Target sites for the transposition of rat long interspersed repeated DNA elements (LINEs) are not random.

PubMed Central

Furano, A V; Somerville, C C; Tsichlis, P N; D'Ambrosio, E

1986-01-01

The long interspersed repeated DNA family of rats (LINE or L1Rn family) contains about 40,000 6.7-kilobase (kb) long members (1). LINE members may be currently mobile since their presence or absence causes allelic variation at three single copy loci (2, 3): insulin 1, Moloney leukemia virus integration 2 (Mlvi-2) (4), and immunoglobulin heavy chain (Igh). To characterize target sites for LINE insertion, we compared the DNA sequences of the unoccupied Mlvi-2 target site, its LINE-containing allele, and several other LINE-containing sites. Although not homologous overall, the target sites share three characteristics: First, depending on the site, they are from 68% to 86% (A+T) compared to 58% (A+T) for total rat DNA (5). Depending on the site, a 7- to 15-bp target site sequence becomes duplicated and flanks the inserted LINE member. The second is a version (0 or 1 mismatch) of the hexanucleotide, TACTCA, which is also present in the LINE member, in a highly conserved region located just before the A-rich right end of the LINE member. The third is a stretch of alternating purine/pyrimidine (PQ). The A-rich right ends of different LINE members vary in length and composition, and the sequence of a particularly long one suggests that it contains the A-rich target site from a previous transposition. PMID:3012480

Efficacy and safety of third-line molecular-targeted therapy in metastatic renal cell carcinoma resistant to first-line vascular endothelial growth factor receptor tyrosine kinase inhibitor and second-line therapy.

PubMed

Ishihara, Hiroki; Takagi, Toshio; Kondo, Tsunenori; Tachibana, Hidekazu; Yoshida, Kazuhiko; Omae, Kenji; Iizuka, Junpei; Kobayashi, Hirohito; Tanabe, Kazunari

2018-06-01

The number of studies evaluating the efficacy and safety of third-line molecular-targeted therapy for metastatic renal cell carcinoma (mRCC) is limited. The data for 48 patients with disease progression after first-line vascular endothelial growth factor receptor tyrosine kinase inhibitor (TKI) and second-line targeted therapy were evaluated. Patients with prior cytokine therapy were excluded. Overall survival (OS) after first- and second-line therapy initiation was compared between patients with and without third-line therapy. In addition, dose-limiting toxicities (DLTs) were evaluated. Twenty-two of 48 patients (45.8%) received third-line therapy, and TKI and mammalian target of rapamycin inhibitor were each administered in 11 patients (50%). Patients with third-line therapy had significantly longer median OS after first-line therapy (26.6 vs. 14.6 months, p = 0.0010) and second-line therapy (18.2 vs. 7.4 months, p < 0.0001) compared to those without third-line therapy. Multivariate analysis showed that the use of third-line therapy following second-line therapy was an independent prognosticator for longer OS (hazard ratio 0.29, 95% confidence interval 0.14-0.58, p = 0.0005). The median progression-free survival and OS after third-line therapy was 2.76 and 8.71 months, respectively. Although a high frequency of DLTs was observed (n = 10, 45.5%), the frequencies were similar among the sequential therapies. Third-line therapy has a beneficial therapeutic effect in patients with mRCC that is resistant to previous therapies. However, there is a need to evaluate in detail the high frequency of adverse events, including DLTs.

Selection of Phage Display Peptides Targeting Human Pluripotent Stem Cell-Derived Progenitor Cell Lines.

PubMed

Bignone, Paola A; Krupa, Rachel A; West, Michael D; Larocca, David

2016-01-01

The ability of human pluripotent stem cells (hPS) to both self-renew and differentiate into virtually any cell type makes them a promising source of cells for cell-based regenerative therapies. However, stem cell identity, purity, and scalability remain formidable challenges that need to be overcome for translation of pluripotent stem cell research into clinical applications. Directed differentiation from hPS cells is inefficient and residual contamination with pluripotent cells that have the potential to form tumors remains problematic. The derivation of scalable (self-renewing) embryonic progenitor stem cell lines offers a solution because they are well defined and clonally pure. Clonally pure progenitor stem cell lines also provide a means for identifying cell surface targeting reagents that are useful for identification, tracking, and repeated derivation of the corresponding progenitor stem cell types from additional hPS cell sources. Such stem cell targeting reagents can then be applied to the manufacture of genetically diverse banks of human embryonic progenitor cell lines for drug screening, disease modeling, and cell therapy. Here we present methods to identify human embryonic progenitor stem cell targeting peptides by selection of phage display libraries on clonal embryonic progenitor cell lines and demonstrate their use for targeting quantum dots (Qdots) for stem cell labeling.

Methodology for the Evaluation of the Algorithms for Text Line Segmentation Based on Extended Binary Classification

NASA Astrophysics Data System (ADS)

Brodic, D.

2011-01-01

Text line segmentation represents the key element in the optical character recognition process. Hence, testing of text line segmentation algorithms has substantial relevance. All previously proposed testing methods deal mainly with text database as a template. They are used for testing as well as for the evaluation of the text segmentation algorithm. In this manuscript, methodology for the evaluation of the algorithm for text segmentation based on extended binary classification is proposed. It is established on the various multiline text samples linked with text segmentation. Their results are distributed according to binary classification. Final result is obtained by comparative analysis of cross linked data. At the end, its suitability for different types of scripts represents its main advantage.

Obscurin Targets Ankyrin-B and Protein Phosphatase 2A to the Cardiac M-line*

PubMed Central

Cunha, Shane R.; Mohler, Peter J.

2008-01-01

Ankyrin-B targets ion channels and transporters in excitable cells. Dysfunction in ankyrin-B-based pathways results in defects in cardiac physiology. Despite a wealth of knowledge regarding the role of ankyrin-B for cardiac function, little is known regarding the mechanisms underlying ankyrin-B regulation. Moreover, the pathways underlying ankyrin-B targeting in heart are unclear. We report that alternative splicing regulates ankyrin-B localization and function in cardiomyocytes. Specifically, we identify a novel exon (exon 43′) in the ankyrin-B regulatory domain that mediates interaction with the Rho-GEF obscurin. Ankyrin-B transcripts harboring exon 43′ represent the primary cardiac isoform in human and mouse. We demonstrate that ankyrin-B and obscurin are co-localized at the M-line of myocytes and co-immunoprecipitate from heart. We define the structural requirements for ankyrin-B/obscurin interaction to two motifs in the ankyrin-B regulatory domain and demonstrate that both are critical for obscurin/ankyrin-B interaction. In addition, we demonstrate that interaction with obscurin is required for ankyrin-B M-line targeting. Specifically, both obscurin-binding motifs are required for the M-line targeting of a GFP-ankyrin-B regulatory domain. Moreover, this construct acts as a dominant-negative by competing with endogenous ankyrin-B for obscurin-binding at the M-line, thus providing a powerful new tool to evaluate the function of obscurin/ankyrin-B interactions. With this new tool, we demonstrate that the obscurin/ankyrin-B interaction is critical for recruitment of PP2A to the cardiac M-line. Together, these data provide the first evidence for the molecular basis of ankyrin-B and PP2A targeting and function at the cardiac M-line. Finally, we report that ankyrin-B R1788W is localized adjacent to the ankyrin-B obscurin-binding motif and increases binding activity for obscurin. In summary, our new findings demonstrate that ANK2 is subject to alternative splicing

Recombinant cell lines expressing shRNA targeting herpes simplex virus 2 VP16 inhibit virus replication.

PubMed

Zhang, Rui; Wang, Yan; Song, Bo; Han, Zhi Qiang; Xu, Yu Ming

2012-01-01

To establish HSV2 VP16 targeting shRNA-expressing cell lines and investigate the antiviral effect of shRNA targeting HSV2 VP16. The cell lines Vero-shRNAs and negative-control Vero-shCON were established. Their inhibition effects on VP16 mRNA expression were tested by real-time fluorescent quantitative polymerase chain reaction (PCR) and their antiviral effects were evaluated by yield reduction assay. The influence of passage numbers on the inhibition ability of cell lines was researched. Vero-shRNA24 targeting the upper stream, Vero-shRNA642 targeting the lower stream and Vero-shCON were established. Vero-shRNA24, Vero-shRNA642 and Vero-shRNA24 + 642 could reduce the VP16 mRNA significantly. Vero-shRNA24 was the most efficient. The HSV2 titers in Vero and Vero-shCON were the highest at 72 h after infection, and started decreasing thereafter. The viral titers of the Vero-shRNA groups reached a peak after 84 h and the highest titers were lower than in the Vero group. The inhibiting effect on VP16 mRNA expression and viral replication of Vero-shRNA24 cell lines of passages 10 and 20 were not significantly different from the primary cell line. Although of no statistical significance, the passage 50 cell line showed decreased inhibiting ability. Recombinant cell lines expressing shRNA targeting HSV2 VP16 were established. They can stably inhibit HSV2 VP16 mRNA expression and viral replication within passage 50. Copyright © 2012 S. Karger AG, Basel.

Determinants for DNA target structure selectivity of the human LINE-1 retrotransposon endonuclease.

PubMed

Repanas, Kostas; Zingler, Nora; Layer, Liliana E; Schumann, Gerald G; Perrakis, Anastassis; Weichenrieder, Oliver

2007-01-01

The human LINE-1 endonuclease (L1-EN) is the targeting endonuclease encoded by the human LINE-1 (L1) retrotransposon. L1-EN guides the genomic integration of new L1 and Alu elements that presently account for approximately 28% of the human genome. L1-EN bears considerable technological interest, because its target selectivity may ultimately be engineered to allow the site-specific integration of DNA into defined genomic locations. Based on the crystal structure, we generated L1-EN mutants to analyze and manipulate DNA target site recognition. Crystal structures and their dynamic and functional analysis show entire loop grafts to be feasible, resulting in altered specificity, while individual point mutations do not change the nicking pattern of L1-EN. Structural parameters of the DNA target seem more important for recognition than the nucleotide sequence, and nicking profiles on DNA oligonucleotides in vitro are less well defined than the respective integration site consensus in vivo. This suggests that additional factors other than the DNA nicking specificity of L1-EN contribute to the targeted integration of non-LTR retrotransposons.

Targeting ceramide metabolic pathway induces apoptosis in human breast cancer cell lines

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

Vethakanraj, Helen Shiphrah; Babu, Thabraz Ahmed; Sudarsanan, Ganesh Babu

2015-08-28

The sphingolipid ceramide is a pro apoptotic molecule of ceramide metabolic pathway and is hydrolyzed to proliferative metabolite, sphingosine 1 phosphate by the action of acid ceramidase. Being upregulated in the tumors of breast, acid ceramidase acts as a potential target for breast cancer therapy. We aimed at targeting this enzyme with a small molecule acid ceramidase inhibitor, Ceranib 2 in human breast cancer cell lines MCF 7 and MDA MB 231. Ceranib 2 effectively inhibited the growth of both the cell lines in dose and time dependant manner. Morphological apoptotic hallmarks such as chromatin condensation, fragmented chromatin were observedmore » in AO/EtBr staining. Moreover, ladder pattern of fragmented DNA observed in DNA gel electrophoresis proved the apoptotic activity of Ceranib 2 in breast cancer cell lines. The apoptotic events were associated with significant increase in the expression of pro-apoptotic genes (Bad, Bax and Bid) and down regulation of anti-apoptotic gene (Bcl 2). Interestingly, increase in sub G1 population of cell cycle phase analysis and elevated Annexin V positive cells after Ceranib 2 treatment substantiated its apoptotic activity in MCF 7 and MDA MB 231 cell lines. Thus, we report Ceranib 2 as a potent therapeutic agent against both ER{sup +} and ER{sup −} breast cancer cell lines. - Highlights: • Acid Ceramidase inhibitor, Ceranib 2 induced apoptosis in Breast cancer cell lines (MCF 7 and MDA MB 231 cell lines). • Apoptosis is mediated by DNA fragmentation and cell cycle arrest. • Ceranib 2 upregulated the expression of pro-apoptotic genes and down regulated anti-apoptotic gene expression. • More potent compared to the standard drug Tamoxifen.« less

Examining the Conditions of Using an On-Line Dictionary to Learn Words and Comprehend Texts

ERIC Educational Resources Information Center

Dilenschneider, Robert Francis

2018-01-01

This study investigated three look-up conditions for language learners to learn unknown target words and comprehend a reading passage when their attention is transferred away to an on-line dictionary. The research questions focused on how each look-up condition impacted the recall and recognition of word forms, word meanings, and passage…

Southeast Asian palm leaf manuscript images: a review of handwritten text line segmentation methods and new challenges

NASA Astrophysics Data System (ADS)

Kesiman, Made Windu Antara; Valy, Dona; Burie, Jean-Christophe; Paulus, Erick; Sunarya, I. Made Gede; Hadi, Setiawan; Sok, Kim Heng; Ogier, Jean-Marc

2017-01-01

Due to their specific characteristics, palm leaf manuscripts provide new challenges for text line segmentation tasks in document analysis. We investigated the performance of six text line segmentation methods by conducting comparative experimental studies for the collection of palm leaf manuscript images. The image corpus used in this study comes from the sample images of palm leaf manuscripts of three different Southeast Asian scripts: Balinese script from Bali and Sundanese script from West Java, both from Indonesia, and Khmer script from Cambodia. For the experiments, four text line segmentation methods that work on binary images are tested: the adaptive partial projection line segmentation approach, the A* path planning approach, the shredding method, and our proposed energy function for shredding method. Two other methods that can be directly applied on grayscale images are also investigated: the adaptive local connectivity map method and the seam carving-based method. The evaluation criteria and tool provided by ICDAR2013 Handwriting Segmentation Contest were used in this experiment.

Providing Controlled Exposure To Target Vocabulary through the Screening and Arranging of Texts.

ERIC Educational Resources Information Center

Ghadirian, Sina

2002-01-01

Considers how to bring foreign language students with limited vocabulary knowledge, consisting mainly of high-frequency words, to where they can comprehend authentic texts in a target domain. Proposes bridging the vocabulary gap by determining which word families account for 95% of the target domain's running words, and having students learn these…

CRISPR/Cas9 mediated generation of stable chondrocyte cell lines with targeted gene knockouts; analysis of an aggrecan knockout cell line.

PubMed

Yang, Maozhou; Zhang, Liang; Stevens, Jeff; Gibson, Gary

2014-12-01

The Swarm rat chondrosarcoma (RCS) cell lines derived from a spontaneous neoplasm in a rat spine several decades ago have provided excellent models of chondrosarcoma tumor development. In addition the robust chondrocyte phenotype (expression of a large panel of genes identical to that seen in normal rat cartilage) and the ability to generate cell clones have facilitated their extensive use in the identification of chondrocyte proteins and genes. The clustered regularly interspersed short palindromic repeat (CRISPR) technology employing the RNA-guided nuclease Cas9 has rapidly dominated the genome engineering field as a unique and powerful gene editing tool. We have generated a stable RCS cell line (RCS Cas9) expressing the nuclease Cas9 that enables the editing of any target gene or non-coding RNA by simple transfection with a guide RNA. As proof of principle, stable cell lines with targeted ablation of aggrecan expression (Acan KO) were generated and characterized. The studies show that stable chondrocyte cell lines with targeted genome editing can be quickly generated from RCS Cas9 cells using this system. The Acan KO cell lines also provided a tool for characterizing the response of chondrocytes to aggrecan loss and the role of aggrecan in chondrosarcoma development. Loss of aggrecan expression while not affecting the chondrocyte phenotype resulted in a much firmer attachment of cells to their substrate in culture. Large changes in the expression of several genes were observed in response to the absence of the proteoglycan matrix, including those for several small leucine rich proteoglycans (SLRPs), transcription factors and membrane transporters. Acan KO cells failed to form a substantial chondrosarcoma when injected subcutaneously in nude mice consistent with previous suggestions that the glycosaminoglycan-rich matrix surrounding the chondrosarcoma protects it from destruction by the host immune system. The studies provide new understanding of aggrecan

Identification of potential target genes of ROR-alpha in THP1 and HUVEC cell lines.

PubMed

Gulec, Cagri; Coban, Neslihan; Ozsait-Selcuk, Bilge; Sirma-Ekmekci, Sema; Yildirim, Ozlem; Erginel-Unaltuna, Nihan

2017-04-01

ROR-alpha is a nuclear receptor, activity of which can be modulated by natural or synthetic ligands. Due to its possible involvement in, and potential therapeutic target for atherosclerosis, we aimed to identify ROR-alpha target genes in monocytic and endothelial cell lines. We performed chromatin immunoprecipitation (ChIP) followed by tiling array (ChIP-on-chip) for ROR-alpha in monocytic cell line THP1 and endothelial cell line HUVEC. Following bioinformatic analysis of the array data, we tested four candidate genes in terms of dependence of their expression level on ligand-mediated ROR-alpha activity, and two of them in terms of promoter occupancy by ROR-alpha. Bioinformatic analyses of ChIP-on-chip data suggested that ROR-alpha binds to genomic regions near the transcription start site (TSS) of more than 3000 genes in THP1 and HUVEC. Potential ROR-alpha target genes in both cell types seem to be involved mainly in membrane receptor activity, signal transduction and ion transport. While SPP1 and IKBKA were shown to be direct target genes of ROR-alpha in THP1 monocytes, inflammation related gene HMOX1 and heat shock protein gene HSPA8 were shown to be potential target genes of ROR-alpha. Our results suggest that ROR-alpha may regulate signaling receptor activity, and transmembrane transport activity through its potential target genes. ROR-alpha seems also to play role in cellular sensitivity to environmental substances like arsenite and chloroprene. Although, the expression analyses have shown that synthetic ROR-alpha ligands can modulate some of potential ROR-alpha target genes, functional significance of ligand-dependent modulation of gene expression needs to be confirmed with further analyses. Copyright © 2017 Elsevier Inc. All rights reserved.

Text Line Detection from Rectangle Traffic Panels of Natural Scene

NASA Astrophysics Data System (ADS)

Wang, Shiyuan; Huang, Linlin; Hu, Jian

2018-01-01

Traffic sign detection and recognition is very important for Intelligent Transportation. Among traffic signs, traffic panel contains rich information. However, due to low resolution and blur in the rectangular traffic panel, it is difficult to extract the character and symbols. In this paper, we propose a coarse-to-fine method to detect the Chinese character on traffic panels from natural scenes. Given a traffic panel Color Quantization is applied to extract candidate regions of Chinese characters. Second, a multi-stage filter based on learning is applied to discard the non-character regions. Third, we aggregate the characters for text lines by Distance Metric Learning method. Experimental results on real traffic images from Baidu Street View demonstrate the effectiveness of the proposed method.

Targeted genome editing in a quail cell line using a customized CRISPR/Cas9 system.

PubMed

Ahn, Jinsoo; Lee, Joonbum; Park, Ju Yeon; Oh, Keon Bong; Hwang, Seongsoo; Lee, Chang-Won; Lee, Kichoon

2017-05-01

Soon after RNA-guided Cas9 (CRISPR-associated protein 9) endonuclease opened a new era of targeted genome editing, the CRISPR/Cas9 platform began to be extensively used to modify genes in various types of cells and organisms. However, successful CRISPR/Cas9-mediated insertion/deletion (indel) mutation remains to be demonstrated in avian cell lines. The objective of this study was to design a poultry-specific CRISPR/Cas9 system to efficiently introduce targeted deletion mutation in chromosomes of the quail muscle clone 7 (QM7) cell line using a customized quail CRISPR vector. In this study, two avian-specific promoters, quail 7SK (q7SK) promoter and CBh promoter, the hybrid form of cytomegalovirus and chicken β-actin promoters, were cloned into a CRISPR vector for the expression of guide RNA and Cas9 protein, respectively. Then, guide RNA, which was designed to target 20-base pair (bp) nucleotides in the quail melanophilin (MLPH) locus, was ligated to the modified CRISPR vector and transfected to QM7 cells. Our results showed multiple indel mutations in the quail MLPH locus in nearly half of the alleles being tested, suggesting the high efficiency of the system for targeted gene modification. The new CRISPR vector developed from this study has the potential application to generate knockout avian cell lines and knockout poultry. © 2016 Poultry Science Association Inc.

A targeted neuroglial reporter line generated by homologous recombination in human embryonic stem cells.

PubMed

Xue, Haipeng; Wu, Sen; Papadeas, Sophia T; Spusta, Steve; Swistowska, Anna Maria; MacArthur, Chad C; Mattson, Mark P; Maragakis, Nicholas J; Capecchi, Mario R; Rao, Mahendra S; Zeng, Xianmin; Liu, Ying

2009-08-01

In this study, we targeted Olig2, a basic helix-loop-helix transcription factor that plays an important role in motoneuron and oligodendrocyte development, in human embryonic stem cell (hESC) line BG01 by homologous recombination. One allele of Olig2 locus was replaced by a green fluorescent protein (GFP) cassette with a targeting efficiency of 5.7%. Targeted clone R-Olig2 (like the other clones) retained pluripotency, typical hESC morphology, and a normal parental karyotype 46,XY. Most importantly, GFP expression recapitulated endogenous Olig2 expression when R-Olig2 was induced by sonic hedgehog and retinoic acid, and GFP-positive cells could be purified by fluorescence-activated cell sorting. Consistent with previous reports on rodents, early GFP-expressing cells appeared biased to a neuronal fate, whereas late GFP-expressing cells appeared biased to an oligodendrocytic fate. This was corroborated by myoblast coculture, transplantation into the rat spinal cords, and whole genome expression profiling. The present work reports an hESC reporter line generated by homologous recombination targeting a neural lineage-specific gene, which can be differentiated and sorted to obtain pure neural progenitor populations.

Low-dose non-targeted radiation effects in human esophageal adenocarcinoma cell lines.

PubMed

Hanu, Christine; Wong, Raimond; Sur, Ranjan K; Hayward, Joseph E; Seymour, Colin; Mothersill, Carmel

2017-02-01

To investigate non-targeted radiation effects in esophageal adenocarcinoma cell lines (OE19 and OE33) using human keratinocyte and colorectal cancer cell reporters following γ-ray exposure. Both clonogenic assays and ratiometric calcium endpoints were used to check for the occurrence of bystander signals in reporter cells. We report data suggesting that γ-irradiation increases cell killing over the expected linear quadratic (LQ) model levels in the OE19 cell line exposed to doses below 1 Gy, i.e. which may be suggestive to be a low hyper-radiosensitive (HRS) response to direct irradiation. Both EAC cell lines (OE19 and OE33) have the ability to produce bystander signals when irradiated cell conditioned medium (ICCM) is placed onto human keratinocyte reporters, but do not seem to be capable of responding to bystander signals when placed on their autologous reporters. Further work with human keratinocyte reporter models showed statistically significant intracellular calcium fluxes following exposure of the reporters to ICCM harvested from both EAC cell lines exposed to 0.5 Gy. These experiments suggest that the OE19 and OE33 cell lines produce bystander signals in human keratinocyte reporter cells. However, the radiosensitivity of the EAC cell lines used in this study cannot be enhanced by the bystander response since both cell lines could not respond to bystander signals.

Seeing the hand while reaching speeds up on-line responses to a sudden change in target position

PubMed Central

Reichenbach, Alexandra; Thielscher, Axel; Peer, Angelika; Bülthoff, Heinrich H; Bresciani, Jean-Pierre

2009-01-01

Goal-directed movements are executed under the permanent supervision of the central nervous system, which continuously processes sensory afferents and triggers on-line corrections if movement accuracy seems to be compromised. For arm reaching movements, visual information about the hand plays an important role in this supervision, notably improving reaching accuracy. Here, we tested whether visual feedback of the hand affects the latency of on-line responses to an external perturbation when reaching for a visual target. Two types of perturbation were used: visual perturbation consisted in changing the spatial location of the target and kinesthetic perturbation in applying a force step to the reaching arm. For both types of perturbation, the hand trajectory and the electromyographic (EMG) activity of shoulder muscles were analysed to assess whether visual feedback of the hand speeds up on-line corrections. Without visual feedback of the hand, on-line responses to visual perturbation exhibited the longest latency. This latency was reduced by about 10% when visual feedback of the hand was provided. On the other hand, the latency of on-line responses to kinesthetic perturbation was independent of the availability of visual feedback of the hand. In a control experiment, we tested the effect of visual feedback of the hand on visual and kinesthetic two-choice reaction times – for which coordinate transformation is not critical. Two-choice reaction times were never facilitated by visual feedback of the hand. Taken together, our results suggest that visual feedback of the hand speeds up on-line corrections when the position of the visual target with respect to the body must be re-computed during movement execution. This facilitation probably results from the possibility to map hand- and target-related information in a common visual reference frame. PMID:19675067

Tailored first-line and second-line CDK4-targeting treatment combinations in mouse models of pancreatic cancer.

PubMed

Chou, Angela; Froio, Danielle; Nagrial, Adnan M; Parkin, Ashleigh; Murphy, Kendelle J; Chin, Venessa T; Wohl, Dalia; Steinmann, Angela; Stark, Rhys; Drury, Alison; Walters, Stacey N; Vennin, Claire; Burgess, Andrew; Pinese, Mark; Chantrill, Lorraine A; Cowley, Mark J; Molloy, Timothy J; Waddell, Nicola; Johns, Amber; Grimmond, Sean M; Chang, David K; Biankin, Andrew V; Sansom, Owen J; Morton, Jennifer P; Grey, Shane T; Cox, Thomas R; Turchini, John; Samra, Jaswinder; Clarke, Stephen J; Timpson, Paul; Gill, Anthony J; Pajic, Marina

2017-10-28

Extensive molecular heterogeneity of pancreatic ductal adenocarcinoma (PDA), few effective therapies and high mortality make this disease a prime model for advancing development of tailored therapies. The p16-cyclin D-cyclin-dependent kinase 4/6-retinoblastoma (RB) protein (CDK4) pathway, regulator of cell proliferation, is deregulated in PDA. Our aim was to develop a novel personalised treatment strategy for PDA based on targeting CDK4. Sensitivity to potent CDK4/6 inhibitor PD-0332991 (palbociclib) was correlated to protein and genomic data in 19 primary patient-derived PDA lines to identify biomarkers of response. In vivo efficacy of PD-0332991 and combination therapies was determined in subcutaneous, intrasplenic and orthotopic tumour models derived from genome-sequenced patient specimens and genetically engineered model. Mechanistically, monotherapy and combination therapy were investigated in the context of tumour cell and extracellular matrix (ECM) signalling. Prognostic relevance of companion biomarker, RB protein, was evaluated and validated in independent PDA patient cohorts (>500 specimens). Subtype-specific in vivo efficacy of PD-0332991-based therapy was for the first time observed at multiple stages of PDA progression: primary tumour growth, recurrence (second-line therapy) and metastatic setting and may potentially be guided by a simple biomarker (RB protein). PD-0332991 significantly disrupted surrounding ECM organisation, leading to increased quiescence, apoptosis, improved chemosensitivity, decreased invasion, metastatic spread and PDA progression in vivo. RB protein is prevalent in primary operable and metastatic PDA and may present a promising predictive biomarker to guide this therapeutic approach. This study demonstrates the promise of CDK4 inhibition in PDA over standard therapy when applied in a molecular subtype-specific context. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights

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

PubMed Central

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

2016-01-01

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

Toward Routine Automatic Pathway Discovery from On-line Scientific Text Abstracts.

PubMed

Ng; Wong

1999-01-01

We are entering a new era of research where the latest scientific discoveries are often first reported online and are readily accessible by scientists worldwide. This rapid electronic dissemination of research breakthroughs has greatly accelerated the current pace in genomics and proteomics research. The race to the discovery of a gene or a drug has now become increasingly dependent on how quickly a scientist can scan through voluminous amount of information available online to construct the relevant picture (such as protein-protein interaction pathways) as it takes shape amongst the rapidly expanding pool of globally accessible biological data (e.g. GENBANK) and scientific literature (e.g. MEDLINE). We describe a prototype system for automatic pathway discovery from on-line text abstracts, combining technologies that (1) retrieve research abstracts from online sources, (2) extract relevant information from the free texts, and (3) present the extracted information graphically and intuitively. Our work demonstrates that this framework allows us to routinely scan online scientific literature for automatic discovery of knowledge, giving modern scientists the necessary competitive edge in managing the information explosion in this electronic age.

Effects of seed mixture sowing with transgenic Bt rice and its parental line on the population dynamics of target stemborers and leafrollers, and non-target planthoppers.

PubMed

Li, Zhuo; Li, Li-Kun; Liu, Bin; Wang, Long; Parajulee, Megha N; Chen, Fa-Jun

2018-01-24

The widespread planting of insect-resistant crops has caused a dramatic shift in agricultural landscapes, thus raising concerns about the potential impacts on both target and non-target pests. In this study, we examined the potential effects of intra-specific seed mixture sowing with transgenic Bt rice (Bt) and its parental non-transgenic line (Nt) (100% Bt rice [Bt 100 ], 5% Nt+95% Bt [Nt 05 Bt 95 ], 10% Nt+90% Bt [Nt 10 Bt 90 ], 20% Nt+80% Bt [Nt 20 Bt 80 ], 40% Nt+60% Bt [Nt 40 Bt 60 ] and 100% Nt rice [Nt 100 ]) on target and non-target pests in a 2-year field trial in southern China. The occurrence of target pests, Sesamia inferens, Chilo suppressalis and Cnaphalocrocis medinalis, decreased with the increased ratio of Bt rice, and the mixture ratios with more than 90% Bt rice (Bt 100 and Nt 05 Bt 95 ) significantly increased the pest suppression efficiency, with the lowest occurrences of non-target planthoppers, Nilaparvata lugens and Sogatella furcifera in Nt 100 and Nt 05 Bt 95 . Furthermore, there were no significant differences in 1000-grain dry weight and grain dry weight per 100 plants between Bt 100 and Nt 05 Bt 95 . Seed mixture sowing of Bt rice with ≤10% (especially 5%) of its parent line was sufficient to overcome potential compliance issues that exist with the use of block or structured refuge to provide most effective control of both target and non-target pests without compromising the grain yield. It is also expected that the strategy of seed mixture sowing with transgenic Bt rice and the non-transgenic parental line would provide rice yield stability while decreasing the insecticide use frequency in rice production. © 2018 Institute of Zoology, Chinese Academy of Sciences.

Incidence and trends of central line associated pneumothorax using radiograph report text search versus administrative database codes.

PubMed

Reeson, Marc; Forster, Alan; van Walraven, Carl

2018-05-25

Central line associated pneumothorax (CLAP) could be a good quality of care indicator because they are objectively measured, clearly undesirable and possibly avoidable. We measured the incidence and trends of CLAP using radiograph report text search with manual review and compared them with measures using routinely collected health administrative data. For each hospitalisation to a tertiary care teaching hospital between 2002 and 2015, we searched all chest radiography reports for a central line with a sensitive computer algorithm. Screen positive reports were manually reviewed to confirm central lines. The index and subsequent chest radiography reports were screened for pneumothorax followed by manual confirmation. Diagnostic and procedural codes were used to identify CLAP in administrative data. In 685 044 hospitalisations, 10 819 underwent central line insertion (1.6%) with CLAP occurring 181 times (1.7%). CLAP risk did not change over time. Codes for CLAP were inaccurate (sensitivity 13.8%, positive predictive value 6.6%). However, overall code-based CLAP risk (1.8%) was almost identical to actual values possibly because patient strata with inflated CLAP risk were balanced by more common strata having underestimated CLAP risk. Code-based methods inflated central line incidence 2.2 times and erroneously concluded that CLAP risk decreased significantly over time. Using valid methods, CLAP incidence was similar to those in the literature but has not changed over time. Although administrative database codes for CLAP were very inaccurate, they generated CLAP risks very similar to actual values because of offsetting errors. In contrast to those from radiograph report text search with manual review, CLAP trends decreased significantly using administrative data. Hospital CLAP risk should not be measured using administrative data. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial

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

PubMed

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

2018-06-11

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

MiRNA-Target Interaction Reveals Cell-Specific Post-Transcriptional Regulation in Mammalian Cell Lines

PubMed Central

Kulkarni, Varun; Naqvi, Afsar Raza; Uttamani, Juhi Raju; Nares, Salvador

2016-01-01

MicroRNAs are 18–22 nucleotides long, non-coding RNAs that bind transcripts with complementary sequences leading to either mRNA degradation or translational suppression. However, the inherent differences in preferred mode of miRNA regulation among cells of different origin have not been examined. In our previous transcriptome profiling studies, we observed that post-transcriptional regulation can differ substantially depending on the cell in context. Here we examined mechanistic differences in the regulation of a let-7a targeted (wild type) or resistant (mutant) engineered renilla transcript across various mammalian cell lines of diverse origin. Dual luciferase assays show that compared to mutant (mut), the reporter gene containing wild type (wt) let-7a binding sites was efficiently suppressed upon transfection in various cell lines. Importantly, the strength of miRNA regulation varied across the cell lines. Total RNA analysis demonstrates that wt renilla mRNA was expressed to similar or higher levels compared to mut suggesting that translation repression is a predominant mode of miRNA regulation. Nonetheless, transcript degradation was observed in some cell lines. Ago-2 immunoprecipitation show that miRNA repressed renilla mRNA are associated with functional mi-RISC (miRNA-RNA induced silencing complex). Given the immense potential of miRNA as a therapeutic option, these findings highlight the necessity to thoroughly examine the mode of mRNA regulation in order to achieve the beneficial effects in targeting cells. PMID:26761000

Research on infrared dim-point target detection and tracking under sea-sky-line complex background

NASA Astrophysics Data System (ADS)

Dong, Yu-xing; Li, Yan; Zhang, Hai-bo

2011-08-01

Target detection and tracking technology in infrared image is an important part of modern military defense system. Infrared dim-point targets detection and recognition under complex background is a difficulty and important strategic value and challenging research topic. The main objects that carrier-borne infrared vigilance system detected are sea-skimming aircrafts and missiles. Due to the characteristics of wide field of view of vigilance system, the target is usually under the sea clutter. Detection and recognition of the target will be taken great difficulties .There are some traditional point target detection algorithms, such as adaptive background prediction detecting method. When background has dispersion-decreasing structure, the traditional target detection algorithms would be more useful. But when the background has large gray gradient, such as sea-sky-line, sea waves etc .The bigger false-alarm rate will be taken in these local area .It could not obtain satisfactory results. Because dim-point target itself does not have obvious geometry or texture feature ,in our opinion , from the perspective of mathematics, the detection of dim-point targets in image is about singular function analysis .And from the perspective image processing analysis , the judgment of isolated singularity in the image is key problem. The foregoing points for dim-point targets detection, its essence is a separation of target and background of different singularity characteristics .The image from infrared sensor usually accompanied by different kinds of noise. These external noises could be caused by the complicated background or from the sensor itself. The noise might affect target detection and tracking. Therefore, the purpose of the image preprocessing is to reduce the effects from noise, also to raise the SNR of image, and to increase the contrast of target and background. According to the low sea-skimming infrared flying small target characteristics , the median filter is used to

Improving panicle exsertion of rice cytoplasmic male sterile line by combination of artificial microRNA and artificial target mimic.

PubMed

Chen, Hao; Jiang, Shan; Zheng, Jie; Lin, Yongjun

2013-04-01

The adoption of hybrid rice caused the second leap in rice yield after the 'green revolution' and contributes substantially to food security of China and the world. However, almost all cytoplasmic male sterile lines (A lines) as females of hybrid rice have a natural deficiency of 'panicle enclosure', which blocks pollination between the A line and the fertility restorer line as the male (R line) of hybrid rice and decreases seed yield. In hybrid rice seed production, exogenous '920' (the active ingredient is gibberellin A3 ) must be applied to eliminate or alleviate panicle enclosure of the A line; however, this not only increases production cost and pollutes the environment, it also decreases seed quality. In this study, we designed a transgenic approach to improve plant height and panicle exsertion of the A line to facilitate hybrid rice production and maintain the semi-dwarf plant type of the hybrid. This approach comprising two components-artificial microRNA (amiRNA) and artificial target mimicry-can manipulate the differential expression of the endogenous Eui1 gene that is associated with rice internode elongation in the A line and the hybrid. amiRNA is a recently developed gene silencing method with high specificity, while target mimicry is a natural mechanism inhibiting the miRNA function that was also recently characterized. This approach provides a paradigm to tune the expression of endogenous genes to achieve the desired phenotype by combining amiRNA and artificial target mimicry technologies. © 2012 The Authors Plant Biotechnology Journal © 2012 Society for Experimental Biology, Association of Applied Biologists and Blackwell Publishing Ltd.

The effects of color cues on typically developing preschoolers' speed of locating a target line drawing: implications for augmentative and alternative communication display design.

PubMed

Thistle, Jennifer J; Wilkinson, Krista

2009-08-01

This research examined how the presence of color in relation to a target within an augmentative and alternative communication array influenced the speed with which typically developing preschoolers located a target line drawing. Fifteen children over the age of 4 years (from 4;2 [years;months] to 5;4) and 15 children under the age of 4 years (2;10-3;11) participated. Participants were asked to find a target line drawing of foods (e.g., banana and tomato) among an array of 12. The reaction time of locating the target was measured across 4 conditions in which the foreground color and the background color of the line drawing were manipulated. For all participants, line drawings featuring foreground color provided greater advantages in the speed of locating the target compared with drawings featuring only background color. Younger participants demonstrated faster reaction times when color was limited to the foreground. Clinicians should consider incorporating color in the foreground of the line drawing when constructing visual displays. Targets that contain only background color but no foreground color appear to have a negative effect on the speed with which younger children can locate a target. Further research is needed to determine the effects in children with disabilities.

Animal models for medications development targeting alcohol abuse using selectively bred rat lines: Neurobiological and pharmacological validity

PubMed Central

Bell, Richard L.; Sable, Helen J.K.; Colombo, Giancarlo; Hyytia, Petri; Rodd, Zachary A.; Lumeng, Lawrence

2012-01-01

The purpose of this review paper is to present evidence that rat animal models of alcoholism provide an ideal platform for developing and screening medications that target alcohol abuse and dependence. The focus is on the 5 oldest international rat lines that have been selectively bred for a high alcohol-consumption phenotype. The behavioral and neurochemical phenotypes of these rat lines are reviewed and placed in the context of the clinical literature. The paper presents behavioral models for assessing the efficacy of pharmaceuticals for the treatment of alcohol abuse and dependence in rodents, with particular emphasis on rats. Drugs that have been tested for their effectiveness in reducing alcohol/ethanol consumption and/or self-administration by these rat lines and their putative site of action are summarized. The paper also presents some current and future directions for developing pharmacological treatments targeting alcohol abuse and dependence. PMID:22841890

Enhanced Text Spacing Improves Reading Performance in Individuals with Macular Disease

PubMed Central

Blackmore-Wright, Sally; Georgeson, Mark A.; Anderson, Stephen J.

2013-01-01

The search by many investigators for a solution to the reading problems encountered by individuals with no central vision has been long and, to date, not very fruitful. Most textual manipulations, including font size, have led to only modest gains in reading speed. Previous work on spatial integrative properties of peripheral retina suggests that ‘visual crowding’ may be a major factor contributing to inefficient reading. Crowding refers to the fact that juxtaposed targets viewed eccentrically may be difficult to identify. The purpose of this study was to assess the combined effects of line spacing and word spacing on the ability of individuals with age-related macular degeneration (ARMD) to read short passages of text that were printed with either high (87.5%) or low contrast (17.5%) letters. Low contrast text was used to avoid potential ceiling effects and to mimic a possible reduction in letter contrast with light scatter from media opacities. For both low and high contrast text, the fastest reading speeds we measured were for passages of text with double line and double word spacing. In comparison with standard single spacing, double word/line spacing increased reading speed by approximately 26% with high contrast text (p < 0.001), and by 46% with low contrast text (p < 0.001). In addition, double line/word spacing more than halved the number of reading errors obtained with single spaced text. We compare our results with previous reading studies on ARMD patients, and conclude that crowding is detrimental to reading and that its effects can be reduced with enhanced text spacing. Spacing is particularly important when the contrast of the text is reduced, as may occur with intraocular light scatter or poor viewing conditions. We recommend that macular disease patients should employ double line spacing and double-character word spacing to maximize their reading efficiency. PMID:24244676

Supporting narrative retells for people with aphasia using augmentative and alternative communication: photographs or line drawings? Text or no text?

PubMed

Griffith, Julie; Dietz, Aimee; Weissling, Kristy

2014-05-01

The purpose of this study was to examine how the interface design of an augmentative and alternative communication (AAC) device influences the communication behaviors of people with aphasia during a narrative retell task. A case-series design was used. Four narratives were created on an AAC device with combinations of personally relevant (PR) photographs, line drawings (LDs), and text for each participant. The narrative retells were analyzed to describe the expressive modality units (EMUs) used, trouble sources experienced, and whether trouble sources were repaired. The researchers also explored the participants' perceived helpfulness of the interface features. The participants primarily used spoken EMUs to retell their narratives. They relied on PR photographs more frequently than LDs; however, they reported both picture types to be equally helpful. Text was frequently used and reported as helpful by all 4 people with aphasia. Participants experienced similar rates of trouble sources across conditions; however, they displayed unique trends for successful repairs of trouble sources. For narrative retells, LDs may serve as an effective visual support when PR photographs are unavailable. Individual assessment is necessary to determine the optimum combination of supports in AAC systems for people with aphasia.

An off-line method to characterize the fission product release from uranium carbide-target prototypes developed for SPIRAL2 project

NASA Astrophysics Data System (ADS)

Hy, B.; Barré-Boscher, N.; Özgümüs, A.; Roussière, B.; Tusseau-Nenez, S.; Lau, C.; Cheikh Mhamed, M.; Raynaud, M.; Said, A.; Kolos, K.; Cottereau, E.; Essabaa, S.; Tougait, O.; Pasturel, M.

2012-10-01

In the context of radioactive ion beams, fission targets, often based on uranium compounds, have been used for more than 50 years at isotope separator on line facilities. The development of several projects of second generation facilities aiming at intensities two or three orders of magnitude higher than today puts an emphasis on the properties of the uranium fission targets. A study, driven by Institut de Physique Nucléaire d'Orsay (IPNO), has been started within the SPIRAL2 project to try and fully understand the behavior of these targets. In this paper, we have focused on five uranium carbide based targets. We present an off-line method to characterize their fission product release and the results are examined in conjunction with physical characteristics of each material such as the microstructure, the porosity and the chemical composition.

In situ Proteomic Profiling of Curcumin Targets in HCT116 Colon Cancer Cell Line.

PubMed

Wang, Jigang; Zhang, Jianbin; Zhang, Chong-Jing; Wong, Yin Kwan; Lim, Teck Kwang; Hua, Zi-Chun; Liu, Bin; Tannenbaum, Steven R; Shen, Han-Ming; Lin, Qingsong

2016-02-26

To date, the exact targets and mechanism of action of curcumin, a natural product with anti-inflammatory and anti-cancer properties, remain elusive. Here we synthesized a cell permeable curcumin probe (Cur-P) with an alkyne moiety, which can be tagged with biotin for affinity enrichment, or with a fluorescent dye for visualization of the direct-binding protein targets of curcumin in situ. iTRAQ(TM) quantitative proteomics approach was applied to distinguish the specific binding targets from the non-specific ones. In total, 197 proteins were confidently identified as curcumin binding targets from HCT116 colon cancer cell line. Gene Ontology analysis showed that the targets are broadly distributed and enriched in the nucleus, mitochondria and plasma membrane, and they are involved in various biological functions including metabolic process, regulation, response to stimulus and cellular process. Ingenuity Pathway Analysis(TM) (IPA) suggested that curcumin may exert its anticancer effects over multiple critical biological pathways including the EIF2, eIF4/p70S6K, mTOR signaling and mitochondrial dysfunction pathways. Functional validations confirmed that curcumin downregulates cellular protein synthesis, and induces autophagy, lysosomal activation and increased ROS production, thus leading to cell death.

In situ Proteomic Profiling of Curcumin Targets in HCT116 Colon Cancer Cell Line

PubMed Central

Wang, Jigang; Zhang, Jianbin; Zhang, Chong-Jing; Wong, Yin Kwan; Lim, Teck Kwang; Hua, Zi-Chun; Liu, Bin; Tannenbaum, Steven R.; Shen, Han-Ming; Lin, Qingsong

2016-01-01

To date, the exact targets and mechanism of action of curcumin, a natural product with anti-inflammatory and anti-cancer properties, remain elusive. Here we synthesized a cell permeable curcumin probe (Cur-P) with an alkyne moiety, which can be tagged with biotin for affinity enrichment, or with a fluorescent dye for visualization of the direct-binding protein targets of curcumin in situ. iTRAQTM quantitative proteomics approach was applied to distinguish the specific binding targets from the non-specific ones. In total, 197 proteins were confidently identified as curcumin binding targets from HCT116 colon cancer cell line. Gene Ontology analysis showed that the targets are broadly distributed and enriched in the nucleus, mitochondria and plasma membrane, and they are involved in various biological functions including metabolic process, regulation, response to stimulus and cellular process. Ingenuity Pathway AnalysisTM (IPA) suggested that curcumin may exert its anticancer effects over multiple critical biological pathways including the EIF2, eIF4/p70S6K, mTOR signaling and mitochondrial dysfunction pathways. Functional validations confirmed that curcumin downregulates cellular protein synthesis, and induces autophagy, lysosomal activation and increased ROS production, thus leading to cell death. PMID:26915414

Third-line Targeted Therapy in Metastatic Renal Cell Carcinoma: Results from the International Metastatic Renal Cell Carcinoma Database Consortium.

PubMed

Wells, J Connor; Stukalin, Igor; Norton, Craig; Srinivas, Sandy; Lee, Jae Lyun; Donskov, Frede; Bjarnason, Georg A; Yamamoto, Haru; Beuselinck, Benoit; Rini, Brian I; Knox, Jennifer J; Agarwal, Neeraj; Ernst, D Scott; Pal, Sumanta K; Wood, Lori A; Bamias, Aristotelis; Alva, Ajjai S; Kanesvaran, Ravindran; Choueiri, Toni K; Heng, Daniel Y C

2017-02-01

The use of third-line targeted therapy (TTT) in metastatic renal cell carcinoma (mRCC) is not well characterized and varies due to the lack of robust data to guide treatment decisions. This study examined the use of third-line therapy in a large international population. To evaluate the use and efficacy of targeted therapy in a third-line setting. Twenty-five international cancer centers provided consecutive data on 4824 mRCC patients who were treated with an approved targeted therapy. One thousand and twelve patients (21%) received TTT and were included in the analysis. Patients were analyzed for overall survival (OS) and progression-free survival using Kaplan-Meier curves, and were evaluated for overall response. Cox regression analyses were used to determine the statistical association between OS and the six factors included in the International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) prognostic model. Subgroup analysis was performed on patients stratified by their IMDC prognostic risk status. Everolimus was the most prevalent third-line therapy (27.5%), but sunitinib, sorafenib, pazopanib, temsirolimus, and axitinib were all utilized in over ≥9% of patients. Patients receiving any TTT had an OS of 12.4 mo, a progression-free survival of 3.9 mo, and 61.1% of patients experienced an overall response of stable disease or better. Patients not receiving TTT had an OS of 2.1 mo. Patients with favorable- (7.2%) or intermediate-risk (65.3%) disease had the highest OS with TTT, 29.9 mo and 15.5 mo, respectively, while poor-risk (27.5%) patients survived 5.5 mo. Results are limited by the retrospective nature of the study. TTT remains highly heterogeneous. The IMDC prognostic criteria can be used to stratify third-line patients. TTT use in favorable- and intermediate-risk patients was associated with the greatest OS. Patients with favorable- and intermediate-prognostic criteria disease treated with third-line targeted therapy have an associated

A system for the measurement of gene targeting efficiency in human cell lines using an antibiotic resistance-GFP fusion gene.

PubMed

Konishi, Yuko; Karnan, Sivasundaram; Takahashi, Miyuki; Ota, Akinobu; Damdindorj, Lkhagvasuren; Hosokawa, Yoshitaka; Konishi, Hiroyuki

2012-09-01

Gene targeting in a broad range of human somatic cell lines has been hampered by inefficient homologous recombination. To improve this technology and facilitate its widespread application, it is critical to first have a robust and efficient research system for measuring gene targeting efficiency. Here, using a fusion gene consisting of hygromycin B phosphotransferase and 3'-truncated enhanced GFP (HygR-5' EGFP) as a reporter gene, we created a molecular system monitoring the ratio of homologous to random integration (H/R ratio) of targeting vectors into the genome. Cell clones transduced with a reporter vector containing HygR-5' EGFP were efficiently established from two human somatic cell lines. Established HygR-5' EGFP reporter clones retained their capacity to monitor gene targeting efficiency for a longer duration than a conventional reporter system using an unfused 5' EGFP gene. With the HygR-5' EGFP reporter system, we reproduced previous findings of gene targeting frequency being up-regulated by the use of an adeno-associated viral (AAV) backbone, a promoter-trap system, or a longer homology arm in a targeting vector, suggesting that this system accurately monitors H/R ratio. Thus, our HygR-5' EGFP reporter system will assist in the development of an efficient AAV-based gene targeting technology.

Target-based drug discovery for [Formula: see text]-globin disorders: drug target prediction using quantitative modeling with hybrid functional Petri nets.

PubMed

Mehraei, Mani; Bashirov, Rza; Tüzmen, Şükrü

2016-10-01

Recent molecular studies provide important clues into treatment of [Formula: see text]-thalassemia, sickle-cell anaemia and other [Formula: see text]-globin disorders revealing that increased production of fetal hemoglobin, that is normally suppressed in adulthood, can ameliorate the severity of these diseases. In this paper, we present a novel approach for drug prediction for [Formula: see text]-globin disorders. Our approach is centered upon quantitative modeling of interactions in human fetal-to-adult hemoglobin switch network using hybrid functional Petri nets. In accordance with the reverse pharmacology approach, we pose a hypothesis regarding modulation of specific protein targets that induce [Formula: see text]-globin and consequently fetal hemoglobin. Comparison of simulation results for the proposed strategy with the ones obtained for already existing drugs shows that our strategy is the optimal as it leads to highest level of [Formula: see text]-globin induction and thereby has potential beneficial therapeutic effects on [Formula: see text]-globin disorders. Simulation results enable verification of model coherence demonstrating that it is consistent with qPCR data available for known strategies and/or drugs.

Beam Transport of 4 GeV Protons from AGS to the Proton Interrogation Target of the Neutrino Line (Z_line) and Effect of the Air on the Transported Beam

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

Tsoupas,N.; Ahrens, L.; Pile, P.

2008-10-01

As part of the preparation for the Proton Interrogation Experiment, we have calculated the beam optics for the transport of 4 GeV protons, from the AGS extraction point, to the 'Cross-Section Target Wheel 1' and to the 'Proton Interrogation Target'. In this technical note we present three possible beam-transports each corresponding to a particular Fast Extracted Beam W B setup of the AGS. In addition we present results on the effect of the atmospheric air, (which fills the drift space of the last 100 [m] of the transport line), on the size of the beam, at two locations along themore » drift space, one location at the middle of the drift space and the other at the end where the 'Proton Interrogation Target' is placed. All the beam transports mentioned above require the removal of the WD1 dipole magnet, which is the first magnet of the W-line, because it acts as a limiting beam aperture, and the magnet is not used in the beam transport. An alternative solution of a beam transport, which does not require the removal of the WD1 magnet, is also presented. In this solution, which models the transport line using the TURTLE computer code[7], the vertical beam sizes at the location of the WD1 magnet is minimized to allow 'lossless' beam transport at the location of the WD1 magnet. A similar solution, but using a MAD model of the line, is also presented.« less

The IATH ELAN Text-Sync Tool: A Simple System for Mobilizing ELAN Transcripts On- or Off-Line

ERIC Educational Resources Information Center

Dobrin, Lise M.; Ross, Douglas

2017-01-01

In this article we present the IATH ELAN Text-Sync Tool (ETST; see http://community.village.virginia.edu/etst), a series of scripts and workflow for playing ELAN files and associated audiovisual media in a web browser either on- or off-line. ELAN has become an indispensable part of documentary linguists' toolkit, but it is less than ideal for…

Plasma Membrane Proteomics of Human Breast Cancer Cell Lines Identifies Potential Targets for Breast Cancer Diagnosis and Treatment

PubMed Central

Ziegler, Yvonne S.; Moresco, James J.; Tu, Patricia G.; Yates, John R.; Nardulli, Ann M.

2014-01-01

The use of broad spectrum chemotherapeutic agents to treat breast cancer results in substantial and debilitating side effects, necessitating the development of targeted therapies to limit tumor proliferation and prevent metastasis. In recent years, the list of approved targeted therapies has expanded, and it includes both monoclonal antibodies and small molecule inhibitors that interfere with key proteins involved in the uncontrolled growth and migration of cancer cells. The targeting of plasma membrane proteins has been most successful to date, and this is reflected in the large representation of these proteins as targets of newer therapies. In view of these facts, experiments were designed to investigate the plasma membrane proteome of a variety of human breast cancer cell lines representing hormone-responsive, ErbB2 over-expressing and triple negative cell types, as well as a benign control. Plasma membranes were isolated by using an aqueous two-phase system, and the resulting proteins were subjected to mass spectrometry analysis. Overall, each of the cell lines expressed some unique proteins, and a number of proteins were expressed in multiple cell lines, but in patterns that did not always follow traditional clinical definitions of breast cancer type. From our data, it can be deduced that most cancer cells possess multiple strategies to promote uncontrolled growth, reflected in aberrant expression of tyrosine kinases, cellular adhesion molecules, and structural proteins. Our data set provides a very rich and complex picture of plasma membrane proteins present on breast cancer cells, and the sorting and categorizing of this data provides interesting insights into the biology, classification, and potential treatment of this prevalent and debilitating disease. PMID:25029196

SAFARI, an On-Line Text-Processing System User's Manual.

ERIC Educational Resources Information Center

Chapin, P.G.; And Others.

This report describes for the potential user a set of procedures for processing textual materials on-line. In this preliminary model an information analyst can scan through messages, reports, and other documents on a display scope and select relevant facts, which are processed linguistically and then stored in the computer in the form of logical…

BEAM TRANSPORT LINES FOR THE BSNS.

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

WEI, J.

2006-06-26

This paper presents the design of two beam transport lines at the BSNS: one is the injection line from the Linac to the RCS and the other is the target line from the RCS to the target station. In the injection beam line, space charge effects, transverse halo collimation, momentum tail collimation and debunching are the main concerned topics. A new method of using triplet cells and stripping foils is used to collimate transverse halo. A long straight section is reserved for the future upgrading linac and debuncher. In the target beam line, large halo emittance, beam stability at themore » target due to kicker failures and beam jitters, shielding of back-scattering neutrons from the target are main concerned topics. Special bi-gap magnets will be used to reduce beam losses in the collimators in front of the target.« less

Potential role for mammalian target of rapamycin inhibitors as first-line therapy in hormone receptor–positive advanced breast cancer

PubMed Central

Beck, J Thaddeus

2015-01-01

Despite advances in cytotoxic chemotherapy and targeted therapies, 5-year survival rates remain low for patients with advanced breast cancer at diagnosis. This highlights the limited effectiveness of current treatment options. An improved understanding of cellular functions associated with the development and progression of breast cancer has resulted in the creation of a number of novel targeted molecular therapies. However, more work is needed to improve outcomes, particularly in the first-line recurrent or metastatic hormone receptor–positive breast cancer setting. The phosphatidylinositol 3-kinase/protein kinase B/mammalian target of rapamycin (mTOR) pathway is a major intracellular signaling pathway that is often upregulated in breast cancer, and overactivation of this pathway has been associated with primary or developed resistance to endocrine treatment. Clinical data from the Phase III Breast Cancer Trials of Oral Everolimus-2 (BOLERO-2) study of the mTOR inhibitor everolimus combined with exemestane in hormone receptor–positive advanced breast cancer were very promising, highlighting the potential role of mTOR inhibitors in combination with endocrine therapies as a first-line treatment option for these patients. It is hoped that the use of mTOR inhibitors combined with current standard-of-care endocrine therapies, such as aromatase inhibitors, in the first-line advanced breast cancer setting may result in greater antitumor effects and also delay or reverse treatment resistance. PMID:26675495

High-fidelity Glucagon-CreER mouse line generated by CRISPR-Cas9 assisted gene targeting.

PubMed

Ackermann, Amanda M; Zhang, Jia; Heller, Aryel; Briker, Anna; Kaestner, Klaus H

2017-03-01

α-cells are the second most prominent cell type in pancreatic islets and are responsible for producing glucagon to increase plasma glucose levels in times of fasting. α-cell dysfunction and inappropriate glucagon secretion occur in both type 1 and type 2 diabetes. Thus, there is growing interest in studying both normal function and pathophysiology of α-cells. However, tools to target gene ablation or activation specifically of α-cells have been limited, compared to those available for β-cells. Previous Glucagon-Cre and Glucagon-CreER transgenic mouse lines have suffered from transgene silencing, and the only available Glucagon-CreER "knock-in" mouse line results in glucagon haploinsufficiency, which can confound the interpretation of gene deletion analyses. Therefore, we sought to develop a Glucagon-CreER T2 mouse line that would maintain normal glucagon expression and would be less susceptible to transgene silencing. We utilized CRISPR-Cas9 technology to insert an IRES-CreER T2 sequence into the 3' UTR of the Glucagon ( Gcg ) locus in mouse embryonic stem cells (ESCs). Targeted ESC clones were then injected into mouse blastocysts to obtain Gcg-CreER T2 mice. Recombination efficiency in GCG + pancreatic α-cells and glucagon-like peptide 1 positive (GLP1 + ) enteroendocrine L-cells was measured in Gcg-CreER T2 ; Rosa26-LSL-YFP mice injected with tamoxifen during fetal development and adulthood. Tamoxifen injection of Gcg-CreER T2 ; Rosa26-LSL-YFP mice induced high recombination efficiency of the Rosa26-LSL-YFP locus in perinatal and adult α-cells (88% and 95%, respectively), as well as in first-wave fetal α-cells (36%) and adult enteroendocrine L-cells (33%). Mice homozygous for the Gcg-CreER T2 allele were phenotypically normal. We successfully derived a Gcg-CreER T2 mouse line that expresses CreER T2 in pancreatic α-cells and enteroendocrine L-cells without disrupting preproglucagon gene expression. These mice will be a useful tool for performing

When a text is translated does the complexity of its vocabulary change? Translations and target readerships.

PubMed

Rêgo, Hênio Henrique Aragão; Braunstein, Lidia A; D'Agostino, Gregorio; Stanley, H Eugene; Miyazima, Sasuke

2014-01-01

In linguistic studies, the academic level of the vocabulary in a text can be described in terms of statistical physics by using a "temperature" concept related to the text's word-frequency distribution. We propose a "comparative thermo-linguistic" technique to analyze the vocabulary of a text to determine its academic level and its target readership in any given language. We apply this technique to a large number of books by several authors and examine how the vocabulary of a text changes when it is translated from one language to another. Unlike the uniform results produced using the Zipf law, using our "word energy" distribution technique we find variations in the power-law behavior. We also examine some common features that span across languages and identify some intriguing questions concerning how to determine when a text is suitable for its intended readership.

MicroRNA-218 inhibits the proliferation of human choriocarcinoma JEG-3 cell line by targeting Fbxw8

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

Shi, Dazun; Tan, Zhihui; Lu, Rong

2014-08-08

Highlights: • The miR-218 expression was decreased in choriocarcinoma cell lines. • The Fbxw8 protein expression was increased in choriocarcinoma cell lines. • We show that Fbxw8 is bona-fide target of miR-218 in JEG-3. • Ectopic miR-218 expression inhibits the proliferation of JEG-3 via Fbxw8. • Overexpression of miR-218 affected cyclin A and p27 expression via Fbxw8. - Abstract: MicroRNAs (miRNAs) are endogenous 19–25 nucleotide noncoding single-stranded RNAs that regulate gene expression by blocking the translation or decreasing the stability of mRNAs. In this study, we showed that miR-218 expression levels were decreased while Fbxw8 expression levels were increased inmore » human choriocarcinoma cell lines, and identified Fbxw8 as a novel direct target of miR-218. Overexpression of miR-218 inhibited cell growth arrest at G2/M phase, suppressed the protein levels of cyclin A and up-regulated the expression levels of p27 through decreasing the levels of Fbxw8. On the other hand, forced expression of Fbxw8 partly rescued the effect of miR-218 in the cells, attenuated cell proliferation decrease the percentage of cells at G2/M phase, induced cyclin A protein expression and suppressed the protein level of p27 through up-regulating the levels of Fbxw8. Taken together, these findings will shed light the role to mechanism of miR-218 in regulating JEG-3 cells proliferation via miR-218/Fbxw8 axis, and miR-218 may serve as a novel potential therapeutic target in human choriocarcinoma in the future.« less

When a Text Is Translated Does the Complexity of Its Vocabulary Change? Translations and Target Readerships

PubMed Central

Rêgo, Hênio Henrique Aragão; Braunstein, Lidia A.; D′Agostino, Gregorio; Stanley, H. Eugene; Miyazima, Sasuke

2014-01-01

In linguistic studies, the academic level of the vocabulary in a text can be described in terms of statistical physics by using a “temperature” concept related to the text's word-frequency distribution. We propose a “comparative thermo-linguistic” technique to analyze the vocabulary of a text to determine its academic level and its target readership in any given language. We apply this technique to a large number of books by several authors and examine how the vocabulary of a text changes when it is translated from one language to another. Unlike the uniform results produced using the Zipf law, using our “word energy” distribution technique we find variations in the power-law behavior. We also examine some common features that span across languages and identify some intriguing questions concerning how to determine when a text is suitable for its intended readership. PMID:25353343

Is health literacy related to health behaviors and cell phone usage patterns among the text4baby target population?

PubMed

Poorman, Elisabeth; Gazmararian, Julie; Elon, Lisa; Parker, Ruth

2014-01-01

Text4baby provides educational text messages to pregnant and postpartum women and targets underserved women. The primary purpose of this study is to examine the health behaviors and cell phone usage patterns of a text4baby target population and the associations with health literacy. Pregnant and postpartum women were recruited from two Women, Infant and Children clinics in Atlanta. Women were asked about their demographics, selected pregnancy or postpartum health behaviors, and cell phone usage patterns. Health literacy skills were measured with the English version of the Newest Vital Sign. Multivariable logistic regression was used to examine health behaviors and cell usage patterns by health literacy classification, controlling for commonly accepted confounders. Four hundred sixty-eight women were recruited, and 445 completed the Newest Vital Sign. Of these, 22% had inadequate health literacy, 50% had intermediate health literacy, and 28% had adequate health literacy skills. Compared to adequate health literacy, limited literacy was independently associated with not taking a daily vitamin during pregnancy (OR 3.6, 95% CI: 1.6, 8.5) and never breastfeeding their infant (OR 1.4, 95% CI: 1.1, 1.8). The majority (69.4%) of respondents received nine or more text messages a day prior to enrollment, one in four participants (24.6%) had changed their number within the last six months, and 7.0% of study participants shared a cell phone. Controlling for potentially confounding factors, those with limited health literacy were more likely to share a cell phone than those with adequate health literacy (OR 2.57, 95% CI: 1.79, 3.69). Text4baby messages should be appropriate for low health literacy levels, especially as this population may have higher prevalence of targeted unhealthy behaviors. Text4baby and other mhealth programs targetting low health literacy populations should also be aware of the different ways that these populations use their cell phones, including: sharing

Address substrates as promising targets for laser histochemical surgery as a nontraditional line in medicine

NASA Astrophysics Data System (ADS)

Piruzyan, L. A.; Mikhailovskiy, Ye. M.; Piruzyan, A. L.

