Multi-Intelligence Fusion Targeting Initiative (NCMIFTI) is to develop an airborne real-time intelligence gathering and targeting system that can be used to detect concealed, camouflaged, and mobile targets. The multi-INT sensor suite will include high-resolution visible/infrared (EO/IR) dual-band cameras, hyperspectral imaging (HSI) sensors in the visible-to-near infrared, short-wave and long-wave infrared (VNIR/SWIR/LWIR) bands, Synthetic Aperture Radar (SAR), electronics intelligence sensors (ELINT), and off-board networked sensors. Other sensors are also being considered for inclusion in the suite to address unique target detection needs. Integrating a suite of multi-INT sensors on a single platform should optimize real-time fusion of the on-board sensor streams, thereby improving the detection probability and reducing the false alarms that occur in reconnaissance systems that use single-sensor types on separate platforms, or that use independent target detection algorithms on multiple sensors. In addition to the integration and fusion of the multi-INT sensors, the effort is establishing an open-systems net-centric architecture that will provide a modular "plug and play" capability for additional sensors and system components and provide distributed connectivity to multiple sites for remote system control and exploitation.

Linear high-boost fusion of Stokes vector imagery for effective discrimination and recognition of real targets in the presence of multiple identical decoys

NASA Astrophysics Data System (ADS)

El-Saba, Aed; Sakla, Wesam A.

2010-04-01

Recently, the use of imaging polarimetry has received considerable attention for use in automatic target recognition (ATR) applications. In military remote sensing applications, there is a great demand for sensors that are capable of discriminating between real targets and decoys. Accurate discrimination of decoys from real targets is a challenging task and often requires the fusion of various sensor modalities that operate simultaneously. In this paper, we use a simple linear fusion technique known as the high-boost fusion method for effective discrimination of real targets in the presence of multiple decoys. The HBF assigns more weight to the polarization-based imagery in forming the final fused image that is used for detection. We have captured both intensity and polarization-based imagery from an experimental laboratory arrangement containing a mixture of sand/dirt, rocks, vegetation, and other objects for the purpose of simulating scenery that would be acquired in a remote sensing military application. A target object and three decoys that are identical in physical appearance (shape, surface structure and color) and different in material composition have also been placed in the scene. We use the wavelet-filter joint transform correlation (WFJTC) technique to perform detection between input scenery and the target object. Our results show that use of the HBF method increases the correlation performance metrics associated with the WFJTC-based detection process when compared to using either the traditional intensity or polarization-based images.

Distributed ISAR Subimage Fusion of Nonuniform Rotating Target Based on Matching Fourier Transform.

PubMed

Li, Yuanyuan; Fu, Yaowen; Zhang, Wenpeng

2018-06-04

In real applications, the image quality of the conventional monostatic Inverse Synthetic Aperture Radar (ISAR) for the maneuvering target is subject to the strong fluctuation of Radar Cross Section (RCS), as the target aspect varies enormously. Meanwhile, the maneuvering target introduces nonuniform rotation after translation motion compensation which degrades the imaging performance of the conventional Fourier Transform (FT)-based method in the cross-range dimension. In this paper, a method which combines the distributed ISAR technique and the Matching Fourier Transform (MFT) is proposed to overcome these problems. Firstly, according to the characteristics of the distributed ISAR, the multiple channel echoes of the nonuniform rotation target from different observation angles can be acquired. Then, by applying the MFT to the echo of each channel, the defocused problem of nonuniform rotation target which is inevitable by using the FT-based imaging method can be avoided. Finally, after preprocessing, scaling and rotation of all subimages, the noncoherent fusion image containing all the RCS information in all channels can be obtained. The accumulation coefficients of all subimages are calculated adaptively according to the their image qualities. Simulation and experimental data are used to validate the effectiveness of the proposed approach, and fusion image with improved recognizability can be obtained. Therefore, by using the distributed ISAR technique and MFT, subimages of high-maneuvering target from different observation angles can be obtained. Meanwhile, by employing the adaptive subimage fusion method, the RCS fluctuation can be alleviated and more recognizable final image can be obtained.

SNARE-mediated rapid lysosome fusion in membrane raft clustering and dysfunction of bovine coronary arterial endothelium

PubMed Central

Han, Wei-Qing; Xia, Min; Zhang, Chun; Zhang, Fan; Xu, Ming; Li, Ning-Jun

2011-01-01

The present study attempted to evaluate whether soluble N-ethylmaleimide-sensitive factor attachment protein receptors (SNAREs) mediate lysosome fusion in response to death receptor activation and contribute to membrane raft (MR) clustering and consequent endothelial dysfunction in coronary arterial endothelial cells. By immunohistochemical analysis, vesicle-associated membrane proteins 2 (VAMP-2, vesicle-SNAREs) were found to be abundantly expressed in the endothelium of bovine coronary arteries. Direct lysosome fusion monitoring by N-(3-triethylammoniumpropyl)-4-[4-(dibutylamino)styryl]pyridinium dibromide (FM1-43) quenching demonstrated that the inhibition of VAMP-2 with tetanus toxin or specific small interfering ribonucleic acid (siRNA) almost completely blocked lysosome fusion to plasma membrane induced by Fas ligand (FasL), a well-known MR clustering stimulator. The involvement of SNAREs was further confirmed by an increased interaction of VAMP-2 with a target-SNARE protein syntaxin-4 after FasL stimulation in coimmunoprecipitation analysis. Also, the inhibition of VAMP-2 with tetanus toxin or VAMP-2 siRNA abolished FasL-induced MR clustering, its colocalization with a NADPH oxidase unit gp91phox, and increased superoxide production. Finally, FasL-induced impairment of endothelium-dependent vasodilation was reversed by the treatment of bovine coronary arteries with tetanus toxin or VAMP-2 siRNA. VAMP-2 is critical to lysosome fusion in MR clustering, and this VAMP-2-mediated lysosome-MR signalosomes contribute to redox regulation of coronary endothelial function. PMID:21926345

Organotypic three-dimensional culture model of mesenchymal ...

EPA Pesticide Factsheets

Tissue fusion during early mammalian development requires coordination of multiple cell types, the extracellular matrix, and complex signaling pathways. Fusion events during processes including heart development, neural tube closure, and palatal fusion are dependent on signaling pathways elucidated using gene knockout mouse models. A broad analysis of literature, ToxRefDB, and ToxCast identified 63 chemicals that are related to cleft palate. However,the influence of these putative teratogens on human palatal fusion has not been studied due to the lack of in vitro models. We sought to engineer the stratified mesenchymal and epithelial structure of the developing palate in vitro via organotypic culture of human mesenchymal stem cell (hMSC) spheroids coated with a single layer of human primary epidermalkeratinocytes (hPEKp). hMSC spheroids exhibited uniform size over time (175 ± 21 µm mean diameter) proportional to starting cell density. Further, we developed a novel procedure to coat hMSC spheroids homogeneously with a single layer of hPEKp cells using a seeding ratio of 0.1-0.2 hPEKp per hMSC, and hMSC/hPEKp spheroids expressed mesenchymal markers (vim+, C044+, CD105+, CD34-) and epithelial markers (krt17+, itga6+) via qRT-PCR. Analysis of adverse outcome pathways related to palate fusion points to an EGF/TGFj33 switch that could be a target for cleft palate teratogens, and both egf and egfr were expressed by hMSC/hPEKp spheres. Finally, hMSCs and hPE

Characterization of the Mammalian CORVET and HOPS Complexes and Their Modular Restructuring for Endosome Specificity*

PubMed Central

van der Kant, Rik; Jonker, Caspar T. H.; Wijdeven, Ruud H.; Bakker, Jeroen; Janssen, Lennert; Klumperman, Judith; Neefjes, Jacques

2015-01-01

Trafficking of cargo through the endosomal system depends on endosomal fusion events mediated by SNARE proteins, Rab-GTPases, and multisubunit tethering complexes. The CORVET and HOPS tethering complexes, respectively, regulate early and late endosomal tethering and have been characterized in detail in yeast where their sequential membrane targeting and assembly is well understood. Mammalian CORVET and HOPS subunits significantly differ from their yeast homologues, and novel proteins with high homology to CORVET/HOPS subunits have evolved. However, an analysis of the molecular interactions between these subunits in mammals is lacking. Here, we provide a detailed analysis of interactions within the mammalian CORVET and HOPS as well as an additional endosomal-targeting complex (VIPAS39-VPS33B) that does not exist in yeast. We show that core interactions within CORVET and HOPS are largely conserved but that the membrane-targeting module in HOPS has significantly changed to accommodate binding to mammalian-specific RAB7 interacting lysosomal protein (RILP). Arthrogryposis-renal dysfunction-cholestasis (ARC) syndrome-associated mutations in VPS33B selectively disrupt recruitment to late endosomes by RILP or binding to its partner VIPAS39. Within the shared core of CORVET/HOPS, we find that VPS11 acts as a molecular switch that binds either CORVET-specific TGFBRAP1 or HOPS-specific VPS39/RILP thereby allowing selective targeting of these tethering complexes to early or late endosomes to time fusion events in the endo/lysosomal pathway. PMID:26463206

Conceptual design of a laser fusion power plant. Part I. An integrated facility

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

Not Available

This study is a new preliminary conceptual design and economic analysis of an inertial confinement fusion (ICF) power plant performed by Bechtel under the direction of Lawrence Livermore National Laboratory (LLNL). The purpose of a new conceptual design is to examine alternatives to the LLNL HYLIFE power plant and to incorporate information from the recent liquid metal cooled power plant conceptual design study (CDS) into the reactor system and balance of plant design. A key issue in the design of a laser fusion power plant is the degree of symmetry in the illumination of the target that will be requiredmore » for a proper burn. Because this matter is expected to remain unresolved for some time, another purpose of this study is to determine the effect of symmetry requirements on the total plant size, layout, and cost.« less

In-beam fissio study at JAEA for heavy element synthesis

NASA Astrophysics Data System (ADS)

Nishio, K.; Ikezoe, H.; Hofmann, S.; Ackermann, D.; Aritomo, Y.; Comas, V. F.; Düllmann, Ch. E.; Heinz, S.; Heredia, J. A.; Heßberger, F. P.; Hirose, K.; Khuyagbaatar, J.; Kindler, B.; Kojouharov, I.; Lommel, B.; Makii, M.; Mann, R.; Mitsuoka, S.; Nishinaka, I.; Ohtsuki, T.; Saro, S.; Schädel, M.; Popeko, A. G.; Türler, A.; Wakabayashi, Y.; Watanabe, Y.; Yakushev, A.; Yeremin, A.

2013-04-01

Fission fragment mass distributions were measured in the heavy-ion induced fission using 238U target nucleus. The mass distributions changed drastically with incident energy. The results are explained by a change of the ratio between fusion and qasifission with nuclear orientation. A calculation based on a fluctuation dissipation model reproduced the mass distributions and their incident energy dependence. Fusion probability was determined in the analysis. Evaporation residue cross sections were calculated with a statistical model in the reactions of 30Si+238U and 34S+238U using the obtained fusion probability in the entrance channel. The results agree with the measured cross sections of 263,264Sg and 267,268Hs, produced by 30Si+238U and 34S+238U, respectively. It is also suggested that the sub-barrier energies can be used for heavy element synthesis.

Comparison of the complications of traditional 12 cores transrectal prostate biopsy with image fusion guided transperineal prostate biopsy.

PubMed

Huang, Haifeng; Wang, Wei; Lin, Tingsheng; Zhang, Qing; Zhao, Xiaozhi; Lian, Huibo; Guo, Hongqian

2016-11-17

To compare the complications of traditional transrectal (TR) prostate biopsy and image fusion guided transperineal (TP) prostate biopsy in our center. Two hundred and fourty-two patients who underwent prostate biopsy from August 2014 to January 2015were reviewed. Among them, 144 patients underwent systematic 12-core transrectal ultrasonography (TRUS) guided prostate biopsy (TR approach) while 98 patients underwent free-hand transperineal targeted biopsy with TRUS and multi-parameter magnetic resonance imaging (mpMRI) fusion images (TP approach). The complications of the two groups were presented and a simple statistical analysis was performed to compare the two groups. The cohort of our study include242 patients, including 144 patients underwent TR biopsies while 98 patients underwentTP biopsies. There was no significant difference of major complications, including sepsis, bleeding and other complication requiring admissionbetween the two groups (P > 0.05). The incidence rate of infection and rectal bleeding in TR was much higher than TP (p < 0.05), but the incidence rate of perineal swelling in TP was much higher than TR (p < 0.05). There were no significant differences of minor complications including hematuria, lower urinary tract symptoms (LUTS), dysuria, and acuteurinary retention between the two groups (p > 0.05). The present study supports the safety of both techniques. Free-handTP targeted prostate biopsy with real-time fusion imaging of mpMRI and TR ultrasound is a good approach for prostate biopsy.

Synaptotagmin-mediated bending of the target membrane is a critical step in Ca2+-regulated fusion

PubMed Central

Hui, Enfu; Johnson, Colin P.; Yao, Jun; Dunning, F. Mark; Chapman, Edwin R.

2009-01-01

Summary Decades ago it was proposed that exocytosis involves invagination of the target membrane, resulting in a highly localized site of contact between the bilayers destined to fuse. The vesicle protein synaptotagmin-I (syt) bends membranes in response to Ca2+, but whether this drives localized invagination of the target membrane to accelerate fusion has not been determined; previous studies relied on reconstituted vesicles that were already highly curved and used mutations in syt that were not selective for membrane-bending activity. Here, we directly address this question by utilizing vesicles with different degrees of curvature. A tubulation-defective syt mutant was able to promote fusion between highly curved SNARE-bearing liposomes, but exhibited a marked loss of activity when the membranes were relatively flat. Moreover, bending of flat membranes by adding an N-BAR domain rescued the function of the tubulation-deficient syt mutant. Hence, syt-mediated membrane bending is a critical step in membrane fusion. PMID:19703397

High-Energy Space Propulsion Based on Magnetized Target Fusion

NASA Technical Reports Server (NTRS)

Thio, Y. C. F.; Landrum, D. B.; Freeze, B.; Kirkpatrick, R. C.; Gerrish, H.; Schmidt, G. R.

1999-01-01

Magnetized target fusion is an approach in which a magnetized target plasma is compressed inertially by an imploding material wall. A high energy plasma liner may be used to produce the required implosion. The plasma liner is formed by the merging of a number of high momentum plasma jets converging towards the center of a sphere where two compact toroids have been introduced. Preliminary 3-D hydrodynamics modeling results using the SPHINX code of Los Alamos National Laboratory have been very encouraging and confirm earlier theoretical expectations. The concept appears ready for experimental exploration and plans for doing so are being pursued. In this talk, we explore conceptually how this innovative fusion approach could be packaged for space propulsion for interplanetary travel. We discuss the generally generic components of a baseline propulsion concept including the fusion engine, high velocity plasma accelerators, generators of compact toroids using conical theta pinches, magnetic nozzle, neutron absorption blanket, tritium reprocessing system, shock absorber, magnetohydrodynamic generator, capacitor pulsed power system, thermal management system, and micrometeorite shields.

Nike Facility Diagnostics and Data Acquisition System

NASA Astrophysics Data System (ADS)

Chan, Yung; Aglitskiy, Yefim; Karasik, Max; Kehne, David; Obenschain, Steve; Oh, Jaechul; Serlin, Victor; Weaver, Jim

2013-10-01

The Nike laser-target facility is a 56-beam krypton fluoride system that can deliver 2 to 3 kJ of laser energy at 248 nm onto targets inside a two meter diameter vacuum chamber. Nike is used to study physics and technology issues related to laser direct-drive ICF fusion, including hydrodynamic and laser-plasma instabilities, material behavior at extreme pressures, and optical and x-ray diagnostics for laser-heated targets. A suite of laser and target diagnostics are fielded on the Nike facility, including high-speed, high-resolution x-ray and visible imaging cameras, spectrometers and photo-detectors. A centrally-controlled, distributed computerized data acquisition system provides robust data management and near real-time analysis feedback capability during target shots. Work supported by DOE/NNSA.

Method of making foam-encapsulated laser targets

DOEpatents

Rinde, James A.; Fulton, Fred J.

1977-01-01

Foam-encapsulated laser fusion targets are fabricated by suspending fusion fuel filled shells in a solution of cellulose acetate, extruding the suspension through a small orifice into a bath of ice water, soaking the thus formed shell containing cellulose acetate gel in the water to extract impurities, freezing the gel, and thereafter freeze-drying wherein water and solvents sublime and the gel structure solidifies into a low-density microcellular foam containing one or more encapsulated fuel-filled shells. The thus formed material is thereafter cut and mounted on a support to provide laser fusion targets containing a fuel-filled shell surrounded by foam having a thickness of 10 to 60 .mu.m, a cell size of less than 2 .mu.m, and density of 0.08 to 0.6.times.10.sup.3 kg/m.sup.3. Various configured foam-encapsulated targets capable of being made by the encapsulation method are illustrated.

Lead (Pb) Hohlraum: Target for Inertial Fusion Energy

PubMed Central

Ross, J. S.; Amendt, P.; Atherton, L. J.; Dunne, M.; Glenzer, S. H.; Lindl, J. D.; Meeker, D.; Moses, E. I.; Nikroo, A.; Wallace, R.

2013-01-01

Recent progress towards demonstrating inertial confinement fusion (ICF) ignition at the National Ignition Facility (NIF) has sparked wide interest in Laser Inertial Fusion Energy (LIFE) for carbon-free large-scale power generation. A LIFE-based fleet of power plants promises clean energy generation with no greenhouse gas emissions and a virtually limitless, widely available thermonuclear fuel source. For the LIFE concept to be viable, target costs must be minimized while the target material efficiency or x-ray albedo is optimized. Current ICF targets on the NIF utilize a gold or depleted uranium cylindrical radiation cavity (hohlraum) with a plastic capsule at the center that contains the deuterium and tritium fuel. Here we show a direct comparison of gold and lead hohlraums in efficiently ablating deuterium-filled plastic capsules with soft x rays. We report on lead hohlraum performance that is indistinguishable from gold, yet costing only a small fraction. PMID:23486285

Lead (Pb) hohlraum: target for inertial fusion energy.

PubMed

Ross, J S; Amendt, P; Atherton, L J; Dunne, M; Glenzer, S H; Lindl, J D; Meeker, D; Moses, E I; Nikroo, A; Wallace, R

2013-01-01

Recent progress towards demonstrating inertial confinement fusion (ICF) ignition at the National Ignition Facility (NIF) has sparked wide interest in Laser Inertial Fusion Energy (LIFE) for carbon-free large-scale power generation. A LIFE-based fleet of power plants promises clean energy generation with no greenhouse gas emissions and a virtually limitless, widely available thermonuclear fuel source. For the LIFE concept to be viable, target costs must be minimized while the target material efficiency or x-ray albedo is optimized. Current ICF targets on the NIF utilize a gold or depleted uranium cylindrical radiation cavity (hohlraum) with a plastic capsule at the center that contains the deuterium and tritium fuel. Here we show a direct comparison of gold and lead hohlraums in efficiently ablating deuterium-filled plastic capsules with soft x rays. We report on lead hohlraum performance that is indistinguishable from gold, yet costing only a small fraction.

Data fusion approach to threat assessment for radar resources management

NASA Astrophysics Data System (ADS)

Komorniczak, Wojciech; Pietrasinski, Jerzy; Solaiman, Basel

2002-03-01

The paper deals with the problem of the multifunction radar resources management. The problem consists of target/tasks ranking and tasks scheduling. The paper is focused on the target ranking, with the data fusion approach. The data from the radar (object's velocity, range, altitude, direction etc.), IFF system (Identification Friend or Foe) and ESM system (Electronic Support Measures - information concerning threat's electro - magnetic activities) is used to decide of the importance assignment for each detected target. The main problem consists of the multiplicity of various types of the input information. The information from the radar is of the probabilistic or ambiguous imperfection type and the IFF information is of evidential type. To take the advantage of these information sources the advanced data fusion system is necessary. The system should deal with the following situations: fusion of the evidential and fuzzy information, fusion of the evidential information and a'priori information. The paper describes the system which fuses the fuzzy and the evidential information without previous change to the same type of information. It is also described the proposal of using of the dynamic fuzzy qualifiers. The paper shows the results of the preliminary system's tests.

Proposed Generation and Compression of a Target Plasma for MTF

DTIC Science & Technology

1995-07-01

essential ingredient that has been implicit in the quest: a net energy gain. That is, they do not provide more fusion energy than the energy require...to establish the fusion conditions. This points to the primary motivation for the quest, a fusion energy production system. Such a system is

Magnetized Target Fusion Collaboration. Final report

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

Slough, John

Nuclear fusion has the potential to satisfy the prodigious power that the world will demand in the future, but it has yet to be harnessed as a practical energy source. The entry of fusion as a viable, competitive source of power has been stymied by the challenge of finding an economical way to provide for the confinement and heating of the plasma fuel. It is the contention here that a simpler path to fusion can be achieved by creating fusion conditions in a different regime at small scale (~ a few cm). One such program now under study, referred tomore » as Magnetized Target Fusion (MTF), is directed at obtaining fusion in this high energy density regime by rapidly compressing a compact toroidal plasmoid commonly referred to as a Field Reversed Configuration (FRC). To make fusion practical at this smaller scale, an efficient method for compressing the FRC to fusion gain conditions is required. In one variant of MTF a conducting metal shell is imploded electrically. This radially compresses and heats the FRC plasmoid to fusion conditions. The closed magnetic field in the target plasmoid suppresses the thermal transport to the confining shell, thus lowering the imploding power needed to compress the target. The undertaking described in this report was to provide a suitable target FRC, as well as a simple and robust method for inserting and stopping the FRC within the imploding liner. The FRC must also survive during the time it takes for the metal liner to compress the FRC target. The initial work at the UW was focused on developing adequate preionization and flux trapping that were found to be essential in past experiments for obtaining the density, flux and most critically, FRC lifetime required for MTF. The timescale for testing and development of such a source can be rapidly accelerated by taking advantage of a new facility funded by the Department of Energy. At this facility, two inductive plasma accelerators (IPA) were constructed and tested. Recent experiments with these IPAs have demonstrated the ability to rapidly form, accelerate and merge two hypervelocity FRCs into a compression chamber. The resultant FRC that was formed was hot (T{sub ion} ~ 400 eV), stationary, and stable with a configuration lifetime several times that necessary for the MTF liner experiments. The accelerator length was less than 1 meter, and the time from the initiation of formation to the establishment of the final equilibrium was less than 10 microseconds. With some modification, each accelerator can be made capable of producing FRCs suitable for the production of the target plasma for the MTF liner experiment. Based on the initial FRC merging/compression results, the design and methodology for an experimental realization of the target plasma for the MTF liner experiment can now be defined. The construction and testing of the key components for the formation of the target plasma at the Air Force Research Laboratory (AFRL) will be performed on the IPA experiment, now at MSNW. A high density FRC plasmoid will be formed and accelerated out of each IPA into a merging/compression chamber similar to the imploding liner at AFRL. The properties of the resultant FRC plasma (size, temperature, density, flux, lifetime) will be obtained. The process will be optimized, and a final design for implementation at AFRL will be carried out. When implemented at AFRL it is anticipated that the colliding/merging FRCs will then be compressed by the liner. In this manner it is hoped that ultimately a plasma with ion temperatures reaching the 10 keV range and fusion gain near unity can be obtained.« less

Polyvinyl alcohol coating of polystyrene inertial confinement fusion targets

NASA Technical Reports Server (NTRS)

Annamalai, P.; Lee, M. C.; Crawley, R. L.; Downs, R. L.

1985-01-01

An inertial confinement fusion (ICF) target made of polystyrene is first levitated in an acoustic field. The surface of the target is then etched using an appropriate solution (e.g., cyclohexane) to enhance the wetting characteristics. A specially prepared polyvinyl alcohol solution is atomized using an acoustic atomizer and deposited on the surface of the target. The solution is air dried to form a thin coating (2 microns) on the target (outside diameter of about 350-850 microns). Thicker coatings are obtained by repeated applications of the coating solutions. Preliminary results indicate that uniform coatings may be achievable on the targets with a background surface smoothness in the order of 1000 A.

Shock effects in particle beam fusion targets

NASA Astrophysics Data System (ADS)

Sweeney, M. A.; Perry, F. C.; Asay, J. R.; Widner, M. M.

1982-04-01

At Sandia National Laboratorics we are assessing the response of fusion target materials to shock loading with the particle beam accelerators HYDRA and PROTO I and the gas gun facility. Nonlinear shock-accelerated unstable growth of fabriction irregularities has been demonstrated, and jetting is found to occur in imploding targets because of asymmetric beam deposition. Cylindrical ion targets display an instability due either to beam or target nonuniformity. However, the data suggest targets with aspect ratios of 30 may implode stably. The first time- and space-resolved measurements of shock-induced vaporization have been made. A homogeneous mixed phase EOS model cannot adequately explain the results because of the kinetic effects of vapor formation and expansion.

Tyrosine kinase gene rearrangements in epithelial malignancies

PubMed Central

Shaw, Alice T.; Hsu, Peggy P.; Awad, Mark M.; Engelman, Jeffrey A.

2014-01-01

Chromosomal rearrangements that lead to oncogenic kinase activation are observed in many epithelial cancers. These cancers express activated fusion kinases that drive the initiation and progression of malignancy, and often have a considerable response to small-molecule kinase inhibitors, which validates these fusion kinases as ‘druggable’ targets. In this Review, we examine the aetiologic, pathogenic and clinical features that are associated with cancers harbouring oncogenic fusion kinases, including anaplastic lymphoma kinase (ALK), ROS1 and RET. We discuss the clinical outcomes with targeted therapies and explore strategies to discover additional kinases that are activated by chromosomal rearrangements in solid tumours. PMID:24132104

Antibody-cytokine fusion proteins for improving efficacy and safety of cancer therapy.

PubMed

Valedkarimi, Zahra; Nasiri, Hadi; Aghebati-Maleki, Leili; Majidi, Jafar

2017-11-01

Cytokines are key players in the regulation of immune responses both in physiological and pathological states. A number of cytokines have been evaluated in clinical trials and shown promising results in the treatment of different malignancies. Despite this, the clinical application of these molecules may be plagued by undesirable side effects The development of recombinant antibody-cytokine fusion proteins, which offer a means for target delivery of cytokines toward the tumor site, has significantly improved the therapeutic index of these immunomodulatory molecules. Selective tumor localization is provided by the monoclonal antibody component of the fusion protein that binds to the molecules present on the surface of tumor cells or accumulated preferentially in the diseased site. In this manner, the cytokine element is specifically located at the tumor site and can stimulate immune cells with appropriate cytokine receptors. Over the recent years, several antibody-cytokine fusion proteins have been developed with the capacity to target a wide variety of cancers whose application, in some cases, has led to complete rejection of the tumor. These findings support the notion that antibody-cytokine fusion proteins represent huge potential for cancer therapy. This review presents an overview of the advances made in the field of targeted cytokine delivery, which is made possible by genetically engineering antibody-cytokine fusion proteins. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Inhibition of Nipah Virus Infectin In Vivo: Targeting an Early Stage of Paramyxovirus Fusion Activation during Viral Entry

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

M Porotto; B Rockx; C Yokoyama

2011-12-31

In the paramyxovirus cell entry process, receptor binding triggers conformational changes in the fusion protein (F) leading to viral and cellular membrane fusion. Peptides derived from C-terminal heptad repeat (HRC) regions in F have been shown to inhibit fusion by preventing formation of the fusogenic six-helix bundle. We recently showed that the addition of a cholesterol group to HRC peptides active against Nipah virus targets these peptides to the membrane where fusion occurs, dramatically increasing their antiviral effect. In this work, we report that unlike the untagged HRC peptides, which bind to the postulated extended intermediate state bridging the viralmore » and cell membranes, the cholesterol tagged HRC-derived peptides interact with F before the fusion peptide inserts into the target cell membrane, thus capturing an earlier stage in the F-activation process. Furthermore, we show that cholesterol tagging renders these peptides active in vivo: the cholesterol-tagged peptides cross the blood brain barrier, and effectively prevent and treat in an established animal model what would otherwise be fatal Nipah virus encephalitis. The in vivo efficacy of cholesterol-tagged peptides, and in particular their ability to penetrate the CNS, suggests that they are promising candidates for the prevention or therapy of infection by Nipah and other lethal paramyxoviruses.« less

Signaling networks in TMPRSS2-ERG positive prostate cancers: Do we need a Pied Piper or sharpshooter to deal with "at large" fused oncoprotein.

PubMed

Lin, X; Qureshi, M Z; Romero, M A; Yaylim, I; Arif, S; Ucak, I; Fayyaz, S; Farooqi, A A; Mansoor, Q; Ismail, M

2017-02-28

Overwhelmingly increasing scientific evidence has provided near complete resolution of prostate cancer landscape and it is now more understandable that wide ranging factors underlies its development and progression. Increasingly it is being realized that genetic/epigenetic factors, Intra-tumoral and inter-tumoral heterogeneity, loss of apoptosis, dysregulations of spatio-temporally controlled signaling cascades, Darwinian evolution in response to therapeutic pressures play instrumental role in prostate carcinogenesis. Moreover, multi-directional patterns of spread between primary tumors and metastatic sites have also been studied extensively in prostate cancer. Research over the years has gradually and systematically revealed closer association between tumor phenotype and type of gene fusion. Latest developments in deep sequencing technologies have shown that gene fusions originate in a non-random, cell type dependent manner and are much more frequent than previously surmised. These findings enabled sub-classification and categorization of seemingly identical diseases. Furthermore, research methodologies have shown that many gene fusions inform us about risk stratification and many chimeric proteins encoded by the fused genes are being studied as drug target/s. We partition this multi-component review into the molecular basis of formation of fusion transcripts, how protein network is regulated in fusion positive prostate cancer cells and therapeutic strategies which are currently being investigated to efficiently target fusion transcript and its protein product.

Automated target classification in high resolution dual frequency sonar imagery

NASA Astrophysics Data System (ADS)

Aridgides, Tom; Fernández, Manuel

2007-04-01

An improved computer-aided-detection / computer-aided-classification (CAD/CAC) processing string has been developed. The classified objects of 2 distinct strings are fused using the classification confidence values and their expansions as features, and using "summing" or log-likelihood-ratio-test (LLRT) based fusion rules. The utility of the overall processing strings and their fusion was demonstrated with new high-resolution dual frequency sonar imagery. Three significant fusion algorithm improvements were made. First, a nonlinear 2nd order (Volterra) feature LLRT fusion algorithm was developed. Second, a Box-Cox nonlinear feature LLRT fusion algorithm was developed. The Box-Cox transformation consists of raising the features to a to-be-determined power. Third, a repeated application of a subset feature selection / feature orthogonalization / Volterra feature LLRT fusion block was utilized. It was shown that cascaded Volterra feature LLRT fusion of the CAD/CAC processing strings outperforms summing, baseline single-stage Volterra and Box-Cox feature LLRT algorithms, yielding significant improvements over the best single CAD/CAC processing string results, and providing the capability to correctly call the majority of targets while maintaining a very low false alarm rate. Additionally, the robustness of cascaded Volterra feature fusion was demonstrated, by showing that the algorithm yields similar performance with the training and test sets.

