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Sample records for coralyne induces triple

  1. Dual hairpin-like molecular beacon based on coralyne-adenosine interaction for sensing melamine in dairy products.

    Science.gov (United States)

    Wang, Guangfeng; Zhu, Yanhong; Chen, Ling; Zhang, Xiaojun

    2014-11-01

    This study presents a novel dual hairpin-like molecular beacon (MB) for the selective and sensitive detection of melamine (MA) based on the conjugation of MA and thymine. In this protocol, the coordination between coralyne and adenosine (A) leaded a dual hairpin-like MB and the fluorophore-quencher pair is close proximity resulting in the fluorescence quenching. With the addition of MA, it conjugated with thymine in the loop part of dual hairpin-like MB by triple H-bonds, triggering the dissociation of the dual hairpin-like MB. The resulting spatial separation of the fluorophore from quencher induced the enhancement in fluorescence emission. Under the optimized conditions, the sensor exhibited a wide linear range of 8×10(-9)-1.6×10(-5) M (R(2)=0.9969) towards MA, with a low detection limit of 5 nM, approximately 4000 times lower than the Drug Administration and the US Food estimated MA safety limit. The real milk samples were also investigated with a satisfying result.

  2. Accurate detection of triple vessel disease in patients with exercise induced ST segment depression after infarction.

    OpenAIRE

    Mannering, D; Bennett, E D; Ward, D. E.; Dawkins, K; Dancy, M; Valantine, H; Mehta, N.

    1987-01-01

    The severity of coronary artery disease is an important determinant of prognosis after acute myocardial infarction. The ability of a symptom limited exercise test to predict the presence of triple vessel disease was assessed in 221 patients three weeks after infarction. Coronary angiography was performed in patients with exercise induced ST segment depression. The presence of ST segment depression alone was poorly indicative of triple vessel disease; however, some specific features of ST segm...

  3. Divalent counterion-induced condensation of triple-strand DNA.

    Science.gov (United States)

    Qiu, Xiangyun; Parsegian, V Adrian; Rau, Donald C

    2010-12-14

    Understanding and manipulation of the forces assembling DNA/RNA helices have broad implications for biology, medicine, and physics. One subject of significance is the attractive force between dsDNA mediated by polycations of valence ≥ 3. Despite extensive studies, the physical origin of the "like-charge attraction" remains unsettled among competing theories. Here we show that triple-strand DNA (tsDNA), a more highly charged helix than dsDNA, is precipitated by alkaline-earth divalent cations that are unable to condense dsDNA. We further show that our observation is general by examining several cations (Mg(2+), Ba(2+), and Ca(2+)) and two distinct tsDNA constructs. Cation-condensed tsDNA forms ordered hexagonal arrays that redissolve upon adding monovalent salts. Forces between tsDNA helices, measured by osmotic stress, follow the form of hydration forces observed with condensed dsDNA. Probing a well-defined system of point-like cations and tsDNAs with more evenly spaced helical charges, the counterintuitive observation that the more highly charged tsDNA (vs. dsDNA) is condensed by cations of lower valence provides new insights into theories of polyelectrolytes and the biological and pathological roles of tsDNA. Cations and tsDNAs also hold promise as a model system for future studies of DNA-DNA interactions and electrostatic interactions in general.

  4. Tunneling-induced transparency and Autler-Townes splitting in a triple quantum dot

    CERN Document Server

    Luo, Xiao-Qing; Jing, Jun; Li, Tie-Fu; Yu, Ting; You, J Q

    2015-01-01

    We theoretically investigate the tunneling-induced transparency (TIT) and the Autler-Townes (AT) doublet and triplet in a triple-quantum-dot system. For the resonant tunneling case, we show that the TIT induces a transparency dip in a weak-tunneling regime and no anticrossing occurs in the eigenenergies of the system Hamiltonian. However, in a strong-tunneling regime, we show that the TIT evolves to the AT splitting, which results in a well-resolved doublet and double anticrossings. For the off-resonance case, we demonstrate that, in the weak-tunneling regime, the double TIT is realized with a new detuning-dependent dip, where the anticrossing is also absent. In the strong-tunneling regime, the AT triplet is realized with triple anticrossings and a wide detuning-dependent transparency window by manipulating one of the energy-level detunings. Our results can be applied to quantum measurement and quantum-optics devices in solid systems.

  5. Alterations in tumorigenicity of embryonal carcinoma cells by IGF-I triple-helix induced changes in immunogenicity and apoptosis.

    Science.gov (United States)

    Ly, A; Francois, J C; Upegui-Gonzalez, L C; Swiercz, B; Bedel, C; Duc, H T; Bout, D; Trojan, J

    2000-12-08

    IGF-I antisense gene therapy has been applied successfully to animal models of glioma, hepatoma and teratocarcinoma. The antisense strategy has shown that tumor cells transfected with vectors encoding IGF-I antisense RNA lose tumorigenicity, become immunogenic and are associated with tumor specific immune response involving CD8+ lymphocytes. An IGF-I triple helix approach to gene therapy for glioma was recently described. The approach we have taken is to establish parameters of change using the IGF-I triple helix strategy. PCC-3 embryonal carcinoma cells derived from murine teratocarcinoma which express IGF-I were used as a model. The cells were transfected with vector which encodes an oligoribonucleotide that forms RNA-IGF-I DNA triple-helix structure. The triple-helix stops the production of IGF-I. Cells transfected in this manner underwent changes in phenotype and an increase in MHC-I and B-7 cell surface molecules. They also showed enhancement in the production of apoptotic cells (60-70%). The "triple helix" transfected cells lost the ability to induce tumor when injected subcutaneously in syngeneic 129 Sv mice. When co-transfected in vitro with expression vectors encoding both MHC-I and B-7 cDNA in antisense orientation, the "triple-helix" transfected cells were down-regulated in expression of MHC-I and B-7 and the number of apoptotic cells was significantly decreased. Injection of the doubly co-transfected cells into 129 Sv mice was associated with induction of teratocarcinoma. Comparison between antisense and triple-helix transfected cells strategies showed similar immunogenic and apoptotic changes. The findings suggest that triple-helix technology may offer a new clinical approach to treatement of tumors expressing IGF-I.

  6. A triple-helix forming oligonucleotide targeting genomic DNA fails to induce mutation.

    Science.gov (United States)

    Reshat, Reshat; Priestley, Catherine C; Gooderham, Nigel J

    2012-11-01

    Purine tracts in duplex DNA can bind oligonucleotide strands in a sequence specific manner to form triple-helix structures. Triple-helix forming oligonucleotides (TFOs) targeting supFG1 constructs have previously been shown to be mutagenic raising safety concerns for oligonucleotide-based pharmaceuticals. We have engineered a TFO, TFO27, to target the genomic Hypoxanthine-guanine phosphoribosyltransferase (HPRT) locus to define the mutagenic potential of such structures at genomic DNA. We report that TFO27 was resistant to nuclease degradation and readily binds to its target motif in a cell free system. Contrary to previous studies using the supFG1 reporter construct, TFO27 failed to induce mutation within the genomic HPRT locus. We suggest that it is possible that previous reports of triplex-mediated mutation using the supFG1 reporter construct could be confounded by DNA quadruplex formation. Although the present study indicates that a TFO targeting a genomic locus lacks mutagenic activity, it is unclear if this finding can be generalised to all TFOs and their targets. For the present, we suggest that it is prudent to avoid large purine stretches in oligonucleotide pharmaceutical design to minimise concern regarding off-target genotoxicity.

  7. Supramolecular coordination chemistry in aqueous solution: lanthanide ion-induced triple helix formation.

    Science.gov (United States)

    Lessmann, J J; Horrocks, W D

    2000-07-24

    The self-assembly of dinuclear triple helical lanthanide ion complexes (helicates), in aqueous solution, is investigated utilizing laser-induced, lanthanide luminescence spectroscopy. A series of dinuclear lanthanide (III) helicates (Ln(III)) based on 2,6-pyridinedicarboxylic acid (dipicolinic acid, dpa) coordinating units was synthesized by linking two dpa moieties using the organic diamines (1R,2R)-diaminocyclohexane (chxn-R,R) and 4,4'-diaminodiphenylmethane (dpm). Luminescence excitation spectroscopy of the Eu3+ 7F0-->5D0 transition shows the apparent cooperative formation of neutral triple helical complexes in aqueous solution, with a [Eu2L3] stoichiometry. Eu3+ excitation peak wavelengths and excited-state lifetimes correspond to those of the [Eu(dpa)3]3- model complex. CD studies of the Nd(III) helicate Nd2(dpa-chxn-R,R)3 reveal optical activity of the f-f transitions, indicating that the chiral linking group induces a stable chirality at the metal ion center. Molecular mechanics calculations using CHARMm suggest that the delta delta configuration at the Nd3+ ion centers is induced by the chxn-R,R linker. Stability constants were determined for both ligands with Eu3+, yielding identical results: log K = 31.6 +/- 0.2 (K in units of M-4). Metal-metal distances calculated from Eu3+-->Nd3+ energy-transfer experiments show that the complexes have metal-metal distances close to those calculated by molecular modeling. The fine structure in the Tb3+ emission bands is consistent with the approximate D3 symmetry as anticipated for helicates.

  8. Cyclooxygenase-2 regulates TGFβ-induced cancer stemness in triple-negative breast cancer

    Science.gov (United States)

    Tian, Jun; Hachim, Mahmood Y.; Hachim, Ibrahim Y.; Dai, Meiou; Lo, Chieh; Raffa, Fatmah Al; Ali, Suhad; Lebrun, Jean Jacques

    2017-01-01

    Triple negative breast cancer (TNBC), an aggressive subtype of breast cancer, display poor prognosis and exhibit resistance to conventional therapies, partly due to an enrichment in breast cancer stem cells (BCSCs). Here, we investigated the role of the cyclooxygenase-2 (COX-2), a downstream target of TGFβ, in regulating BCSCs in TNBC. Bioinformatics analysis revealed that COX-2 is highly expressed in TNBC and that its expression correlated with poor survival outcome in basal subtype of breast cancer. We also found TGFβ-mediated COX-2 expression to be Smad3-dependent and to be required for BCSC self-renewal and expansion in TNBCs. Knocking down COX-2 expression strikingly blocked TGFβ-induced tumorsphere formation and TGFβ-induced enrichment of the two stem-like cell populations, CD24lowCD44high and ALDH+ BCSCs. Blocking COX-2 activity, using a pharmacological inhibitor also prevented TGFβ-induced BCSC self-renewal. Moreover, we found COX-2 to be required for TGFβ-induced expression of mesenchymal and basal breast cancer markers. In particular, we found that TGFβ-induced expression of fibronectin plays a central role in TGFβ-mediated breast cancer stemness. Together, our results describe a novel role for COX-2 in mediating the TGFβ effects on BCSC properties and imply that targeting the COX-2 pathway may prove useful for the treatment of TNBC by eliminating BCSCs. PMID:28054666

  9. A novel curcumin-like dienone induces apoptosis in triple-negative breast cancer cells

    Science.gov (United States)

    Robles-Escajeda, Elisa; Das, Umashankar; Ortega, Nora M.; Parra, Karla; Francia, Giulio; Dimmock, Jonathan R.; Varela-Ramirez, Armando; Aguilera, Renato J.

    2016-01-01

    Purpose According to the World Health Organization (WHO), breast cancer is the most common cancer affecting women worldwide. In the USA ~12.3 % of all women are expected to be diagnosed with various types of breast cancer, exhibiting varying degrees of therapeutic response rates. Therefore, the identification of novel anti-breast cancer drugs is of paramount importance. Methods The 1,5-diaryl-3-oxo-1,4-pentadienyl pharmacophore was incorporated into a number of cytotoxins. Three of the resulting dienones, 2a, 2b and 2c, were tested for their antineoplastic potencies in a variety of human breast cancer-derived cell lines, including the triple negative MDA-MB-231 cell line and its metastatic variant, using a live-cell bio-imaging method. Special emphasis was put on dienone 2c, since its anti-cancer activity and its mode of inflicting cell death have so far not been reported. Results We found that all three dienones exhibited potent cytotoxicities towards the breast cancer-derived cell lines tested, whereas significantly lower toxicities were observed towards the non-cancerous human breast cell line MCF-10A. The dienones 2b and 2c exhibited the greatest selective cytotoxicity at submicromolar concentration levels. We found that these two dienones induced phosphatidylserine externalization in MDA-MB-231 cells in a concentration-dependent manner, suggesting that their cytotoxic effect might be mediated by apoptosis. This possibility was confirmed by our observation that the dienone 2c can induce mitochondrial depolarization, caspase-3 activation, cell cycle disruption and DNA fragmentation in MDA-MB-231 cells. Conclusion Our findings indicate that dienone 2c uses the mitochondrial/intrinsic pathway to inflict apoptosis in triple negative MDA-MB-231 breast cancer-derived cells. This observation warrants further assessment of dienone 2c as a potential anti-breast cancer drug. PMID:26920032

  10. Mesenchymal Stem Cell-Induced Doxorubicin Resistance in Triple Negative Breast Cancer

    Directory of Open Access Journals (Sweden)

    Dar-Ren Chen

    2014-01-01

    Full Text Available Triple negative breast cancer (TNBC is an aggressive histological subtype with limited treatment options and a worse clinical outcome compared with other breast cancer subtypes. Doxorubicin is considered to be one of the most effective agents in the treatment of TNBC. Unfortunately, resistance to this agent is common. In some drug-resistant cells, drug efflux is mediated by adenosine triphosphate-dependent membrane transporter termed adenosine triphosphate-binding cassette (ABC transporter, which can drive the substrates across membranes against concentration gradient. In the tumor microenvironment, upon interaction with mesenchymal stem cells (MSCs, tumor cells exhibit altered biological functions of certain gene clusters, hence increasing stemness of tumor cells, migration ability, angiogenesis, and drug resistance. In our present study, we investigated the mechanism of TNBC drug resistance induced by adipose-derived MSCs. Upon exposure of TNBC to MSC-secreted conditioned medium (CM, noticeable drug resistance against doxorubicin with markedly increased BCRP protein expression was observed. Intracellular doxorubicin accumulation of TNBC was also decreased by MSC-secreted CM. Furthermore, we found that doxorubicin resistance of TNBC was mediated by IL-8 presented in the MSC-secreted CM. These findings may enrich the list of potential targets for overcoming drug resistance induced by MSCs in TNBC patients.

  11. Mesenchymal stem cell-induced doxorubicin resistance in triple negative breast cancer.

    Science.gov (United States)

    Chen, Dar-Ren; Lu, Dah-Yuu; Lin, Hui-Yi; Yeh, Wei-Lan

    2014-01-01

    Triple negative breast cancer (TNBC) is an aggressive histological subtype with limited treatment options and a worse clinical outcome compared with other breast cancer subtypes. Doxorubicin is considered to be one of the most effective agents in the treatment of TNBC. Unfortunately, resistance to this agent is common. In some drug-resistant cells, drug efflux is mediated by adenosine triphosphate-dependent membrane transporter termed adenosine triphosphate-binding cassette (ABC) transporter, which can drive the substrates across membranes against concentration gradient. In the tumor microenvironment, upon interaction with mesenchymal stem cells (MSCs), tumor cells exhibit altered biological functions of certain gene clusters, hence increasing stemness of tumor cells, migration ability, angiogenesis, and drug resistance. In our present study, we investigated the mechanism of TNBC drug resistance induced by adipose-derived MSCs. Upon exposure of TNBC to MSC-secreted conditioned medium (CM), noticeable drug resistance against doxorubicin with markedly increased BCRP protein expression was observed. Intracellular doxorubicin accumulation of TNBC was also decreased by MSC-secreted CM. Furthermore, we found that doxorubicin resistance of TNBC was mediated by IL-8 presented in the MSC-secreted CM. These findings may enrich the list of potential targets for overcoming drug resistance induced by MSCs in TNBC patients.

  12. Transient cracks and triple junctions induced by Cocos-Nazca propagating rift

    Science.gov (United States)

    Schouten, H.; Smith, D. K.; Zhu, W.; Montesi, L. G.; Mitchell, G. A.; Cann, J. R.

    2009-12-01

    The Galapagos triple junction is a ridge-ridge-ridge triple junction where the Cocos, Nazca, and Pacific plates meet around the Galapagos microplate (GMP). On the Cocos plate, north of the large gore that marks the propagating Cocos-Nazca (C-N) Rift, a 250-km-long and 50-km-wide band of NW-SE-trending cracks crosscuts the N-S-trending abyssal hills of the East Pacific Rise (EPR). These appear as a succession of minor rifts, accommodating some NE-SW extension of EPR-generated seafloor. The rifts successively intersected the EPR in triple junctions at distances of 50-100 km north of the tip of the C-N Rift. We proposed a simple crack interaction model to explain the location of the transient rifts and their junction with the EPR. The model predicts that crack locations are controlled by the stress perturbation along the EPR, induced by the dominant C-N Rift, and scaled by the distance of its tip to the EPR (Schouten et al., 2008). The model also predicts that tensile stresses are symmetric about the C-N Rift and thus, similar cracks should have occurred south of the C-N Rift prior to formation of the GMP about 1 Ma. There were no data at the time to test this prediction. In early 2009 (AT 15-41), we mapped an area on the Nazca plate south of the C-N rift out to 4 Ma. The new bathymetric data confirm the existence of a distinctive pattern of cracks south of the southern C-N gore that mirrors the pattern on the Cocos plate until about 1 Ma, and lends support to the crack interaction model. The envelope of the symmetric cracking pattern indicates that the distance between the C-N Rift tip and the EPR varied between 40 and 65 km during this time (1-4 Ma). The breakdown of the symmetry at 1 Ma accurately dates the onset of a southern plate boundary of the GMP, now Dietz Deep Rift. At present, the southern rift boundary of the GMP joins the EPR with a steep-sided, 80 km long ridge. This ridge releases the stress perturbation otherwise induced along the EPR by elastic

  13. Molecular mechanisms of Triple H therapy in the treatment of SAH-induced vasospasm

    Institute of Scientific and Technical Information of China (English)

    Masanori Ishiguro; Corey B.Puryear; Erica Bisson; Ryan Jewell; David J. Nathan; Bruce I. Tranmer; George C. Wellman

    2004-01-01

    Objective Cerebral artery vasospasm is a major cause of death and disability in patients experiencing subarachnoid hemorrhage (SAH). Vasospasm typically has been evaluated using angiography to examine narrowing of large diameter (>1 mm) cerebral arteries. Currently, little is known regarding the impact of SAH on small diameter (100~200 μm) cerebral arteries, which play an important role in the autoregulation of cerebral blood flow. The goal of the current study was to examine the influence of SAH on the pressure-diameter relationship of these small diameter blood vessels. Methods Small diameter cerebral arteries were obtained from a rabbit SAH model. Isolated artery segments were canulated and placed in a myograph chamber superfused with warmed, oxygenated, physiological saline solution. Diameter measurements were then recorded to step-wise increases in intravascular pressure. Results Cerebral arteries from SAH animals exhibited a significant increase in pressure-induced constrictions (myogenic tone) at intravascular pressures between 40 mmHg and 120 mmHg. At intravascular pressures above 120 mmHg, myogenic tone began to decrease and was abolished at pressures above 180 mmHg. Conclusion These data suggest that in the days following SAH, myogenic tone is enhanced in small diameter cerebral arteries subjected to physiological levels of intravascular pressure. However, supra-physiological intravascular pressures causes vasodilation, suggesting small diameter cerebral arteries may act as therapeutic targets of hypervolemia, hemodilution, and hypertension "Triple H therapy" used in the treatment of cerebral artery vasospasm.

