Synthesis and evaluation of 18F-labeled ATP competitive inhibitors of topoisomerase II as probes for imaging topoisomerase II expression

PubMed Central

Daumar, Pierre; Zeglis, Brian M.; Ramos, Nicholas; Divilov, Vadim; Sevak, Kuntal Kumar; Pillarsetty, NagaVaraKishore; Lewis, Jason S.

2015-01-01

Type II topoisomerase (Topo-II) is an ATP-dependent enzyme that is essential in the transcription, replication, and chromosome segregation processes and, as such, represents an attractive target for cancer therapy. Numerous studies indicate that the response to treatment with Topo-II inhibitors is highly dependent on both the levels and the activity of the enzyme. Consequently, a non-invasive assay to measure tumoral Topo-II levels has the potential to differentiate responders from non-responders. With the ultimate goal of developing a radiofluorinated tracer for positron emission tomography (PET) imaging, we have designed, synthesized, and evaluated a set of fluorinated compounds based on the structure of the ATP-competitive Topo-II inhibitor QAP1. Compounds 18 and 19b showed inhibition of Topo-II in in vitro assays and exhibited moderate, Topo-II level dependent cytotoxicity in SK-BR-3 and MCF-7 cell lines. Based on these results, 18F-labeled analogs of these two compounds were synthesized and evaluated as PET probes for imaging Topo-II overexpression in mice bearing SK-BR-3 xenografts. [18F]-18 and [18F]-19b were synthesized from their corresponding protected tosylated derivatives by fluorination and subsequent deprotection. Small animal PET imaging studies indicated that both compounds do not accumulate in tumors and exhibit poor pharmacokinetics, clearing from the blood pool very rapidly and getting metabolized over. The insights gained from the current study will surely aid in the design and construction of future generations of PET agents for the non-invasive delineation of Topo-II expression. PMID:25240701

Visualization of Metal Ion Buffering via Three-Dimensional Topographic Surfaces (Topos) of Complexometric Titrations

ERIC Educational Resources Information Center

Smith, Garon C.; Hossain, Md Mainul

2017-01-01

"Complexation TOPOS" is a free software package to generate 3-D topographic surfaces ("topos") for metal-ligand complexometric titrations in aqueous media. It constructs surfaces by plotting computed equilibrium parameters above a composition grid with "volume of ligand added" as the x-axis and overall system dilution…

Molecular docking studies of curcumin natural derivatives with DNA topoisomerase I and II-DNA complexes.

PubMed

Kumar, Anil; Bora, Utpal

2014-12-01

DNA topoisomerase I (topo I) and II (topo II) are essential enzymes that solve the topological problems of DNA by allowing DNA strands or double helices to pass through each other during cellular processes such as replication, transcription, recombination, and chromatin remodeling. Their critical roles make topoisomerases an attractive drug target against cancer. The present molecular docking study provides insights into the inhibition of topo I and II by curcumin natural derivatives. The binding modes suggested that curcumin natural derivatives docked at the site of DNA cleavage parallel to the axis of DNA base pairing. Cyclocurcumin and curcumin sulphate were predicted to be the most potent inhibitors amongst all the curcumin natural derivatives docked. The binding modes of cyclocurcumin and curcumin sulphate were similar to known inhibitors of topo I and II. Residues like Arg364, Asn722 and base A113 (when docked to topo I-DNA complex) and residues Asp479, Gln778 and base T9 (when docked to topo II-DNA complex) seem to play important role in the binding of curcumin natural derivatives at the site of DNA cleavage.

US Topo Maps 2014: Program updates and research

USGS Publications Warehouse

Fishburn, Kristin A.

2014-01-01

The U. S. Geological Survey (USGS) US Topo map program is now in year two of its second three-year update cycle. Since the program was launched in 2009, the product and the production system tools and processes have undergone enhancements that have made the US Topo maps a popular success story. Research and development continues with structural and content product enhancements, streamlined and more fully automated workflows, and the evaluation of a GIS-friendly US Topo GIS Packet. In addition, change detection methodologies are under evaluation to further streamline product maintenance and minimize resource expenditures for production in the future. The US Topo map program will continue to evolve in the years to come, providing traditional map users and Geographic Information System (GIS) analysts alike with a convenient, freely available product incorporating nationally consistent data that are quality assured to high standards.

Identification of one of the apurinic/apyrimidinic lyase active sites of topoisomerase V by structural and functional studies

PubMed Central

Rajan, Rakhi; Prasad, Rajendra; Taneja, Bhupesh; Wilson, Samuel H.; Mondragón, Alfonso

2013-01-01

Topoisomerase V (Topo-V) is the only member of a novel topoisomerase subtype. Topo-V is unique because it is a bifunctional enzyme carrying both topoisomerase and DNA repair lyase activities within the same protein. Previous studies had shown that the topoisomerase domain spans the N-terminus of the protein and is followed by 12 tandem helix–hairpin–helix [(HhH)2] domains. There are at least two DNA repair lyase active sites for apurinic/apyrimidinic (AP) site processing, one within the N-terminal region and the second within the C-terminal domain of Topo-V, but their exact locations and characteristics are unknown. In the present study, the N-terminal 78-kDa fragment of Topo-V (Topo-78), containing the topoisomerase domain and one of the lyase DNA repair domains, was characterized by structural and biochemical studies. The results show that an N-terminal 69-kDa fragment is the minimal fragment with both topoisomerase and AP lyase activities. The lyase active site of Topo-78 is at the junction of the fifth and sixth (HhH)2 domains. From the biochemical and structural data, it appears that Lys571 is the most probable nucleophile responsible for the lyase activity. Our experiments also suggest that Topo-V most likely acts as a Class I AP endonuclease in vivo. PMID:23125368

Operational Overreach or Academic Under Reach: Preventing Culmination Through Sustainment

DTIC Science & Technology

2013-12-10

Third US Army, 1 August 1944-9 May 1945. Volume 1 & 2 reproduced jointly by 652nd Engineering (TOPO) Bn., CO. B, 942nd Engineer AVN ., (TOPO) Bn...942nd Engineer AVN ., (TOPO) Bn. 26Peter Dye, “To What Extent Were Logistics Shortages Responsible for Patton’s Culmination on the Meuse in 1944

XPO1 Inhibition Using Selinexor Synergizes With Chemotherapy in Acute Myeloid Leukemia (AML) by Targeting DNA Repair and Restoring Topoisomerase IIα to the Nucleus

PubMed Central

Ranganathan, Parvathi; Kashyap, Trinayan; Yu, Xueyan; Meng, Xiaomei; Lai, Tzung-Huei; McNeil, Betina; Bhatnagar, Bhavana; Shacham, Sharon; Kauffman, Michael; Dorrance, Adrienne M.; Blum, William; Sampath, Deepa; Landesman, Yosef; Garzon, Ramiro

2016-01-01

Purpose Selinexor, a selective inhibitor of XPO1, is currently being tested as single agent in clinical trials in acute myeloid leukemia (AML). However, considering the molecular complexity of AML, it is unlikely that AML can be cured with monotherapy. Therefore we asked whether adding already established effective drugs such as Topoisomerase (Topo) II inhibitors to selinexor will enhance its anti-leukemic effects in AML. Experimental Design The efficacy of combinatorial drug treatment using Topo II inhibitors (idarubicin, daunorubicin, mitoxantrone, etoposide) and selinexor was evaluated in established cellular and animal models of AML. Results Concomitant treatment with selinexor and Topo II inhibitors resulted in therapeutic synergy in AML cell lines and patient samples. Using a xenograft MV4-11 AML mouse model, we show that treatment with selinexor and idarubicin significantly prolongs survival of leukemic mice compared to each single therapy. Conclusions Aberrant nuclear export and cytoplasmic localization of Topo IIα has been identified as one of the mechanisms leading to drug resistance in cancer. Here, we show that in a subset of AML patients that express cytoplasmic Topo IIα, selinexor treatment results in nuclear retention of Topo IIα protein, resulting in increased sensitivity to idarubicin. Selinexor treatment of AML cells resulted in a c-MYC dependent reduction of DNA damage repair genes (Rad51 and Chk1) mRNA and protein expression, and subsequent inhibition of homologous recombination repair and increased sensitivity to Topo II inhibitors. The preclinical data reported here support further clinical studies using selinexor and Topo II inhibitors in combination to treat AML. PMID:27358488

Topoisomerase I peptide-loaded dendritic cells induce autoantibody response as well as skin and lung fibrosis.

PubMed

Mehta, Heena; Goulet, Philippe-Olivier; Nguyen, Vinh; Pérez, Gemma; Koenig, Martial; Senécal, Jean-Luc; Sarfati, Marika

2016-12-01

DNA Topoisomerase I (TopoI) is a candidate autoantigen for diffuse cutaneous systemic sclerosis (dcSSc) associated with fatal lung disease. Dendritic cells (DCs) contribute to bleomycin-induced lung fibrosis. However, the possibility that TopoI-loaded DCs are involved in the initiation and/or perpetuation of dcSSc has not been explored. Here, we show that immunization with TopoI peptide-loaded DCs induces anti-TopoI autoantibody response and long-term fibrosis. Mice were repeatedly immunized with unpulsed DCs or DCs loaded with either TOPOIA or TOPOIB peptides, selected from different regions of TopoI. At week 12 after initial DC immunization, TOPOIA DCs but not TOPOIB DCs immunization induced mixed inflammation and fibrosis in lungs and skin. At a late time point (week 18), both TOPOIA DCs and TOPOIB DCs groups displayed increased alpha-smooth muscle actin expression in lungs and dermis along with skin fibrosis distal from the site of injection when compared with unpulsed DCs. Both TopoI peptide-DC-immunized groups developed IgG2a anti-TopoI autoantibody response. At week 10, signs of perivascular, peribronchial, and parenchymal pulmonary inflammation were already observed in the TOPOIA DCs group, together with transient elevation in bronchoalveolar lavage cell counts, IL-17A expression, and CXCL4 production, a biomarker of early human dcSSc. Collectively, TopoI peptide DCs induce progressive autoantibody response as well as development of protracted skin and lung dcSSc-like disease. Pronounced lung inflammation, transient IL-17A, and CXCL4 expression precede fibrosis development. Our immunization strategy, that uses self immune system and autoantigen, will help to further investigate the pathogenesis of this complex autoimmune disorder with unmet medical needs.

Actin homolog MreB affects chromosome segregation by regulating topoisomerase IV in Escherichia coli.

PubMed

Madabhushi, Ram; Marians, Kenneth J

2009-01-30

In Escherichia coli, topoisomerase IV, a type II topoisomerase, mediates the resolution of topological linkages between replicated daughter chromosomes and is essential for chromosome segregation. Topo IV activity is restricted to only a short interval late in the cell cycle. However, the mechanism that confers this temporal regulation is unknown. Here we report that the bacterial actin homolog MreB participates in the temporal oscillation of Topo IV activity. We show that mreB mutant strains are deficient in Topo IV activity. In addition, we demonstrate that, depending upon whether it is in a monomeric or polymerized state, MreB affects Topo IV activity differentially. In addition, MreB physically interacts with the ParC subunit of Topo IV. Together, these results may explain how dynamics of the bacterial cytoskeleton are coordinated with the timing of chromosome segregation.

CENP-A and topoisomerase-II antagonistically affect chromosome length.

PubMed

Ladouceur, A-M; Ranjan, Rajesh; Smith, Lydia; Fadero, Tanner; Heppert, Jennifer; Goldstein, Bob; Maddox, Amy Shaub; Maddox, Paul S

2017-09-04

The size of mitotic chromosomes is coordinated with cell size in a manner dependent on nuclear trafficking. In this study, we conducted an RNA interference screen of the Caenorhabditis elegans nucleome in a strain carrying an exceptionally long chromosome and identified the centromere-specific histone H3 variant CENP-A and the DNA decatenizing enzyme topoisomerase-II (topo-II) as candidate modulators of chromosome size. In the holocentric organism C. elegans , CENP-A is positioned periodically along the entire length of chromosomes, and in mitosis, these genomic regions come together linearly to form the base of kinetochores. We show that CENP-A protein levels decreased through development coinciding with chromosome-size scaling. Partial loss of CENP-A protein resulted in shorter mitotic chromosomes, consistent with a role in setting chromosome length. Conversely, topo-II levels were unchanged through early development, and partial topo-II depletion led to longer chromosomes. Topo-II localized to the perimeter of mitotic chromosomes, excluded from the centromere regions, and depletion of topo-II did not change CENP-A levels. We propose that self-assembly of centromeric chromatin into an extended linear array promotes elongation of the chromosome, whereas topo-II promotes chromosome-length shortening. © 2017 Ladouceur et al.

Nitric oxide inhibits topoisomerase II activity and induces resistance to topoisomerase II-poisons in human tumor cells.

PubMed

Kumar, Ashutosh; Ehrenshaft, Marilyn; Tokar, Erik J; Mason, Ronald P; Sinha, Birandra K

2016-07-01

Etoposide and doxorubicin, topoisomerase II poisons, are important drugs for the treatment of tumors in the clinic. Topoisomerases contain several free sulfhydryl groups which are important for their activity and are also potential targets for nitric oxide (NO)-induced nitrosation. NO, a physiological signaling molecule nitrosates many cellular proteins, causing altered protein and cellular functions. Here, we have evaluated the roles of NO/NO-derived species in the activity/stability of topo II both in vitro and in human tumor cells, and in the cytotoxicity of topo II-poisons, etoposide and doxorubicin. Treatment of purified topo IIα with propylamine propylamine nonoate (PPNO), an NO donor, resulted in inhibition of both the catalytic and relaxation activity in vitro, and decreased etoposide-dependent cleavable complex formation in both human HT-29 colon and MCF-7 breast cancer cells. PPNO treatment also induced significant nitrosation of topo IIα protein in these human tumor cells. These events, taken together, caused a significant resistance to etoposide in both cell lines. However, PPNO had no effect on doxorubicin-induced cleavable complex formation, or doxorubicin cytotoxicity in these cell lines. Inhibition of topo II function by NO/NO-derived species induces significant resistance to etoposide, without affecting doxorubicin cytotoxicity in human tumor cells. As tumors express inducible nitric oxide synthase and generate significant amounts of NO, modulation of topo II functions by NO/NO-derived species could render tumors resistant to certain topo II-poisons in the clinic. Published by Elsevier B.V.

Topologies on quantum topoi induced by quantization

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

Nakayama, Kunji

2013-07-15

In the present paper, we consider effects of quantization in a topos approach of quantum theory. A quantum system is assumed to be coded in a quantum topos, by which we mean the topos of presheaves on the context category of commutative subalgebras of a von Neumann algebra of bounded operators on a Hilbert space. A classical system is modeled by a Lie algebra of classical observables. It is shown that a quantization map from the classical observables to self-adjoint operators on the Hilbert space naturally induces geometric morphisms from presheaf topoi related to the classical system to the quantummore » topos. By means of the geometric morphisms, we give Lawvere-Tierney topologies on the quantum topos (and their equivalent Grothendieck topologies on the context category). We show that, among them, there exists a canonical one which we call a quantization topology. We furthermore give an explicit expression of a sheafification functor associated with the quantization topology.« less

Kinase-dead ATM protein is highly oncogenic and can be preferentially targeted by Topo-isomerase I inhibitors.

PubMed

Yamamoto, Kenta; Wang, Jiguang; Sprinzen, Lisa; Xu, Jun; Haddock, Christopher J; Li, Chen; Lee, Brian J; Loredan, Denis G; Jiang, Wenxia; Vindigni, Alessandro; Wang, Dong; Rabadan, Raul; Zha, Shan

2016-06-15

Missense mutations in ATM kinase, a master regulator of DNA damage responses, are found in many cancers, but their impact on ATM function and implications for cancer therapy are largely unknown. Here we report that 72% of cancer-associated ATM mutations are missense mutations that are enriched around the kinase domain. Expression of kinase-dead ATM (Atm(KD/-)) is more oncogenic than loss of ATM (Atm(-/-)) in mouse models, leading to earlier and more frequent lymphomas with Pten deletions. Kinase-dead ATM protein (Atm-KD), but not loss of ATM (Atm-null), prevents replication-dependent removal of Topo-isomerase I-DNA adducts at the step of strand cleavage, leading to severe genomic instability and hypersensitivity to Topo-isomerase I inhibitors. Correspondingly, Topo-isomerase I inhibitors effectively and preferentially eliminate Atm(KD/-), but not Atm-proficientor Atm(-/-) leukemia in animal models. These findings identify ATM kinase-domain missense mutations as a potent oncogenic event and a biomarker for Topo-isomerase I inhibitor based therapy.

Alteration of Escherichia coli topoisomerase IV conformation upon enzyme binding to positively supercoiled DNA.

PubMed

Crisona, Nancy J; Cozzarelli, Nicholas R

2006-07-14

Escherichia coli topoisomerase IV (topo IV) is an essential enzyme that unlinks the daughter chromosomes for proper segregation at cell division. In vitro, topo IV readily distinguishes between the two possible chiralities of crossing segments in a DNA substrate. The enzyme relaxes positive supercoils and left-handed braids 20 times faster, and with greater processivity, than negative supercoils and right-handed braids. Here, we used chemical cross-linking of topo IV to demonstrate that enzyme bound to positively supercoiled DNA is in a different conformation from that bound to other forms of DNA. Using three different reagents, we observed novel cross-linked species of topo IV when positively supercoiled DNA was in the reaction. We show that the ParE subunits are in close enough proximity to be cross-linked only when the enzyme is bound to positively supercoiled DNA. We suggest that the altered conformation reflects efficient binding by topo IV of the two DNA segments that participate in the strand passage reaction.

Topos quantum theory on quantization-induced sheaves

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

Nakayama, Kunji, E-mail: nakayama@law.ryukoku.ac.jp

2014-10-15

In this paper, we construct a sheaf-based topos quantum theory. It is well known that a topos quantum theory can be constructed on the topos of presheaves on the category of commutative von Neumann algebras of bounded operators on a Hilbert space. Also, it is already known that quantization naturally induces a Lawvere-Tierney topology on the presheaf topos. We show that a topos quantum theory akin to the presheaf-based one can be constructed on sheaves defined by the quantization-induced Lawvere-Tierney topology. That is, starting from the spectral sheaf as a state space of a given quantum system, we construct sheaf-basedmore » expressions of physical propositions and truth objects, and thereby give a method of truth-value assignment to the propositions. Furthermore, we clarify the relationship to the presheaf-based quantum theory. We give translation rules between the sheaf-based ingredients and the corresponding presheaf-based ones. The translation rules have “coarse-graining” effects on the spaces of the presheaf-based ingredients; a lot of different proposition presheaves, truth presheaves, and presheaf-based truth-values are translated to a proposition sheaf, a truth sheaf, and a sheaf-based truth-value, respectively. We examine the extent of the coarse-graining made by translation.« less

Histone Deacetylase Inhibitors Trichostatin A and MCP30 Relieve Benzene-Induced Hematotoxicity via Restoring Topoisomerase IIα.

PubMed

Chen, Jingjing; Zheng, Zhouyi; Chen, Yi; Li, Jiaqi; Qian, Shanhu; Shi, Yifen; Sun, Lan; Han, Yixiang; Zhang, Shenghui; Yu, Kang

2016-01-01

Dysfunction of histone acetylation inhibits topoisomerase IIα (Topo IIα), which is implicated in benzene-induced hematotoxicity in patients with chronic benzene exposure. Whether histone deacetylase (HDAC) inhibitors can relieve benzene-induced hematotoxicity remains unclear. Here we showed that hydroquinone, a main metabolite of benzene, increased the HDAC activity, decreased the Topo IIα expression and induced apoptosis in human bone marrow mononuclear cells in vitro, and treatment with two HDAC inhibitors, namely trichostatin A (TSA) or a mixture of ribosome-inactivating proteins MCP30, almost completely reversed these effects. We further established a benzene poisoning murine model by inhaling benzene vapor in a container and found that benzene poisoning decreased the expression and activity of Topo IIα, and impaired acetylation of histone H4 and H3. The analysis of regulatory factors of Topo IIα promoter found that benzene poisoning decreased the mRNA levels of SP1 and C-MYB, and increased the mRNA level of SP3. Both TSA and MCP30 significantly enhanced the acetylation of histone H3 and H4 in Topo IIα promoter and increased the expression and activity of Topo IIα in benzene poisoning mice, which contributed to relieve the symptoms of hematotoxicity. Thus, treatment with HDAC inhibitors represents an attractive approach to reduce benzene-induced hematotoxicity.

A “Double-Edged” Scaffold: Antitumor Power within the 
Antibacterial Quinolone

PubMed Central

Bisacchi, Gregory S.; Hale, Michael R.

2016-01-01

In the late 1980s, reports emerged describing experimental antibacterial quinolones having significant potency against eukaryotic Type II topoisomerases (topo II) and showing cytotoxic activity against tumor cell lines. As a result, several pharmaceutical companies initiated quinolone anticancer programs to explore the potential of this class in comparison to conventional human topo II inhibiting antitumor drugs such as doxorubicin and etoposide. In this review, we present a modern re-evaluation of the anticancer potential of the quinolone class in the context of today’s predominantly pathway-based (rather than cytotoxicity-based) oncology drug R&D environment. The quinolone eukaryotic SAR is comprehensively discussed, contrasted with the corresponding prokaryotic data, and merged with recent structural biology information which is now beginning to help explain the basis for that SAR. Quinolone topo II inhibitors appear to be much less susceptible to efflux-mediated resistance, a current limitation of therapy with conventional agents. Recent advances in the biological understanding of human topo II isoforms suggest that significant progress might now be made in overcoming two other treatment-limiting disadvantages of conventional topo II inhibitors, namely cardiotoxicity and drug-induced secondary leukemias. We propose that quinolone class topo II inhibitors could have a useful future therapeutic role due to the continued need for effective topo II drugs in many cancer treatment settings, and due to the recent biological and structural advances which can now provide, for the first time, specific guidance for the design of a new class of inhibitors potentially superior to existing agents. PMID:26695512

Tetramethylpyrazine induces SH-SY5Y cell differentiation toward the neuronal phenotype through activation of the PI3K/Akt/Sp1/TopoIIβ pathway.

PubMed

Yan, Yong-Xin; Zhao, Jun-Xia; Han, Shuo; Zhou, Na-Jing; Jia, Zhi-Qiang; Yao, Sheng-Jie; Cao, Cui-Li; Wang, Yan-Ling; Xu, Yan-Nan; Zhao, Juan; Yan, Yun-Li; Cui, Hui-Xian

2015-12-01

Tetramethylpyrazine (TMP) is an active compound extracted from the traditional Chinese medicinal herb Chuanxiong. Previously, we have shown that TMP induces human SH-SY5Y neuroblastoma cell differentiation toward the neuronal phenotype by targeting topoisomeraseIIβ (TopoIIβ), a protein implicated in neural development. In the present study, we aimed to elucidate whether the transcriptional factors specificity protein 1 (Sp1) and nuclear factor Y (NF-Y), in addition to the upstream signaling pathways ERK1/2 and PI3K/Akt, are involved in modulating TopoIIβ expression in the neuronal differentiation process. We demonstrated that SH-SY5Y cells treated with TMP (80μM) terminally differentiated into neurons, characterized by increased neuronal markers, tubulin βIII and microtubule associated protein 2 (MAP2), and increased neurite outgrowth, with no negative effect on cell survival. TMP also increased the expression of TopoIIβ, which was accompanied by increased expression of Sp1 in the differentiated neuron-like cells, whereas NF-Y protein levels remained unchanged following the differentiation progression. We also found that the phosphorylation level of Akt, but not ERK1/2, was significantly increased as a result of TMP stimulation. Furthermore, as established by chromatin immunoprecipitation (ChIP) assay, activation of the PI3K/Akt pathway increased Sp1 binding to the promoter of the TopoIIβ gene. Blockage of PI3K/Akt was shown to lead to subsequent inhibition of TopoIIβ expression and neuronal differentiation. Collectively, the results indicate that the PI3K/Akt/Sp1/TopoIIβ signaling pathway is necessary for TMP-induced neuronal differentiation. Our findings offer mechanistic insights into understanding the upstream regulation of TopoIIβ in neuronal differentiation, and suggest potential applications of TMP both in neuroscience research and clinical practice to treat relevant diseases of the nervous system. Copyright © 2015 Elsevier GmbH. All rights reserved.

DNA Topoisomerase IB as a Potential Ionizing Radiation Exposure and Dose Biomarker.

PubMed

Daudee, Rotem; Gonen, Rafi; German, Uzi; Orion, Itzhak; Alfassi, Zeev B; Priel, Esther

2018-06-01

In radiation exposure scenarios where physical dosimetry is absent or inefficient, dose estimation must rely on biological markers. A reliable biomarker is of utmost importance in correlating biological system changes with radiation exposure. Human DNA topoisomerase ІB (topo І) is a ubiquitous nuclear enzyme, which is involved in essential cellular processes, including transcription, DNA replication and DNA repair, and is the target of anti-cancer drugs. It has been shown that the cellular activity of this enzyme is significantly sensitive to various DNA lesions, including radiation-induced DNA damages. Therefore, we investigated the potential of topo I as a biomarker of radiation exposure and dose. We examined the effect of exposure of different human cells to beta, X-ray and gamma radiation on the cellular catalytic activity of topo I. The results demonstrate a significant reduction in the DNA relaxation activity of topo I after irradiation and the level of the reduction was correlated with radiation dose. In normal human peripheral blood lymphocytes, exposure for 3 h to an integral dose of 0.065 mGy from tritium reduced the enzyme activity to less than 25%. In MG-63 osteoblast-like cells and in human pulmonary fibroblast (HPF) cells exposed to gamma radiation from a 60 Co source (up to 2 Gy) or to X rays (up to 2.8 Gy), a significant decrease in topo I catalytic activity was also observed. We observed that the enzyme-protein level was not altered but was partially posttranslational modified by ADP-ribosylation of the enzyme protein that is known to reduce topo I activity. The results of this study suggest that the decrease in the cellular topo I catalytic activity after low-dose exposure to different radiation types may be considered as a novel biomarker of ionizing radiation exposure and dose. For this purpose, a suitable ELISA-based method for large-scale analysis of radiation-induced topo I modification is under development.

Rac1 Protein Signaling Is Required for DNA Damage Response Stimulated by Topoisomerase II Poisons*

PubMed Central

Huelsenbeck, Stefanie C.; Schorr, Anne; Roos, Wynand P.; Huelsenbeck, Johannes; Henninger, Christian; Kaina, Bernd; Fritz, Gerhard

2012-01-01

To investigate the potency of the topoisomerase II (topo II) poisons doxorubicin and etoposide to stimulate the DNA damage response (DDR), S139 phosphorylation of histone H2AX (γH2AX) was analyzed using rat cardiomyoblast cells (H9c2). Etoposide caused a dose-dependent increase in the γH2AX level as shown by Western blotting. By contrast, the doxorubicin response was bell-shaped with high doses failing to increase H2AX phosphorylation. Identical results were obtained by immunohistochemical analysis of γH2AX focus formation, comet assay-based DNA strand break analysis, and measuring the formation of the topo II-DNA cleavable complex. At low dose, doxorubicin activated ataxia telangiectasia mutated (ATM) but not ATM and Rad3-related (ATR). Both the lipid-lowering drug lovastatin and the Rac1-specific inhibitor NSC23766 attenuated doxorubicin- and etoposide-stimulated H2AX phosphorylation, induction of DNA strand breaks, and topo II-DNA complex formation. Lovastatin and NSC23766 acted in an additive manner. They did not attenuate doxorubicin-induced increase in p-ATM and p-Chk2 levels. DDR stimulated by topo II poisons was partially blocked by inhibition of type I p21-associated kinases. DDR evoked by the topoisomerase I poison topotecan remained unaffected by lovastatin. The data show that the mechanisms involved in DDR stimulated by topo II poisons are agent-specific with anthracyclines lacking DDR-stimulating activity at high doses. Pharmacological inhibition of Rac1 signaling counteracts doxorubicin- and etoposide-stimulated DDR by disabling the formation of the topo II-DNA cleavable complex. Based on the data we suggest that Rac1-regulated mechanisms are required for DNA damage induction and subsequent activation of the DDR following treatment with topo II but not topo I poisons. PMID:23012366

Rac1 protein signaling is required for DNA damage response stimulated by topoisomerase II poisons.

PubMed

Huelsenbeck, Stefanie C; Schorr, Anne; Roos, Wynand P; Huelsenbeck, Johannes; Henninger, Christian; Kaina, Bernd; Fritz, Gerhard

2012-11-09

To investigate the potency of the topoisomerase II (topo II) poisons doxorubicin and etoposide to stimulate the DNA damage response (DDR), S139 phosphorylation of histone H2AX (γH2AX) was analyzed using rat cardiomyoblast cells (H9c2). Etoposide caused a dose-dependent increase in the γH2AX level as shown by Western blotting. By contrast, the doxorubicin response was bell-shaped with high doses failing to increase H2AX phosphorylation. Identical results were obtained by immunohistochemical analysis of γH2AX focus formation, comet assay-based DNA strand break analysis, and measuring the formation of the topo II-DNA cleavable complex. At low dose, doxorubicin activated ataxia telangiectasia mutated (ATM) but not ATM and Rad3-related (ATR). Both the lipid-lowering drug lovastatin and the Rac1-specific inhibitor NSC23766 attenuated doxorubicin- and etoposide-stimulated H2AX phosphorylation, induction of DNA strand breaks, and topo II-DNA complex formation. Lovastatin and NSC23766 acted in an additive manner. They did not attenuate doxorubicin-induced increase in p-ATM and p-Chk2 levels. DDR stimulated by topo II poisons was partially blocked by inhibition of type I p21-associated kinases. DDR evoked by the topoisomerase I poison topotecan remained unaffected by lovastatin. The data show that the mechanisms involved in DDR stimulated by topo II poisons are agent-specific with anthracyclines lacking DDR-stimulating activity at high doses. Pharmacological inhibition of Rac1 signaling counteracts doxorubicin- and etoposide-stimulated DDR by disabling the formation of the topo II-DNA cleavable complex. Based on the data we suggest that Rac1-regulated mechanisms are required for DNA damage induction and subsequent activation of the DDR following treatment with topo II but not topo I poisons.

Tetramethylpyrazine promotes SH-SY5Y cell differentiation into neurons through epigenetic regulation of Topoisomerase IIβ.

PubMed

Yan, Y; Zhao, J; Cao, C; Jia, Z; Zhou, N; Han, S; Wang, Y; Xu, Y; Zhao, J; Yan, Y; Cui, H

2014-10-10

Tetramethylpyrazine (TMP) is an active compound extracted from the traditional Chinese medicinal herb Chuanxiong. Recently, it has been reported that TMP enhances neurogenesis, and promotes neural stem cell differentiation toward neurons. However, its molecular basis remains unknown. Topoisomerase IIβ (TopoIIβ) is a nuclear enzyme with an essential role in neuronal development. This study aimed to investigate whether TopoIIβ is involved in TMP-induced neuronal differentiation. We examined the effect of TMP on neuronal differentiation of SH-SY5Y cells. It was found that TMP inhibited cell proliferation and induced G0/G1 cell cycle arrest. TMP promoted SH-SY5Y cells to differentiate toward post-mitotic neurons characterized by long, out-branched neurites and up-regulated neuronal markers, microtubule-associated protein 2 (MAP2) and tau. Meanwhile, we demonstrated that TopoIIβ was highly expressed following TMP treatment. To unravel how TMP affects TopoIIβ expression, two chromatin active markers, acetylated histone H3 (Ac-H3) and acetylated histone H4 (Ac-H4) were examined in this study. Our data showed that the levels of Ac-H3 and Ac-H4 were positively correlated with TopoIIβ expression in the processes of neuronal differentiation. We further performed chromatin immunoprecipitation (ChIP) analysis and identified that TMP enhanced the recruitment of Ac-H3 and Ac-H4 to the TopoIIβ gene promoter region. Therefore, we concluded that TMP may stimulate neuronal differentiation of SH-SY5Y cells through epigenetic regulation of TopoIIβ. These results suggest a novel molecular mechanism underlying TMP-promoted neuronal differentiation. Copyright © 2014 IBRO. Published by Elsevier Ltd. All rights reserved.

Expression of multidrug resistance-related protein (MRP-1), lung resistance-related protein (LRP) and topoisomerase-II (TOPO-II) in Wilms' tumor: immunohistochemical study using TMA methodology.

PubMed

Fridman, Eduard; Skarda, Jozef; Pinthus, Jonatan H; Ramon, Jonathan; Mor, Yoran

2008-06-01

MRP-1, LRP and TOPO-II are all associated with protection of the cells from the adverse effects of various chemotherapeutics. The aim of this study was to measure the expression of these proteins in Wilms' tumor (WT). TMA block was constructed from 14 samples of WT's and from xenografts derived from them. Sections of the TMA were used for immunostaining against MRP-1, LRP and TOPO-IIa. All normal kidneys expressed MRP-1 but were either weakly or negatively stained for LRP and TOPO-IIa. In WT samples, MRP-1 was universally expressed, exclusively in the tubular component, while there was no expression of LRP and TOPO-IIa showed heterogeneous distribution. The xenografts varied in their MRP-1 and TOPO-IIa expression and exhibited weak/negative staining of LRP. This study shows that although all the proteins evaluated, had different expression patterns in the tumor samples, the most prominent changes in expression were found for MRP-1. The exact clinical implications of these changes in expression and their relevance to the resistance of these tumors to chemotherapy requires further investigation. The finding of different expression profiles for the multidrug resistance proteins in the original WT's and their xenografts suggests that the results of animal cancer models may be difficult to interpret.

Histone Deacetylase Inhibitors Trichostatin A and MCP30 Relieve Benzene-Induced Hematotoxicity via Restoring Topoisomerase IIα

PubMed Central

Chen, Yi; Li, Jiaqi; Qian, Shanhu; Shi, Yifen; Sun, Lan; Han, Yixiang; Zhang, Shenghui; Yu, Kang

2016-01-01

Dysfunction of histone acetylation inhibits topoisomerase IIα (Topo IIα), which is implicated in benzene-induced hematotoxicity in patients with chronic benzene exposure. Whether histone deacetylase (HDAC) inhibitors can relieve benzene-induced hematotoxicity remains unclear. Here we showed that hydroquinone, a main metabolite of benzene, increased the HDAC activity, decreased the Topo IIα expression and induced apoptosis in human bone marrow mononuclear cells in vitro, and treatment with two HDAC inhibitors, namely trichostatin A (TSA) or a mixture of ribosome-inactivating proteins MCP30, almost completely reversed these effects. We further established a benzene poisoning murine model by inhaling benzene vapor in a container and found that benzene poisoning decreased the expression and activity of Topo IIα, and impaired acetylation of histone H4 and H3. The analysis of regulatory factors of Topo IIα promoter found that benzene poisoning decreased the mRNA levels of SP1 and C-MYB, and increased the mRNA level of SP3. Both TSA and MCP30 significantly enhanced the acetylation of histone H3 and H4 in Topo IIα promoter and increased the expression and activity of Topo IIα in benzene poisoning mice, which contributed to relieve the symptoms of hematotoxicity. Thus, treatment with HDAC inhibitors represents an attractive approach to reduce benzene-induced hematotoxicity. PMID:27058040

Topoisomerase II Inhibitors and Poisons, and the Influence of Cell Cycle Checkpoints.

PubMed

D Arcy, Nicholas; Gabrielli, Brian

2017-01-01

Interactions between the decatenation checkpoint and Topoisomerase II (TopoII) are vital for maintaining integrity of the genome. Agents that target this enzyme have been in clinical use in cancer therapy for over 30 years with great success. The types of compounds that have been developed to target TopoII are broadly divided into poisons and catalytic inhibitors. The TopoII poisons are in clinical use as anti-cancer therapies, although in common to most chemotherapeutic agents, they display considerable normal tissue toxicity. Inhibition of the TopoIIb isoform has been implicated in this cytotoxicity. Response to TopoII active agents is determined by several factors, but cell cycle checkpoints play a large role in sensitivity and resistance. The G2/M phase checkpoints are of particular importance in considering the effectiveness of these drugs and are reviewed in this article. Functionality of the ATM dependent decatenation checkpoint may represent a new avenue for selective cancer therapy. Here we review the function of TopoII, the anti-cancer mechanisms and limitations of current catalytic inhibitors and poisons, and their influence on cell cycle checkpoints. We will also assess potential new mechanisms for targeting this enzyme to limit normal tissue toxicity, and how the cell cycle checkpoint triggered by these drugs may provide an alternative and possibly better target for novel therapies. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Topoisomerase expression and amplification in solid tumours: Analysis of 24,262 patients

PubMed Central

Heestand, Gregory M.; Schwaederle, Maria; Gatalica, Zoran; Arguello, David; Kurzrock, Razelle

2017-01-01

Background Topoisomerase I (TOPO1) and topoisomerase IIα (TOP2A) are specific targets of multiple chemotherapy drugs. Increased expression of TOPO1 protein and amplification of the TOP2A gene have been associated with treatment response in colorectal and breast cancers, respectively. TOPO1 and TOP2A may be potential therapeutic targets in other malignancies as well. Summary of methods We analysed TOPO1 protein expression and TOP2A gene amplification in patients (n = 24,262 specimens) with diverse cancers. Since HER2 and TOP2A co-amplification have been investigated for predictive value regarding anthracycline benefit, we analysed specimens for HER2 amplification as well. Results Overexpressed TOPO1 protein was present in 51% of the tumours. Four percent of the tumours had TOP2A amplification, with gallbladder tumours and gastroesophageal/oesophageal tumours having rates over 10%. Overall, 4903 specimens were assessed for both TOP2A and HER2 amplification; 129 (2.6%) had co-amplification. High rates (>40%) of HER2 amplification were seen in patients with TOP2A amplification in breast, ovarian, gastroesophageal/oesophageal and pancreatic cancer. Conclusion Our data indicate that increased TOPO1 expression and TOP2A amplification, as well as HER2 co-alterations, are present in multiple malignancies. The implications of these observations regarding sensitivity to chemotherapy not traditionally administered to these tumour types merits investigation. PMID:28728050

Renal medullary carcinoma: molecular, pathological and clinical evidence for treatment with topoisomerase-inhibiting therapy.

PubMed

Schaeffer, Edward M; Guzzo, Thomas J; Furge, Kyle A; Netto, George; Westphal, Michael; Dykema, Karl; Yang, Ximing; Zhou, Ming; Teh, Bin Tean; Pavlovich, Christian P

2010-07-01

Aetiology (case series) Level of Evidence 4. To present the molecular rationale and potential clinical benefit of topoisomerase II (TopoII)-inhibiting therapy for renal medullary carcinoma (RMC), a rare but extremely lethal form of kidney cancer that classically afflicts young men with sickle-cell trait. The current therapeutic approach with these aggressive tumours is radical nephrectomy followed by systemic chemotherapy, but the prognosis remains dismal. The whole-genome expression was analysed in four RMC tumours. We also report a case of metastatic RMC in which a complete response was achieved for 9 months using a TopoII-inhibiting therapy. Expanded whole-genome expression analysis showed increases of TopoII in all cases. There was also overall deregulation of DNA remodelling and repair, and an ontological association between RMC and urothelial carcinoma. Using a TopoII-inhibiting agent, there was a complete response for 9 months in a patient with metastatic RMC. This report provides molecular evidence for the rational use of TopoII inhibitors in the treatment of RMC.

Enhanced malignant transformation is accompanied by increased survival recovery after ionizing radiation in Chinese hamster embryo fibroblasts

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

Boothman, D.A.

Transformed Chinese hamster embryo fibroblasts (CHEF), which gradually increase in tumor-forming ability in nude mice, were isolated from normal diploid CHEF/18 cells. Transformed CHEF cells (i.e., T30-4 > 21-2M3 > 21-2 > normal CHEF/18) showed gradual increases in potentially lethal damage (PLD) survival recovery. {beta}-Lapachone and camptothecin, modulators of topoisomerase I (Topo I) activity, not only prevented survival recovery in normal as well as in tumor cells, but enhanced unscheduled DNA synthesis. These seemingly conflicting results are due to the fact that Topo I activity can be modulated by inhibitors to convert single-stranded DNA lesions into double-stranded breaks. Increases inmore » unscheduled DNA synthesis may result from a continual supply of free ends, on which DNA repair processes may act. Altering Topo I activity with modulators appears to increase X-ray lethality via a DNA lesion modification suicide pathway. Cells down-regulate Topo I immediately after ionizing radiation to prevent Topo I-mediated lesion modification and to enhance survival recovery. 16 refs., 3 figs., 1 tab.« less

Tyrosyl-DNA Phosphodiesterase I a critical survival factor for neuronal development and homeostasis

PubMed Central

van Waardenburg, Robert C.A.M.

2016-01-01

Tyrosyl-DNA phosphodiesterase I (TDP1), like most DNA repair associated proteins, is not essential for cell viability. However, dysfunctioning TDP1 or ATM (ataxia telangiectasia mutated) results in autosomal recessive neuropathology with similar phenotypes, including cerebellar atrophy. Dual inactivation of TDP1 and ATM causes synthetic lethality. A TDP1H493R catalytic mutant is associated with spinocerebellar ataxia with axonal neuropathy (SCAN1), and stabilizes the TDP1 catalytic obligatory enzyme-DNA covalent complex. The ATM kinase activates proteins early on in response to DNA damage. Tdp1−/− and Atm−/− mice exhibit accumulation of DNA topoisomerase I-DNA covalent complexes (TOPO1-cc) explicitly in neuronal tissue during development. TDP1 resolves 3’- and 5’-DNA adducts including trapped TOPO1-cc and TOPO1 protease resistant peptide-DNA complex. ATM appears to regulate the response to TOPO1-cc via a noncanonical function by regulating SUMO/ubiquitin-mediated TOPO1 degradation. In conclusion, TDP1 and ATM are critical factors for neuronal cell viability via two independent but cooperative pathways. PMID:27747316

Tyrosyl-DNA Phosphodiesterase I a critical survival factor for neuronal development and homeostasis.

PubMed

van Waardenburg, Robert C A M

2016-01-01

Tyrosyl-DNA phosphodiesterase I (TDP1), like most DNA repair associated proteins, is not essential for cell viability. However, dysfunctioning TDP1 or ATM (ataxia telangiectasia mutated) results in autosomal recessive neuropathology with similar phenotypes, including cerebellar atrophy. Dual inactivation of TDP1 and ATM causes synthetic lethality. A TDP1H 493 R catalytic mutant is associated with spinocerebellar ataxia with axonal neuropathy (SCAN1), and stabilizes the TDP1 catalytic obligatory enzyme-DNA covalent complex. The ATM kinase activates proteins early on in response to DNA damage. Tdp1-/- and Atm-/- mice exhibit accumulation of DNA topoisomerase I-DNA covalent complexes (TOPO1-cc) explicitly in neuronal tissue during development. TDP1 resolves 3'- and 5'-DNA adducts including trapped TOPO1-cc and TOPO1 protease resistant peptide-DNA complex. ATM appears to regulate the response to TOPO1-cc via a noncanonical function by regulating SUMO/ubiquitin-mediated TOPO1 degradation. In conclusion, TDP1 and ATM are critical factors for neuronal cell viability via two independent but cooperative pathways.

Kinase-dead ATM protein is highly oncogenic and can be preferentially targeted by Topo-isomerase I inhibitors

PubMed Central

Yamamoto, Kenta; Wang, Jiguang; Sprinzen, Lisa; Xu, Jun; Haddock, Christopher J; Li, Chen; Lee, Brian J; Loredan, Denis G; Jiang, Wenxia; Vindigni, Alessandro; Wang, Dong; Rabadan, Raul; Zha, Shan

2016-01-01

Missense mutations in ATM kinase, a master regulator of DNA damage responses, are found in many cancers, but their impact on ATM function and implications for cancer therapy are largely unknown. Here we report that 72% of cancer-associated ATM mutations are missense mutations that are enriched around the kinase domain. Expression of kinase-dead ATM (AtmKD/-) is more oncogenic than loss of ATM (Atm-/-) in mouse models, leading to earlier and more frequent lymphomas with Pten deletions. Kinase-dead ATM protein (Atm-KD), but not loss of ATM (Atm-null), prevents replication-dependent removal of Topo-isomerase I-DNA adducts at the step of strand cleavage, leading to severe genomic instability and hypersensitivity to Topo-isomerase I inhibitors. Correspondingly, Topo-isomerase I inhibitors effectively and preferentially eliminate AtmKD/-, but not Atm-proficientor Atm-/- leukemia in animal models. These findings identify ATM kinase-domain missense mutations as a potent oncogenic event and a biomarker for Topo-isomerase I inhibitor based therapy. DOI: http://dx.doi.org/10.7554/eLife.14709.001 PMID:27304073

Expression of P-gp, MRP, LRP, GST-π and TopoIIα and intrinsic resistance in human lung cancer cell lines.

PubMed

Wang, Jiarui; Zhang, Jinhui; Zhang, Lichuan; Zhao, Long; Fan, Sufang; Yang, Zhonghai; Gao, Fei; Kong, Ying; Xiao, Gary Guishan; Wang, Qi

2011-11-01

This study aimed to determine the relationship between the endogenous levels of P-glycoprotein (P-gp), multidrug resistance-associated protein (MRP), lung resistance-related protein (LRP), glutathione-s-transferase-π (GST‑π) and topoisomerase IIα (TopoIIα) and intrinsic drug resistance in four human lung cancer cell lines, SK-MES-1, SPCA-1, NCI-H-460 and NCI-H-446, of different histological types. The expression of P-gp, MRP, LRP, GST-π and TopoIIα was measured by immunofluorescence, Western blotting and RT-PCR. Drug resistance to cisplatin, doxorubicin and VP-16 was determined using MTT assays. The correlation between expression of the resistance-related proteins and their roles in the resistance to drugs in these cancer cell lines was analyzed. We found that the endogenous levels of P-gp, MRP, LRP, GST-π and TopoIIα in the four cell lines varied. The level of GST-π in the SK-MES-1 cells was the highest, whereas the level of P-gp in the SPCA-1 cells was the lowest. The chemoresistance to cisplatin, doxorubicin and VP-16 in the four cell lines was different. The SPCA-1 cell line was most resistance to cisplatin; SK-MES-1 was most resistance to VP-16; whereas SK-MES-1 was most sensitive to doxorubicin. There was a positive correlation between GST-π expression and resistance to cisplatin, between TopoIIα expression and resistance to VP-16; and a negative correlation was noted between TopoIIα expression and resistance to doxorubicin. In summary, the endogenous expression of P-gp, MRP, LRP, GST-π and TopoIIα was different in the four human lung cancer cell lines of different histological types, and this variance may be associated with the variation in chemosensitivity to cisplatin, doxorubicin and VP-16. Among the related proteins, GST-π may be useful for the prediction of the intrinsic resistance to cisplatin, whereas TopoIIα may be useful to predict resistance to doxorubicin and VP-16 in human lung cancer cell lines.

Clinical associations of anticentromere antibodies and antibodies to topoisomerase I. A study of 355 patients.

PubMed

Weiner, E S; Earnshaw, W C; Senécal, J L; Bordwell, B; Johnson, P; Rothfield, N F

1988-03-01

Anticentromere antibodies (ACA) and anti-topoisomerase I (anti-topo I) were assayed in serum samples from 355 patients: 89 with proximal scleroderma; 54 with CREST syndrome (calcinosis, Raynaud's phenomenon, esophageal dysmotility, sclerodactyly, telangiectasias), without proximal scleroderma; 154 with primary and secondary Raynaud's disease; and 58 with other rheumatic diseases, without Raynaud's disease. Sera from healthy control subjects were also assayed. Using immunoblotting techniques, anti-topo I was detected in 28% of the patients with proximal scleroderma; using immunodiffusion techniques, this antibody was found in only 20% of the same group of patients. Anti-topo I and ACA were found primarily in patients with scleroderma, CREST syndrome, and Raynaud's phenomenon. ACA identified patients with less severe disease, whereas anti-topo I identified patients with skin and cardiac involvement and patients with malignancies.

TopoIIα prevents telomere fragility and formation of ultra thin DNA bridges during mitosis through TRF1-dependent binding to telomeres.

PubMed

d'Alcontres, Martina Stagno; Palacios, Jose Alejandro; Mejias, Diego; Blasco, Maria A

2014-01-01

Telomeres are repetitive nucleoprotein structures at the ends of chromosomes. Like most genomic regions consisting of repetitive DNA, telomeres are fragile sites prone to replication fork stalling and generation of chromosomal instability. In particular, abrogation of the TRF1 telomere binding protein leads to stalled replication forks and aberrant telomere structures known as "multitelomeric signals". Here, we report that TRF1 deficiency also leads to the formation of "ultra-fine bridges" (UFB) during mitosis, and to an increased time to complete mitosis mediated by the spindle assembly checkpoint proteins (SAC). We find that topoisomerase IIα (TopoIIα), an enzyme essential for resolution of DNA replication intermediates, binds telomeres in a TRF1-mediated manner. Indeed, similar to TRF1 abrogation, TopoIIα downregulation leads to telomere fragility and UFB, suggesting that these phenotypes are due to decreased TopoIIα at telomeres. We find that SAC proteins bind telomeres in vivo, and that this is disrupted upon TRF1 deletion. These findings suggest that TRF1 links TopoIIα and SAC proteins in a pathway that ensures correct telomere replication and mitotic segregation, unveiling how TRF1 protects from telomere fragility and mitotic defects.

Highly efficient organic light-emitting diodes with a quantum dot interfacial layer.

PubMed

Ryu, Seung Yoon; Hwang, Byoung Har; Park, Ki Wan; Hwang, Hyeon Seok; Sung, Jin Woo; Baik, Hong Koo; Lee, Chang Ho; Song, Seung Yong; Lee, Jun Yeob

2009-02-11

Advanced organic light-emitting diodes (OLEDs), based on a multiple structure, were achieved in combination with a quantum dot (QD) interfacial layer. The authors used core/shell CdSe/ZnS QDs passivated with trioctylphosphine oxide (TOPO) and TOPO-free QDs as interlayers. Multiple-structure OLEDs (MOLEDs) with TOPO-free QDs showed higher device efficiency because of a well-defined interfacial monolayer formation. Additionally, the three-unit MOLED showed high performance for device efficiency with double-structured QD interfacial layers due to the enhanced charge balance and recombination probability.

Screening for Natural Inhibitors of Topoisomerases I from Rhamnus davurica by Affinity Ultrafiltration and High-Performance Liquid Chromatography–Mass Spectrometry

PubMed Central

Chen, Guilin; Guo, Mingquan

2017-01-01

Topoisomerase I (Topo I) catalyzes topological interconversion of duplex DNA during DNA replication and transcription, and has been deemed as important antineoplastic targets. In this study, the fraction R.d-60 from ethyl acetate extracts of Rhamnus davurica showed higher inhibitory rates against SGC-7901 and HT-29 compared with the R.d-30 fraction in vitro. However, the specific active components of R.d-60 fraction remain elusive. To this end, a method based on bio-affinity ultrafiltration and high performance liquid chromatography/electrospray mass spectrometry (HPLC- ESI-MS/MS) was developed to rapidly screen and identify the Topo I inhibitors in this fraction. The enrichment factors (EFs) were calculated to evaluate the binding affinities between the bioactive constituents and Topo I. As a result, eight ligands were identified and six of which with higher EFs showed more potential antitumor activity. Furthermore, antiproliferative assays in vitro (IC50 values) with two representative candidates (apigenin, quercetin) against SGC-7901, HT-29 and Hep G2 cells were conducted and further validated. Finally, the structure-activity relationships revealed that flavones contain a C2-C3 double bond of C ring exhibited higher bio-affinities to Topo I than those without it. This integrated method combining Topo I ultrafiltration with HPLC-MS/MS proved to be very efficient in rapid screening and identification of potential Topo I inhibitors from the complex extracts of medicinal plants, and could be further explored as a valuable high-throughput screening platform in the early drug discovery stage. PMID:28919906

Calcium-regulatory proteins as modulators of chemotherapy in human neuroblastoma.

PubMed

Florea, Ana-Maria; Varghese, Elizabeth; McCallum, Jennifer E; Mahgoub, Safa; Helmy, Irfan; Varghese, Sharon; Gopinath, Neha; Sass, Steffen; Theis, Fabian J; Reifenberger, Guido; Büsselberg, Dietrich

2017-04-04

Neuroblastoma (NB) is a pediatric cancer treated with poly-chemotherapy including platinum complexes (e.g. cisplatin (CDDP), carboplatin), DNA alkylating agents, and topoisomerase I inhibitors (e.g. topotecan (TOPO)). Despite aggressive treatment, NB may become resistant to chemotherapy. We investigated whether CDDP and TOPO treatment of NB cells interacts with the expression and function of proteins involved in regulating calcium signaling. Human neuroblastoma cell lines SH-SY5Y, IMR-32 and NLF were used to investigate the effects of CDDP and TOPO on cell viability, apoptosis, calcium homeostasis, and expression of selected proteins regulating intracellular calcium concentration ([Ca2+]i). In addition, the impact of pharmacological inhibition of [Ca2+]i-regulating proteins on neuroblastoma cell survival was studied. Treatment of neuroblastoma cells with increasing concentrations of CDDP (0.1-10 μM) or TOPO (0.1 nM-1 μM) induced cytotoxicity and increased apoptosis in a concentration- and time-dependent manner. Both drugs increased [Ca2+]i over time. Treatment with CDDP or TOPO also modified mRNA expression of selected genes encoding [Ca2+]i-regulating proteins. Differentially regulated genes included S100A6, ITPR1, ITPR3, RYR1 and RYR3. With FACS and confocal laser scanning microscopy experiments we validated their differential expression at the protein level. Importantly, treatment of neuroblastoma cells with pharmacological modulators of [Ca2+]i-regulating proteins in combination with CDDP or TOPO increased cytotoxicity. Thus, our results confirm an important role of calcium signaling in the response of neuroblastoma cells to chemotherapy and suggest [Ca2+]i modulation as a promising strategy for adjunctive treatment.