Identification of a Region in the Stalk Domain of the Nipah Virus Receptor Binding Protein That Is Critical for Fusion Activation

PubMed Central

Talekar, Aparna; DeVito, Ilaria; Salah, Zuhair; Palmer, Samantha G.; Chattopadhyay, Anasuya; Rose, John K.; Xu, Rui; Wilson, Ian A.; Moscona, Anne

2013-01-01

Paramyxoviruses, including the emerging lethal human Nipah virus (NiV) and the avian Newcastle disease virus (NDV), enter host cells through fusion of the viral and target cell membranes. For paramyxoviruses, membrane fusion is the result of the concerted action of two viral envelope glycoproteins: a receptor binding protein and a fusion protein (F). The NiV receptor binding protein (G) attaches to ephrin B2 or B3 on host cells, whereas the corresponding hemagglutinin-neuraminidase (HN) attachment protein of NDV interacts with sialic acid moieties on target cells through two regions of its globular domain. Receptor-bound G or HN via its stalk domain triggers F to undergo the conformational changes that render it competent to mediate fusion of the viral and cellular membranes. We show that chimeric proteins containing the NDV HN receptor binding regions and the NiV G stalk domain require a specific sequence at the connection between the head and the stalk to activate NiV F for fusion. Our findings are consistent with a general mechanism of paramyxovirus fusion activation in which the stalk domain of the receptor binding protein is responsible for F activation and a specific connecting region between the receptor binding globular head and the fusion-activating stalk domain is required for transmitting the fusion signal. PMID:23903846

A framework for small infrared target real-time visual enhancement

NASA Astrophysics Data System (ADS)

Sun, Xiaoliang; Long, Gucan; Shang, Yang; Liu, Xiaolin

2015-03-01

This paper proposes a framework for small infrared target real-time visual enhancement. The framework is consisted of three parts: energy accumulation for small infrared target enhancement, noise suppression and weighted fusion. Dynamic programming based track-before-detection algorithm is adopted in the energy accumulation to detect the target accurately and enhance the target's intensity notably. In the noise suppression, the target region is weighted by a Gaussian mask according to the target's Gaussian shape. In order to fuse the processed target region and unprocessed background smoothly, the intensity in the target region is treated as weight in the fusion. Experiments on real small infrared target images indicate that the framework proposed in this paper can enhances the small infrared target markedly and improves the image's visual quality notably. The proposed framework outperforms tradition algorithms in enhancing the small infrared target, especially for image in which the target is hardly visible.

Magnetized Target Fusion: Prospects for Low-Cost Fusion Energy

NASA Technical Reports Server (NTRS)

Siemon, Richard E.; Turchi, Peter J.; Barnes, Daniel C.; Degnan, James; Parks, Paul; Ryutov, Dmitri D.; Thio, Y. C. Francis; Schafer, Charles (Technical Monitor)

2001-01-01

Magnetized Target Fusion (MTF) has attracted renewed interest in recent years because it has the potential to resolve one of the major problems with conventional fusion energy research - the high cost of facilities to do experiments and in general develop practical fusion energy. The requirement for costly facilities can be traced to fundamental constraints. The Lawson condition implies large system size in the case of conventional magnetic confinement, or large heating power in the case of conventional inertial confinement. The MTF approach is to use much higher fuel density than with conventional magnetic confinement (corresponding to megabar pressures), which results in a much-reduced system size to achieve Lawson conditions. Intrinsically the system must be pulsed because the pressures exceed the strength of any known material. To facilitate heating the fuel (or "target") to thermonuclear conditions with a high-power high-intensity source of energy, magnetic fields are used to insulate the high-pressure fuel from material surroundings (thus "magnetized target"). Because of magnetic insulation, the required heating power intensity is reduced by many orders of magnitude compared to conventional inertial fusion, even with relatively poor energy confinement in the magnetic field, such as that characterized by Bohm diffusion. In this paper we show semi-quantitatively why MTF-should allow fusion energy production without costly facilities within the same generally accepted physical constraints used for conventional magnetic and inertial fusion. We also briefly discuss potential applications of this technology ranging from nuclear rockets for space propulsion to a practical commercial energy system. Finally, we report on the exploratory research underway, and the interesting physics issues that arise in the MTF regime of parameters. Experiments at Los Alamos are focused on formation of a suitable plasma target for compression, utilizing the knowledge base for compact toroids called Field-Reversed Configurations. As reported earlier, it appears that the existing pulsed-power Shiva Star facility at the Air Force Research Laboratory in Albuquerque, NM can satisfy the heating requirements by means of imploding a thin metal cylinder (called a "liner") surrounding an FRC of the type presently being developed. The proposed next step is an integrated liner-on-plasma experiment in which an FRC would be heated to 10 keV by the imploding liner.

Block Ignition Inertial Confinement Fusion (ICF) with Condensed Matter Cluster Type Targets for p-B11 Powered Space Propulsion

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

Miley, George H.; Hora, H.; Badziak, J.

The use of laser-driven Inertial Confinement Fusion (ICF) for space propulsion has been the subject of several earlier conceptual design studies, (see: Orth, 1998; and other references therein). However, these studies were based on older ICF technology using either 'direct' or 'in-direct x-ray driven' type target irradiation. Important new directions have opened for laser ICF in recent years following the development of 'chirped' lasers capable of ultra short pulses with powers of TW up to few PW which leads to the concept of 'fast ignition (FI)' to achieve higher energy gains from target implosions. In a recent publication the authorsmore » showed that use of a modified type of FI, termed 'block ignition' (Miley et al., 2008), could meet many of the requirements anticipated (but not then available) by the designs of the Vehicle for Interplanetary Space Transport Applications (VISTA) ICF fusion propulsion ship (Orth, 2008) for deep space missions. Subsequently the first author devised and presented concepts for imbedding high density condensed matter 'clusters' of deuterium into the target to obtain ultra high local fusion reaction rates (Miley, 2008). Such rates are possible due to the high density of the clusters (over an order of magnitude above cryogenic deuterium). Once compressed by the implosion, the yet higher density gives an ultra high reaction rate over the cluster volume since the fusion rate is proportional to the square of the fuel density. Most recently, a new discovery discussed here indicates that the target matrix could be composed of B{sup 11} with proton clusters imbedded. This then makes p-B{sup 11} fusion practical, assuming all of the physics issues such as stability of the clusters during compression are resolved. Indeed, p-B{sup 11} power is ideal for fusion propulsion since it has a minimum of unwanted side products while giving most of the reaction energy to energetic alpha particles which can be directed into an exhaust (propulsion) nozzle. Power plants using p-B{sup 11} have been discussed for such applications before, but prior designs face formidable physics/technology issues, largely overcome with the present approach.« less

Dynamical approach to heavy-ion induced fusion using actinide target

NASA Astrophysics Data System (ADS)

Aritomo, Y.; Hagino, K.; Chiba, S.; Nishio, K.

2012-10-01

To treat heavy-ion reactions using actinide target nucleus, we propose a model which takes into account the coupling to the collective states of interacting nuclei in the penetration of the Coulomb barrier and the dynamical evolution of nuclear shape from the contact configuration. A fluctuation-dissipation model (Langevin equation) was applied in the dynamical calculation, where effect of nuclear orientation at the initial impact on the prolately deformed target nucleus was considered. Using this model, we analyzed the experimental data for the mass distribution of fission fragments (MDFF) in the reaction of 36S+238U at several incident energies. Fusion-fission, quasifission and deep-quasi-fission are separated as different trajectories on the potential energy surface. We estimated the fusion cross section of the reaction.

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.

Data fusion for target tracking and classification with wireless sensor network

NASA Astrophysics Data System (ADS)

Pannetier, Benjamin; Doumerc, Robin; Moras, Julien; Dezert, Jean; Canevet, Loic

2016-10-01

In this paper, we address the problem of multiple ground target tracking and classification with information obtained from a unattended wireless sensor network. A multiple target tracking (MTT) algorithm, taking into account road and vegetation information, is proposed based on a centralized architecture. One of the key issue is how to adapt classical MTT approach to satisfy embedded processing. Based on track statistics, the classification algorithm uses estimated location, velocity and acceleration to help to classify targets. The algorithms enables tracking human and vehicles driving both on and off road. We integrate road or trail width and vegetation cover, as constraints in target motion models to improve performance of tracking under constraint with classification fusion. Our algorithm also presents different dynamic models, to palliate the maneuvers of targets. The tracking and classification algorithms are integrated into an operational platform (the fusion node). In order to handle realistic ground target tracking scenarios, we use an autonomous smart computer deposited in the surveillance area. After the calibration step of the heterogeneous sensor network, our system is able to handle real data from a wireless ground sensor network. The performance of system is evaluated in a real exercise for intelligence operation ("hunter hunt" scenario).

Application of an E. coli signal sequence as a versatile inclusion body tag.

PubMed

Jong, Wouter S P; Vikström, David; Houben, Diane; van den Berg van Saparoea, H Bart; de Gier, Jan-Willem; Luirink, Joen

2017-03-21

Heterologous protein production in Escherichia coli often suffers from bottlenecks such as proteolytic degradation, complex purification procedures and toxicity towards the expression host. Production of proteins in an insoluble form in inclusion bodies (IBs) can alleviate these problems. Unfortunately, the propensity of heterologous proteins to form IBs is variable and difficult to predict. Hence, fusing the target protein to an aggregation prone polypeptide or IB-tag is a useful strategy to produce difficult-to-express proteins in an insoluble form. When screening for signal sequences that mediate optimal targeting of heterologous proteins to the periplasmic space of E. coli, we observed that fusion to the 39 amino acid signal sequence of E. coli TorA (ssTorA) did not promote targeting but rather directed high-level expression of the human proteins hEGF, Pla2 and IL-3 in IBs. Further analysis revealed that ssTorA even mediated IB formation of the highly soluble endogenous E. coli proteins TrxA and MBP. The ssTorA also induced aggregation when fused to the C-terminus of target proteins and appeared functional as IB-tag in E. coli K-12 as well as B strains. An additive effect on IB-formation was observed upon fusion of multiple ssTorA sequences in tandem, provoking almost complete aggregation of TrxA and MBP. The ssTorA-moiety was successfully used to produce the intrinsically unstable hEGF and the toxic fusion partner SymE, demonstrating its applicability as an IB-tag for difficult-to-express and toxic proteins. We present proof-of-concept for the use of ssTorA as a small, versatile tag for robust E. coli-based expression of heterologous proteins in IBs.

A Conserved Region between the Heptad Repeats of Paramyxovirus Fusion Proteins is Critical for Proper F Protein Folding†

PubMed Central

Gardner, Amanda E.; Martin, Kimberly L.; Dutch, Rebecca E.

2008-01-01

Paramyxoviruses are a diverse family which utilizes a fusion (F) protein to enter cells via fusion of the viral lipid bilayer with a target cell membrane. Although certain regions of F are known to play critical roles in membrane fusion, the function of much of the protein remains unclear. Sequence alignment of a set of paramyxovirus F proteins and analysis utilizing Block Maker identified a region of conserved amino acid sequence in a large domain between the heptad repeats of F1, designated CBF1. We employed site-directed mutagenesis to analyze the function of completely conserved residues of CBF1 in both the simian virus 5 (SV5) and Hendra virus F proteins. The majority of CBF1 point mutants were deficient in homotrimer formation, proteolytic processing, and transport to the cell surface. For some SV5 F mutants, proteolytic cleavage and surface expression could be restored by expression at 30°C, and varying levels of fusion promotion were observed at this temperature. In addition, the mutant SV5 F V402A displayed a hyperfusogenic phenotype at both 30°C and 37°C, indicating this mutation allows for efficient fusion with only an extremely small amount of cleaved, active protein. The recently published prefusogenic structure of PIV5/SV5 F [Yin, H.S., et al. (2006) Nature 439, 38–44] indicates that residues within and flanking CBF1 interact with the fusion peptide domain. Together, these data suggest that CBF1-fusion peptide interactions are critical for the initial folding of paramyxovirus F proteins from across this important viral family, and can also modulate subsequent membrane fusion promotion. PMID:17417875

Kinase impact assessment in the landscape of fusion genes that retain kinase domains: a pan-cancer study

PubMed Central

Kim, Pora; Jia, Peilin; Zhao, Zhongming

2018-01-01

Abstract Assessing the impact of kinase in gene fusion is essential for both identifying driver fusion genes (FGs) and developing molecular targeted therapies. Kinase domain retention is a crucial factor in kinase fusion genes (KFGs), but such a systematic investigation has not been done yet. To this end, we analyzed kinase domain retention (KDR) status in chimeric protein sequences of 914 KFGs covering 312 kinases across 13 major cancer types. Based on 171 kinase domain-retained KFGs including 101 kinases, we studied their recurrence, kinase groups, fusion partners, exon-based expression depth, short DNA motifs around the break points and networks. Our results, such as more KDR than 5′-kinase fusion genes, combinatorial effects between 3′-KDR kinases and their 5′-partners and a signal transduction-specific DNA sequence motif in the break point intronic sequences, supported positive selection on 3′-kinase fusion genes in cancer. We introduced a degree-of-frequency (DoF) score to measure the possible number of KFGs of a kinase. Interestingly, kinases with high DoF scores tended to undergo strong gene expression alteration at the break points. Furthermore, our KDR gene fusion network analysis revealed six of the seven kinases with the highest DoF scores (ALK, BRAF, MET, NTRK1, NTRK3 and RET) were all observed in thyroid carcinoma. Finally, we summarized common features of ‘effective’ (highly recurrent) kinases in gene fusions such as expression alteration at break point, redundant usage in multiple cancer types and 3′-location tendency. Collectively, our findings are useful for prioritizing driver kinases and FGs and provided insights into KFGs’ clinical implications. PMID:28013235

Screening Fusion Tags for Improved Recombinant Protein Expression in E. coli with the Expresso® Solubility and Expression Screening System.

PubMed

Steinmetz, Eric J; Auldridge, Michele E

2017-11-01

The simplicity, speed, and low cost of bacterial culture make E. coli the system of choice for most initial trials of recombinant protein expression. However, many heterologous proteins are either poorly expressed in bacteria, or are produced as incorrectly folded, insoluble aggregates that lack the activity of the native protein. In many cases, fusion to a partner protein can allow for improved expression and/or solubility of a difficult target protein. Although several different fusion partners have gained favor, none are universally effective, and identifying the one that best improves soluble expression of a given target protein is an empirical process. This unit presents a strategy for parallel screening of fusion partners for enhanced expression or solubility. The Expresso® Solubility and Expression Screening System includes a panel of seven distinct fusion partners and utilizes an extremely simple cloning strategy to enable rapid screening and identification of the most effective fusion partner. © 2017 by John Wiley & Sons, Inc. Copyright © 2017 John Wiley & Sons, Inc.

Distinct Requirements for HIV-Cell Fusion and HIV-mediated Cell-Cell Fusion*

PubMed Central

Kondo, Naoyuki; Marin, Mariana; Kim, Jeong Hwa; Desai, Tanay M.; Melikyan, Gregory B.

2015-01-01

Whether HIV-1 enters cells by fusing with the plasma membrane or with endosomes is a subject of active debate. The ability of HIV-1 to mediate fusion between adjacent cells, a process referred to as “fusion-from-without” (FFWO), shows that this virus can fuse with the plasma membrane. To compare FFWO occurring at the cell surface with HIV-cell fusion through a conventional entry route, we designed an experimental approach that enabled the measurements of both processes in the same sample. The following key differences were observed. First, a very small fraction of viruses fusing with target cells participated in FFWO. Second, whereas HIV-1 fusion with adherent cells was insensitive to actin inhibitors, post-CD4/coreceptor binding steps during FFWO were abrogated. A partial dependence of HIV-cell fusion on actin remodeling was observed in CD4+ T cells, but this effect appeared to be due to the actin dependence of virus uptake. Third, deletion of the cytoplasmic tail of HIV-1 gp41 dramatically enhanced the ability of the virus to promote FFWO, while having a modest effect on virus-cell fusion. Distinct efficiencies and actin dependences of FFWO versus HIV-cell fusion are consistent with the notion that, except for a minor fraction of particles that mediate fusion between the plasma membranes of adjacent cells, HIV-1 enters through an endocytic pathway. We surmise, however, that cell-cell contacts enabling HIV-1 fusion with the plasma membrane could be favored at the sites of high density of target cells, such as lymph nodes. PMID:25589785

Label fusion based brain MR image segmentation via a latent selective model

NASA Astrophysics Data System (ADS)

Liu, Gang; Guo, Xiantang; Zhu, Kai; Liao, Hengxu

2018-04-01

Multi-atlas segmentation is an effective approach and increasingly popular for automatically labeling objects of interest in medical images. Recently, segmentation methods based on generative models and patch-based techniques have become the two principal branches of label fusion. However, these generative models and patch-based techniques are only loosely related, and the requirement for higher accuracy, faster segmentation, and robustness is always a great challenge. In this paper, we propose novel algorithm that combines the two branches using global weighted fusion strategy based on a patch latent selective model to perform segmentation of specific anatomical structures for human brain magnetic resonance (MR) images. In establishing this probabilistic model of label fusion between the target patch and patch dictionary, we explored the Kronecker delta function in the label prior, which is more suitable than other models, and designed a latent selective model as a membership prior to determine from which training patch the intensity and label of the target patch are generated at each spatial location. Because the image background is an equally important factor for segmentation, it is analyzed in label fusion procedure and we regard it as an isolated label to keep the same privilege between the background and the regions of interest. During label fusion with the global weighted fusion scheme, we use Bayesian inference and expectation maximization algorithm to estimate the labels of the target scan to produce the segmentation map. Experimental results indicate that the proposed algorithm is more accurate and robust than the other segmentation methods.

Magnetic resonance imaging-ultrasound fusion biopsy for prediction of final prostate pathology.

PubMed

Le, Jesse D; Stephenson, Samuel; Brugger, Michelle; Lu, David Y; Lieu, Patricia; Sonn, Geoffrey A; Natarajan, Shyam; Dorey, Frederick J; Huang, Jiaoti; Margolis, Daniel J A; Reiter, Robert E; Marks, Leonard S

2014-11-01

We explored the impact of magnetic resonance imaging-ultrasound fusion prostate biopsy on the prediction of final surgical pathology. A total of 54 consecutive men undergoing radical prostatectomy at UCLA after fusion biopsy were included in this prospective, institutional review board approved pilot study. Using magnetic resonance imaging-ultrasound fusion, tissue was obtained from a 12-point systematic grid (mapping biopsy) and from regions of interest detected by multiparametric magnetic resonance imaging (targeted biopsy). A single radiologist read all magnetic resonance imaging, and a single pathologist independently rereviewed all biopsy and whole mount pathology, blinded to prior interpretation and matched specimen. Gleason score concordance between biopsy and prostatectomy was the primary end point. Mean patient age was 62 years and median prostate specific antigen was 6.2 ng/ml. Final Gleason score at prostatectomy was 6 (13%), 7 (70%) and 8-9 (17%). A tertiary pattern was detected in 17 (31%) men. Of 45 high suspicion (image grade 4-5) magnetic resonance imaging targets 32 (71%) contained prostate cancer. The per core cancer detection rate was 20% by systematic mapping biopsy and 42% by targeted biopsy. The highest Gleason pattern at prostatectomy was detected by systematic mapping biopsy in 54%, targeted biopsy in 54% and a combination in 81% of cases. Overall 17% of cases were upgraded from fusion biopsy to final pathology and 1 (2%) was downgraded. The combination of targeted biopsy and systematic mapping biopsy was needed to obtain the best predictive accuracy. In this pilot study magnetic resonance imaging-ultrasound fusion biopsy allowed for the prediction of final prostate pathology with greater accuracy than that reported previously using conventional methods (81% vs 40% to 65%). If confirmed, these results will have important clinical implications. Copyright © 2014 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

Proton spectra diagnostics for shock-compression studies

NASA Astrophysics Data System (ADS)

Welch, D. R.; Harris, D. B.; Bennish, A. H.; Miley, G. H.

1984-12-01

The energy spectra of fusion products escaping long-pulse-length laser-imploded deuterium-tritium filled glass microballoons have been measured with a time-of-flight spectrometer. The D(d,p)T reaction proton energy spectra showed two distinct peaks, indicating two burn phases in the target. The first burn phase is attributed to a spherically converging shock, while the second is attributed to subsequent compression heating. The analysis of these spectra provides the first conclusive proof of significant compression yields in these targets, where approximately half of the yield occurs during the compression burn phase.

CDCC calculations of fusion of 6Li with targets 144Sm and 154Sm: effect of resonance states

NASA Astrophysics Data System (ADS)

Gómez Camacho, A.; Lubian, J.; Zhang, H. Q.; Zhou, Shan-Gui

2017-12-01

Continuum Discretized Coupled-Channel (CDCC) model calculations of total, complete and incomplete fusion cross sections for reactions of the weakly bound 6Li with 144,154Sm targets at energies around the Coulomb barrier are presented. In the cluster structure frame of 6Li→α+d, short-range absorption potentials are considered for the interactions between the ground state of the projectile 6Li and α-d fragments with the target. In order to separately calculate complete and incomplete fusion and to reduce double-counting, the corresponding absorption potentials are chosen to be of different range. Couplings to low-lying excited states 2+, 3- of 144Sm and 2+, 4+ of 154Sm are included. So, the effect on total fusion from the excited states of the target is investigated. Similarly, the effect on fusion due to couplings to resonance breakup states of 6Li, namely, l=2, J π =3+,2+,1+ is also calculated. The latter effect is determined by using two approaches, (a) by considering only resonance state couplings and (b) by omitting these states from the full discretized energy space. Among other things, it is found that both resonance and non-resonance continuum breakup couplings produce fusion suppression at all the energies considered. A. Gómez Camacho from CONACYT, México, J. Lubian from CNPq, FAPERJ, Pronex, Brazil. S.G.Z was partly supported by the NSF of China (11120101005, 11275248, 11525524, 11621131001, 11647601, 11711540016), 973 Program of China (2013CB834400) and the Key Research Program of Frontier Sciences of CAS. H.Q.Z. from NSF China (11375266)

A generic screening platform for inhibitors of virus induced cell fusion using cellular electrical impedance

PubMed Central

Watterson, Daniel; Robinson, Jodie; Chappell, Keith J.; Butler, Mark S.; Edwards, David J.; Fry, Scott R.; Bermingham, Imogen M.; Cooper, Matthew A.; Young, Paul R.

2016-01-01

Fusion of the viral envelope with host cell membranes is an essential step in the life cycle of all enveloped viruses. Despite such a clear target for antiviral drug development, few anti-fusion drugs have progressed to market. One significant hurdle is the absence of a generic, high-throughput, reproducible fusion assay. Here we report that real time, label-free measurement of cellular electrical impedance can quantify cell-cell fusion mediated by either individually expressed recombinant viral fusion proteins, or native virus infection. We validated this approach for all three classes of viral fusion and demonstrated utility in quantifying fusion inhibition using antibodies and small molecule inhibitors specific for dengue virus and respiratory syncytial virus. PMID:26976324

Magnetic resonance imaging-transectal ultrasound image-fusion biopsies accurately characterize the index tumor: correlation with step-sectioned radical prostatectomy specimens in 135 patients.

PubMed

Baco, Eduard; Ukimura, Osamu; Rud, Erik; Vlatkovic, Ljiljana; Svindland, Aud; Aron, Manju; Palmer, Suzanne; Matsugasumi, Toru; Marien, Arnaud; Bernhard, Jean-Christophe; Rewcastle, John C; Eggesbø, Heidi B; Gill, Inderbir S

2015-04-01

Prostate biopsies targeted by elastic fusion of magnetic resonance (MR) and three-dimensional (3D) transrectal ultrasound (TRUS) images may allow accurate identification of the index tumor (IT), defined as the lesion with the highest Gleason score or the largest volume or extraprostatic extension. To determine the accuracy of MR-TRUS image-fusion biopsy in characterizing ITs, as confirmed by correlation with step-sectioned radical prostatectomy (RP) specimens. Retrospective analysis of 135 consecutive patients who sequentially underwent pre-biopsy MR, MR-TRUS image-fusion biopsy, and robotic RP at two centers between January 2010 and September 2013. Image-guided biopsies of MR-suspected IT lesions were performed with tracking via real-time 3D TRUS. The largest geographically distinct cancer focus (IT lesion) was independently registered on step-sectioned RP specimens. A validated schema comprising 27 regions of interest was used to identify the IT center location on MR images and in RP specimens, as well as the location of the midpoint of the biopsy trajectory, and variables were correlated. The concordance between IT location on biopsy and RP specimens was 95% (128/135). The coefficient for correlation between IT volume on MRI and histology was r=0.663 (p<0.001). The maximum cancer core length on biopsy was weakly correlated with RP tumor volume (r=0.466, p<0.001). The concordance of primary Gleason pattern between targeted biopsy and RP specimens was 90% (115/128; κ=0.76). The study limitations include retrospective evaluation of a selected patient population, which limits the generalizability of the results. Use of MR-TRUS image fusion to guide prostate biopsies reliably identified the location and primary Gleason pattern of the IT lesion in >90% of patients, but showed limited ability to predict cancer volume, as confirmed by step-sectioned RP specimens. Biopsies targeted using magnetic resonance images combined with real-time three-dimensional transrectal ultrasound allowed us to reliably identify the spatial location of the most important tumor in prostate cancer and characterize its aggressiveness. Copyright © 2014 European Association of Urology. Published by Elsevier B.V. All rights reserved.

Parametric PET/MR Fusion Imaging to Differentiate Aggressive from Indolent Primary Prostate Cancer with Application for Image-Guided Prostate Cancer Biopsies

DTIC Science & Technology

2013-10-01

AD_________________ Award Number: W81XWH-12-1-0597 TITLE: Parametric PET /MR Fusion Imaging to...Parametric PET /MR Fusion Imaging to Differentiate Aggressive from Indolent Primary Prostate Cancer with Application for Image-Guided Prostate Cancer Biopsies...The study investigates whether fusion PET /MRI imaging with 18F-choline PET /CT and diffusion-weighted MRI can be successfully applied to target prostate

A Unique Opportunity to Test Whether Cell Fusion is a Mechanism of Breast Cancer Metastasis

DTIC Science & Technology

2013-07-01

populations. Last cycle we optimized electroporation conditions for T47D and human mesenchymal stem cell populations and this cycle we have improved our...specific receptor-ligand interactions necessary for cell fusion, to produce a target for drug therapy. Post-fusion events might also be investigated...new tools for the study of the complex processes of cell fusion. The inducible bipartite nature of these strategies assures the accurate

FGFR1/3 tyrosine kinase fusions define a unique molecular subtype of non-small cell lung cancer.

PubMed

Wang, Rui; Wang, Lei; Li, Yuan; Hu, Haichuan; Shen, Lei; Shen, Xuxia; Pan, Yunjian; Ye, Ting; Zhang, Yang; Luo, Xiaoyang; Zhang, Yiliang; Pan, Bin; Li, Bin; Li, Hang; Zhang, Jie; Pao, William; Ji, Hongbin; Sun, Yihua; Chen, Haiquan

2014-08-01

The fibroblast growth factor receptor (FGFR)-3 fusion genes have been recently demonstrated in a subset of non-small cell lung cancer (NSCLC). To aid in identification and treatment of these patients, we examined the frequency, clinicopathologic characteristics, and treatment outcomes of patients who had NSCLC with or without FGFR fusions. Fourteen known FGFR fusion variants, including FGFR1, FGFR2, and FGFR3, were detected by RT-PCR and verified by direct sequencing in 1,328 patients with NSCLC. All patients were also analyzed for mutations in EGFR, KRAS, HER2, BRAF, ALK, RET, and ROS1. Clinical characteristics, including age, sex, smoking status, stage, subtypes of lung adenocarcinoma, relapse-free survival, and overall survival, were collected. Of 1,328 tumors screened, two (0.2%) were BAG4-FGFR1 fusion and 15 (1.1%) were FGFR3-TACC3 fusion. Six of 1,016 patients with lung adenocarcinoma were FGFR3-TACC3 fusions and 11 of 312 lung squamous cell carcinoma harbored BAG4-FGFR1 or FGFR3-TACC3 fusions. Compared with the FGFR fusion-negative group, patients with FGFR fusions were more likely to be smokers (94.1%, 16 of 17 patients, P < 0.001), significantly associated with larger tumor (>3 cm; 88.2%, 15 of 17 patients, P < 0.001) and with a tendency to be more poorly differentiated (53.9%, nine of 17 patients, P = 0.095). FGFR fusions define a molecular subset of NSCLC with distinct clinical characteristics. FGFR is a druggable target and patients with FGFR fusions may benefit from FGFR-targeted therapy, which needs further clinical investigation. ©2014 American Association for Cancer Research.

Strong FGFR3 staining is a marker for FGFR3 fusions in diffuse gliomas

PubMed Central

Annala, Matti; Lehtinen, Birgitta; Kesseli, Juha; Haapasalo, Joonas; Ruusuvuori, Pekka; Yli-Harja, Olli; Visakorpi, Tapio; Haapasalo, Hannu; Nykter, Matti; Zhang, Wei

2017-01-01

Abstract Background Inhibitors of fibroblast growth factor receptors (FGFRs) have recently arisen as a promising treatment option for patients with FGFR alterations. Gene fusions involving FGFR3 and transforming acidic coiled-coil protein 3 (TACC3) have been detected in diffuse gliomas and other malignancies, and fusion-positive cases have responded well to FGFR inhibition. As high FGFR3 expression has been detected in fusion-positive tumors, we sought to determine the clinical significance of FGFR3 protein expression level as well as its potential for indicating FGFR3 fusions. Methods We performed FGFR3 immunohistochemistry on tissue microarrays containing 676 grades II–IV astrocytomas and 116 grades II–III oligodendroglial tumor specimens. Fifty-one cases were further analyzed using targeted sequencing. Results Moderate to strong FGFR3 staining was detected in gliomas of all grades, was more common in females, and was associated with poor survival in diffuse astrocytomas. Targeted sequencing identified FGFR3-TACC3 fusions and an FGFR3-CAMK2A fusion in 10 of 15 strongly stained cases, whereas no fusions were found in 36 negatively to moderately stained cases. Fusion-positive cases were predominantly female and negative for IDH and EGFR/PDGFRA/MET alterations. These and moderately stained cases show lower MIB-1 proliferation index than negatively to weakly stained cases. Furthermore, stronger FGFR3 expression was commonly observed in malignant tissue regions of lower cellularity in fusion-negative cases. Importantly, subregional negative FGFR3 staining was also observed in a few fusion-positive cases. Conclusions Strong FGFR3 protein expression is indicative of FGFR3 fusions and may serve as a clinically applicable predictive marker for treatment regimens based on FGFR inhibitors. PMID:28379477

The Light Ion Pulsed Power Induction Accelerator for ETF

DTIC Science & Technology

1995-07-01

the technical development necessary to demonstrate scientific and engineering feasibility for fusion energy production with a reprated driver. In...order for ETF to be cost effective, the accelerator system must be able to drive several target chambers which will test various Inertial Fusion ... Energy (IFE) reactor technologies. We envision an elevator system positioning and removing multiple target chambers from the center area of the ion beam

Modelling debris and shrapnel generation in inertial confinement fusion experiments

DOE PAGES

Eder, D. C.; Fisher, A. C.; Koniges, A. E.; ...

2013-10-24

Modelling and mitigation of damage are crucial for safe and economical operation of high-power laser facilities. Experiments at the National Ignition Facility use a variety of targets with a range of laser energies spanning more than two orders of magnitude (~14 kJ to ~1.9 MJ). Low-energy inertial confinement fusion experiments are used to study early-time x-ray load symmetry on the capsule, shock timing, and other physics issues. For these experiments, a significant portion of the target is not completely vaporized and late-time (hundreds of ns) simulations are required to study the generation of debris and shrapnel from these targets. Damagemore » to optics and diagnostics from shrapnel is a major concern for low-energy experiments. Here, we provide the first full-target simulations of entire cryogenic targets, including the Al thermal mechanical package and Si cooling rings. We use a 3D multi-physics multi-material hydrodynamics code, ALE-AMR, for these late-time simulations. The mass, velocity, and spatial distribution of shrapnel are calculated for three experiments with laser energies ranging from 14 to 250 kJ. We calculate damage risk to optics and diagnostics for these three experiments. For the lowest energy re-emit experiment, we provide a detailed analysis of the effects of shrapnel impacts on optics and diagnostics and compare with observations of damage sites.« less

A toolkit for GFP-mediated tissue-specific protein degradation in C. elegans.

PubMed

Wang, Shaohe; Tang, Ngang Heok; Lara-Gonzalez, Pablo; Zhao, Zhiling; Cheerambathur, Dhanya K; Prevo, Bram; Chisholm, Andrew D; Desai, Arshad; Oegema, Karen

2017-07-15

Proteins that are essential for embryo production, cell division and early embryonic events are frequently reused later in embryogenesis, during organismal development or in the adult. Examining protein function across these different biological contexts requires tissue-specific perturbation. Here, we describe a method that uses expression of a fusion between a GFP-targeting nanobody and a SOCS-box containing ubiquitin ligase adaptor to target GFP-tagged proteins for degradation. When combined with endogenous locus GFP tagging by CRISPR-Cas9 or with rescue of a null mutant with a GFP fusion, this approach enables routine and efficient tissue-specific protein ablation. We show that this approach works in multiple tissues - the epidermis, intestine, body wall muscle, ciliated sensory neurons and touch receptor neurons - where it recapitulates expected loss-of-function mutant phenotypes. The transgene toolkit and the strain set described here will complement existing approaches to enable routine analysis of the tissue-specific roles of C. elegans proteins. © 2017. Published by The Company of Biologists Ltd.