1999-12-01

The priority concept of the laser histochemical surgery as a potentially novel line in medicine is presented. The histochemical stains, selectively coloring some targets (address substrates), that are cells or their biochemical ingredients, sensitize them to the laser irradiation. Such sensitization to laser irradiation by staining turns the colored targets into targets for the laser beam. The action of the irradiation onto its specific targets beats out of the cell its ingredients which participate in a pathology process. In particular, the beating of a stained ferment out of the general stage of biochemical processes characteristic for the pathology interrupts their currence. The laser beam, when beating out its stained targets without any damage of the unstained tissues, acts like a scalpel that cuts off affected tissues not brushing healthy ones. A scheme for testing stains as sensitizers of the `address substrates' to the laser irradiation is presented. As the criterion of the stain sensitization the fact was chosen of absence or weakness of pathomorphologic and biochemical signs of the disease in an experimental model of the pathology irradiated with laser after a stain use, while the pathology signs are present in a control sample. The basis is done for study of the histochemical stains as potential means for the laser histochemical surgery of disseminated sclerosis, mucopolysaccharidosis, hypercholesterolemia, myocardial infarction, cardiosclerosis, caries and parodontosis.

Vesicle-associated membrane protein 7 (VAMP-7) is essential for target cell killing in a natural killer cell line

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

Marcet-Palacios, Marcelo; Odemuyiwa, Solomon O.; Coughlin, Jason J.

2008-02-15

Natural killer cells recognize and induce apoptosis in foreign, transformed or virus-infected cells through the release of perforin and granzymes from secretory lysosomes. Clinically, NK-cell mediated killing is a major limitation to successful allo- and xenotransplantation. The molecular mechanisms that regulate the fusion of granzyme B-containing secretory lysosomes to the plasma membrane in activated NK cells, prior to target cell killing, are not fully understood. Using the NK cell line YT-Indy as a model, we have investigated the expression of SNAP REceptors (SNAREs), both target (t-) and vesicular (v-) SNAREs, and their function in granzyme B-mediated target cell killing. Ourmore » data showed that YT-Indy cells express VAMP-7 and SNAP-23, but not VAMP-2. VAMP-7 was associated with granzyme B-containing lysosomal granules. Using VAMP-7 small interfering RNA (siRNA), we successfully knocked down the expression of VAMP-7 protein in YT-Indy to less than 10% of untreated cells in 24 h. VAMP7-deficient YT-Indy cells activated via co-culture with Jurkat cells released <1 ng/mL of granzyme B, compared to 1.5-2.5 {mu}g/mL from controls. Using Jurkat cells as targets, we showed a 7-fold reduction in NK cell-mediated killing by VAMP-7 deficient YT-Indy cells. Our results show that VAMP-7 is a crucial component of granzyme B release and target cell killing in the NK cell line YT-Indy. Thus, targeting VAMP-7 expression specifically with siRNA, following transplantation, may be a viable strategy for preventing NK cell-mediated transplant rejection, in vivo.« less

Surrogate Endpoints in Second-Line Trials of Targeted Agents in Metastatic Colorectal Cancer: A Literature-Based Systematic Review and Meta-Analysis.

PubMed

Cremolini, Chiara; Antoniotti, Carlotta; Pietrantonio, Filippo; Berenato, Rosa; Tampellini, Marco; Baratelli, Chiara; Salvatore, Lisa; Marmorino, Federica; Borelli, Beatrice; Nichetti, Federico; Bironzo, Paolo; Sonetto, Cristina; Bartolomeo, Maria Di; Braud, Filippo de; Loupakis, Fotios; Falcone, Alfredo; Di Maio, M

2017-07-01

The purpose of this study was to evaluate progression-free survival (PFS) and objective response rate (ORR) as surrogate endpoints of overall survival (OS) in modern clinical trials investigating the efficacy of targeted agents in the second-line treatment of metastatic colorectal cancer (mCRC). A systematic search of literature pertaining to randomized phase II and III trials evaluating targeted agents as second-line treatments for mCRC was performed. The strength of the correlation between both PFS and ORR and OS was assessed based on the Pearson's correlation coefficient (R) and the coefficient of determination (R 2 ). Twenty trials, including a total of 7,571 patients, met the search criteria. The median duration of post-progression survival (PPS) was 7.6 months. The median differences between experimental and control arms were 0.65 months (range, -2.4 to 3.4) for the median PFS and 0.7 months (range, -5.8 to 3.9) for the median OS. PFS and ORR showed moderate (R=0.734, R 2 =0.539, p < 0.001) and poor correlation (R=0.169, R 2 =0.029, p=0.476) with OS, respectively. No differences between anti-angiogenic agents and other drugs were evident. Targeted agents investigated in the second-line treatment of mCRC provided minimal PFS gains translating into modest OS improvements. Considering both the moderate correlation between PFS and OS and the short duration of PPS, the OS should remain the preferred primary endpoint for randomized clinical trials in the second-line treatment of mCRC.

Targeted erlotinib for first-line treatment of advanced non-small cell lung cancer: a budget impact analysis.

PubMed

Bajaj, Preeti S; Veenstra, David L; Goertz, Hans-Peter; Carlson, Josh J

2014-08-01

A recent phase III trial showed that patients with advanced non-small cell lung cancer (NSCLC) whose tumors harbor specific EGFR mutations significantly benefit from first-line treatment with erlotinib compared to chemotherapy. This study sought to estimate the budget impact if coverage for EGFR testing and erlotinib as first-line therapy were provided in a hypothetical 500,000-member managed care plan. The budget impact model was developed from a US health plan perspective to evaluate administration of the EGFR test and treatment with erlotinib for EGFR-positive patients, compared to non-targeted treatment with chemotherapy. The eligible patient population was estimated from age-stratified SEER incidence data. Clinical data were derived from key randomized controlled trials. Costs related to drug, administration, and adverse events were included. Sensitivity analyses were conducted to assess uncertainty. In a plan of 500,000 members, it was estimated there would be 91 newly diagnosed advanced NSCLC patients annually; 11 are expected to be EGFR-positive. Based on the testing and treatment assumptions, it was estimated that 3 patients in Scenario 1 and 6 patients in Scenario 2 receive erlotinib. Overall health plan expenditures would increase by $0.013 per member per month (PMPM). This increase is largely attributable to erlotinib drug costs, in part due to lengthened progression-free survival and treatment periods experienced in erlotinib-treated patients. EGFR testing contributes slightly, whereas adverse event costs mitigate the budget impact. The budget impact did not exceed $0.019 PMPM in sensitivity analyses. Coverage for targeted first-line erlotinib therapy in NSCLC likely results in a small budget impact for US health plans. The estimated impact may vary by plan, or if second-line or maintenance therapy, dose changes/interruptions, or impact on patients' quality-of-life were included.

[On-line processing mechanisms in text comprehension: a theoretical review on constructing situation models].

PubMed

Iseki, Ryuta

2004-12-01

This article reviewed research on construction of situation models during reading. To position variety of research in overall process appropriately, an unitary framework was devised in terms of three theories for on-line processing: resonance process, event-indexing model, and constructionist theory. Resonance process was treated as a basic activation mechanism in the framework. Event-indexing model was regarded as a screening system which selected and encoded activated information in situation models along with situational dimensions. Constructionist theory was considered to have a supervisory role based on coherence and explanation. From a view of the unitary framework, some problems concerning each theory were examined and possible interpretations were given. Finally, it was pointed out that there were little theoretical arguments on associative processing at global level and encoding text- and inference-information into long-term memory.

Text-image alignment for historical handwritten documents

NASA Astrophysics Data System (ADS)

Zinger, S.; Nerbonne, J.; Schomaker, L.

2009-01-01

We describe our work on text-image alignment in context of building a historical document retrieval system. We aim at aligning images of words in handwritten lines with their text transcriptions. The images of handwritten lines are automatically segmented from the scanned pages of historical documents and then manually transcribed. To train automatic routines to detect words in an image of handwritten text, we need a training set - images of words with their transcriptions. We present our results on aligning words from the images of handwritten lines and their corresponding text transcriptions. Alignment based on the longest spaces between portions of handwriting is a baseline. We then show that relative lengths, i.e. proportions of words in their lines, can be used to improve the alignment results considerably. To take into account the relative word length, we define the expressions for the cost function that has to be minimized for aligning text words with their images. We apply right to left alignment as well as alignment based on exhaustive search. The quality assessment of these alignments shows correct results for 69% of words from 100 lines, or 90% of partially correct and correct alignments combined.

Orion Exploration Mission Entry Interface Target Line

NASA Technical Reports Server (NTRS)

Rea, Jeremy R.

2016-01-01

The Orion Multi-Purpose Crew Vehicle is required to return to the continental United States at any time during the month. In addition, it is required to provide a survivable entry from a wide range of trans-lunar abort trajectories. The Entry Interface (EI) state must be targeted to ensure that all requirements are met for all possible return scenarios, even in the event of no communication with the Mission Control Center to provide an updated EI target. The challenge then is to functionalize an EI state constraint manifold that can be used in the on-board targeting algorithm, as well as the ground-based trajectory optimization programs. This paper presents the techniques used to define the EI constraint manifold and to functionalize it as a set of polynomials in several dimensions.

A novel, volumizing cosmetic formulation significantly improves the appearance of target Glabellar lines, nasolabial folds, and crow's feet in a double-blind, vehicle-controlled clinical trial.

PubMed

Farris, Patricia K; Edison, Brenda L; Weinkauf, Ronni L; Green, Barbara A

2014-01-01

Facial lines and wrinkles are caused by many factors including constant exposure to external elements, such as UV rays, as well as the dynamic nature of facial expression. Many cosmetic products and procedures provide global improvement to aging skin, whereas injectable therapies are frequently utilized to diminish specific, target wrinkles. Despite their broad availability, some patients are unwilling to undergo injectables and would benefit from an effective topical option. A noninvasive option to volumize target wrinkle areas could also extend benefits of commonly used cosmetic anti-aging products. To this end, a two-step formulation containing the novel, cosmetic anti-aging ingredient, N-acetyl tyrosinamide, was developed for use on targeted wrinkle areas. The tolerability and efficacy of the serum plus cream were tested for 16 weeks in women with moderate facial photodamage on predetermined wrinkle areas (glabellar lines, nasolabial folds, under eye lines, and lateral canthal (crow's feet) wrinkles) in a single-center, randomized, double-blind, vehicle-controlled, clinical trial. Seventy women (47 Active group, 23 Vehicle group) completed the study. Digital photography, clinical grading, ultrasound and self-assessment scores confirmed improvement to wrinkle areas. The topical cosmetic formulation was statistically superior (P<0.05) to its vehicle in visually improving nasolabial folds, glabellar lines, crow's feet, and under eye wrinkles and in reducing pinch recoil time. Both the test formulation and its vehicle were tolerated well. The novel, two-step cosmetic formulation reduced the appearance of wrinkles and increased skin elasticity thus providing an effective anti-aging option for target wrinkle areas. This study suggests that in addition to its use as monotherapy for reducing targeted lines and wrinkles this cosmetic formulation may be also serve as an adjuvant to injectable therapies.

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

PubMed

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

2016-08-12

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

SU-E-T-486: Effect of the Normalized Prescription Isodose Line On Target Dose Deficiency in Lung SBRT Based On Monte Carlo Calculation

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

Zheng, D; Zhang, Q; Zhou, S

Purpose: To investigate the impact of normalized prescription isodose line on target dose deficiency calculated with Monte Carlo (MC) vs. pencil Beam (PB) in lung SBRT. RTOG guidelines recommend prescription lines between 60% and 90% for lung SBRT. How this affects the magnitude of MC-calculated target dose deficiency has never been studied. Methods: Under an IRB-approved protocol, four lung SBRT patients were replanned following RTOG0813 by a single physicist. For each patient, four alternative plans were generated based on PB calculation prescribing to 60–90% isodose lines, respectively. Each plan consisted of 360o coplanar dynamic conformal arcs with beam apertures manuallymore » optimized to achieve similar dose coverage and conformity for all plans of the same patient. Dose distribution was calculated with MC and compared to that with PB. PTV dose-volume endpoints were compared, including Dmin, D5, Dmean, D95, and Dmax. PTV V100 coverage, conformity index (CI), and heterogeneity index (HI) were also evaluated. Results: For all 16 plans, median (range) PTV V100 and CI were 99.7% (97.5–100%) and 1.27 (1.20–1.41), respectively. As expected, lower prescription line resulted in higher target dose heterogeneity, yielding median (range) HI of 1.26 (1.05–1.51) for all plans. Comparing MC to PB, median (range) D95, Dmean, D5 PTV dose deficiency were 18.9% (11.2–23.2%), 15.6% (10.0–22.7%), and 9.4%(5.5–13.6%) of the prescription dose, respectively. The Dmean, D5, and Dmax deficiency was found to monotonically increase with decreasing prescription line from 90% to 60%, while the Dmin deficiency monotonically decreased. D95 deficiency exhibited more complex trend, reaching the largest deficiency at 80% for all patients. Conclusion: Dependence on prescription isodose line was found for MC-calculated PTV dose deficiency of lung SBRT. When comparing reported MC dose deficiency values from different institutions, their individual selections of prescription

The Effects of Color Cues on Typically Developing Preschoolers' Speed of Locating a Target Line Drawing: Implications for Augmentative and Alternative Communication Display Design

ERIC Educational Resources Information Center

Thistle, Jennifer J.; Wilkinson, Krista

2009-01-01

Purpose: This research examined how the presence of color in relation to a target within an augmentative and alternative communication array influenced the speed with which typically developing preschoolers located a target line drawing. Method: Fifteen children over the age of 4 years (from 4;2 [years;months] to 5;4) and 15 children under the age…

MiR-21 is enriched in the RNA-induced silencing complex and targets COL4A1 in human granulosa cell lines.

PubMed

Mase, Yuri; Ishibashi, Osamu; Ishikawa, Tomoko; Takizawa, Takami; Kiguchi, Kazushige; Ohba, Takashi; Katabuchi, Hidetaka; Takeshita, Toshiyuki; Takizawa, Toshihiro

2012-10-01

MicroRNAs (miRNAs) are noncoding small RNAs that play important roles in a variety of physiological and pathological events. In this study, we performed large-scale profiling of EIF2C2-bound miRNAs in 3 human granulosa-derived cell lines (ie, KGN, HSOGT, and GC1a) by high-throughput sequencing and found that miR-21 accounted for more than 80% of EIF2C2-bound miRNAs, suggesting that it was enriched in the RNA-induced silencing complex (RISC) and played a functional role in human granulosa cell (GC) lines. We also found high expression levels of miR-21 in primary human GCs. Assuming that miR-21 target mRNAs are enriched in RISC, we performed cDNA cloning of EIF2C2-bound mRNAs in KGN cells. We identified COL4A1 mRNA as a miR-21 target in the GC lines. These data suggest that miR-21 is involved in the regulation of the synthesis of COL4A1, a component of the basement membrane surrounding the GC layer and granulosa-embedded extracellular structure.

Multiple-hypothesis multiple-model line tracking

NASA Astrophysics Data System (ADS)

Pace, Donald W.; Owen, Mark W.; Cox, Henry

2000-07-01

Passive sonar signal processing generally includes tracking of narrowband and/or broadband signature components observed on a Lofargram or on a Bearing-Time-Record (BTR) display. Fielded line tracking approaches to date have been recursive and single-hypthesis-oriented Kalman- or alpha-beta filters, with no mechanism for considering tracking alternatives beyond the most recent scan of measurements. While adaptivity is often built into the filter to handle changing track dynamics, these approaches are still extensions of single target tracking solutions to multiple target tracking environment. This paper describes an application of multiple-hypothesis, multiple target tracking technology to the sonar line tracking problem. A Multiple Hypothesis Line Tracker (MHLT) is developed which retains the recursive minimum-mean-square-error tracking behavior of a Kalman Filter in a maximum-a-posteriori delayed-decision multiple hypothesis context. Multiple line track filter states are developed and maintained using the interacting multiple model (IMM) state representation. Further, the data association and assignment problem is enhanced by considering line attribute information (line bandwidth and SNR) in addition to beam/bearing and frequency fit. MHLT results on real sonar data are presented to demonstrate the benefits of the multiple hypothesis approach. The utility of the system in cluttered environments and particularly in crossing line situations is shown.

Differential plasma membrane targeting of voltage-dependent calcium channel subunits expressed in a polarized epithelial cell line

PubMed Central

Brice, Nicola L; Dolphin, Annette C

1999-01-01

Voltage-dependent calcium channels (VDCCs) show a highly non-uniform distribution in many cell types, including neurons and other polarized secretory cells. We have examined whether this can be mimicked in a polarized epithelial cell line (Madin-Darby canine kidney), which has been used extensively to study the targeting of proteins. We expressed the VDCC α1A, α1B or α1C subunits either alone or in combination with accessory subunits α2-δ and the different β subunits, and examined their localization immunocytochemically. An α1 subunit was only targeted to the plasma membrane if co-expressed with the accessory subunits. The combination α1C/α2-δ and all β subunits was always localized predominantly to the basolateral membrane. It has been suggested that this is equivalent to somatodendritic targeting in neurons. In contrast, the α1B subunit was expressed at the apical membrane with all the accessory subunit combinations, by 24 h after microinjection. This membrane destination shows some parallels with axonal targeting in neurons. The α1A subunit was consistently observed at the apical membrane in the combinations α1A/α2-δ/β1b or β4. In contrast, when co-expressed with α2-δ/β2a, α1A was clearly targeted to the basolateral membrane. In conclusion, the VDCC α1 subunit appears to be the primary determinant for targeting the VDCC complex, but the β subunit can modify this destination, particularly for α1A. PMID:10066897

Application of a haematopoetic progenitor cell-targeted adeno-associated viral (AAV) vector established by selection of an AAV random peptide library on a leukaemia cell line

PubMed Central

Stiefelhagen, Marius; Sellner, Leopold; Kleinschmidt, Jürgen A; Jauch, Anna; Laufs, Stephanie; Wenz, Frederik; Zeller, W Jens; Fruehauf, Stefan; Veldwijk, Marlon R

2008-01-01

Background For many promising target cells (e.g.: haematopoeitic progenitors), the susceptibility to standard adeno-associated viral (AAV) vectors is low. Advancements in vector development now allows the generation of target cell-selected AAV capsid mutants. Methods To determine its suitability, the method was applied on a chronic myelogenous leukaemia (CML) cell line (K562) to obtain a CML-targeted vector and the resulting vectors tested on leukaemia, non-leukaemia, primary human CML and CD34+ peripheral blood progenitor cells (PBPC); standard AAV2 and a random capsid mutant vector served as controls. Results Transduction of CML (BV173, EM3, K562 and Lama84) and AML (HL60 and KG1a) cell lines with the capsid mutants resulted in an up to 36-fold increase in CML transduction efficiency (K562: 2-fold, 60% ± 2% green fluorescent protein (GFP)+ cells; BV173: 9-fold, 37% ± 2% GFP+ cells; Lama84: 36-fold, 29% ± 2% GFP+ cells) compared to controls. For AML (KG1a, HL60) and one CML cell line (EM3), no significant transduction (<1% GFP+ cells) was observed for any vector. Although the capsid mutant clone was established on a cell line, proof-of-principle experiments using primary human cells were performed. For CML (3.2-fold, mutant: 1.75% ± 0.45% GFP+ cells, p = 0.03) and PBPC (3.5-fold, mutant: 4.21% ± 3.40% GFP+ cells) a moderate increase in gene transfer of the capsid mutant compared to control vectors was observed. Conclusion Using an AAV random peptide library on a CML cell line, we were able to generate a capsid mutant, which transduced CML cell lines and primary human haematopoietic progenitor cells with higher efficiency than standard recombinant AAV vectors. PMID:18789140

A perceptive method for handwritten text segmentation

NASA Astrophysics Data System (ADS)

Lemaitre, Aurélie; Camillerapp, Jean; Coüasnon, Bertrand

2011-01-01

This paper presents a new method to address the problem of handwritten text segmentation into text lines and words. Thus, we propose a method based on the cooperation among points of view that enables the localization of the text lines in a low resolution image, and then to associate the pixels at a higher level of resolution. Thanks to the combination of levels of vision, we can detect overlapping characters and re-segment the connected components during the analysis. Then, we propose a segmentation of lines into words based on the cooperation among digital data and symbolic knowledge. The digital data are obtained from distances inside a Delaunay graph, which gives a precise distance between connected components, at the pixel level. We introduce structural rules in order to take into account some generic knowledge about the organization of a text page. This cooperation among information gives a bigger power of expression and ensures the global coherence of the recognition. We validate this work using the metrics and the database proposed for the segmentation contest of ICDAR 2009. Thus, we show that our method obtains very interesting results, compared to the other methods of the literature. More precisely, we are able to deal with slope and curvature, overlapping text lines and varied kinds of writings, which are the main difficulties met by the other methods.

Disclosing the Parameters Leading to High Productivity of Retroviral Producer Cells Lines: Evaluating Random Versus Targeted Integration.

PubMed

Bandeira, Vanessa S; Tomás, Hélio A; Alici, Evren; Carrondo, Manuel J T; Coroadinha, Ana S

2017-04-01

Gammaretrovirus and lentivirus are the preferred viral vectors to genetically modify T and natural killer cells to be used in immune cell therapies. The transduction efficiency of hematopoietic and T cells is more efficient using gibbon ape leukemia virus (GaLV) pseudotyping. In this context gammaretroviral vector producer cells offer competitive higher titers than transient lentiviral vectors productions. The main aim of this work was to identify the key parameters governing GaLV-pseudotyped gammaretroviral vector productivity in stable producer cells, using a retroviral vector expression cassette enabling positive (facilitating cell enrichment) and negative cell selection (allowing cell elimination). The retroviral vector contains a thymidine kinase suicide gene fused with a ouabain-resistant Na + ,K + -ATPase gene, a potential safer and faster marker. The establishment of retroviral vector producer cells is traditionally performed by randomly integrating the retroviral vector expression cassette codifying the transgene. More recently, recombinase-mediated cassette exchange methodologies have been introduced to achieve targeted integration. Herein we compared random and targeted integration of the retroviral vector transgene construct. Two retroviral producer cell lines, 293 OuaS and 293 FlexOuaS, were generated by random and targeted integration, respectively, producing high titers (on the order of 10 7 infectious particles·ml -1 ). Results showed that the retroviral vector transgene cassette is the key retroviral vector component determining the viral titers notwithstanding, single-copy integration is sufficient to provide high titers. The expression levels of the three retroviral constructs (gag-pol, GaLV env, and retroviral vector transgene) were analyzed. Although gag-pol and GaLV env gene expression levels should surpass a minimal threshold, we found that relatively modest expression levels of these two expression cassettes are required. Their levels of

Text Coherence in Translation

ERIC Educational Resources Information Center

Zheng, Yanping

2009-01-01

In the thesis a coherent text is defined as a continuity of senses of the outcome of combining concepts and relations into a network composed of knowledge space centered around main topics. And the author maintains that in order to obtain the coherence of a target language text from a source text during the process of translation, a translator can…

Beam heating of thick targets for on-line mass separators

NASA Astrophysics Data System (ADS)

Eaton, T. W.; Ravn, H. L.; Isolde Collaboration

1987-05-01

Energy deposition computations have been made on a variety of target materials utilized for the production of radioisotopes by means of 600-MeV protons. Results have shown that, when a proton current of 100 μA is assumed, dispersed target materials, such as uranium carbide powder and magnesium oxide, are best able to withstand the energy absorption and consequent beam heating without the need of additional cooling. Modified foil targets of titanium, zirconium and tantalum also appear capable of withstanding a full beam current, whilst liquid metal targets in their present form appear to have limitations in terms of the maximum allowable beam current. A redesign of the target container is proposed which allows higher proton currents to be used with these targets also.

A hybrid approach for text detection in natural scenes

NASA Astrophysics Data System (ADS)

Wang, Runmin; Sang, Nong; Wang, Ruolin; Kuang, Xiaoqin

2013-10-01

In this paper, a hybrid approach is proposed to detect texts in natural scenes. It is performed by the following steps: Firstly, the edge map and the text saliency region are obtained. Secondly, the text candidate regions are detected by connected components (CC) based method and are identified by an off-line trained HOG classifier. And then, the remaining CCs are grouped into text lines with some heuristic strategies to make up for the false negatives. Finally, the text lines are broken into separate words. The performance of the proposed approach is evaluated on the location detection database of ICDAR 2003 robust reading competition. Experimental results demonstrate the validity of our approach and are competitive with other state-of-the-art algorithms.

Imaging Ultrasound Guidance and on-line Estimation of Thermal Behavior in HIFU Exposed Targets

NASA Astrophysics Data System (ADS)

Chauhan, Sunita; Haryanto, Amir

2006-05-01

Elevated temperatures have been used for many years to combat several diseases including treatment of certain types of cancers/tumors. High Intensity Focused Ultrasound (HIFU) has emerged as a potential non-invasive modality for trackless targeting of deep-seated cancers of human body. For the procedures which require thermal elevation such as hyperthermia and tissue ablation, temperature becomes a parameter of vital importance in order to monitor the treatment on-line. Also, embedding invasive temperature probes for this purpose beats the supremacy of the non-invasive ablating modality. In this paper, we describe the use of a non-invasive and inexpensive conventional imaging ultrasound modality for lesion positioning and estimation of thermal behavior of the tissue on exposure to HIFU. Representative results of our online lesion tracking algorithm for discerning lesioning behavior using image capture, processing and phase-shift measurements are presented.

AAVS1-Targeted Plasmid Integration in AAV Producer Cell Lines.

PubMed

Luo, Yuxia; Frederick, Amy; Martin, John M; Scaria, Abraham; Cheng, Seng H; Armentano, Donna; Wadsworth, Samuel C; Vincent, Karen A

2017-06-01

Adeno-associated virus (AAV) producer cell lines are created via transfection of HeLaS3 cells with a single plasmid containing three components (the vector sequence, the AAV rep and cap genes, and a selectable marker gene). As this plasmid contains both the cis (Rep binding sites) and trans (Rep protein encoded by the rep gene) elements required for site-specific integration, it was predicted that plasmid integration might occur within the AAVS1 locus on human chromosome 19 (chr19). The objective of this study was to investigate whether integration in AAVS1 might be correlated with vector yield. Plasmid integration sites within several independent cell lines were assessed via Southern, fluorescence in situ hybridization (FISH) and PCR analyses. In the Southern analyses, the presence of fragments detected by both rep- and AAVS1-specific probes suggested that for several mid- and high-producing lines, plasmid DNA had integrated into the AAVS1 locus. Analysis with puroR and AAVS1-specific probes suggested that integration in AAVS1 was a more widespread phenomenon. High-producing AAV2-secreted alkaline phosphatase (SEAP) lines (masterwell 82 [MW82] and MW278) were evaluated via FISH using probes specific for the plasmid, AAVS1, and a chr19 marker. FISH analysis detected two plasmid integration sites in MW278 (neither in AAVS1), while a total of three sites were identified in MW82 (two in AAVS1). An inverse PCR assay confirmed integration within AAVS1 for several mid- and high-producing lines. In summary, the FISH, Southern, and PCR data provide evidence of site-specific integration of the plasmid within AAVS1 in several AAV producer cell lines. The data also suggest that integration in AAVS1 is a general phenomenon that is not necessarily restricted to high producers. The results also suggest that plasmid integration within the AAVS1 locus is not an absolute requirement for a high vector yield.

Co-targeting the HER and IGF/insulin receptor axis in breast cancer, with triple targeting with endocrine therapy for hormone-sensitive disease.

PubMed

Chakraborty, Ashok; Hatzis, Christos; DiGiovanna, Michael P

2017-05-01

Interactions between HER2, estrogen receptor (ER), and insulin-like growth factor I receptor (IGF1R) are implicated in resistance to monotherapies targeting these receptors. We have previously shown in pre-clinical studies synergistic anti-tumor effects for co-targeting each pairwise combination of HER2, IGF1R, and ER. Strikingly, synergy for HER2/IGF1R targeting occurred not only in a HER2+ model, but also in a HER2-normal model. The purpose of the current study was therefore to determine the generalizability of synergistic anti-tumor effects of co-targeting HER2/IGF1R, the anti-tumor activity of triple-targeting HER2/IGF1R/ER in hormone-dependent cell lines, and the effect of using the multi-targeting drugs neratinib (pan-HER) and BMS-754807 (dual IGF1R/insulin receptor). Proliferation and apoptosis assays were performed in a large panel of cell lines representing varying receptor expression levels. Mechanistic effects were studied using phospho-protein immunoblotting. Analyses of drug interaction effects were performed using linear mixed-effects regression models. Enhanced anti-proliferative effects of HER/IGF-insulin co-targeting were seen in most, though not all, cell lines, including HER2-normal lines. For ER+ lines, triple targeting with inclusion of anti-estrogen generally resulted in the greatest anti-tumor effects. Double or triple targeting generally resulted in marked increases in apoptosis in the sensitive lines. Mechanistic studies demonstrated that the synergy between drugs was correlated with maximal inhibition of Akt and ERK pathway signaling. Dual HER/IGF-insulin targeting, and triple targeting with inclusion of anti-estrogen drugs, shows striking anti-tumor activity across breast cancer types, and drugs with broader receptor specificity may be more effective than single receptor selective drugs, particularly for ER- cells.

Mutational analysis of genes coding for cell surface proteins in colorectal cancer cell lines reveal novel altered pathways, druggable mutations and mutated epitopes for targeted therapy

PubMed Central

Correa, Bruna R.; Bettoni, Fabiana; Koyama, Fernanda C.; Navarro, Fabio C.P.; Perez, Rodrigo O.; Mariadason, John; Sieber, Oliver M.; Strausberg, Robert L.; Simpson, Andrew J.G.; Jardim, Denis L.F.; Reis, Luiz Fernando L.; Parmigiani, Raphael B.; Galante, Pedro A.F.; Camargo, Anamaria A.

2014-01-01

We carried out a mutational analysis of 3,594 genes coding for cell surface proteins (Surfaceome) in 23 colorectal cancer cell lines, searching for new altered pathways, druggable mutations and mutated epitopes for targeted therapy in colorectal cancer. A total of 3,944 somatic non-synonymous substitutions and 595 InDels, occurring in 2,061 (57%) Surfaceome genes were catalogued. We identified 48 genes not previously described as mutated in colorectal tumors in the TCGA database, including genes that are mutated and expressed in >10% of the cell lines (SEMA4C, FGFRL1, PKD1, FAM38A, WDR81, TMEM136, SLC36A1, SLC26A6, IGFLR1). Analysis of these genes uncovered important roles for FGF and SEMA4 signaling in colorectal cancer with possible therapeutic implications. We also found that cell lines express on average 11 druggable mutations, including frequent mutations (>20%) in the receptor tyrosine kinases AXL and EPHA2, which have not been previously considered as potential targets for colorectal cancer. Finally, we identified 82 cell surface mutated epitopes, however expression of only 30% of these epitopes was detected in our cell lines. Notwithstanding, 92% of these epitopes were expressed in cell lines with the mutator phenotype, opening new venues for the use of “general” immune checkpoint drugs in this subset of patients. PMID:25193853

piRNA pathway targets active LINE1 elements to establish the repressive H3K9me3 mark in germ cells

PubMed Central

Pezic, Dubravka; Manakov, Sergei A.; Sachidanandam, Ravi; Aravin, Alexei A.

2014-01-01

Transposable elements (TEs) occupy a large fraction of metazoan genomes and pose a constant threat to genomic integrity. This threat is particularly critical in germ cells, as changes in the genome that are induced by TEs will be transmitted to the next generation. Small noncoding piwi-interacting RNAs (piRNAs) recognize and silence a diverse set of TEs in germ cells. In mice, piRNA-guided transposon repression correlates with establishment of CpG DNA methylation on their sequences, yet the mechanism and the spectrum of genomic targets of piRNA silencing are unknown. Here we show that in addition to DNA methylation, the piRNA pathway is required to maintain a high level of the repressive H3K9me3 histone modification on long interspersed nuclear elements (LINEs) in germ cells. piRNA-dependent chromatin repression targets exclusively full-length elements of actively transposing LINE families, demonstrating the remarkable ability of the piRNA pathway to recognize active elements among the large number of genomic transposon fragments. PMID:24939875

Target CLAB Zero: A national improvement collaborative to reduce central line-associated bacteraemia in New Zealand intensive care units.

PubMed

Gray, Jonathon; Proudfoot, Suzanne; Power, Maxine; Bennett, Brandon; Wells, Sue; Seddon, Mary

2015-09-04

Central line-associated bacteraemia (CLAB) is a preventable cause of patient morbidity and mortality in intensive care units. Target CLAB Zero was a national campaign that ran from October 2011 to March 2013 across all New Zealand ICUs (intensive care units). The campaign aimed to reduce the national CLAB rate to less than one incident per 1,000 line days and to establish a national measurement system for CLAB. We used Institute for Healthcare Improvement (IHI) Breakthrough Series methodology to structure the campaign. IHI bundles of care for catheter insertion and maintenance were implemented across 25 New Zealand ICUs. We collected monthly data on line days, CLAB infections and compliance with the bundles. Data were analysed using run charts. The rate of CLAB per 1,000 line days fell from 3.32 at baseline to an average of 0.28 between April 2012 and March 2013. In the final 3-month period, January to March 2013, average insertion bundle compliance was 80% and average maintenance bundle compliance was 75%. All ICUs participated in the collaborative. Over 90% of those invited attended all three national learning sessions and bi-monthly regional learning sessions. National collaboratives can effect improvement and shared learning in New Zealand. International evidence combined with New Zealand experience, a supportive methodology, partnership, clinical respect and an effective communication plan were keys to successful engagement.

Targeting tachykinin receptors in neuroblastoma.

PubMed

Henssen, Anton G; Odersky, Andrea; Szymansky, Annabell; Seiler, Marleen; Althoff, Kristina; Beckers, Anneleen; Speleman, Frank; Schäfers, Simon; De Preter, Katleen; Astrahanseff, Kathy; Struck, Joachim; Schramm, Alexander; Eggert, Angelika; Bergmann, Andreas; Schulte, Johannes H

2017-01-03

Neuroblastoma is the most common extracranial tumor in children. Despite aggressive multimodal treatment, high-risk neuroblastoma remains a clinical challenge with survival rates below 50%. Adding targeted drugs to first-line therapy regimens is a promising approach to improve survival in these patients. TACR1 activation by substance P has been reported to be mitogenic in cancer cell lines. Tachykinin receptor (TACR1) antagonists are approved for clinical use as an antiemetic remedy since 2003. Tachykinin receptor inhibition has recently been shown to effectively reduce growth of several tumor types. Here, we report that neuroblastoma cell lines express TACR1, and that targeting TACR1 activity significantly reduced cell viability and induced apoptosis in neuroblastoma cell lines. Gene expression profiling revealed that TACR1 inhibition repressed E2F2 and induced TP53 signaling. Treating mice harboring established neuroblastoma xenograft tumors with Aprepitant also significantly reduced tumor burden. Thus, we provide evidence that the targeted inhibition of tachykinin receptor signaling shows therapeutic efficacy in preclinical models for high-risk neuroblastoma.

Epidermal growth factor receptor (EGFR) density may not be the only determinant for the efficacy of EGFR-targeted photoimmunotherapy in human head and neck cancer cell lines.

PubMed

Peng, Wei; de Bruijn, Henriette S; Farrell, Eric; Sioud, Mouldy; Mashayekhi, Vida; Oliveira, Sabrina; van Dam, Go M; Roodenburg, Jan L N; Witjes, Max J H; Robinson, Dominic J

2018-05-19

The aim of this study was to investigate the effects of targeted photoimmunotherapy (PIT) in vitro on cell lines with various expression levels of epidermal growth factor receptor (EGFR) using an anti-EGFR targeted conjugate composed of Cetuximab and IR700DX, phthalocyanine dye. Relative EGFR density and cell binding assay was conducted in three human head & neck cancer cell lines (scc-U2, scc-U8, and OSC19) and one reference cell line A431. After incubation with the conjugate for 1 or 24 hours, cellular uptake and localization were investigated by confocal laser scanning microscopy and quantified by image analysis. Cell survival was determined using the MTS assay and alamarBlue assay after PIT with a 690 nm laser to a dose of 7 J.cm -2 (at 5 mW.cm -2 ). The mode of cell death was examined with flow cytometry using apoptosis/necrosis staining by Annexin V/propidium iodide, together with immunoblots of anti-apoptotic Bcl-2 family proteins Bcl-2 and Bcl-xL. A431 cells had the highest EGFR density followed by OSC19, and then scc-U2 and scc-U8. The conjugates were localized both on the surface and in the cytosol of the cells after 1- and 24-hour incubation. After 24-hour incubation the granular pattern was more pronounced and in a similar pattern of a lysosomal probe, suggesting that the uptake of conjugates by cells was via receptor-mediated endocytosis. The results obtained from the quantitative imaging analysis correlate with the level of EGFR expression. Targeted PIT killed scc-U8 and A431 cells efficiently; while scc-U2 and OSC19 were less sensitive to this treatment, despite having similar EGFR density, uptake and localization pattern. Scc-U2 cells showed less apoptotic cell dealth than in A431 after 24-hour targeted PIT. Immunoblots showed significantly higher expression of anti-apoptotic Bcl-2 and Bcl-xL proteins in scc-U2 cell lines compared to scc-U8. Our study suggests that the effectiveness of EGFR targeted PIT is not only dependent upon EGFR density

β-Catenin transcriptional activity is minimal in canine osteosarcoma and its targeted inhibition results in minimal changes to cell line behaviour.

PubMed

Piskun, Caroline M; Stein, Timothy J

2016-06-01

Canine osteosarcoma (OS) is an aggressive malignancy associated with poor outcomes. Therapeutic improvements are likely to develop from an improved understanding of signalling pathways contributing to OS development and progression. The Wnt signalling pathway is of interest for its role in osteoblast differentiation, its dysregulation in numerous cancer types, and the relative frequency of cytoplasmic accumulation of β-catenin in canine OS. This study aimed to determine the biological impact of inhibiting canonical Wnt signalling in canine OS, by utilizing either β-catenin siRNA or a dominant-negative T-cell factor (TCF) construct. There were no consistent, significant changes in cell line behaviour with either method compared to parental cell lines. Interestingly, β-catenin transcriptional activity was three-fold higher in normal canine primary osteoblasts compared to canine OS cell lines. These results suggest canonical Wnt signalling is minimally active in canine OS and its targeted inhibition is not a relevant therapeutic strategy. © 2013 John Wiley & Sons Ltd.

Text Processing and Formatting: Composure, Composition and Eros.

ERIC Educational Resources Information Center

Blair, John C., Jr.

1984-01-01

Review of computer software offering text editing/processing capabilities highlights work habits, elements of computer style and composition, buffers, the CRT, line- and screen-oriented text editors, video attributes, "swapping,""cache" memory, "disk emulators," text editing versus text processing, and UNIX operating…

Biomechanical patterns of text-message distraction.

PubMed

Le, Peter; Hwang, Jaejin; Grawe, Sarah; Li, Jing; Snyder, Alison; Lee, Christina; Marras, William S

2015-01-01

The objective of this study was to identify biomechanical measures that can distinguish texting distraction in a laboratory-simulated driving environment. The goal would be to use this information to provide an intervention for risky driving behaviour. Sixteen subjects participated in this study. Three independent variables were tested: task (texting, visual targeting, weighted and non-weighted movements), task direction (front and side) and task distance (close and far). Dependent variables consisted of biomechanical moments, head displacement and the length of time to complete each task. Results revealed that the time to complete each task was higher for texting compared to other tasks. Peak moments during texting were only distinguishable from visual targeting. Peak head displacement and cumulative biomechanical exposure measures indicated that texting can be distinguished from other tasks. Therefore, it may be useful to take into account both temporal and biomechanical measures when considering warning systems to detect texting distraction.

Magnetically attached sputter targets

DOEpatents

Makowiecki, Daniel M.; McKernan, Mark A.

1994-01-01

An improved method and assembly for attaching sputtering targets to cathode assemblies of sputtering systems which includes a magnetically permeable material. The magnetically permeable material is imbedded in a target base that is brazed, welded, or soldered to the sputter target, or is mechanically retained in the target material. Target attachment to the cathode is achieved by virtue of the permanent magnets and/or the pole pieces in the cathode assembly that create magnetic flux lines adjacent to the backing plate, which strongly attract the magnetically permeable material in the target assembly.

Stakeholder Views of Nanosilver Linings: Macroethics Education and Automated Text Analysis Through Participatory Governance Role Play in a Workshop Format.

PubMed

Dempsey, Joshua; Stamets, Justin; Eggleson, Kathleen

2017-06-01

The Nanosilver Linings role play case offers participants first-person experience with interpersonal interaction in the context of the wicked problems of emerging technology macroethics. In the fictional scenario, diverse societal stakeholders convene at a town hall meeting to consider whether a nanotechnology-enabled food packaging industry should be offered incentives to establish an operation in their economically struggling Midwestern city. This original creative work was built with a combination of elements, selected for their established pedagogical efficacy (e.g. active learning, case-based learning) and as topical dimensions of the realistic scenario (e.g. nanosilver in food packaging, occupational safety and health). The product life cycle is used as a framework for integrated consideration of scientific, societal, and ethical issues. The Nanosilver Linings hypothetical case was delivered through the format of the 3-hour workshop Ethics when Biocomplexity meets Human Complexity, providing an immersive, holistic ethics learning experience for STEM graduate students. Through their participation in the Nanosilver Linings case and Ethics when Biocomplexity meets Human Complexity workshop, four cohorts of science and engineering doctoral students reported the achievement of specific learning objectives pertaining to a range of macroethics concepts and professional practices, including stakeholder perspectives, communication, human values, and ethical frameworks. Automated text analysis of workshop transcripts revealed differences in sentiment and in ethical framework (consequentialism/deontology) preference between societal stakeholder roles. These resources have been recognized as ethics education exemplars by the U.S. National Academy of Engineering .

Intonation Miscues and Apprehension of Text.

ERIC Educational Resources Information Center

Flippo, Rona F.

Working on the theory that intonation miscues caused by confusion over punctuation and other phrase boundaries will make the apprehension of text more difficult than necessary for young developing readers, a study reviewed the research and literature relevant to the effects of location of punctuation, phrasing, and line breaks in text and on the…

Using Refutational Text in Mathematics Education

ERIC Educational Resources Information Center

Lem, Stephanie; Onghena, Patrick; Verschaffel, Lieven; Van Dooren, Wim

2017-01-01

Refutational text is one of the many instructional techniques that have been proposed to be used in education as a way to achieve effective learning. The aim of refutational text is to transform misconceptions into conceptions that are in line with current scientific concepts. This is done by explicitly stating a misconception, refuting it, and…

Development of a transgenic Plasmodium berghei line (Pb pfpkg) expressing the P. falciparum cGMP-dependent protein kinase, a novel antimalarial drug target.

PubMed

Tewari, Rita; Patzewitz, Eva-Maria; Poulin, Benoit; Stewart, Lindsay; Baker, David A

2014-01-01

With the inevitable selection of resistance to antimalarial drugs in treated populations, there is a need for new medicines to enter the clinic and new targets to progress through the drug discovery pipeline. In this study we set out to develop a transgenic rodent model for testing inhibitors of the Plasmodium falciparum cyclic GMP-dependent kinase in vivo. A model was needed that would allow us to investigate whether differences in amino acid sequence of this enzyme between species influences in vivo efficacy. Here we report the successful development of a transgenic P. berghei line in which the cyclic GMP-dependent protein kinase (PKG) was replaced by the P. falciparum orthologue. We demonstrate that the P. falciparum orthologue was able to functionally complement the endogenous P. berghei pkg gene throughout blood stage development and early sexual development. However, subsequent development in the mosquito was severely compromised. We show that this is due to a defect in the female lineage of the transgenic by using genetic crosses with both male and female deficient P. berghei lines. This defect could be due to expression of a female-specific target in the mosquito stages of P. berghei that cannot be phosphorylated by the P. falciparum kinase. Using a previously reported anti-coccidial inhibitor of the cyclic GMP-dependent protein kinase, we show no difference in in vivo efficacy between the transgenic and control P. berghei lines. This in vivo model will be useful for screening future generations of cyclic GMP-dependent protein kinase inhibitors and allowing us to overcome any species-specific differences in the enzyme primary sequence that would influence in vivo efficacy in the rodent model. The approach will also be applicable to in vivo testing of other antimalarial compounds where the target is known.

System for line drawings interpretation

NASA Astrophysics Data System (ADS)

Boatto, L.; Consorti, Vincenzo; Del Buono, Monica; Eramo, Vincenzo; Esposito, Alessandra; Melcarne, F.; Meucci, Mario; Mosciatti, M.; Tucci, M.; Morelli, Arturo

1992-08-01

This paper describes an automatic system that extracts information from line drawings, in order to feed CAD or GIS systems. The line drawings that we analyze contain interconnected thin lines, dashed lines, text, and symbols. Characters and symbols may overlap with lines. Our approach is based on the properties of the run representation of a binary image that allow giving the image a graph structure. Using this graph structure, several algorithms have been designed to identify, directly in the raster image, straight segments, dashed lines, text, symbols, hatching lines, etc. Straight segments and dashed lines are converted into vectors, with high accuracy and good noise immunity. Characters and symbols are recognized by means of a recognizer, specifically developed for this application, designed to be insensitive to rotation and scaling. Subsequent processing steps include an `intelligent'' search through the graph in order to detect closed polygons, dashed lines, text strings, and other higher-level logical entities, followed by the identification of relationships (adjacency, inclusion, etc.) between them. Relationships are further translated into a formal description of the drawing. The output of the system can be used as input to a Geographic Information System package. The system is currently used by the Italian Land Register Authority to process cadastral maps.

Text String Detection from Natural Scenes by Structure-based Partition and Grouping

PubMed Central

Yi, Chucai; Tian, YingLi

2012-01-01

Text information in natural scene images serves as important clues for many image-based applications such as scene understanding, content-based image retrieval, assistive navigation, and automatic geocoding. However, locating text from complex background with multiple colors is a challenging task. In this paper, we explore a new framework to detect text strings with arbitrary orientations in complex natural scene images. Our proposed framework of text string detection consists of two steps: 1) Image partition to find text character candidates based on local gradient features and color uniformity of character components. 2) Character candidate grouping to detect text strings based on joint structural features of text characters in each text string such as character size differences, distances between neighboring characters, and character alignment. By assuming that a text string has at least three characters, we propose two algorithms of text string detection: 1) adjacent character grouping method, and 2) text line grouping method. The adjacent character grouping method calculates the sibling groups of each character candidate as string segments and then merges the intersecting sibling groups into text string. The text line grouping method performs Hough transform to fit text line among the centroids of text candidates. Each fitted text line describes the orientation of a potential text string. The detected text string is presented by a rectangle region covering all characters whose centroids are cascaded in its text line. To improve efficiency and accuracy, our algorithms are carried out in multi-scales. The proposed methods outperform the state-of-the-art results on the public Robust Reading Dataset which contains text only in horizontal orientation. Furthermore, the effectiveness of our methods to detect text strings with arbitrary orientations is evaluated on the Oriented Scene Text Dataset collected by ourselves containing text strings in non

Text string detection from natural scenes by structure-based partition and grouping.

PubMed

Yi, Chucai; Tian, YingLi

2011-09-01

Text information in natural scene images serves as important clues for many image-based applications such as scene understanding, content-based image retrieval, assistive navigation, and automatic geocoding. However, locating text from a complex background with multiple colors is a challenging task. In this paper, we explore a new framework to detect text strings with arbitrary orientations in complex natural scene images. Our proposed framework of text string detection consists of two steps: 1) image partition to find text character candidates based on local gradient features and color uniformity of character components and 2) character candidate grouping to detect text strings based on joint structural features of text characters in each text string such as character size differences, distances between neighboring characters, and character alignment. By assuming that a text string has at least three characters, we propose two algorithms of text string detection: 1) adjacent character grouping method and 2) text line grouping method. The adjacent character grouping method calculates the sibling groups of each character candidate as string segments and then merges the intersecting sibling groups into text string. The text line grouping method performs Hough transform to fit text line among the centroids of text candidates. Each fitted text line describes the orientation of a potential text string. The detected text string is presented by a rectangle region covering all characters whose centroids are cascaded in its text line. To improve efficiency and accuracy, our algorithms are carried out in multi-scales. The proposed methods outperform the state-of-the-art results on the public Robust Reading Dataset, which contains text only in horizontal orientation. Furthermore, the effectiveness of our methods to detect text strings with arbitrary orientations is evaluated on the Oriented Scene Text Dataset collected by ourselves containing text strings in nonhorizontal

Effectiveness of a Text Messaging-Based Intervention Targeting Alcohol Consumption Among University Students: Randomized Controlled Trial.

PubMed

Thomas, Kristin; Müssener, Ulrika; Linderoth, Catharina; Karlsson, Nadine; Bendtsen, Preben; Bendtsen, Marcus

2018-06-25

Excessive drinking among university students is a global challenge, leading to significant health risks. However, heavy drinking among students is widely accepted and socially normalized. Mobile phone interventions have attempted to reach students who engage in excessive drinking. A growing number of studies suggest that text message-based interventions could potentially reach many students and, if effective, such an intervention might help reduce heavy drinking in the student community. The objective of this study was to test the effectiveness of a behavior change theory-based 6-week text message intervention among university students. This study was a two-arm, randomized controlled trial with an intervention group receiving a 6-week text message intervention and a control group that was referred to treatment as usual at the local student health care center. Outcome measures were collected at baseline and at 3 months after the initial invitation to participate in the intervention. The primary outcome was total weekly alcohol consumption. Secondary outcomes were frequency of heavy episodic drinking, highest estimated blood alcohol concentration, and number of negative consequences attributable to excessive drinking. A total of 896 students were randomized to either the intervention or control group. The primary outcome analysis included 92.0% of the participants in the intervention group and 90.1% of the control group. At follow-up, total weekly alcohol consumption decreased in both groups, but no significant between-group difference was seen. Data on the secondary outcomes included 49.1% of the participants in the intervention group and 41.3% of the control group. No significant between-group difference was seen for any of the secondary outcomes. The present study was under-powered, which could partly explain the lack of significance. However, the intervention, although theory-based, needs to be re-assessed and refined to better support the target group. Apart

Magnetically attached sputter targets

DOEpatents

Makowiecki, D.M.; McKernan, M.A.

1994-02-15

An improved method and assembly for attaching sputtering targets to cathode assemblies of sputtering systems which includes a magnetically permeable material is described. The magnetically permeable material is imbedded in a target base that is brazed, welded, or soldered to the sputter target, or is mechanically retained in the target material. Target attachment to the cathode is achieved by virtue of the permanent magnets and/or the pole pieces in the cathode assembly that create magnetic flux lines adjacent to the backing plate, which strongly attract the magnetically permeable material in the target assembly. 11 figures.

Reading Speed Does Not Benefit from Increased Line Spacing in AMD Patients

PubMed Central

CHUNG, SUSANA T. L.; JARVIS, SAMUEL H.; WOO, STANLEY Y.; HANSON, KARA; JOSE, RANDALL T.

2009-01-01

Purpose Crowding, the adverse spatial interaction due to the proximity of adjacent targets, has been suggested as an explanation for slow reading in peripheral vision. Previously, we showed that increased line spacing, which presumably reduces crowding between adjacent lines of text, improved reading speed in the normal periphery (Chung, Optom Vis Sci 2004;81:525–35). The purpose of this study was to examine whether or not individuals with age-related macular degeneration (AMD) would benefit from increased line spacing for reading. Methods Experiment 1: Eight subjects with AMD read aloud 100-word passages rendered at five line spacings: the standard single spacing, 1.5×, 2×, 3×, and 4× the standard spacing. Print sizes were 1× and 2× of the critical print size. Reading time and number of reading errors for each passage were measured to compute the reading speed. Experiment 2: Four subjects with AMD read aloud sequences of six 4-letter words, presented on a computer monitor using the rapid serial visual presentation (RSVP) paradigm. Target words were presented singly, or flanked above and below by two other words that changed in synchrony with the target word, at various vertical word separations. Print size was 2× the critical print size. Reading speed was calculated based on the RSVP exposure duration that yielded 80% of the words read correctly. Results Averaged across subjects, reading speeds for passages were virtually constant for the range of line spacings tested. For sequences of unrelated words, reading speeds were also virtually constant for the range of vertical word separations tested, except at the smallest (standard) separation at which reading speed was lower. Conclusions Contrary to the previous finding that reading speed improved in normal peripheral vision, increased line spacing in passages, or increased vertical separation between words in RSVP, did not lead to improved reading speed in people with AMD. PMID:18772718

Functional validation of the oncogenic cooperativity and targeting potential of tuberous sclerosis mutation in medulloblastoma using a MYC-amplified model cell line.

PubMed

Henderson, Jacob J; Wagner, Jacob P; Hofmann, Nicolle E; Eide, Christopher A; Cho, Yoon-Jae; Druker, Brian J; Davare, Monika A

2017-10-01

Medulloblastoma is the most common malignant brain tumor of childhood. To identify targetable vulnerabilities, we employed inhibitor screening that revealed mTOR inhibitor hypersensitivity in the MYC-overexpressing medulloblastoma cell line, D341. Concomitant exome sequencing unveiled an uncharacterized missense mutation, TSC2 A415V , in these cells. We biochemically demonstrate that the TSC2 A415V mutation is functionally deleterious, leading to shortened half-life and proteasome-mediated protein degradation. These data suggest that MYC cooperates with activated kinase pathways, enabling pharmacologic intervention in these treatment refractory tumors. We propose that identification of activated kinase pathways may allow for tailoring targeted therapy to improve survival and treatment-related morbidity in medulloblastoma. © 2017 Wiley Periodicals, Inc.

Targeted Recombinant Progeny: a design for ultra-high resolution mapping of Quantitative Trait Loci in crosses between inbred or pure lines.

PubMed

Heifetz, Eliyahu M; Soller, Morris

2015-07-07

High-resolution mapping of the loci (QTN) responsible for genetic variation in quantitative traits is essential for positional cloning of candidate genes, and for effective marker assisted selection. The confidence interval (QTL) flanking the point estimate of QTN-location is proportional to the number of individuals in the mapping population carrying chromosomes recombinant in the given interval. Consequently, many designs for high resolution QTN mapping are based on increasing the proportion of recombinants in the mapping population. The "Targeted Recombinant Progeny" (TRP) design is a new design for high resolution mapping of a target QTN in crosses between pure, or inbred lines. It is a three-generation procedure generating a large number of recombinant individuals within a QTL previously shown to contain a QTN. This is achieved by having individuals that carry chromosomes recombinant across the target QTL interval as parents of a large mapping population; most of whom will therefore carry recombinant chromosomes targeted to the given QTL. The TRP design is particularly useful for high resolution mapping of QTN that differentiate inbred or pure lines, and hence are not amenable to high resolution mapping by genome-wide association tests. In the absence of residual polygenic variation, population sizes required for achieving given mapping resolution by the TRP-F2 design relative to a standard F2 design ranged from 0.289 for a QTN with standardized allele substitution effect = 0.2, mapped to an initial QTL of 0.2 Morgan to 0.041 for equivalent QTN mapped to an initial QTL of 0.02 M. In the presence of residual polygenic variation, the relative effectiveness of the TRP design ranges from 1.068 to 0.151 for the same initial QTL intervals and QTN effect. Thus even in the presence of polygenic variation, the TRP can still provide major savings. Simulation showed that mapping by TRP should be based on 30-50 markers spanning the initial interval; and on at least 50 or

Literature evidence in open targets - a target validation platform.

PubMed

Kafkas, Şenay; Dunham, Ian; McEntyre, Johanna

2017-06-06

We present the Europe PMC literature component of Open Targets - a target validation platform that integrates various evidence to aid drug target identification and validation. The component identifies target-disease associations in documents and ranks the documents based on their confidence from the Europe PMC literature database, by using rules utilising expert-provided heuristic information. The confidence score of a given document represents how valuable the document is in the scope of target validation for a given target-disease association by taking into account the credibility of the association based on the properties of the text. The component serves the platform regularly with the up-to-date data since December, 2015. Currently, there are a total number of 1168365 distinct target-disease associations text mined from >26 million PubMed abstracts and >1.2 million Open Access full text articles. Our comparative analyses on the current available evidence data in the platform revealed that 850179 of these associations are exclusively identified by literature mining. This component helps the platform's users by providing the most relevant literature hits for a given target and disease. The text mining evidence along with the other types of evidence can be explored visually through https://www.targetvalidation.org and all the evidence data is available for download in json format from https://www.targetvalidation.org/downloads/data .

Effectiveness of off-line and web-based promotion of health information web sites.

PubMed

Jones, Craig E; Pinnock, Carole B

2002-01-01

The relative effectiveness of off-line and web-based promotional activities in increasing the use of health information web sites by target audiences were compared. Visitor sessions were classified according to their method of arrival at the site (referral) as external web site, search engine, or "no referrer" (i.e., visitor arriving at the site by inputting URL or using bookmarks). The number of Australian visitor sessions correlated with no referrer referrals but not web site or search-engine referrals. Results showed that the targeted consumer group is more likely to access the web site as a result of off-line promotional activities. The properties of target audiences likely to influence the effectiveness of off-line versus on-line promotional strategies include the size of the Internet using population of the target audience, their proficiency in the use of the Internet, and the increase in effectiveness of off-line promotional activities when applied to locally defined target audiences.

Targeted Knock-Down of miR21 Primary Transcripts Using snoMEN Vectors Induces Apoptosis in Human Cancer Cell Lines.

PubMed

Ono, Motoharu; Yamada, Kayo; Avolio, Fabio; Afzal, Vackar; Bensaddek, Dalila; Lamond, Angus I

2015-01-01

We have previously reported an antisense technology, 'snoMEN vectors', for targeted knock-down of protein coding mRNAs using human snoRNAs manipulated to contain short regions of sequence complementarity with the mRNA target. Here we characterise the use of snoMEN vectors to target the knock-down of micro RNA primary transcripts. We document the specific knock-down of miR21 in HeLa cells using plasmid vectors expressing miR21-targeted snoMEN RNAs and show this induces apoptosis. Knock-down is dependent on the presence of complementary sequences in the snoMEN vector and the induction of apoptosis can be suppressed by over-expression of miR21. Furthermore, we have also developed lentiviral vectors for delivery of snoMEN RNAs and show this increases the efficiency of vector transduction in many human cell lines that are difficult to transfect with plasmid vectors. Transduction of lentiviral vectors expressing snoMEN targeted to pri-miR21 induces apoptosis in human lung adenocarcinoma cells, which express high levels of miR21, but not in human primary cells. We show that snoMEN-mediated suppression of miRNA expression is prevented by siRNA knock-down of Ago2, but not by knock-down of Ago1 or Upf1. snoMEN RNAs colocalise with Ago2 in cell nuclei and nucleoli and can be co-immunoprecipitated from nuclear extracts by antibodies specific for Ago2.

Faint CO Line Wings in Four Star-forming (Ultra)luminous Infrared Galaxies

NASA Astrophysics Data System (ADS)

Leroy, Adam K.; Walter, Fabian; Decarli, Roberto; Bolatto, Alberto; Zschaechner, Laura; Weiss, Axel

2015-09-01

We report the results of a search for large velocity width, low-intensity line wings—a commonly used signature of molecular outflows—in four low redshift (ultra)luminous infrared galaxies that appear to be dominated by star formation. The targets were drawn from a sample of fourteen targets presented in Chung et al., who showed the stacked CO spectrum of the sample to exhibit 1000 km s-1-wide line wings. We obtained sensitive, wide bandwidth imaging of our targets using the IRAM Plateau de Bure Interferometer. We detect each target at very high significance but do not find the claimed line wings in these four targets. Instead, we constrain the flux in the line wings to be only a few percent. Casting our results as mass outflow rates following Cicone et al. we show them to be consistent with a picture in which very high mass loading factors preferentially occur in systems with high active galactic nucleus contributions to their bolometric luminosity. We identify one of our targets, IRAS 05083 (VII Zw 31), as a candidate molecular outflow.

A specialized bioengineering ion beam line

NASA Astrophysics Data System (ADS)

Yu, L. D.; Sangyuenyongpipat, S.; Sriprom, C.; Thongleurm, C.; Suwanksum, R.; Tondee, N.; Prakrajang, K.; Vilaithong, T.; Brown, I. G.; Wiedemann, H.

2007-04-01

A specialized bioengineering ion beam line has recently been completed at Chiang Mai University to meet rapidly growing needs of research and application development in low-energy ion beam biotechnology. This beam line possesses special features: vertical main beam line, low-energy (30 keV) ion beams, double swerve of the beam, a fast pumped target chamber, and an in-situ atomic force microscope (AFM) system chamber. The whole beam line is situated in a bioclean environment, occupying two stories. The quality of the ion beam has been studied. It has proved that this beam line has significantly contributed to our research work on low-energy ion beam biotechnology.

Analyzing asset management data using data and text mining.

DOT National Transportation Integrated Search

2014-07-01

Predictive models using text from a sample competitively bid California highway projects have been used to predict a construction : projects likely level of cost overrun. A text description of the project and the text of the five largest project line...

Accuracy of off-line bioluminescence imaging to localize targets in preclinical radiation research.

PubMed

Tuli, Richard; Armour, Michael; Surmak, Andrew; Reyes, Juvenal; Iordachita, Iulian; Patterson, Michael; Wong, John

2013-04-01

In this study, we investigated the accuracy of using off-line bioluminescence imaging (BLI) and tomography (BLT) to guide irradiation of small soft tissue targets on a small animal radiation research platform (SARRP) with on-board cone beam CT (CBCT) capability. A small glass bulb containing BL cells was implanted as a BL source in the abdomen of 11 mouse carcasses. Bioluminescence imaging and tomography were acquired for each carcass. Six carcasses were setup visually without immobilization and 5 were restrained in position with tape. All carcasses were setup in treatment position on the SARRP where the centroid position of the bulb on CBCT was taken as "truth". In the 2D visual setup, the carcass was setup by aligning the point of brightest luminescence with the vertical beam axis. In the CBCT assisted setup, the pose of the carcass on CBCT was aligned with that on the 2D BL image for setup. For both 2D setup methods, the offset of the bulb centroid on CBCT from the vertical beam axis was measured. In the BLT-CBCT fusion method, the 3D torso on BLT and CBCT was registered and the 3D offset of the respective source centroids was calculated. The setup results were independent of the carcass being immobilized or not due to the onset of rigor mortis. The 2D offset of the perceived BL source position from the CBCT bulb position was 2.3 mm ± 1.3 mm. The 3D offset between BLT and CBCT was 1.5 mm ± 0.9 mm. Given the rigidity of the carcasses, the setup results represent the best that can be achieved with off-line 2D BLI and 3D BLT. The setup uncertainty would require the use of undesirably large margin of 4-5 mm. The results compel the implementation of on-board BLT capability on the SARRP to eliminate setup error and to improve BLT accuracy.