TopoCad - A unified system for geospatial data and services

NASA Astrophysics Data System (ADS)

Felus, Y. A.; Sagi, Y.; Regev, R.; Keinan, E.

2013-10-01

"E-government" is a leading trend in public sector activities in recent years. The Survey of Israel set as a vision to provide all of its services and datasets online. The TopoCad system is the latest software tool developed in order to unify a number of services and databases into one on-line and user friendly system. The TopoCad system is based on Web 1.0 technology; hence the customer is only a consumer of data. All data and services are accessible for the surveyors and geo-information professional in an easy and comfortable way. The future lies in Web 2.0 and Web 3.0 technologies through which professionals can upload their own data for quality control and future assimilation with the national database. A key issue in the development of this complex system was to implement a simple and easy (comfortable) user experience (UX). The user interface employs natural language dialog box in order to understand the user requirements. The system then links spatial data with alpha-numeric data in a flawless manner. The operation of the TopoCad requires no user guide or training. It is intuitive and self-taught. The system utilizes semantic engines and machine understanding technologies to link records from diverse databases in a meaningful way. Thus, the next generation of TopoCad will include five main modules: users and projects information, coordinates transformations and calculations services, geospatial data quality control, linking governmental systems and databases, smart forms and applications. The article describes the first stage of the TopoCad system and gives an overview of its future development.

US Topo—Topographic maps for the Nation

USGS Publications Warehouse

Fishburn, Kristin A.; Carswell, William J.

2017-06-23

Building on the success of 125 years of mapping, the U.S. Geological Survey created US Topo, a georeferenced digital map produced from The National Map data. US Topo maps are designed to be used like the traditional 7.5-minute quadrangle paper topographic maps for which the U.S. Geological Survey is so well known. However, in contrast to paper-based maps, US Topo maps provide modern technological advantages that support faster, wider public distribution and basic, onscreen geospatial analysis, including the georeferencing capability to display the ground coordinate location as the user moves the cursor around the map.

Ginkgo biloba leaf extract induces DNA damage by inhibiting topoisomerase II activity in human hepatic cells.

PubMed

Zhang, Zhuhong; Chen, Si; Mei, Hu; Xuan, Jiekun; Guo, Xiaoqing; Couch, Letha; Dobrovolsky, Vasily N; Guo, Lei; Mei, Nan

2015-09-30

Ginkgo biloba leaf extract has been shown to increase the incidence in liver tumors in mice in a 2-year bioassay conducted by the National Toxicology Program. In this study, the DNA damaging effects of Ginkgo biloba leaf extract and many of its constituents were evaluated in human hepatic HepG2 cells and the underlying mechanism was determined. A molecular docking study revealed that quercetin, a flavonoid constituent of Ginkgo biloba, showed a higher potential to interact with topoisomerase II (Topo II) than did the other Ginkgo biloba constituents; this in silico prediction was confirmed by using a biochemical assay to study Topo II enzyme inhibition. Moreover, as measured by the Comet assay and the induction of γ-H2A.X, quercetin, followed by keampferol and isorhamnetin, appeared to be the most potent DNA damage inducer in HepG2 cells. In Topo II knockdown cells, DNA damage triggered by Ginkgo biloba leaf extract or quercetin was dramatically decreased, indicating that DNA damage is directly associated with Topo II. DNA damage was also observed when cells were treated with commercially available Ginkgo biloba extract product. Our findings suggest that Ginkgo biloba leaf extract- and quercetin-induced in vitro genotoxicity may be the result of Topo II inhibition.

Ginkgo biloba leaf extract induces DNA damage by inhibiting topoisomerase II activity in human hepatic cells

PubMed Central

Zhang, Zhuhong; Chen, Si; Mei, Hu; Xuan, Jiekun; Guo, Xiaoqing; Couch, Letha; Dobrovolsky, Vasily N.; Guo, Lei; Mei, Nan

2015-01-01

Ginkgo biloba leaf extract has been shown to increase the incidence in liver tumors in mice in a 2-year bioassay conducted by the National Toxicology Program. In this study, the DNA damaging effects of Ginkgo biloba leaf extract and many of its constituents were evaluated in human hepatic HepG2 cells and the underlying mechanism was determined. A molecular docking study revealed that quercetin, a flavonoid constituent of Ginkgo biloba, showed a higher potential to interact with topoisomerase II (Topo II) than did the other Ginkgo biloba constituents; this in silico prediction was confirmed by using a biochemical assay to study Topo II enzyme inhibition. Moreover, as measured by the Comet assay and the induction of γ-H2A.X, quercetin, followed by keampferol and isorhamnetin, appeared to be the most potent DNA damage inducer in HepG2 cells. In Topo II knockdown cells, DNA damage triggered by Ginkgo biloba leaf extract or quercetin was dramatically decreased, indicating that DNA damage is directly associated with Topo II. DNA damage was also observed when cells were treated with commercially available Ginkgo biloba extract product. Our findings suggest that Ginkgo biloba leaf extract- and quercetin-induced in vitro genotoxicity may be the result of Topo II inhibition. PMID:26419945

Functionalization of Cadmium Selenide Quantum Dots with Poly(ethylene glycol): Ligand Exchange, Surface Coverage, and Dispersion Stability.

PubMed

Wenger, Whitney Nowak; Bates, Frank S; Aydil, Eray S

2017-08-22

Semiconductor quantum dots synthesized using rapid mixing of precursors by injection into a hot solution of solvents and surfactants have surface ligands that sterically stabilize the dispersions in nonpolar solvents. Often, these ligands are exchanged to disperse the quantum dots in polar solvents, but quantitative studies of quantum dot surfaces before and after ligand exchange are scarce. We studied exchanging trioctylphosphine (TOP) and trioctylphosphine oxide (TOPO) ligands on as-synthesized CdSe quantum dots dispersed in hexane with a 2000 g/mol thiolated poly(ethylene glycol) (PEG) polymer. Using infrared spectroscopy we quantify the absolute surface concentration of TOP/TOPO and PEG ligands per unit area before and after ligand exchange. While 50-85% of the TOP/TOPO ligands are removed upon ligand exchange, only a few are replaced with PEG. Surprisingly, the remaining TOP/TOPO ligands outnumber the PEG ligands, but these few PEG ligands are sufficient to disperse the quantum dots in polar solvents such as chloroform, tetrahydrofuran, and water. Moreover, as-synthesized quantum dots once easily dispersed in hexane are no longer dispersible in nonpolar solvents after ligand exchange. A subtle coverage-dependent balance between attractive PEG-solvent interactions and repulsive TOP/TOPO-solvent interactions determines the dispersion stability.

Regulation of Hepatic Cholesteryl Ester Transfer Protein Expression and Reverse Cholesterol Transport by Inhibition of DNA Topoisomerase II.

PubMed

Liu, Mengyang; Chen, Yuanli; Zhang, Ling; Wang, Qixue; Ma, Xingzhe; Li, Xiaoju; Xiang, Rong; Zhu, Yan; Qin, Shucun; Yu, Yang; Jiang, Xian-cheng; Duan, Yajun; Han, Jihong

2015-06-05

Cholesteryl ester transfer protein (CETP) transfers cholesteryl esters from high density lipoprotein to triglyceride-rich lipoproteins. CETP expression can be transcriptionally activated by liver X receptor (LXR). Etoposide and teniposide are DNA topoisomerase II (Topo II) inhibitors. Etoposide has been reported to inhibit atherosclerosis in rabbits with un-fully elucidated mechanisms. In this study we determined if Topo II activity can influence cholesterol metabolism by regulating hepatic CETP expression. Inhibition of Topo II by etoposide, teniposide, or Topo II siRNA increased CETP expression in human hepatic cell line, HepG2 cells, which was associated with increased CETP secretion and mRNA expression. Meanwhile, inhibition of LXR expression by LXR siRNA attenuated induction of CETP expression by etoposide and teniposide. Etoposide and teniposide induced LXRα expression and LXRα/β nuclear translocation while inhibiting expression of receptor interacting protein 140 (RIP140), an LXR co-repressor. In vivo, administration of teniposide moderately reduced serum lipid profiles, induced CETP expression in the liver, and activated reverse cholesterol transport in CETP transgenic mice. Our study demonstrates a novel function of Topo II inhibitors in cholesterol metabolism by activating hepatic CETP expression and reverse cholesterol transport. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

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

Shen, Yan; Chen, Wang; Zhao, Baobing

Highlights: • CS1 is a novel nonintercalating topoisomerase IIα poison. • CS1 shows potent in vitro and in vivo antitumor activity. • CS1 shows 6–10-fold less toxicity to normal cells compared with etoposide. • CS1 is not a substrate of P-glycoprotein and multidrug resistance irrelevant. - Abstract: DNA topoisomerase II (Topo II) is an essential nuclear enzyme and a validated target for anticancer agent screening. CS1, a novel 2-phenylnaphthalene, had potent cytotoxicity against nine tested tumor cell lines and showed 6–10-fold less toxicity against normal cell lines compared with etoposide. In addition, CS1 showed potential anti-multidrug resistance capabilities. kDNA decatenation,more » DNA relaxation and cleavage complex assays indicated that CS1 acted as a nonintercalating topoisomerase IIα (Topo IIα) inhibitor by stabilizing the DNA-Topo IIα cleavage complex. CS1 also induced DNA breaks in MDA-MB-231 cells evidenced by comet tails and the accumulation of γH2AX foci. The ability of CS1 in inducing DNA breaks mediated by Topo II resulted in G2/M phase arrest and apoptosis. Moreover, CS1 exhibited dramatic in vivo antitumor activity and lower toxicity compared with etoposide. This work supports the development of CS1 as a promising candidate for the treatment of cancer by targeting Topo IIα.« less

Induction of apoptosis by plumbagin through reactive oxygen species-mediated inhibition of topoisomerase II

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

Kawiak, Anna; Piosik, Jacek; Stasilojc, Grzegorz

2007-09-15

Reactive oxygen species (ROS) have been recognized as key molecules, which can selectively modify proteins and therefore regulate cellular signalling including apoptosis. Plumbagin, a naphthoquinone exhibiting antitumor activity, is known to generate ROS and has been found to inhibit the activity of topoisomerase II (Topo II) through the stabilization of the Topo II-DNA cleavable complex. The objective of this research was to clarify the role of ROS and Topo II inhibition in the induction of apoptosis mediated by plumbagin. As determined by the comet assay, plumbagin induced DNA cleavage in HL-60 cells, whereas in a cell line with reduced Topomore » II activity-HL-60/MX2, the level of DNA damage was significantly decreased. The onset of DNA strand break formation in HL-60 cells was delayed in comparison with the generation of intracellular ROS. In HL-60/MX2 cells, ROS were generated at a similar rate, whereas a significant reduction in the level of DNA damage was detected. The pretreatment of cells with N-acetylcysteine (NAC) attenuated plumbagin-induced DNA damage, pointing out to the involvement of ROS generation in cleavable complex formation. These results suggest that plumbagin-induced ROS does not directly damage DNA but requires the involvement of Topo II. Furthermore, experiments carried out using light spectroscopy indicated no direct interactions between plumbagin and DNA. The induction of apoptosis was significantly delayed in HL-60/MX2 cells indicating the involvement of Topo II inhibition in plumbagin-mediated apoptosis. Thus, these findings strongly suggest ROS-mediated inhibition of Topo II as an important mechanism contributing to the apoptosis-inducing properties of plumbagin.« less

Synthesis, characterization, and hydrogen uptake studies of magnesium nanoparticles by solution reduction method

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

Rather, Sami ullah, E-mail: rathersami@gmail.com

2014-12-15

Graphical abstract: X-ray diffraction (XRD) pattern of magnesium nanoparticles synthesized by solution reduction method with and without TOPO. - Highlights: • Simple and convenient method of preparing Mg nanoparticles. • Characterized by XRD, SEM, FESEM and TEM. • Trioctylphosphine oxide offers a greater control over the size of the particles. • Hydrogen uptake of samples at different temperatures and pressure of 4.5 MPa. - Abstract: Facile and simple, surfactant-mediated solution reduction method was used to synthesize monodisperse magnesium nanoparticles. Little amount of magnesium oxide nanoparticles were also formed due to the presence of TOPO and easy oxidation of magnesium, eventhough,more » all precautions were taken to avoid oxidation of the sample. Precise size control of particles was achieved by carefully varying the concentration ratio of two different types of surfactants, – trioctylphosphine oxide and hexadecylamine. Recrystallized magnesium nanoparticle samples with and without TOPO were analyzed by X-ray diffraction, scanning electron microscope, field emission scanning electron microscope, and transmission electron microscope. The peak diameters of particles were estimated from size distribution analysis of the morphological data. The particles synthesized in the presence and absence of TOPO found to have diameters 46.5 and 34.8 nm, respectively. This observed dependence of particle size on the presence of TOPO offers a convenient method to control the particle size by simply using appropriate surfactant concentrations. Exceptional enhancement in hydrogen uptake and kinetics in synthesized magnesium nanoparticles as compared to commercial magnesium sample was due to the smaller particle size and improved morphology. Overall hydrogen uptake not affected by the little variation in particle size with and without TOPO.« less

Calcium-regulatory proteins as modulators of chemotherapy in human neuroblastoma

PubMed Central

Florea, Ana-Maria; Varghese, Elizabeth; McCallum, Jennifer E.; Mahgoub, Safa; Helmy, Irfan; Varghese, Sharon; Gopinath, Neha; Sass, Steffen; Theis, Fabian J.; Reifenberger, Guido; Büsselberg, Dietrich

2017-01-01

Neuroblastoma (NB) is a pediatric cancer treated with poly-chemotherapy including platinum complexes (e.g. cisplatin (CDDP), carboplatin), DNA alkylating agents, and topoisomerase I inhibitors (e.g. topotecan (TOPO)). Despite aggressive treatment, NB may become resistant to chemotherapy. We investigated whether CDDP and TOPO treatment of NB cells interacts with the expression and function of proteins involved in regulating calcium signaling. Human neuroblastoma cell lines SH-SY5Y, IMR-32 and NLF were used to investigate the effects of CDDP and TOPO on cell viability, apoptosis, calcium homeostasis, and expression of selected proteins regulating intracellular calcium concentration ([Ca2+]i). In addition, the impact of pharmacological inhibition of [Ca2+]i-regulating proteins on neuroblastoma cell survival was studied. Treatment of neuroblastoma cells with increasing concentrations of CDDP (0.1−10 μM) or TOPO (0.1 nM−1 μM) induced cytotoxicity and increased apoptosis in a concentration- and time-dependent manner. Both drugs increased [Ca2+]i over time. Treatment with CDDP or TOPO also modified mRNA expression of selected genes encoding [Ca2+]i-regulating proteins. Differentially regulated genes included S100A6, ITPR1, ITPR3, RYR1 and RYR3. With FACS and confocal laser scanning microscopy experiments we validated their differential expression at the protein level. Importantly, treatment of neuroblastoma cells with pharmacological modulators of [Ca2+]i-regulating proteins in combination with CDDP or TOPO increased cytotoxicity. Thus, our results confirm an important role of calcium signaling in the response of neuroblastoma cells to chemotherapy and suggest [Ca2+]i modulation as a promising strategy for adjunctive treatment. PMID:28206967

TopoToolbox: using sensor topography to calculate psychologically meaningful measures from event-related EEG/MEG.

PubMed

Tian, Xing; Poeppel, David; Huber, David E

2011-01-01

The open-source toolbox "TopoToolbox" is a suite of functions that use sensor topography to calculate psychologically meaningful measures (similarity, magnitude, and timing) from multisensor event-related EEG and MEG data. Using a GUI and data visualization, TopoToolbox can be used to calculate and test the topographic similarity between different conditions (Tian and Huber, 2008). This topographic similarity indicates whether different conditions involve a different distribution of underlying neural sources. Furthermore, this similarity calculation can be applied at different time points to discover when a response pattern emerges (Tian and Poeppel, 2010). Because the topographic patterns are obtained separately for each individual, these patterns are used to produce reliable measures of response magnitude that can be compared across individuals using conventional statistics (Davelaar et al. Submitted and Huber et al., 2008). TopoToolbox can be freely downloaded. It runs under MATLAB (The MathWorks, Inc.) and supports user-defined data structure as well as standard EEG/MEG data import using EEGLAB (Delorme and Makeig, 2004).

CES2, ABCG2, TS and Topo-I primary and synchronous metastasis expression and clinical outcome in metastatic colorectal cancer patients treated with first-line FOLFIRI regimen.

PubMed

Silvestris, Nicola; Simone, Giovanni; Partipilo, Giulia; Scarpi, Emanuela; Lorusso, Vito; Brunetti, Anna Elisabetta; Maiello, Evaristo; Paradiso, Angelo; Mangia, Anita

2014-09-05

Enzymatic activation of irinotecan (CPT-11) is due to carboxylesterase (CES), and its pharmacological behavior is influenced by drug resistance-related proteins. We previously reported that the clinical response and prognosis of metastatic colorectal cancer (mCRC) patients did not differ in tumors with different thymidylate synthase (TS) or topoisomerase-I (Topo-I) expression. Using immunohistochemistry (IHC), we evaluated the biological role of CES2 and the expression of breast cancer resistance protein (BCRP/ABCG2) in 58 consecutive mCRC patients, who had undergone a first-line CPT-11/5-FU/leucovirin (FOLFIRI) regimen. The expression of these proteins was also examined in a group of synchronous lymph nodes and liver metastases. Furthermore, all samples were revaluated for TS and Topo-I expression. High expression of CES2, ABCG2, TS and Topo-I was observed in 55%, 56%, 38% and 49% of patients, respectively. There was a significant association between high TS and high ABCG2 expression (p = 0.049). Univariate analysis showed that only TS expression significantly impacted on time to progression (p = 0.005). Moreover, Cox' multivariate analysis revealed that TS expression was significantly associated with overall survival (p = 0.01). No significant correlation was found between investigated markers expression and clinical response. Topo-I expression resulted in being significantly higher in liver metastases with respect to the corresponding primary tumors (p < 0.0001), emphasizing the role of Topo-I expression in metastatic cancer biology. In primary tumor tissues, CES2 expression tended to be higher than that observed in liver metastasis tissues (p = 0.05). These preliminary data may suggest CES2 over-expression as a potential marker of malignant phenotype. In light of these findings, we suggest that Topo-I expression together with TS expression could be associated with metastatic progression of CRC. Further studies are warranted with the aim of evaluating the potential predictive and prognostic role of CES2 and ABCG2 in larger series of patients.

Using StorAge Selection Functions to Improve Simulation of Groundwater Nitrate Lag Times in the SWAT Modeling Framework.

NASA Astrophysics Data System (ADS)

Wilusz, D. C.; Fuka, D.; Cho, C.; Ball, W. P.; Easton, Z. M.; Harman, C. J.

2017-12-01

Intensive agriculture and atmospheric deposition have dramatically increased the input of reactive nitrogen into many watersheds worldwide. Reactive nitrogen can leach as nitrate into groundwater, which is stored and eventually released over years to decades into surface waters, potentially degrading water quality. To simulate the fate and transport of groundwater nitrate, many researchers and practitioners use the Soil and Water Assessment Tool (SWAT) or an enhanced version of SWAT that accounts for topographically-driven variable source areas (TopoSWAT). Both SWAT and TopoSWAT effectively assume that nitrate in the groundwater reservoir is well-mixed, which is known to be a poor assumption at many sites. In this study, we describe modifications to TopoSWAT that (1) relax the assumption of groundwater well-mixedness, (2) more flexibly parameterize groundwater transport as a time-varying distribution of travel times using the recently developed theory of rank StorAge Selection (rSAS) functions, and (3) allow for groundwater age to be represented by position on the hillslope or hydrological distance from the stream. The approach conceptualizes the groundwater aquifer as a population of water parcels entering as recharge with a particular nitrate concentration, aging as they move through storage, and eventually exiting as baseflow. The rSAS function selects the distribution of parcel ages that exit as baseflow based on a parameterized probability distribution; this distribution can be adjusted to preferentially select different distributions of young and old parcels in storage so as to reproduce (in principle) any form of transport. The modified TopoSWAT model (TopoSWAT+rSAS) is tested at a small agricultural catchment in the Eastern Shore, MD with an extensive hydrologic and hydrochemical data record for calibration and evaluation. The results examine (1) the sensitivity of TopoSWAT+rSAS modeling of nitrate transport to assumptions about the distribution of travel times of the groundwater aquifer, (2) which travel times are most likely at our study site based on available data, and (3) how TopoSWAT+rSAS performs and can be applied to other catchments.

Mechanism of Growth Inhibition of Human Cancer Cells by Conjugated Eicosapentaenoic Acid, an Inhibitor of DNA Polymerase and Topoisomerase

PubMed Central

Yonezawa, Yuko; Yoshida, Hiromi; Mizushina, Yoshiyuki

2007-01-01

DNA topoisomerases (topos) and DNA polymerases (pols) are involved in many aspects of DNA metabolism such as replication reactions. We found that long chain unsaturated fatty acids such as polyunsaturated fatty acids (PUFA) (i.e., eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA)) inhibited the activities of eukaryotic pols and topos in vitro, and the inhibitory effect of conjugated fatty acids converted from EPA and DHA (cEPA and cDHA) on pols and topos was stronger than that of normal EPA and DHA. cEPA and cDHA did not affect the activities of plant and prokaryotic pols or other DNA metabolic enzymes tested. cEPA was a stronger inhibitor than cDHA with IC50 values for mammalian pols and human topos of 11.0 – 31.8 and 0.5 – 2.5 μM, respectively. cEPA inhibited the proliferation of two human leukemia cell lines, NALM-6, which is a p53-wild type, and HL-60, which is a p53-null mutant, and the inhibitory effect was stronger than that of normal EPA. In both cell lines, cEPA arrested in the G1 phase, and increased cyclin E protein levels, indicating that it blocks the primary step of in vivo DNA replication by inhibiting the activity of replicative pols rather than topos. DNA replication-related proteins, such as RPA70, ATR and phosphorylated-Chk1/2, were increased by cEPA treatment in the cell lines, suggesting that cEPA led to DNA replication fork stress inhibiting the activities of pols and topos, and the ATR-dependent DNA damage response pathway could respond to the inhibitor of DNA replication. The compound induced cell apoptosis through both p53-dependent and p53-independent pathways in cell lines NALM-6 and HL-60, respectively. These results suggested the therapeutic potential of conjugated PUFA, such as cEPA, as a leading anti-cancer compound that inhibited pols and topos activities.

Topoisomerase II Mediates Meiotic Crossover Interference

PubMed Central

Zhang, Liangran; Wang, Shunxin; Yin, Shen; Hong, Soogil; Kim, Keun P.; Kleckner, Nancy

2014-01-01

Summary Spatial patterning is a ubiquitous feature of biological systems. Meiotic crossovers provide an interesting example, defined by the classical phenomenon of crossover interference. Here, analysis of crossover patterns in budding yeast identifies a molecular pathway for interference. Topoisomerase II (Topo II) plays a central role, thus identifying a new function for this critical molecule. SUMOylation [of TopoII and axis component Red1] and ubiquitin-mediated removal of SUMOylated proteins are also required. These and other findings support the hypothesis that crossover interference involves accumulation, relief and redistribution of mechanical stress along the protein/DNA meshwork of meiotic chromosome axes, with TopoII required to adjust spatial relationships among DNA segments. PMID:25043020

Monitoring and risk assessment of the spruce bark beetle, Ips typographus

Treesearch

S. Netherer; J. Pennerstorfer; P. Baier; E. Fuhrer; A. Schopf

2003-01-01

A model describing development of the spruce bark beetle, Ips typographus, combines topo-climatic aspects of the terrain with eco-physiological aspects of the bark beetle. By correlating air temperature and solar irradiation measured at a reference station, along with topographic data and microclimatic conditions of terrain plots, topo-climatic...

Impact of DEM and soils on topographic index, as used in TopoSWAT

USDA-ARS?s Scientific Manuscript database

A topographic index (TI), comprised of slope and upstream contributing area, is used in TopoSWAT to help account for variable source runoff and soil moisture. The level of precision in the GIS input data layers can substantially impact the calculations of the topographic index layer and affect the a...

Pharmacophore Hybridization To Discover Novel Topoisomerase II Poisons with Promising Antiproliferative Activity.

PubMed

Ortega, Jose Antonio; Riccardi, Laura; Minniti, Elirosa; Borgogno, Marco; Arencibia, Jose M; Greco, Maria L; Minarini, Anna; Sissi, Claudia; De Vivo, Marco

2018-02-08

We used a pharmacophore hybridization strategy to combine key structural elements of merbarone and etoposide and generated new type II topoisomerase (topoII) poisons. This first set of hybrid topoII poisons shows promising antiproliferative activity on human cancer cells, endorsing their further exploration for anticancer drug discovery.

Publications - PIR 2002-2 | Alaska Division of Geological & Geophysical

Science.gov Websites

for more information. Quadrangle(s): Philip Smith Mountains Bibliographic Reference Harris, E.E., Mull , scale 1:63,360 (14.0 M) Digital Geospatial Data Digital Geospatial Data Philip Smith Mountains: Geologic Smith Mountains: Topo Data Download psm-topo Shapefile 11.5 M Metadata - Read me Keywords Alaska, State

Cumulative River Dynamic Assessment using Topo-Hydrographical High Definition Surveying in the Danube River area - Km 347-Km344

NASA Astrophysics Data System (ADS)

Nichersu, Iulian; Mierla, Marian; Trifanov, Cristian

2013-04-01

Cumulative River Dynamic Assessment using Topo-Hydrographical High Definition Surveying in the Danube River area - Km 347-Km344 Iulian NICHERSU, Cristian TRIFANOV, Marian MIERLA The purpose of this paper is to depict and illustrate the benefits of Topo-Hydrographical High Definition Surveying (THHDS), also known as 3D multi-beam scanning, on a topo-hydrological survey application in Danube Valley. This research investigates the evolution of Danube river dynamics. We start with cross-sections made in 2002, 2007 and 2010 in this area and we coupled with 2012 THHDS. 3D multi-beam scanning method of data acquisition improve the spatial hydrological model and offers better dynamics assessment for future studies, considering that this area is carried out dredging works to improve navigation conditions - THHDS technique true modeling capabilities have applications in hydrotechnical works. Dynamics stands out on all 3 axes and cartographic documents have used both the 1930, 1950, and orthophoto images taken during flight to obtain the 3D model of the floodplain through LIDAR method, in 2007.

TopoToolbox: Using Sensor Topography to Calculate Psychologically Meaningful Measures from Event-Related EEG/MEG

PubMed Central

Tian, Xing; Poeppel, David; Huber, David E.

2011-01-01

The open-source toolbox “TopoToolbox” is a suite of functions that use sensor topography to calculate psychologically meaningful measures (similarity, magnitude, and timing) from multisensor event-related EEG and MEG data. Using a GUI and data visualization, TopoToolbox can be used to calculate and test the topographic similarity between different conditions (Tian and Huber, 2008). This topographic similarity indicates whether different conditions involve a different distribution of underlying neural sources. Furthermore, this similarity calculation can be applied at different time points to discover when a response pattern emerges (Tian and Poeppel, 2010). Because the topographic patterns are obtained separately for each individual, these patterns are used to produce reliable measures of response magnitude that can be compared across individuals using conventional statistics (Davelaar et al. Submitted and Huber et al., 2008). TopoToolbox can be freely downloaded. It runs under MATLAB (The MathWorks, Inc.) and supports user-defined data structure as well as standard EEG/MEG data import using EEGLAB (Delorme and Makeig, 2004). PMID:21577268

Cloning and characterization of a cDNA encoding topoisomerase II in pea and analysis of its expression in relation to cell proliferation.

PubMed

Reddy, M K; Nair, S; Tewari, K K; Mudgil, Y; Yadav, B S; Sopory, S K

1999-09-01

We have isolated and sequenced four overlapping cDNA clones to identify the full-length cDNA for topoisomerase II (PsTopII) from pea. Using degenerate primers, based on the conserved amino acid sequences of other eukaryotic type II topoisomerases, a 680 bp fragment was PCR-amplified with pea cDNA as template. This fragment was used as a probe to screen an oligo-dT-primed pea cDNA library. A partial cDNA clone was isolated that was truncated at the 3' end. RACE-PCR was employed to isolate the remaining portion of the gene. The total size of PsTopII is 4639 bp with an open reading frame of 4392 bp. The deduced amino acid sequence shows a strong homology to other eukaryotic topoisomerase II (topo II) at the N-terminus end. The topo II transcript was abundant in proliferative tissues. We also show that the level of topo II transcripts could be stimulated by exogenous application of growth factors that induced proliferation in vitro cultures. Light irradiation to etiolated tissue strongly stimulated the expression of topo II. These results suggest that topo II gene expression is up-regulated in response to light and hormones and correlates with cell proliferation. Besides, we have also isolated and analysed the 5'-flanking region of the pea TopII gene. This is first report on the isolation of a putative promoter for topoisomerase II from plants.

In vitro inhibition of African swine fever virus-topoisomerase II disrupts viral replication.

PubMed

Freitas, Ferdinando B; Frouco, Gonçalo; Martins, Carlos; Leitão, Alexandre; Ferreira, Fernando

2016-10-01

African swine fever virus (ASFV) is the etiological agent of a highly-contagious and fatal disease of domestic pigs, leading to serious socio-economic impact in affected countries. To date, neither a vaccine nor a selective anti-viral drug are available for prevention or treatment of African swine fever (ASF), emphasizing the need for more detailed studies at the role of ASFV proteins involved in viral DNA replication and transcription. Notably, ASFV encodes for a functional type II topoisomerase (ASFV-Topo II) and we recently showed that several fluoroquinolones (bacterial DNA topoisomerase inhibitors) fully abrogate ASFV replication in vitro. Here, we report that ASFV-Topo II gene is actively transcribed throughout infection, with transcripts being detected as early as 2 hpi and reaching a maximum peak concentration around 16 hpi, when viral DNA synthesis, transcription and translation are more active. siRNA knockdown experiments showed that ASFV-Topo II plays a critical role in viral DNA replication and gene expression, with transfected cells presenting lower viral transcripts (up to 89% decrease) and reduced cytopathic effect (-66%) when compared to the control group. Further, a significant decrease in the number of both infected cells (75.5%) and viral factories per cell and in virus yields (up to 99.7%, 2.5 log) was found only in cells transfected with siRNA targeting ASFV-Topo II. We also demonstrate that a short exposure to enrofloxacin during the late phase of infection (from 15 to 1 hpi) induces fragmentation of viral genomes, whereas no viral genomes were detected when enrofloxacin was added from the early phase of infection (from 2 to 16 hpi), suggesting that fluoroquinolones are ASFV-Topo II poisons. Altogether, our results demonstrate that ASFV-Topo II enzyme has an essential role during viral genome replication and transcription, emphasizing the idea that this enzyme can be a potential target for drug and vaccine development against ASF. Copyright © 2016 Elsevier B.V. All rights reserved.

Chemically Functional Alkanethiol Derivitized Magnetic Nanoparticles

DTIC Science & Technology

2003-01-01

reactive groups such as alcohols, amines and carboxylic acids . This paper presents our preliminary investigations of the voltammetry of the former class of...1.62 mmol) TOPO, 1.75g (7.25 mmol) HDA and 0. l4mL (1.06 mmol) Fe(CO)5 is heated and injected into the TOPO mixture, and stirred for at least an

75 FR 20023 - Self-Regulatory Organizations; Notice of Filing of a Proposed Rule Change by NASDAQ OMX PHLX, Inc...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-04-16

... fee schedule by establishing fees for a direct data product, Top of Phlx Options Plus Orders (``TOPO Plus Orders''), which currently provides disseminated Exchange top-of- market data (including orders... instead offer TOPO Plus Orders to participants that wish to continue to receive the data currently...

Design, synthesis, molecular modeling and anti-proliferative evaluation of novel quinoxaline derivatives as potential DNA intercalators and topoisomerase II inhibitors.

PubMed

Ibrahim, M K; Taghour, M S; Metwaly, A M; Belal, A; Mehany, A B M; Elhendawy, M A; Radwan, M M; Yassin, A M; El-Deeb, N M; Hafez, E E; ElSohly, M A; Eissa, I H

2018-06-04

New series of [1,2,4]triazolo [4,3-a]quinoxaline and bis([1,2,4]triazolo)[4,3-a:3',4'-c]quinoxaline derivatives have been designed, synthesized and biologically evaluated for their cytotoxic activities against three tumor cell lines (HePG-2, Hep-2 and Caco-2). Compounds 16 e , 21, 25 a and 25 b exhibited the highest activities against the examined cell lines with IC 50 values ranging from 0.29 to 0.90 μM comparable to that of doxorubicin (IC 50 ranging from 0.51 to 0.73 μM). The most active members were further evaluated for their topoisomerase II (Topo II) inhibitory activities and DNA intercalating affinities as potential mechanisms for their anti-proliferative activities. Interestingly, the results of Topo II inhibition and DNA binding assays were consistent with that of the cytotoxicity data, where the most potent anti-proliferative derivatives exhibited good Topo II inhibitory activities and DNA binding affinities, comparable to that of doxorubicin. Moreover, the most active compound 25 a caused cell cycle arrest at G2/M phase and induced apoptosis in Caco-2 cells. In addition, Furthermore, molecular docking studies were performed for the novel compounds against DNA-Topo II complex to investigate their binding patterns. Based on these studies, it was concluded that DNA binding and/or Topo II inhibition may contribute to the observed cytotoxicity of the synthesized compounds. Copyright © 2018. Published by Elsevier Masson SAS.

3-D Surface Visualization of pH Titration "Topos": Equivalence Point Cliffs, Dilution Ramps, and Buffer Plateaus

ERIC Educational Resources Information Center

Smith, Garon C.; Hossain, Md Mainul; MacCarthy, Patrick

2014-01-01

3-D topographic surfaces ("topos") can be generated to visualize how pH behaves during titration and dilution procedures. The surfaces are constructed by plotting computed pH values above a composition grid with volume of base added in one direction and overall system dilution on the other. What emerge are surface features that…

GS-2, a pyrazolo[1,5-a]indole derivative with inhibitory activity of topoisomerases, exerts its potent cytotoxic activity by ROS generation.

PubMed

Ji, Yuan Yuan; Zhu, Yong Ming; Wang, Jian Wen

2013-11-01

Pyrazolo[1,5-a]indole derivatives, a new type of topoisomerase (topo) inhibitor, demonstrate a broad spectrum of antitumor activities. However, the mechanism underlying the induced cytotoxicity remains unclear. In this study, we investigated whether GS-2, one of the derivatives, altered the levels of ROS in breast cancer MDA-231 cells and whether these ROS contributed to the observed antitumoral activity. Our data revealed that GS-2 caused a time- and dose-dependent elevation of intracellular ROS level in MDA-231 cells. GS-2 subsequently elicited notable inhibition on the expression of topos, DNA damage, activation of caspase-3, -9. The loss of mitochondrial membrane potential (MMP) was observed during the induction. The addition of N-acetyl cysteine (NAC, a well-known antioxidant) could effectively attenuate the GS-2-induced ROS enhancement and subsequent apoptosis. NAC attenuated the induced inhibition on expression of topos, indicating that topos might be the target of GS-2-induced ROS. The finding of the induced ROS provides new evidence for the molecular mechanisms of antitumor activity of pyrazolo[1,5-a]indole derivatives. Copyright © 2013 Elsevier B.V. All rights reserved.

The Principle of General Tovariance

NASA Astrophysics Data System (ADS)

Heunen, C.; Landsman, N. P.; Spitters, B.

2008-06-01

We tentatively propose two guiding principles for the construction of theories of physics, which should be satisfied by a possible future theory of quantum gravity. These principles are inspired by those that led Einstein to his theory of general relativity, viz. his principle of general covariance and his equivalence principle, as well as by the two mysterious dogmas of Bohr's interpretation of quantum mechanics, i.e. his doctrine of classical concepts and his principle of complementarity. An appropriate mathematical language for combining these ideas is topos theory, a framework earlier proposed for physics by Isham and collaborators. Our principle of general tovariance states that any mathematical structure appearing in the laws of physics must be definable in an arbitrary topos (with natural numbers object) and must be preserved under so-called geometric morphisms. This principle identifies geometric logic as the mathematical language of physics and restricts the constructions and theorems to those valid in intuitionism: neither Aristotle's principle of the excluded third nor Zermelo's Axiom of Choice may be invoked. Subsequently, our equivalence principle states that any algebra of observables (initially defined in the topos Sets) is empirically equivalent to a commutative one in some other topos.

Epidermal Growth Factor Receptor (EGFR) and its Cross-Talks with Topoisomerases: Challenges and Opportunities for Multi-Target Anticancer Drugs.

PubMed

Chauhan, Monika; Sharma, Gourav; Joshi, Gaurav; Kumar, Raj

2016-01-01

The interactions of Epidermal Growth Factor Receptor (EGFR) and topoisomerases have been seen in various cancer including brain, breast, ovarian, colorectal, gastric, etc. The studies in adenocarcinoma patients, chromogenic in situ hybridization, western blotting, receptor binding assay and electromobility shift assays, etc. threw light on the biophysical and biochemical features of EGFR and Topoisomerase cross-talks. It has been revealed that both the isomers of topoisomerase (Topo I and Topo II) interact via different mechanisms with EGFR. Topo II and HER2 share the same location i.e. 17q12-21 regions which could be a possible cause of predominant interactions seen between them. Topo I and EGFR interactions are mechanically related to the nucleolar translocation of heparenase by EGF and c-Jun. We compiled literature findings including the mechanistic interventions, signaling pathways, patents, in vitro and in vivo data of tested inhibitors and combinations in clinical trials, which provide convincing confirmations for the interactions of EGFR and topoisomerases. These interactions may be used for deriving a consistent route of mechanism, design and development of standard drug combinations and dual or multi inhibitors.

US Topo - A new national map series

USGS Publications Warehouse

Moore, Laurence R.

2011-01-01

In the second half of the 20th century, the foundation of the U.S. Geological Survey's national map series was the handcrafted 7.5-minute topographic map. Times change, budgets get squeezed and currency expectations become ever more challenging. The USGS's Larry Moore, who oversees data production operations at two National Geospatial Technical Operations Centers, provides an introduction to the new US Topo quadrangle maps.

Comparative analysis of topoisomerase IB inhibition and DNA intercalation by flavonoids and similar compounds: structural determinates of activity

PubMed Central

2004-01-01

Flavonoids and other polyphenolic compounds have been shown to inhibit human topoisomerase IB (topo I) through both inhibition of relaxation activity and through stabilization of the cleavable complex (poisoning). Some flavonoids have also been shown to intercalate DNA, and an association of topoisomerase inhibition with intercalation has been noted. We surveyed 34 polyphenolic compounds, primarily flavonoid glycones and aglycones, for their ability to inhibit topo I and to intercalate DNA using an in vitro gel electrophoresis method. We show that the most potent topo I poisons are the flavones and flavonols, and that these generally, but not always, are found to be DNA intercalators. There was no clear correlation, however, of topo-I-poisoning activity with the degree of DNA unwinding. Surprisingly, both DNA intercalation and topo I poisoning were shown to occur with some flavone glycones, including the C-glycosylflavone orientin. Inhibition of relaxation activity by flavonoids was found to be difficult to quantify and was most likely to be due to non-specific inhibition through flavonoid aggregation. As part of a structure–activity analysis, we also investigated the acid–base chemistry of flavonoids and determined that many flavonoids show acid–base activity with a pKa in the physiological pH region. For this reason, subtle pH changes can have significant effects on solution activity of flavonoids and their concomitant biological activity. In addition, these effects may be complicated by pH-dependent aggregation and oxidative degradation. Finally, we develop a simple model for the intercalation of flavonoids into DNA and discuss possible consequences of intercalation and topoisomerase inhibition on a number of cellular processes. PMID:15312049

Aberrant activation of ubiquitin D at G2 phase and apoptosis by carcinogens that evoke cell proliferation after 28-day administration in rats.

PubMed

Taniai, Eriko; Yafune, Atsunori; Hayashi, Hitomi; Itahashi, Megu; Hara-Kudo, Yukiko; Suzuki, Kazuhiko; Mitsumori, Kunitoshi; Shibutani, Makoto

2012-01-01

We have previously reported that renal carcinogens examined in rats increase tubular cell proliferation and topoisomerase (Topo) IIα(+) cells. The present study was aimed at identifying early prediction markers of carcinogens after 28-day treatment in rats. Following gene expression screening by microarrays in renal tubules with renal carcinogens, immunohistochemical analysis and TUNEL-assay were performed with carcinogens targeting different organs. All renal carcinogens tested (ferric nitrilotriacetic acid, ochratoxin A (OTA), monuron, tris(2-chloroethyl) phosphate, and potassium bromate) increased tubular cells immunoreactive for minichromosome maintenance 3 (Mcm3) or ubiquitin D (Ubd) or those showing apoptosis, compared with untreated controls or non-carcinogenic renal toxicants. Carcinogens targeting the liver (thioacetamide (TAA), fenbendazole, piperonyl butoxide (PBO) and methyleugenol), thyroid (sulfadimethoxine), urinary bladder (phenylethyl isothiocyanate), forestomach (butylated hydroxyanisole), glandular stomach (catechol), and colon (chenodeoxycholic acid and 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine) were examined for induction of Mcm3, Ubd, Topo IIα, Ki-67 and apoptosis using non-carcinogenic toxicants as negative controls. All carcinogens increased Mcm3(+), Ubd(+), Topo IIα(+), Ki-67(+) or TUNEL(+) cells, except for hepatocarcinogen PBO and both colon carcinogens, which did not increase cell proliferation. Ubd(+) cells co-expressing Topo IIα was increased without changing phospho-Histone H3-co-expressing cell population as examined with OTA and TAA. Results revealed cooperative responses of Topo IIα, Ubd and apoptosis by carcinogens inducing high proliferation activity, irrespective of target organs, examined here after a 28-day administration. Aberrant expression of Ubd at G(2) phase and increased apoptosis reflecting aberrant cell cycle regulation may be the common feature of these carcinogens.

Synoptic channel morphodynamics with topo-bathymetric airborne lidar: promises, pitfalls and research needs

NASA Astrophysics Data System (ADS)

Lague, D.; Launeau, P.; Gouraud, E.

2017-12-01

Topo-bathymetric airborne lidar sensors using a green laser penetrating water and suitable for hydrography are now sold by major manufacturers. In the context of channel morphodynamics, repeat surveys could offer synoptic high resolution measurement of topo-bathymetric change, a key data that is currently missing. Yet, beyond the technological promise, what can we really achieve with these sensors in terms of depth penetration and bathymetric accuracy ? Can all rivers be surveyed ? How easy it is to process this new type of data to get the data needed by geomorphologists ? Here we report on the use of the Optech Titan dual wavelength (1064 nm & 532 nm) operated by the universities of Rennes and Nantes (France) and deployed over several rivers and lakes in France, including repeat surveys. We will illustrate cases where the topo-bathymetric survey is complete, reaching up to 6 m in rivers and offers unprecedented data for channel morphology analysis over tens of kilometres. We will also present challenging cases for which the technology will never work, or for which new algorithms to process full waveform are required. We will illustrate new developments for automated processing of large datasets, including the critical step of water surface detection and refraction correction. In suitable rivers, airborne topo-bathymetric surveys offer unprecedented synoptic 3D data at very high resolution (> 15 pts/m² in bathy) and precision (better than 10 cm for the bathy) down to 5-6 meters depth, with a perfectly continuous topography to bathymetry transition. This presentation will illustrate how this new type of data, when combined with 2D hydraulics modelling offers news insights into the spatial variations of friction in relation to channel bedforms, and the connectivity between rivers and floodplains.

DNA G-segment bending is not the sole determinant of topology simplification by type II DNA topoisomerases.

PubMed

Thomson, Neil H; Santos, Sergio; Mitchenall, Lesley A; Stuchinskaya, Tanya; Taylor, James A; Maxwell, Anthony

2014-08-21

DNA topoisomerases control the topology of DNA. Type II topoisomerases exhibit topology simplification, whereby products of their reactions are simplified beyond that expected based on thermodynamic equilibrium. The molecular basis for this process is unknown, although DNA bending has been implicated. To investigate the role of bending in topology simplification, the DNA bend angles of four enzymes of different types (IIA and IIB) were measured using atomic force microscopy (AFM). The enzymes tested were Escherichia coli topo IV and yeast topo II (type IIA enzymes that exhibit topology simplification), and Methanosarcina mazei topo VI and Sulfolobus shibatae topo VI (type IIB enzymes, which do not). Bend angles were measured using the manual tangent method from topographical AFM images taken with a novel amplitude-modulated imaging mode: small amplitude small set-point (SASS), which optimises resolution for a given AFM tip size and minimises tip convolution with the sample. This gave improved accuracy and reliability and revealed that all 4 topoisomerases bend DNA by a similar amount: ~120° between the DNA entering and exiting the enzyme complex. These data indicate that DNA bending alone is insufficient to explain topology simplification and that the 'exit gate' may be an important determinant of this process.

Performance testing of LiDAR exploitation software

NASA Astrophysics Data System (ADS)

Varela-González, M.; González-Jorge, H.; Riveiro, B.; Arias, P.

2013-04-01

Mobile LiDAR systems are being used widely in recent years for many applications in the field of geoscience. One of most important limitations of this technology is the large computational requirements involved in data processing. Several software solutions for data processing are available in the market, but users are often unknown about the methodologies to verify their performance accurately. In this work a methodology for LiDAR software performance testing is presented and six different suites are studied: QT Modeler, AutoCAD Civil 3D, Mars 7, Fledermaus, Carlson and TopoDOT (all of them in x64). Results depict as QTModeler, TopoDOT and AutoCAD Civil 3D allow the loading of large datasets, while Fledermaus, Mars7 and Carlson do not achieve these powerful performance. AutoCAD Civil 3D needs large loading time in comparison with the most powerful softwares such as QTModeler and TopoDOT. Carlson suite depicts the poorest results among all the softwares under study, where point clouds larger than 5 million points cannot be loaded and loading time is very large in comparison with the other suites even for the smaller datasets. AutoCAD Civil 3D, Carlson and TopoDOT show more threads than other softwares like QTModeler, Mars7 and Fledermaus.

The Effect of Dimethyl Sulfoxide on Supercoiled DNA Relaxation Catalyzed by Type I Topoisomerases

PubMed Central

Lv, Bei; Dai, Yunjia; Liu, Ju; Zhuge, Qiang; Li, Dawei

2015-01-01

The effects of dimethyl sulfoxide (DMSO) on supercoiled plasmid DNA relaxation catalyzed by two typical type I topoisomerases were investigated in our studies. It is shown that DMSO in a low concentration (less than 20%, v/v) can induce a dose-related enhancement of the relaxation efficiency of Escherichia coli topoisomerase I (type IA). Conversely, obvious inhibitory effect on the activity of calf thymus topoisomerase I (type IB) was observed when the same concentration of DMSO is used. In addition, our studies demonstrate that 20% DMSO has an ability to reduce the inhibitory effect on EcTopo I, which was induced by double-stranded oligodeoxyribonucleotides while the same effect cannot be found in the case of CtTopo I. Moreover, our AFM examinations suggested that DMSO can change the conformation of negatively supercoiled plasmid by creating some locally loose regions in DNA molecules. Combining all the lines of evidence, we proposed that DMSO enhanced EcTopo I relaxation activity by (1) increasing the single-stranded DNA regions for the activities of EcTopo I in the early and middle stages of the reaction and (2) preventing the formation of double-stranded DNA-enzyme complex in the later stage, which can elevate the effective concentration of the topoisomerase in the reaction solution. PMID:26682217

DNA G-segment bending is not the sole determinant of topology simplification by type II DNA topoisomerases

NASA Astrophysics Data System (ADS)

Thomson, Neil H.; Santos, Sergio; Mitchenall, Lesley A.; Stuchinskaya, Tanya; Taylor, James A.; Maxwell, Anthony

2014-08-01

DNA topoisomerases control the topology of DNA. Type II topoisomerases exhibit topology simplification, whereby products of their reactions are simplified beyond that expected based on thermodynamic equilibrium. The molecular basis for this process is unknown, although DNA bending has been implicated. To investigate the role of bending in topology simplification, the DNA bend angles of four enzymes of different types (IIA and IIB) were measured using atomic force microscopy (AFM). The enzymes tested were Escherichia coli topo IV and yeast topo II (type IIA enzymes that exhibit topology simplification), and Methanosarcina mazei topo VI and Sulfolobus shibatae topo VI (type IIB enzymes, which do not). Bend angles were measured using the manual tangent method from topographical AFM images taken with a novel amplitude-modulated imaging mode: small amplitude small set-point (SASS), which optimises resolution for a given AFM tip size and minimises tip convolution with the sample. This gave improved accuracy and reliability and revealed that all 4 topoisomerases bend DNA by a similar amount: ~120° between the DNA entering and exiting the enzyme complex. These data indicate that DNA bending alone is insufficient to explain topology simplification and that the `exit gate' may be an important determinant of this process.

Topology simplification: Important biological phenomenon or evolutionary relic?. Comment on "Disentangling DNA molecules" by Alexander Vologodskii

NASA Astrophysics Data System (ADS)

Bates, Andrew D.; Maxwell, Anthony

2016-09-01

The review, Disentangling DNA molecules[1], gives an excellent technical description of the phenomenon of topology simplification (TS) by type IIA DNA topoisomerases (topos). In the 20 years since its discovery [2], this effect has attracted a good deal of attention, probably because of its apparently magical nature, and because it seemed to offer a solution to the conundrum that all type II topos rely on ATP hydrolysis, but only bacterial DNA gyrases were known to transduce the free energy of hydrolysis into torsion (supercoiling) in the DNA. It made good sense to think that the other enzymes are using the energy to reduce the level of supercoiling, knotting, and particularly decatenation (unlinking), below equilibrium, since the key activity of the non-supercoiling topos is the removal of links between daughter chromosomes [3]. As Vologodskii discusses [1], there have been a number of theoretical models developed to explain how the local effect of a type II topo can influence the global level of knotting and catenation in large DNA molecules, and he explains how features of two of the most successful models (bent G segment and hooked juxtapositions) may be combined to explain the magnitude of the effect and overcome a kinetic problem with the hooked juxtaposition model.

The Integrative Studies of Genetic and Environmental Factors in Systemic Sclerosis

DTIC Science & Technology

2010-05-01

nucleolus and the nucleoplasm, but is enriched in the nucleolus where there is a high level of transcription and replication of the ribosomal DNA (6,7...residues. Sumoylation of topo I has been shown to facilitate its movement between the nucleolus and the nucleoplasm (8-10). The purpose of this...strong nucleoplasm staining (multiple speckles) compared to normal fibroblasts in which topo I staining showed normal enrichment in the nucleolus

Surface ligands affect photoinduced modulation of the quantum dots optical performance

NASA Astrophysics Data System (ADS)

Krivenkov, Victor A.; Samokhvalov, Pavel S.; Linkov, Pavel A.; Solovyeva, Daria O.; Kotkovskii, Gennadii E.; Chistyakov, Alexander A.; Nabiev, Igor

2014-05-01

Changes of optical properties of the solutions of CdSe/ZnS quantum dots (QDs) covered with the trioctylphosphine oxide (TOPO) ligands under the pulsed ultraviolet (UV) laser irradiation are observed. The fluorescence quantum yield (QY) of QDs decreases by more than an order of magnitude when the radiation dose approaches 2 × 10-15 J per particle. This process is accompanied by a blue shift of both fluorescence and the first excitonic absorption peaks. The fluorescence quenching becomes less pronounced when the overall TOPO content in the solution is increased. When ТОРО ligands are replaced with n-hexadecylamine (HDA), QY and spectral properties are not changed at the same irradiation conditions. We assume that the above changes of the optical properties are associated with photooxidation of TOPO ligands by excited QD. Such process is less probable for the HDA ligand due to its different energy structure.

BLM and RMI1 alleviate RPA inhibition of TopoIIIα decatenase activity.