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

NASA Astrophysics Data System (ADS)

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

2004-08-01

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

Permeation fill-tube design for inertial confinement fusion target capsules

DOE PAGES

Rice, B. S.; Ulreich, J.; Fella, C.; ...

2017-03-22

A unique approach for permeation filling of nonpermeable inertial confinement fusion target capsules with deuterium–tritium (DT) is presented. This process uses a permeable capsule coupled into the final target capsule with a 0.03-mm-diameter fill tube. Leak free permeation filling of glow-discharge polymerization (GDP) targets using this method have been successfully demonstrated, as well as ice layering of the target, yielding an inner ice surface roughness of 1-more » $$\\unicode[STIX]{x03BC}$$m rms (root mean square). Finally, the measured DT ice-thickness profile for this experiment was used to validate a thermal model’s prediction of the same thickness profile.« less

Thought-action fusion as a causal factor in the development of intrusions.

PubMed

Rassin, E; Merckelbach, H; Muris, P; Spaan, V

1999-03-01

Thought-action fusion refers to the tendency to treat thoughts and actions as equivalents. Some authors (e.g., Rachman, 1997; Behaviour Research and Therapy, 35, 793-802) have suggested that thought-action fusion plays a role in the etiology of obsessive intrusions. The present study sought to test this idea. Subjects (n = 19) in the experimental condition underwent a bogus EEG recording session. They were informed that the apparatus was able to pick up the word 'apple' and that thoughts of that word could result in the administration of electrical shocks to another person. After having spent 15 minutes in the EEG laboratory, experimental subjects and controls (n = 26) completed a short questionnaire containing items about characteristics of the target thought (e.g., frequency, aversiveness). Results indicate that thought-action fusion, indeed, promotes intrusive thinking in that it results in a higher frequency of target thoughts, more discomfort, and more resistance. Thus, the current findings support the idea that thought-action fusion may contribute to the development of obsessive intrusions.

Chromophore-assisted laser inactivation of alpha- and gamma-tubulin SNAP-tag fusion proteins inside living cells.

PubMed

Keppler, Antje; Ellenberg, Jan

2009-02-20

Chromophore-assisted laser inactivation (CALI) can help to unravel localized activities of target proteins at defined times and locations within living cells. Covalent SNAP-tag labeling of fusion proteins with fluorophores such as fluorescein is a fast and highly specific tool to attach the photosensitizer to its target protein in vivo for selective inactivation of the fusion protein. Here, we demonstrate the effectiveness and specificity of SNAP-tag-based CALI by acute inactivation of alpha-tubulin and gamma-tubulin SNAP-tag fusions during live imaging assays of cell division. Singlet oxygen is confirmed as the reactive oxygen species that leads to loss of fusion protein function. The major advantage of SNAP-tag CALI is the ease, reliability, and high flexibility in labeling: the genetically encoded protein tag can be covalently labeled with various dyes matching the experimental requirements. This makes SNAP-tag CALI a very useful tool for rapid inactivation of tagged proteins in living cells.

Minimizing scatter-losses during pre-heat for magneto-inertial fusion targets

NASA Astrophysics Data System (ADS)

Geissel, Matthias; Harvey-Thompson, Adam J.; Awe, Thomas J.; Bliss, David E.; Glinsky, Michael E.; Gomez, Matthew R.; Harding, Eric; Hansen, Stephanie B.; Jennings, Christopher; Kimmel, Mark W.; Knapp, Patrick; Lewis, Sean M.; Peterson, Kyle; Schollmeier, Marius; Schwarz, Jens; Shores, Jonathon E.; Slutz, Stephen A.; Sinars, Daniel B.; Smith, Ian C.; Speas, C. Shane; Vesey, Roger A.; Weis, Matthew R.; Porter, John L.

2018-02-01

The size, temporal and spatial shape, and energy content of a laser pulse for the pre-heat phase of magneto-inertial fusion affect the ability to penetrate the window of the laser-entrance-hole and to heat the fuel behind it. High laser intensities and dense targets are subject to laser-plasma-instabilities (LPI), which can lead to an effective loss of pre-heat energy or to pronounced heating of areas that should stay unexposed. While this problem has been the subject of many studies over the last decades, the investigated parameters were typically geared towards traditional laser driven Inertial Confinement Fusion (ICF) with densities either at 10% and above or at 1% and below the laser's critical density, electron temperatures of 3-5 keV, and laser powers near (or in excess of) 1 × 1015 W/cm2. In contrast, Magnetized Liner Inertial Fusion (MagLIF) [Slutz et al., Phys. Plasmas 17, 056303 (2010) and Slutz and Vesey, Phys. Rev. Lett. 108, 025003 (2012)] currently operates at 5% of the laser's critical density using much thicker windows (1.5-3.5 μm) than the sub-micron thick windows of traditional ICF hohlraum targets. This article describes the Pecos target area at Sandia National Laboratories using the Z-Beamlet Laser Facility [Rambo et al., Appl. Opt. 44(12), 2421 (2005)] as a platform to study laser induced pre-heat for magneto-inertial fusion targets, and the related progress for Sandia's MagLIF program. Forward and backward scattered light were measured and minimized at larger spatial scales with lower densities, temperatures, and powers compared to LPI studies available in literature.

Study of Plasma Liner Driven Magnetized Target Fusion Via Advanced Simulations

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

Samulyak, Roman V.; Brookhaven National Lab.; Parks, Paul

The feasibility of the plasma liner driven Magnetized Target Fusion (MTF) via terascale numerical simulations will be assessed. In the MTF concept, a plasma liner, formed by merging of a number (60 or more) of radial, highly supersonic plasma jets, implodes on the target in the form of two compact plasma toroids, and compresses it to conditions of the fusion ignition. By avoiding major difficulties associated with both the traditional laser driven inertial confinement fusion and solid liner driven MTF, the plasma liner driven MTF potentially provides a low-cost and fast R&D path towards the demonstration of practical fusion energy.more » High fidelity numerical simulations of full nonlinear models associated with the plasma liner MTF using state-of-art numerical algorithms and terascale computing are necessary in order to resolve uncertainties and provide guidance for future experiments. At Stony Brook University, we have developed unique computational capabilities that ideally suite the MTF problem. The FronTier code, developed in collaboration with BNL and LANL under DOE funding including SciDAC for the simulation of 3D multi-material hydro and MHD flows, has beenbenchmarked and used for fundamental and engineering problems in energy science applications. We have performed 3D simulations of converging supersonic plasma jets, their merger and the formation of the plasma liner, and a study of the corresponding oblique shock problem. We have studied the implosion of the plasma liner on the magnetized plasma target by resolving Rayleigh-Taylor instabilities in 2D and 3D and other relevant physics and estimate thermodynamic conditions of the target at the moment of maximum compression and the hydrodynamic efficiency of the method.« less

Acoustically Driven Magnetized Target Fusion At General Fusion: An Overview

NASA Astrophysics Data System (ADS)

O'Shea, Peter; Laberge, M.; Donaldson, M.; Delage, M.; the Fusion Team, General

2016-10-01

Magnetized Target Fusion (MTF) involves compressing an initial magnetically confined plasma of about 1e23 m-3, 100eV, 7 Tesla, 20 cm radius, >100 μsec life with a 1000x volume compression in 100 microseconds. If near adiabatic compression is achieved, the final plasma of 1e26 m-3, 10keV, 700 Tesla, 2 cm radius, confined for 10 μsec would produce interesting fusion energy gain. General Fusion (GF) is developing an acoustic compression system using pneumatic pistons focusing a shock wave on the CT plasma in the center of a 3 m diameter sphere filled with liquid lead-lithium. Low cost driver, straightforward heat extraction, good tritium breeding ratio and excellent neutron protection could lead to a practical power plant. GF (65 employees) has an active plasma R&D program including both full scale and reduced scale plasma experiments and simulation of both. Although acoustic driven compression of full scale plasmas is the end goal, present compression studies use reduced scale plasmas and chemically accelerated Aluminum liners. We will review results from our plasma target development, motivate and review the results of dynamic compression field tests and briefly describe the work to date on the acoustic driver front.

High energy primary knock-on process in metal deuterium systems initiated by bombardment with noble gas ions

NASA Astrophysics Data System (ADS)

Gann, V. V.; Tolstolutskaya, G. D.

2008-08-01

An experimental study confirms the possibility of nuclear fusion reactions initiating in metal-deuterium targets by bombarding them with ions that are not the reagents of the fusion reaction, in particular, with noble gas ions. The yields of (d,d) and (d,t) reactions were measured as functions of energy (0.4-3.2 MeV) and mass of incident ions (He +, Ne +, Ar +, Kr + and Xe +). Irradiation by heavy ions produced a number of energetic deuterium atoms in the deuteride and deuterium + tritium metal targets. At ion energies of ˜0.1-1 MeV the d-d reaction yields are relatively high. A model of nuclear fusion reaction cross-sections in atomic collision cascades initiated by noble gas ion beam in metal-deuterium target is developed. The method for calculation tritium or deuterium recoil fluxes and the yield of d-d fusion reaction in subsequent collisions was proposed. It was shown that D(d,p)t and D(t,n) 4He reactions mainly occur in energy region of the recoiled D-atom from 10 keV to 250 keV. The calculated probabilities of d-d and d-t fusion reactions were found to be in a good agreement with the experimental data.

Critical Science Issues for Direct Drive Inertial Fusion Energy

NASA Astrophysics Data System (ADS)

Dahlburg, Jill P.; Gardner, John H.; Schmitt, Andrew J.; Obenschain, S. P.

1998-09-01

There are several topics that require resolution prior to the construction of an Inertial Fusion Energy [IFE] laboratory Engineering Test Facility [ETF]: a pellet that produces high gain; a pellet fabrication system that cost-effectively and rapidly manufactures these pellets; a sufficiently uniform and durable high repetition-rate laser pellet driver; a practical target injection system that provides accurate pellet aiming; and, a target chamber that will survive the debris and radiation of repeated high-gain pellet implosions. In this summary we describe the science issues and opportunities that are involved in the design of a successful high gain direct drive Inertial Confinement Fusion [ICF] pellet.

OSIRIS and SOMBRERO Inertial Fusion Power Plant Designs, Volume 2: Designs, Assessments, and Comparisons

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

Meier, W. R.; Bieri, R. L.; Monsler, M. J.

1992-03-01

This is a comprehensive design study of two Inertial Fusion Energy (IFE) electric power plants. Conceptual designs are presented for a fusion reactor (called Osiris) using an induction-linac heavy-ion beam driver, and another (called SOMBRERO) using a KrF laser driver. The designs covered all aspects of IFE power plants, including the chambers, heat transport and power conversion systems, balance-of-plant facilities, target fabrication, target injection and tracking, as well as the heavy-ion and KrF drivers. The point designs were assessed and compared in terms of their environmental & safety aspects, reliability and availability, economics, and technology development needs.

Staggered scheduling of sensor estimation and fusion for tracking over long-haul links

DOE PAGES

Liu, Qiang; Rao, Nageswara S. V.; Wang, Xin

2016-08-01

Networked sensing can be found in a multitude of real-world applications. Here, we focus on the communication-and computation-constrained long-haul sensor networks, where sensors are remotely deployed over a vast geographical area to perform certain tasks. Of special interest is a class of such networks where sensors take measurements of one or more dynamic targets and send their state estimates to a remote fusion center via long-haul satellite links. The severe loss and delay over such links can easily reduce the amount of sensor data received by the fusion center, thereby limiting the potential information fusion gain and resulting in suboptimalmore » tracking performance. In this paper, starting with the temporal-domain staggered estimation for an individual sensor, we explore the impact of the so-called intra-state prediction and retrodiction on estimation errors. We then investigate the effect of such estimation scheduling across different sensors on the spatial-domain fusion performance, where the sensing time epochs across sensors are scheduled in an asynchronous and staggered manner. In particular, the impact of communication delay and loss as well as sensor bias on such scheduling is explored by means of numerical and simulation studies that demonstrate the validity of our analysis.« less

Evolution of Magnetized Liner Inertial Fusion (MagLIF) Targets

DOE PAGES

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

2017-12-19

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

Evolution of Magnetized Liner Inertial Fusion (MagLIF) Targets

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

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

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

Fusion enhancement at near and sub-barrier energies in 19O + 12C

DOE PAGES

Singh, Varinderjit; Vadas, J.; Steinbach, T. K.; ...

2016-12-12

Measuring the fusion excitation function for an isotopic chain of projectile nuclei provides a stringent test of a microscopic description of fusion. We report the first measurement of the fusion excitation function at near-barrier energies for the 19O+ 12C system. The measured excitation function is compared with the fusion excitation function of 18O+ 12C. A significant enhancement in the fusion probability of 19O ions with a 12C target as compared to 18O ions is observed. As a result, the experimental cross-sections observed at near-barrier energies are compared with a state-of-the-art microscopic model.

Energy research: accelerator builders eager to aid fusion work.

PubMed

Metz, W D

1976-10-15

Useful fusion energy may be generated by means of heavy ion accelerator driven implosions if the contraints dictated by the physics and economics of thermonuclear targets and reactors can be satisfied.

Biosensing of BCR/ABL fusion gene using an intensity-interrogation surface plasmon resonance imaging system

NASA Astrophysics Data System (ADS)

Wu, Jiangling; Huang, Yu; Bian, Xintong; Li, DanDan; Cheng, Quan; Ding, Shijia

2016-10-01

In this work, a custom-made intensity-interrogation surface plasmon resonance imaging (SPRi) system has been developed to directly detect a specific sequence of BCR/ABL fusion gene in chronic myelogenous leukemia (CML). The variation in the reflected light intensity detected from the sensor chip composed of gold islands array is proportional to the change of refractive index due to the selective hybridization of surface-bound DNA probes with target ssDNA. SPRi measurements were performed with different concentrations of synthetic target DNA sequence. The calibration curve of synthetic target sequence shows a good relationship between the concentration of synthetic target and the change of reflected light intensity. The detection limit of this SPRi measurement could approach 10.29 nM. By comparing SPRi images, the target ssDNA and non-complementary DNA sequence are able to be distinguished. This SPRi system has been applied for assay of BCR/ABL fusion gene extracted from real samples. This nucleic acid-based SPRi biosensor therefore offers an alternative high-effective, high-throughput label-free tool for DNA detection in biomedical research and molecular diagnosis.

Ion acceleration and D-D nuclear fusion in laser-generated plasma from advanced deuterated polyethylene.

PubMed

Torrisi, Lorenzo

2014-10-23

Deuterated polyethylene targets have been irradiated by means of a 1016 W/cm2 laser using 600 J pulse energy, 1315 nm wavelength, 300 ps pulse duration and 70 micron spot diameter. The plasma parameters were measured using on-line diagnostics based on ion collectors, SiC detectors and plastic scintillators, all employed in time-of-flight configuration. In addition, a Thomson parabola spectrometer, an X-ray streak camera, and calibrated neutron dosimeter bubble detectors were employed. Characteristic protons and neutrons at maximum energies of 3.0 MeV and 2.45 MeV, respectively, were detected, confirming that energy spectra of reaction products coming from deuterium-deuterium nuclear fusion occur. In thick advanced targets a fusion rate of the order of 2 × 108 fusions per laser shot was calculated.

Annexin-directed β-glucuronidase for the targeted treatment of solid tumors.

PubMed

Guillen, Katrin P; Ruben, Eliza A; Virani, Needa; Harrison, Roger G

2017-02-01

Enzyme prodrug therapy has the potential to remedy the lack of selectivity associated with the systemic administration of chemotherapy. However, most current systems are immunogenic and constrained to a monotherapeutic approach. We developed a new class of fusion proteins centered about the human enzyme β-glucuronidase (βG), capable of converting several innocuous prodrugs into chemotherapeutics. We targeted βG to phosphatidylserine on tumor cells, tumor vasculature and metastases via annexin A1/A5. Phosphatidylserine shows promise as a universal marker for solid tumors and allows for tumor type-independent targeting. To create fusion proteins, human annexin A1/A5 was genetically fused to the activity-enhancing 16a3 mutant of human βG, expressed in chemically defined, fed-batch suspension culture, and chromatographically purified. All fusion constructs achieved >95% purity with yields up to 740 μg/l. Fusion proteins displayed cancer selective cell-surface binding with cell line-dependent binding stability. One fusion protein in combination with the prodrug SN-38 glucuronide was as effective as the drug SN-38 on Panc-1 pancreatic cancer cells and HAAE-1 endothelial cells, and demonstrated efficacy against MCF-7 breast cancer cells. βG fusion proteins effectively enable localized combination therapy that can be tailored to each patient via prodrug selection, with promising clinical potential based on their near fully human design. © The Author 2016. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Development of an inducible platform for intercellular protein delivery.

PubMed

Siller, Richard; Dufour, Eric; Lycke, Max; Wilmut, Ian; Jung, Yong-Wook; Park, In Hyun; Sullivan, Gareth J

2017-04-30

A challenge to protein based therapies is the ability to produce biologically active proteins and their ensured delivery. Various approaches have been utilised including fusion of protein transduction domains with a protein or biomolecule of interest. A compounding issue is lack of specificity, efficiency and indeed whether the protein fusions are actually translocated into the cell and not merely an artefact of the fixation process. Here we present a novel platform, allowing the inducible export and uptake of a protein of interest. The system utilises a combination of the Tetracyline repressor system, combined with a fusion protein containing the N-terminal signal peptide from human chorionic gonadotropin beta-subunit, and a C-terminal poly-arginine domain for efficient uptake by target cells. This novel platform was validated using enhanced green fluorescent protein as the gene of interest. Doxycycline efficiently induced expression of the fusion protein. The human chorionic gonadotropin beta-subunit facilitated the export of the fusion protein into the cell culture media. Finally, the fusion protein was able to efficiently enter into neighbouring cells (target cells), mediated by the poly-arginine cell penetrating peptide. Importantly we have addressed the issue of whether the observed uptake is an artefact of the fixation process or indeed genuine translocation. In addition this platform provides a number of potential applications in diverse areas such as stem cell biology, immune therapy and cancer targeting therapies. Copyright © 2017 Elsevier B.V. All rights reserved.

Process for manufacture of inertial confinement fusion targets and resulting product

DOEpatents

Masnari, Nino A.; Rensel, Walter B.; Robinson, Merrill G.; Solomon, David E.; Wise, Kensall D.; Wuttke, Gilbert H.

1982-01-01

An ICF target comprising a spherical pellet of fusion fuel surrounded by a concentric shell; and a process for manufacturing the same which includes the steps of forming hemispheric shells of a silicon or other substrate material, adhering the shell segments to each other with a fuel pellet contained concentrically therein, then separating the individual targets from the parent substrate. Formation of hemispheric cavities by deposition or coating of a mold substrate is also described. Coatings or membranes may also be applied to the interior of the hemispheric segments prior to joining.

Design and Evaluation of Fusion Approach for Combining Brain and Gaze Inputs for Target Selection

PubMed Central

Évain, Andéol; Argelaguet, Ferran; Casiez, Géry; Roussel, Nicolas; Lécuyer, Anatole

2016-01-01

Gaze-based interfaces and Brain-Computer Interfaces (BCIs) allow for hands-free human–computer interaction. In this paper, we investigate the combination of gaze and BCIs. We propose a novel selection technique for 2D target acquisition based on input fusion. This new approach combines the probabilistic models for each input, in order to better estimate the intent of the user. We evaluated its performance against the existing gaze and brain–computer interaction techniques. Twelve participants took part in our study, in which they had to search and select 2D targets with each of the evaluated techniques. Our fusion-based hybrid interaction technique was found to be more reliable than the previous gaze and BCI hybrid interaction techniques for 10 participants over 12, while being 29% faster on average. However, similarly to what has been observed in hybrid gaze-and-speech interaction, gaze-only interaction technique still provides the best performance. Our results should encourage the use of input fusion, as opposed to sequential interaction, in order to design better hybrid interfaces. PMID:27774048

Undifferentiated Sarcomas in Children Harbor Clinically Relevant Oncogenic Fusions and Gene Copy-Number Alterations: A Report from the Children's Oncology Group.

PubMed

Laetsch, Theodore W; Roy, Angshumoy; Xu, Lin; Black, Jennifer O; Coffin, Cheryl M; Chi, Yueh-Yun; Tian, Jing; Spunt, Sheri L; Hawkins, Douglas S; Bridge, Julia A; Parsons, D Williams; Skapek, Stephen X

2018-04-24

Purpose: A comprehensive analysis of the genomics of undifferentiated sarcomas (UDS) is lacking. We analyzed copy-number alterations and fusion status in patients with UDS prospectively treated on Children's Oncology Group protocol ARST0332. Experimental Design: Copy-number alterations were assessed by OncoScan FFPE Express on 32 UDS. Whole-exome and transcriptome libraries from eight tumors with sufficient archived material were sequenced on HiSeq (2 × 100 bp). Targeted RNA-sequencing using Archer chemistry was performed on two additional cases. Results: Five-year overall survival for patients with UDS was 83% (95% CI, 69%-97%) with risk-adapted therapy (surgery, chemotherapy, and radiotherapy). Both focal and arm-level copy-number alterations were common including gain of 1q (8/32, 25%) and loss of 1p (7/32, 22%), both of which occurred more often in clinically defined high-risk tumors. Tumors with both loss of 1p and gain of 1q carried an especially poor prognosis with a 5-year event-free survival of 20%. GISTIC analysis identified recurrent amplification of FGF1 on 5q31.3 ( q = 0.03) and loss of CDKN2A and CDKN2B on 9p21.3 ( q = 0.07). Known oncogenic fusions were identified in eight of 10 cases analyzed by next-generation sequencing. Conclusions: Pediatric UDS generally has a good outcome with risk-adapted therapy. A high-risk subset of patients whose tumors have copy-number loss of 1p and gain of 1q was identified with only 20% survival. Oncogenic fusions are common in UDS, and next-generation sequencing should be considered for children with UDS to refine the diagnosis and identify potentially targetable drivers. Clin Cancer Res; 1-10. ©2018 AACR. ©2018 American Association for Cancer Research.

Indirect drive targets for fusion power

DOEpatents

Amendt, Peter A.; Miles, Robin R.

2016-10-11

A hohlraum for an inertial confinement fusion power plant is disclosed. The hohlraum includes a generally cylindrical exterior surface, and an interior rugby ball-shaped surface. Windows over laser entrance holes at each end of the hohlraum enclose inert gas. Infrared reflectors on opposite sides of the central point reflect fusion chamber heat away from the capsule. P2 shields disposed on the infrared reflectors help assure an enhanced and more uniform x-ray bath for the fusion fuel capsule.

[Construction and expression of a fusion protein made of tissue-type plasminogen activator and hirudin in Pichia pastoris].

PubMed

Yu, Ai-Ping; Shi, Bing-Xing; Dong, Chun-Na; Jiang, Zhong-Hua; Wu, Zu-Ze

2005-07-01

To combine the fibrinolytic with anticoagulant activities for therapy of thrombotic deseases, a fusion protein made of tissue-type plasminogen activator (t-PA) and hirudin was constructed and expressed in chia pastoris. To improve thrombolytic properties of t-PA and reduce bleeding side effect of hirudin, FXa-recognition sequence was introduced between t-PA and hirudin molecules.The anticoagulant activity of hirudin can be target-released through cleavage of FXa at thrombus site. t-PA gene and hirudin gene with FXa-recognition sequence at its 5'-terminal were obtained by RT-PCR and PCR respectively. The fusion protein gene was cloned into plasmid pIC9K and electroporated into the genome of Pichia pastoris GS115. The expression of fusion protein was induced by methanol in shaking flask and secreted into the culture medium. Two forms of the fusion protein, single-chain and double-chain linked by a disulfide bond (due to the cleveage of t-PA at Arg275-Ile276), were obtained. The intact fusion protein retained the fibrinolytic activity but lacked any anticoagulant activity. After cleavage by FXa, the fusion protein liberated intact free hirudin to exert its anticoagulant activity. So, the fusion protein is a bifunctional molecule having good prospect to develop into a new targeted therapeutic agent with reduced bleeding side effect for thrombotic diseases.

Accumulation of specific sterol precursors targets a MAP kinase cascade mediating cell-cell recognition and fusion.

PubMed

Weichert, Martin; Lichius, Alexander; Priegnitz, Bert-Ewald; Brandt, Ulrike; Gottschalk, Johannes; Nawrath, Thorben; Groenhagen, Ulrike; Read, Nick D; Schulz, Stefan; Fleißner, André

2016-10-18

Sterols are vital components of eukaryotic cell membranes. Defects in sterol biosynthesis, which result in the accumulation of precursor molecules, are commonly associated with cellular disorders and disease. However, the effects of these sterol precursors on the metabolism, signaling, and behavior of cells are only poorly understood. In this study, we show that the accumulation of only ergosterol precursors with a conjugated double bond in their aliphatic side chain specifically disrupts cell-cell communication and fusion in the fungus Neurospora crassa Genetically identical germinating spores of this fungus undergo cell-cell fusion, thereby forming a highly interconnected supracellular network during colony initiation. Before fusion, the cells use an unusual signaling mechanism that involves the coordinated and alternating switching between signal sending and receiving states of the two fusion partners. Accumulation of only ergosterol precursors with a conjugated double bond in their aliphatic side chain disrupts this coordinated cell-cell communication and suppresses cell fusion. These specific sterol precursors target a single ERK-like mitogen-activated protein (MAP) kinase (MAK-1)-signaling cascade, whereas a second MAP kinase pathway (MAK-2), which is also involved in cell fusion, is unaffected. These observations indicate that a minor specific change in sterol structure can exert a strong detrimental effect on a key signaling pathway of the cell, resulting in the absence of cell fusion.

Accumulation of specific sterol precursors targets a MAP kinase cascade mediating cell–cell recognition and fusion

PubMed Central

Weichert, Martin; Lichius, Alexander; Priegnitz, Bert-Ewald; Brandt, Ulrike; Gottschalk, Johannes; Nawrath, Thorben; Groenhagen, Ulrike; Read, Nick D.; Schulz, Stefan; Fleißner, André

2016-01-01

Sterols are vital components of eukaryotic cell membranes. Defects in sterol biosynthesis, which result in the accumulation of precursor molecules, are commonly associated with cellular disorders and disease. However, the effects of these sterol precursors on the metabolism, signaling, and behavior of cells are only poorly understood. In this study, we show that the accumulation of only ergosterol precursors with a conjugated double bond in their aliphatic side chain specifically disrupts cell–cell communication and fusion in the fungus Neurospora crassa. Genetically identical germinating spores of this fungus undergo cell–cell fusion, thereby forming a highly interconnected supracellular network during colony initiation. Before fusion, the cells use an unusual signaling mechanism that involves the coordinated and alternating switching between signal sending and receiving states of the two fusion partners. Accumulation of only ergosterol precursors with a conjugated double bond in their aliphatic side chain disrupts this coordinated cell–cell communication and suppresses cell fusion. These specific sterol precursors target a single ERK-like mitogen-activated protein (MAP) kinase (MAK-1)-signaling cascade, whereas a second MAP kinase pathway (MAK-2), which is also involved in cell fusion, is unaffected. These observations indicate that a minor specific change in sterol structure can exert a strong detrimental effect on a key signaling pathway of the cell, resulting in the absence of cell fusion. PMID:27708165

Performance of ITER as a burning plasma experiment

NASA Astrophysics Data System (ADS)

Shimada, M.; Mukhovatov, V.; Federici, G.; Gribov, Y.; Kukushkin, A.; Murakami, Y.; Polevoi, A.; Pustovitov, V.; Sengoku, S.; Sugihara, M.

2004-02-01

Recent performance analysis has improved confidence in achieving Q (= fusion power/auxiliary heating power)geq 10 in inductive operation in ITER. Performance analysis based on empirical scalings shows the feasibility of achieving Q geq 10 in inductive operation, particularly with improved modelling of helium exhaust. Analysis has also indicated the possibility that ITER can potentially demonstrate Q ~ 50, enabling studies of self-heated plasmas. Theory-based core modelling indicates the need for a high pedestal temperature (3.2-5.3 keV) to achieve Q geq 10, which is in the range of projections with presently available pedestal scalings. Pellet injection from the high-field side would be useful in enhancing Q and reducing edge localized mode (ELM) heat load in high plasma current operation. If the ELM heat load is not acceptable, it could be made tolerable by further tilting the target plate. Steady state operation scenarios at Q = 5 have been developed with modest requirements on confinement improvement and beta (HH98(y,2) geq 1.3 and bgrN geq 2.6). Stabilization of the resistive wall modes (RWMs), required in such regimes, is feasible with the present saddle coils and power supplies with double-wall structures taken into account. Recent analysis shows a potential of high power steady state operation with a fusion power of 0.7 GW at Q ~ 8. Achievement of the required bgrN ~ 3.6 by RWM stabilization is a possibility. Further analysis is also needed on reduction of the divertor target heat load.

A targeted IL-15 fusion protein with potent anti-tumor activity

PubMed Central

Chen, Siqi; Huang, Qiang; Liu, Jiayu; Xing, Jieyu; Zhang, Ning; Liu, Yawei; Wang, Zhong; Li, Qing

2015-01-01

IL-15 has been actively investigated for its potential in tumor immunotherapy. To enhance the anti-tumor activity of IL-15, the novel PFC-1 construct was designed, which comprises the following 3 parts: (1) IL-15Rα fused with IL-15 to enhance IL-15 activity, (2) an Fc fragment to increase protein half-life, and (3) an integrin-targeting RGD peptide to enhance tumor targeting. PFC-1 showed tumor cell targeting without compromising IL-15 activity. PFC-1 also had potent anti-tumor activities in xenograft models, suggesting the potential application of this multi-functional fusion protein in tumor therapy. PMID:26176990

Laser fusion neutron source employing compression with short pulse lasers

DOEpatents

Sefcik, Joseph A; Wilks, Scott C

2013-11-05

A method and system for achieving fusion is provided. The method includes providing laser source that generates a laser beam and a target that includes a capsule embedded in the target and filled with DT gas. The laser beam is directed at the target. The laser beam helps create an electron beam within the target. The electron beam heats the capsule, the DT gas, and the area surrounding the capsule. At a certain point equilibrium is reached. At the equilibrium point, the capsule implodes and generates enough pressure on the DT gas to ignite the DT gas and fuse the DT gas nuclei.

Science and Technology Review October/November 2009

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

Bearinger, J P

2009-08-21

This month's issue has the following articles: (1) Award-Winning Collaborations Provide Solutions--Commentary by Steven D. Liedle; (2) Light-Speed Spectral Analysis of a Laser Pulse--An optical device inspects and stops potentially damaging laser pulses; (3) Capturing Waveforms in a Quadrillionth of a Second--The femtoscope, a time microscope, improves the temporal resolution and dynamic range of conventional recording instruments; (4) Gamma-Ray Spectroscopy in the Palm of Your Hand--A miniature gamma-ray spectrometer provides increased resolution at a reduced cost; (5) Building Fusion Targets with Precision Robotics--A robotic system assembles tiny fusion targets with nanometer precision; (6) ROSE: Making Compiler Technology More Accessible--An open-sourcemore » software infrastructure makes powerful compiler techniques available to all programmers; (7) Restoring Sight to the Blind with an Artificial Retina--A retinal prosthesis could restore vision to people suffering from eye diseases; (8) Eradicating the Aftermath of War--A remotely operated system precisely locates buried land mines; (9) Compact Alignment for Diagnostic Laser Beams--A smaller, less expensive device aligns diagnostic laser beams onto targets; and (10) Securing Radiological Sources in Africa--Livermore and other national laboratories are helping African countries secure their nuclear materials.« less

Mammalian target of rapamycin (mTOR) signaling is required for a late-stage fusion process during skeletal myotube maturation.