  14. Aptamer/target binding-induced triple helix forming for signal-on electrochemical biosensing.

    Science.gov (United States)

    Mao, Yinfei; Liu, Jinquan; He, Dinggen; He, Xiaoxiao; Wang, Kemin; Shi, Hui; Wen, Li

    2015-10-01

    Owing to its diversified structures, high affinity, and specificity for binding a wide range of non-nucleic acid targets, aptamer is a useful molecular recognition tool for the design of various biosensors. Herein, we report a new signal-on electrochemical biosensing platform which is based on an aptamer/target binding-induced strand displacement and triple-helix forming. The biosensing platform is composed of a signal transduction probe (STP) modified with a methylene blue (MB) and a sulfhydryl group, a triplex-forming oligonucleotides probe (TFO) and a target specific aptamer probe (Apt). Through hybridization with the TFO probe and the Apt probe, the self-assembled STP on Au electrode via Au-S bonding keeps its rigid structure. The MB on the STP is distal to the Au electrode surface. It is eT off state. Target binding releases the Apt probe and liberates the end of the MB tagged STP to fold back and form a triplex-helix structure with TFO (STP/TFO/STP), allowing MB to approach the Au electrode surface and generating measurable electrochemical signals (eT ON). As test for the feasibility and universality of this signal-on electrochemical biosensing platform, two aptamers which bind to adenosine triphosphate (ATP) and human α-thrombin (Tmb), respectively, are selected as models. The detection limit of ATP was 7.2 nM, whereas the detection limit of Tmb was 0.86 nM.

  15. RB1 deficiency in triple-negative breast cancer induces mitochondrial protein translation

    Science.gov (United States)

    Jones, Robert A.; Robinson, Tyler J.; Liu, Jeff C.; Shrestha, Mariusz; Voisin, Veronique; Ju, YoungJun; Chung, Philip E.D.; Pellecchia, Giovanna; Fell, Victoria L.; Bae, SooIn; Muthuswamy, Lakshmi; Egan, Sean E.; Jiang, Zhe; Leone, Gustavo; Bader, Gary D.; Schimmer, Aaron

    2016-01-01

    Triple-negative breast cancer (TNBC) includes basal-like and claudin-low subtypes for which no specific treatment is currently available. Although the retinoblastoma tumor-suppressor gene (RB1) is frequently lost together with TP53 in TNBC, it is not directly targetable. There is thus great interest in identifying vulnerabilities downstream of RB1 that can be therapeutically exploited. Here, we determined that combined inactivation of murine Rb and p53 in diverse mammary epithelial cells induced claudin-low–like TNBC with Met, Birc2/3-Mmp13-Yap1, and Pvt1-Myc amplifications. Gene set enrichment analysis revealed that Rb/p53-deficient tumors showed elevated expression of the mitochondrial protein translation (MPT) gene pathway relative to tumors harboring p53 deletion alone. Accordingly, bioinformatic, functional, and biochemical analyses showed that RB1-E2F complexes bind to MPT gene promoters to regulate transcription and control MPT. Additionally, a screen of US Food and Drug Administration–approved (FDA-approved) drugs identified the MPT antagonist tigecycline (TIG) as a potent inhibitor of Rb/p53-deficient tumor cell proliferation. TIG preferentially suppressed RB1-deficient TNBC cell proliferation, targeted both the bulk and cancer stem cell fraction, and strongly attenuated xenograft growth. It also cooperated with sulfasalazine, an FDA-approved inhibitor of cystine xCT antiporter, in culture and xenograft assays. Our results suggest that RB1 deficiency promotes cancer cell proliferation in part by enhancing mitochondrial function and identify TIG as a clinically approved drug for RB1-deficient TNBC. PMID:27571409

  16. On the Mordell-Weil group of elliptic curves induced by families of Diophantine triples

    OpenAIRE

    Mikić, Miljen

    2015-01-01

    The problem of the extendibility of Diophantine triples is closely connected with the Mordell-Weil group of the associated elliptic curve. In this paper, we examine Diophantine triples $\\{k-1,k+1,c_l(k)\\}$ and prove that the torsion group of the associated curves is $\\mathbb{Z}/2\\mathbb{Z} \\times \\mathbb{Z}/2\\mathbb{Z}$ for $l=3,4$ and $l\\equiv 1$ or $2 \\pmod{4}$. Additionally, we prove that the rank is greater than or equal to 2 for all $l\\ge2$. This represents an improvement of previous res...

  17. Triple-helix formation induces recombination in mammalian cells via a nucleotide excision repair-dependent pathway.

    Science.gov (United States)

    Faruqi, A F; Datta, H J; Carroll, D; Seidman, M M; Glazer, P M

    2000-02-01

    The ability to stimulate recombination in a site-specific manner in mammalian cells may provide a useful tool for gene knockout and a valuable strategy for gene therapy. We previously demonstrated that psoralen adducts targeted by triple-helix-forming oligonucleotides (TFOs) could induce recombination between tandem repeats of a supF reporter gene in a simian virus 40 vector in monkey COS cells. Based on work showing that triple helices, even in the absence of associated psoralen adducts, are able to provoke DNA repair and cause mutations, we asked whether intermolecular triplexes could stimulate recombination. Here, we report that triple-helix formation itself is capable of promoting recombination and that this effect is dependent on a functional nucleotide excision repair (NER) pathway. Transfection of COS cells carrying the dual supF vector with a purine-rich TFO, AG30, designed to bind as a third strand to a region between the two mutant supF genes yielded recombinants at a frequency of 0.37%, fivefold above background, whereas a scrambled sequence control oligomer was ineffective. In human cells deficient in the NER factor XPA, the ability of AG30 to induce recombination was eliminated, but it was restored in a corrected subline expressing the XPA cDNA. In comparison, the ability of triplex-directed psoralen cross-links to induce recombination was only partially reduced in XPA-deficient cells, suggesting that NER is not the only pathway that can metabolize targeted psoralen photoadducts into recombinagenic intermediates. Interestingly, the triplex-induced recombination was unaffected in cells deficient in DNA mismatch repair, challenging our previous model of a heteroduplex intermediate and supporting a model based on end joining. This work demonstrates that oligonucleotide-mediated triplex formation can be recombinagenic, providing the basis for a potential strategy to direct genome modification by using high-affinity DNA binding ligands.

  18. Non-uniform Stress Field and Stress Concentration Induced by Grain Boundary and Triple Junction of Tricrystal

    Institute of Scientific and Technical Information of China (English)

    Jiansong WAN; Zhufeng YUE

    2003-01-01

    The stress characteristics in the anisotropic bicrystal and tricrystal specimens were analyzed using the anisotropic elastic model, orthotropic Hill's model and rate-dependent crystallographic model. The finite element analysis results show that non-uniform stresses are induced by the grain boundary. For bicrystal specimens in different crystallographic orientations, there exist stress concentrations and high stress gradients nearby the boundaries. The activation and slipping of the slip systems are dependent on the crystallographic orientations of the grains and also on the relative crystallographic orientations of the two adjoining grains. For the tricrystal specimens, there is not always any stress concentrations in the triple junction, and the concentration degree depends on the relative crystallographic orientations of the three grains. Different from the bicrystal specimens, there may be or no stress concentration in the vicinity of grain boundaries for the tricrystal specimens, which depends on the relative crystallographic orientations of the three grains. The stress concentration near to the grain boundaries and triple junction can be high enough for the local plastic deformation, damage and voiding or cracking even when the whole specimen is still under the elastic state.It can be further concluded that homogeneous assumption for polycrystalline materials is not suitable to study the detailed meso- or micro-mechanisms for damaging and fracturing.

  19. TNF-α Gene Knockout in Triple Negative Breast Cancer Cell Line Induces Apoptosis

    Directory of Open Access Journals (Sweden)

    Valentina Pileczki

    2012-12-01

    Full Text Available Tumor necrosis factor alpha (TNF-α is a pro-inflammatory cytokine involved in the promotion and progression of cancer, including triple negative breast cancer cells. Thus, there is significant interest in understanding the molecular signaling pathways that connect TNF-α with the survival of tumor cells. In our experiments, we used as an in vitro model for triple negative breast cancer the cell line Hs578T. The purpose of this study is to determine the gene expression profiling of apoptotic signaling networks after blocking TNF-α formation by using specially designed siRNA molecules to target TNF-α messenger RNA. Knockdown of TNF-α gene was associated with cell proliferation inhibition and apoptosis, as observed by monitoring the cell index using the xCELLigence RTCA System and flow cytometry. PCR array technology was used to examine the transcript levels of 84 genes involved in apoptosis. 15 genes were found to be relevant after comparing the treated group with the untreated one of which 3 were down-regulated and 12 up-regulated. The down-regulated genes are all involved in cell survival, whereas the up-regulated ones are involved in and interact with pro-apoptotic pathways. The results described here indicate that the direct target of TNF-α in the Hs578T breast cancer cell line increases the level of certain pro-apoptotic factors that modulate different cellular networks that direct the cells towards death.

  20. Substance P Receptor Signaling Mediates Doxorubicin-Induced Cardiomyocyte Apoptosis and Triple-Negative Breast Cancer Chemoresistance.

    Science.gov (United States)

    Robinson, Prema; Kasembeli, Moses; Bharadwaj, Uddalak; Engineer, Nikita; Eckols, Kris T; Tweardy, David J

    2016-01-01

    Doxorubicin (DOX), an anthracycline, is broadly considered the most active single agent available for treating breast cancer but has been known to induce cardiotoxicity. Although DOX is highly effective in treating triple-negative breast cancer (TNBC), DOX can have poor outcomes owing to induction of chemoresistance. There is an urgent need to develop new therapies for TNBC aimed at improving DOX outcome and DOX-induced cardiotoxicity. Substance P (SP), a neuropeptide involved in pain transmission is known to stimulate production of reactive oxygen species (ROS). Elevated cardiac ROS is linked with heart injury and failure. We investigated the role of SP in chemotherapy-associated death of cardiomyocytes and chemoresistance. We showed that pretreating a cardiomyocyte cell line (H9C2) and a TNBC cell line (MDA-MB 231) with aprepitant, a SP receptor antagonist that is routinely used to treat chemotherapy-associated associated nausea, decreased DOX-induced reduction of cell viability, apoptotic cell death, and ROS production in cardiomyocytes and increased DOX-induced reduction of cell viability, apoptotic cell death, and ROS production in TNBC cells compared with cells treated with DOX alone. Our findings demonstrate the ability of aprepitant to decrease DOX-induced killing of cardiomyocytes and to increase cancer cell sensitivity to DOX, which has tremendous clinical significance.

  1. Substance P Receptor Signaling Mediates Doxorubicin-Induced Cardiomyocyte Apoptosis and Triple-Negative Breast Cancer Chemoresistance

    Directory of Open Access Journals (Sweden)

    Prema Robinson

    2016-01-01

    Full Text Available Doxorubicin (DOX, an anthracycline, is broadly considered the most active single agent available for treating breast cancer but has been known to induce cardiotoxicity. Although DOX is highly effective in treating triple-negative breast cancer (TNBC, DOX can have poor outcomes owing to induction of chemoresistance. There is an urgent need to develop new therapies for TNBC aimed at improving DOX outcome and DOX-induced cardiotoxicity. Substance P (SP, a neuropeptide involved in pain transmission is known to stimulate production of reactive oxygen species (ROS. Elevated cardiac ROS is linked with heart injury and failure. We investigated the role of SP in chemotherapy-associated death of cardiomyocytes and chemoresistance. We showed that pretreating a cardiomyocyte cell line (H9C2 and a TNBC cell line (MDA-MB 231 with aprepitant, a SP receptor antagonist that is routinely used to treat chemotherapy-associated associated nausea, decreased DOX-induced reduction of cell viability, apoptotic cell death, and ROS production in cardiomyocytes and increased DOX-induced reduction of cell viability, apoptotic cell death, and ROS production in TNBC cells compared with cells treated with DOX alone. Our findings demonstrate the ability of aprepitant to decrease DOX-induced killing of cardiomyocytes and to increase cancer cell sensitivity to DOX, which has tremendous clinical significance.

  2. The novel triple monoamine reuptake inhibitor tesofensine induces sustained weight loss and improves glycemic control in the diet-induced obese rat: comparison to sibutramine and rimonabant

    DEFF Research Database (Denmark)

    Hansen, Henrik H; Hansen, Gitte; Tang-Christensen, Mads

    2010-01-01

    Tesofensine, a novel triple monoamine reuptake inhibitor, produces a significant weight loss in humans. The present study aimed at characterizing the weight-reducing effects of tesofensine in a rat model of diet-induced obesity. Sibutramine and rimonabant were used as reference comparators....... Compared to baseline, long-term treatment with tesofensine (28 days, 1.0 or 2.5mg/kg, p.o.) resulted in a significant, dose-dependent and sustained weight loss of 5.7 and 9.9%, respectively. Sibutramine (7.5mg/kg, p.o.) treatment caused a sustained weight loss of 7.6%, whereas the employed dose...

  3. Triple point induced by targeted autonomization on interdependent scale free networks

    CERN Document Server

    Valdez, L D; Braunstein, L A

    2013-01-01

    Many man-made networks support each other to provide efficient services and resources to the customers, despite that this support produces a strong interdependency between the individual networks. Thus an initial failure of a fraction $1-p$ of nodes in one network, exposes the system to cascade of failures and, as a consequence, to a full collapse of the overall system. Therefore it is important to develop efficient strategies to avoid the collapse by increasing the robustness of the individual networks against failures. Here, we provide an exact theoretical approach to study the evolution of the cascade of failures on interdependent networks when a fraction $\\alpha$ of the nodes with higher connectivity in each individual network are autonomous. With this pattern of interdependency we found, for pair of heterogeneous networks, two critical percolation thresholds that depend on $\\alpha$, separating three regimes with very different network's final sizes that converge into a triple point in the plane $p-\\alpha...

  4. Tunneling induced transparency and controllable group velocity in triple and multiple quantum-dot molecules

    CERN Document Server

    Tian, Si-Cong; Wan, Ren-Gang; Ning, Yong-Qiang; Wang, Li-Jun

    2013-01-01

    We analyze the interaction of a triple quantum dot molecules controlled by the tunneling coupling instead of coupling laser. A general analytic expression for the steady-state linear susceptibility for a probe-laser field is obtained and we show that the system can exhibit two transparency windows. The group velocity of the probe-laser pulse is also analyzed. By changing the tunneling couplings, two laser pulses with different central frequency can propagate with the same group velocity. And the group velocity can be as low as 300 m/s in our system. We extend our analysis to the case of multiple quantum dot molecules (the number of the quantum dots is N) and show that the system can exhibit at most N-1 transparency windows. And at most N-1 laser pulses with different central frequencies can be slowed down.

  5. Lévy-noise-induced transport in a rough triple-well potential

    Science.gov (United States)

    Li, Yongge; Xu, Yong; Kurths, Jürgen; Yue, Xiaole

    2016-10-01

    Rough energy landscape and noisy environment are two common features in many subjects, such as protein folding. Due to the wide findings of bursting or spiking phenomenon in biology science, small diffusions mixing large jumps are adopted to model the noisy environment that can be properly described by Lévy noise. We combine the Lévy noise with the rough energy landscape, modeled by a potential function superimposed by a fast oscillating function, and study the transport of a particle in a rough triple-well potential excited by Lévy noise, rather than only small perturbations. The probabilities of a particle staying in the middle well are considered under different amplitudes of roughness to find out how roughness affects the steady-state probability density function. Variations in the mean first passage time from the middle well to the right well have been investigated with respect to Lévy parameters and amplitudes of the roughness. In addition, we have examined the influences of roughness on the splitting probabilities of the first escape from the middle well. We uncover that the roughness can enhance significantly the first escape of a particle from the middle well, especially for different skewness parameters, but weak differences are found for stability index and noise intensity on the probabilities a particle staying in the middle well and splitting probability to the right.

  6. Exponential triples

    CERN Document Server

    Sisto, Alessandro

    2011-01-01

    Using ultrafilter techniques we show that in any partition of $\\mathbb{N}$ into 2 cells there is one cell containing infinitely many exponential triples, i.e. triples of the kind $a,b,a^b$ (with $a,b>1$). Also, we will show that any multiplicative $IP^*$ set is an "exponential $IP$ set", the analogue of an $IP$ set with respect to exponentiation.

  7. Administration of ascorbic acid to prevent bleaching-induced tooth sensitivity: a randomized triple-blind clinical trial.

    Science.gov (United States)

    de Paula, E A; Kossatz, S; Fernandes, D; Loguercio, A D; Reis, A

    2014-01-01

    This study evaluated the effect of ascorbic acid, 500 mg every eight hours, on bleaching-induced tooth sensitivity. A triple-blind, parallel design, and placebo-controlled randomized clinical trial was conducted on 39 adults. The pills (placebo or ascorbic acid) were administered three times per day for 48 hours; the first dose was given one hour prior to each bleaching session. Two bleaching sessions with 35% hydrogen peroxide gel were performed with a one-week interval. Tooth sensitivity was recorded up to 48 hours after bleaching. The color evaluation was performed before and 30 days after bleaching. The absolute risk and intensity of tooth sensitivity were evaluated by Fisher exact and Mann-Whitney U-tests, respectively. Color changes were evaluated by unpaired t-test (α=0.05). There were no significant differences in the absolute risk and intensity of tooth sensitivity and color change between the groups. Both groups showed a similar risk of tooth sensitivity (p>0.05). The perioperative use of an antioxidant, such as ascorbic acid (500 mg, three times daily) perorally, was not able to prevent bleaching-induced tooth sensitivity or reduce its intensity.