PubMed

Yang, Jay; Bachrati, Csanad Z; Hickson, Ian D; Brown, Grant W

2012-01-01

RPA is a single-stranded DNA binding protein that physically associates with the BLM complex. RPA stimulates BLM helicase activity as well as the double Holliday junction dissolution activity of the BLM-topoisomerase IIIα complex. We investigated the effect of RPA on the ssDNA decatenase activity of topoisomerase IIIα. We found that RPA and other ssDNA binding proteins inhibit decatenation by topoisomerase IIIα. Complex formation between BLM, TopoIIIα, and RMI1 ablates inhibition of decatenation by ssDNA binding proteins. Together, these data indicate that inhibition by RPA does not involve species-specific interactions between RPA and BLM-TopoIIIα-RMI1, which contrasts with RPA modulation of double Holliday junction dissolution. We propose that topoisomerase IIIα and RPA compete to bind to single-stranded regions of catenanes. Interactions with BLM and RMI1 enhance toposiomerase IIIα activity, promoting decatenation in the presence of RPA.

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

Schellenberg, Matthew J; Appel, C Denise; Adhikari, Sanjay

The topoisomerase II (topo II) DNA incision-and-ligation cycle can be poisoned (for example following treatment with cancer chemotherapeutics) to generate cytotoxic DNA double-strand breaks (DSBs) with topo II covalently conjugated to DNA. Tyrosyl-DNA phosphodiesterase 2 (Tdp2) protects genomic integrity by reversing 5'-phosphotyrosyl–linked topo II–DNA adducts. Here, X-ray structures of mouse Tdp2–DNA complexes reveal that Tdp2 β–2-helix–β DNA damage–binding 'grasp', helical 'cap' and DNA lesion–binding elements fuse to form an elongated protein-DNA conjugate substrate-interaction groove. The Tdp2 DNA-binding surface is highly tailored for engagement of 5'-adducted single-stranded DNA ends and restricts nonspecific endonucleolytic or exonucleolytic processing. Structural, mutational and functional analysesmore » support a single–metal ion catalytic mechanism for the exonuclease-endonuclease-phosphatase (EEP) nuclease superfamily and establish a molecular framework for targeted small-molecule blockade of Tdp2-mediated resistance to anticancer topoisomerase drugs.« less

TOPoS. IV. Chemical abundances from high-resolution observations of seven extremely metal-poor stars

NASA Astrophysics Data System (ADS)

Bonifacio, P.; Caffau, E.; Spite, M.; Spite, F.; Sbordone, L.; Monaco, L.; François, P.; Plez, B.; Molaro, P.; Gallagher, A. J.; Cayrel, R.; Christlieb, N.; Klessen, R. S.; Koch, A.; Ludwig, H.-G.; Steffen, M.; Zaggia, S.; Abate, C.

2018-04-01

Context. Extremely metal-poor (EMP) stars provide us with indirect information on the first generations of massive stars. The TOPoS survey has been designed to increase the census of these stars and to provide a chemical inventory that is as detailed as possible. Aims: Seven of the most iron-poor stars have been observed with the UVES spectrograph at the ESO VLT Kueyen 8.2 m telescope to refine their chemical composition. Methods: We analysed the spectra based on 1D LTE model atmospheres, but also used 3D hydrodynamical simulations of stellar atmospheres. Results: We measured carbon in six of the seven stars: all are carbon-enhanced and belong to the low-carbon band, defined in the TOPoS II paper. We measured lithium (A(Li) = 1.9) in the most iron-poor star (SDSS J1035+0641, [Fe/H] <-5.2). We were also able to measure Li in three stars at [Fe/H] -4.0, two of which lie on the Spite plateau. We confirm that SDSS J1349+1407 is extremely rich in Mg, but not in Ca. It is also very rich in Na. Several of our stars are characterised by low α-to-iron ratios. Conclusions: The lack of high-carbon band stars at low metallicity can be understood in terms of evolutionary timescales of binary systems. The detection of Li in SDSS J1035+0641 places a strong constraint on theories that aim at solving the cosmological lithium problem. The Li abundance of the two warmer stars at [Fe/H] -4.0 places them on the Spite plateau, while the third, cooler star, lies below. We argue that this suggests that the temperature at which Li depletion begins increases with decreasing [Fe/H]. SDSS J1349+1407 may belong to a class of Mg-rich EMP stars. We cannot assess if there is a scatter in α-to-iron ratios among the EMP stars or if there are several discrete populations. However, the existence of stars with low α-to-iron ratios is supported by our observations. Based on observations obtained at ESO Paranal Observatory, Programmes 189.D-0165,090.D-0306, 093.D-0136, and 096.D-0468.

The possibility of identifying the spatial location of single dislocations by topo-tomography on laboratory setups

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

Zolotov, D. A., E-mail: zolotovden@crys.ras.ru; Buzmakov, A. V.; Elfimov, D. A.

2017-01-15

The spatial arrangement of single linear defects in a Si single crystal (input surface (111)) has been investigated by X-ray topo-tomography using laboratory X-ray sources. The experimental technique and the procedure of reconstructing a 3D image of dislocation half-loops near the Si crystal surface are described. The sizes of observed linear defects with a spatial resolution of about 10 μm are estimated.

SANS study of HC1 extraction by selected neutral organophosphorus compounds in n-octane.

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

Chiarizia, R.; Stepinski, D.; Antonio, M. R.

2010-01-01

The extraction of HCl by tri(2-ethylhexyl) phosphate (TEHP), tri-n-octyl phosphate (TOP), and tri-n-octylphosphine oxide (TOPO) in n-octane was investigated by liquid-liquid distribution of acid and water and small-angle neutron scattering (SANS) measurements. No formation of a heavy organic phase (third phase) was observed with TEHP and TOP under the experimental conditions used, whereas for 0.4 M TOPO the HCl limiting organic concentration (LOC) at 23 C was 0.32 M (with 5.1 M HCl in the equilibrium aqueous phase). For higher HCl concentrations in the aqueous phase, the organic phase splits into a light and a heavy layer. For TEHP andmore » TOP, the SANS results, interpreted using the Baxter model for hard spheres with surface adhesion, indicated the formation of only small reverse micelles with little intermicellar attraction. For TOPO, the scattering signals suggested the formation of much larger and strongly interacting micelles. The critical values of the stickiness parameter, {tau}{sup -1}, and the interaction potential energy, U(r), for the LOC sample in the TOPO system were consistent with the model for third-phase formation previously developed for tri-n-butyl phosphate (TBP). According to this model, organic phase splitting is due to van der Waals interactions between the polar cores of reverse micelles formed by the extractants in the organic phase.« less

Methanopyrus kandleri topoisomerase V contains three distinct AP lyase active sites in addition to the topoisomerase active site

PubMed Central

Rajan, Rakhi; Osterman, Amy; Mondragón, Alfonso

2016-01-01

Topoisomerase V (Topo-V) is the only topoisomerase with both topoisomerase and DNA repair activities. The topoisomerase activity is conferred by a small alpha-helical domain, whereas the AP lyase activity is found in a region formed by 12 tandem helix-hairpin-helix ((HhH)2) domains. Although it was known that Topo-V has multiple repair sites, only one had been mapped. Here, we show that Topo-V has three AP lyase sites. The atomic structure and Small Angle X-ray Scattering studies of a 97 kDa fragment spanning the topoisomerase and 10 (HhH)2 domains reveal that the (HhH)2 domains extend away from the topoisomerase domain. A combination of biochemical and structural observations allow the mapping of the second repair site to the junction of the 9th and 10th (HhH)2 domains. The second site is structurally similar to the first one and to the sites found in other AP lyases. The 3rd AP lyase site is located in the 12th (HhH)2 domain. The results show that Topo-V is an unusual protein: it is the only known protein with more than one (HhH)2 domain, the only known topoisomerase with dual activities and is also unique by having three AP lyase repair sites in the same polypeptide. PMID:26908655

Cell-cycle-dependent three-dimensional redistribution of nuclear proteins, P 120, pKi-67, and SC 35 splicing factor, in the presence of the topoisomerase I inhibitor camptothecin.

PubMed

Elias, Emmanuel; Lalun, Nathalie; Lorenzato, Marianne; Blache, Laurent; Chelidze, Pavel; O'Donohue, Marie-Françoise; Ploton, Dominique; Bobichon, Hélène

2003-11-15

Topoisomerase I (Topo I) is mostly known for its role in DNA relaxation, which is required for duplication and transcription. Topo I acts as a protein kinase mainly directed to the mRNA splicing factor SC35. Camptothecin is one of the specific Topo I inhibitors and is effective on the two functions of the enzyme. In this study we demonstrated that treatment of KB cells with camptothecin for only 30 min induced the 3D reorganization and redistribution of three proteins involved in the nucleus machinery, P 120, pKi-67, and SC 35, and this occurred in a cell cycle-dependent manner. Our data were obtained from confocal microscopic studies after immunolabeling, 3D reconstruction, and measurement of the nuclear components volumes. In the presence of camptothecin, P 120, which occupied the nucleolar volume, lost its reticulation and pKi-67 was redistributed within the nucleoplasm and even into the cytoplasm. Finally, for SC 35 the fusion of its dots into bigger volumes was observed specifically during the G1 phase. Variations of volumes were also observed for the nucleolus and for the nucleus. These results pointed out that, depending on the cell cycle phase, Topo I functions were selective toward the three different proteins.

Estimating patient dose from CT exams that use automatic exposure control: Development and validation of methods to accurately estimate tube current values.

PubMed

McMillan, Kyle; Bostani, Maryam; Cagnon, Christopher H; Yu, Lifeng; Leng, Shuai; McCollough, Cynthia H; McNitt-Gray, Michael F

2017-08-01

The vast majority of body CT exams are performed with automatic exposure control (AEC), which adapts the mean tube current to the patient size and modulates the tube current either angularly, longitudinally or both. However, most radiation dose estimation tools are based on fixed tube current scans. Accurate estimates of patient dose from AEC scans require knowledge of the tube current values, which is usually unavailable. The purpose of this work was to develop and validate methods to accurately estimate the tube current values prescribed by one manufacturer's AEC system to enable accurate estimates of patient dose. Methods were developed that took into account available patient attenuation information, user selected image quality reference parameters and x-ray system limits to estimate tube current values for patient scans. Methods consistent with AAPM Report 220 were developed that used patient attenuation data that were: (a) supplied by the manufacturer in the CT localizer radiograph and (b) based on a simulated CT localizer radiograph derived from image data. For comparison, actual tube current values were extracted from the projection data of each patient. Validation of each approach was based on data collected from 40 pediatric and adult patients who received clinically indicated chest (n = 20) and abdomen/pelvis (n = 20) scans on a 64 slice multidetector row CT (Sensation 64, Siemens Healthcare, Forchheim, Germany). For each patient dataset, the following were collected with Institutional Review Board (IRB) approval: (a) projection data containing actual tube current values at each projection view, (b) CT localizer radiograph (topogram) and (c) reconstructed image data. Tube current values were estimated based on the actual topogram (actual-topo) as well as the simulated topogram based on image data (sim-topo). Each of these was compared to the actual tube current values from the patient scan. In addition, to assess the accuracy of each method in estimating patient organ doses, Monte Carlo simulations were performed by creating voxelized models of each patient, identifying key organs and incorporating tube current values into the simulations to estimate dose to the lungs and breasts (females only) for chest scans and the liver, kidney, and spleen for abdomen/pelvis scans. Organ doses from simulations using the actual tube current values were compared to those using each of the estimated tube current values (actual-topo and sim-topo). When compared to the actual tube current values, the average error for tube current values estimated from the actual topogram (actual-topo) and simulated topogram (sim-topo) was 3.9% and 5.8% respectively. For Monte Carlo simulations of chest CT exams using the actual tube current values and estimated tube current values (based on the actual-topo and sim-topo methods), the average differences for lung and breast doses ranged from 3.4% to 6.6%. For abdomen/pelvis exams, the average differences for liver, kidney, and spleen doses ranged from 4.2% to 5.3%. Strong agreement between organ doses estimated using actual and estimated tube current values provides validation of both methods for estimating tube current values based on data provided in the topogram or simulated from image data. © 2017 American Association of Physicists in Medicine.

Variola Type IB DNA Topoisomerase: DNA Binding and Supercoil Unwinding Using Engineered DNA Minicircles

PubMed Central

2015-01-01

Type IB topoisomerases unwind positive and negative DNA supercoils and play a key role in removing supercoils that would otherwise accumulate at replication and transcription forks. An interesting question is whether topoisomerase activity is regulated by the topological state of the DNA, thereby providing a mechanism for targeting the enzyme to highly supercoiled DNA domains in genomes. The type IB enzyme from variola virus (vTopo) has proven to be useful in addressing mechanistic questions about topoisomerase function because it forms a reversible 3′-phosphotyrosyl adduct with the DNA backbone at a specific target sequence (5′-CCCTT-3′) from which DNA unwinding can proceed. We have synthesized supercoiled DNA minicircles (MCs) containing a single vTopo target site that provides highly defined substrates for exploring the effects of supercoil density on DNA binding, strand cleavage and ligation, and unwinding. We observed no topological dependence for binding of vTopo to these supercoiled MC DNAs, indicating that affinity-based targeting to supercoiled DNA regions by vTopo is unlikely. Similarly, the cleavage and religation rates of the MCs were not topologically dependent, but topoisomers with low superhelical densities were found to unwind more slowly than highly supercoiled topoisomers, suggesting that reduced torque at low superhelical densities leads to an increased number of cycles of cleavage and ligation before a successful unwinding event. The K271E charge reversal mutant has an impaired interaction with the rotating DNA segment that leads to an increase in the number of supercoils that were unwound per cleavage event. This result provides evidence that interactions of the enzyme with the rotating DNA segment can restrict the number of supercoils that are unwound. We infer that both superhelical density and transient contacts between vTopo and the rotating DNA determine the efficiency of supercoil unwinding. Such determinants are likely to be important in regulating the steady-state superhelical density of DNA domains in the cell. PMID:24945825

Switch in Site of Inhibition: A Strategy for Structure-Based Discovery of Human Topoisomerase IIα Catalytic Inhibitors

PubMed Central

2015-01-01

A study of structure-based modulation of known ligands of hTopoIIα, an important enzyme involved in DNA processes, coupled with synthesis and in vitro assays led to the establishment of a strategy of rational switch in mode of inhibition of the enzyme’s catalytic cycle. 6-Arylated derivatives of known imidazopyridine ligands were found to be selective inhibitors of hTopoIIα, while not showing TopoI inhibition and DNA binding. Interestingly, while the parent imidazopyridines acted as ATP-competitive inhibitors, arylated derivatives inhibited DNA cleavage similar to merbarone, indicating a switch in mode of inhibition from ATP-hydrolysis to the DNA-cleavage stage of catalytic cycle of the enzyme. The 6-aryl-imidazopyridines were relatively more cytotoxic than etoposide in cancer cells and less toxic to normal cells. Such unprecedented strategy will encourage research on “choice-based change” in target-specific mode of action for rapid drug discovery. PMID:25941559

USGS US topo maps for Alaska

USGS Publications Warehouse

Anderson, Becci; Fuller, Tracy

2014-01-01

In July 2013, the USGS National Geospatial Program began producing new topographic maps for Alaska, providing a new map series for the state known as US Topo. Prior to the start of US Topo map production in Alaska, the most detailed statewide USGS topographic maps were 15-minute 1:63,360-scale maps, with their original production often dating back nearly fifty years. The new 7.5-minute digital maps are created at 1:25,000 map scale, and show greatly increased topographic detail when compared to the older maps. The map scale and data specifications were selected based on significant outreach to various map user groups in Alaska. This multi-year mapping initiative will vastly enhance the base topographic maps for Alaska and is possible because of improvements to key digital map datasets in the state. The new maps and data are beneficial in high priority applications such as safety, planning, research and resource management. New mapping will support science applications throughout the state and provide updated maps for parks, recreation lands and villages.

Topoisomerase VI senses and exploits both DNA crossings and bends to facilitate strand passage

PubMed Central

Wendorff, Timothy J

2018-01-01

Type II topoisomerases manage DNA supercoiling and aid chromosome segregation using a complex, ATP-dependent duplex strand passage mechanism. Type IIB topoisomerases and their homologs support both archaeal/plant viability and meiotic recombination. Topo VI, a prototypical type IIB topoisomerase, comprises two Top6A and two Top6B protomers; how these subunits cooperate to engage two DNA segments and link ATP turnover to DNA transport is poorly understood. Using multiple biochemical approaches, we show that Top6B, which harbors the ATPase activity of topo VI, recognizes and exploits the DNA crossings present in supercoiled DNA to stimulate subunit dimerization by ATP. Top6B self-association in turn induces extensive DNA bending, which is needed to support duplex cleavage by Top6A. Our observations explain how topo VI tightly coordinates DNA crossover recognition and ATP binding with strand scission, providing useful insights into the operation of type IIB topoisomerases and related meiotic recombination and GHKL ATPase machineries. PMID:29595473

Idea and implementation studies of populating TOPO250 component with the data from TOPO10 - generalization of geographic information in the BDG database. (Polish Title: Koncepcja i studium implementacji procesu zasilania komponentu TOPO250 danymi TOPO10 - generalizacja informacji geograficznej w bazie danych BDG )

NASA Astrophysics Data System (ADS)

Olszewski, R.; Pillich-Kolipińska, A.; Fiedukowicz, A.

2013-12-01

Implementation of INSPIRE Directive in Poland requires not only legal transposition but also development of a number of technological solutions. The one of such tasks, associated with creation of Spatial Information Infrastructure in Poland, is developing a complex model of georeference database. Significant funding for GBDOT project enables development of the national basic topographical database as a multiresolution database (MRDB). Effective implementation of this type of database requires developing procedures for generalization of geographic information (generalization of digital landscape model - DLM), which, treating TOPO10 component as the only source for creation of TOPO250 component, will allow keeping conceptual and classification consistency between those database elements. To carry out this task, the implementation of the system's concept (prepared previously for Head Office of Geodesy and Cartography) is required. Such system is going to execute the generalization process using constrained-based modeling and allows to keep topological relationships between the objects as well as between the object classes. Full implementation of the designed generalization system requires running comprehensive tests which would help with its calibration and parameterization of the generalization procedures (related to the character of generalized area). Parameterization of this process will allow determining the criteria of specific objects selection, simplification algorithms as well as the operation order. Tests with the usage of differentiated, related to the character of the area, generalization process parameters become nowadays the priority issue. Parameters are delivered to the system in the form of XML files, which, with the help of dedicated tool, are generated from the spreadsheet files (XLS) filled in by user. Using XLS file makes entering and modifying the parameters easier. Among the other elements defined by the external parametric files there are: criteria of object selection, metric parameters of generalization algorithms (e.g. simplification or aggregation) and the operations' sequence. Testing on the trial areas of diverse character will allow developing the rules of generalization process' realization, its parameterization with the proposed tool within the multiresolution reference database. The authors have attempted to develop a generalization process' parameterization for a number of different trial areas. The generalization of the results will contribute to the development of a holistic system of generalized reference data stored in the national geodetic and cartographic resources.

Separation of Gadolinium (Gd) using Synergic Solvent Mixed Topo-D2EHPA with Extraction Method.

NASA Astrophysics Data System (ADS)

Effendy, N.; Basuki, K. T.; Biyantoro, D.; Perwira, N. K.

2018-04-01

The main problem to obtain Gd with high purity is the similarity of chemical properties and physical properties with the other rare earth elements (REE) such as Y and Dy, it is necessary to do separation by the extraction process. The purpose of this research to determine the best solvent type, amount of solvent, feed and solvent ratio in the Gd extraction process, to determine the rate order and the value of the rate constant of Gd concentration based on experimental data of aqueous phase concentration as a function of time and to know the effect of temperature on the reaction speed constant. This research was conducted on variation of solvent, amount of solvent, feed and solvent ratio in the extraction process of Gd separation, extraction time to determine the order value and the rate constant of Gd concentration in extraction process based on the aqueous phase concentration data as a function of time, to the rate constant of decreasing concentration of Gd. Based on the calculation results, the solvent composition was obtained with the best feed to separate the rare earth elements Gd in the extraction process is 1 : 4 with 15% concentration of TOPO and 10% concentration of D2EHPA. The separation process of Gd using extraction method by solvent TOPO-D2EHPA 2 : 1 comparison is better than single solvent D2EHPA / TOPO because of the synergistic effect. The rate order of separation process of Gd follows order 1. The Arrhenius Gd equation becomes k = 1.46 x 10-7 exp (-6.96 kcal / mol / RT).

Crizotinib Synergizes with Chemotherapy in Preclinical Models of Neuroblastoma

PubMed Central

Krytska, Kateryna; Ryles, Hannah T.; Sano, Renata; Raman, Pichai; Infarinato, Nicole R.; Hansel, Theodore D.; Makena, Monish R.; Song, Michael M.; Reynolds, C. Patrick; Mossé, Yael P.

2015-01-01

Purpose The presence of an ALK aberration correlates with inferior survival for patients with high-risk neuroblastoma. The emergence of ALK inhibitors such as crizotinib has provided novel treatment opportunities. However, certain ALK mutations result in de novo crizotinib resistance, and a phase I trial of crizotinib showed a lack of response in patients harboring those ALK mutations. Thus, understanding mechanisms of resistance and defining circumvention strategies for the clinic is critical. Experimental Design The sensitivity of human neuroblastoma-derived cell lines, cell line-derived and patient-derived xenograft (PDX) models with varying ALK statuses to crizotinib combined with topotecan and cyclophosphamide (topo/cyclo) was examined. Cultured cells and xenografts were evaluated for effects of these drugs on proliferation, signaling, and cell death, and assessment of synergy. Results In neuroblastoma murine xenografts harboring the most common ALK mutations, including those mutations associated with resistance to crizotinib (but not in those with wild-type ALK), crizotinib combined with topo/cyclo enhanced tumor responses and mouse event-free-survival. Crizotinib + topo/cyclo showed synergistic cytotoxicity and higher caspase-dependent apoptosis than crizotinib or topo/cyclo alone in neuroblastoma cell lines with ALK aberrations (mutation or amplification). Conclusions Combining crizotinib with chemotherapeutic agents commonly used in treating newly diagnosed patients with high-risk neuroblastoma restores sensitivity in preclinical models harboring both sensitive ALK aberrations and de novo resistant ALK mutations. These data support clinical testing of crizotinib and conventional chemotherapy with the goal of integrating ALK inhibition into multi-agent therapy for ALK-aberrant neuroblastoma patients. PMID:26438783

TopoDrive and ParticleFlow--Two Computer Models for Simulation and Visualization of Ground-Water Flow and Transport of Fluid Particles in Two Dimensions

USGS Publications Warehouse

Hsieh, Paul A.

2001-01-01

This report serves as a user?s guide for two computer models: TopoDrive and ParticleFlow. These two-dimensional models are designed to simulate two ground-water processes: topography-driven flow and advective transport of fluid particles. To simulate topography-driven flow, the user may specify the shape of the water table, which bounds the top of the vertical flow section. To simulate transport of fluid particles, the model domain is a rectangle with overall flow from left to right. In both cases, the flow is under steady state, and the distribution of hydraulic conductivity may be specified by the user. The models compute hydraulic head, ground-water flow paths, and the movement of fluid particles. An interactive visual interface enables the user to easily and quickly explore model behavior, and thereby better understand ground-water flow processes. In this regard, TopoDrive and ParticleFlow are not intended to be comprehensive modeling tools, but are designed for modeling at the exploratory or conceptual level, for visual demonstration, and for educational purposes.

Structure-activity relationships of aminocoumarin-type gyrase and topoisomerase IV inhibitors obtained by combinatorial biosynthesis.

PubMed

Flatman, Ruth H; Eustaquio, Alessandra; Li, Shu-Ming; Heide, Lutz; Maxwell, Anthony

2006-04-01

Novobiocin and clorobiocin are gyrase inhibitors produced by Streptomyces strains. Structurally, the two compounds differ only by substitution at two positions: CH3 versus Cl at position 8' of the aminocoumarin ring and carbamoyl versus 5-methyl-pyrrol-2-carbonyl (MePC) at the 3"-OH of noviose. Using genetic engineering, we generated a series of analogs carrying H, CH3, or Cl at 8' and H, carbamoyl, or MePC at 3"-OH. Comparison of the gyrase inhibitory activities of all nine structural permutations confirmed that acylation of 3"-OH is essential for activity, with MePC being more effective than carbamoyl. Substitution at 8' further enhanced activity, but the effect of CH3 or Cl depended on the nature of the acyl group at 3": in the presence of carbamoyl at 3", CH3 resulted in higher activity; in the presence of MePC at 3", Cl resulted in higher activity. This suggests that the structures of both natural compounds are highly evolved for optimal interaction with gyrase. In a second series of experiments, clorobiocin derivatives with and without the methyl group at 4"-OH of noviose, and with different positions of the MePC group of noviose, were tested. Again clorobiocin was superior to all of its analogs. The activities of all compounds were also tested against topoisomerase IV (topo IV). Clorobiocin stood out as a remarkably effective topo IV inhibitor. The relative activities of the different compounds toward topo IV showed a pattern similar to that of the relative gyrase-inhibitory activities. This is the first report of a systematic evaluation of a series of aminocoumarins against both gyrase and topo IV. The results give further insight into the structure-activity relationships of aminocoumarin antibiotics.

Recovery of precious metals from space

NASA Technical Reports Server (NTRS)

Freiser, Henry

1991-01-01

The overall objective is to develop efficient and economical separation and recovery methods for the platinum group and other precious metals. The separation of Pd(II) from Pt(II), Ir(III), and Rh(III) with trioctylphosphine oxide (TOPO) in heptane using centrifugal partition chromatography (CPC) was investigated. Activities to achieve this objective focussed on selection and evaluation of extraction systems for the PGM and modification of selected systems for multistage operation with a view to scaling up to desired macro levels. On the basis of preliminary evaluation of a series of simple metal complexing agents and chelating agents, the TOPO in heptane was selected as a likely system for isolating of Pd(II) and Pt(II) from the other PGM. A multistage apparatus capable of configuration as a simple rugged device, a centrifugal partition chromatograph (CPC), was shown to be effective. The extraction of Pd(II) was studied by CPC and batch solvent extraction. The distribution ratios for Pd(II) determined by both methods agree well. In low HCl concentrations (less than 0.1 M), the extracted species was PdCl2.(TOPO)2, irrespective of the chloride concentration, while at acid concentrations above 0.1 M, the Pd was extracted as the ion pair, 2(TOPO.H+).(PdCl4)2-. Base line separation of Pd(II) and Pt(II) in CPC was obtained under a variety of chloride and HCl concentration. It was demonstrated that the efficiency of CPC for metal separation was limited by chemical kinetic factors rather than instrumental factors, strongly suggesting that dramatic improvements can be achieved by studying reaction kinetics of formation and dissociation of the extractable metal complex.

Structure-Activity Relationships of Aminocoumarin-Type Gyrase and Topoisomerase IV Inhibitors Obtained by Combinatorial Biosynthesis

PubMed Central

Flatman, Ruth H.; Eustaquio, Alessandra; Li, Shu-Ming; Heide, Lutz; Maxwell, Anthony

2006-01-01

Novobiocin and clorobiocin are gyrase inhibitors produced by Streptomyces strains. Structurally, the two compounds differ only by substitution at two positions: CH3 versus Cl at position 8′ of the aminocoumarin ring and carbamoyl versus 5-methyl-pyrrol-2-carbonyl (MePC) at the 3"-OH of noviose. Using genetic engineering, we generated a series of analogs carrying H, CH3, or Cl at 8′ and H, carbamoyl, or MePC at 3"-OH. Comparison of the gyrase inhibitory activities of all nine structural permutations confirmed that acylation of 3"-OH is essential for activity, with MePC being more effective than carbamoyl. Substitution at 8′ further enhanced activity, but the effect of CH3 or Cl depended on the nature of the acyl group at 3": in the presence of carbamoyl at 3", CH3 resulted in higher activity; in the presence of MePC at 3", Cl resulted in higher activity. This suggests that the structures of both natural compounds are highly evolved for optimal interaction with gyrase. In a second series of experiments, clorobiocin derivatives with and without the methyl group at 4"-OH of noviose, and with different positions of the MePC group of noviose, were tested. Again clorobiocin was superior to all of its analogs. The activities of all compounds were also tested against topoisomerase IV (topo IV). Clorobiocin stood out as a remarkably effective topo IV inhibitor. The relative activities of the different compounds toward topo IV showed a pattern similar to that of the relative gyrase-inhibitory activities. This is the first report of a systematic evaluation of a series of aminocoumarins against both gyrase and topo IV. The results give further insight into the structure-activity relationships of aminocoumarin antibiotics. PMID:16569821

The benzene metabolite, hydroquinone and etoposide both induce endoreduplication in human lymphoblastoid TK6 cells

PubMed Central

Ji, Zhiying; Zhang, Luoping; Guo, Weihong; McHale, Cliona M.; Smith, Martyn T.

2009-01-01

Both occupational exposure to the leukemogen benzene and in vitro exposure to its metabolite hydroquinone (HQ) lead to the induction of numerical and structural chromosome changes. Several studies have shown that HQ can form DNA adducts, disrupt microtubule assembly and inhibit DNA topoisomerase II (topo II) activity. As these are potential mechanisms underlying endoreduplication (END), a phenomenon that involves DNA amplification without corresponding cell division, we hypothesized that HQ could cause END. We measured END in the human lymphoblastoid cell line, TK6, treated with HQ (0–20 μM) and etoposide (0–0.2 μM) for 48 h. Etoposide was used as a positive control as it is a topo II poison and established human leukemogen that has previously been shown to induce END in Chinese hamster ovary cells. Both HQ and etoposide significantly induced END in a dose-dependent manner (Ptrend < 0.0001 and Ptrend = 0.0003, respectively). Since END may underlie the acquisition of high chromosome numbers by tumour cells, it may play a role in inducing genomic instability and subsequent carcinogenesis from HQ and etoposide. In order to further explore the cytogenetic effects of HQ and etoposide, we also examined specific structural changes. HQ did not induce translocations of chromosome 11 [t(11;?)] but significantly induced translocations of chromosome 21 [t(21;?)] and structural chromosome aberrations (SCA) (Ptrend = 0.0415 and Ptrend < 0.0001, respectively). Etoposide potently induced all these structural changes (Ptrend < 0.0001). The lack of an effect of HQ on t(11;?) and the reduced ability of HQ to induce t(21;?) and SCA, compared with etoposide, further suggests that HQ acts primarily as a topo II catalytic inhibitor rather than as a topo II poison in intact human cells. PMID:19491217

US Topo Product Standard

USGS Publications Warehouse

Cooley, Michael J.; Davis, Larry R.; Fishburn, Kristin A.; Lestinsky, Helmut; Moore, Laurence R.

2011-01-01

A full-size style sheet template in PDF that defines the placement of map elements, marginalia, and font sizes and styles accompanies this standard. The GeoPDF US Topo maps are fashioned to conform to this style sheet so that a user can print out a map at the 1:24,000-scale using the dimensions of the traditional standard 7.5-minute quadrangle. Symbology and type specifications for feature content are published separately. In addition, the GeoPDF design allows for custom printing, so that a user may zoom in and out, turn layers on and off, and view or print any combination of layers or any map portion at any desired scale.

Functionalized magnetic-fluorescent hybrid nanoparticles for cell labelling.

PubMed

Lou, Lei; Yu, Ke; Zhang, Zhengli; Li, Bo; Zhu, Jianzhong; Wang, Yiting; Huang, Rong; Zhu, Ziqiang

2011-05-01

A facile method of synthesizing 60 nm magnetic-fluorescent core-shell bifunctional nanocomposites with the ability to label cells is presented. Hydrophobic trioctylphosphine oxide (TOPO)-capped CdSe@ZnS quantum dots (QDs) were assembled on polyethyleneimine (PEI)-coated Fe(3)O(4) nanoparticles (MNP). Polyethyleneimine was utilized for the realization of multifunction, including attaching 4 nm TOPO capped CdSe@ZnS quantum dots onto magnetite particles, altering the surface properties of quantum dots from hydrophobic to hydrophilic as well as preventing the formation of large aggregates. Results show that these water-soluble hybrid nanocomposites exhibit good colloidal stability and retain good magnetic and fluorescent properties. Because TOPO-capped QDs are assembled instead of their water-soluble equivalents, the nanocomposites are still highly luminescent with no shift in the PL peak position and present long-term fluorescence stability. Moreover, TAT peptide (GRKKRRQRRRPQ) functionalized hybrid nanoparticles were also studied due to their combined magnetic enrichment and optical detection for cell separation and rapid cell labelling. A cell viability assay revealed good biocompatibility of these hybrid nanoparticles. The potential application of the new magnetic-fluorescent nanocomposites in biological and medicine is demonstrated. © The Royal Society of Chemistry 2011

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

Zalupski, Peter R.; Klaehn, John R.; Peterman, Dean R.

The feasibility of simultaneous separation of uranium, neptunium, plutonium, americium, and curium from a simulated dissolved used fuel simulant adjusted to 1.0 M nitric acid is investigated using a mixture of the soft donor bis(bis-3,5-trifluoromethyl)phenyl) dithiophosphinic acid (“0”) and the hard donor synergist trioctylphosphine oxide (TOPO) dissolved in toluene. The results reported in this work are compared to our recent demonstration of a complete actinide recovery from a simulated dissolved fuel solution using a synergistic combination of bis(o-trifluoromethylphenyl)dithiophosphinic acid (“1”) and TOPO dissolved in either toluene or trifluoromethylphenyl sulfone. While the extraction efficiency of americium was enhanced for the liquid-liquidmore » system containing “0”, enabling to accomplish a trivalent An/Ln separation at 1.0 M HNO3, the extraction of neptunium was drastically diminished, relative to “1”. The partitioning behavior of curium was also negatively impacted, introducing an effective opportunity for americium/curium separation. Radiometric and spectrophotometric studies demonstrate that the complete actinide recovery using the solvent based upon “0” and TOPO is not feasible. Additionally, the importance of radiolytic degradation processes is discussed through the comparisons of extraction properties of liquid-liquid systems based on both soft donor reagents.« less

CIP-36, a novel topoisomerase II-targeting agent, induces the apoptosis of multidrug-resistant cancer cells in vitro.

PubMed

Cao, Bo; Chen, Hong; Gao, Ying; Niu, Cong; Zhang, Yuan; Li, Ling

2015-03-01

The need to overcome cancer multidrug resistance (MDR) has fueled considerable interest in the development of novel synthetic antitumor agents with cytotoxicity against cancer cell lines with MDR. In this study, we aimed to investigate CIP-36, a novel podophyllotoxin derivative, for its inhibitory effects on human cancer cells from multiple sources, particularly cells with MDR in vitro. The human leukemia cell line, K562, and the adriamycin-resistant subline, K562/A02, were exposed to CIP-36 or anticancer agents, and various morphological and biochemical properties were assessed by Hoechst 33342 staining under a fluorescence microscope. Subsequently, cytotoxicity, cell growth curves and the cell cycle were analyzed. Finally, the effects of CIP-36 on topoisomerase IIα (Topo IIα) activity were determined. Treatment with CIP-36 significantly inhibited the growth of the K562 and MDR K562/A02 cells. Our data demonstrated that CIP-36 induced apoptosis, inhibited cell cycle progression and inhibited Topo IIα activity. These findings suggest that CIP-36 has the potential to overcome the multidrug resistance of K562/A02 cells by mediating Topo IIα activity.

TopoLens: Building a cyberGIS community data service for enhancing the usability of high-resolution National Topographic datasets

USGS Publications Warehouse

Hu, Hao; Hong, Xingchen; Terstriep, Jeff; Liu, Yan; Finn, Michael P.; Rush, Johnathan; Wendel, Jeffrey; Wang, Shaowen

2016-01-01

Geospatial data, often embedded with geographic references, are important to many application and science domains, and represent a major type of big data. The increased volume and diversity of geospatial data have caused serious usability issues for researchers in various scientific domains, which call for innovative cyberGIS solutions. To address these issues, this paper describes a cyberGIS community data service framework to facilitate geospatial big data access, processing, and sharing based on a hybrid supercomputer architecture. Through the collaboration between the CyberGIS Center at the University of Illinois at Urbana-Champaign (UIUC) and the U.S. Geological Survey (USGS), a community data service for accessing, customizing, and sharing digital elevation model (DEM) and its derived datasets from the 10-meter national elevation dataset, namely TopoLens, is created to demonstrate the workflow integration of geospatial big data sources, computation, analysis needed for customizing the original dataset for end user needs, and a friendly online user environment. TopoLens provides online access to precomputed and on-demand computed high-resolution elevation data by exploiting the ROGER supercomputer. The usability of this prototype service has been acknowledged in community evaluation.

In vitro characterization of the antibacterial spectrum of novel bacterial type II topoisomerase inhibitors of the aminobenzimidazole class.

PubMed

Mani, Nagraj; Gross, Christian H; Parsons, Jonathan D; Hanzelka, Brian; Müh, Ute; Mullin, Steve; Liao, Yusheng; Grillot, Anne-Laure; Stamos, Dean; Charifson, Paul S; Grossman, Trudy H

2006-04-01

Antibiotics with novel mechanisms of action are becoming increasingly important in the battle against bacterial resistance to all currently used classes of antibiotics. Bacterial DNA gyrase and topoisomerase IV (topoIV) are the familiar targets of fluoroquinolone and coumarin antibiotics. Here we present the characterization of two members of a new class of synthetic bacterial topoII ATPase inhibitors: VRT-125853 and VRT-752586. These aminobenzimidazole compounds were potent inhibitors of both DNA gyrase and topoIV and had excellent antibacterial activities against a wide spectrum of problematic pathogens responsible for both nosocomial and community-acquired infections, including staphylococci, streptococci, enterococci, and mycobacteria. Consistent with the novelty of their structures and mechanisms of action, antibacterial potency was unaffected by commonly encountered resistance phenotypes, including fluoroquinolone resistance. In time-kill assays, VRT-125853 and VRT-752586 were bactericidal against Staphylococcus aureus, Streptococcus pneumoniae, Enterococcus faecalis, and Haemophilus influenzae, causing 3-log reductions in viable cells within 24 h. Finally, similar to the fluoroquinolones, relatively low frequencies of spontaneous resistance to VRT-125853 and VRT-752586 were found, a property consistent with their in vitro dual-targeting activities.

In Vitro Characterization of the Antibacterial Spectrum of Novel Bacterial Type II Topoisomerase Inhibitors of the Aminobenzimidazole Class

PubMed Central

Mani, Nagraj; Gross, Christian H.; Parsons, Jonathan D.; Hanzelka, Brian; Müh, Ute; Mullin, Steve; Liao, Yusheng; Grillot, Anne-Laure; Stamos, Dean; Charifson, Paul S.; Grossman, Trudy H.

2006-01-01

Antibiotics with novel mechanisms of action are becoming increasingly important in the battle against bacterial resistance to all currently used classes of antibiotics. Bacterial DNA gyrase and topoisomerase IV (topoIV) are the familiar targets of fluoroquinolone and coumarin antibiotics. Here we present the characterization of two members of a new class of synthetic bacterial topoII ATPase inhibitors: VRT-125853 and VRT-752586. These aminobenzimidazole compounds were potent inhibitors of both DNA gyrase and topoIV and had excellent antibacterial activities against a wide spectrum of problematic pathogens responsible for both nosocomial and community-acquired infections, including staphylococci, streptococci, enterococci, and mycobacteria. Consistent with the novelty of their structures and mechanisms of action, antibacterial potency was unaffected by commonly encountered resistance phenotypes, including fluoroquinolone resistance. In time-kill assays, VRT-125853 and VRT-752586 were bactericidal against Staphylococcus aureus, Streptococcus pneumoniae, Enterococcus faecalis, and Haemophilus influenzae, causing 3-log reductions in viable cells within 24 h. Finally, similar to the fluoroquinolones, relatively low frequencies of spontaneous resistance to VRT-125853 and VRT-752586 were found, a property consistent with their in vitro dual-targeting activities. PMID:16569833

Topographic Maps from a Kiosk

USGS Publications Warehouse

,

2001-01-01

In April 2000, the U.S. Geological Survey (USGS) and National Geographic (NG) TOPO entered into a cooperative research and development agreement (CRADA) to explore a new technology that would allow a person to walk into a map retail store and print a personalized topographic map, vending machine style, from a self-service kiosk. Work began to develop systems that offer seamless, digitally stored USGS topographic maps using map-on-demand software from NG TOPO. The vending machine approach ensures that maps are never out of stock, allows customers to define their own map boundaries, and gives customers choices regarding shaded relief and the grids to be printed on the maps to get the exact maps they need.

A comparative appraisal of hydrological behavior of SRTM DEM at catchment level

NASA Astrophysics Data System (ADS)

Sharma, Arabinda; Tiwari, K. N.

2014-11-01

The Shuttle Radar Topography Mission (SRTM) data has emerged as a global elevation data in the past one decade because of its free availability, homogeneity and consistent accuracy compared to other global elevation dataset. The present study explores the consistency in hydrological behavior of the SRTM digital elevation model (DEM) with reference to easily available regional 20 m contour interpolated DEM (TOPO DEM). Analysis ranging from simple vertical accuracy assessment to hydrological simulation of the studied Maithon catchment, using empirical USLE model and semidistributed, physical SWAT model, were carried out. Moreover, terrain analysis involving hydrological indices was performed for comparative assessment of the SRTM DEM with respect to TOPO DEM. Results reveal that the vertical accuracy of SRTM DEM (±27.58 m) in the region is less than the specified standard (±16 m). Statistical analysis of hydrological indices such as topographic wetness index (TWI), stream power index (SPI), slope length factor (SLF) and geometry number (GN) shows a significant differences in hydrological properties of the two studied DEMs. Estimation of soil erosion potentials of the catchment and conservation priorities of microwatersheds of the catchment using SRTM DEM and TOPO DEM produce considerably different results. Prediction of soil erosion potential using SRTM DEM is far higher than that obtained using TOPO DEM. Similarly, conservation priorities determined using the two DEMs are found to be agreed for only 34% of microwatersheds of the catchment. ArcSWAT simulation reveals that runoff predictions are less sensitive to selection of the two DEMs as compared to sediment yield prediction. The results obtained in the present study are vital to hydrological analysis as it helps understanding the hydrological behavior of the DEM without being influenced by the model structural as well as parameter uncertainty. It also reemphasized that SRTM DEM can be a valuable dataset for hydrological analysis provided any error/uncertainty therein is being properly evaluated and characterized.

Exploring the DNA binding/cleavage, cellular accumulation and topoisomerase inhibition of 2-hydroxy-3-(aminomethyl)-1,4-naphthoquinone Mannich bases and their platinum(II) complexes.

PubMed

Neves, Amanda P; Pereira, Michelle X G; Peterson, Erica J; Kipping, Ralph; Vargas, Maria D; Silva, Floriano P; Carneiro, J Walkimar M; Farrell, Nicholas P

2013-02-01

Several chlorido and amino Pt(2+) complexes of 2-hydroxy-3-(aminomethyl)-1,4-naphthoquinone Mannich bases HL exhibiting moderate to high cytotoxicity against cancer cell lines were studied in order to investigate their modes of DNA binding, in vitro DNA strand breaks, mechanism of topoisomerase (Topo I) inhibition and cellular accumulation. DNA model base studies have shown that complex 1a [Pt(HL1)Cl(2)] was capable of binding covalently to 9-ethylguanine (9-EtG) and 5'-GMP. (1)H NMR and mass spectrometry studies have shown that both chlorides were substituted by 9-EtG ligands, whereas 5'-GMP was able to replace only one chlorido ligand, due to steric hindrance. The chlorido Pt(2+) complexes [Pt(HL)Cl(2)] highly accumulate in prostate (PC-3) and melanoma (MDA-MB-435) cell lines, being able to induce DNA strand breaks in vitro and inhibit Topo I by a catalytic mode. On the other hand, the free 2-hydroxy-3-(aminomethyl)-1,4-naphthoquinones HL and the amino Pt(2+) complexes [Pt(L(-))(NH(3))(2)]NO(3) neither cause DNA strand breakage nor exhibit strong DNA interaction, nevertheless the latter were also found to be catalytic inhibitors of Topo I at 100μM. Thus, coordination of the Mannich bases HL to the "PtCl(2)" fragment substantially affects the chemical and biophysical properties of the pro-ligands, leading to an improvement of their DNA binding properties and generating compounds that cleave DNA and catalytically inhibit Topo I. Finally, the high cytotoxicity exhibited by the free (uncomplexed) 2-hydroxy-3-(aminomethyl)-1,4-naphthoquinones might be associated with their decomposition in solution, which is not observed for the Pt(2+) complexes. Copyright © 2012 Elsevier Inc. All rights reserved.

NanoTopoChip: High-throughput nanotopographical cell instruction.

PubMed

Hulshof, Frits F B; Zhao, Yiping; Vasilevich, Aliaksei; Beijer, Nick R M; de Boer, Meint; Papenburg, Bernke J; van Blitterswijk, Clemens; Stamatialis, Dimitrios; de Boer, Jan

2017-10-15

Surface topography is able to influence cell phenotype in numerous ways and offers opportunities to manipulate cells and tissues. In this work, we develop the Nano-TopoChip and study the cell instructive effects of nanoscale topographies. A combination of deep UV projection lithography and conventional lithography was used to fabricate a library of more than 1200 different defined nanotopographies. To illustrate the cell instructive effects of nanotopography, actin-RFP labeled U2OS osteosarcoma cells were cultured and imaged on the Nano-TopoChip. Automated image analysis shows that of many cell morphological parameters, cell spreading, cell orientation and actin morphology are mostly affected by the nanotopographies. Additionally, by using modeling, the changes of cell morphological parameters could by predicted by several feature shape parameters such as lateral size and spacing. This work overcomes the technological challenges of fabricating high quality defined nanoscale features on unprecedented large surface areas of a material relevant for tissue culture such as PS and the screening system is able to infer nanotopography - cell morphological parameter relationships. Our screening platform provides opportunities to identify and study the effect of nanotopography with beneficial properties for the culture of various cell types. The nanotopography of biomaterial surfaces can be modified to influence adhering cells with the aim to improve the performance of medical implants and tissue culture substrates. However, the necessary knowledge of the underlying mechanisms remains incomplete. One reason for this is the limited availability of high-resolution nanotopographies on relevant biomaterials, suitable to conduct systematic biological studies. The present study shows the fabrication of a library of nano-sized surface topographies with high fidelity. The potential of this library, called the 'NanoTopoChip' is shown in a proof of principle HTS study which demonstrates how cells are affected by nanotopographies. The large dataset, acquired by quantitative high-content imaging, allowed us to use predictive modeling to describe how feature dimensions affect cell morphology. Copyright © 2017 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

[Suppression of the growth of subcutaneous transplanted human liver cancer and lung metastasis in nude mice treated by sorafenib combined with fluorouracil].

PubMed

Shen, Hu-jia; Wang, Yan-hong; Xu, Jian

2013-02-01

The aim of this study was to explore the inhibitory effect of sorafenib and 5-Fu on transplanted human liver cancer in nude mice, and to investigate the synergistic effect and mechanism between sorafenib and 5-Fu. The nude mouse model of human liver cancer was made by transplantation of human highly metastatic liver cancer cell line HCCLM3 cells, and the tumor-bearing nude mice were treated with sorafenib, 5-Fu or both, respectively, and mock-treated tumor-bearing nude mice as negative control. To assess the anti-tumor effect of sorafenib and the synergistic effect of sorafenib combined with 5-Fu by measuring the tumor weight and number of lung metastases. Moreover, the expressions of phosphorylated extracellular signal-regulated kinase (p-ERK), P-glycoprotein (P-gp) and topoisomerase 2-alpha (Topo IIa) in the nude mice were assayed by immunocytochemistry and Western blot. The tumor weights and numbers of lung metastases were: (2.7 ± 0.825) g and 12.714 ± 6.317 in the negative control group, (0.933 ± 0.333) g and 4.333 ± 3.983 in the sorafenib group, (0.786 ± 0.212) g and 5.429 ± 4.315 in the Sorafenib + 5-Fu combination group, and (2.438 ± 0.793) g and 10.429 ± 6.241 in the 5-Fu group. Statistically, the tumor weights and numbers of lung metastases in the sorafenib group and combination group were significantly decreased, compared with that in the control group (P < 0.05). There was no significant difference in the tumor weight and number of lung metastases between the sorafenib group and the combination treatment group (P > 0.05). The expression levels of p-ERK, P-gp and Topo IIa proteins in the tumors after normalization were: negative control (0.017 ± 0.010, 0.085 ± 0.012, 0.103 ± 0.093), sorafenib group (0.010 ± 0.008, 0.044 ± 0.020, 0.020 ± 0.018), combination group (0.011 ± 0.007, 0.043 ± 0.023, 0.062 ± 0.026), and 5-Fu group (0.018 ± 0.009, 0.063 ± 0.032, 0.065 ± 0.034), respectively. Statistically, the expression of p-ERK, P-gp and Topo IIa in the Sorafenib group was significantly reduced compared with that of the control group (P < 0.05), and there was no significant difference in the expression of p-ERK, P-gp and Topo IIa between the sorafenib group and the combination treatment group (P > 0.05). Sorafenib can inhibit not only the tumor growth and lung metastsis in the nude mouse models, but also reduce the expression of multidrug resistance proteins P-gp and Topo IIa as well. There is no significant advantage for the sorafenib + 5-Fu combination treatment than Sorafenib alone in inhibiting the expression of p-ERK, P-gp and Topo IIa.

Ordered CdSe nanoparticles within self-assembled block copolymer domains on surfaces.

PubMed

Zou, Shan; Hong, Rui; Emrick, Todd; Walker, Gilbert C

2007-02-13

Hierarchical, high-density, ordered patterns were fabricated on Si substrates by self-assembly of CdSe nanoparticles within approximately 20-nm-thick diblock copolymer films in a controlled manner. Surface-modified CdSe nanoparticles formed well-defined structures within microphase-separated polystyrene-b-poly(2-vinylpyridine) (PS-b-P2VP) domains. Trioctylphosphine oxide (TOPO)-coated CdSe nanoparticles were incorporated into PS domains and polyethylene glycol-coated CdSe nanoparticles were located primarily in the P2VP domains. Nearly close-packed CdSe nanoparticles were clearly identified within the highly ordered patterns on Si substrates by scanning electron microscopy (SEM). Contact angle measurements together with SEM results indicate that TOPO-CdSe nanoparticles were partially placed at the air/copolymer interface.

Wieland's nude bathers: visual pleasure and the female gaze.

PubMed

Robertson, Ritchie

2011-01-01

In her essays on Wieland, written around 1980, Elizabeth Boa went against contemporary fashion both by praising a neglected writer and by vindicating the role of pleasure in the reception of literature. She noted how Wieland varies a literary topos – a man watching a woman bathing naked – by letting women watch men bathing naked. This topos most often occurs in the pastoral, a popular eighteenth-century genre. Various examples are examined to show that they suggest equality rather than male dominance in relations between the sexes: men watching women bathing in James Thomson and Gottfried Keller; an example involving cross-dressing in Kleist; and finally women watching men bathing naked in Swift, Voltaire and Wieland's Idris und Zenide.

Negative supercoiling of DNA by gyrase is inhibited in Salmonella enterica serovar Typhimurium during adaptation to acid stress.

PubMed

Colgan, Aoife M; Quinn, Heather J; Kary, Stefani C; Mitchenall, Lesley A; Maxwell, Anthony; Cameron, Andrew D S; Dorman, Charles J

2018-03-01

DNA in intracellular Salmonella enterica serovar Typhimurium relaxes during growth in the acidified (pH 4-5) macrophage vacuole and DNA relaxation correlates with the upregulation of Salmonella genes involved in adaptation to the macrophage environment. Bacterial ATP levels did not increase during adaptation to acid pH unless the bacterium was deficient in MgtC, a cytoplasmic-membrane-located inhibitor of proton-driven F 1 F 0 ATP synthase activity. Inhibiting ATP binding by DNA gyrase and topo IV with novobiocin enhanced the effect of low pH on DNA relaxation. Bacteria expressing novobiocin-resistant (Nov R ) derivatives of gyrase or topo IV also exhibited DNA relaxation at acid pH, although further relaxation with novobiocin was not seen in the strain with Nov R gyrase. Thus, inhibition of the negative supercoiling activity of gyrase was the primary cause of enhanced DNA relaxation in drug-treated bacteria. The Salmonella cytosol reaches pH 5-6 in response to an external pH of 4-5: the ATP-dependent DNA supercoiling activity of purified gyrase was progressively inhibited by lowering the pH in this range, as was the ATP-dependent DNA relaxation activity of topo IV. We propose that DNA relaxation in Salmonella within macrophage is due to acid-mediated impairment of the negative supercoiling activity of gyrase. © 2018 John Wiley & Sons Ltd.