Accuracy of Off-Line Bioluminescence Imaging to Localize Targets in Preclinical Radiation Research

PubMed Central

Tuli, Richard; Armour, Michael; Surmak, Andrew; Reyes, Juvenal; Iordachita, Iulian; Patterson, Michael; Wong, John

2013-01-01

In this study, we investigated the accuracy of using off-line bioluminescence imaging (BLI) and tomography (BLT) to guide irradiation of small soft tissue targets on a small animal radiation research platform (SARRP) with on-board cone beam CT (CBCT) capability. A small glass bulb containing BL cells was implanted as a BL source in the abdomen of 11 mouse carcasses. Bioluminescence imaging and tomography were acquired for each carcass. Six carcasses were setup visually without immobilization and 5 were restrained in position with tape. All carcasses were setup in treatment position on the SARRP where the centroid position of the bulb on CBCT was taken as “truth”. In the 2D visual setup, the carcass was setup by aligning the point of brightest luminescence with the vertical beam axis. In the CBCT assisted setup, the pose of the carcass on CBCT was aligned with that on the 2D BL image for setup. For both 2D setup methods, the offset of the bulb centroid on CBCT from the vertical beam axis was measured. In the BLT-CBCT fusion method, the 3D torso on BLT and CBCT was registered and the 3D offset of the respective source centroids was calculated. The setup results were independent of the carcass being immobilized or not due to the onset of rigor mortis. The 2D offset of the perceived BL source position from the CBCT bulb position was 2.3 mm ± 1.3 mm. The 3D offset between BLT and CBCT was 1.5 mm ± 0.9 mm. Given the rigidity of the carcasses, the setup results represent the best that can be achieved with off-line 2D BLI and 3D BLT. The setup uncertainty would require the use of undesirably large margin of 4–5 mm. The results compel the implementation of on-board BLT capability on the SARRP to eliminate setup error and to improve BLT accuracy. PMID:23578189

How do typographical factors affect reading text and comprehension performance in Arabic?

PubMed

Ganayim, Deia; Ibrahim, Raphiq

2013-04-01

The objective of this study was to establish basic reading performance that could lead to useful design recommendations for print display text formats and layouts for the improvement of reading and comprehension performance of print text, such as academic writings, books, and newspapers, of Arabic language. Readability of English print text has been shown to be influenced by a number of typographical variables, including interline spacing, column setting and line length, and so on.Therefore, it is very important to improve the reading efficiency and satisfaction of print text reading and comprehension by following simple design guidelines. Most existing research on readability of print text is oriented to build guidelines for designing English texts rather than Arabic. However, guidelines built for English script cannot be simply applied for Arabic script because of orthographic differences. In the current study, manipulating interline spacing and column setting and line length generated nine text layouts. The reading and comprehension performance of 210 native Arab students assigned randomly to the different text layouts was compared. Results showed that the use of multicolumn setting (with medium or short line length) affected comprehension achievement but not reading and comprehension speed. Participants' comprehension scores were better for the single-column (with long line length) than for the multicolumn setting. However, no effect was found for interline spacing. The recommendations for appropriate print text format and layout in Arabic language based on the results of objective measures facilitating reading and comprehension performance is a single-column (with long line length) layout with no relevance of the interline spacing.

Pharmacodynamics of levofloxacin in a murine pneumonia model of Pseudomonas aeruginosa infection: determination of epithelial lining fluid targets.

PubMed

Louie, Arnold; Fregeau, Christine; Liu, Weiguo; Kulawy, Robert; Drusano, G L

2009-08-01

The dose choice for Pseudomonas aeruginosa remains a matter of debate. The actual exposure targets required for multilog killing of organisms at the primary infection site have not been delineated. We studied Pseudomonas aeruginosa PAO1 using a murine model of pneumonia. We employed a large mathematical model to fit all the concentration-time data in plasma and epithelial lining fluid (ELF) as well as colony counts in lung simultaneously for all drug doses. Penetration into ELF was calculated to be approximately 77.7%, as indexed to the ratio of the area under the concentration-time curve for ELF (AUC(ELF)) to the AUC(plasma). We determined the ELF concentration-time profile required to drive a stasis response as well as 1-, 2-, or 3-log(10)(CFU/g) kill. AUC/MIC ratios of 12.4, 31.2, 62.8, and 127.6 were required to drive these bacterial responses. Emergence of resistance was seen only at the two lowest doses (three of five animals at 50 mg/kg [body weight] and one of five animals at 100 mg/kg). The low exposure targets were likely driven by a low mutational frequency to resistance. Bridging to humans was performed using Monte Carlo simulation. With a 750-mg levofloxacin dose, target attainment rates fell below 90% at 4 mg/liter, 1 mg/liter, and 0.5 mg/liter for 1-, 2-, and 3-log kills, respectively. Given the low exposure targets seen with this strain, we conclude that levofloxacin at a 750-mg dose is not adequate for serious Pseudomonas aeruginosa pneumonia as a single agent. More isolates need to be studied to make these observations more robust.

Conducting Qualitative Data Analysis: Reading Line-by-Line, but Analyzing by Meaningful Qualitative Units

ERIC Educational Resources Information Center

Chenail, Ronald J.

2012-01-01

In the first of a series of "how-to" essays on conducting qualitative data analysis, Ron Chenail points out the challenges of determining units to analyze qualitatively when dealing with text. He acknowledges that although we may read a document word-by-word or line-by-line, we need to adjust our focus when processing the text for purposes of…

Dual responsive PNIPAM-chitosan targeted magnetic nanopolymers for targeted drug delivery

NASA Astrophysics Data System (ADS)

Yadavalli, Tejabhiram; Ramasamy, Shivaraman; Chandrasekaran, Gopalakrishnan; Michael, Isaac; Therese, Helen Annal; Chennakesavulu, Ramasamy

2015-04-01

A dual stimuli sensitive magnetic hyperthermia based drug delivery system has been developed for targeted cancer treatment. Thermosensitive amine terminated poly-N-isopropylacrylamide complexed with pH sensitive chitosan nanoparticles was prepared as the drug carrier. Folic acid and fluorescein were tagged to the nanopolymer complex via N-hydroxysuccinimide and ethyl-3-(3-dimethylaminopropyl)carbodiimide reaction to form a fluorescent and cancer targeting magnetic carrier system. The formation of the polymer complex was confirmed using infrared spectroscopy. Gadolinium doped nickel ferrite nanoparticles prepared by a hydrothermal method were encapsulated in the polymer complex to form a magnetic drug carrier system. The proton relaxation studies on the magnetic carrier system revealed a 200% increase in the T1 proton relaxation rate. These magnetic carriers were loaded with curcumin using solvent evaporation method with a drug loading efficiency of 86%. Drug loaded nanoparticles were tested for their targeting and anticancer properties on four cancer cell lines with the help of MTT assay. The results indicated apoptosis of cancer cell lines within 3 h of incubation.

Reader, Text, Translation, and Interpretive Potentials.

ERIC Educational Resources Information Center

Dollerup, Cay; And Others

No matter what pains translators take to produce a target-language text "identical" to the source-language text, criticism and/or translation of an original literary work cannot be the same in different language communities. That translation may change potentialities in the textual experience is particularly obvious in literature with a…

Validating presupposed versus focused text information.

PubMed

Singer, Murray; Solar, Kevin G; Spear, Jackie

2017-04-01

There is extensive evidence that readers continually validate discourse accuracy and congruence, but that they may also overlook conspicuous text contradictions. Validation may be thwarted when the inaccurate ideas are embedded sentence presuppositions. In four experiments, we examined readers' validation of presupposed ("given") versus new text information. Throughout, a critical concept, such as a truck versus a bus, was introduced early in a narrative. Later, a character stated or thought something about the truck, which therefore matched or mismatched its antecedent. Furthermore, truck was presented as either given or new information. Mismatch target reading times uniformly exceeded the matching ones by similar magnitudes for given and new concepts. We obtained this outcome using different grammatical constructions and with different antecedent-target distances. In Experiment 4, we examined only given critical ideas, but varied both their matching and the main verb's factivity (e.g., factive know vs. nonfactive think). The Match × Factivity interaction closely resembled that previously observed for new target information (Singer, 2006). Thus, readers can successfully validate given target information. Although contemporary theories tend to emphasize either deficient or successful validation, both types of theory can accommodate the discourse and reader variables that may regulate validation.

Targeting of GLUT1-GLUT5 chimeric proteins in the polarized cell line Caco-2.

PubMed

Inukai, K; Takata, K; Asano, T; Katagiri, H; Ishihara, H; Nakazaki, M; Fukushima, Y; Yazaki, Y; Kikuchi, M; Oka, Y

1997-04-01

Caco-2, a human differentiated intestinal epithelial cell line, is a promising model for investigating the mechanism of polarized targeting of apical and basolateral membrane proteins. We stably transfected rat GLUT5 cDNA and rabbit GLUT1 cDNA into Caco-2 cells with an expression vector. Immunohistochemical study revealed that the GLUT5 protein expressed was localized at apical membranes and that the GLUT1 expressed was present primarily in the basolateral membranes of cells grown on permeable support. Next, to investigate the domain responsible for determining apical vs. basolateral sorting in glucose transporters, we prepared several GLUT1-GLUT5 chimeric cDNAs and transfected them into Caco-2 cells. A GLUT1 [N terminus approximately sixth transmembrane domain (TM6)]-GLUT5 [intracellular loop (IL) approximately C terminus] chimera was observed exclusively at the apical membrane, while GLUT1 (N terminus approximately IL)-GLUT5 (TM7 approximately C terminus) and GLUT1 (N terminus approximately TM12)-GLUT5 (C-terminal domain) chimeras were observed mainly at the basolateral membrane, a localization similar to that of GLUT1. Moreover, using a recombinant adenovirus expression system, we expressed a GLUT5 (N terminus approximately TM6)-GLUT1(IL)-GLUT5(TM7 approximately C-terminus) chimera, which was observed at the basolateral membrane. Based on these results, the C-terminal domain does not determine isoform-specific targeting of GLUT1 and GLUT5. Rather, it is the intracellular loop in glucose transporters that appears to play a pivotal role in apical-basolateral sorting signals in Caco-2 cells.

Targeting MET kinase with the small-molecule inhibitor amuvatinib induces cytotoxicity in primary myeloma cells and cell lines

PubMed Central

2013-01-01

Background MET is a receptor tyrosine kinase that is activated by the ligand HGF and this pathway promotes cell survival, migration, and motility. In accordance with its oncogenic role, MET is constitutively active, mutated, or over-expressed in many cancers. Corollary to its impact, inhibition of MET kinase activity causes reduction of the downstream signaling and demise of cells. In myeloma, a B-cell plasma malignancy, MET is neither mutated nor over-expressed, however, HGF is increased in plasma or serum obtained from myeloma patients and this was associated with poor prognosis. The small-molecule, amuvatinib, inhibits MET receptor tyrosine kinase. Based on this background, we hypothesized that targeting the HGF/MET signaling pathway is a rational approach to myeloma therapy and that myeloma cells would be sensitive to amuvatinib. Methods Expression of MET and HGF mRNAs in normal versus malignant plasma cells was compared during disease progression. Cell death and growth as well as MET signaling pathway were assessed in amuvatinib treated primary myeloma cells and cell lines. Results There was a progressive increase in the transcript levels of HGF (but not MET) from normal plasma cells to refractory malignant plasma cells. Amuvatinib readily inhibited MET phosphorylation in primary CD138+ cells from myeloma patients and in concordance, increased cell death. A 48-hr amuvatinib treatment in high HGF-expressing myeloma cell line, U266, resulted in growth inhibition. Levels of cytotoxicity were time-dependent; at 24, 48, and 72 h, amuvatinib (25 μM) resulted in 28%, 40%, and 55% cell death. Consistent with these data, there was an amuvatinib-mediated decrease in MET phosphorylation in the cell line. Amuvatinib at concentrations of 5, 10, or 25 μM readily inhibited HGF-dependent MET, AKT, ERK and GSK-3-beta phosphorylation. MET-mediated effects were not observed in myeloma cell line that has low MET and/or HGF expression. Conclusions These data suggest that at

Mapping genetic vulnerabilities reveals BTK as a novel therapeutic target in oesophageal cancer.

PubMed

Chong, Irene Yushing; Aronson, Lauren; Bryant, Hanna; Gulati, Aditi; Campbell, James; Elliott, Richard; Pettitt, Stephen; Wilkerson, Paul; Lambros, Maryou B; Reis-Filho, Jorge S; Ramessur, Anisha; Davidson, Michael; Chau, Ian; Cunningham, David; Ashworth, Alan; Lord, Christopher J

2017-08-22

Oesophageal cancer is the seventh most common cause of cancer-related death worldwide. Disease relapse is frequent and treatment options are limited. To identify new biomarker-defined therapeutic approaches for patients with oesophageal cancer, we integrated the genomic profiles of 17 oesophageal tumour-derived cell lines with drug sensitivity data from small molecule inhibitor profiling, identifying drug sensitivity effects associated with cancer driver gene alterations. We also interrogated recently described RNA interference screen data for these tumour cell lines to identify candidate genetic dependencies or vulnerabilities that could be exploited as therapeutic targets. By integrating the genomic features of oesophageal tumour cell lines with siRNA and drug screening data, we identified a series of candidate targets in oesophageal cancer, including a sensitivity to inhibition of the kinase BTK in MYC amplified oesophageal tumour cell lines. We found that this genetic dependency could be elicited with the clinical BTK/ERBB2 kinase inhibitor, ibrutinib. In both MYC and ERBB2 amplified tumour cells, ibrutinib downregulated ERK-mediated signal transduction, cMYC Ser-62 phosphorylation and levels of MYC protein, and elicited G 1 cell cycle arrest and apoptosis, suggesting that this drug could be used to treat biomarker-selected groups of patients with oesophageal cancer. BTK represents a novel candidate therapeutic target in oesophageal cancer that can be targeted with ibrutinib. On the basis of this work, a proof-of-concept phase II clinical trial evaluating the efficacy of ibrutinib in patients with MYC and/or ERBB2 amplified advanced oesophageal cancer is currently underway (NCT02884453). NCT02884453; Pre-results. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Expanding Suicide Crisis Services to Text and Chat.

PubMed

Predmore, Zachary; Ramchand, Rajeev; Ayer, Lynsay; Kotzias, Virginia; Engel, Charles; Ebener, Patricia; Kemp, Janet E; Karras, Elizabeth; Haas, Gretchen L

2017-07-01

Crisis support services have historically been offered by phone-based suicide prevention hotlines, but are increasingly becoming available through alternative modalities, including Internet chat and text messaging. To better understand differences in the use of phone and chat/text services. We conducted semistructured interviews with call responders at the Veterans Crisis Line who utilize multimodal methods to respond to veterans in crisis. Responders indicated that veterans may access the chat/text service primarily for reasons that included a desire for anonymity and possible inability to use the phone. Responders were divided on whether callers and chatters presented with different issues or risk of suicide; however, they suggested that veterans frequently use chat/text to make their first contact with mental health services. We spoke with call responders, not the veterans themselves. Additionally, as this is qualitative research, applicability to other settings may be limited. While new platforms offer promise, participants also indicated that chat services can supplement phone lines, but not replace them.

Studies of uranium carbide targets of a high density

NASA Astrophysics Data System (ADS)

Panteleev, V. N.; Alyakrinskiy, O.; Barbui, M.; Barzakh, A. E.; Dubois, M.; Eleon, C.; Essabaa, S.; Fedorov, D. V.; Gaubert, G.; Ionan, A. M.; Ivanov, V. S.; Jardin, P.; Lau, C.; Leroy, R.; Lhersonneau, G.; Mezilev, K. A.; Mhamed, C.; Molkanov, P. L.; Moroz, F. V.; Orlov, S. Yu.; Saint Laurent, M. G.; Stroe, L.; Tecchio, L. B.; Tonezzer, M.; Villari, A. C. C.; Volkov, Yu. M.

2008-10-01

Production of Cs and Fr isotopes from uranium carbide targets of a high density has been investigated at IRIS (Investigation Radioactive Isotopes at Synchrocyclotron), Gatchina. The UC target material with a density of 12 g/cm3 was prepared in a form of pellets. Two targets were tested on-line under the same temperature conditions: (a) a reference small target with a thickness of 4.5 g/cm2; (b) a heavier (so called intermediate) target with a thickness of 91 g/cm2. Yields and release efficiencies of nuclides with half-lives from some minutes to some milliseconds produced by 1 GeV protons in these targets are presented. It is remarkable that yields, even those of very short-lived isotopes such as 214Fr (T1/2 = 5 ms) and 219Fr (T1/2 = 20 ms), increase proportionally to the target thickness. A one month off-line heating test of the 91 g/cm2 target at a temperature of 2000 °C has been carried out successfully. The yields and release efficiencies of Cs and Fr measured on-line before and after the heating test coincided within the limits of measurement errors, thereby demonstrating the conservation of the target unit parameters. Based on these very promising results, a heavier target with a mass about 0.7 kg is prepared presently at IRIS.

Outcome of Molecular Targeted Agents Plus Chemotherapy for Second-Line Therapy of Metastatic Colorectal Cancer: A Meta-Analysis of Randomized Trials.

PubMed

Pei, Xueqing; Liu, Yu; Sun, Liwei; Zhang, Jun; Fang, Yuanyuan; Liao, Xin; Liu, Jian; Zhang, Cuntai; Yin, Tiejun

2016-12-01

The aim of this study was to evaluate the efficacy and toxicity of molecular targeted agents plus chemotherapy compared with chemotherapy alone as second-line therapy for patients with metastatic colorectal cancer (mCRC). We identified randomized controlled trials that compared molecular targeted agents plus chemotherapy with chemotherapy alone by searching the PubMed and Embase databases for articles published between January 2000 and September 2015. The outcome measures included progression-free survival, overall survival, objective response rate, and adverse events. Two investigators independently performed the information retrieval, screening, and data extraction. Stata 10.0 software was used to statistically analyze the extracted data. In accordance with our inclusion criteria, 11 trials, with a total of 7440 patients, were included in this meta-analysis through rounds of selection. We divided the biologic agents used into 3 subgroups based on the type of biologic agents-vascular endothelial growth factor (VEGF) inhibitor, epidermal growth factor receptor inhibitor, and other pathway inhibitors. Our results suggested that the regimen of a molecular targeted agent plus chemotherapy had a significant advantage in progression-free survival, overall survival, and objective response rate over chemotherapy alone (hazard ratio, 0.74; 95% confidence interval [CI], 0.70-0.78; hazard ratio, 0.88; 95% CI, 0.83-0.93; risk ratio, 2.24; 95% CI: 1.58-3.17, respectively). However, the rate of grade ≥ 3 adverse events was also higher in the combination therapy arm (risk ratio, 1.25; 95% CI, 1.17-1.33). Subgroup analysis showed that the combination of VEGF inhibitor with chemotherapy had a significant advantage in PFS, OS, and ORR over chemotherapy alone, but there was also a higher risk ratio in adverse events for this combination compared with the control group. In conclusion, a molecular targeted agent, especially VEGF inhibitor, plus chemotherapy is a worthwhile

Nebular line emission from z > 7 galaxies in a cosmological simulation: rest-frame UV to optical lines

NASA Astrophysics Data System (ADS)

Shimizu, Ikkoh; Inoue, Akio K.; Okamoto, Takashi; Yoshida, Naoki

2016-10-01

We have performed very large and high-resolution cosmological hydrodynamic simulations in order to investigate detectability of nebular lines in the rest-frame ultraviolet (UV) to optical wavelength range from galaxies at z > 7. We find that the expected line fluxes are very well correlated with the apparent UV magnitudes. The C IV 1549 Å and C III] 1909 Å lines of galaxies brighter than 26 AB magnitudes are detectable with current facilities such as the Very Large Telescope (VLT) XShooter and the Keck Multi-Object Spectrometer for Infra-Red Exploration (MOSFIRE). Metal lines such as C IV 1549 Å, C III] 1909 Å, [O II] 3727 Å and [O III] 4959/5007 Å are good targets for spectroscopic observation with the Thirty-Metre Telescope (TMT), European Extremely Large Telescope (E-ELT), Giant Magellan Telescope (GMT) and James Webb Space Telescope (JWST). We also expect Hα and Hβ lines to be detectable with these telescopes. Additionally, we predict the detectability of nebular lines for z > 10 galaxies, which will be found with JWST, the Wide-Field Infrared Survey Telescope (WFIRST) and First Light And Reionization Explorer (FLARE) (11 ≤ z ≤ 15). We conclude that the C IV 1549 Å, C III] 1909 Å, [O III] 4959/5007 Å and Hβ lines from even z ˜15 galaxies could be strong targets for TMT, E-ELT and JWST. We also find that magnification by gravitational lensing is of great help in detecting such high-z galaxies. According to our model, the C III] 1909 Å line in z > 9 galaxy candidates is detectable even using current facilities.

Towards large scale multi-target tracking

NASA Astrophysics Data System (ADS)

Vo, Ba-Ngu; Vo, Ba-Tuong; Reuter, Stephan; Lam, Quang; Dietmayer, Klaus

2014-06-01

Multi-target tracking is intrinsically an NP-hard problem and the complexity of multi-target tracking solutions usually do not scale gracefully with problem size. Multi-target tracking for on-line applications involving a large number of targets is extremely challenging. This article demonstrates the capability of the random finite set approach to provide large scale multi-target tracking algorithms. In particular it is shown that an approximate filter known as the labeled multi-Bernoulli filter can simultaneously track one thousand five hundred targets in clutter on a standard laptop computer.

Generating Automated Text Complexity Classifications That Are Aligned with Targeted Text Complexity Standards. Research Report. ETS RR-10-28

ERIC Educational Resources Information Center

Sheehan, Kathleen M.; Kostin, Irene; Futagi, Yoko; Flor, Michael

2010-01-01

The Common Core Standards call for students to be exposed to a much greater level of text complexity than has been the norm in schools for the past 40 years. Textbook publishers, teachers, and assessment developers are being asked to refocus materials and methods to ensure that students are challenged to read texts at steadily increasing…

Prognostic outcome in patients treated with tyrosine kinase inhibitors as first-line molecular-targeted therapy for metastatic renal cell carcinoma: Experience in real-world clinical practice in Japan

PubMed Central

MIYAZAKI, AKIRA; MIYAKE, HIDEAKI; HARADA, KEN-ICHI; INOUE, TAKA-AKI; FUJISAWA, MASATO

2015-01-01

The aim of this study was to evaluate the oncological efficacy of tyrosine kinase inhibitors (TKIs) as first-line molecular-targeted therapy for Japanese patients with metastatic renal cell carcinoma (mRCC) in a routine clinical setting. This study included a total of 271 consecutive Japanese patients with TKI-naive mRCC, including 172 patients who received sorafenib and 99 who received sunitinib for ≥2 months as a first-line molecular-targeted agent. The prognostic outcomes of these patients were retrospectively assessed. During the observation period (median, 19 months), 126 patients (46.5%) succumbed to the disease and the median overall survival (OS) for the entire cohort was 33.1 months. The univariate analysis identified the Memorial Sloan-Kettering Cancer Center (MSKCC) classification, C-reactive protein (CRP) level, lymph node metastasis, bone metastasis, liver metastasis, histological subtype and sarcomatoid characteristics as significant predictors of OS. Of these factors, only the MSKCC classification, CRP level and liver metastasis were found to be independently associated with OS in the multivariate analysis. Furthermore, there were significant differences in OS according to the positivity for these 3 independent risk factors (i.e., negative for all factors vs. positive for a single factor vs. positive for 2 or 3 factors). These findings suggest that the introduction of TKIs as first-line molecular-targeted agents resulted in favorable cancer control outcomes in Japanese mRCC patients and that the prognosis of these patients may be stratified by 3 potential parameters, including the MSKCC classification, CRP level and liver metastasis. PMID:26137274

Interactive-predictive detection of handwritten text blocks

NASA Astrophysics Data System (ADS)

Ramos Terrades, O.; Serrano, N.; Gordó, A.; Valveny, E.; Juan, A.

2010-01-01

A method for text block detection is introduced for old handwritten documents. The proposed method takes advantage of sequential book structure, taking into account layout information from pages previously transcribed. This glance at the past is used to predict the position of text blocks in the current page with the help of conventional layout analysis methods. The method is integrated into the GIDOC prototype: a first attempt to provide integrated support for interactive-predictive page layout analysis, text line detection and handwritten text transcription. Results are given in a transcription task on a 764-page Spanish manuscript from 1891.

Cost-effectiveness analysis of 1st through 3rd line sequential targeted therapy in HER2-positive metastatic breast cancer in the United States

PubMed Central

Adunlin, Georges; Ali, Askal A.; Zeichner, Simon B.; de Lima Lopes, Gilberto; Kohn, Christine G.; Montero, Alberto J.

2016-01-01

Purpose Based on available phase III trial data, we performed a cost-effectiveness analysis of different treatment strategies that can be used in patients with newly diagnosed HER2-positive metastatic breast cancer (mBC). Patients and Methods We constructed a Markov model to assess the cost-effectiveness of four different HER2 targeted treatment sequences in patients with HER2-positive mBC treated in the U.S. The model followed patients weekly over their remaining life expectancies. Health states considered were progression free survival (PFS) 1st to 3rd lines, and death. Transitional probabilities were based on published phase III trials. Cost data (2015 US dollars) was captured from the U.S. Centers for Medicare and Medicaid Services (CMS) drug payment table and physician fee schedule. Health utility data were extracted from published studies. The outcomes considered were PFS, OS, costs, QALYs, the incremental cost per QALY gained ratio, and the net monetary benefit. Deterministic and probabilistic sensitivity analyses assessed the uncertainty around key model parameters and their joint impact on the base-case results. Results The combination of trastuzumab, pertuzumab, and docetaxel (THP) as first-line therapy, trastuzumab emtansine (T-DM1) as second-line therapy, and lapatinib/capecitabine third-line resulted in 1.81 QALYs, at a cost of $335,231.35. The combination of trastuzumab/docetaxel as first line without subsequent T-DM1 or pertuzumab yielded 1.41 QALYs, at a cost of $175,240.69. The least clinically effective sequence (1.27 QALYs), but most cost-effective at a total cost of $149,250.19, was trastuzumab/docetaxel as first-line therapy, T-DM1 as second-line therapy, and trastuzumab/lapatinib as third line therapy. Conclusion Our results suggest that THP as first-line therapy, followed by T-DM1 as second-line therapy, would require at least a 50% reduction in the total drug acquisition cost for it to be considered a cost-effective strategy. PMID:27654970

Cost-effectiveness of precision medicine in the fourth-line treatment of metastatic lung adenocarcinoma: An early decision analytic model of multiplex targeted sequencing.

PubMed

Doble, Brett; John, Thomas; Thomas, David; Fellowes, Andrew; Fox, Stephen; Lorgelly, Paula

2017-05-01

To identify parameters that drive the cost-effectiveness of precision medicine by comparing the use of multiplex targeted sequencing (MTS) to select targeted therapy based on tumour genomic profiles to either no further testing with chemotherapy or no further testing with best supportive care in the fourth-line treatment of metastatic lung adenocarcinoma. A combined decision tree and Markov model to compare costs, life-years, and quality-adjusted life-years over a ten-year time horizon from an Australian healthcare payer perspective. Data sources included the published literature and a population-based molecular cohort study (Cancer 2015). Uncertainty was assessed using deterministic sensitivity analyses and quantified by estimating expected value of perfect/partial perfect information. Uncertainty due to technological/scientific advancement was assessed through a number of plausible future scenario analyses. Point estimate incremental cost-effective ratios indicate that MTS is not cost-effective for selecting fourth-line treatment of metastatic lung adenocarcinoma. Lower mortality rates during testing and for true positive patients, lower health state utility values for progressive disease, and targeted therapy resulting in reductions in inpatient visits, however, all resulted in more favourable cost-effectiveness estimates for MTS. The expected value to decision makers of removing all current decision uncertainty was estimated to be between AUD 5,962,843 and AUD 13,196,451, indicating that additional research to reduce uncertainty may be a worthwhile investment. Plausible future scenarios analyses revealed limited improvements in cost-effectiveness under scenarios of improved test performance, decreased costs of testing/interpretation, and no biopsy costs/adverse events. Reductions in off-label targeted therapy costs, when considered together with the other scenarios did, however, indicate more favourable cost-effectiveness of MTS. As more clinical evidence is

Teaching Braille Line Tracking Using Stimulus Fading

ERIC Educational Resources Information Center

Scheithauer, Mindy C.; Tiger, Jeffrey H.

2014-01-01

Line tracking is a prerequisite skill for braille literacy that involves moving one's finger horizontally across a line of braille text and identifying when a line ends so the reader may reset his or her finger on the subsequent line. Current procedures for teaching line tracking are incomplete, because they focus on tracking lines with only…

An analysis of possible off target effects following CAS9/CRISPR targeted deletions of neuropeptide gene enhancers from the mouse genome.

PubMed

Hay, Elizabeth Anne; Khalaf, Abdulla Razak; Marini, Pietro; Brown, Andrew; Heath, Karyn; Sheppard, Darrin; MacKenzie, Alasdair

2017-08-01

We have successfully used comparative genomics to identify putative regulatory elements within the human genome that contribute to the tissue specific expression of neuropeptides such as galanin and receptors such as CB1. However, a previous inability to rapidly delete these elements from the mouse genome has prevented optimal assessment of their function in-vivo. This has been solved using CAS9/CRISPR genome editing technology which uses a bacterial endonuclease called CAS9 that, in combination with specifically designed guide RNA (gRNA) molecules, cuts specific regions of the mouse genome. However, reports of "off target" effects, whereby the CAS9 endonuclease is able to cut sites other than those targeted, limits the appeal of this technology. We used cytoplasmic microinjection of gRNA and CAS9 mRNA into 1-cell mouse embryos to rapidly generate enhancer knockout mouse lines. The current study describes our analysis of the genomes of these enhancer knockout lines to detect possible off-target effects. Bioinformatic analysis was used to identify the most likely putative off-target sites and to design PCR primers that would amplify these sequences from genomic DNA of founder enhancer deletion mouse lines. Amplified DNA was then sequenced and blasted against the mouse genome sequence to detect off-target effects. Using this approach we were unable to detect any evidence of off-target effects in the genomes of three founder lines using any of the four gRNAs used in the analysis. This study suggests that the problem of off-target effects in transgenic mice have been exaggerated and that CAS9/CRISPR represents a highly effective and accurate method of deleting putative neuropeptide gene enhancer sequences from the mouse genome. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

Characterization of endogenous calcium responses in neuronal cell lines.

PubMed

Vetter, Irina; Lewis, Richard J

2010-03-15

An increasing number of putative therapeutic targets have been identified in recent years for the treatment of neuronal pathophysiologies including pain, epilepsy, stroke and schizophrenia. Many of these targets signal through calcium (Ca(2+)), either by directly facilitating Ca(2+) influx through an ion channel, or through activation of G proteins that couple to intracellular Ca(2+) stores or voltage-gated Ca(2+) channels. Immortalized neuronal cell lines are widely used models to study neuropharmacology. However, systematic pharmacological characterization of the receptors and ion channels expressed in these cell lines is lacking. In this study, we systematically assessed endogenous Ca(2+) signaling in response to addition of agonists at potential therapeutic targets in a range of cell lines of neuronal origin (ND7/23, SH-SY5Y, 50B11, F11 and Neuro2A cells) as well as HEK293 cells, a cell line commonly used for over-expression of receptors and ion channels. This study revealed a remarkable diversity of endogenous Ca(2+) responses in these cell lines, with one or more cell lines responding to addition of trypsin, bradykinin, ATP, nicotine, acetylcholine, histamine and neurotensin. Subtype specificity of these responses was inferred from agonist potency and the effect of receptor subtype specific antagonist. Surprisingly, HEK293 and SH-SY5Y cells responded to the largest number of agonists with potential roles in neuronal signaling. These findings have implications for the heterologous expression of neuronal receptors and ion channels in these cell lines, and highlight the potential of neuron-derived cell lines for the study of a range of endogenously expressed receptors and ion channels that signal through Ca(2+). Crown Copyright 2009. Published by Elsevier Inc. All rights reserved.

A new ETV6-NTRK3 cell line model reveals MALAT1 as a novel therapeutic target - a short report.

PubMed

Chen, Suning; Nagel, Stefan; Schneider, Bjoern; Dai, Haiping; Geffers, Robert; Kaufmann, Maren; Meyer, Corinna; Pommerenke, Claudia; Thress, Kenneth S; Li, Jiao; Quentmeier, Hilmar; Drexler, Hans G; MacLeod, Roderick A F

2018-02-01

Previously, the chromosomal translocation t(12;15)(p13;q25) has been found to recurrently occur in both solid tumors and leukemias. This translocation leads to ETV6-NTRK3 (EN) gene fusions resulting in ectopic expression of the NTRK3 neurotropic tyrosine receptor kinase moiety as well as oligomerization through the donated ETV6-sterile alpha motif domain. As yet, no in vitro cell line model carrying this anomaly is available. Here we genetically characterized the acute promyelocytic leukemia (APL) cell line AP-1060 and, by doing so, revealed the presence of a t(12;15)(p13;q25). Subsequently, we evaluated its suitability as a model for this important clinical entity. Spectral karyotyping, fluorescence in situ hybridization (FISH), and genomic and transcriptomic microarray-based profiling were used to screen for the presence of EN fusions. qRT-PCR was used for quantitative expression analyses. Responses to AZ-23 (NTRK) and wortmannin (PI3K) inhibitors, as well as to arsenic trioxide (ATO), were assessed using colorimetric assays. An AZ-23 microarray screen was used to define the EN targetome, which was parsed bioinformatically. MAPK1 and MALAT1 activation were assayed using Western blotting and RNA-FISH, respectively, whereas an AML patient cohort was used to assess the clinical occurrence of MALAT1 activation. An EN fusion was detected in AP1060 cells which, accordingly, turned out to be hypersensitive to AZ-23. We also found that AZ-23 can potentiate the effect of ATO and inhibit the phosphorylation of its canonical target MAPK1. The AZ-23 microarray screen highlighted a novel EN target, MALAT1, which also proved sensitive to wortmannin. Finally, we found that MALAT1 was massively up-regulated in a subset of AML patients. From our data we conclude that AP-1060 may serve as a first publicly available preclinical model for EN. In addition, we conclude that these EN-positive cells are sensitive to the NTRK inhibitor AZ-23 and that this inhibitor may potentiate the

Film clips and narrative text as subjective emotion elicitation techniques.

PubMed

Zupan, Barbra; Babbage, Duncan R

2017-01-01

Film clips and narrative text are useful techniques in eliciting emotion in a laboratory setting but have not been examined side-by-side using the same methodology. This study examined the self-identification of emotions elicited by film clip and narrative text stimuli to confirm that selected stimuli appropriately target the intended emotions. Seventy participants viewed 30 film clips, and 40 additional participants read 30 narrative texts. Participants identified the emotion experienced (happy, sad, angry, fearful, neutral-six stimuli each). Eighty-five percent of participants self-identified the target emotion for at least two stimuli for all emotion categories of film clips, except angry (only one) and for all categories of narrative text, except fearful (only one). The most effective angry text was correctly identified 74% of the time. Film clips were more effective in eliciting all target emotions in participants for eliciting the correct emotion (angry), intensity rating (happy, sad), or both (fearful).

Building Background Knowledge through Reading: Rethinking Text Sets

ERIC Educational Resources Information Center

Lupo, Sarah M.; Strong, John Z.; Lewis, William; Walpole, Sharon; McKenna, Michael C.

2018-01-01

To increase reading volume and help students access challenging texts, the authors propose a four-dimensional framework for text sets. The quad text set framework is designed around a target text: a challenging content area text, such as a canonical literary work, research article, or historical primary source document. The three remaining…

CAPABILITY TO RECOVER PLUTONIUM-238 IN H-CANYON/HB-LINE

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

Fuller, Kenneth S. Jr.; Smith, Robert H. Jr.; Goergen, Charles R.

2013-01-09

Plutonium-238 is used in Radioisotope Thermoelectric Generators (RTGs) to generate electrical power and in Radioisotope Heater Units (RHUs) to produce heat for electronics and environmental control for deep space missions. The domestic supply of Pu-238 consists of scrap material from previous mission production or material purchased from Russia. Currently, the United States has no significant production scale operational capability to produce and separate new Pu-238 from irradiated neptunium-237 targets. The Department of Energy - Nuclear Energy is currently evaluating and developing plans to reconstitute the United States capability to produce Pu-238 from irradiated Np-237 targets. The Savannah River Site hadmore » previously produced and/or processed all the Pu-238 utilized in Radioisotope Thermoelectric Generators (RTGs) for deep space missions up to and including the majority of the plutonium for the Cassini Mission. The previous full production cycle capabilities included: Np-237 target fabrication, target irradiation, target dissolution and Np-237 and Pu-238 separation and purification, conversion of Np-237 and Pu-238 to oxide, scrap recovery, and Pu-238 encapsulation. The capability and equipment still exist and could be revitalized or put back into service to recover and purify Pu-238/Np-237 or broken General Purpose Heat Source (GPHS) pellets utilizing existing process equipment in HB-Line Scrap Recovery, and H-anyon Frame Waste Recovery processes. The conversion of Np-237 and Pu-238 to oxide can be performed in the existing HB-Line Phase-2 and Phase-3 Processes. Dissolution of irradiated Np-237 target material, and separation and purification of Np-237 and Pu-238 product streams would be possible at production rates of ~ 2 kg/month of Pu-238 if the existing H-Canyon Frames Process spare equipment were re-installed. Previously, the primary H-Canyon Frames equipment was removed to be replaced: however, the replacement project was stopped. The spare

Recombinant protein production from stable mammalian cell lines and pools.

PubMed

Hacker, David L; Balasubramanian, Sowmya

2016-06-01

We highlight recent developments for the production of recombinant proteins from suspension-adapted mammalian cell lines. We discuss the generation of stable cell lines using transposons and lentivirus vectors (non-targeted transgene integration) and site-specific recombinases (targeted transgene integration). Each of these methods results in the generation of cell lines with protein yields that are generally superior to those achievable through classical plasmid transfection that depends on the integration of the transfected DNA by non-homologous DNA end-joining. This is the main reason why these techniques can also be used for the generation of stable cell pools, heterogenous populations of recombinant cells generated by gene delivery and genetic selection without resorting to single cell cloning. This allows the time line from gene transfer to protein production to be reduced. Copyright © 2016 Elsevier Ltd. All rights reserved.

Line-of-sight deposition method

DOEpatents

Patten, J.W.; McClanahan, E.D.; Bayne, M.A.

1980-04-16

A line-of-sight method of depositing a film having substantially 100% of theoretical density on a substrate. A pressure vessel contains a target source having a surface thereof capable of emitting particles therefrom and a substrate with the source surface and the substrate surface positioned such that the source surface is substantially parallel to the direction of the particles impinging upon the substrate surface, the distance between the most remote portion of the substrate surface receiving the particles and the source surface emitting the particles in a direction parallel to the substrate surface being relatively small. The pressure in the vessel is maintained less than about 5 microns to prevent scattering and permit line-of-sight deposition. By this method the angles of incidence of the particles impinging upon the substrate surface are in the range of from about 45/sup 0/ to 90/sup 0/ even when the target surface area is greatly expanded to increase the deposition rate.

Line-of-sight deposition method

DOEpatents

Patten, James W.; McClanahan, Edwin D.; Bayne, Michael A.

1981-01-01

A line-of-sight method of depositing a film having substantially 100% of theoretical density on a substrate. A pressure vessel contains a target source having a surface thereof capable of emitting particles therefrom and a substrate with the source surface and the substrate surface positioned such that the source surface is substantially parallel to the direction of the particles impinging upon the substrate surface, the distance between the most remote portion of the substrate surface receiving the particles and the source surface emitting the particles in a direction parallel to the substrate surface being relatively small. The pressure in the vessel is maintained less than about 5 microns to prevent scattering and permit line-of-sight deposition. By this method the angles of incidence of the particles impinging upon the substrate surface are in the range of from about 45.degree. to 90.degree. even when the target surface area is greatly expanded to increase the deposition rate.

Reverberation Mapping of Optical Emission Lines in Five Active Galaxies

DOE PAGES

Fausnaugh, M. M.; Grier, C. J.; Bentz, M. C.; ...

2017-05-10

We present the first results from an optical reverberation mapping campaign executed in 2014 targeting the active galactic nuclei (AGNs) MCG+08-11-011, NGC 2617, NGC 4051, 3C 382, and Mrk 374. Our targets have diverse and interesting observational properties, including a “changing look” AGN and a broad-line radio galaxy. Based on continuum-Hβ lags, we measure black hole masses for all five targets. We also obtain Hγ and He II λ4686 lags for all objects except 3C 382. The He II λ4686 lags indicate radial stratification of the BLR, and the masses derived from different emission lines are in general agreement. Themore » relative responsivities of these lines are also in qualitative agreement with photoionization models. Finally, these spectra have extremely high signal-to-noise ratios (100–300 per pixel) and there are excellent prospects for obtaining velocity-resolved reverberation signatures.« less

Reverberation Mapping of Optical Emission Lines in Five Active Galaxies

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

Fausnaugh, M. M.; Denney, K. D.; Peterson, B. M.

2017-05-10

We present the first results from an optical reverberation mapping campaign executed in 2014 targeting the active galactic nuclei (AGNs) MCG+08-11-011, NGC 2617, NGC 4051, 3C 382, and Mrk 374. Our targets have diverse and interesting observational properties, including a “changing look” AGN and a broad-line radio galaxy. Based on continuum-H β lags, we measure black hole masses for all five targets. We also obtain H γ and He ii λ 4686 lags for all objects except 3C 382. The He ii λ 4686 lags indicate radial stratification of the BLR, and the masses derived from different emission lines aremore » in general agreement. The relative responsivities of these lines are also in qualitative agreement with photoionization models. These spectra have extremely high signal-to-noise ratios (100–300 per pixel) and there are excellent prospects for obtaining velocity-resolved reverberation signatures.« less

Temporal reasoning over clinical text: the state of the art

PubMed Central

Sun, Weiyi; Rumshisky, Anna; Uzuner, Ozlem

2013-01-01

Objectives To provide an overview of the problem of temporal reasoning over clinical text and to summarize the state of the art in clinical natural language processing for this task. Target audience This overview targets medical informatics researchers who are unfamiliar with the problems and applications of temporal reasoning over clinical text. Scope We review the major applications of text-based temporal reasoning, describe the challenges for software systems handling temporal information in clinical text, and give an overview of the state of the art. Finally, we present some perspectives on future research directions that emerged during the recent community-wide challenge on text-based temporal reasoning in the clinical domain. PMID:23676245

Comparison of steroid receptors from the androgen responsive DDT1 cell line and the nonresponsive HVP cell line.

PubMed

Norris, J S; Kohler, P O

1978-01-01

Two hamster cell lines have been isolated from androgen target tissue. The DDT1 cells derived from ductus deferens tissue exhibit a growth response to androgens, while the HVP cells derived from ventral prostate are androgen unresponsive. Both cell lines contain androgen receptors, that are similar when compared by kinetic methods, sedimentation velocity, chromatographic procedures or nuclear translocation ability. The forms of the high salt extracted nuclear receptors are indistinguishable chromatographically. Therefore, we postulate that the lesion preventing androgen induced growth in the HVP cell line is subseqent to nuclear translocation of the steroid receptor complex.

Hybrid adaptive radiotherapy with on-line MRI in cervix cancer IMRT.

PubMed

Oh, Seungjong; Stewart, James; Moseley, Joanne; Kelly, Valerie; Lim, Karen; Xie, Jason; Fyles, Anthony; Brock, Kristy K; Lundin, Anna; Rehbinder, Henrik; Milosevic, Michael; Jaffray, David; Cho, Young-Bin

2014-02-01

Substantial organ motion and tumor shrinkage occur during radiotherapy for cervix cancer. IMRT planning studies have shown that the quality of radiation delivery is influenced by these anatomical changes, therefore the adaptation of treatment plans may be warranted. Image guidance with off-line replanning, i.e. hybrid-adaptation, is recognized as one of the most practical adaptation strategies. In this study, we investigated the effects of soft tissue image guidance using on-line MR while varying the frequency of off-line replanning on the adaptation of cervix IMRT. 33 cervical cancer patients underwent planning and weekly pelvic MRI scans during radiotherapy. 5 patients of 33 were identified in a previous retrospective adaptive planning study, in which the coverage of gross tumor volume/clinical target volume (GTV/CTV) was not acceptable given single off-line IMRT replan using a 3mm PTV margin with bone matching. These 5 patients and a randomly selected 10 patients from the remaining 28 patients, a total of 15 patients of 33, were considered in this study. Two matching methods for image guidance (bone to bone and soft tissue to dose matrix) and three frequencies of off-line replanning (none, single, and weekly) were simulated and compared with respect to target coverage (cervix, GTV, lower uterus, parametrium, upper vagina, tumor related CTV and elective lymph node CTV) and OAR sparing (bladder, bowel, rectum, and sigmoid). Cost (total process time) and benefit (target coverage) were analyzed for comparison. Hybrid adaptation (image guidance with off-line replanning) significantly enhanced target coverage for both 5 difficult and 10 standard cases. Concerning image guidance, bone matching was short of delivering enough doses for 5 difficult cases even with a weekly off-line replan. Soft tissue image guidance proved successful for all cases except one when single or more frequent replans were utilized in the difficult cases. Cost and benefit analysis preferred

Processing and Recall of Seductive Details in Scientific Text

ERIC Educational Resources Information Center

Lehman, Stephen; Schraw, Gregory; McCrudden, Matthew T.; Hartley, Kendall

2007-01-01

This study examined how seductive details affect on-line processing of a technical, scientific text. In Experiment 1, each sentence from the experimental text was rated for interest and importance. Participants rated seductive details as being more interesting but less important than main ideas. In Experiment 2, we examined the effect of seductive…

Enabling Quantitative Optical Imaging for In-die-capable Critical Dimension Targets

PubMed Central

Barnes, B.M.; Henn, M.-A.; Sohn, M. Y.; Zhou, H.; Silver, R. M.

2017-01-01

Dimensional scaling trends will eventually bring semiconductor critical dimensions (CDs) down to only a few atoms in width. New optical techniques are required to address the measurement and variability for these CDs using sufficiently small in-die metrology targets. Recently, Qin et al. [Light Sci Appl, 5, e16038 (2016)] demonstrated quantitative model-based measurements of finite sets of lines with features as small as 16 nm using 450 nm wavelength light. This paper uses simulation studies, augmented with experiments at 193 nm wavelength, to adapt and optimize the finite sets of features that work as in-die-capable metrology targets with minimal increases in parametric uncertainty. A finite element based solver for time-harmonic Maxwell's equations yields two- and three-dimensional simulations of the electromagnetic scattering for optimizing the design of such targets as functions of reduced line lengths, fewer number of lines, fewer focal positions, smaller critical dimensions, and shorter illumination wavelength. Metrology targets that exceeded performance requirements are as short as 3 μm for 193 nm light, feature as few as eight lines, and are extensible to sub-10 nm CDs. Target areas measured at 193 nm can be fifteen times smaller in area than current state-of-the-art scatterometry targets described in the literature. This new methodology is demonstrated to be a promising alternative for optical model-based in-die CD metrology. PMID:28757674

D 2 and DT Liquid-Layer Target Shots on NIF

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

Walters, Curtis; Alger, Ethan; Bhandarkar, Suhas

Experiments at the National Ignition Facility (NIF) using targets containing a Deuterium-Tritium (DT) fuel layer have, until recently, required that a high-quality layer of solid deuterium-tritium (herein referred to as an "ice-layer") be formed in the capsule. The development of a process to line the inner surface of a target capsule with a foam layer of a thickness that is typical of icelayers has resulted in the ability to field targets with liquid layers wetting the foam. Successful fielding of liquid-layer targets on NIF required not only a foam lined capsule, but also changes to the capsule filling process andmore » the manner with which the inventory is maintained in the capsule. Additionally, changes to target heater power and the temperature drops across target components were required in order to achieve the desired range of shot temperatures. These changes, and the target's performance during four target shots on NIF will be discussed.« less

Dual-targeting siRNAs

PubMed Central

Tiemann, Katrin; Höhn, Britta; Ehsani, Ali; Forman, Stephen J.; Rossi, John J.; Sætrom, Pål

2010-01-01

We have developed an algorithm for the prediction of dual-targeting short interfering RNAs (siRNAs) in which both strands are deliberately designed to separately target different mRNA transcripts with complete complementarity. An advantage of this approach versus the use of two separate duplexes is that only two strands, as opposed to four, are competing for entry into the RNA-induced silencing complex. We chose to design our dual-targeting siRNAs as Dicer substrate 25/27mer siRNAs, since design features resembling pre-microRNAs (miRNAs) can be introduced for Dicer processing. Seven different dual-targeting siRNAs targeting genes that are potential targets in cancer therapy have been developed including Bcl2, Stat3, CCND1, BIRC5, and MYC. The dual-targeting siRNAs have been characterized for dual target knockdown in three different cell lines (HEK293, HCT116, and PC3), where they were as effective as their corresponding single-targeting siRNAs in target knockdown. The algorithm developed in this study should prove to be useful for predicting dual-targeting siRNAs in a variety of different targets and is available from http://demo1.interagon.com/DualTargeting/. PMID:20410240

Automatic target alignment of the Helios laser system

NASA Astrophysics Data System (ADS)

Liberman, I.; Viswanathan, V. K.; Klein, M.; Seery, B. D.

1980-05-01

An automatic target-alignment technique for the Helios laser facility is reported and verified experimentally. The desired alignment condition is completely described by an autocollimation test. A computer program examines the autocollimated return pattern from the surrogate target and correctly describes any changes required in mirror orientation to yield optimum target alignment with either aberrated or misaligned beams. Automated on-line target alignment is thus shown to be feasible.

From Covert Processes to Overt Outcomes of Refutation Text Reading: The Interplay of Science Text Structure and Working Memory Capacity through Eye Fixations

ERIC Educational Resources Information Center

Ariasi, Nicola; Mason, Lucia

2014-01-01

This study extends current research on the refutation text effect by investigating it in learners with different levels of working memory capacity. The purpose is to outline the link between online processes (revealed by eye fixation indices) and off-line outcomes in these learners. In science education, unlike a standard text, a refutation text…

Dynamics of the Molten Contact Line

NASA Technical Reports Server (NTRS)

Sonin, Ain A.; Duthaler, Gregg; Liu, Michael; Torresola, Javier; Qiu, Taiqing

1999-01-01

The purpose of this program is to develop a basic understanding of how a molten material front spreads over a solid that is below its melting point, arrests, and freezes. Our hope is that the work will contribute toward a scientific knowledge base for certain new applications involving molten droplet deposition, including the "printing" of arbitrary three-dimensional objects by precise deposition of individual molten microdrops that solidify after impact. Little information is available at this time on the capillarity-driven motion and arrest of molten contact line regions. Schiaffino and Sonin investigated the arrest of the contact line of a molten microcrystalline wax spreading over a subcooled solid "target" of the same material. They found that contact line arrest takes place at an apparent liquid contact angle that depends primarily on the Stefan number S=c(T(sub f) -T(sub t)/L based on the temperature difference between the fusion point and the target temperature, and proposed that contact line arrest occurs when the liquid's dynamic contact angle approaches the angle of attack of the solidification front just behind the contact line. They also showed, however, that the conventional continuum equations and boundary conditions have no meaningful solution for this angle. The solidification front angle is determined by the heat flux just behind the contact line, and the heat flux is singular at that point. By comparing experiments with numerical computations, Schiaffino and Sonin estimated that the conventional solidification model must break down within a distance of order 0.1 - 1 microns of the contact line. The physical mechanism for this breakdown is as yet undetermined, and no first-principles theory exists for the contact angle at arrest. Schiaffino and Sonin also presented a framework for understanding how to moderate Weber number molten droplet deposition in terms of similarity laws and experimentation. The study is based on experiments with three molten

Capability to Recover Plutonium-238 in H-Canyon/HB-Line - 13248

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

Fuller, Kenneth S. Jr.; Smith, Robert H. Jr.; Goergen, Charles R.

2013-07-01

Plutonium-238 is used in Radioisotope Thermoelectric Generators (RTGs) to generate electrical power and in Radioisotope Heater Units (RHUs) to produce heat for electronics and environmental control for deep space missions. The domestic supply of Pu-238 consists of scrap material from previous mission production or material purchased from Russia. Currently, the United States has no significant production scale operational capability to produce and separate new Pu-238 from irradiated neptunium-237 targets. The Department of Energy - Nuclear Energy is currently evaluating and developing plans to reconstitute the United States capability to produce Pu-238 from irradiated Np-237 targets. The Savannah River Site hadmore » previously produced and/or processed all the Pu-238 utilized in Radioisotope Thermoelectric Generators (RTGs) for deep space missions up to and including the majority of the plutonium for the Cassini Mission. The previous full production cycle capabilities included: Np- 237 target fabrication, target irradiation, target dissolution and Np-237 and Pu-238 separation and purification, conversion of Np-237 and Pu-238 to oxide, scrap recovery, and Pu-238 encapsulation. The capability and equipment still exist and could be revitalized or put back into service to recover and purify Pu-238/Np-237 or broken General Purpose Heat Source (GPHS) pellets utilizing existing process equipment in HB-Line Scrap Recovery, and H-Canyon Frame Waste Recovery processes. The conversion of Np-237 and Pu-238 to oxide can be performed in the existing HB-Line Phase-2 and Phase- 3 Processes. Dissolution of irradiated Np-237 target material, and separation and purification of Np-237 and Pu-238 product streams would be possible at production rates of ∼2 kg/month of Pu-238 if the existing H-Canyon Frames Process spare equipment were re-installed. Previously, the primary H-Canyon Frames equipment was removed to be replaced: however, the replacement project was stopped. The spare

Predicting selective drug targets in cancer through metabolic networks

PubMed Central

Folger, Ori; Jerby, Livnat; Frezza, Christian; Gottlieb, Eyal; Ruppin, Eytan; Shlomi, Tomer

2011-01-01

The interest in studying metabolic alterations in cancer and their potential role as novel targets for therapy has been rejuvenated in recent years. Here, we report the development of the first genome-scale network model of cancer metabolism, validated by correctly identifying genes essential for cellular proliferation in cancer cell lines. The model predicts 52 cytostatic drug targets, of which 40% are targeted by known, approved or experimental anticancer drugs, and the rest are new. It further predicts combinations of synthetic lethal drug targets, whose synergy is validated using available drug efficacy and gene expression measurements across the NCI-60 cancer cell line collection. Finally, potential selective treatments for specific cancers that depend on cancer type-specific downregulation of gene expression and somatic mutations are compiled. PMID:21694718

Antitumor Activity of a Mesenchymal Stem Cell Line Stably Secreting a Tumor-Targeted TNF-Related Apoptosis-Inducing Ligand Fusion Protein

PubMed Central

Marini, Irene; Siegemund, Martin; Hutt, Meike; Kontermann, Roland E.; Pfizenmaier, Klaus

2017-01-01

Mesenchymal stem cells (MSCs) are currently exploited as gene delivery systems for transient in situ expression of cancer therapeutics. As an alternative to the prevailing viral expression, we here describe a murine MSC line stably expressing a therapeutic protein for up to 42 passages, yet fully maintaining MSC features. Because of superior antitumoral activity of hexavalent TNF-related apoptosis-inducing ligand (TRAIL) formats and the advantage of a tumor-targeted action, we choose expression of a dimeric EGFR-specific diabody single-chain TRAIL (Db-scTRAIL) as a model. The bioactivity of Db-scTRAIL produced from an isolated clone (MSC.TRAIL) was revealed from cell death induction in Colo205 cells treated with either culture supernatants from or cocultured with MSC.TRAIL. In vivo, therapeutic activity of MSC.TRAIL was shown upon peritumoral injection in a Colo205 xenograft tumor model. Best antitumor activity in vitro and in vivo was observed upon combined treatment of MSC.TRAIL with bortezomib. Importantly, in vivo combination treatment did not cause apparent hepatotoxicity, weight loss, or behavioral changes. The development of well characterized stocks of stable drug-producing human MSC lines has the potential to establish standardized protocols of cell-based therapy broadly applicable in cancer treatment. PMID:28553285

On-Line Fringe Tracking and Prediction at IOTA

NASA Technical Reports Server (NTRS)

Wilson, Edward; Mah, Robert; Lau, Sonie (Technical Monitor)

1999-01-01

The Infrared/Optical Telescope Array (IOTA) is a multi-aperture Michelson interferometer located on Mt. Hopkins near Tucson, Arizona. To enable viewing of fainter targets, an on-line fringe tracking system is presently under development at NASA Ames Research Center. The system has been developed off-line using actual data from IOTA, and is presently undergoing on-line implementation at IOTA. The system has two parts: (1) a fringe tracking system that identifies the center of a fringe packet by fitting a parametric model to the data; and (2) a fringe packet motion prediction system that uses characteristics of past fringe packets to predict fringe packet motion. Combined, this information will be used to optimize on-line the scanning trajectory, resulting in improved visibility of faint targets. Fringe packet identification is highly accurate and robust (99% of the 4000 fringe packets were identified correctly, the remaining 1% were either out of the scan range or too noisy to be seen) and is performed in 30-90 milliseconds on a Pentium II-based computer. Fringe packet prediction, currently performed using an adaptive linear predictor, delivers a 10% improvement over the baseline of predicting no motion.

Optimization of routine KRAS mutation PCR-based testing procedure for rational individualized first-line-targeted therapy selection in metastatic colorectal cancer.

PubMed

Chretien, Anne-Sophie; Harlé, Alexandre; Meyer-Lefebvre, Magali; Rouyer, Marie; Husson, Marie; Ramacci, Carole; Harter, Valentin; Genin, Pascal; Leroux, Agnès; Merlin, Jean-Louis

2013-02-01

KRAS mutation detection represents a crucial issue in metastatic colorectal cancer (mCRC). The optimization of KRAS mutation detection delay enabling rational prescription of first-line treatment in mCRC including anti-EGFR-targeted therapy requires robust and rapid molecular biology techniques. Routine analysis of mutations in codons 12 and 13 on 674 paraffin-embedded tissue specimens of mCRC has been performed for KRAS mutations detection using three molecular biology techniques, that is, high-resolution melting (HRM), polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP), and allelic discrimination PCR (TaqMan PCR). Discordant cases were assessed with COBAS 4800 KRAS CE-IVD assay. Among the 674 tumor specimens, 1.5% (10/674) had excessive DNA degradation and could not be analyzed. KRAS mutations were detected in 38.0% (256/674) of the analysable specimens (82.4% in codon 12 and 17.6% in codon 13). Among 613 specimens in whom all three techniques were used, 12 (2.0%) cases of discordance between the three techniques were observed. 83.3% (10/12) of the discordances were due to PCR-RFLP as confirmed by COBAS 4800 retrospective analysis. The three techniques were statistically comparable (κ > 0.9; P < 0.001). From these results, optimization of the routine procedure consisted of proceeding to systematic KRAS detection using HRM and TaqMan and PCR-RFLP in case of discordance and allowed significant decrease in delays. The results showed an excellent correlation between the three techniques. Using HRM and TaqMan warrants high-quality and rapid-routine KRAS mutation detection in paraffin-embedded tumor specimens. The new procedure allowed a significant decrease in delays for reporting results, enabling rational prescription of first-line-targeted therapy in mCRC.

The texting and driving epidemic : changing norms to change behavior.

DOT National Transportation Integrated Search

2013-09-01

This campaign was created to reduce texting and driving and to increase awareness of the serious risks involved with texting and driving. The target audience of the campaign is University of Kansas students. This plan proposes an Anti-Texting and ...

An automated flow system incorporating in-line acid dissolution of bismuth metal from a cyclotron irradiated target assembly for use in the isolation of astatine-211

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

O’Hara, Matthew J.; Krzysko, Anthony J.; Niver, Cynthia M.

Astatine-211 (211At) is a promising cyclotron-produced radionuclide being investigated for use in targeted alpha therapy of blood borne and metastatic cancers, as well as treatment of tumor remnants after surgical resections. The isolation of trace quantities of 211At, produced within several grams of a Bi metal cyclotron target, involves a complex, multi-step procedure: (1) Bi metal dissolution in strong HNO3, (2) distillation of the HNO3 to yield Bi salts containing 211At, (3) dissolution of the salts in strong HCl, (4) solvent extraction of 211At from bismuth salts with diisopropyl ether (DIPE), and (5) back-extraction of 211At from DIPE into NaOH,more » leading to a purified 211At product. Step (1) has been addressed first to begin the process of automating the onerous 211At isolation process. A computer-controlled Bi target dissolution system has been designed. The system performs in-line dissolution of Bi metal from the target assembly using an enclosed target dissolution block, routing the resulting solubilized 211At/Bi mixture to the subsequent process step. The primary parameters involved in Bi metal solubilization (HNO3 concentration and influent flow rate) were optimized prior to evaluation of the system performance on replicate cyclotron irradiated targets. The results indicate that the system performs reproducibly, having nearly quantitative release of 211At from irradiated targets, with cumulative 211At recoveries that follow a sigmoidal function. The predictable nature of the 211At release profile allows the user to tune the system to meet target processing requirements.« less

Targeted Nanoparticles for Kidney Cancer Therapy

DTIC Science & Technology

2013-10-01

AD_________________ Award Number: W81XWH-10-1-0434 TITLE: Targeted Nanoparticles for Kidney Cancer Therapy PRINCIPAL...Targeted Nanoparticles for Kidney Cancer Therapy 5b. GRANT NUMBER W81XWH-10-1-0434 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) 5d. PROJECT...lines following treatment with D5 nanotubes. Tthermoablation will be studied initially. Human kidney cancer cells will be injected into the kidney

Effects of incidental pictorial and verbal adjuncts on text learning.

PubMed

Terry, W S; Howe, D C

1988-01-01

In this study, college students read and studied texts on historical figures in psychology, which were supplemented by drawings and/or brief biographies of these persons. In Experiment 1, a 2 x 2 between-groups design was conducted in which students received one adjunct with each text, both adjuncts, or neither. In Experiment 2, a single group of students received a within-subjects manipulation of the same adjunct conditions. In the between-groups comparison, students receiving biographies learned less of the target text passages, with the group receiving illustrations and biographies performing least accurately. In the within-subject conditions, texts accompanied by an illustration were better learned, with these students doing best on the text with both picture and biography. The results suggest that adjuncts may emphasize some texts, at the expense of learning from the other texts, but that too much adjunct material interferes with the learning of the target passages.

Strategic Key Word Instruction: Increasing Fluency in Connected Expository Text

ERIC Educational Resources Information Center

Coulter, Gail; Lambert, Michael C.

2015-01-01

The effects of preteaching key words on fluency in connected text were examined with three third-grade general education participants. Researchers used a multiple base-line design (i.e., Baseline and Wordlist Intervention) and found that preteaching increased fluency in connected text written above the participant's instructional level of reading…

Aphasia and text writing.

PubMed

Behrns, Ingrid; Ahlsén, Elisabeth; Wengelin, Asa

2010-01-01

Good writing skills are needed in almost every aspect of life today, and there is a growing interest in research into acquired writing difficulties. Most of the findings reported so far, however, are based on words produced in isolation. The present study deals with the production of entire texts. The aim was to characterize written narratives produced by a group of participants with aphasia. Eight persons aged 28-63 years with aphasia took part in the study. They were compared with a reference group consisting of ten participants aged 21-30 years. All participants were asked to write a personal narrative titled 'I have never been so afraid' and to perform a picture-based story-generation task called the 'Frog Story'. The texts were written on a computer. The group could be divided into participants with low, moderate, and high general performance, respectively. The texts written by the participants in the group with moderate and high writing performance had comparatively good narrative structure despite indications of difficulties on other linguistic levels. Aphasia appeared to influence text writing on different linguistic levels. The impact on overall structure and coherence was in line with earlier findings from the analysis of spoken and written discourse and the implication of this is that the written modality should also be included in language rehabilitation. 2010 Royal College of Speech & Language Therapists.

Selective tumor cell targeting by the disaccharide moiety of bleomycin.