  8. Applying Roberts' Triple ABCD Model in the aftermath of crisis-inducing and trauma-inducing community disasters.

    Science.gov (United States)

    Roberts, Albert R

    2006-01-01

    Natural and man-made community disasters, such as hurricanes, earthquakes, school shootings, and mass terrorist attacks, heavily impact the safety, mental health, and well-being of large numbers of individuals, families and groups. Millions of individuals who experience acute crisis episodes or psychological trauma are not consistently provided with the early psychological interventions they urgently need. There is a critical need for tools and a framework to quickly and effectively promote interventions. This article presents one such effort, the Roberts' Triple ABCD Model. This model is an up-to-date and integrated conceptual framework that helps to provide the foundation for developing a unified standard of care for crisis and disaster mental health interventions. This model can be useful in determining which early intervention methods and techniques are most likely to reduce traumatic stress, treat acute crisis and psychosocial symptoms, and promote recovery.

  9. Down-regulation of hypoxia-inducible factor-1 suppresses malignant biological behavior of triple-negative breast cancer cells.

    Science.gov (United States)

    Wang, Fang; Chang, Miaomiao; Shi, Yonghong; Jiang, Lili; Zhao, Jing; Hai, Ling; Sharen, Gaowa; Du, Hua

    2014-01-01

    This study is to investigate the effect and mechanism of reduced hypoxia-inducible factor (HIF)-1a expression on malignant behavior of MDA-MB-231 cells. HIF-1α expression was interfered by siRNA. Western blot was used to detect protein expression of HIF-1α, active fragments of caspase 3 and vimentin. Cell count, flow cytometry and Hoechst staining were used to evaluate cell growth and apoptosis. Matrigel invasion and wound scratch assay were performed to measure the ability of cell invasion and migration. After MDA-MB-231 cells were transfected with HIF-1α-targeted siRNA, HIF-1α protein expression was successfully interrupted and cell growth was retarded. Compared with random siRNA group, reduced HIF-1α protein expression in HIF-1α-targeted siRNA group facilitated cell apoptosis but had no effect on cell cycle. In addition, cells treated with HIF-1α-targeted siRNA expressed active fragments of caspase 3 (17 and 12 kD) after serum starvation for 0 to 60 h. Caspase 3 activity assay further confirmed the above finding. Reduced HIF-1α expression impaired the migration and invasiveness with a reduction in the expression of vimentin and CK18 protein. Inhibition of HIF-1α protein synthesis or enhancement of its degradation reversed its malignant phenotypes and could probably be a potential means for the treatment of triple-negative breast cancer.

  10. Dillenia suffruticosa dichloromethane root extract induced apoptosis towards MDA-MB-231 triple-negative breast cancer cells.

    Science.gov (United States)

    Foo, Jhi Biau; Saiful Yazan, Latifah; Tor, Yin Sim; Wibowo, Agustono; Ismail, Norsharina; Armania, Nurdin; Cheah, Yoke Kqueen; Abdullah, Rasedee

    2016-07-01

    Dillenia suffruticosa is traditionally used for treatment of cancerous growth including breast cancer in Malaysia. Dillenia suffruticosa is a well-known medicinal plant in Malaysia for the treatment of cancer. Nevertheless, no study has been reported the cytotoxicity of this plant towards MDA-MB-231 triple-negative breast cancer cells. The present study was designed to investigate the mode of cell death and signalling pathways of MDA-MB-231 cells treated with dichloromethane Dillenia suffruticosa root extract (DCM-DS). Extraction of Dillenia suffruticosa root was performed by the use of sequential solvent procedure. The cytotoxicity of DCM-DS was determined by using MTT assay. The mode of cell death was evaluated by using an inverted light microscope and flow cytometry analysis using Annexin-V/PI. Cell cycle analysis and measurement of reactive oxygen species level were performed by using flow cytometry. The cells were treated with DCM-DS and antioxidants α-tocopherol or ascorbic acid to evaluate the involvement of ROS in the cytotoxicity of DCM-DS. Effect of DCM-DS on the expression of antioxidant, apoptotic, growth, survival genes and proteins were analysed by using GeXP-based multiplex system and Western blot, respectively. The cytotoxicity of compounds isolated from DCM-DS was evaluated towards MDA-MB-231 cells using MTT assay. DCM-DS induced apoptosis, G2/M phase cell cycle arrest and oxidative stress in MDA-MB-231 cells. The induction of apoptosis in MDA-MB-231 cells by DCM-DS is possibly due to the activation of pro-apoptotic JNK1 and down-regulation of anti-apoptotic ERK1, which in turn down-regulates anti-apoptotic BCL-2 to increase the BAX/BCL-2 ratio to initiate the mitochondrial apoptotic pathway. The cell cycle arrest in DCM-DS-treated MDA-MB-231 cells is possibly via p53-independent but p21-dependent pathway. A total of 3 triterpene compounds were isolated from DCM-DS. Betulinic acid appears to be the most major and most cytotoxic compound in DCM

  11. Silver nanoparticles induce tight junction disruption and astrocyte neurotoxicity in a rat blood–brain barrier primary triple coculture model

    Directory of Open Access Journals (Sweden)

    Xu L

    2015-09-01

    Full Text Available Liming Xu,1,2,* Mo Dan,1,* Anliang Shao,1 Xiang Cheng,1,3 Cuiping Zhang,4 Robert A Yokel,5 Taro Takemura,6 Nobutaka Hanagata,6 Masami Niwa,7,8 Daisuke Watanabe7,81National Institutes for Food and Drug Control, No 2, Temple of Heaven, Beijing, 2School of Information and Engineering, Wenzhou Medical University, Wenzhou, 3School of Materials Science and Engineering, Southwest Jiaotong University, Chengdu, 4Beijing Neurosurgical Institute, Capital Medical University, Beijing, People’s Republic of China; 5College of Pharmacy, University of Kentucky, Lexington, KY, USA; 6Nanotechnology Innovation Station for Nanoscale Science and Technology, National Institute for Materials Science, Tsukuba, Ibaraki, 7Department of Pharmacology, Nagasaki University, 8BBB Laboratory, PharmaCo-Cell Company, Ltd., Nagasaki, Japan*These authors contributed equally to this workBackground: Silver nanoparticles (Ag-NPs can enter the brain and induce neurotoxicity. However, the toxicity of Ag-NPs on the blood–brain barrier (BBB and the underlying mechanism(s of action on the BBB and the brain are not well understood.Method: To investigate Ag-NP suspension (Ag-NPS-induced toxicity, a triple coculture BBB model of rat brain microvascular endothelial cells, pericytes, and astrocytes was established. The BBB permeability and tight junction protein expression in response to Ag-NPS, NP-released Ag ions, and polystyrene-NP exposure were investigated. Ultrastructural changes of the microvascular endothelial cells, pericytes, and astrocytes were observed using transmission electron microscopy (TEM. Global gene expression of astrocytes was measured using a DNA microarray.Results: A triple coculture BBB model of primary rat brain microvascular endothelial cells, pericytes, and astrocytes was established, with the transendothelial electrical resistance values >200 Ω·cm2. After Ag-NPS exposure for 24 hours, the BBB permeability was significantly increased and expression of the

  12. Suppression of the emittance growth induced by coherent synchrotron radiation in triple-bend achromat

    CERN Document Server

    Huang, Xiyang; Cui, Xiaohao; Xu, Gang

    2014-01-01

    Coherent synchrotron radiation (CSR) effect at a bending path plays an important role in transverse emittance dilution in high-brightness light sources and linear colliders, where the electron beams are of short bunch length and of high peak current. Suppression of the emittance growth induced by CSR is essential and critical to preserve the beam quality and to help improve the machine performance. To evaluate the CSR effect analytically, we have proposed a novel method, which enabled us to obtain generic conditions of cancelling the CSR linear effect in a two-dipole achromat. In this paper, it illustrates that with this method the CSR-cancellation condition can be obtained for a TBA with symmetric layout, which is independent of concrete element parameters, and to a large extent, the initial beam distribution. Implementation of found condition in concrete optics design of a TBA is discussed, and the proposed condition is verified through numerical simulations.

  13. p53 deficiency induces cancer stem cell pool expansion in a mouse model of triple-negative breast tumors.

    Science.gov (United States)

    Chiche, A; Moumen, M; Romagnoli, M; Petit, V; Lasla, H; Jézéquel, P; de la Grange, P; Jonkers, J; Deugnier, M-A; Glukhova, M A; Faraldo, M M

    2016-10-24

    Triple-negative breast cancer is a heterogeneous disease characterized by the expression of basal cell markers, no estrogen or progesterone receptor expression and a lack of HER2 overexpression. Triple-negative tumors often display activated Wnt/β-catenin signaling and most have impaired p53 function. We studied the interplay between p53 loss and Wnt/β-catenin signaling in stem cell function and tumorigenesis, by deleting p53 from the mammary epithelium of K5ΔNβcat mice displaying a constitutive activation of Wnt/β-catenin signaling in basal cells. K5ΔNβcat transgenic mice present amplification of the basal stem cell pool and develop triple-negative mammary carcinomas. The loss of p53 in K5ΔNβcat mice led to an early expansion of mammary stem/progenitor cells and accelerated the formation of triple-negative tumors. In particular, p53-deficient tumors expressed high levels of integrins and extracellular matrix components and were enriched in cancer stem cells. They also overexpressed the tyrosine kinase receptor Met, a feature characteristic of human triple-negative breast tumors. The inhibition of Met kinase activity impaired tumorsphere formation, demonstrating the requirement of Met signaling for cancer stem cell growth in this model. Human basal-like breast cancers with predicted mutated p53 status had higher levels of MET expression than tumors with wild-type p53. These results connect p53 loss and β-catenin activation to stem cell regulation and tumorigenesis in triple-negative cancer and highlight the role of Met signaling in maintaining cancer stem cell properties, revealing new cues for targeted therapies.Oncogene advance online publication, 24 October 2016; doi:10.1038/onc.2016.396.

  14. Increase of hematopoietic responses by triple or single helical conformer of an antitumor (1-->3)-beta-D-glucan preparation, Sonifilan, in cyclophosphamide-induced leukopenic mice.

    Science.gov (United States)

    Tsuzuki, A; Tateishi, T; Ohno, N; Adachi, Y; Yadomae, T

    1999-01-01

    It has been suggested that the immunopharmacological activity of soluble (1-->3)-beta-D-glucan depends on its conformation in mice. In this study, we examined the relationship between the conformation of Sonifilan (SPG) and hematopietic responses in cyclophosphamide (Cy)-induced leukopenic mice. SPG, a high molecular weight (1-->3)-beta-D-glucan, has a triple helical conformation in water, and it was changed by treatment with aqueous sodium hydroxide to the single helical conformer (SPG-OH). The effects of SPG or SPG-OH on hematopoietic responses in cyclophosphamide induced leukopenic mice were investigated by monitoring i) gene expression of cytokines by RT-PCR, ii) protein synthesis of interleukin 6 (IL-6) by ELISA and iii) colony formation of bone marrow cells (BMC). The mice administered Cy and SPG or SPG-OH expressed and produced higher levels of IL-6 mRNA and protein than the mice administered only Cy. Gene expression of NK1.1 was also induced by Cy/SPG (or SPG-OH) treatment. Induced gene expression of stem cell factor (SCF) and macrophage-colony stimulating factor (M-CSF) by SPG/SPG-OH were also found in in vitro culture of BMC from Cy treated mice. These results strongly suggested that conformation of the glucans, single and triple helix, are independent of the hematopietic response.

  15. Design of a triple-bend isochronous achromat with minimum coherent-synchrotron-radiation-induced emittance growth

    Science.gov (United States)

    Venturini, M.

    2016-06-01

    Using a 1D steady-state free-space coherent synchrotron radiation (CSR) model, we identify a special design setting for a triple-bend isochronous achromat that yields vanishing emittance growth from CSR. When a more refined CSR model with transient effects is included in the analysis, numerical simulations show that the main effect of the transients is to shift the emittance growth minimum slightly, with the minimum changing only modestly.

  16. Reconstruction of pathway modification induced by nicotinamide using multi-omic network analyses in triple negative breast cancer

    OpenAIRE

    Kim, Ji Young; Lee, Hyebin; Woo, Jongmin; Yue, Wang; Kim, Kwangsoo; Choi, Seongmin; Jang, Ja-June; Kim, Youngsoo; Park, In Ae; Han, Dohyun; Ryu, Han Suk

    2017-01-01

    Triple negative breast cancer (TNBC) is characterized by an aggressive biological behavior in the absence of a specific target agent. Nicotinamide has recently been proven to be a novel therapeutic agent for skin tumors in an ONTRAC trial. We performed combinatory transcriptomic and in-depth proteomic analyses to characterize the network of molecular interactions in TNBC cells treated with nicotinamide. The multi-omic profiles revealed that nicotinamide drives significant functional alteratio...

  17. Quercetin induces apoptosis and cell cycle arrest in triple-negative breast cancer cells through modulation of Foxo3a activity.

    Science.gov (United States)

    Nguyen, Lich Thi; Lee, Yeon-Hee; Sharma, Ashish Ranjan; Park, Jong-Bong; Jagga, Supriya; Sharma, Garima; Lee, Sang-Soo; Nam, Ju-Suk

    2017-03-01

    Quercetin, a plant-derived flavonoid found in fruits, vegetables and tea, has been known to possess bioactive properties such as anti-oxidant, anti-inflammatory and anti-cancer. In this study, anti-cancer effect of quercetin and its underlying mechanisms in triple-negative breast cancer cells was investigated. MTT assay showed that quercetin reduced breast cancer cell viability in a time and dose dependent manner. For this, quercetin not only increased cell apoptosis but also inhibited cell cycle progression. Moreover, quercetin increased FasL mRNA expression and p51, p21 and GADD45 signaling activities. We also observed that quercetin induced protein level, transcriptional activity and nuclear translocation of Foxo3a. Knockdown of Foxo3a caused significant reduction in the effect of quercetin on cell apoptosis and cell cycle arrest. In addition, treatment of JNK inhibitor (SP 600125) abolished quercetin-stimulated Foxo3a activity, suggesting JNK as a possible upstream signaling in regulation of Foxo3a activity. Knockdown of Foxo3a and inhibition of JNK activity reduced the signaling activities of p53, p21 and GADD45, triggered by quercetin. Taken together, our study suggests that quercetin induces apoptosis and cell cycle arrest via modification of Foxo3a signaling in triple-negative breast cancer cells.

  18. Quercetin induces apoptosis and cell cycle arrest in triple-negative breast cancer cells through modulation of Foxo3a activity

    Science.gov (United States)

    Nguyen, Lich Thi; Lee, Yeon-Hee; Sharma, Ashish Ranjan; Park, Jong-Bong; Jagga, Supriya; Sharma, Garima

    2017-01-01

    Quercetin, a plant-derived flavonoid found in fruits, vegetables and tea, has been known to possess bioactive properties such as anti-oxidant, anti-inflammatory and anti-cancer. In this study, anti-cancer effect of quercetin and its underlying mechanisms in triple-negative breast cancer cells was investigated. MTT assay showed that quercetin reduced breast cancer cell viability in a time and dose dependent manner. For this, quercetin not only increased cell apoptosis but also inhibited cell cycle progression. Moreover, quercetin increased FasL mRNA expression and p51, p21 and GADD45 signaling activities. We also observed that quercetin induced protein level, transcriptional activity and nuclear translocation of Foxo3a. Knockdown of Foxo3a caused significant reduction in the effect of quercetin on cell apoptosis and cell cycle arrest. In addition, treatment of JNK inhibitor (SP 600125) abolished quercetin-stimulated Foxo3a activity, suggesting JNK as a possible upstream signaling in regulation of Foxo3a activity. Knockdown of Foxo3a and inhibition of JNK activity reduced the signaling activities of p53, p21 and GADD45, triggered by quercetin. Taken together, our study suggests that quercetin induces apoptosis and cell cycle arrest via modification of Foxo3a signaling in triple-negative breast cancer cells. PMID:28280414

  19. Vitamin D compounds inhibit cancer stem-like cells and induce differentiation in triple negative breast cancer.

    Science.gov (United States)

    Shan, Naing Lin; Wahler, Joseph; Lee, Hong Jin; Bak, Min Ji; Gupta, Soumyasri Das; Maehr, Hubert; Suh, Nanjoo

    2017-10-01

    Triple-negative breast cancer is one of the least responsive breast cancer subtypes to available targeted therapies due to the absence of hormonal receptors, aggressive phenotypes, and the high rate of relapse. Early breast cancer prevention may therefore play an important role in delaying the progression of triple-negative breast cancer. Cancer stem cells are a subset of cancer cells that are thought to be responsible for tumor progression, treatment resistance, and metastasis. We have previously shown that vitamin D compounds, including a Gemini vitamin D analog BXL0124, suppress progression of ductal carcinoma in situ in vivo and inhibit cancer stem-like cells in MCF10DCIS mammosphere cultures. In the present study, the effects of vitamin D compounds in regulating breast cancer stem-like cells and differentiation in triple-negative breast cancer were assessed. Mammosphere cultures, which enriches for breast cancer cells with stem-like properties, were used to assess the effects of 1α,25(OH)2D3 and BXL0124 on cancer stem cell markers in the triple-negative breast cancer cell line, SUM159. Vitamin D compounds significantly reduced the mammosphere forming efficiency in primary, secondary and tertiary passages of mammospheres compared to control groups. Key markers of cancer stem-like phenotype and pluripotency were analyzed in mammospheres treated with 1α,25(OH)2D3 and BXL0124. As a result, OCT4, CD44 and LAMA5 levels were decreased. The vitamin D compounds also down-regulated the Notch signaling molecules, Notch1, Notch2, Notch3, JAG1, JAG2, HES1 and NFκB, which are involved in breast cancer stem cell maintenance. In addition, the vitamin D compounds up-regulated myoepithelial differentiating markers, cytokeratin 14 and smooth muscle actin, and down-regulated the luminal marker, cytokeratin 18. Cytokeratin 5, a biomarker associated with basal-like breast cancer, was found to be significantly down-regulated by the vitamin D compounds. These results suggest that

  20. Cyclotriveratrylene (CTV) as a new chiral triacid scaffold capable of inducing triple helix formation of collagen peptides containing either a native sequence or Pro-Hyp-Gly repeats.