PubMed

Park, In-Hyun; Chen, Jie

2005-09-09

Skeletal myogenesis is a well orchestrated cascade of events regulated by multiple signaling pathways, one of which is recently characterized by its sensitivity to the bacterial macrolide rapamycin. Previously we reported that the mammalian target of rapamycin (mTOR) regulates the initiation of the differentiation program in mouse C2C12 myoblasts by controlling the expression of insulin-like growth factor-II in a kinase-independent manner. Here we provide experimental evidence suggesting that a different mode of mTOR signaling regulates skeletal myogenesis at a later stage. In the absence of endogenous mTOR function in C2C12 cells treated with rapamycin, a kinase-inactive mTOR fully supports myogenin expression, but causes a delay in contractile protein expression. Myoblasts fuse to form nascent myotubes in the absence of kinase-active mTOR, whereas the formation of mature myotubes by further fusion requires the catalytic activity of mTOR. Therefore, the two stages of myocyte fusion are molecularly separable at the level of mTOR signaling. In addition, our data suggest that a factor secreted into the culture medium is responsible for mediating the function of mTOR in regulating the late-stage fusion leading to mature myotubes. Furthermore, taking advantage of the unique features of cells stably expressing a mutant mTOR, we have performed cDNA microarray analysis to compare global gene expression profiles between mature and nascent myotubes, the results of which have implicated classes of genes and revealed candidate regulators in myotube maturation or functions of mature myotubes.

Driver Fusions and Their Implications in the Development and Treatment of Human Cancers.

PubMed

Gao, Qingsong; Liang, Wen-Wei; Foltz, Steven M; Mutharasu, Gnanavel; Jayasinghe, Reyka G; Cao, Song; Liao, Wen-Wei; Reynolds, Sheila M; Wyczalkowski, Matthew A; Yao, Lijun; Yu, Lihua; Sun, Sam Q; Chen, Ken; Lazar, Alexander J; Fields, Ryan C; Wendl, Michael C; Van Tine, Brian A; Vij, Ravi; Chen, Feng; Nykter, Matti; Shmulevich, Ilya; Ding, Li

2018-04-03

Gene fusions represent an important class of somatic alterations in cancer. We systematically investigated fusions in 9,624 tumors across 33 cancer types using multiple fusion calling tools. We identified a total of 25,664 fusions, with a 63% validation rate. Integration of gene expression, copy number, and fusion annotation data revealed that fusions involving oncogenes tend to exhibit increased expression, whereas fusions involving tumor suppressors have the opposite effect. For fusions involving kinases, we found 1,275 with an intact kinase domain, the proportion of which varied significantly across cancer types. Our study suggests that fusions drive the development of 16.5% of cancer cases and function as the sole driver in more than 1% of them. Finally, we identified druggable fusions involving genes such as TMPRSS2, RET, FGFR3, ALK, and ESR1 in 6.0% of cases, and we predicted immunogenic peptides, suggesting that fusions may provide leads for targeted drug and immune therapy. Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.

Structural basis of influenza virus fusion inhibition by the antiviral drug Arbidol

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

Kadam, Rameshwar U.; Wilson, Ian A.

The broad-spectrum antiviral drug Arbidol shows efficacy against influenza viruses by targeting the hemagglutinin (HA) fusion machinery. However, the structural basis of the mechanism underlying fusion inhibition by Arbidol has remained obscure, thereby hindering its further development as a specific and optimized influenza therapeutic. We determined crystal structures of Arbidol in complex with influenza virus HA from pandemic 1968 H3N2 and recent 2013 H7N9 viruses. Arbidol binds in a hydrophobic cavity in the HA trimer stem at the interface between two protomers. This cavity is distal to the conserved epitope targeted by broadly neutralizing stem antibodies and is ~16 Åmore » from the fusion peptide. Arbidol primarily makes hydrophobic interactions with the binding site but also induces some conformational rearrangements to form a network of inter- and intraprotomer salt bridges. By functioning as molecular glue, Arbidol stabilizes the prefusion conformation of HA that inhibits the large conformational rearrangements associated with membrane fusion in the low pH of the endosome. This unique binding mode compared with the small-molecule inhibitors of other class I fusion proteins enhances our understanding of how small molecules can function as fusion inhibitors and guides the development of broad-spectrum therapeutics against influenza virus.« less

Biochemistry and biophysics of HIV-1 gp41 - membrane interactions and implications for HIV-1 envelope protein mediated viral-cell fusion and fusion inhibitor design.

PubMed

Cai, Lifeng; Gochin, Miriam; Liu, Keliang

2011-12-01

Human immunodeficiency virus type 1 (HIV-1), the pathogen of acquired immunodeficiency syndrome (AIDS), causes ~2 millions death every year and still defies an effective vaccine. HIV-1 infects host cells through envelope protein - mediated virus-cell fusion. The transmembrane subunit of envelope protein, gp41, is the molecular machinery which facilitates fusion. Its ectodomain contains several distinguishing functional domains, fusion peptide (FP), Nterminal heptad repeat (NHR), C-terminal heptad repeat (CHR) and membrane proximal extracellular region (MPER). During the fusion process, FP inserts into the host cell membrane, and an extended gp41 prehairpin conformation bridges the viral and cell membranes through MPER and FP respectively. Subsequent conformational change of the unstable prehairpin results in a coiled-coil 6-helix bundle (6HB) structure formed between NHR and CHR. The energetics of 6HB formation drives membrane apposition and fusion. Drugs targeting gp41 functional domains to prevent 6HB formation inhibit HIV-1 infection. T20 (enfuvirtide, Fuzeon) was approved by the US FDA in 2003 as the first fusion inhibitor. It is a 36-residue peptide from the gp41 CHR, and it inhibits 6HB formation by targeting NHR and lipids. Development of new fusion inhibitors, especially small molecule drugs, is encouraged to overcome the shortcomings of T20 as a peptide drug. Hydrophobic characteristics and membrane association are critical for gp41 function and mechanism of action. Research in gp41-membrane interactions, using peptides corresponding to specific functional domains, or constructs including several interactive domains, are reviewed here to get a better understanding of gp41 mediated virus-cell fusion that can inform or guide the design of new HIV-1 fusion inhibitors.

Development and characterization of a Rift Valley fever virus cell-cell fusion assay using alphavirus replicon vectors

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

Filone, Claire Marie; Heise, Mark; Doms, Robert W.

2006-12-20

Rift Valley fever virus (RVFV), a member of the Phlebovirus genus in the Bunyaviridae family, is transmitted by mosquitoes and infects both humans and domestic animals, particularly cattle and sheep. Since primary RVFV strains must be handled in BSL-3+ or BSL-4 facilities, a RVFV cell-cell fusion assay will facilitate the investigation of RVFV glycoprotein function under BSL-2 conditions. As for other members of the Bunyaviridae family, RVFV glycoproteins are targeted to the Golgi, where the virus buds, and are not efficiently delivered to the cell surface. However, overexpression of RVFV glycoproteins using an alphavirus replicon vector resulted in the expressionmore » of the glycoproteins on the surface of multiple cell types. Brief treatment of RVFV glycoprotein expressing cells with mildly acidic media (pH 6.2 and below) resulted in rapid and efficient syncytia formation, which we quantified by {beta}-galactosidase {alpha}-complementation. Fusion was observed with several cell types, suggesting that the receptor(s) for RVFV is widely expressed or that this acid-dependent virus does not require a specific receptor to mediate cell-cell fusion. Fusion occurred over a broad temperature range, as expected for a virus with both mosquito and mammalian hosts. In contrast to cell fusion mediated by the VSV-G glycoprotein, RVFV glycoprotein-dependent cell fusion could be prevented by treating target cells with trypsin, indicating that one or more proteins (or protein-associated carbohydrate) on the host cell surface are needed to support membrane fusion. The cell-cell fusion assay reported here will make it possible to study the membrane fusion activity of RVFV glycoproteins in a high-throughput format and to screen small molecule inhibitors for the ability to block virus-specific membrane fusion.« less

Improving Echo-Guided Procedures Using an Ultrasound-CT Image Fusion System.

PubMed

Diana, Michele; Halvax, Peter; Mertz, Damien; Legner, Andras; Brulé, Jean-Marcel; Robinet, Eric; Mutter, Didier; Pessaux, Patrick; Marescaux, Jacques

2015-06-01

Image fusion between ultrasound (US) and computed tomography (CT) scan or magnetic resonance can increase operator accuracy in targeting liver lesions, particularly when those are undetectable with US alone. We have developed a modular gel to simulate hepatic solid lesions for educational purposes in imaging and minimally invasive ablation techniques. We aimed to assess the impact of image fusion in targeting artificial hepatic lesions during the hands-on part of 2 courses (basic and advanced) in hepatobiliary surgery. Under US guidance, 10 fake tumors of various sizes were created in the livers of 2 pigs, by percutaneous injection of a biocompatible gel engineered to be hyperdense on CT scanning and barely detectable on US. A CT scan was obtained and a CT-US image fusion was performed using the ACUSON S3000 US system (Siemens Healthcare, Germany). A total of 12 blinded course attendants, were asked in turn to perform a 10-minute liver scan with US alone followed by a 10-minute scan using image fusion. Using US alone, the expert managed to identify all lesions successfully. The true positive rate for course attendants with US alone was 14/36 and 2/24 in the advanced and basic courses, respectively. The total number of false positives identified was 26. With image fusion, the rate of true positives significantly increased to 31/36 (P < .001) in the advanced group and 16/24 in the basic group (P < .001). The total number of false positives, considering all participants, decreased to 4 (P < .001). Image fusion significantly increases accuracy in targeting hepatic lesions and might improve echo-guided procedures. © The Author(s) 2015.

Motorized fusion guided prostate biopsy: phantom study

NASA Astrophysics Data System (ADS)

Seifabadi, Reza; Xu, Sheng; Aalamifar, Fereshteh; Pinto, Peter; Wood, Bradford J.

2017-03-01

Purpose: Fusion of Magnetic Resonance Imaging (MRI) with intraoperative real-time Ultrasound (US) during prostate biopsy has significantly improved the sensitivity of transrectal ultrasound (TRUS) guided cancer detection. Currently, sweeping of the TRUS probe to build a 3D volume as part of the fusion process and the TRUS probe manipulation for needle guidance are both done manually. A motorized, joystick controlled, probe holder was custom fabricated that can potentially reduce inter-operator variability, provide standardization of needle placement, improve repeatability and uniformity of needle placement, which may have impacts upon the learning curve after clinical deployment of this emerging approach. Method: a 2DOF motorized probe holder was designed to provide translation and rotation of a triplane TRUS end firing probe for prostate biopsy. The probe holder was joystick controlled and can assist manipulation of the probe during needle insertion as well as in acquiring a smoother US 2D to 3D sweep in which the 3D US volume for fusion is built. A commercial MRI-US fusion platform was used. Three targets were specified on MR image of a commercial prostate phantom. After performing the registration, two operators performed targeting, once manually and once with the assistance of the motorized probe holder. They repeated these tasks 5 times resulting in a total of 30 targeting events. Time of completion and mechanical error i.e. distance of the target from the needle trajectory in the software user interface were measured. Repeatability in reaching a given target in a systematic and consistent way was measured using a scatter plot showing all targets in the US coordinate system. Pearson product-moment correlation coefficient (PPMCC) was used to demonstrate the probe steadiness during targeting. Results: the completion time was 25+/-17 sec, 25+/-24 sec, and 27+/-15 sec for free hand and 24+/-10 sec, 22.5+/-10 sec, and 37+/-10 sec for motorized insertion, for target 1, 2, and 3, respectively. The mechanical error was 0.75+/-0.4 mm, 0.45+/-0.4 mm, and 0.55+/-0.4 mm, for free hand approach while it was 1.0+/-0.57 mm, 0.45+/-0.4 mm, and 0.35+/-0.25 mm, for motorized approach, for target 1, 2, and 3, respectively. PPMCC remained almost at 1.0 for the motorized approach while having a variation between 0.9 and 1.0 for the free hand approach. Conclusions: motorized fusion guided prostate biopsy in a phantom study was feasible and non-inferior or comparable to the free hand manual approach in terms of accuracy and speed of targeting, while being superior in terms of repeatability and steadiness.

Self-consistent modeling of CFETR baseline scenarios for steady-state operation

NASA Astrophysics Data System (ADS)

Chen, Jiale; Jian, Xiang; Chan, Vincent S.; Li, Zeyu; Deng, Zhao; Li, Guoqiang; Guo, Wenfeng; Shi, Nan; Chen, Xi; CFETR Physics Team

2017-07-01

Integrated modeling for core plasma is performed to increase confidence in the proposed baseline scenario in the 0D analysis for the China Fusion Engineering Test Reactor (CFETR). The steady-state scenarios are obtained through the consistent iterative calculation of equilibrium, transport, auxiliary heating and current drives (H&CD). Three combinations of H&CD schemes (NB + EC, NB + EC + LH, and EC + LH) are used to sustain the scenarios with q min > 2 and fusion power of ˜70-150 MW. The predicted power is within the target range for CFETR Phase I, although the confinement based on physics models is lower than that assumed in 0D analysis. Ideal MHD stability analysis shows that the scenarios are stable against n = 1-10 ideal modes, where n is the toroidal mode number. Optimization of RF current drive for the RF-only scenario is also presented. The simulation workflow for core plasma in this work provides a solid basis for a more extensive research and development effort for the physics design of CFETR.

Records for conversion of laser energy to nuclear energy in exploding nanostructures

NASA Astrophysics Data System (ADS)

Jortner, Joshua; Last, Isidore

2017-09-01

Table-top nuclear fusion reactions in the chemical physics laboratory can be driven by high-energy dynamics of Coulomb exploding, multicharged, deuterium containing nanostructures generated by ultraintense, femtosecond, near-infrared laser pulses. Theoretical-computational studies of table-top laser-driven nuclear fusion of high-energy (up to 15 MeV) deuterons with 7Li, 6Li and D nuclei demonstrate the attainment of high fusion yields within a source-target reaction design, which constitutes the highest table-top fusion efficiencies obtained up to date. The conversion efficiency of laser energy to nuclear energy (0.1-1.0%) for table-top fusion is comparable to that for DT fusion currently accomplished for 'big science' inertial fusion setups.

Scientific and technological advancements in inertial fusion energy

DOE PAGES

Hinkel, D. E.

2013-09-26

Scientific advancements in inertial fusion energy (IFE) were reported on at the IAEA Fusion Energy Conference, October 2012. Results presented transect the different ways to assemble the fuel, different scenarios for igniting the fuel, and progress in IFE technologies. The achievements of the National Ignition Campaign within the USA, using the National Ignition Facility (NIF) to indirectly drive laser fusion, have found beneficial the achievements in other IFE arenas such as directly driven laser fusion and target fabrication. Moreover, the successes at NIF have pay-off to alternative scenarios such as fast ignition, shock ignition, and heavy-ion fusion as well asmore » to directly driven laser fusion. As a result, this synergy is summarized here, and future scientific studies are detailed.« less

Fusion of raft-like lipid bilayers operated by a membranotropic domain of the HSV-type I glycoprotein gH occurs through a cholesterol-dependent mechanism.

PubMed

Vitiello, Giuseppe; Falanga, Annarita; Petruk, Ariel Alcides; Merlino, Antonello; Fragneto, Giovanna; Paduano, Luigi; Galdiero, Stefania; D'Errico, Gerardino

2015-04-21

A wealth of evidence indicates that lipid rafts are involved in the fusion of the viral lipid envelope with the target cell membrane. However, the interplay between these sterol- and sphingolipid-enriched ordered domains and viral fusion glycoproteins has not yet been clarified. In this work we investigate the molecular mechanism by which a membranotropic fragment of the glycoprotein gH of the Herpes Simplex Virus (HSV) type I (gH625) drives fusion of lipid bilayers formed by palmitoyl oleoyl phosphatidylcholine (POPC)-sphingomyelin (SM)-cholesterol (CHOL) (1 : 1 : 1 wt/wt/wt), focusing on the role played by each component. The comparative analysis of the liposome fusion assays, Dynamic Light Scattering (DLS), spectrofluorimetry, Neutron Reflectivity (NR) and Electron Spin Resonance (ESR) experiments, and Molecular Dynamics (MD) simulations shows that CHOL is fundamental for liposome fusion to occur. In detail, CHOL stabilizes the gH625-bilayer association by specific interactions with the peptide Trp residue. The interaction with gH625 causes an increased order of the lipid acyl chains, whose local rotational motion is significantly hampered. SM plays only a minor role in the process, favoring the propagation of lipid perturbation to the bilayer inner core. The stiffening of the peptide-interacting bilayer leaflet results in an asymmetric perturbation of the membrane, which is locally destabilized thus favoring fusion events. Our results show that viral fusion glycoproteins are optimally suited to exert a high fusogenic activity on lipid rafts and support the relevance of cholesterol as a key player of membrane-related processes.

Systematic identification and analysis of frequent gene fusion events in metabolic pathways

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

Henry, Christopher S.; Lerma-Ortiz, Claudia; Gerdes, Svetlana Y.

Here, gene fusions are the most powerful type of in silico-derived functional associations. However, many fusion compilations were made when <100 genomes were available, and algorithms for identifying fusions need updating to handle the current avalanche of sequenced genomes. The availability of a large fusion dataset would help probe functional associations and enable systematic analysis of where and why fusion events occur. As a result, here we present a systematic analysis of fusions in prokaryotes. We manually generated two training sets: (i) 121 fusions in the model organism Escherichia coli; (ii) 131 fusions found in B vitamin metabolism. These setsmore » were used to develop a fusion prediction algorithm that captured the training set fusions with only 7 % false negatives and 50 % false positives, a substantial improvement over existing approaches. This algorithm was then applied to identify 3.8 million potential fusions across 11,473 genomes. The results of the analysis are available in a searchable database. A functional analysis identified 3,000 reactions associated with frequent fusion events and revealed areas of metabolism where fusions are particularly prevalent. In conclusion, customary definitions of fusions were shown to be ambiguous, and a stricter one was proposed. Exploring the genes participating in fusion events showed that they most commonly encode transporters, regulators, and metabolic enzymes. The major rationales for fusions between metabolic genes appear to be overcoming pathway bottlenecks, avoiding toxicity, controlling competing pathways, and facilitating expression and assembly of protein complexes. Finally, our fusion dataset provides powerful clues to decipher the biological activities of domains of unknown function.« less

Systematic identification and analysis of frequent gene fusion events in metabolic pathways

DOE PAGES

Henry, Christopher S.; Lerma-Ortiz, Claudia; Gerdes, Svetlana Y.; ...

2016-06-24

Here, gene fusions are the most powerful type of in silico-derived functional associations. However, many fusion compilations were made when <100 genomes were available, and algorithms for identifying fusions need updating to handle the current avalanche of sequenced genomes. The availability of a large fusion dataset would help probe functional associations and enable systematic analysis of where and why fusion events occur. As a result, here we present a systematic analysis of fusions in prokaryotes. We manually generated two training sets: (i) 121 fusions in the model organism Escherichia coli; (ii) 131 fusions found in B vitamin metabolism. These setsmore » were used to develop a fusion prediction algorithm that captured the training set fusions with only 7 % false negatives and 50 % false positives, a substantial improvement over existing approaches. This algorithm was then applied to identify 3.8 million potential fusions across 11,473 genomes. The results of the analysis are available in a searchable database. A functional analysis identified 3,000 reactions associated with frequent fusion events and revealed areas of metabolism where fusions are particularly prevalent. In conclusion, customary definitions of fusions were shown to be ambiguous, and a stricter one was proposed. Exploring the genes participating in fusion events showed that they most commonly encode transporters, regulators, and metabolic enzymes. The major rationales for fusions between metabolic genes appear to be overcoming pathway bottlenecks, avoiding toxicity, controlling competing pathways, and facilitating expression and assembly of protein complexes. Finally, our fusion dataset provides powerful clues to decipher the biological activities of domains of unknown function.« less

Stereotactic radiation treatment planning and follow-up studies involving fused multimodality imaging.

PubMed

Hamm, Klaus D; Surber, Gunnar; Schmücking, Michael; Wurm, Reinhard E; Aschenbach, Rene; Kleinert, Gabriele; Niesen, A; Baum, Richard P

2004-11-01

Innovative new software solutions may enable image fusion to produce the desired data superposition for precise target definition and follow-up studies in radiosurgery/stereotactic radiotherapy in patients with intracranial lesions. The aim is to integrate the anatomical and functional information completely into the radiation treatment planning and to achieve an exact comparison for follow-up examinations. Special conditions and advantages of BrainLAB's fully automatic image fusion system are evaluated and described for this purpose. In 458 patients, the radiation treatment planning and some follow-up studies were performed using an automatic image fusion technique involving the use of different imaging modalities. Each fusion was visually checked and corrected as necessary. The computerized tomography (CT) scans for radiation treatment planning (slice thickness 1.25 mm), as well as stereotactic angiography for arteriovenous malformations, were acquired using head fixation with stereotactic arc or, in the case of stereotactic radiotherapy, with a relocatable stereotactic mask. Different magnetic resonance (MR) imaging sequences (T1, T2, and fluid-attenuated inversion-recovery images) and positron emission tomography (PET) scans were obtained without head fixation. Fusion results and the effects on radiation treatment planning and follow-up studies were analyzed. The precision level of the results of the automatic fusion depended primarily on the image quality, especially the slice thickness and the field homogeneity when using MR images, as well as on patient movement during data acquisition. Fully automated image fusion of different MR, CT, and PET studies was performed for each patient. Only in a few cases was it necessary to correct the fusion manually after visual evaluation. These corrections were minor and did not materially affect treatment planning. High-quality fusion of thin slices of a region of interest with a complete head data set could be performed easily. The target volume for radiation treatment planning could be accurately delineated using multimodal information provided by CT, MR, angiography, and PET studies. The fusion of follow-up image data sets yielded results that could be successfully compared and quantitatively evaluated. Depending on the quality of the originally acquired image, automated image fusion can be a very valuable tool, allowing for fast (approximately 1-2 minute) and precise fusion of all relevant data sets. Fused multimodality imaging improves the target volume definition for radiation treatment planning. High-quality follow-up image data sets should be acquired for image fusion to provide exactly comparable slices and volumetric results that will contribute to quality contol.

C+C Fusion Cross Sections Measurements for Nuclear Astrophysics

DOE PAGES

Almaraz-Calderon, S.; Carnelli, P. F. F.; Rehm, K. E.; ...

2015-06-02

Total fusion cross section of carbon isotopes were obtained using the newly developed MUSIC detector. MUSIC is a highly efficient, active target-detector system designed to measure fusion excitation functions with radioactive beams. The present measurements are relevant for understanding x-ray superbursts. The results of the first MUSIC campaign as well as the astrophysical implications are presented in this work.

C+C Fusion Cross Sections Measurements for Nuclear Astrophysics

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

Almaraz-Calderon, S.; Carnelli, P. F. F.; Rehm, K. E.

Total fusion cross section of carbon isotopes were obtained using the newly developed MUSIC detector. MUSIC is a highly efficient, active target-detector system designed to measure fusion excitation functions with radioactive beams. The present measurements are relevant for understanding x-ray superbursts. The results of the first MUSIC campaign as well as the astrophysical implications are presented in this work.

Antiproton catalyzed microfission/fusion propulsion

NASA Technical Reports Server (NTRS)

Chiang, Pi-Ren; Lewis, Raymond A.; Smith, Gerald A.; Newton, Richard; Dailey, James; Werthman, W. Lance; Chakrabarti, Suman

1994-01-01

Inertial confinement fusion (ICF) utilizing an antiproton catalyzed hybrid fission/fusion target is discussed as a potential energy source for interplanetary propulsion. A proof-of-principle experiment underway at Phillips Laboratory, Kirtland AFB and antiproton trapping experiments at CERN, Geneva, Switzerland, are presented. The ICAN propulsion concept is described and results of performance analyses are reviewed. Future work to further define the ICAN concept is outlined.

Two-Plasmon Decay Mitigation in Direct-Drive Inertial-Confinement-Fusion Experiments Using Multilayer Targets.

PubMed

Follett, R K; Delettrez, J A; Edgell, D H; Goncharov, V N; Henchen, R J; Katz, J; Michel, D T; Myatt, J F; Shaw, J; Solodov, A A; Stoeckl, C; Yaakobi, B; Froula, D H

2016-04-15

Multilayer direct-drive inertial-confinement-fusion targets are shown to significantly reduce two-plasmon decay (TPD) driven hot-electron production while maintaining high hydrodynamic efficiency. Implosion experiments on the OMEGA laser used targets with silicon layered between an inner beryllium and outer silicon-doped plastic ablator. A factor-of-5 reduction in hot-electron generation (>50  keV) was observed in the multilayer targets relative to pure CH targets. Three-dimensional simulations of the TPD-driven hot-electron production using a laser-plasma interaction code (lpse) that includes nonlinear and kinetic effects show good agreement with the measurements. The simulations suggest that the reduction in hot-electron production observed in the multilayer targets is primarily caused by increased electron-ion collisional damping.

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

Singh, Varinderjit; Vadas, J.; Steinbach, T. K.

Measuring the fusion excitation function for an isotopic chain of projectile nuclei provides a stringent test of a microscopic description of fusion. We report the first measurement of the fusion excitation function at near-barrier energies for the 19O+ 12C system. The measured excitation function is compared with the fusion excitation function of 18O+ 12C. A significant enhancement in the fusion probability of 19O ions with a 12C target as compared to 18O ions is observed. As a result, the experimental cross-sections observed at near-barrier energies are compared with a state-of-the-art microscopic model.

Fusion partners can increase the expression of recombinant interleukins via transient transfection in 2936E cells

PubMed Central

Carter, Jane; Zhang, Jue; Dang, Thien-Lan; Hasegawa, Haruki; Cheng, Janet D; Gianan, Irene; O'Neill, Jason W; Wolfson, Martin; Siu, Sophia; Qu, Sheldon; Meininger, David; Kim, Helen; Delaney, John; Mehlin, Christopher

2010-01-01

The expression levels of five secreted target interleukins (IL-11, 15, 17B, 32, and IL23 p19 subunit) were tested with three different fusion partners in 2936E cells. When fused to the N-terminus, human serum albumin (HSA) was found to enhance the expression of both IL-17B and IL-15, cytokines which did not express at measurable levels on their own. Although the crystallizable fragment of an antibody (Fc) was also an effective fusion partner for IL-17B, Fc did not increase expression of IL-15. Fc was superior to HSA for the expression of the p19 subunit of IL-23, but no partner led to measurable levels of IL-32γ secretion. Glutathione S-transferase (GST) did not enhance the expression of any target and suppressed the production of IL-11, a cytokine which expressed robustly both on its own and when fused to HSA or Fc. Cleavage of the fusion partner was not always possible. The use of HSA or Fc as N-terminal fusions can be an effective technique to express difficult proteins, especially for applications in which the fusion partner need not be removed. PMID:20014434

Targeted expression, purification, and cleavage of fusion proteins from inclusion bodies in Escherichia coli.

PubMed

Hwang, Peter M; Pan, Jonathan S; Sykes, Brian D

2014-01-21

Today, proteins are typically overexpressed using solubility-enhancing fusion tags that allow for affinity chromatographic purification and subsequent removal by site-specific protease cleavage. In this review, we present an alternative approach to protein production using fusion partners specifically designed to accumulate in insoluble inclusion bodies. The strategy is appropriate for the mass production of short peptides, intrinsically disordered proteins, and proteins that can be efficiently refolded in vitro. There are many fusion protein systems now available for insoluble expression: TrpLE, ketosteroid isomerase, PurF, and PagP, for example. The ideal fusion partner is effective at directing a wide variety of target proteins into inclusion bodies, accumulates in large quantities in a highly pure form, and is readily solubilized and purified in commonly used denaturants. Fusion partner removal under denaturing conditions is biochemically challenging, requiring harsh conditions (e.g., cyanogen bromide in 70% formic acid) that can result in unwanted protein modifications. Recent advances in metal ion-catalyzed peptide bond cleavage allow for more mild conditions, and some methods involving nickel or palladium will likely soon appear in more biological applications. Copyright © 2013 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.

Transmembrane Domains of Highly Pathogenic Viral Fusion Proteins Exhibit Trimeric Association In Vitro

PubMed Central

Webb, Stacy R.; Smith, Stacy E.; Fried, Michael G.

2018-01-01

ABSTRACT Enveloped viruses require viral fusion proteins to promote fusion of the viral envelope with a target cell membrane. To drive fusion, these proteins undergo large conformational changes that must occur at the right place and at the right time. Understanding the elements which control the stability of the prefusion state and the initiation of conformational changes is key to understanding the function of these important proteins. The construction of mutations in the fusion protein transmembrane domains (TMDs) or the replacement of these domains with lipid anchors has implicated the TMD in the fusion process. However, the structural and molecular details of the role of the TMD in these fusion events remain unclear. Previously, we demonstrated that isolated paramyxovirus fusion protein TMDs associate in a monomer-trimer equilibrium, using sedimentation equilibrium analytical ultracentrifugation. Using a similar approach, the work presented here indicates that trimeric interactions also occur between the fusion protein TMDs of Ebola virus, influenza virus, severe acute respiratory syndrome coronavirus (SARS CoV), and rabies virus. Our results suggest that TM-TM interactions are important in the fusion protein function of diverse viral families. IMPORTANCE Many important human pathogens are enveloped viruses that utilize membrane-bound glycoproteins to mediate viral entry. Factors that contribute to the stability of these glycoproteins have been identified in the ectodomain of several viral fusion proteins, including residues within the soluble ectodomain. Although it is often thought to simply act as an anchor, the transmembrane domain of viral fusion proteins has been implicated in protein stability and function as well. Here, using a biophysical approach, we demonstrated that the fusion protein transmembrane domains of several deadly pathogens—Ebola virus, influenza virus, SARS CoV, and rabies virus—self-associate. This observation across various viral families suggests that transmembrane domain interactions may be broadly relevant and serve as a new target for therapeutic development. PMID:29669880

Enfuvirtide (T20)-Based Lipopeptide Is a Potent HIV-1 Cell Fusion Inhibitor: Implications for Viral Entry and Inhibition.

PubMed

Ding, Xiaohui; Zhang, Xiujuan; Chong, Huihui; Zhu, Yuanmei; Wei, Huamian; Wu, Xiyuan; He, Jinsheng; Wang, Xinquan; He, Yuxian

2017-09-15

The peptide drug enfuvirtide (T20) is the only viral fusion inhibitor used in combination therapy for HIV-1 infection, but it has relatively low antiviral activity and easily induces drug resistance. Emerging studies demonstrate that lipopeptide-based fusion inhibitors, such as LP-11 and LP-19, which mainly target the gp41 pocket site, have greatly improved antiviral potency and in vivo stability. In this study, we focused on developing a T20-based lipopeptide inhibitor that lacks pocket-binding sequence and targets a different site. First, the C-terminal tryptophan-rich motif (TRM) of T20 was verified to be essential for its target binding and inhibition; then, a novel lipopeptide, termed LP-40, was created by replacing the TRM with a fatty acid group. LP-40 showed markedly enhanced binding affinity for the target site and dramatically increased inhibitory activity on HIV-1 membrane fusion, entry, and infection. Unlike LP-11 and LP-19, which required a flexible linker between the peptide sequence and the lipid moiety, addition of a linker to LP-40 sharply reduced its potency, implying different binding modes with the extended N-terminal helices of gp41. Also, interestingly, LP-40 showed more potent activity than LP-11 in inhibiting HIV-1 Env-mediated cell-cell fusion while it was less active than LP-11 in inhibiting pseudovirus entry, and the two inhibitors displayed synergistic antiviral effects. The crystal structure of LP-40 in complex with a target peptide revealed their key binding residues and motifs. Combined, our studies have not only provided a potent HIV-1 fusion inhibitor, but also revealed new insights into the mechanisms of viral inhibition. IMPORTANCE T20 is the only membrane fusion inhibitor available for treatment of viral infection; however, T20 requires high doses and has a low genetic barrier for resistance, and its inhibitory mechanism and structural basis remain unclear. Here, we report the design of LP-40, a T20-based lipopeptide inhibitor that has greatly improved anti-HIV activity and is a more potent inhibitor of cell-cell fusion than of cell-free virus infection. The binding modes of two classes of membrane-anchoring lipopeptides (LP-40 and LP-11) verify the current fusion model in which an extended prehairpin structure bridges the viral and cellular membranes, and their complementary effects suggest a vital strategy for combination therapy of HIV-1 infection. Moreover, our understanding of the mechanism of action of T20 and its derivatives benefits from the crystal structure of LP-40. Copyright © 2017 American Society for Microbiology.