PubMed

Yu, Zhiqiang; Schmaltz, Ryan M; Bozeman, Trevor C; Paul, Rakesh; Rishel, Michael J; Tsosie, Krystal S; Hecht, Sidney M

2013-02-27

In a recent study, the well-documented tumor targeting properties of the antitumor agent bleomycin (BLM) were studied in cell culture using microbubbles that had been derivatized with multiple copies of BLM. It was shown that BLM selectively targeted MCF-7 human breast carcinoma cells but not the "normal" breast cell line MCF-10A. Furthermore, it was found that the BLM analogue deglycobleomycin, which lacks the disaccharide moiety of BLM, did not target either cell line, indicating that the BLM disaccharide moiety is necessary for tumor selectivity. Not resolved in the earlier study were the issues of whether the BLM disaccharide moiety alone is sufficient for tumor cell targeting and the possible cellular uptake of the disaccharide. In the present study, we conjugated BLM, deglycoBLM, and BLM disaccharide to the cyanine dye Cy5**. It was found that the BLM and BLM disaccharide conjugates, but not the deglycoBLM conjugate, bound selectively to MCF-7 cells and were internalized. The same was also true for the prostate cancer cell line DU-145 (but not for normal PZ-HPV-7 prostate cells) and for the pancreatic cancer cell line BxPC-3 (but not for normal SVR A221a pancreas cells). The targeting efficiency of the disaccharide was only slightly less than that of BLM in MCF-7 and DU-145 cells and comparable to that of BLM in BxPC-3 cells. These results establish that the BLM disaccharide is both necessary and sufficient for tumor cell targeting, a finding with obvious implications for the design of novel tumor imaging and therapeutic agents.

Teaching braille line tracking using stimulus fading.

PubMed

Scheithauer, Mindy C; Tiger, Jeffrey H

2014-01-01

Line tracking is a prerequisite skill for braille literacy that involves moving one's finger horizontally across a line of braille text and identifying when a line ends so the reader may reset his or her finger on the subsequent line. Current procedures for teaching line tracking are incomplete, because they focus on tracking lines with only small gaps between characters. The current study extended previous line-tracking instruction using stimulus fading to teach tracking across larger gaps. After instruction, all participants showed improvement in line tracking, and 2 of 3 participants met mastery criteria for tracking across extended spaces. © Society for the Experimental Analysis of Behavior.

Inertial confinement fusion method producing line source radiation fluence

DOEpatents

Rose, Ronald P.

1984-01-01

An inertial confinement fusion method in which target pellets are imploded in sequence by laser light beams or other energy beams at an implosion site which is variable between pellet implosions along a line. The effect of the variability in position of the implosion site along a line is to distribute the radiation fluence in surrounding reactor components as a line source of radiation would do, thereby permitting the utilization of cylindrical geometry in the design of the reactor and internal components.

The recommendation of line-balancing improvement on MCM product line 1 using genetics algorithm and moodie young at XYZ Company, Co.

NASA Astrophysics Data System (ADS)

Sriwana, I. K.; Marie, I. A.; Mangala, D.

2017-12-01

Kencana Gemilang, Co. is one electronics industry engaging in the manufacture sector. This company manufactures and assembles household electronic products, such as rice cooker, fan, iron, blender, etc. The company deals with an issue of underachievement of an established production target on MCM products line 1. This study aimed to calculate line efficiencies, delay times, and initial line smoothness indexes. The research was carried out by means of depicting a precedence diagram and gathering time data of each work element followed by examination and calculation of standard time as well as line balancing using methods of Moodie Young and Generics Algorithm. Based on results of calculation, better line balancing than the existing initial conditions, i.e. improvement in the line efficiency by 18.39%, deterioration in balanced delay by 28.39%, and deterioration of a smoothness index by 23.85% was obtained.

Optimizing text for an individual's visual system: The contribution of visual crowding to reading difficulties.

PubMed

Joo, Sung Jun; White, Alex L; Strodtman, Douglas J; Yeatman, Jason D

2018-06-01

Reading is a complex process that involves low-level visual processing, phonological processing, and higher-level semantic processing. Given that skilled reading requires integrating information among these different systems, it is likely that reading difficulty-known as dyslexia-can emerge from impairments at any stage of the reading circuitry. To understand contributing factors to reading difficulties within individuals, it is necessary to diagnose the function of each component of the reading circuitry. Here, we investigated whether adults with dyslexia who have impairments in visual processing respond to a visual manipulation specifically targeting their impairment. We collected psychophysical measures of visual crowding and tested how each individual's reading performance was affected by increased text-spacing, a manipulation designed to alleviate severe crowding. Critically, we identified a sub-group of individuals with dyslexia showing elevated crowding and found that these individuals read faster when text was rendered with increased letter-, word- and line-spacing. Our findings point to a subtype of dyslexia involving elevated crowding and demonstrate that individuals benefit from interventions personalized to their specific impairments. Copyright © 2018 Elsevier Ltd. All rights reserved.

Incoherent imaging of radar targets

NASA Astrophysics Data System (ADS)

van Ommen, A.; van der Spek, G. A.

1986-05-01

Theory suggests that, if a target can be modeled as a rigid constellation of point scatterers, the RCS pattern over a certain aspect change can be used to produce a one-dimensional image. The results for actual measured RCS patterns, however, are not promising. This is illustrated by processing on 4 s of echo data obtained from a Boeing 737 in straight flight, during which its aspect change is 2 deg. The conclusion might be that, for the application considered, aircraft cannot be modeled as a rigid constellation of point scatterers; this is partly due to the treatment of a three-dimensional target as a line target.

Conservative site-specific and single-copy transgenesis in human LINE-1 elements

PubMed Central

Vijaya Chandra, Shree Harsha; Makhija, Harshyaa; Peter, Sabrina; Myint Wai, Cho Mar; Li, Jinming; Zhu, Jindong; Ren, Zhonglu; D'Alcontres, Martina Stagno; Siau, Jia Wei; Chee, Sharon; Ghadessy, Farid John; Dröge, Peter

2016-01-01

Genome engineering of human cells plays an important role in biotechnology and molecular medicine. In particular, insertions of functional multi-transgene cassettes into suitable endogenous sequences will lead to novel applications. Although several tools have been exploited in this context, safety issues such as cytotoxicity, insertional mutagenesis and off-target cleavage together with limitations in cargo size/expression often compromise utility. Phage λ integrase (Int) is a transgenesis tool that mediates conservative site-specific integration of 48 kb DNA into a safe harbor site of the bacterial genome. Here, we show that an Int variant precisely recombines large episomes into a sequence, termed attH4X, found in 1000 human Long INterspersed Elements-1 (LINE-1). We demonstrate single-copy transgenesis through attH4X-targeting in various cell lines including hESCs, with the flexibility of selecting clones according to transgene performance and downstream applications. This is exemplified with pluripotency reporter cassettes and constitutively expressed payloads that remain functional in LINE1-targeted hESCs and differentiated progenies. Furthermore, LINE-1 targeting does not induce DNA damage-response or chromosomal aberrations, and neither global nor localized endogenous gene expression is substantially affected. Hence, this simple transgene addition tool should become particularly useful for applications that require engineering of the human genome with multi-transgenes. PMID:26673710

Design of an On-Line Query Language for Full Text Patent Search.

ERIC Educational Resources Information Center

Glantz, Richard S.

The design of an English-like query language and an interactive computer environment for searching the full text of the U.S. patent collection are discussed. Special attention is paid to achieving a transparent user interface, to providing extremely broad search capabilities (including nested substitution classes, Kleene star events, and domain…

Seismoelectric imaging of shallow targets

USGS Publications Warehouse

Haines, S.S.; Pride, S.R.; Klemperer, S.L.; Biondi, B.

2007-01-01

We have undertaken a series of controlled field experiments to develop seismoelectric experimental methods for near-surface applications and to improve our understanding of seismoelectric phenomena. In a set of off-line geometry surveys (source separated from the receiver line), we place seismic sources and electrode array receivers on opposite sides of a man-made target (two sand-filled trenches) to record separately two previously documented seismoelectric modes: (1) the electromagnetic interface response signal created at the target and (2) the coseismic electric fields located within a compressional seismic wave. With the seismic source point in the center of a linear electrode array, we identify the previously undocumented seismoelectric direct field, and the Lorentz field of the metal hammer plate moving in the earth's magnetic field. We place the seismic source in the center of a circular array of electrodes (radial and circumferential orientations) to analyze the source-related direct and Lorentz fields and to establish that these fields can be understood in terms of simple analytical models. Using an off-line geometry, we create a multifold, 2D image of our trenches as dipping layers, and we also produce a complementary synthetic image through numerical modeling. These images demonstrate that off-line geometry (e.g., crosswell) surveys offer a particularly promising application of the seismoelectric method because they effectively separate the interface response signal from the (generally much stronger) coseismic and source-related fields. ?? 2007 Society of Exploration Geophysicists.

The novel EpCAM-targeting monoclonal antibody 3–17I linked to saporin is highly cytotoxic after photochemical internalization in breast, pancreas and colon cancer cell lines

PubMed Central

Lund, Kaja; Bostad, Monica; Skarpen, Ellen; Braunagel, Michael; Kiprijanov, Sergej; Krauss, Stefan; Duncan, Alex; Høgset, Anders; Selbo, Pål K.

2014-01-01

The epithelial cell adhesion molecule (EpCAM) is expressed by a wide range of human carcinomas, making it an attractive diagnostic and therapeutic target in oncology. Its recent identification on cancer stem cells has raised further interest in its use for tumor targeting and therapy. Here, we present the characterization and therapeutic potential of 3–17I, a novel human EpCAM-targeting monoclonal antibody. Strong reaction of 3–17I was observed in all lung, colon, and breast human tumor biopsies evaluated. By flow cytometry and confocal fluorescence microscopy, we demonstrate that 3–17I specifically targets EpCAM-positive cell lines. We also show evidence for mAb-sequestration in endo-/lysosomes, suggesting internalization of 3–17I by receptor-mediated endocytosis. The ribosomal-inactivating toxin saporin was linked to 3–17I, creating the per se non-toxic immunotoxin 3–17I-saporin, a promising candidate for the drug delivery technology photochemical internalization (PCI). PCI is based on a light-controlled destruction of endolysosomal membranes and subsequent cytosolic release of the sequestered payload upon light exposure. EpCAM-positive human cancer cell lines MCF7 (breast), BxPC-3 (pancreas), WiDr (colon), and the EpCAM-negative COLO320DM (colon), were treated with 3–17I-saporin in combination with the clinically relevant photosensitizer TPCS2a (Amphinex), followed by exposure to light. No cytotoxicity was observed after treatment with 3–17I-saporin without light exposure. However, cell viability, proliferation and colony-forming capacity was strongly reduced in a light-dependent manner after PCI of 3–17I. Our results show that 3–17I is an excellent candidate for diagnosis of EpCAM-positive tumors and for development of clinically relevant antibody-drug conjugates, using PCI for the treatment of localized tumors. PMID:24525727

Stitch and hem and line and flight

NASA Astrophysics Data System (ADS)

Thorp, John Daniel

Stitch and hem and line and flight appears in four formats. There is this present one, which adheres to the manuscript design requirements as outlined by The Graduate School at The University of Utah; there is another which is a book six inches high by nine inches wide, printed in three colors, with text aligned to its gutter; and there is a broadside printed from the same forms of standing metal type on a single twelve-inch-high by nineteen-inch-wide page, where all spreads are registered to the same points so that all lines of all sections overlap exactly, excluding the last lines of the longest section, which are left immediately readable. The second and the third formats were produced in editions of fifty each, and copies are available to the reader through the Special Collections Library at the J. Willard Marriott Library. The text in the book you're holding is built from scans taken from the original letterpress pages, and so honors typos not caught before production during proofreading, but does not honor the final runs of production which overprint eight typos and overprint one duplicated "no." The text here stands as an uncorrected and reformatted transcript of the letterpress-printed pages, since all "characters must be clear and sharp. Smudged, indistinct, or blurred letters are not acceptable." The present format cannot ask (at least not in the same way) if the techniques and repetitive labor of hand printing can be read just as one might read any of the other more familiar small crises in a work: the line break, the influence of a culture or history on that work, anagnorisis, exegesis, etc. The present format doesn't seem to ask questions like: what happens to a love song when you can't read it or hear it? How does a line or letter make itself mean when cast in metal, stood up and pressed onto paper? Still, the present format is concerned with how a line sits on a page and how a line is like love is like highs is like sand. The text all these formats

Facility target insert shielding assessment

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

Mocko, Michal

2015-10-06

Main objective of this report is to assess the basic shielding requirements for the vertical target insert and retrieval port. We used the baseline design for the vertical target insert in our calculations. The insert sits in the 12”-diameter cylindrical shaft extending from the service alley in the top floor of the facility all the way down to the target location. The target retrieval mechanism is a long rod with the target assembly attached and running the entire length of the vertical shaft. The insert also houses the helium cooling supply and return lines each with 2” diameter. In themore » present study we focused on calculating the neutron and photon dose rate fields on top of the target insert/retrieval mechanism in the service alley. Additionally, we studied a few prototypical configurations of the shielding layers in the vertical insert as well as on the top.« less

Changes in Renal Function of Patients with Metastatic Renal Cell Carcinoma During Treatment with Molecular-Targeted Agents.

PubMed

Miyake, Hideaki; Muramaki, Mototsugu; Imai, Satoshi; Harada, Ken-Ichi; Fujisawa, Masato

2016-06-01

Impairment of renal function is a serious issue that should be considered in patients undergoing treatment with molecular-targeted agents for metastatic renal cell carcinoma (mRCC). The objective of this study was to assess the impact of molecular-targeted therapy on changes in renal function among patients with mRCC. The study included 408 mRCC patients treated with sunitinib, sorafenib, axitinib, everolimus and/or temsirolimus. Among these, 185, 128 and 95 received molecular-targeted agents as first-line (group 1), second-line (group 2) and third-line (group 3) therapy, respectively. No significant differences between the estimated glomerular filtration rate (eGFR) at baseline and that at the end of molecular-targeted therapy were noted among the three groups of patients. In addition, there were no significant differences between eGFR prior to the introduction of molecular-targeted therapy and that at the end of therapy across agents and lines of targeted therapy, with the exception of patients treated with axitinib and everolimus in second-line and third-line therapy, respectively. In group 1, a reduction in eGFR of >10 % from baseline was independently associated with performance status, hypertension and treatment duration, while in groups 2 and 3, only treatment duration was independently related to a reduction in eGFR of >10 %. It appears that renal function in patients with mRCC is not markedly impaired by molecular-targeted therapies, irrespective of the specific agents introduced; however, it may be necessary to pay special attention to deterioration in renal function when molecular-targeted therapy is continued for longer periods.

Can An Evolutionary Process Create English Text?

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

Bailey, David H.

Critics of the conventional theory of biological evolution have asserted that while natural processes might result in some limited diversity, nothing fundamentally new can arise from 'random' evolution. In response, biologists such as Richard Dawkins have demonstrated that a computer program can generate a specific short phrase via evolution-like iterations starting with random gibberish. While such demonstrations are intriguing, they are flawed in that they have a fixed, pre-specified future target, whereas in real biological evolution there is no fixed future target, but only a complicated 'fitness landscape'. In this study, a significantly more sophisticated evolutionary scheme is employed tomore » produce text segments reminiscent of a Charles Dickens novel. The aggregate size of these segments is larger than the computer program and the input Dickens text, even when comparing compressed data (as a measure of information content).« less

Estrogen Regulates Bone Turnover by Targeting RANKL Expression in Bone Lining Cells.

PubMed

Streicher, Carmen; Heyny, Alexandra; Andrukhova, Olena; Haigl, Barbara; Slavic, Svetlana; Schüler, Christiane; Kollmann, Karoline; Kantner, Ingrid; Sexl, Veronika; Kleiter, Miriam; Hofbauer, Lorenz C; Kostenuik, Paul J; Erben, Reinhold G

2017-07-25

Estrogen is critical for skeletal homeostasis and regulates bone remodeling, in part, by modulating the expression of receptor activator of NF-κB ligand (RANKL), an essential cytokine for bone resorption by osteoclasts. RANKL can be produced by a variety of hematopoietic (e.g. T and B-cell) and mesenchymal (osteoblast lineage, chondrocyte) cell types. The cellular mechanisms by which estrogen acts on bone are still a matter of controversy. By using murine reconstitution models that allow for selective deletion of estrogen receptor-alpha (ERα) or selective inhibition of RANKL in hematopoietic vs. mesenchymal cells, in conjunction with in situ expression profiling in bone cells, we identified bone lining cells as important gatekeepers of estrogen-controlled bone resorption. Our data indicate that the increase in bone resorption observed in states of estrogen deficiency in mice is mainly caused by lack of ERα-mediated suppression of RANKL expression in bone lining cells.

The On-Line Investigation of Reading a Text: Methods and a Model.

ERIC Educational Resources Information Center

Hyona, Jukka

Five methods for studying the process of reading a text are presented, and a model for discourse processing is outlined. Discourse processing refers to comprehension of the meaning underlying the verbal message. The methods discussed here investigate the reading process as it occurs, and focus on the amount of time taken to complete a task or…

Note: Development of target changeable palm-top pyroelectric x-ray tube

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

Imashuku, Susumu; Kawai, Jun

2012-01-15

A target changeable palm-top size x-ray tube was realized using pyroelectric crystal and detachable vacuum flanges. The target metals can be exchanged easily by attaching them on the brass stage with carbon tape. When silver and titanium palates (area: 10 mm{sup 2}) were used as targets, silver L{alpha} and titanium K lines were clearly observed by bombarding electrons on the targets for 90 s. The intensities were the same or higher than those of previously reported pyroelectric x-ray tubes. Chromium, iron, nickel, copper, and zinc K lines in the x-ray tube (stainless steel and brass) disappeared by replacing the brassmore » stage and the stainless steel vacuum flange with a carbon stage and a glass tube, respectively.« less

Text-Based On-Line Conferencing: A Conceptual and Empirical Analysis Using a Minimal Prototype.

ERIC Educational Resources Information Center

McCarthy, John C.; And Others

1993-01-01

Analyzes requirements for text-based online conferencing through the use of a minimal prototype. Topics discussed include prototyping with a minimal system; text-based communication; the system as a message passer versus the system as a shared data structure; and three exercises that showed how users worked with the prototype. (Contains 61…

High temperature ion source for an on-line isotope separator

DOEpatents

Mlekodaj, Ronald L.

1979-01-01

A reduced size ion source for on-line use with a cyclotron heavy-ion beam is provided. A sixfold reduction in source volume while operating with similar input power levels results in a 2000.degree. C. operating temperature. A combined target/window normally provides the reaction products for ionization while isolating the ion source plasma from the cyclotron beam line vacuum. A graphite felt catcher stops the recoiling reaction products and releases them into the plasma through diffusion and evaporation. Other target arrangements are also possible. A twenty-four hour lifetime of unattended operation is achieved, and a wider range of elements can be studied than was heretofore possible.

How many genomics targets can a portfolio afford?

PubMed

Betz, Ulrich A K

2005-08-01

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

S3 targets monitoring with an electron gun

NASA Astrophysics Data System (ADS)

Kallunkathariyil, J.; Stodel, Ch.; Marry, C.; Frémont, G.; Bastin, B.; Piot, J.; Clément, E.; Le Moal, S.; Morel, V.; Thomas, J.-C.; Kamalou, O.; Spitaëls, C.; Savajols, H.; Vostinar, M.; Pellemoine, F.; Mittig, W.

2018-05-01

The monitoring of targets under irradiation was investigated using a 20 keV electron beam. An integrated and automated electron beam deflection was developed allowing a monitoring over the whole surface of target materials. Thus, local defects could be identified on-line during an experiment performed at GANIL involving different materials irradiated with a focused krypton beam at 10.5 MeV/u. Performances of this target monitoring system are presented in this paper.

Effects of Text, Audio and Learner Control on Text-Sound Association and Cognitive Load of EFL Learners

ERIC Educational Resources Information Center

Enciso Bernal, Ana Maria

2014-01-01

This study investigated the effects of concurrent audio and equivalent onscreen text on the ability of learners of English as a foreign language (EFL) to form associations between textual and aural forms of target vocabulary words. The study also looked at the effects of learner control over an audio sequence on the association of textual and…

Millimeter-wave Line Ratios and Sub-beam Volume Density Distributions

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

Leroy, Adam K.; Gallagher, Molly; Usero, Antonio

We explore the use of mm-wave emission line ratios to trace molecular gas density when observations integrate over a wide range of volume densities within a single telescope beam. For observations targeting external galaxies, this case is unavoidable. Using a framework similar to that of Krumholz and Thompson, we model emission for a set of common extragalactic lines from lognormal and power law density distributions. We consider the median density of gas that produces emission and the ability to predict density variations from observed line ratios. We emphasize line ratio variations because these do not require us to know themore » absolute abundance of our tracers. Patterns of line ratio variations have the potential to illuminate the high-end shape of the density distribution, and to capture changes in the dense gas fraction and median volume density. Our results with and without a high-density power law tail differ appreciably; we highlight better knowledge of the probability density function (PDF) shape as an important area. We also show the implications of sub-beam density distributions for isotopologue studies targeting dense gas tracers. Differential excitation often implies a significant correction to the naive case. We provide tabulated versions of many of our results, which can be used to interpret changes in mm-wave line ratios in terms of adjustments to the underlying density distributions.« less

Targeted therapies in gastric cancer and future perspectives.

PubMed

Yazici, Ozan; Sendur, M Ali Nahit; Ozdemir, Nuriye; Aksoy, Sercan

2016-01-14

Advanced gastric cancer (AGC) is associated with a high mortality rate and, despite multiple new chemotherapy options, the survival rates of patients with AGC remains poor. After the discovery of targeted therapies, research has focused on the new treatment options for AGC. In the last two decades, many targeted molecules were developed against AGC. Currently, two targeted therapy molecules have been approved for patients with AGC. In 2010, trastuzumab was the first molecule shown to improve survival in patients with HER2-positive AGC as part of a first-line combination regimen. In 2014, ramucirumab was the second targeted molecule to improve survival rates and was suggested as treatment for patients with AGC who had progressed after first-line platinum plus fluoropyrimidine with or without anthracycline chemotherapy. Ramucirumab was the first targeted therapy acting as a single agent in patients with advanced gastroesophageal cancers. Although these two molecules were introduced into clinical use, many other promising molecules have been tested in phase I-II trials. It is obvious that in the near future many different targeted therapies will be in use for treatment of AGC. In this review, the current status of targeted therapies in the treatment of AGC and gastroesophageal junction tumors, including HER (2-3) inhibitors, epidermal growth factor receptor inhibitors, tyrosine kinase inhibitors, antiangiogenic agents, c-MET inhibitors, mammalian target of rapamycin inhibitors, agents against other molecular pathways fibroblast growth factor, Claudins, insulin-like growth factor, heat shock proteins, and immunotherapy, will be discussed.

Molecular Targeted Drugs and Biomarkers in NSCLC, the Evolving Role of Individualized Therapy

PubMed Central

Domvri, Kalliopi; Zarogoulidis, Paul; Darwiche, Kaid; Browning, Robert F.; Li, Qiang; Turner, J. Francis; Kioumis, Ioannis; Spyratos, Dionysios; Porpodis, Konstantinos; Papaiwannou, Antonis; Tsiouda, Theodora; Freitag, Lutz; Zarogoulidis, Konstantinos

2013-01-01

Lung cancer first line treatment has been directed from the non-specific cytotoxic doublet chemotherapy to the molecular targeted. The major limitation of the targeted therapies still remains the small number of patients positive to gene mutations. Furthermore, the differentiation between second line and maintenance therapy has not been fully clarified and differs in the clinical practice between cancer centers. The authors present a segregation between maintenance treatment and second line and present a possible definition for the term “maintenance” treatment. In addition, cancer cell evolution induces mutations and therefore either targeted therapies or non-specific chemotherapy drugs in many patients become ineffective. In the present work pathways such as epidermal growth factor, anaplastic lymphoma kinase, met proto-oncogene and PI3K are extensively presented and correlated with current chemotherapy treatment. Future, perspectives for targeted treatment are presented based on the current publications and ongoing clinical trials. PMID:24312144

Design of a Covert RFID Tag Network for Target Discovery and Target Information Routing

PubMed Central

Pan, Qihe; Narayanan, Ram M.

2011-01-01

Radio frequency identification (RFID) tags are small electronic devices working in the radio frequency range. They use wireless radio communications to automatically identify objects or people without the need for line-of-sight or contact, and are widely used in inventory tracking, object location, environmental monitoring. This paper presents a design of a covert RFID tag network for target discovery and target information routing. In the design, a static or very slowly moving target in the field of RFID tags transmits a distinct pseudo-noise signal, and the RFID tags in the network collect the target information and route it to the command center. A map of each RFID tag’s location is saved at command center, which can determine where a RFID tag is located based on each RFID tag’s ID. We propose the target information collection method with target association and clustering, and we also propose the information routing algorithm within the RFID tag network. The design and operation of the proposed algorithms are illustrated through examples. Simulation results demonstrate the effectiveness of the design. PMID:22163693

Design of a covert RFID tag network for target discovery and target information routing.

PubMed

Pan, Qihe; Narayanan, Ram M

2011-01-01

Radio frequency identification (RFID) tags are small electronic devices working in the radio frequency range. They use wireless radio communications to automatically identify objects or people without the need for line-of-sight or contact, and are widely used in inventory tracking, object location, environmental monitoring. This paper presents a design of a covert RFID tag network for target discovery and target information routing. In the design, a static or very slowly moving target in the field of RFID tags transmits a distinct pseudo-noise signal, and the RFID tags in the network collect the target information and route it to the command center. A map of each RFID tag's location is saved at command center, which can determine where a RFID tag is located based on each RFID tag's ID. We propose the target information collection method with target association and clustering, and we also propose the information routing algorithm within the RFID tag network. The design and operation of the proposed algorithms are illustrated through examples. Simulation results demonstrate the effectiveness of the design.

Performance Analysis of GFDL's GCM Line-By-Line Radiative Transfer Model on GPU and MIC Architectures

NASA Astrophysics Data System (ADS)

Menzel, R.; Paynter, D.; Jones, A. L.

2017-12-01

Due to their relatively low computational cost, radiative transfer models in global climate models (GCMs) run on traditional CPU architectures generally consist of shortwave and longwave parameterizations over a small number of wavelength bands. With the rise of newer GPU and MIC architectures, however, the performance of high resolution line-by-line radiative transfer models may soon approach those of the physical parameterizations currently employed in GCMs. Here we present an analysis of the current performance of a new line-by-line radiative transfer model currently under development at GFDL. Although originally designed to specifically exploit GPU architectures through the use of CUDA, the radiative transfer model has recently been extended to include OpenMP in an effort to also effectively target MIC architectures such as Intel's Xeon Phi. Using input data provided by the upcoming Radiative Forcing Model Intercomparison Project (RFMIP, as part of CMIP 6), we compare model results and performance data for various model configurations and spectral resolutions run on both GPU and Intel Knights Landing architectures to analogous runs of the standard Oxford Reference Forward Model on traditional CPUs.

Musashi Protein-directed Translational Activation of Target mRNAs Is Mediated by the Poly(A) Polymerase, Germ Line Development Defective-2*

PubMed Central

Cragle, Chad; MacNicol, Angus M.

2014-01-01

The mRNA-binding protein, Musashi, has been shown to regulate translation of select mRNAs and to control cellular identity in both stem cells and cancer cells. Within the mammalian cells, Musashi has traditionally been characterized as a repressor of translation. However, we have demonstrated that Musashi is an activator of translation in progesterone-stimulated oocytes of the frog Xenopus laevis, and recent evidence has revealed Musashi's capability to function as an activator of translation in mammalian systems. The molecular mechanism by which Musashi directs activation of target mRNAs has not been elucidated. Here, we report a specific association of Musashi with the noncanonical poly(A) polymerase germ line development defective-2 (GLD2) and map the association domain to 31 amino acids within the C-terminal domain of Musashi. We show that loss of GLD2 interaction through deletion of the binding domain or treatment with antisense oligonucleotides compromises Musashi function. Additionally, we demonstrate that overexpression of both Musashi and GLD2 significantly enhances Musashi function. Finally, we report a similar co-association also occurs between murine Musashi and GLD2 orthologs, suggesting that coupling of Musashi to the polyadenylation apparatus is a conserved mechanism to promote target mRNA translation. PMID:24644291

Space-based infrared sensors of space target imaging effect analysis

NASA Astrophysics Data System (ADS)

Dai, Huayu; Zhang, Yasheng; Zhou, Haijun; Zhao, Shuang

2018-02-01

Target identification problem is one of the core problem of ballistic missile defense system, infrared imaging simulation is an important means of target detection and recognition. This paper first established the space-based infrared sensors ballistic target imaging model of point source on the planet's atmosphere; then from two aspects of space-based sensors camera parameters and target characteristics simulated atmosphere ballistic target of infrared imaging effect, analyzed the camera line of sight jitter, camera system noise and different imaging effects of wave on the target.

Diagnosis of high-temperature implosions using low- and high-opacity Krypton lines

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

Yaakobi, B.; Epstein, R.; Hooper, C.F. Jr.

1996-04-01

High-temperature laser target implosions can be achieved by using relatively thin-shell targets, and they can be. diagnosed by doping the fuel with krypton and measuring K-shell and L-shell lines. Electron temperatures of up to 5 keV at modest compressed densities ({approximately}1-5g/cm{sup 3}) are predicted for such experiments, with ion temperatures peaking above 10 keV at the center. It is found that the profiles of low-opacity (optically thin) lines in the expected density range are dominated by the Doppler broadening and can provide a measurement of the ion temperature if spectrometers of spectral resolution {Delta}{lambda}/{lambda} {ge} 1000 are used. For high-opacitymore » lines, obtained with a higher krypton fill pressure, the measurement of the escape factor can yield the {rho}R of the compressed fuel. At higher densities, Stark broadening of low-opacity lines becomes important and can provide a density measurement, whereas lines of higher opacity can be used to estimate the extent of mixing.« less

Rescue of Targeted Regions of Mammalian Chromosomes by in Vivo Recombination in Yeast

PubMed Central

Kouprina, Natalya; Kawamoto, Kensaku; Barrett, J. Carl; Larionov, Vladimir; Koi, Minoru

1998-01-01

In contrast to other animal cell lines, the chicken pre-B cell lymphoma line, DT40, exhibits a high level of homologous recombination, which can be exploited to generate site-specific alterations in defined target genes or regions. In addition, the ability to generate human/chicken monochromosomal hybrids in the DT40 cell line opens a way for specific targeting of human genes. Here we describe a new strategy for direct isolation of a human chromosomal region that is based on targeting of the chromosome with a vector containing a yeast selectable marker, centromere, and an ARS element. This procedure allows rescue of the targeted region by transfection of total genomic DNA into yeast spheroplasts. Selection for the yeast marker results in isolation of chromosome sequences in the form of large circular yeast artificial chromosomes (YACs) up to 170 kb in size containing the targeted region. These YACs are generated by homologous recombination in yeast between common repeated sequences in the targeted chromosomal fragment. Alternatively, the targeted region can be rescued as a linear YACs when a YAC fragmentation vector is included in the yeast transformation mixture. Because the entire isolation procedure of the chromosomal region, once a target insertion is obtained, can be accomplished in ∼1 week, the new method greatly expands the utility of the homologous recombinationproficient DT40 chicken cell system. PMID:9647640

Hierarchy for targeting prosurvival BCL2 family proteins in multiple myeloma: pivotal role of MCL1.

PubMed

Gong, Jia-Nan; Khong, Tiffany; Segal, David; Yao, Yuan; Riffkin, Chris D; Garnier, Jean-Marc; Khaw, Seong Lin; Lessene, Guillaume; Spencer, Andrew; Herold, Marco J; Roberts, Andrew W; Huang, David C S

2016-10-06

New therapeutic targets are needed to address the poor prognosis of patients with high-risk multiple myeloma. Myeloma cells usually express a range of the prosurvival BCL2 proteins. To define the hierarchy of their relative importance for maintaining the survival of myeloma cells, we targeted each of them in a large panel of cell lines, using pharmacological inhibitors or gene editing or by peptide-based approaches, alone or in combination. The majority of well-established immortalized cell lines (17/25) or low-passage myeloma cell lines (5/7) are readily killed when MCL1 is targeted, even including those cell lines sensitive to BCL2 inhibition. Targeting MCL1 also constrained the growth of myeloma in vivo. We also identified a previously unrecognized subset of myeloma that is highly BCLXL-dependent, and has the potential for cotargeting MCL1 and BCLXL. As MCL1 is pivotal for maintaining survival of most myelomas, it should be prioritized for targeting in the clinic once high-quality, validated inhibitors become available. © 2016 by The American Society of Hematology.

Motivating Smoking Cessation Text Messages: Perspectives from Pregnant Smokers.

PubMed

Schindler-Ruwisch, Jennifer M; Leavitt, Leah E; Macherelli, Laura E; Turner, Monique M; Abroms, Lorien C

2018-06-01

The purpose of this research is to analyze cessation text-messages written by pregnant smokers to elucidate the target population's preferred content and message attributes. To achieve this goal, the objectives of this study are three-fold; to qualitatively code messages written by pregnant smokers for frame, type of appeal, and intended target. Study participants were recruited as part of a larger trial of pregnant smokers who were enrolled in a text-messaging program or control group and surveyed 1 month post-enrollment. Each participant was asked to write a brief message to another pregnant smoker and two independent coders qualitatively analyzed responses. User generated messages (N = 51) were equally loss and gain framed, and the most common appeals were: fear, guilt, cognitive, hope and empathy, in order of most to least frequent. The target of the majority of the messages was the baby. Allowing pregnant smokers to write cessation text-messages for other pregnant women can provide relevant insight into intervention content. Specifically, pregnant smokers appear to equally promote gain and loss frames, but may prefer messages that include components of fear and guilt related to the impact of smoking on their baby. Additional research is needed to systematically uncover perspectives of pregnant smokers to ensure interventions are optimally effective.

Downstream targets of HOXB4 in a cell line model of primitive hematopoietic progenitor cells.

PubMed

Lee, Han M; Zhang, Hui; Schulz, Vincent; Tuck, David P; Forget, Bernard G

2010-08-05

Enforced expression of the homeobox transcription factor HOXB4 has been shown to enhance hematopoietic stem cell self-renewal and expansion ex vivo and in vivo. To investigate the downstream targets of HOXB4 in hematopoietic progenitor cells, HOXB4 was constitutively overexpressed in the primitive hematopoietic progenitor cell line EML. Two genome-wide analytical techniques were used: RNA expression profiling using microarrays and chromatin immunoprecipitation (ChIP)-chip. RNA expression profiling revealed that 465 gene transcripts were differentially expressed in KLS (c-Kit(+), Lin(-), Sca-1(+))-EML cells that overexpressed HOXB4 (KLS-EML-HOXB4) compared with control KLS-EML cells that were transduced with vector alone. In particular, erythroid-specific gene transcripts were observed to be highly down-regulated in KLS-EML-HOXB4 cells. ChIP-chip analysis revealed that the promoter region for 1910 genes, such as CD34, Sox4, and B220, were occupied by HOXB4 in KLS-EML-HOXB4 cells. Side-by-side comparison of the ChIP-chip and RNA expression profiling datasets provided correlative information and identified Gp49a and Laptm4b as candidate "stemness-related" genes. Both genes were highly ranked in both dataset lists and have been previously shown to be preferentially expressed in hematopoietic stem cells and down-regulated in mature hematopoietic cells, thus making them attractive candidates for future functional studies in hematopoietic cells.

About miRNAs, miRNA seeds, target genes and target pathways.

PubMed

Kehl, Tim; Backes, Christina; Kern, Fabian; Fehlmann, Tobias; Ludwig, Nicole; Meese, Eckart; Lenhof, Hans-Peter; Keller, Andreas

2017-12-05

miRNAs are typically repressing gene expression by binding to the 3' UTR, leading to degradation of the mRNA. This process is dominated by the eight-base seed region of the miRNA. Further, miRNAs are known not only to target genes but also to target significant parts of pathways. A logical line of thoughts is: miRNAs with similar (seed) sequence target similar sets of genes and thus similar sets of pathways. By calculating similarity scores for all 3.25 million pairs of 2,550 human miRNAs, we found that this pattern frequently holds, while we also observed exceptions. Respective results were obtained for both, predicted target genes as well as experimentally validated targets. We note that miRNAs target gene set similarity follows a bimodal distribution, pointing at a set of 282 miRNAs that seems to target genes with very high specificity. Further, we discuss miRNAs with different (seed) sequences that nonetheless regulate similar gene sets or pathways. Most intriguingly, we found miRNA pairs that regulate different gene sets but similar pathways such as miR-6886-5p and miR-3529-5p. These are jointly targeting different parts of the MAPK signaling cascade. The main goal of this study is to provide a general overview on the results, to highlight a selection of relevant results on miRNAs, miRNA seeds, target genes and target pathways and to raise awareness for artifacts in respective comparisons. The full set of information that allows to infer detailed results on each miRNA has been included in miRPathDB, the miRNA target pathway database (https://mpd.bioinf.uni-sb.de).

Timing of saccadic eye movements during visual search for multiple targets

PubMed Central

Wu, Chia-Chien; Kowler, Eileen

2013-01-01

Visual search requires sequences of saccades. Many studies have focused on spatial aspects of saccadic decisions, while relatively few (e.g., Hooge & Erkelens, 1999) consider timing. We studied saccadic timing during search for targets (thin circles containing tilted lines) located among nontargets (thicker circles). Tasks required either (a) estimating the mean tilt of the lines, or (b) looking at targets without a concurrent psychophysical task. The visual similarity of targets and nontargets affected both the probability of hitting a target and the saccade rate in both tasks. Saccadic timing also depended on immediate conditions, specifically, (a) the type of currently fixated location (dwell time was longer on targets than nontargets), (b) the type of goal (dwell time was shorter prior to saccades that hit targets), and (c) the ordinal position of the saccade in the sequence. The results show that timing decisions take into account the difficulty of finding targets, as well as the cost of delays. Timing strategies may be a compromise between the attempt to find and locate targets, or other suitable landing locations, using eccentric vision (at the cost of increased dwell times) versus a strategy of exploring less selectively at a rapid rate. PMID:24049045

Reading Behind the Lines: The Factors Affecting the Text Reception Threshold in Hearing Aid Users.

PubMed

Zekveld, Adriana A; Pronk, Marieke; Danielsson, Henrik; Rönnberg, Jerker

2018-03-15

The visual Text Reception Threshold (TRT) test (Zekveld et al., 2007) has been designed to assess modality-general factors relevant for speech perception in noise. In the last decade, the test has been adopted in audiology labs worldwide. The 1st aim of this study was to examine which factors best predict interindividual differences in the TRT. Second, we aimed to assess the relationships between the TRT and the speech reception thresholds (SRTs) estimated in various conditions. First, we reviewed studies reporting relationships between the TRT and the auditory and/or cognitive factors and formulated specific hypotheses regarding the TRT predictors. These hypotheses were tested using a prediction model applied to a rich data set of 180 hearing aid users. In separate association models, we tested the relationships between the TRT and the various SRTs and subjective hearing difficulties, while taking into account potential confounding variables. The results of the prediction model indicate that the TRT is predicted by the ability to fill in missing words in incomplete sentences, by lexical access speed, and by working memory capacity. Furthermore, in line with previous studies, a moderate association between higher age, poorer pure-tone hearing acuity, and poorer TRTs was observed. Better TRTs were associated with better SRTs for the correct perception of 50% of Hagerman matrix sentences in a 4-talker babble, as well as with better subjective ratings of speech perception. Age and pure-tone hearing thresholds significantly confounded these associations. The associations of the TRT with SRTs estimated in other conditions and with subjective qualities of hearing were not statistically significant when adjusting for age and pure-tone average. We conclude that the abilities tapped into by the TRT test include processes relevant for speeded lexical decision making when completing partly masked sentences and that these processes require working memory capacity. Furthermore

Non-targeted Metabolomics in Diverse Sorghum Breeding Lines Indicates Primary and Secondary Metabolite Profiles Are Associated with Plant Biomass Accumulation and Photosynthesis

DOE PAGES

Turner, Marie F.; Heuberger, Adam L.; Kirkwood, Jay S.; ...

2016-07-11

Metabolomics is an emerging method to improve our understanding of how genetic diversity affects phenotypic variation in plants. Recent studies have demonstrated that genotype has a major influence on biochemical variation in several types of plant tissues, however, the association between metabolic variation and variation in morphological and physiological traits is largely unknown. Sorghum bicolor (L.) is an important food and fuel crop with extensive genetic and phenotypic variation. Sorghum lines have been bred for differing phenotypes beneficial for production of grain (food), stem sugar (food, fuel), and cellulosic biomass (forage, fuel), and these varying phenotypes are the end productsmore » of innate metabolic programming which determines how carbon is allocated during plant growth and development. Further, sorghum has been adapted among highly diverse environments. Because of this geographic and phenotypic variation, the sorghum metabolome is expected to be highly divergent; however, metabolite variation in sorghum has not been characterized. Here, we utilize a phenotypically diverse panel of sorghum breeding lines to identify associations between leaf metabolites and morpho-physiological traits. The panel (11 lines) exhibited significant variation for 21 morpho-physiological traits, as well as broader trends in variation by sorghum type (grain vs. biomass types). Variation was also observed for cell wall constituents (glucan, xylan, lignin, ash). Non-targeted metabolomics analysis of leaf tissue showed that 956 of 1181 metabolites varied among the lines (81%, ANOVA, FDR adjusted p < 0.05). Both univariate and multivariate analyses determined relationships between metabolites and morpho-physiological traits, and 384 metabolites correlated with at least one trait (32%, p < 0.05), including many secondary metabolites such as glycosylated flavonoids and chlorogenic acids. The use of metabolomics to explain relationships between two or more morpho

Non-targeted Metabolomics in Diverse Sorghum Breeding Lines Indicates Primary and Secondary Metabolite Profiles Are Associated with Plant Biomass Accumulation and Photosynthesis

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

Turner, Marie F.; Heuberger, Adam L.; Kirkwood, Jay S.

Metabolomics is an emerging method to improve our understanding of how genetic diversity affects phenotypic variation in plants. Recent studies have demonstrated that genotype has a major influence on biochemical variation in several types of plant tissues, however, the association between metabolic variation and variation in morphological and physiological traits is largely unknown. Sorghum bicolor (L.) is an important food and fuel crop with extensive genetic and phenotypic variation. Sorghum lines have been bred for differing phenotypes beneficial for production of grain (food), stem sugar (food, fuel), and cellulosic biomass (forage, fuel), and these varying phenotypes are the end productsmore » of innate metabolic programming which determines how carbon is allocated during plant growth and development. Further, sorghum has been adapted among highly diverse environments. Because of this geographic and phenotypic variation, the sorghum metabolome is expected to be highly divergent; however, metabolite variation in sorghum has not been characterized. Here, we utilize a phenotypically diverse panel of sorghum breeding lines to identify associations between leaf metabolites and morpho-physiological traits. The panel (11 lines) exhibited significant variation for 21 morpho-physiological traits, as well as broader trends in variation by sorghum type (grain vs. biomass types). Variation was also observed for cell wall constituents (glucan, xylan, lignin, ash). Non-targeted metabolomics analysis of leaf tissue showed that 956 of 1181 metabolites varied among the lines (81%, ANOVA, FDR adjusted p < 0.05). Both univariate and multivariate analyses determined relationships between metabolites and morpho-physiological traits, and 384 metabolites correlated with at least one trait (32%, p < 0.05), including many secondary metabolites such as glycosylated flavonoids and chlorogenic acids. The use of metabolomics to explain relationships between two or more morpho

Building Cre Knockin Rat Lines Using CRISPR/Cas9.

PubMed

Ma, Yuanwu; Zhang, Lianfeng; Huang, Xingxu

2017-01-01

Conditional gene inactivation strategy helps researchers to study the gene functions that are critical in embryogenesis or in defined tissues of adulthood. The Cre/loxP system is widely used for conditional gene inactivation/activation in cells or organisms. Cre knockin animal lines are essential for gene expression or inactivation in a spatially and temporally restricted manner. However, to generate a Cre knockin line by traditional approach is laborious. Recently, the clustered regularly interspaced short palindromic repeats and CRISPR-associated protein 9 (CRISPR/Cas9) has been proven as a simple and efficient genome-editing tool. We have used CRISPR/Cas9 system to generate rat strains that carry Cre genes in different targeted gene loci by direct delivery of gRNAs/Cas9/donors into fertilized eggs. Here, we described a stepwise procedure for the generation of Cre knockin rat, including target site selection, RNA preparation, the construction of the template donor, pronuclear injection, and the genotyping of precise Cre insertion in F 0 rats. Taken together, the establishment of Cre knockin line can be achieved within 6 weeks.

miR-221 and miR-222 expression affects the proliferation potential of human prostate carcinoma cell lines by targeting p27Kip1.

PubMed

Galardi, Silvia; Mercatelli, Neri; Giorda, Ezio; Massalini, Simone; Frajese, Giovanni Vanni; Ciafrè, Silvia Anna; Farace, Maria Giulia

2007-08-10

MicroRNAs are short regulatory RNAs that negatively modulate protein expression at a post-transcriptional level and are deeply involved in the pathogenesis of several types of cancers. Here we show that miR-221 and miR-222, encoded in tandem on chromosome X, are overexpressed in the PC3 cellular model of aggressive prostate carcinoma, as compared with LNCaP and 22Rv1 cell line models of slowly growing carcinomas. In all cell lines tested, we show an inverse relationship between the expression of miR-221 and miR-222 and the cell cycle inhibitor p27(Kip1). We recognize two target sites for the microRNAs in the 3' untranslated region of p27 mRNA, and we show that miR-221/222 ectopic overexpression directly results in p27 down-regulation in LNCaP cells. In those cells, we demonstrate that the ectopic overexpression of miR-221/222 strongly affects their growth potential by inducing a G(1) to S shift in the cell cycle and is sufficient to induce a powerful enhancement of their colony-forming potential in soft agar. Consistently, miR-221 and miR-222 knock-down through antisense LNA oligonucleotides increases p27(Kip1) in PC3 cells and strongly reduces their clonogenicity in vitro. Our results suggest that miR-221/222 can be regarded as a new family of oncogenes, directly targeting the tumor suppressor p27(Kip1), and that their overexpression might be one of the factors contributing to the oncogenesis and progression of prostate carcinoma through p27(Kip1) down-regulation.

High intensity proton beam transportation through fringe field of 70 MeV compact cyclotron to beam line targets

NASA Astrophysics Data System (ADS)

Zhang, Xu; Li, Ming; Wei, Sumin; Xing, Jiansheng; Hu, Yueming; Johnson, Richard R.; Piazza, Leandro; Ryjkov, Vladimir

2016-06-01

From the stripping points, the high intensity proton beam of a compact cyclotron travels through the fringe field area of the machine to the combination magnet. Starting from there the beams with various energy is transferred to the switching magnet for distribution to the beam line targets. In the design of the extraction and transport system for the compact proton cyclotron facilities, such as the 70 MeV in France and the 100 MeV in China, the space charge effect as the beam crosses the fringe field has not been previously considered; neither has the impact on transverse beam envelope coupled from the longitudinal direction. Those have been concerned much more with the higher beam-power because of the beam loss problem. In this paper, based on the mapping data of 70 MeV cyclotron including the fringe field by BEST Cyclotron Inc (BEST) and combination magnet field by China Institute of Atomic Energy (CIAE), the beam extraction and transport are investigated for the 70 MeV cyclotron used on the SPES project at Istituto Nazionale di Fisica Nucleare, Laboratori Nazionali di Legnaro (INFN-LNL). The study includes the space charge effect and longitudinal and transverse coupling mentioned above, as well as the matching of beam optics using the beam line for medical isotope production as an example. In addition, the designs of the ±45° switching magnets and the 60° bending magnet for the extracted beam with the energy from 35 MeV to 70 MeV have been made. Parts of the construction and field measurements of those magnets have been done as well. The current result shows that, the design considers the complexity of the compact cyclotron extraction area and fits the requirements of the extraction and transport for high intensity proton beam, especially at mA intensity levels.

Translation Assessment: Notes on the Interlingual Transfer of an Advertising Text.

ERIC Educational Resources Information Center

Horton, David

1998-01-01

Attempts to measure translation quality raise important questions about the nature of textual transfer, the relationship between source- and target-language texts, and translation functions. Examination of a typical advertising text, translated from English to German, shows the degree of freedom with which texts are manipulated in professional…

Phenotypic high-throughput screening elucidates target pathway in breast cancer stem cell-like cells.

PubMed

Carmody, Leigh C; Germain, Andrew R; VerPlank, Lynn; Nag, Partha P; Muñoz, Benito; Perez, Jose R; Palmer, Michelle A J

2012-10-01

Cancer stem cells (CSCs) are resistant to standard cancer treatments and are likely responsible for cancer recurrence, but few therapies target this subpopulation. Due to the difficulty in propagating CSCs outside of the tumor environment, previous work identified CSC-like cells by inducing human breast epithelial cells into an epithelial-to-mesenchymal transdifferentiated state (HMLE_sh_ECad). A phenotypic screen was conducted against HMLE_sh_ECad with 300 718 compounds from the Molecular Libraries Small Molecule Repository to identify selective inhibitors of CSC growth. The screen yielded 2244 hits that were evaluated for toxicity and selectivity toward an isogenic control cell line. An acyl hydrazone scaffold emerged as a potent and selective scaffold targeting HMLE_sh_ECad. Fifty-three analogues were acquired and tested; compounds ranged in potency from 790 nM to inactive against HMLE_sh_ECad. Of the analogues, ML239 was best-in-class with an IC(50)= 1.18 µM against HMLE_sh_ECad, demonstrated a >23-fold selectivity over the control line, and was toxic to another CSC-like line, HMLE_shTwist, and a breast carcinoma cell line, MDA-MB-231. Gene expression studies conducted with ML239-treated cells showed altered gene expression in the NF-κB pathway in the HMLE_sh_ECad line but not in the isogenic control line. Future studies will be directed toward the identification of ML239 target(s).

Towards text simplification for poor readers with intellectual disability: when do connectives enhance text cohesion?

PubMed

Fajardo, Inmaculada; Tavares, Gema; Ávila, Vicenta; Ferrer, Antonio

2013-04-01

Cohesive elements of texts such as connectives (e.g., but, in contrast) are expected to facilitate inferential comprehension in poor readers. Two experiments tested this prediction in poor readers with intellectual disability (ID) by: (a) comparing literal and inferential text comprehension of texts with and without connectives and/or high frequency content words (Experiment 1) and (b) exploring the effects of type and familiarity of connectives on two-clause text comprehension by means of a cloze task (Experiment 2). Neither the addition of high frequency content words nor connectives in general produced inferential comprehension improvements. However, although readers with ID were less likely to select the target connective in the cloze task than chronologically age-matched readers (mean age=21 years) in general, their performance was affected by the type of connective and its familiarity. Familiarity had a facilitative effect for additive and contrastive connectives, but interfered in the case of temporal and causal connectives. The average performance of a reading level-matched control group (typically developing children) was similar to the group of readers with ID although the pattern of interaction between familiarity and type of connectives varied between groups. The implications of these findings for the adaptation of texts in special education contexts are discussed. Copyright © 2013 Elsevier Ltd. All rights reserved.

M68000 RNF text formatter user's manual

NASA Technical Reports Server (NTRS)

Will, R. W.; Grantham, C.

1985-01-01

A powerful, flexible text formatting program, RNF, is described. It is designed to automate many of the tedious elements of typing, including breaking a document into pages with titles and page numbers, formatting chapter and section headings, keeping track of page numbers for use in a table of contents, justifying lines by inserting blanks to give an even right margin, and inserting figures and footnotes at appropriate places on the page. The RNF program greatly facilitates both preparing and modifying a document because it allows you to concentrate your efforts on the content of the document instead of its appearance and because it removes the necessity of retyping text that has not changed.

A Three-Dimensional Target Depth-Resolution Method with a Single-Vector Sensor.

PubMed

Zhao, Anbang; Bi, Xuejie; Hui, Juan; Zeng, Caigao; Ma, Lin

2018-04-12

This paper mainly studies and verifies the target number category-resolution method in multi-target cases and the target depth-resolution method of aerial targets. Firstly, target depth resolution is performed by using the sign distribution of the reactive component of the vertical complex acoustic intensity; the target category and the number resolution in multi-target cases is realized with a combination of the bearing-time recording information; and the corresponding simulation verification is carried out. The algorithm proposed in this paper can distinguish between the single-target multi-line spectrum case and the multi-target multi-line spectrum case. This paper presents an improved azimuth-estimation method for multi-target cases, which makes the estimation results more accurate. Using the Monte Carlo simulation, the feasibility of the proposed target number and category-resolution algorithm in multi-target cases is verified. In addition, by studying the field characteristics of the aerial and surface targets, the simulation results verify that there is only amplitude difference between the aerial target field and the surface target field under the same environmental parameters, and an aerial target can be treated as a special case of a surface target; the aerial target category resolution can then be realized based on the sign distribution of the reactive component of the vertical acoustic intensity so as to realize three-dimensional target depth resolution. By processing data from a sea experiment, the feasibility of the proposed aerial target three-dimensional depth-resolution algorithm is verified.

At-Line Cellular Screening Methodology for Bioactives in Mixtures Targeting the α7-Nicotinic Acetylcholine Receptor.

PubMed

Otvos, Reka A; Mladic, Marija; Arias-Alpizar, Gabriela; Niessen, Wilfried M A; Somsen, Govert W; Smit, August B; Kool, Jeroen

2016-06-01

The α7-nicotinic acetylcholine receptor (α7-nAChR) is a ligand-gated ion channel expressed in different regions of the central nervous system (CNS). The α7-nAChR has been associated with Alzheimer's disease, epilepsy, and schizophrenia, and therefore is extensively studied as a drug target for the treatment of these diseases. Important sources for new compounds in drug discovery are natural extracts. Since natural extracts are complex mixtures, identification of the bioactives demands the use of analytical techniques to separate a bioactive from inactive compounds. This study describes screening methodology for identifying bioactive compounds in mixtures acting on the α7-nAChR. The methodology developed combines liquid chromatography (LC) coupled via a split with both an at-line calcium (Ca(2+))-flux assay and high-resolution mass spectrometry (MS). This allows evaluation of α7-nAChR responses after LC separation, while parallel MS enables compound identification. The methodology was optimized for analysis of agonists and positive allosteric modulators, and was successfully applied to screening of the hallucinogen mushroom Psilocybe Mckennaii The crude mushroom extract was analyzed using both reversed-phase and hydrophilic interaction liquid chromatography. Matching retention times and peak shapes of bioactives found with data from the parallel MS measurements allowed rapid pinpointing of accurate masses corresponding to the bioactives. © 2016 Society for Laboratory Automation and Screening.

Diagrams increase the recall of nondepicted text when understanding is also increased.

PubMed

Serra, Michael J

2010-02-01

Multimedia presentations typically produce better memory and understanding than do single-medium presentations. Little research, however, has considered the effect of multimedia on memory for nonmultimedia information within a large multimedia presentation (e.g., nondepicted text in a large text with diagrams). To this end, the present two experiments compared memory for target text information that was either depicted in diagrams or not. Participants (n = 180) studied either a text-only version of a text about lightning or a text-with-diagrams version in which half the target information was depicted in diagrams. Memory was tested with both free recall and cued recall questions. Overall, diagrams did not affect memory for the entire text; diagrams increased memory only for the information they depicted. Diagrams exerted a generalized effect on free recall only when diagrams increased the overall understanding of the text (i.e., when the participants studied the materials twice before the test).

In vitro Development of Chemotherapy and Targeted Therapy Drug-Resistant Cancer Cell Lines: A Practical Guide with Case Studies

PubMed Central

McDermott, Martina; Eustace, Alex J.; Busschots, Steven; Breen, Laura; Crown, John; Clynes, Martin; O’Donovan, Norma; Stordal, Britta

2014-01-01

The development of a drug-resistant cell line can take from 3 to 18 months. However, little is published on the methodology of this development process. This article will discuss key decisions to be made prior to starting resistant cell line development; the choice of parent cell line, dose of selecting agent, treatment interval, and optimizing the dose of drug for the parent cell line. Clinically relevant drug-resistant cell lines are developed by mimicking the conditions cancer patients experience during chemotherapy and cell lines display between two- and eight-fold resistance compared to their parental cell line. Doses of drug administered are low, and a pulsed treatment strategy is often used where the cells recover in drug-free media. High-level laboratory models are developed with the aim of understanding potential mechanisms of resistance to chemotherapy agents. Doses of drug are higher and escalated over time. It is common to have difficulty developing stable clinically relevant drug-resistant cell lines. A comparative selection strategy of multiple cell lines or multiple chemotherapeutic agents mitigates this risk and gives insight into which agents or type of cell line develops resistance easily. Successful selection strategies from our research are presented. Pulsed-selection produced platinum or taxane-resistant large cell lung cancer (H1299 and H460) and temozolomide-resistant melanoma (Malme-3M and HT144) cell lines. Continuous selection produced a lapatinib-resistant breast cancer cell line (HCC1954). Techniques for maintaining drug-resistant cell lines are outlined including; maintaining cells with chemotherapy, pulse treating with chemotherapy, or returning to master drug-resistant stocks. The heterogeneity of drug-resistant models produced from the same parent cell line with the same chemotherapy agent is explored with reference to P-glycoprotein. Heterogeneity in drug-resistant cell lines reflects the heterogeneity that can occur in clinical

SDSS-IV eBOSS emission-line galaxy pilot survey

DOE PAGES

Comparat, J.; Delubac, T.; Jouvel, S.; ...

2016-08-09

The Sloan Digital Sky Survey IV extended Baryonic Oscillation Spectroscopic Survey (SDSS-IV/eBOSS) will observe 195,000 emission-line galaxies (ELGs) to measure the Baryonic Acoustic Oscillation standard ruler (BAO) at redshift 0.9. To test different ELG selection algorithms, 9,000 spectra were observed with the SDSS spectrograph as a pilot survey based on data from several imaging surveys. First, using visual inspection and redshift quality flags, we show that the automated spectroscopic redshifts assigned by the pipeline meet the quality requirements for a reliable BAO measurement. We also show the correlations between sky emission, signal-to-noise ratio in the emission lines, and redshift error.more » Then we provide a detailed description of each target selection algorithm we tested and compare them with the requirements of the eBOSS experiment. As a result, we provide reliable redshift distributions for the different target selection schemes we tested. Lastly, we determine an target selection algorithms that is best suited to be applied on DECam photometry because they fulfill the eBOSS survey efficiency requirements.« less

Advances of Molecular Targeted Therapy in Gastric Cancer.

PubMed

Cetin, Bulent; Gumusay, Ozge; Cengiz, Mustafa; Ozet, Ahmet

2016-06-01

Gastric cancer is the second most common cause of cancer-related death in the world, and its prognosis remains poor with a median overall survival of 12 months for advanced disease. Advances in the understanding of molecular genetics have led to the development of directed molecular targeted therapy in gastric cancer, leading to improve patient outcomes and quality of life. In the treatment of human epidermal growth factor receptor 2 (HER2)-positive gastric cancer, the addition of trastuzumab significantly improves survival in the first-line setting of therapy. Ramucirumab, an antibody directed against vascular endothelial growth factor receptor 2, significantly improved progression-free and overall survival and has been approved for second-line treatment of gastric cancer. Anti-mesenchymal-epithelial transition (c-MET), mammalian target of rapamycin inhibitors, and polo-like kinase 1 inhibitors are under investigation as a novel therapeutic option for the treatment of gastric cancer. The novel therapies target the key immune checkpoint interaction between a T cell co-inhibitory receptor called programmed death 1 (PD-1) and one of its immunosuppressive ligands, PD-L1. This article reviews molecular targeted therapies in gastric cancer, in light of recent advances.

Formulation and evaluation of targeted nanoparticles for breast cancer theranostic system.

PubMed

Dadras, Pegah; Atyabi, Fatemeh; Irani, Shiva; Ma'mani, Leila; Foroumadi, Alireza; Mirzaie, Zahra Hadavand; Ebrahimi, Marzieh; Dinarvand, R

2017-01-15

Theranostic polymeric NPs developed for both cancer diagnosis and cancer therapy. This multifunctional polymeric vehicle was prepared by a single emulsion evaporation method, using carboxyl-terminated PLGA. LHRH as a targeting moiety, was conjugated to the surface of polymeric carrier by applying polyethylene glycol. The results indicated that the diameter of NPs was ~185.4±4.6nm as defined by DLS. The entrapment efficacy of docetaxel, silibinin, and SPIONs was 84.6±4.1%, 80.6±2.7%, and 77.9±4.3%, respectively. The NPs showed a triphasic in-vitro drug release pattern. MTT assay was done on two cell lines, MCF-7 and SKOV-3. Enhanced cellular uptake ability of the targeted NPs to MCF-7 was evaluated in-vitro by confocal laser scanning microscopy. The results indicated that compared to non-targeted NPs, the LHRH targeted NPs had significant efficacy at IC50 concentration. The effect of the NPs on VEGF expression in MCF-7 and SKOV-3 cells was investigated by Real-Time PCR method. VEGF mRNA level expression in MCF-7 cell line reduced by 83% in comparison to control cell line. The designed NPs can be used as promising multifunctional platform for detection and targeted drug delivery in breast cancer. Copyright © 2016 Elsevier B.V. All rights reserved.

Making Inferences from Text: It's Vocabulary That Matters

ERIC Educational Resources Information Center

Lucas, Rebecca; Norbury, Courtenay Frazier

2015-01-01

Purpose: Many children with communication disorders have reading comprehension difficulties, and in order to target interventions effectively it is important to identify which specific components of comprehension are especially challenging. The current study explored the relationship between text-inferencing skill, autistic symptomatology, and…

Simultaneous targeting of EGFR, HER2, and HER4 by afatinib overcomes intrinsic and acquired cetuximab resistance in head and neck squamous cell carcinoma cell lines.

PubMed

De Pauw, Ines; Lardon, Filip; Van den Bossche, Jolien; Baysal, Hasan; Fransen, Erik; Deschoolmeester, Vanessa; Pauwels, Patrick; Peeters, Marc; Vermorken, Jan Baptist; Wouters, An

2018-06-01

The epidermal growth factor receptor (EGFR, HER1) is a therapeutic target in head and neck squamous cell carcinoma (HNSCC). After initial promising results with EGFR-targeted therapies such as cetuximab, therapeutic resistance has become a major clinical problem, and new treatment options are therefore necessary. Moreover, the relationship between HER receptors, anti-EGFR therapies, and the human papillomavirus (HPV) status in HNSCC is not fully understood. In contrast to first-generation EGFR inhibitors, afatinib irreversibly inhibits multiple HER receptors simultaneously. Therefore, treatment with afatinib might result in a more pronounced therapeutic benefit, even in patients experiencing cetuximab resistance. In this study, the cytotoxic effect of afatinib as single agent and in combination with cisplatin was investigated in cetuximab-sensitive, intrinsically cetuximab-resistant, and acquired cetuximab-resistant HNSCC cell lines with different HPV status under normoxia and hypoxia. Furthermore, the influence of cetuximab resistance, HPV, and hypoxia on the expression of HER receptors was investigated. Our results demonstrated that afatinib was able to establish cytotoxicity in cetuximab-sensitive, intrinsically cetuximab-resistant, and acquired cetuximab-resistant HNSCC cell lines, independent of the HPV status. However, cross-resistance between cetuximab and afatinib might be possible. Treatment with afatinib caused a G 0 /G 1 cell cycle arrest as well as induction of apoptotic cell death. Additive to antagonistic interactions between afatinib and cisplatin could be observed. Neither cetuximab resistance nor HPV status significantly influenced the expression of HER receptors in HNSCC cell lines. In contrast, the expression of EGFR, HER2, and HER3 was significantly altered under hypoxia. Oxygen deficiency is a common characteristic of HNSCC tumors, and these hypoxic tumor regions often contain cells that are more resistant to treatment. However, we observed

Naproxen induces cell cycle arrest and apoptosis in human urinary bladder cancer cell lines and chemically induced cancers by targeting PI3-K

PubMed Central

Kim, Mi-Sung; Kim, Jong-Eun; Lim, Do Young; Huang, Zunnan; Chen, Hanyong; Langfald, Alyssa; Lubet, Ronald A.; Grubbs, Clinton J.; Dong, Zigang; Bode, Ann M.