    Science.gov (United States)

    Rump, Erik T; Rijkers, Dirk T S; Hilbers, Hans W; de Groot, Philip G; Liskamp, Rob M J

    2002-10-18

    A new triacid scaffold is described based on the cone-shaped cyclotriveratrylene (CTV) molecule that facilitates the triple helical folding of peptides containing either a unique blood platelet binding collagen sequence or collagen peptides composed of Pro-Hyp-Gly repeats. The latter were synthesized by segment condensation using Fmoc-Pro-Hyp-Gly-OH. Peptides were coupled to this CTV scaffold and also coupled to the Kemp's triacid (KTA) scaffold. After assembly of peptide H-Gly-[Pro-Hyp-Gly]2-Phe-Hyp-Gly-Glu(OAll)-Arg-Gly-Val-Glu (OAll)-Gly-[Pro-Hyp-Gly]2-NH2 (13) by an orthogonal synthesis strategy to both triacid scaffolds, followed by deprotection of the allyl groups, the molecular constructs spontaneously folded into a triple helical structure. In contrast, the non-assembled peptides did not. The melting temperature (Tm) of (+/-) CTV[CH2C(O)N(H)Gly-[Pro-Hyp-Gly]2-Phe-Hyp-Gly-Glu-Arg-Gly-Val-Glu-Gly- [Pro-Hyp-Gly]2-NH2]3 (14) is 19 degrees C, whereas KTA[Gly-Gly-[Pro-Hyp-Gly]2-Phe-Hyp-Gly-Glu-Arg-Gly-Val-Glu-Gly- [Pro-Hyp-Gly]2-NH2]3 (15) has a Tm of 20 degrees C. Thus, it was shown for the first time that scaffolds were also effective in stabilizing the triple helix of native collagen sequences. The different stabilizing properties of the two CTV enantiomers could be measured after coupling of racemic CTV triacid to the collagen peptide, and subsequent chromatographic separation of the diastereomers. After assembly of the two chiral CTV scaffolds to the model peptide H-Gly-Gly-(Pro-Hyp-Gly)5-NH2 (24), the (+)-enantiomer of CTV 28b was found to serve as a better triple helix-inducing scaffold than the (-)-enantiomer 28a. In addition to an effect of the chirality of the CTV scaffold, a certain degree of flexibility between the CTV cone and the folded peptide was also shown to be of importance. Restricting the flexibility from two to one glycine residues resulted in a significant difference between the two collagen mimics 20a and 20b, whereas the difference was

  1. Highly improved photo-induced bias stability of sandwiched triple layer structure in sol-gel processed fluorine-doped indium zinc oxide thin film transistor

    Directory of Open Access Journals (Sweden)

    Dongha Kim

    2016-03-01

    Full Text Available In order to improve the reliability of TFT, an Al2O3 insulating layer is inserted between active fluorine doped indium zinc oxide (IZO:F thin films to form a sandwiched triple layer. All the thin films were fabricated via low-cost sol-gel process. Due to its large energy bandgap and high bonding energy with oxygen atoms, the Al2O3 layer acts as a photo-induced positive charge blocking layer that effectively blocks the migration of both holes and V o2+ toward the interface between the gate insulator and the semiconductor. The inserted Al2O3 triple layer exhibits a noticeably low turn on voltage shift of −0.7 V under NBIS as well as the good TFT performance with a mobility of 10.9 cm2/V ⋅ s. We anticipate that this approach can be used to solve the stability issues such as NBIS, which is caused by inescapable oxygen vacancies.

  2. Zerumbone suppresses IL-1β-induced cell migration and invasion by inhibiting IL-8 and MMP-3 expression in human triple-negative breast cancer cells.

    Science.gov (United States)

    Han, Jeonghun; Bae, Soo Youn; Oh, Soo-Jin; Lee, Jeongmin; Lee, Jun Ho; Lee, Hyun-Chul; Lee, Se Kyung; Kil, Won Ho; Kim, Seok Won; Nam, Seok Jin; Kim, Sangmin; Lee, Jeong Eon

    2014-11-01

    Inflammation is a key regulatory process in cancer development. Prolonged exposure of breast tumor cells to inflammatory cytokines leads to epithelial-mesenchymal transition, which is the principal mechanism involved in metastasis and tumor invasion. Interleukin (IL)-1β is a major inflammatory cytokine in a variety of tumors. To date, the regulatory mechanism of IL-1β-induced cell migration and invasion has not been fully elucidated. Here, we investigated the effect of zerumbone (ZER) on IL-1β-induced cell migration and invasion in breast cancer cells. The levels of IL-8 and matrix metalloproteinase (MMP)-3 mRNA were analyzed by real-time polymerase chain reaction. The levels of secreted IL-8 and MMP-3 protein were analyzed by enzyme-linked immunosorbent assay and western blot analysis, respectively. Cell invasion and migration was detected by Boyden chamber assay. The levels of IL-8 and MMP-3 expression were significantly increased by IL-1β treatment in Hs578T and MDA-MB231 cells. On the other hand, IL-1β-induced IL-8 and MMP-3 expression was decreased by ZER. Finally, IL-1β-induced cell migration and invasion were decreased by ZER in Hs578T and MDA-MB231 cells. ZER suppresses IL-1β-induced cell migration and invasion by inhibiting IL-8 expression and MMP-3 expression in TNBC cells. ZER could be a promising therapeutic drug for treatment of triple-negative breast cancer patients.

  3. Sorafenib analogue SC-60 induces apoptosis through the SHP-1/STAT3 pathway and enhances docetaxel cytotoxicity in triple-negative breast cancer cells.

    Science.gov (United States)

    Liu, Chun-Yu; Su, Jung-Chen; Huang, Tzu-Ting; Chu, Pei-Yi; Huang, Chun-Teng; Wang, Wan-Lun; Lee, Chia-Han; Lau, Ka-Yi; Tsai, Wen-Chun; Yang, Hsiu-Ping; Shiau, Chung-Wai; Tseng, Ling-Ming; Chen, Kuen-Feng

    2017-03-01

    Recurrent triple-negative breast cancer (TNBC) needs new therapeutic targets. Src homology region 2 domain-containing phosphatase-1 (SHP-1) can act as a tumor suppressor by dephosphorylating oncogenic kinases. One major target of SHP-1 is STAT3, which is highly activated in TNBC. In this study, we tested a sorafenib analogue SC-60, which lacks angiokinase inhibition activity, but acts as a SHP-1 agonist, in TNBC cells. SC-60 inhibited proliferation and induced apoptosis by dephosphorylating STAT3 in both a dose- and time-dependent manner in TNBC cells (MDA-MB-231, MDA-MB-468, and HCC1937). By contrast, ectopic expression of STAT3 rescued the anticancer effect induced by SC-60. SC-60 also increased the SHP-1 activity, but this effect was inhibited when the N-SH2 domain (DN1) was deleted or with SHP-1 point mutation (D61A), implying that SHP-1 is the major target of SC-60 in TNBC. The use of SC-60 in combination with docetaxel synergized the anticancer effect induced by SC-60 through the SHP-1/STAT3 pathway in TNBC cells. Importantly, SC-60 also displayed a significant antitumor effect in an MDA-MB-468 xenograft model by modulating the SHP-1/STAT3 axis, indicating the anticancer potential of SC-60 in TNBC treatment. Targeting SHP-1/p-STAT3 and the potential combination of SHP-1 agonist with chemotherapeutic docetaxel is a feasible therapeutic strategy for TNBC.

  4. Comparative Efficacy of Aloe vera and Benzydamine Mouthwashes on Radiation-induced Oral Mucositis: A Triple-blind, Randomised, Controlled Clinical Trial.

    Science.gov (United States)

    Sahebjamee, Mahnaz; Mansourian, Arash; Hajimirzamohammad, Mohammad; Mohammad, Haji Mirza Mohammad; Zadeh, Mohsen Taghi; Bekhradi, Reza; Kazemian, Ali; Manifar, Soheila; Ashnagar, Sajjad; Doroudgar, Kiavash

    2015-01-01

    To compare the efficacy of an Aloe vera mouthwash with a benzydamine mouthwash in the alleviation of radiation- induced mucositis in head and neck cancer patients using a triple-blind, randomised controlled trial. Twenty-six eligible head and neck cancer patients who were to receive conventional radiation therapy at the radiation oncology department were randomised to receive an Aloe vera mouthwash or a benzydamine mouthwash. Mucositis severity was assessed during the course of radiation therapy using the WHO grading system. At baseline, there was no difference in the distribution of mucositis severity between the two groups. The mean interval between radiation therapy and onset of mucositis was similar for both groups (Aloe vera 15.69±7.77 days, benzydamine 15.85±12.96 days). The mean interval between the start of radiation therapy and the maximum severity of mucositis were was also similar in both the Aloe vera and benzydamine groups (Aloe vera 23.38±10.75 days, benzydamine 23.54±15.45 days). Mean changes of mucositis severity over time in both groups were statistically similar and the effect of both treatments did not change signficantly with time (p=0.09). Aloe vera mouthwash was as beneficial as benzydamine mouthwash in alleviating the severity of radiation-induced mucositis and showed no side effects. The Aloe vera mouthwash could be an alternative agent in the treatment of radiation-induced mucositis in patients with head and neck cancers.

  5. Aggregation-induced white-light emission from the triple-stranded dinuclear Sm(iii) complex.

    Science.gov (United States)

    Leng, Jiaqi; Li, Hongfeng; Chen, Peng; Sun, Wenbin; Gao, Ting; Yan, Pengfei

    2014-08-28

    A novel bis-β-diketone ligand, 4,4'-bis(4,4,4-trifluoro-1,3-dioxobutyl)(phenoxy)-1,1'-binaphthalene (BTPB), is designed for synthesis of a white light emissive lanthanide complex. The ligand bears two benzoyl β-diketonate sites linked by a 1,1'-binaphthoxy spacer. Reaction of the doubly negatively charged bis-bidentate ligand with lanthanide ions forms triple-stranded dinuclear complexes Sm2(BTPB)3(H2O)4 () and Gd2(BTPB)3(H2O)4 (), which have been fully characterized by various spectroscopic techniques. UV-Vis absorption and emission spectroscopic techniques are used to investigate photophysical properties of the ligand and its complexes in THF and CHCl3. In some cases aggregation of the ligand results in the appearance of a new luminescence band at about 510 nm in addition to the monomer fluorescence. In complex , partial energy transfer from BTPB results in Sm(iii)-based red light emission in addition to the BTPB-based blue/green emission. With the variation of the excited wavelength and concentration of the solution, complex shows a tunable white light emission with the balance of three primary colors. This is an unusual case of observation of white light emission from a single molecule Sm(iii) complex.

  6. Expression of the hypoxia-inducible monocarboxylate transporter MCT4 is increased in triple negative breast cancer and correlates independently with clinical outcome

    Energy Technology Data Exchange (ETDEWEB)

    Doyen, J. [Department of Radiation Oncology, Centre A. Lacassagne, Nice (France); Trastour, C. [Department of Gynecology, Archet II Hospital, 06202 Nice (France); Ettore, F.; Peyrottes, I.; Toussant, N. [Department of Pathology, Centre A. Lacassagne, Nice (France); Gal, J. [Department of Medical Statistics, Centre A. Lacassagne, Nice (France); Ilc, K.; Roux, D. [Institute for Research on Cancer and Aging (IRCAN), University of Nice, Centre A. Lacassagne, 06189 Nice (France); Parks, S.K. [Centre Scientifique de Monaco (CSM) (Monaco); Ferrero, J.M. [Department of Medical Oncology, Centre A. Lacassagne, Nice (France); Pouysségur, J., E-mail: jacques.pouyssegur@unice.fr [Institute for Research on Cancer and Aging (IRCAN), University of Nice, Centre A. Lacassagne, 06189 Nice (France); Centre Scientifique de Monaco (CSM) (Monaco)

    2014-08-15

    Highlights: • Glycolytic markers are highly expressed in triple negative breast cancers. • Lactate/H{sup +} symporter MCT4 demonstrated the strongest deleterious impact on survival. • MCT4 should serve as a new prognostic factor in node-negative breast cancers. - Abstract: Background: {sup 18}Fluor-deoxy-glucose PET-scanning of glycolytic metabolism is being used for staging in many tumors however its impact on prognosis has never been studied in breast cancer. Methods: Glycolytic and hypoxic markers: glucose transporter (GLUT1), carbonic anhydrase IX (CAIX), monocarboxylate transporter 1 and 4 (MCT1, 4), MCT accessory protein basigin and lactate-dehydrogenase A (LDH-A) were assessed by immunohistochemistry in two cohorts of breast cancer comprising 643 node-negative and 127 triple negative breast cancers (TNBC) respectively. Results: In the 643 node-negative breast tumor cohort with a median follow-up of 124 months, TNBC were the most glycolytic (≈70%), followed by Her-2 (≈50%) and RH-positive cancers (≈30%). Tumoral MCT4 staining (without stromal staining) was a strong independent prognostic factor for metastasis-free survival (HR = 0.47, P = 0.02) and overall-survival (HR = 0.38, P = 0.002). These results were confirmed in the independent cohort of 127 cancer patients. Conclusion: Glycolytic markers are expressed in all breast tumors with highest expression occurring in TNBC. MCT4, the hypoxia-inducible lactate/H{sup +} symporter demonstrated the strongest deleterious impact on survival. We propose that MCT4 serves as a new prognostic factor in node-negative breast cancer and can perhaps act soon as a theranostic factor considering the current pharmacological development of MCT4 inhibitors.

  7. Toxicity evaluation of magnetic hyperthermia induced by remote actuation of magnetic nanoparticles in 3D micrometastasic tumor tissue analogs for triple negative breast cancer.

    Science.gov (United States)

    Stocke, Nathanael A; Sethi, Pallavi; Jyoti, Amar; Chan, Ryan; Arnold, Susanne M; Hilt, J Zach; Upreti, Meenakshi

    2017-03-01

    Magnetic hyperthermia as a treatment modality is acquiring increased recognition for loco-regional therapy of primary and metastatic lung malignancies by pulmonary delivery of magnetic nanoparticles (MNP). The unique characteristic of magnetic nanoparticles to induce localized hyperthermia in the presence of an alternating magnetic field (AMF) allows for preferential killing of cells at the tumor site. In this study we demonstrate the effect of hyperthermia induced by low and high dose of MNP under the influence of an AMF using 3D tumor tissue analogs (TTA) representing the micrometastatic, perfusion independent stage of triple negative breast cancer (TNBC) that infiltrates the lungs. While application of inhalable magnetic nanocomposite microparticles or magnetic nanocomposites (MnMs) to the micrometastatic TNBC model comprised of TTA generated from cancer and stromal cells, showed no measureable adverse effects in the absence of AMF-exposure, magnetic hyperthermia generated under the influence of an AMF in TTA incubated in a high concentration of MNP (1 mg/mL) caused significant increase in cellular death/damage with mechanical disintegration and release of cell debris indicating the potential of these inhalable composites as a promising approach for thermal treatment of diseased lungs. The novelty and significance of this study lies in the development of methods to evaluate in vitro the application of inhalable composites containing MNPs in thermal therapy using a physiologically relevant metastatic TNBC model representative of the microenvironmental characteristics in secondary lung malignancies.

  8. Preventing and Therapeutic Effect of Propolis in Radiotherapy Induced Mucositis of Head and Neck Cancers: A Triple-Blind, Randomized, Placebo-Controlled Trial

    Science.gov (United States)

    Javadzadeh Bolouri, Abbas; Pakfetrat, Atessa; Tonkaboni, Arghavan; Aledavood, Seyed Amir; Fathi Najafi, Mohsen; Delavarian, Zahra; Shakeri, Mohammad Taghi; Mohtashami, Azade

    2015-01-01

    Background: Mucositis is one of the acute complications of radiotherapy which can ulcerate oral mucosa and cause severe pain and discomfort which can affect oral normal function. Propolis is a natural source of flavenoid which has antiulcer, antibacterial, antifungal, healing and anti-inflammatory effects. Using such an affordable compound without any bad smell or taste that has reasonable price can help the radiotherapy undergoing patients. Objectives: Our goal is assessing the preventing and therapeutic effect of propolis in radiotherapy induced mucositis in patients with head and neck cancer. Patients and Methods: In a randomized triple blind clinical trial, 20 patient were selected randomly to swish and swallow 15 ml of water based extract of propolis mouth wash 3 times a day in the case group (n = 10) and 15 ml placebo mouth wash in control group (n = 10). we use NIC-CTC scale for determining mucositis grading. Results: We use T-test, Man-Whitney, Chi-square, and Friedman as analyzing tests. Case group had significantly (P 0.05). Conclusions: This is a pilot study which shows water based extract of propolis efficiently prevents and heals radiotherapy induced mucositis. PMID:26634113

  9. Stromal Fibroblasts from the Interface Zone of Triple Negative Breast Carcinomas Induced Epithelial-Mesenchymal Transition and its Inhibition by Emodin

    Science.gov (United States)

    Wang, Hao-Yu; Hung, Chao-Ming; Lin, Ying-Chao; Ho, Chi-Tang; Way, Tzong-Der

    2017-01-01

    Triple negative breast cancer” (TNBC) is associated with a higher rate and earlier time of recurrence and worse prognosis after recurrence. In this study, we aimed to examine the crosstalk between fibroblasts and TNBC cells. The fibroblasts were isolated from TNBC patients’ tissue in tumor burden zones, distal normal zones and interface zones. The fibroblasts were indicated as cancer-associated fibroblasts (CAFs), normal zone fibroblasts (NFs) and interface zone fibroblasts (INFs). Our study found that INFs grew significantly faster than NFs and CAFs in vitro. The epithelial BT20 cells cultured with the conditioned medium of INFs (INFs-CM) and CAFs (CAFs-CM) showed more spindle-like shape and cell scattering than cultured with the conditioned medium of NFs (NFs-CM). These results indicated that factors secreted by INFs-CM or CAFs-CM could induce the epithelial-mesenchymal transition (EMT) phenotype in BT20 cells. Using an in vitro co-culture model, INFs or CAFs induced EMT and promoted cancer cell migration in BT20 cells. Interestingly, we found that emodin inhibited INFs-CM or CAFs-CM-induced EMT programming and phenotype in BT20 cells. Previous studies reported that CAFs and INFs-secreted TGF-β promoted human breast cancer cell proliferation, here; our results indicated that TGF-β initiated EMT in BT20 cells. Pretreatment with emodin significantly suppressed the TGF-β-induced EMT and cell migration in BT20 cells. These results suggest that emodin may be used as a novel agent for the treatment of TNBC. PMID:28060811

  10. Transcranial direct current stimulation over the opercular somatosensory region does not influence experimentally induced pain: a triple blind, sham-controlled study

    Science.gov (United States)

    Koyama, Soichiro; Nakagawa, Kei

    2017-01-01

    Transcranial magnetic stimulation (TMS) over the opercular somatosensory region (OP), which includes the secondary somatosensory cortex and the insular cortex, suppresses pain sensation. However, whether transcranial direct current stimulation (tDCS) over the OP has a similar effect on pain sensation remains unknown. We examined whether pain sensation would be suppressed by tDCS over the OP. Our experiment with a triple-blind, sham-controlled, crossover design involved 12 healthy participants. Participants were asked to rate their subjective pain intensity during and after three types of bihemispheric tDCS: right anodal/left cathodal OP tDCS, left anodal/right cathodal OP tDCS (2 mA, 12 min), and sham tDCS (15 s). Pain stimuli were alternately applied to the dorsum of each index finger using intraepidermal electrical stimulation. We observed no significant effect of tDCS over the OP on the perception of experimentally induced pain. Subjective pain intensity did not differ significantly between the three tDCS conditions. The present null results have crucial implications for the selection of optimal stimulation regions and parameters for clinical pain treatment. PMID:27984542

  11. Vaccine-induced protection from egg production losses in commercial turkey breeder hens following experimental challenge with a triple-reassortant H3N2 avian influenza virus.