A Fusion Architecture for Tracking a Group of People Using a Distributed Sensor Network

DTIC Science & Technology

2013-07-01

Determining the composition of the group is done using several classifiers. The fusion is done at the UGS level to fuse information from all the modalities to...to classification and counting of the targets. Section III also presents the algorithms for fusion of distributed sensor data at the UGS level and...ultrasonic sensors. Determining the composition of the group is done using several classifiers. The fusion is done at the UGS level to fuse

Development of position measurement unit for flying inertial fusion energy target

NASA Astrophysics Data System (ADS)

Tsuji, R.; Endo, T.; Yoshida, H.; Norimatsu, T.

2016-03-01

We have reported the present status in the development of a position measurement unit (PMU) for a flying inertial fusion energy (IFE) target. The PMU, which uses Arago spot phenomena, is designed to have a measurement accuracy smaller than 1 μm. By employing divergent, pulsed orthogonal laser beam illumination, we can measure the time and the target position at the pulsed illumination. The two-dimensional Arago spot image is compressed into one-dimensional image by a cylindrical lens for real-time processing. The PMU are set along the injection path of the flying target. The local positions of the target in each PMU are transferred to the controller and analysed to calculate the target trajectory. Two methods are presented to calculate the arrival time and the arrival position of the target at the reactor centre.

DARPin-Based Crystallization Chaperones Exploit Molecular Geometry as a Screening Dimension in Protein Crystallography.

PubMed

Batyuk, Alexander; Wu, Yufan; Honegger, Annemarie; Heberling, Matthew M; Plückthun, Andreas

2016-04-24

DARPin libraries, based on a Designed Ankyrin Repeat Protein consensus framework, are a rich source of binding partners for a wide variety of proteins. Their modular structure, stability, ease of in vitro selection and high production yields make DARPins an ideal starting point for further engineering. The X-ray structures of around 30 different DARPin complexes demonstrate their ability to facilitate crystallization of their target proteins by restricting flexibility and preventing undesired interactions of the target molecule. However, their small size (18 kDa), very hydrophilic surface and repetitive structure can limit the DARPins' ability to provide essential crystal contacts and their usefulness as a search model for addressing the crystallographic phase problem in molecular replacement. To optimize DARPins for their application as crystallization chaperones, rigid domain-domain fusions of the DARPins to larger proteins, proven to yield high-resolution crystal structures, were generated. These fusions were designed in such a way that they affect only one of the terminal capping repeats of the DARPin and do not interfere with residues involved in target binding, allowing to exchange at will the binding specificities of the DARPin in the fusion construct. As a proof of principle, we designed rigid fusions of a stabilized version of Escherichia coli TEM-1 β-lactamase to the C-terminal capping repeat of various DARPins in six different relative domain orientations. Five crystal structures representing four different fusion constructs, alone or in complex with the cognate target, show the predicted relative domain orientations and prove the validity of the concept. Copyright © 2016 Elsevier Ltd. All rights reserved.

K/T age for the popigai impact event

NASA Technical Reports Server (NTRS)

Deino, A. L.; Garvin, J. B.; Montanari, S.

1991-01-01

The multi-ringed POPIGAI structure, with an outer ring diameter of over 100 km, is the largest impact feature currently recognized on Earth with an Phanerozoic age. The target rocks in this relatively unglaciated region consist of upper Proterozoic through Mesozoic platform sediments and igneous rocks overlying Precambrian crystalline basement. The reported absolute age of the Popigai impact event ranges from 30.5 to 39 Ma. With the intent of refining this age estimate, a melt-breccia (suevite) sample from the inner regions of the Popigai structure was prepared for total fusion and step-wise heating Ar-40/Ar-39 analysis. Although the total fusion and step-heating experiments suggest some degree of age heterogeneity, the recurring theme is an age of around 64 to 66 Ma.

Neural network fusion capabilities for efficient implementation of tracking algorithms

NASA Astrophysics Data System (ADS)

Sundareshan, Malur K.; Amoozegar, Farid

1997-03-01

The ability to efficiently fuse information of different forms to facilitate intelligent decision making is one of the major capabilities of trained multilayer neural networks that is now being recognized. While development of innovative adaptive control algorithms for nonlinear dynamical plants that attempt to exploit these capabilities seems to be more popular, a corresponding development of nonlinear estimation algorithms using these approaches, particularly for application in target surveillance and guidance operations, has not received similar attention. We describe the capabilities and functionality of neural network algorithms for data fusion and implementation of tracking filters. To discuss details and to serve as a vehicle for quantitative performance evaluations, the illustrative case of estimating the position and velocity of surveillance targets is considered. Efficient target- tracking algorithms that can utilize data from a host of sensing modalities and are capable of reliably tracking even uncooperative targets executing fast and complex maneuvers are of interest in a number of applications. The primary motivation for employing neural networks in these applications comes from the efficiency with which more features extracted from different sensor measurements can be utilized as inputs for estimating target maneuvers. A system architecture that efficiently integrates the fusion capabilities of a trained multilayer neural net with the tracking performance of a Kalman filter is described. The innovation lies in the way the fusion of multisensor data is accomplished to facilitate improved estimation without increasing the computational complexity of the dynamical state estimator itself.

Expression of the B subunit of Escherichia coli heat-labile enterotoxin as a fusion protein in transgenic tomato.

PubMed

Walmsley, A M; Alvarez, M L; Jin, Y; Kirk, D D; Lee, S M; Pinkhasov, J; Rigano, M M; Arntzen, C J; Mason, H S

2003-06-01

Epitopes often require co-delivery with an adjuvant or targeting protein to enable recognition by the immune system. This paper reports the ability of transgenic tomato plants to express a fusion protein consisting of the B subunit of the Escherichia coli heat-labile enterotoxin (LTB) and an immunocontraceptive epitope. The fusion protein was found to assemble into pentamers, as evidenced by its ability to bind to gangliosides, and had an average expression level of 37.8 microg g(-1) in freeze-dried transgenic tissues. Processing of selected transgenic fruit resulted in a 16-fold increase in concentration of the antigen with minimal loss in detectable antigen. The species-specific nature of this epitope was shown by the inability of antibodies raised against non-target species to detect the LTB fusion protein. The immunocontraceptive ability of this vaccine will be tested in future pilot mice studies.

Soft X-ray streak camera for laser fusion applications

NASA Astrophysics Data System (ADS)

Stradling, G. L.

1981-04-01

The development and significance of the soft x-ray streak camera (SXRSC) in the context of inertial confinement fusion energy development is reviewed as well as laser fusion and laser fusion diagnostics. The SXRSC design criteria, the requirement for a subkilovolt x-ray transmitting window, and the resulting camera design are explained. Theory and design of reflector-filter pair combinations for three subkilovolt channels centered at 220 eV, 460 eV, and 620 eV are also presented. Calibration experiments are explained and data showing a dynamic range of 1000 and a sweep speed of 134 psec/mm are presented. Sensitivity modifications to the soft x-ray streak camera for a high-power target shot are described. A preliminary investigation, using a stepped cathode, of the thickness dependence of the gold photocathode response is discussed. Data from a typical Argus laser gold-disk target experiment are shown.

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.

Semi-analytic model of plasma-jet-driven magneto-inertial fusion

DOE PAGES

Langendorf, Samuel J.; Hsu, Scott C.

2017-03-01

A semi-analytic model for plasma-jet-driven magneto-inertial fusion is presented here. Compressions of a magnetized plasma target by a spherically imploding plasma liner are calculated in one dimension (1D), accounting for compressible hydrodynamics and ionization of the liner material, energy losses due to conduction and radiation, fusion burn and alpha deposition, separate ion and electron temperatures in the target, magnetic pressure, and fuel burn-up. Results show 1D gains of 3–30 at spherical convergence ratio <15 and 20–40 MJ of liner energy, for cases in which the liner thickness is 1 cm and the initial radius of a preheated magnetized target ismore » 4 cm. Some exploration of parameter space and physics settings is presented. The yields observed suggest that there is a possibility of igniting additional dense fuel layers to reach high gain.« less

Use Of Adaptive Optics Element For Wavefront Error Correction In The Gemini CO2 Laser Fusion System

NASA Astrophysics Data System (ADS)

Viswanathan, V. K.; Parker, J. V.; Nussmier, T. A.; Swigert, C. J.; King, W.; Lau, A. S.; Price, K.

1980-11-01

The Gemini two beam CO2 laser fusion system incorporates a complex optical system with nearly 100 surfaces per beam, associated with the generation, transport and focusing of CO2 laser beams for irradiating laser fusion targets. Even though the system is nominally diffraction limited, in practice the departure from the ideal situation drops the Strehl ratio to 0.24. This departure is caused mostly by the imperfections in the large (34 cm optical clear aperture diameter) state-of-the-art components like the sodium chloride windows and micromachined mirrors. While the smaller optical components also contribute to this degradation, the various possible misalignments and nonlinear effects are considered to contribute very little to it. Analysis indicates that removing the static or quasi-static errors can dramatically improve the Strehl ratio. A deformable mirror which can comfortably achieve the design goal Strehl ratio of >= 0.7 is described, along with the various system trade-offs in the design of the mirror and the control system.

Expression of a synthetic neutralizing epitope of porcine epidemic diarrhea virus fused with synthetic B subunit of Escherichia coli heat labile enterotoxin in rice endosperm.

PubMed

Oszvald, Maria; Kang, Tae-Jin; Tomoskozi, Sandor; Tamas, Cecilia; Tamas, Laszlo; Kim, Tae-Geum; Yang, Moon-Sik

2007-03-01

Epitopes often require co-delivery with adjuvant and targeting proteins to enable recognition by the immune system, and this approach may also increase the efficacy of the antigen. In this study, we assess and describe the ability of transgenic rice plants to express a fusion protein consisting of the B-subunit of the Escherichia coli heat-labile enterotoxin (LTB) and a synthetic core-neutralizing epitope (COE) of porcine epidemic diarrhea virus (PEDV), inducing an enteric disease that is seen most predominantly in piglets. Both components of the fusion proteins were detected with Western blot analysis. The fusion protein was determined to assemble into pentamers, as was evidenced by its ability to bind to GM1 gangliosides, and evidenced an average level of expression in a transgenic rice endosperm. This indicates that the expression system of the plant is capable of generating a sizable amount of antigen, possibly allowing for the successful development of an edible vaccine.

Sensor Fusion and Smart Sensor in Sports and Biomedical Applications.

PubMed

Mendes, José Jair Alves; Vieira, Mário Elias Marinho; Pires, Marcelo Bissi; Stevan, Sergio Luiz

2016-09-23

The following work presents an overview of smart sensors and sensor fusion targeted at biomedical applications and sports areas. In this work, the integration of these areas is demonstrated, promoting a reflection about techniques and applications to collect, quantify and qualify some physical variables associated with the human body. These techniques are presented in various biomedical and sports applications, which cover areas related to diagnostics, rehabilitation, physical monitoring, and the development of performance in athletes, among others. Although some applications are described in only one of two fields of study (biomedicine and sports), it is very likely that the same application fits in both, with small peculiarities or adaptations. To illustrate the contemporaneity of applications, an analysis of specialized papers published in the last six years has been made. In this context, the main characteristic of this review is to present the largest quantity of relevant examples of sensor fusion and smart sensors focusing on their utilization and proposals, without deeply addressing one specific system or technique, to the detriment of the others.

Magnetized Target Fusion Driven by Plasma Liners

NASA Technical Reports Server (NTRS)

Thio, Y. C. Francis; Eskridge, Richard; Smith, James; Lee, Michael; Richeson, Jeff; Schmidt, George; Knapp, Charles E.; Kirkpatrick, Ronald C.; Turchi, Peter J.; Rodgers, Stephen L. (Technical Monitor)

2001-01-01

Magnetized target fusion (MTF) attempts to combine the favorable attributes of magnetic confinement fusion (MCF) for energy confinement with the attributes of inertial confinement fusion (ICF) for efficient compression heating and wall-free containment of the fusing plasma. It uses a material liner to compress and contain a magnetized plasma. For practical applications, standoff drivers to deliver the imploding momentum flux to the target plasma remotely are required. Spherically converging plasma jets have been proposed as standoff drivers for this purpose. The concept involves the dynamic formation of a spherical plasma liner by the merging of plasma jets, and the use of the liner so formed to compress a spheromak or a field reversed configuration (FRC). For the successful implementation of the scheme, plasma jets of the requisite momentum flux density need to be produced. Their transport over sufficiently large distances (a few meters) needs to be assured. When they collide and merge into a liner, relative differences in velocity, density and temperature of the jets could give rise to instabilities in the development of the liner. Variation in the jet properties must be controlled to ensure that the growth rate of the instabilities are not significant over the time scale of the liner formation before engaging with the target plasma. On impact with the target plasma, some plasma interpenetration might occur between the liner and the target. The operating parameter space needs to be identified to ensure that a reasonably robust and conducting contact surface is formed between the liner and the target. A mismatch in the "impedance" between the liner and the target plasma could give rise to undesirable shock heating of the liner leading to increased entropy (thermal losses) in the liner. Any irregularities in the liner will accentuate the Rayleigh-Taylor instabilities during the compression of the target plasma by the liner.

[Analysis of EML4-ALK gene fusion mutation in patients 
with non-small cell lung cancer].

PubMed

Wang, Xuzhou; Chen, Weisheng; Yu, Yinghao

2015-02-01

Non-small cell lung cancer (NSCLC) is the main type of lung cancer, and the related locus mutation detection research has become a hot direction of molecular targeted therapy, studying on gene mutation status of echinodem microtubule associated protein like 4-Anaplastic lymphoma kinase (EML4-ALK) and epidermal growth factor receptor (EGFR), detecting the sensitivity of EML4-ALK gene fusion and gene mutation of EGFR. EML4-ALK gene fusion in 85 cases of paraffin embedded tumor tissue and adjacent lung tissue was detected with the application of immunohistochemistry (IHC), Scorpions amplification refractory mutation system (Scorpions ARMS) fluorescence quantitative PCR and fluorescence in situ hybridization (FISH) technology, and EGFR gene in 18, 19, 20 and 21 exon mutation status was detected with the application of ARMS method. In 115 cases of NSCLC, IHC showed 32 cases with ALK (D5F3) expression, the expression rate was 27.8%; ARMS showed 27 cases with EML4-ALK fusion gene mutation, the mutation detection rate was 23.5%; 53 cases were detected with EGFR mutation, the mutation rate was 46%. While FISH showed 23 cases with EML4-ALK fusion gene mutation, the detection rate was 20%, slightly lower than the ARMS detection results, suggesting that ARMS more sensitive. The application of IHC, ARMS fluorescence quantitative PCR and FISH technology can make a rapid and accurate evaluation of EML4-ALK gene fusion.

Structural requirements of oleosin domains for subcellular targeting to the oil body.

PubMed Central

van Rooijen, G J; Moloney, M M

1995-01-01

We have investigated the protein domains responsible for the correct subcellular targeting of plant seed oleosins. We have attempted to study this targeting in vivo using "tagged" oleosins in transgenic plants. Different constructs were prepared lacking gene sequences encoding one of three structural domains of natural oleosins. Each was fused in frame to the Escherichia coli uid A gene encoding beta-glucuronidase (GUS). These constructs were introduced into Brassica napus using Agrobacterium-mediated transformation. GUS activity was measured in washed oil bodies and in the soluble protein fraction of the transgenic seeds. It was found that complete Arabidopsis oleosin-GUS fusions undergo correct subcellular targeting in transgenic Brassica seeds. Removal of the C-terminal domain of the Arabidopsis oleosin comprising the last 48 amino acids had no effect on overall subcellular targeting. In contrast, loss of the first 47 amino acids (N terminus) or amino acids 48 to 113 (which make up a lipophilic core) resulted in impaired targeting of the fusion protein to the oil bodies and greatly reduced accumulation of the fusion protein. Northern blotting revealed that this reduction is not due to differences in mRNA accumulation. Results from these measurements indicated that both the N-terminal and central oleosin domain are important for targeting to the oil body and show that there is a direct correlation between the inability to target to the oil body and protein stability. PMID:8539295

Blood-brain barrier drug delivery of IgG fusion proteins with a transferrin receptor monoclonal antibody.

PubMed

Pardridge, William M

2015-02-01

Biologic drugs are large molecules that do not cross the blood- brain barrier (BBB). Brain penetration is possible following the re-engineering of the biologic drug as an IgG fusion protein. The IgG domain is a MAb against an endogenous BBB receptor such as the transferrin receptor (TfR). The TfRMAb acts as a molecular Trojan horse to ferry the fused biologic drug into the brain via receptor-mediated transport on the endogenous BBB TfR. This review discusses TfR isoforms, models of BBB transport of transferrin and TfRMAbs, and the genetic engineering of TfRMAb fusion proteins, including BBB penetrating IgG-neurotrophins, IgG-decoy receptors, IgG-lysosomal enzyme therapeutics and IgG-avidin fusion proteins, as well as BBB transport of bispecific antibodies formed by fusion of a therapeutic antibody to a TfRMAb targeting antibody. Also discussed are quantitative aspects of the plasma pharmacokinetics and brain uptake of TfRMAb fusion proteins, as compared to the brain uptake of small molecules, and therapeutic applications of TfRMAb fusion proteins in mouse models of neural disease, including Parkinson's disease, stroke, Alzheimer's disease and lysosomal storage disorders. The review covers the engineering of TfRMAb-avidin fusion proteins for BBB targeted delivery of biotinylated peptide radiopharmaceuticals, low-affinity TfRMAb Trojan horses and the safety pharmacology of chronic administration of TfRMAb fusion proteins. The BBB delivery of biologic drugs is possible following re-engineering as a fusion protein with a molecular Trojan horse such as a TfRMAb. The efficacy of this technology will be determined by the outcome of future clinical trials.

Brief Report: A mass spectrometry assay to simultaneously analyze ROS1 and RET fusion gene expression in non-small cell lung cancer

PubMed Central

Wijesinghe, Priyanga; Bepler, Gerold

2014-01-01

Introduction ROS1 and RET gene fusions were recently discovered in non-small cell lung cancer (NSCLC) as potential therapeutic targets with small molecule kinase inhibitors. The conventional screening methods of these fusions are time consuming and require samples of high quality and quantity. Here, we describe a novel and efficient method by coupling the power of multiplexing PCR and the sensitivity of mass spectrometry. Methods The multiplex mass spectrometry platform simultaneously tests samples for the expression of nine ROS1 and six RET fusion genes. The assay incorporates detection of wild-type exon junctions immediately upstream and downstream of the fusion junction to exclude false negative results. To flag false positives, the system also comprises two independent assays for each fusion gene junction. Results The characteristic mass spectrometric peaks of the gene fusions were obtained using engineered plasmid constructs. Specific assays targeting the wild-type gene exon junctions were validated using cDNA from lung tissue of healthy individuals. The system was further validated using cDNA derived from NSCLC cell lines that express endogenous fusion genes. The expressed ROS1-SLC34A2 and CCDC6-RET gene fusions from the NSCLC cell lines HCC78 and LC-2/ad, respectively, were accurately detected by the novel assay. The assay is extremely sensitive, capable of detecting an event in test specimens containing 0.5% positive tumors. Conclusion The novel multiplexed assay is robustly capable of detecting 15 different clinically relevant RET and ROS1 fusion variants. The benefits of this detection method include exceptionally low sample input, high cost efficiency, flexibility, and rapid turnover. PMID:25384172

Nuclear Fusion In Gases Of Deuterium Clusters And Hot Electron Generation In Droplet Sprays Under Irradiation With An Intense Femtosecond Laser

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

T. Ditmire; Zweiback, J; Cowan, T E

In conclusion, we have observed the production of 2.45 MeV deuterium fusion neutrons when a gas of deuterium clusters is irradiated with a 120 mJ, 35 fs laser pulse. When the focal position is optimized, we have observed as many as 10{sup 4} neutrons per laser shot. This yield is consistent with some simple estimates for the fusion yield. We also find that the fusion yield is a sensitive function of the deuterium cluster size in the target jet, a consequence of the Coulomb explosion origin of the fast deuterons. We also find that the neutron pulse duration is fast,more » with a characteristic burn time of well under 1 ns. This experiment may represent a means for producing a compact, table-top source of short pulse fusion neutrons for applications. Furthermore, we have measured hard x-ray yield from femtosecond laser interactions with both solid and micron scale droplet targets. Strong hard x-ray production is observed from both targets. However, the inferred electron temperature is somewhat higher in the case of irradiation of the droplets. These data are consistent with PIC simulations. This finding indicates that quite unique hot electron dynamics occur during the irradiation of wavelength scale particles by an intense laser field and likely warrants further study.« less

Bio-mimetic Nanostructure Self-assembled from Au@Ag Heterogeneous Nanorods and Phage Fusion Proteins for Targeted Tumor Optical Detection and Photothermal Therapy

NASA Astrophysics Data System (ADS)

Wang, Fei; Liu, Pei; Sun, Lin; Li, Cuncheng; Petrenko, Valery A.; Liu, Aihua

2014-10-01

Nanomaterials with near-infrared (NIR) absorption have been widely studied in cancer detection and photothermal therapy (PTT), while it remains a great challenge in targeting tumor efficiently with minimal side effects. Herein we report a novel multifunctional phage-mimetic nanostructure, which was prepared by layer-by-layer self-assembly of Au@Ag heterogenous nanorods (NRs) with rhodamine 6G, and specific pVIII fusion proteins. Au@Ag NRs, first being applied for PTT, exhibited excellent stability, cost-effectivity, biocompatibility and tunable NIR absorption. The fusion proteins were isolated from phage DDAGNRQP specifically selected from f8/8 landscape phage library against colorectal cancer cells in a high-throughput way. Considering the definite charge distribution and low molecular weight, phage fusion proteins were assembled on the negatively charged NR core by electrostatic interactions, exposing the N-terminus fused with DDAGNRQP peptide on the surface. The fluorescent images showed that assembled phage fusion proteins can direct the nanostructure into cancer cells. The nanostructure was more efficient than gold nanorods and silver nanotriangle-based photothermal agents and was capable of specifically ablating SW620 cells after 10 min illumination with an 808 nm laser in the light intensity of 4 W/cm2. The prepared nanostructure would become an ideal reagent for simutaneously targeted optical imaging and PTT of tumor.

ALK Inhibitor Response in Melanomas Expressing EML4-ALK Fusions and Alternate ALK Isoforms.

PubMed

Couts, Kasey L; Bemis, Judson; Turner, Jacqueline A; Bagby, Stacey M; Murphy, Danielle; Christiansen, Jason; Hintzsche, Jennifer D; Le, Anh; Pitts, Todd M; Wells, Keith; Applegate, Allison; Amato, Carol; Multani, Pratik; Chow-Maneval, Edna; Tentler, John J; Shellman, Yiqun G; Rioth, Matthew J; Tan, Aik-Choon; Gonzalez, Rene; Medina, Theresa; Doebele, Robert C; Robinson, William A

2018-01-01

Oncogenic ALK fusions occur in several types of cancer and can be effectively treated with ALK inhibitors; however, ALK fusions and treatment response have not been characterized in malignant melanomas. Recently, a novel isoform of ALK ( ALK ATI ) was reported in 11% of melanomas but the response of melanomas expressing ALK ATI to ALK inhibition has not been well characterized. We analyzed 45 melanoma patient-derived xenograft models for ALK mRNA and protein expression. ALK expression was identified in 11 of 45 (24.4%) melanomas. Ten melanomas express wild-type (wt) ALK and/or ALK ATI and one mucosal melanoma expresses multiple novel EML4-ALK fusion variants. Melanoma cells expressing different ALK variants were tested for response to ALK inhibitors. Whereas the melanoma expressing EML4-ALK were sensitive to ALK inhibitors in vitro and in vivo , the melanomas expressing wt ALK or ALK ATI were not sensitive to ALK inhibitors. In addition, a patient with mucosal melanoma expressing ALK ATI was treated with an ALK/ROS1/TRK inhibitor (entrectinib) on a phase I trial but did not respond. Our results demonstrate ALK fusions occur in malignant melanomas and respond to targeted therapy, whereas melanomas expressing ALK ATI do not respond to ALK inhibitors. Targeting ALK fusions is an effective therapeutic option for a subset of melanoma patients, but additional clinical studies are needed to determine the efficacy of targeted therapies in melanomas expressing wt ALK or ALK ATI Mol Cancer Ther; 17(1); 222-31. ©2017 AACR . ©2017 American Association for Cancer Research.

Present status of liquid metal research for a fusion reactor

NASA Astrophysics Data System (ADS)

Tabarés, Francisco L.

2016-01-01

Although the use of solid materials as targets of divertor plasmas in magnetic fusion research is accepted as the standard solution for the very challenging issue of power and particle handling in a fusion reactor, a generalized feeling that the present options chosen for ITER will not represent the best choice for a reactor is growing up. The problems found for tungsten, the present selection for the divertor target of ITER, in laboratory tests and in hot plasma fusion devices suggest so. Even in the absence of the strong neutron irradiation expected in a reactor, issues like surface melting, droplet ejection, surface cracking, dust generation, etc., call for alternative solutions in a long pulse, high efficient fusion energy-producing continuous machine. Fortunately enough, decades of research on plasma facing materials based on liquid metals (LMs) have produced a wealth of appealing ideas that could find practical application in the route to the realization of a commercial fusion power plant. The options presently available, although in a different degree of maturity, range from full coverage of the inner wall of the device with liquid metals, so that power and particle exhaust together with neutron shielding could be provided, to more conservative combinations of liquid metal films and conventional solid targets basically representing a sort of high performance, evaporative coating for the alleviation of the surface degradation issues found so far. In this work, an updated review of worldwide activities on LM research is presented, together with some open issues still remaining and some proposals based on simple physical considerations leading to the optimization of the most conservative alternatives.

Fabrication of 121Sb isotopic targets for the study of nuclear high spin features

NASA Astrophysics Data System (ADS)

Devi, K. Rojeeta; Kumar, Suresh; Kumar, Neeraj; Abhilash, S. R.; Kabiraj, D.

2018-06-01

Isotopic 121Sb targets with 197Au backing have been prepared by Physical Vapor Deposition (PVD) method using the diffusion pump based coating unit at target laboratory, Inter University Accelerator Centre (IUAC), New Delhi, India. The target thickness was measured by stylus profilo-meter and the purity of the targets was investigated by Energy Dispersive X-ray Analysis (EDXA). One of these targets has been used in an experiment which was performed at IUAC for nuclear structure study through fusion evaporation reaction. The excitation function of the 121Sb(12C, yxnγ) reaction has been performed for energies 58 to 70 MeV in steps of 4 MeV. The experimental results were compared with the calculations of statistical models : PACE4 and CASCADE. The methods adopted to achieve best quality foils and good deposition efficiency are reported in this paper.

A dual-channel fusion system of visual and infrared images based on color transfer

NASA Astrophysics Data System (ADS)

Pei, Chuang; Jiang, Xiao-yu; Zhang, Peng-wei; Liang, Hao-cong

2013-09-01

A dual-channel fusion system of visual and infrared images based on color transfer The increasing availability and deployment of imaging sensors operating in multiple spectrums has led to a large research effort in image fusion, resulting in a plethora of pixel-level image fusion algorithms. However, most of these algorithms have gray or false color fusion results which are not adapt to human vision. Transfer color from a day-time reference image to get natural color fusion result is an effective way to solve this problem, but the computation cost of color transfer is expensive and can't meet the request of real-time image processing. We developed a dual-channel infrared and visual images fusion system based on TMS320DM642 digital signal processing chip. The system is divided into image acquisition and registration unit, image fusion processing unit, system control unit and image fusion result out-put unit. The image registration of dual-channel images is realized by combining hardware and software methods in the system. False color image fusion algorithm in RGB color space is used to get R-G fused image, then the system chooses a reference image to transfer color to the fusion result. A color lookup table based on statistical properties of images is proposed to solve the complexity computation problem in color transfer. The mapping calculation between the standard lookup table and the improved color lookup table is simple and only once for a fixed scene. The real-time fusion and natural colorization of infrared and visual images are realized by this system. The experimental result shows that the color-transferred images have a natural color perception to human eyes, and can highlight the targets effectively with clear background details. Human observers with this system will be able to interpret the image better and faster, thereby improving situational awareness and reducing target detection time.

The three lives of viral fusion peptides

PubMed Central

Apellániz, Beatriz; Huarte, Nerea; Largo, Eneko; Nieva, José L.

2014-01-01

Fusion peptides comprise conserved hydrophobic domains absolutely required for the fusogenic activity of glycoproteins from divergent virus families. After 30 years of intensive research efforts, the structures and functions underlying their high degree of sequence conservation are not fully elucidated. The long-hydrophobic viral fusion peptide (VFP) sequences are structurally constrained to access three successive states after biogenesis. Firstly, the VFP sequence must fulfill the set of native interactions required for (meta) stable folding within the globular ectodomains of glycoprotein complexes. Secondly, at the onset of the fusion process, they get transferred into the target cell membrane and adopt specific conformations therein. According to commonly accepted mechanistic models, membrane-bound states of the VFP might promote the lipid bilayer remodeling required for virus-cell membrane merger. Finally, at least in some instances, several VFPs co-assemble with transmembrane anchors into membrane integral helical bundles, following a locking movement hypothetically coupled to fusion-pore expansion. Here we review different aspects of the three major states of the VFPs, including the functional assistance by other membrane-transferring glycoprotein regions, and discuss briefly their potential as targets for clinical intervention. PMID:24704587

Fusion technologies for Laser Inertial Fusion Energy (LIFE)

NASA Astrophysics Data System (ADS)

Kramer, K. J.; Latkowski, J. F.; Abbott, R. P.; Anklam, T. P.; Dunne, A. M.; El-Dasher, B. S.; Flowers, D. L.; Fluss, M. J.; Lafuente, A.; Loosmore, G. A.; Morris, K. R.; Moses, E.; Reyes, S.

2013-11-01

The Laser Inertial Fusion-based Energy (LIFE) engine design builds upon on going progress at the National Ignition Facility (NIF) and offers a near-term pathway to commercial fusion. Fusion technologies that are critical to success are reflected in the design of the first wall, blanket and tritium separation subsystems. The present work describes the LIFE engine-related components and technologies. LIFE utilizes a thermally robust indirect-drive target and a chamber fill gas. Coolant selection and a large chamber solid-angle coverage provide ample tritium breeding margin and high blanket gain. Target material selection eliminates the need for aggressive chamber clearing, while enabling recycling. Demonstrated tritium separation and storage technologies limit the site tritium inventory to attractive levels. These key technologies, along with the maintenance and advanced materials qualification program have been integrated into the LIFE delivery plan. This describes the development of components and subsystems, through prototyping and integration into a First Of A Kind power plant. This work performed under the auspices of the U.S. Department of Energy by Lawrence Livermore National Laboratory under Contract DE-AC52-07NA27344.

Developing DIII-D To Prepare For ITER And The Path To Fusion Energy

NASA Astrophysics Data System (ADS)

Buttery, Richard; Hill, David; Solomon, Wayne; Guo, Houyang; DIII-D Team

2017-10-01

DIII-D pursues the advancement of fusion energy through scientific understanding and discovery of solutions. Research targets two key goals. First, to prepare for ITER we must resolve how to use its flexible control tools to rapidly reach Q =10, and develop the scientific basis to interpret results from ITER for fusion projection. Second, we must determine how to sustain a high performance fusion core in steady state conditions, with minimal actuators and a plasma exhaust solution. DIII-D will target these missions with: (i) increased electron heating and balanced torque neutral beams to simulate burning plasma conditions (ii) new 3D coil arrays to resolve control of transients (iii) off axis current drive to study physics in steady state regimes (iv) divertors configurations to promote detachment with low upstream density (v) a reactor relevant wall to qualify materials and resolve physics in reactor-like conditions. With new diagnostics and leading edge simulation, this will position the US for success in ITER and a unique knowledge to accelerate the approach to fusion energy. Supported by the US DOE under DE-FC02-04ER54698.

Soft x-ray streak camera for laser fusion applications

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

Stradling, G.L.

This thesis reviews the development and significance of the soft x-ray streak camera (SXRSC) in the context of inertial confinement fusion energy development. A brief introduction of laser fusion and laser fusion diagnostics is presented. The need for a soft x-ray streak camera as a laser fusion diagnostic is shown. Basic x-ray streak camera characteristics, design, and operation are reviewed. The SXRSC design criteria, the requirement for a subkilovolt x-ray transmitting window, and the resulting camera design are explained. Theory and design of reflector-filter pair combinations for three subkilovolt channels centered at 220 eV, 460 eV, and 620 eV aremore » also presented. Calibration experiments are explained and data showing a dynamic range of 1000 and a sweep speed of 134 psec/mm are presented. Sensitivity modifications to the soft x-ray streak camera for a high-power target shot are described. A preliminary investigation, using a stepped cathode, of the thickness dependence of the gold photocathode response is discussed. Data from a typical Argus laser gold-disk target experiment are shown.« less

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.