The Ubiquitin-Conjugating Enzyme E2-EPF Is Overexpressed in Primary Breast Cancer and Modulates Sensitivity to Topoisomerase II Inhibition1

PubMed Central

Tedesco, Donato; Zhang, Jianhuan; Trinh, Lan; Lalehzadeh, Guita; Meisner, Rene; Yamaguchi, Ken D; Ruderman, Daniel L; Dinter, Harald; Zajchowski, Deborah A

2007-01-01

We identified the ubiquitin-conjugating enzyme E2-EPF mRNA as differentially expressed in breast tumors relative to normal tissues and performed studies to elucidate its putative role in cancer. We demonstrated that overexpression of E2-EPF protein correlated with estrogen receptor (ER) negativity in breast cancer specimens and that its expression is cell cycle-regulated, suggesting a potential function for E2-EPF in cell cycle progression. However, reduction of E2-EPF protein levels by > 80% using RNAi had no significant effects on the proliferation of HeLa cervical cancer cells or ER- MDA-MB-231 or MDA-MB-453 breast cancer cells. Because E2-EPF protein levels were elevated during the G2/M phase of the cell cycle and because E2-EPF mRNA in tumor specimens was frequently coexpressed with genes involved in cell cycle control, spindle assembly, and mitotic surveillance, the possibility that E2-EPF might have a function in the cellular response to agents that induce a G2 checkpoint or an M checkpoint was investigated. E2-EPF knockdown sensitized HeLa cells to the topoisomerase (topo) II inhibitors etoposide and doxorubicin and also increased topo IIα protein levels. These data suggest that combined administration of topo II-directed drugs and E2-EPF inhibitors may enhance their clinical effectiveness. PMID:17710163

The ubiquitin-conjugating enzyme E2-EPF is overexpressed in primary breast cancer and modulates sensitivity to topoisomerase II inhibition.

PubMed

Tedesco, Donato; Zhang, Jianhuan; Trinh, Lan; Lalehzadeh, Guita; Meisner, Rene; Yamaguchi, Ken D; Ruderman, Daniel L; Dinter, Harald; Zajchowski, Deborah A

2007-07-01

We identified the ubiquitin-conjugating enzyme E2-EPF mRNA as differentially expressed in breast tumors relative to normal tissues and performed studies to elucidate its putative role in cancer. We demonstrated that overexpression of E2-EPF protein correlated with estrogen receptor (ER) negativity in breast cancer specimens and that its expression is cell cycle-regulated, suggesting a potential function for E2-EPF in cell cycle progression. However, reduction of E2-EPF protein levels by > 80% using RNAi had no significant effects on the proliferation of HeLa cervical cancer cells or ER(-) MDA-MB-231 or MDA-MB-453 breast cancer cells. Because E2-EPF protein levels were elevated during the G(2)/M phase of the cell cycle and because E2-EPF mRNA in tumor specimens was frequently coexpressed with genes involved in cell cycle control, spindle assembly, and mitotic surveillance, the possibility that E2-EPF might have a function in the cellular response to agents that induce a G(2) checkpoint or an M checkpoint was investigated. E2-EPF knockdown sensitized HeLa cells to the topoisomerase (topo) II inhibitors etoposide and doxorubicin and also increased topo IIalpha protein levels. These data suggest that combined administration of topo II-directed drugs and E2-EPF inhibitors may enhance their clinical effectiveness.

The selective effect of glycyrrhizin and glycyrrhetinic acid on topoisomerase IIα and apoptosis in combination with etoposide on triple negative breast cancer MDA-MB-231 cells.

PubMed

Cai, Yun; Zhao, Boxin; Liang, Qianying; Zhang, Yunqi; Cai, Jieying; Li, Guofeng

2017-08-15

Triple negative breast cancer(TNBC) has generated growing interests due to its aggressive biologic behavior and absence of targeted therapy approach. Glycyrrhizin(GL) from licorice root and its metabolite, glycyrrhetinic acid(GA) have shown extensive bioactivities in clinic. Here, we demonstrate that GL and GA have contrary anti-cancer effect on TNBC MDA-MB-231 cells. Beside its inhibition of cell proliferation, GA at non-cytotoxic concentration showed synergistic effect in combination with anti-cancer drug, etoposide(VP-16). Specifically, GA enhanced cytotoxicity through regulating topoisomerase IIα(TOPO 2A) targeted by etoposide. GA sensitized the cells to etoposide through elevating TOPO 2A with a 2.4 fold rate at 12h. From 12 to 48h, GA halved the expression of TOPO 2A and stimulated apoptosis, which exhibited its antineoplastic effect. Our experiments showed that GSH depletion, modulation of MAPK and AKT pathways accounted for the regulation of topoisomerase IIα and apoptosis. However, GL showed protection and detoxication by decreasing reactive oxygen species generation, maintaining GSH and differentially modulating apoptosis, AKT pathway, ERK and JNK of MAPK pathway. Collectively, our results demonstrate that GA, instead of GL, is a better candidate for TNBC treatment because of its anti-cancer effect and sensitization of topoisomerase IIα inhibitor. Copyright © 2017 Elsevier B.V. All rights reserved.

Reproducible, Component-based Modeling with TopoFlow, A Spatial Hydrologic Modeling Toolkit

DOE PAGES

Peckham, Scott D.; Stoica, Maria; Jafarov, Elchin; ...

2017-04-26

Modern geoscientists have online access to an abundance of different data sets and models, but these resources differ from each other in myriad ways and this heterogeneity works against interoperability as well as reproducibility. The purpose of this paper is to illustrate the main issues and some best practices for addressing the challenge of reproducible science in the context of a relatively simple hydrologic modeling study for a small Arctic watershed near Fairbanks, Alaska. This study requires several different types of input data in addition to several, coupled model components. All data sets, model components and processing scripts (e.g. formore » preparation of data and figures, and for analysis of model output) are fully documented and made available online at persistent URLs. Similarly, all source code for the models and scripts is open-source, version controlled and made available online via GitHub. Each model component has a Basic Model Interface (BMI) to simplify coupling and its own HTML help page that includes a list of all equations and variables used. The set of all model components (TopoFlow) has also been made available as a Python package for easy installation. Three different graphical user interfaces for setting up TopoFlow runs are described, including one that allows model components to run and be coupled as web services.« less

Reproducible, Component-based Modeling with TopoFlow, A Spatial Hydrologic Modeling Toolkit

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

Peckham, Scott D.; Stoica, Maria; Jafarov, Elchin

Modern geoscientists have online access to an abundance of different data sets and models, but these resources differ from each other in myriad ways and this heterogeneity works against interoperability as well as reproducibility. The purpose of this paper is to illustrate the main issues and some best practices for addressing the challenge of reproducible science in the context of a relatively simple hydrologic modeling study for a small Arctic watershed near Fairbanks, Alaska. This study requires several different types of input data in addition to several, coupled model components. All data sets, model components and processing scripts (e.g. formore » preparation of data and figures, and for analysis of model output) are fully documented and made available online at persistent URLs. Similarly, all source code for the models and scripts is open-source, version controlled and made available online via GitHub. Each model component has a Basic Model Interface (BMI) to simplify coupling and its own HTML help page that includes a list of all equations and variables used. The set of all model components (TopoFlow) has also been made available as a Python package for easy installation. Three different graphical user interfaces for setting up TopoFlow runs are described, including one that allows model components to run and be coupled as web services.« less

Complete recovery of actinides from UREX-like raffinates using a combination of hard and soft donor ligands. II. soft donor structure variation

DOE PAGES

Zalupski, Peter R.; Klaehn, John R.; Peterman, Dean R.

2015-07-30

The feasibility of simultaneous separation of uranium, neptunium, plutonium, americium, and curium from a simulated dissolved used fuel simulant adjusted to 1.0 M nitric acid is investigated using a mixture of the soft donor bis(bis-3,5-trifluoromethyl)phenyl) dithiophosphinic acid (“0”) and the hard donor synergist trioctylphosphine oxide (TOPO) dissolved in toluene. The results reported in this work are compared to our recent demonstration of a complete actinide recovery from a simulated dissolved fuel solution using a synergistic combination of bis(o-trifluoromethylphenyl)dithiophosphinic acid (“1”) and TOPO dissolved in either toluene or trifluoromethylphenyl sulfone. While the extraction efficiency of americium was enhanced for the liquid-liquidmore » system containing “0”, enabling to accomplish a trivalent An/Ln separation at 1.0 M HNO3, the extraction of neptunium was drastically diminished, relative to “1”. The partitioning behavior of curium was also negatively impacted, introducing an effective opportunity for americium/curium separation. Radiometric and spectrophotometric studies demonstrate that the complete actinide recovery using the solvent based upon “0” and TOPO is not feasible. Additionally, the importance of radiolytic degradation processes is discussed through the comparisons of extraction properties of liquid-liquid systems based on both soft donor reagents.« less

Evaluating the genotoxicity of topoisomerase-targeted antibiotics

PubMed Central

Smart, Daniel J.; Lynch, Anthony M.

2012-01-01

Antibiotics like fluoroquinolones (FQs) that target bacterial type II topoisomerases pose a potential genotoxic risk due to interactions with mammalian topoisomerase II (TOPO II) counterparts. Inhibition of TOPO II can lead to the generation of clastogenic DNA double-strand breaks (DSBs) that can in turn manifest in mutagenesis. Thus, methods that allow early identification of drugs that present the greatest hazard are warranted. A rapid, medium-throughput and predictive genotoxicity screen that can be applied to bacterial type II topoisomerase inhibitors is described herein. Maximal induction of the DSB biomarker serine139-phosphorylated histone H2AX (γH2AX) in L5178Y cells was quantified via flow cytometry and correlated with data derived from the mouse lymphoma screen (MLS), a default assay used to rank genotoxic potential. When applied to a class of novel bacterial type II topoisomerase inhibitors (NBTIs) in lead-optimisation, maximal γH2AX induction >1.4-fold (relative to controls) identified 22/27 NBTIs that induced >6-fold relative mutation frequency (MF) in MLS. Moreover, response signatures comprising of γH2AX induction and G2M cell cycle arrest elucidated using this approach suggested that these NBTIs, primarily of the H class, operated via a TOPO II poison-like mechanism of action (MoA) similar to FQs. NBTIs that induced ≤6-fold relative MF, which were mainly A class-derived, had less impact on γH2AX (≤1.4-fold) and also evoked G1 arrest, indicating that their cytotoxic effects were likely mediated through a non-poison MoA. Concordance between assays was 86% (54/63) when 1.4- and 6-fold ‘cut offs’ were applied. These findings were corroborated through inspection of human TOPO IIα IC50 data as NBTIs exhibiting equivalent inhibitory capacities had differing genotoxic potencies. Deployed in an early screening capacity, the γH2AX by flow assay coupled with structure–activity relationship evaluation can provide insight into MoA and impact medicinal chemistry efforts, ultimately leading to the production of inherently safer molecules. PMID:22155972

A Model to Aid Topo-Map Interpretation

ERIC Educational Resources Information Center

Westerback, Mary

1976-01-01

Describes how to construct models of contour lines from flexible, colored bell wire. These models are used to illustrate three-dimensional terrain characteristics represented by contour lines printed on a flat map. (MLH)

Design, synthesis, anticancer screening, docking studies and in silico ADME prediction of some β-carboline derivatives.

PubMed

Abdelsalam, Mohamed A; AboulWafa, Omaima M; M Badawey, El-Sayed A; El-Shoukrofy, Mai S; El-Miligy, Mostafa M; Gouda, Noha; Elaasser, Mahmoud M

2018-05-22

Medicinal interest has focused on β-carbolines as anticancer agents. Several β-carbolines were designed, synthesized and evaluated for their cytotoxic activity against MCF-7 and A-549 cancer cell lines using MTT assay. Compounds 13a, 13c, 13d and 20a were the most promising showing high selectivity indices. Compounds 13c and 20a showed potent inhibition of topoisomerase (topo-I) and kinesin spindle protein (KSP/Eg5 ATPase) which was confirmed by their docking results into the active site of both enzymes. In silico physicochemical calculations predicted that compounds 13a, 13d and 20a obeyed Lipinski's rule of five. Compounds 13c and 20a are multitarget anticancer leads that act as potent inhibitors for both topo-I and/or KSP ATPase.

TOPoS: chemical study of extremely metal-poor stars.

NASA Astrophysics Data System (ADS)

Caffau, E.; Sbordone, L.; Bonifacio, P.; Cayrel, R.; Christlieb, N.; Clark, P.; François, P.; Glover, S.; Klessen, R.; Koch, A.; Ludwig, H.-G.; Monaco, L.; Plez, B.; Spite, F.; Spite, M.; Steffen, M.; Zaggia, S.

The extremely metal-poor (EMP) stars hold in their atmospheres the fossil record of the chemical composition of the early phases of the Galactic evolution. The chemical analysis of such objects provides important constraints on these early phases. EMP stars are very rare objects; to dig them out, large amounts of data have to be processed. With an automatic procedure, we analysed objects with colours of Turn-Off stars from the Sloan Digital Sky Survey to select a sample of good candidate EMP stars. In the latest years, we observed a sample of these candidates with X-Shooter and UVES, and we have an ongoing ESO large programme to use these spectrographs to observe EMP stars. I will report here the results on metallicity and Strontium abundance. Based on observations obtained at ESO Paranal Observatory, programme 189.D-0165(A)

A PCR-aided transcript titration assay (PATTY) to measure topoisomerase I gene expression in human tumor specimens.

PubMed

Meersma, G J; Bakker, M; Groen, H J; Van der Zee, A G; Jensen, P B; Giaccone, G; De Vries, E G; Smit, E F

1999-01-01

Topoisomerase I (topo I) inhibitors are promising anticancer agents with demonstrated activity against a wide range of solid tumors. Quantitative information on topol mRNA levels in tumor biopsies may predict response to topo I inhibitors. A polymerase chain reaction aided transcript titration assay (PATTY) was developed to allow quantitation of topol mRNA in small samples. Concentrations of topol mRNA in total RNA samples were estimated by RT-PCR analysis in a human small cell lung cancer (SCLC) cell line (GLC,) and its topotecan (GL2C/SK and F) and camptothecin (GL2C/Campt) resistant sublines, human non-small cell lung cancer (NSCLC) and ovarian carcinoma samples. Topol PATTY showed a decreased topo I mRNA level in GLC2/SK and F (4.5 pg/100 ng total RNA) and GLC,/Campt (2.2 pg/100 ng total RNA), respectively, compared to the parent cell line GLC2 (5.4 pg/100 ng total RNA). Topol protein levels as measured by Western blotting were compatible with topol mRNA levels. Median (range) topol mRNA levels were 3.23 (2.33-5.10) pg/100 ng total RNA in resected NSCLC specimen (n = 6), and 2.03 (0.54-0.95) pg/100 ng total RNA in resected ovarian cancer specimen (n = 6). We conclude that topol PATTY is a new assay that quantitates topol mRNA levels in cell lines and small tumor samples.

Determination of amlodipine using terbium-sensitized luminescence in the presence of europium(III) as a co-luminescence reagent.

PubMed

Al-Kindy, Salma M Z; Al-Snedi, Abdalla; Suliman, Fakhr Eldin O; Al-Lawati, Haidar A J

2014-09-01

A sensitive time-resolved luminescence method for the determination of amlodipine (AM) in methanol and in aqueous solution is described. The method is based on the luminescence sensitization of terbium (Tb(3+) ) by formation of a ternary complex with AM in the presence of tri-n-octylphosphine oxide (TOPO) as co-ligand, dodecylbenzenesulfate as surfactant and europium ion as a co-luminescence reagent. The signal for Tb-AM-TOPO is monitored at λex  = 242 nm and λem  = 550 nm. Optimum conditions for the formation of the complex in aqueous system were 0.015 m Tris (hydroxylmethyl) amino methane buffer, pH 9.0, TOPO (1.0 × 10(-4) m), Eu(3+) (2.0 × 10(-7) m), dodecylbenzenesulfate (0.14%) and 6.0 × 10(-5) m of Tb(3+) , which allows the determination of 10-50 ppb of AM with a limit of detection of 1.2 ppb. The relative standard deviations of the method range between 0.1 and 0.2% indicated excellent reproducibility of the method. The proposed method was successfully applied for the assay of AM in pharmaceutical formulations and in plasma samples. Average recoveries of 98.5 ± 0.2% and 95.2 ± 0.2% were obtained for AM in tablet and plasma samples respectively. Copyright © 2013 John Wiley & Sons, Ltd.

Features of the Thermodynamics of Trivalent Lanthanide/Actinide Distribution Reactions by Tri-n-Octylphosphine Oxide and Bis(2-EthylHexyl) Phosphoric Acid

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

Travis S. Grimes; Peter R. Zalupski

2014-11-01

A new methodology has been developed to study the thermochemical features of the biphasic transfer reactions of trisnitrato complexes of lanthanides and americium by a mono-functional solvating ligand (tri-n-octyl phosphine oxide - TOPO). Stability constants for successive nitrato complexes (M(NO3)x3-x (aq) where M is Eu3+, Am3+ or Cm3+) were determined to assist in the calculation of the extraction constant, Kex, for the metal ions under study. Enthalpies of extraction (?Hextr) for the lanthanide series (excluding Pm3+) and Am3+ by TOPO have been measured using isothermal titration calorimetry. The observed ?Hextr were found to be constant at ~29 kJ mol-1across themore » series from La3+-Er3+, with a slight decrease observed from Tm3+-Lu3+. These heats were found to be consistent with enthalpies determined using van ’t Hoff analysis of temperature dependent extraction studies. A complete set of thermodynamic parameters (?G, ?H, ?S) was calculated for Eu(NO3)3, Am(NO3)3 and Cm(NO3)3 extraction by TOPO and Am3+ and Cm3+ extraction by bis(2-ethylhexyl) phosphoric acid (HDEHP). A discussion comparing the energetics of these systems is offered. The measured biphasic extraction heats for the transplutonium elements, ?Hextr, presented in these studies are the first ever direct measurements offered using two-phase calorimetric techniques.« less

Improvement of the cloud point extraction of uranyl ions by the addition of ionic liquids.

PubMed

Gao, Song; Sun, Taoxiang; Chen, Qingde; Shen, Xinghai

2013-12-15

The cloud point extraction (CPE) of uranyl ions by different kinds of extractants in Triton X-114 (TX-114) micellar solution was investigated upon the addition of ionic liquids (ILs) with various anions, i.e., bromide (Br(-)), tetrafluoroborate (BF4(-)), hexafluorophosphate (PF6(-)) and bis[(trifluoromethyl)sulfonyl]imide (NTf2(-)). A significant increase of the extraction efficiency was found on the addition of NTf2(-) based ILs when using neutral extractant tri-octylphosphine oxide (TOPO), and the extraction efficiency kept high at both nearly neutral and high acidity. However, the CPE with acidic extractants, e.g., bis(2-ethylhexyl) phosphoric acid (HDEHP) and 8-hydroxyquinoline (8-HQ) which are only effective at nearly neutral condition, was not improved by ILs. The results of zeta potential and (19)F NMR measurements indicated that the anion NTf2(-) penetrated into the TX-114 micelles and was enriched in the surfactant-rich phase during the CPE process. Meanwhile, NTf2(-) may act as a counterion in the CPE of UO2(2+) by TOPO. Furthermore, the addition of IL increased the separation factor of UO2(2+) and La(3+), which implied that in the micelle TOPO, NTf2(-) and NO3(-) established a soft template for UO2(2+). Therefore, the combination of CPE and IL provided a supramolecular recognition to concentrate UO2(2+) efficiently and selectively. Copyright © 2013 Elsevier B.V. All rights reserved.

6. Photocopy of photograph (original in possession of NYC Economic ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

6. Photocopy of photograph (original in possession of NYC Economic Development Corp.) Topo-Metrics, Inc, 1992. Aerial view of the Brooklyn Army Terminal - Brooklyn Army Supply Base, Pier 2, Brooklyn, Kings County, NY

Novel 20(S)-sulfonylamidine derivatives of camptothecin and the use thereof as a potent antitumor agent: a patent evaluation of WO2015048365 (A1).

PubMed

Beretta, Giovanni Luca; Zaffaroni, Nadia; Varchi, Greta

2016-05-01

A series of camptothecin (CPT) derivatives featuring acyl-esterification of the 20(S)-hydroxyl group with a residue containing a sulfonylamidine moiety is synthesized via a Cu catalyzed three-component reaction. The compounds show remarkable cytotoxicity against a panel of tumor cells, including a cell line exhibiting Multi-Drug Resistant (MDR) phenotype. The patent develops 9a, the best derivative of the series, that i) selectively poisons DNA Topoisomerase I (TopoI); ii) induces cell-cycle S-phase arrest with activation of the DNA damage response pathway and apoptosis induction and iii) shows considerable in vivo antitumor potency. We envision that the peculiar modification of the 20(S)-hydroxyl group of CPT with a sulfonylamidine residue will play a continuing role in affording new TopoI poison drug candidates for therapeutic applications.

Atomic level characterization of cadmium selenide nanocrystal systems using atomic number contrast scanning transmission electron microscopy and Rutherford backscattering spectroscopy

NASA Astrophysics Data System (ADS)

McBride, James R.

This project involved the characterization of CdSe nanocrystals. Through the use of Atomic Number Contrast Scanning Transmission Electron Microscopy (Z-STEM) and Rutherford Backscattering Spectroscopy (RBS), atomic level structure and chemical information was obtained. Specifically, CdSe nanocrystals produced using a mixture of hexadecylamine (HDA) and trioctylphosphine oxide (TOPO) were determined to be spherical compared to nanocrystals produced in TOPO only, which had elongated (101) facets. Additionally, the first Z-STEM images of CdSe/ZnS core/shell nanocrystals were obtained. From these images, the growth mechanism of the ZnS shell was determined and the existence of non-fluorescent ZnS particles was confirmed. Through collaboration with Quantum Dot Corp., core/shell nanocrystals with near unity quantum yield were developed. These core/shell nanocrystals included a US intermediate layer to improve shell coverage.

Genotoxicity of topoisomerase II inhibitors: an anti-infective perspective.

PubMed

Smart, Daniel J

2008-12-30

At present, an inevitable consequence of a chemical's inhibitory activity on key regulators of DNA topology in bacteria, the type II topoisomerases, is a less pronounced effect on their eukaryotic counterparts. In the context of anti-infectives drug development, this may pose a risk to patient safety as inhibition of eukaryotic type II topoisomerases (TOPO II) can result in the generation of DNA double-strand breaks (DSBs), which have the potential to manifest as mutations, chromosome breakage or cell death. The biological effects of several TOPO II inhibitors in mammalian cells are described herein; their modulation of DSB damage response parameters is examined and evidence for the existence of a threshold concept for genotoxicity and its relevance in safety assessment is discussed. The potential utility of gammaH2AX, a promising and highly sensitive molecular marker for DSBs, in a novel genotoxicity 'pre-screen' to conventional assays is also highlighted.

Arabidopsis thaliana DNA gyrase is targeted to chloroplasts and mitochondria.

PubMed

Wall, Melisa K; Mitchenall, Lesley A; Maxwell, Anthony

2004-05-18

DNA gyrase is the bacterial DNA topoisomerase (topo) that supercoils DNA by using the free energy of ATP hydrolysis. The enzyme, an A(2)B(2) tetramer encoded by the gyrA and gyrB genes, catalyses topological changes in DNA during replication and transcription, and is the only topo that is able to introduce negative supercoils. Gyrase is essential in bacteria and apparently absent from eukaryotes and is, consequently, an important target for antibacterial agents (e.g., quinolones and coumarins). We have identified four putative gyrase genes in the model plant Arabidopsis thaliana; one gyrA and three gyrB homologues. DNA gyrase protein A (GyrA) has a dual translational initiation site targeting the mature protein to both chloroplasts and mitochondria, and there are individual targeting sequences for two of the DNA gyrase protein B (GyrB) homologues. N-terminal fusions of the organellar targeting sequences to GFPs support the hypothesis that one enzyme is targeted to the chloroplast and another to the mitochondrion, which correlates with supercoiling activity in isolated organelles. Treatment of seedlings and cultured cells with gyrase-specific drugs leads to growth inhibition. Knockout of A. thaliana gyrA is embryo-lethal whereas knockouts in the gyrB genes lead to seedling-lethal phenotypes or severely stunted growth and development. The A. thaliana genes have been cloned in Escherichia coli and found to complement gyrase temperature-sensitive strains. This report confirms the existence of DNA gyrase in eukaryotes and has important implications for drug targeting, organelle replication, and the evolution of topos in plants.

A topo-graph model for indistinct target boundary definition from anatomical images.

PubMed

Cui, Hui; Wang, Xiuying; Zhou, Jianlong; Gong, Guanzhong; Eberl, Stefan; Yin, Yong; Wang, Lisheng; Feng, Dagan; Fulham, Michael

2018-06-01

It can be challenging to delineate the target object in anatomical imaging when the object boundaries are difficult to discern due to the low contrast or overlapping intensity distributions from adjacent tissues. We propose a topo-graph model to address this issue. The first step is to extract a topographic representation that reflects multiple levels of topographic information in an input image. We then define two types of node connections - nesting branches (NBs) and geodesic edges (GEs). NBs connect nodes corresponding to initial topographic regions and GEs link the nodes at a detailed level. The weights for NBs are defined to measure the similarity of regional appearance, and weights for GEs are defined with geodesic and local constraints. NBs contribute to the separation of topographic regions and the GEs assist the delineation of uncertain boundaries. Final segmentation is achieved by calculating the relevance of the unlabeled nodes to the labels by the optimization of a graph-based energy function. We test our model on 47 low contrast CT studies of patients with non-small cell lung cancer (NSCLC), 10 contrast-enhanced CT liver cases and 50 breast and abdominal ultrasound images. The validation criteria are the Dice's similarity coefficient and the Hausdorff distance. Student's t-test show that our model outperformed the graph models with pixel-only, pixel and regional, neighboring and radial connections (p-values <0.05). Our findings show that the topographic representation and topo-graph model provides improved delineation and separation of objects from adjacent tissues compared to the tested models. Copyright © 2018 Elsevier B.V. All rights reserved.

Structural Characterization of Biocompatible Reverse Micelles Using Small-Angle X-ray Scattering, 31P Nuclear Magnetic Resonance, and Fluorescence Spectroscopy.

PubMed

Odella, Emmanuel; Falcone, R Darío; Ceolín, Marcelo; Silber, Juana J; Correa, N Mariano

2018-04-19

The most critical problem regarding the use of reverse micelles (RMs) in several fields is the toxicity of their partial components. In this sense, many efforts have been made to characterize nontoxic RM formulations on the basis of biological amphiphiles and/or different oils. In this contribution, the microstructure of biocompatible mixed RMs formulated by sodium 1,4-bis-2-ethylhexylsulfosuccinate (AOT) and tri- n-octylphosphine oxide (TOPO) surfactants dispersed in the friendly solvent methyl laurate was studied by using SAXS and 31 P NMR and by following the solvatochromic behavior of the molecular probe 4-aminophthalimide (4-AP). The results indicated the presence of RM aggregates upon TOPO incorporation with a droplet size reduction and an increase in the interfacial fluidity in comparison with pure AOT RMs. When confined inside the mixed systems, 4-AP showed a red-edge excitation shift and confirmed the increment of interfacial fluidity upon TOPO addition. Also, the partition between the external nonpolar solvent and the RM interface and an increase in both the local micropolarity and the capability to form a hydrogen bond interaction between 4-AP and a mixed interface were observed. The findings have been explained in terms of the nonionic surfactant structure and its complexing nature expressed at the interfacial level. Notably, we show how two different approaches, i.e., SAXS and the solvatochromism of the probe 4-AP, can be used in a complementary way to enhance our understanding of the interfacial fluidity of RMs, a parameter that is difficult to measure directly.

Helix–hairpin–helix motifs confer salt resistance and processivity on chimeric DNA polymerases

PubMed Central

Pavlov, Andrey R.; Belova, Galina I.; Kozyavkin, Sergei A.; Slesarev, Alexei I.

2002-01-01

Helix–hairpin–helix (HhH) is a widespread motif involved in sequence-nonspecific DNA binding. The majority of HhH motifs function as DNA-binding modules with typical occurrence of one HhH motif or one or two (HhH)2 domains in proteins. We recently identified 24 HhH motifs in DNA topoisomerase V (Topo V). Although these motifs are dispensable for the topoisomerase activity of Topo V, their removal narrows the salt concentration range for topoisomerase activity tenfold. Here, we demonstrate the utility of Topo V's HhH motifs for modulating DNA-binding properties of the Stoffel fragment of TaqDNA polymerase and Pfu DNA polymerase. Different HhH cassettes fused with either NH2 terminus or COOH terminus of DNA polymerases broaden the salt concentration range of the polymerase activity significantly (up to 0.5 M NaCl or 1.8 M potassium glutamate). We found that anions play a major role in the inhibition of DNA polymerase activity. The resistance of initial extension rates and the processivity of chimeric polymerases to salts depend on the structure of added HhH motifs. Regardless of the type of the construct, the thermal stability of chimeric Taq polymerases increases under the optimal ionic conditions, as compared with that of TaqDNA polymerase or its Stoffel fragment. Our approach to raise the salt tolerance, processivity, and thermostability of Taq and Pfu DNA polymerases may be applied to all pol1- and polB-type polymerases, as well as to other DNA processing enzymes. PMID:12368475

International Space Station (ISS) External Thermal Control System (ETCS) Loop A Pump Module (PM) Jettison Options Assessment

NASA Technical Reports Server (NTRS)

Murri, Daniel G.; Dwyer Cianciolo, Alicia; Shidner, Jeremy D.; Powell, Richard W.

2014-01-01

On December 11, 2013, the International Space Station (ISS) experienced a failure of the External Thermal Control System (ETCS) Loop A Pump Module (PM). To minimize the number of extravehicular activities (EVA) required to replace the PM, jettisoning the faulty pump was evaluated. The objective of this study was to independently evaluate the jettison options considered by the ISS Trajectory Operations Officer (TOPO) and to provide recommendations for safe jettison of the ETCS Loop A PM. The simulation selected to evaluate the TOPO options was the NASA Engineering and Safety Center's (NESC) version of Program to Optimize Simulated Trajectories II (POST2) developed to support another NESC assessment. The objective of the jettison analysis was twofold: (1) to independently verify TOPO posigrade and retrograde jettison results, and (2) to determine jettison guidelines based on additional sensitivity, trade study, and Monte Carlo (MC) analysis that would prevent PM recontact. Recontact in this study designates a propagated PM trajectory that comes within 500 m of the ISS propagated trajectory. An additional simulation using Systems Tool Kit (STK) was run for independent verification of the POST2 simulation results. Ultimately, the ISS Program removed the PM jettison option from consideration. However, prior to the Program decision, the retrograde jettison option remained part of the EVA contingency plan. The jettison analysis presented showed that, in addition to separation velocity/direction and the atmosphere conditions, the key variables in determining the time to recontact the ISS is highly dependent on the ballistic number (BN) difference between the object being jettisoned and the ISS.

US Topo–A new national map series, 2012 update

USGS Publications Warehouse

Moore, Laurence R.

2013-01-01

The U.S. Geological Survey's Larry Moore provides an update on the US Topo effort, the Survey’s general purpose, digital, quadrangle map series. He outlines the successes thus far and the obstacles still ahead in 2013.

The neural correlates of highly iconic structures and topographic discourse in French Sign Language as observed in six hearing native signers.

PubMed

Courtin, C; Hervé, P-Y; Petit, L; Zago, L; Vigneau, M; Beaucousin, V; Jobard, G; Mazoyer, B; Mellet, E; Tzourio-Mazoyer, N

2010-09-01

"Highly iconic" structures in Sign Language enable a narrator to act, switch characters, describe objects, or report actions in four-dimensions. This group of linguistic structures has no real spoken-language equivalent. Topographical descriptions are also achieved in a sign-language specific manner via the use of signing-space and spatial-classifier signs. We used functional magnetic resonance imaging (fMRI) to compare the neural correlates of topographic discourse and highly iconic structures in French Sign Language (LSF) in six hearing native signers, children of deaf adults (CODAs), and six LSF-naïve monolinguals. LSF materials consisted of videos of a lecture excerpt signed without spatially organized discourse or highly iconic structures (Lect LSF), a tale signed using highly iconic structures (Tale LSF), and a topographical description using a diagrammatic format and spatial-classifier signs (Topo LSF). We also presented texts in spoken French (Lect French, Tale French, Topo French) to all participants. With both languages, the Topo texts activated several different regions that are involved in mental navigation and spatial working memory. No specific correlate of LSF spatial discourse was evidenced. The same regions were more activated during Tale LSF than Lect LSF in CODAs, but not in monolinguals, in line with the presence of signing-space structure in both conditions. Motion processing areas and parts of the fusiform gyrus and precuneus were more active during Tale LSF in CODAs; no such effect was observed with French or in LSF-naïve monolinguals. These effects may be associated with perspective-taking and acting during personal transfers. 2010 Elsevier Inc. All rights reserved.

Quercetin alters the DNA damage response in human hematopoietic stem and progenitor cells via TopoII- and PI3K-dependent mechanisms synergizing in leukemogenic rearrangements.

PubMed

Biechonski, Shahar; Gourevich, Dana; Rall, Melanie; Aqaqe, Nasma; Yassin, Muhammad; Zipin-Roitman, Adi; Trakhtenbrot, Luba; Olender, Leonid; Raz, Yael; Jaffa, Ariel J; Grisaru, Dan; Wiesmuller, Lisa; Elad, David; Milyavsky, Michael

2017-02-15

Quercetin (Que) is an abundant flavonoid in the human diet and high-concentration food supplement with reported pro- and anti-carcinogenic activities. Topoisomerase II (TopoII) inhibition and subsequent DNA damage induction by Que was implicated in the mixed lineage leukemia gene (MLL) rearrangements that can induce infant and adult leukemias. This notion raised concerns regarding possible genotoxicities of Que in hematopoietic stem and progenitor cells (HSPCs). However, molecular targets mediating Que effects on DNA repair relevant to MLL translocations have not been defined. In this study we describe novel and potentially genotoxic Que activities in suppressing non-homologous end joining and homologous recombination pathways downstream of MLL cleavage. Using pharmacological dissection of DNA-PK, ATM and PI3K signalling we defined PI3K inhibition by Que with a concomitant decrease in the abundance of key DNA repair genes to be responsible for DNA repair inhibition. Evidence for the downstream TopoII-independent mutagenic potential of Que was obtained by documenting further increased frequencies of MLL rearrangements in human HSPCs concomitantly treated with Etoposide and Que versus single treatments. Importantly, by engaging a tissue engineered placental barrier, we have established the extent of Que transplacental transfer and hence provided the evidence for Que reaching fetal HSPCs. Thus, Que exhibits genotoxic effects in human HSPCs via different mechanisms when applied continuously and at high concentrations. In light of the demonstrated Que transfer to the fetal compartment our findings are key to understanding the mechanisms underlying infant leukemia and provide molecular markers for the development of safety values. © 2016 UICC.

Anticancer activity of botanical alkyl hydroquinones attributed to topoisomerase II poisoning

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

Huang, C.-P.; Fang, W.-H.; Lin, L.-I.

2008-03-15

Cytotoxic alkyl hydroquinone compounds have been isolated from many plants. We previously isolated 3 structurally similar cytotoxic alkyl hydroquinone compounds from the sap of the lacquer tree Rhus succedanea L. belonging to the sumac family, which have a long history of medicinal use in Asia. Each has an unsaturated alkyl chain attached to the 2-position of a hydroquinone ring. One of these isolates, 10'(Z),13'(E),15'(E)-heptadecatrienylhydroquinone [HQ17(3)], being the most cytotoxic, was chosen for studying the anticancer mechanism of these compounds. We found that HQ17(3) was a topoisomerase (Topo) II poison. It irreversibly inhibited Topo II{alpha} activity through the accumulation of Topomore » II-DNA cleavable complexes. A cell-based assay showed that HQ17(3) inhibited the growth of leukemia HL-60 cells with an EC{sub 50} of 0.9 {mu}M, inhibited the topoisomerase-II-deficient cells HL-60/MX2 with an EC{sub 50} of 9.6 {mu}M, and exerted no effect on peripheral blood mononuclear cells at concentrations up to 50 {mu}M. These results suggest that Topo II is the cellular drug target. In HL-60 cells, HQ17(3) promptly inhibited DNA synthesis, induced chromosomal breakage, and led to cell death with an EC{sub 50} about one-tenth that of hydroquinone. Pretreatment of the cells with N-acetylcysteine could not attenuate the cytotoxicity and DNA damage induced by HQ17(3). However, N-acetylcysteine did significantly reduce the cytotoxicity of hydroquinone. In F344 rats, intraperitoneal injection of HQ17(3) for 28 days induced no clinical signs of toxicity. These results indicated that HQ17(3) is a potential anticancer agent, and its structural features could be a model for anticancer drug design.« less

6. Photocopy of photograph (original in possession of NYC Economic ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

6. Photocopy of photograph (original in possession of NYC Economic Development Corp.) Topo-Metrics, Inc, 1992. Aerial view of the Brooklyn Army Terminal - Wood's Grist Mill, South bank of Indian River, 1 mile east of Breached Mill Dam, Antwerp, Jefferson County, NY

Facile patterning of hybrid CdSe nanoparticle films by photoinduced surface defects.

PubMed

Park, Yushin; Felipe, Mary Jane; Advincula, Rigoberto C

2011-11-01

The photopatterning of CdSe quantum dots (QDs) films is facilitated by preparing defect-rich QDs on selective sites on the film. A key step is UV irradiation in the presence of a polar solvent such as methanol in situ as a "developer" which readily dissolves trioctylphosphine oxide (TOPO) but not the QDs. This results in a dramatically reduced photopatterning time and irradiation intensity requirement. The optical property changes were examined by UV-vis and fluorescence spectroscopy. Furthermore, the photo-oxidized pattern of the CdSe QD film was readily observed by fluorescence microscopy. The chemical change due to attenuation of the P═O vibration of TOPO (due to its removal) could be detected by FT-IR imaging or FT-IR chemical mapping. Thus, the protocol is a simple yet effective way of patterning PL properties of QD films at much reduced exposure time compared to previously reported methods. It may find utility for a host of cell-based film assays and PL display device applications at various resolutions.

Molecular cloning and expression of the gene encoding the kinetoplast-associated type II DNA topoisomerase of Crithidia fasciculata.

PubMed

Pasion, S G; Hines, J C; Aebersold, R; Ray, D S

1992-01-01

A type II DNA topoisomerase, topoIImt, was shown previously to be associated with the kinetoplast DNA of the trypanosomatid Crithidia fasciculata. The gene encoding this kinetoplast-associated topoisomerase has been cloned by immunological screening of a Crithidia genomic expression library with monoclonal antibodies raised against the purified enzyme. The gene CfaTOP2 is a single copy gene and is expressed as a 4.8-kb polyadenylated transcript. The nucleotide sequence of CfaTOP2 has been determined and encodes a predicted polypeptide of 1239 amino acids with a molecular mass of 138,445. The identification of the cloned gene is supported by immunoblot analysis of the beta-galactosidase-CfaTOP2 fusion protein expressed in Escherichia coli and by analysis of tryptic peptide sequences derived from purified topoIImt. CfaTOP2 shares significant homology with nuclear type II DNA topoisomerases of other eukaryotes suggesting that in Crithidia both nuclear and mitochondrial forms of topoisomerase II are encoded by the same gene.

Decreasing luminescence lifetime of evaporating phosphorescent droplets

NASA Astrophysics Data System (ADS)

van der Voort, D. D.; Dam, N. J.; Sweep, A. M.; Kunnen, R. P. J.; van Heijst, G. J. F.; Clercx, H. J. H.; van de Water, W.

2016-12-01

Laser-induced phosphorescence has been used extensively to study spray dynamics. It is important to understand the influence of droplet evaporation in the interpretation of such measurements, as it increases luminescence quenching. By suspending a single evaporating n-heptane droplet in an acoustic levitator, the properties of lanthanide-complex europium-thenoyltrifluoroacetone-trioctylphosphine oxide (Eu-TTA-TOPO) phosphorescence are determined through high-speed imaging. A decrease was found in the measured phosphorescence decay coefficient (780 → 200 μs) with decreasing droplet volumes (10-9 → 10-11 m3) corresponding to increasing concentrations (10-4 → 10-2 M). This decrease continues up to the point of shell-formation at supersaturated concentrations. The diminished luminescence is shown not to be attributable to triplet-triplet annihilation, quenching between excited triplet-state molecules. Instead, the pure exponential decays found in the measurements show that a non-phosphorescent quencher, such as free TTA/TOPO, can be attributable to this decay. The concentration dependence of the phosphorescence lifetime can therefore be used as a diagnostic of evaporation in sprays.

It's 1984 and Robots Are in the Classroom.

ERIC Educational Resources Information Center

Howe, Samuel F.

1984-01-01

Describes the features of TOPO, HERO, RB5X, and Tasman Turtle, personal robots used in elementary and secondary schools and colleges to introduce concepts of artificial intelligence, advanced high school and college computer science, and elementary level programming. Mechanical arms are also briefly mentioned. (MBR)

MO-E-17A-01: BEST IN PHYSICS (IMAGING) - Calculating SSDE From CT Exams Using Size Data Available in the DICOM Header of CT Localizer Radiographs

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

McMillan, K; Bostani, M; McNitt-Gray, M

2014-06-15

Purpose: To demonstrate the feasibility of using existing data stored within the DICOM header of certain CT localizer radiographs as a patient size metric for calculating CT size-specific dose estimates (SSDE). Methods: For most Siemens CT scanners, the CT localizer radiograph (topogram) contains a private DICOM field that stores an array of numbers describing AP and LAT attenuation-based measures of patient dimension. The square root of the product of the AP and LAT size data, which provides an estimate of water-equivalent-diameter (WED), was calculated retrospectively from topogram data of 20 patients who received clinically-indicated abdomen/pelvis (n=10) and chest (n=10) scansmore » (WED-topo). In addition, slice-by-slice water-equivalent-diameter (WED-image) and effective diameter (ED-image) values were calculated from the respective image data. Using TG-204 lookup tables, size-dependent conversion factors were determined based upon WED-topo, WED-image and ED-image values. These conversion factors were used with the reported CTDIvol to calculate slice-by-slice SSDE for each method. Averaging over all slices, a single SSDE value was determined for each patient and size metric. Patientspecific SSDE and CTDIvol values were then compared with patientspecific organ doses derived from detailed Monte Carlo simulations of fixed tube current scans. Results: For abdomen/pelvis scans, the average difference between liver dose and CTDIvol, SSDE(WED-topo), SSDE(WED-image), and SSDE(ED-image) was 18.70%, 8.17%, 6.84%, and 7.58%, respectively. For chest scans, the average difference between lung dose and CTDIvol, SSDE(WED-topo), SSDE(WED-image), and SSDE(ED-image) was 25.80%, 3.33%, 4.11%, and 7.66%, respectively. Conclusion: SSDE calculated using WED derived from data in the DICOM header of the topogram was comparable to SSDE calculated using WED and ED derived from axial images; each of these estimated organ dose to within 10% for both abdomen/pelvis and chest CT examinations. The topogrambased method has the advantage that WED data are already provided and therefore available without additional post-processing of the image data. Funding Support: NIH Grant R01-EB017095; Disclosures - Michael McNitt-Gray: Institutional Research Agreement, Siemens AG; Research Support, Siemens AG; Consultant, Flaherty Sensabaugh Bonasso PLLC; Consultant, Fulbright and Jaworski; Disclosures - Cynthia McCollough: Research Grant, Siemens Healthcare.« less

Topo-Iberia GPS network: installation complete

NASA Astrophysics Data System (ADS)

Khazaradze, G.

2009-04-01

As part of the project, titled "Geociencias en Iberia: Estudios integrados de topografía y evolución 4D: Topo-Iberia", we have established a network of 26 continuous GPS stations, covering the Spanish part of the Iberian Peninsula (22 stations) and Morocco (4 stations). A major objective behind the establishment of this array is to monitor millimeter level deformation of the crust due to the collision of African and Eurasian (including Iberian) tectonic plates. More specific goals of the project include the identification of the areas and/or specific seismic faults which exhibit higher deformation rates, which could imply an increased seismic hazard in these specific areas. The network has been designed as two X-shaped transects crossing the peninsula from NE to SW and NW to SE, with relatively coarse distribution of the stations, superimposed with denser coverage in the seismically active areas of the Betics, Pyrenees and Cantabrian chains. The majority of the built monuments consist of 1.5-1.8 m tall concrete pillars of 40 cm in diameter anchored to the bedrock using iron rebars. One station in Huesca was built according the UNAVCO's short drilled braced monument (SDBM) specifications. All the monuments were equipped with the SCIGN leveling mounts to ensure the precise antenna alignment and re-alignment in case of the antenna replacement, as well as, tamper resistance of the monument mark. In places were the snow accumulation was possible the antennas were covered with plastic radomes. The instrumentation used is Trimble NetRS dual-frequency receivers with choke-ring antennas. The communication is mainly via cellular telephone system. As of December 2008, the network installation has been competed and all the stations are fully operational. Here we report the milestones of the installation of the network and, as well as, present the first preliminary results of the analysis of the data. Besides the newly established Topo-Iberia CGPS stations, we have included in our daily analysis the data from the selected IGS and EUREF stations located within the region of our interest. In our analysis we also include data from the regional GPS network in Spain: CATNET in Catalonia, ERVA in Valencia, RAP in Andalucía and several other stations from Rioja, Basque country and Castilla León. The GPS data were analyzed using GAMIT/GLOBK software from MIT employing a network mode, where all the stations (including IGS continuous GPS sites) are analyzed simultaneously, followed by carrier phase ambiguity resolution. The work has been supported by the Spanish Ministry of Science and Innovation project: Topo-Iberia (CSD2006-00041).

Detectability and geomorphometry of tufa barrages in a small forested karstic river using airborne LiDAR topo-bathymetry

NASA Astrophysics Data System (ADS)

Profe, Jörn; Höfle, Bernhard

2017-04-01

Tufas are secondary carbonate precipitations which occur ubiquitously in karstic environments. Thus, freshwater tufas are increasingly noticed as a high-resolution terrestrial paleoclimate archive. However, complex interactions between climate, hydrology and geomorphology drive tufa landscapes as a self-organizing system that creates a patchy transition zone between land and water at the decimeter scale. These feedbacks challenge the modern analogue technique to understand paleo-tufa evolution and require a detailed 3D characterization of tufa geomorphometry to better understand their shaping processes in relation to channel bed morphology. Due to the complex geometric nature of tufa landscapes and predominant land-water transition zones, new remote sensing techniques such as airborne sub-meter footprint LiDAR topo-bathymetry (ALTB) are necessary to enable a detailed 3D description. Using the Riegl VQ-820-G at the Kaisinger Brunnenbach, Germany, we successfully detected submerged and subaerial tufas with maximum total dam heights from 0.3 m up to 1.6 m (cf. Profe et al. 2016). In addition, slope and openness derived from a high-resolution digital terrain model (DTM) with 0.2 m spatial resolution provide insights into barrage morphology and orientation. We found that longitudinal slope analysis along the river course relates tufa morphology to channel bed morphology. Raster-based data quality control of the LiDAR topo-bathymetric DTM reveals an overall vertical data precision of 3 cm and an overall vertical data accuracy of 15.4 cm (1σ) (Profe et al. 2016). The 3D characterization of tufa landscapes facilitates the identification of monitoring and drilling sites for subsequent hydrological and geochemical studies that deepen our knowledge about the complex barrage formation processes. In the advent of UAV-borne LiDAR platforms, we are convinced that it becomes possible to reduce data uncertainty and to better represent e.g. tufa overhangs, vegetation cover and incorporated plant material. Furthermore, our findings may foster research in other disciplines that work on small-scale land-water transition zones and are interested in a detailed 3D geomorphometric description derived from 3D point clouds directly. Reference: Profe, J., Höfle, B., Hämmerle, M., Steinbacher, F., Yang, M.-S., Schröder-Ritzrau, A., Frank, N., 2016. Characterizing tufa barrages in relation to channel bed morphology in a small karstic river by airborne LiDAR topo-bathymetry. Proceedings of the Geologists' Association 127: 664-675. doi:10.1016/j.pgeola.2016.10.004

Theorizing Space-Time Relations in Education: The Concept of Chronotope

ERIC Educational Resources Information Center

Ritella, Giuseppe; Ligorio, Maria Beatrice; Hakkarainen, Kai

2016-01-01

Due to ongoing cultural-historical transformations, the space-time of learning is radically changing, and theoretical conceptualizations are needed to investigate how such evolving space-time frames can function as a ground for learning. In this article, we argue that the concept of chronotope--from Greek chronos and topos, meaning time and…

Synthesis, DNA binding, topoisomerase inhibition and cytotoxic properties of 2-chloroethylnitrosourea derivatives of hoechst 33258.

PubMed

Bielawski, Krzysztof; Bielawska, Anna; Anchim, Tomasz; Wołczyński, Sławomir

2005-06-01

A number of novel 2-chloroethylnitrosourea derivatives of Hoechst 33258 were synthesized and examined for cytotoxicity in breast cancer cell cultures and for inhibition of topoisomerases I and II. Evaluation of the cytotoxicity of these compounds employing a MTT assay and inhibition of [3H]thymidine incorporation into DNA in both MDA-MB-231 and MCF-7 breast cancer cells demonstrated that these compounds were more active than Hoechst 33258. The DNA-binding ability of these compounds was evaluated by an ultrafiltration method using calf thymus DNA, poly(dA-dT)2 and poly(dG-dC)2, indicated that these compounds as well as Hoechst 33258 well interact with AT base pair compared with GC pair. Binding studies indicate that these compounds bind more tightly to double-stranded DNA than the parent compound Hoechst 33258. The degree to which these compounds inhibited cell growth breast cancer cells was generally consistent with their relative DNA binding affinity. Mechanistic studies revealed that these compounds act as topoisomerase I (topo I) or topoisomerase II (topo II) inhibitors in plasmid relaxation assays.

The Topo-trigger: a new concept of stereo trigger system for imaging atmospheric Cherenkov telescopes

NASA Astrophysics Data System (ADS)

López-Coto, R.; Mazin, D.; Paoletti, R.; Blanch Bigas, O.; Cortina, J.

2016-04-01

Imaging atmospheric Cherenkov telescopes (IACTs) such as the Major Atmospheric Gamma-ray Imaging Cherenkov (MAGIC) telescopes endeavor to reach the lowest possible energy threshold. In doing so the trigger system is a key element. Reducing the trigger threshold is hampered by the rapid increase of accidental triggers generated by ambient light (the so-called Night Sky Background NSB). In this paper we present a topological trigger, dubbed Topo-trigger, which rejects events on the basis of their relative orientation in the telescope cameras. We have simulated and tested the trigger selection algorithm in the MAGIC telescopes. The algorithm was tested using MonteCarlo simulations and shows a rejection of 85% of the accidental stereo triggers while preserving 99% of the gamma rays. A full implementation of this trigger system would achieve an increase in collection area between 10 and 20% at the energy threshold. The analysis energy threshold of the instrument is expected to decrease by ~ 8%. The selection algorithm was tested on real MAGIC data taken with the current trigger configuration and no γ-like events were found to be lost.

MORC Proteins: Novel Players in Plant and Animal Health

PubMed Central

Koch, Aline; Kang, Hong-Gu; Steinbrenner, Jens; Dempsey, D'Maris A.; Klessig, Daniel F.; Kogel, Karl-Heinz

2017-01-01

Microrchidia (MORC) proteins comprise a family of proteins that have been identified in prokaryotes and eukaryotes. They are defined by two hallmark domains: a GHKL-type ATPase and an S5 fold. MORC proteins in plants were first discovered via a genetic screen for Arabidopsis mutants compromised for resistance to a viral pathogen. Subsequent studies expanded their role in plant immunity and revealed their involvement in gene silencing and transposable element repression. Emerging data suggest that MORC proteins also participate in pathogen-induced chromatin remodeling and epigenetic gene regulation. In addition, biochemical analyses recently demonstrated that plant MORCs have topoisomerase II (topo II)-like DNA modifying activities that may be important for their function. Interestingly, animal MORC proteins exhibit many parallels with their plant counterparts, as they have been implicated in disease development and gene silencing. In addition, human MORCs, like plant MORCs, bind salicylic acid and this inhibits some of their topo II-like activities. In this review, we will focus primarily on plant MORCs, although relevant comparisons with animal MORCs will be provided. PMID:29093720

MORC Proteins: Novel Players in Plant and Animal Health.

PubMed

Koch, Aline; Kang, Hong-Gu; Steinbrenner, Jens; Dempsey, D'Maris A; Klessig, Daniel F; Kogel, Karl-Heinz

2017-01-01

Microrchidia (MORC) proteins comprise a family of proteins that have been identified in prokaryotes and eukaryotes. They are defined by two hallmark domains: a GHKL-type ATPase and an S5 fold. MORC proteins in plants were first discovered via a genetic screen for Arabidopsis mutants compromised for resistance to a viral pathogen. Subsequent studies expanded their role in plant immunity and revealed their involvement in gene silencing and transposable element repression. Emerging data suggest that MORC proteins also participate in pathogen-induced chromatin remodeling and epigenetic gene regulation. In addition, biochemical analyses recently demonstrated that plant MORCs have topoisomerase II (topo II)-like DNA modifying activities that may be important for their function. Interestingly, animal MORC proteins exhibit many parallels with their plant counterparts, as they have been implicated in disease development and gene silencing. In addition, human MORCs, like plant MORCs, bind salicylic acid and this inhibits some of their topo II-like activities. In this review, we will focus primarily on plant MORCs, although relevant comparisons with animal MORCs will be provided.