    Science.gov (United States)

    Kapczynski, Darrell R; Gonder, Eric; Liljebjelke, Karen; Lippert, Ron; Petkov, Daniel; Tilley, Becky

    2009-03-01

    Infections of avian influenza virus (AIV) in turkey breeder hens can cause a decrease in both egg production and quality, resulting in significant production losses. In North Carolina in 2003, a triple-reassortant H3N2 AIV containing human, swine, and avian gene segments was isolated from turkey breeder hens (A/turkey/NC/16108/03). This viral subtype was subsequently isolated from both turkeys and swine in Ohio in 2004, and in Minnesota in 2005, and was responsible for significant losses in turkey production. The objective of this study was to determine if currently available commercial, inactivated avian influenza H3 subtype oil-emulsion vaccines would protect laying turkey hens from egg production losses following challenge with the 2003 H3N2 field virus isolate from North Carolina. Laying turkey hens were vaccinated in the field with two injections of either a commercial monovalent (A/duck/Minnesota/79/79 [H3N4]) or autogenous bivalent (A/turkey/North Carolina/05 (H3N2)-A/turkey/North Carolina/88 [H1N1]) vaccine, at 26 and 30 wk of age, and subsequently challenged under BSL 3-Ag conditions at 32 wk of age. Vaccine-induced efficacy was determined as protection from a 50% decrease in egg production and from a decrease in egg quality within 21 days postchallenge. Results indicate that, following a natural route of challenge (eye drop and intranasal), birds vaccinated with the 2005 North Carolina H3N2 subtype were significantly protected from the drop in egg production observed in both the H3N4 vaccinated and sham-vaccinated hens. The results demonstrate that groups receiving vaccines containing either H3 subtype had a decreased number of unsettable eggs, increased hemagglutination inhibition titers following challenge, and decreased virus isolations from cloacal swabs as compared to the sham-vaccinated group. Phylogenetic analysis of the nucleotide sequence of the HA1 gene segment from the three H3 viruses used in these studies indicated that the two North Carolina

  12. Administration of NaHS attenuates footshock-induced pathologies and emotional and cognitive dysfunction in triple transgenic Alzheimer’s mice

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    Hei-Jen eHuang

    2015-11-01

    Full Text Available Alzheimer's disease (AD is characterized by progressive cognitive decline and neuropsychiatric symptoms. Increasing evidence indicates that environmental risk factors in young adults may accelerate cognitive loss in AD and that hydrogen sulfide (H2S may represent an innovative treatment to slow the progression of AD. Therefore, the aim of this study was to evaluate the effects of NaHS, an H2S donor, in a triple transgenic AD mouse model (3×Tg-AD under footshock with situational reminders (SRs. Inescapable footshock with SRs induced anxiety and cognitive dysfunction as well as a decrease in the levels of plasma H2S and GSH and an increase in IL-6 levels in 3×Tg-AD mice. Under footshock with SR stimulus, amyloid deposition, tau protein hyperphosphorylation, and microgliosis were highly increased in the stress-responsive brain structures, including the hippocampus and amygdala, of the AD mice. Oxidative stress, inflammatory response, and β-site APP cleaving enzyme 1 (BACE1 levels were also increased, and the level of inactivated glycogen synthase kinase-3β (GSK3β (pSer9 was decreased in the hippocampi of AD mice subjected to footshock with SRs. Furthermore, the numbers of cholinergic neurons in the medial septum/diagonal band of Broca (MS/DB and noradrenergic neurons in the locus coeruleus (LC were also decreased in the 3×Tg-AD mice under footshock with SRs. These biochemical hallmarks and pathological presentations were all alleviated by the semi-acute administration of NaHS in the AD mice. Together, these findings suggest that footshock with SRs induces the impairment of spatial cognition and emotion, which involve pathological changes in the peripheral and central systems, including the hippocampus, MS/DB, LC, and BLA, and that the administration of NaHS may be a candidate strategy to ameliorate the progression of neurodegeneration.

  13. Phemindole, a synthetic di-indole derivative maneuvers the store operated calcium entry (SOCE to induce potent anti-carcinogenic activity in human triple negative breast cancer cells

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    Supriya eChakraborty

    2016-05-01

    Full Text Available Triple-negative breast cancer (TNBC, is a specific subtype of epithelial breast tumours that are immuno-histochemically negative for the protein expression of the estrogen receptor (ER, the progesterone receptor (PR and lack over expression/gene amplification of HER2. This subtype of breast cancers is highly metastatic, shows poor prognosis and hence represents an important clinical challenge to researchers worldwide. Thus alternative approaches of drug development for TNBC have gained utmost importance in the present times. Dietary indole and its derivatives have gained prominence as anti-cancer agents and new therapeutic approaches are being developed to target them against TNBC. But a major drawback with 3, 3’di Indolyl methane (DIM is their poor bioavailability and high effective concentration against TNBC. However the Aryl methyl ring substituted analogs of DIM display interesting anti-cancer activity in breast cancer cells. In the current study we report the synthesis of a novel synthetic aryl methyl ring substituted analog of DIM, named as Phemindole as an effective anti-tumor agent against TNBC cells. Furthermore, we enumerated that Phemindole caused ROS mediated mitochondrial-dependent apoptosis in MDAMB-231 cells. Furthermore, Phemindole mediated Store Operated Calcium Entry (SOCE retardation favored inactivation of STIM1 and henceforth activated ER stress to induce apoptosis in TNBC cells. Simultaneously, Phemindole was also found to restrict the in-vitro cell migration through its anti mitotic property and pFAK regulation. Studies extended to ex-ovo and in-vivo mice models further validated the efficacy of Phemindole. Thus our results cumulatively propose Phemindole as a new chemotherapeutic regime which might be effective to target the deadly aspects of the TNBC.

  14. Triple monoamine inhibitor tesofensine decreases food intake, body weight, and striatal dopamine D2/D3 receptor availability in diet-induced obese rats.

    Science.gov (United States)

    van de Giessen, Elsmarieke; de Bruin, Kora; la Fleur, Susanne E; van den Brink, Wim; Booij, Jan

    2012-04-01

    The novel triple monoamine inhibitor tesofensine blocks dopamine, serotonin and norepinephrine re-uptake and is a promising candidate for the treatment of obesity. Obesity is associated with lower striatal dopamine D2 receptor availability, which may be related to disturbed regulation of food intake. This study assesses the effects of chronic tesofensine treatment on food intake and body weight in association with changes in striatal dopamine D2/D3 receptor (D2/3R) availability of diet-induced obese (DIO) rats. Four groups of 15 DIO rats were randomized to one of the following treatments for 28 days: 1. tesofensine (2.0 mg/kg), 2. vehicle, 3. vehicle+restricted diet isocaloric to caloric intake of group 1, and 4. tesofensine (2.0 mg/kg)+ a treatment-free period of 28 days. Caloric intake and weight gain decreased significantly more in the tesofensine-treated rats compared to vehicle-treated rats, which confirms previous findings. After treatment discontinuation, caloric intake and body weight gain gradually increased again. Tesofensine-treated rats showed significantly lower D2/3R availability in nucleus accumbens and dorsal striatum than both vehicle-treated rats and vehicle-treated rats on restricted isocaloric diet. No correlations were observed between food intake or body weight and D2/3R availability. Thus, chronic tesofensine treatment leads to decreased food intake and weight gain. However, this appears not to be directly related to the decreased striatal D2/3R availability, which is mainly a pharmacological effect. Copyright © 2011 Elsevier B.V. and ECNP. All rights reserved.

  15. Delay-Induced Triple-Zero Bifurcation in a Delayed Leslie-Type Predator-Prey Model with Additive Allee Effect

    Science.gov (United States)

    Jiang, Jiao; Song, Yongli; Yu, Pei

    2016-06-01

    In this paper, a Leslie-type predator-prey model with ratio-dependent functional response and Allee effect on prey is considered. We first study the existence of the multiple positive equilibria and their stability. Then we investigate the effect of delay on the distribution of the roots of characteristic equation and obtain the conditions for the occurrence of simple-zero, double-zero and triple-zero singularities. The formulations for calculating the normal form of the triple-zero bifurcation of the delay differential equations are derived. We show that, under certain conditions on the parameters, the system exhibits homoclinic orbit, heteroclinic orbit and periodic orbit.

  16. Temporal Lorentzian spectral triples

    Science.gov (United States)

    Franco, Nicolas

    2014-09-01

    We present the notion of temporal Lorentzian spectral triple which is an extension of the notion of pseudo-Riemannian spectral triple with a way to ensure that the signature of the metric is Lorentzian. A temporal Lorentzian spectral triple corresponds to a specific 3 + 1 decomposition of a possibly noncommutative Lorentzian space. This structure introduces a notion of global time in noncommutative geometry. As an example, we construct a temporal Lorentzian spectral triple over a Moyal-Minkowski spacetime. We show that, when time is commutative, the algebra can be extended to unbounded elements. Using such an extension, it is possible to define a Lorentzian distance formula between pure states with a well-defined noncommutative formulation.

  17. Cyclotriveratrylene (CTV) as a new chiral triacid scaffold capable of inducing triple helix formation of collagen peptides containing either a native sequence or Pro-Hyp-Gly repeats

    NARCIS (Netherlands)

    Rump, ET; Rijkers, DTS; Hilbers, HW; de Groot, PG; Liskamp, RMJ

    2002-01-01

    A new triacid scaffold is described based on the cone-shaped cyclotriveratrylene (CTV) molecule that facilitates the triple, helical folding of peptides containing either a unique blood platelet binding collagen sequence or collagen peptides composed of Pro-Hyp-Gly repeats. The latter were synthesiz

  18. Cellular responses of BRCA1-defective and triple-negative breast cancer cells and in vitro BRCA1 interactions induced by metallo-intercalator ruthenium(II) complexes containing chloro-substituted phenylazopyridine.

    Science.gov (United States)

    Nhukeaw, Tidarat; Temboot, Pornvichai; Hansongnern, Kanidtha; Ratanaphan, Adisorn

    2014-02-07

    Triple-negative breast cancer (TNBC) is defined by the absence of expression of estrogen receptor, progesterone receptor and human epidermal growth factor receptor 2. Breast cancers with a BRCA1 mutation are also frequently triple-negative. Currently, there is a lack of effective therapies and known specific molecular targets for this aggressive breast cancer subtype. To address this concern, we have explored the cellular responses of BRCA1-defective and triple-negative breast cancer cells, and in vitro BRCA1 interactions induced by the ruthenium(II) complexes containing the bidentate ligand, 5-chloro-2-(phenylazo)pyridine. Triple-negative MDA-MB-231, BRCA1-defective HCC1937 and BRCA1-competent MCF-7 breast cancer cell lines were treated with ruthenium(II) complexes. The cytoxoxicity of ruthenium-induced breast cancer cells was evaluated by a real time cellular analyzer (RTCA). Cellular uptake of ruthenium complexes was determined by ICP-MS. Cell cycle progression and apoptosis were assessed using propidium iodide and Annexin V flow cytometry. The N-terminal BRCA1 RING protein was used for conformational and functional studies using circular dichroism and in vitro ubiquitination. HCC1937 cells were significantly more sensitive to the ruthenium complexes than the MDA-MB-231 and MCF-7 cells. Treatment demonstrated a higher degree of cytotoxicity than cisplatin against all three cell lines. Most ruthenium atoms were retained in the nuclear compartment, particularly in HCC1937 cells, after 24 h of incubation, and produced a significant block at the G2/M phase. An increased induction of apoptotic cells as well as an upregulation of p53 mRNA was observed in all tested breast cancer cells. It was of interest that BRCA1 mRNA and replication of BRCA1-defective cells were downregulated. Changes in the conformation and binding constants of ruthenium-BRCA1 adducts were observed, causing inactivation of the RING heterodimer BRCA1/BARD1-mediated E3 ubiquitin ligase activity

  19. Waardecreatie in triple helix : Recepten voor triple helix samenwerking

    NARCIS (Netherlands)

    Vos, P.M.; Vries, F. de

    2016-01-01

    Om innovaties in het veiligheidsdomein te realiseren worden triple helix samenwerkingen gezien als een belangrijke motor. Een triple helix samenwerking is een tijdelijk samenwerkingsverband tussen drie of meer organisaties die middelen, risico’s en opbrengsten delen om individuele organisatiedoelen,

  20. Triple Point Topological Metals

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    Ziming Zhu

    2016-07-01

    Full Text Available Topologically protected fermionic quasiparticles appear in metals, where band degeneracies occur at the Fermi level, dictated by the band structure topology. While in some metals these quasiparticles are direct analogues of elementary fermionic particles of the relativistic quantum field theory, other metals can have symmetries that give rise to quasiparticles, fundamentally different from those known in high-energy physics. Here, we report on a new type of topological quasiparticles—triple point fermions—realized in metals with symmorphic crystal structure, which host crossings of three bands in the vicinity of the Fermi level protected by point group symmetries. We find two topologically different types of triple point fermions, both distinct from any other topological quasiparticles reported to date. We provide examples of existing materials that host triple point fermions of both types and discuss a variety of physical phenomena associated with these quasiparticles, such as the occurrence of topological surface Fermi arcs, transport anomalies, and topological Lifshitz transitions.

  1. Pythagorean Triples from Harmonic Sequences.

    Science.gov (United States)

    DiDomenico, Angelo S.; Tanner, Randy J.

    2001-01-01

    Shows how all primitive Pythagorean triples can be generated from harmonic sequences. Use inductive and deductive reasoning to explore how Pythagorean triples are connected with another area of mathematics. (KHR)

  2. Rational design of a triple helix-specific intercalating ligand.

    Science.gov (United States)

    Escudé, C; Nguyen, C H; Kukreti, S; Janin, Y; Sun, J S; Bisagni, E; Garestier, T; Hélène, C

    1998-03-31

    DNA triple helices offer new perspectives toward oligonucleotide-directed gene regulation. However, the poor stability of some of these structures might limit their use under physiological conditions. Specific ligands can intercalate into DNA triple helices and stabilize them. Molecular modeling and thermal denaturation experiments suggest that benzo[f]pyrido[3, 4-b]quinoxaline derivatives intercalate into triple helices by stacking preferentially with the Hoogsteen-paired bases. Based on this model, it was predicted that a benzo[f]quino[3,4-b]quinoxaline derivative, which possesses an additional aromatic ring, could engage additional stacking interactions with the pyrimidine strand of the Watson-Crick double helix upon binding of this pentacyclic ligand to a triplex structure. This compound was synthesized. Thermal denaturation experiments and inhibition of restriction enzyme cleavage show that this new compound can indeed stabilize triple helices with great efficiency and specificity and/or induce triple helix formation under physiological conditions.

  3. Normalization for triple-target microarray experiments

    Directory of Open Access Journals (Sweden)

    Magniette Frederic

    2008-04-01

    Full Text Available Abstract Background Most microarray studies are made using labelling with one or two dyes which allows the hybridization of one or two samples on the same slide. In such experiments, the most frequently used dyes are Cy3 and Cy5. Recent improvements in the technology (dye-labelling, scanner and, image analysis allow hybridization up to four samples simultaneously. The two additional dyes are Alexa488 and Alexa494. The triple-target or four-target technology is very promising, since it allows more flexibility in the design of experiments, an increase in the statistical power when comparing gene expressions induced by different conditions and a scaled down number of slides. However, there have been few methods proposed for statistical analysis of such data. Moreover the lowess correction of the global dye effect is available for only two-color experiments, and even if its application can be derived, it does not allow simultaneous correction of the raw data. Results We propose a two-step normalization procedure for triple-target experiments. First the dye bleeding is evaluated and corrected if necessary. Then the signal in each channel is normalized using a generalized lowess procedure to correct a global dye bias. The normalization procedure is validated using triple-self experiments and by comparing the results of triple-target and two-color experiments. Although the focus is on triple-target microarrays, the proposed method can be used to normalize p differently labelled targets co-hybridized on a same array, for any value of p greater than 2. Conclusion The proposed normalization procedure is effective: the technical biases are reduced, the number of false positives is under control in the analysis of differentially expressed genes, and the triple-target experiments are more powerful than the corresponding two-color experiments. There is room for improving the microarray experiments by simultaneously hybridizing more than two samples.