Determination of cDNA encoding BCR/ABL fusion gene in patients with chronic myelogenous leukemia using a novel FRET-based quantum dots-DNA nanosensor.

PubMed

Shamsipur, Mojtaba; Nasirian, Vahid; Barati, Ali; Mansouri, Kamran; Vaisi-Raygani, Asad; Kashanian, Soheila

2017-05-08

In the present study, we developed a sensitive method based on fluorescence resonance energy transfer (FRET) for the determination of the BCR/ABL fusion gene, which is used as a biomarker to confirm the clinical diagnosis of both chronic myelogenous leukemia (CML) and acute lymphocytic leukemia (ALL). For this purpose, CdTe quantum dots (QDs) were conjugated to amino-modified 18-mer oligonucleotide ((N)DNA) to form the QDs-(N)DNA nanosensor. In the presence of methylene blue (MB) as an intercalator, the hybridization of QDs-(N)DNA with the target BCR/ABL fusion gene (complementary DNA), brings the MB (acceptor) at close proximity of the QDs (donor), leading to FRET upon photoexcitation of the QDs. The enhancement in the emission intensity of MB was used to follow up the hybridization, which was linearly proportional to concentration of the target complementary DNA in a range from 1.0 × 10 -9 to 1.25 × 10 -7  M. The detection limit of the proposed method was obtained to be 1.5 × 10 -10  M. Finally, the feasibility and selectivity of the proposed nanosensor was evaluated by the analysis of derived nucleotides from both mismatched sequences and clinical samples of patients with leukemia as real samples. Copyright © 2017 Elsevier B.V. All rights reserved.

Ubiquitin fusion expression and tissue-dependent targeting of hG-CSF in transgenic tobacco

PubMed Central

2011-01-01

Background Human granulocyte colony-stimulating factor (hG-CSF) is an important human cytokine which has been widely used in oncology and infection protection. To satisfy clinical needs, expression of recombinant hG-CSF has been studied in several organisms, including rice cell suspension culture and transient expression in tobacco leaves, but there was no published report on its expression in stably transformed plants which can serve as a more economical expression platform with potential industrial application. Results In this study, hG-CSF expression was investigated in transgenic tobacco leaves and seeds in which the accumulation of hG-CSF could be enhanced through fusion with ubiquitin by up to 7 fold in leaves and 2 fold in seeds, leading to an accumulation level of 2.5 mg/g total soluble protein (TSP) in leaves and 1.3 mg/g TSP in seeds, relative to hG-CSF expressed without a fusion partner. Immunoblot analysis showed that ubiquitin was processed from the final protein product, and ubiquitination was up-regulated in all transgenic plants analyzed. Driven by CaMV 35S promoter and phaseolin signal peptide, hG-CSF was observed to be secreted into apoplast in leaves but deposited in protein storage vacuole (PSV) in seeds, indicating that targeting of the hG-CSF was tissue-dependent in transgenic tobacco. Bioactivity assay showed that hG-CSF expressed in both seeds and leaves was bioactive to support the proliferation of NFS-60 cells. Conclusions In this study, the expression of bioactive hG-CSF in transgenic plants was improved through ubiquitin fusion strategy, demonstrating that protein expression can be enhanced in both plant leaves and seeds through fusion with ubiquitin and providing a typical case of tissue-dependent expression of recombinant protein in transgenic plants. PMID:21985646

Thermal-stress analysis of IFMIF target back-wall made of reduced-activation ferritic steel and austenitic stainless steel

NASA Astrophysics Data System (ADS)

Ida, Mizuho; Chida, Teruo; Furuya, Kazuyuki; Wakai, Eiichi; Nakamura, Hiroo; Sugimoto, Masayoshi

2009-04-01

For long time operation of a liquid lithium target of the International Fusion Materials Irradiation Facility, annual replacement of a back-wall, a part of the flow channel, is planned, since the target suffers neutron damage of more than 50 dpa/fpy. Considering irradiation/activation conditions, remote weld on stainless steel 316L between a back-wall and a target assembly was employed. Furthermore, dissimilar weld between the 316L and a reduced-activation ferritic/martensitic steel F82H in the back-wall was employed. The objective of this study is to clarify structures and materials of the back-wall with acceptable thermal-stress under nuclear heating. Thermal-stress analysis was done using a code ABAQUS and data of the nuclear heating. As a result, thermal-stress in the back-wall is acceptable level, if thickness of the stress-mitigation part is more than 5 mm. With results of the analysis, necessity of material data for F82H and 316L under conditions of irradiation tests and mechanical tests are clarified.

SCAR/WAVE and Arp2/3 are critical for cytoskeletal remodeling at the site of myoblast fusion

PubMed Central

Richardson, Brian E.; Beckett, Karen; Nowak, Scott J.; Baylies, Mary K.

2010-01-01

Summary Myoblast fusion is critical for formation and repair of skeletal muscle. Here we show that active remodeling of the actin cytoskeleton is essential for fusion in Drosophila. Using live imaging, we have identified a dynamic F-actin accumulation (actin focus) at the site of fusion. Dissolution of the actin focus directly precedes a fusion event. Whereas several known fusion components regulate these actin foci, others target additional behaviors required for fusion. Mutations in kette/Nap1, an actin polymerization regulator, lead to enlarged foci that do not dissolve, consistent with the observed block in fusion. Kette is required to positively regulate SCAR/WAVE, which in turn activates the Arp2/3 complex. Mutants in SCAR and Arp2/3 have a fusion block and foci phenotype, suggesting that Kette-SCAR-Arp2/3 participate in an actin polymerization event required for focus dissolution. Our data identify a new paradigm for understanding the mechanisms underlying fusion in myoblasts and other tissues. PMID:18003739

Belief Function Based Decision Fusion for Decentralized Target Classification in Wireless Sensor Networks

PubMed Central

Zhang, Wenyu; Zhang, Zhenjiang

2015-01-01

Decision fusion in sensor networks enables sensors to improve classification accuracy while reducing the energy consumption and bandwidth demand for data transmission. In this paper, we focus on the decentralized multi-class classification fusion problem in wireless sensor networks (WSNs) and a new simple but effective decision fusion rule based on belief function theory is proposed. Unlike existing belief function based decision fusion schemes, the proposed approach is compatible with any type of classifier because the basic belief assignments (BBAs) of each sensor are constructed on the basis of the classifier’s training output confusion matrix and real-time observations. We also derive explicit global BBA in the fusion center under Dempster’s combinational rule, making the decision making operation in the fusion center greatly simplified. Also, sending the whole BBA structure to the fusion center is avoided. Experimental results demonstrate that the proposed fusion rule has better performance in fusion accuracy compared with the naïve Bayes rule and weighted majority voting rule. PMID:26295399

Study of breakup and transfer of weakly bound nucleus 6Li to explore the low energy reaction dynamics

NASA Astrophysics Data System (ADS)

Zhang, G. L.; Zhang, G. X.; Hu, S. P.; Zhang, H. Q.; Gomes, P. R. S.; Lubian, J.; Guo, C. L.; Wu, X. G.; Yang, J. C.; Zheng, Y.; Li, C. B.; He, C. Y.; Zhong, J.; Li, G. S.; Yao, Y. J.; Guo, M. F.; Sun, H. B.; Valiente-Dobòn, J. J.; Goasduff, A.; Siciliano, M.; Galtarosa, F.; Francesco, R.; Testov, D.; Mengoni, D.; Bazzacco, D.; John, P. R.; Qu, W. W.; Wang, F.; Zheng, L.; Yu, L.; Chen, Q. M.; Luo, P. W.; Li, H. W.; Wu, Y. H.; Zhou, W. K.; Zhu, B. J.; Li, E. T.; Hao, X.

2017-11-01

Investigation of the breakup and transfer effect of weakly bound nuclei on the fusion process has been an interesting research topic in the past several years. However, owing to the low intensities of the presently available radioactive ion beam (RIB), it is difficult to clearly explore the reaction mechanisms of nuclear systems with unstable nuclei. In comparison with RIB, the beam intensities of stable weakly bound nuclei such as 6,7Li and 9Be, which have significant breakup probability, are orders of magnitude higher. Precise fusion measurements have already been performed with those stable weakly bound nuclei, and the effect of breakup of those nuclei on the fusion process has been extensively studied. Those nuclei indicated large production cross sections for particles other than the α + x breakup. The particles are originated from non-capture breakup (NCBU), incomplete fusion (ICF) and transfer processes. However, the conclusion of reaction dynamics was not clear and has the contradiction. In our previous experiments we have performed 6Li+96Zr and 154Sm at HI-13 Tandem accelerator of China Institute of Atomic Energy (CIAE) by using HPGe array. It is shown that there is a small complete fusion (CF) suppression on medium-mass target nucleus 96Zr different from about 35% suppression on heavier target nucleus 154Sm at near-barrier energies. It seems that the CF suppression factor depends on the charge of target nuclei. We also observed one neutron transfer process. However, the experimental data are scarce for medium-mass target nuclei. In order to have a proper understanding of the influence of breakup and transfer of weakly bound projectiles on the fusion process, we performed the 6Li+89Y experiment with incident energies of 22 MeV and 34 MeV on Galileo array in cooperation with Si-ball EUCLIDES at Legnaro National Laboratory (LNL) in Italy. Using particle-particle and particle-γ coincidences, the different reaction mechanisms can be clearly explored.

Robust multi-atlas label propagation by deep sparse representation

PubMed Central

Zu, Chen; Wang, Zhengxia; Zhang, Daoqiang; Liang, Peipeng; Shi, Yonghong; Shen, Dinggang; Wu, Guorong

2016-01-01

Recently, multi-atlas patch-based label fusion has achieved many successes in medical imaging area. The basic assumption in the current state-of-the-art approaches is that the image patch at the target image point can be represented by a patch dictionary consisting of atlas patches from registered atlas images. Therefore, the label at the target image point can be determined by fusing labels of atlas image patches with similar anatomical structures. However, such assumption on image patch representation does not always hold in label fusion since (1) the image content within the patch may be corrupted due to noise and artifact; and (2) the distribution of morphometric patterns among atlas patches might be unbalanced such that the majority patterns can dominate label fusion result over other minority patterns. The violation of the above basic assumptions could significantly undermine the label fusion accuracy. To overcome these issues, we first consider forming label-specific group for the atlas patches with the same label. Then, we alter the conventional flat and shallow dictionary to a deep multi-layer structure, where the top layer (label-specific dictionaries) consists of groups of representative atlas patches and the subsequent layers (residual dictionaries) hierarchically encode the patchwise residual information in different scales. Thus, the label fusion follows the representation consensus across representative dictionaries. However, the representation of target patch in each group is iteratively optimized by using the representative atlas patches in each label-specific dictionary exclusively to match the principal patterns and also using all residual patterns across groups collaboratively to overcome the issue that some groups might be absent of certain variation patterns presented in the target image patch. Promising segmentation results have been achieved in labeling hippocampus on ADNI dataset, as well as basal ganglia and brainstem structures, compared to other counterpart label fusion methods. PMID:27942077

Robust multi-atlas label propagation by deep sparse representation.

PubMed

Zu, Chen; Wang, Zhengxia; Zhang, Daoqiang; Liang, Peipeng; Shi, Yonghong; Shen, Dinggang; Wu, Guorong

2017-03-01

Recently, multi-atlas patch-based label fusion has achieved many successes in medical imaging area. The basic assumption in the current state-of-the-art approaches is that the image patch at the target image point can be represented by a patch dictionary consisting of atlas patches from registered atlas images. Therefore, the label at the target image point can be determined by fusing labels of atlas image patches with similar anatomical structures. However, such assumption on image patch representation does not always hold in label fusion since (1) the image content within the patch may be corrupted due to noise and artifact; and (2) the distribution of morphometric patterns among atlas patches might be unbalanced such that the majority patterns can dominate label fusion result over other minority patterns. The violation of the above basic assumptions could significantly undermine the label fusion accuracy. To overcome these issues, we first consider forming label-specific group for the atlas patches with the same label. Then, we alter the conventional flat and shallow dictionary to a deep multi-layer structure, where the top layer ( label-specific dictionaries ) consists of groups of representative atlas patches and the subsequent layers ( residual dictionaries ) hierarchically encode the patchwise residual information in different scales. Thus, the label fusion follows the representation consensus across representative dictionaries. However, the representation of target patch in each group is iteratively optimized by using the representative atlas patches in each label-specific dictionary exclusively to match the principal patterns and also using all residual patterns across groups collaboratively to overcome the issue that some groups might be absent of certain variation patterns presented in the target image patch. Promising segmentation results have been achieved in labeling hippocampus on ADNI dataset, as well as basal ganglia and brainstem structures, compared to other counterpart label fusion methods.

Discovering and understanding oncogenic gene fusions through data intensive computational approaches

PubMed Central

Latysheva, Natasha S.; Babu, M. Madan

2016-01-01

Abstract Although gene fusions have been recognized as important drivers of cancer for decades, our understanding of the prevalence and function of gene fusions has been revolutionized by the rise of next-generation sequencing, advances in bioinformatics theory and an increasing capacity for large-scale computational biology. The computational work on gene fusions has been vastly diverse, and the present state of the literature is fragmented. It will be fruitful to merge three camps of gene fusion bioinformatics that appear to rarely cross over: (i) data-intensive computational work characterizing the molecular biology of gene fusions; (ii) development research on fusion detection tools, candidate fusion prioritization algorithms and dedicated fusion databases and (iii) clinical research that seeks to either therapeutically target fusion transcripts and proteins or leverages advances in detection tools to perform large-scale surveys of gene fusion landscapes in specific cancer types. In this review, we unify these different—yet highly complementary and symbiotic—approaches with the view that increased synergy will catalyze advancements in gene fusion identification, characterization and significance evaluation. PMID:27105842

Targeted delivery of siRNA into breast cancer cells via phage fusion proteins.

PubMed

Bedi, Deepa; Gillespie, James W; Petrenko, Vasily A; Ebner, Andreas; Leitner, Michael; Hinterdorfer, Peter; Petrenko, Valery A

2013-02-04

Nucleic acids, including antisense oligonucleotides, small interfering RNA (siRNA), aptamers, and rybozymes, emerged as versatile therapeutics due to their ability to interfere in a well-planned manner with the flow of genetic information from DNA to protein. However, a systemic use of NAs is hindered by their instability in physiological liquids and inability of intracellular accumulation in the site of action. We first evaluated the potential of cancer specific phage fusion proteins as targeting ligands that provide encapsulation, protection, and navigation of siRNA to the target cell. The tumor-specific proteins were isolated from phages that were affinity selected from a landscape phage library against target breast cancer cells. It was found that fusion phage coat protein fpVIII displaying cancer-targeting peptides can effectively encapsulate siRNAs and deliver them into the cells leading to specific silencing of the model gene GAPDH. Complexes of siRNA and phage protein form nanoparticles (nanophages), which were characterized by atomic force microscopy and ELISA, and their stability was demonstrated by resistance of encapsulated siRNA to degradation by serum nucleases. The phage protein/siRNA complexes can make a new type of highly selective, stable, active, and physiologically acceptable cancer nanomedicine.

Sensor fusion approaches for EMI and GPR-based subsurface threat identification

NASA Astrophysics Data System (ADS)

Torrione, Peter; Morton, Kenneth, Jr.; Besaw, Lance E.

2011-06-01

Despite advances in both electromagnetic induction (EMI) and ground penetrating radar (GPR) sensing and related signal processing, neither sensor alone provides a perfect tool for detecting the myriad of possible buried objects that threaten the lives of Soldiers and civilians. However, while neither GPR nor EMI sensing alone can provide optimal detection across all target types, the two approaches are highly complementary. As a result, many landmine systems seek to make use of both sensing modalities simultaneously and fuse the results from both sensors to improve detection performance for targets with widely varying metal content and GPR responses. Despite this, little work has focused on large-scale comparisons of different approaches to sensor fusion and machine learning for combining data from these highly orthogonal phenomenologies. In this work we explore a wide array of pattern recognition techniques for algorithm development and sensor fusion. Results with the ARA Nemesis landmine detection system suggest that nonlinear and non-parametric classification algorithms provide significant performance benefits for single-sensor algorithm development, and that fusion of multiple algorithms can be performed satisfactorily using basic parametric approaches, such as logistic discriminant classification, for the targets under consideration in our data sets.

Two-plasmon decay mitigation in direct-drive inertial-confinement-fusion experiments using multilayer targets

DOE PAGES

Follett, R. K.; Delettrez, J. A.; Edgell, D. H.; ...

2016-04-15

Multilayer direct-drive inertial-confinement-fusion (ICF) targets are shown to significantly reduce two-plasmon-decay (TPD) driven hot-electron production while maintaining high hydrodynamic efficiency. Implosion experiments on the OMEGA Laser used targets with silicon layered between an inner beryllium and outer silicon-doped plastic ablator. A factor of five reduction in hot-electron generation (> 50 keV) was observed in the multilayer targets relative to pure CH targets. Three-dimensional simulations of the TPD driven hot-electron production using a laser-plasma interaction code (LPSE) that includes nonlinear and kinetic effects show excellent agreement with the measurements. As a result, the simulations suggest that the reduction in hot-electron productionmore » observed in the multilayer targets is primarily due to increased electron-ion collisional damping.« less

Uniform hydrogen fuel layers for inertial fusion targets by microgravity

NASA Technical Reports Server (NTRS)

Parks, P. B.; Fagaly, Robert L.

1994-01-01

A critical concern in the fabrication of targets for inertial confinement fusion (ICF) is ensuring that the hydrogenic (D(sub 2) or DT) fuel layer maintains spherical symmetry. Solid layered targets have structural integrity, but lack the needed surface smoothness. Liquid targets are inherently smooth, but suffer from gravitationally induced sagging. One method to reduce the effective gravitational field environment is freefall insertion into the target chamber. Another method to counterbalance field gravitational force is to use an applied magnetic field combined with a gradient field to induce a magnetic dipole force on the liquid fuel layer. Based on time dependent calculations of the dynamics of the liquid fuel layer in microgravity environments, we show that it may be possible to produce a liquid layered ICF target that satisfies both smoothness and symmetry requirements.

Fuzzy Neural Network-Based Interacting Multiple Model for Multi-Node Target Tracking Algorithm

PubMed Central

Sun, Baoliang; Jiang, Chunlan; Li, Ming

2016-01-01

An interacting multiple model for multi-node target tracking algorithm was proposed based on a fuzzy neural network (FNN) to solve the multi-node target tracking problem of wireless sensor networks (WSNs). Measured error variance was adaptively adjusted during the multiple model interacting output stage using the difference between the theoretical and estimated values of the measured error covariance matrix. The FNN fusion system was established during multi-node fusion to integrate with the target state estimated data from different nodes and consequently obtain network target state estimation. The feasibility of the algorithm was verified based on a network of nine detection nodes. Experimental results indicated that the proposed algorithm could trace the maneuvering target effectively under sensor failure and unknown system measurement errors. The proposed algorithm exhibited great practicability in the multi-node target tracking of WSNs. PMID:27809271

MMWR/FLIR/ATR sensor fusion: Proof of concept

NASA Astrophysics Data System (ADS)

Woolett, Jerry F.

1988-06-01

To improve the relocatable target capabilities of strategic aircraft a sensor fusion concept using a millimeter-wave radar (MMWR) and a forward-looking infrared (FLIR) system providing inputs to an auto target recognizer (ATR) has been developed. To prove this concept, a cooperative research effort is being conducted by a group of industry leaders in bomber avionics, MMWR, and ATR technologies. The author discusses the concept and the plan developed to test, evaluate, and demonstrate the expected performance.

Research on polarization imaging information parsing method

NASA Astrophysics Data System (ADS)

Yuan, Hongwu; Zhou, Pucheng; Wang, Xiaolong

2016-11-01

Polarization information parsing plays an important role in polarization imaging detection. This paper focus on the polarization information parsing method: Firstly, the general process of polarization information parsing is given, mainly including polarization image preprocessing, multiple polarization parameters calculation, polarization image fusion and polarization image tracking, etc.; And then the research achievements of the polarization information parsing method are presented, in terms of polarization image preprocessing, the polarization image registration method based on the maximum mutual information is designed. The experiment shows that this method can improve the precision of registration and be satisfied the need of polarization information parsing; In terms of multiple polarization parameters calculation, based on the omnidirectional polarization inversion model is built, a variety of polarization parameter images are obtained and the precision of inversion is to be improve obviously; In terms of polarization image fusion , using fuzzy integral and sparse representation, the multiple polarization parameters adaptive optimal fusion method is given, and the targets detection in complex scene is completed by using the clustering image segmentation algorithm based on fractal characters; In polarization image tracking, the average displacement polarization image characteristics of auxiliary particle filtering fusion tracking algorithm is put forward to achieve the smooth tracking of moving targets. Finally, the polarization information parsing method is applied to the polarization imaging detection of typical targets such as the camouflage target, the fog and latent fingerprints.

Multiscale Medical Image Fusion in Wavelet Domain

PubMed Central

Khare, Ashish

2013-01-01

Wavelet transforms have emerged as a powerful tool in image fusion. However, the study and analysis of medical image fusion is still a challenging area of research. Therefore, in this paper, we propose a multiscale fusion of multimodal medical images in wavelet domain. Fusion of medical images has been performed at multiple scales varying from minimum to maximum level using maximum selection rule which provides more flexibility and choice to select the relevant fused images. The experimental analysis of the proposed method has been performed with several sets of medical images. Fusion results have been evaluated subjectively and objectively with existing state-of-the-art fusion methods which include several pyramid- and wavelet-transform-based fusion methods and principal component analysis (PCA) fusion method. The comparative analysis of the fusion results has been performed with edge strength (Q), mutual information (MI), entropy (E), standard deviation (SD), blind structural similarity index metric (BSSIM), spatial frequency (SF), and average gradient (AG) metrics. The combined subjective and objective evaluations of the proposed fusion method at multiple scales showed the effectiveness and goodness of the proposed approach. PMID:24453868

Fusion and quality analysis for remote sensing images using contourlet transform

NASA Astrophysics Data System (ADS)

Choi, Yoonsuk; Sharifahmadian, Ershad; Latifi, Shahram

2013-05-01

Recent developments in remote sensing technologies have provided various images with high spatial and spectral resolutions. However, multispectral images have low spatial resolution and panchromatic images have low spectral resolution. Therefore, image fusion techniques are necessary to improve the spatial resolution of spectral images by injecting spatial details of high-resolution panchromatic images. The objective of image fusion is to provide useful information by improving the spatial resolution and the spectral information of the original images. The fusion results can be utilized in various applications, such as military, medical imaging, and remote sensing. This paper addresses two issues in image fusion: i) image fusion method and ii) quality analysis of fusion results. First, a new contourlet-based image fusion method is presented, which is an improvement over the wavelet-based fusion. This fusion method is then applied to a case study to demonstrate its fusion performance. Fusion framework and scheme used in the study are discussed in detail. Second, quality analysis for the fusion results is discussed. We employed various quality metrics in order to analyze the fusion results both spatially and spectrally. Our results indicate that the proposed contourlet-based fusion method performs better than the conventional wavelet-based fusion methods.

BCR-ABL fusion regions as a source of multiple leukemia-specific CD8+ T-cell epitopes.

PubMed

Kessler, J H; Bres-Vloemans, S A; van Veelen, P A; de Ru, A; Huijbers, I J G; Camps, M; Mulder, A; Offringa, R; Drijfhout, J W; Leeksma, O C; Ossendorp, F; Melief, C J M

2006-10-01

For immunotherapy of residual disease in patients with Philadelphia-positive leukemias, the BCR-ABL fusion regions are attractive disease-specific T-cell targets. We analyzed these regions for the prevalence of cytotoxic T lymphocyte (CTL) epitopes by an advanced reverse immunology procedure. Seventeen novel BCR-ABL fusion peptides were identified to bind efficiently to the human lymphocyte antigen (HLA)-A68, HLA-B51, HLA-B61 or HLA-Cw4 HLA class I molecules. Comprehensive enzymatic digestion analysis showed that 10 out of the 28 HLA class I binding fusion peptides were efficiently excised after their C-terminus by the proteasome, which is an essential requirement for efficient cell surface expression. Therefore, these peptides are prime vaccine candidates. The other peptides either completely lacked C-terminal liberation or were only inefficiently excised by the proteasome, rendering them inappropriate or less suitable for inclusion in a vaccine. CTL raised against the properly processed HLA-B61 epitope AEALQRPVA from the BCR-ABL e1a2 fusion region, expressed in acute lymphoblastic leukemia (ALL), specifically recognized ALL tumor cells, proving cell surface presentation of this epitope, its applicability for immunotherapy and underlining the accuracy of our epitope identification strategy. Our study provides a reliable basis for the selection of optimal peptides to be included in immunotherapeutic BCR-ABL vaccines against leukemia.

Identification of Novel Fusion Inhibitors of Influenza A Virus by Chemical Genetics

PubMed Central

Lai, Kin Kui; Cheung, Nam Nam; Yang, Fang; Dai, Jun; Liu, Li; Chen, Zhiwei; Sze, Kong Hung; Chen, Honglin

2015-01-01

ABSTRACT A previous screening of more than 50,000 compounds led to the identification of a pool of bioactive small molecules with inhibitory effect on the influenza A virus. One of these compounds, now widely known as nucleozin, is a small molecule that targets the influenza A virus nucleoprotein. Here we identify and characterize two structurally different novel fusion inhibitors of the influenza A virus group 1 hemagglutinin (HA), FA-583 and FA-617, with low nanomolar activities. Escape mutants that are highly resistant to each of these compounds were generated, and both were found to carry mutations localized in close proximity to the B-loop of the hemagglutinin 2 protein, which plays a crucial role in the virion-host cell fusion process. Recombinant virus, generated through reverse genetics, confirmed the resistance phenotype. In addition, the proposed binding pockets predicted by molecular docking studies are in accordance with the resistance-bearing mutation sites. We show through mechanistic studies that FA-583 and FA-617 act as fusion inhibitors by prohibiting the low-pH-induced conformational change of hemagglutinin. Our study has offered concrete biological and mechanistic explorations for the strategic development of novel fusion inhibitors of influenza A viruses. IMPORTANCE Here we report two structurally distinctive novel fusion inhibitors of influenza A virus that act by interfering with the structural change of HA at acidic pH, a process necessary for successful entry of the virus. Mutational and molecular docking studies have identified their binding pockets situated in close proximity to the B-loop region of hemagglutinin 2. The reduced sensitivity of FA-583- or FA-617-associated mutants to another compound suggests a close proximity and even partial overlap of their binding sites on hemagglutinin. Amino acid sequence alignments and crystal structure analyses of group 1 and group 2 hemagglutinins have shed light on the possible binding mode of these two compounds. This report offers new lead compounds for the design of fusion inhibitors for influenza A viruses and further shows that analysis by forward chemical genetics is a highly effective approach for the identification of novel compounds that can perturb the infectivity of viruses and to probe new druggable targets or druggable domains in various viruses. PMID:26676787

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

Kwon, Soon Won; Sohn, Eun Jeong; Kim, Dae Won

Highlights: {yields} Recombinant PEP-1 heme oxygenase-1 expression vector was constructed and overexpressed. {yields} We investigated transduction efficiency of PEP-1-HO-1 protein in Raw 264.7 cells. {yields} PEP-1-HO-1 was efficiently transduced into Raw 264.7 cells in a dose and time dependent manner. {yields} PEP-1-HO-1 exerted anti-inflammatory activity in Raw 264.7 cells and in a mice edema model. {yields} PEP-1-HO-1 could be used as a therapeutic drug against inflammatory diseases. -- Abstract: Heme oxygenase-1 (HO-1), which catalyzes the degradation of free heme to biliverdin, carbon monoxide (CO), and free iron (Fe{sup 2+}), is up-regulated by several cellular stress and cell injuries, including inflammation,more » ischemia and hypoxia. In this study, we examined whether fusion of HO-1 with PEP-1, a protein transduction domain that is able to deliver exogenous molecules to living cells or tissues, would facilitate HO-1 delivery to target cells and tissues, and thereby effectively exert a therapeutically useful response against inflammation. Western blot analysis demonstrated that PEP-1-HO-1 fusion proteins were transduced into Raw 264.7 cells in time- and dose-dependent manners, and were stably maintained in the cells for about 60 h. In addition, fluorescence analysis revealed that only PEP-1-HO-1 fusion proteins were significantly transduced into the cytoplasm of cells, while HO-1 proteins failed to be transduced. In lipopolysaccharide (LPS)-stimulated Raw 264.7 cells and 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced mouse edema model, transduced PEP-1-HO-1 fusion proteins effectively inhibited the overexpression of pro-inflammatory mediators and cytokines. Also, histological analysis demonstrated that PEP-1-HO-1 remarkably suppressed ear edema. The results suggest that the PEP-1-HO-1 fusion protein can be used as a therapeutic molecule against reactive oxygen species-related inflammatory diseases.« less

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.

Association of quantitative magnetic resonance imaging parameters with histological findings from MRI/ultrasound fusion prostate biopsy.

PubMed

Dianat, Seyed Saeid; Carter, H Ballentine; Schaeffer, Edward M; Hamper, Ulrik M; Epstein, Jonathan I; Macura, Katarzyna J

2015-10-01

Purpose of this pilot study was to correlate quantitative parameters derived from the multiparametric magnetic resonance imaging (MP-MRI) of the prostate with results from MRI guided transrectal ultrasound (MRI/TRUS) fusion prostate biopsy in men with suspected prostate cancer. Thirty-nine consecutive patients who had 3.0T MP-MRI and subsequent MRI/TRUS fusion prostate biopsy were included and 73 MRI-identified targets were sampled by 177 cores. The pre-biopsy MP-MRI consisted of T2-weighted, diffusion weighted (DWI), and dynamic contrast enhanced (DCE) images. The association of quantitative MRI measurements with biopsy histopathology findings was assessed by Mann-Whitney U- test and Kruskal-Wallis test. Of 73 targets, biopsy showed benign prostate tissue in 46 (63%), cancer in 23 (31.5%), and atypia/high grade prostatic intraepithelial neoplasia in four (5.5%) targets. The median volume of cancer-positive targets was 1.3 cm3. The cancer-positive targets were located in the peripheral zone (56.5%), transition zone (39.1%), and seminal vesicle (4.3%). Nine of 23 (39.1%) cancer-positive targets were higher grade cancer (Gleason grade > 6). Higher grade targets and cancer-positive targets compared to benign lesions exhibited lower mean apparent diffusion coefficient (ADC) value (952.7 < 1167.9 < 1278.9), and lower minimal extracellular volume fraction (ECF) (0.13 < 0.185 < 0.213), respectively. The difference in parameters was more pronounced between higher grade cancer and benign lesions. Our findings from a pilot study indicate that quantitative MRI parameters can predict malignant histology on MRI/TRUS fusion prostate biopsy, which is a valuable technique to ensure adequate sampling of MRI-visible suspicious lesions under TRUS guidance and may impact patient management. The DWI-based quantitative measurement exhibits a stronger association with biopsy findings than the other MRI parameters.

Assessing infrared intensity using the evaporation rate of liquid hydrogen inside a cryogenic integrating sphere for laser fusion targets

NASA Astrophysics Data System (ADS)

Iwano, K.; Iwamoto, A.; Asahina, T.; Yamanoi, K.; Arikawa, Y.; Nagatomo, H.; Nakai, M.; Norimatsu, T.; Azechi, H.

2017-07-01

Infrared (IR) heating processes have been studied to form a deuterium layer in an inertial confinement fusion target. To understand the relationship between the IR intensity and the fuel layering time constant, we have developed a new method to assess the IR intensity during irradiation. In our method, a glass flask acting as a dummy target is filled with liquid hydrogen (LH2) and is then irradiated with 2-μm light. The IR intensity is subsequently calculated from the time constant of the LH2 evaporation rate. Although LH2 evaporation is also caused by the heat inflow from the surroundings and by the background heat, the evaporation rate due to IR heating can be accurately determined by acquiring the time constant with and without irradiation. The experimentally measured IR intensity is 0.66 mW/cm2, which agrees well with a value estimated by considering the IR photon energy balance. Our results suggest that the present method can be used to measure the IR intensity inside a cryogenic system during IR irradiation of laser fusion targets.