2014-01-01

Naproxen ((S)-6-methoxy-α-methyl-2-naphthaleneacetic acid) is a potent nonsteroidal anti-inflammatory drug that inhibits both COX-1 and COX-2 and is widely used as an over-the-counter medication. Naproxen exhibits analgesic, anti-pyretic, and anti-inflammatory activities. Naproxen, as well as other NSAIDS, has been reported to be effective in the prevention of urinary bladder cancer in rodents. However, potential targets other than the COX isozymes have not been reported. We examined potential additional targets in urinary bladder cancer cells and in rat bladder cancers. Computer kinase profiling results suggested that phosphatidylinositol 3-kinase (PI3-K) is a potential target for naproxen. In vitro kinase assay data revealed that naproxen interacts with PI3-K and inhibits its kinase activity. Pull-down binding assay data confirmed that PI3-K directly binds with naproxen in vitro and ex vivo. Western blot data showed that naproxen decreased phosphorylation of Akt, and subsequently decreased Akt signaling in UM-UC-5 and UMUC-14 urinary bladder cancer cells. Furthermore, naproxen suppressed anchorage-independent cell growth and decreased cell viability by targeting PI3-K in both cell lines. Naproxen caused an accumulation of cells at the G1 phase mediated through CDK4, cyclin D1 and p21. Moreover, naproxen induced significant apoptosis, accompanied with increased levels of cleaved caspase 3, caspase 7, and poly (ADP-ribose) polymerase (PARP) in both cell types. Naproxen-induced cell death was mainly due to apoptosis in which a prominent down-regulation of Bcl-2 and up-regulation of Bax were involved. Naproxen also caused apoptosis and inhibited Akt phosphorylation in rat urinary bladder cancers induced by N-butyl-N-(4-hydroxybutyl)-nitrosamine (OH-BBN). PMID:24327721

Line-Editor Computer Program

NASA Technical Reports Server (NTRS)

Scott, Peter J.

1989-01-01

ZED editing program for DEC VAX computer simple, powerful line editor for text, program source code, and nonbinary data. Excels in processing of text by use of procedure files. Also features versatile search qualifiers, global changes, conditionals, online help, hexadecimal mode, space compression, looping, logical combinations of search strings, journaling, visible control characters, and automatic detabbing. Users of Cambridge implementation devised such ZED procedures as chess games, calculators, and programs for evaluating pi. Written entirely in C.

Calibrating Reach Distance to Visual Targets

ERIC Educational Resources Information Center

Mon-Williams, Mark; Bingham, Geoffrey P.

2007-01-01

The authors investigated the calibration of reach distance by gradually distorting the haptic feedback obtained when participants grasped visible target objects. The authors found that the modified relationship between visually specified distance and reach distance could be captured by a straight-line mapping function. Thus, the relation could be…

Analysis of line structure in handwritten documents using the Hough transform

NASA Astrophysics Data System (ADS)

Ball, Gregory R.; Kasiviswanathan, Harish; Srihari, Sargur N.; Narayanan, Aswin

2010-01-01

In the analysis of handwriting in documents a central task is that of determining line structure of the text, e.g., number of text lines, location of their starting and end-points, line-width, etc. While simple methods can handle ideal images, real world documents have complexities such as overlapping line structure, variable line spacing, line skew, document skew, noisy or degraded images etc. This paper explores the application of the Hough transform method to handwritten documents with the goal of automatically determining global document line structure in a top-down manner which can then be used in conjunction with a bottom-up method such as connected component analysis. The performance is significantly better than other top-down methods, such as the projection profile method. In addition, we evaluate the performance of skew analysis by the Hough transform on handwritten documents.

A Three-Dimensional Target Depth-Resolution Method with a Single-Vector Sensor

PubMed Central

Zhao, Anbang; Bi, Xuejie; Hui, Juan; Zeng, Caigao; Ma, Lin

2018-01-01

This paper mainly studies and verifies the target number category-resolution method in multi-target cases and the target depth-resolution method of aerial targets. Firstly, target depth resolution is performed by using the sign distribution of the reactive component of the vertical complex acoustic intensity; the target category and the number resolution in multi-target cases is realized with a combination of the bearing-time recording information; and the corresponding simulation verification is carried out. The algorithm proposed in this paper can distinguish between the single-target multi-line spectrum case and the multi-target multi-line spectrum case. This paper presents an improved azimuth-estimation method for multi-target cases, which makes the estimation results more accurate. Using the Monte Carlo simulation, the feasibility of the proposed target number and category-resolution algorithm in multi-target cases is verified. In addition, by studying the field characteristics of the aerial and surface targets, the simulation results verify that there is only amplitude difference between the aerial target field and the surface target field under the same environmental parameters, and an aerial target can be treated as a special case of a surface target; the aerial target category resolution can then be realized based on the sign distribution of the reactive component of the vertical acoustic intensity so as to realize three-dimensional target depth resolution. By processing data from a sea experiment, the feasibility of the proposed aerial target three-dimensional depth-resolution algorithm is verified. PMID:29649173

Probing microbubble targeting with atomic force microscopy.

PubMed

Sboros, V; Glynos, E; Ross, J A; Moran, C M; Pye, S D; Butler, M; McDicken, W N; Brown, S B; Koutsos, V

2010-10-01

Microbubble science is expanding beyond ultrasound imaging applications to biological targeting and drug/gene delivery. The characteristics of molecular targeting should be tested by a measurement system that can assess targeting efficacy and strength. Atomic force microscopy (AFM) is capable of piconewton force resolution, and is reported to measure the strength of single hydrogen bonds. An in-house targeted microbubble modified using the biotin-avidin chemistry and the CD31 antibody was used to probe cultures of Sk-Hep1 hepatic endothelial cells. We report that the targeted microbubbles provide a single distribution of adhesion forces with a median of 93pN. This interaction is assigned to the CD31 antibody-antigen unbinding event. Information on the distances between the interaction forces was obtained and could be important for future microbubble fabrication. In conclusion, the capability of single microbubbles to target cell lines was shown to be feasible with AFM.

The effects of visual crowding, text size, and positional uncertainty on text legibility at a glance.

PubMed

Dobres, Jonathan; Wolfe, Benjamin; Chahine, Nadine; Reimer, Bryan

2018-07-01

Reading at a glance, once a relatively infrequent mode of reading, is becoming common. Mobile interaction paradigms increasingly dominate the way in which users obtain information about the world, which often requires reading at a glance, whether from a smartphone, wearable device, or in-vehicle interface. Recent research in these areas has shown that a number of factors can affect text legibility when words are briefly presented in isolation. Here we expand upon this work by examining how legibility is affected by more crowded presentations. Word arrays were combined with a lexical decision task, in which the size of the text elements and the inter-line spacing (leading) between individual items were manipulated to gauge their relative impacts on text legibility. In addition, a single-word presentation condition that randomized the location of presentation was compared with previous work that held position constant. Results show that larger text was more legible than smaller text. Wider leading significantly enhanced legibility as well, but contrary to expectations, wider leading did not fully counteract decrements in legibility at smaller text sizes. Single-word stimuli presented with random positioning were more difficult to read than stationary counterparts from earlier studies. Finally, crowded displays required much greater processing time compared to single-word displays. These results have implications for modern interface design, which often present interactions in the form of scrollable and/or selectable lists. The present findings are of practical interest to the wide community of graphic designers and interface engineers responsible for developing our interfaces of daily use. Copyright © 2018 Elsevier Ltd. All rights reserved.

Examining competing hypotheses for the effects of diagrams on recall for text.

PubMed

Ortegren, Francesca R; Serra, Michael J; England, Benjamin D

2015-01-01

Supplementing text-based learning materials with diagrams typically increases students' free recall and cued recall of the presented information. In the present experiments, we examined competing hypotheses for why this occurs. More specifically, although diagrams are visual, they also serve to repeat information from the text they accompany. Both visual presentation and repetition are known to aid students' recall of information. To examine to what extent diagrams aid recall because they are visual or repetitive (or both), we had college students in two experiments (n = 320) read a science text about how lightning storms develop before completing free-recall and cued-recall tests over the presented information. Between groups, we manipulated the format and repetition of target pieces of information in the study materials using a 2 (visual presentation of target information: diagrams present vs. diagrams absent) × 2 (repetition of target information: present vs. absent) between-participants factorial design. Repetition increased both the free recall and cued recall of target information, and this occurred regardless of whether that repetition was in the form of text or a diagram. In contrast, the visual presentation of information never aided free recall. Furthermore, visual presentation alone did not significantly aid cued recall when participants studied the materials once before the test (Experiment 1) but did when they studied the materials twice (Experiment 2). Taken together, the results of the present experiments demonstrate the important role of repetition (i.e., that diagrams repeat information from the text) over the visual nature of diagrams in producing the benefits of diagrams for recall.

High-speed countercurrent chromatographic recovery and off-line electrospray ionization mass spectrometry profiling of bisdesmodic saponins from Saponaria officinalis possessing synergistic toxicity enhancing properties on targeted antitumor toxins.

PubMed

Thakur, Mayank; Jerz, Gerold; Tuwalska, Dorota; Gilabert-Oriol, Roger; Wybraniec, Sławomir; Winterhalter, Peter; Fuchs, Hendrik; Weng, Alexander

2014-04-01

Saponaria officinalis L. (Caryophyllaceae), also known as fuller's herb or soapwort is a medicinal plant, which grows from Europe to Central Asia. Medicinal properties attributed to this plant include its antitussive and galactogogue properties. Recently, bisdesmodic saponins with very specific structural features from S. officinalis have been shown to strongly enhance the efficacy of specific targeted toxins (anti-tumor antibodies connected to protein toxins) in-vitro and in-vivo in a synergistic manner. In the presently reported novel approach we used preparative all-liquid high-speed countercurrent chromatography (HSCCC) to recover a total of 22 fractions using biphasic solvent system tert-butylmethylether/n-butanol/acetonitrile/water 1:3:1:5 (v/v/v/v) from a complex precipitated crude saponin mixture. Out of these 22 fractions, 3 fractions had the enhancer effect on anti-tumor toxins out of which one fraction (F7) was further tested elaborately in different cell lines. The molecular weight distribution and compound profiles of separated saponins were monitored by off-line injections of the sequentially collected fractions to an electrospray ion-trap mass-spectrometry system (ESI-IT-MS). The functional saponin fractions were mainly bisdesmosidc and contained saponin m/z 1861 amongst other. Using the bio-assay guided monitoring, the highly active fractions containing 2 to 3 bisdesmodic saponins (5μg/mL) were screened for their effectiveness in enhancing the anti-tumor activity of targeted toxin Sap3-EGF, which was determined using the impedance based real-time cell cytotoxicity evaluation. This novel combination of HSCCC fractionation, MS-target-guided profiling procedure and bio-assay guided fractionation yielded 100mg of functional saponins from a 60g crude drug powder in a rapid and convenient manner. Copyright © 2014 Elsevier B.V. All rights reserved.

The Time-domain Spectroscopic Survey: Target Selection for Repeat Spectroscopy

NASA Astrophysics Data System (ADS)

MacLeod, Chelsea L.; Green, Paul J.; Anderson, Scott F.; Eracleous, Michael; Ruan, John J.; Runnoe, Jessie; Nielsen Brandt, William; Badenes, Carles; Greene, Jenny; Morganson, Eric; Schmidt, Sarah J.; Schwope, Axel; Shen, Yue; Amaro, Rachael; Lebleu, Amy; Filiz Ak, Nurten; Grier, Catherine J.; Hoover, Daniel; McGraw, Sean M.; Dawson, Kyle; Hall, Patrick B.; Hawley, Suzanne L.; Mariappan, Vivek; Myers, Adam D.; Pâris, Isabelle; Schneider, Donald P.; Stassun, Keivan G.; Bershady, Matthew A.; Blanton, Michael R.; Seo, Hee-Jong; Tinker, Jeremy; Fernández-Trincado, J. G.; Chambers, Kenneth; Kaiser, Nick; Kudritzki, R.-P.; Magnier, Eugene; Metcalfe, Nigel; Waters, Chris Z.

2018-01-01

As astronomers increasingly exploit the information available in the time domain, spectroscopic variability in particular opens broad new channels of investigation. Here we describe the selection algorithms for all targets intended for repeat spectroscopy in the Time Domain Spectroscopic Survey (TDSS), part of the extended Baryon Oscillation Spectroscopic Survey within the Sloan Digital Sky Survey (SDSS)-IV. Also discussed are the scientific rationale and technical constraints leading to these target selections. The TDSS includes a large “repeat quasar spectroscopy” (RQS) program delivering ∼13,000 repeat spectra of confirmed SDSS quasars, and several smaller “few-epoch spectroscopy” (FES) programs targeting specific classes of quasars as well as stars. The RQS program aims to provide a large and diverse quasar data set for studying variations in quasar spectra on timescales of years, a comparison sample for the FES quasar programs, and an opportunity for discovering rare, serendipitous events. The FES programs cover a wide variety of phenomena in both quasars and stars. Quasar FES programs target broad absorption line quasars, high signal-to-noise ratio normal broad line quasars, quasars with double-peaked or very asymmetric broad emission line profiles, binary supermassive black hole candidates, and the most photometrically variable quasars. Strongly variable stars are also targeted for repeat spectroscopy, encompassing many types of eclipsing binary systems, and classical pulsators like RR Lyrae. Other stellar FES programs allow spectroscopic variability studies of active ultracool dwarf stars, dwarf carbon stars, and white dwarf/M dwarf spectroscopic binaries. We present example TDSS spectra and describe anticipated sample sizes and results.

Transferrin receptor-targeted theranostic gold nanoparticles for photosensitizer delivery in brain tumors

PubMed Central

Dixit, Suraj; Novak, Thomas; Miller, Kayla; Zhu, Yun; Kenney, Malcolm E.

2015-01-01

Therapeutic drug delivery across the blood-brain barrier (BBB) is not only inefficient, but also nonspecific to brain stroma. These are major limitations in the effective treatment of brain cancer. Transferrin peptide (Tfpep) targeted gold nanoparticles (Tfpep-Au NPs) loaded with the photodynamic pro-drug, Pc 4, have been designed and compared with untargeted Au NPs for delivery of the photosensitizer to brain cancer cell lines. In vitro studies of human glioma cancer lines (LN229 and U87) overexpressing the transferrin receptor (TfR) show a significant increase in cellular uptake for targeted conjugates as compared to un-targeted particles. Pc 4 delivered from Tfpep-Au NPs clusters within vesicles after targeting with the Tfpep. Pc 4 continues to accumulate over a 4 hour period. Our work suggests that TfR-targeted Au NPs may have important therapeutic implications for delivering brain tumor therapies and/or providing a platform for noninvasive imaging. PMID:25519743

Line-edge roughness performance targets for EUV lithography

NASA Astrophysics Data System (ADS)

Brunner, Timothy A.; Chen, Xuemei; Gabor, Allen; Higgins, Craig; Sun, Lei; Mack, Chris A.

2017-03-01

Our paper will use stochastic simulations to explore how EUV pattern roughness can cause device failure through rare events, so-called "black swans". We examine the impact of stochastic noise on the yield of simple wiring patterns with 36nm pitch, corresponding to 7nm node logic, using a local Critical Dimension (CD)-based fail criteria Contact hole failures are examined in a similar way. For our nominal EUV process, local CD uniformity variation and local Pattern Placement Error variation was observed, but no pattern failures were seen in the modest (few thousand) number of features simulated. We degraded the image quality by incorporating Moving Standard Deviation (MSD) blurring to degrade the Image Log-Slope (ILS), and were able to find conditions where pattern failures were observed. We determined the Line Width Roughness (LWR) value as a function of the ILS. By use of an artificial "step function" image degraded by various MSD blur, we were able to extend the LWR vs ILS curve into regimes that might be available for future EUV imagery. As we decreased the image quality, we observed LWR grow and also began to see pattern failures. For high image quality, we saw CD distributions that were symmetrical and close to Gaussian in shape. Lower image quality caused CD distributions that were asymmetric, with "fat tails" on the low CD side (under-exposed) which were associated with pattern failures. Similar non-Gaussian CD distributions were associated with image conditions that caused missing contact holes, i.e. CD=0.

The Broad Institute: Screening for Dependencies in Cancer Cell Lines Using Small Molecules | Office of Cancer Genomics

Cancer.gov

Using cancer cell-line profiling, we established an ongoing resource to identify, as comprehensively as possible, the drug-targetable dependencies that specific genomic alterations impart on human cancers. We measured the sensitivity of hundreds of genetically characterized cancer cell lines to hundreds of small-molecule probes and drugs that have highly selective interactions with their targets, and that collectively modulate many distinct nodes in cancer cell circuitry.

D 2 and D-T Liquid-Layer Target Shots at the National Ignition Facility

DOE PAGES

Walters, Curtis; Alger, Ethan; Bhandarkar, Suhas; ...

2018-01-19

Experiments at the National Ignition Facility (NIF) using targets containing a deuterium-tritium (D-T) fuel layer have, until recently, required that a high-quality layer of solid D-T (herein referred to as an ice layer) be formed in the capsule. The development of a process to line the inner surface of a target capsule with a foam layer of a thickness that is typical of ice layers has resulted in the ability to field targets with liquid layers wetting the foam. Successful fielding of liquid-layer targets on NIF required not only a foam-lined capsule but also changes to the capsule filling processmore » and the manner with which the inventory is maintained in the capsule. Additionally, changes to target heater power and the temperature drops across target components were required in order to achieve the desired range of shot temperatures. Finally, these changes and the target’s performance during four target shots on NIF are discussed.« less

D 2 and D-T Liquid-Layer Target Shots at the National Ignition Facility

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

Walters, Curtis; Alger, Ethan; Bhandarkar, Suhas

Experiments at the National Ignition Facility (NIF) using targets containing a deuterium-tritium (D-T) fuel layer have, until recently, required that a high-quality layer of solid D-T (herein referred to as an ice layer) be formed in the capsule. The development of a process to line the inner surface of a target capsule with a foam layer of a thickness that is typical of ice layers has resulted in the ability to field targets with liquid layers wetting the foam. Successful fielding of liquid-layer targets on NIF required not only a foam-lined capsule but also changes to the capsule filling processmore » and the manner with which the inventory is maintained in the capsule. Additionally, changes to target heater power and the temperature drops across target components were required in order to achieve the desired range of shot temperatures. Finally, these changes and the target’s performance during four target shots on NIF are discussed.« less

Cascaded Segmentation-Detection Networks for Word-Level Text Spotting.

PubMed

Qin, Siyang; Manduchi, Roberto

2017-11-01

We introduce an algorithm for word-level text spotting that is able to accurately and reliably determine the bounding regions of individual words of text "in the wild". Our system is formed by the cascade of two convolutional neural networks. The first network is fully convolutional and is in charge of detecting areas containing text. This results in a very reliable but possibly inaccurate segmentation of the input image. The second network (inspired by the popular YOLO architecture) analyzes each segment produced in the first stage, and predicts oriented rectangular regions containing individual words. No post-processing (e.g. text line grouping) is necessary. With execution time of 450 ms for a 1000 × 560 image on a Titan X GPU, our system achieves good performance on the ICDAR 2013, 2015 benchmarks [2], [1].

Flat-walled multilayered anechoic linings: Optimization and application

NASA Astrophysics Data System (ADS)

Xu, Jingfeng; Buchholz, Jörg M.; Fricke, Fergus R.

2005-11-01

The concept of flat-walled multilayered absorbent linings for anechoic rooms was proposed three decades ago. Flat-walled linings have the advantage of being less complicated and, hence, less costly to manufacture and install than the individual units such as wedges. However, there are difficulties in optimizing the design of such absorbent linings. In the present work, the design of a flat-walled multilayered anechoic lining that targeted a 250 Hz cut-off frequency and a 300 mm maximum lining thickness was first optimized using an evolutionary algorithm. Sixteen of the most commonly used commercial fibrous building insulation materials available in Australia were investigated and fourteen design options (i.e., material combinations) were found by the evolutionary algorithm. These options were then evaluated in accordance with their costs and measured acoustic absorption performances. Finally, the completed anechoic room, where the optimized design was applied, was qualified and the results showed that a large percentage (75%-85%) of the distance between the sound source and the room boundaries, on the traverses made, were anechoic.

The RIB production target for the SPES project

NASA Astrophysics Data System (ADS)

Monetti, Alberto; Andrighetto, Alberto; Petrovich, Carlo; Manzolaro, Mattia; Corradetti, Stefano; Scarpa, Daniele; Rossetto, Francesco; Martinez Dominguez, Fernando; Vasquez, Jesus; Rossignoli, Massimo; Calderolla, Michele; Silingardi, Roberto; Mozzi, Aldo; Borgna, Francesca; Vivian, Gianluca; Boratto, Enrico; Ballan, Michele; Prete, Gianfranco; Meneghetti, Giovanni

2015-10-01

Facilities making use of the Isotope Separator On-Line (ISOL) method for the production of Radioactive Ion Beams (RIB) attract interest because they can be used for nuclear structure and reaction studies, astrophysics research and interdisciplinary applications. The ISOL technique is based on the fast release of the nuclear reaction products from the chosen target material together with their ionization into short-lived nuclei beams. Within this context, the SPES (Selective Production of Exotic Species) facility is now under construction in Italy at INFN-LNL (Istituto Nazionale di Fisica Nucleare — Laboratori Nazionali di Legnaro). The SPES facility will produce RIBs mainly from n-rich isotopes obtained by a 40 MeV cyclotron proton beam (200 μA) directly impinging on a uranium carbide multi-foil fission target. The aim of this work is to describe and update, from a comprehensive point of view, the most important results obtained by the analysis of the on-line behavior of the SPES production target assembly. In particular an improved target configuration has been studied by comparing different codes and physics models: the thermal analyses and the isotope production are re-evaluated. Then some consequent radioprotection aspects, which are essential for the installation and operation of the facility, are presented.

Targeting tissue factor as a novel therapeutic oncotarget for eradication of cancer stem cells isolated from tumor cell lines, tumor xenografts and patients of breast, lung and ovarian cancer.

PubMed

Hu, Zhiwei; Xu, Jie; Cheng, Jijun; McMichael, Elizabeth; Yu, Lianbo; Carson, William E

2017-01-03

Targeting cancer stem cell (CSC) represents a promising therapeutic approach as it can potentially fight cancer at its root. The challenge is to identify a surface therapeutic oncotarget on CSC. Tissue factor (TF) is known as a common yet specific surface target for cancer cells and tumor neovasculature in several solid cancers. However, it is unknown if TF is expressed by CSCs. Here we demonstrate that TF is constitutively expressed on CD133 positive (CD133+) or CD24-CD44+ CSCs isolated from human cancer cell lines, tumor xenografts from mice and breast tumor tissues from patients. TF-targeted agents, i.e., a factor VII (fVII)-conjugated photosensitizer (fVII-PS for targeted photodynamic therapy) and fVII-IgG1Fc (Immunoconjugate or ICON for immunotherapy), can eradicate CSC via the induction of apoptosis and necrosis and via antibody-dependent cellular cytotoxicity and complement-dependent cytotoxicity, respectively. In conclusion, these results demonstrate that TF is a novel surface therapeutic oncotarget for CSC, in addition to cancer cell TF and tumor angiogenic vascular endothelial TF. Moreover, this research highlights that TF-targeting therapeutics can effectively eradicate CSCs, without drug resistance, isolated from breast, lung and ovarian cancer with potential to translate into other most commonly diagnosed solid cancer, in which TF is also highly expressed.

Enhanced targeting of triple-negative breast carcinoma and malignant melanoma by photochemical internalization of CSPG4-targeting immunotoxins.

PubMed

Eng, M S; Kaur, J; Prasmickaite, L; Engesæter, B Ø; Weyergang, A; Skarpen, E; Berg, K; Rosenblum, M G; Mælandsmo, G M; Høgset, A; Ferrone, S; Selbo, P K

2018-05-16

Triple-negative breast cancer (TNBC) and malignant melanoma are highly aggressive cancers that widely express the cell surface chondroitin sulfate proteoglycan 4 (CSPG4/NG2). CSPG4 plays an important role in tumor cell growth and survival and promotes chemo- and radiotherapy resistance, suggesting that CSPG4 is an attractive target in cancer therapy. In the present work, we applied the drug delivery technology photochemical internalization (PCI) in combination with the novel CSPG4-targeting immunotoxin 225.28-saporin as an efficient and specific strategy to kill aggressive TNBC and amelanotic melanoma cells. Light-activation of the clinically relevant photosensitizer TPCS2a (fimaporfin) and 225.28-saporin was found to act in a synergistic manner, and was superior to both PCI of saporin and PCI-no-drug (TPCS2a + light only) in three TNBC cell lines (MDA-MB-231, MDA-MB-435 and SUM149) and two BRAFV600E mutated malignant melanoma cell lines (Melmet 1 and Melmet 5). The cytotoxic effect was highly dependent on the light dose and expression of CSPG4 since no enhanced cytotoxicity of PCI of 225.28-saporin compared to PCI of saporin was observed in the CSPG4-negative MCF-7 cells. The PCI of a smaller, and clinically relevant CSPG4-targeting toxin (scFvMEL-rGel) validated the CSPG4-targeting concept in vitro and induced a strong inhibition of tumor growth in the amelanotic melanoma xenograft A-375 model. In conclusion, the combination of the drug delivery technology PCI and CSPG4-targeting immunotoxins is an efficient, specific and light-controlled strategy for the elimination of aggressive cells of TNBC and malignant melanoma origin. This study lays the foundation for further preclinical evaluation of PCI in combination with CSPG4-targeting.

The Three Bacterial Lines of Defense against Antimicrobial Agents.

PubMed

Zhou, Gang; Shi, Qing-Shan; Huang, Xiao-Mo; Xie, Xiao-Bao

2015-09-09

Antimicrobial agents target a range of extra- and/or intracellular loci from cytoplasmic wall to membrane, intracellular enzymes and genetic materials. Meanwhile, many resistance mechanisms employed by bacteria to counter antimicrobial agents have been found and reported in the past decades. Based on their spatially distinct sites of action and distribution of location, antimicrobial resistance mechanisms of bacteria were categorized into three groups, coined the three lines of bacterial defense in this review. The first line of defense is biofilms, which can be formed by most bacteria to overcome the action of antimicrobial agents. In addition, some other bacteria employ the second line of defense, the cell wall, cell membrane, and encased efflux pumps. When antimicrobial agents permeate the first two lines of defense and finally reach the cytoplasm, many bacteria will make use of the third line of defense, including alterations of intracellular materials and gene regulation to protect themselves from harm by bactericides. The presented three lines of defense theory will help us to understand the bacterial resistance mechanisms against antimicrobial agents and design efficient strategies to overcome these resistances.

First-line nurse leaders' health-care change management initiatives.

PubMed

Macphee, Maura; Suryaprakash, Nitya

2012-03-01

To examine nurse leaders' change management projects within British Columbia, Canada. British Columbia Nursing Leadership Institute 2007-10 attendees worked on year-long change management initiatives/projects of importance to their respective health-care institutions. Most leaders were in first-line positions with <3 years' experience. Consenting leaders' project reports (N = 133) were content analysed for specific themes: types of projects; scope of projects (e.g. unit or local level, departmental, institutional); influence targets or key stakeholder groups targeted by the projects; leadership successes and challenges. Of study participants, 77% successfully completed their projects. Staff tool and resource development and existing services improvement were major project types. Care delivery teams were the major influence targets. Only 25% of projects were at the unit level. Many projects had broader scopes, such as institutional levels. Participants cited multiple leadership successes, including enhanced leadership styles and organizational skills. First-line nurse leaders were able to successfully manage projects beyond their traditional scope of responsibilities. The majority of projects dealt with staff needs and healthcare restructuring initiatives. Constant change is a global reality. Change management, a universal competency, must be included in leadership development programmes. © 2011 Blackwell Publishing Ltd.

Mining Consumer Health Vocabulary from Community-Generated Text

PubMed Central

Vydiswaran, V.G. Vinod; Mei, Qiaozhu; Hanauer, David A.; Zheng, Kai

2014-01-01

Community-generated text corpora can be a valuable resource to extract consumer health vocabulary (CHV) and link them to professional terminologies and alternative variants. In this research, we propose a pattern-based text-mining approach to identify pairs of CHV and professional terms from Wikipedia, a large text corpus created and maintained by the community. A novel measure, leveraging the ratio of frequency of occurrence, was used to differentiate consumer terms from professional terms. We empirically evaluated the applicability of this approach using a large data sample consisting of MedLine abstracts and all posts from an online health forum, MedHelp. The results show that the proposed approach is able to identify synonymous pairs and label the terms as either consumer or professional term with high accuracy. We conclude that the proposed approach provides great potential to produce a high quality CHV to improve the performance of computational applications in processing consumer-generated health text. PMID:25954426

Preclinical evaluation of potential therapeutic targets in dedifferentiated liposarcoma.

PubMed

Hanes, Robert; Grad, Iwona; Lorenz, Susanne; Stratford, Eva W; Munthe, Else; Reddy, Chilamakuri Chandra Sekhar; Meza-Zepeda, Leonardo A; Myklebost, Ola

2016-08-23

Sarcomas are rare cancers with limited treatment options. Patients are generally treated by chemotherapy and/or radiotherapy in combination with surgery, and would benefit from new personalized approaches. In this study we demonstrate the potential of combining personal genomic characterization of patient tumors to identify targetable mutations with in vitro testing of specific drugs in patient-derived cell lines. We have analyzed three metastases from a patient with high-grade metastatic dedifferentiated liposarcoma (DDLPS) by exome and transcriptome sequencing as well as DNA copy number analysis. Genomic aberrations of several potentially targetable genes, including amplification of KITLG and FRS2, in addition to amplification of CDK4 and MDM2, characteristic of this disease, were identified. We evaluated the efficacy of drugs targeting these aberrations or the corresponding signaling pathways in a cell line derived from the patient. Interestingly, the pan-FGFR inhibitor NVP-BGJ398, which targets FGFR upstream of FRS2, strongly inhibited cell proliferation in vitro and induced an accumulation of cells into the G0 phase of the cell cycle. This study indicates that FGFR inhibitors have therapeutic potential in the treatment of DDLPS with amplified FRS2.

Design of a line-VISAR interferometer system for the Sandia Z Machine

NASA Astrophysics Data System (ADS)

Galbraith, J.; Austin, K.; Baker, J.; Bettencourt, R.; Bliss, E.; Celeste, J.; Clancy, T.; Cohen, S.; Crosley, M.; Datte, P.; Fratanduono, D.; Frieders, G.; Hammer, J.; Jackson, J.; Johnson, D.; Jones, M.; Koen, D.; Lusk, J.; Martinez, A.; Massey, W.; McCarville, T.; McLean, H.; Raman, K.; Rodriguez, S.; Spencer, D.; Springer, P.; Wong, J.

2017-08-01

A joint team comprised of Lawrence Livermore National Laboratory (LLNL) and Sandia National Laboratory (SNL) personnel is designing a line-VISAR (Velocity Interferometer System for Any Reflector) for the Sandia Z Machine, Z Line-VISAR. The diagnostic utilizes interferometry to assess current delivery as a function of radius during a magnetically-driven implosion. The Z Line-VISAR system is comprised of the following: a two-leg line-VISAR interferometer, an eight-channel Gated Optical Imager (GOI), and a fifty-meter transport beampath to/from the target of interest. The Z Machine presents unique optomechanical design challenges. The machine utilizes magnetically driven pulsed power to drive a target to elevated temperatures and pressures useful for high energy density science. Shock accelerations exceeding 30g and a strong electromagnetic pulse (EMP) are generated during the shot event as the machine discharges currents of over 25 million amps. Sensitive optical components must be protected from shock loading, and electrical equipment must be adequately shielded from the EMP. The optical design must accommodate temperature and humidity fluctuations in the facility as well as airborne hydrocarbons from the pulsed power components. We will describe the engineering design and concept of operations of the Z Line-VISAR system. Focus will be on optomechanical design.

The SPES High Power ISOL production target

NASA Astrophysics Data System (ADS)

Andrighetto, A.; Corradetti, S.; Ballan, M.; Borgna, F.; Manzolaro, M.; Scarpa, D.; Monetti, A.; Rossignoli, M.; Silingardi, R.; Mozzi, A.; Vivian, G.; Boratto, E.; De Ruvo, L.; Sattin, N.; Meneghetti, G.; Oboe, R.; Guerzoni, M.; Margotti, A.; Ferrari, M.; Zenoni, A.; Prete, G.

2016-11-01

SPES (Selective Production of Exotic Species) is a facility under construction at INFN-LNL (Istituto Nazionale di Fisica Nucleare - Laboratori Nazionali di Legnaro), aimed to produce intense neutron-rich radioactive ion beams (RIBs). These will be obtained using the ISOL (Isotope Separation On-Line) method, bombarding a uranium carbide target with a proton beam of 40MeV energy and currents up to 200μA. The target configuration was designed to obtain a high number of fissions, up to 1013 per second, low power deposition and fast release of the produced isotopes. The exotic isotopes generated in the target are ionized, mass separated and re-accelerated by the ALPI superconducting LINAC at energies of 10AMeV and higher, for masses in the region of A = 130 amu , with an expected rate on the secondary target up to 109 particles per second. In this work, recent results on the R&D activities regarding the SPES RIB production target-ion source system are reported.

Localized Optogenetic Targeting of Rotors in Atrial Cardiomyocyte Monolayers.

PubMed

Feola, Iolanda; Volkers, Linda; Majumder, Rupamanjari; Teplenin, Alexander; Schalij, Martin J; Panfilov, Alexander V; de Vries, Antoine A F; Pijnappels, Daniël A

2017-11-01

Recently, a new ablation strategy for atrial fibrillation has emerged, which involves the identification of rotors (ie, local drivers) followed by the localized targeting of their core region by ablation. However, this concept has been subject to debate because the mode of arrhythmia termination remains poorly understood, as dedicated models and research tools are lacking. We took a unique optogenetic approach to induce and locally target a rotor in atrial monolayers. Neonatal rat atrial cardiomyocyte monolayers expressing a depolarizing light-gated ion channel (Ca 2+ -translocating channelrhodopsin) were subjected to patterned illumination to induce single, stable, and centralized rotors by optical S1-S2 cross-field stimulation. Next, the core region of these rotors was specifically and precisely targeted by light to induce local conduction blocks of circular or linear shapes. Conduction blocks crossing the core region, but not reaching any unexcitable boundary, did not lead to termination. Instead, electric waves started to propagate along the circumference of block, thereby maintaining reentrant activity, although of lower frequency. If, however, core-spanning lines of block reached at least 1 unexcitable boundary, reentrant activity was consistently terminated by wave collision. Lines of block away from the core region resulted merely in rotor destabilization (ie, drifting). Localized optogenetic targeting of rotors in atrial monolayers could lead to both stabilization and destabilization of reentrant activity. For termination, however, a line of block is required reaching from the core region to at least 1 unexcitable boundary. These findings may improve our understanding of the mechanisms involved in rotor-guided ablation. © 2017 American Heart Association, Inc.

Irradiated KHYG-1 retains cytotoxicity: potential for adoptive immunotherapy with a natural killer cell line.

PubMed

Suck, G; Branch, D R; Keating, A

2006-05-01

To evaluate gamma-irradiation on KHYG-1, a highly cytotoxic natural killer (NK) cell line and potential candidate for cancer immunotherapy. The NK cell line KHYG-1 was irradiated at 1 gray (Gy) to 50 Gy with gamma-irradiation, and evaluated for cell proliferation, cell survival, and cytotoxicity against tumor targets. We showed that a dose of at least 10 Gy was sufficient to inhibit proliferation of KHYG-1 within the first day but not its cytolytic activity. While 50 Gy had an apoptotic effect in the first hours after irradiation, the killing of K562 and HL60 targets was not different from non-irradiated cells but was reduced for the Ph + myeloid leukemia lines, EM-2 and EM-3. gamma-irradiation (at least 10 Gy) of KHYG-1 inhibits cell proliferation but does not diminish its enhanced cytolytic activity against several tumor targets. This study suggests that KHYG-1 may be a feasible immunotherapeutic agent in the treatment of cancers.

Population kinetics on K alpha lines of partially ionized Cl atoms.

PubMed

Kawamura, Tohru; Nishimura, Hiroaki; Koike, Fumihiro; Ochi, Yoshihiro; Matsui, Ryoji; Miao, Wen Yong; Okihara, Shinichiro; Sakabe, Shuji; Uschmann, Ingo; Förster, Eckhart; Mima, Kunioki

2002-07-01

A population kinetics code was developed to analyze K alpha emission from partially ionized chlorine atoms in hydrocarbon plasmas. Atomic processes are solved under collisional-radiative equilibrium for two-temperature plasmas. It is shown that the fast electrons dominantly contribute to ionize the K-shell bound electrons (i.e., inner-shell ionization) and the cold electrons to the outer-shell bound ones. Ratios of K alpha lines of partially ionized atoms are presented as a function of cold-electron temperature. The model was validated by observation of the K alpha lines from a chlorinated plastic target irradiated with 1 TW Ti:sapphire laser pulses at 1.5 x 10(17) W/cm(2), inferring a plasma temperature of about 100 eV on the target surface.

Three-photon-excited luminescence from unsymmetrical cyanostilbene aggregates: morphology tuning and targeted bioimaging.

PubMed

Mandal, Amal Kumar; Sreejith, Sivaramapanicker; He, Tingchao; Maji, Swarup Kumar; Wang, Xiao-Jun; Ong, Shi Li; Joseph, James; Sun, Handong; Zhao, Yanli

2015-05-26

We report an experimental observation of aggregation-induced enhanced luminescence upon three-photon excitation in aggregates formed from a class of unsymmetrical cyanostilbene derivatives. Changing side chains (-CH3, -C6H13, -C7H15O3, and folic acid) attached to the cyanostilbene core leads to instantaneous formation of aggregates with sizes ranging from micrometer to nanometer scale in aqueous conditions. The crystal structure of a derivative with a methyl side chain reveals the planarization in the unsymmetrical cyanostilbene core, causing luminescence from corresponding aggregates upon three-photon excitation. Furthermore, folic acid attached cyanostilbene forms well-dispersed spherical nanoaggregates that show a high three-photon cross-section of 6.0 × 10(-80) cm(6) s(2) photon(-2) and high luminescence quantum yield in water. In order to demonstrate the targeted bioimaging capability of the nanoaggregates, three cell lines (HEK293 healthy cell line, MCF7 cancerous cell line, and HeLa cancerous cell line) were employed for the investigations on the basis of their different folate receptor expression level. Two kinds of nanoaggregates with and without the folic acid targeting ligand were chosen for three-photon bioimaging studies. The cell viability of three types of cells incubated with high concentration of nanoaggregates still remained above 70% after 24 h. It was observed that the nanoaggregates without the folic acid unit could not undergo the endocytosis by both healthy and cancerous cell lines. No obvious endocytosis of folic acid attached nanoaggregates was observed from the HEK293 and MCF7 cell lines having a low expression of the folate receptor. Interestingly, a significant amount of endocytosis and internalization of folic acid attached nanoaggregates was observed from HeLa cells with a high expression of the folate receptor under three-photon excitation, indicating targeted bioimaging of folic acid attached nanoaggregates to the cancer cell line

X-Ray Continua of Broad Absorption Line Quasars

NASA Technical Reports Server (NTRS)

Mathur, S.

1999-01-01

The targets for this program, PG1416-129 and LBQS 2212-1759 were known to be Broad Absorption Line Quasars (BALQSOs). BALQSOs are highly absorbed in soft X-rays. Good high energy response of Rossi-XTE made them ideal targets for observation. We observed LBQS 2212-1759 with PCA. We have now analyzed the data and found that the source was not detected. Since our target was expected to be faint, reliable estimate of background was very important. With the release of new FTOOLS (version 4.1) we were able to do so. We also analyzed a well known bright object and verified our results with the published data. This gave us confidence in the non-detection of our target LBQS 2212-1759. We are currently investigating the implications of this non-detection. Due to some scheduling problems, our second target PG1416-129 was not observed in A01. It was observed on 06/26/98. This target was detected with RXTE. We are now working on the spectral analysis with XSPEC.

Effect of verteporfin-PDT on epithelial growth factor receptor (EGFR) signaling pathway in cholangiocarcinoma cell lines

NASA Astrophysics Data System (ADS)

Andreola, Fausto; Cerec, Virginie; Pereira, Stephen P.

2009-06-01

EGFR, a member of the ERBB family, plays a pivotal role in carcinogenesis. EGFR overexpression is implicated in DNA repair and synergistic interactions between EGFR-targeting drugs and conventional chemo/radiotherapy have been reported in preclinical studies for different cancers but not cholangiocarcinoma (CCA). To date there are no in vitro data available on the cellular response and effect of either photodynamic therapy (PDT) or EGFR-targeting drugs on CCA. Therefore, we aimed to study the: (i) response to Verteporfin PDT and to EGFR-targeting drugs, as single agents; (ii) effect of PDT on ERBBs expression, phosporylation status and activation of its signaling pathways; (iii) response to combination of PDT and EGFR-targeting agents. We showed that two cholangiocarcinoma cell lines (HuCCT1 and TFK1 cells, intra- and extrahepatic, respectively) differentially respond to verteporfin-PDT treatment and are resistant to EGFR-targeting agents. A constitutive activation of EGFR in both cell lines was also observed, which could partly account for the observed resistance to EGFR-targeting drugs. In addition, verteporfin-PDT induced further phosphorylation of both EGFR and other Receptor Tyrosine Kinases. Mitochondria-independent apoptosis was induced by PDT in both CCA cell lines; in particular, PDT modulated the expression of members of the Inhibitor of Apoptosis (IAP) family of proteins. Interestingly, there was a PDT-induced EGFR nuclear translocation in both cell lines; co-treatment with either an EGFR-inhibitor (Cetuximab) or a nuclear import blocking agent (Wheat Germ Agglutinin) had an additive effect on PDT cell killing, thus implying a role of EGFR in repairing the potential PDT-induced DNA damage.

A Study of Readability of Texts in Bangla through Machine Learning Approaches

ERIC Educational Resources Information Center

Sinha, Manjira; Basu, Anupam

2016-01-01

In this work, we have investigated text readability in Bangla language. Text readability is an indicator of the suitability of a given document with respect to a target reader group. Therefore, text readability has huge impact on educational content preparation. The advances in the field of natural language processing have enabled the automatic…

Texting and Walking: Strategies for Postural Control and Implications for Safety

PubMed Central

Schabrun, Siobhan M.; van den Hoorn, Wolbert; Moorcroft, Alison; Greenland, Cameron; Hodges, Paul W.

2014-01-01

There are concerns about the safety of texting while walking. Although evidence of negative effects of mobile phone use on gait is scarce, cognitive distraction, altered mechanical demands, and the reduced visual field associated with texting are likely to have an impact. In 26 healthy individuals we examined the effect of mobile phone use on gait. Individuals walked at a comfortable pace in a straight line over a distance of ∼8.5 m while; 1) walking without the use of a phone, 2) reading text on a mobile phone, or 3) typing text on a mobile phone. Gait performance was evaluated using a three-dimensional movement analysis system. In comparison with normal waking, when participants read or wrote text messages they walked with: greater absolute lateral foot position from one stride to the next; slower speed; greater rotation range of motion (ROM) of the head with respect to global space; the head held in a flexed position; more in-phase motion of the thorax and head in all planes, less motion between thorax and head (neck ROM); and more tightly organized coordination in lateral flexion and rotation directions. While writing text, participants walked slower, deviated more from a straight line and used less neck ROM than reading text. Although the arms and head moved with the thorax to reduce relative motion of the phone and facilitate reading and texting, movement of the head in global space increased and this could negatively impact the balance system. Texting, and to a lesser extent reading, modify gait performance. Texting or reading on a mobile phone may pose an additional risk to safety for pedestrians navigating obstacles or crossing the road. PMID:24465402

HERACLES: THE HERA CO LINE EXTRAGALACTIC SURVEY

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

Leroy, Adam K.; Walter, Fabian; Bigiel, Frank

2009-06-15

We present the Heterodyne Receiver Array CO Line Extragalactic Survey, an atlas of CO emission from 18 nearby galaxies that are also part of The H I Nearby Galaxy Survey and the Spitzer Infrared Nearby Galaxies Survey. We used the HERA multipixel receiver on the IRAM 30-m telescope to map the CO J = 2 {yields} 1 line over the full optical disk (defined by the isophotal radius r {sub 25}) of each target, at 13'' angular resolution and 2.6 km s{sup -1} velocity resolution. Here we describe the observations and reduction of the data and show channel maps, azimuthallymore » averaged profiles, integrated intensity maps, and peak intensity maps. The implied H{sub 2} masses range from 7 x 10{sup 6} to 6 x 10{sup 9} M {sub sun}, with four low metallicity dwarf irregular galaxies yielding only upper limits. In the cases where CO is detected, the integrated H{sub 2}-to-H I ratios range from 0.02 to 1.13 and H{sub 2}-to-stellar mass ratios from 0.01 to 0.25. Exponential scale lengths of the CO emission for our targets are in the range 0.8-3.2 kpc, or 0.2 {+-} 0.05r {sub 25}. The intensity-weighted mean velocity of CO matches that of H I very well, with a 1{sigma} scatter of only 6 km s{sup -1}. The CO J = 2 {yields} 1/J = 1 {yields} 0 line ratio varies over a range similar to that found in the Milky Way and other nearby galaxies, {approx}0.6-1.0, with higher values found in the centers of galaxies. The typical line ratio, {approx}0.8, could be produced by optically thick gas with an excitation temperature of {approx}10 K.« less

Dissecting and Targeting Latent Metastasis

DTIC Science & Technology

2013-09-01

particular. Developing and using experimental models of LMBC to elucidate these survival mechanisms will provide a basis for therapeutically targeting...stochastic, low frequency generation of lethal macrometastatic lesion. Progress Item 1.1. Using this approach, we have successfully isolated latent...cells lines are being used to illuminate the molecular basis for the latent metastasis state. Progress Item 1.2. In parallel with the isolation of

Background distraction during vertical solid and character line bisections.

PubMed

Rodriguez, Julio A; Lamb, Damon G; Salazar, Liliana; Correa, Lauren N; Mosquera, Diana M; Schwartz, Zared J; Cohen, Ronald A; Falchook, Adam D; Heilman, Kenneth M

2018-04-04

Background-objectives: When vertical lines are positioned above or below the center of the page, line bisection deviates toward the center of the page, suggesting that the edges of the page distract the allocation of attention to the line. A letter-character line (LCL) bisection requires both global and focal attention, to identify the target letter closest to the line's center. If more focal and less global attention is allocated to a LCL, more global attentional resources may be available and inadvertently allocated to the page. Alternatively, if the allocation of focal attention to a LCL inhibits global attentional processing, there may be less distraction by the page. Twenty-four healthy adults (12 older) bisected vertical solid and character lines centered, or positioned closer to the top or bottom of the page. There was no difference between bisection of solid and character lines centered on the page. Page-related deviations were greater with character lines than solid line bisections, and greater for lines positioned toward the top than the bottom of the page. With lines positioned toward the top, the older participants' attempted bisections were higher than those of the younger participants. These results suggest that the allocation of focal attention increases global attentional distractibility and that global-background attentional distraction is greater when the vertical lines are placed in the upper part of the page. Older participants appeared to be less distracted when lines were placed toward the top of the page, but the reason for this age difference requires further research.

Automatic target validation based on neuroscientific literature mining for tractography

PubMed Central

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

2015-01-01

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

A targeted drug delivery system based on dopamine functionalized nano graphene oxide

NASA Astrophysics Data System (ADS)

Masoudipour, Elham; Kashanian, Soheila; Maleki, Nasim

2017-01-01

The cellular targeting property of a biocompatible drug delivery system can widely increase the therapeutic effect against various diseases. Here, we report a dopamine conjugated nano graphene oxide (DA-nGO) carrier for cellular delivery of the anticancer drug, Methotrexate (MTX) into DA receptor positive human breast adenocarcinoma cell line. The material was characterized using scanning electron microscopy, atomic force microscopy, Fourier transform infrared spectroscopy and UV-vis spectroscopy. Furthermore, the antineoplastic action of MTX loaded DA-nGO against DA receptor positive and negative cell lines were explored. The results presented in this article demonstrated that the application of DA functionalized GO as a targeting drug carrier can improve the drug delivery efficacy for DA receptor positive cancer cell lines and promise future designing of carrier conjugates based on it.

Category-based attentional guidance can operate in parallel for multiple target objects.

PubMed

Jenkins, Michael; Grubert, Anna; Eimer, Martin

2018-05-01

The question whether the control of attention during visual search is always feature-based or can also be based on the category of objects remains unresolved. Here, we employed the N2pc component as an on-line marker for target selection processes to compare the efficiency of feature-based and category-based attentional guidance. Two successive displays containing pairs of real-world objects (line drawings of kitchen or clothing items) were separated by a 10 ms SOA. In Experiment 1, target objects were defined by their category. In Experiment 2, one specific visual object served as target (exemplar-based search). On different trials, targets appeared either in one or in both displays, and participants had to report the number of targets (one or two). Target N2pc components were larger and emerged earlier during exemplar-based search than during category-based search, demonstrating the superior efficiency of feature-based attentional guidance. On trials where target objects appeared in both displays, both targets elicited N2pc components that overlapped in time, suggesting that attention was allocated in parallel to these target objects. Critically, this was the case not only in the exemplar-based task, but also when targets were defined by their category. These results demonstrate that attention can be guided by object categories, and that this type of category-based attentional control can operate concurrently for multiple target objects. Copyright © 2018 Elsevier B.V. All rights reserved.

On-line range prediction system, part 2

NASA Technical Reports Server (NTRS)

Levan, Nhan

1988-01-01

The on-line range prediction system is designed for providing a prediction of the target range in the case of a laser data dropout. It consists of real time implementation of a Kalman filter on an IBM PC/AT equipped with necessary hardware. The system was set up and tested at Crows Landing in the Fall of 1987. The improvements made on the on-line range prediction system during 1988 are examined. Solutions are proposed and discussed to the several problems encountered during system tests. Then, the improvements made on the filter software are explained, namely, accounting for the time lag and providing data continously. Finally, the ideas are mentioned that can be considered in the future.

Rapid development of stable transgene CHO cell lines by CRISPR/Cas9-mediated site-specific integration into C12orf35.

PubMed

Zhao, Menglin; Wang, Jiaxian; Luo, Manyu; Luo, Han; Zhao, Meiqi; Han, Lei; Zhang, Mengxiao; Yang, Hui; Xie, Yueqing; Jiang, Hua; Feng, Lei; Lu, Huili; Zhu, Jianwei

2018-07-01

Chinese hamster ovary (CHO) cells are the most widely used mammalian hosts for recombinant protein production. However, by conventional random integration strategy, development of a high-expressing and stable recombinant CHO cell line has always been a difficult task due to the heterogenic insertion and its caused requirement of multiple rounds of selection. Site-specific integration of transgenes into CHO hot spots is an ideal strategy to overcome these challenges since it can generate isogenic cell lines with consistent productivity and stability. In this study, we investigated three sites with potential high transcriptional activities: C12orf35, HPRT, and GRIK1, to determine the possible transcriptional hot spots in CHO cells, and further construct a reliable site-specific integration strategy to develop recombinant cell lines efficiently. Genes encoding representative proteins mCherry and anti-PD1 monoclonal antibody were targeted into these three loci respectively through CRISPR/Cas9 technology. Stable cell lines were generated successfully after a single round of selection. In comparison with a random integration control, all the targeted integration cell lines showed higher productivity, among which C12orf35 locus was the most advantageous in both productivity and cell line stability. Binding affinity and N-glycan analysis of the antibody revealed that all batches of product were of similar quality independent on integrated sites. Deep sequencing demonstrated that there was low level of off-target mutations caused by CRISPR/Cas9, but none of them contributed to the development process of transgene cell lines. Our results demonstrated the feasibility of C12orf35 as the target site for exogenous gene integration, and strongly suggested that C12orf35 targeted integration mediated by CRISPR/Cas9 is a reliable strategy for the rapid development of recombinant CHO cell lines.

Human immune cell targeting of protein nanoparticles - caveospheres

NASA Astrophysics Data System (ADS)

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

2016-04-01

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

How Generalization Inferences Are Constructed in Expository Text Comprehension

ERIC Educational Resources Information Center

Ritchey, Kristin A.

2011-01-01

Three questions regarding adult readers' processing of generalization inferences (conceptually broad statements that subsume several specific statements) are investigated. College students (N=193) read expository texts containing target statements that were consistent, inconsistent, or off-topic in relation to a generalization implied by one…

Wavelength Locking to CO2 Absorption Line-Center for 2-Micron Pulsed IPDA Lidar Application

NASA Technical Reports Server (NTRS)

Refaat, Tamer F.; Petros, Mulugeta; Antill, Charles W.; Singh, Upendra N.; Yu, Jirong

2016-01-01

An airborne 2-micron triple-pulse integrated path differential absorption (IPDA) lidar is currently under development at NASA Langley Research Center (LaRC). This IPDA lidar system targets both atmospheric carbon dioxide (CO2) and water vapor (H2O) column measurements. Independent wavelength control of each of the transmitted laser pulses is a key feature for the success of this instrument. The wavelength control unit provides switching, tuning and locking for each pulse in reference to a 2-micron CW (Continuous Wave) laser source locked to CO2 line-center. Targeting the CO2 R30 line center, at 2050.967 nanometers, a wavelength locking unit has been integrated using semiconductor laser diode. The CO2 center-line locking unit includes a laser diode current driver, temperature controller, center-line locking controller and CO2 absorption cell. This paper presents the CO2 center-line locking unit architecture, characterization procedure and results. Assessment of wavelength jitter on the IPDA measurement error will also be addressed by comparison to the system design.

The texting and driving epidemic : changing norms to change behavior, [technical summary].

DOT National Transportation Integrated Search

2013-09-01

TXT L8R is a strategic campaign developed for the Kansas Department of Transportation to reduce texting and driving and to increase awareness of the serious risks involved with texting and driving. The target audience of the campaign is University of...

Authentic Text Types and Corresponding Activities: A List for the Foreign Language Instructor.

ERIC Educational Resources Information Center

Geltrich-Ludgate, Brigitta; Tovar, Deanna

1987-01-01

The study of authentic texts gives students the opportunity to become functional in target-language situations. An exhaustive alphabetical list of authentic text types and corresponding learning activities are presented. Text types include: advertisements, bank materials, bills and receipts, calendars, captions, comics, commercials, decals, forms,…

Precision targeting in guided munition using IR sensor and MmW radar

NASA Astrophysics Data System (ADS)

Sreeja, S.; Hablani, H. B.; Arya, H.

2015-10-01

Conventional munitions are not guided with sensors and therefore miss the target, particularly if the target is mobile. The miss distance of these munitions can be decreased by incorporating sensors to detect the target and guide the munition during flight. This paper is concerned with a Precision Guided Munition(PGM) equipped with an infrared sensor and a millimeter wave radar [IR and MmW, for short]. Three-dimensional flight of the munition and its pitch and yaw motion models are developed and simulated. The forward and lateral motion of a target tank on the ground is modeled as two independent second-order Gauss-Markov process. To estimate the target location on the ground and the line-of-sight rate to intercept it an Extended Kalman Filter is composed whose state vector consists of cascaded state vectors of missile dynamics and target dynamics. The line-of-sight angle measurement from the infrared seeker is by centroiding the target image in 40 Hz. The centroid estimation of the images in the focal plane is at a frequency of 10 Hz. Every 10 Hz, centroids of four consecutive images are averaged, yielding a time-averaged centroid, implying some measurement delay. The miss distance achieved by including by image processing delays is 1:45m.

Transferrin receptor-targeted theranostic gold nanoparticles for photosensitizer delivery in brain tumors

NASA Astrophysics Data System (ADS)

Dixit, Suraj; Novak, Thomas; Miller, Kayla; Zhu, Yun; Kenney, Malcolm E.; Broome, Ann-Marie

2015-01-01

Therapeutic drug delivery across the blood-brain barrier (BBB) is not only inefficient, but also nonspecific to brain stroma. These are major limitations in the effective treatment of brain cancer. Transferrin peptide (Tfpep) targeted gold nanoparticles (Tfpep-Au NPs) loaded with the photodynamic pro-drug, Pc 4, have been designed and compared with untargeted Au NPs for delivery of the photosensitizer to brain cancer cell lines. In vitro studies of human glioma cancer lines (LN229 and U87) overexpressing the transferrin receptor (TfR) show a significant increase in cellular uptake for targeted conjugates as compared to untargeted particles. Pc 4 delivered from Tfpep-Au NPs clusters within vesicles after targeting with the Tfpep. Pc 4 continues to accumulate over a 4 hour period. Our work suggests that TfR-targeted Au NPs may have important therapeutic implications for delivering brain tumor therapies and/or providing a platform for noninvasive imaging.

ABCF2, an Nrf2 target gene, contributes to cisplatin resistance in ovarian cancer cells.

PubMed

Bao, Lingjie; Wu, Jianfa; Dodson, Matthew; Rojo de la Vega, Elisa Montserrat; Ning, Yan; Zhang, Zhenbo; Yao, Ming; Zhang, Donna D; Xu, Congjian; Yi, Xiaofang

2017-06-01

Previously, we have demonstrated that NRF2 plays a key role in mediating cisplatin resistance in ovarian cancer. To further explore the mechanism underlying NRF2-dependent cisplatin resistance, we stably overexpressed or knocked down NRF2 in parental and cisplatin-resistant human ovarian cancer cells, respectively. These two pairs of stable cell lines were then subjected to microarray analysis, where we identified 18 putative NRF2 target genes. Among these genes, ABCF2, a cytosolic member of the ABC superfamily of transporters, has previously been reported to contribute to chemoresistance in clear cell ovarian cancer. A detailed analysis on ABCF2 revealed a functional antioxidant response element (ARE) in its promoter region, establishing ABCF2 as an NRF2 target gene. Next, we investigated the contribution of ABCF2 in NRF2-mediated cisplatin resistance using our stable ovarian cancer cell lines. The NRF2-overexpressing cell line, containing high levels of ABCF2, was more resistant to cisplatin-induced apoptosis compared to its control cell line; whereas the NRF2 knockdown cell line with low levels of ABCF2, was more sensitive to cisplatin treatment than its control cell line. Furthermore, transient overexpression of ABCF2 in the parental cells decreased apoptosis and increased cell viability following cisplatin treatment. Conversely, knockdown of ABCF2 using specific siRNA notably increased apoptosis and decreased cell viability in cisplatin-resistant cells treated with cisplatin. This data indicate that the novel NRF2 target gene, ABCF2, plays a critical role in cisplatin resistance in ovarian cancer, and that targeting ABCF2 may be a new strategy to improve chemotherapeutic efficiency. © 2017 Wiley Periodicals, Inc.

[Current Status of Targeted Treatment in Breast Cancer].

PubMed

Seiffert, Katharina; Schmalfeldt, Barbara; Müller, Volkmar

2017-11-01

Within the last years, significant improvements have been achieved in breast cancer treatment, particularly with the development of targeted therapies. Major progress has been made in identifying the drivers malignant growth in oestrogen-receptor-positive breast cancer and the mechanisms of resistance to endocrine therapy. This progress has translated into several targeted therapies that enhance the efficacy of endocrine therapy; inhibitors of the cyclin-dependent kinases CDK4 and CDK6 like palbociclib and inhibitors of mTOR substantially improve progression-free survival. For patients with HER2-positive disease the addition of Pertuzumab to Trastuzumab in combination with chemotherapy has been a significant improvement in anti-HER2 therapy in early as well as metastatic breast cancer. Evidence-based further line therapy options in the metastatic setting include T-DM1 and in later lines Lapatinib. For triple negative disease the angiogenesis inhibitor Bevacizumab is approved, which increases progression free survival. Immune checkpoint inhibitors, PARP-inhibitors or anti-androgens represent promising strategies, all of which are currently being evaluated in clinical trials. The development of predictive biomarkers to guide targeted therapies is still the subject of research. © Georg Thieme Verlag KG Stuttgart · New York.

The Three Bacterial Lines of Defense against Antimicrobial Agents

PubMed Central

Zhou, Gang; Shi, Qing-Shan; Huang, Xiao-Mo; Xie, Xiao-Bao

2015-01-01

Antimicrobial agents target a range of extra- and/or intracellular loci from cytoplasmic wall to membrane, intracellular enzymes and genetic materials. Meanwhile, many resistance mechanisms employed by bacteria to counter antimicrobial agents have been found and reported in the past decades. Based on their spatially distinct sites of action and distribution of location, antimicrobial resistance mechanisms of bacteria were categorized into three groups, coined the three lines of bacterial defense in this review. The first line of defense is biofilms, which can be formed by most bacteria to overcome the action of antimicrobial agents. In addition, some other bacteria employ the second line of defense, the cell wall, cell membrane, and encased efflux pumps. When antimicrobial agents permeate the first two lines of defense and finally reach the cytoplasm, many bacteria will make use of the third line of defense, including alterations of intracellular materials and gene regulation to protect themselves from harm by bactericides. The presented three lines of defense theory will help us to understand the bacterial resistance mechanisms against antimicrobial agents and design efficient strategies to overcome these resistances. PMID:26370986

Extended target recognition in cognitive radar networks.

PubMed

Wei, Yimin; Meng, Huadong; Liu, Yimin; Wang, Xiqin

2010-01-01

We address the problem of adaptive waveform design for extended target recognition in cognitive radar networks. A closed-loop active target recognition radar system is extended to the case of a centralized cognitive radar network, in which a generalized likelihood ratio (GLR) based sequential hypothesis testing (SHT) framework is employed. Using Doppler velocities measured by multiple radars, the target aspect angle for each radar is calculated. The joint probability of each target hypothesis is then updated using observations from different radar line of sights (LOS). Based on these probabilities, a minimum correlation algorithm is proposed to adaptively design the transmit waveform for each radar in an amplitude fluctuation situation. Simulation results demonstrate performance improvements due to the cognitive radar network and adaptive waveform design. Our minimum correlation algorithm outperforms the eigen-waveform solution and other non-cognitive waveform design approaches.

Lawmakers target PURPA for repeal

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

Burkhart, L.A.

This article is a review of current legislative initiatives to repeal certain sections of the Public Utilities Regulatory Policy Act (PURPA). Targeted for repeal is Section 210 of PURPA, which mandates purchases from qualifying facilities at avoided-cost rates. Pros and cons of this proposed repeal are reviewed, with Administration officials lining up against the repeal and industry casting their vote for repeal of this and other sections of PURPA.

Rapid extraction of gist from visual text and its influence on word recognition.