Knockdown of RMI1 impairs DNA repair under DNA replication stress.

PubMed

Xu, Chang; Fang, Lianying; Kong, Yangyang; Xiao, Changyan; Yang, Mengmeng; Du, Li-Qing; Liu, Qiang

2017-12-09

RMI1 (RecQ-mediated genome instability protein 1) forms a conserved BTR complex with BLM, Topo IIIα, and RMI2, and its absence causes genome instability. It has been revealed that RMI1 localizes to nuclear foci with BLM and Topo IIIα in response to replication stress, and that RMI1 functions downstream of BLM in promoting replication elongation. However, the precise functions of RMI1 during replication stress are not completely understood. Here we report that RMI1 knockdown cells are hypersensitive to hydroxyurea (HU). Using comet assay, we show that RMI1 knockdown cells exhibit accumulation of broken DNAs after being released from HU treatment. Moreover, we demonstrate that RMI1 facilitates the recovery from activated checkpoint and resuming the cell cycle after replicative stress. Surprisingly, loss of RMI1 results in a failure of RAD51 loading onto DNA damage sites. These findings reveal the importance of RMI1 in response to replication stress, which could explain the molecular basis for its function in maintaining genome integrity. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

Exclusive Ni-N4 Sites Realize Near-Unity CO Selectivity for Electrochemical CO2 Reduction.

PubMed

Li, Xiaogang; Bi, Wentuan; Chen, Minglong; Sun, Yuexiang; Ju, Huanxin; Yan, Wensheng; Zhu, Junfa; Wu, Xiaojun; Chu, Wangsheng; Wu, Changzheng; Xie, Yi

2017-10-25

Electrochemical reduction of carbon dioxide (CO 2 ) to value-added carbon products is a promising approach to reduce CO 2 levels and mitigate the energy crisis. However, poor product selectivity is still a major obstacle to the development of CO 2 reduction. Here we demonstrate exclusive Ni-N 4 sites through a topo-chemical transformation strategy, bringing unprecedentedly high activity and selectivity for CO 2 reduction. Topo-chemical transformation by carbon layer coating successfully ensures preservation of the Ni-N 4 structure to a maximum extent and avoids the agglomeration of Ni atoms to particles, providing abundant active sites for the catalytic reaction. The Ni-N 4 structure exhibits excellent activity for electrochemical reduction of CO 2 with particularly high selectivity, achieving high faradaic efficiency over 90% for CO in the potential range from -0.5 to -0.9 V and gives a maximum faradaic efficiency of 99% at -0.81 V with a current density of 28.6 mA cm -2 . We anticipate exclusive catalytic sites will shed new light on the design of high-efficiency electrocatalysts for CO 2 reduction.

Surface characterization of hydrophobic core-shell QDs using NMR techniques

NASA Astrophysics Data System (ADS)

Zhang, Chengqi; Zeng, Birong; Palui, Goutam; Mattoussi, Hedi

2018-02-01

Using a few solution phase NMR spectroscopy techniques, including 1H NMR and 31P NMR, we have characterized the organic shell on CdSe-ZnS core-shell quantum dots and tracked changes in its composition when the QD dispersions are subjected to varying degrees of purification. Combining solution phase NMR with diffusion ordered spectroscopy (DOSY), we were able to distinguish between freely diffusing ligands in the sample from those bound on the surfaces. Additionally, matrix assisted laser desorption ionization (MALDI) and FTIR measurements were used to provide complementary and supporting information on the organic ligand coating for these nanocrystals. We found that the organic shell is dominated by monomeric or oligomeric n-hexylphosphonic acid (HPA), along with small portion of 1-hexadecyl amine (HDA). The presence of TOP/TOPO (tri-n-octylphosphine / tri-noctylphosphine oxide) molecules is much smaller, even though large excess of TOP/TOPO were used during the QD growth. These results indicate that HPA (alkyl phosphonate) exhibits the strongest coordination affinity to ZnS-rich QD surfaces grown using the high temperature injection route.

New modulated design, docking and synthesis of carbohydrate-conjugate heterobimetallic CuII-SnIV complex as potential topoisomerase II inhibitor: in vitro DNA binding, cleavage and cytotoxicity against human cancer cell lines.

PubMed

Tabassum, Sartaj; Afzal, Mohd; Arjmand, Farukh

2014-03-03

New carbohydrate-conjugate heterobimetallic complexes [C₂₂H₅₀N₆O₁₃CuSnCl₂] (3) and [C₂₂H₅₈N₆O₁₇NiSnCl₂] (4) were synthesized from their monometallic analogs [C₂₂H₅₂N₆O₁₃Cu] (1) and [C₂₂H₆₀N₆O₁₇Ni] (2) containing N-glycoside ligand (L). In vitro DNA binding studies of L and complexes (1-4) with CT DNA were carried out by employing various biophysical and molecular docking techniques which revealed that heterobimetallic complex 3 strongly binds to DNA in comparison to 4, monometallic complexes (1 and 2) and the free ligand. Complex 3 cleaves pBR322 DNA via hydrolytic pathway (confirmed by T4 DNA ligase assay) and inhibited Topo-II activity in a dose-dependent manner. Furthermore, complex 3 was docked into the ATPase domain of human-Topo-II in order to probe the possible mechanism of inhibition. Copyright © 2013 Elsevier Masson SAS. All rights reserved.

Comparative Study of the Volumetric Methods Calculation Using GNSS Measurements

NASA Astrophysics Data System (ADS)

Şmuleac, Adrian; Nemeş, Iacob; Alina Creţan, Ioana; Sorina Nemeş, Nicoleta; Şmuleac, Laura

2017-10-01

This paper aims to achieve volumetric calculations for different mineral aggregates using different methods of analysis and also comparison of results. To achieve these comparative studies and presentation were chosen two software licensed, namely TopoLT 11.2 and Surfer 13. TopoLT program is a program dedicated to the development of topographic and cadastral plans. 3D terrain model, level courves and calculation of cut and fill volumes, including georeferencing of images. The program Surfer 13 is produced by Golden Software, in 1983 and is active mainly used in various fields such as agriculture, construction, geophysical, geotechnical engineering, GIS, water resources and others. It is also able to achieve GRID terrain model, to achieve the density maps using the method of isolines, volumetric calculations, 3D maps. Also, it can read different file types, including SHP, DXF and XLSX. In these paper it is presented a comparison in terms of achieving volumetric calculations using TopoLT program by two methods: a method where we choose a 3D model both for surface as well as below the top surface and a 3D model in which we choose a 3D terrain model for the bottom surface and another 3D model for the top surface. The comparison of the two variants will be made with data obtained from the realization of volumetric calculations with the program Surfer 13 generating GRID terrain model. The topographical measurements were performed with equipment from Leica GPS 1200 Series. Measurements were made using Romanian position determination system - ROMPOS which ensures accurate positioning of reference and coordinates ETRS through the National Network of GNSS Permanent Stations. GPS data processing was performed with the program Leica Geo Combined Office. For the volumetric calculating the GPS used point are in 1970 stereographic projection system and for the altitude the reference is 1975 the Black Sea projection system.

DNA damage response (DDR) induced by topoisomerase II poisons requires nuclear function of the small GTPase Rac.

PubMed

Wartlick, Friedrich; Bopp, Anita; Henninger, Christian; Fritz, Gerhard

2013-12-01

Here, we investigated the influence of Rac family small GTPases on mechanisms of the DNA damage response (DDR) stimulated by topoisomerase II poisons. To this end, we examined the influence of the Rac-specific small molecule inhibitor EHT1864 on Ser139 phosphorylation of histone H2AX, a widely used marker of the DDR triggered by DNA double-strand breaks. EHT1864 attenuated the doxorubicin-stimulated DDR in a subset of cell lines tested, including HepG2 hepatoma cells. EHT1864 reduced the level of DNA strand breaks and increased viability following treatment of HepG2 cells with topo II poisons. Protection by EHT1864 was observed in both p53 wildtype (HepG2) and p53 deficient (Hep3B) human hepatoma cells and, furthermore, remained unaffected upon pharmacological inhibition of p53 in HepG2. Apparently, the impact of Rac on the DDR is independent of p53. Protection from doxorubicin-induced DNA damage by EHT1864 comprises both S and G2 phase cells. The inhibitory effect of EHT1864 on doxorubicin-stimulated DDR was mimicked by pharmacological inhibition of various protein kinases, including JNK, ERK, PI3K, PAK and CK1. EHT1864 and protein kinase inhibitors also attenuated the formation of the topo II-DNA cleavable complex. Moreover, EHT1864 mitigated the constitutive phosphorylation of topoisomerase IIα at positions S1106, S1213 and S1247. Doxorubicin transport, nuclear import/export of topoisomerase II and Hsp90-related mechanisms are likely not of relevance for doxorubicin-stimulated DDR impaired by EHT1864. We suggest that multiple kinase-dependent but p53- and heat shock protein-independent Rac-regulated nuclear mechanisms are required for activation of the DDR following treatment with topo II poisons. © 2013.

Development of a fluorescent label tool based on lanthanide nanophosphors for viral biomedical application

NASA Astrophysics Data System (ADS)

Le, Quoc Minh; Huong Tran, Thu; Huong Nguyen, Thanh; Khuyen Hoang, Thi; Binh Nguyen, Thanh; Do, Khanh Tung; Tran, Kim Anh; Hien Nguyen, Dang; Luan Le, Thi; Quy Nguyen, Thi; Dung Dang, Mai; Thu Nguyen, Nu Anh; Nguyen, Van Man

2012-09-01

We report for the first time the preparation of luminescent lanthanide nanomaterial (LLN) linked bioconjugates and their application as a label tool for recognizing virus in the processing line of vaccine industrial fabrication. Several LLNs with the nanostructure forms of particles or rods/wires with europium (III) and terbium (III) ions in lattices of vanadate, phosphate and metal organic complex were prepared to develop novel fluorescent conjugates able to be applied as labels in fluorescence immunoassay analysis of virus/vaccine. With regard to the LLNs, we have successfully synthesized nanoparticles around 10 nm of YVO4:Eu(III), with high emission in the red spectral region, nanorod and nanowire of TbPO4·H2O and Eu1-xTbxPO4·H2O, width 5-7 nm and length 300 nm, showing very bright luminescence in green, and core/shell nanosized Eu(III) and Tb(III)/Eu(III) complexes with naphthoyl trifluoroacetone and tri-n-octylphosphineoxide (Eu.NTA.TOPO@PVP, EuXTb1-X.NTA.TOPO). The appropriated core/shell structures can play a double role, one for enhancing luminescence efficiency and another for providing nanophosphors with better stability in water media for facilitating the penetration of nanophosphor core into a biomedical environment. The organic functionalizations of the obtained LLNs were done through their surface encapsulation with a functional polysiloxane including active groups such as amine (NH2), thiocyanate (SCN) or mecarpto (SH). The properties of functional sol-gel matrix have great influence on the luminescence properties, especially luminescence intensity of YVO4:Eu(III), Eu.NTA.TOPO@PVP, TbPO4·H2O and EuxTb1-xPO4·H2O. Bioconjugation processes of the functionalized LLNs have been studied with some bioactive molecules such as biotin, protein immunoglobulin G (IgG) or bovine serum albumin (BSA). The results of LLN-bioconjugate linking with IgG for recognizing virus (vaccine) will be presented in brief. It is consistent to state that the LLN bioconjugates prepared from YVO4:Eu(III)-nanoparticles, TbPO4·H2O nanorod or wire and EuNTA.TOPO@PVP nanosized core/shell complex could be used as labels for recognizing virus in diagnosis or in vaccine production by use of the fluorescence immunoassay (FIA) method. The fluorescence images of the incubated specimens consisting of LLN bioconjugate and vaccine fabricate could be obtained well in terms of sharpness, reproductivity and stability. However, much work still needs to be done to develop an ordinary LLN-conjugate using the FIA method for analysis of virus and, moreover, to extend the study of biomedical cell processes at nano/microscale in practical application.

Donning Sackcloth and Ashes: "Webster vs. Reproductive Health Services" and Moral Agony in Abortion Rights Rhetoric.

ERIC Educational Resources Information Center

Tonn, Mari Boor

1996-01-01

Argues that the topos of moral agony (resembling Kenneth Burke's purifying concept of mortification) adopted by some abortion rights rhetors to allay public discomfort with abortion is rhetorically and politically self-defeating. Shows how it couches moral anguish in atypical tales of tragic circumstances and unattainable motherhood. Argues that…

MX Siting Investigation. Geotechnical Evaluation. Verification Study - Lake Valley, Nevada. Volume I. Synthesis.

DTIC Science & Technology

1981-07-31

attitudes, topo- graphic slopes, evidence of erosional features such as pedi - ments, and the presence or absence of young volcanic rocks. 1 jb. Depth...subgrade, subbase, or 4’ EIM mom ! E-TR-27-LV-J A-34 base. Parameters used to make these qualitative assessments were characteristics related to CBR, frost

Toward a "Topos" of Visual Rhetoric: Teaching Aesthetics through Color and Typography

ERIC Educational Resources Information Center

Welhausen, Candice A.

2018-01-01

This article proposes a heuristic that teachers and students can use together to create a vocabulary for discussing the aesthetic aspects of color and typography in document design work. By using this framework, teachers and students can generate a collection of shared "visual topoi" or commonplaces for describing the aesthetic value of…

Archaeological Data Recovery in the Abiquiu Reservoir Multiple Resource Area, New Mexico,

DTIC Science & Technology

1982-09-01

location probably does not represent a locus of past human activity. Iso i .... .. 2 *1 . .. . .A LA27006 (AR56) Description: The site is a small...25566 27021 27047 25378 No topo map location for site (n 3) 27001 27002 27037 118 TABLE 10 ESTIMATED AND ACTUAL FREQUENCIES OF ARTIFACT CLASSES AT

How Theories of Perception Deploy the Line: Reconfiguring Students' Bodies through Topo-Philosophy

ERIC Educational Resources Information Center

de Freitas, Elizabeth

2014-01-01

In this essay Elizabeth de Freitas follows Tim Ingold's groundbreaking anthropological work on lines and their cultural and material significance to argue that the line is the engine of theory, be it the drawn line of inscription or mathematical measure, the exclusionary line of delineation, or the undulating generative line of flight. De…

78 FR 1886 - Self-Regulatory Organizations; NASDAQ OMX PHLX LLC; Notice of Filing and Immediate Effectiveness...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-01-09

... amend its fee schedule for the four direct data feed products. While changes to the Pricing Schedule... account, for the purpose of executing a particular investment strategy. See Exchange Rule 1080.08(a)(i... TOPO, PHLX Orders, or PHLX Depth of Market.\\7\\ \\7\\ PHLX proposes to move the definitions in the rule...

Targeting Mycobacterium tuberculosis Topoisomerase I by Small-Molecule Inhibitors

PubMed Central

Godbole, Adwait Anand; Ahmed, Wareed; Bhat, Rajeshwari Subray; Bradley, Erin K.; Ekins, Sean

2014-01-01

We describe inhibition of Mycobacterium tuberculosis topoisomerase I (MttopoI), an essential mycobacterial enzyme, by two related compounds, imipramine and norclomipramine, of which imipramine is clinically used as an antidepressant. These molecules showed growth inhibition of both Mycobacterium smegmatis and M. tuberculosis cells. The mechanism of action of these two molecules was investigated by analyzing the individual steps of the topoisomerase I (topoI) reaction cycle. The compounds stimulated cleavage, thereby perturbing the cleavage-religation equilibrium. Consequently, these molecules inhibited the growth of the cells overexpressing topoI at a low MIC. Docking of the molecules on the MttopoI model suggested that they bind near the metal binding site of the enzyme. The DNA relaxation activity of the metal binding mutants harboring mutations in the DxDxE motif was differentially affected by the molecules, suggesting that the metal coordinating residues contribute to the interaction of the enzyme with the drug. Taken together, the results highlight the potential of these small molecules, which poison the M. tuberculosis and M. smegmatis topoisomerase I, as leads for the development of improved molecules to combat mycobacterial infections. Moreover, targeting metal coordination in topoisomerases might be a general strategy to develop new lead molecules. PMID:25534741

Crystal Structures of RMI1 and RMI2, Two OB-Fold Regulatory Subunits of the BLM Complex

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

Wang, Feng; Yang, Yuting; Singh, Thiyam Ramsing

Mutations in BLM, a RecQ-like helicase, are linked to the autosomal recessive cancer-prone disorder Bloom's syndrome. BLM associates with topoisomerase (Topo) III{alpha}, RMI1, and RMI2 to form the BLM complex that is essential for genome stability. The RMI1-RMI2 heterodimer stimulates the dissolution of double Holliday junction into non-crossover recombinants mediated by BLM-Topo III{alpha} and is essential for stabilizing the BLM complex. However, the molecular basis of these functions of RMI1 and RMI2 remains unclear. Here we report the crystal structures of multiple domains of RMI1-RMI2, providing direct confirmation of the existence of three oligonucleotide/oligosaccharide binding (OB)-folds in RMI1-RMI2. Our structuralmore » and biochemical analyses revealed an unexpected insertion motif in RMI1N-OB, which is important for stimulating the dHJ dissolution. We also revealed the structural basis of the interaction between RMI1C-OB and RMI2-OB and demonstrated the functional importance of the RMI1-RMI2 interaction in genome stability maintenance.« less

The Rhetoric of the Norwegian Constitution Day: A Topos Analysis of Young Norwegian Students' May 17 Speeches, 2011 and 2012

ERIC Educational Resources Information Center

Tønnesson, Johan Laurits; Sivesind, Kirsten

2016-01-01

National Day, or Constitution Day, in Norway, May 17, is often referred to as Children's Day. On this day, thousands of young Norwegian students march in parades and participate in celebrations in schoolyards and similar meeting places. Some students are selected to give speeches, performed in front of family members, neighbors, classmates, and…

MR-Compatible Integrated Eye Tracking System

DTIC Science & Technology

2016-03-10

SECURITY CLASSIFICATION OF: This instrumentation grant was used to purchase state-of-the-art, high-resolution video eye tracker that can be used to...P.O. Box 12211 Research Triangle Park, NC 27709-2211 video eye tracking, eye movments, visual search; camouflage-breaking REPORT DOCUMENTATION PAGE...Report: MR-Compatible Integrated Eye Tracking System Report Title This instrumentation grant was used to purchase state-of-the-art, high-resolution video

Develop advanced nonlinear signal analysis topographical mapping system

NASA Technical Reports Server (NTRS)

1994-01-01

The Space Shuttle Main Engine (SSME) has been undergoing extensive flight certification and developmental testing, which involves some 250 health monitoring measurements. Under the severe temperature, pressure, and dynamic environments sustained during operation, numerous major component failures have occurred, resulting in extensive engine hardware damage and scheduling losses. To enhance SSME safety and reliability, detailed analysis and evaluation of the measurements signal are mandatory to assess its dynamic characteristics and operational condition. Efficient and reliable signal detection techniques will reduce catastrophic system failure risks and expedite the evaluation of both flight and ground test data, and thereby reduce launch turn-around time. The basic objective of this contract are threefold: (1) develop and validate a hierarchy of innovative signal analysis techniques for nonlinear and nonstationary time-frequency analysis. Performance evaluation will be carried out through detailed analysis of extensive SSME static firing and flight data. These techniques will be incorporated into a fully automated system; (2) develop an advanced nonlinear signal analysis topographical mapping system (ATMS) to generate a Compressed SSME TOPO Data Base (CSTDB). This ATMS system will convert tremendous amount of complex vibration signals from the entire SSME test history into a bank of succinct image-like patterns while retaining all respective phase information. High compression ratio can be achieved to allow minimal storage requirement, while providing fast signature retrieval, pattern comparison, and identification capabilities; and (3) integrate the nonlinear correlation techniques into the CSTDB data base with compatible TOPO input data format. Such integrated ATMS system will provide the large test archives necessary for quick signature comparison. This study will provide timely assessment of SSME component operational status, identify probable causes of malfunction, and indicate feasible engineering solutions. The final result of this program will yield an ATMS system of nonlinear and nonstationary spectral analysis software package integrated with the Compressed SSME TOPO Data Base (CSTDB) on the same platform. This system will allow NASA engineers to retrieve any unique defect signatures and trends associated with different failure modes and anomalous phenomena over the entire SSME test history across turbo pump families.

Develop advanced nonlinear signal analysis topographical mapping system

NASA Technical Reports Server (NTRS)

Jong, Jen-Yi

1993-01-01

The SSME has been undergoing extensive flight certification and developmental testing, which involves some 250 health monitoring measurements. Under the severe temperature pressure, and dynamic environments sustained during operation, numerous major component failures have occurred, resulting in extensive engine hardware damage and scheduling losses. To enhance SSME safety and reliability, detailed analysis and evaluation of the measurements signal are mandatory to assess its dynamic characteristics and operational condition. Efficient and reliable signal detection techniques will reduce catastrophic system failure risks and expedite the evaluation of both flight and ground test data, and thereby reduce launch turn-around time. The basic objective of this contract are threefold: (1) Develop and validate a hierarchy of innovative signal analysis techniques for nonlinear and nonstationary time-frequency analysis. Performance evaluation will be carried out through detailed analysis of extensive SSME static firing and flight data. These techniques will be incorporated into a fully automated system. (2) Develop an advanced nonlinear signal analysis topographical mapping system (ATMS) to generate a Compressed SSME TOPO Data Base (CSTDB). This ATMS system will convert tremendous amounts of complex vibration signals from the entire SSME test history into a bank of succinct image-like patterns while retaining all respective phase information. A high compression ratio can be achieved to allow the minimal storage requirement, while providing fast signature retrieval, pattern comparison, and identification capabilities. (3) Integrate the nonlinear correlation techniques into the CSTDB data base with compatible TOPO input data format. Such integrated ATMS system will provide the large test archives necessary for a quick signature comparison. This study will provide timely assessment of SSME component operational status, identify probable causes of malfunction, and indicate feasible engineering solutions. The final result of this program will yield an ATMS system of nonlinear and nonstationary spectral analysis software package integrated with the Compressed SSME TOPO Data Base (CSTDB) on the same platform. This system will allow NASA engineers to retrieve any unique defect signatures and trends associated with different failure modes and anomalous phenomena over the entire SSME test history across turbo pump families.

TOPO-capped silver selenide nanoparticles and their incorporation into polymer nanofibers using electrospinning technique

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

More, D.S.; Moloto, M.J., E-mail: makwenam@vut.ac.za; Moloto, N.

Highlights: • Ag{sub 2}Se nanoparticles produced spherical particles with sizes 12 nm (180 °C) and 27 nm (200 °C). • Higher temperature produced increased particle size (∼75 nm) and changed in shape. • Ag{sub 2}Se nanoparticles (0.2–0.6%) added into PVP (35–45%) to yield reduced fiber beading. • Polymer nanofibers electrospun at 11–20 kV produced fiber diameters of 425–461 nm. • Optical properties in the fibers were observed due to the Ag{sub 2}Se nanoparticles loaded. - Abstract: Electrospinning is the most common technique for fabricating polymer fibers as well as nanoparticles embedded polymer fibers. Silver selenide nanoparticles were synthesized using tri-n-octylphosphinemore » (TOP) as solvent and tri-n-octylphosphine oxide (TOPO) as capping environment. Silver selenide was prepared by reacting silver nitrate and selenium with tri-n-octylphosphine (TOP) to form TOP–Ag and TOP–Se solutions. Both absorption and emission spectra signify the formation of nanoparticles as well as the TEM which revealed spherical particles with an average particle size of 22 nm. The polymer, PVP used was prepared at concentrations ranging from (35 to 45 wt%) and the TOPO-capped silver selenide nanoparticles (0.2 and 0.6 wt%) were incorporated into them and electrospun by varying the voltage from 11 to 20 kV. The SEM images of the Ag{sub 2}Se/PVP composite fibers revealed the fibers of diameters with average values of 425 and 461 nm. The X-ray diffraction results show peaks which were identified due to α-Ag{sub 2}Se body centered cubic compound. The sharp peak observed for all the samples at 2θ = 44.5 suggest the presence of Ag in the face centered cubic which can be attributed to higher concentration of silver nitrate used with molar ratio of selenium to silver and the abundance of silver in the silver selenide crystal. Fourier transform infrared spectroscopy, thermogravimetric analysis (TGA) and ultraviolet–visible spectroscopy were used to characterize the structure of the PVP/Ag{sub 2}Se composite fibers.« less

ERBB-Receptors and Drug Response in Breast Cancer

DTIC Science & Technology

1997-09-01

in topoisomerase II a (topo II a ) levels seen may be understood by global changes in DNA repair enzymes, brought about by signaling through the EGFR...ErbB-mediated signaling and topoisomerase II a levels specifically as they relate to drug sensitivity/resistance. This information will allow the use...topoisomerase II a levels and increased sensitivity to doxorubicin. In order to determine which, if any, of the specific receptors involved are

Use of the Köppen-Trewartha climate classification to evaluate climatic refugia in statistically derived ecoregions for the People’s Republic of China

Treesearch

B. Baker; Henry Diaz; William Hargrove; Forrest Hoffman

2010-01-01

Changes in climate as projected by state-of-the-art climate models are likely to result in novel combinations of climate and topo-edaphic factors that will have substantial impacts on the distribution and persistence of natural vegetation and animal species. We have used multivariate techniques to quantify some of these changes; the...

SERDP CU-1129 Biological Assessment for Characterizing Contamination Risk at the Genetic-, Individual-, and Population-Level

DTIC Science & Technology

2004-04-14

albimanus Quetzal : a Tc1 transposon (Sum P(2) = 8.3e-07) Transposase_5, E = 5.9e-08 Topo 6-2L3 LpTc1.1 A. albimanus Quetzal : a Tc1 transposon (Sum P(2...transposon LpTc1, A. albimanus Quetzal = Anopheles albimanus Quetzal transposase (AAB02109). The clones tank and tank.1 did not have sufficient

Modeling Nanocomposites for Molecular Dynamics (MD) Simulations

DTIC Science & Technology

2015-01-01

Parallel Simulator ( LAMMPS ) is used as the MD simulator [9], the coordinates must be formatted for use in LAMMPSs. VMD has a set of tools (TopoTools...that can be used to generate a LAMMPS -readable format [6]. 3 Figure 4. Ethylene Monomer Produced From Coordinates in PDB and Rendered Using...where, i and j are the atom subscripts. Simulations are performed using LAMMPS simulation software. Periodic boundary conditions are

From Topos to Oikos: The Standardization of Glass Containers as Epistemic Boundaries in Modern Laboratory Research (1850-1900).

PubMed

Espahangizi, Kijan

2015-09-01

Glass vessels such as flasks and test tubes play an ambiguous role in the historiography of modern laboratory research. In spite of the strong focus on the role of materiality in the last decades, the scientific glass vessel - while being symbolically omnipresent - has remained curiously neglected in regard to its materiality. The popular image or topos of the transparent, neutral, and quasi-immaterial glass container obstructs the view of the physico-chemical functionality of this constitutive inner boundary in modern laboratory environments and its material historicity. In order to understand how glass vessels were able to provide a stable epistemic containment of spatially enclosed experimental phenomena in the new laboratory ecologies emerging in the nineteenth and early twentieth century, I will focus on the history of the material standardization of laboratory glassware. I will follow the rise of a new awareness for measurement errors due to the chemical agency of experimental glass vessels, then I will sketch the emergence of a whole techno-scientific infrastructure for the improvement of glass container quality in late nineteenth-century Germany. In the last part of my argument, I will return to the laboratory by looking at the implementation of this glass reform that created a new oikos for the inner experimental milieus of modern laboratory research.

Building Materials from Colloidal Nanocrystal Assemblies: Molecular Control of Solid/Solid Interfaces in Nanostructured Tetragonal ZrO 2

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

Shaw, Santosh; Silva, Tiago F.; Bobbitt, Jonathan M.

We describe in this paper a bottom-up approach to control the composition of solid/solid interfaces in nanostructured materials, and we test its effectiveness on tetragonal ZrO 2, an inorganic phase of great technological significance. Colloidal nanocrystals capped with trioctylphosphine oxide (TOPO) or oleic acid (OA) are deposited, and the organic fraction of the ligands is selectively etched with O 2 plasma. The interfaces in the resulting all-inorganic colloidal nanocrystal assemblies are either nearly bare (for OA-capped nanocrystals) or terminated with phosphate groups (for TOPO-capped nanocrystals) resulting from the reaction of phosphine oxide groups with plasma species. The chemical modification ofmore » the interfaces has extensive effects on the thermodynamics and kinetics of the material. Different growth kinetics indicate different rate limiting processes of growth (surface diffusion for the phosphate-terminated surfaces and dissolution for the “bare” surfaces). Phosphate termination led to a higher activation energy of growth, and a 3-fold reduction in interfacial energy, and facilitated significantly the conversion of the tetragonal phase into the monoclinic phase. Finally, films devoid of residual ligands persisted in the tetragonal phase at temperatures as high as 900 °C for 24 h.« less

Oxabicyclooctane-Linked Novel Bacterial Topoisomerase Inhibitors as Broad Spectrum Antibacterial Agents

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

Singh, Sheo B.; Kaelin, David E.; Wu, Jin

Bacterial resistance is eroding the clinical utility of existing antibiotics necessitating the discovery of new agents. Bacterial type II topoisomerase is a clinically validated, highly effective, and proven drug target. This target is amenable to inhibition by diverse classes of inhibitors with alternative and distinct binding sites to quinolone antibiotics, thus enabling the development of agents that lack cross-resistance to quinolones. Described here are novel bacterial topoisomerase inhibitors (NBTIs), which are a new class of gyrase and topo IV inhibitors and consist of three distinct structural moieties. The substitution of the linker moiety led to discovery of potent broad-spectrum NBTIsmore » with reduced off-target activity (hERG IC50 > 18 μM) and improved physical properties. AM8191 is bactericidal and selectively inhibits DNA synthesis and Staphylococcus aureus gyrase (IC50 = 1.02 μM) and topo IV (IC50 = 10.4 μM). AM8191 showed parenteral and oral efficacy (ED50) at less than 2.5 mg/kg doses in a S. aureus murine infection model. A cocrystal structure of AM8191 bound to S. aureus DNA-gyrase showed binding interactions similar to that reported for GSK299423, displaying a key contact of Asp83 with the basic amine at position-7 of the linker.« less

Building Materials from Colloidal Nanocrystal Assemblies: Molecular Control of Solid/Solid Interfaces in Nanostructured Tetragonal ZrO 2

DOE PAGES

Shaw, Santosh; Silva, Tiago F.; Bobbitt, Jonathan M.; ...

2017-08-28

We describe in this paper a bottom-up approach to control the composition of solid/solid interfaces in nanostructured materials, and we test its effectiveness on tetragonal ZrO 2, an inorganic phase of great technological significance. Colloidal nanocrystals capped with trioctylphosphine oxide (TOPO) or oleic acid (OA) are deposited, and the organic fraction of the ligands is selectively etched with O 2 plasma. The interfaces in the resulting all-inorganic colloidal nanocrystal assemblies are either nearly bare (for OA-capped nanocrystals) or terminated with phosphate groups (for TOPO-capped nanocrystals) resulting from the reaction of phosphine oxide groups with plasma species. The chemical modification ofmore » the interfaces has extensive effects on the thermodynamics and kinetics of the material. Different growth kinetics indicate different rate limiting processes of growth (surface diffusion for the phosphate-terminated surfaces and dissolution for the “bare” surfaces). Phosphate termination led to a higher activation energy of growth, and a 3-fold reduction in interfacial energy, and facilitated significantly the conversion of the tetragonal phase into the monoclinic phase. Finally, films devoid of residual ligands persisted in the tetragonal phase at temperatures as high as 900 °C for 24 h.« less

Thiazole-based nitrogen mustards: Design, synthesis, spectroscopic studies, DFT calculation, molecular docking, and antiproliferative activity against selected human cancer cell lines

NASA Astrophysics Data System (ADS)

Łączkowski, Krzysztof Z.; Świtalska, Marta; Baranowska-Łączkowska, Angelika; Plech, Tomasz; Paneth, Agata; Misiura, Konrad; Wietrzyk, Joanna; Czaplińska, Barbara; Mrozek-Wilczkiewicz, Anna; Malarz, Katarzyna; Musioł, Robert; Grela, Izabela

2016-09-01

Synthesis, characterization and investigation of antiproliferative activity of ten thiazole-based nitrogen mustard against human cancer cells lines (MV4-11, A549, MCF-7 and HCT116) and normal mouse fibroblast (BALB/3T3) is presented. The structures of novel compounds were determined using 1H and 13C NMR, FAB(+)-MS, and elemental analyses. Among the derivatives, 5b, 5c, 5e, 5f and 5i were found to exhibit high activity against human leukaemia MV4-11 cells with IC50 values of 2.17-4.26 μg/ml. The cytotoxic activity of compound 5c and 5f against BALB/3T3 cells is up to 20 times lower than against cancer cell lines. Our results also show that compounds 5e and 5i have very strong activity against MCF-7 and HCT116 with IC50 values of 3.02-4.13 μg/ml. Moreover, spectroscopic characterization and cellular localization for selected compound were performed. In order to identify potential drug targets we perform computer simulations with DNA-binding site of hTopoI and hTopoII and quantum chemical calculation of interaction and binding energies in complexes of the five most active compounds with guanine.

Go Ahead of Malware’s Infections and Controls: Towards New Techniques for Proactive Cyber Defense

DTIC Science & Technology

2016-12-08

in SDN (such as topology poisoning attacks and data-to-control plan saturation attacks) and developed new defense for SDN (such as TopoGuard and... Poisoning Network Visibility in Software-Defined Networks: New Attacks and Countermeasures As part of our research on discovering new vulnerabilities...future network- ing paradigm. We demonstrate that this new attacks can effectively poison the network topology information, then further successfully

Integrated DoD Voice and Data Networks and Ground Packet Radio Technology

DTIC Science & Technology

1976-08-01

as the traffic requirement level increases. Moreover, the satellite switch selection problem is only meaningful over a limited traffic range. When...5: CPU TIMES VS. NUMBER OF SWITCHES SATELLITE SWITCH SELECTION ALGORITHM Computer Used: PDP-10 ♦O’S" means 0 minutes and 5 seconds. 5.30...Saturation Algorithm for Topo\\ogical Design of Parket-Switched Communications Networks," National Te3 ecommunications Conference Proceed- ings, San

Revised genetic requirements for the decatenation G2 checkpoint: the role of ATM

PubMed Central

Bower, Jacquelyn J.; Zhou, Yingchun; Zhou, Tong; Simpson, Dennis A.; Arlander, Sonnet J.; Paules, Richard S.; Cordeiro-Stone, Marila; Kaufmann, William K.

2010-01-01

The decatenation G2 checkpoint is proposed to delay cellular progression from G2 into mitosis when intertwined daughter chromatids are insufficiently decatenated. Previous studies indicated that the ATM- and Rad3-related (ATR) checkpoint kinase, but not the ataxia telangiectasia-mutated (ATM) kinase, was required for decatenation G2 checkpoint function. Here, we show that the method used to quantify decatenation G2 checkpoint function can influence the identification of genetic requirements for the checkpoint. Normal human diploid fibroblast (NHDF) lines responded to the topoisomerase II (topo II) catalytic inhibitor ICRF-193 with a stringent G2 arrest and a reduction in the mitotic index. While siRNA-mediated depletion of ATR and CHEK1 increased the mitotic index in ICRF-193 treated NHDF lines, depletion of these proteins did not affect the mitotic entry rate, indicating that the decatenation G2 checkpoint was functional. These results suggest that ATR and CHEK1 are not required for the decatenation G2 checkpoint, but may influence mitotic exit after inhibition of topo II. A re-evaluation of ataxia telangiectasia (AT) cell lines using the mitotic entry assay indicated that ATM was required for the decatenation G2 checkpoint. Three NHDF cell lines responded to ICRF-193 with a mean 98% inhibition of the mitotic entry rate. Examination of the mitotic entry rates in AT fibroblasts upon treatment with ICRF-193 revealed a significantly attenuated decatenation G2 checkpoint response, with a mean 59% inhibition of the mitotic entry rate. In addition, a normal lymphoblastoid line exhibited a 95% inhibition of the mitotic entry rate after incubation with ICRF-193, whereas two AT lymphoblastoid lines displayed only 36% and 20% inhibition of the mitotic entry rate. Stable depletion of ATM in normal human fibroblasts with short hairpin RNA also attenuated decatenation G2 checkpoint function by an average of 40%. Western immunoblot analysis demonstrated that treatment with ICRF-193 induced ATM autophosphorylation and ATM-dependent phosphorylation of Ser15-p53 and Thr68 in CHEK2, but no appreciable phosphorylation of Ser139 on H2AX. The results suggest that inhibition of topo II induces ATM to phosphorylate selected targets that contribute to a G2 arrest independently of DNA damage. PMID:20372057

Scaling between reanalyses and high-resolution land-surface modelling in mountainous areas - enabling better application and testing of reanalyses in heterogeneous environments

NASA Astrophysics Data System (ADS)

Gruber, S.; Fiddes, J.

2013-12-01

In mountainous topography, the difference in scale between atmospheric reanalyses (typically tens of kilometres) and relevant processes and phenomena near the Earth surface, such as permafrost or snow cover (meters to tens of meters) is most obvious. This contrast of scales is one of the major obstacles to using reanalysis data for the simulation of surface phenomena and to confronting reanalyses with independent observation. At the example of modelling permafrost in mountain areas (but simple to generalise to other phenomena and heterogeneous environments), we present and test methods against measurements for (A) scaling atmospheric data from the reanalysis to the ground level and (B) smart sampling of the heterogeneous landscape in order to set up a lumped model simulation that represents the high-resolution land surface. TopoSCALE (Part A, see http://dx.doi.org/10.5194/gmdd-6-3381-2013) is a scheme, which scales coarse-grid climate fields to fine-grid topography using pressure level data. In addition, it applies necessary topographic corrections e.g. those variables required for computation of radiation fields. This provides the necessary driving fields to the LSM. Tested against independent ground data, this scheme has been shown to improve the scaling and distribution of meteorological parameters in complex terrain, as compared to conventional methods, e.g. lapse rate based approaches. TopoSUB (Part B, see http://dx.doi.org/10.5194/gmd-5-1245-2012) is a surface pre-processor designed to sample a fine-grid domain (defined by a digital elevation model) along important topographical (or other) dimensions through a clustering scheme. This allows constructing a lumped model representing the main sources of fine-grid variability and applying a 1D LSM efficiently over large areas. Results can processed to derive (i) summary statistics at coarse-scale re-analysis grid resolution, (ii) high-resolution data fields spatialized to e.g., the fine-scale digital elevation model grid, or (iii) validation products for locations at which measurements exist, only. The ability of TopoSUB to approximate results simulated by a 2D distributed numerical LSM at a factor of ~10,000 less computations is demonstrated by comparison of 2D and lumped simulations. Successful application of the combined scheme in the European Alps is reported and based on its results, open issues for future research are outlined.

Mutations reducing replication from R-loops suppress the defects of growth, chromosome segregation and DNA supercoiling in cells lacking topoisomerase I and RNase HI activity.

PubMed

Usongo, Valentine; Martel, Makisha; Balleydier, Aurélien; Drolet, Marc

2016-04-01

R-loop formation occurs when the nascent RNA hybridizes with the template DNA strand behind the RNA polymerase. R-loops affect a wide range of cellular processes and their use as origins of replication was the first function attributed to them. In Escherichia coli, R-loop formation is promoted by the ATP-dependent negative supercoiling activity of gyrase (gyrA and gyrB) and is inhibited by topoisomerase (topo) I (topA) relaxing transcription-induced negative supercoiling. RNase HI (rnhA) degrades the RNA moiety of R-loops. The depletion of RNase HI activity in topA null mutants was previously shown to lead to extensive DNA relaxation, due to DNA gyrase inhibition, and to severe growth and chromosome segregation defects that were partially corrected by overproducing topo III (topB). Here, DNA gyrase assays in crude cell extracts showed that the ATP-dependent activity (supercoiling) of gyrase but not its ATP-independent activity (relaxation) was inhibited in topA null cells lacking RNase HI. To characterize the cellular event(s) triggered by the absence of RNase HI, we performed a genetic screen for suppressors of the growth defect of topA rnhA null cells. Suppressors affecting genes in replication (holC2::aph and dnaT18::aph) nucleotide metabolism (dcd49::aph), RNA degradation (rne59::aph) and fimbriae synthesis (fimD22::aph) were found to reduce replication from R-loops and to restore supercoiling, thus pointing to a correlation between R-loop-dependent replication in topA rnhA mutants and the inhibition of gyrase activity and growth. Interestingly, the position of fimD on the E. coli chromosome corresponds to the site of one of the five main putative origins of replication from R-loops in rnhA null cells recently identified by next-generation sequencing, thus suggesting that the fimD22::aph mutation inactivated one of these origins. Furthermore, we show that topo III overproduction is unable to complement the growth defect of topA rnhA null mutants at low temperatures that stabilizes hyper-negatively supercoiled DNA. Copyright © 2016 Elsevier B.V. All rights reserved.

Digital Data Dubbing Capability.

DTIC Science & Technology

1987-10-13

DUBBING CAPABILITY 12. PERSONAL AUTHOR(S) WILLIAM B. BRIERLY...NOTATION 17. COSATI CODES 18. SUBJECT TERMS (Continue on reverse if necessary and identify by block number) FIELD GROUP SUB-GROUP DIGITAL DATA DUBBING ...34 ."*~ " ** "." ...- ,.-...." . . " ." .. ." " "."." .. " ","" ."e"....". "’"’ .*.." . """ ’. "."’,"’."’ TENTH ANNUAL ARMY TOPO CONFERENCE, OCTOBER 1987 DIGITAL DATA DUBBING

Topological Valley Transport at Bilayer Graphene Domain Walls

DTIC Science & Technology

2015-04-22

2015. Published online 22 April 2015. 1. McCann, E. Asymmetry gap in the electronic band structure of bilayer graphene . Phys. Rev. B 74, 161403 (2006...6. Yao, W., Yang, S. A. & Niu, Q. Edge states in graphene : from gapped flat- band to gapless chiral modes. Phys. Rev. Lett. 102, 096801 (2009). 7...induced in bilayer graphene by an external electric field1–5, and such gapped bilayer graphene is predicted to be a topo- logical insulating phase

Electron Irradiation Effects on Nanocrystal Quantum Dots Used in Bio-Sensing Applications

NASA Technical Reports Server (NTRS)

Leon, R.; Nadeau, J.; Evans, K.; Paskova, T.; Monemar, B.

2004-01-01

Effects of electron irradiation on some of the optical properties in organic CdSe nanocrystals coated in trioctylphosphine oxide (TOPO) and biologically compatible CdSe nanocrystals coated in mercaptoacetic acid, as CdSe as CdSe nanocrystals conjugated with the protein are investigated using the technique of cathodoluminescence. Effects of varying the beam energy and temperatures were examined and faster degradation at cryogenic temperatures and higher beam energies was found under some conditions.

Subinertial Slope-Trapped Waves in the Northeastern Gulf of Mexico

DTIC Science & Technology

2009-06-01

describe low-frequency varia- bility in the GOM and its interaction with the topo- graphy. Oey and Lee (2002) describe modeled deep eddy kinetic...deep energy can penetrate onto the upper part of the slope in this region; Oey and Lee (2002) state that their model cannot adequately resolve...slope topography in the NE GOM is described by Cames et al. (2008), Hamilton and Lee (2005), and Wang et al. (2003). Hamilton and Lee (2005) found

Automated Topographic Change Detection via Dem Differencing at Large Scales Using The Arcticdem Database

NASA Astrophysics Data System (ADS)

Candela, S. G.; Howat, I.; Noh, M. J.; Porter, C. C.; Morin, P. J.

2016-12-01

In the last decade, high resolution satellite imagery has become an increasingly accessible tool for geoscientists to quantify changes in the Arctic land surface due to geophysical, ecological and anthropomorphic processes. However, the trade off between spatial coverage and spatial-temporal resolution has limited detailed, process-level change detection over large (i.e. continental) scales. The ArcticDEM project utilized over 300,000 Worldview image pairs to produce a nearly 100% coverage elevation model (above 60°N) offering the first polar, high spatial - high resolution (2-8m by region) dataset, often with multiple repeats in areas of particular interest to geo-scientists. A dataset of this size (nearly 250 TB) offers endless new avenues of scientific inquiry, but quickly becomes unmanageable computationally and logistically for the computing resources available to the average scientist. Here we present TopoDiff, a framework for a generalized. automated workflow that requires minimal input from the end user about a study site, and utilizes cloud computing resources to provide a temporally sorted and differenced dataset, ready for geostatistical analysis. This hands-off approach allows the end user to focus on the science, without having to manage thousands of files, or petabytes of data. At the same time, TopoDiff provides a consistent and accurate workflow for image sorting, selection, and co-registration enabling cross-comparisons between research projects.

Metal complexes of 3-(4-bromophenyl)-1-pyridin-2-ylprop-2-en-1-one thiosemicarbazone: cytotoxic activity and investigation on the mode of action of the gold(III) complex.

PubMed

Sâmia, Luciana B P; Parrilha, Gabrieli L; Da Silva, Jeferson G; Ramos, Jonas P; Souza-Fagundes, Elaine M; Castelli, Silvia; Vutey, Venn; Desideri, Alessandro; Beraldo, Heloisa

2016-06-01

Complexes [Au(PyCT4BrPh)Cl]Cl (1), [Pt(PyCT4BrPh)Cl]0.5KCl (2), and [Pd(PyCT4BrPh)Cl]KCl (3) were obtained with 3-(4-bromophenyl)-1-pyridin-2-ylprop-2-en-1-one thiosemicarbazone (HPyCT4BrPh). Although complexes (2) and (3) did not exhibit potent cytotoxic activity, HPyCT4BrPh and its gold(III) complex (1) proved to be highly cytotoxic against HL-60 (human promyelocytic leukemia) and THP-1 (human monocytic leukemia) cells, and against MDA-MB 231 and MCF-7 (human breast adenocarcinoma) solid tumor cells. Except for HL-60 cells, upon coordination to gold(III) a 2- to 3-fold increase in the cytotoxic effect was observed. An investigation on the possible biological targets of the gold(III) complex was carried out. Complex (1) but not the free thiosemicarbazone inhibits the enzymatic activity of thioredoxin reductase (TrxR). The affinity of 1 for TrxR suggests metal binding to a selenol residue in the active site of the enzyme. While HPyCT4BrPh was inactive, 1 was able to inhibit topoisomerase IB (Topo IB) activity. Hence, inhibition of TrxR and Topo IB could contribute to the mechanism of cytotoxic action of complex (1).

Using Remote Sensing Observations and Empirical-Statistical Methods to Understand the Present State and Predictable Future Changes in the State of Permafrost Distribution in North-Western Himalayas

NASA Astrophysics Data System (ADS)

Baral, P.; Haq, M. A.; Mangan, P.

2017-12-01

The impacts of climate change on extent of permafrost degradation in the Himalayas and its effect upon the carbon cycle and ecosystem changes are not well understood due to lack of historical ground-based observations. We have used high resolution optical and satellite radar observations and applied empirical-statistical methods for the estimation of spatial and altitudinal limits of permafrost distribution in North-Western Himalayas. Visual interpretations of morphological characteristics using high resolution optical images have been used for mapping, identification and classification of distinctive geomorphological landforms. Subsequently, we have created a detail inventory of different types of rock glaciers and studied the contribution of topo climatic factors in their occurrence and distribution through Logistic Regression modelling. This model establishes the relationship between presence of permafrost and topo-climatic factors like Mean Annual Air Temperature (MAAT), Potential Incoming Solar Radiation (PISR), altitude, aspect and slope. This relationship has been used to estimate the distributed probability of permafrost occurrence, within a GIS environment. The ability of the model to predict permafrost occurrence has been tested using locations of mapped rock glaciers and the area under the Receiver Operating Characteristic (ROC) curve. Additionally, interferometric properties of Sentinel and ALOS PALSAR datasets are used for the identification and assessment of rock glacier activity in the region.

Circulating Bone-related Markers and YKL-40 Versus HER2 and TOPO2a in Bone Metastatic and Nonmetastatic Breast Cancer: Diagnostic Implications.

PubMed

Shaker, Olfat Gamil; Helmy, Hebatullah Samy

2018-06-01

The bone represents one of the most common sites of metastases in breast cancer. The aim of the current study was to evaluate the diagnostic potential of several circulating markers to detect metastasis to bones in patients with breast cancer. Receptor activator of Nuclear Factor-kappa β (NF-Kβ) ligand (RANKL), osteoprotegrin (OPG), vitamin D (VIT D), Chitinase-3-like protein 1; also known as YKL-40, topoisomerase IIα (TOPO2a), and human epidermal growth factor receptor 2 (HER2) were measured in blood samples obtained from 122 patients with breast cancer and 25 healthy controls. All biomarkers were significantly elevated in patients with breast cancer with bone metastasis compared with nonmetastatic patients except YKL-40. RANKL had the highest diagnostic performance for bone metastasis detection with an area under the curve of 97.3, a sensitivity of 85%, and a specificity of 98.6%. Furthermore, logistic regression analysis resulted in a model of RANKL combined with HER2 that had even higher discriminatory power of metastasis to bones than that of RANKL alone. Overall correct classification of the model was 98.9%. We recommend that measuring RANKL together with HER2 can be routinely applied to allow early detection of bone metastases in patients with breast cancer. Copyright © 2017 Elsevier Inc. All rights reserved.

TopoGromacs: Automated Topology Conversion from CHARMM to GROMACS within VMD.

PubMed

Vermaas, Josh V; Hardy, David J; Stone, John E; Tajkhorshid, Emad; Kohlmeyer, Axel

2016-06-27

Molecular dynamics (MD) simulation engines use a variety of different approaches for modeling molecular systems with force fields that govern their dynamics and describe their topology. These different approaches introduce incompatibilities between engines, and previously published software bridges the gaps between many popular MD packages, such as between CHARMM and AMBER or GROMACS and LAMMPS. While there are many structure building tools available that generate topologies and structures in CHARMM format, only recently have mechanisms been developed to convert their results into GROMACS input. We present an approach to convert CHARMM-formatted topology and parameters into a format suitable for simulation with GROMACS by expanding the functionality of TopoTools, a plugin integrated within the widely used molecular visualization and analysis software VMD. The conversion process was diligently tested on a comprehensive set of biological molecules in vacuo. The resulting comparison between energy terms shows that the translation performed was lossless as the energies were unchanged for identical starting configurations. By applying the conversion process to conventional benchmark systems that mimic typical modestly sized MD systems, we explore the effect of the implementation choices made in CHARMM, NAMD, and GROMACS. The newly available automatic conversion capability breaks down barriers between simulation tools and user communities and allows users to easily compare simulation programs and leverage their unique features without the tedium of constructing a topology twice.

Carbohydrate linked organotin(IV) complexes as human topoisomerase Iα inhibitor and their antiproliferative effects against the human carcinoma cell line.

PubMed

Khan, Rais Ahmad; Yadav, Shipra; Hussain, Zahid; Arjmand, Farukh; Tabassum, Sartaj

2014-02-14

Dimethyltin(IV) complexes with ethanolamine (1) and biologically significant N-glycosides (2 and 3) were designed and synthesized. The structural elucidation of complexes 1-3 was done using elemental and spectroscopic methods; in addition, complex 1 was studied by single crystal X-ray diffraction studies. The in vitro DNA binding profile of complexes 2 and 3 was carried out by employing different biophysical methods to ascertain the feasibility of glycosylated complexes. Further, the cleaving ability of 2 and 3 was investigated by the agarose gel electrophoretic mobility assay with supercoiled pBR322 DNA, and demonstrated significantly good nuclease activity. Furthermore, both the complexes exhibited significant inhibitory effects on the catalytic activity of human Topo I at lower concentration than standard drugs. Computer-aided molecular docking techniques were used to ascertain the mode and mechanism of action towards the molecular target DNA and Topo I. The cytotoxicity of 2 and 3 against human hepatoma cancer cells (Huh7) was evaluated, which revealed significant regression in cancerous cells as compared with the standard drug. The antiproliferative activities of 2 and 3 were tested against human hepatoma cancer cells (Huh7), and results showed significantly good activity. Additionally, to validate the remarkable antiproliferative activity of complexes 2 and 3, specific regulatory gene expression (MMP-2 and TGF-β) was obtained by real time PCR.