  4. Expression of GATA3 in MDA-MB-231 triple-negative breast cancer cells induces a growth inhibitory response to TGFß.

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    Isabel M Chu

    Full Text Available Transforming growth factor (ß1TGFß1 can promote proliferation in late stage cancers but acts as a tumor suppressor in normal epithelial cells and in early stage cancers. Although, the TGFß pathway has been shown to play a key role in tumorigenesis and metastasis, only a limited number of models have been developed to understand this process. Here, we present a novel model system to discern this paradoxical role of TGFß1 using the MDA-MB-231 (MB-231 cell line. The MB-231 triple-negative breast cancer cell line has been extensively characterized and has been shown to continue to proliferate and undergo epithelial-to-mesenchymal transition (EMT upon TGFß1 stimulation. We have previously shown by microarray analysis that expression of GATA3 in MB-231 cells results in reprogramming of these cells from a basal to a luminal subtype associated with a reduction of metastasis and tumorigenesis when implanted as xenografts. We now demonstrate that GATA3 overexpression in these cells results in a reduction of TGFß1 response, reversal of EMT, and most importantly, restoration of sensitivity to the inhibitory effects on proliferation of TGFß1. Microarray analysis revealed that TGFß1 treatment resulted in reduction of several cell cycle effectors in 231-GATA3 cells but not in control cells. Furthermore, our microarray analysis revealed a significant increase of BMP5 in 231-GATA3 cells. We demonstrate that combined treatment of MB-231 control cells with TGFß1 and BMP5 results in a significant reduction of cellular proliferation. Thus, this model offers a means to further investigate potentially novel mechanisms involved in the switch in response to TGFß1 from tumor promoter to tumor suppressor through the reprogramming of a triple-negative breast cancer cell line by the GATA3 transcription factor.

  5. C-MYC-induced upregulation of lncRNA SNHG12 regulates cell proliferation, apoptosis and migration in triple-negative breast cancer.

    Science.gov (United States)

    Wang, Ouchen; Yang, Fan; Liu, Yehuan; Lv, Lin; Ma, Ruimin; Chen, Chuanzhi; Wang, Jiao; Tan, Qiufan; Cheng, Yue; Xia, Erjie; Chen, Yizuo; Zhang, Xiaohua

    2017-01-01

    Triple-negative breast cancer (TNBC) is one of the most aggressive subtypes of breast cancer, with a significantly higher recurrence and mortality rate. There is an urgent need to uncover the mechanism underlying TNBC and establish therapeutic targets. Long non-coding RNAs (lncRNAs) are involved in a series of biological functions and provide novel insights into the molecular mechanism of cancer. Based on their expression specificity and large number, lncRNAs are likely to serve as the basis for clinical applications in oncology. In our previous study, we utilized RNA sequencing (RNA-seq) to explore the lncRNAs expression profiles in TNBC and identified that small nucleolar RNA host gene 12 (SNHG12) was remarkably increased in TNBC. However, the role of SNHG12 in TNBC has not been clarified. Herein, we determine that SNHG12 is upregulated in TNBC, and its high expression is significantly correlated with tumor size and lymph node metastasis. Mechanistic investigations show that SNHG12 is a direct transcriptional target of c-MYC. Silencing SNHG12 expression inhibits TNBC cells proliferation and apoptosis promotion, whereas SNHG12 overexpression has the opposite effect. In addition, we reveal that SNHG12 may promote cells migration by regulating MMP13 expression. To the best of our knowledge, it is the first report indicating that SNHG12 is involved in breast cancer. Taken together, our findings suggest that SNHG12 contributes to the oncogenic potential of TNBC and may be a promising therapeutic target.

  6. Caffeic Acid Phenethyl Ester and Ethanol Extract of Propolis Induce the Complementary Cytotoxic Effect on Triple-Negative Breast Cancer Cell Lines

    Directory of Open Access Journals (Sweden)

    Anna Rzepecka-Stojko

    2015-05-01

    Full Text Available Chemotherapy of breast cancer could be improved by bioactive natural substances, which may potentially sensitize the carcinoma cells’ susceptibility to drugs. Numerous phytochemicals, including propolis, have been reported to interfere with the viability of carcinoma cells. We evaluated the in vitro cytotoxic activity of ethanol extract of propolis (EEP and its derivative caffeic acid phenethyl ester (CAPE towards two triple-negative breast cancer (TNBC cell lines, MDA-MB-231 and Hs578T, by implementation of the MTT and lactate dehydrogenase (LDH assays. The morphological changes of breast carcinoma cells were observed following exposure to EEP and CAPE. The IC50 of EEP was 48.35 µg∙mL−1 for MDA-MB-23 cells and 33.68 µg∙mL−1 for Hs578T cells, whereas the CAPE IC50 was 14.08 µM and 8.01 µM for the MDA-MB-231 and Hs578T cell line, respectively. Here, we report that propolis and CAPE inhibited the growth of the MDA-MB-231 and Hs578T lines in a dose-dependent and exposure time-dependent manner. EEP showed less cytotoxic activity against both types of TNBC cells. EEP and, particularly, CAPE may markedly affect the viability of breast cancer cells, suggesting the potential role of bioactive compounds in chemoprevention/chemotherapy by potentiating the action of standard anti-cancer drugs.

  7. Caffeic Acid phenethyl ester and ethanol extract of propolis induce the complementary cytotoxic effect on triple-negative breast cancer cell lines.

    Science.gov (United States)

    Rzepecka-Stojko, Anna; Kabała-Dzik, Agata; Moździerz, Aleksandra; Kubina, Robert; Wojtyczka, Robert D; Stojko, Rafał; Dziedzic, Arkadiusz; Jastrzębska-Stojko, Żaneta; Jurzak, Magdalena; Buszman, Ewa; Stojko, Jerzy

    2015-05-20

    Chemotherapy of breast cancer could be improved by bioactive natural substances, which may potentially sensitize the carcinoma cells' susceptibility to drugs. Numerous phytochemicals, including propolis, have been reported to interfere with the viability of carcinoma cells. We evaluated the in vitro cytotoxic activity of ethanol extract of propolis (EEP) and its derivative caffeic acid phenethyl ester (CAPE) towards two triple-negative breast cancer (TNBC) cell lines, MDA-MB-231 and Hs578T, by implementation of the MTT and lactate dehydrogenase (LDH) assays. The morphological changes of breast carcinoma cells were observed following exposure to EEP and CAPE. The IC50 of EEP was 48.35 µg∙mL-1 for MDA-MB-23 cells and 33.68 µg∙mL-1 for Hs578T cells, whereas the CAPE IC50 was 14.08 µM and 8.01 µM for the MDA-MB-231 and Hs578T cell line, respectively. Here, we report that propolis and CAPE inhibited the growth of the MDA-MB-231 and Hs578T lines in a dose-dependent and exposure time-dependent manner. EEP showed less cytotoxic activity against both types of TNBC cells. EEP and, particularly, CAPE may markedly affect the viability of breast cancer cells, suggesting the potential role of bioactive compounds in chemoprevention/chemotherapy by potentiating the action of standard anti-cancer drugs.

  8. Pterostilbene inhibits triple-negative breast cancer metastasis via inducing microRNA-205 expression and negatively modulates epithelial-to-mesenchymal transition.

    Science.gov (United States)

    Su, Chih-Ming; Lee, Wei-Hwa; Wu, Alexander T H; Lin, Yen-Kuang; Wang, Liang-Shun; Wu, Chih-Hsiung; Yeh, Chi-Tai

    2015-06-01

    Breast cancer is the leading cause of cancer-related deaths among females in economically developing countries. Greater than 95% of breast malignancies are of epithelial origin; the induction of epithelial-to-mesenchymal transition (EMT) has been shown to initiate the metastatic process in breast carcinoma and remains the key target for drug development. Here, we examine the anti-metastatic potential of pterostilbene in modulating EMT process in breast cancer cells both in vitro and in vivo. The differential invasive ability among MCF7, Hs578t and MDA-MB-231 breast cancer cell lines were closely correlated with the expression of EMT markers, determined by Western blots and Matrigel-coated transwells assay. Pterostilbene inhibited the migratory and invasive potential of triple-negative MDA-MB-231 and Hs578t cells, accompanied by the up-regulation of E-cadherin and down-regulation of Snail, Slug, vimentin and ZEB1. Mechanistic investigations revealed a significant up-regulation of miR-205, which resulted in the reduction of Src expression in pterostilbene-treated breast cancer cells. Importantly, pterostilbene suppressed tumor growth and metastasis in MDA-MB-231-bearing NOD/SCID mice by reducing Src/Fak signaling; this observation was consistent with the negative correlations between miR-205 and Src expression in both normal and malignant breast tissues. Our findings provide supports for the usage of pterostilbene as an inhibitor of EMT process and potential candidate for adjuvant therapy.

  9. [10]-Gingerol, a major phenolic constituent of ginger root, induces cell cycle arrest and apoptosis in triple-negative breast cancer cells.

    Science.gov (United States)

    Bernard, Megan M; McConnery, Jason R; Hoskin, David W

    2017-03-16

    The ginger rhizome is rich in bioactive compounds, including [6]-gingerol, [8]-gingerol, and [10]-gingerol; however, to date, most research on the anti-cancer activities of gingerols have focused on [6]-gingerol. In this study, we compared [10]-gingerol with [8]-gingerol and [6]-gingerol in terms of their ability to inhibit the growth of human and mouse mammary carcinoma cells. A colorimetric assay based on the enzymatic reduction of 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide revealed that [10]-gingerol was more potent than [6]-gingerol and at least as potent as [8]-gingerol for the inhibition of triple-negative human (MDA-MB-231, MDA-MB-468) and mouse (4T1, E0771) mammary carcinoma cell growth. Further investigation of [10]-gingerol showed that it suppressed the growth of estrogen receptor-bearing (MCF-7, T47D) and HER2-overexpressing (SKBR3) breast cancer cells. The inhibitory effect of [10]-gingerol on the growth of MDA-MB-231 cells was associated with a reduction in the number of rounds of cell division and evidence of S phase-cell cycle arrest, as well as induction of apoptosis due to mitochondrial outer membrane permeabilization and the release of proapoptotic mitochondrial cytochrome c and SMAC/DIABLO into the cytoplasm. Surprisingly, killing of MDA-MB-231 cells by [10]-gingerol was not affected by a pan-caspase inhibitor (zVAD-fmk) or an anti-oxidant (N-acetylcysteine), suggesting that the cytotoxic effect of [10]-gingerol did not require caspase activation or the accumulation of reactive oxygen species. These findings suggest that further investigation of [10]-gingerol is warranted for its possible use in the treatment of breast cancer.

  10. Effect of dendritic cell/cytokine-induced killer cell immunobiological cancer therapy combined with adjuvant chemotherapy in patients with triple-negative breast cancer

    Institute of Scientific and Technical Information of China (English)

    Ranran Zhang; Dongchu Ma; Xiaodong Xie; Wanqing Xie Co-first author; Tao Han; Yongye Liu; Zhaozhe Liu; Fang Guo; Yaling Han; Zhenyu Ding; Yinghui Sun

    2015-01-01

    Objective The aim of the present study was to investigate the ef ect of dendritic cel (DC)/cytokine-in-duced kil er cel (CIK) immunobiological cancer therapy in patients with triple-negative breast cancer (TNBC) who underwent adjuvant chemotherapy. Methods From January 2010 to October 2013, 120 patients with postoperative TNBC were recruited and included in the study. Patients were enrol ed in one of two groups according to whether they accepted DC/CIK immunobiological cancer therapy during adjuvant chemotherapy; the patients in the DC/CIK group underwent adjuvant chemotherapy combined with DC/CIK immunobiological cancer therapy, and the control group underwent adjuvant chemotherapy alone. When six cycles of adjuvant chemotherapy and six cycles of DC/CIK immunobiological cancer therapy had been completed, dif erences between the two groups with regard to quality of life (QoL), immunological indicators (CD3, CD4, CD8, and NK cel levels), disease-free survival (DFS), and side ef ects of chemotherapy and DC/CIK treatment were evaluated. Results In the DC/CIK group, the proportion of NK cel s and CD3+ and CD4+ T-cel subgroups significantly increased, and the proportion of CD8+ cel s decreased when they were compared before and after DC/CIK therapy (P Conclusion The DC/CIK treatment had potential benefits for patients with TNBC compared with the con-trol group, and was not associated with any obvious side ef ects. Therefore, DC/CIK therapy is a safe and ef ective method for the treatment of TNBC.

  11. SIRT1 induces tumor invasion by targeting epithelial mesenchymal transition-related pathway and is a prognostic marker in triple negative breast cancer.

    Science.gov (United States)

    Jin, Min-Sun; Hyun, Chang Lim; Park, In Ae; Kim, Ji Young; Chung, Yul Ri; Im, Seock-Ah; Lee, Kyung-Hun; Moon, Hyeong-Gon; Ryu, Han Suk

    2016-04-01

    Absence of therapeutic targets poses a critical hurdle in improving prognosis for patients with triple negative breast cancer (TNBC). We evaluated interaction between SIRT1 and epithelial mesenchymal transition (EMT)-associated proteins as well as the role of combined protein expression as a predictor of lymph node metastasis and clinical outcome in TNBC through in vivo and vitro studies. Three hundred nineteen patients diagnosed with TNBC were chosen, immunohistochemical staining for SIRT1 and EMT-related markers' expression was performed on tissue microarrays, and in vitro experiments with each of the three human TNBC cell lines were carried out. The cohort was reclassified according to the use of adjuvant chemotherapy, tumor size, and AJCC stage to analyze the prognostic role of SIRT1 and EMT-related proteins' expression considering different therapeutic modalities and AJCC stages. Combination of four proteins including SIRT1 and three EMT-related proteins was revealed to be a statistically significant independent predictor of lymph node metastasis in the tumor size cohort as well as in the total patient population. Upon Cox regression analysis, increased expression level of the combined proteins correlated with decreased disease-free survival in the total patients as well as those who received adjuvant chemotherapy and those who had early stage breast cancer. In additional in vitro experiments, inhibition of SIRT1 expression with small interfering RNA (siRNA) suppressed tumor invasion in three different TNBC cell lines, and altered expression levels of EMT-related proteins following SIRT1 gene inhibition were identified on western blotting and fluorescence activated cell sorting (FACS) analysis; on the other hand, no change in expression levels of the cell cycle-related factors was observed. Our analysis showed the potential role of SIRT1 in association with EMT-related factors on tumor invasion, metastasis, and disease-free survival in TNBC, SIRT1, and

  12. Triple-resonant transducers.

    Science.gov (United States)

    Butler, Stephen C

    2012-06-01

    A detailed analysis is presented of two novel multiple-resonant transducers which produce a wider transmit response than that of a conventional Tonpilz-type transducer. These multi-resonant transducers are Tonpilz-type longitudinal vibrators that produce three coupled resonances and are referred to as triple-resonant transducers (TRTs). One of these designs is a mechanical series arrangement of a tail mass, piezoelectric ceramic stack, central mass, compliant spring, second central mass, second compliant spring, and a piston-radiating head mass. The other TRT design is a mechanical series arrangement of a tail mass, piezoelectric ceramic stack, central mass, compliant spring, and head mass with a quarter-wave matching layer of poly(methyl methacrylate) on the head mass. Several prototype transducer element designs were fabricated that demonstrated proof-of-concept.

  13. Co-Targeting IGF-1R and Autophagy Enhances the Effects of Cell Growth Suppression and Apoptosis Induced by the IGF-1R Inhibitor NVP-AEW541 in Triple-Negative Breast Cancer Cells

    Science.gov (United States)

    Shao, Nan; Shi, Yawei; Liu, Ruiming; Li, Wen; Lin, Yin; Wang, Shenming

    2017-01-01

    Background Triple-negative breast cancer (TNBC) is the most intractable type of breast cancer, and there is a lack of effective targeted therapy. Insulin-like growth factor-1 receptor (IGF-1R) is reportedly a potential target for TNBC treatment. However, satisfying treatment outcomes in breast cancer patients have yet to be achieved with IGF-1R-targeted agents. Methods To confirm whether inhibiting IGF-1R could induce autophagy, we detected autophagy-related proteins by western blotting and immunofluorescence staining of LC3-II. The IGF-1R inhibitor NVP-AEW541, autophagy inhibitor 3-methyladenine (3-MA) and Atg7 small interfering RNA (siRNA) were used to further investigate the effects of autophagy induced by IGF-1R inhibition in TNBC cells. The CCK8 assay, EdU assay, apoptosis and cell cycle analyses were applied to test cell function after treatment. Results NVP-AEW541 markedly induced autophagy in TNBC cells by increasing the levels of the autophagy-related protein Beclin-1 and the LC3-II/LC-I ratio and reducing the selective autophagy substrate p62. Joint application of 3-MA or Atg7 siRNA enhanced the cell growth inhibition and apoptosis effects of NVP-AEW541 by arresting cells at G1/G0 phase and increasing Bax expression and decreasing that of Bcl-2. Conclusion Targeting IGF-1R in TNBC induces cell-protective autophagy, thereby weakening the therapeutic effect of agents directed toward IGF-1R. Our findings reveal that combined use autophagy-disrupting agents can enhance the therapeutic efficacy of IGF-1R inhibitors in TNBC cells and may provide a valuable treatment strategy for IGF-1R inhibitor-based therapies for TNBC and other IGF-1 signaling-associated tumors. PMID:28046018

  14. Harmonic analysis on triple spaces

    DEFF Research Database (Denmark)

    Danielsen, Thomas Hjortgaard

    In this thesis we study examples of triple spaces, both their structure theory, their invariant differential operators as well as analysis on them. The first major results provide us with some examples of triple spaces which are strongly spherical, i.e. satisfy some conditions reminiscent...... of properties of symmetric spaces. The algebras of invariant differential operators for these spaces are studied and the conclusion is that most of them are non-commutative. Finally, we restrict our attention to a single triple space, giving a specific polar decomposition and corresponding integration formula......, and studying the relations between open orbits of parabolic subgroups, multiplicities and distribution vectors....

  15. On Split Lie Triple Systems

    Indian Academy of Sciences (India)

    Antonio J Calderón Martín

    2009-04-01

    We begin the study of arbitrary split Lie triple systems by focussing on those with a coherent 0-root space. We show that any such triple systems with a symmetric root system is of the form $T=\\mathcal{U}+\\sum_j I_j$ with $\\mathcal{U}$ a subspace of the 0-root space $T_0$ and any $I_j$ a well described ideal of , satisfying $[I_j,T,I_k]=0$ if $j≠ k$. Under certain conditions, it is shown that is the direct sum of the family of its minimal ideals, each one being a simple split Lie triple system, and the simplicity of is characterized. The key tool in this job is the notion of connection of roots in the framework of split Lie triple systems.