PubMed

Asano, Michiko; Yokosawa, Kazuhiko

2011-01-01

Two experiments explored rapid extraction of gist from a visual text and its influence on word recognition. In both, a short text (sentence) containing a target word was presented for 200 ms and was followed by a target recognition task. Results showed that participants recognized contextually anomalous word targets less frequently than contextually consistent counterparts (Experiment 1). This context effect was obtained when sentences contained the same semantic content but with disrupted syntactic structure (Experiment 2). Results demonstrate that words in a briefly presented visual sentence are processed in parallel and that rapid extraction of sentence gist relies on a primitive representation of sentence context (termed protocontext) that is semantically activated by the simultaneous presentation of multiple words (i.e., a sentence) before syntactic processing.

Increased efficacy of photodynamic therapy via sequential targeting

NASA Astrophysics Data System (ADS)

Kessel, David; Aggarwal, Neha; Sloane, Bonnie F.

2014-03-01

Photokilling depends on the generation of death signals after photosensitized cells are irradiated. A variety of intracellular organelles can be targeted for photodamage, often with a high degree of specificity. We have discovered that a low level of photodamage directed against lysosomes can sensitize both a murine hepatoma cell line (in 2D culture) and an inflammatory breast cancer line of human origin (in a 3D model) to subsequent photodamage directed at mitochondria. Additional studies were carried out with hepatoma cells to explore possible mechanisms. The phototoxic effect of the `sequential targeting' approach was associated with an increased apoptotic response. The low level of lysosomal photodamage did not lead to any detectable migration of Fe++ from lysosomes to mitochondria or increased reactive oxygen species (ROS) formation after subsequent mitochondrial photodamage. Instead, there appears to be a signal generated that can amplify the pro-apoptotic effect of subsequent mitochondrial photodamage.

Different methods for anatomical targeting.

PubMed

Iacopino, D G; Conti, A; Angileri, F F; Tomasello, F

2003-03-01

Several procedures are used in the different neurosurgical centers in order to perform stereotactic surgery for movement disorders. At the moment no procedure can really be considered superior to the other. We contribute with our experience of targeting method. Ten patients were selected, in accordance to the guidelines for the treatment of Parkinson disease, and operated by several methods including pallidotomy, bilateral insertion of chronic deep brain electrodes within the internal pallidum and in the subthalamic nucleus (18 procedures). in each patient an MR scan was performed the day before surgery. Scans were performed axially parallel to the intercommissural line. The operating day a contrast CT scan was performed under stereotactic conditions. after digitalization of the MRI images, it was possible to visualize the surgical target and to relate it to parenchimal and vascular anatomic structures readable at the CT examination. The CT scan obtained was confronted with the MR previously performed, the geometrical relation between the different parenchimal and vascular structures and the selected targets were obtained. Stereotactic coordinates were obtained on the CT examination. It was possible to calculate the position of the subthalamic nucleus and of the internal pallidum on the CT scan, not only relating to the intercommissural line, but considering also the neurovascular structures displayed both on the MRI and the CT scans. The technique that our group presents consist in an integration between information derived from the CT and the MR techniques, so that we can benefit from the advantages of both methods and overcome the disadvantages.

High energy irradiations simulating cosmic-ray-induced planetary gamma ray production. I - Fe target

NASA Technical Reports Server (NTRS)

Metzger, A. E.; Parker, R. H.; Yellin, J.

1986-01-01

Two thick Fe targets were bombarded by a series of 6 GeV proton irradiations for the purpose of simulating the cosmic ray bombardment of planetary objects in space. Gamma ray energy spectra were obtained with a germanium solid state detector during the bombardment, and 46 of the gamma ray lines were ascribed to the Fe targets. A comparison between observed and predicted values showed good agreement for Fe lines from neutron inelastic scattering and spallation reactions, and less satisfactory agreement for neutron capture reactions, the latter attributed to the difference in composition between the Fe target and the mean lunar abundance used in the modeling. Through an analysis of the irradiation results together with continuum data obtained in lunar orbit, it was found that 100 hours of measurement with a current instrument should generate a spectrum containing approximately 20 lines due to Fe alone, with a 2-sigma sensitivity for detection of about 0.2 percent.

The Research Progress of the J-TEXT Tokamak

NASA Astrophysics Data System (ADS)

Zhuang, Ge; Wang, Zhijiang; Ding, Yonghua; Zhang, Ming; Yang, Zhoujun; Gao, Li; Zhang, Xiaoqing; Hu, Xiwei; Pan, Yuan

2010-11-01

In 2004, the TEXT-U tokamak was disassembled and shipped to China, and later on settle down in Huazhong University of Science and Technology. The machine was renamed as the Joint TEXT (J-TEXT) tokamak and obtained its first plasma in 2007. The typical J-TEXT Ohmic discharge was performed in the limiter configuration with the main parameters as follows: major radius R=1.05 m, minor radius a=0.27m, toroidal magnetic field BT=2.2T, plasma current Ip>200kA, line-averaged density ne˜ 2-3 . 1019/m^3, and electron temperature Te0˜ 700eV. Up till now, a few diagnostic systems used to facilitate routine operation and experimental studies were designed and developed. Benefiting from these diagnostic tools, the observation of MHD activities and the statistical analysis of disruption events were done. And measurements of the electrostatic fluctuations in the edge region and conditional analysis of the intermittent burst events near the LCFS were also made as well. The preliminary results will be presented in detail in the meeting.

Gold nano-popcorn attached SWCNT hybrid nanomaterial for targeted diagnosis and photothermal therapy of human breast cancer cells.

PubMed

Beqa, Lule; Fan, Zhen; Singh, Anant Kumar; Senapati, Dulal; Ray, Paresh Chandra

2011-09-01

Breast cancer presents greatest challenge in health care in today's world. The key to ultimately successful treatment of breast cancer disease is an early and accurate diagnosis. Current breast cancer treatments are often associated with severe side effects. Driven by the need, we report the design of novel hybrid nanomaterial using gold nano popcorn-attached single wall carbon nanotube for targeted diagnosis and selective photothermal treatment. Targeted SK-BR-3 human breast cancer cell sensing have been performed in 10 cancer cells/mL level, using surface enhanced Raman scattering of single walls carbon nanotube's D and G bands. Our data show that S6 aptamer attached hybrid nanomaterial based SERS assay is highly sensitive to targeted human breast cancer SK-BR-3 cell line and it will be able to distinguish it from other non targeted MDA-MB breast cancer cell line and HaCaT normal skin cell line. Our results also show that 10 min of photothermal therapy treatment by 1.5 W/cm(2) power, 785 nm laser is enough to kill cancer cells very effectively using S6 aptamer attached hybrid nanomaterials. Possible mechanisms for targeted sensing and operating principle for highly efficient photothermal therapy have been discussed. Our experimental results reported here open up a new possibility for using aptamers modified hybrid nanomaterial for reliable diagnosis and targeted therapy of cancer cell lines quickly.

Texting preferences in a Paediatric residency.

PubMed

Draper, Lauren; Kuklinski, Cadence; Ladley, Amy; Adamson, Greg; Broom, Matthew

2017-12-01

Text messaging is ubiquitous among residents, but remains an underused educational tool. Though feasibility has been demonstrated, evidence of its ability to improve standardised test scores and provide insight on resident texting preferences is lacking. The authors set out to evaluate: (1) satisfaction with a hybrid question-and-answer (Q&A) texting format; and (2) pre-/post-paediatric in-training exam (ITE) performance. A prospective study with paediatrics and internal medicine-paediatrics residents. Residents were divided into subgroups: adolescent medicine (AM) and developmental medicine (DM). Messages were derived from ITE questions and sent Monday-Friday with a 20 per cent variance in messages specific to the sub-group. Residents completed surveys gauging perceptions of the programme, and pre- and post-programme ITE scores were analysed. Forty-one residents enrolled and 32 (78%) completed a post-programme survey. Of those, 21 (66%) preferred a Q&A format with an immediate text response versus information-only texts. The percentage change in ITE scores between 2013 and 2014 was significant. Comparing subgroups, there was no significant difference between the percentage change in ITE scores. Neither group performed significantly better on either the adolescent or developmental sections of the ITE. Text messaging… remains an underused educational tool CONCLUSIONS: Overall, participants improved their ITE scores, but no improvement was seen in the targeted subgroups on the exam. Although Q&A texts are preferred by residents, further assessment is required to assess the effect on educational outcomes. © 2017 John Wiley & Sons Ltd and The Association for the Study of Medical Education.

ZED- A LINE EDITOR FOR THE DEC VAX

NASA Technical Reports Server (NTRS)

Scott, P. J.

1994-01-01

The ZED editor for the DEC VAX is a simple, yet powerful line editor for text, program source code, and non-binary data. Line editors can be superior to screen editors in some cases, such as executing complex multiple or conditional commands, or editing via slow modem lines. ZED excels in the area of text processing by using procedure files. For example, such procedures can reformat a file of addresses or remove all comment lines from a FORTRAN program. In addition to command files, ZED also features versatile search qualifiers, global changes, conditionals, on-line help, hexadecimal mode, space compression, looping, logical combinations of search strings, journaling, visible control characters, and automatic detabbing. The ZED editor was originally developed at Cambridge University in London and has been continuously enhanced since 1976. Users of the Cambridge implementation have devised such elaborate ZED procedures as chess games, calculators, and programs for evaluating Pi. This implementation of ZED strives to maintain the characteristics of the Cambridge editor. A complete ZED manual is included on the tape. ZED is written entirely in C for either batch or interactive execution on the DEC VAX under VMS 4.X and requires 80,896 bytes of memory. This program was released in 1988 and updated in 1989.

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

PubMed Central

Koivunen, Peppi; Koivunen, Jussi P.

2014-01-01

Treatment resistance significantly inhibits the efficiency of targeted cancer therapies in drug-sensitive genotypes. In the current work, we studied mechanisms for rapidly occurring, adaptive resistance in targeted therapy-sensitive lung, breast, and melanoma cancer cell lines. The results show that in ALK translocated lung cancer lines H3122 and H2228, cells with cancer stem-like cell features characterized by high expression of cancer stem cell markers and/or in vivo tumorigenesis can mediate adaptive resistance to oncogene ablative therapy. When pharmacological ablation of ALK oncogene was accompanied with PI3K inhibitor or salinomycin therapy, cancer stem-like cell features were reversed which was accompanied with decreased colony formation. Furthermore, co-targeting was able to block the formation of acquired resistance in H3122 line. The results suggest that cells with cancer stem-like cell features can mediate adaptive resistance to targeted therapies. Since these cells follow the stochastic model, concurrent therapy with an oncogene ablating agent and a stem-like cell-targeting drug is needed for maximal therapeutic efficiency. PMID:25238228

Performance of selected eastern oyster lines across northeastern US estuaries

USDA-ARS?s Scientific Manuscript database

Eastern oyster production derived from aquaculture has expanded, but growth potential is constrained by losses to disease. Breeding programs supporting industry in the Northeast have targeted resistance to three diseases: MSX, Dermo, and ROD. Selected lines should possess some level of resistance a...

Directed Activities Related to Text: Text Analysis and Text Reconstruction.

ERIC Educational Resources Information Center

Davies, Florence; Greene, Terry

This paper describes Directed Activities Related to Text (DART), procedures that were developed and are used in the Reading for Learning Project at the University of Nottingham (England) to enhance learning from texts and that fall into two broad categories: (1) text analysis procedures, which require students to engage in some form of analysis of…

A novel antibody-drug conjugate targeting SAIL for the treatment of hematologic malignancies.

PubMed

Kim, S Y; Theunissen, J-W; Balibalos, J; Liao-Chan, S; Babcock, M C; Wong, T; Cairns, B; Gonzalez, D; van der Horst, E H; Perez, M; Levashova, Z; Chinn, L; D'Alessio, J A; Flory, M; Bermudez, A; Jackson, D Y; Ha, E; Monteon, J; Bruhns, M F; Chen, G; Migone, T-S

2015-05-29

Although several new therapeutic approaches have improved outcomes in the treatment of hematologic malignancies, unmet need persists in acute myeloid leukemia (AML), multiple myeloma (MM) and non-Hodgkin's lymphoma. Here we describe the proteomic identification of a novel cancer target, SAIL (Surface Antigen In Leukemia), whose expression is observed in AML, MM, chronic lymphocytic leukemia (CLL), diffuse large B-cell lymphoma (DLBCL) and follicular lymphoma (FL). While SAIL is widely expressed in CLL, AML, MM, DLBCL and FL patient samples, expression in cancer cell lines is mostly limited to cells of AML origin. We evaluated the antitumor activity of anti-SAIL monoclonal antibodies, 7-1C and 67-7A, conjugated to monomethyl auristatin F. Following internalization, anti-SAIL antibody-drug conjugates (ADCs) exhibited subnanomolar IC50 values against AML cell lines in vitro. In pharmacology studies employing AML cell line xenografts, anti-SAIL ADCs resulted in significant tumor growth inhibition. The restricted expression profile of this target in normal tissues, the high prevalence in different types of hematologic cancers and the observed preclinical activity support the clinical development of SAIL-targeted ADCs.

Line Segmentation in Handwritten Assamese and Meetei Mayek Script Using Seam Carving Based Algorithm

NASA Astrophysics Data System (ADS)

Kumar, Chandan Jyoti; Kalita, Sanjib Kr.

Line segmentation is a key stage in an Optical Character Recognition system. This paper primarily concerns the problem of text line extraction on color and grayscale manuscript pages of two major North-east Indian regional Scripts, Assamese and Meetei Mayek. Line segmentation of handwritten text in Assamese and Meetei Mayek scripts is an uphill task primarily because of the structural features of both the scripts and varied writing styles. Line segmentation of a document image is been achieved by using the Seam carving technique, in this paper. Researchers from various regions used this approach for content aware resizing of an image. However currently many researchers are implementing Seam Carving for line segmentation phase of OCR. Although it is a language independent technique, mostly experiments are done over Arabic, Greek, German and Chinese scripts. Two types of seams are generated, medial seams approximate the orientation of each text line, and separating seams separated one line of text from another. Experiments are performed extensively over various types of documents and detailed analysis of the evaluations reflects that the algorithm performs well for even documents with multiple scripts. In this paper, we present a comparative study of accuracy of this method over different types of data.

Predictors of injury among adult recreational in-line skaters: a multicity study.

PubMed Central

Seldes, R M; Grisso, J A; Pavell, J R; Berlin, J A; Tan, V; Bowman, B; Kinman, J L; Fitzgerald, R H

1999-01-01

OBJECTIVES: This study examined risk factors for injury, injury prevalence, safety gear use, and skating habits of adult recreational in-line skaters. METHODS: Randomly selected in-line skaters in 6 major US cities were interviewed. RESULTS: Only 6% of skaters consistently wore all 4 recommended types of safety gear. Skaters with greater skating experience were more likely to perform tricks, wear less safety gear, and sustain an injury. CONCLUSION: More experienced adult recreational in-line skaters are at increased risk for injury. Safety gear use in alarmingly low in adult recreational in-line skaters, especially experienced skaters. Safe skating education programs should consider targeting this newly recognized at-risk skating population. PMID:9949756

Expanding Academic Vocabulary with an Interactive On-Line Database

ERIC Educational Resources Information Center

Horst, Marlise; Cobb, Tom; Nicolae, Ioana

2005-01-01

University students used a set of existing and purpose-built on-line tools for vocabulary learning in an experimental ESL course. The resources included concordance, dictionary, cloze-builder, hypertext, and a database with interactive self-quizzing feature (all freely available at www.lextutor.ca). The vocabulary targeted for learning consisted…

Innovative T Cell-Targeted Therapy for Ovarian Cancer

DTIC Science & Technology

2012-10-01

from co-culture with EL4 -ROR1neg and EL4 -ROR1+ tumor targets. Ovarian cancer cell lines (A2780, EFO21, EFO27, IGROV1, OC314, and UPN251) were...profiled for ROR1 expression in normoxia (20% O2) and hypoxia (1% O2). Four-hour CRA was used to evaluate cytotoxicity against the OvCa and EL4 tumor...loaded aAPC for negative controls. EL4 is a murine T cell lymphoma cell line used to test specificity of CAR+ T cells with limited allo-reactivity

Targeted mitochondrial uncoupling beyond UCP1 - The fine line between death and metabolic health.

PubMed

Ost, Mario; Keipert, Susanne; Klaus, Susanne

2017-03-01

In the early 1930s, the chemical uncoupling agent 2,4-dinitrophenol (DNP) was promoted for the very first time as a powerful and effective weight loss pill but quickly withdrawn from the market due to its lack of tissue-selectivity with resulting dangerous side effects, including hyperthermia and death. Today, novel mitochondria- or tissue-targeted chemical uncouplers with higher safety and therapeutic values are under investigation in order to tackle obesity, diabetes and fatty liver disease. Moreover, in the past 20 years, transgenic mouse models were generated to understand the molecular and metabolic consequences of targeted uncoupling, expressing functional uncoupling protein 1 (UCP1) ectopically in white adipose tissue or skeletal muscle. Similar to the action of chemical mitochondrial uncouplers, UCP1 protein dissipates the proton gradient across the inner mitochondrial membrane, thus allowing maximum activity of the respiratory chain and compensatory increase in oxygen consumption, uncoupled from ATP synthesis. Consequently, targeted mitochondrial uncoupling in adipose tissue and skeletal muscle of UCP1-transgenic mice increased substrate metabolism and ameliorates obesity, hypertriglyceridemia and insulin resistance. Further, muscle-specific decrease in mitochondrial efficiency promotes a cell-autonomous and cell-non-autonomous adaptive metabolic remodeling with increased oxidative stress tolerance. This review provides an overview of novel chemical uncouplers as well as the metabolic consequences and adaptive processes of targeted mitochondrial uncoupling on metabolic health and survival. Copyright © 2016 Elsevier B.V. and Société Française de Biochimie et Biologie Moléculaire (SFBBM). All rights reserved.

Exploiting the CRISPR/Cas9 System for Targeted Genome Mutagenesis in Petunia.

PubMed

Zhang, Bin; Yang, Xia; Yang, Chunping; Li, Mingyang; Guo, Yulong

2016-02-03

Recently, CRISPR/Cas9 technology has emerged as a powerful approach for targeted genome modification in eukaryotic organisms from yeast to human cell lines. Its successful application in several plant species promises enormous potential for basic and applied plant research. However, extensive studies are still needed to assess this system in other important plant species, to broaden its fields of application and to improve methods. Here we showed that the CRISPR/Cas9 system is efficient in petunia (Petunia hybrid), an important ornamental plant and a model for comparative research. When PDS was used as target gene, transgenic shoot lines with albino phenotype accounted for 55.6%-87.5% of the total regenerated T0 Basta-resistant lines. A homozygous deletion close to 1 kb in length can be readily generated and identified in the first generation. A sequential transformation strategy--introducing Cas9 and sgRNA expression cassettes sequentially into petunia--can be used to make targeted mutations with short indels or chromosomal fragment deletions. Our results present a new plant species amenable to CRIPR/Cas9 technology and provide an alternative procedure for its exploitation.

Exploiting the CRISPR/Cas9 System for Targeted Genome Mutagenesis in Petunia

PubMed Central

Zhang, Bin; Yang, Xia; Yang, Chunping; Li, Mingyang; Guo, Yulong

2016-01-01

Recently, CRISPR/Cas9 technology has emerged as a powerful approach for targeted genome modification in eukaryotic organisms from yeast to human cell lines. Its successful application in several plant species promises enormous potential for basic and applied plant research. However, extensive studies are still needed to assess this system in other important plant species, to broaden its fields of application and to improve methods. Here we showed that the CRISPR/Cas9 system is efficient in petunia (Petunia hybrid), an important ornamental plant and a model for comparative research. When PDS was used as target gene, transgenic shoot lines with albino phenotype accounted for 55.6%–87.5% of the total regenerated T0 Basta-resistant lines. A homozygous deletion close to 1 kb in length can be readily generated and identified in the first generation. A sequential transformation strategy—introducing Cas9 and sgRNA expression cassettes sequentially into petunia—can be used to make targeted mutations with short indels or chromosomal fragment deletions. Our results present a new plant species amenable to CRIPR/Cas9 technology and provide an alternative procedure for its exploitation. PMID:26837606

Lentiviral and targeted cellular barcoding reveals ongoing clonal dynamics of cell lines in vitro and in vivo

PubMed Central

2014-01-01

Background Cell lines are often regarded as clonal, even though this simplifies what is known about mutagenesis, transformation and other processes that destabilize them over time. Monitoring these clonal dynamics is important for multiple areas of biomedical research, including stem cell and cancer biology. Tracking the contributions of individual cells to large populations, however, has been constrained by limitations in sensitivity and complexity. Results We utilize cellular barcoding methods to simultaneously track the clonal contributions of tens of thousands of cells. We demonstrate that even with optimal culturing conditions, common cell lines including HeLa, K562 and HEK-293 T exhibit ongoing clonal dynamics. Starting a population with a single clone diminishes but does not eradicate this phenomenon. Next, we compare lentiviral and zinc-finger nuclease barcode insertion approaches, finding that the zinc-finger nuclease protocol surprisingly results in reduced clonal diversity. We also document the expected reduction in clonal complexity when cells are challenged with genotoxic stress. Finally, we demonstrate that xenografts maintain clonal diversity to a greater extent than in vitro culturing of the human non-small-cell lung cancer cell line HCC827. Conclusions We demonstrate the feasibility of tracking and quantifying the clonal dynamics of entire cell populations within multiple cultured cell lines. Our results suggest that cell heterogeneity should be considered in the design and interpretation of in vitro culture experiments. Aside from clonal cell lines, we propose that cellular barcoding could prove valuable in modeling the clonal behavior of heterogeneous cell populations over time, including tumor populations treated with chemotherapeutic agents. PMID:24886633

Microsputterer with integrated ion-drag focusing for additive manufacturing of thin, narrow conductive lines

NASA Astrophysics Data System (ADS)

Kornbluth, Y. S.; Mathews, R. H.; Parameswaran, L.; Racz, L. M.; Velásquez-García, L. F.

2018-04-01

We report the design, modelling, and proof-of-concept demonstration of a continuously fed, atmospheric-pressure microplasma metal sputterer that is capable of printing conductive lines narrower than the width of the target without the need for post-processing or lithographic patterning. Ion drag-induced focusing is harnessed to print narrow lines; the focusing mechanism is modelled via COMSOL Multiphysics simulations and validated with experiments. A microplasma sputter head with gold target is constructed and used to deposit imprints with minimum feature sizes as narrow as 9 µm, roughness as small as 55 nm, and electrical resistivity as low as 1.1 µΩ · m.

Light-controlled endosomal escape of the novel CD133-targeting immunotoxin AC133-saporin by photochemical internalization - A minimally invasive cancer stem cell-targeting strategy.

PubMed

Bostad, Monica; Olsen, Cathrine Elisabeth; Peng, Qian; Berg, Kristian; Høgset, Anders; Selbo, Pål Kristian

2015-05-28

The cancer stem cell (CSC) marker CD133 is an attractive target to improve antitumor therapy. We have used photochemical internalization (PCI) for the endosomal escape of the novel CD133-targeting immunotoxin AC133-saporin (PCIAC133-saporin). PCI employs an endocytic vesicle-localizing photosensitizer, which generates reactive oxygen species upon light-activation causing a rupture of the vesicle membranes and endosomal escape of entrapped drugs. Here we show that AC133-saporin co-localizes with the PCI-photosensitizer TPCS2a, which upon light exposure induces cytosolic release of AC133-saporin. PCI of picomolar levels of AC133-saporin in colorectal adenocarcinoma WiDr cells blocked cell proliferation and induced 100% inhibition of cell viability and colony forming ability at the highest light doses, whereas no cytotoxicity was obtained in the absence of light. Efficient PCI-based CD133-targeting was in addition demonstrated in the stem-cell-like, triple negative breast cancer cell line MDA-MB-231 and in the aggressive malignant melanoma cell line FEMX-1, whereas no enhanced targeting was obtained in the CD133-negative breast cancer cell line MCF-7. PCIAC133-saporin induced mainly necrosis and a minimal apoptotic response based on assessing cleavage of caspase-3 and PARP, and the TUNEL assay. PCIAC133-saporin resulted in S phase arrest and reduced LC3-II conversion compared to control treatments. Notably, co-treatment with Bafilomycin A1 and PCIAC133-saporin blocked LC3-II conversion, indicating a termination of the autophagic flux in WiDr cells. For the first time, we demonstrate laser-controlled targeting of CD133 in vivo. After only one systemic injection of AC133-saporin and TPCS2a, a strong anti-tumor response was observed after PCIAC133-saporin. The present PCI-based endosomal escape technology represents a minimally invasive strategy for spatio-temporal, light-controlled targeting of CD133+ cells in localized primary tumors or metastasis. Copyright © 2015

Generating Text from Functional Brain Images

PubMed Central

Pereira, Francisco; Detre, Greg; Botvinick, Matthew

2011-01-01

Recent work has shown that it is possible to take brain images acquired during viewing of a scene and reconstruct an approximation of the scene from those images. Here we show that it is also possible to generate text about the mental content reflected in brain images. We began with images collected as participants read names of concrete items (e.g., “Apartment’’) while also seeing line drawings of the item named. We built a model of the mental semantic representation of concrete concepts from text data and learned to map aspects of such representation to patterns of activation in the corresponding brain image. In order to validate this mapping, without accessing information about the items viewed for left-out individual brain images, we were able to generate from each one a collection of semantically pertinent words (e.g., “door,” “window” for “Apartment’’). Furthermore, we show that the ability to generate such words allows us to perform a classification task and thus validate our method quantitatively. PMID:21927602

Targeting Quiescence in Prostate Cancer

DTIC Science & Technology

2017-10-01

CRISPR /Cas9 to generate cell lines where the reporters are integrated endogenously into 5 essential cell cycle genes to avoid epigenetic silencing. In...Developed and began an improved CRISPR /Cas9-based strategy to target reporters to endogenous gene loci in PC3 and C4-2B cells to prevent silencing...serum. An improved CRISPR /Cas9-based strategy to avoid cell cycle reporter silencing and incorporate a constitutive nuclear marker As described

Enantioselective Effects of Chiral Pesticides on their Primary Targets and Secondary Targets.

PubMed

Yang, Ye; Zhang, Jianyun; Yao, Yijun

2017-01-01

Enantioselectivity has been well recognized in the environmental fate and effects of chiral pesticides. Enantiospecific action of the optical enantiomers on the biological molecules establishes the mechanistic basis for the enantioselective toxicity of chiral pesticides to both target and non-target organisms. We undertook a structured search of bibliographic databases for research literature concerning the enantioselective effects of chiral pesticides, including insecticides, herbicides and fungicides, on biomolecules in various species by using some key words. The results of the relevant literatures were reviewed in the text and summarized in tables. Pesticides generally exert their activity on the target organisms via disrupting the primary target biomolecules. In non-target species, effects of pesticides on the secondary targets distinguished from the primary ones make great contribution to their toxicity. Recent investigations have provided convincing evidence of enantioselective toxicity of chiral pesticides to both target and non-target species which is recognized to result from their enantiospecific action on the primary or secondary targets in organisms. This review confirms that chiral pesticides have enantiospecific effects on both primary and secondary target biomolecules in organisms. Future studies regarding toxicological effects of chiral pesticides should focus on the relationship between the enantiomeric difference in the compound-biomolecules interaction and the enantioselectivity in their toxicity.

Coordinated Search for a Random Walk Target Motion

NASA Astrophysics Data System (ADS)

El-Hadidy, Mohamed Abd Allah; Abou-Gabal, Hamdy M.

This paper presents the cooperation between two searchers at the origin to find a Random Walk moving target on the real line. No information is not available about the target’s position all the time. Rather than finding the conditions that make the expected value of the first meeting time between one of the searchers and the target is finite, we show the existence of the optimal search strategy which minimizes this first meeting time. The effectiveness of this model is illustrated using a numerical example.

Targeting FOXM1 Improves Cytotoxicity of Paclitaxel and Cisplatinum in Platinum-Resistant Ovarian Cancer.

PubMed

Westhoff, Gina L; Chen, Yi; Teng, Nelson N H

2017-10-01

Aberrantly activated FOXM1 (forkhead box protein M1) leading to uncontrolled cell proliferation and dysregulation of FOXM1 transcription network occurs in 84% of ovarian cancer cases. It was demonstrated that thiostrepton, a thiazole antibiotic, decreases FOXM1 expression. We aimed to determine if targeting the FOXM1 pathway with thiostrepton could improve the efficacy of paclitaxel and cisplatin in human ovarian cancer ascites cells ex vivo. Human ovarian cancer cell lines and patients' ascites cells were treated with paclitaxel, cisplatin, and thiostrepton or a combination for 48 hours, and cytotoxicity was assessed. Drug combination effects were determined by calculating the combination index values using the Chou and Talalay method. Quantitative reverse transcriptase-polymerase chain reaction was performed to determine changes in FOXM1 expression and its downstream targets. Ovarian cancer cell lines and the patients' ascites cancer cells had an overexpression of FOXM1 expression levels. Targeting FOXM1 with thiostrepton decreased FOXM1 mRNA expression and its downstream targets such as CCNB1 and CDC25B, leading to cell death in both cell lines and patients' ascites cancer cells. Furthermore, addition of thiostrepton to paclitaxel and cisplatin showed synergistic effects in chemoresistant ovarian cancer patients' ascites cells ex vivo. Targeting FOXM1 may lead to novel therapeutics for chemoresistant epithelial ovarian cancer.

Polarized deuterium internal target at AmPS (NIKHEF)

NASA Astrophysics Data System (ADS)

Ferro-Luzzi, M.; Zhou, Z.-L.; van den Brand, J. F. J.; Bulten, H. J.; Alarcon, R.; van Bakel, N.; Botto, T.; Bouwhuis, M.; van Buuren, L.; Comfort, J.; Doets, M.; Dolfini, S.; Ent, R.; Geurts, D.; Heimberg, P.; Higinbotham, D. W.; de Jager, C. W.; Lang, J.; de Lange, D. J.; Norum, B.; Passchier, I.; Poolman, H. R.; Six, E.; Steijger, J.; Szczerba, D.; Unal, O.; de Vries, H.

1998-01-01

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

Photometric redshifts and clustering of emission line galaxies selected jointly by DES and eBOSS

DOE PAGES

Jouvel, S.; Delubac, T.; Comparat, J.; ...

2017-03-24

We present the results of the first test plates of the extended Baryon Oscillation Spectroscopic Survey. This paper focuses on the emission line galaxies (ELG) population targetted from the Dark Energy Survey (DES) photometry. We analyse the success rate, efficiency, redshift distribution, and clustering properties of the targets. From the 9000 spectroscopic redshifts targetted, 4600 have been selected from the DES photometry. The total success rate for redshifts between 0.6 and 1.2 is 71\\% and 68\\% respectively for a bright and faint, on average more distant, samples including redshifts measured from a single strong emission line. We find a meanmore » redshift of 0.8 and 0.87, with 15 and 13\\% of unknown redshifts respectively for the bright and faint samples. In the redshift range 0.6« less

Photometric redshifts and clustering of emission line galaxies selected jointly by DES and eBOSS

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

Jouvel, S.; Delubac, T.; Comparat, J.

We present the results of the first test plates of the extended Baryon Oscillation Spectroscopic Survey. This paper focuses on the emission line galaxies (ELG) population targetted from the Dark Energy Survey (DES) photometry. We analyse the success rate, efficiency, redshift distribution, and clustering properties of the targets. From the 9000 spectroscopic redshifts targetted, 4600 have been selected from the DES photometry. The total success rate for redshifts between 0.6 and 1.2 is 71\\% and 68\\% respectively for a bright and faint, on average more distant, samples including redshifts measured from a single strong emission line. We find a meanmore » redshift of 0.8 and 0.87, with 15 and 13\\% of unknown redshifts respectively for the bright and faint samples. In the redshift range 0.6« less

Identify Fractions and Decimals on a Number Line

ERIC Educational Resources Information Center

Shaughnessy, Meghan M.

2011-01-01

Tasks that ask students to label rational number points on a number line are common not only in curricula in the upper elementary school grades but also on state assessments. Such tasks target foundational rational number concepts: A fraction (or a decimal) is more than a shaded part of an area, a part of a pizza, or a representation using…

Fabrication High Resolution Metrology Target By Step And Repeat Method

NASA Astrophysics Data System (ADS)

Dusa, Mircea

1983-10-01

Based on the photolithography process generally used to generate high resolution masks for semiconductor I.C.S, we found a very useful industrial application of laser technology.First, we have generated high resolution metrology targets which are used in industrial measurement laser interferometers as difra.ction gratings. Secondi we have generated these targets using step and repeat machine, with He-Ne laser interferometer controlled state, as a pattern generator, due to suitable computer programming.Actually, high resolution metrology target, means two chromium plates, one of which is called the" rule" the other one the "vernier". In Fig.1 we have the configuration of the rule and the vernier. The rule has a succesion of 3 μM lines generated as a difraction grating on a 4 x 4 inch chromium blank. The vernier has several exposed fields( areas) having 3 - 15 μm lines, fields placed on very precise position on the chromium blank surface. High degree of uniformity, tight CD tolerances, low defect density required by the targets, creates specialised problems during processing. Details of the processing, together with experimental results will be presented. Before we start to enter into process details, we have to point out that the dimensional requirements of the reticle target, are quite similar or perhaps more strict than LSI master casks. These requirements presented in Fig.2.

Specific c-Jun target genes in malignant melanoma.

PubMed

Schummer, Patrick; Kuphal, Silke; Vardimon, Lily; Bosserhoff, Anja K; Kappelmann, Melanie

2016-05-03

A fundamental event in the development and progression of malignant melanoma is the de-regulation of cancer-relevant transcription factors. We recently showed that c-Jun is a main regulator of melanoma progression and, thus, is the most important member of the AP-1 transcription factor family in this disease. Surprisingly, no cancer-related specific c-Jun target genes in melanoma were described in the literature, so far. Therefore, we focused on pre-existing ChIP-Seq data (Encyclopedia of DNA Elements) of 3 different non-melanoma cell lines to screen direct c-Jun target genes. Here, a specific c-Jun antibody to immunoprecipitate the associated promoter DNA was used. Consequently, we identified 44 direct c-Jun targets and a detailed analysis of 6 selected genes confirmed their deregulation in malignant melanoma. The identified genes were differentially regulated comparing 4 melanoma cell lines and normal human melanocytes and we confirmed their c-Jun dependency. Direct interaction between c-Jun and the promoter/enhancer regions of the identified genes was confirmed by us via ChIP experiments. Interestingly, we revealed that the direct regulation of target gene expression via c-Jun can be independent of the existence of the classical AP-1 (5´-TGA(C/G)TCA-3´) consensus sequence allowing for the subsequent down- or up-regulation of the expression of these cancer-relevant genes. In summary, the results of this study indicate that c-Jun plays a crucial role in the development and progression of malignant melanoma via direct regulation of cancer-relevant target genes and that inhibition of direct c-Jun targets through inhibition of c-Jun is a potential novel therapeutic option for treatment of malignant melanoma.

Metformin targets multiple signaling pathways in cancer.

PubMed

Lei, Yong; Yi, Yanhua; Liu, Yang; Liu, Xia; Keller, Evan T; Qian, Chao-Nan; Zhang, Jian; Lu, Yi

2017-01-26

Metformin, an inexpensive and well-tolerated oral agent commonly used in the first-line treatment of type 2 diabetes, has become the focus of intense research as a candidate anticancer agent. Here, we discuss the potential of metformin in cancer therapeutics, particularly its functions in multiple signaling pathways, including AMP-activated protein kinase, mammalian target of rapamycin, insulin-like growth factor, c-Jun N-terminal kinase/mitogen-activated protein kinase (p38 MAPK), human epidermal growth factor receptor-2, and nuclear factor kappaB pathways. In addition, cutting-edge targeting of cancer stem cells by metformin is summarized.

Differential acceleration in the final beam lines of a Heavy Ion Fusion driver

DOE PAGES

Friedman, Alex

2013-10-19

A long-standing challenge in the design of a Heavy Ion Fusion power plant is that the ion beams entering the target chamber, which number of order a hundred, all need to be routed from one or two multi-beam accelerators through a set of transport lines. The beams are divided into groups, which each have unique arrival times and may have unique kinetic energies. It is also necessary to arrange for each beam to enter the target chamber from a prescribed location on the periphery of that chamber. Furthermore, it has generally been assumed that additional constraints must be obeyed: thatmore » the path lengths of the beams in a group must be equal, and that any delay of \\main-pulse" beams relative to \\foot-pulse" beams must be provided by the insertion of large delay-arcs in the main beam transport lines. Here we introduce the notion of applying \\di erential acceleration" to individual beams or sets of beam at strategic stages of the transport lines. That is, by accelerating some beams \\sooner" and others \\later," it is possible to simplify the beam line con guration in a number of cases. For example, the time delay between the foot and main pulses can be generated without resorting to large arcs in the main-pulse beam lines. It is also possible to use di erential acceleration to e ect the simultaneous arrival on target of a set of beams ( e.g., for the foot-pulse) without requiring that their path lengths be precisely equal. We illustrate the technique for two model con gurations, one corresponding to a typical indirect-drive scenario requiring distinct foot and main energies, and the other to an ion-driven fast-ignition scenario wherein the foot and main beams share a common energy.« less

Gold Nano Popcorn Attached SWCNT Hybrid Nanomaterial for Targeted Diagnosis and Photothermal Therapy of Human Breast Cancer Cells

PubMed Central

Beqa, Lule; Fan, Zhen; Singh, Anant Kumar; Senapati, Dulal; Ray, Paresh Chandra

2011-01-01

Breast cancer presents greatest challenge in health care in today’s world. The key to ultimately successful treatment of breast cancer disease is an early and accurate diagnosis. Current breast cancer treatments are often associated with severe side effects. Driven by the need, we report the design of novel hybrid nanomaterial using gold nano popcorn-attached single wall carbon nanotube for targeted diagnosis and selective photothermal treatment. Targeted SK-BR-3 human breast cancer cell sensing have been performed in 10 cancer cells/mL level, using surface enhanced Raman scattering of single walls carbon nanotube’s D and G bands. Our data show that S6 aptamer attached hybrid nanomaterial based SERS assay is highly sensitive to targeted human breast cancer SK-BR-3 cell line and it will be able to distinguish it from other non targeted MDA-MB breast cancer cell line and HaCaT normal skin cell line. Our results also show that 10 minutes of photothermal therapy treatment by 1.5 W/cm2 power, 785 nm laser is enough to kill cancer cells very effectively using S6 aptamer attached hybrid nanomaterials. Possible mechanisms for targeted sensing and operating principle for highly efficient photothermal therapy have been discussed. Our experimental results reported here open up a new possibility for using aptamers modified hybrid nanomaterial for reliable diagnosis and targeted therapy of cancer cell lines quickly. PMID:21842867

P41IDENTIFICATION OF GLIOMA SPECIFIC APTAMER TARGETS

PubMed Central

Arora, Mohit; Alder, Jane; Lawrence, Clare; Davis, Charles; Dawson, Tim; Hall, Greg; Shaw, Lisa

2014-01-01

INTRODUCTION: Aptamers are in vitro generated DNA and RNA sequences which are randomly created as a library, with multiple permutations and combinations. These are then exposed to the target structure against which we want an aptamer ‘selected’ using Sequential Enumeration of Ligands by Exponential enrichment (SELEX). METHOD: Commercially available glioma and glial cell lines and in-house generated primary glioma cultures were used. Modified aptamers based on published sequences against glioma cell lines and newly generated sequences were used in the project to identify their binding targets. Cy3 or biotin- conjugated aptamers were incubated with live glioma cell cultures and imaged using confocal or light microscopy.To determine the target ligand, aptamers were then reacted with glial cell lysate and subjected to precipitation using streptavidin agarose beads and SDS polyacrylamide electrophoresis. Proteins were analysed by mass spectroscopy. RESULTS: Known and unknown aptamer protein ligands were co-precipitated. Ku70, Ku80 were precipitated along with nucleolin and related proteins. CONCLUSION: The aptamer has shown preferential binding to glioma cells and could act as a delivery system for therapeutic payloads. The aptamer targets Ku70 and Ku80, which are known to be over expressed in other forms of cancer but their role in gliomagenesis has not been fully elucidated. Other novel proteins have also been identified. Thus the aptamer co-precipitation technique has identified potential glioma biomarkers that may be of clinical significance.

Activation Levels, Handling, and Storage of Activated Components in the Target Hall at FRIB

NASA Astrophysics Data System (ADS)

Georgobiani, D.; Bennett, R.; Bollen, G.; Kostin, M.; Ronningen, R.

2018-06-01

The Facility for Rare Isotope Beams (FRIB) is a major new scientific user facility under construction in the United States for nuclear science research with beams of rare isotopes. 400 kW beam operations with heavy ions ranging from oxygen to uranium will create a high radiation environment for many components, particularly for the beam line components located in the target hall, where approximately 100 kW of beam power are dissipated in the target and another 300 kW are dissipated in the beam dump. Detailed studies of the component activation, their remote handling, storage, and transport, have been performed to ensure safe operation levels in this environment. Levels of activation are calculated for the beam line components within the FRIB target hall.

An after-market, five-port vertical beam line extension for the PETtrace

NASA Astrophysics Data System (ADS)

Barnhart, T. E.; Engle, J. W.; Severin, G. W.; Valdovinos, H. F.; Gagnon, K.; Nickles, R. J.

2012-12-01

Most commercial cyclotrons intended for medical isotope production provide a limited number of beam ports crowded into a minimal vault space. Taking advantage of our new lab construction, we planned and installed a beam-line on port ♯2 of our GEMS PETtrace to bring beam to an additional 5 target positions. These are oriented in the vertical plane, with the downward directed beam well suited for molten target substrates.

Annotated chemical patent corpus: a gold standard for text mining.

PubMed

Akhondi, Saber A; Klenner, Alexander G; Tyrchan, Christian; Manchala, Anil K; Boppana, Kiran; Lowe, Daniel; Zimmermann, Marc; Jagarlapudi, Sarma A R P; Sayle, Roger; Kors, Jan A; Muresan, Sorel

2014-01-01

Exploring the chemical and biological space covered by patent applications is crucial in early-stage medicinal chemistry activities. Patent analysis can provide understanding of compound prior art, novelty checking, validation of biological assays, and identification of new starting points for chemical exploration. Extracting chemical and biological entities from patents through manual extraction by expert curators can take substantial amount of time and resources. Text mining methods can help to ease this process. To validate the performance of such methods, a manually annotated patent corpus is essential. In this study we have produced a large gold standard chemical patent corpus. We developed annotation guidelines and selected 200 full patents from the World Intellectual Property Organization, United States Patent and Trademark Office, and European Patent Office. The patents were pre-annotated automatically and made available to four independent annotator groups each consisting of two to ten annotators. The annotators marked chemicals in different subclasses, diseases, targets, and modes of action. Spelling mistakes and spurious line break due to optical character recognition errors were also annotated. A subset of 47 patents was annotated by at least three annotator groups, from which harmonized annotations and inter-annotator agreement scores were derived. One group annotated the full set. The patent corpus includes 400,125 annotations for the full set and 36,537 annotations for the harmonized set. All patents and annotated entities are publicly available at www.biosemantics.org.

Annotated Chemical Patent Corpus: A Gold Standard for Text Mining

PubMed Central

Akhondi, Saber A.; Klenner, Alexander G.; Tyrchan, Christian; Manchala, Anil K.; Boppana, Kiran; Lowe, Daniel; Zimmermann, Marc; Jagarlapudi, Sarma A. R. P.; Sayle, Roger; Kors, Jan A.; Muresan, Sorel

2014-01-01

Exploring the chemical and biological space covered by patent applications is crucial in early-stage medicinal chemistry activities. Patent analysis can provide understanding of compound prior art, novelty checking, validation of biological assays, and identification of new starting points for chemical exploration. Extracting chemical and biological entities from patents through manual extraction by expert curators can take substantial amount of time and resources. Text mining methods can help to ease this process. To validate the performance of such methods, a manually annotated patent corpus is essential. In this study we have produced a large gold standard chemical patent corpus. We developed annotation guidelines and selected 200 full patents from the World Intellectual Property Organization, United States Patent and Trademark Office, and European Patent Office. The patents were pre-annotated automatically and made available to four independent annotator groups each consisting of two to ten annotators. The annotators marked chemicals in different subclasses, diseases, targets, and modes of action. Spelling mistakes and spurious line break due to optical character recognition errors were also annotated. A subset of 47 patents was annotated by at least three annotator groups, from which harmonized annotations and inter-annotator agreement scores were derived. One group annotated the full set. The patent corpus includes 400,125 annotations for the full set and 36,537 annotations for the harmonized set. All patents and annotated entities are publicly available at www.biosemantics.org. PMID:25268232

Text Generation: The Problem of Text Structure.

ERIC Educational Resources Information Center

Mann, William C.

One of the major problems in artificial intelligence (AI) text generation is text organization; a poorly organized text can be unreadable or even misleading. A comparison of two AI approaches to text organization--McKeown's TEXT system and Rhetorical Structure Theory (RST)--shows that, although they share many assumptions about the nature of text,…

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

Processing and Memory of Information Presented in Narrative or Expository Texts

ERIC Educational Resources Information Center

Wolfe, Michael B. W.; Woodwyk, Joshua M.

2010-01-01

Background: Previous research suggests that narrative and expository texts differ in the extent to which they prompt students to integrate to-be-learned content with relevant prior knowledge during comprehension. Aims: We expand on previous research by examining on-line processing and representation in memory of to-be-learned content that is…

Use of Microsphere Technology for Targeted Delivery of Rifampin to Mycobacterium tuberculosis-Infected Macrophages

PubMed Central

Barrow, Esther L. W.; Winchester, Gary A.; Staas, Jay K.; Quenelle, Debra C.; Barrow, William W.

1998-01-01

Microsphere technology was used to develop formulations of rifampin for targeted delivery to host macrophages. These formulations were prepared by using biocompatible polymeric excipients of lactide and glycolide copolymers. Release characteristics were examined in vitro and also in two monocytic cell lines, the murine J774 and the human Mono Mac 6 cell lines. Bioassay assessment of cell culture supernatants from monocyte cell lines showed release of bioactive rifampin during a 7-day experimental period. Treatment of Mycobacterium tuberculosis H37Rv-infected monocyte cell lines with rifampin-loaded microspheres resulted in a significant decrease in numbers of CFU at 7 days following initial infection, even though only 8% of the microsphere-loaded rifampin was released. The levels of rifampin released from microsphere formulations within monocytes were more effective at reducing M. tuberculosis intracellular growth than equivalent doses of rifampin given as a free drug. These results demonstrate that rifampin-loaded microspheres can be formulated for effective sustained and targeted delivery to host macrophages. PMID:9756777

Metacomprehension judgements reflect the belief that diagrams improve learning from text.

PubMed

Serra, Michael J; Dunlosky, John

2010-10-01

In two experiments we systematically explored whether people consider the format of text materials when judging their text learning, and whether doing so might inappropriately bias their judgements. Participants studied either text with diagrams (multimedia) or text alone and made both per-paragraph judgements and global judgements of their text learning. In Experiment 1 they judged their learning to be better for text with diagrams than for text alone. In that study, however, test performance was greater for multimedia, so the judgements may reflect either a belief in the power of multimedia or on-line processing. Experiment 2 replicated this finding and also included a third group that read texts with pictures that did not improve text performance. Judgements made by this group were just as high as those made by participants who received the effective multimedia format. These results confirm the hypothesis that people's metacomprehension judgements can be influenced by their beliefs about text format. Over-reliance on this multimedia heuristic, however, might reduce judgement accuracy in situations where it is invalid.

Mars Target Encyclopedia: Information Extraction for Planetary Science

NASA Astrophysics Data System (ADS)

Wagstaff, K. L.; Francis, R.; Gowda, T.; Lu, Y.; Riloff, E.; Singh, K.

2017-06-01

Mars surface targets / and published compositions / Seek and ye will find. We used text mining methods to extract information from LPSC abstracts about the composition of Mars surface targets. Users can search by element, mineral, or target.

Phosphotyrosine profiling identifies ephrin receptor A2 as a potential therapeutic target in esophageal squamous‐cell carcinoma

PubMed Central

Syed, Nazia; Barbhuiya, Mustafa A.; Pinto, Sneha M.; Nirujogi, Raja Sekhar; Renuse, Santosh; Datta, Keshava K.; Khan, Aafaque Ahmad; Srikumar, Kotteazeth; Prasad, T. S. Keshava; Kumar, M. Vijaya; Kumar, Rekha Vijay; Chatterjee, Aditi; Pandey, Akhilesh

2015-01-01

Esophageal squamous‐cell carcinoma (ESCC) is one of the most common malignancies in Asia. Currently, surgical resection of early‐stage tumor is the best available treatment. However, most patients present late when surgery is not an option. Data suggest that chemotherapy regimens are inadequate for clinical management of advanced cancer. Targeted therapy has emerged as one of the most promising approaches to treat several malignancies. A prerequisite for developing targeted therapy is prior knowledge of proteins and pathways that drive proliferation in malignancies. We carried out phosphotyrosine profiling across four different ESCC cell lines and compared it to non‐neoplastic Het‐1A cell line to identify activated tyrosine kinase signaling pathways in ESCC. A total of 278 unique phosphopeptides were identified across these cell lines. This included several tyrosine kinases and their substrates that were hyperphosphorylated in ESCC. Ephrin receptor A2 (EPHA2), a receptor tyrosine kinase, was hyperphosphorylated in all the ESCC cell lines used in the study. EPHA2 is reported to be oncogenic in several cancers and is also known to promote metastasis. Immunohistochemistry‐based studies have revealed EPHA2 is overexpressed in nearly 50% of ESCC. We demonstrated EPHA2 as a potential therapeutic target in ESCC by carrying out siRNA‐based knockdown studies. Knockdown of EPHA2 in ESCC cell line TE8 resulted in significant decrease in cell proliferation and invasion, suggesting it is a promising therapeutic target in ESCC that warrants further evaluation. PMID:25366905

Folate-targeted nanoparticles show efficacy in the treatment of inflammatory arthritis

PubMed Central

Thomas, Thommey P.; Goonewardena, Sascha N.; Majoros, Istvan; Kotlyar, Alina; Cao, Zhengyi; Leroueil, Pascale R.; Baker, James R.

2011-01-01

Objective To investigate the uptake of a poly(amidoamine) dendrimer (generation 5 (G5)) nanoparticle covalently conjugated to polyvalent folic acid (FA) as the targeting ligand into macrophages, and the activity of a FA- and methotrexate-conjugated dendrimer (G5-FA-MTX) as a therapeutic for the inflammatory disease of arthritis. Methods In vitro studies were performed in macrophage cell lines and in isolated mouse macrophages to check the cellular uptake of fluorescently tagged G5-FA nanoparticles, using flow cytometry and confocal microscopy. In vivo studies were conducted in a rat model of collagen-induced arthritis to evaluate the therapeutic potential of G5-FA-MTX. Results Folate targeted dendrimer bound and internalized in a receptor-specific manner into both folate receptor β-expressing macrophage cell lines and primary mouse macrophages. The G5-FA-MTX acts as a potent anti-inflammatory agent and reduces arthritis-induced inflammatory parameters such as ankle swelling, paw volume, cartilage damage, bone resorption and body weight decrease. Conclusion The use of folate-targeted nanoparticles to specifically target MTX into macrophages may provide an effective clinical approach for anti-inflammatory therapy in rheumatoid arthritis. PMID:21618461

Two-dimensional particle-in-cell plasma source ion implantation of a prolate spheroid target

NASA Astrophysics Data System (ADS)

Liu, Cheng-Sen; Han, Hong-Ying; Peng, Xiao-Qing; Chang, Ye; Wang, De-Zhen

2010-03-01

A two-dimensional particle-in-cell simulation is used to study the time-dependent evolution of the sheath surrounding a prolate spheroid target during a high voltage pulse in plasma source ion implantation. Our study shows that the potential contour lines pack more closely in the plasma sheath near the vertex of the major axis, i.e. where a thinner sheath is formed, and a non-uniform total ion dose distribution is incident along the surface of the prolate spheroid target due to the focusing of ions by the potential structure. Ion focusing takes place not only at the vertex of the major axis, where dense potential contour lines exist, but also at the vertex of the minor axis, where sparse contour lines exist. This results in two peaks of the received ion dose, locating at the vertices of the major and minor axes of the prolate spheroid target, and an ion dose valley, staying always between the vertices, rather than at the vertex of the minor axis.

The advanced linked extended reconnaissance and targeting technology demonstration project

NASA Astrophysics Data System (ADS)

Cruickshank, James; de Villers, Yves; Maheux, Jean; Edwards, Mark; Gains, David; Rea, Terry; Banbury, Simon; Gauthier, Michelle

2007-06-01

The Advanced Linked Extended Reconnaissance & Targeting (ALERT) Technology Demonstration (TD) project is addressing key operational needs of the future Canadian Army's Surveillance and Reconnaissance forces by fusing multi-sensor and tactical data, developing automated processes, and integrating beyond line-of-sight sensing. We discuss concepts for displaying and fusing multi-sensor and tactical data within an Enhanced Operator Control Station (EOCS). The sensor data can originate from the Coyote's own visible-band and IR cameras, laser rangefinder, and ground-surveillance radar, as well as beyond line-of-sight systems such as a mini-UAV and unattended ground sensors. The authors address technical issues associated with the use of fully digital IR and day video cameras and discuss video-rate image processing developed to assist the operator to recognize poorly visible targets. Automatic target detection and recognition algorithms processing both IR and visible-band images have been investigated to draw the operator's attention to possible targets. The machine generated information display requirements are presented with the human factors engineering aspects of the user interface in this complex environment, with a view to establishing user trust in the automation. The paper concludes with a summary of achievements to date and steps to project completion.

Polarized deuterium internal target at AmPS (NIKHEF)

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

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

1998-01-20

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

PSMA-targeted bispecific Fab conjugates that engage T cells.

PubMed

Patterson, James T; Isaacson, Jason; Kerwin, Lisa; Atassi, Ghazi; Duggal, Rohit; Bresson, Damien; Zhu, Tong; Zhou, Heyue; Fu, Yanwen; Kaufmann, Gunnar F

2017-12-15

Bioconjugate formats provide alternative strategies for antigen targeting with bispecific antibodies. Here, PSMA-targeted Fab conjugates were generated using different bispecific formats. Interchain disulfide bridging of an αCD3 Fab enabled installation of either the PSMA-targeting small molecule DUPA (SynFab) or the attachment of an αPSMA Fab (BisFab) by covalent linkage. Optimization of the reducing conditions was critical for selective interchain disulfide reduction and good bioconjugate yield. Activity of αPSMA/CD3 Fab conjugates was tested by in vitro cytotoxicity assays using prostate cancer cell lines. Both bispecific formats demonstrated excellent potency and antigen selectivity. Copyright © 2017. Published by Elsevier Ltd.

Temperature dependence of yields from multi-foil SPES target

NASA Astrophysics Data System (ADS)

Corradetti, S.; Biasetto, L.; Manzolaro, M.; Scarpa, D.; Andrighetto, A.; Carturan, S.; Prete, G.; Zanonato, P.; Stracener, D. W.

2011-10-01

The temperature dependence of neutron-rich isotope yields was studied within the framework of the HRIBF-SPES Radioactive Ion Beams (RIB) project. On-line release measurements of fission fragments from a uranium carbide target at ensuremath 1600 {}^{circ}C , ensuremath 1800 {}^{circ}C and ensuremath 2000 {}^{circ}C were performed at ORNL (USA). The fission reactions were induced by a 40MeV proton beam accelerated into a uranium carbide target coupled to a plasma ion source. The experiments allowed for tests of performance of the SPES multi-foil target prototype loaded with seven UC2/graphite discs (ratio C/ U = 4 with density about 4g/cm3.

Targeted silver nanoparticles for ratiometric cell phenotyping

NASA Astrophysics Data System (ADS)

Willmore, Anne-Mari A.; Simón-Gracia, Lorena; Toome, Kadri; Paiste, Päärn; Kotamraju, Venkata Ramana; Mölder, Tarmo; Sugahara, Kazuki N.; Ruoslahti, Erkki; Braun, Gary B.; Teesalu, Tambet

2016-04-01

Affinity targeting is used to deliver nanoparticles to cells and tissues. For efficient targeting, it is critical to consider the expression and accessibility of the relevant receptors in the target cells. Here, we describe isotopically barcoded silver nanoparticles (AgNPs) as a tool for auditing affinity ligand receptors in cells. Tumor penetrating peptide RPARPAR (receptor: NRP-1) and tumor homing peptide GKRK (receptor: p32) were used as affinity ligands on the AgNPs. The binding and uptake of the peptide-functionalized AgNPs by cultured PPC-1 prostate cancer and M21 melanoma cells was dependent on the cell surface expression of the cognate peptide receptors. Barcoded peptide-functionalized AgNPs were synthesized from silver and palladium isotopes. The cells were incubated with a cocktail of the barcoded nanoparticles [RPARPAR (R), GKRK (K), and control], and cellular binding and internalization of each type of nanoparticle was assessed by inductively coupled plasma mass spectrometry. The results of isotopic analysis were in agreement with data obtained using optical methods. Using ratiometric measurements, we were able to classify the PPC-1 cell line as mainly NRP-1-positive, with 75 +/- 5% R-AgNP uptake, and the M21 cell line as only p32-positive, with 89 +/- 9% K-AgNP uptake. The isotopically barcoded multiplexed AgNPs are useful as an in vitro ratiometric phenotyping tool and have potential uses in functional evaluation of the expression of accessible homing peptide receptors in vivo.Affinity targeting is used to deliver nanoparticles to cells and tissues. For efficient targeting, it is critical to consider the expression and accessibility of the relevant receptors in the target cells. Here, we describe isotopically barcoded silver nanoparticles (AgNPs) as a tool for auditing affinity ligand receptors in cells. Tumor penetrating peptide RPARPAR (receptor: NRP-1) and tumor homing peptide GKRK (receptor: p32) were used as affinity ligands on the AgNPs. The

Advances in targeted genome editing.

PubMed

Perez-Pinera, Pablo; Ousterout, David G; Gersbach, Charles A

2012-08-01

New technologies have recently emerged that enable targeted editing of genomes in diverse systems. This includes precise manipulation of gene sequences in their natural chromosomal context and addition of transgenes to specific genomic loci. This progress has been facilitated by advances in engineering targeted nucleases with programmable, site-specific DNA-binding domains, including zinc finger proteins and transcription activator-like effectors (TALEs). Recent improvements have enhanced nuclease performance, accelerated nuclease assembly, and lowered the cost of genome editing. These advances are driving new approaches to many areas of biotechnology, including biopharmaceutical production, agriculture, creation of transgenic organisms and cell lines, and studies of genome structure, regulation, and function. Genome editing is also being investigated in preclinical and clinical gene therapies for many diseases. Copyright © 2012 Elsevier Ltd. All rights reserved.

Encoder: A Connectionist Model of How Learning to Visually Encode Fixated Text Images Improves Reading Fluency

ERIC Educational Resources Information Center

Martin, Gale L.

2004-01-01

This article proposes that visual encoding learning improves reading fluency by widening the span over which letters are recognized from a fixated text image so that fewer fixations are needed to cover a text line. Encoder is a connectionist model that learns to convert images like the fixated text images human readers encode into the…

Analysis and Modeling of Target Echo and Reverberation: FY15 Annual Report for ONR

DTIC Science & Technology

2015-09-30

particular interest is the target echo, which has not yet received a lot of attention , and for which good data were obtained during the TREX...essentially cut off all paths steeper than the critical angle. The coloured lines lines correspond to the differences between the group velocity formulation

Are On-Line Data Bases in Your Library's Future?

ERIC Educational Resources Information Center

Deacon, Jim

1983-01-01

THE FOLLOWING IS THE FULL TEXT OF THIS DOCUMENT: Today there are over 900 on-line data banks available for public access. Most microcomputers can use them through the aid of a modem and communication program. Major public information utilities that offer access to these on-line data bases are growing and expanding. The Source, a data base utility…

Bringing text display digital radio to consumers with hearing loss.

PubMed

Sheffield, Ellyn G; Starling, Michael; Schwab, Daniel

2011-01-01

Radio is migrating to digital transmission, expanding its offerings to include captioning for individuals with hearing loss. Text display radio requires a large amount of word throughput with minimal screen display area, making good user interface design crucial to its success. In two experiments, we presented hearing, hard-of-hearing, and deaf consumers with National Public Radio stories converted to text and examined their preferences for and reactions to midsized and small radio text displays. We focused on physical display attributes such as text color, font style, line length, and scrolling type as well as emergency alert messages and emergency prompts for drivers, announcer identification schemes, and synchronization of audio and text. Results suggest that midsized, Global Positioning System (GPS)-style displays were well liked, synchronization of audio and text was important to comprehension and retrieval of story details, identification of announcers was served best with a combination of name change in parenthesis and color change, and a mixture of color and flashing symbols was preferred for emergency alerting.

A novel antibody–drug conjugate targeting SAIL for the treatment of hematologic malignancies

PubMed Central

Kim, S Y; Theunissen, J-W; Balibalos, J; Liao-Chan, S; Babcock, M C; Wong, T; Cairns, B; Gonzalez, D; van der Horst, E H; Perez, M; Levashova, Z; Chinn, L; D‘Alessio, J A; Flory, M; Bermudez, A; Jackson, D Y; Ha, E; Monteon, J; Bruhns, M F; Chen, G; Migone, T-S

2015-01-01

Although several new therapeutic approaches have improved outcomes in the treatment of hematologic malignancies, unmet need persists in acute myeloid leukemia (AML), multiple myeloma (MM) and non-Hodgkin's lymphoma. Here we describe the proteomic identification of a novel cancer target, SAIL (Surface Antigen In Leukemia), whose expression is observed in AML, MM, chronic lymphocytic leukemia (CLL), diffuse large B-cell lymphoma (DLBCL) and follicular lymphoma (FL). While SAIL is widely expressed in CLL, AML, MM, DLBCL and FL patient samples, expression in cancer cell lines is mostly limited to cells of AML origin. We evaluated the antitumor activity of anti-SAIL monoclonal antibodies, 7-1C and 67-7A, conjugated to monomethyl auristatin F. Following internalization, anti-SAIL antibody–drug conjugates (ADCs) exhibited subnanomolar IC50 values against AML cell lines in vitro. In pharmacology studies employing AML cell line xenografts, anti-SAIL ADCs resulted in significant tumor growth inhibition. The restricted expression profile of this target in normal tissues, the high prevalence in different types of hematologic cancers and the observed preclinical activity support the clinical development of SAIL-targeted ADCs. PMID:26024286

Biomarkers for immunotherapy in bladder cancer: a moving target.

PubMed

Aggen, David H; Drake, Charles G

2017-11-21

Treatment options for metastatic urothelial carcinoma (mUC) remained relative unchanged over the last 30 years with combination chemotherapy as the mainstay of treatment. Within the last year the landscape for mUC has seismically shifted following the approval of five therapies targeting the programmed cell death protein (PD-1)/programmed cell death ligand 1 (PD-L1) axis. Notably, the anti-PD-1 antibody pembrolizumab demonstrated improved OS relative to chemotherapy in a randomized phase III study for second line treatment of mUC; this level 1 evidence led to approval from the U.S. Food and Drug Administration (FDA). The PD-1 antibody nivolumab also demonstrated an overall survival benefit, in this case in comparison to historical controls. Similarly, antibodies targeting PD-L1 including atezolizumab, durvalumab, and avelumab have now received accelerated approval from the FDA as second line treatments for mUC, with durable response lasting more than 1 year in some patients. Some of these agents are approved in the first line setting as well - based on single-arm phase II studies atezolizumab and pembrolizumab received accelerated approval for first-line treatment of cisplatin ineligible patients. Despite these multiple approvals, the development of clinically useful biomarkers to determine the optimal treatment for patients remains somewhat elusive. In this review, we examine key clinical trial results with anti-PD1/PD-L1 antibodies and discuss progress towards developing novel biomarkers beyond PD-L1 expression.