Directed Assembly of Quantum Dots in Diblock Copolymer Matrix

DTIC Science & Technology

2007-08-01

behavior of a diblock copolymer, PS - b -poly(2-vinylpyridene) ( PS - b - P2VP ). Addition of 2.5-nm-diameter gold nanoparticles, functionalized with short...dispersion of variations in the relative surface coverage by short thiol-terminated PS ligands (3400 g/mol), also in a PS - b - P2VP matrix. As a result of...film of PS - b - P2VP . In that case, the particles were stabilized with tri-n-octylphosphine oxide (TOPO) ligands. When thin films were prepared from

Lanthanide-based laser-induced phosphorescence for spray diagnostics

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

Voort, D. D. van der, E-mail: d.d.v.d.voort@tue.nl; Water, W. van de; Kunnen, R. P. J.

2016-03-15

Laser-induced phosphorescence (LIP) is a relatively recent and versatile development for studying flow dynamics. This work investigates certain lanthanide-based molecular complexes for their use in LIP for high-speed sprays. Lanthanide complexes in solutions have been shown to possess long phosphorescence lifetimes (∼1-2 ms) and to emit light in the visible wavelength range. In particular, europium and terbium complexes are investigated using fluorescence/phosphorescence spectrometry, showing that europium-thenoyltrifluoracetone-trioctylphosphineoxide (Eu-TTA-TOPO) can be easily and efficiently excited using a standard frequency-tripled Nd:YAG laser. The emitted spectrum, with maximum intensity at a wavelength of 614 nm, is shown not to vary strongly with temperature (293-383more » K). The decay constant of the phosphorescence, while independent of ambient pressure, decreases by approximately 12 μs/K between 323 and 373 K, with the base level of the decay constant dependent on the used solvent. The complex does not luminesce in the gas or solid state, meaning only the liquid phase is visualized, even in an evaporating spray. By using an internally excited spray containing the phosphorescent complex, the effect of vaporization is shown through the decrease in measured intensity over the length of the spray, together with droplet size measurements using interferometric particle imaging. This study shows that LIP, using the Eu-TTA-TOPO complex, can be used with different solvents, including diesel surrogates. Furthermore, it can be easily handled and used in sprays to investigate spray breakup and evaporation.« less

Mapping current and potential distribution of non-native Prosopis juliflora in the Afar region of Ethiopia

USGS Publications Warehouse

Wakie, Tewodros; Evangelista, Paul H.; Jarnevich, Catherine S.; Laituri, Melinda

2014-01-01

We used correlative models with species occurrence points, Moderate Resolution Imaging Spectroradiometer (MODIS) vegetation indices, and topo-climatic predictors to map the current distribution and potential habitat of invasive Prosopis juliflora in Afar, Ethiopia. Time-series of MODIS Enhanced Vegetation Indices (EVI) and Normalized Difference Vegetation Indices (NDVI) with 250 m2 spatial resolution were selected as remote sensing predictors for mapping distributions, while WorldClim bioclimatic products and generated topographic variables from the Shuttle Radar Topography Mission product (SRTM) were used to predict potential infestations. We ran Maxent models using non-correlated variables and the 143 species-occurrence points. Maxent generated probability surfaces were converted into binary maps using the 10-percentile logistic threshold values. Performances of models were evaluated using area under the receiver-operating characteristic (ROC) curve (AUC). Our results indicate that the extent of P. juliflora invasion is approximately 3,605 km2 in the Afar region (AUC = 0.94), while the potential habitat for future infestations is 5,024 km2 (AUC = 0.95). Our analyses demonstrate that time-series of MODIS vegetation indices and species occurrence points can be used with Maxent modeling software to map the current distribution of P. juliflora, while topo-climatic variables are good predictors of potential habitat in Ethiopia. Our results can quantify current and future infestations, and inform management and policy decisions for containing P. juliflora. Our methods can also be replicated for managing invasive species in other East African countries.

Phylogenetic analysis of the core histone doublet and DNA topo II genes of Marseilleviridae: evidence of proto-eukaryotic provenance.

PubMed

Erives, Albert J

2017-11-28

While the genomes of eukaryotes and Archaea both encode the histone-fold domain, only eukaryotes encode the core histone paralogs H2A, H2B, H3, and H4. With DNA, these core histones assemble into the nucleosomal octamer underlying eukaryotic chromatin. Importantly, core histones for H2A and H3 are maintained as neofunctionalized paralogs adapted for general bulk chromatin (canonical H2 and H3) or specialized chromatin (H2A.Z enriched at gene promoters and cenH3s enriched at centromeres). In this context, the identification of core histone-like "doublets" in the cytoplasmic replication factories of the Marseilleviridae (MV) is a novel finding with possible relevance to understanding the origin of eukaryotic chromatin. Here, we analyze and compare the core histone doublet genes from all known MV genomes as well as other MV genes relevant to the origin of the eukaryotic replisome. Using different phylogenetic approaches, we show that MV histone domains encode obligate H2B-H2A and H4-H3 dimers of possible proto-eukaryotic origin. MV core histone moieties form sister clades to each of the four eukaryotic clades of canonical and variant core histones. This suggests that MV core histone moieties diverged prior to eukaryotic neofunctionalizations associated with paired linear chromosomes and variant histone octamer assembly. We also show that MV genomes encode a proto-eukaryotic DNA topoisomerase II enzyme that forms a sister clade to eukaryotes. This is a relevant finding given that DNA topo II influences histone deposition and chromatin compaction and is the second most abundant nuclear protein after histones. The combined domain architecture and phylogenomic analyses presented here suggest that a primitive origin for MV histone genes is a more parsimonious explanation than horizontal gene transfers + gene fusions + sufficient divergence to eliminate relatedness to eukaryotic neofunctionalizations within the H2A and H3 clades without loss of relatedness to each of the four core histone clades. We thus suggest MV histone doublet genes and their DNA topo II gene possibly were acquired from an organism with a chromatinized replisome that diverged prior to the origin of eukaryotic core histone variants for H2/H2A.Z and H3/cenH3. These results also imply that core histones were utilized ancestrally in viral DNA compaction and/or protection from host endonucleases.

Extractant composition

DOEpatents

Smith, Barbara F.; Jarvinen, Gordon D.; Ryan, Robert R.

1990-01-01

An organic extracting solution useful for separating elements of the actinide series of the periodic table from elements of the lanthanide series, where both are in trivalent form. The extracting solution consists of a primary ligand and a secondary ligand, preferably in an organic solvent. The primary ligand is a substituted monothio-1,3-dicarbonyl, which includes a substituted 4-acyl-2-pyrazolin-5-thione, such as 4-benzoyl-2,4-dihydro-5-methyl-2-phenyl-3H-pyrazol-3-thione (BMPPT). The secondary ligand is a substituted phosphine oxide, such as trioctylphosphine oxide (TOPO).

Structural, morphological and optical properties of chromium oxide nanoparticles

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

Babukutty, Blessy; Parakkal, Fasalurahman; Nair, Swapna S., E-mail: swapna.s.nair@gmail.com

2015-06-24

Chromium oxide nanoparticles are synthesized by reduction route from chloride precursors with surfactant, trioctylphosphine oxide (TOPO). Structural and morphological characterization are analyzed using X-ray Diffraction (XRD) and Transmission Electron Microscopy (TEM). Transmission Electron micrographs show that the average grain size lies in the range 5nm to 10nm. Optical characterization has been done by UV-VIS spectrophotometer. Distinct optical absorptions of Cr{sup 3+} ions show hinting towards the presence of Cr{sub 2}O{sub 3}. Presence of oxygen is also confirmed from Electron Energy Loss Spectroscopy (EELS) studies.

Develop advanced nonlinear signal analysis topographical mapping system

NASA Technical Reports Server (NTRS)

Jong, Jen-Yi

1993-01-01

This study will provide timely assessment of SSME component operational status, identify probable causes of malfunction, and indicate feasible engineering solutions. The final result of this program will yield an advanced nonlinear signal analysis topographical mapping system (ATMS) of nonlinear and nonstationary spectral analysis software package integrated with the Compressed SSME TOPO Data Base (CSTDB) on the same platform. This system will allow NASA engineers to retrieve any unique defect signatures and trends associated with different failure modes and anomalous phenomena over the entire SSME test history across turbopump families.

Field Operational and Environmental Evaluation of the Automated Integrated Surveying Instrument (AISI). Volume 1

DTIC Science & Technology

1988-04-01

Astro Observation. May 1966 - Ma, 1967: U.S. Army Engineering School, Fort Belvoir, Virginia. Second phase leader, topo computing course. June 1967 - May...17P P 00000!.46 041 041 2 00 00 2 -0013P- F� 020@ 020 0- 0. 00 0.@ 0 ( i -00! FX X 0000007 001000(V 0000000 0000000 0000000 0000000 000o0...SHEET - ERROR OF CLOSURE - RETRIEVER SOFTWARE JOB: Fx ORIGIN POINT NORTHING: /</𔄃ZV-O_0a UNADJUSTED NORTHING :/’ 2f6Jf: 0 NORTHING ERROR: ,00. ORIGIN

Hybrid Nanotechnologies for Detection and Synergistic Therapies for Breast Cancer

DTIC Science & Technology

2012-10-01

5%-TCA TCG ATG GAG GTG CAG CTG GTG GAG-3%) and FdSeq1 and ligated into pCR2.1 TOPO. The ClaI/NotI-digested frag- ment was ligated into the ClaI/NotI...binding of each scFv clone (bold line) and the backgrounds of phycoerythrin-conjugated secondary antibodies ( gray ). FIGURE 3. Targeting of fluorescently...of the neuropilin family, is a high affinity receptor for the semaphorins Sema E and Sema IV but not Sema III. Neuron 19: 547–559. Dallas NA, Gray MJ

Restriction limits and main drivers of fruit production in palm in central Amazonia

NASA Astrophysics Data System (ADS)

Freitas, Cintia; Costa, Flávia R. C.; Barbosa, Carlos Eduardo; Cintra, Renato

2016-11-01

Adult plants incapable of producing viable offspring inflate our perception of the size of population distribution. We propose that species occurrence is limited to a subset of the environmental gradient and that it changes as ontogenetic development progresses. Moreover, fruit production is associated with site-specific environmental conditions. We sampled 2988 adult individuals from nine palm species in 30 plots (40 × 250 m) and used a larger data set including 42 other plots distributed along a continuous topo-edaphic gradient in a terra firme forest near Manaus, Brazil. Five out of nine palm species were more restricted to a sub-section of the topo-edaphic gradient in the adult-size phase. More specifically, reproductive individuals of species Attalea attaleoides and A. microcarpa had even more restricted distributions than adult-sized, non-reproductive plants. Successive environmental filtering and competition probably acting through selective mortality led to increasing habitat restriction, with reproductive adults being restricted to a smaller part of the region than juveniles and adults. Water availability and nutrients limited both the ability to produce fruits and the amount of fruit production. Previous studies have reported stronger habitat associations for older plants than for seedlings or juveniles, but we show here that some species are more restricted at their reproductive stage. Plant specializations to local conditions may be more common than currently acknowledged, and a significant portion of individuals in a population might represent sinks. Such strong environmental limitations of reproductive plants should also be considered in management of species with economic value and in conservation planning.

New porous titanium–niobium oxide for photocatalytic degradation of bromocresol green dye in aqueous solution

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

Chaleshtori, Maryam Zarei, E-mail: mzarei@utep.edu; Hosseini, Mahsa; Edalatpour, Roya

2013-10-15

Graphical abstract: The photocatalytic activity of different porous titanium–niobium oxides was evaluated toward degradation of bromocresol green (BG) under UV light. A better catalytic activity was observed for all samples at lower pH. Catalysts have a stronger ability for degradation of BG in acid media than in alkaline media. - Highlights: • Different highly structured titanium–niobium oxides have been prepared using improved methods of synthesis. • Photo-degradation of bromocresol green dye (BG) with nanostructure titanium–niobium oxide catalysts was carried out under UV light. • The photo-catalytic activity of all catalysts was higher in lower pH. • Titanium–niobium oxide catalysts aremore » considerably stable and reusable. - Abstract: In this study, high surface area semiconductors, non porous and porous titanium–niobium oxides derived from KTiNbO{sub 5} were synthesized, characterized and developed for their utility as photocatalysts for decontamination with sunlight. These materials were then used in the photocatalytic degradation of bromocresol green dye (BG) in aqueous solution using UV light and their catalytic activities were evaluated at various pHs. For all catalysts, the photocatalytic degradation of BG was most efficient in acidic solutions. Results show that the new porous oxides have large porous and high surface areas and high catalytic activity. A topotactic dehydration treatment greatly improves catalyst performance at various pHs. Stability and long term activity of porous materials (topo and non-topo) in photocatalysis reactions was also tested. These results suggest that the new materials can be used to efficiently purify contaminated water.« less

Sheaf theoretic formulation for consciousness and qualia and relationship to the idealism of non-dual philosophies.

PubMed

Kafatos, Menas C; Kato, Goro C

2017-12-01

Questions about the nature of reality, whether Consciousness is the fundamental reality in the universe, and what is Consciousness itself, have no answer in systems that assume an external reality independent of Consciousness. Ultimately, the ontological foundation of such systems is the absolute division of subject and object. We advocate instead what we consider to be an approach that is in agreement with the foundation of quantum reality, which is based on Rāmānuja's version of Vedanta philosophy and non-dual Kashmir Śaivism. Quantum mechanics opened the door to consciousness, but it cannot account for consciousness. However, the quantum measurement problem implies that we cannot remove subjective experience from the practice of science. It is then appropriate to seek mathematical formalisms for the workings of consciousness that don't rely on specific interpretations of quantum mechanics. Temporal topos provides such a framework. In the theory of temporal topos, which we outline here, the difference between a subject and an object involves the direction of a morphism in a category. We also note that in the dual category, the direction of the morphism is in the opposite direction compared with the original direction of the original category. The resulting formalism provides powerful ways to address consciousness and qualia, beyond attempts to account for consciousness through physical theories. We also discuss the implications of the mathematics presented here for the convergence of science and non-dualist philosophies, as an emerging science of Consciousness, that may bring out the underlying unity of physics, life and mind. Copyright © 2017. Published by Elsevier Ltd.

Effect of NaeI-L43K mutation on protein dynamics and DNA conformation: Insights from molecular dynamics simulations.

PubMed

Ramachandrakurup, Sreelakshmi; Ramakrishnan, Vigneshwar

2017-09-01

Protein-DNA interactions are an important class of biomolecular interactions inside the cell. Delineating the mechanisms of protein-DNA interactions and more specifically, how proteins search and bind to their specific cognate sequences has been the quest of many in the scientific community. Restriction enzymes have served as useful model systems to this end. In this work, we have investigated using molecular dynamics simulations the effect of L43K mutation on NaeI, a type IIE restriction enzyme. NaeI has two domains, the Topo and the Endo domains, each binding to identical strands of DNA sequences (GCCGGC) 2 . The binding of the DNA to the Topo domain is thought to enhance the binding and cleavage of DNA at the Endo domain. Interestingly, it has been found that the mutation of an amino acid that is distantly-located from the DNA cleavage site (L43K) converts the restriction endonuclease to a topoisomerase. Our investigations reveal that the L43K mutation not only induces local structural changes (as evidenced by changes in hydrogen bond propensities and differences in the percentage of secondary structure assignments of the residues in the ligase-like domain) but also alters the overall protein dynamics and DNA conformation which probably leads to the loss of specific cleavage of the recognition site. In a larger context, our study underscores the importance of considering the role of distantly-located amino acids in understanding protein-DNA interactions. Copyright © 2017 Elsevier Inc. All rights reserved.

The CSM testbed matrix processors internal logic and dataflow descriptions

NASA Technical Reports Server (NTRS)

Regelbrugge, Marc E.; Wright, Mary A.

1988-01-01

This report constitutes the final report for subtask 1 of Task 5 of NASA Contract NAS1-18444, Computational Structural Mechanics (CSM) Research. This report contains a detailed description of the coded workings of selected CSM Testbed matrix processors (i.e., TOPO, K, INV, SSOL) and of the arithmetic utility processor AUS. These processors and the current sparse matrix data structures are studied and documented. Items examined include: details of the data structures, interdependence of data structures, data-blocking logic in the data structures, processor data flow and architecture, and processor algorithmic logic flow.

Separation of actinides from lanthanides

DOEpatents

Smith, B.F.; Jarvinen, G.D.; Ryan, R.R.

1988-03-31

An organic extracting solution and an extraction method useful for separating elements of the actinide series of the periodic table from elements of the lanthanide series, where both are in trivalent form is described. The extracting solution consists of a primary ligand and a secondary ligand, preferably in an organic solvent. The primary ligand is a substituted monothio-1,3-dicarbonyl, which includes a substituted 4-acyl-2-pyrazolin-5-thione, such as 4-benzoyl-2,4- dihydro-5-methyl-2-phenyl-3H-pyrazol-3-thione (BMPPT). The secondary ligand is a substituted phosphine oxide, such as trioctylphosphine oxide (TOPO).

Separation of actinides from lanthanides

DOEpatents

Smith, Barbara F.; Jarvinen, Gordon D.; Ryan, Robert R.

1989-01-01

An organic extracting solution and an extraction method useful for separating elements of the actinide series of the periodic table from elements of the lanthanide series, where both are in trivalent form. The extracting solution consists of a primary ligand and a secondary ligand, preferably in an organic solvent. The primary ligand is a substituted monothio-1,3-dicarbonyl, which includes a substituted 4-acyl-2-pyrazolin-5-thione, such as 4-benzoyl-2,4-dihydro-5-methyl-2-phenyl-3H-pyrazol-3-thione (BMPPT). The secondary ligand is a substituted phosphine oxide, such as trioctylphosphine oxide (TOPO).

Imaging the continental mantle beneath Iberia and Northern Morocco: the contribution of the Topo-Iberia project.

NASA Astrophysics Data System (ADS)

Diaz, Jordi

2013-04-01

One of the key assets of the Topo-Iberia research program, aiming to unravel the complex structure and mantle processes in the area of interaction between the African and European continental plates, has been the deploying of a technological observational platform, named IberArray, to provide new seismological, magnetotelluric and geodetical data with unprecedented resolution and coverage. Topo-Iberia has also benefited from the interaction with subsequent projects investigating the same area, as the USA Picasso, the French Pyrope or the Portuguese Wilas. This interaction includes sharing the available data to better assess the key geological questions. This contribution aims to present the current state of the most significant scientific investigations concerning the lithosphere-asthenosphere system beneath Iberia and Northern Morocco which are arising from the data acquired using the Iberarray platform. The area so far investigated extends from the Variscan Central Iberian Massif in the North to the border of the Sahara Platform in the South and includes areas of complex and still not completely understood geodynamics, as the Alboran domain or the Atlas Mountains. SKS splitting analysis clearly image this complexity; the fast polarization directions (FPD) beneath the Betics-Alboran show a spectacular rotation along the Gibraltar arc following the curvature of the Rif-Betic chain. Beneath the High Atlas and SW Iberia, there are a very significant number of high quality events without evidence for anisotropy, suggesting the presence of a large vertical component of flow in the upper mantle. These observations allow inferring a model of mantle flow at regional scale. New body wave tomographic images have confirmed the presence of a high-velocity slab beneath the Gibraltar Arc and allowed to define more precisely its geometry, appearing as a near-vertical feature extending from 50-75 km to about 600 km. Magnetotelluric profiles acquired using broad-band and long-period instrumentation along different N-S profiles from North Iberia to the Atlas have also provided relevant information along a 1500 km long N-S lithospheric transect. Receiver functions have revealed large crustal thickness variations, including a crustal root beneath the Rif not clearly documented previously. Beneath Iberia, the Variscan domain shows a quite uniform Moho depth, but the areas affected by the Alpine orogeny show significant variations, consistent with the results arising from ambient noise interferometry. Moving to the base of the upper mantle, the geometry of the 410-km and 660-km upper mantle discontinuities have been investigated using novel cross-correlation/stacking techniques, which have allowed to obtain a detailed map of the transition zone thickness variations.

Decoupled dimensions of leaf economic and anti-herbivore defense strategies in a tropical canopy tree community.

PubMed

Chauvin, K McManus; Asner, G P; Martin, R E; Kress, W J; Wright, S J; Field, C B

2018-03-01

Trade-offs among plant functional traits indicate diversity in plant strategies of growth and survival. The leaf economics spectrum (LES) reflects a trade-off between short-term carbon gain and long-term leaf persistence. A related trade-off, between foliar growth and anti-herbivore defense, occurs among plants growing in contrasting resource regimes, but it is unclear whether this trade-off is maintained within plant communities, where resource gradients are minimized. The LES and the growth-defense trade-off involve related traits, but the extent to which these trade-off dimensions are correlated is poorly understood. We assessed the relationship between leaf economic and anti-herbivore defense traits among sunlit foliage of 345 canopy trees in 83 species on Barro Colorado Island, Panama. We quantified ten traits related to resource allocation and defense, and identified patterns of trait co-variation using multivariate ordination. We tested whether traits and ordination axes were correlated with patterns of phylogenetic relatedness, juvenile demographic trade-offs, or topo-edaphic variation. Two independent axes described ~ 60% of the variation among canopy trees. Axis 1 revealed a trade-off between leaf nutritional and structural investment, consistent with the LES. Physical defense traits were largely oriented along this axis. Axis 2 revealed a trade-off between investments in phenolic defenses versus other foliar defenses, which we term the leaf defense spectrum. Phylogenetic relationships and topo-edaphic variation largely did not explain trait co-variation. Our results suggest that some trade-offs among the growth and defense traits of outer-canopy trees may be captured by the LES, while others may occur along additional resource allocation dimensions.

Hollow fiber supported ionic liquid membrane microextraction for determination of sulfonamides in environmental water samples by high-performance liquid chromatography.

PubMed

Tao, Yong; Liu, Jing-Fu; Hu, Xia-Lin; Li, Hong-Cheng; Wang, Thanh; Jiang, Gui-Bin

2009-08-28

By using ionic liquid as membrane liquid and tri-n-octylphosphine oxide (TOPO) as additive, hollow fiber supported liquid phase microextraction (HF-LPME) was developed for the determination of five sulfonamides in environmental water samples by high-performance liquid chromatography with ultraviolet detection The extraction solvent and the parameters affecting the extraction enrichment factor such as the type and amount of carrier, pH and volume ratio of donor phase and acceptor phase, extraction time, salt-out effect and matrix effect were optimized. Under the optimal extraction conditions (organic liquid membrane phase: [C(8)MIM][PF(6)] with 14% TOPO (w/v); donor phase: 4mL, pH 4.5 KH(2)PO(4) with 2M Na(2)SO(4); acceptor phase: 25microL, pH 13 NaOH; extraction time: 8 h), low detection limits (0.1-0.4microg/L, RSDor=0.999) were obtained for all the analytes. The presence of humic acid (0-25mg/L dissolved organic carbon) and bovine serum albumin (0-100microg/mL) had no significant effect on the extraction efficiency. Good spike recoveries over the range of 82.2-103.2% were obtained when applying the proposed method on five real environmental water samples. These results indicated that this present method was very sensitive and reliable with good repeatabilities and excellent clean-up in water samples. The proposed method confirmed hollow fiber supported ionic liquid membrane based LPME to be robust to monitoring trace levels of sulfadiazine, sulfamerazine, sulfamethazine, sulfadimethoxine and sulfamethoxazole in aqueous samples.

Dilution effects on combined magnetic and electric dipole interactions: A study of ferromagnetic cobalt nanoparticles with tuneable interactions

NASA Astrophysics Data System (ADS)

Hod, M.; Dobroserdova, A.; Samin, S.; Dobbrow, C.; Schmidt, A. M.; Gottlieb, M.; Kantorovich, S.

2017-08-01

Improved understanding of complex interactions between nanoparticles will facilitate the control over the ensuing self-assembled structures. In this work, we consider the dynamic changes occurring upon dilution in the self-assembly of a system of ferromagnetic cobalt nanoparticles that combine magnetic, electric, and steric interactions. The systems examined here vary in the strength of the magnetic dipole interactions and the amount of point charges per particle. Scattering techniques are employed for the characterization of the self-assembly aggregates, and zeta-potential measurements are employed for the estimation of surface charges. Our experiments show that for particles with relatively small initial number of surface electric dipoles, an increase in particle concentration results in an increase in diffusion coefficients; whereas for particles with relatively high number of surface dipoles, no effect is observed upon concentration changes. We attribute these changes to a shift in the adsorption/desorption equilibrium of the tri-n-octylphosphine oxide (TOPO) molecules on the particle surface. We put forward an explanation, based on the combination of two theoretical models. One predicts that the growing concentration of electric dipoles, stemming from the addition of tri-n-octylphosphine oxide (TOPO) as co-surfactant during particle synthesis, on the surface of the particles results in the overall repulsive interaction. Secondly, using density functional theory, we explain that the observed behaviour of the diffusion coefficient can be treated as a result of the concentration dependent nanoparticle self-assembly: additional repulsion leads to the reduction in self-assembled aggregate size despite the shorter average interparticle distances, and as such provides the growth of the diffusion coefficient.

Dilution effects on combined magnetic and electric dipole interactions: A study of ferromagnetic cobalt nanoparticles with tuneable interactions.

PubMed

Hod, M; Dobroserdova, A; Samin, S; Dobbrow, C; Schmidt, A M; Gottlieb, M; Kantorovich, S

2017-08-28

Improved understanding of complex interactions between nanoparticles will facilitate the control over the ensuing self-assembled structures. In this work, we consider the dynamic changes occurring upon dilution in the self-assembly of a system of ferromagnetic cobalt nanoparticles that combine magnetic, electric, and steric interactions. The systems examined here vary in the strength of the magnetic dipole interactions and the amount of point charges per particle. Scattering techniques are employed for the characterization of the self-assembly aggregates, and zeta-potential measurements are employed for the estimation of surface charges. Our experiments show that for particles with relatively small initial number of surface electric dipoles, an increase in particle concentration results in an increase in diffusion coefficients; whereas for particles with relatively high number of surface dipoles, no effect is observed upon concentration changes. We attribute these changes to a shift in the adsorption/desorption equilibrium of the tri-n-octylphosphine oxide (TOPO) molecules on the particle surface. We put forward an explanation, based on the combination of two theoretical models. One predicts that the growing concentration of electric dipoles, stemming from the addition of tri-n-octylphosphine oxide (TOPO) as co-surfactant during particle synthesis, on the surface of the particles results in the overall repulsive interaction. Secondly, using density functional theory, we explain that the observed behaviour of the diffusion coefficient can be treated as a result of the concentration dependent nanoparticle self-assembly: additional repulsion leads to the reduction in self-assembled aggregate size despite the shorter average interparticle distances, and as such provides the growth of the diffusion coefficient.

Preparation of water soluble L-arginine capped CdSe/ZnS QDs and their interaction with synthetic DNA: Picosecond-resolved FRET study

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

Giri, Anupam; Goswami, Nirmal; Lemmens, Peter

2012-08-15

Graphical abstract: Förster resonance energy transfer (FRET) studies on the interaction of water soluble arginine-capped CdSe/ZnS QDs with ethidium bromide (EB) labeled synthetic dodecamer DNA. Highlights: ► We have solubilized CdSe/ZnS QD in water replacing their TOPO ligand by L-arginine. ► We have studied arginine@QD–DNA interaction using FRET technique. ► Arginine@QDs act as energy donor and ethidium bromide-DNA acts as energy acceptor. ► We have applied a kinetic model to understand the kinetics of energy transfer. ► Circular dichroism studies revealed negligible perturbation in the DNA B-form in the arg@QD-DNA complex. -- Abstract: We have exchanged TOPO (trioctylphosphine oxide) ligandmore » of CdSe/ZnS core/shell quantum dots (QDs) with an amino acid L-arginine (Arg) at the toluene/water interface and eventually rendered the QDs from toluene to aqueous phase. We have studied the interaction of the water soluble Arg-capped QDs (energy donor) with ethidium (EB) labeled synthetic dodecamer DNA (energy acceptor) using picoseconds resolved Förster resonance energy transfer (FRET) technique. Furthermore, we have applied a model developed by M. Tachiya to understand the kinetics of energy transfer and the distribution of acceptor (EB-DNA) molecules around the donor QDs. Circular dichroism (CD) studies revealed a negligible perturbation in the native B-form structure of the DNA upon interaction with Arg-capped QDs. The melting and the rehybridization pathways of the DNA attached to the QDs have been monitored by the CD which reveals hydrogen bonding is the associative mechanism for interaction between Arg-capped QDs and DNA.« less

Chemical exposure and infant leukaemia: development of an adverse outcome pathway (AOP) for aetiology and risk assessment research.

PubMed

Pelkonen, Olavi; Terron, Andrea; Hernandez, Antonio F; Menendez, Pablo; Bennekou, Susanne Hougaard

2017-08-01

Infant leukaemia (<1 year old) is a rare disease of an in utero origin at an early phase of foetal development. Rearrangements of the mixed-lineage leukaemia (MLL) gene producing abnormal fusion proteins are the most frequent genetic/molecular findings in infant B cell-acute lymphoblastic leukaemia. In small epidemiological studies, mother/foetus exposures to some chemicals including pesticides have been associated with infant leukaemia; however, the strength of evidence and power of these studies are weak at best. Experimental in vitro or in vivo models do not sufficiently recapitulate the human disease and regulatory toxicology studies are unlikely to capture this kind of hazard. Here, we develop an adverse outcome pathway (AOP) based substantially on an analogous disease-secondary acute leukaemia caused by the topoisomerase II (topo II) poison etoposide-and on cellular and animal models. The hallmark of the AOP is the formation of MLL gene rearrangements via topo II poisoning, leading to fusion genes and ultimately acute leukaemia by global (epi)genetic dysregulation. The AOP condenses molecular, pathological, regulatory and clinical knowledge in a pragmatic, transparent and weight of evidence-based framework. This facilitates the interpretation and integration of epidemiological studies in the process of risk assessment by defining the biologically plausible causative mechanism(s). The AOP identified important gaps in the knowledge relevant to aetiology and risk assessment, including the specific embryonic target cell during the short and spatially restricted period of susceptibility, and the role of (epi)genetic features modifying the initiation and progression of the disease. Furthermore, the suggested AOP informs on a potential Integrated Approach to Testing and Assessment to address the risk caused by environmental chemicals in the future.

Relationship between DNA damage response, initiated by camptothecin or oxidative stress, and DNA replication, analyzed by quantitative 3D image analysis.

PubMed

Berniak, K; Rybak, P; Bernas, T; Zarębski, M; Biela, E; Zhao, H; Darzynkiewicz, Z; Dobrucki, J W

2013-10-01

A method of quantitative analysis of spatial (3D) relationship between discrete nuclear events detected by confocal microscopy is described and applied in analysis of a dependence between sites of DNA damage signaling (γH2AX foci) and DNA replication (EdU incorporation) in cells subjected to treatments with camptothecin (Cpt) or hydrogen peroxide (H2O2). Cpt induces γH2AX foci, likely reporting formation of DNA double-strand breaks (DSBs), almost exclusively at sites of DNA replication. This finding is consistent with the known mechanism of induction of DSBs by DNA topoisomerase I (topo1) inhibitors at the sites of collisions of the moving replication forks with topo1-DNA "cleavable complexes" stabilized by Cpt. Whereas an increased level of H2AX histone phosphorylation is seen in S-phase of cells subjected to H2O2, only a minor proportion of γH2AX foci coincide with DNA replication sites. Thus, the increased level of H2AX phosphorylation induced by H2O2 is not a direct consequence of formation of DNA lesions at the sites of moving DNA replication forks. These data suggest that oxidative stress induced by H2O2 and formation of the primary H2O2-induced lesions (8-oxo-7,8-dihydroguanosine) inhibits replication globally and triggers formation of γH2AX at various distances from replication forks. Quantitative analysis of a frequency of DNA replication sites and γH2AX foci suggests also that stalling of replicating forks by Cpt leads to activation of new DNA replication origins. © 2013 International Society for Advancement of Cytometry. Copyright © 2013 International Society for Advancement of Cytometry.

Association between Twist and multidrug resistance gene-associated proteins in Taxol®-resistant MCF-7 cells and a 293 cell model of Twist overexpression.

PubMed

Wang, Li; Tan, Rui-Zhi; Zhang, Zhi-Xia; Yin, Rui; Zhang, Yong-Liang; Cui, Wei-Jia; He, Tao

2018-01-01

Multidrug resistance (MDR) severely limits the effectiveness of chemotherapy. Previous studies have identified Twist as a key factor of acquired MDR in breast, gastric and prostate cancer. However, the underlying mechanisms of action of Twist in MDR remain unclear. In the present study, the expression levels of MDR-associated proteins, including lung resistance-related protein (LRP), topoisomerase IIα (TOPO IIα), MDR-associated protein (MRP) and P-glycoprotein (P-gp), and the expression of Twist in cancerous tissues and pericancerous tissues of human breast cancer, were examined. In order to simulate Taxol ® resistance in cells, a Taxol ® -resistant human mammary adenocarcinoma cell subline (MCF-7/Taxol ® ) was established by repeatedly exposing MCF-7 cells to high concentrations of Taxol ® (up to 15 µg/ml). Twist was also overexpressed in 293 cells by transfecting this cell line with pcDNA5/FRT/TO vector containing full-length hTwist cDNA to explore the dynamic association between Twist and MDR gene-associated proteins. It was identified that the expression levels of Twist, TOPO IIα, MRP and P-gp were upregulated and LRP was downregulated in human breast cancer tissues, which was consistent with the expression of these proteins in the Taxol ® -resistant MCF-7 cell model. Notably, the overexpression of Twist in 293 cells increased the resistance to Taxol ® , Trichostatin A and 5-fluorouracil, and also upregulated the expression of MRP and P-gp. Taken together, these data demonstrated that Twist may promote drug resistance in cells and cancer tissues through regulating the expression of MDR gene-associated proteins, which may assist in understanding the mechanisms of action of Twist in drug resistance.

Multiscale topo-morphologic opening of arteries and veins: a validation study on phantoms and CT imaging of pulmonary vessel casting of pigs

NASA Astrophysics Data System (ADS)

Gao, Zhiyun; Holtze, Colin; Sonka, Milan; Hoffman, Eric; Saha, Punam K.

2010-03-01

Distinguishing pulmonary arterial and venous (A/V) trees via in vivo imaging is a critical first step in the quantification of vascular geometry for purposes of determining, for instance, pulmonary hypertension, detection of pulmonary emboli and more. A multi-scale topo-morphologic opening algorithm has recently been introduced by us separating A/V trees in pulmonary multiple-detector X-ray computed tomography (MDCT) images without contrast. The method starts with two sets of seeds - one for each of A/V trees and combines fuzzy distance transform, fuzzy connectivity, and morphologic reconstruction leading to multi-scale opening of two mutually fused structures while preserving their continuity. The method locally determines the optimum morphological scale separating the two structures. Here, a validation study is reported examining accuracy of the method using mathematically generated phantoms with different levels of fuzziness, overlap, scale, resolution, noise, and geometric coupling and MDCT images of pulmonary vessel casting of pigs. After exsanguinating the animal, a vessel cast was generated using rapid-hardening methyl methacrylate compound with additional contrast by 10cc of Ethiodol in the arterial side which was scanned in a MDCT scanner at 0.5mm slice thickness and 0.47mm in plane resolution. True segmentations of A/V trees were computed from these images by thresholding. Subsequently, effects of distinguishing A/V contrasts were eliminated and resulting images were used for A/V separation by our method. Experimental results show that 92% - 98% accuracy is achieved using only one seed for each object in phantoms while 94.4% accuracy is achieved in MDCT cast images using ten seeds for each of A/V trees.

Quercetin exerts synergetic anti-cancer activity with 10-hydroxy camptothecin.

PubMed

Tang, Qin; Ji, Fangling; Wang, Jingyun; Guo, Lianying; Li, Yachen; Bao, Yongming

2017-11-15

Quercetin (Qu) is known as a dietary antioxidant with numerous bioactivities, but its function in anti-cancer has not been fully investigated. Here, we show that Qu at low doses (≤10μM) significantly enhances the inhibition of 10-hydroxy camptothecin (HCPT) on the proliferation of MCF7, BGC823 and HepG2 cells. A plasmid DNA relaxation assay indicates that the inhibition of HCPT on the catalytic activity of topoisomerase I (Topo I) is increased by Qu at 10μM. Compared to the treatment by Qu or HCPT alone, phosphorylation at Ser 139 of γH2A.X in MCF7 cells starts to increase significantly (P<0.05) at 6h when treated by the combination of 10μM Qu and 0.62μM HCPT. Moreover, the combinational group successively arrests MCF7 cells at G1, S and G2/M phases from 12h to 48h via up-regulation of p21 and induces apoptosis at 24h by triggering intrinsic cell death pathways. In addition, the inhibition effects of the combinational group on the proliferation of MCF7 cells are eliminated by pretreatment with 100μM Z-VAD-FMK (a caspase inhibitor). Finally, by using nude mice xenografting assay of MCF7 cells, we demonstrate that tumor inhibition rates of combinational group are significantly higher than single-drug group. In summary, the synergic anti-cancer mechanism of Qu and HCPT in MCF7 cells is through the combined inhibitory effects of Qu and HCPT on Topo I, which synergistically induce cell cycle arrest and apoptosis by triggering DNA damage. Copyright © 2017. Published by Elsevier B.V.

A multi-locus analysis of phylogenetic relationships within grass subfamily Pooideae (Poaceae) inferred from sequences of nuclear single copy gene regions compared with plastid DNA.

PubMed

Hochbach, Anne; Schneider, Julia; Röser, Martin

2015-06-01

To investigate phylogenetic relationships within the grass subfamily Pooideae we studied about 50 taxa covering all recognized tribes, using one plastid DNA (cpDNA) marker (matK gene-3'trnK exon) and for the first time four nuclear single copy gene loci. DNA sequence information from two parts of the nuclear genes topoisomerase 6 (Topo6) spanning the exons 8-13 and 17-19, the exons 9-13 encoding plastid acetyl-CoA-carboxylase (Acc1) and the partial exon 1 of phytochrome B (PhyB) were generated. Individual and nuclear combined data were evaluated using maximum parsimony, maximum likelihood and Bayesian methods. All of the phylogenetic results show Brachyelytrum and the tribe Nardeae as earliest diverging lineages within the subfamily. The 'core' Pooideae (Hordeeae and the Aveneae/Poeae tribe complex) are also strongly supported, as well as the monophyly of the tribes Brachypodieae, Meliceae and Stipeae (except PhyB). The beak grass tribe Diarrheneae and the tribe Duthieeae are not monophyletic in some of the analyses. However, the combined nuclear DNA (nDNA) tree yields the highest resolution and the best delimitation of the tribes, and provides the following evolutionary hypothesis for the tribes: Brachyelytrum, Nardeae, Duthieeae, Meliceae, Stipeae, Diarrheneae, Brachypodieae and the 'core' Pooideae. Within the individual datasets, the phylogenetic trees obtained from Topo6 exon 8-13 shows the most interesting results. The divergent positions of some clone sequences of Ampelodesmos mauritanicus and Trikeraia pappiformis, for instance, may indicate a hybrid origin of these stipoid taxa. Copyright © 2015 Elsevier Inc. All rights reserved.

Understanding processes that generate flash floods in the arid Judean Desert to the Dead Sea - a measurement network

NASA Astrophysics Data System (ADS)

Hennig, Hanna; Rödiger, Tino; Laronne, Jonathan B.; Geyer, Stefan; Merz, Ralf

2016-04-01

Flash floods in (semi-) arid regions are fascinating in their suddenness and can be harmful for humans, infrastructure, industry and tourism. Generated within minutes, an early warning system is essential. A hydrological model is required to quantify flash floods. Current models to predict flash floods are often based on simplified concepts and/or on concepts which were developed for humid regions. To more closely relate such models to local conditions, processes within catchments where flash floods occur require consideration. In this study we present a monitoring approach to decipher different flash flood generating processes in the ephemeral Wadi Arugot on the western side of the Dead Sea. To understand rainfall input a dense rain gauge network was installed. Locations of rain gauges were chosen based on land use, slope and soil cover. The spatiotemporal variation of rain intensity will also be available from radar backscatter. Level pressure sensors located at the outlet of major tributaries have been deployed to analyze in which part of the catchment water is generated. To identify the importance of soil moisture preconditions, two cosmic ray sensors have been deployed. At the outlet of the Arugot water is sampled and level is monitored. To more accurately determine water discharge, water velocity is measured using portable radar velocimetry. A first analysis of flash flood processes will be presented following the FLEX-Topo concept .(Savenije, 2010), where each landscape type is represented using an individual hydrological model according to the processes within the three hydrological response units: plateau, desert and outlet. References: Savenije, H. H. G.: HESS Opinions "Topography driven conceptual modelling (FLEX-Topo)", Hydrol. Earth Syst. Sci., 14, 2681-2692, doi:10.5194/hess-14-2681-2010, 2010.

Upper mantle and crustal structure of southwestern Scandinavia: Results of the TopoScandiaDeep project

NASA Astrophysics Data System (ADS)

Köhler, A.; Balling, N.; Ebbing, J.; England, R.; Frassetto, A.; Gradmann, S.; Jacobsen, B. H.; Kvarven, T.; Maupin, V.; Medhus, A. Bondo; Mjelde, R.; Ritter, J.; Schweizer, J.; Stratford, W.; Thybo, H.; Wawerzinek, B.; Weidle, C.

2012-04-01

The origin of the Scandinavian mountains, located far away from any presently active plate margin, is still not well understood. In particular, it is not clear if the mountains are sustained isostatically either by crustal thickening or by light upper mantle material. Within the TopoScandiaDeep project (a collaborative research project within the ESF TOPO-EUROPE programme), we therefore analyse recently collected passive seismological and active seismic data in the southern Scandes and surrounding regions. We infer crustal and upper mantle (velocity) structures and relate them to results of gravity and temperature-composition modelling. The Moho under the high topography of southern Norway appears from controlled source seismic refraction and Receiver Functions as relatively shallow (<= 45 km) compared to the deeper conversion (>55 km) imaged beneath the low topography in Sweden and elsewhere in the Baltic Shield area outside Norway. The Receiver Function modeling as well as the active seismic results suggest that the differences in the observed Moho response may represent the transition between tectonically reworked Moho under southern Norway and an intact, cratonic crust-mantle boundary beneath the Baltic Shield. Furthermore, the 410km-discontinuity and the LAB is imaged, the latter one suggesting a lithospheric thickening in NE direction. Upper mantle P-wave and S-wave velocities in southern Sweden and southern Norway east of the Oslo Graben are correspondingly relatively high while lower velocities are observed in the southwestern part of Norway and northern Denmark. The lateral velocity gradient, interpreted as the southwestern boundary of thick Baltic Shield lithosphere, is remarkably sharp. Differences in upper mantle velocities are found at depths of 100-400 km and amount to ± 2-3%. S-to-P wave conversions, interpreted to originate from the lithosphere-asthenosphere boundary, are preliminary estimated to 90-120 km depth. Inversion of Rayleigh and Love surface wave phase velocity dispersion curves from observations of ambient noise and earthquakes yield another independent model of the crust and upper mantle structure below southern Norway. Inverted crustal velocities and Moho depths are consistent with the results of seismic refraction and receiver functions. Additionally, indications for radial crustal anisotropy of up to about 3% are found. The inferred upper mantle S-wave velocities show that the lithosphere under southern Norway has characteristics usually found under continental platforms and changes towards a cratonic-like velocity structure in the East, in agreement with the body wave tomography. All in all, these separate investigations give a very consistent and stable picture of the crust and upper mantle configuration. Integrated geophysical modeling of the results shows that a lateral transition from thinner, warmer lithosphere under southern Norway towards thicker, colder lithosphere under Sweden results in a density distribution that significantly adds to the isostatic support of Norway's high topography.

Determination of trace amounts of tin in geological materials by atomic absorption spectrometry

USGS Publications Warehouse

Welsch, E.P.; Chao, T.T.

1976-01-01

An atomic absorption method is described for the determination of traces of tin in rocks, soils, and stream sediments. A dried mixture of the sample and ammonium iodide is heated to volatilize tin tetraiodide -which is then dissolved in 5 % hydrochloric acid, extracted into TOPO-MIBK, and aspirated into a nitrous oxide-acetylene flame. The limit of determination is 2 p.p.m. tin and the relative standard deviation ranges from 2 to 14 %. Up to 20 % iron and 1000 p.p.m. Cu, Pb, Zn, Mn, Hg, Mo, V, or W in the sample do not interfere. As many as 50 samples can be easily analyzed per man-day. ?? 1976.

Snow survey and vegetation growth in the Swiss Alps

NASA Technical Reports Server (NTRS)

Haefner, H. (Principal Investigator)

1975-01-01

The author has identified the following significant results. Analog processing of S190A and B color and infrared color transparencies showed that it is possible to evaluate the courses of the temporary snow line and the upper limit of vegetation growth over large areas. By transferring the results from S190A onto a topo-map 1:200,000, an accuracy of + or - 50 m could be achieved. With S190B transferred onto a map 1:100,000, an accuracy of + or - 20 m was reached. Digital processing of S192 multispectral data allowed a separation of snow and clouds by combining the information from channels 9, 15, and 18.

The Unseen Déjà-Vu: From Erkki Huhtamo's Topoi to Ken Jacobs' Remakes: Commentary to Edwin Carels "Revisiting Tom Tom: Performative anamnesis and autonomous vision in Ken Jacobs' appropriations of Tom Tom the Piper's Son".

PubMed

Strauven, Wanda

2018-01-01

This commentary on Edwin Carels' essay "Revisiting Tom Tom : Performative anamnesis and autonomous vision in Ken Jacobs' appropriations of Tom Tom the Piper's Son " broadens up the media-archaeological framework in which Carels places his text. Notions such as Huhtamo's topos and Zielinski's "deep time" are brought into the discussion in order to point out the difficulty to see what there is to see and to question the position of the viewer in front of experimental films like Tom Tom the Piper's Son and its remakes.

Control of complex dynamics and chaos in distributed parameter systems

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

Chakravarti, S.; Marek, M.; Ray, W.H.

This paper discusses a methodology for controlling complex dynamics and chaos in distributed parameter systems. The reaction-diffusion system with Brusselator kinetics, where the torus-doubling or quasi-periodic (two characteristic incommensurate frequencies) route to chaos exists in a defined range of parameter values, is used as an example. Poincare maps are used for characterization of quasi-periodic and chaotic attractors. The dominant modes or topos, which are inherent properties of the system, are identified by means of the Singular Value Decomposition. Tested modal feedback control schemas based on identified dominant spatial modes confirm the possibility of stabilization of simple quasi-periodic trajectories in themore » complex quasi-periodic or chaotic spatiotemporal patterns.« less

Creation of next generation U.S. Geological Survey topographic maps

USGS Publications Warehouse

Craun, Kari J.

2010-01-01

The U.S. Geological Survey (USGS) is 2 years into a 3-year cycle to create new digital topographic map products for the conterminous United States from data acquired and maintained as part of The National Map databases. These products are in the traditional, USGS topographic quadrangle, 7.5-minute (latitude and longitude) cell format. The 3-year cycle was conceived to follow the acquisition of National Aerial Imagery Program (NAIP) orthorectified imagery, a key layer in the new product. In fiscal year (FY) 2009 (ending September 30, 2009), the first year of the 3-year cycle, the USGS produced 13,200 products. These initial products of the “Digital MapBeta” series had limited feature content, including only the NAIP image, some roads, geographic names, and grid and collar information. The products were created in layered georegistered Portable Document Format (PDF) files, allowing users with freely available Adobe® Reader® software to view, print, and perform simple Geographic Information System-like functions. In FY 2010 (ending September 30, 2010), the USGS produced 20,380 products. These products of the “US Topo” series added hydrography (surface water features), contours, and some boundaries. In FY 2011 (ending September 30, 2011), the USGS will complete the initial coverage with US Topo products and will add additional feature content to the maps. The design, development, and production associated with the US Topo products provide management and technical challenges for the USGS and its public and private sector partners. One challenge is the acquisition and maintenance of nationally consistent base map data from multiple sources. Another is the use of these data to create a consistent, current series of cartographic products that can be used by the broad spectrum of traditional topographic map users. Although the USGS and its partners have overcome many of these challenges, many, such as establishing and funding a sustainable base data-maintenance program, remain to be resolved for the long term.

qnrA6 genetic environment and quinolone resistance conferred on Proteus mirabilis.

PubMed

Jayol, Aurélie; Janvier, Frédéric; Guillard, Thomas; Chau, Françoise; Mérens, Audrey; Robert, Jérôme; Fantin, Bruno; Berçot, Béatrice; Cambau, Emmanuelle

2016-04-01

To determine the genetic location and environment of the qnrA6 gene in Proteus mirabilis PS16 where it was first described and to characterize the quinolone resistance qnrA6 confers. Transformation experiments and Southern blotting were performed for plasmid and genomic DNA of P. mirabilis PS16 to determine the qnrA6 location. Combinatorial PCRs with primers in qnrA6 and genes usually surrounding qnrA genes were used to determine the genetic environment. The qnrA6 coding region, including or not the promoter region, was cloned into vectors pTOPO and pBR322 and the MICs of six quinolones were measured for transformants of Escherichia coli TOP10 and P. mirabilis ATCC 29906 Rif(R). qnrA6 was shown to be chromosomally encoded in P. mirabilis PS16 and its genetic environment was 81%-87% similar to that of qnrA2 in the Shewanella algae chromosome. The 5138 bp region up- and downstream of qnrA6 contained an IS10 sequence surrounded by two ISCR1. This resulted in qnrA6 being displaced 1.9 kb from its native promoter but supplied a promoter present in ISCR1. qnrA6 cloned into pTOPO and pBR322 conferred a 4-32-fold increase in fluoroquinolone MICs when expressed in E. coli but only 2-3-fold in P. mirabilis. When including the promoter region, a further increase in resistance was observed in both species, reaching MIC values above clinical breakpoints for only P. mirabilis. qnrA6 is the first chromosomally located qnrA gene described in Enterobacteriaceae. The quinolone resistance conferred by qnrA6 depends on the proximity of an efficient promoter and the host strain where it is expressed. © The Author 2016. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Size and ligand effects on the electrochemical and spectroelectrochemical responses of CdSe nanocrystals.

PubMed

Querner, Claudia; Reiss, Peter; Sadki, Said; Zagorska, Malgorzata; Pron, Adam

2005-09-07

The electrochemical properties of CdSe quantum dots with electrochemically inactive surface ligands (TOPO) have been investigated in comparison with the analogous nanocrystals containing electrochemically active oligoaniline ligands. The TOPO-capped nanocrystals have been studied in a wide size range (from 3 to 6.5 nm) with the goal to amplify the influence of the quantum confinement effect on the electrochemical response. The determined HOMO and LUMO levels have been found in good agreement with the ones obtained from photoluminescence studies and those predicted theoretically. Ligand exchange with aniline tetramer significantly influences the voltammetric peaks associated with the HOMO oxidation and the LUMO reduction of the quantum dots, which are shifted to higher and lower potentials, respectively. These shifts are interpreted in terms of the positive ligand charging which precedes the oxidation of the nanocrystals and the insulating nature of the ligand in the case of the nanocrystal reduction. The ligand-nanocrystal interactions have also been studied by UV-Vis-NIR and Raman spectroelectrochemistry in comparison with a specially prepared model compound which, apart from the anchoring function is identical to the grafted oligoaniline ligand. Both spectroelectrochemical techniques clearly indicate the same nature of the oxidation/reduction pathway for both the model compound and the grafted ligand. The influence of the grafting is manifested by a shift in the onset of the ligand oxidation as compared to the case of the "free" model compound. Since both components (ligands and nanocrystals) mutually influence their electrochemical and spectroelectrochemical properties, the newly developed system can be considered as a true molecular hybrid. Such hybrids are of interest because the potential zone of the ligand electroactivity is well separated from that of the nanocrystals and, as a result, the organic part can be electrochemically switched between the semiconducting and the conducting states with no change in the oxidation state of the nanocrystal. The newly developed system offers therefore the possibility of an electrical addressing of individual nanocrystals via the conducting ligands.

New modulated design and synthesis of quercetin-Cu(II)/Zn(II)-Sn2(IV) scaffold as anticancer agents: in vitro DNA binding profile, DNA cleavage pathway and Topo-I activity.

PubMed

Tabassum, Sartaj; Zaki, Mehvash; Afzal, Mohd; Arjmand, Farukh

2013-07-21

New molecular topologies quercetin-Cu(II)-Sn2(IV) and Zn(II)-Sn2(IV)1 and 2 were designed and synthesized to act as potential cancer chemotherapeutic agents. Their interaction with CT DNA by UV-vis and fluorescence spectroscopy was evaluated revealing an electrostatic mode of binding. Quercetin complexes are capable of promoting DNA cleavage involving both single and double strand breaks. Complex 1 cleaved pBR322 DNA via an oxidative mechanism while 2 followed a hydrolytic pathway, accessible to the minor groove of the DNA double helix in accordance with molecular docking studies with the DNA duplex of sequence d(CGCGAATTCGCG)2 dodecamer demonstrating that the complex was stabilized by additional electrostatic and hydrogen bonding interactions with the DNA. ROS such as OH˙, H2O2 and O2˙(-) are the major metabolites responsible for chronic diseases such as cancer, respiratory disorders, HIV, and diabetes etc., therefore eliminating ROS by molecular scaffolds involving SOD enzymatic activity has emerged as a potential way to develop a novel class of drugs. Therefore, in vitro superoxide dismutase activity of redox active complex 1 was evaluated by using a xanthine/xanthine oxidase-NBT assay which showed an IC50 value of 2.26 μM. Moreover, the cytotoxicity of both the complexes were screened on a panel of human carcinoma cell lines (GI50 values <8.7 μM) which revealed that 1 has a better prospect of acting as a cancer chemotherapeutic agent, and to elucidate the mechanism of tumor inhibition, Topo-I enzymatic activity was carried out. Furthermore, molecular modeling studies were carried out to understand molecular features important for drug-enzyme interactions which offer new insights into the experimental model observations.

p27kip1 expression distinguishes papillary hyperplasia in Graves' disease from papillary thyroid carcinoma.