  16. Triple-band metamaterial absorption utilizing single rectangular hole

    Science.gov (United States)

    Kim, Seung Jik; Yoo, Young Joon; Kim, Young Ju; Lee, YoungPak

    2017-01-01

    In the general metamaterial absorber, the single absorption band is made by the single meta-pattern. Here, we introduce the triple-band metamaterial absorber only utilizing single rectangular hole. We also demonstrate the absorption mechanism of the triple absorption. The first absorption peak was caused by the fundamental magnetic resonance in the metallic part between rectangular holes. The second absorption was generated by induced tornado magnetic field. The process of realizing the second band is also presented. The third absorption was induced by the third-harmonic magnetic resonance in the metallic region between rectangular holes. In addition, the visible-range triple-band absorber was also realized by using similar but smaller single rectangular-hole structure. These results render the simple metamaterials for high frequency in large scale, which can be useful in the fabrication of metamaterials operating in the optical range.

  17. Liquid chromatography coupled with ultraviolet absorbance detection, electrospray ionization, collision-induced dissociation and tandem mass spectrometry on a triple quadrupole for the on-line characterization of polyphenols and methylxanthines in green coffee beans.

    Science.gov (United States)

    Alonso-Salces, Rosa Maria; Guillou, Claude; Berrueta, Luis A

    2009-02-01

    Liquid chromatography coupled with a photodiode array detector, electrospray ionization, collision-induced dissociation and tandem mass spectrometry (LC-DAD/ESI-CID-MS/MS) on a triple quadrupole (QqQ) has been used to detect and characterize polyphenols and methylxanthines in green coffee beans: three phenolic acids (caffeic acid, ferulic acid and dimethoxycinnamic acid), three isomeric caffeoylquinic acids (M(r) 354), three feruloylquinic acids (M(r) 368), one p-coumaroylquinic acid (M(r) 338), three dicaffeoylquinic acids (M(r) 516), three feruloyl-caffeoylquinic acids (M(r) 530), four p-coumaroyl-caffeoylquinic acids (M(r) 500), three diferuloylquinic acids (M(r) 544), six dimethoxycinnamoyl-caffeoylquinic acids (M(r) 544), three dimethoxycinnamoyl-feruloylquinic acids (M(r) 558), six cinnamoyl-amino acid conjugates, three cinnamoyl glycosides, and three methylxanthines (caffeine, theobromine and theophylline). Dimethoxycinnamic acid, three isomers of dimethoxycinnamoyl-caffeoylquinic acids and another three of dimethoxycinnamoyl-feruloylquinic acids, as well as the three cinnamoyl glycosides, had not previously been reported in coffee beans. Structures have been assigned on the basis of the complementary information obtained from UV-visible spectra, relative hydrophobicity, scan mode MS spectra, and fragmentation patterns in MS(2) spectra (both in the positive and negative ion modes) obtained using a QqQ at different collision energies. A structure diagnosis scheme is provided for the identification of different isomers of polyphenols and methylxanthines.

  18. Orbit Alignment in Triple Stars

    Science.gov (United States)

    Tokovinin, Andrei

    2017-08-01

    The statistics of the angle Φ between orbital angular momenta in hierarchical triple systems with known inner visual or astrometric orbits are studied. A correlation between apparent revolution directions proves the partial orbit alignment known from earlier works. The alignment is strong in triples with outer projected separation less than ∼50 au, where the average Φ is about 20^\\circ . In contrast, outer orbits wider than 1000 au are not aligned with the inner orbits. It is established that the orbit alignment decreases with the increasing mass of the primary component. The average eccentricity of inner orbits in well-aligned triples is smaller than in randomly aligned ones. These findings highlight the role of dissipative interactions with gas in defining the orbital architecture of low-mass triple systems. On the other hand, chaotic dynamics apparently played a role in shaping more massive hierarchies. The analysis of projected configurations and triples with known inner and outer orbits indicates that the distribution of Φ is likely bimodal, where 80% of triples have {{Φ }}< 70^\\circ and the remaining ones are randomly aligned.

  19. Zero Triple Product Determined Matrix Algebras

    Directory of Open Access Journals (Sweden)

    Hongmei Yao

    2012-01-01

    triple product in the aforementioned definition is replaced by Jordan triple product, then A is called zero Jordan triple product determined. This paper mainly shows that matrix algebra Mn(B, n≥3, where B is any commutative unital algebra even different from the above mentioned commutative unital algebra C, is always zero triple product determined, and Mn(F, n≥3, where F is any field with chF≠2, is also zero Jordan triple product determined.

  20. 冻干重组人三突变型低氧诱导因子-1α腺病毒的制备%Preparation of freeze-dried recombinant adenovirus expressing hypoxia inducible factor-1 alpha of triple mutant

    Institute of Scientific and Technical Information of China (English)

    陶宇; 杨丽; 魏旋; 李明琰; 陈建威; 吴平生

    2011-01-01

    目的:研制冻干重组人三突变型低氧诱导因子-1α(HIF-1α)腺病毒.方法:将重组人三突变型HIF-1α腺病毒与不同配比的保护剂按适当比例混合,进行冻干,根据冻干后外观、病毒滴度测定、热稳定性试验、PCR、基因测序等结果,筛选冻干保护剂并评价冻干品质量.结果:冻干腺病毒所携带的目的基因信息无丢失或变异;以10%海藻糖、0.5%明胶、3%山梨醇等成分配制的保护剂作用较好,冻干后腺病毒感染性滴度下降0.33 LgPFU/mL;37℃放置3周,滴度下降0.8 LgPFU/mL.结论:以合适的保护剂制备冻干重组人三突变型HIF-1α腺病毒能达到较满意的效果.%Objective To prepare freeze-dried recomhinant adenovirus expressing hypoxia inducible factor-1 alpha (HIF-lα) of triple mutant (Ad-HIF-lα-564/402/803). Methods Ad-HIF-Iα-564/402/803 were mixed with different stabilizers in an appropriate proportion and then lyophilized. The optimum stabilizer was selected and the product quality was evaluated according to appearance, virus titer, thermostahility, PCR and DNA sequence analvsis. Results PCR and gene sequence suggested the correct construction of freeze-dried recombinant adenovirus. The protective agent containing 10% trehalose , 0.5% gelatin, 3% sorbitol had better protecting effects. After lyophilization, the infectious titer of adenovirus was decreased by 0.33 LgPFU/mL, the titer of lyophilized adenovirus was decreased by 0.8 LgPFU/mL for 3 weeks at 37℃. Conclusions When prepared with proper stabilizer, the freeze-dried recombinant adenovirus expressing HIF-Iα of triple mutant can have a good performance.

  1. Comparison of the Effect of PRP, PRF and Induced Bleeding in the Revascularization of Teeth with Necrotic Pulp and Open Apex: A Triple Blind Randomized Clinical Trial.

    Science.gov (United States)

    Shivashankar, Vasundara Yayathi; Johns, Dexton Antony; Maroli, Ramesh Kumar; Sekar, Mahalaxmi; Chandrasekaran, Rathinavel; Karthikeyan, Shanmugavel; Renganathan, Senthil Kumar

    2017-06-01

    Treatment of a tooth with necrotic pulp and open apex is a special challenge to the clinicians. Apexification with calcium hydroxide and MTA barrier technique fails to induce continued root maturation which makes the tooth susceptible to root fracture. Hence, an ideal outcome for such a tooth should be regeneration of pulp like tissue into the root canal capable of continuing normal root maturation. This study aims to compare the effect of Platelet Rich Fibrin (PRF), induced bleeding technique and Platelet Rich Plasma (PRP) in the revascularization of tooth with necrotic pulp and open apex. The main objectives of the study were to: (a) Radiographically evaluate the continuation of root development, increase in the dentin wall thickness and narrowing of canal space, apical closure and resolution of the periapical lesion; and to (b) To clinically evaluate the response to pulp sensibility testing and response to percussion and palpation tests. Sixty patients (6 to 28 years) with necrotic immature permanent tooth were randomly categorised into three groups after the root canal disinfection procedure. PRF as scaffolding material (Group A: n=20), revascularization with conventional induced bleeding technique (Group B: n=20), and PRP as the biomaterial (Group C: n=20). The primary outcome variable was measured using Periapical Index (PAI) (for periapical healing), Chen and Chen index (for apical responses), Schei's ruler (for root lengthening and root thickening) and other clinical parameters. The Chi-square test was used to interpret the data among the three groups at the end of 12 months for the variables root lengthening and lateral wall thickness. ANOVA test was performed to compare the mean of the PAI scores of the three groups at preoperative stage and 12 months. If statistically significant, Bonferroni test was done to compare the outcome among the three groups. The significant level was set at pPRF and induced bleeding technique with respect to periapical wound

  2. Synthesis and in vitro anti-proliferative activity of some novel isatins conjugated with quinazoline/phthalazine hydrazines against triple-negative breast cancer MDA-MB-231 cells as apoptosis-inducing agents.

    Science.gov (United States)

    Eldehna, Wagdy M; Almahli, Hadia; Al-Ansary, Ghada H; Ghabbour, Hazem A; Aly, Mohamed H; Ismael, Omnia E; Al-Dhfyan, Abdullah; Abdel-Aziz, Hatem A

    2017-12-01

    Treatment of patients with triple-negative breast cancer (TNBC) is challenging due to the absence of well- defined molecular targets and the heterogeneity of such disease. In our endeavor to develop potent isatin-based anti-proliferative agents, we utilized the hybrid-pharmacophore approach to synthesize three series of novel isatin-based hybrids 5a-h, 10a-h and 13a-c, with the prime goal of developing potent anti-proliferative agents toward TNBC MDA-MB-231 cell line. In particular, compounds 5e and 10g were the most active hybrids against MDA-MB-231 cells (IC50 = 12.35 ± 0.12 and 12.00 ± 0.13 μM), with 2.37- and 2.44-fold increased activity than 5-fluorouracil (5-FU) (IC50 = 29.38 ± 1.24 μM). Compounds 5e and 10g induced the intrinsic apoptotic mitochondrial pathway in MDA-MB-231; evidenced by the reduced expression of the anti-apoptotic protein Bcl-2, the enhanced expression of the pro-apoptotic protein Bax and the up-regulated active caspase-9 and caspase-3 levels. Furthermore, 10g showed significant increase in the percent of annexin V-FITC positive apoptotic cells from 3.88 to 31.21% (8.4 folds compared to control).

  3. Responses of a triple mutant defective in three iron deficiency-induced Basic Helix-Loop-Helix genes of the subgroup Ib(2) to iron deficiency and salicylic acid.

    Science.gov (United States)

    Maurer, Felix; Naranjo Arcos, Maria Augusta; Bauer, Petra

    2014-01-01

    Plants are sessile organisms that adapt to external stress by inducing molecular and physiological responses that serve to better cope with the adverse growth condition. Upon low supply of the micronutrient iron, plants actively increase the acquisition of soil iron into the root and its mobilization from internal stores. The subgroup Ib(2) BHLH genes function as regulators in this response, however their concrete functions are not fully understood. Here, we analyzed a triple loss of function mutant of BHLH39, BHLH100 and BHLH101 (3xbhlh mutant). We found that this mutant did not have any iron uptake phenotype if iron was provided. However, under iron deficiency the mutant displayed a more severe leaf chlorosis than the wild type. Microarray-based transcriptome analysis revealed that this mutant phenotype resulted in the mis-regulation of 198 genes, out of which only 15% were associated with iron deficiency regulation itself. A detailed analysis revealed potential targets of the bHLH transcription factors as well as genes reflecting an exaggerated iron deficiency response phenotype. Since the BHLH genes of this subgroup have been brought into the context of the plant hormone salicylic acid, we investigated whether the 3xbhlh mutant might have been affected by this plant signaling molecule. Although a very high number of genes responded to SA, also in a differential manner between mutant and wild type, we did not find any indication for an association of the BHLH gene functions in SA responses upon iron deficiency. In summary, our study indicates that the bHLH subgroup Ib(2) transcription factors do not only act in iron acquisition into roots but in other aspects of the adaptation to iron deficiency in roots and leaves.

  4. Responses of a triple mutant defective in three iron deficiency-induced Basic Helix-Loop-Helix genes of the subgroup Ib(2 to iron deficiency and salicylic acid.

    Directory of Open Access Journals (Sweden)

    Felix Maurer

    Full Text Available Plants are sessile organisms that adapt to external stress by inducing molecular and physiological responses that serve to better cope with the adverse growth condition. Upon low supply of the micronutrient iron, plants actively increase the acquisition of soil iron into the root and its mobilization from internal stores. The subgroup Ib(2 BHLH genes function as regulators in this response, however their concrete functions are not fully understood. Here, we analyzed a triple loss of function mutant of BHLH39, BHLH100 and BHLH101 (3xbhlh mutant. We found that this mutant did not have any iron uptake phenotype if iron was provided. However, under iron deficiency the mutant displayed a more severe leaf chlorosis than the wild type. Microarray-based transcriptome analysis revealed that this mutant phenotype resulted in the mis-regulation of 198 genes, out of which only 15% were associated with iron deficiency regulation itself. A detailed analysis revealed potential targets of the bHLH transcription factors as well as genes reflecting an exaggerated iron deficiency response phenotype. Since the BHLH genes of this subgroup have been brought into the context of the plant hormone salicylic acid, we investigated whether the 3xbhlh mutant might have been affected by this plant signaling molecule. Although a very high number of genes responded to SA, also in a differential manner between mutant and wild type, we did not find any indication for an association of the BHLH gene functions in SA responses upon iron deficiency. In summary, our study indicates that the bHLH subgroup Ib(2 transcription factors do not only act in iron acquisition into roots but in other aspects of the adaptation to iron deficiency in roots and leaves.

  5. Triple gastric peptic ulcer perforation.

    Science.gov (United States)

    Radojkovic, Milan; Mihajlovic, Suncica; Stojanovic, Miroslav; Stanojevic, Goran; Damnjanovic, Zoran

    2016-03-01

    Patients with advanced or metastatic cancer have compromised nutritional, metabolic, and immune conditions. Nevertheless, little is known about gastroduodenal perforation in cancer patients. Described in the present report is the case of a 41-year old woman with stage IV recurrent laryngeal cancer, who used homeopathic anticancer therapy and who had triple peptic ulcer perforation (PUP) that required surgical repair. Triple gastric PUP is a rare complication. Self-administration of homeopathic anticancer medication should be strongly discouraged when evidence-based data regarding efficacy and toxicity is lacking.

  6. Solution Patterns Predicting Pythagorean Triples

    Science.gov (United States)

    Ezenweani, Ugwunna Louis

    2013-01-01

    Pythagoras Theorem is an old mathematical treatise that has traversed the school curricula from secondary to tertiary levels. The patterns it produced are quite interesting that many researchers have tried to generate a kind of predictive approach to identifying triples. Two attempts, namely Diophantine equation and Brahmagupta trapezium presented…

  7. Local derivations on Jordan triples

    OpenAIRE

    Mackey, Michael

    2013-01-01

    R. V. Kadison (J. Algebra 130 (1990) 494–509) defined the notion of local derivation on an algebra and proved that every continuous local derivation on a von Neumann algebra is a derivation. We provide the analogous result in the setting of Jordan triples.

  8. Thioamides in the collagen triple helix.

    Science.gov (United States)

    Newberry, Robert W; VanVeller, Brett; Raines, Ronald T

    2015-06-14

    To probe noncovalent interactions within the collagen triple helix, backbone amides were replaced with a thioamide isostere. This subtle substitution is the first in the collagen backbone that does not compromise thermostability. A triple helix with a thioamide as a hydrogen bond donor was found to be more stable than triple helices assembled from isomeric thiopeptides.

  9. Classifying Two-dimensional Hyporeductive Triple Algebras

    CERN Document Server

    Issa, A Nourou

    2010-01-01

    Two-dimensional real hyporeductive triple algebras (h.t.a.) are investigated. A classification of such algebras is presented. As a consequence, a classification of two-dimensional real Lie triple algebras (i.e. generalized Lie triple systems) and two-dimensional real Bol algebras is given.

  10. Triple-Negative Breast Carcinoma.

    Science.gov (United States)

    Livasy, Chad A

    2009-06-01

    Triple-negative breast carcinomas (TNBCs) comprise approximately 15% to 20% of breast cancers. Accurate assessment of tumor estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2 (HER2) status is an essential part of classifying tumors into this group. As a group, these tumors are associated with poor clinical outcomes and have been shown to exhibit an increased propensity for hematogenous metastasis to the brain and lungs. Many TNBCs, particularly ductal, not otherwise specified (NOS), and metaplastic carcinomas, show an overlapping characteristic gene expression pattern when evaluated by cDNA microarrays. This group has been termed basal-like because of the similarity with normal breast basal/myoepithelial cells including basal cytokeratin expression and lack of hormone receptor and HER2 expression. The array data have been used to develop multiple immunohistochemical surrogates to identify basal-like tumors in formalin-fixed, paraffin-embedded tissues, most employing basal cytokeratins and epidermal growth factor receptor. Currently, there is no international consensus on biomarkers used to identify tumors as basal-like, and the routine use of the term basal-like in surgical pathology reports is premature. Tumor morphologic features associated with triple-negative status include Nottingham grade 3 with high mitotic rate, pushing border of invasion, geographic tumor necrosis, solid/sheet-like growth pattern, lymphocytic infiltrate, and large central acellular zone. Most breast cancers arising in patients who have a germ-line BRCA1 mutation show similar histologic features and a triple-negative phenotype. Not all TNBCs are associated with an unfavorable prognosis, drawing attention to the heterogeneity of this tumor group and the continued need to link tumor morphology and grade with triple-negative status. This article focuses on histopathology, molecular characterization, carcinogenesis, clinical behavior, and treatment of these

  11. The evolution of triple-star systems

    Science.gov (United States)

    Toonen, Silvia; Hamers, Adrian; Portegies Zwart, Simon

    2017-01-01

    While the principles of stellar and binary evolution theory have been accepted for a long time, our understanding of triple-star evolution is lagging behind. It is important to understand these systems, as triples are common in the field. About 15% of low-mass stellar systems are triples, but for high-mass stars the fraction increases to over 50%. At the same time, triple evolution is often invoked to explain exotic systems which cannot be explained easily by binary evolution. Examples are low-mass X-ray binaries, supernova type Ia progenitors and blue stragglers.Modeling triple evolution, however, is challenging as it is a combination of three-body dynamics and stellar evolution. In the past, most studies of three-body systems have focused on purely dynamical aspects without taking stellar evolution into account. However, in recent years, the first interdisciplinary studies have taken place which demonstrate the richness of the interacting regime. Here, I will show the first results of our new code TRES for simulating the evolution of stellar triples, which combines stellar evolution and interactions with three-body dynamics. In this talk, I will give an overview of the evolution of realistic (stellar) triples and I will discuss how triple evolution differs from binary evolution. What are the common evolutionary pathways that triple systems evolve through? Are there any evolutionary pathways open to triples, which are not open to isolated binaries? These are some of the important questions we want to answer.