Assessing infrared intensity using the evaporation rate of liquid hydrogen inside a cryogenic integrating sphere for laser fusion targets.

PubMed

Iwano, K; Iwamoto, A; Asahina, T; Yamanoi, K; Arikawa, Y; Nagatomo, H; Nakai, M; Norimatsu, T; Azechi, H

2017-07-01

Infrared (IR) heating processes have been studied to form a deuterium layer in an inertial confinement fusion target. To understand the relationship between the IR intensity and the fuel layering time constant, we have developed a new method to assess the IR intensity during irradiation. In our method, a glass flask acting as a dummy target is filled with liquid hydrogen (LH 2 ) and is then irradiated with 2-μm light. The IR intensity is subsequently calculated from the time constant of the LH 2 evaporation rate. Although LH 2 evaporation is also caused by the heat inflow from the surroundings and by the background heat, the evaporation rate due to IR heating can be accurately determined by acquiring the time constant with and without irradiation. The experimentally measured IR intensity is 0.66 mW/cm 2 , which agrees well with a value estimated by considering the IR photon energy balance. Our results suggest that the present method can be used to measure the IR intensity inside a cryogenic system during IR irradiation of laser fusion targets.

A dual-PIXE tomography setup for reconstruction of Germanium in ICF target

NASA Astrophysics Data System (ADS)

Guo, N.; Lu, H. Y.; Wang, Q.; Meng, J.; Gao, D. Z.; Zhang, Y. J.; Liang, X. X.; Zhang, W.; Li, J.; Ma, X. J.; Shen, H.

2017-08-01

Inertial Confinement Fusion (ICF) is one type of fusion energy research which could initiate nuclear fusion reactions through heating and compressing thermonuclear fuel. Compared to a pure plastic target, Germanium doping into the CH ablator layer by Glow Discharge Polymer (GDP) technique can increase the ablation velocity and the standoff distance between the ablation front and laser-deposition region. During target fabrication process, quantitative doping of Ge should be accurately controlled. Particle Induced X-ray Emission Tomography (PIXE-T) can make not only quantification of the concentration, but also reconstruction of the spatial distribution of doped element. The Si (Li) detector for PIXE tomography technique had a disadvantage of low counting rate. To make up this deficiency, another detector of Si (Li) with the same configuration positioned at the opposite side with the same detective angle 135° have been implemented. Simultaneously acquired elemental maps of Ge obtained using two detectors may be different because of the X-ray absorption along the X-ray exit route in the target. In this paper, the X-ray detection efficiency is drastically improved by this dual-PIXE tomography system.

Simulations of High-Gain Shock-Ignited Inertial-Confinement-Fusion Implosions Using Less Than 1 MJ of Direct KrF Laser Energy

DTIC Science & Technology

2009-05-01

transport, and thermonuclear burn. Using FAST, three classes of shock-ignited targets were designed that achieve one-dimensional fusion - energy gains in the...MJ) G a in Figure 1: Results of one-dimensional simulations showing the fusion energy gain as a function of KrF laser energy for three classes of...rises smoothly (according to a double power (a) Spike width: 160 ps (b) Spike power: 1530 TW Figure 4: Examples of fusion - energy gain contours for a shock

Direct Drive Fusion Energy Shock Ignition Designs for Sub-MJ Lasers

DTIC Science & Technology

2008-09-01

FUSION ENERGY SHOCK IGNITION DESIGNS FOR SUB-MJ LASERS Andrew J. Schmitt, J. W. Bates, S. P. Obenschain, and S. T. Zalesak Plasma Physics Division, Naval Research Laboratory, Washington DC 20375 andrew.schmitt@nrl.navy.mil D. E. Fyfe LCP&FD, Naval Research Laboratory, Washington DC 20375 R. Betti Fusion Science Center and Laboratory for Laser Energetics, University of Rochester, Rochester NY New approaches in target design have increased the pos- sibility that useful fusion power can be generated with sub-MJ lasers. We have performed many 1D and 2D

Incomplete fusion analysis of the 7Li-induced reaction on 93Nb within 3-6.5 MeV/nucleon

NASA Astrophysics Data System (ADS)

Kumar, Deepak; Maiti, Moumita

2017-10-01

Background: It is understood from the recent experimental studies that prompt/resonant breakup, and transfer followed by breakup in the weakly bound Li,76-induced reactions play a significant role in the complete-incomplete fusion (CF-ICF), suppression/enhancement in the fusion cross section around the Coulomb barrier. Purpose: Investigation of ICF over CF by measuring cross sections of the populated residues, produced via different channels in the 7Li-induced reaction on a natNb target within the 3-6.5 MeV/nucleon energy region. Method: The 7Li beam was allowed to hit the self-supporting 93Nb targets, backed by the aluminium (Al) foil alternately, within 3-6.5 MeV/nucleon energy. Populated residues were identified by offline γ -ray spectrometry. Measured excitation functions of different channels were compared with different equilibrium and pre-equilibrium models. Result: The enhancement in cross sections in the proton (˜20 -30 MeV) and α -emitting channels, which may be ascribed to ICF, was observed in the measured energy range when compared to the Hauser-Feshbach and exciton model calculations using empire, which satisfactorily reproduces the neutron channels, compared to the Weisskopf-Ewing model and hybrid Monte Carlo calculations. The increment of the incomplete fusion fraction was observed with rising projectile energy. Conclusion: Contrary to the alice14, experimental results are well reproduced by the empire throughout the measured energy range. The signature of ICF over CF indicates that the breakup/transfer processes are involved in the weakly bound 7Li-induced reaction on 93Nb slightly above the Coulomb barrier.

ROS1 fusions rarely overlap with other oncogenic drivers in non-small cell lung cancer

PubMed Central

Lin, Jessica J.; Ritterhouse, Lauren L.; Ali, Siraj M.; Bailey, Mark; Schrock, Alexa B.; Gainor, Justin F.; Ferris, Lorin A.; Mino-Kenudson, Mari; Miller, Vincent A.; Iafrate, Anthony J.; Lennerz, Jochen K.; Shaw, Alice T.

2017-01-01

Introduction Chromosomal rearrangements involving the ROS proto-oncogene 1 receptor tyrosine kinase gene (ROS1) define a distinct molecular subset of non-small cell lung cancer (NSCLC) with sensitivity to ROS1 inhibitors. Recent reports have suggested a significant overlap between ROS1 fusions and other oncogenic driver alterations, including mutations in epidermal growth factor receptor (EGFR) and KRAS proto-oncogene (KRAS). Methods We identified patients at our institution with ROS1-rearranged NSCLC who had undergone testing for genetic alterations in additional oncogenes, including EGFR, KRAS, and anaplastic lymphoma kinase (ALK). Clinicopathologic features and genetic testing results were reviewed. We also examined a separate database of ROS1-rearranged NSCLCs identified through a commercial FoundationOne assay. Results Among 62 patients with ROS1-rearranged NSCLC evaluated at our institution, none harbored concurrent ALK fusions (0%) or EGFR activating mutations (0%). KRAS mutations were detected in two cases (3.2%), one of which harbored a concurrent non-canonical KRAS I24N mutation of unknown biological significance. In a separate ROS1 FISH-positive case, targeted sequencing failed to confirm a ROS1 fusion, but instead identified a KRAS G13D mutation. No concurrent mutations in BRAF, ERBB2, PIK3CA, AKT1, or MAP2K1 were detected. Analysis of an independent dataset of 166 ROS1-rearranged NSCLCs identified by FoundationOne demonstrated rare cases with co-occurring driver mutations in EGFR (1/166) and KRAS (3/166), and no cases with co-occurring ROS1 and ALK rearrangements. Conclusions ROS1 rearrangements rarely overlap with alterations in EGFR, KRAS, ALK, or other targetable oncogenes in NSCLC. PMID:28088512

Characterization of distinct classes of differential gene expression in osteoblast cultures from non-syndromic craniosynostosis bone.

PubMed

Rojas-Peña, Monica L; Olivares-Navarrete, Rene; Hyzy, Sharon; Arafat, Dalia; Schwartz, Zvi; Boyan, Barbara D; Williams, Joseph; Gibson, Greg

2014-01-01

Craniosynostosis, the premature fusion of one or more skull sutures, occurs in approximately 1 in 2500 infants, with the majority of cases non-syndromic and of unknown etiology. Two common reasons proposed for premature suture fusion are abnormal compression forces on the skull and rare genetic abnormalities. Our goal was to evaluate whether different sub-classes of disease can be identified based on total gene expression profiles. RNA-Seq data were obtained from 31 human osteoblast cultures derived from bone biopsy samples collected between 2009 and 2011, representing 23 craniosynostosis fusions and 8 normal cranial bones or long bones. No differentiation between regions of the skull was detected, but variance component analysis of gene expression patterns nevertheless supports transcriptome-based classification of craniosynostosis. Cluster analysis showed 4 distinct groups of samples; 1 predominantly normal and 3 craniosynostosis subtypes. Similar constellations of sub-types were also observed upon re-analysis of a similar dataset of 199 calvarial osteoblast cultures. Annotation of gene function of differentially expressed transcripts strongly implicates physiological differences with respect to cell cycle and cell death, stromal cell differentiation, extracellular matrix (ECM) components, and ribosomal activity. Based on these results, we propose non-syndromic craniosynostosis cases can be classified by differences in their gene expression patterns and that these may provide targets for future clinical intervention.

Characterization of Distinct Classes of Differential Gene Expression in Osteoblast Cultures from Non-Syndromic Craniosynostosis Bone

PubMed Central

Rojas-Peña, Monica L.; Olivares-Navarrete, Rene; Hyzy, Sharon; Arafat, Dalia; Schwartz, Zvi; Boyan, Barbara D.; Williams, Joseph; Gibson, Greg

2014-01-01

Craniosynostosis, the premature fusion of one or more skull sutures, occurs in approximately 1 in 2500 infants, with the majority of cases non-syndromic and of unknown etiology. Two common reasons proposed for premature suture fusion are abnormal compression forces on the skull and rare genetic abnormalities. Our goal was to evaluate whether different sub-classes of disease can be identified based on total gene expression profiles. RNA-Seq data were obtained from 31 human osteoblast cultures derived from bone biopsy samples collected between 2009 and 2011, representing 23 craniosynostosis fusions and 8 normal cranial bones or long bones. No differentiation between regions of the skull was detected, but variance component analysis of gene expression patterns nevertheless supports transcriptome-based classification of craniosynostosis. Cluster analysis showed 4 distinct groups of samples; 1 predominantly normal and 3 craniosynostosis subtypes. Similar constellations of sub-types were also observed upon re-analysis of a similar dataset of 199 calvarial osteoblast cultures. Annotation of gene function of differentially expressed transcripts strongly implicates physiological differences with respect to cell cycle and cell death, stromal cell differentiation, extracellular matrix (ECM) components, and ribosomal activity. Based on these results, we propose non-syndromic craniosynostosis cases can be classified by differences in their gene expression patterns and that these may provide targets for future clinical intervention. PMID:25184005

The novel ER membrane protein PRO41 is essential for sexual development in the filamentous fungus Sordaria macrospora.

PubMed

Nowrousian, Minou; Frank, Sandra; Koers, Sandra; Strauch, Peter; Weitner, Thomas; Ringelberg, Carol; Dunlap, Jay C; Loros, Jennifer J; Kück, Ulrich

2007-05-01

The filamentous fungus Sordaria macrospora develops complex fruiting bodies (perithecia) to propagate its sexual spores. Here, we present an analysis of the sterile mutant pro41 that is unable to produce mature fruiting bodies. The mutant carries a deletion of 4 kb and is complemented by the pro41 open reading frame that is contained within the region deleted in the mutant. In silico analyses predict PRO41 to be an endoplasmic reticulum (ER) membrane protein, and a PRO41-EGFP fusion protein colocalizes with ER-targeted DsRED. Furthermore, Western blot analysis shows that the PRO41-EGFP fusion protein is present in the membrane fraction. A fusion of the predicted N-terminal signal sequence of PRO41 with EGFP is secreted out of the cell, indicating that the signal sequence is functional. pro41 transcript levels are upregulated during sexual development. This increase in transcript levels was not observed in the sterile mutant pro1 that lacks a transcription factor gene. Moreover, microarray analysis of gene expression in the mutants pro1, pro41 and the pro1/41 double mutant showed that pro41 is partly epistatic to pro1. Taken together, these data show that PRO41 is a novel ER membrane protein essential for fruiting body formation in filamentous fungi.

The novel ER membrane protein PRO41 is essential for sexual development in the filamentous fungus Sordaria macrospora

PubMed Central

Nowrousian, Minou; Frank, Sandra; Koers, Sandra; Strauch, Peter; Weitner, Thomas; Ringelberg, Carol; Dunlap, Jay C.; Loros, Jennifer J.; Kück, Ulrich

2013-01-01

Summary The filamentous fungus Sordaria macrospora develops complex fruiting bodies (perithecia) to propagate its sexual spores. Here, we present an analysis of the sterile mutant pro41 that is unable to produce mature fruiting bodies. The mutant carries a deletion of 4 kb and is complemented by the pro41 open reading frame that is contained within the region deleted in the mutant. In silico analyses predict PRO41 to be an endoplasmic reticulum (ER) membrane protein, and a PRO41–EGFP fusion protein colocalizes with ER-targeted DsRED. Furthermore, Western blot analysis shows that the PRO41–EGFP fusion protein is present in the membrane fraction. A fusion of the predicted N-terminal signal sequence of PRO41 with EGFP is secreted out of the cell, indicating that the signal sequence is functional. pro41 transcript levels are upregulated during sexual development. This increase in transcript levels was not observed in the sterile mutant pro1 that lacks a transcription factor gene. Moreover, microarray analysis of gene expression in the mutants pro1, pro41 and the pro1/41 double mutant showed that pro41 is partly epistatic to pro1. Taken together, these data show that PRO41 is a novel ER membrane protein essential for fruiting body formation in filamentous fungi. PMID:17501918

Dichotomy of Genetic Abnormalities in PEComas with Therapeutic Implications

PubMed Central

Agaram, Narasimhan P; Sung, Yun-Shao; Zhang, Lei; Chen, Chun-Liang; Chen, Hsiao-Wei; Singer, Samuel; Dickson, Mark A.; Berger, Michael F.; Antonescu, Cristina R

2014-01-01

Perivascular epithelioid cell neoplasms (PEComa) are a family of rare mesenchymal tumors with hybrid myo-melanocytic differentiation. Although most PEComas harbor loss of function TSC1/TSC2 mutations, a small subset were reported to carry TFE3 gene rearrangements. As no comprehensive genomic study has addressed the molecular classification of PEComa, we sought to investigate by multiple methodologies the incidence and spectrum of genetic abnormalities and their potential genotype-phenotype correlations in a large group of 38 PEComas. The tumors were located in soft tissue (11 cases) and visceral sites (27) including uterus, kidney, liver, lung and urinary bladder. Combined RNA sequencing and Fluorescence In Situ Hybridization (FISH) analysis identified 9 (23%) TFE3 gene rearranged tumors, with 3 cases showing a SFPQ/PSF-TFE3 fusion and one case a novel DVL2-TFE3 gene fusion. The TFE3-positive lesions showed a distinctive nested/alveolar morphology and were equally distributed between soft tissue and visceral sites. Additionally, novel RAD51B gene rearrangements were identified in 3 (8%) uterine PEComas, which showed a complex fusion pattern and were fused to RRAGB/OPHN1 genes in two cases. Other non-recurrent gene fusions, HTR4-ST3GAL1 and RASSF1-PDZRN3, were identified in 2 cases. Targeted exome sequencing using the IMPACT assay was used to address if the presence of gene fusions are mutually exclusive from TSC gene abnormalities. TSC2 mutations were identified in 80% of the TFE3 fusion-negative cases tested. Co-existent TP53 mutations were identified in 63% of the TSC2 mutated PEComas. Our results showed that TFE3-rearranged PEComas lacked co-existing TSC2 mutations, indicating alternative pathways of tumorigenesis. In summary, this comprehensive genetic analysis significantly expands our understanding of molecular alterations in PEComas and brings forth the genetic heterogeneity of these tumors. PMID:25651471

A general approach for chemical labeling and rapid, spatially controlled protein inactivation

PubMed Central

Marks, Kevin M.; Braun, Patrick D.; Nolan, Garry P.

2004-01-01

Chemical labeling of proteins inside of living cells can enable studies of the location, movement, and function of proteins in vivo. Here we demonstrate an approach for chemical labeling of proteins that uses the high-affinity interaction between an FKBP12 mutant (F36V) and a synthetic, engineered ligand (SLF′). A fluorescein conjugate to the engineered ligand (FL-SLF′) retained binding to FKBP12(F36V) and possessed similar fluorescence properties as parental fluorescein. FL-SLF′ labeled FKBP12(F36V) fusion proteins in live mammalian cells, and was used to monitor the subcellular localization of a membrane targeted FKBP12(F36V) construct. Chemical labeling of FKBP12(F36V) fusion proteins with FL-SLF′ was readily detectable at low expression levels of the FKBP12(F36V) fusion, and the level of fluorescent staining with FL-SLF′ was proportional to the FKBP12(F36V) expression level. This FL-SLF′-FKBP12(F36V) labeling technique was tested in fluorophore assisted laser inactivation (FALI), a light-mediated technique to rapidly inactivate fluorophore-labeled target proteins. FL-SLF′ mediated FALI of a β-galactosidase-FKBP12(F36V) fusion protein, causing rapid inactivation of >90% of enzyme activity upon irradiation in vitro. FL-SLF′ also mediated FALI of a β-galactosidase fusion expressed in living NIH 3T3 cells, where β-galactosidase activity was reduced in 15 s. Thus, FL-SLF′ can be used to monitor proteins in vivo and to target rapid, spatially and temporally defined inactivation of target proteins in living cells in a process that we call FK-FALI. PMID:15218100

Clinical Potential of Prefusion RSV F-specific Antibodies.

PubMed

Rossey, Iebe; McLellan, Jason S; Saelens, Xavier; Schepens, Bert

2018-03-01

Human respiratory syncytial virus (RSV) is the leading cause of lower respiratory tract infections in the very young. The RSV fusion protein (F) is essential for virus entry because it mediates viral and host membrane fusion. During this fusion process F is converted from a metastable prefusion conformation into an energetically favored postfusion state. Antibodies that target F can prevent viral entry and reduce disease caused by RSV. During recent years, many prefusion F-specific antibodies have been described. These antibodies typically have stronger RSV-neutralizing activity compared to those that also bind F in the postfusion conformation. Here, we describe how F-specific antibodies protect against RSV and why specifically targeting prefusion F could have great clinical potential. Copyright © 2017 Elsevier Ltd. All rights reserved.

Nuclear science experiments with a bright neutron source from fusion reactions on the OMEGA Laser System

NASA Astrophysics Data System (ADS)

Forrest, C. J.; Knauer, J. P.; Schroeder, W. U.; Glebov, V. Yu.; Radha, P. B.; Regan, S. P.; Sangster, T. C.; Sickles, M.; Stoeckl, C.; Szczepanski, J.

2018-04-01

Subnanosecond impulses of 1013 to 1014 neutrons, produced in direct-drive laser inertial confinement fusion implosions, have been used to irradiate deuterated targets at the OMEGA Laser System (Boehly et al., 1997). The target compounds include heavy water (D2O) and deuterated benzene (C6D6). Yields and energy spectra of neutrons from D(n,2n)p to study the breakup reaction have been measured at a forward angle of θlab = 3 .5∘ ± 3.5° with a sensitive, high-dynamic-range neutron time-of-flight spectrometer to infer the double-differential breakup cross section d2 σ/dE d Ω for 14-MeV D-T fusion neutrons.

Thick Nano-Crystalline Diamond films for fusion applications

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

Dawedeit, Christoph

This Diplomarbeit deals with the characterization of 9 differently grown diamond samples. Several techniques were used to determine the quality of these specimens for inertial confinement fusion targets. The quality of chemical vapor deposition diamond is usually considered in terms of the proportion of sp3-bonded carbon to sp2-bonded carbon in the sample. For fusion targets smoothness, Hydrogen content and density of the diamonds are further important characteristics. These characteristics are analyzed in this thesis. The research for thesis was done at Lawrence Livermore National Laboratory in collaboration with the Fraunhofer Institut für angewandte Festkörperphysik Freiburg, Germany. Additionally the Lehrstuhl fuermore » Nukleartechnik at Technical University of Germany supported the work.« less

Forskolin-mediated BeWo cell fusion involves down-regulation of miR-92a-1-5p that targets dysferlin and protein kinase cAMP-activated catalytic subunit alpha.

PubMed

Dubey, Richa; Malhotra, Sudha S; Gupta, Satish K

2018-06-01

To study the role of miRNA(s) during trophoblastic BeWo cell fusion. Changes in miRNA(s) profile of BeWo cells treated with forskolin were analyzed using Affymetrix miRNA microarray platform. Down-regulated miRNA, miR-92a-1-5p, was overexpressed in BeWo cells followed by forskolin treatment to understand its relevance in the process of BeWo cell fusion by desmoplakin I+II staining and hCG secretion by ELISA. Predicted targets of miR-92a-1-5p were also confirmed by qRT-PCR/Western blotting. The miRNA profiling of BeWo cells after forskolin (25 μmol/L) treatment identified miR-92a-1-5p as the most significantly down-regulated miRNA both at 24 and 48 hours time points. Overexpression of miR-92a-1-5p in these cells led to a significant decrease in forskolin-mediated cell fusion and hCG secretion. miRNA target prediction software, TargetScan, revealed dysferlin (DYSF) and protein kinase cAMP-activated catalytic subunit alpha (PRKACA), as target genes of miR-92a-1-5p. Overexpression of miR-92a-1-5p in BeWo cells showed reduction in forskolin-induced transcripts for DYSF and PRKACA. Further, reduction in DYSF (~2.6-fold) at protein level and PRKACA-encoded protein kinase A catalytic subunit alpha (PKAC-α; ~1.6-fold) were also observed. These observations suggest that miR-92a-1-5p regulates forskolin-mediated BeWo cell fusion and hCG secretion by regulating PKA signaling pathway and dysferlin expression. © 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Trans-rectal ultrasound visibility of prostate lesions identified by magnetic resonance imaging increases accuracy of image-fusion targeted biopsies.

PubMed

Ukimura, Osamu; Marien, Arnaud; Palmer, Suzanne; Villers, Arnauld; Aron, Manju; de Castro Abreu, Andre Luis; Leslie, Scott; Shoji, Sunao; Matsugasumi, Toru; Gross, Mitchell; Dasgupta, Prokar; Gill, Inderbir S

2015-11-01

To compare the diagnostic yield of targeted prostate biopsy using image-fusion of multi-parametric magnetic resonance (mp-MR) with real-time trans-rectal ultrasound (TRUS) for clinically significant lesions that are suspicious only on mp-MR versus lesions that are suspicious on both mp-MR and TRUS. Pre-biopsy MRI and TRUS were each scaled on a 3-point score: highly suspicious, likely, and unlikely for clinically significant cancer (sPCa). Using an MR-TRUS elastic image-fusion system (Koelis), a 127 consecutive patients with a suspicious clinically significant index lesion on pre-biopsy mp-MR underwent systematic biopsies and MR/US-fusion targeted biopsies (01/2010-09/2013). Biopsy histological outcomes were retrospectively compared with MR suspicion level and TRUS-visibility of the MR-suspicious lesion. sPCa was defined as biopsy Gleason score ≥7 and/or maximum cancer core length ≥5 mm. Targeted biopsies outperformed systematic biopsies in overall cancer detection rate (61 vs. 41 %; p = 0.007), sPCa detection rate (43 vs. 23 %; p = 0.0013), cancer core length (7.5 vs. 3.9 mm; p = 0.0002), and cancer rate per core (56 vs. 12 %; p < 0.0001), respectively. Highly suspicious lesions on mp-MR correlated with higher positive biopsy rate (p < 0.0001), higher Gleason score (p = 0.018), and greater cancer core length (p < 0.0001). Highly suspicious lesions on TRUS in corresponding to MR-suspicious lesion had a higher biopsy yield (p < 0.0001) and higher sPCa detection rate (p < 0.0001). Since majority of MR-suspicious lesions were also suspicious on TRUS, TRUS-visibility allowed selection of the specific MR-visible lesion which should be targeted from among the multiple TRUS suspicious lesions in each prostate. MR-TRUS fusion-image-guided biopsies outperformed systematic biopsies. TRUS-visibility of a MR-suspicious lesion facilitates image-guided biopsies, resulting in higher detection of significant cancer.

Tumor-targeted IL-2 amplifies T cell-mediated immune response induced by gene therapy with single-chain IL-12

PubMed Central

Lode, Holger N.; Xiang, Rong; Duncan, Steven R.; Theofilopoulos, Argyrios N.; Gillies, Stephen D.; Reisfeld, Ralph A.

1999-01-01

Induction, maintenance, and amplification of tumor-protective immunity after cytokine gene therapy is essential for the clinical success of immunotherapeutic approaches. We investigated whether this could be achieved by single-chain IL-12 (scIL-12) gene therapy followed by tumor-targeted IL-2 using a fusion protein containing a tumor-specific recombinant anti-ganglioside GD2 antibody and IL-2 (ch14.18-IL-2) in a poorly immunogenic murine neuroblastoma model. Herein, we demonstrate the absence of liver and bone marrow metastases after a lethal challenge with NXS2 wild-type cells only in mice (five of six animals) vaccinated with scIL-12-producing NXS2 cells and given a booster injection of low-dose ch14.18-IL-2 fusion protein. This tumor-protective immunity was effective 3 months after initial vaccination, in contrast to control animals treated with a nonspecific fusion protein or an equivalent mixture of antibody and IL-2. Only vaccinated mice receiving the tumor-specific ch14.18-IL-2 fusion protein revealed a reactivation of CD8+ T cells and subsequent MHC class I-restricted tumor target cell lysis in vitro. The sequential increase in the usage of TCR chains Vβ11 and -13 in mouse CD8+ T cells after vaccination and amplification with ch14.18-IL-2 suggests that the initial polyclonal CD8+ T cell response is effectively boosted by targeted IL-2. In conclusion, we demonstrate that a successful boost of a partially protective memory T cell immune response that is induced by scIL-12 gene therapy could be generated by tumor-specific targeting of IL-2 with a ch14.18-IL-2 fusion protein. This approach could increase success rates of clinical cancer vaccine trials. PMID:10411920

Development of a cryogenically cooled platform for the Magnetized Liner Inertial Fusion (MagLIF) Program [Development of a cryogenically-cooled platform for the Magnetized Liner Inertial Fusion (MagLIF) Concept

DOE PAGES

Awe, T. J.; Shelton, K. P.; Sefkow, A. B.; ...

2017-09-25

A cryogenically cooled hardware platform has been developed and commissioned on the Z Facility at Sandia National Laboratories in support of the Magnetized Liner Inertial Fusion (MagLIF) Program. MagLIF is a magneto-inertial fusion concept that employs a magnetically imploded metallic tube (liner) to compress and inertially confine premagnetized and preheated fusion fuel. The fuel is preheated using a ~2 kJ laser that must pass through a ~1.5-3.5-μm-thick polyimide “window” at the target’s laser entrance hole (LEH). As the terawatt-class laser interacts with the dense window, laser plasma instabilities (LPIs) can develop, which reduce the preheat energy delivered to the fuel,more » initiate fuel contamination, and degrade target performance. Cryogenically cooled targets increase the parameter space accessible to MagLIF target designs by allowing nearly 10 times thinner windows to be used for any accessible gas density. Thinner LEH windows reduce the deleterious effects of difficult to model LPIs. The Z Facility’s cryogenic infrastructure has been significantly altered to enable compatibility with the premagnetization and fuel preheat stages of MagLIF. The MagLIF cryostat brings the liquid helium coolant directly to the target via an electrically resistive conduit. This design maximizes cooling power while allowing rapid diffusion of the axial magnetic field supplied by external Helmholtz-like coils. A variety of techniques have been developed to mitigate the accumulation of ice from vacuum chamber contaminants on the cooled LEH window, as even a few hundred nanometers of ice would impact laser energy coupling to the fuel region. Here, the MagLIF cryostat has demonstrated compatibility with the premagnetization and preheat stages of MagLIF and the ability to cool targets to liquid deuterium temperatures in approximately 5 min.« less

Development of a cryogenically cooled platform for the Magnetized Liner Inertial Fusion (MagLIF) Program [Development of a cryogenically-cooled platform for the Magnetized Liner Inertial Fusion (MagLIF) Concept

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

Awe, T. J.; Shelton, K. P.; Sefkow, A. B.

A cryogenically cooled hardware platform has been developed and commissioned on the Z Facility at Sandia National Laboratories in support of the Magnetized Liner Inertial Fusion (MagLIF) Program. MagLIF is a magneto-inertial fusion concept that employs a magnetically imploded metallic tube (liner) to compress and inertially confine premagnetized and preheated fusion fuel. The fuel is preheated using a ~2 kJ laser that must pass through a ~1.5-3.5-μm-thick polyimide “window” at the target’s laser entrance hole (LEH). As the terawatt-class laser interacts with the dense window, laser plasma instabilities (LPIs) can develop, which reduce the preheat energy delivered to the fuel,more » initiate fuel contamination, and degrade target performance. Cryogenically cooled targets increase the parameter space accessible to MagLIF target designs by allowing nearly 10 times thinner windows to be used for any accessible gas density. Thinner LEH windows reduce the deleterious effects of difficult to model LPIs. The Z Facility’s cryogenic infrastructure has been significantly altered to enable compatibility with the premagnetization and fuel preheat stages of MagLIF. The MagLIF cryostat brings the liquid helium coolant directly to the target via an electrically resistive conduit. This design maximizes cooling power while allowing rapid diffusion of the axial magnetic field supplied by external Helmholtz-like coils. A variety of techniques have been developed to mitigate the accumulation of ice from vacuum chamber contaminants on the cooled LEH window, as even a few hundred nanometers of ice would impact laser energy coupling to the fuel region. Here, the MagLIF cryostat has demonstrated compatibility with the premagnetization and preheat stages of MagLIF and the ability to cool targets to liquid deuterium temperatures in approximately 5 min.« less

HIV-1 virion fusion assay: uncoating not required and no effect of Nef on fusion

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

Cavrois, Marielle; Neidleman, Jason; Yonemoto, Wes

2004-10-15

We recently described a sensitive and specific assay that detects the fusion of HIV-1 virions to a broad range of target cells, including primary CD4 cells. This assay involves the use of virions containing {beta}-lactamase-Vpr (BlaM-Vpr) and the loading of target cells with CCF2, a fluorogenic substrate of {beta}-lactamase. Since Vpr strongly associates with the viral core, uncoating of the viral particle might be required for effective cleavage of CCF2 by BlaM-Vpr. Here, we show that BlaM-Vpr within mature viral cores effectively cleaves CCF2, indicating that this assay measures virion fusion independently of uncoating. We also show that wildtype andmore » Nef-deficient HIV-1 virions fuse with equivalent efficiency to HeLa-CD4 cells, SupT1 T cells, and primary CD4 T cells. Since Nef enhances cytoplasmic delivery of viral cores and increases viral infectivity, these findings indicate that Nef enhances an early post-fusion event in the multistep process of viral entry. Possible sites of Nef action include enlargement of the fusion pore, enhanced uncoating of viral particles, and more efficient passage of viral cores through the dense cortical actin network located immediately beneath the plasma membrane.« less

Alectinib shows potent antitumor activity against RET-rearranged non-small cell lung cancer.

PubMed

Kodama, Tatsushi; Tsukaguchi, Toshiyuki; Satoh, Yasuko; Yoshida, Miyuki; Watanabe, Yoshiaki; Kondoh, Osamu; Sakamoto, Hiroshi

2014-12-01

Alectinib/CH5424802 is a known inhibitor of anaplastic lymphoma kinase (ALK) and is being evaluated in clinical trials for the treatment of ALK fusion-positive non-small cell lung cancer (NSCLC). Recently, some RET and ROS1 fusion genes have been implicated as driver oncogenes in NSCLC and have become molecular targets for antitumor agents. This study aims to explore additional target indications of alectinib by testing its ability to inhibit the activity of kinases other than ALK. We newly verified that alectinib inhibited RET kinase activity and the growth of RET fusion-positive cells by suppressing RET phosphorylation. In contrast, alectinib hardly inhibited ROS1 kinase activity unlike other ALK/ROS1 inhibitors such as crizotinib and LDK378. It also showed antitumor activity in mouse models of tumors driven by the RET fusion. In addition, alectinib showed kinase inhibitory activity against RET gatekeeper mutations (RET V804L and V804M) and blocked cell growth driven by the KIF5B-RET V804L and V804M. Our results suggest that alectinib is effective against RET fusion-positive tumors. Thus, alectinib might be a therapeutic option for patients with RET fusion-positive NSCLC. ©2014 American Association for Cancer Research.