PubMed

Erickson, L A; Yousef, O M; Jin, L; Lohse, C M; Pankratz, V S; Lloyd, R V

2000-09-01

In most cases, the histopathologic and cytologic distinction between Graves' disease and papillary thyroid carcinoma is relatively easy, but on occasion Graves' disease may simulate a thyroid papillary carcinoma. For example, papillary fronds with fibrovascular cores may be present in both Graves' disease and papillary carcinoma. p27kip1 (p27) is a cyclin-dependent kinase inhibitory protein that has been shown to be an independent prognostic factor in a variety of human tumors. Our previous studies of p27 expression in hyperplastic and neoplastic endocrine lesions showed that the level of p27 was quite different in these two conditions. To determine if this distinction could also be made between Graves' disease and papillary carcinoma, we analyzed expression of p27 and other cell cycle proteins in a series of cases of Graves' disease with papillary hyperplasia and a series of papillary thyroid carcinomas. Formalin-fixed paraffin-embedded tissues from 61 randomly selected patients with thyroid disease, including 29 cases of Graves' disease with papillary architectural features and 32 cases of papillary carcinoma, were analyzed for expression of p27, Ki-67, and DNA topoisomerase II alpha (topo II alpha) by immunostaining. The distribution of immunoreactivity was analyzed by quantifying the percentage of positive nuclei that was expressed as the labeling index (LI) plus or minus the standard error of the mean. The papillary hyperplasia of Graves' disease had a p27 LI of 68.2 +/- 3.1 (range, 24 to 88), whereas papillary carcinomas had a LI of 25.6 +/- 2.5 (range, 12 to 70) (P < .0001). No significant differences in Ki-67 or topo II alpha expression were identified between papillary hyperplasia in Graves' disease and papillary carcinoma. These results indicate that p27 protein expression is significantly higher in papillary hyperplasia of Graves' disease compared to papillary carcinoma, which may be diagnostically useful in difficult cases.

Two structurally distinct chalcone dimers from Helichrysum zivojinii and their activities in cancer cell lines.

PubMed

Aljančić, Ivana S; Vučković, Ivan; Jadranin, Milka; Pešić, Milica; Dorđević, Iris; Podolski-Renić, Ana; Stojković, Sonja; Menković, Nebojša; Vajs, Vlatka E; Milosavljević, Slobodan M

2014-02-01

Dimers tomoroside A (1) and tomoroside B (2) of the co-occuring known chalcone monomer (3), along with the seven known flavonoid glucosides (4-10), were isolated from the aerial parts of Helichrysum zivojinii Černjavski & Soška. The structures of the isolated compounds were elucidated by spectroscopic techniques. Compound 1 inhibited topo IIα and hif-1α expression and stimulated doxorubicin anticancer effect, while 2 increased the expression of hif-1α, probably acting as antioxidant and redox status modulator. Notably, 2 synergized with Tipifarnib showing potential to improve the action of this new chemotherapeutic involved in the modulation of mitogene activated protein (MAP) kinase signaling pathway. Copyright © 2013 Elsevier Ltd. All rights reserved.

Multidirectional Scanning Model, MUSCLE, to Vectorize Raster Images with Straight Lines

PubMed Central

Karas, Ismail Rakip; Bayram, Bulent; Batuk, Fatmagul; Akay, Abdullah Emin; Baz, Ibrahim

2008-01-01

This paper presents a new model, MUSCLE (Multidirectional Scanning for Line Extraction), for automatic vectorization of raster images with straight lines. The algorithm of the model implements the line thinning and the simple neighborhood methods to perform vectorization. The model allows users to define specified criteria which are crucial for acquiring the vectorization process. In this model, various raster images can be vectorized such as township plans, maps, architectural drawings, and machine plans. The algorithm of the model was developed by implementing an appropriate computer programming and tested on a basic application. Results, verified by using two well known vectorization programs (WinTopo and Scan2CAD), indicated that the model can successfully vectorize the specified raster data quickly and accurately. PMID:27879843

Acid extraction by supported liquid membranes containing basic carriers

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

Danesi, P.R.; Cianetti, C.; Horwitz, E.P.

1983-01-01

The extraction of HNO/sub 3/ (nitric acid) from aqueous solutions by permeation through a number of supported liquid membranes containing basic carriers dissolved in diethylbenzene has been studied. The results have shown that the best permeations are obtained with long chain aliphatic amines (TLA, Primene JM-T) followed by TOPO (trioctylphosphine oxide) and then by other monofunctional and bifunctional organophosphorous basic carriers. The influence of an aliphatic diluent on the permeability of HNO/sub 3/ through a supported liquid membrane containing TLA as carrier was also investigated. In this case the permeability to HNO/sub 3/ decreases as a result of the lowermore » diffusion coefficient of the acid-carrier complex in the more vicous aliphatic solvent. 4 figures.« less

Multidirectional Scanning Model, MUSCLE, to Vectorize Raster Images with Straight Lines.

PubMed

Karas, Ismail Rakip; Bayram, Bulent; Batuk, Fatmagul; Akay, Abdullah Emin; Baz, Ibrahim

2008-04-15

This paper presents a new model, MUSCLE (Multidirectional Scanning for Line Extraction), for automatic vectorization of raster images with straight lines. The algorithm of the model implements the line thinning and the simple neighborhood methods to perform vectorization. The model allows users to define specified criteria which are crucial for acquiring the vectorization process. In this model, various raster images can be vectorized such as township plans, maps, architectural drawings, and machine plans. The algorithm of the model was developed by implementing an appropriate computer programming and tested on a basic application. Results, verified by using two well known vectorization programs (WinTopo and Scan2CAD), indicated that the model can successfully vectorize the specified raster data quickly and accurately.

A method for topological analysis of high nuclearity coordination clusters and its application to Mn coordination compounds.

PubMed

Kostakis, George E; Blatov, Vladislav A; Proserpio, Davide M

2012-04-21

A novel method for the topological description of high nuclearity coordination clusters (CCs) was improved and applied to all compounds containing only manganese as a metal center, the data on which are collected in the CCDC (CCDC 5.33 Nov. 2011). Using the TOPOS program package that supports this method, we identified 539 CCs with five or more Mn centers adopting 159 topologically different graphs. In the present database all the Mn CCs are collected and illustrated in such a way that can be searched by cluster topological symbol and nuclearity, compound name and Refcode. The main principles for such an analysis are described herein as well as useful applications of this method.

NASA Conjunction Assessment Organizational Approach and the Associated Determination of Screening Volume Sizes

NASA Technical Reports Server (NTRS)

Newman, Lauri K.; Hejduk, Matthew D.

2015-01-01

NASA is committed to safety of flight for all of its operational assets Performed by CARA at NASA GSFC for robotic satellites Focus of this briefing Performed by TOPO at NASA JSC for human spaceflight he Conjunction Assessment Risk Analysis (CARA) was stood up to offer this service to all NASA robotic satellites Currently provides service to 70 operational satellites NASA unmanned operational assets Other USG assets (USGS, USAF, NOAA) International partner assets Conjunction Assessment (CA) is the process of identifying close approaches between two orbiting objects; sometimes called conjunction screening The Joint Space Operations Center (JSpOC) a USAF unit at Vandenberg AFB, maintains the high accuracy catalog of space objects, screens CARA-supported assets against the catalog, performs OD tasking, and generates close approach data.

Is rock slope instability in high-mountain systems driven by topo-climatic, paraglacial or rock mechanical factors? - A question of scale!

NASA Astrophysics Data System (ADS)

Messenzehl, Karoline; Dikau, Richard

2016-04-01

Due to the emergent and (often non-linear) complex nature of mountain systems the key small-scale system properties responsible for rock slope instability contrast to those being dominant at larger spatial scales. This geomorphic system behaviour has major epistemological consequences for the study of rockfalls and associated form-process-relationships. As each scale requires its own scientific explanation, we cannot simply upscale bedrock-scale findings and, in turn, we cannot downscale the valley-scale knowledge to smaller phenomena. Here, we present a multi-scale study from the Turtmann Valley (Swiss Alps), that addresses rock slope properties at three different geomorphic levels: (i) regional valley scale, (ii) the hillslope scale and (iii) the bedrock scale. Using this hierarchical approach, we aim to understand the key properties of high-mountain systems responsible for rockfall initiation with respect to the resulting form-process-relationship at each scale. (i) At the valley scale (110 km2) rock slope instability was evaluated using a GIS-based modelling approach. Topo-climatic parameters, i.e. the permafrost distribution and the time since deglaciation after LGM were found to be the key variables causative for the regional-scale bedrock erosion and the storage of 62.3 - 65.3 x 106 m3 rockfall sediments in the hanging valleys (Messenzehl et al. 2015). (ii) At the hillslope scale (0.03 km2) geotechnical scanline surveys of 16 rock slopes and one-year rock temperature data of 25 ibuttons reveal that the local rockfall activity and the resulting deposition of individual talus slope landforms is mainly controlled by the specific rock mass strength with respect to the slope aspect, than being a paraglacial reaction. Permafrost might be only of secondary importance for the present-day rock mechanical state as geophysical surveys disprove the existence of frozen bedrock below 2600 m asl. (Messenzehl & Draebing 2015). (iii) At the bedrock scale (0.01 mm - 10 m) the spacing, persistence and orientation of joints turned out to be the most causative bedrock properties for the higher-scale rock mass strength. Rock temperature data suggest that high-frequent, surficial thermal processes, daily freeze-thaw cycles and seasonal ice segregation coupled with a winter snow cover are the major rock breakdown mechanisms. By linking the rockwalls' joint geometric pattern to the size and shape of rockfall blocks lying on the corresponding talus slopes, different rockfall magnitudes and frequencies were identified. Here we show, that the decrease in spatial scale is linked with a shift in variable importance, from topo-climatic and paraglacial factors at the largest scale to rock mechanical parameters at the smallest scale. Therefore, to understand the key destabilising factors of rock slopes in mountain systems and the resulting landforms, a holistic research approach is needed which considers the nested, hierarchical structure of geomorphic systems. Messenzehl, K., Meyer, H., Otto, J.-C., Hoffmann, T., Dikau, R., 2015. Regional-scale controls on the spatial activity of rockfalls. (Turtmann valley, Swiss Alps) - A multivariate modelling approach. In: Geomorphology. Messenzehl, K., Draebing, D., 2015. Multidisciplinary investigations on coupled rockwall talus-systems (Turtmann valley, Swiss Alps). Geophysical Research Abstracts, 17 (EGU2015-1935, 2015).

From the Atlas to the Variscan Core of Iberia: Progress on the Knowledge of Mantle Anisotropy from SKS Splitting

NASA Astrophysics Data System (ADS)

Diaz Cusi, J.; Grevemeyer, I.; Thomas, C.; Harnafi, M.

2012-12-01

The data provided by the dense Iberarray broad-band seismic network deployed in the framework of the large-scale TopoIberia project, as well as from permanent broad-band stations operating in Morocco, Portugal and Spain has allowed to get a large scale view of the anisotropic properties of the mantle beneath the western termination of the Mediterranean region and its transition to the Atlantic ocean. In this contribution we will gather the previously presented results with the analysis of the data provided by IberArray stations in the central part of Iberia, broad-band OBSs deployments in the Alboran Sea and the Gulf of Cadiz and new seismic networks deployed in the High Atlas and the Moroccan Meseta. The High Atlas has been investigated using data from a broad-band network installed by the Univ. of Munster with a primary focus on the study of the properties of the deep mantle. Additionally, up to 10 Iberarray stations have been shifted southward to complete the survey along the Atlas and to investigate the Moroccan Meseta. In agreement with the results presented by the Picasso team along a profile crossing the Atlas northward, the anisotropy observed in this area is small (0.6 - 0.9 s) with a fast polarization direction (FPD) oriented roughly E-W. It is important to note that there is a very significant number of high quality events without evidence for anisotropy. This may be the result of the combined effect of two or more anisotropic layers or of the presence of a large vertical component of flow in the upper mantle. Moving northwards, the first TopoIberia-Iberarray deployment in the Betics-Alboran zone has evidenced a spectacular rotation of the FPD along the Gibraltar arc following the curvature of the Rif-Betic chain, from roughly N65E beneath the Betics to close to N65W beneath the Rif chain. To complete this image, we have now processed data from two OBS deployments in the Alboran Sea and Gulf of Cadiz installed by Geomar as part of the TopoMed project. The short period of registration and the intrinsic problems related to noise and instrument stability in the seafloor has not allowed getting a large database of anisotropic measurements. However, the few events providing good quality SKS measurements show interesting results which may provide significant clues to the knowledge of the geodynamic evolution of this area. Beneath Iberia, the second Iberarray deployment encompasses mainly the Variscan units of the Central Iberian Massif. The results show a small amount of anisotropy and suggest complex anisotropy features, confirming what has been observed in the first deployment. A significant change in both FPD and delay times across the two main units of the Variscan domain, the Ossa-Morena and the Central Iberian zones seem to exist. Permanent stations in southern Portugal show a significant number of null measurements, similar to what has previously discussed for the High Atlas stations. Beneath Eastern Iberia, the FPD have a roughly E-W orientation. No significant changes are observed between the anisotropic parameters beneath the Balearic Islands and those in the Eastern Betics.

Using the rate of bacterial clearance determined by real-time polymerase chain reaction as a timely surrogate marker to evaluate the appropriateness of antibiotic usage in critical patients with Acinetobacter baumannii bacteremia.

PubMed

Chuang, Yu-Chung; Chang, Shan-Chwen; Wang, Wei-Kung

2012-08-01

Bacteremia caused by Acinetobacter baumannii is becoming more frequent among critically ill patients, and has been associated with high mortality and prolonged hospital stay. Multidrug resistance and delay in blood culture have been shown to be significant barriers to appropriate antibiotic treatment. Quantitative polymerase chain reaction assays were recently used to monitor bacterial loads; we hypothesized that the rate of bacterial clearance determined by quantitative polymerase chain reaction can be used as a timely surrogate marker to evaluate the appropriateness of antibiotic usage. Prospective observational study. University hospital and research laboratory. Patients with culture-proven A. baumannii bacteremia in the intensive care units were prospectively enrolled from April 2008 to February 2009. Plasmid Oxa-51/pCRII-TOPO, which contained a 431-bp fragment of the A. baumannii-specific Oxa-51 gene in a pCRII-TOPO vector, was used as the standard. Sequential bacterial DNA loads in the blood were measured by a quantitative polymerase chain reaction assay. We enrolled 51 patients with A. baumannii bacteremia, and examined 318 sequential whole blood samples. The initial mean bacterial load was 2.15 log copies/mL, and the rate of bacterial clearance was 0.088 log copies/mL/day. Multivariate linear regression using the generalized estimation equation approach revealed that the use of immunosuppressants was an independent predictor for slower bacterial clearance (coefficient, 1.116; p<.001), and appropriate antibiotic usage was an independent predictor for more rapid bacterial clearance (coefficient, -0.995; p<.001). Patients with a slower rate of bacterial clearance experienced higher in-hospital mortality (odds ratio, 2.323; p=.04) Immunosuppression and appropriate antibiotic usage were independent factors affecting the rate of clearance of A. baumannii bacteremia in critical patients. These findings highlight the importance of appropriate antibiotic usage and development of effective antibiotics against A. baumannii in an era of emerging antibiotic resistance. The rate of bacterial clearance could serve as a timely surrogate marker for evaluating the appropriateness of antibiotics.

On the origin of the anisotropy observed beneath the westernmost Mediterranean region

NASA Astrophysics Data System (ADS)

Diaz, Jordi

2017-04-01

The Iberian Peninsula and Northern Morocco region provides an excellent opportunity to investigate the origin of subcrustal anisotropy. Following the TopoIberia-Iberarray experiment, anisotropic properties have been explored in a dense network of 60x60 km spaced broad-band stations, resulting in more than 300 sites investigated over an area extending from the Bay of Biscay to the Sahara platform and covering more than 6000.000 km2. The rather uniform N100°E FPD retrieved beneath the Variscan Central Iberian Massif is consistent with global mantle flow models taking into account contributions of surface plate motion, density variations and net lithosphere rotation. The origin of this anisotropy is hence globally related to the lattice preferred orientation of mantle minerals generated by mantle flow at asthenospheric depths, although significant regional variations are observed. The anisotropic parameters retrieved from single events providing high quality data show significant differences for stations located in the Variscan units of NW Iberia, suggesting that the region includes multiple anisotropic layers or complex anisotropy systems have to be considered there. The rotation of the FDE along the Gibraltar arc following the curvature of the Rif-Betic chain has been interpreted as an evidence of mantle flow deflected around the high velocity slab beneath the Gibraltar Arc. Beneath the SW corner of Iberia and the High Atlas zone, small delay times and inconsistent FPD have been detected, suggesting the presence of vertical mantle flow affecting the anisotropic structure of the asthenosphere. Future developments will include a better integration with the anisotropic estimations provided by Pn tomography and, in particular, with those arising from surface wave tomographic inversions using TopoIberia-Ibearray results. Additionally, the contribution of crustal anisotropy could be estimated from the analysis of receiver functions. The detailed knowledge on the anisotropic structure of this area could be used to test the recently developed multiparametric modeling methods inverting jointly observables as surface waves dispersion, receiver functions, surface heat flow, geoid height, elevation and anisotropy. (partially founded by: MISTERIOS project, CGL2013-48601-C2-1-R)

Regional-scale controls on the spatial activity of rockfalls (Turtmann Valley, Swiss Alps) - A multivariate modeling approach

NASA Astrophysics Data System (ADS)

Messenzehl, Karoline; Meyer, Hanna; Otto, Jan-Christoph; Hoffmann, Thomas; Dikau, Richard

2017-06-01

In mountain geosystems, rockfalls are among the most effective sediment transfer processes, reflected in the regional-scale distribution of talus slopes. However, the understanding of the key controlling factors seems to decrease with increasing spatial scale, due to emergent and complex system behavior and not least to recent methodological shortcomings in rockfall modeling research. In this study, we aim (i) to develop a new approach to identify major regional-scale rockfall controls and (ii) to quantify the relative importance of these controls. Using a talus slope inventory in the Turtmann Valley (Swiss Alps), we applied for the first time the decision-tree based random forest algorithm (RF) in combination with a principal component logistic regression (PCLR) to evaluate the spatial distribution of rockfall activity. This study presents new insights into the discussion on whether periglacial rockfall events are controlled more by topo-climatic, cryospheric, paraglacial or/and rock mechanical properties. Both models explain the spatial rockfall pattern very well, given the high areas under the Receiver Operating Characteristic (ROC) curves of > 0.83. Highest accuracy was obtained by the RF, correctly predicting 88% of the rockfall source areas. The RF appears to have a great potential in geomorphic research involving multicollinear data. The regional permafrost distribution, coupled to the bedrock curvature and valley topography, was detected to be the primary rockfall control. Rockfall source areas cluster within a low-radiation elevation belt (2900-3300 m a.s.l,) consistent with a permafrost probability of > 90%. The second most important factor is the time since deglaciation, reflected by the high abundance of rockfalls along recently deglaciated (< 100 years), north-facing slopes. However, our findings also indicate a strong rock mechanical control on the paraglacial rockfall activity, declining either exponentially or linearly since deglaciation. The study demonstrates the benefit of combined statistical approaches for predicting rockfall activity in deglaciated, permafrost-affected mountain valleys and highlights the complex interplay between rock mechanical, paraglacial and topo-climatic controls at the regional scale.

Development of an extractive spectrophotometric method for estimation of uranium in ore leach solutions using 2-ethylhexyl phosphonic acid-mono-2-ethylhexyl ester (PC88A) and tri-n-octyl phosphine oxide (TOPO) mixture as extractant and 2-(5-bromo-2-pyridylozo)-5-diethyl aminophenol (Br-PADAP) as chromophore

NASA Astrophysics Data System (ADS)

Biswas, Sujoy; Pathak, P. N.; Roy, S. B.

2012-06-01

An extractive spectrophotometric analytical method has been developed for the determination of uranium in ore leach solution. This technique is based on the selective extraction of uranium from multielement system using a synergistic mixture of 2-ethylhexyl phosphonic acid-mono-2-ethylhexyl ester (PC88A) and tri-n-octyl phosphine oxide (TOPO) in cyclohexane and color development from the organic phase aliquot using 2-(5-Bromo-2-pyridylazo)-5-diethyl aminophenol (Br-PADAP) as chromogenic reagent. The absorption maximum (λmax) for UO22+-Br-PADAP complex in organic phase samples, in 64% (v/v) ethanol containing buffer solution (pH 7.8) and 1,2-cyclohexylenedinitrilotetraacetic acid (CyDTA) complexing agent, has been found to be at 576 nm (molar extinction coefficient, ɛ: 36,750 ± 240 L mol-1 cm-1). Effects of various parameters like stability of complex, ethanol volume, ore matrix, interfering ions etc. on the determination of uranium have also been evaluated. Absorbance measurements as a function of time showed that colored complex is stable up to >24 h. Presence of increased amount of ethanol in colored solution suppresses the absorption of a standard UO22+-Br-PADAP solution. Analyses of synthetic standard as well as ore leach a solution show that for 10 determination relative standard deviation (RSD) is <2%. The accuracy of the developed method has been checked by determining uranium using standard addition method and was found to be accurate with a 98-105% recovery rate. The developed method has been applied for the analysis of a number of uranium samples generated from uranium ore leach solutions and results were compared with standard methods like inductively coupled plasma emission spectrometry (ICPAES). The determined values of uranium concentrations by these methods are within ±2%. This method can be used to determine 2.5-250 μg mL-1 uranium in ore leach solutions with high accuracy and precision.

TTLEM - an implicit-explicit (IMEX) scheme for modelling landscape evolution in MATLAB

NASA Astrophysics Data System (ADS)

Campforts, Benjamin; Schwanghart, Wolfgang

2016-04-01

Landscape evolution models (LEM) are essential to unravel interdependent earth surface processes. They are proven very useful to bridge several temporal and spatial timescales and have been successfully used to integrate existing empirical datasets. There is a growing consensus that landscapes evolve at least as much in the horizontal as in the vertical direction urging for an efficient implementation of dynamic drainage networks. Here we present a spatially explicit LEM, which is based on the object-oriented function library TopoToolbox 2 (Schwanghart and Scherler, 2014). Similar to other LEMs, rivers are considered to be the main drivers for simulated landscape evolution as they transmit pulses of tectonic perturbations and set the base level of surrounding hillslopes. Highly performant graph algorithms facilitate efficient updates of the flow directions to account for planform changes in the river network and the calculation of flow-related terrain attributes. We implement the model using an implicit-explicit (IMEX) scheme, i.e. different integrators are used for different terms in the diffusion-incision equation. While linear diffusion is solved using an implicit scheme, we calculate incision explicitly. Contrary to previously published LEMS, however, river incision is solved using a total volume method which is total variation diminishing in order to prevent numerical diffusion when solving the stream power law (Campforts and Govers, 2015). We show that the use of this updated numerical scheme alters both landscape topography and catchment wide erosion rates at a geological time scale. Finally, the availability of a graphical user interface facilitates user interaction, making the tool very useful both for research and didactical purposes. References Campforts, B., Govers, G., 2015. Keeping the edge: A numerical method that avoids knickpoint smearing when solving the stream power law. J. Geophys. Res. Earth Surf. 120, 1189-1205. doi:10.1002/2014JF003376 Schwanghart, W., Scherler, D., 2014. TopoToolbox 2 - MATLAB-based software for topographic analysis and modeling in Earth surface sciences. Earth Surf. Dyn. 2, 1-7. doi:10.5194/esurf-2-1-2014

Remote sensing-based predictors improve distribution models of rare, early successional and broadleaf tree species in Utah

USGS Publications Warehouse

Zimmermann, N.E.; Edwards, T.C.; Moisen, Gretchen G.; Frescino, T.S.; Blackard, J.A.

2007-01-01

1. Compared to bioclimatic variables, remote sensing predictors are rarely used for predictive species modelling. When used, the predictors represent typically habitat classifications or filters rather than gradual spectral, surface or biophysical properties. Consequently, the full potential of remotely sensed predictors for modelling the spatial distribution of species remains unexplored. Here we analysed the partial contributions of remotely sensed and climatic predictor sets to explain and predict the distribution of 19 tree species in Utah. We also tested how these partial contributions were related to characteristics such as successional types or species traits. 2. We developed two spatial predictor sets of remotely sensed and topo-climatic variables to explain the distribution of tree species. We used variation partitioning techniques applied to generalized linear models to explore the combined and partial predictive powers of the two predictor sets. Non-parametric tests were used to explore the relationships between the partial model contributions of both predictor sets and species characteristics. 3. More than 60% of the variation explained by the models represented contributions by one of the two partial predictor sets alone, with topo-climatic variables outperforming the remotely sensed predictors. However, the partial models derived from only remotely sensed predictors still provided high model accuracies, indicating a significant correlation between climate and remote sensing variables. The overall accuracy of the models was high, but small sample sizes had a strong effect on cross-validated accuracies for rare species. 4. Models of early successional and broadleaf species benefited significantly more from adding remotely sensed predictors than did late seral and needleleaf species. The core-satellite species types differed significantly with respect to overall model accuracies. Models of satellite and urban species, both with low prevalence, benefited more from use of remotely sensed predictors than did the more frequent core species. 5. Synthesis and applications. If carefully prepared, remotely sensed variables are useful additional predictors for the spatial distribution of trees. Major improvements resulted for deciduous, early successional, satellite and rare species. The ability to improve model accuracy for species having markedly different life history strategies is a crucial step for assessing effects of global change. ?? 2007 The Authors.

Remote sensing-based predictors improve distribution models of rare, early successional and broadleaf tree species in Utah

PubMed Central

ZIMMERMANN, N E; EDWARDS, T C; MOISEN, G G; FRESCINO, T S; BLACKARD, J A

2007-01-01

Compared to bioclimatic variables, remote sensing predictors are rarely used for predictive species modelling. When used, the predictors represent typically habitat classifications or filters rather than gradual spectral, surface or biophysical properties. Consequently, the full potential of remotely sensed predictors for modelling the spatial distribution of species remains unexplored. Here we analysed the partial contributions of remotely sensed and climatic predictor sets to explain and predict the distribution of 19 tree species in Utah. We also tested how these partial contributions were related to characteristics such as successional types or species traits. We developed two spatial predictor sets of remotely sensed and topo-climatic variables to explain the distribution of tree species. We used variation partitioning techniques applied to generalized linear models to explore the combined and partial predictive powers of the two predictor sets. Non-parametric tests were used to explore the relationships between the partial model contributions of both predictor sets and species characteristics. More than 60% of the variation explained by the models represented contributions by one of the two partial predictor sets alone, with topo-climatic variables outperforming the remotely sensed predictors. However, the partial models derived from only remotely sensed predictors still provided high model accuracies, indicating a significant correlation between climate and remote sensing variables. The overall accuracy of the models was high, but small sample sizes had a strong effect on cross-validated accuracies for rare species. Models of early successional and broadleaf species benefited significantly more from adding remotely sensed predictors than did late seral and needleleaf species. The core-satellite species types differed significantly with respect to overall model accuracies. Models of satellite and urban species, both with low prevalence, benefited more from use of remotely sensed predictors than did the more frequent core species. Synthesis and applications. If carefully prepared, remotely sensed variables are useful additional predictors for the spatial distribution of trees. Major improvements resulted for deciduous, early successional, satellite and rare species. The ability to improve model accuracy for species having markedly different life history strategies is a crucial step for assessing effects of global change. PMID:18642470

What are the most crucial soil factors for predicting the distribution of alpine plant species?

NASA Astrophysics Data System (ADS)

Buri, A.; Pinto-Figueroa, E.; Yashiro, E.; Guisan, A.

2017-12-01

Nowadays the use of species distribution models (SDM) is common to predict in space and time the distribution of organisms living in the critical zone. The realized environmental niche concept behind the development of SDM imply that many environmental factors must be accounted for simultaneously to predict species distributions. Climatic and topographic factors are often primary included, whereas soil factors are frequently neglected, mainly due to the paucity of soil information available spatially and temporally. Furthermore, among existing studies, most included soil pH only, or few other soil parameters. In this study we aimed at identifying what are the most crucial soil factors for explaining alpine plant distributions and, among those identified, which ones further improve the predictive power of plant SDMs. To test the relative importance of the soil factors, we performed plant SDMs using as predictors 52 measured soil properties of various types such as organic/inorganic compounds, chemical/physical properties, water related variables, mineral composition or grain size distribution. We added them separately to a standard set of topo-climatic predictors (temperature, slope, solar radiation and topographic position). We used ensemble forecasting techniques combining together several predictive algorithms to model the distribution of 116 plant species over 250 sites in the Swiss Alps. We recorded the variable importance for each model and compared the quality of the models including different soil proprieties (one at a time) as predictors to models having only topo-climatic variables as predictors. Results show that 46% of the soil proprieties tested become the second most important variable, after air temperature, to explain spatial distribution of alpine plants species. Moreover, we also assessed that addition of certain soil factors, such as bulk soil water density, could improve over 80% the quality of some plant species models. We confirm that soil pH remains one of the most important soil factor for predicting plant species distributions, closely followed by water, organic and inorganic carbon related properties. Finally, we were able to extract three main categories of important soil properties for plant species distributions: grain size distribution, acidity and water in the soil.

Using environmental isotopes in the study of the recharge-discharge mechanisms of the Yarmouk catchment area in Jordan

NASA Astrophysics Data System (ADS)

Salameh, Elias

The recharge sources, the flow mechanisms and discharge areas of the different groundwater bodies underlying the Yarmouk River catchment area in Jordan, have, until now, not been adequately explained, although a wide range of hydrological, hydrogeological, and hydrochemical studies have been done. Along the Jordanian part of the catchment area of the Yarmouk River, groundwater issues from different aquifers with a variety of chemistries and types within the same aquifer and in between the different aquifers. Conventional recharge/discharge mechanisms, water balances and chemical analyses did not adequately explain the chemical variations and the different water types found in the area. Applying environmental isotopic tools combined with their altitude effects due to topographic variations (250-1,300 m a.s.l. within a distance of 20 km), and taking into consideration re-evaporation effects on the isotopic depletion and enrichment of rainwater, has greatly helped in understanding the recharge discharge mechanisms of the different aquifers. Precipitation along the highlands of an average of 600 mm/year is found to be depleted in its isotopic content of δO18 = -7.0 to -7.26 and δD = -32.2 to -33.28, whereas that of the Jordan Valley of 350 mm/year is highly enriched in isotopes with δO18 = -4.06 and δD = -14.5. The groundwater recharged along the highlands is depleted in isotopes (δO18 = -6, δD = -30), groundwater at the intermediate elevations is enriched (δO18 = -5, δD = -23) and that of the Jordan Valley aquifers containing meteoric water is highly enriched (δO18 -3.8, δD = -18). The deep aquifers in the Jordan Valley foothills are depleted in isotopes (δO18 -18 = -6, δD = -30) and resemble those of the highland aquifers. Only through using isotopes as a tool, were the sources of the different groundwater bodies and recharge and discharge mechanisms unambiguously explained. It was found that recharge takes place all over the study area and produces groundwater, which, from the highlands towards the Jordan Valley, shows increasing enrichment in isotopes. The highlands aquifer, with its groundwater depleted in isotopes, becomes confined towards the Jordan Valley; and, due to its confining pressure, leaks water upwards into the overlying aquifers causing their water to become less enriched in isotopes. Water depleted in its isotopic composition also seeps upward to the ground surface at the mountain foothills through faults and fissures. Les zones de recharge, les mécanismes d'écoulement et les zones de décharges des différentes masses d'eau souterraine sous le bassin versant de la rivière Yarmouk en Jordanie, étaient expliquées de manière ambiguë par les seuls outils isotopiques. Le long de la parti Jordanienne du bassin versant de la rivière Yarmouk l'eau souterraine provient de différents aquifères et se distinguent par leur type et leur composition chimique, selon que l'eau provient du même ou des différents aquifères. Les mécanismes conventionnels de recharge et de décharge, bilan hydrologique ne donnaient pas d'explications satisfaisantes concernant les variations chimiques et les différents types d'eau. En appliquant les isotopes environnementaux combinés aux effets de l'altitude sur les variations des teneurs isotopiques (l'altitude varie de 250 à 1,300 m sur une distance de 20 km.) et en prenant en considération les effets de ré-évaporation sur l'appauvrissement et l'enrichissement isotopique des eaux pluviales ont fortement contribués à une meilleure compréhension des mécanismes de recharge des différents aquifères. Les précipitations annuelles sont comprises entre 600 mm dans les zones en altitude et 350 mm dans la vallée de la Jordanie. Les écoulements de l'eau souterraine sont dirigés des zones en altitude vers la vallée de la Jordanie. Les eaux souterraines des zones en altitude sont isotopiquement appauvries (δO18 = -6, δD = -30), les eaux souterraines des zones de moyenne altitude sont enrichies (δO18 = -5, δD = -23) et les eaux de la vallée très enrichies (δO18 -3.8, δD = -18). Les aquifers profonds dans la vallée de la Jordanie sont appauvris (δO18 -18 = -6, δD = -30) et se confondent avec les eaux des zones situées en altitude. En appliquant uniquement les isotopes environnementaux comme des outils de compréhension des phénomènes hydrogéologiques, la source des différentes masses d'eau souterraines, les mécanismes de la recharge et de la décharge pourraient être expliqués de manière ambiguë. Las fuentes de recarga, los mecanismos de flujo y las áreas de descarga de los diferentes cuerpos de agua subterránea que subyacen el área de la cuenca del Río Yarmouk en Jordania, se han explicado de manera no ambigua únicamente mediante la aplicación de los isótopos como herramienta. A lo largo de la parte Jordana del área de la cuenca del Río Yarmouk el agua subterránea emerge de diferentes acuíferos con una variedad de tipos y composiciones, ya sea que provengan del mismo acuífero o de diferentes acuíferos. Los mecanismos convencionales de recarga/descarga, balances hídricos y variaciones químicas no han podido explicar las variaciones químicas y los diferentes tipos de aguas. La aplicación de herramientas de isótopos ambientales combinadas con los efectos de altitud derivados de variaciones topográficas (250 hasta 1,300 m s.n.m. en una distancia de 20 km) y tomando en consideración los efectos de re-evaporación en el empobrecimiento de isótopos y enriquecimiento del agua de lluvia han ayudado fuertemente en el entendimiento de los mecanismos de recarga/descarga de los diferentes acuíferos. La precipitación en el área varía de 600 mm/año, a lo largo de las tierras altas, a 350 mm/año en el área del Valle Jordán. El flujo de agua subterránea ocurre de las tierras altas hacia el Valle Jordán. El agua subterránea de las tierras altas está empobrecida en isótopos (δO18 = -6, δD = -30), el agua subterránea de elevaciones intermedias está enriquecida (δO18 = -5, δD = -23), y el agua de los acuíferos del Valle Jordan contiene agua meteórica que se encuentra altamente enriquecida (δO18 = -3.8, δD = -18). Los acuíferos profundos que se localizan al pie de las tierras altas del Valle Jordán están empobrecidos en isótopos (δO18 = -6, δD = -30) y son similares a los acuíferos de las tierras altas. Solo al aplicar los isótopos ambientales como herramienta pudo explicarse de manera inequívoca las fuentes de los diferentes cuerpos de agua subterránea y los mecanismos de recarga y descarga.

Improved photoluminescence quantum yield and stability of CdSe-TOP, CdSe-ODA-TOPO, CdSe/CdS and CdSe/EP nanocomposites

NASA Astrophysics Data System (ADS)

Wei, Shutian; Zhu, Zhilin; Wang, Zhixiao; Wei, Gugangfen; Wang, Pingjian; Li, Hai; Hua, Zhen; Lin, Zhonghai

2016-07-01

Size-controllable monodisperse CdSe nanocrystals with different organic capping were prepared based on the hot-injection method. The effective separation of nucleation and growth was achieved by rapidly mixing two highly reactive precursors. As a contrast, we prepared CdSe/CdS nanocrystals (NCs) successfully based on the selective ion layer adsorption and reaction (SILAR) technique. This inorganic capping obtained higher photoluminescence quantum yield (PLQY) of 59.3% compared with organic capping of 40.8%. Furthermore, the CdSe-epoxy resin (EP) composites were prepared by adopting a flexible ex situ method, and showed excellent stability in the ambient environment for one year. So the composites with both high PLQY of nanocrystals and excellent stability are very promising to device application.

Separation of Ce and La from Synthetic Chloride Leach Solution of Monazite Sand by Precipitation and Solvent Extraction

NASA Astrophysics Data System (ADS)

Banda, Raju; Jeon, Ho Seok; Lee, Man Seung

2014-12-01

Precipitation and solvent extraction experiments have been performed to recover light rare earths from simulated monazite sand chloride leach solutions. Precipitation conditions were obtained to recover Ce by adding NaClO as an oxidant. Among some cationic extractants (PC 88A, D2EHPA, Cyanex 272, LIX 63), PC 88A showed the best performance to separate La from the resulting chloride solution. Furthermore, the mixture of PC 88A with other solvating (TBP, TOPO) and amine extractants (Alamine 336, Aliquat 336) was tested to increase the separation factor of La from Pr and Nd. The use of mixed extractants greatly enhanced the separation of La from the two other metals. McCabe-Thiele diagrams for the extraction of Pr and Nd with the PC 88A/Alamine 336 mixture were constructed.

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

Chen Min; Mikecz, Anna von

Despite of their exponentially growing use, little is known about cell biological effects of nanoparticles. Here, we report uptake of silica (SiO{sub 2}) nanoparticles to the cell nucleus where they induce aberrant clusters of topoisomerase I (topo I) in the nucleoplasm that additionally contain signature proteins of nuclear domains, and protein aggregation such as ubiquitin, proteasomes, cellular glutamine repeat (polyQ) proteins, and huntingtin. Formation of intranuclear protein aggregates (1) inhibits replication, transcription, and cell proliferation; (2) does not significantly alter proteasomal activity or cell viability; and (3) is reversible by Congo red and trehalose. Since SiO{sub 2} nanoparticles trigger amore » subnuclear pathology resembling the one occurring in expanded polyglutamine neurodegenerative disorders, we suggest that integrity of the functional architecture of the cell nucleus should be used as a read out for cytotoxicity and considered in the development of safe nanotechnology.« less

Human autoantibody to topoisomerase II.

PubMed

Hoffmann, A; Heck, M M; Bordwell, B J; Rothfield, N F; Earnshaw, W C

1989-02-01

The rheumatic diseases are characterized by the production of autoantibodies that are usually directed against components of the cell nucleus. In this communication, we describe autoantibodies that recognize DNA topoisomerase II (anti-topoII) present in the serum of a patient with systemic lupus erythematosus. Several lines of evidence indicate that this antibody recognizes topoisomerase II. First, it binds to the native enzyme in soluble extracts prepared from isolated chromosomes and effectively depletes such extracts of active enzyme. Second, the serum binds to topoisomerase II in immunoblots of mitotic chromosomes and chromosome scaffolds. Finally, the antiserum binds strongly to a fusion protein encoded by a cloned cDNA and expressed in Escherichia coli that (based on immunological evidence) represents the carboxy-terminal portion of chicken topoisomerase II. Autoantibodies such as the one described here may provide useful reagents for the study of human topoisomerase II.

Soft X-ray multilayers produced by sputtering and molecular beam epitaxy (MBE) - Substrate and interfacial roughness

NASA Astrophysics Data System (ADS)

Kearney, Patrick A.; Slaughter, J. M.; Powers, K. D.; Falco, Charles M.

1988-01-01

Roughness measurements were made on uncoated silicon wafers and float glass using a WYKO TOPO-3D phase shifting interferometry, and the results are reported. The wafers are found to be slightly smoother than the flat glass. The effects of different cleaning methods and of the deposition of silicon 'buffer layers' on substrate roughness are examined. An acid cleaning method is described which gives more consistent results than detergent cleaning. Healing of the roughness due to sputtered silicon buffer layers was not observed on the length scale probed by the WYKO. Sputtered multilayers are characterized using both the WYKO interferometer and low-angle X-ray diffraction in order to yield information about the roughness of the top surface and of the multilayer interfaces. Preliminary results on film growth using molecular beam epitaxy are also presented.

ResistoMap-online visualization of human gut microbiota antibiotic resistome.

PubMed

Yarygin, Konstantin S; Kovarsky, Boris A; Bibikova, Tatyana S; Melnikov, Damir S; Tyakht, Alexander V; Alexeev, Dmitry G

2017-07-15

We created ResistoMap—a Web-based interactive visualization of the presence of genetic determinants conferring resistance to antibiotics, biocides and heavy metals in human gut microbiota. ResistoMap displays the data on more than 1500 published gut metagenomes of world populations including both healthy subjects and patients. Multiparameter display filters allow visual assessment of the associations between the meta-data and proportions of resistome. The geographic map navigation layer allows to state hypotheses regarding the global trends of antibiotic resistance and correlates the gut resistome variations with the national clinical guidelines on antibiotics application. ResistoMap was implemented using AngularJS, CoffeeScript, D3.js and TopoJSON. The tool is publicly available at http://resistomap.rcpcm.org. yarygin@phystech.edu. Supplementary data are available at Bioinformatics online. © The Author(s) 2017. Published by Oxford University Press.

3-[(E)-(acridin-9‧-ylmethylidene)amino]-1-substituted thioureas and their biological activity

NASA Astrophysics Data System (ADS)

Bečka, Michal; Vilková, Mária; Salem, Othman; Kašpárková, Jana; Brabec, Viktor; Kožurková, Mária

2017-06-01

This paper describes the synthesis of a novel series of acridine thiosemicarbazones through a two-step reaction between various isothiocyanates and hydrazine followed by treatment with acridin-9-carbaldehyde. The properties of this series of seven new derivatives are studied using NMR and biochemical techniques, and the DNA-binding properties of the compounds are determined using spectrophotometric studies (UV-vis absorption, fluorescence, and circular/linear dichroism) and viscometry. The binding constants K are estimated as being in the range of 2.2 to 7.8 × 104 M- 1 and the percentage of hypochromism was found to be 22.11-49.75% (from UV-vis spectral titration). Electrophoretic experiments prove that the novel compounds demonstrate moderate inhibitory effects against Topo I activity at a concentration of 60 × 10- 6 M.

Physical preparation and optical properties of CuSbS2 nanocrystals by mechanical alloying process

NASA Astrophysics Data System (ADS)

Zhang, Huihui; Xu, Qishu; Tan, Guolong

2016-09-01

CuSbS2 nanocrystals have been synthesized through mechanical alloying Cu, Sb and S elemental powders for 40 hs. The optical spectrum of as-milled CuSbS2 nano-powders demonstrates a direct gap of 1.35 eV and an indirect gap of 0.36 eV, which are similar to that of silicon and reveals the evidence for the indirect semiconductor characterization of CuSbS2. Afterwards, CuSbS2 nanocrystals were capped with trioctylphosphine oxide/trioctylphosphine/pyridine (TOPO/TOP). There appear four sharp absorption peaks within the region of 315 to 355 nm for the dispersion solution containing the capped nanocrystals. The multiple peaks are proposed to be originating from the energy level splitting of 1S electronic state into four discrete sub-levels, where electrons were excited into the conduction band and thus four exciton absorption peaks were produced.

Historical Topographic Map Collection bookmark

USGS Publications Warehouse

Fishburn, Kristin A.; Allord, Gregory J.

2017-06-29

The U.S. Geological Survey (USGS) National Geospatial Program is scanning published USGS 1:250,000-scale and larger topographic maps printed between 1884, the inception of the topographic mapping program, and 2006. The goal of this project, which began publishing the historical scanned maps in 2011, is to provide a digital repository of USGS topographic maps, available to the public at no cost. For more than 125 years, USGS topographic maps have accurately portrayed the complex geography of the Nation. The USGS is the Nation’s largest producer of printed topographic maps, and prior to 2006, USGS topographic maps were created using traditional cartographic methods and printed using a lithographic printing process. As the USGS continues the release of a new generation of topographic maps (US Topo) in electronic form, the topographic map remains an indispensable tool for government, science, industry, land management planning, and leisure.

A General Cp*CoIII -Catalyzed Intramolecular C-H Activation Approach for the Efficient Total Syntheses of Aromathecin, Protoberberine, and Tylophora Alkaloids.

PubMed

Lerchen, Andreas; Knecht, Tobias; Koy, Maximilian; Daniliuc, Constantin G; Glorius, Frank

2017-09-07

Herein, we report a Cp*Co III -catalyzed C-H activation approach as the key step to create highly valuable isoquinolones and pyridones as building blocks that can readily be applied in the total syntheses of a variety of aromathecin, protoberberine, and tylophora alkaloids. This particular C-H activation/annulation reaction was achieved with several terminal as well as internal alkyne coupling partners delivering a broad scope with excellent functional group tolerance. The synthetic applicability of this protocol reported herein was demonstrated in the total syntheses of two Topo-I-Inhibitors and two 8-oxyprotoberberine cores that can be further elaborated into the tetrahydroprotoberberine and the protoberberine alkaloid core. Moreover these building blocks were also transformed to six different tylophora alkaloids in expedient fashion. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Validity of the toposequence approach along a rainfall gradient at a desert fringe

NASA Astrophysics Data System (ADS)

Yair, Aaron

2017-04-01

According to the "classic" toposequence approach soil's properties are closely related to the position of a soil along a slope. The positional differences in soil properties are usually attributed to spatial differences in runoff; erosion and deposition processes. These processes reflect long term effects of the spatial redistribution of water, solids and soluble materials, which are of great importance in respect of nutrient cycling on the landscape scale, and the structuring of natural ecosystems. The "classic" toposequence approach has been seriously questioned by Sommer and Schlichting (1997). They were followed by many scientists of various disciplines (hydrology, ecology, paleopedology, paleoclimate etc). The present study covers three topo-sequences, located in southern Israel, along an average annual rainfall gradient of 90-300 mm. The classic toposequence approach does not apply to none of them, and the controlling factors vary from one site to another.

Antiferromagnetic Skyrmion: Stability, Creation and Manipulation

NASA Astrophysics Data System (ADS)

Zhang, Xichao; Zhou, Yan; Ezawa, Motohiko

2016-04-01

Magnetic skyrmions are particle-like topological excitations in ferromagnets, which have the topo-logical number Q = ± 1, and hence show the skyrmion Hall effect (SkHE) due to the Magnus force effect originating from the topology. Here, we propose the counterpart of the magnetic skyrmion in the antiferromagnetic (AFM) system, that is, the AFM skyrmion, which is topologically protected but without showing the SkHE. Two approaches for creating the AFM skyrmion have been described based on micromagnetic lattice simulations: (i) by injecting a vertical spin-polarized current to a nanodisk with the AFM ground state; (ii) by converting an AFM domain-wall pair in a nanowire junction. It is demonstrated that the AFM skyrmion, driven by the spin-polarized current, can move straightly over long distance, benefiting from the absence of the SkHE. Our results will open a new strategy on designing the novel spintronic devices based on AFM materials.

Scanning and georeferencing historical USGS quadrangles

USGS Publications Warehouse

Fishburn, Kristin A.; Davis, Larry R.; Allord, Gregory J.

2017-06-23

The U.S. Geological Survey (USGS) National Geospatial Program is scanning published USGS 1:250,000-scale and larger topographic maps printed between 1884, the inception of the topographic mapping program, and 2006. The goal of this project, which began publishing the Historical Topographic Map Collection in 2011, is to provide access to a digital repository of USGS topographic maps that is available to the public at no cost. For more than 125 years, USGS topographic maps have accurately portrayed the complex geography of the Nation. The USGS is the Nation’s largest producer of traditional topographic maps, and, prior to 2006, USGS topographic maps were created using traditional cartographic methods and printed using a lithographic process. The next generation of topographic maps, US Topo, is being released by the USGS in digital form, and newer technologies make it possible to also deliver historical maps in the same electronic format that is more publicly accessible.

Fluorescence in the system Eu(III) - oxytetracycline - co-ligand -sodium dodecylbenzene sulphonate micelles and its analytical application

NASA Astrophysics Data System (ADS)

Shtykov, Sergei N.; Smirnova, Tatyana D.; Kalashnikova, Natalja V.; Bylinkin, Yurii G.; Zhemerichkin, Dmitry A.

2006-07-01

Fluorescence enhancement of the Eu 3+ - oxytetracycline (OTC) chelate by addition of phenanthroline (Phen) and trioctyiphosphine oxide (TOPO) as well as micelles of anionic, catiomic and nonionic surfactants has been studied. As was found, in the presence of Phen as co-ligand and micelles of dodecylbenzene sulfonate as anionic surfactant the analytical signal increased by a factor of 8.5 and reached maximum value at pH 8.0 +/- 0.5. The dynamic concentration range of OTC determination was found to be 8.0 x 10 -8 - 4.0 × 10 -5 M (R2 = 0.991) and the detection limit 5.3 × 10 -8 M (3 σ criterion). The procedure based on europium-sensitized fluorescence has been developed for the determination of OTC in chicken meat with the recovery of 98.0-103.3%.

Simulation of SiO2 etching in an inductively coupled CF4 plasma

NASA Astrophysics Data System (ADS)

Xu, Qing; Li, Yu-Xing; Li, Xiao-Ning; Wang, Jia-Bin; Yang, Fan; Yang, Yi; Ren, Tian-Ling

2017-02-01

Plasma etching technology is an indispensable processing method in the manufacturing process of semiconductor devices. Because of the high fluorine/carbon ratio of CF4, the CF4 gas is often used for etching SiO2. A commercial software ESI-CFD is used to simulate the process of plasma etching with an inductively coupled plasma model. For the simulation part, CFD-ACE is used to simulate the chamber, and CFD-TOPO is used to simulate the surface of the sample. The effects of chamber pressure, bias voltage and ICP power on the reactant particles were investigated, and the etching profiles of SiO2 were obtained. Simulation can be used to predict the effects of reaction conditions on the density, energy and angular distributions of reactant particles, which can play a good role in guiding the etching process.

Centromeric Heterochromatin: The Primordial Segregation Machine

PubMed Central

Bloom, Kerry S.

2014-01-01

Centromeres are specialized domains of heterochromatin that provide the foundation for the kinetochore. Centromeric heterochromatin is characterized by specific histone modifications, a centromere-specific histone H3 variant (CENP-A), and the enrichment of cohesin, condensin, and topo-isomerase II. Centromere DNA varies orders of magnitude in size from 125 bp (budding yeast) to several megabases (human). In metaphase, sister kinetochores on the surface of replicated chromosomes face away from each other, where they establish microtubule attachment and bi-orientation. Despite the disparity in centromere size, the distance between separated sister kinetochores is remarkably conserved (approximately 1 μm) throughout phylogeny. The centromere functions as a molecular spring that resists microtubule-based extensional forces in mitosis. This review explores the physical properties of DNA in order to understand how the molecular spring is built and how it contributes to the fidelity of chromosome segregation. PMID:25251850

INL DPAH STAAR 2015 Annual Report

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

Peterman, Dean Richard

2015-09-15

Research conducted at the INL has demonstrated the synergistic extraction of americium using solvents comprised of bis(o,o-(trifluoromethyl)phenyl) dithiophosphinic acid (DPAH “1”) and trioctylphosphine oxide (TOPO), butyl bis(2,4,4-trimethylpentyl) phosphinate (BuCy272), or dibutyl butylphosphonate (DBBP). One potential drawback of this separations scheme is that soft metals such as silver, cadmium, or palladium and fission products such as zirconium are well extracted by these solvents. Several potential scrubbing reagents were examined. Of the scrubbing reagents studied, cysteine and methione exhibited some ability to scrub soft metals from the loaded solvent. More conventional scrub reagents such as ammonium fluoride or oxalic acid were notmore » effective. Reagents like Bimet and CDTA were not soluble at the acidities used in these studies. Unfortunately, these results indicate that the identification of effective scrubbing reagents for use in a flowsheet based upon the INL DPAH is going to be very difficult.« less

Mixing Categories and Modal Logics in the Quantum Setting

NASA Astrophysics Data System (ADS)

Cinà, Giovanni

The study of the foundations of Quantum Mechanics, especially after the advent of Quantum Computation and Information, has benefited from the application of category-theoretic tools and modal logics to the analysis of Quantum processes: we witness a wealth of theoretical frameworks casted in either of the two languages. This paper explores the interplay of the two formalisms in the peculiar context of Quantum Theory. After a review of some influential abstract frameworks, we show how different modal logic frames can be extracted from the category of finite dimensional Hilbert spaces, connecting the Categorical Quantum Mechanics approach to some modal logics that have been proposed for Quantum Computing. We then apply a general version of the same technique to two other categorical frameworks, the `topos approach' of Doering and Isham and the sheaf-theoretic work on contextuality by Abramsky and Brandenburger, suggesting how some key features can be expressed with modal languages.