An after-market, five-port vertical beam line extension for the PETtrace

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

Barnhart, T. E.; Engle, J. W.; Severin, G. W.

2012-12-19

Most commercial cyclotrons intended for medical isotope production provide a limited number of beam ports crowded into a minimal vault space. Taking advantage of our new lab construction, we planned and installed a beam-line on port Music-Sharp-Sign 2 of our GEMS PETtrace to bring beam to an additional 5 target positions. These are oriented in the vertical plane, with the downward directed beam well suited for molten target substrates.

Line Spread as a Visual Clinical Tool for Thickened Liquids

ERIC Educational Resources Information Center

Lund, Annelise Masters; Mertz Garcia, Jane; Chambers, Edgar, IV.

2013-01-01

Purpose: Preparing modified liquids to a target level of consistency is critical to patients' nutritional care. This study examined the relationship of line spread (i.e., the distance a liquid flows) to viscometer measurements for a variety of product/liquid combinations and determined if flow distance visually differentiated nectar-thick…

Enrolling Underserved Women in mHealth Programs: Results From Text4baby Outreach Campaigns.

PubMed

Bushar, Jessica A; Fishman, Jodie; Garfinkel, Danielle; Pirretti, Amy

2018-03-01

Public health practitioners have increasingly leveraged technology-based communication to get health information into the hands of hard-to-reach populations; however, best practices for outreach and enrollment into mobile health (mHealth) programs are lacking. This article describes enrollment results from campaigns focused on enrolling underserved pregnant women and mothers in Text4baby-a free, mHealth service-to inform outreach strategies for mHealth programs. Text4baby participants receive health and safety information, interactive surveys, alerts, and appointment reminders through at least three weekly texts and a free app-timed to users' due date or babies' birth date. Text4baby worked with partners to implement national, state, and community-based enrollment campaigns. Descriptive statistics were used to compare baseline enrollment prior to a campaign with enrollment during a campaign to generate enrollment estimates. Enrollment rates were calculated for campaigns for which the number targeted/reached was available. National television campaigns resulted in more than 10,000 estimated enrollments. Campaigns that were integrated with an existing program and text-based recruitment had the highest enrollment rates, ranging from 7% to 24%. Facebook advertisements and traditional media targeting providers and consumers were least effective. mHealth programs should consider text-based recruitment and outreach via existing programs; additional research is needed on return on investment for different outreach strategies and on the effectiveness of different outreach strategies at reaching and enrolling specific target populations.

Text Messaging Intervention for Teens and Young Adults With Diabetes

PubMed Central

Cousineau, Tara; Franko, Debra L.; Schultz, Alan T.; Trant, Meredith; Rodgers, Rachel; Laffel, Lori M. B.

2014-01-01

Adolescents and young adults use text messaging as their primary mode of communication, thus providing an opportunity to use this mode of communication for mobile health (mHealth) interventions. Youth with diabetes are an important group for these mHealth initiatives, as diabetes management requires an enormous amount of daily effort and this population has difficulty achieving optimal diabetes management. Goal setting and self-efficacy are 2 factors in the management of diabetes. We examined the feasibility of a healthy lifestyle text messaging program targeting self-efficacy and goal setting among adolescents and young adults with diabetes. Participants, ages 16-21, were assigned to either a text messaging group, which received daily motivational messages about nutrition and physical activity, or a control group, which received paper-based information about healthy lifestyle. Both groups set goals for nutrition and physical activity and completed a measure of self-efficacy. Participants’ mean age was 18.7 ± 1.6 years old, with diabetes duration of 10.0 ± 4.6 years, and A1c of 8.7 ± 1.7%. The text messaging intervention was rated highly and proved to be acceptable to participants. Self-efficacy, glycemic control, and body mass index did not change over the course of the short, 1-month pilot study. Positive, daily, motivational text messages may be effective in increasing motivation for small goal changes in the areas of nutrition and physical activity. These interventions may be used in the future in youth with diabetes to improve diabetes care. Utilizing more targeted text messages is an area for future research. PMID:25172879

Text messaging intervention for teens and young adults with diabetes.

PubMed

Markowitz, Jessica T; Cousineau, Tara; Franko, Debra L; Schultz, Alan T; Trant, Meredith; Rodgers, Rachel; Laffel, Lori M B

2014-09-01

Adolescents and young adults use text messaging as their primary mode of communication, thus providing an opportunity to use this mode of communication for mobile health (mHealth) interventions. Youth with diabetes are an important group for these mHealth initiatives, as diabetes management requires an enormous amount of daily effort and this population has difficulty achieving optimal diabetes management. Goal setting and self-efficacy are 2 factors in the management of diabetes. We examined the feasibility of a healthy lifestyle text messaging program targeting self-efficacy and goal setting among adolescents and young adults with diabetes. Participants, ages 16-21, were assigned to either a text messaging group, which received daily motivational messages about nutrition and physical activity, or a control group, which received paper-based information about healthy lifestyle. Both groups set goals for nutrition and physical activity and completed a measure of self-efficacy. Participants' mean age was 18.7 ± 1.6 years old, with diabetes duration of 10.0 ± 4.6 years, and A1c of 8.7 ± 1.7%. The text messaging intervention was rated highly and proved to be acceptable to participants. Self-efficacy, glycemic control, and body mass index did not change over the course of the short, 1-month pilot study. Positive, daily, motivational text messages may be effective in increasing motivation for small goal changes in the areas of nutrition and physical activity. These interventions may be used in the future in youth with diabetes to improve diabetes care. Utilizing more targeted text messages is an area for future research. © 2014 Diabetes Technology Society.

In-line digital holography with phase-shifting Greek-ladder sieves

NASA Astrophysics Data System (ADS)

Xie, Jing; Zhang, Junyong; Zhang, Yanli; Zhou, Shenlei; Zhu, Jianqiang

2018-04-01

Phase shifting is the key technique in in-line digital holography, but traditional phase shifters have their own limitations in short wavelength regions. Here, phase-shifting Greek-ladder sieves with amplitude-only modulation are introduced into in-line digital holography, which are essentially a kind of diffraction lens with three-dimensional array diffraction-limited foci. In the in-line digital holographic experiment, we design two kinds of sieves by lithography and verify the validity of their phase-shifting function by measuring a 1951 U.S. Air Force resolution test target and three-dimensional array foci. With advantages of high resolving power, low cost, and no limitations at shorter wavelengths, phase-shifting Greek-ladder sieves have great potential in X-ray holography or biochemical microscopy for the next generation of synchrotron light sources.

Transgenic mouse lines for non-invasive ratiometric monitoring of intracellular chloride

PubMed Central

Batti, Laura; Mukhtarov, Marat; Audero, Enrica; Ivanov, Anton; Paolicelli, Rosa Chiara; Zurborg, Sandra; Gross, Cornelius; Bregestovski, Piotr; Heppenstall, Paul A.

2013-01-01

Chloride is the most abundant physiological anion and participates in a variety of cellular processes including trans-epithelial transport, cell volume regulation, and regulation of electrical excitability. The development of tools to monitor intracellular chloride concentration ([Cli]) is therefore important for the evaluation of cellular function in normal and pathological conditions. Recently, several Cl-sensitive genetically encoded probes have been described which allow for non-invasive monitoring of [Cli]. Here we describe two mouse lines expressing a CFP-YFP-based Cl probe called Cl-Sensor. First, we generated transgenic mice expressing Cl-Sensor under the control of the mouse Thy1 mini promoter. Cl-Sensor exhibited good expression from postnatal day two (P2) in neurons of the hippocampus and cortex, and its level increased strongly during development. Using simultaneous whole-cell monitoring of ionic currents and Cl-dependent fluorescence, we determined that the apparent EC50 for Cli was 46 mM, indicating that this line is appropriate for measuring neuronal [Cli] in postnatal mice. We also describe a transgenic mouse reporter line for Cre-dependent conditional expression of Cl-Sensor, which was targeted to the Rosa26 locus and by incorporating a strong exogenous promoter induced robust expression upon Cre-mediated recombination. We demonstrate high levels of tissue-specific expression in two different Cre-driver lines targeting cells of the myeloid lineage and peripheral sensory neurons. Using these mice the apparent EC50 for Cli was estimated to be 61 and 54 mM in macrophages and DRG, respectively. Our data suggest that these mouse lines will be useful models for ratiometric monitoring of Cli in specific cell types in vivo. PMID:23734096

Metastatic melanoma: results of 'classical' second-line treatment with cytotoxic chemotherapies.

PubMed

Perrin, Christophe; Pracht, Marc; Talour, Karen; Adamski, Henri; Cumin, Isabelle; Porneuf, Marc; Talarmin, Marie; Mesbah, Habiba; Audrain, Odile; Moignet, Aline; Lefeuvre-Plesse, Claudia; Lesimple, Thierry

2014-10-01

Metastatic melanoma is one of the most aggressive tumours, with a median survival that does not exceed 12 months. None of the cytotoxic first-line therapies have shown survival benefit in randomised clinical trials. To describe clinical benefit of second-line cytotoxic chemotherapy in the second line of treatment for metastatic melanoma. In a retrospective study, we analyse the outcome of patients with metastatic melanoma who had received two lines or more of cytotoxic treatments in four French dermato-oncology departments between 1999 and 2009. We describe the outcomes for 109 patients. Most of these patients received dacarbazine for the first line of chemotherapy and fotemustine for the second line of chemotherapy (67.0 and 64.2%, respectively). A clinical benefit was observed in 24.1% of the patients and overall survival was 4.1 months after the second-line treatment. At least 23.8% of patients suffered from grade 3 or 4 toxicities. The presence of more than two sites of metastasis and an M1c staging according to the AJCC classification represented negative predictive factors of clinical benefit. This study shows the modest benefit of a second line of cytotoxic chemotherapy in a nonselected population. If eligible, these patients should be proposed for ongoing clinical trials or for targeted therapies.

Alleviating line overload by line switching

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

Brown, H.E.

1988-01-01

Traditionally, the method used by power system dispatchers to reduce or to eliminate line overload conditions has been to shift generation. Such shifts are generally in conflict with the carefully considered economic dispatch of generation. A proper generation schedule has taken into account many factors, such as generator limits, transmission penalties, incremental costs, var support, and system security. Any deviation from this schedule results in increased production cost. Recently, consideration has been given to alleviating line overloads by line switching. In many situations, line switching does not greatly change the transmission penalty factors and, therefore, can be undertaken without seriouslymore » affecting the economic dispatch. It would be convenient for system operators to have a fast, easy-to-operate computer and program available for the evaluation of the efficacy of a line removal (or addition) in dealing with an overload. It is imperative that the operator be properly advised, that a certain line switching reduces the overload and not aggravate the condition. After it has been determined that a line opening (or closing) produces the desired effect, the operator still must assess the consequence of such switching on system security before actually taking such action.« less

Identification and Characterization of a Suite of Tumor Targeting Peptides for Non-Small Cell Lung Cancer

NASA Astrophysics Data System (ADS)

McGuire, Michael J.; Gray, Bethany Powell; Li, Shunzi; Cupka, Dorothy; Byers, Lauren Averett; Wu, Lei; Rezaie, Shaghayegh; Liu, Ying-Horng; Pattisapu, Naveen; Issac, James; Oyama, Tsukasa; Diao, Lixia; Heymach, John V.; Xie, Xian-Jin; Minna, John D.; Brown, Kathlynn C.

2014-03-01

Tumor targeting ligands are emerging components in cancer therapies. Widespread use of targeted therapies and molecular imaging is dependent on increasing the number of high affinity, tumor-specific ligands. Towards this goal, we biopanned three phage-displayed peptide libraries on a series of well-defined human non-small cell lung cancer (NSCLC) cell lines, isolating 11 novel peptides. The peptides show distinct binding profiles across 40 NSCLC cell lines and do not bind normal bronchial epithelial cell lines. Binding of specific peptides correlates with onco-genotypes and activation of particular pathways, such as EGFR signaling, suggesting the peptides may serve as surrogate markers. Multimerization of the peptides results in cell binding affinities between 0.0071-40 nM. The peptides home to tumors in vivo and bind to patient tumor samples. This is the first comprehensive biopanning for isolation of high affinity peptidic ligands for a single cancer type and expands the diversity of NSCLC targeting ligands.

Identification and Characterization of a Suite of Tumor Targeting Peptides for Non-Small Cell Lung Cancer

PubMed Central

McGuire, Michael J.; Gray, Bethany Powell; Li, Shunzi; Cupka, Dorothy; Byers, Lauren Averett; Wu, Lei; Rezaie, Shaghayegh; Liu, Ying-Horng; Pattisapu, Naveen; Issac, James; Oyama, Tsukasa; Diao, Lixia; Heymach, John V.; Xie, Xian-Jin; Minna, John D.; Brown, Kathlynn C.

2014-01-01

Tumor targeting ligands are emerging components in cancer therapies. Widespread use of targeted therapies and molecular imaging is dependent on increasing the number of high affinity, tumor-specific ligands. Towards this goal, we biopanned three phage-displayed peptide libraries on a series of well-defined human non-small cell lung cancer (NSCLC) cell lines, isolating 11 novel peptides. The peptides show distinct binding profiles across 40 NSCLC cell lines and do not bind normal bronchial epithelial cell lines. Binding of specific peptides correlates with onco-genotypes and activation of particular pathways, such as EGFR signaling, suggesting the peptides may serve as surrogate markers. Multimerization of the peptides results in cell binding affinities between 0.0071–40 nM. The peptides home to tumors in vivo and bind to patient tumor samples. This is the first comprehensive biopanning for isolation of high affinity peptidic ligands for a single cancer type and expands the diversity of NSCLC targeting ligands. PMID:24670678

HER2 activating mutations are targets for colorectal cancer treatment.

PubMed

Kavuri, Shyam M; Jain, Naveen; Galimi, Francesco; Cottino, Francesca; Leto, Simonetta M; Migliardi, Giorgia; Searleman, Adam C; Shen, Wei; Monsey, John; Trusolino, Livio; Jacobs, Samuel A; Bertotti, Andrea; Bose, Ron

2015-08-01

The Cancer Genome Atlas project identified HER2 somatic mutations and gene amplification in 7% of patients with colorectal cancer. Introduction of the HER2 mutations S310F, L755S, V777L, V842I, and L866M into colon epithelial cells increased signaling pathways and anchorage-independent cell growth, indicating that they are activating mutations. Introduction of these HER2 activating mutations into colorectal cancer cell lines produced resistance to cetuximab and panitumumab by sustaining MAPK phosphorylation. HER2 mutants are potently inhibited by low nanomolar doses of the irreversible tyrosine kinase inhibitors neratinib and afatinib. HER2 gene sequencing of 48 cetuximab-resistant, quadruple (KRAS, NRAS, BRAF, and PIK3CA) wild-type (WT) colorectal cancer patient-derived xenografts (PDX) identified 4 PDXs with HER2 mutations. HER2-targeted therapies were tested on two PDXs. Treatment with a single HER2-targeted drug (trastuzumab, neratinib, or lapatinib) delayed tumor growth, but dual HER2-targeted therapy with trastuzumab plus tyrosine kinase inhibitors produced regression of these HER2-mutated PDXs. HER2 activating mutations cause EGFR antibody resistance in colorectal cell lines, and PDXs with HER2 mutations show durable tumor regression when treated with dual HER2-targeted therapy. These data provide a strong preclinical rationale for clinical trials targeting HER2 activating mutations in metastatic colorectal cancer. ©2015 American Association for Cancer Research.

Gender differences in psychosocial predictors of texting while driving.

PubMed

Struckman-Johnson, Cindy; Gaster, Samuel; Struckman-Johnson, Dave; Johnson, Melissa; May-Shinagle, Gabby

2015-01-01

A sample of 158 male and 357 female college students at a midwestern university participated in an on-line study of psychosocial motives for texting while driving. Men and women did not differ in self-reported ratings of how often they texted while driving. However, more women sent texts of less than a sentence while more men sent texts of 1-5 sentences. More women than men said they would quit texting while driving due to police warnings, receiving information about texting dangers, being shown graphic pictures of texting accidents, and being in a car accident. A hierarchical regression for men's data revealed that lower levels of feeling distracted by texting while driving (20% of the variance), higher levels of cell phone dependence (11.5% of the variance), risky behavioral tendencies (6.5% of the variance) and impulsivity (2.3%) of the variance) were significantly associated with more texting while driving (total model variance=42%). A separate regression for women revealed that higher levels of cell phone dependence (10.4% of the variance), risky behavioral tendencies (9.9% of the variance), texting distractibility (6.2%), crash risk estimates (2.2% of the variance) and driving confidence (1.3% of the variance) were significantly associated with more texting while driving (total model variance=31%.) Friendship potential and need for intimacy were not related to men's or women's texting while driving. Implications of the results for gender-specific prevention strategies are discussed. Copyright © 2014 Elsevier Ltd. All rights reserved.

Scene text detection by leveraging multi-channel information and local context

NASA Astrophysics Data System (ADS)

Wang, Runmin; Qian, Shengyou; Yang, Jianfeng; Gao, Changxin

2018-03-01

As an important information carrier, texts play significant roles in many applications. However, text detection in unconstrained scenes is a challenging problem due to cluttered backgrounds, various appearances, uneven illumination, etc.. In this paper, an approach based on multi-channel information and local context is proposed to detect texts in natural scenes. According to character candidate detection plays a vital role in text detection system, Maximally Stable Extremal Regions(MSERs) and Graph-cut based method are integrated to obtain the character candidates by leveraging the multi-channel image information. A cascaded false positive elimination mechanism are constructed from the perspective of the character and the text line respectively. Since the local context information is very valuable for us, these information is utilized to retrieve the missing characters for boosting the text detection performance. Experimental results on two benchmark datasets, i.e., the ICDAR 2011 dataset and the ICDAR 2013 dataset, demonstrate that the proposed method have achieved the state-of-the-art performance.

Text and Structural Data Mining of Influenza Mentions in Web and Social Media

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

Corley, Courtney D.; Cook, Diane; Mikler, Armin R.

Text and structural data mining of Web and social media (WSM) provides a novel disease surveillance resource and can identify online communities for targeted public health communications (PHC) to assure wide dissemination of pertinent information. WSM that mention influenza are harvested over a 24-week period, 5-October-2008 to 21-March-2009. Link analysis reveals communities for targeted PHC. Text mining is shown to identify trends in flu posts that correlate to real-world influenza-like-illness patient report data. We also bring to bear a graph-based data mining technique to detect anomalies among flu blogs connected by publisher type, links, and user-tags.

Lexicality, morphological structure, and semantic transparency in the processing of German ver-verbs: The complementarity of on-line and off-line evidence.

PubMed

Schirmeier, Matthias K; Derwing, Bruce L; Libben, Gary

2004-01-01

Two types of experiments investigate the visual on-line and off-line processing of German ver-verbs (e.g., verbittern 'to embitter'). In Experiments 1 and 2 (morphological priming), latency patterns revealed the existence of facilitation effects for the morphological conditions (BITTER-VERBITTERN and BITTERN-VERBITTERN) as compared to the neutral conditions (SAUBER-VERBITTERN and SAUBERN-VERBITTERN). In Experiments 3 and 4 (rating tasks) participants had to judge whether the target (VERBITTERN) "comes from," "contains a form of," or "contains the meaning of" the root (BITTER) or the root+en substring (BITTERN). Taken together, these studies revealed the combined influence of the three factors of lexicality (real word status), morphological structure, and semantic transparency.

RNAi phenotype profiling of kinases identifies potential therapeutic targets in Ewing's sarcoma.

PubMed

Arora, Shilpi; Gonzales, Irma M; Hagelstrom, R Tanner; Beaudry, Christian; Choudhary, Ashish; Sima, Chao; Tibes, Raoul; Mousses, Spyro; Azorsa, David O

2010-08-18

Ewing's sarcomas are aggressive musculoskeletal tumors occurring most frequently in the long and flat bones as a solitary lesion mostly during the teen-age years of life. With current treatments, significant number of patients relapse and survival is poor for those with metastatic disease. As part of novel target discovery in Ewing's sarcoma, we applied RNAi mediated phenotypic profiling to identify kinase targets involved in growth and survival of Ewing's sarcoma cells. Four Ewing's sarcoma cell lines TC-32, TC-71, SK-ES-1 and RD-ES were tested in high throughput-RNAi screens using a siRNA library targeting 572 kinases. Knockdown of 25 siRNAs reduced the growth of all four Ewing's sarcoma cell lines in replicate screens. Of these, 16 siRNA were specific and reduced proliferation of Ewing's sarcoma cells as compared to normal fibroblasts. Secondary validation and preliminary mechanistic studies highlighted the kinases STK10 and TNK2 as having important roles in growth and survival of Ewing's sarcoma cells. Furthermore, knockdown of STK10 and TNK2 by siRNA showed increased apoptosis. In summary, RNAi-based phenotypic profiling proved to be a powerful gene target discovery strategy, leading to successful identification and validation of STK10 and TNK2 as two novel potential therapeutic targets for Ewing's sarcoma.

Bypassing Protein Corona Issue on Active Targeting: Zwitterionic Coatings Dictate Specific Interactions of Targeting Moieties and Cell Receptors.

PubMed

Safavi-Sohi, Reihaneh; Maghari, Shokoofeh; Raoufi, Mohammad; Jalali, Seyed Amir; Hajipour, Mohammad J; Ghassempour, Alireza; Mahmoudi, Morteza

2016-09-07

Surface functionalization strategies for targeting nanoparticles (NP) to specific organs, cells, or organelles, is the foundation for new applications of nanomedicine to drug delivery and biomedical imaging. Interaction of NPs with biological media leads to the formation of a biomolecular layer at the surface of NPs so-called as "protein corona". This corona layer can shield active molecules at the surface of NPs and cause mistargeting or unintended scavenging by the liver, kidney, or spleen. To overcome this corona issue, we have designed biotin-cysteine conjugated silica NPs (biotin was employed as a targeting molecule and cysteine was used as a zwitterionic ligand) to inhibit corona-induced mistargeting and thus significantly enhance the active targeting capability of NPs in complex biological media. To probe the targeting yield of our engineered NPs, we employed both modified silicon wafer substrates with streptavidin (i.e., biotin receptor) to simulate a target and a cell-based model platform using tumor cell lines that overexpress biotin receptors. In both cases, after incubation with human plasma (thus forming a protein corona), cellular uptake/substrate attachment of the targeted NPs with zwitterionic coatings were significantly higher than the same NPs without zwitterionic coating. Our results demonstrated that NPs with a zwitterionic surface can considerably facilitate targeting yield of NPs and provide a promising new type of nanocarriers in biological applications.

Target materials for exotic ISOL beams

NASA Astrophysics Data System (ADS)

Gottberg, A.

2016-06-01

The demand for intensity, purity, reliability and availability of short-lived isotopes far from stability is steadily high, and considerably exceeding the supply. In many cases the ISOL (Isotope Separation On-Line) method can provide beams of high intensity and purity. Limitations in terms of accessible chemical species and minimum half-life are driven mainly by chemical reactions and physical processes inside of the thick target. A wide range of materials are in use, ranging from thin metallic foils and liquids to refractory ceramics, while poly-phasic mixed uranium carbides have become the reference target material for most ISOL facilities world-wide. Target material research and development is often complex and especially important post-irradiation analyses are hindered by the high intrinsic radiotoxicity of these materials. However, recent achievements have proven that these investigations are possible if the effort of different facilities is combined, leading to the development of new material matrices that can supply new beams of unprecedented intensity and beam current stability.

A hand and a field effect in on-line motor control in unilateral optic ataxia.

PubMed

Blangero, Annabelle; Gaveau, Valérie; Luauté, Jacques; Rode, Gilles; Salemme, Romeo; Guinard, Marine; Boisson, Dominique; Rossetti, Yves; Pisella, Laure

2008-05-01

Patients with bilateral optic ataxia fail to show rapid perturbation-induced corrections during manual aiming movements. Based on this, it has been proposed that this pathology results from a disruption of processes of on-line motor control in the posterior parietal cortex (PPC). Here, we show that on-line motor control performance in a patient with unilateral optic ataxia is similar to that of pointing towards stationary targets in peripheral vision, showing the same combination of hand and field effects. We also show that in the patient, manual correction towards his ataxic field was possible only when a preceding saccade (100msec earlier) rapidly provides foveal information about the new target location. In control subjects, manual correction was often, but not necessarily preceded by a saccade. These results allow us to put forward a model of visuo-manual transformation, which involves updating of the reach plan based on the target-eye error, and rely upon two dissociated spatial representations (of the hand and of the target, respectively) within the PPC.

On-Line and Off-Line Assessment of Metacognition

ERIC Educational Resources Information Center

Saraç, Seda; Karakelle, Sema

2012-01-01

The study investigates the interrelationships between different on-line and off-line measures for assessing metacognition. The participants were 47 fifth grade elementary students. Metacognition was assessed through two off-line and two on-line measures. The off-line measures consisted of a teacher rating scale and a self-report questionnaire. The…

Runwien: a text-based interface for the WIEN package

NASA Astrophysics Data System (ADS)

Otero de la Roza, A.; Luaña, Víctor

2009-05-01

A new text-based interface for WIEN2k, the full-potential linearized augmented plane-waves (FPLAPW) program, is presented. This code provides an easy to use, yet powerful way of generating arbitrarily large sets of calculations. Thus, properties over a potential energy surface and WIEN2k parameter exploration can be calculated using a simple input text file. This interface also provides new capabilities to the WIEN2k package, such as the calculation of elastic constants on hexagonal systems or the automatic gathering of relevant information. Additionally, runwien is modular, flexible and intuitive. Program summaryProgram title: runwien Catalogue identifier: AECM_v1_0 Program summary URL:http://cpc.cs.qub.ac.uk/summaries/AECM_v1_0.html Program obtainable from: CPC Program Library, Queen's University, Belfast, N. Ireland Licensing provisions: GPL version 3 No. of lines in distributed program, including test data, etc.: 62 567 No. of bytes in distributed program, including test data, etc.: 610 973 Distribution format: tar.gz Programming language: gawk (with locale POSIX or similar) Computer: All running Unix, Linux Operating system: Unix, GNU/Linux Classification: 7.3 External routines: WIEN2k ( http://www.wien2k.at/), GAWK ( http://www.gnu.org/software/gawk/), rename by L. Wall, a Perl script which renames files, modified by R. Barker to check for the existence of target files, gnuplot ( http://www.gnuplot.info/) Subprograms used:Cat Id: ADSY_v1_0/AECB_v1_0, Title: GIBBS/CRITIC, Reference: CPC 158 (2004) 57/CPC 999 (2009) 999 Nature of problem: Creation of a text-based, batch-oriented interface for the WIEN2k package. Solution method: WIEN2k solves the Kohn-Sham equations of a solid using the FPLAPW formalism. Runwien interprets an input file containing the description of the geometry and structure of the solid and drives the execution of the WIEN2k programs. The input is simplified thanks to the default values of the WIEN2k parameters known to runwien. Additional

Potentiation by Tumor Necrosis Factor of Mitoxantrone Cytotoxicity to Human Ovarian Cancer Cell Lines

PubMed Central

Parodi, Silvio; Billi, Giovanna; Oliva, Cristina; Venturing, Marco; Noviello, Elvira; Conte, PierFranco

1992-01-01

The cytotoxic activity of human recombinant tumor necrosis factor (rHuTNF) (from 0.01 to 10000 U/ml) was assayed on six human ovarian cancer cell lines and one human cervical carcinoma cell line using a crystal violet assay. rHuTNF was cytotoxic to four cell lines (A2780, A2774, SW626, PAD, while 3 cell lines (IGROV1, SKOV3, Mel80) were marginally sensitive to its activity. However, under the same experimental conditions rHuTNF markedly enhanced the cytotoxicity of mitoxantrone, a chemotherapeutic drug targeted at DNA topoisomerase II, in six cell lines. The potentiation of mitoxantrone cytotoxicity was not caused by increased drug accumulation after rHuTNF treatment. No significant increase in cytotoxicity to Me180 cell line was seen when rHuTNF was added to mitoxantrone. PMID:1517145

Image-based mobile service: automatic text extraction and translation

NASA Astrophysics Data System (ADS)

Berclaz, Jérôme; Bhatti, Nina; Simske, Steven J.; Schettino, John C.

2010-01-01

We present a new mobile service for the translation of text from images taken by consumer-grade cell-phone cameras. Such capability represents a new paradigm for users where a simple image provides the basis for a service. The ubiquity and ease of use of cell-phone cameras enables acquisition and transmission of images anywhere and at any time a user wishes, delivering rapid and accurate translation over the phone's MMS and SMS facilities. Target text is extracted completely automatically, requiring no bounding box delineation or related user intervention. The service uses localization, binarization, text deskewing, and optical character recognition (OCR) in its analysis. Once the text is translated, an SMS message is sent to the user with the result. Further novelties include that no software installation is required on the handset, any service provider or camera phone can be used, and the entire service is implemented on the server side.

Feasibility of on-line temperature-based hyperthermia treatment planning to improve tumour temperatures during locoregional hyperthermia.

PubMed

Kok, H P; Korshuize-van Straten, L; Bakker, A; de Kroon-Oldenhof, R; Westerveld, G H; Versteijne, E; Stalpers, L J A; Crezee, J

2017-11-16

The effectiveness of hyperthermia is strongly dependent on the achieved tumour temperatures. Phased-array systems allow flexible power steering to realise good tumour heating while avoiding excessive heating in normal tissue, but the limited quantitative accuracy of pre-treatment planning complicates realising optimal tumour heating. On-line hyperthermia treatment planning could help to improve the heating quality. This paper demonstrates the feasibility of using on-line temperature-based treatment planning to improve the heating quality during hyperthermia in three patients. Hyperthermia treatment planning was performed using the Plan2Heat software package combined with a dedicated graphical user interface for on-line application. Electric fields were pre-calculated to allow instant update and visualisation of the predicted temperature distribution for user-selected phase-amplitude settings during treatment. On-line treatment planning using manual variation of system settings for the AMC-8 hyperthermia system was applied in one patient with a deep-seated pelvic melanoma metastasis and two cervical cancer patients. For a clinically relevant improvement the increase in average target temperature should be at least 0.2 °C. With the assistance of on-line treatment planning a substantial improvement in tumour temperatures was realised for all three patients. In the melanoma patient, the average measured target temperature increased from 38.30 °C to 39.15 °C (i.e. +0.85 °C). In the cervical cancer patients, the average measured target temperature increased from 41.30 °C to 42.05 °C (i.e. +0.75 °C) and from 41.70 °C to 42.80 °C (i.e. +1.1 °C), respectively. On-line temperature-based treatment planning is clinically feasible to improve tumour temperatures. A next, worthwhile step is automatic optimisation for a larger number of patients.

Lattice design and beam dynamics studies of the high energy beam transport line in the RAON heavy ion accelerator

NASA Astrophysics Data System (ADS)

Jin, Hyunchang; Jang, Ji-Ho; Jang, Hyojae; Jeon, Dong-O.

2015-12-01

In RAON heavy ion accelerator, beams generated by superconducting electron cyclotron resonance ion source (ECR-IS) or Isotope Separation On-Line (ISOL) system are accelerated by lower energy superconducting linac and high energy superconducting linac. The accelerated beams are used in the high energy experimental hall which includes bio-medical and muon-SR facilities, after passing through the high energy beam transport lines. At the targets of those two facilities, the stable and small beams meeting the requirements rigorously are required in the transverse plane. Therefore the beams must be safely sent to the targets and simultaneously satisfy the two requirements, the achromatic condition and the mid-plane symmetric condition, of the targets. For this reason, the lattice design of the high energy beam transport lines in which the long deflecting sections are included is considered as a significant issue in the RAON accelerator. In this paper, we will describe the calculated beam optics satisfying the conditions and present the result of particle tracking simulations with the designed lattice of the high energy beam transport lines in the RAON accelerator. Also, the orbit distortion caused by the machine imperfections and the orbit correction with correctors will be discussed.

Systems for Teaching Complex Texts: A Proof-of-Concept Investigation

ERIC Educational Resources Information Center

Fisher, Douglas; Frey, Nancy

2016-01-01

In this article we investigate the systems that need to be in place for students to learn from increasingly complex texts. Our concept, drawn from past research, includes clear learning targets, teacher modeling, collaborative conversations, close reading, small group reading, and wide reading. Using a "proof of concept" model, we follow…

Evolving phage vectors for cell targeted gene delivery.

PubMed

Larocca, David; Burg, Michael A; Jensen-Pergakes, Kristen; Ravey, Edward Prenn; Gonzalez, Ana Maria; Baird, Andrew

2002-03-01

We adapted filamentous phage vectors for targeted gene delivery to mammalian cells by inserting a mammalian reporter gene expression cassette (GFP) into the vector backbone and fusing the pIII coat protein to a cell targeting ligand (i.e. FGF2, EGF). Like transfection with animal viral vectors, targeted phage gene delivery is concentration, time, and ligand dependent. Importantly, targeted phage particles are specific for the appropriate target cell surface receptor. Phage have distinct advantages over existing gene therapy vectors because they are simple, economical to produce at high titer, have no intrinsic tropism for mammalian cells, and are relatively simple to genetically modify and evolve. Initially transduction by targeted phage particles was low resulting in foreign gene expression in 1-2% of transfected cells. We increased transduction efficiency by modifying both the transfection protocol and vector design. For example, we stabilized the display of the targeting ligand to create multivalent phagemid-based vectors with transduction efficiencies of up to 45% in certain cell lines when combined with genotoxic treatment. Taken together, these studies establish that the efficiency of phage-mediated gene transfer can be significantly improved through genetic modification. We are currently evolving phage vectors with enhanced cell targeting, increased stability, reduced immunogenicity and other properties suitable for gene therapy.

Antihyperlipidemic therapies targeting PCSK9.

PubMed

Weinreich, Michael; Frishman, William H

2014-01-01

Hyperlipidemia is a major cause of cardiovascular disease despite the availability of first-line cholesterol-lowering agents such as statins. A new therapeutic approach to lowering low-density lipoprotein-cholesterol (LDL-C) acts by blocking LDL-receptor degradation by serum proprotein convertase subtilisin kexin 9 (PCSK9). Human monoclonal antibodies that target PCSK9 and its interaction with the LDL receptor are now in clinical trials (REGN727/SAR23653, AMG145, and RN316). These agents are administered by either subcutaneous or intravenous routes, and have been shown to have major LDL-C and apolipoprotein B effects when combined with statins. A phase III clinical trial program evaluating clinical endpoints is now in progress. Other PCSK9-targeted approaches are in early stages of investigation, including natural inhibitors of PCSK9, RNA interference, and antisense inhibitors.

Targeting neuropilin-1 in human leukemia and lymphoma.

PubMed

Karjalainen, Katja; Jaalouk, Diana E; Bueso-Ramos, Carlos E; Zurita, Amado J; Kuniyasu, Akihiko; Eckhardt, Bedrich L; Marini, Frank C; Lichtiger, Benjamin; O'Brien, Susan; Kantarjian, Hagop M; Cortes, Jorge E; Koivunen, Erkki; Arap, Wadih; Pasqualini, Renata

2011-01-20

Targeted drug delivery offers an opportunity for the development of safer and more effective therapies for the treatment of cancer. In this study, we sought to identify short, cell-internalizing peptide ligands that could serve as directive agents for specific drug delivery in hematologic malignancies. By screening of human leukemia cells with a combinatorial phage display peptide library, we isolated a peptide motif, sequence Phe-Phe/Tyr-Any-Leu-Arg-Ser (F(F)/(Y)XLRS), which bound to different leukemia cell lines and to patient-derived bone marrow samples. The motif was internalized through a receptor-mediated pathway, and we next identified the corresponding receptor as the transmembrane glycoprotein neuropilin-1 (NRP-1). Moreover, we observed a potent anti-leukemia cell effect when the targeting motif was synthesized in tandem to the pro-apoptotic sequence (D)(KLAKLAK)₂. Finally, our results confirmed increased expression of NRP-1 in representative human leukemia and lymphoma cell lines and in a panel of bone marrow specimens obtained from patients with acute lymphoblastic leukemia or acute myelogenous leukemia compared with normal bone marrow. These results indicate that NRP-1 could potentially be used as a target for ligand-directed therapy in human leukemias and lymphomas and that the prototype CGFYWLRSC-GG-(D)(KLAKLAK)₂ is a promising drug candidate in this setting.

The insect ecdysone receptor is a good potential target for RNAi-based pest control.

PubMed

Yu, Rong; Xu, Xinping; Liang, Yongkang; Tian, Honggang; Pan, Zhanqing; Jin, Shouheng; Wang, Na; Zhang, Wenqing

2014-01-01

RNA interference (RNAi) has great potential for use in insect pest control. However, some significant challenges must be overcome before RNAi-based pest control can become a reality. One challenge is the proper selection of a good target gene for RNAi. Here, we report that the insect ecdysone receptor (EcR) is a good potential target for RNAi-based pest control in the brown planthopper Nilaparvata lugens, a serious insect pest of rice plants. We demonstrated that the use of a 360 bp fragment (NlEcR-c) that is common between NlEcR-A and NlEcR-B for feeding RNAi experiments significantly decreased the relative mRNA expression levels of NlEcR compared with those in the dsGFP control. Feeding RNAi also resulted in a significant reduction in the number of offspring per pair of N. lugens. Consequently, a transgenic rice line expressing NlEcR dsRNA was constructed by Agrobacterium- mediated transformation. The results of qRT-PCR showed that the total copy number of the target gene in all transgenic rice lines was 2. Northern blot analysis showed that the small RNA of the hairpin dsNlEcR-c was successfully expressed in the transgenic rice lines. After newly hatched nymphs of N. lugens fed on the transgenic rice lines, effective RNAi was observed. The NlEcR expression levels in all lines examined were decreased significantly compared with the control. In all lines, the survival rate of the nymphs was nearly 90%, and the average number of offspring per pair in the treated groups was significantly less than that observed in the control, with a decrease of 44.18-66.27%. These findings support an RNAi-based pest control strategy and are also important for the management of rice insect pests.

Measurement of prompt and nonprompt [Formula: see text] production in [Formula: see text] and [Formula: see text] collisions at [Formula: see text].

PubMed

Sirunyan, A M; Tumasyan, A; Adam, W; Asilar, E; Bergauer, T; Brandstetter, J; Brondolin, E; Dragicevic, M; Erö, J; Flechl, M; Friedl, M; Frühwirth, R; Ghete, V M; Hartl, C; Hörmann, N; Hrubec, J; Jeitler, M; König, A; Krätschmer, I; Liko, D; Matsushita, T; Mikulec, I; Rabady, D; Rad, N; Rahbaran, B; Rohringer, H; Schieck, J; Strauss, J; Waltenberger, W; Wulz, C-E; Dvornikov, O; Makarenko, V; Mossolov, V; Suarez Gonzalez, J; Zykunov, V; Shumeiko, N; Alderweireldt, S; De Wolf, E A; Janssen, X; Lauwers, J; Van De Klundert, M; Van Haevermaet, H; Van Mechelen, P; Van Remortel, N; Van Spilbeeck, A; Abu Zeid, S; Blekman, F; D'Hondt, J; Daci, N; De Bruyn, I; Deroover, K; Lowette, S; Moortgat, S; Moreels, L; Olbrechts, A; Python, Q; Skovpen, K; Tavernier, S; Van Doninck, W; Van Mulders, P; Van Parijs, I; Brun, H; Clerbaux, B; De Lentdecker, G; Delannoy, H; Fasanella, G; Favart, L; Goldouzian, R; Grebenyuk, A; Karapostoli, G; Lenzi, T; Léonard, A; Luetic, J; Maerschalk, T; Marinov, A; Randle-Conde, A; Seva, T; Vander Velde, C; Vanlaer, P; Vannerom, D; Yonamine, R; Zenoni, F; Zhang, F; Cimmino, A; Cornelis, T; Dobur, D; Fagot, A; Gul, M; Khvastunov, I; Poyraz, D; Salva, S; Schöfbeck, R; Tytgat, M; Van Driessche, W; Yazgan, E; Zaganidis, N; Bakhshiansohi, H; Beluffi, C; Bondu, O; Brochet, S; Bruno, G; Caudron, A; De Visscher, S; Delaere, C; Delcourt, M; Francois, B; Giammanco, A; Jafari, A; Komm, M; Krintiras, G; Lemaitre, V; Magitteri, A; Mertens, A; Musich, M; Piotrzkowski, K; Quertenmont, L; Selvaggi, M; Vidal Marono, M; Wertz, S; Beliy, N; Aldá Júnior, W L; Alves, F L; Alves, G A; Brito, L; Hensel, C; Moraes, A; Pol, M E; Rebello Teles, P; Belchior Batista Das Chagas, E; Carvalho, W; Chinellato, J; Custódio, A; Da Costa, E M; Da Silveira, G G; De Jesus Damiao, D; De Oliveira Martins, C; Fonseca De Souza, S; Huertas Guativa, L M; Malbouisson, H; Matos Figueiredo, D; Mora Herrera, C; Mundim, L; Nogima, H; Prado Da Silva, W L; Santoro, A; Sznajder, A; Tonelli Manganote, E J; Torres Da Silva De Araujo, F; Vilela Pereira, A; Ahuja, S; Bernardes, C A; Dogra, S; Fernandez Perez Tomei, T R; Gregores, E M; Mercadante, P G; Moon, C S; Novaes, S F; Padula, Sandra S; Romero Abad, D; Ruiz Vargas, J C; Aleksandrov, A; Hadjiiska, R; Iaydjiev, P; Rodozov, M; Stoykova, S; Sultanov, G; Vutova, M; Dimitrov, A; Glushkov, I; Litov, L; Pavlov, B; Petkov, P; Fang, W; Ahmad, M; Bian, J G; Chen, G M; Chen, H S; Chen, M; Chen, Y; Cheng, T; Jiang, C H; Leggat, D; Liu, Z; Romeo, F; Ruan, M; Shaheen, S M; Spiezia, A; Tao, J; Wang, C; Wang, Z; Zhang, H; Zhao, J; Ban, Y; Chen, G; Li, Q; Liu, S; Mao, Y; Qian, S J; Wang, D; Xu, Z; Avila, C; Cabrera, A; Chaparro Sierra, L F; Florez, C; Gomez, J P; González Hernández, C F; Ruiz Alvarez, J D; Sanabria, J C; Godinovic, N; Lelas, D; Puljak, I; Ribeiro Cipriano, P M; Sculac, T; Antunovic, Z; Kovac, M; Brigljevic, V; Ferencek, D; Kadija, K; Mesic, B; Susa, T; Attikis, A; Mavromanolakis, G; Mousa, J; Nicolaou, C; Ptochos, F; Razis, P A; Rykaczewski, H; Tsiakkouri, D; Finger, M; 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Sorokin, P; Aggleton, R; Ball, F; Beck, L; Brooke, J J; Burns, D; Clement, E; Cussans, D; Flacher, H; Goldstein, J; Grimes, M; Heath, G P; Heath, H F; Jacob, J; Kreczko, L; Lucas, C; Newbold, D M; Paramesvaran, S; Poll, A; Sakuma, T; Seif El Nasr-Storey, S; Smith, D; Smith, V J; Belyaev, A; Brew, C; Brown, R M; Calligaris, L; Cieri, D; Cockerill, D J A; Coughlan, J A; Harder, K; Harper, S; Olaiya, E; Petyt, D; Shepherd-Themistocleous, C H; Thea, A; Tomalin, I R; Williams, T; Baber, M; Bainbridge, R; Buchmuller, O; Bundock, A; Burton, D; Casasso, S; Citron, M; Colling, D; Corpe, L; Dauncey, P; Davies, G; De Wit, A; Della Negra, M; Di Maria, R; Dunne, P; Elwood, A; Futyan, D; Haddad, Y; Hall, G; Iles, G; James, T; Lane, R; Laner, C; Lucas, R; Lyons, L; Magnan, A-M; Malik, S; Mastrolorenzo, L; Nash, J; Nikitenko, A; Pela, J; Penning, B; Pesaresi, M; Raymond, D M; Richards, A; Rose, A; Scott, E; Seez, C; Summers, S; Tapper, A; Uchida, K; Vazquez Acosta, M; Virdee, T; Wright, J; Zenz, S C; Cole, J E; Hobson, P R; Khan, A; Kyberd, P; Reid, I D; Symonds, P; Teodorescu, L; Turner, M; Borzou, A; Call, K; Dittmann, J; Hatakeyama, K; Liu, H; Pastika, N; Bartek, R; Dominguez, A; Buccilli, A; Cooper, S I; Henderson, C; Rumerio, P; West, C; Arcaro, D; Avetisyan, A; Bose, T; Gastler, D; Rankin, D; Richardson, C; Rohlf, J; Sulak, L; Zou, D; Benelli, G; Cutts, D; Garabedian, A; Hakala, J; Heintz, U; Hogan, J M; Jesus, O; Kwok, K H M; Laird, E; Landsberg, G; Mao, Z; Narain, M; Piperov, S; Sagir, S; Spencer, E; Syarif, R; Breedon, R; Burns, D; Calderon De La Barca Sanchez, M; Chauhan, S; Chertok, M; Conway, J; Conway, R; Cox, P T; Erbacher, R; Flores, C; Funk, G; Gardner, M; Ko, W; Lander, R; Mclean, C; Mulhearn, M; Pellett, D; Pilot, J; Shalhout, S; Shi, M; Smith, J; Squires, M; Stolp, D; Tos, K; Tripathi, M; Bachtis, M; Bravo, C; Cousins, R; Dasgupta, A; Florent, A; Hauser, J; Ignatenko, M; Mccoll, N; Saltzberg, D; Schnaible, C; Valuev, V; Weber, M; Bouvier, E; Burt, K; Clare, R; Ellison, J; Gary, J W; Ghiasi Shirazi, S M A; Hanson, G; Heilman, J; Jandir, P; Kennedy, E; Lacroix, F; Long, O R; Olmedo Negrete, M; Paneva, M I; Shrinivas, A; Si, W; Wei, H; Wimpenny, S; Yates, B R; Branson, J G; Cerati, G B; Cittolin, S; Derdzinski, M; Gerosa, R; Holzner, A; Klein, D; Krutelyov, V; Letts, J; Macneill, I; Olivito, D; Padhi, S; Pieri, M; Sani, M; Sharma, V; Simon, S; Tadel, M; Vartak, A; Wasserbaech, S; Welke, C; Wood, J; Würthwein, F; Yagil, A; Zevi Della Porta, G; Amin, N; Bhandari, R; Bradmiller-Feld, J; Campagnari, C; Dishaw, A; Dutta, V; Franco Sevilla, M; George, C; Golf, F; Gouskos, L; Gran, J; Heller, R; Incandela, J; Mullin, S D; Ovcharova, A; Qu, H; Richman, J; Stuart, D; Suarez, I; Yoo, J; Anderson, D; Bendavid, J; Bornheim, A; Bunn, J; Duarte, J; Lawhorn, J M; Mott, A; Newman, H B; Pena, C; Spiropulu, M; Vlimant, J R; Xie, S; Zhu, R Y; Andrews, M B; Ferguson, T; Paulini, M; Russ, J; Sun, M; Vogel, H; Vorobiev, I; Weinberg, M; Cumalat, J P; Ford, W T; Jensen, F; Johnson, A; Krohn, M; Leontsinis, S; Mulholland, T; Stenson, K; Wagner, S R; Alexander, J; Chaves, J; Chu, J; Dittmer, S; Mcdermott, K; Mirman, N; Nicolas Kaufman, G; Patterson, J R; Rinkevicius, A; Ryd, A; Skinnari, L; Soffi, L; Tan, S M; Tao, Z; Thom, J; Tucker, J; Wittich, P; Zientek, M; Winn, D; Abdullin, S; Albrow, M; Apollinari, G; Apresyan, A; Banerjee, S; Bauerdick, L A T; Beretvas, A; Berryhill, J; Bhat, P C; Bolla, G; Burkett, K; Butler, J N; Cheung, H W K; Chlebana, F; Cihangir, S; Cremonesi, M; Elvira, V D; Fisk, I; Freeman, J; Gottschalk, E; Gray, L; Green, D; Grünendahl, S; Gutsche, O; Hare, D; Harris, R M; Hasegawa, S; Hirschauer, J; Hu, Z; Jayatilaka, B; Jindariani, S; Johnson, M; Joshi, U; Klima, B; Kreis, B; Lammel, S; Linacre, J; Lincoln, D; Lipton, R; Liu, M; Liu, T; Lopes De Sá, R; Lykken, J; Maeshima, K; Magini, N; Marraffino, J M; Maruyama, S; Mason, D; McBride, P; Merkel, P; Mrenna, S; Nahn, S; O'Dell, V; Pedro, K; Prokofyev, O; Rakness, G; Ristori, L; Sexton-Kennedy, E; Soha, A; Spalding, W J; Spiegel, L; Stoynev, S; Strait, J; Strobbe, N; Taylor, L; Tkaczyk, S; Tran, N V; Uplegger, L; Vaandering, E W; Vernieri, C; Verzocchi, M; Vidal, R; Wang, M; Weber, H A; Whitbeck, A; Wu, Y; Acosta, D; Avery, P; Bortignon, P; Bourilkov, D; Brinkerhoff, A; Carnes, A; Carver, M; Curry, D; Das, S; Field, R D; Furic, I K; Konigsberg, J; Korytov, A; Low, J F; Ma, P; Matchev, K; Mei, H; Mitselmakher, G; Rank, D; Shchutska, L; Sperka, D; Thomas, L; Wang, J; Wang, S; Yelton, J; Linn, S; Markowitz, P; Martinez, G; Rodriguez, J L; Ackert, A; Adams, T; Askew, A; Bein, S; Hagopian, S; Hagopian, V; Johnson, K F; Prosper, H; Santra, A; Yohay, R; Baarmand, M M; Bhopatkar, V; Colafranceschi, S; Hohlmann, M; Noonan, D; Roy, T; Yumiceva, F; Adams, M R; Apanasevich, L; Berry, D; Betts, R R; Bucinskaite, I; Cavanaugh, R; Evdokimov, O; Gauthier, L; Gerber, C E; Hofman, D J; Jung, K; Sandoval Gonzalez, I D; Varelas, N; Wang, H; Wu, Z; Zakaria, M; Zhang, J; Bilki, B; Clarida, W; Dilsiz, K; Durgut, S; Gandrajula, R P; Haytmyradov, M; Khristenko, V; Merlo, J-P; Mermerkaya, H; Mestvirishvili, A; Moeller, A; Nachtman, J; Ogul, H; Onel, Y; Ozok, F; Penzo, A; Snyder, C; Tiras, E; Wetzel, J; Yi, K; Anderson, I; Blumenfeld, B; Cocoros, A; Eminizer, N; Fehling, D; Feng, L; Gritsan, A V; Maksimovic, P; Roskes, J; Sarica, U; Swartz, M; Xiao, M; Xin, Y; You, C; Al-Bataineh, A; Baringer, P; Bean, A; Boren, S; Bowen, J; Castle, J; Forthomme, L; Kenny, R P; Khalil, S; Kropivnitskaya, A; Majumder, D; Mcbrayer, W; Murray, M; Sanders, S; Stringer, R; Tapia Takaki, J D; Wang, Q; Ivanov, A; Kaadze, K; Maravin, Y; Mohammadi, A; Saini, L K; Skhirtladze, N; Toda, S; Rebassoo, F; Wright, D; Anelli, C; Baden, A; Baron, O; Belloni, A; Calvert, B; Eno, S C; Ferraioli, C; Gomez, J A; Hadley, N J; Jabeen, S; Jeng, G Y; Kellogg, R G; Kolberg, T; Kunkle, J; Mignerey, A C; Ricci-Tam, F; Shin, Y H; Skuja, A; Tonjes, M B; Tonwar, S C; Abercrombie, D; Allen, B; Apyan, A; Azzolini, V; Barbieri, R; Baty, A; Bi, R; Bierwagen, K; Brandt, S; Busza, W; Cali, I A; D'Alfonso, M; Demiragli, Z; Di Matteo, L; Gomez Ceballos, G; Goncharov, M; Hsu, D; Iiyama, Y; Innocenti, G M; Klute, M; Kovalskyi, D; Krajczar, K; Lai, Y S; Lee, Y-J; Levin, A; Luckey, P D; Maier, B; Marini, A C; Mcginn, C; Mironov, C; Narayanan, S; Niu, X; Paus, C; Roland, C; Roland, G; Salfeld-Nebgen, J; Stephans, G S F; Tatar, K; Varma, M; Velicanu, D; Veverka, J; Wang, J; Wang, T W; Wyslouch, B; Yang, M; Benvenuti, A C; Chatterjee, R M; Evans, A; Hansen, P; Kalafut, S; Kao, S C; Kubota, Y; Lesko, Z; Mans, J; Nourbakhsh, S; Ruckstuhl, N; Rusack, R; Tambe, N; Turkewitz, J; Acosta, J G; Oliveros, S; Avdeeva, E; Bloom, K; Claes, D R; Fangmeier, C; Gonzalez Suarez, R; Kamalieddin, R; Kravchenko, I; Malta Rodrigues, A; Monroy, J; Siado, J E; Snow, G R; Stieger, B; Alyari, M; Dolen, J; Godshalk, A; Harrington, C; Iashvili, I; Kaisen, J; Nguyen, D; Parker, A; Rappoccio, S; Roozbahani, B; Alverson, G; Barberis, E; Hortiangtham, A; Massironi, A; Morse, D M; Nash, D; Orimoto, T; Teixeira De Lima, R; Trocino, D; Wang, R-J; Wood, D; Bhattacharya, S; Charaf, O; Hahn, K A; Kumar, A; Mucia, N; Odell, N; Pollack, B; Schmitt, M H; Sung, K; Trovato, M; Velasco, M; Dev, N; Hildreth, M; Hurtado Anampa, K; Jessop, C; Karmgard, D J; Kellams, N; Lannon, K; Marinelli, N; Meng, F; Mueller, C; Musienko, Y; Planer, M; Reinsvold, A; Ruchti, R; Rupprecht, N; Smith, G; Taroni, S; Wayne, M; Wolf, M; Woodard, A; Alimena, J; Antonelli, L; Bylsma, B; Durkin, L S; Flowers, S; Francis, B; Hart, A; Hill, C; Hughes, R; Ji, W; Liu, B; Luo, W; Puigh, D; Winer, B L; Wulsin, H W; Cooperstein, S; Driga, O; Elmer, P; Hardenbrook, J; Hebda, P; Lange, D; Luo, J; Marlow, D; Medvedeva, T; Mei, K; Ojalvo, I; Olsen, J; Palmer, C; Piroué, P; Stickland, D; Svyatkovskiy, A; Tully, C; Malik, S; Barker, A; Barnes, V E; Folgueras, S; Gutay, L; Jha, M K; Jones, M; Jung, A W; Khatiwada, A; Miller, D H; Neumeister, N; Schulte, J F; Shi, X; Sun, J; Wang, F; Xie, W; Parashar, N; Stupak, J; Adair, A; Akgun, B; Chen, Z; Ecklund, K M; Geurts, F J M; Guilbaud, M; Li, W; Michlin, B; Northup, M; Padley, B P; Roberts, J; Rorie, J; Tu, Z; Zabel, J; Betchart, B; Bodek, A; de Barbaro, P; Demina, R; Duh, Y T; Ferbel, T; Galanti, M; Garcia-Bellido, A; Han, J; Hindrichs, O; Khukhunaishvili, A; Lo, K H; Tan, P; Verzetti, M; Agapitos, A; Chou, J P; Gershtein, Y; Gómez Espinosa, T A; Halkiadakis, E; Heindl, M; Hughes, E; Kaplan, S; Kunnawalkam Elayavalli, R; Kyriacou, S; Lath, A; Nash, K; Osherson, M; Saka, H; Salur, S; Schnetzer, S; Sheffield, D; Somalwar, S; Stone, R; Thomas, S; Thomassen, P; Walker, M; Delannoy, A G; Foerster, M; Heideman, J; Riley, G; Rose, K; Spanier, S; Thapa, K; Bouhali, O; Celik, A; Dalchenko, M; De Mattia, M; Delgado, A; Dildick, S; Eusebi, R; Gilmore, J; Huang, T; Juska, E; Kamon, T; Mueller, R; Pakhotin, Y; Patel, R; Perloff, A; Perniè, L; Rathjens, D; Safonov, A; Tatarinov, A; Ulmer, K A; Akchurin, N; Cowden, C; Damgov, J; De Guio, F; Dragoiu, C; Dudero, P R; Faulkner, J; Gurpinar, E; Kunori, S; Lamichhane, K; Lee, S W; Libeiro, T; Peltola, T; Undleeb, S; Volobouev, I; Wang, Z; Greene, S; Gurrola, A; Janjam, R; Johns, W; Maguire, C; Melo, A; Ni, H; Sheldon, P; Tuo, S; Velkovska, J; Xu, Q; Arenton, M W; Barria, P; Cox, B; Goodell, J; Hirosky, R; Ledovskoy, A; Li, H; Neu, C; Sinthuprasith, T; Sun, X; Wang, Y; Wolfe, E; Xia, F; Clarke, C; Harr, R; Karchin, P E; Sturdy, J; Belknap, D A; Buchanan, J; Caillol, C; Dasu, S; Dodd, L; Duric, S; Gomber, B; Grothe, M; Herndon, M; Hervé, A; Klabbers, P; Lanaro, A; Levine, A; Long, K; Loveless, R; Perry, T; Pierro, G A; Polese, G; Ruggles, T; Savin, A; Smith, N; Smith, W H; Taylor, D; Woods, N

2017-01-01

This paper reports the measurement of [Formula: see text] meson production in proton-proton ([Formula: see text]) and proton-lead ([Formula: see text]) collisions at a center-of-mass energy per nucleon pair of [Formula: see text] by the CMS experiment at the LHC. The data samples used in the analysis correspond to integrated luminosities of 28[Formula: see text] and 35[Formula: see text] for [Formula: see text] and [Formula: see text] collisions, respectively. Prompt and nonprompt [Formula: see text] mesons, the latter produced in the decay of [Formula: see text] hadrons, are measured in their dimuon decay channels. Differential cross sections are measured in the transverse momentum range of [Formula: see text], and center-of-mass rapidity ranges of [Formula: see text] ([Formula: see text]) and [Formula: see text] ([Formula: see text]). The nuclear modification factor, [Formula: see text], is measured as a function of both [Formula: see text] and [Formula: see text]. Small modifications to the [Formula: see text] cross sections are observed in [Formula: see text] relative to [Formula: see text] collisions. The ratio of [Formula: see text] production cross sections in [Formula: see text]-going and Pb-going directions, [Formula: see text], studied as functions of [Formula: see text] and [Formula: see text], shows a significant decrease for increasing transverse energy deposited at large pseudorapidities. These results, which cover a wide kinematic range, provide new insight on the role of cold nuclear matter effects on prompt and nonprompt [Formula: see text] production.

Identification of an "Exceptional Responder" Cell Line to MEK1 Inhibition: Clinical Implications for MEK-Targeted Therapy | Office of Cancer Genomics

Cancer.gov

The identification of somatic genetic alterations that confer sensitivity to pharmacologic inhibitors has led to new cancer therapies. To identify mutations that confer an exceptional dependency, shRNA-based loss-of-function data were analyzed from a dataset of numerous cell lines to reveal genes that are essential in a small subset of cancer cell lines. Once these cell lines were determined, detailed genomic characterization from these cell lines was utilized to ascertain the genomic aberrations that led to this extreme dependency.

Uncovering Small RNA-Mediated Responses to Cold Stress in a Wheat Thermosensitive Genic Male-Sterile Line by Deep Sequencing1[W][OA

PubMed Central

Tang, Zhonghui; Zhang, Liping; Xu, Chenguang; Yuan, Shaohua; Zhang, Fengting; Zheng, Yonglian; Zhao, Changping

2012-01-01

The male sterility of thermosensitive genic male sterile (TGMS) lines of wheat (Triticum aestivum) is strictly controlled by temperature. The early phase of anther development is especially susceptible to cold stress. MicroRNAs (miRNAs) play an important role in plant development and in responses to environmental stress. In this study, deep sequencing of small RNA (smRNA) libraries obtained from spike tissues of the TGMS line under cold and control conditions identified a total of 78 unique miRNA sequences from 30 families and trans-acting small interfering RNAs (tasiRNAs) derived from two TAS3 genes. To identify smRNA targets in the wheat TGMS line, we applied the degradome sequencing method, which globally and directly identifies the remnants of smRNA-directed target cleavage. We identified 26 targets of 16 miRNA families and three targets of tasiRNAs. Comparing smRNA sequencing data sets and TaqMan quantitative polymerase chain reaction results, we identified six miRNAs and one tasiRNA (tasiRNA-ARF [for Auxin-Responsive Factor]) as cold stress-responsive smRNAs in spike tissues of the TGMS line. We also determined the expression profiles of target genes that encode transcription factors in response to cold stress. Interestingly, the expression of cold stress-responsive smRNAs integrated in the auxin-signaling pathway and their target genes was largely noncorrelated. We investigated the tissue-specific expression of smRNAs using a tissue microarray approach. Our data indicated that miR167 and tasiRNA-ARF play roles in regulating the auxin-signaling pathway and possibly in the developmental response to cold stress. These data provide evidence that smRNA regulatory pathways are linked with male sterility in the TGMS line during cold stress. PMID:22508932

Integrated mechanism for the generation of the 5' junctions of LINE inserts.

PubMed

Yamaguchi, Katsumi; Kajikawa, Masaki; Okada, Norihiro

2014-12-01

To elucidate the molecular mechanism of the integration of long interspersed elements (LINEs), we characterized the 5' ends of more than 200 LINE de novo retrotransposition events into chicken DT40 or human HeLa cells. Human L1 inserts produced 15-bp target-site duplications (TSDs) and zebrafish ZfL2-1 inserts produced 5-bp TSDs in DT40 cells, suggesting that TSD length depends on the LINE species. Further analysis of 5' junctions revealed that the 5'-end-joining pathways of LINEs can be divided into two fundamental types-annealing or direct. We also found that the generation of 5' inversions depends on host and LINE species. These results led us to propose a new model for 5'-end joining, the type of which is determined by the extent of exposure of 3' overhangs generated after the second-strand cleavage and by the involvement of host factors. © The Author(s) 2014. Published by Oxford University Press on behalf of Nucleic Acids Research.

Heart failure—potential new targets for therapy

PubMed Central

Nabeebaccus, Adam; Zheng, Sean; Shah, Ajay M.