Application of Magnetized Target Fusion to High-Energy Space Propulsion

NASA Technical Reports Server (NTRS)

Thio, Y. C. F.; Schmidt, G. R.; Kirkpatrick, R. C.; Rodgers, Stephen L. (Technical Monitor)

2001-01-01

Most fusion propulsion concepts that have been investigated in the past employ some form of inertial or magnetic confinement. Although the prospective performance of these concepts is excellent, the fusion processes on which these concepts are based still require considerable development before they can be seriously considered for actual applications. Furthermore, these processes are encumbered by the need for sophisticated plasma and power handling systems that are generally quite inefficient and have historically resulted in large, massive spacecraft designs. Here we present a comparatively new approach, Magnetized Target Fusion (MTF), which offers a nearer-term avenue for realizing the tremendous performance benefits of fusion propulsion'. The key advantage of MTF is its less demanding requirements for driver energy and power processing. Additional features include: 1) very low system masses and volumes, 2) high gain and relatively low waste heat, 3) substantial utilization of energy from product neutrons, 4) efficient, low peak-power drivers based on existing pulsed power technology, and 5) very high Isp, specific power and thrust. MTF overcomes many of the problems associated with traditional fusion techniques, thus making it particularly attractive for space applications. Isp greater than 50,000 seconds and specific powers greater than 50 kilowatts/kilogram appear feasible using relatively near-term pulse power and plasma gun technology.

Information-Theoretic Performance Analysis of Sensor Networks via Markov Modeling of Time Series Data.

PubMed

Li, Yue; Jha, Devesh K; Ray, Asok; Wettergren, Thomas A; Yue Li; Jha, Devesh K; Ray, Asok; Wettergren, Thomas A; Wettergren, Thomas A; Li, Yue; Ray, Asok; Jha, Devesh K

2018-06-01

This paper presents information-theoretic performance analysis of passive sensor networks for detection of moving targets. The proposed method falls largely under the category of data-level information fusion in sensor networks. To this end, a measure of information contribution for sensors is formulated in a symbolic dynamics framework. The network information state is approximately represented as the largest principal component of the time series collected across the network. To quantify each sensor's contribution for generation of the information content, Markov machine models as well as x-Markov (pronounced as cross-Markov) machine models, conditioned on the network information state, are constructed; the difference between the conditional entropies of these machines is then treated as an approximate measure of information contribution by the respective sensors. The x-Markov models represent the conditional temporal statistics given the network information state. The proposed method has been validated on experimental data collected from a local area network of passive sensors for target detection, where the statistical characteristics of environmental disturbances are similar to those of the target signal in the sense of time scale and texture. A distinctive feature of the proposed algorithm is that the network decisions are independent of the behavior and identity of the individual sensors, which is desirable from computational perspectives. Results are presented to demonstrate the proposed method's efficacy to correctly identify the presence of a target with very low false-alarm rates. The performance of the underlying algorithm is compared with that of a recent data-driven, feature-level information fusion algorithm. It is shown that the proposed algorithm outperforms the other algorithm.

Molecular breakdown: a comprehensive view of anaplastic lymphoma kinase (ALK)-rearranged non-small cell lung cancer.

PubMed

Noh, Ka-Won; Lee, Mi-Sook; Lee, Seung Eun; Song, Ji-Young; Shin, Hyun-Tae; Kim, Yu Jin; Oh, Doo Yi; Jung, Kyungsoo; Sung, Minjung; Kim, Mingi; An, Sungbin; Han, Joungho; Shim, Young Mog; Zo, Jae Ill; Kim, Jhingook; Park, Woong-Yang; Lee, Se-Hoon; Choi, Yoon-La

2017-11-01

Most anaplastic lymphoma kinase (ALK)-rearranged non-small cell lung cancers (NSCLCs) show good clinical response to ALK inhibitors. However, some ALK-rearranged NSCLC patients show various primary responses with unknown reasons. Previous studies focused on the clinical aspects of ALK fusions in small cohorts, or were conducted in vitro and/or in vivo to investigate the function of ALK. One of the suggested theories describes how echinoderm microtubule-associated protein-like 4 (EML4)-ALK variants play a role towards different sensitivities in ALK inhibitors. Until now, there has been no integrated comprehensive study that dissects ALK at the molecular level in a large scale. Here, we report the largest extensive molecular analysis of 158 ALK-rearranged NSCLCs and have investigated these findings in a cell line construct experiment. We discovered that NSCLCs with EML4-ALK short forms (variant 3/others) had more advanced stage and frequent metastases than cases with the long forms (variant 1/others) (p = 0.057, p < 0.05). In vitro experiments revealed that EML4-ALK short forms show lower sensitivity to ALK inhibitors than do long forms. Clinical analysis also showed a trend for the short forms showing worse PFS. Interestingly, we found that breakpoints of ALK are evenly distributed mainly in intron 19 and almost all of them undergo a non-homologous end-joining repair to generate ALK fusions. We also discovered four novel somatic ALK mutations in NSCLC (T1151R, R1192P, A1280V, and L1535Q) that confer primary resistance; all of them showed strong resistance to ALK inhibitors, as G1202R does. Through targeted deep sequencing, we discovered three novel ALK fusion partners (GCC2, LMO7, and PHACTR1), and different ALK fusion partners showed different intracellular localization. With our findings that the EML4-ALK variants, new ALK somatic mutations, and novel ALK-fusion partners may affect sensitivity to ALK inhibitors, we stress the importance of targeted therapy to take the ALK molecular profiling into consideration. Copyright © 2017 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. Copyright © 2017 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

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

Slough, John

The entry of fusion as a viable, competitive source of power has been stymied by the challenge of finding an economical way to provide for the confinement and heating of the plasma fuel. The main impediment for current nuclear fusion concepts is the complexity and large mass associated with the confinement systems. To take advantage of the smaller scale, higher density regime of magnetic fusion, an efficient method for achieving the compressional heating required to reach fusion gain conditions must be found. The very compact, high energy density plasmoid commonly referred to as a Field Reversed Configuration (FRC) provides formore » an ideal target for this purpose. To make fusion with the FRC practical, an efficient method for repetitively compressing the FRC to fusion gain conditions is required. A novel approach to be explored in this endeavor is to remotely launch a converging array of small macro-particles (macrons) that merge and form a more massive liner inside the reactor which then radially compresses and heats the FRC plasmoid to fusion conditions. The closed magnetic field in the target FRC plasmoid suppresses the thermal transport to the confining liner significantly lowering the imploding power needed to compress the target. With the momentum flux being delivered by an assemblage of low mass, but high velocity macrons, many of the difficulties encountered with the liner implosion power technology are eliminated. The undertaking to be described in this proposal is to evaluate the feasibility achieving fusion conditions from this simple and low cost approach to fusion. During phase I the design and testing of the key components for the creation of the macron formed liner have been successfully carried out. Detailed numerical calculations of the merging, formation and radial implosion of the Macron Formed Liner (MFL) were also performed. The phase II effort will focus on an experimental demonstration of the macron launcher at full power, and the demonstration of megagauss magnetic field compression by a small array of full scale macrons. In addition the physics of the compression of an FRC to fusion conditions will be undertaken with a smaller scale MFL. The timescale for testing will be rapidly accelerated by taking advantage of other facilities at MSNW where the target FRC will be created and translated inside the MFL just prior to implosion of the MFL. Experimental success would establish the concept at the proof of principle level and the following phase III effort would focus on the full development of the concept into a fusion gain device. Successful operation would lead to several benefits in various fields. It would have application to high energy density physics, as well as nuclear waste transmutation and alternate fission fuel cycles. The smaller scale device could find immediate application as an intense source of neutrons for diagnostic imaging and non-invasive object interrogation.« less

Rho GTPase activity modulates paramyxovirus fusion protein-mediated cell-cell fusion

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

Schowalter, Rachel M.; Wurth, Mark A.; Aguilar, Hector C.

2006-07-05

The paramyxovirus fusion protein (F) promotes fusion of the viral envelope with the plasma membrane of target cells as well as cell-cell fusion. The plasma membrane is closely associated with the actin cytoskeleton, but the role of actin dynamics in paramyxovirus F-mediated membrane fusion is unclear. We examined cell-cell fusion promoted by two different paramyxovirus F proteins in three cell types in the presence of constitutively active Rho family GTPases, major cellular coordinators of actin dynamics. Reporter gene and syncytia assays demonstrated that expression of either Rac1{sup V12} or Cdc42{sup V12} could increase cell-cell fusion promoted by the Hendra ormore » SV5 glycoproteins, though the effect was dependent on the cell type expressing the viral glycoproteins. In contrast, RhoA{sup L63} decreased cell-cell fusion promoted by Hendra glycoproteins but had little affect on SV5 F-mediated fusion. Also, data suggested that GTPase activation in the viral glycoprotein-containing cell was primarily responsible for changes in fusion. Additionally, we found that activated Cdc42 promoted nuclear rearrangement in syncytia.« less

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

Walker, Johnnie A.; Takasuka, Taichi E.; Deng, Kai

Carbohydrate binding modules (CBMs) bind polysaccharides and help target glycoside hydrolases catalytic domains to their appropriate carbohydrate substrates. To better understand how CBMs can improve cellulolytic enzyme reactivity, representatives from each of the 18 families of CBM found in Ruminoclostridium thermocellum were fused to the multifunctional GH5 catalytic domain of CelE (Cthe_0797, CelEcc), which can hydrolyze numerous types of polysaccharides including cellulose, mannan, and xylan. Since CelE is a cellulosomal enzyme, none of these fusions to a CBM previously existed. CelEcc_CBM fusions were assayed for their ability to hydrolyze cellulose, lichenan, xylan, and mannan. Several CelEcc_CBM fusions showed enhanced hydrolyticmore » activity with different substrates relative to the fusion to CBM3a from the cellulosome scaffoldin, which has high affinity for binding to crystalline cellulose. Additional binding studies and quantitative catalysis studies using nanostructure-initiator mass spectrometry (NIMS) were carried out with the CBM3a, CBM6, CBM30, and CBM44 fusion enzymes. In general, and consistent with observations of others, enhanced enzyme reactivity was correlated with moderate binding affinity of the CBM. Numerical analysis of reaction time courses showed that CelEcc_CBM44, a combination of a multifunctional enzyme domain with a CBM having broad binding specificity, gave the fastest rates for hydrolysis of both the hexose and pentose fractions of ionic-liquid pretreated switchgrass. In conclusion, we have shown that fusions of different CBMs to a single multifunctional GH5 catalytic domain can increase its rate of reaction with different pure polysaccharides and with pretreated biomass. This fusion approach, incorporating domains with broad specificity for binding and catalysis, provides a new avenue to improve reactivity of simple combinations of enzymes within the complexity of plant biomass.« less

CEP72-ROS1: A novel ROS1 oncogenic fusion variant in lung adenocarcinoma identified by next-generation sequencing.

PubMed

Zhu, You-Cai; Zhou, Yue-Fen; Wang, Wen-Xian; Xu, Chun-Wei; Zhuang, Wu; Du, Kai-Qi; Chen, Gang

2018-05-01

ROS1 rearrangement is a validated therapeutic driver gene in non-small cell lung cancer (NSCLC) and represents a small subset (1-2%) of NSCLC. A total of 17 different fusion partner genes of ROS1 in NSCLC have been reported. The multi-targeted MET/ALK/ROS1 tyrosine kinase inhibitor (TKI) crizotinib has demonstrated remarkable efficacy in ROS1-rearranged NSCLC. Consequently, ROS1 detection assays include fluorescence in situ hybridization, immunohistochemistry, and real-time PCR. Next-generation sequencing (NGS) assay covers a range of fusion genes and approaches to discover novel receptor-kinase rearrangements in lung cancer. A 63-year-old male smoker with stage IV NSCLC (TxNxM1) was detected with a novel ROS1 fusion. Histological examination of the tumor showed lung adenocarcinoma. NGS analysis of the hydrothorax cellblocks revealed a novel CEP72-ROS1 rearrangement. This novel CEP72-ROS1 fusion variant is generated by the fusion of exons 1-11 of CEP72 on chromosome 5p15 to exons 23-43 of ROS1 on chromosome 6q22. The predicted CEP72-ROS1 protein product contains 1202 amino acids comprising the N-terminal amino acids 594-647 of CEP72 and C-terminal amino acid 1-1148 of ROS1. CEP72-ROS1 is a novel ROS1 fusion variant in NSCLC discovered by NGS and could be included in ROS1 detection assay, such as reverse transcription PCR. Pleural effusion samples show good diagnostic performance in clinical practice. © 2018 The Authors. Thoracic Cancer published by China Lung Oncology Group and John Wiley & Sons Australia, Ltd.

CEP72‐ROS1: A novel ROS1 oncogenic fusion variant in lung adenocarcinoma identified by next‐generation sequencing

PubMed Central

Zhu, You‐cai; Zhou, Yue‐fen; Zhuang, Wu; Du, Kai‐qi; Chen, Gang

2018-01-01

ROS1 rearrangement is a validated therapeutic driver gene in non‐small cell lung cancer (NSCLC) and represents a small subset (1–2%) of NSCLC. A total of 17 different fusion partner genes of ROS1 in NSCLC have been reported. The multi‐targeted MET/ALK/ROS1 tyrosine kinase inhibitor (TKI) crizotinib has demonstrated remarkable efficacy in ROS1‐rearranged NSCLC. Consequently, ROS1 detection assays include fluorescence in situ hybridization, immunohistochemistry, and real‐time PCR. Next‐generation sequencing (NGS) assay covers a range of fusion genes and approaches to discover novel receptor‐kinase rearrangements in lung cancer. A 63‐year‐old male smoker with stage IV NSCLC (TxNxM1) was detected with a novel ROS1 fusion. Histological examination of the tumor showed lung adenocarcinoma. NGS analysis of the hydrothorax cellblocks revealed a novel CEP72‐ROS1 rearrangement. This novel CEP72‐ROS1 fusion variant is generated by the fusion of exons 1–11 of CEP72 on chromosome 5p15 to exons 23–43 of ROS1 on chromosome 6q22. The predicted CEP72‐ROS1 protein product contains 1202 amino acids comprising the N‐terminal amino acids 594–647 of CEP72 and C‐terminal amino acid 1‐1148 of ROS1. CEP72‐ROS1 is a novel ROS1 fusion variant in NSCLC discovered by NGS and could be included in ROS1 detection assay, such as reverse transcription PCR. Pleural effusion samples show good diagnostic performance in clinical practice. PMID:29517860

Comprehensive Analysis of CBFβ-MYH11 Fusion Transcripts in Acute Myeloid Leukemia by RT-PCR Analysis

PubMed Central

Kadkol, ShriHari S.; Bruno, Annette; Dodge, Carol; Lindgren, Valerie; Ravandi, Farhad

2004-01-01

CBFβ-MYH11 fusion transcripts are expressed in acute myeloid leukemias of the M4Eo subtype. Patients who express CBFβ-MYH11 fusion transcripts respond favorably to high-dose chemotherapy and are generally spared allogeneic bone marrow transplantation. Hence it is important to identify this fusion in all patients with acute myeloid leukemia M4Eo leukemia. The fusion can be detected by cytogenetics, fluorescence in-situ hybridization (FISH), or by molecular analysis with RT-PCR. Multiple fusion transcripts arising as a result of various breakpoints in the CBFβ and MYH11 have been identified. In this report we describe a comprehensive RT-PCR assay to identify all known fusion transcripts and provide an algorithm for molecular analysis of CBFβ-MYH11 fusions from patient specimens. Further, identification of the fusion transcript by such an assay would help in the diagnosis and follow up of patients with cryptic inversion 16 translocations (such as patient 2 in this report) not detected by standard cytogenetics or FISH and for rational design of probes for quantitative analysis by real-time PCR. PMID:14736823

Sensor fusion II: Human and machine strategies; Proceedings of the Meeting, Philadelphia, PA, Nov. 6-9, 1989

NASA Technical Reports Server (NTRS)

Schenker, Paul S. (Editor)

1990-01-01

Various papers on human and machine strategies in sensor fusion are presented. The general topics addressed include: active vision, measurement and analysis of visual motion, decision models for sensor fusion, implementation of sensor fusion algorithms, applying sensor fusion to image analysis, perceptual modules and their fusion, perceptual organization and object recognition, planning and the integration of high-level knowledge with perception, using prior knowledge and context in sensor fusion.

Integrated Genomic Characterization Reveals Novel, Therapeutically Relevant Drug Targets in FGFR and EGFR Pathways in Sporadic Intrahepatic Cholangiocarcinoma

PubMed Central

Liang, Winnie S.; Fonseca, Rafael; Bryce, Alan H.; McCullough, Ann E.; Barrett, Michael T.; Hunt, Katherine; Patel, Maitray D.; Young, Scott W.; Collins, Joseph M.; Silva, Alvin C.; Condjella, Rachel M.; Block, Matthew; McWilliams, Robert R.; Lazaridis, Konstantinos N.; Klee, Eric W.; Bible, Keith C.; Harris, Pamela; Oliver, Gavin R.; Bhavsar, Jaysheel D.; Nair, Asha A.; Middha, Sumit; Asmann, Yan; Kocher, Jean-Pierre; Schahl, Kimberly; Kipp, Benjamin R.; Barr Fritcher, Emily G.; Baker, Angela; Aldrich, Jessica; Kurdoglu, Ahmet; Izatt, Tyler; Christoforides, Alexis; Cherni, Irene; Nasser, Sara; Reiman, Rebecca; Phillips, Lori; McDonald, Jackie; Adkins, Jonathan; Mastrian, Stephen D.; Placek, Pamela; Watanabe, Aprill T.; LoBello, Janine; Han, Haiyong; Von Hoff, Daniel; Craig, David W.; Stewart, A. Keith; Carpten, John D.

2014-01-01

Advanced cholangiocarcinoma continues to harbor a difficult prognosis and therapeutic options have been limited. During the course of a clinical trial of whole genomic sequencing seeking druggable targets, we examined six patients with advanced cholangiocarcinoma. Integrated genome-wide and whole transcriptome sequence analyses were performed on tumors from six patients with advanced, sporadic intrahepatic cholangiocarcinoma (SIC) to identify potential therapeutically actionable events. Among the somatic events captured in our analysis, we uncovered two novel therapeutically relevant genomic contexts that when acted upon, resulted in preliminary evidence of anti-tumor activity. Genome-wide structural analysis of sequence data revealed recurrent translocation events involving the FGFR2 locus in three of six assessed patients. These observations and supporting evidence triggered the use of FGFR inhibitors in these patients. In one example, preliminary anti-tumor activity of pazopanib (in vitro FGFR2 IC50≈350 nM) was noted in a patient with an FGFR2-TACC3 fusion. After progression on pazopanib, the same patient also had stable disease on ponatinib, a pan-FGFR inhibitor (in vitro, FGFR2 IC50≈8 nM). In an independent non-FGFR2 translocation patient, exome and transcriptome analysis revealed an allele specific somatic nonsense mutation (E384X) in ERRFI1, a direct negative regulator of EGFR activation. Rapid and robust disease regression was noted in this ERRFI1 inactivated tumor when treated with erlotinib, an EGFR kinase inhibitor. FGFR2 fusions and ERRFI mutations may represent novel targets in sporadic intrahepatic cholangiocarcinoma and trials should be characterized in larger cohorts of patients with these aberrations. PMID:24550739

Biochemistry and Biophysics of HIV-1 gp41 – membrane interactions

PubMed Central

Cai, Lifeng; Gochin, Miriam; Liu, Keliang

2011-01-01

Human immunodeficiency virus type 1 (HIV-1), the pathogen of acquired immunodeficiency syndrome (AIDS), causes ~2 millions death every year and still defies an effective vaccine. HIV-1 infects host cells through envelope protein – mediated virus-cell fusion. The transmembrane subunit of envelope protein, gp41, is the molecular machinery which facilitates fusion. Its ectodomain contains several distinguishing functional domains, fusion peptide (FP), N-terminal heptad repeat (NHR), C-terminal heptad repeat (CHR) and membrane proximal extracellular region (MPER). During the fusion process, FP inserts into the host cell membrane, and an extended gp41 prehairpin conformation bridges the viral and cell membranes through MPER and FP respectively. Subsequent conformational change of the unstable prehairpin results in a coiled-coil 6-helix bundle (6HB) structure formed between NHR and CHR. The energetics of 6HB formation drives membrane apposition and fusion. Drugs targeting gp41 functional domains to prevent 6HB formation inhibit HIV-1 infection. T20 (enfuvirtide, Fuzeon) was approved by the US FDA in 2003 as the first fusion inhibitor. It is a 36-residue peptide from the gp41 CHR, and it inhibits 6HB formation by targeting NHR and lipids. Development of new fusion inhibitors, especially small molecule drugs, is encouraged to overcome the shortcomings of T20 as a peptide drug. Hydrophobic characteristics and membrane association are critical for gp41 function and mechanism of action. Research in gp41-membrane interactions, using peptides corresponding to specific functional domains, or constructs including several interactive domains, are reviewed here to get a better understanding of gp41 mediated virus-cell fusion that can inform or guide the design of new HIV-1 fusion inhibitors. PMID:22044229

Sensitivity of low-energy incomplete fusion to various entrance-channel parameters

NASA Astrophysics Data System (ADS)

Kumar, Harish; Tali, Suhail A.; Afzal Ansari, M.; Singh, D.; Ali, Rahbar; Kumar, Kamal; Sathik, N. P. M.; Ali, Asif; Parashari, Siddharth; Dubey, R.; Bala, Indu; Kumar, R.; Singh, R. P.; Muralithar, S.

2018-03-01

The disentangling of incomplete fusion dependence on various entrance channel parameters has been made from the forward recoil range distribution measurement for the 12C+175Lu system at ≈ 88 MeV energy. It gives the direct measure of full and/or partial linear momentum transfer from the projectile to the target nucleus. The comparison of observed recoil ranges with theoretical ranges calculated using the code SRIM infers the production of evaporation residues via complete and/or incomplete fusion process. Present results show that incomplete fusion process contributes significantly in the production of α xn and 2α xn emission channels. The deduced incomplete fusion probability (F_{ICF}) is compared with that obtained for systems available in the literature. An interesting behavior of F_{ICF} with ZP ZT is observed in the reinvestigation of incomplete fusion dependency with the Coulomb factor (ZPZT), contrary to the recent observations. The present results based on (ZPZT) are found in good agreement with recent observations of our group. A larger F_{ICF} value for 12C induced reactions is found than that for 13C, although both have the same ZPZT. A nonsystematic behavior of the incomplete fusion process with the target deformation parameter (β2) is observed, which is further correlated with a new parameter (ZP ZT . β2). The projectile α -Q-value is found to explain more clearly the discrepancy observed in incomplete fusion dependency with parameters ( ZPZT) and (ZP ZT . β2). It may be pointed out that any single entrance channel parameter (mass-asymmetry or (ZPZT) or β2 or projectile α-Q-value) may not be able to explain completely the incomplete fusion process.

Oncogenic BRAF fusions in mucosal melanomas activate the MAPK pathway and are sensitive to MEK/PI3K inhibition or MEK/CDK4/6 inhibition.

PubMed

Kim, H S; Jung, M; Kang, H N; Kim, H; Park, C-W; Kim, S-M; Shin, S J; Kim, S H; Kim, S G; Kim, E K; Yun, M R; Zheng, Z; Chung, K Y; Greenbowe, J; Ali, S M; Kim, T-M; Cho, B C

2017-06-08

Despite remarkable progress in cutaneous melanoma genomic profiling, the mutational landscape of primary mucosal melanomas (PMM) remains unclear. Forty-six PMMs underwent targeted exome sequencing of 111 cancer-associated genes. Seventy-six somatic nonsynonymous mutations in 42 genes were observed, and recurrent mutations were noted on eight genes, including TP53 (13%), NRAS (13%), SNX31 (9%), NF1 (9%), KIT (7%) and APC (7%). Mitogen-activated protein kinase (MAPK; 37%), cell cycle (20%) and phosphatidylinositol 3-kinase (PI3K)-mTOR (15%) pathways were frequently mutated. We biologically characterized a novel ZNF767-BRAF fusion found in a vemurafenib-refractory respiratory tract PMM, from which cell line harboring ZNF767-BRAF fusion were established for further molecular analyses. In an independent data set, NFIC-BRAF fusion was identified in an oral PMM case and TMEM178B-BRAF fusion and DGKI-BRAF fusion were identified in two malignant melanomas with a low mutational burden (number of mutation per megabase, 0.8 and 4, respectively). Subsequent analyses revealed that the ZNF767-BRAF fusion protein promotes RAF dimerization and activation of the MAPK pathway. We next tested the in vitro and in vivo efficacy of vemurafenib, trametinib, BKM120 or LEE011 alone and in combination. Trametinib effectively inhibited tumor cell growth in vitro, but the combination of trametinib and BKM120 or LEE011 yielded more than additive anti-tumor effects both in vitro and in vivo in a melanoma cells harboring the BRAF fusion. In conclusion, BRAF fusions define a new molecular subset of PMM that can be targeted therapeutically by the combination of a MEK inhibitor with PI3K or cyclin-dependent kinase 4/6 inhibitors.

Role of Abl kinase and the Wave2 signaling complex in HIV-1 entry at a post-hemifusion step.

PubMed

Harmon, Brooke; Campbell, Nancy; Ratner, Lee

2010-06-17

Entry of human immunodeficiency virus type 1 (HIV-1) commences with binding of the envelope glycoprotein (Env) to the receptor CD4, and one of two coreceptors, CXCR4 or CCR5. Env-mediated signaling through coreceptor results in Galphaq-mediated Rac activation and actin cytoskeleton rearrangements necessary for fusion. Guanine nucleotide exchange factors (GEFs) activate Rac and regulate its downstream protein effectors. In this study we show that Env-induced Rac activation is mediated by the Rac GEF Tiam-1, which associates with the adaptor protein IRSp53 to link Rac to the Wave2 complex. Rac and the tyrosine kinase Abl then activate the Wave2 complex and promote Arp2/3-dependent actin polymerization. Env-mediated cell-cell fusion, virus-cell fusion and HIV-1 infection are dependent on Tiam-1, Abl, IRSp53, Wave2, and Arp3 as shown by attenuation of fusion and infection in cells expressing siRNA targeted to these signaling components. HIV-1 Env-dependent cell-cell fusion, virus-cell fusion and infection were also inhibited by Abl kinase inhibitors, imatinib, nilotinib, and dasatinib. Treatment of cells with Abl kinase inhibitors did not affect cell viability or surface expression of CD4 and CCR5. Similar results with inhibitors and siRNAs were obtained when Env-dependent cell-cell fusion, virus-cell fusion or infection was measured, and when cell lines or primary cells were the target. Using membrane curving agents and fluorescence microscopy, we showed that inhibition of Abl kinase activity arrests fusion at the hemifusion (lipid mixing) step, suggesting a role for Abl-mediated actin remodeling in pore formation and expansion. These results suggest a potential utility of Abl kinase inhibitors to treat HIV-1 infected patients.

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

Friedman, A.; Barnard, J. J.; Cohen, R. H.

The Heavy Ion Fusion Science Virtual National Laboratory(a collaboration of LBNL, LLNL, and PPPL) is using intense ion beams to heat thin foils to the"warm dense matter" regime at<~;; 1 eV, and is developing capabilities for studying target physics relevant to ion-driven inertial fusion energy. The need for rapid target heating led to the development of plasma-neutralized pulse compression, with current amplification factors exceeding 50 now routine on the Neutralized Drift Compression Experiment (NDCX). Construction of an improved platform, NDCX-II, has begun at LBNL with planned completion in 2012. Using refurbished induction cells from the Advanced Test Accelerator at LLNL,more » NDCX-II will compress a ~;;500 ns pulse of Li+ ions to ~;;1 ns while accelerating it to 3-4 MeV over ~;;15 m. Strong space charge forces are incorporated into the machine design at a fundamental level. We are using analysis, an interactive 1D PIC code (ASP) with optimizing capabilities and centroid tracking, and multi-dimensional Warpcode PIC simulations, to develop the NDCX-II accelerator. This paper describes the computational models employed, and the resulting physics design for the accelerator.« less

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

Friedman, A; Barnard, J J; Cohen, R H

The Heavy Ion Fusion Science Virtual National Laboratory (a collaboration of LBNL, LLNL, and PPPL) is using intense ion beams to heat thin foils to the 'warm dense matter' regime at {approx}< 1 eV, and is developing capabilities for studying target physics relevant to ion-driven inertial fusion energy. The need for rapid target heating led to the development of plasma-neutralized pulse compression, with current amplification factors exceeding 50 now routine on the Neutralized Drift Compression Experiment (NDCX). Construction of an improved platform, NDCX-II, has begun at LBNL with planned completion in 2012. Using refurbished induction cells from the Advanced Testmore » Accelerator at LLNL, NDCX-II will compress a {approx}500 ns pulse of Li{sup +} ions to {approx} 1 ns while accelerating it to 3-4 MeV over {approx} 15 m. Strong space charge forces are incorporated into the machine design at a fundamental level. We are using analysis, an interactive 1D PIC code (ASP) with optimizing capabilities and centroid tracking, and multi-dimensional Warpcode PIC simulations, to develop the NDCX-II accelerator. This paper describes the computational models employed, and the resulting physics design for the accelerator.« less

Stability of the recombinant anti‑erbB2 scFv‑Fc‑interleukin‑2 fusion protein and its inhibition of HER2‑overexpressing tumor cells.

PubMed

Du, Yu-Jia; Lin, Ze-Min; Zhao, Ying-Hua; Feng, Xiu-Ping; Wang, Chang-Qing; Wang, Gang; Wang, Chun-Di; Shi, Wei; Zuo, Jian-Ping; Li, Fan; Wang, Cheng-Zhong

2013-02-01

The anti‑erbB2 scFv‑Fc‑IL‑2 fusion protein (HFI) is the basis for development of a novel targeted anticancer drug, in particular for the treatment of HER2‑positive cancer patients. HFI was fused with the anti‑erbB2 antibody and human IL‑2 by genetic engineering technology and by antibody targeting characteristics of HFI. IL‑2 was recruited to target cells to block HER2 signaling, inhibit or kill tumor cells, improve the immune capacity, reduce the dose of antibody and IL‑2 synergy. In order to analyse HFI drug ability, HFI plasmid stability was verified by HFI expression of the trend of volume changes. Additionally, HFI could easily precipitate and had progressive characteristics and thus, the buffer system of the additive phosphate‑citric acid buffer, arginine, Triton X‑100 or Tween‑80, the establishment of a microfiltration, ion exchange, affinity chromatography and gel filtration chromatography‑based purification process were explored. HFI samples were obtained according to the requirements of purity, activity and homogeneity. In vivo, HFI significantly delayed HER2 overexpression of non‑small cell lung cancer (Calu‑3) in human non‑small cell lung cancer xenografts in nude mice, and the inhibition rate was more than 60% (P<0.05) in the group treated with 1 mg/kg the HFI dose; HFI significantly inhibited HER2 expression of breast cancer (FVB/neu) transgenic mouse tumor growth in 1 mg/kg of the HFI dose group, and in the following treatment the 400 mm3 tumors disappeared completely. Combined with other HFI test data analysis, HFI not only has good prospects, but also laid the foundation for the development of antibody‑cytokine fusion protein‑like drugs.

Method for nondestructive fuel assay of laser fusion targets

DOEpatents

Farnum, Eugene H.; Fries, R. Jay

1976-01-01

A method for nondestructively determining the deuterium and tritium content of laser fusion targets by counting the x rays produced by the interaction of tritium beta particles with the walls of the microballoons used to contain the deuterium and tritium gas mixture under high pressure. The x rays provide a direct measure of the tritium content and a means for calculating the deuterium content using the initial known D-T ratio and the known deuterium and tritium diffusion rates.