Analyzing Patents Generated by SBIR Firms

DTIC Science & Technology

2014-04-30

ac/ido/oeip/ taf /us_gov.htm   ^Åèìáëáíáçå=oÉëÉ~êÅÜ=mêçÖê~ãW= `êÉ~íáåÖ=póåÉêÖó=Ñçê=fåÑçêãÉÇ=`Ü~åÖÉ= = - 392 - A 2006 RAND report on the DoD SBIR...ac/ido/oeip/ taf /reports.htm#misc_info ^Åèìáëáíáçå=oÉëÉ~êÅÜ=mêçÖê~ãW= `êÉ~íáåÖ=póåÉêÖó=Ñçê=fåÑçêãÉÇ=`Ü~åÖÉ= = - 400 - patent protection and are...view of the many variations which may occur in corporate identifications. http://www.uspto.gov/web/offices/ac/ido/oeip/ taf /topo_04.htm#Desc 16

Crustal and lithospheric imaging of the Atlas Mountains of Morocco inferred from magnetotelluric data

NASA Astrophysics Data System (ADS)

Kiyan, D.; Jones, A. G.; Fullea, J.; Hogg, C.; Ledo, J.; Sinischalchi, A.; Campanya, J.; Picasso Phase II Team

2010-12-01

The Atlas System of Morocco is an intra-continental mountain belt extending for more than 2,000 km along the NW African plate with a predominant NE-SW trend. The System comprises three main branches: the High Atlas, the Middle Atlas, and the Anti Atlas. We present the results of a very recent multi-institutional magnetotelluric (MT) experiment across the Atlas Mountains region that started in September, 2009 and ended in February, 2010, comprising acquisition of broadband and long-period MT data. The experiment consisted of two profiles: (1) a N-S oriented profile crossing the Middle Atlas through the Central High Atlas to the east and (2) a NE-SW profile crossing the western High Atlas towards the Anti Atlas to the west. The MT measurements are part of the PICASSO (Program to Investigate Convective Alboran Sea System Overturn) and the concomitant TopoMed (Plate re-organization in the western Mediterranean: Lithospheric causes and topographic consequences - an ESF EUROCORES TOPO-EUROPE project) projects, to develop a better understanding of the internal structure and evolution of the crust and lithosphere of the Atlas Mountains. The MT data have been processed with robust remote reference methods and submitted to comprehensive strike and dimensionality analysis. Two clearly depth-differentiated strike directions are apparent for crustal (5-35 km) and lithospheric (50-150 km) depth ranges. These two orientations are roughly consistent with the NW-SE Africa-Eurasia convergence acting since the late Cretaceous, and the NNE-SSW Middle Atlas, where Miocene to recent Alkaline volcanism is present. Two-dimensional (2-D) smooth electrical resistivity models were computed independently for both 50 degrees and 20 degrees E of N strike directions. At the crustal scale, our preliminary results reveal a middle to lower-crustal conductive layer stretching from the Middle Atlas southward towards the High Moulouya basin. The most resistive (and therefore potentially thickest) lithosphere is found beneath the Central High Atlas. The inversion results are to be tested against other geophysical observables (i.e. topography, geoid and gravity anomalies, surface heat flow and seismic velocities) using the software package LitMod. This software combines petrological and geophysical modelling of the lithosphere and sub-lithospheric upper mantle within an internally consistent thermodynamic-geophysical framework, where all relevant properties are functions of temperature, pressure and composition.

The contribution of the seismic component of Topo-Iberia to the imaging of the deep structure of the Iberian Peninsula and North Morocco

NASA Astrophysics Data System (ADS)

Diaz, Jordi; Gallart, Josep; de Lis Mancilla, Flor; Villaseñor, Antonio; Bonatto, Luciana; Schimmel, Martin; Harnafi, Mimoun; El Moudnib, Lahcen

2015-04-01

Topo-Iberia has been a large-scale Spanish project running from 2007 to 2013 that integrated more than 150 researchers on Earth Sciences. One of its key assets was the management of an observatory platform, named IberArray, aimed to provide new geophysical datasets (seismic, GPS, MT) to constrain the structure of Iberia with unprecedented resolution. The IberArray seismic pool was composed by 70+ BB stations, covering the study area in 3 deployments with a site-density of 60km x 60km. The data base holds ~300 sites, including the permanent networks in the area. Hence it forms a unique seismic database in Europe that allows for multiple analyses to constrain the complex geodinamics of the Western Mediterranean. A summary of new results coming from different techniques is presented here. The SKS splitting analysis has provided a spectacular image of the rotation of the fast velocity direction along the Gibraltar Arc. In central and northern Iberia, the fast polarization directions are close to EW, consistently with global mantle flow models considering contributions of surface plate motion, density variations and net lithosphere rotation. Those results suggest an asthenospheric origin of the observed anisotropy related to present-day mantle flow. Receiver functions have revealed the crustal thickness variations beneath the Atlas, Rif and southern Iberia, evidencing a relevant crustal root beneath the Rif, in agreement with recent, high-density active seismic experiments. The Variscan Iberian massif shows a flat Moho discontinuity, while the areas reworked in the Alpine orogeny show a slightly thicker crust. Beneath N Iberia, the imbrication of the Iberian and Eurasian crusts results in complex receiver functions. Depths exceeding 45 km are observed along the Pyrenean range, while the crust thins to values of 26-28 km close to the Atlantic coasts. The geometry of the 410-km and 660-km discontinuities has been investigated using novel cross-correlation/stacking techniques. Ambient noise tomography allows to identify the main sedimentary basins and to discriminate between the Variscan and the Alpine reworked areas. Local body-wave tomography in North Morocco has improved the location of the small magnitude events on the area and the details of the crustal structure. Teleseismic tomography has confirmed, using an independent data set, the presence of a high-velocity slab beneath the Gibraltar Arc.

The IberArray BB seismic network of Topo-Iberia: new constraints revealing the deep structure of the Iberian Peninsula and North Morocco

NASA Astrophysics Data System (ADS)

Gallart, J.; Diaz Cusi, J.; Villasenor, A.; Mancilla, F. D. L.; Bonatto, L.; Schimmel, M.; El moudnib, L.

2014-12-01

Topo-Iberia has been a large-scale Spanish project running from 2007 to 2013 that integrated more than 150 researchers on Earth Sciences. One of its key assets was the management of an observatory platform, named IberArray, aimed to provide new geophysical datasets (seismic, GPS, MT) to constrain the structure of Iberia with unprecedented resolution. The IberArray seismic pool was composed by 70+ BB stations, covering the study area in 3 deployments with a site-density of 60km x 60km. The data base holds ~300 sites, including the permanent networks in the area. Hence it forms a unique seismic database in Europe that allow for multiple analyses to constrain the complex geodinamics of the Western Mediterranean. A summary of new results coming from different techniques is presented here. The SKS splitting analysis has provided a spectacular image of the rotation of the fast velocity direction along the Gibraltar Arc. In central and northern Iberia, the fast polarization directions are close to EW, consistently with global mantle flow models considering contributions of surface plate motion, density variations and net lithosphere rotation. Those results suggest an asthenospheric origin of the observed anisotropy related to present-day mantle flow. Receiver functions have revealed the crustal thickness variations beneath the Rif and southern Iberia, including a crustal root beneath the Rif. The Variscan Iberian massif shows a flat Moho discontinuity, while the areas reworked in the Alpine orogeny show a slightly thicker crust. Beneath N Iberia, the imbrication of the Iberian and Eurasian crusts results in complex receiver functions. Depths exceeding 45 km are observed along the Pyrenean range, while the crust thins to values of 26-28 km close to the Atlantic coasts. The geometry of the 410-km and 660-km discontinuities has been investigated using novel cross-correlation/stacking techniques. Ambient noise tomography allows to identify the main sedimentary basins and to discriminate between the Variscan and the Alpine reworked areas. Local body-wave tomography in North Morocco has improved the location of the small magnitude events on the area and the details of the crustal structure. Teleseismic tomography has confirmed, using an independent data set, the presence of a high-velocity slab beneath the Gibraltar Arc.

Is there a self-organization principle of river deltas?

NASA Astrophysics Data System (ADS)

Tejedor, Alejandro; Longjas, Anthony; Foufoula-Georgiou, Efi

2017-04-01

River deltas are known to possess a complex topological and flux-partitioning structure which has recently been quantified using spectral graph theory [Tejedor et al., 2015a,b]. By analysis of real and simulated deltas it has also been shown that there is promise in formalizing relationships between this topo-dynamic delta structure and the underlying delta forming processes [e.g., Tejedor et al., 2016]. The question we pose here is whether there exists a first order organizational principle behind the self-organization of river deltas and whether this principle can be unraveled from the co-evolving topo-dynamic structure encoded in the delta planform. To answer this question, we introduce a new metric, the nonlocal Entropy Rate (nER) that captures the information content of a delta network in terms of the degree of uncertainty in delivering fluxes from any point of the network to the shoreline. We hypothesize that if the "guiding principle" of undisturbed deltas is to efficiently and robustly build land by increasing the diversity of their flux pathways over the delta plane, then they would exhibit maximum nonlocal Entropy Rate at states at which geometry and flux dynamics are at equilibrium. At the same time, their nER would be non-optimal at transient states, such as before and after major avulsions during which topology and dynamics adjust to each other to reach a new equilibrium state. We will present our results for field and simulated deltas, which confirm this hypothesis and open up new ways of thinking about self-organization, complexity and robustness in river deltas. One particular connection of interest might have important implications since entropy rate and resilience are related by the fluctuation theorem [Demetrius and Manke, 2005], and therefore our results suggest that deltas might in fact self-organize to maximize their resilience to structural and dynamic perturbations. References: Tejedor, A., A. Longjas, I. Zaliapin, and E. Foufoula­-Georgiou (2015), Water Resour. Res., 51, 3998-4018. Tejedor, A., A. Longjas, I. Zaliapin, and E. Foufoula-­Georgiou (2015), Water Resour. Res., 51, 4019-4045. Tejedor, A., A. Longjas, R. Caldwell, D. A. Edmonds, I. Zaliapin, and E. Foufoula­-Georgiou (2016), Geophys. Res. Lett., 43, 3280-3287. Demetrius, L., and T. Manke (2005), Phys. A Stat. Mech. Appl., 346, 682-696.

Development of an extractive spectrophotometric method for estimation of uranium in ore leach solutions using 2-ethylhexyl phosphonic acid-mono-2-ethylhexyl ester (PC88A) and tri-n-octyl phosphine oxide (TOPO) mixture as extractant and 2-(5-bromo-2-pyridylozo)-5-diethyl aminophenol (Br-PADAP) as chromophore.

PubMed

Biswas, Sujoy; Pathak, P N; Roy, S B

2012-06-01

An extractive spectrophotometric analytical method has been developed for the determination of uranium in ore leach solution. This technique is based on the selective extraction of uranium from multielement system using a synergistic mixture of 2-ethylhexyl phosphonic acid-mono-2-ethylhexyl ester (PC88A) and tri-n-octyl phosphine oxide (TOPO) in cyclohexane and color development from the organic phase aliquot using 2-(5-Bromo-2-pyridylazo)-5-diethyl aminophenol (Br-PADAP) as chromogenic reagent. The absorption maximum (λ(max)) for UO(2)(2+)-Br-PADAP complex in organic phase samples, in 64% (v/v) ethanol containing buffer solution (pH 7.8) and 1,2-cyclohexylenedinitrilotetraacetic acid (CyDTA) complexing agent, has been found to be at 576 nm (molar extinction coefficient, ɛ: 36,750 ± 240 L mol(-1)cm(-1)). Effects of various parameters like stability of complex, ethanol volume, ore matrix, interfering ions etc. on the determination of uranium have also been evaluated. Absorbance measurements as a function of time showed that colored complex is stable up to > 24h. Presence of increased amount of ethanol in colored solution suppresses the absorption of a standard UO(2)(2+)-Br-PADAP solution. Analyses of synthetic standard as well as ore leach a solution show that for 10 determination relative standard deviation (RSD) is < 2%. The accuracy of the developed method has been checked by determining uranium using standard addition method and was found to be accurate with a 98-105% recovery rate. The developed method has been applied for the analysis of a number of uranium samples generated from uranium ore leach solutions and results were compared with standard methods like inductively coupled plasma emission spectrometry (ICPAES). The determined values of uranium concentrations by these methods are within ± 2%. This method can be used to determine 2.5-250 μg mL(-1) uranium in ore leach solutions with high accuracy and precision. Copyright © 2012 Elsevier B.V. All rights reserved.

Minimum deltaV Burn Planning for the International Space Station Using a Hybrid Optimization Technique, Level 1

NASA Technical Reports Server (NTRS)

Brown, Aaron J.

2015-01-01

The International Space Station's (ISS) trajectory is coordinated and executed by the Trajectory Operations and Planning (TOPO) group at NASA's Johnson Space Center. TOPO group personnel routinely generate look-ahead trajectories for the ISS that incorporate translation burns needed to maintain its orbit over the next three to twelve months. The burns are modeled as in-plane, horizontal burns, and must meet operational trajectory constraints imposed by both NASA and the Russian Space Agency. In generating these trajectories, TOPO personnel must determine the number of burns to model, each burn's Time of Ignition (TIG), and magnitude (i.e. deltaV) that meet these constraints. The current process for targeting these burns is manually intensive, and does not take advantage of more modern techniques that can reduce the workload needed to find feasible burn solutions, i.e. solutions that simply meet the constraints, or provide optimal burn solutions that minimize the total DeltaV while simultaneously meeting the constraints. A two-level, hybrid optimization technique is proposed to find both feasible and globally optimal burn solutions for ISS trajectory planning. For optimal solutions, the technique breaks the optimization problem into two distinct sub-problems, one for choosing the optimal number of burns and each burn's optimal TIG, and the other for computing the minimum total deltaV burn solution that satisfies the trajectory constraints. Each of the two aforementioned levels uses a different optimization algorithm to solve one of the sub-problems, giving rise to a hybrid technique. Level 2, or the outer level, uses a genetic algorithm to select the number of burns and each burn's TIG. Level 1, or the inner level, uses the burn TIGs from Level 2 in a sequential quadratic programming (SQP) algorithm to compute a minimum total deltaV burn solution subject to the trajectory constraints. The total deltaV from Level 1 is then used as a fitness function by the genetic algorithm in Level 2 to select the number of burns and their TIGs for the next generation. In this manner, the two levels solve their respective sub-problems separately but collaboratively until a burn solution is found that globally minimizes the deltaV across the entire trajectory. Feasible solutions can also be found by simply using the SQP algorithm in Level 1 with a zero cost function. This paper discusses the formulation of the Level 1 sub-problem and the development of a prototype software tool to solve it. The Level 2 sub-problem will be discussed in a future work. Following the Level 1 formulation and solution, several look-ahead trajectory examples for the ISS are explored. In each case, the burn targeting results using the current process are compared against a feasible solution found using Level 1 in the proposed technique. Level 1 is then used to find a minimum deltaV solution given the fixed number of burns and burn TIGs. The optimal solution is compared with the previously found feasible solution to determine the deltaV (and therefore propellant) savings. The proposed technique seeks to both improve the current process for targeting ISS burns, and to add the capability to optimize ISS burns in a novel fashion. The optimal solutions found using this technique can potentially save hundreds of kilograms of propellant over the course of the ISS mission compared to feasible solutions alone. While the software tool being developed to implement this technique is specific to ISS, the concept is extensible to other long-duration, central-body orbiting missions that must perform orbit maintenance burns to meet operational trajectory constraints.

Environmental isotopes (18O, 2H, and 87Sr/86Sr) as a tool in groundwater investigations in the Keta Basin, Ghana

NASA Astrophysics Data System (ADS)

Jørgensen, Niels; Banoeng-Yakubo, Bruce

2001-03-01

Analyses of environmental isotopes (18O, 2H, and 87Sr/86Sr) are applied to groundwater studies with emphasis on saline groundwater in aquifers in the Keta Basin, Ghana. The 87Sr/86Sr ratios of groundwater and surface water of the Keta Basin primarily reflect the geology and the mineralogical composition of the formations in the catchments and recharge areas. The isotopic compositions of 18O and 2H of deep groundwater have small variations and plot close to the global meteoric water line. Shallow groundwater and surface water have considerably larger variations in isotopic compositions, which reflect evaporation and preservation of seasonal fluctuations. A significant excess of chloride in shallow groundwater in comparison to the calculated evaporation loss is the result of a combination of evaporation and marine sources. Groundwaters from deep wells and dug wells in near-coastal aquifers are characterized by relatively high chloride contents, and the significance of marine influence is evidenced by well-defined mixing lines for strontium isotopes, and hydrogen and oxygen stable isotopes, with isotopic compositions of seawater as one end member. The results derived from environmental isotopes in this study demonstrate that a multi-isotope approach is a useful tool to identify the origin and sources of saline groundwater. Résumé. L'analyse des isotopes du milieu (18O, 2H, et 87Sr/86Sr) a été mise en œuvre pour des études hydrogéologiques portant sur des eaux souterraines salées des aquifères du bassin de Keta (Ghana). Les rapports isotopiques 87Sr/86Sr de l'eau souterraine et de l'eau de surface du bassin de Keta reflètent principalement la géologie et la composition minéralogique des formations des bassins d'alimentation et des zones de recharge. Les compositions isotopiques en 18O et en 2H des eaux souterraines profondes présentent de faibles variations et se placent près de la droite des eaux météoriques mondiales. Les eaux des nappes peu profondes et les eaux de surface subissent des variations beaucoup plus fortes de leurs compositions isotopiques, dues à l'évaporation et aux fluctuations saisonnières. Un excès significatif en chlorures dans les eaux souterraines peu profondes, compte tenu de l'évaporation calculée, résulte à la fois de l'évaporation et d'apports marins. Les eaux souterraines de forages profonds et de puits dans les aquifères proches de la côte sont caractérisées par des concentrations relativement élevées en chlorure; une influence marine significative est mise en évidence par des droites de mélange bien définies pour les isotopes du strontium et les isotopes stables de l'oxygène et de l'hydrogène, avec les compositions de l'eau de mer pour l'un des termes du mélange. Les résultats fournis par les isotopes du milieu dans cette étude montrent qu'une approche multi-isotopique est un outil pertinent pour identifier l'origine et les sources d'eaux souterraines salées. Resumen. Se ha aplicado el análisis de los isótopos ambientales (18O, 2H y 87Sr/86Sr) al estudio de las aguas subterráneas en la Cuenca de Keta (Ghana), haciendo énfasis en acuíferos salinizados. Las proporciones de 87Sr/86Sr en las aguas subterráneas y superficiales de la Cuenca de Keta reflejan, fundamentalmente, la geología y la composición mineralógica de las formaciones dominantes en las zonas de captación y de recarga. La composición isotópica de las aguas subterráneas profundas presenta variaciones pequeñas en 18O y 2H y se acerca a la línea meteórica mundial. Las aguas subterráneas someras y las superficiales presentan variaciones considerablemente mayores en la composición isotópica, hecho que refleja la evaporación y las fluctuaciones estacionales. Como resultado de la combinación entre evaporación e influencia marina, se observa un exceso significativo de cloruros en las aguas subterráneas someras en comparación con las pérdidas por evaporación. Las aguas subterráneas de pozos profundos y de pozos excavados en acuíferos cercanos a la costa se caracterizan por sus contenidos relativamente altos de cloruros. La influencia marina se evidencia por las líneas de mezcla bien definidas por los isótopos del estroncio y los isótopos estables del hidrógeno y oxígeno, mientras que la composición isotópica del agua marina se comporta como punto extremo de dichas líneas. Los resultados obtenidos en este trabajo a partir de los isótopos ambientales demuestran que el enfoque multi-isotópico es una herramienta útil para identificar el origen y las fuentes de aguas subterráneas salinas.

Theoretical crystal chemistry of M{sub x}(TO{sub 4}){sub y} sulfates and selenates: Topological analysis and classification of suprapolyhedral invariants

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

Ilyushin, G. D.; Blatov, V. A.

2006-05-15

A geometric topological analysis of orthotetrahedral phases M{sub x}(TO{sub 4}){sub y} (T = S or Se) is performed for 46 sulfates and 17 selenates with the TOPOS 3.2 software package. The values of coordination sequences {l_brace}N{sub k}{r_brace} of T atoms are used as classification parameters of topologically different MTO nets. The crystal structures are analyzed within 12 coordination spheres of T sites and assigned to 26 topological types. It is established that only 7 types are common for the structures of sulfates and selenates, 16 types include only sulfates, and 3 types include only selenates. The average values of themore » bond lengths are determined: = 1.48(2) A and = 1.63(2) A. The hierarchical ordering of the crystal structure is performed using the concept of a polyhedral microensemble of the structure.« less

Transition probability spaces in loop quantum gravity

NASA Astrophysics Data System (ADS)

Guo, Xiao-Kan

2018-03-01

We study the (generalized) transition probability spaces, in the sense of Mielnik and Cantoni, for spacetime quantum states in loop quantum gravity. First, we show that loop quantum gravity admits the structures of transition probability spaces. This is exemplified by first checking such structures in covariant quantum mechanics and then identifying the transition probability spaces in spin foam models via a simplified version of general boundary formulation. The transition probability space thus defined gives a simple way to reconstruct the discrete analog of the Hilbert space of the canonical theory and the relevant quantum logical structures. Second, we show that the transition probability space and in particular the spin foam model are 2-categories. Then we discuss how to realize in spin foam models two proposals by Crane about the mathematical structures of quantum gravity, namely, the quantum topos and causal sites. We conclude that transition probability spaces provide us with an alternative framework to understand various foundational questions of loop quantum gravity.

Transition from CZTSe to CZTS via multicomponent CZTSSe: Potential low cost photovoltaic absorbers

NASA Astrophysics Data System (ADS)

Chawla, Parul; Jain, Shefali; Vashishtha, Parth; Ahamed, Mansoor; Sharma, Shailesh Narain

2018-01-01

A quintessential perspective for elaborating the pivotal role of quinary chalogenides such as CZTSSe plunges the thrust for exploration of non-vacuum approach for development of multicomponent chalcogenides utilizing organic surfactants and solvents for the nanocrystals ideal for photovoltaic applications. The piece of study envisages employment of TOPO-TOP as capping agents-cum-solvents for the very first time and have not been reported for CZTSSe-based materials till date. The work has been forwarded with the variation of anionic ratios in pristine counterparts of CZTSSe; i.e. CZTSe and CZTS in order to envision the potential of quinary chalcogenides wherein properties of two different materials coalesce to impart improved characteristics in CZTSSe. Varying Se:S ratios gradually during nanocrystals' synthesis by high-temperature colloidal route ensued precise control over the phase formation and morphology. With the employment of these capping agents, as-synthesized nanocrystals' are inherently Se-rich and high crystallinity restrains the need for selenization and high temperature annnealing respectively.

Anti-ferromagnetic/ferromagnetic transition in half-metallic Co9Se8 nanoparticles

NASA Astrophysics Data System (ADS)

Singh, Jai; Kumar, Pushpendra

2015-09-01

The size, shape and defects of the half-metallic Co9Se8 nanoparticles (NPs) play a crucial role in the magnetic transition at the local magnetic regime at low temperatures. A general, non-injection, one-pot reaction route without toxic reagents, such as TOPO/TOPSe, surfactant and/or chelating agent, were used to synthesize gram scale of well-dispersed, high-quality Co9Se8 NPs. The calculated mean crystallite size of the NPs was ∼10 nm, which is consistent with the transmission electron microscope data. This study reveals an unusual anti-ferromagnetic/ferromagnetic transition with some super-paramagnetic character in the low temperature region of Co9Se8 NPs. These investigations are expected not only to help the observed phenomenon, but also help in identifying new half-metallic magnetic NPs for spintronics devices. The outcome provides better understanding of the occurrence of superparamagnetism at low temperatures in the nano-regime, for half-metallic systems.

Atomic absorption spectrometric determination of copper, zinc, and lead in geological materials

USGS Publications Warehouse

Sanzolone, R.F.; Chao, T.T.

1976-01-01

An atomic absorption spectrometric method is described for the determination of copper, zinc, and lead in geological materials. The sample is digested with HF-HCl-H2O2; the final solution for analysis is in 10 % (v/v) HCl. Copper and zinc are determined directly by aspirating the solution into an air-acetylene flame. A separate aliquot of the solution is used for determination of lead; lead is extracted into TOPO-MIBK from the acidic solution in the presence of iodide and ascorbic acid. For a 0.50-g sample, the limits of determination are 10-2000 p.p.m. for Cu and Zn, and 5-5000 p.p.m. for Pb. As much as 40 % Fe or Ca. and 10 % Al, Mg, or Mn in the sample do not interfere. The proposed method can be applied to the determination of copper, zinc, and lead in a wide range of geological materials including iron- and manganese-rich, calcareous and carbonate samples. ?? 1976.

Simulation and experimental verification of silicon dioxide deposition by PECVD

NASA Astrophysics Data System (ADS)

Xu, Qing; Li, Yu-Xing; Li, Xiao-Ning; Wang, Jia-Bin; Yang, Fan; Yang, Yi; Ren, Tian-Ling

2017-02-01

Deposition of silicon dioxide in high-density plasma is an important process in integrated circuit manufacturing. A software named CFD-ACE was used to simulate the mechanism of plasma in the chamber of plasma enhanced chemical vapor deposition (PECVD) system, and the evolution of the feature profile was simulated based on CFD-TOPO. Simulation and experiment of silicon dioxide that deposited in SiH4/N2O mixture by PECVD system was researched. The particle density, energy and angular distribution in the chamber were simulated and discussed. We also studied how the depth/width ratio affected the step coverage of the trench and analyzed the deposition rate of silicon dioxide on the feature scale. X-ray photoelectron spectroscopy (XPS) was used to analyze the elemental composition of thin films. Images of the feature profiles were taken by scanning electron microscope (SEM). The simulation results were in good agreement with experimental, which could guide the semiconductor device manufacture.

The Whole World In Your Hands: Using an Interactive Virtual Reality Sandbox for Geospatial Education and Outreach

NASA Astrophysics Data System (ADS)

Clucas, T.; Wirth, G. S.; Broderson, D.

2014-12-01

Traditional geospatial education tools such as maps and computer screens don't convey the rich topography present on Earth. Translating lines on a contour lines on a topo map to relief in a landscape can be a challenging concept to convey.A partnership between Alaska EPSCoR and the Geographic Information Network of Alaska has successfully constructed an Interactive Virtual Reality Sandbox, an education tool that in real-time projects and updates topographic contours on the surface of a sandbox. The sandbox has been successfully deployed at public science events as well as professional geospatial and geodesy conferences. Landscape change, precipitation, and evaporation can all be modeled, much to the delight of our enthusiasts, who range in age from 3 to 90. Visually, as well as haptically, demonstrating the effects of events (such as dragging a hand through the sand) on a landscape, as well as the intuitive realization of meaning of topographic contour lines, has proven to be engaging.

Broadband X-ray edge-enhancement imaging of a boron fibre on lithium fluoride thin film detector

NASA Astrophysics Data System (ADS)

Nichelatti, E.; Bonfigli, F.; Vincenti, M. A.; Cecilia, A.; Vagovič, P.; Baumbach, T.; Montereali, R. M.

2016-10-01

The white beam (∼6-80 keV) available at the TopoTomo X-ray beamline of the ANKA synchrotron facility (KIT, Karlsruhe, Germany) was used to perform edge-enhancement imaging tests on lithium fluoride radiation detectors. The diffracted X-ray image of a microscopic boron fibre, consisting of tungsten wire wrapped by boron cladding, was projected onto lithium fluoride thin films placed at several distances, from contact to 1 m . X-ray photons cause the local formation of primary and aggregate colour centres in lithium fluoride; these latter, once illuminated under blue light, luminesce forming visible-light patterns-acquired by a confocal laser scanning microscope-that reproduce the intensity of the X-ray diffracted images. The tests demonstrated the excellent performances of lithium fluoride films as radiation detectors at the investigated photon energies. The experimental results are here discussed and compared with those calculated with a model that takes into account all the processes that concern image formation, storing and readout.

Mapping snow avalanche risk using GIS technique and 3D modeling in Ceahlau Mountain

NASA Astrophysics Data System (ADS)

Covasnianu, A.; Grigoras, I. R.; State, L. E.; Balin, D.; Hogas, S.; Balin, I.

2009-04-01

This study consisted in a precise mapping project (GPS field campaign and on-screen digitization of the topographic maps at 1:5.000 scale) of the Ceahlau mountain area in Romanian Carpathians in order to address the snow avalanche risk management, surveying and monitoring. Thus we considered the slope, aspect, altitude, landforms and roughness derived from a high resolute numerical terrain model (31 km2 at 1: 5.000 scale resulted in a spatial resolution of 3 m by the help of Topo to Raster tool). These parameters were classified according to a model applied into Tatra Mountains and used over Ceahlau Massive. The results were adapted and interpreted considering to the European Avalanche Hazard Scale. This work was made in the context of the elaboration of Risk Map and is directly concerning both the security of tourism activities but also the management of the Natural Park Ceahlau. The extension of this method to similar mountain areas is ongoing.

Overview of post Cohen-Boyer methods for single segment cloning and for multisegment DNA assembly

PubMed Central

Sands, Bryan; Brent, Roger

2016-01-01

In 1973, Cohen and coworkers published a foundational paper describing the cloning of DNA fragments into plasmid vectors. In it, they used DNA segments made by digestion with restriction enzymes and joined these in vitro with DNA ligase. These methods established working recombinant DNA technology and enabled the immediate start of the biotechnology industry. Since then, “classical” recombinant DNA technology using restriction enzymes and DNA ligase has matured. At the same time, researchers have developed numerous ways to generate large, complex, multisegment DNA constructions that offer advantages over classical techniques. Here, we provide an overview of “post-Cohen-Boyer” techniques used for cloning single segments into vectors (T/A, Topo cloning, Gateway and Recombineering) and for multisegment DNA assembly (Biobricks, Golden Gate, Gibson, Yeast homologous recombination in vivo, and Ligase Cycling Reaction). We compare and contrast these methods and also discuss issues that researchers should consider before choosing a particular multisegment DNA assembly method. PMID:27152131

Discovery and Optimization of Indolyl-Containing 4-Hydroxy-2-Pyridone Type II DNA Topoisomerase Inhibitors Active against Multidrug Resistant Gram-negative Bacteria.

PubMed

Gerasyuto, Aleksey I; Arnold, Michael A; Wang, Jiashi; Chen, Guangming; Zhang, Xiaoyan; Smith, Sean; Woll, Matthew G; Baird, John; Zhang, Nanjing; Almstead, Neil G; Narasimhan, Jana; Peddi, Srinivasa; Dumble, Melissa; Sheedy, Josephine; Weetall, Marla; Branstrom, Arthur A; Prasad, J V N; Karp, Gary M

2018-05-14

There exists an urgent medical need to identify new chemical entities (NCEs) targeting multidrug resistant (MDR) bacterial infections, particularly those caused by Gram-negative pathogens. 4-Hydroxy-2-pyridones represent a novel class of nonfluoroquinolone inhibitors of bacterial type II topoisomerases active against MDR Gram-negative bacteria. Herein, we report on the discovery and structure-activity relationships of a series of fused indolyl-containing 4-hydroxy-2-pyridones with improved in vitro antibacterial activity against fluoroquinolone resistant strains. Compounds 6o and 6v are representative of this class, targeting both bacterial DNA gyrase and topoisomerase IV (Topo IV). In an abbreviated susceptibility screen, compounds 6o and 6v showed improved MIC 90 values against Escherichia coli (0.5-1 μg/mL) and Acinetobacter baumannii (8-16 μg/mL) compared to the precursor compounds. In a murine septicemia model, both compounds showed complete protection in mice infected with a lethal dose of E. coli.

Synthesis and characterization of Cu(II)-based anticancer chemotherapeutic agent targeting topoisomerase Iα: in vitro DNA binding, pBR322 cleavage, molecular docking studies and cytotoxicity against human cancer cell lines.

PubMed

Tabassum, Sartaj; Zaki, Mehvash; Afzal, Mohd; Arjmand, Farukh

2014-03-03

New metal-based anticancer chemotherapeutic drug candidates [Cu(phen)L](NO₃)₂ (1) and [Zn(phen)L](NO₃)₂ (2) were synthesized from ligand L (derived from pharmacophore scaffold barbituric acid and pyrazole). In vitro DNA binding studies of the L, 1 and 2 were carried out by various biophysical techniques revealing electrostatic mode. Complex 1 cleaves pBR322 DNA via oxidative pathway and recognizes major groove of DNA double helix. The molecular docking study was carried out to ascertain the mode of action towards the molecular target DNA and enzymes. The complex 1 exhibited remarkably good anticancer activity on a panel of human cancer cell lines (GI₅₀ values < 10 μg/ml), and to elucidate the mechanism of cancer inhibition, Topo-I enzymatic activity was carried out. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

3D visualization software to analyze topological outcomes of topoisomerase reactions

PubMed Central

Darcy, I. K.; Scharein, R. G.; Stasiak, A.

2008-01-01

The action of various DNA topoisomerases frequently results in characteristic changes in DNA topology. Important information for understanding mechanistic details of action of these topoisomerases can be provided by investigating the knot types resulting from topoisomerase action on circular DNA forming a particular knot type. Depending on the topological bias of a given topoisomerase reaction, one observes different subsets of knotted products. To establish the character of topological bias, one needs to be aware of all possible topological outcomes of intersegmental passages occurring within a given knot type. However, it is not trivial to systematically enumerate topological outcomes of strand passage from a given knot type. We present here a 3D visualization software (TopoICE-X in KnotPlot) that incorporates topological analysis methods in order to visualize, for example, knots that can be obtained from a given knot by one intersegmental passage. The software has several other options for the topological analysis of mechanisms of action of various topoisomerases. PMID:18440983

Development and evaluation of a prototype tracking system using the treatment couch

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

Lang, Stephanie, E-mail: stephanie.lang@usz.ch; Riesterer, Oliver; Klöck, Stephan

2014-02-15

Purpose: Tumor motion increases safety margins around the clinical target volume and leads to an increased dose to the surrounding healthy tissue. The authors have developed and evaluated a one-dimensional treatment couch tracking system to counter steer respiratory tumor motion. Three different motion detection sensors with different lag times were evaluated. Methods: The couch tracking system consists of a motion detection sensor, which can be the topometrical system Topos (Cyber Technologies, Germany), the respiratory gating system RPM (Varian Medical Systems) or a laser triangulation system (Micro Epsilon), and the Protura treatment couch (Civco Medical Systems). The control of the treatmentmore » couch was implemented in the block diagram environment Simulink (MathWorks). To achieve real time performance, the Simulink models were executed on a real time engine, provided by Real-Time Windows Target (MathWorks). A proportional-integral control system was implemented. The lag time of the couch tracking system using the three different motion detection sensors was measured. The geometrical accuracy of the system was evaluated by measuring the mean absolute deviation from the reference (static position) during motion tracking. This deviation was compared to the mean absolute deviation without tracking and a reduction factor was defined. A hexapod system was moving according to seven respiration patterns previously acquired with the RPM system as well as according to a sin{sup 6} function with two different frequencies (0.33 and 0.17 Hz) and the treatment table compensated the motion. Results: A prototype system for treatment couch tracking of respiratory motion was developed. The laser based tracking system with a small lag time of 57 ms reduced the residual motion by a factor of 11.9 ± 5.5 (mean value ± standard deviation). An increase in delay time from 57 to 130 ms (RPM based system) resulted in a reduction by a factor of 4.7 ± 2.6. The Topos based tracking system with the largest lag time of 300 ms achieved a mean reduction by a factor of 3.4 ± 2.3. The increase in the penumbra of a profile (1 × 1 cm{sup 2}) for a motion of 6 mm was 1.4 mm. With tracking applied there was no increase in the penumbra. Conclusions: Couch tracking with the Protura treatment couch is achievable. To reliably track all possible respiration patterns without prediction filters a short lag time below 100 ms is needed. More scientific work is necessary to extend our prototype to tracking of internal motion.« less

TopoGreenland: crustal structure in central-eastern Greenland along a new refraction profile

NASA Astrophysics Data System (ADS)

Shulgin, Alexey; Thybo, Hans; Field Team TopoGreenland

2013-04-01

We present the seismic structure in the interior of Greenland based on the first measurements by the seismic refraction/wide angle reflection method. Previous seismic surveys have only been carried out offshore and near the coast of Greenland, where the crustal structure is affected by oceanic break-up and may not be representative of the interior of the island. Acquisition of geophysical data in onshore Greenland is logistically complicated by the presence of an up to 3.4 km thick ice sheet, permanently covering most of the land mass. The seismic data was acquired by a team of six people during a two-month long experiment in summer of 2011 on the ice cap in the interior of central-eastern Greenland. The EW-trending profile extends 310 km inland from the approximate edge of the stable ice cap near Scoresby Sund across the center of the ice cap. The planned extension of the profile by use of OBSs and air gun shooting in Scoresbysund Fjord to the east coast of Greenland was unfortunately canceled, because navigation was prevented by ice drift. 350 Reftek Texan receivers recorded high-quality seismic data from 8 equidistant shots along the profile. Explosive charge sizes were 1 ton at the ends and ca. 500 kg along the profile, loaded with about 125 kg at 35-85 m depth in individual boreholes. Two-dimensional velocity model based on tomographic inversion and forward ray tracing modeling shows a decrease of crustal thickness from 47 km below the center of Greenland in the western part to 40 km in the eastern part of the profile. Earlier studies show that crustal thickness further decreases eastward to ca. 30 km below the fjord system, but details of the changes are unknown. Relatively high lower crustal velocities (Vp 6.8 - 7.3) in the western part of the TopoGreenland profile may indicate past collision tectonics or may be related or to the passage of the Iceland mantle plume. The origin of the pronounced circum-Atlantic mountain ranges in Norway and eastern Greenland, which have average elevation above 1500 m with peak elevations of more than 3.5 km close to Scoresby Sund in Eastern Greenland, is unknown. Our new results on the crustal structure provide data for assessment of the isostatic balance of the crust in Greenland, as well as for insight into possible links between crustal composition, rifting history and present-day topography of the North Atlantic Region.

Migration of recharge waters downgradient from the Santa Catalina Mountains into the Tucson basin aquifer, Arizona, USA

NASA Astrophysics Data System (ADS)

Cunningham, Erin E. B.; Long, Austin; Eastoe, Chris; Bassett, R. L.

Aquifers in the arid alluvial basins of the southwestern U.S. are recharged predominantly by infiltration from streams and playas within the basins and by water entering along the margins of the basins. The Tucson basin of southeastern Arizona is such a basin. The Santa Catalina Mountains form the northern boundary of this basin and receive more than twice as much precipitation (ca. 700mm/year) as does the basin itself (ca. 300mm/year). In this study environmental isotopes were employed to investigate the migration of precipitation basinward through shallow joints and fractures. Water samples were obtained from springs and runoff in the Santa Catalina Mountains and from wells in the foothills of the Santa Catalina Mountains. Stable isotopes (δD and δ18O) and thermonuclear-bomb-produced tritium enabled qualitative characterization of flow paths and flow velocities. Stable-isotope measurements show no direct altitude effect. Tritium values indicate that although a few springs and wells discharge pre-bomb water, most springs discharge waters from the 1960s or later. Résumé La recharge des aquifères des bassins alluviaux arides du sud-ouest des États-Unis est assurée surtout à partir des lits des cours d'eau et des playas dans les bassins, ainsi que par l'eau entrant à la bordure de ces bassins. Le bassin du Tucson, dans le sud-est de l'Arizona, est l'un de ceux-ci. La chaîne montagneuse de Santa Catalina constitue la limite nord de ce bassin et reçoit plus de deux fois plus de précipitations (environ 700mm/an) que le bassin (environ 300mm/an). Dans cette étude, les isotopes du milieu ont été utilisés pour analyser le déplacement de l'eau de pluie vers le bassin au travers des fissures et des fractures proches de la surface. Des échantillons d'eau ont été prélevés dans les sources et dans l'écoulement de surface de la chaîne montagneuse et dans des puits au pied de la chaîne. Les isotopes stables (δD et δ18O) et le tritium d'origine thermonucléaire permettent de caractériser qualitativement les cheminements de l'eau et leurs vitesses. Les isotopes stables ne mettent pas en évidence un effet d'altitude. Les teneurs en tritium indiquent que quelques sources et certains puits fournissent une eau ancienne, alors que l'eau de la plupart des sources date des années soixante ou est plus récente. Resumen Los acuíferos en las cuencas aluviales áridas del sudoeste de los Estados Unidos de América se recargan principalmente por la infiltración procedentes de los arroyos y playas de las propias cuencas y por entradas a lo largo de los límites de las mismas. La cuenca de Tucson, en el sudeste de Arizona es una de ellas. Las Montañas de Santa Catalina forman el contorno septentrional de esta cuenca y reciben una precipitación de más del doble (700mm/año) que la media de la propia cuenca (unos 300mm/año). En este estudio, se utilizaron isótopos ambientales para investigar la infiltración a través de fracturas y juntas superficiales. Se obtuvieron muestras de manantiales y de la escorrentía en las Montañas de Santa Catalina, así como de pozos ubicados al pie de las mismas. Los isótopos estables (Deuterio y Oxígeno-18) y el Tritio procedente de las bombas termonucleares permitieron la caracterización cualitativa de las líneas de flujo y de las velocidades. Los datos procedentes de la medida de isótopos estables no parecen presentar un efecto de altitud. Los valores de Tritio indican que aunque algunos pozos y manantiales descargan agua previa a los ensayos termonucleares, la mayoría descargan aguas de fecha posterior a 1960.

Standard for the U.S. Geological Survey Historical Topographic Map Collection

USGS Publications Warehouse

Allord, Gregory J.; Fishburn, Kristin A.; Walter, Jennifer L.

2014-01-01

This document defines the digital map product of the U.S. Geological Survey (USGS) Historical Topographic Map Collection (HTMC). The HTMC is a digital archive of about 190,000 printed topographic quadrangle maps published by the USGS from the inception of the topographic mapping program in 1884 until the last paper topographic map using lithographic printing technology was published in 2006. The HTMC provides a comprehensive digital repository of all scales and all editions of USGS printed topographic maps that is easily discovered, browsed, and downloaded by the public at no cost. Each printed topographic map is scanned “as is” and captures the content and condition of each map. The HTMC provides ready access to maps that are no longer available for distribution in print. A new generation of topographic maps called “US Topo” was defined in 2009. US Topo maps, though modeled on the legacy 7.5-minute topographic maps, conform to different standards. For more information on the HTMC, see the project Web site at: http://nationalmap.gov/historical/.

Extravasation management: clinical update.

PubMed

Schulmeister, Lisa

2011-02-01

To present a clinical update on the prevention, detection, and evidence-based management of vesicant chemotherapy extravasations. Journal articles, published and unpublished case reports, personal experience. In the 4 years that have elapsed since the publication of the original article, much more is known about vesicant chemotherapy extravasation, and effective evidence-based treatments now are available. The antidotes sodium thiosulfate for mechlorethamine extravasations and hyaluronidase for plant alkaloid extravasations are recommended by the manufacturers of these vesicants and cited in nursing guidelines. The anthracycline extravasation treatment dexrazoxane for injection, the first and only extravasation treatment with proven effectiveness, is now available as Totect (dexrazoxane; TopoTarget USA, Rockaway, NJ, USA) in the US and Savene (SpePharm, Amsterdam, The Netherlands) in Europe. Nurses who administer vesicant chemotherapy agents need to be aware of the most current evidence (or lack of evidence) for various types of extravasation treatment. Well-informed nurses are patient advocates and instrumental in detecting, managing, and documenting extravasations. Most importantly, nurses play a key role in preventing vesicant chemotherapy extravasations. Copyright © 2011 Elsevier Inc. All rights reserved.

Identification and characterization of an SPO11 homolog in the mouse.

PubMed

Metzler-Guillemain, C; de Massy, B

2000-01-01

The SPO11/TOPVIA family includes proteins from archaebacteria and eukaryotes. The protein member from the archaebacterium Sulfulobus shibatae is the catalytic subunit of TopoVI DNA topoisomerase. In Saccharomyces cerevisiae, Schizosaccharomyces pombe, Caenorhabditis elegans and Drosophila melanogaster, SPO11 is required for meiotic recombination, suggesting a conserved mechanism for the initiation step of this process. Indeed, S. cerevisiae SPO11 has been shown to be directly involved in the formation of meiotic DNA double-strand breaks that initiate meiotic recombination. Here, we report the identification of a Mus musculus Spo11 cDNA, which encodes a protein closely related to all members of the SPO11/TOPVIA family. cDNAs resulting from alternative splicing were detected, suggesting that there are potential variants of the mouse SPO11 protein. By RNA-blotting analysis, expression of the mouse Spo11 gene was detected only in the testis, in agreement with its predicted function in the initiation of meiotic recombination. We mapped the mouse Spo11 gene to chromosome 2, band H2-H4.

Comparison of carbon-sulfur and carbon-amine bond in therapeutic drug: 4β-S-aromatic heterocyclic podophyllum derivatives display antitumor activity

PubMed Central

Li, Jian-Long; Zhao, Wei; Zhou, Chen; Zhang, Ya-Xuan; Li, Hong-Mei; Tang, Ya-Ling; Liang, Xin-Hua; Chen, Tao; Tang, Ya-Jie

2015-01-01

Herein is a first effort to systematically study the significance of carbon-sulfur (C-S) and carbon-amine (C-NH) bonds on the antitumor proliferation activity of podophyllum derivatives and their precise mechanism of apoptosis. Compared with the derivative modified by a C-NH bond, the derivative modified by a C-S bond exhibited superior antitumor activity, the inhibition activity of target proteins tubulin or Topo II, cell cycle arrest, and apoptosis induction. Antitumor mechanistic studies showed that the death receptor and the mitochondrial apoptotic pathways were simultaneously activated by the C-S bond modified aromatic heterocyclic podophyllum derivatives with a higher cellular uptake percentage of 60–90% and induction of a higher level of reactive oxygen species (ROS). Only the mitochondrial apoptotic pathway was activated by the C-NH bond modified aromatic heterocyclic podophyllum derivatives, with a lower cellular uptake percentage of 40–50%. This study provided insight into effects of the C-S and C-NH bond modification on the improvement of the antitumor activity of Podophyllum derivatives. PMID:26443888

[Cloning of Clostridium perfringens alpha-toxin gene and extracellular expression in Escherichia coli].

PubMed

Inoue, Masaharu; Kikuchi, Maho; Komoriya, Tomoe; Watanabe, Kunitomo; Kouno, Hideki

2007-01-01

Clostridium perfringens (C. perfringens) is a Gram-positive bacterial pathogen that widely propagets in the soil and the gastrointestinal tract of human and animals. This bacteria causes food poisoning, gas gangrene and other various range of infectious diseases. But there is no standard diagnosis method of C. perfringens. In order to develop a new type of immunoassay for clinical purpose, we studied expression and extracellular secretion of recombinant alpha-toxin having enzyme activity in E. coli expression system. Cloning was carried out after PCR amplification from C. perfringens GAI 94074 which was clinical isolate. Three kinds of fragment were cloned using pET100/D-TOPO vector. These fragments coded for ribosome binding site, signal peptide, and alpha-toxin gene respectively. Recombinant pET100 plasmid transformed into TOP 10 cells and the obtained plasmids were transformed into BL21 (DE3) cells. Then, the transformants were induced expression with IPTG. In conclusion, we successfully cloned, expressed and exteracellular secreted C. perfringens alpha-toxin containing signal peptide. Biologically, the obtained recombinant protein was positive for phospholipase C activity.

Roles of Fog and Topography in Redwood Forest Hydrology

NASA Astrophysics Data System (ADS)

Francis, E. J.; Asner, G. P.

2017-12-01

Spatial variability of water in forests is a function of both climatic gradients that control water inputs and topo-edaphic variation that determines the flows of water belowground, as well as interactions of climate with topography. Coastal redwood forests are hydrologically unique because they are influenced by coastal low clouds, or fog, that is advected onto land by a strong coastal-to-inland temperature difference. Where fog intersects the land surface, annual water inputs from summer fog drip can be greater than that of winter rainfall. In this study, we take advantage of mapped spatial gradients in forest canopy water storage, topography, and fog cover in California to better understand the roles and interactions of fog and topography in the hydrology of redwood forests. We test a conceptual model of redwood forest hydrology with measurements of canopy water content derived from high-resolution airborne imaging spectroscopy, topographic variables derived from high-resolution LiDAR data, and fog cover maps derived from NASA MODIS data. Landscape-level results provide insight into hydrological processes within redwood forests, and cross-site analyses shed light on their generality.

[Molecular cloning and expression of the severe acute respiratory syndrome-associated coronavirus nucleocapsid protein and its clinical application].

PubMed

Lu, Jian; Zhou, Bai-ping; Zhou, Yu-sen; Jiang, Xiao-ling; Wen, Li-xia; Le, Xiao-hua; Li, Bing; Xu, Liu-mei; Li, Li-xiong

2005-03-01

To clone and express nucleocapsid (N) protein of the severe acute respiratory syndrome (SARS)-associated coronavirus, and to evaluate its antigenicity and application value in the development of serological diagnostic test for SARS. SARS-associated coronavirus N protein gene was amplified from its genomic RNA by reverse transcript nested polymerase chain reaction (RT-nested-PCR) and cloned into pBAD/Thio-TOPO prokaryotic expression vector. The recombinant N fusion protein was expressed and purified, and its antigenicity and specificity was analyzed by Western Blot, to establish the recombinant N protein-based ELISA for detection of IgG antibodies to SARS-associated coronavirus, and SARS-associated coronavirus lysates-based ELISA was compared parallelly. The recombinant expression vector produced high level of the N fusion protein after induction, and that protein was purified successfully by affinity chromatography and displayed higher antigenicity and specificity as compared with whole virus lysates. The recombinant SARS-associated coronavirus N protein possessed better antigenicity and specificity and could be employed to establish a new, sensitive, and specific ELISA for SARS diagnosis.

Mapping and evaluation of snow avalanche risk using GIS technique in Rodnei National Park

NASA Astrophysics Data System (ADS)

Covǎsnianu, Adrian; Grigoraş, Ioan-Rǎducu; Covǎsnianu, Liliana-Elena; Iordache, Iulian; Balin, Daniela

2010-05-01

The study consisted in a precise mapping project (GPS field campaign, on-screen digitization of the topographic maps at 1:25.000 scale and updated with ASTER mission) of the Rodnei National Park area (Romanian Carpathians) with a focus on snow avalanche risk survey. Parameters taken into account were slope, aspect, altitude, landforms and roughness resulted from a high resolute numerical terrain model obtained by ASTER (Advanced Spaceborne Thermal Emission and Reflection Radiometer) mission. The resulted digital surface model with a spatial resolution of 10 m covered a total area of 187 square kilometers and was improved by the help of Topo to Raster tool. All these parameters were calibrated after a model applied onto Tatra Massive and also Ceahlău Mountain. The results were adapted and interpreted in accordance with European avalanche hazard scale. This work was made in the context of the elaboration of Risk Map and is directly concerning both the security of tourism activities but also the management of the Rodnei Natural Park. The extension of this method to similar mountain areas is ongoing.

Molecular cloning, sequencing, and expression of Eimeria tenella HSP70 partial gene.

PubMed

Bogado, A L G; Martins, G F; Sasse, J P; Guimarães, J da S; Garcia, J L

2017-03-15

Members of the Eimeria genus are protozoan parasites of the subphylum Apicomplexa (Eimeriidae family), and belong to the coccidia group. Eimeria tenella is one of the most pathogenic species owing to its ability to penetrate the mucosa, and cause inflammation and damage. It is an obligate intracellular parasite that causes disease by destroying the host cells during multiplication. Heat shock protein 70 (HSP70) is a molecular chaperone that prevents cellular stress. The objective of this study was to clone, sequence, and express E. tenella HSP70 protein. After selecting the region of highest hydrophilicity in the hsp70 gene, we cloned complementary DNA (cDNA) into a pTrcHis2-TOPO vector and transformed it into TOP10 Escherichia coli cells; after induction, the bacteria expressed a 23-kDa protein with insoluble expression levels of approximately 5 mg/L. In summary, the partial hsp70 gene was successfully expressed in E. coli, producing a 23-kDa protein under insoluble conditions, and the antigen characteristics predicted by hydrophilicity analysis suggest the development of a vaccine for use in avian coccidiosis.

On the use of the fourier modal method for calculation of localized eigenmodes of integrated optical resonators