2016-01-01

Abstract Introduction/background Heart failure is a major cause of cardiovascular morbidity and mortality. This review covers current heart failure treatment guidelines, emerging therapies that are undergoing clinical trial, and potential new therapeutic targets arising from basic science advances. Sources of data A non-systematic search of MEDLINE was carried out. International guidelines and relevant reviews were searched for additional articles. Areas of agreement Angiotensin-converting enzyme inhibitors and beta-blockers are first line treatments for chronic heart failure with reduced left ventricular function. Areas of controversy Treatment strategies to improve mortality in heart failure with preserved left ventricular function are unclear. Growing points Many novel therapies are being tested for clinical efficacy in heart failure, including those that target natriuretic peptides and myosin activators. A large number of completely novel targets are also emerging from laboratory-based research. Better understanding of pathophysiological mechanisms driving heart failure in different settings (e.g. hypertension, post-myocardial infarction, metabolic dysfunction) may allow for targeted therapies. Areas timely for developing research Therapeutic targets directed towards modifying the extracellular environment, angiogenesis, cell viability, contractile function and microRNA-based therapies. PMID:27365454

Beam line shielding calculations for an Electron Accelerator Mo-99 production facility

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

Mocko, Michal

2016-05-03

The purpose of this study is to evaluate the photon and neutron fields in and around the latest beam line design for the Mo-99 production facility. The radiation dose to the beam line components (quadrupoles, dipoles, beam stops and the linear accelerator) are calculated in the present report. The beam line design assumes placement of two cameras: infra red (IR) and optical transition radiation (OTR) for continuous monitoring of the beam spot on target during irradiation. The cameras will be placed off the beam axis offset in vertical direction. We explored typical shielding arrangements for the cameras and report themore » resulting neutron and photon dose fields.« less

Text Extraction from Scene Images by Character Appearance and Structure Modeling

PubMed Central

Yi, Chucai; Tian, Yingli

2012-01-01

In this paper, we propose a novel algorithm to detect text information from natural scene images. Scene text classification and detection are still open research topics. Our proposed algorithm is able to model both character appearance and structure to generate representative and discriminative text descriptors. The contributions of this paper include three aspects: 1) a new character appearance model by a structure correlation algorithm which extracts discriminative appearance features from detected interest points of character samples; 2) a new text descriptor based on structons and correlatons, which model character structure by structure differences among character samples and structure component co-occurrence; and 3) a new text region localization method by combining color decomposition, character contour refinement, and string line alignment to localize character candidates and refine detected text regions. We perform three groups of experiments to evaluate the effectiveness of our proposed algorithm, including text classification, text detection, and character identification. The evaluation results on benchmark datasets demonstrate that our algorithm achieves the state-of-the-art performance on scene text classification and detection, and significantly outperforms the existing algorithms for character identification. PMID:23316111

Implications of high-/low-context communication for target audience member interpretation of messages in the Nimechill abstinence campaign in Nairobi, Kenya.

PubMed

Muraya, Julie Gathoni; Neville Miller, Ann; Mjomba, Leonard

2011-09-01

Although it ran on multiple mass media for the better part of a year, end line evaluation of the Nimechill youth abstinence campaign in Kenya indicated that exposure to the campaign had no relationship to youth decisions to defer sexual debut. One possible explanation of this lack of association could be that target audience members derived inconsistent and confusing meanings from visuals as opposed to text in the campaign. Employing Hall's concept of high- and low-context communication, we assessed target population interpretation of four campaign posters via 12 focus-group discussions and four individual in-depth interviews with Nairobi youth. We found that although participants endorsed and recognized campaign objectives, contextual cues in some campaign visuals were interpreted by participants as being contradictory to the abstinence message in the poster texts. In addition noticeable differences arose between the low-income and middle-/high-income groups in interpretation of one of the posters. We conclude with recommendations regarding use of visuals in high-context cultures and involvement of youth from various socioeconomic strata in campaign planning.

Moving target feature phenomenology data collection at China Lake

NASA Astrophysics Data System (ADS)

Gross, David C.; Hill, Jeff; Schmitz, James L.

2002-08-01

This paper describes the DARPA Moving Target Feature Phenomenology (MTFP) data collection conducted at the China Lake Naval Weapons Center's Junction Ranch in July 2001. The collection featured both X-band and Ku-band radars positioned on top of Junction Ranch's Parrot Peak. The test included seven targets used in eleven configurations with vehicle motion consisting of circular, straight-line, and 90-degree turning motion. Data was collected at 10-degree and 17-degree depression angles. Key parameters in the collection were polarization, vehicle speed, and road roughness. The collection also included a canonical target positioned at Junction Ranch's tilt-deck turntable. The canonical target included rotating wheels (military truck tire and civilian pick-up truck tire) and a flat plate with variable positioned corner reflectors. The canonical target was also used to simulate a rotating antenna and a vibrating plate. The target vehicles were instrumented with ARDS pods for differential GPS and roll, pitch and yaw measurements. Target motion was also documented using a video camera slaved to the X-band radar antenna and by a video camera operated near the target site.

External calibration of polarimetric radar images using distributed targets

NASA Technical Reports Server (NTRS)

Yueh, Simon H.; Nghiem, S. V.; Kwok, R.

1992-01-01

A new technique is presented for calibrating polarimetric synthetic aperture radar (SAR) images using only the responses from natural distributed targets. The model for polarimetric radars is assumed to be X = cRST where X is the measured scattering matrix corresponding to the target scattering matrix S distorted by the system matrices T and R (in general T does not equal R(sup t)). To allow for the polarimetric calibration using only distributed targets and corner reflectors, van Zyl assumed a reciprocal polarimetric radar model with T = R(sup t); when applied for JPL SAR data, a heuristic symmetrization procedure is used by POLCAL to compensate the phase difference between the measured HV and VH responses and then take the average of both. This heuristic approach causes some non-removable cross-polarization responses for corner reflectors, which can be avoided by a rigorous symmetrization method based on reciprocity. After the radar is made reciprocal, a new algorithm based on the responses from distributed targets with reflection symmetry is developed to estimate the cross-talk parameters. The new algorithm never experiences problems in convergence and is also found to converge faster than the existing routines implemented for POLCAL. When the new technique is implemented for the JPL polarimetric data, symmetrization and cross-talk removal are performed on a line-by-line (azimuth) basis. After the cross-talks are removed from the entire image, phase and amplitude calibrations are carried out by selecting distributed targets either with azimuthal symmetry along the looking direction or with some well-known volume and surface scattering mechanisms to estimate the relative phases and amplitude responses of the horizontal and vertical channels.

Genome-wide analyses of LINE–LINE-mediated nonallelic homologous recombination

PubMed Central

Startek, Michał; Szafranski, Przemyslaw; Gambin, Tomasz; Campbell, Ian M.; Hixson, Patricia; Shaw, Chad A.; Stankiewicz, Paweł; Gambin, Anna

2015-01-01

Nonallelic homologous recombination (NAHR), occurring between low-copy repeats (LCRs) >10 kb in size and sharing >97% DNA sequence identity, is responsible for the majority of recurrent genomic rearrangements in the human genome. Recent studies have shown that transposable elements (TEs) can also mediate recurrent deletions and translocations, indicating the features of substrates that mediate NAHR may be significantly less stringent than previously believed. Using >4 kb length and >95% sequence identity criteria, we analyzed of the genome-wide distribution of long interspersed element (LINE) retrotransposon and their potential to mediate NAHR. We identified 17 005 directly oriented LINE pairs located <10 Mbp from each other as potential NAHR substrates, placing 82.8% of the human genome at risk of LINE–LINE-mediated instability. Cross-referencing these regions with CNVs in the Baylor College of Medicine clinical chromosomal microarray database of 36 285 patients, we identified 516 CNVs potentially mediated by LINEs. Using long-range PCR of five different genomic regions in a total of 44 patients, we confirmed that the CNV breakpoints in each patient map within the LINE elements. To additionally assess the scale of LINE–LINE/NAHR phenomenon in the human genome, we tested DNA samples from six healthy individuals on a custom aCGH microarray targeting LINE elements predicted to mediate CNVs and identified 25 LINE–LINE rearrangements. Our data indicate that LINE–LINE-mediated NAHR is widespread and under-recognized, and is an important mechanism of structural rearrangement contributing to human genomic variability. PMID:25613453

Targeted Segment Transfer from Rye Chromosome 2R to Wheat Chromosomes 2A, 2B, and 7B.

PubMed

Ren, Tianheng; Li, Zhi; Yan, Benju; Tan, Feiquan; Tang, Zongxiang; Fu, Shulan; Yang, Manyu; Ren, Zhenglong

2017-01-01

Increased chromosome instability was induced by a rye (Secale cereale L.) monosomic 2R chromosome into wheat (Triticum aestivum L.). Centromere breakage and telomere dysfunction result in high rates of chromosome aberrations, including breakages, fissions, fusions, deletions, and translocations. Plants with target traits were sequentially selected to produce a breeding population, from which 3 translocation lines with target traits have been selected. In these lines, wheat chromosomes 2A, 2B, and 7B recombined with segments of the rye chromosome arm 2RL. This was detected by FISH analysis using repeat sequences pSc119.2, pAs1 and genomic DNA of rye together as probes. The translocation chromosomes in these lines were named as 2ASMR, 2BSMR, and 7BSMR. The small segments that were transferred into wheat consisted of pSc119.2 repeats and other chromatin regions that conferred resistance to stripe rust and expressed target traits. These translocation lines were highly resistant to stripe rust, and expressed several typical traits that were associated with chromosome arm 2RL, which are better than those of its wheat parent, disomic addition, and substitution lines that show agronomic characteristics. The integration of molecular methods and conventional techniques to improve wheat breeding schemes are discussed. © 2017 S. Karger AG, Basel.

Amblyopic deficits in detecting a dotted line in noise.

PubMed

Mussap, A J; Levi, D M

2000-01-01

We compared detectability of a dotted line masked by random-dot noise for the amblyopic versus non-amblyopic eye of two strabismic amblyopes. Small but consistent deficits in the amblyopic eye of these observers were found, and shown to be limited to dotted-line targets composed of greater than seven dots (with performance being normal for targets of less than seven dots). These deficits were unrelated to impaired visual acuity, impaired sensitivity to dot density, and differential positional uncertainty between the eyes of our observers. The deficits were also unlikely to be due to CSF losses due to abnormal low-spatial-frequency filters involved in detecting long chains of collinear dots. Instead, the results of simulations indicate that the inefficiency in utilising large numbers of dots is due to deficits of global, integrative processes in strabismic amblyopes. These simulations also show that while neither undersampling nor positional uncertainty of inputs into integrative processes can themselves account for the amblyopic deficits, if such abnormal inputs lead to the development of stunted integrative processes then impaired sensitivity to long chains of collinear dots is indeed predicted.

Target identification using Zernike moments and neural networks

NASA Astrophysics Data System (ADS)

Azimi-Sadjadi, Mahmood R.; Jamshidi, Arta A.; Nevis, Andrew J.

2001-10-01

The development of an underwater target identification algorithm capable of identifying various types of underwater targets, such as mines, under different environmental conditions pose many technical problems. Some of the contributing factors are: targets have diverse sizes, shapes and reflectivity properties. Target emplacement environment is variable; targets may be proud or partially buried. Environmental properties vary significantly from one location to another. Bottom features such as sand, rocks, corals, and vegetation can conceal a target whether it is partially buried or proud. Competing clutter with responses that closely resemble those of the targets may lead to false positives. All the problems mentioned above contribute to overly difficult and challenging conditions that could lead to unreliable algorithm performance with existing methods. In this paper, we developed and tested a shape-dependent feature extraction scheme that provides features invariant to rotation, size scaling and translation; properties that are extremely useful for any target classification problem. The developed schemes were tested on an electro-optical imagery data set collected under different environmental conditions with variable background, range and target types. The electro-optic data set was collected using a Laser Line Scan (LLS) sensor by the Coastal Systems Station (CSS), located in Panama City, Florida. The performance of the developed scheme and its robustness to distortion, rotation, scaling and translation was also studied.

Effects of curcumin on stem-like cells in human esophageal squamous carcinoma cell lines.

PubMed

Almanaa, Taghreed N; Geusz, Michael E; Jamasbi, Roudabeh J

2012-10-24

Many cancers contain cell subpopulations that display characteristics of stem cells. Because these cancer stem cells (CSCs) appear to provide resistance to chemo-radiation therapy, development of therapeutic agents that target CSCs is essential. Curcumin is a phytochemical agent that is currently used in clinical trials to test its effectiveness against cancer. However, the effect of curcumin on CSCs is not well established. The current study evaluated curcumin-induced cell death in six cancer cell lines derived from human esophageal squamous cell carcinomas. Moreover, these cell lines and the ones established from cells that survived curcumin treatments were characterized. Cell loss was assayed after TE-1, TE-8, KY-5, KY-10, YES-1, and YES-2 cells were exposed to 20-80 μM curcumin for 30 hrs. Cell lines surviving 40 or 60 μM curcumin were established from these six original lines. The stem cell markers aldehyde dehydrogenase-1A1 (ALDH1A1) and CD44 as well as NF-κB were used to compare CSC-like subpopulations within and among the original lines as well as the curcumin-surviving lines. YES-2 was tested for tumorsphere-forming capabilities. Finally, the surviving lines were treated with 40 and 60 μM curcumin to determine whether their sensitivity was different from the original lines. The cell loss after curcumin treatment increased in a dose-dependent manner in all cell lines. The percentage of cells remaining after 60 μM curcumin treatment varied from 10.9% to 36.3% across the six lines. The cell lines were heterogeneous with respect to ALDH1A1, NF-κB and CD44 expression. KY-5 and YES-1 were the least sensitive and had the highest number of stem-like cells whereas TE-1 had the lowest. The curcumin-surviving lines showed a significant loss in the high staining ALDH1A1 and CD44 cell populations. Tumorspheres formed from YES-2 but were small and rare in the YES-2 surviving line. The curcumin-surviving lines showed a small but significant decrease in sensitivity

Application of text mining in the biomedical domain.

PubMed

Fleuren, Wilco W M; Alkema, Wynand

2015-03-01

In recent years the amount of experimental data that is produced in biomedical research and the number of papers that are being published in this field have grown rapidly. In order to keep up to date with developments in their field of interest and to interpret the outcome of experiments in light of all available literature, researchers turn more and more to the use of automated literature mining. As a consequence, text mining tools have evolved considerably in number and quality and nowadays can be used to address a variety of research questions ranging from de novo drug target discovery to enhanced biological interpretation of the results from high throughput experiments. In this paper we introduce the most important techniques that are used for a text mining and give an overview of the text mining tools that are currently being used and the type of problems they are typically applied for. Copyright © 2015 Elsevier Inc. All rights reserved.

Disrupting the male germ line to find infertility and contraception targets.

PubMed

Archambeault, Denise R; Matzuk, Martin M

2014-05-01

Genetically-manipulated mouse models have become indispensible for broadening our understanding of genes and pathways related to male germ cell development. Until suitable in vitro systems for studying spermatogenesis are perfected, in vivo models will remain the gold standard for inquiry into testicular function. Here, we discuss exciting advances that are allowing researchers faster, easier, and more customizable access to their mouse models of interest. Specifically, the trans-NIH Knockout Mouse Project (KOMP) is working to generate knockout mouse models of every gene in the mouse genome. The related Knockout Mouse Phenotyping Program (KOMP2) is performing systematic phenotypic analysis of this genome-wide collection of knockout mice, including fertility screening. Together, these programs will not only uncover new genes involved in male germ cell development but also provide the research community with the mouse models necessary for further investigations. In addition to KOMP/KOMP2, another promising development in the field of mouse models is the advent of CRISPR (clustered regularly interspaced short palindromic repeat)-Cas technology. Utilizing 20 nucleotide guide sequences, CRISPR/Cas has the potential to introduce sequence-specific insertions, deletions, and point mutations to produce null, conditional, activated, or reporter-tagged alleles. CRISPR/Cas can also successfully target multiple genes in a single experimental step, forgoing the multiple generations of breeding traditionally required to produce mouse models with deletions, insertions, or mutations in multiple genes. In addition, CRISPR/Cas can be used to create mouse models carrying variants identical to those identified in infertile human patients, providing the opportunity to explore the effects of such mutations in an in vivo system. Both the KOMP/KOMP2 projects and the CRISPR/Cas system provide powerful, accessible genetic approaches to the study of male germ cell development in the mouse. A

Dividing the Concentrator Target From the Genesis Mission

NASA Technical Reports Server (NTRS)

Lauer, H. V., Jr.; Burkett, P. J.; Clemett, S. J.; Gonzales, C. P.; Nakamura-Messenger, K.; Rodriquez, M. C.; See, T. H.; Sutter, B.

2014-01-01

the risk of losing or breaking the precious requested sample fragment. The Genesis curator determined that the use of laser scribing techniques to "cut" a precise line and subsequently cleave the sample (in a controlled break of the sample along that line) was the best method for accomplishing the sample subdivision. However, there were risks, including excess heating of the sample, that could cause some of the implanted solar wind to be lost via thermal diffusion. Accidentally breaking the sample during the handling and cleaving process was an additional risk. Early in fiscal year 2013, to address this delicate, complicated task, the ARES Directorate assembled its top scientists to develop a cutting plan that would ensure success when applied to the actual concentrator target wafer; i.e., to produce an approximately 1 cm(sup 2) piece from the requested area of the wafer. The team, subsequently referred to as the JSC Genesis Tiger Team, spent months researching and testing parameters and techniques related to scribing, cleaving, transporting, handling, and holding (i.e., mounting) the specimen. The investigation required considerable "thinking outside the box," and many, many trials using nonflight wafer analogs. After all preliminary testing, the following method was adopted as the final cutting plan. It was used in two final end-to-end practice runs before being used on the actual flight target wafer. The wafer was oriented on the laser cutting stage with the 100 and 010 directions of the wafer parallel to the corresponding X and Y directions of the cutting stage. The laser was programed to scribe 31 lines of the appropriate length along the Y stage direction. The programed scribe lines were separated by 5 micron in the X direction. The laser parameters were set as follows: (1) The laser power was 0.5 watts; (2) each line consisted of 50 passes, with the Z position being advanced 5 micron per pass; and (3) 30 s would elapse before the next line was scribed to allow

Search for new phenomena in events containing a same-flavour opposite-sign dilepton pair, jets, and large missing transverse momentum in [Formula: see text] [Formula: see text][Formula: see text] collisions with the ATLAS detector.

PubMed

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Barreiro, F; da Costa, J Barreiro Guimarães; Bartoldus, R; Barton, A E; Bartos, P; Basalaev, A; Bassalat, A; Bates, R L; Batista, S J; Batley, J R; Battaglia, M; Bauce, M; Bauer, F; Bawa, H S; Beacham, J B; Beattie, M D; Beau, T; Beauchemin, P H; Bechtle, P; Beck, H P; Becker, K; Becker, M; Beckingham, M; Becot, C; Beddall, A J; Beddall, A; Bednyakov, V A; Bedognetti, M; Bee, C P; Beemster, L J; Beermann, T A; Begel, M; Behr, J K; Bell, A S; Bella, G; Bellagamba, L; Bellerive, A; Bellomo, M; Belotskiy, K; Beltramello, O; Belyaev, N L; Benary, O; Benchekroun, D; Bender, M; Bendtz, K; Benekos, N; Benhammou, Y; Noccioli, E Benhar; Benitez, J; Benjamin, D P; Bensinger, J R; Bentvelsen, S; Beresford, L; Beretta, M; Berge, D; Kuutmann, E Bergeaas; Berger, N; Beringer, J; Berlendis, S; Bernard, N R; Bernius, C; Bernlochner, F U; Berry, T; Berta, P; Bertella, C; Bertoli, G; Bertolucci, F; Bertram, I A; Bertsche, C; Bertsche, D; Besjes, G J; Bylund, O Bessidskaia; Bessner, M; Besson, N; Betancourt, C; 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Brenner, R; Bressler, S; Bristow, T M; Britton, D; Britzger, D; Brochu, F M; Brock, I; Brock, R; Brooijmans, G; Brooks, T; Brooks, W K; Brosamer, J; Brost, E; Broughton, J H; de Renstrom, P A Bruckman; Bruncko, D; Bruni, A; Bruni, G; Bruni, L S; Brunt, B H; Bruschi, M; Bruscino, N; Bryant, P; Bryngemark, L; Buanes, T; Buat, Q; Buchholz, P; Buckley, A G; Budagov, I A; Buehrer, F; Bugge, M K; Bulekov, O; Bullock, D; Burckhart, H; Burdin, S; Burgard, C D; Burger, A M; Burghgrave, B; Burka, K; Burke, S; Burmeister, I; Burr, J T P; Busato, E; Büscher, D; Büscher, V; Bussey, P; Butler, J M; Buttar, C M; Butterworth, J M; Butti, P; Buttinger, W; Buzatu, A; Buzykaev, A R; Urbán, S Cabrera; Caforio, D; Cairo, V M; Cakir, O; Calace, N; Calafiura, P; Calandri, A; Calderini, G; Calfayan, P; Callea, G; Caloba, L P; Lopez, S Calvente; Calvet, D; Calvet, S; Calvet, T P; Toro, R Camacho; Camarda, S; Camarri, P; Cameron, D; Armadans, R Caminal; Camincher, C; Campana, S; Campanelli, M; Camplani, A; Campoverde, A; Canale, V; Canepa, A; Bret, M Cano; Cantero, J; Cao, T; Garrido, M D M Capeans; Caprini, I; Caprini, M; Capua, M; Carbone, R M; Cardarelli, R; Cardillo, F; Carli, I; Carli, T; Carlino, G; Carlson, B T; Carminati, L; Carney, R M D; Caron, S; Carquin, E; Carrillo-Montoya, G D; Carter, J R; Carvalho, J; Casadei, D; Casado, M P; Casolino, M; Casper, D W; Castelijn, R; Castelli, A; Gimenez, V Castillo; Castro, N F; Catinaccio, A; Catmore, J R; Cattai, A; Caudron, J; Cavaliere, V; Cavallaro, E; Cavalli, D; Cavalli-Sforza, M; Cavasinni, V; Ceradini, F; Alberich, L Cerda; Cerqueira, A S; Cerri, A; Cerrito, L; Cerutti, F; Cervelli, A; Cetin, S A; Chafaq, A; Chakraborty, D; Chan, S K; Chan, Y L; Chang, P; Chapman, J D; Charlton, D G; Chatterjee, A; Chau, C C; Barajas, C A Chavez; Che, S; Cheatham, S; Chegwidden, A; Chekanov, S; Chekulaev, S V; Chelkov, G A; Chelstowska, M A; Chen, C; Chen, H; Chen, S; Chen, S; Chen, X; Chen, Y; Cheng, H C; Cheng, H J; Cheng, Y; Cheplakov, A; Cheremushkina, E; Moursli, R Cherkaoui El; 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Cristinziani, M; Croft, V; Crosetti, G; Cueto, A; Donszelmann, T Cuhadar; Cummings, J; Curatolo, M; Cúth, J; Czirr, H; Czodrowski, P; D'amen, G; D'Auria, S; D'Onofrio, M; De Sousa, M J Da Cunha Sargedas; Via, C Da; Dabrowski, W; Dado, T; Dai, T; Dale, O; Dallaire, F; Dallapiccola, C; Dam, M; Dandoy, J R; Dang, N P; Daniells, A C; Dann, N S; Danninger, M; Hoffmann, M Dano; Dao, V; Darbo, G; Darmora, S; Dassoulas, J; Dattagupta, A; Daubney, T; Davey, W; David, C; Davidek, T; Davies, M; Davison, P; Dawe, E; Dawson, I; De, K; de Asmundis, R; De Benedetti, A; De Castro, S; De Cecco, S; De Groot, N; de Jong, P; De la Torre, H; De Lorenzi, F; De Maria, A; De Pedis, D; De Salvo, A; De Sanctis, U; De Santo, A; De Regie, J B De Vivie; Dearnaley, W J; Debbe, R; Debenedetti, C; Dedovich, D V; Dehghanian, N; Deigaard, I; Del Gaudio, M; Del Peso, J; Del Prete, T; Delgove, D; Deliot, F; Delitzsch, C M; Dell'Acqua, A; Dell'Asta, L; Dell'Orso, M; Della Pietra, M; Della Volpe, D; Delmastro, M; Delsart, P A; 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Pirumov, H; Pitt, M; Plazak, L; Pleier, M-A; Pleskot, V; Plotnikova, E; Pluth, D; Poettgen, R; Poggioli, L; Pohl, D; Polesello, G; Poley, A; Policicchio, A; Polifka, R; Polini, A; Pollard, C S; Polychronakos, V; Pommès, K; Pontecorvo, L; Pope, B G; Popeneciu, G A; Poppleton, A; Pospisil, S; Potamianos, K; Potrap, I N; Potter, C J; Potter, C T; Poulard, G; Poveda, J; Pozdnyakov, V; Astigarraga, M E Pozo; Pralavorio, P; Pranko, A; Prell, S; Price, D; Price, L E; Primavera, M; Prince, S; Prokofiev, K; Prokoshin, F; Protopopescu, S; Proudfoot, J; Przybycien, M; Puddu, D; Purohit, M; Puzo, P; Qian, J; Qin, G; Qin, Y; Quadt, A; Quayle, W B; Queitsch-Maitland, M; Quilty, D; Raddum, S; Radeka, V; Radescu, V; Radhakrishnan, S K; Radloff, P; Rados, P; Ragusa, F; Rahal, G; Raine, J A; Rajagopalan, S; Rammensee, M; Rangel-Smith, C; Ratti, M G; Rauch, D M; Rauscher, F; Rave, S; Ravenscroft, T; Ravinovich, I; Raymond, M; Read, A L; Readioff, N P; Reale, M; Rebuzzi, D M; Redelbach, A; Redlinger, G; Reece, R; Reed, R G; Reeves, K; Rehnisch, L; Reichert, J; Reiss, A; Rembser, C; Ren, H; Rescigno, M; Resconi, S; Resseguie, E D; Rezanova, O L; Reznicek, P; Rezvani, R; Richter, R; Richter, S; Richter-Was, E; Ricken, O; Ridel, M; Rieck, P; Riegel, C J; Rieger, J; Rifki, O; Rijssenbeek, M; Rimoldi, A; Rimoldi, M; Rinaldi, L; Ripellino, G; Ristić, B; Ritsch, E; Riu, I; Rizatdinova, F; Rizvi, E; Rizzi, C; Roberts, R T; Robertson, S H; Robichaud-Veronneau, A; Robinson, D; Robinson, J E M; Robson, A; Roda, C; Rodina, Y; Perez, A Rodriguez; Rodriguez, D Rodriguez; Roe, S; Rogan, C S; Røhne, O; Roloff, J; Romaniouk, A; Romano, M; Saez, S M Romano; Adam, E Romero; Rompotis, N; Ronzani, M; Roos, L; Ros, E; Rosati, S; Rosbach, K; Rose, P; Rosien, N-A; Rossetti, V; Rossi, E; Rossi, L P; Rosten, J H N; Rosten, R; Rotaru, M; Roth, I; Rothberg, J; Rousseau, D; Rozanov, A; Rozen, Y; Ruan, X; Rubbo, F; Rudolph, M S; Rühr, F; Ruiz-Martinez, A; Rurikova, Z; Rusakovich, N A; Ruschke, A; Russell, H L; Rutherfoord, J P; Ruthmann, N; Ryabov, Y F; Rybar, M; Rybkin, G; Ryu, S; Ryzhov, A; Rzehorz, G F; Saavedra, A F; Sabato, G; Sacerdoti, S; Sadrozinski, H F-W; Sadykov, R; Tehrani, F Safai; Saha, P; Sahinsoy, M; Saimpert, M; Saito, T; Sakamoto, H; Sakurai, Y; Salamanna, G; Loyola, J E Salazar; Salek, D; De Bruin, P H Sales; Salihagic, D; Salnikov, A; Salt, J; Salvatore, D; Salvatore, F; Salvucci, A; Salzburger, A; Sammel, D; Sampsonidis, D; Sánchez, J; Martinez, V Sanchez; Pineda, A Sanchez; Sandaker, H; Sandbach, R L; Sandhoff, M; Sandoval, C; Sankey, D P C; Sannino, M; Sansoni, A; Santoni, C; Santonico, R; Santos, H; Castillo, I Santoyo; Sapp, K; Sapronov, A; Saraiva, J G; Sarrazin, B; Sasaki, O; Sato, K; Sauvan, E; Savage, G; Savard, P; Savic, N; Sawyer, C; Sawyer, L; Saxon, J; Sbarra, C; Sbrizzi, A; Scanlon, T; Scannicchio, D A; Scarcella, M; Scarfone, V; Schaarschmidt, J; Schacht, P; Schachtner, B M; Schaefer, D; Schaefer, L; Schaefer, R; Schaeffer, J; Schaepe, S; Schaetzel, S; Schäfer, U; Schaffer, A C; Schaile, D; Schamberger, R D; Scharf, V; Schegelsky, V A; Scheirich, D; Schernau, M; Schiavi, C; Schier, S; Schillo, C; Schioppa, M; Schlenker, S; Schmidt-Sommerfeld, K R; Schmieden, K; Schmitt, C; Schmitt, S; Schmitz, S; Schneider, B; Schnoor, U; Schoeffel, L; Schoening, A; Schoenrock, B D; Schopf, E; Schott, M; Schouwenberg, J F P; Schovancova, J; Schramm, S; Schreyer, M; Schuh, N; Schulte, A; Schultens, M J; Schultz-Coulon, H-C; Schulz, H; Schumacher, M; Schumm, B A; Schune, Ph; Schwartzman, A; Schwarz, T A; Schweiger, H; Schwemling, Ph; Schwienhorst, R; Schwindling, J; Schwindt, T; Sciolla, G; Scuri, F; Scutti, F; Searcy, J; Seema, P; Seidel, S C; Seiden, A; Seifert, F; Seixas, J M; Sekhniaidze, G; Sekhon, K; Sekula, S J; Semprini-Cesari, N; Serfon, C; Serin, L; Serkin, L; Sessa, M; Seuster, R; Severini, H; Sfiligoj, T; Sforza, F; Sfyrla, A; Shabalina, E; Shaikh, N W; Shan, L Y; Shang, R; Shank, J T; Shapiro, M; Shatalov, P B; Shaw, K; Shaw, S M; Shcherbakova, A; Shehu, C Y; Shen, Y; Sherwood, P; Shi, L; Shimizu, S; Shimmin, C O; Shimojima, M; Shirabe, S; Shiyakova, M; Shlomi, J; Shmeleva, A; Saadi, D Shoaleh; Shochet, M J; Shojaii, S; Shope, D R; Shrestha, S; Shulga, E; Shupe, M A; Sicho, P; Sickles, A M; Sidebo, P E; Haddad, E Sideras; Sidiropoulou, O; Sidorov, D; Sidoti, A; Siegert, F; Sijacki, Dj; Silva, J; Silverstein, S B; Simak, V; Simic, Lj; Simion, S; Simioni, E; Simmons, B; Simon, M; Sinervo, P; Sinev, N B; Sioli, M; Siragusa, G; Siral, I; Sivoklokov, S Yu; Sjölin, J; Skinner, M B; Skubic, P; Slater, M; Slavicek, T; Slawinska, M; Sliwa, K; Slovak, R; Smakhtin, V; Smart, B H; Smestad, L; Smiesko, J; Smirnov, S Yu; Smirnov, Y; Smirnova, L N; Smirnova, O; Smith, J W; Smith, M N K; Smith, R W; Smizanska, M; Smolek, K; Snesarev, A A; Snyder, I M; Snyder, S; Sobie, R; Socher, F; Soffer, A; Soh, D A; Sokhrannyi, G; Sanchez, C A Solans; Solar, M; Soldatov, E Yu; Soldevila, U; Solodkov, A A; Soloshenko, A; Solovyanov, O V; Solovyev, V; Sommer, P; Son, H; Song, H Y; Sood, A; Sopczak, A; Sopko, V; Sorin, V; Sosa, D; Sotiropoulou, C L; Soualah, R; Soukharev, A M; South, D; Sowden, B C; Spagnolo, S; Spalla, M; Spangenberg, M; Spanò, F; Sperlich, D; Spettel, F; Spieker, T M; Spighi, R; Spigo, G; Spiller, L A; Spousta, M; Denis, R D St; Stabile, A; Stamen, R; Stamm, S; Stanecka, E; Stanek, R W; Stanescu, C; Stanescu-Bellu, M; Stanitzki, M M; Stapnes, S; Starchenko, E A; Stark, G H; Stark, J; Staroba, P; Starovoitov, P; Stärz, S; Staszewski, R; Steinberg, P; Stelzer, B; Stelzer, H J; Stelzer-Chilton, O; Stenzel, H; Stewart, G A; Stillings, J A; Stockton, M C; Stoebe, M; Stoicea, G; Stolte, P; Stonjek, S; Stradling, A R; Straessner, A; Stramaglia, M E; Strandberg, J; Strandberg, S; Strandlie, A; Strauss, M; Strizenec, P; Ströhmer, R; Strom, D M; Stroynowski, R; Strubig, A; Stucci, S A; Stugu, B; Styles, N A; Su, D; Su, J; Suchek, S; Sugaya, Y; Suk, M; Sulin, V V; Sultansoy, S; Sumida, T; Sun, S; Sun, X; Suruliz, K; Suster, C J E; Sutton, M R; Suzuki, S; Svatos, M; Swiatlowski, M; Swift, S P; Sykora, I; Sykora, T; Ta, D; Tackmann, K; Taenzer, J; Taffard, A; Tafirout, R; Taiblum, N; Takai, H; Takashima, R; Takeshita, T; Takubo, Y; Talby, M; Talyshev, A A; Tanaka, J; Tanaka, M; Tanaka, R; Tanaka, S; Tanioka, R; Tannenwald, B B; Araya, S Tapia; Tapprogge, S; Tarem, S; Tartarelli, G F; Tas, P; Tasevsky, M; Tashiro, T; Tassi, E; Delgado, A Tavares; Tayalati, Y; Taylor, A C; Taylor, G N; Taylor, P T E; Taylor, W; Teischinger, F A; Teixeira-Dias, P; Temming, K K; Temple, D; Kate, H Ten; Teng, P K; Teoh, J J; Tepel, F; Terada, S; Terashi, K; Terron, J; Terzo, S; Testa, M; Teuscher, R J; Theveneaux-Pelzer, T; Thomas, J P; Thomas-Wilsker, J; Thompson, P D; Thompson, A S; Thomsen, L A; Thomson, E; Tibbetts, M J; Torres, R E Ticse; Tikhomirov, V O; Tikhonov, Yu A; Timoshenko, S; Tipton, P; Tisserant, S; Todome, K; Todorova-Nova, S; Tojo, J; Tokár, S; Tokushuku, K; Tolley, E; Tomlinson, L; Tomoto, M; Tompkins, L; Toms, K; Tong, B; Tornambe, P; Torrence, E; Torres, H; Pastor, E Torró; Toth, J; Touchard, F; Tovey, D R; Trefzger, T; Tricoli, A; Trigger, I M; Trincaz-Duvoid, S; Tripiana, M F; Trischuk, W; Trocmé, B; Trofymov, A; Troncon, C; Trottier-McDonald, M; Trovatelli, M; Truong, L; Trzebinski, M; Trzupek, A; Tseng, J C-L; Tsiareshka, P V; Tsipolitis, G; Tsirintanis, N; Tsiskaridze, S; Tsiskaridze, V; Tskhadadze, E G; Tsui, K M; Tsukerman, I I; Tsulaia, V; Tsuno, S; Tsybychev, D; Tu, Y; Tudorache, A; Tudorache, V; Tulbure, T T; Tuna, A N; Tupputi, S A; Turchikhin, S; Turgeman, D; Cakir, I Turk; Turra, R; Tuts, P M; Ucchielli, G; Ueda, I; Ughetto, M; Ukegawa, F; Unal, G; Undrus, A; Unel, G; Ungaro, F C; Unno, Y; Unverdorben, C; Urban, J; Urquijo, P; Urrejola, P; Usai, G; Usui, J; Vacavant, L; Vacek, V; Vachon, B; Valderanis, C; Santurio, E Valdes; Valencic, N; Valentinetti, S; Valero, A; Valery, L; Valkar, S; Ferrer, J A Valls; Van Den Wollenberg, W; Van Der Deijl, P C; van der Graaf, H; van Eldik, N; van Gemmeren, P; Van Nieuwkoop, J; van Vulpen, I; van Woerden, M C; Vanadia, M; Vandelli, W; Vanguri, R; Vaniachine, A; Vankov, P; Vardanyan, G; Vari, R; Varnes, E W; Varol, T; Varouchas, D; Vartapetian, A; Varvell, K E; Vasquez, J G; Vasquez, G A; Vazeille, F; Schroeder, T Vazquez; Veatch, J; Veeraraghavan, V; Veloce, L M; Veloso, F; Veneziano, S; Ventura, A; Venturi, M; Venturi, N; Venturini, A; Vercesi, V; Verducci, M; Verkerke, W; Vermeulen, J C; Vetterli, M C; Viazlo, O; Vichou, I; Vickey, T; Boeriu, O E Vickey; Viehhauser, G H A; Viel, S; Vigani, L; Villa, M; Perez, M Villaplana; Vilucchi, E; Vincter, M G; Vinogradov, V B; Vishwakarma, A; Vittori, C; Vivarelli, I; Vlachos, S; Vlasak, M; Vogel, M; Vokac, P; Volpi, G; Volpi, M; von der Schmitt, H; von Toerne, E; Vorobel, V; Vorobev, K; Vos, M; Voss, R; Vossebeld, J H; Vranjes, N; Milosavljevic, M Vranjes; Vrba, V; Vreeswijk, M; Vuillermet, R; Vukotic, I; Wagner, P; Wagner, W; Wahlberg, H; Wahrmund, S; Wakabayashi, J; Walder, J; Walker, R; Walkowiak, W; Wallangen, V; Wang, C; Wang, C; 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Zobernig, G; Zoccoli, A; Nedden, M Zur; Zwalinski, L

2017-01-01

Two searches for new phenomena in final states containing a same-flavour opposite-sign lepton (electron or muon) pair, jets, and large missing transverse momentum are presented. These searches make use of proton-proton collision data, collected during 2015 and 2016 at a centre-of-mass energy [Formula: see text] [Formula: see text] by the ATLAS detector at the large hadron collider, which correspond to an integrated luminosity of [Formula: see text]. Both searches target the pair production of supersymmetric particles, squarks or gluinos, which decay to final states containing a same-flavour opposite-sign lepton pair via one of two mechanisms: a leptonically decaying Z boson in the final state, leading to a peak in the dilepton invariant-mass distribution around the Z boson mass; and decays of neutralinos (e.g. [Formula: see text]), yielding a kinematic endpoint in the dilepton invariant-mass spectrum. The data are found to be consistent with the Standard Model expectation. Results are interpreted in simplified models of gluino-pair (squark-pair) production, and provide sensitivity to gluinos (squarks) with masses as large as 1.70 [Formula: see text] (980 [Formula: see text]).

Low-enriched uranium high-density target project. Compendium report

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

Vandegrift, George; Brown, M. Alex; Jerden, James L.

2016-09-01

At present, most 99Mo is produced in research, test, or isotope production reactors by irradiation of highly enriched uranium targets. To achieve the denser form of uranium needed for switching from high to low enriched uranium (LEU), targets in the form of a metal foil (~125-150 µm thick) are being developed. The LEU High Density Target Project successfully demonstrated several iterations of an LEU-fission-based Mo-99 technology that has the potential to provide the world’s supply of Mo-99, should major producers choose to utilize the technology. Over 50 annular high density targets have been successfully tested, and the assembly and disassemblymore » of targets have been improved and optimized. Two target front-end processes (acidic and electrochemical) have been scaled up and demonstrated to allow for the high-density target technology to mate up to the existing producer technology for target processing. In the event that a new target processing line is started, the chemical processing of the targets is greatly simplified. Extensive modeling and safety analysis has been conducted, and the target has been qualified to be inserted into the High Flux Isotope Reactor, which is considered above and beyond the requirements for the typical use of this target due to high fluence and irradiation duration.« less

Texting while driving: is speech-based text entry less risky than handheld text entry?

PubMed

He, J; Chaparro, A; Nguyen, B; Burge, R J; Crandall, J; Chaparro, B; Ni, R; Cao, S

2014-11-01

Research indicates that using a cell phone to talk or text while maneuvering a vehicle impairs driving performance. However, few published studies directly compare the distracting effects of texting using a hands-free (i.e., speech-based interface) versus handheld cell phone, which is an important issue for legislation, automotive interface design and driving safety training. This study compared the effect of speech-based versus handheld text entries on simulated driving performance by asking participants to perform a car following task while controlling the duration of a secondary text-entry task. Results showed that both speech-based and handheld text entries impaired driving performance relative to the drive-only condition by causing more variation in speed and lane position. Handheld text entry also increased the brake response time and increased variation in headway distance. Text entry using a speech-based cell phone was less detrimental to driving performance than handheld text entry. Nevertheless, the speech-based text entry task still significantly impaired driving compared to the drive-only condition. These results suggest that speech-based text entry disrupts driving, but reduces the level of performance interference compared to text entry with a handheld device. In addition, the difference in the distraction effect caused by speech-based and handheld text entry is not simply due to the difference in task duration. Copyright © 2014 Elsevier Ltd. All rights reserved.

Detection of Moving Targets Using Soliton Resonance Effect

NASA Technical Reports Server (NTRS)

Kulikov, Igor K.; Zak, Michail

2013-01-01

The objective of this research was to develop a fundamentally new method for detecting hidden moving targets within noisy and cluttered data-streams using a novel "soliton resonance" effect in nonlinear dynamical systems. The technique uses an inhomogeneous Korteweg de Vries (KdV) equation containing moving-target information. Solution of the KdV equation will describe a soliton propagating with the same kinematic characteristics as the target. The approach uses the time-dependent data stream obtained with a sensor in form of the "forcing function," which is incorporated in an inhomogeneous KdV equation. When a hidden moving target (which in many ways resembles a soliton) encounters the natural "probe" soliton solution of the KdV equation, a strong resonance phenomenon results that makes the location and motion of the target apparent. Soliton resonance method will amplify the moving target signal, suppressing the noise. The method will be a very effective tool for locating and identifying diverse, highly dynamic targets with ill-defined characteristics in a noisy environment. The soliton resonance method for the detection of moving targets was developed in one and two dimensions. Computer simulations proved that the method could be used for detection of singe point-like targets moving with constant velocities and accelerations in 1D and along straight lines or curved trajectories in 2D. The method also allows estimation of the kinematic characteristics of moving targets, and reconstruction of target trajectories in 2D. The method could be very effective for target detection in the presence of clutter and for the case of target obscurations.

Learning from Science Text: Role of an Elaborate Analogy. Reading Research Report No. 71.

ERIC Educational Resources Information Center

Glynn, Shawn M.

A study examined the role that an elaborate analogy can play when high school students learn a concept from a leading science textbook. The elaborate analogy had graphic and text components that integrated and mapped key features from the analogy (a factory) to the target concept (an animal cell). The target features were parts of the cell and, by…

Fluorescence In Situ Hybridization–Based Karyotyping of Soybean Translocation Lines

PubMed Central

Findley, Seth D.; Pappas, Allison L.; Cui, Yaya; Birchler, James A.; Palmer, Reid G.; Stacey, Gary

2011-01-01

Soybean (Glycine max [L.] Merr.) is a major crop species and, therefore, a major target of genomic and genetic research. However, in contrast to other plant species, relatively few chromosomal aberrations have been identified and characterized in soybean. This is due in part to the difficulty of cytogenetic analysis of its small, morphologically homogeneous chromosomes. The recent development of a fluorescence in situ hybridization –based karyotyping system for soybean has enabled our characterization of most of the chromosomal translocation lines identified to date. Utilizing genetic data from existing translocation studies in soybean, we identified the chromosomes and approximate breakpoints involved in five translocation lines. PMID:22384324

QUIKVIS- CELESTIAL TARGET AVAILABILITY INFORMATION

NASA Technical Reports Server (NTRS)

Petruzzo, C.

1994-01-01

QUIKVIS computes the times during an Earth orbit when geometric requirements are satisfied for observing celestial objects. The observed objects may be fixed (stars, etc.) or moving (sun, moon, planets). QUIKVIS is useful for preflight analysis by those needing information on the availability of celestial objects to be observed. Two types of analyses are performed by QUIKVIS. One is used when specific objects are known, the other when targets are unknown and potentially useful regions of the sky must be identified. The results are useful in selecting candidate targets, examining the effects of observation requirements, and doing gross assessments of the effects of the orbit's right ascension of the ascending node (RAAN). The results are not appropriate when high accuracy is needed (e.g. for scheduling actual mission operations). The observation duration is calculated as a function of date, orbit node, and geometric requirements. The orbit right ascension of the ascending node can be varied to account for the effects of an uncertain launch time of day. The orbit semimajor axis and inclination are constant throughout the run. A circular orbit is assumed, but a simple program modification will allow eccentric orbits. The geometric requirements that can be processed are: 1) minimum separation angle between the line of sight to the object and the earth's horizon; 2) minimum separation angle between the line of sight to the object and the spacecraft velocity vector; 3) maximum separation angle between the line of sight to the object and the zenith direction; and 4) presence of the spacecraft in the earth's shadow. The user must supply a date or date range, the spacecraft orbit and inclination, up to 700 observation targets, and any geometric requirements to be met. The primary output is the time per orbit that conditions are satisfied, with options for sky survey maps, time since a user-specified orbit event, and bar graphs illustrating overlapping requirements. The

Sentiment analysis of Arabic tweets using text mining techniques

NASA Astrophysics Data System (ADS)

Al-Horaibi, Lamia; Khan, Muhammad Badruddin

2016-07-01

Sentiment analysis has become a flourishing field of text mining and natural language processing. Sentiment analysis aims to determine whether the text is written to express positive, negative, or neutral emotions about a certain domain. Most sentiment analysis researchers focus on English texts, with very limited resources available for other complex languages, such as Arabic. In this study, the target was to develop an initial model that performs satisfactorily and measures Arabic Twitter sentiment by using machine learning approach, Naïve Bayes and Decision Tree for classification algorithms. The datasets used contains more than 2,000 Arabic tweets collected from Twitter. We performed several experiments to check the performance of the two algorithms classifiers using different combinations of text-processing functions. We found that available facilities for Arabic text processing need to be made from scratch or improved to develop accurate classifiers. The small functionalities developed by us in a Python language environment helped improve the results and proved that sentiment analysis in the Arabic domain needs lot of work on the lexicon side.

Polarized deuterium internal target at AmPS (NIKHEF)

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

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

1997-08-01

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

Reading behind the Lines: The Factors Affecting the Text Reception Threshold in Hearing Aid Users

ERIC Educational Resources Information Center

Zekveld, Adriana A.; Pronk, Marieke; Danielsson, Henrik; Rönnberg, Jerker

2018-01-01

Purpose: The visual Text Reception Threshold (TRT) test (Zekveld et al., 2007) has been designed to assess modality-general factors relevant for speech perception in noise. In the last decade, the test has been adopted in audiology labs worldwide. The 1st aim of this study was to examine which factors best predict interindividual differences in…

Perceiving the target's state or state provoked by the target? An analysis of the descriptive and evaluative knowledge in person perception.

PubMed

Mignon, Astrid; Mollaret, Patrick

2012-12-01

In line with the theory of traits as generalized affordances, the present article argues that target's states (TSs) and states provoked by a target (other's states (OSs) towards target) are two components of the meaning of traits referring, respectively, to a descriptive and to an evaluative knowledge of people. A preliminary study confirmed that TS and OS were equally representative of a trait. Two studies were designed to study the effects of practising the use of traits as either TS or OS categories (an induction procedure) on a subsequent person perception task, requiring participants to rate photographed targets on a series of traits. Results show that both the differentiation between targets and evaluative consistency of ratings were enhanced under the OS condition compared to TS and control (with no practice of traits) conditions. Importantly, Study 2 tends to show that the effects of the induction procedure are not limited to the practised traits but also generalize to unpractised traits. Implications of these findings for social perception research are discussed. ©2011 The British Psychological Society.

Parallel mRNA, proteomics and miRNA expression analysis in cell line models of the intestine.

PubMed

O'Sullivan, Finbarr; Keenan, Joanne; Aherne, Sinead; O'Neill, Fiona; Clarke, Colin; Henry, Michael; Meleady, Paula; Breen, Laura; Barron, Niall; Clynes, Martin; Horgan, Karina; Doolan, Padraig; Murphy, Richard

2017-11-07

To identify miRNA-regulated proteins differentially expressed between Caco2 and HT-29: two principal cell line models of the intestine. Exponentially growing Caco-2 and HT-29 cells were harvested and prepared for mRNA, miRNA and proteomic profiling. mRNA microarray profiling analysis was carried out using the Affymetrix GeneChip Human Gene 1.0 ST array. miRNA microarray profiling analysis was carried out using the Affymetrix Genechip miRNA 3.0 array. Quantitative Label-free LC-MS/MS proteomic analysis was performed using a Dionex Ultimate 3000 RSLCnano system coupled to a hybrid linear ion trap/Orbitrap mass spectrometer. Peptide identities were validated in Proteome Discoverer 2.1 and were subsequently imported into Progenesis QI software for further analysis. Hierarchical cluster analysis for all three parallel datasets (miRNA, proteomics, mRNA) was conducted in the R software environment using the Euclidean distance measure and Ward's clustering algorithm. The prediction of miRNA and oppositely correlated protein/mRNA interactions was performed using TargetScan 6.1. GO biological process, molecular function and cellular component enrichment analysis was carried out for the DE miRNA, protein and mRNA lists via the Pathway Studio 11.3 Web interface using their Mammalian database. Differential expression (DE) profiling comparing the intestinal cell lines HT-29 and Caco-2 identified 1795 Genes, 168 Proteins and 160 miRNAs as DE between the two cell lines. At the gene level, 1084 genes were upregulated and 711 were downregulated in the Caco-2 cell line relative to the HT-29 cell line. At the protein level, 57 proteins were found to be upregulated and 111 downregulated in the Caco-2 cell line relative to the HT-29 cell line. Finally, at the miRNAs level, 104 were upregulated and 56 downregulated in the Caco-2 cell line relative to the HT-29 cell line. Gene ontology (GO) analysis of the DE mRNA identified cell adhesion, migration and ECM organization, cellular lipid

Parallel mRNA, proteomics and miRNA expression analysis in cell line models of the intestine

PubMed Central

O’Sullivan, Finbarr; Keenan, Joanne; Aherne, Sinead; O’Neill, Fiona; Clarke, Colin; Henry, Michael; Meleady, Paula; Breen, Laura; Barron, Niall; Clynes, Martin; Horgan, Karina; Doolan, Padraig; Murphy, Richard

2017-01-01

AIM To identify miRNA-regulated proteins differentially expressed between Caco2 and HT-29: two principal cell line models of the intestine. METHODS Exponentially growing Caco-2 and HT-29 cells were harvested and prepared for mRNA, miRNA and proteomic profiling. mRNA microarray profiling analysis was carried out using the Affymetrix GeneChip Human Gene 1.0 ST array. miRNA microarray profiling analysis was carried out using the Affymetrix Genechip miRNA 3.0 array. Quantitative Label-free LC-MS/MS proteomic analysis was performed using a Dionex Ultimate 3000 RSLCnano system coupled to a hybrid linear ion trap/Orbitrap mass spectrometer. Peptide identities were validated in Proteome Discoverer 2.1 and were subsequently imported into Progenesis QI software for further analysis. Hierarchical cluster analysis for all three parallel datasets (miRNA, proteomics, mRNA) was conducted in the R software environment using the Euclidean distance measure and Ward’s clustering algorithm. The prediction of miRNA and oppositely correlated protein/mRNA interactions was performed using TargetScan 6.1. GO biological process, molecular function and cellular component enrichment analysis was carried out for the DE miRNA, protein and mRNA lists via the Pathway Studio 11.3 Web interface using their Mammalian database. RESULTS Differential expression (DE) profiling comparing the intestinal cell lines HT-29 and Caco-2 identified 1795 Genes, 168 Proteins and 160 miRNAs as DE between the two cell lines. At the gene level, 1084 genes were upregulated and 711 were downregulated in the Caco-2 cell line relative to the HT-29 cell line. At the protein level, 57 proteins were found to be upregulated and 111 downregulated in the Caco-2 cell line relative to the HT-29 cell line. Finally, at the miRNAs level, 104 were upregulated and 56 downregulated in the Caco-2 cell line relative to the HT-29 cell line. Gene ontology (GO) analysis of the DE mRNA identified cell adhesion, migration and ECM

Gait Pattern Alterations during Walking, Texting and Walking and Texting during Cognitively Distractive Tasks while Negotiating Common Pedestrian Obstacles

PubMed Central

Licence, Sammy; Smith, Robynne; McGuigan, Miranda P.; Earnest, Conrad P.

2015-01-01

Objectives Mobile phone texting is a common daily occurrence with a paucity of research examining corresponding gait characteristics. To date, most studies have participants walk in a straight line vs. overcoming barriers and obstacles that occur during regular walking. The aim of our study is to examine the effect of mobile phone texting during periods of cognitive distraction while walking and negotiating barriers synonymous with pedestrian traffic. Methods Thirty participants (18-50y) completed three randomized, counter-balanced walking tasks over a course during: (1) normal walking (control), (2) texting and walking, and (3) texting and walking whilst being cognitively distraction via a standard mathematical test performed while negotiating the obstacle course. We analyzed gait characteristics during course negotiation using a 3-dimensional motion analysis system and a general linear model and Dunnet-Hsu post-hoc procedure the normal walking condition to assess gait characteristic differences. Primary outcomes included the overall time to complete the course time and barrier contact. Secondary outcomes included obstacle clearance height, step frequency, step time, double support phase and lateral deviation. Results Participants took significantly longer (mean ± SD) to complete the course while texting (24.96±4.20 sec) and during cognitive distraction COG (24.09±3.36 sec) vs. normal walking (19.32±2.28 sec; all, P<0.001). No significant differences were noted for barrier contacts (P = 0.28). Step frequency, step time, double support phase and lateral deviation all increased in duration during the texting and cognitive distraction trial. Texting and being cognitively distracted also increased obstacle clearance versus the walking condition (all, P<0.02). Conclusions Texting while walking and/or being cognitively distracted significantly affect gait characteristics concordant to mobile phone usage resulting in a more cautious gate pattern. Future research

Multi-dimensional classification of biomedical text: Toward automated, practical provision of high-utility text to diverse users

PubMed Central

Shatkay, Hagit; Pan, Fengxia; Rzhetsky, Andrey; Wilbur, W. John

2008-01-01

Motivation: Much current research in biomedical text mining is concerned with serving biologists by extracting certain information from scientific text. We note that there is no ‘average biologist’ client; different users have distinct needs. For instance, as noted in past evaluation efforts (BioCreative, TREC, KDD) database curators are often interested in sentences showing experimental evidence and methods. Conversely, lab scientists searching for known information about a protein may seek facts, typically stated with high confidence. Text-mining systems can target specific end-users and become more effective, if the system can first identify text regions rich in the type of scientific content that is of interest to the user, retrieve documents that have many such regions, and focus on fact extraction from these regions. Here, we study the ability to characterize and classify such text automatically. We have recently introduced a multi-dimensional categorization and annotation scheme, developed to be applicable to a wide variety of biomedical documents and scientific statements, while intended to support specific biomedical retrieval and extraction tasks. Results: The annotation scheme was applied to a large corpus in a controlled effort by eight independent annotators, where three individual annotators independently tagged each sentence. We then trained and tested machine learning classifiers to automatically categorize sentence fragments based on the annotation. We discuss here the issues involved in this task, and present an overview of the results. The latter strongly suggest that automatic annotation along most of the dimensions is highly feasible, and that this new framework for scientific sentence categorization is applicable in practice. Contact: shatkay@cs.queensu.ca PMID:18718948

Direct cloning of isogenic murine DNA in yeast and relevance of isogenicity for targeting in embryonic stem cells.

PubMed

Andréasson, Claes; Schick, Anna J; Pfeiffer, Susanne M; Sarov, Mihail; Stewart, Francis; Wurst, Wolfgang; Schick, Joel A

2013-01-01

Efficient gene targeting in embryonic stem cells requires that modifying DNA sequences are identical to those in the targeted chromosomal locus. Yet, there is a paucity of isogenic genomic clones for human cell lines and PCR amplification cannot be used in many mutation-sensitive applications. Here, we describe a novel method for the direct cloning of genomic DNA into a targeting vector, pRTVIR, using oligonucleotide-directed homologous recombination in yeast. We demonstrate the applicability of the method by constructing functional targeting vectors for mammalian genes Uhrf1 and Gfap. Whereas the isogenic targeting of the gene Uhrf1 showed a substantial increase in targeting efficiency compared to non-isogenic DNA in mouse E14 cells, E14-derived DNA performed better than the isogenic DNA in JM8 cells for both Uhrf1 and Gfap. Analysis of 70 C57BL/6-derived targeting vectors electroporated in JM8 and E14 cell lines in parallel showed a clear dependence on isogenicity for targeting, but for three genes isogenic DNA was found to be inhibitory. In summary, this study provides a straightforward methodological approach for the direct generation of isogenic gene targeting vectors.

Statistical-Mechanics-Inspired Optimization of Sensor Field Configuration for Detection of Mobile Targets (PREPRINT)

DTIC Science & Technology

2010-11-01

pected target motion. Along this line, Wettergren [5] analyzed the performance of the track - before - detect schemes for the sensor networks. Furthermore...dressed by Baumgartner and Ferrari [11] for the reorganization of the sensor field to achieve the maximum coverage. The track - before - detect -based optimal...confirming a target. In accordance with the track - before - detect paradigm [4], a moving target is detected if the kd (typically kd = 3 or 4) sensors detect

Important Text Characteristics for Early-Grades Text Complexity

ERIC Educational Resources Information Center

Fitzgerald, Jill; Elmore, Jeff; Koons, Heather; Hiebert, Elfrieda H.; Bowen, Kimberly; Sanford-Moore, Eleanor E.; Stenner, A. Jackson

2015-01-01

The Common Core set a standard for all children to read increasingly complex texts throughout schooling. The purpose of the present study was to explore text characteristics specifically in relation to early-grades text complexity. Three hundred fifty primary-grades texts were selected and digitized. Twenty-two text characteristics were identified…

CRISPR/Cas9-mediated gene targeting in Arabidopsis using sequential transformation.

PubMed

Miki, Daisuke; Zhang, Wenxin; Zeng, Wenjie; Feng, Zhengyan; Zhu, Jian-Kang

2018-05-17

Homologous recombination-based gene targeting is a powerful tool for precise genome modification and has been widely used in organisms ranging from yeast to higher organisms such as Drosophila and mouse. However, gene targeting in higher plants, including the most widely used model plant Arabidopsis thaliana, remains challenging. Here we report a sequential transformation method for gene targeting in Arabidopsis. We find that parental lines expressing the bacterial endonuclease Cas9 from the egg cell- and early embryo-specific DD45 gene promoter can improve the frequency of single-guide RNA-targeted gene knock-ins and sequence replacements via homologous recombination at several endogenous sites in the Arabidopsis genome. These heritable gene targeting can be identified by regular PCR. Our approach enables routine and fine manipulation of the Arabidopsis genome.

Large Scale Spectral Line Mapping of Galactic Regions with CCAT-Prime

NASA Astrophysics Data System (ADS)

Simon, Robert

2018-01-01

CCAT-prime is a 6-m submillimeter telescope that is being built on the top of Cerro Chajnantor (5600 m altitude) overlooking the ALMA plateau in the Atacama Desert. Its novel Crossed-Dragone design enables a large field of view without blockage and is thus particularly well suited for large scale surveys in the continuum and spectral lines targeting important questions ranging from star formation in the Milky Way to cosmology. On this poster, we focus on the large scale mapping opportunities in important spectral cooling lines of the interstellar medium opened up by CCAT-prime and the Cologne heterodyne instrument CHAI.

Laser Doppler line scanner for monitoring skin perfusion changes of port wine stains during vascular-targeted photodynamic therapy

NASA Astrophysics Data System (ADS)

Chen, Defu; Ren, Jie; Wang, Ying; Gu, Ying

2014-11-01

Vascular-targeted photodynamic therapy (V-PDT) is known to be an effective therapeutic modality for the treatment of port wine stains (PWS). Monitoring the PWS microvascular response to the V-PDT is crucial for improving the effectiveness of PWS treatment. The objective of this study was to use laser Doppler technique to directly assess the skin perfusion in PWS before and during V-PDT. In this study, 30 patients with PWS were treated with V-PDT. A commercially laser Doppler line scanner (LDLS) was used to record the skin perfusion of PWS immediately before; and at 1, 3, 5, 7, 10, 15 and 20 minutes during V-PDT treatment. Our results showed that there was substantial inter- and intra-patient perfusion heterogeneity in PWS lesion. Before V-PDT, the comparison of skin perfusion in PWS and contralateral healthy control normal skin indicated that PWS skin perfusion could be larger than, or occasionally equivalent to, that of control normal skin. During V-PDT, the skin perfusion in PWS significantly increased after the initiation of V-PDT treatment, then reached a peak within 10 minutes, followed by a slowly decrease to a relatively lower level. Furthermore, the time for reaching peak and the subsequent magnitude of decrease in skin perfusion varied with different patients, as well as different PWS lesion locations. In conclusion, the LDLS system is capable of assessing skin perfusion changes in PWS during V-PDT, and has potential for elucidating the mechanisms of PWS microvascular response to V-PDT.

An Inducible, Isogenic Cancer Cell Line System for Targeting the State of Mismatch Repair Deficiency

PubMed Central

Bailis, Julie M.; Gordon, Marcia L.; Gurgel, Jesse L.; Komor, Alexis C.; Barton, Jacqueline K.; Kirsch, Ilan R.

2013-01-01

The DNA mismatch repair system (MMR) maintains genome stability through recognition and repair of single-base mismatches and small insertion-deletion loops. Inactivation of the MMR pathway causes microsatellite instability and the accumulation of genomic mutations that can cause or contribute to cancer. In fact, 10-20% of certain solid and hematologic cancers are MMR-deficient. MMR-deficient cancers do not respond to some standard of care chemotherapeutics because of presumed increased tolerance of DNA damage, highlighting the need for novel therapeutic drugs. Toward this goal, we generated isogenic cancer cell lines for direct comparison of MMR-proficient and MMR-deficient cells. We engineered NCI-H23 lung adenocarcinoma cells to contain a doxycycline-inducible shRNA designed to suppress the expression of the mismatch repair gene MLH1, and compared single cell subclones that were uninduced (MLH1-proficient) versus induced for the MLH1 shRNA (MLH1-deficient). Here we present the characterization of these MMR-inducible cell lines and validate a novel class of rhodium metalloinsertor compounds that differentially inhibit the proliferation of MMR-deficient cancer cells. PMID:24205301

Integrated QSAR study for inhibitors of hedgehog signal pathway against multiple cell lines:a collaborative filtering method

PubMed Central

2012-01-01

Background The Hedgehog Signaling Pathway is one of signaling pathways that are very important to embryonic development. The participation of inhibitors in the Hedgehog Signal Pathway can control cell growth and death, and searching novel inhibitors to the functioning of the pathway are in a great demand. As the matter of fact, effective inhibitors could provide efficient therapies for a wide range of malignancies, and targeting such pathway in cells represents a promising new paradigm for cell growth and death control. Current research mainly focuses on the syntheses of the inhibitors of cyclopamine derivatives, which bind specifically to the Smo protein, and can be used for cancer therapy. While quantitatively structure-activity relationship (QSAR) studies have been performed for these compounds among different cell lines, none of them have achieved acceptable results in the prediction of activity values of new compounds. In this study, we proposed a novel collaborative QSAR model for inhibitors of the Hedgehog Signaling Pathway by integration the information from multiple cell lines. Such a model is expected to substantially improve the QSAR ability from single cell lines, and provide useful clues in developing clinically effective inhibitors and modifications of parent lead compounds for target on the Hedgehog Signaling Pathway. Results In this study, we have presented: (1) a collaborative QSAR model, which is used to integrate information among multiple cell lines to boost the QSAR results, rather than only a single cell line QSAR modeling. Our experiments have shown that the performance of our model is significantly better than single cell line QSAR methods; and (2) an efficient feature selection strategy under such collaborative environment, which can derive the commonly important features related to the entire given cell lines, while simultaneously showing their specific contributions to a specific cell-line. Based on feature selection results, we have