  12. Tesofensine, a novel triple monoamine reuptake inhibitor, induces appetite suppression by indirect stimulation of alpha1 adrenoceptor and dopamine D1 receptor pathways in the diet-induced obese rat

    DEFF Research Database (Denmark)

    Axel, Anne Marie Dixen; Mikkelsen, Jens D; Hansen, Henrik H

    2010-01-01

    is not clarified. Using a rat model of diet-induced obesity (DIO), we characterized the pharmacological mechanisms underlying the appetite suppressive effect of tesofensine. DIO rats treated with tesofensine (2.0 mg/kg, s.c.) for 16 days showed significantly lower body weights than vehicle-treated DIO rats, being...... reflected by a marked hypophagic response. Using an automatized food intake monitoring system during a 12 h nocturnal test period, tesofensine-induced hypophagia was investigated further by studying the acute interaction of a variety of monoamine receptor antagonists with tesofensine-induced hypophagia...... in the DIO rat. Tesofensine (0.5-3.0 mg/kg, s.c.) induced a dose-dependent and marked decline in food intake with an ED(50) of 1.3 mg/kg. The hypophagic response of tesofensine (1.5 mg/kg, s.c.) was almost completely reversed by co-administration of prazosin (1.0 mg/kg, alpha(1) adrenoceptor antagonist...

  13. Energy Efficient Triple IG Automation EEE (Triple-E)

    Energy Technology Data Exchange (ETDEWEB)

    McGlinchy, Timothy B

    2013-02-28

    GED Integrated Solutions collaborated with US window and door manufactures to investigate, design and verify technical and cost feasibility for producing high performance, high volume, low material and labor cost window, utilizing a modified window design containing a triple insulating glass unit (IGU). This window design approach when combined with a high volume IGU manufacturing system, can produce R5 rated windows for an approximate additional consumer cost of only $4 per square foot when compared to conventional Low-E argon dual pane IG windows, resulting in a verify practical, reliable and affordable high performance window for public use.

  14. Generalized derivations of Lie triple systems

    Directory of Open Access Journals (Sweden)

    Zhou Jia

    2016-01-01

    Full Text Available In this paper, we present some basic properties concerning the derivation algebra Der (T, the quasiderivation algebra QDer (T and the generalized derivation algebra GDer (T of a Lie triple system T, with the relationship Der (T ⊆ QDer (T ⊆ GDer (T ⊆ End (T. Furthermore, we completely determine those Lie triple systems T with condition QDer (T = End (T. We also show that the quasiderivations of T can be embedded as derivations in a larger Lie triple system.

  15. Neutron triples counting data for uranium

    Energy Technology Data Exchange (ETDEWEB)

    Croft, Stephen, E-mail: crofts@ornl.gov [Oak Ridge National laboratory, 1 Bethel Valley Road, Oak Ridge, TN 37831 (United States); LaFleur, Adrienne M. [Los Alamos National Laboratory, Los Alamos , NM 87545 (United States); McElroy, Robert D. [Oak Ridge National laboratory, 1 Bethel Valley Road, Oak Ridge, TN 37831 (United States); Swinhoe, Martyn T. [Los Alamos National Laboratory, Los Alamos , NM 87545 (United States)

    2015-06-01

    Correlated neutron counting using multiplicity shift register logic extracts the first three factorial moments from the detected neutron pulse train. The descriptive properties of the measurement item (mass, the ratio of (α,n) to spontaneous fission neutron production, and leakage self-multiplication) are related to the observed singles (S), doubles (D) and triples (T) rates, and this is the basis of the widely used multiplicity counting assay method. The factorial moments required to interpret and invert the measurement data in the framework of the point kinetics model may be calculated from the spontaneous fission prompt neutron multiplicity distribution P(ν). In the case of {sup 238}U very few measurements of P(ν) are available and the derived values, especially for the higher factorial moments, are not known with high accuracy. In this work, we report the measurement of the triples rate per gram of {sup 238}U based on the analysis of a set of measurements in which a collection of 10 cylinders of UO{sub 2}F{sub 2}, each containing about 230 g of compound, were measured individually and in groups. Special care was taken to understand and compensate the recorded multiplicity histograms for the effect of random cosmic-ray induced background neutrons, which, because they also come in bursts and mimic fissions but with a different and harder multiplicity distribution. We compare our fully corrected (deadtime, background, efficiency, multiplication) experimental results with first principles expectations based on evaluated nuclear data. Based on our results we suspect that the current evaluated nuclear data is biased, which points to a need to undertake new basic measurements of the {sup 238}U prompt neutron multiplicity distribution.

  16. Structural insights into the stabilization of MALAT1 noncoding RNA by a bipartite triple helix.

    Science.gov (United States)

    Brown, Jessica A; Bulkley, David; Wang, Jimin; Valenstein, Max L; Yario, Therese A; Steitz, Thomas A; Steitz, Joan A

    2014-07-01

    Metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) is a highly abundant nuclear long noncoding RNA that promotes malignancy. A 3'-stem-loop structure is predicted to confer stability by engaging a downstream A-rich tract in a triple helix, similar to the expression and nuclear retention element (ENE) from the KSHV polyadenylated nuclear RNA. The 3.1-Å-resolution crystal structure of the human MALAT1 ENE and A-rich tract reveals a bipartite triple helix containing stacks of five and four U•A-U triples separated by a C+•G-C triplet and C-G doublet, extended by two A-minor interactions. In vivo decay assays indicate that this blunt-ended triple helix, with the 3' nucleotide in a U•A-U triple, inhibits rapid nuclear RNA decay. Interruption of the triple helix by the C-G doublet induces a 'helical reset' that explains why triple-helical stacks longer than six do not occur in nature.

  17. Holonomy loops, spectral triples and quantum gravity

    DEFF Research Database (Denmark)

    Johannes, Aastrup; Grimstrup, Jesper Møller; Nest, Ryszard

    2009-01-01

    We review the motivation, construction and physical interpretation of a semi-finite spectral triple obtained through a rearrangement of central elements of loop quantum gravity. The triple is based on a countable set of oriented graphs and the algebra consists of generalized holonomy loops...

  18. Spectral triples and the geometry of fractals

    DEFF Research Database (Denmark)

    Christensen, Erik; Ivan, Cristina; Schroe, Elmar

    2012-01-01

    It is shown that one can construct a spectral triple for the Sierpinski gasket such that it represents any given K-homology class, On the other hand if the geodesic distance and the dimension has to be part of the data from the triple, there are certain restriction....

  19. Existence Regions of Shock Wave Triple Configurations

    Science.gov (United States)

    Bulat, Pavel V.; Chernyshev, Mikhail V.

    2016-01-01

    The aim of the research is to create the classification for shock wave triple configurations and their existence regions of various types: type 1, type 2, type 3. Analytical solutions for limit Mach numbers and passing shock intensity that define existence region of every type of triple configuration have been acquired. The ratios that conjugate…

  20. The Killing Forms of Lie Triple Systems

    Institute of Scientific and Technical Information of China (English)

    ZHANG Zhi Xue; GAO Rui

    2009-01-01

    For Lie triple systems in the characteristic zero setting, we obtain by means of the Killing forms two criterions for semisimplicity and for solvability respectively, and then investigate the relationship among the Killing forms of a real Lie triple system To, the complexification T of To, and the realification of T.

  1. Nonunital Spectral Triples Associated to Degenerate Metrics

    Science.gov (United States)

    Rennie, A.

    We show that one can define (p,∞)-summable spectral triples using degenerate metrics on smooth manifolds. Furthermore, these triples satisfy Connes-Moscovici's discrete and finite dimension spectrum hypothesis, allowing one to use the Local Index Theorem [1] to compute the pairing with K-theory. We demonstrate this with a concrete example.

  2. Intramuscular Immunization of Mice with a Live-Attenuated Triple Mutant of Yersinia pestis CO92 Induces Robust Humoral and Cell-Mediated Immunity To Completely Protect Animals against Pneumonic Plague.

    Science.gov (United States)

    Tiner, Bethany L; Sha, Jian; Ponnusamy, Duraisamy; Baze, Wallace B; Fitts, Eric C; Popov, Vsevolod L; van Lier, Christina J; Erova, Tatiana E; Chopra, Ashok K

    2015-12-01

    Earlier, we showed that the Δlpp ΔmsbB Δail triple mutant of Yersinia pestis CO92 with deleted genes encoding Braun lipoprotein (Lpp), an acyltransferase (MsbB), and the attachment invasion locus (Ail), respectively, was avirulent in a mouse model of pneumonic plague. In this study, we further evaluated the immunogenic potential of the Δlpp ΔmsbB Δail triple mutant and its derivative by different routes of vaccination. Mice were immunized via the subcutaneous (s.c.) or the intramuscular (i.m.) route with two doses (2 × 10(6) CFU/dose) of the above-mentioned triple mutant with 100% survivability of the animals. Upon subsequent pneumonic challenge with 70 to 92 50% lethal doses (LD(50)) of wild-type (WT) strain CO92, all of the mice survived when immunization occurred by the i.m. route. Since Ail has virulence and immunogenic potential, a mutated version of Ail devoid of its virulence properties was created, and the genetically modified ail replaced the native ail gene on the chromosome of the Δlpp ΔmsbB double mutant, creating a Δlpp ΔmsbB::ailL2 vaccine strain. This newly generated mutant was attenuated similarly to the Δlpp ΔmsbB Δail triple mutant when administered by the i.m. route and provided 100% protection to animals against subsequent pneumonic challenge. Not only were the two above-mentioned mutants cleared rapidly from the initial i.m. site of injection in animals with no histopathological lesions, the immunized mice did not exhibit any disease symptoms during immunization or after subsequent exposure to WT CO92. These two mutants triggered balanced Th1- and Th2-based antibody responses and cell-mediated immunity. A substantial increase in interleukin-17 (IL-17) from the T cells of vaccinated mice, a cytokine of the Th17 cells, further augmented their vaccine potential. Thus, the Δlpp ΔmsbB Δail and Δlpp ΔmsbB::ailL2 mutants represent excellent vaccine candidates for plague, with the latter mutant still retaining Ail immunogenicity but

  3. Contractive spectral triples for crossed products

    CERN Document Server

    Paterson, Alan L T

    2012-01-01

    Connes showed that spectral triples encode (noncommutative) metric information. Further, Connes and Moscovici in their metric bundle construction showed that, as with the Takesaki duality theorem, forming a crossed product spectral triple can substantially simplify the structure. In a recent paper, Bellissard, Marcolli and Reihani (among other things) studied in depth metric notions for spectral triples and crossed product spectral triples for $Z$-actions, with applications in number theory and coding theory. In the work of Connes and Moscovici, crossed products involving groups of diffeomorphisms and even of \\'{e}tale groupoids are required. With this motivation, the present paper develops part of the Bellissard-Marcolli-Reihani theory for a general discrete group action, and in particular, introduces coaction spectral triples and their associated metric notions. The isometric condition is replaced by the contractive condition.

  4. Modulation of the BRCA1 Protein and Induction of Apoptosis in Triple Negative Breast Cancer Cell Lines by the Polyphenolic Compound Curcumin

    OpenAIRE

    Rowe, Danica L.; Tuba Ozbay; Ruth M. O’Regan; Rita Nahta

    2009-01-01

    In the current study, we sought to examine the effects of curcumin in a specific type of breast cancer called triple negative breast cancer. These cancers lack expression of the estrogen and progesterone receptors and do not over-express HER2. Current treatment for triple negative breast cancers is limited to cytotoxic chemotherapy, and upon relapse, there are not any therapies currently available. We demonstrate here that the bioactive food compound curcumin induces DNA damage in triple nega...

  5. Collisions in young triple systems

    CERN Document Server

    Rawiraswattana, Krisada; Goodwin, Simon P

    2011-01-01

    We perform N-body simulations of young triple systems consisting of two low-mass companions orbiting around a significantly more massive primary. We find that, when the orbits of the companions are coplanar and not too widely separated, the chance of a collision between the two companions can be as high as 20 per cent. Collisions between one of the companions (always the less massive) and the primary can also occur in systems with unequal-mass companions. The chance of collisions is a few per cent in systems with more realistic initial conditions, such as with slightly non-coplanar orbits and unequal-mass companions. If the companions start widely separated then collision are very rare except in some cases when the total mass of the companions is large. We suggest that collisions between members of young multiple systems may explain some unusual young multiple systems such as apparently non-coeval companions.

  6. The triple system Zeta Aquarii

    CERN Document Server

    Tokovinin, Andrei

    2016-01-01

    Zeta Aquarii is a bright and nearby (28 pc) triple star with a 26-year astrometric subsystem. Almost a half of the outer 540-year visual orbit has been covered in 238 years of its observations. Both inner and outer orbits are revised here taking into account recent direct resolution of the inner pair Aa,Ab. The inner orbit has a high eccentricity of 0.87 and is inclined to the outer orbit by 140+-10 degrees, suggesting that Kozai-Lidov cycles take place. The masses of the stars Aa, B, and Ab are 1.4, 1.4, and 0.6 solar. The age of the system is about 3 Gyr, and the two main components have just left the main sequence. Hypothetically, this system could have formed by a dynamical capture of the small star Ab in the twin binary Aa,B.

  7. Simulation of triple coincidences in PET.

    Science.gov (United States)

    Cal-González, J; Lage, E; Herranz, E; Vicente, E; Udias, J M; Moore, S C; Park, M-A; Dave, S R; Parot, V; Herraiz, J L

    2015-01-07

    Although current PET scanners are designed and optimized to detect double coincidence events, there is a significant amount of triple coincidences in any PET acquisition. Triple coincidences may arise from causes such as: inter-detector scatter (IDS), random triple interactions (RT), or the detection of prompt gamma rays in coincidence with annihilation photons when non-pure positron-emitting radionuclides are used (β(+)γ events). Depending on the data acquisition settings of the PET scanner, these triple events are discarded or processed as a set of double coincidences if the energy of the three detected events is within the scanner's energy window. This latter option introduces noise in the data, as at most, only one of the possible lines-of-response defined by triple interactions corresponds to the line along which the decay occurred. Several novel works have pointed out the possibility of using triple events to increase the sensitivity of PET scanners or to expand PET imaging capabilities by allowing differentiation between radiotracers labeled with non-pure and pure positron-emitting radionuclides. In this work, we extended the Monte Carlo simulator PeneloPET to assess the proportion of triple coincidences in PET acquisitions and to evaluate their possible applications. We validated the results of the simulator against experimental data acquired with a modified version of a commercial preclinical PET/CT scanner, which was enabled to acquire and process triple-coincidence events. We used as figures of merit the energy spectra for double and triple coincidences and the triples-to-doubles ratio for different energy windows and radionuclides. After validation, the simulator was used to predict the relative quantity of triple-coincidence events in two clinical scanners assuming different acquisition settings. Good agreement between simulations and preclinical experiments was found, with differences below 10% for most of the observables considered. For clinical

  8. MOMETASONE-BASED TRIPLE COMBINATION THERAPY IN MELASMA: IS IT REALLY SAFE?

    Science.gov (United States)

    Majid, Imran

    2010-01-01

    Background: Kligman's triple combination formula has been one of the most popular treatment options in melasma over the last three decades. The original Kligman's formula has been modified in many ways over the years and the most recent modification that has been introduced is a triple combination of 2% hydroquinone, 0.025% tretinoin, and 1% mometasone. The use of this triple combination in patients with melasma has seen a sharp rise over the last few years and with this rampant use the side-effect profile of this triple combination has also come to the fore. Aim The aim of the present study was to assess the overall safety of the mometasone-based triple combination treatment in the management of melasma. Materials and Methods: This retrospective study was performed on 60 patients of melasma who had used a mometasone-based triple combination treatment for at least 3 weeks anytime in the previous 1 year. The patients were given a preformed questionnaire wherein they assessed the overall effect of the triple combination treatment on their melasma during its use as well as after its withdrawal. The patients were specifically asked about the status of their disease as well as the sun sensitivity of their skin before and after the use of triple combination treatment. In addition, the patients were assessed by a single trained dermatologist for the presence of any adverse effects arising out of the triple combination treatment in the form of telangiectasia, hypertrichosis, acne, skin atrophy, etc. Results: Majority of patients (51.7%) had used the combination treatment well beyond the recommended duration. About one-third (36.7%) of the patients rated their melasma as worse at the time of filling the questionnaire as compared with their disease before the use of triple combination treatment. On clinical examination, the evidence of steroid side effects was seen in 26 patients (43.3%). Steroid-induced telangiectasia was the commonest finding, seen in all of these 26

  9. Mometasone-based triple combination therapy in melasma: Is it really safe?

    Directory of Open Access Journals (Sweden)

    Majid Imran

    2010-01-01

    Full Text Available Background: Kligman′s triple combination formula has been one of the most popular treatment options in melasma over the last three decades. The original Kligman′s formula has been modified in many ways over the years and the most recent modification that has been introduced is a triple combination of 2% hydroquinone, 0.025% tretinoin, and 1% mometasone. The use of this triple combination in patients with melasma has seen a sharp rise over the last few years and with this rampant use the side-effect profile of this triple combination has also come to the fore. Aim : The aim of the present study was to assess the overall safety of the mometasone-based triple combination treatment in the management of melasma. Materials and Methods: This retrospective study was performed on 60 patients of melasma who had used a mometasone-based triple combination treatment for at least 3 weeks anytime in the previous 1 year. The patients were given a preformed questionnaire wherein they assessed the overall effect of the triple combination treatment on their melasma during its use as well as after its withdrawal. The patients were specifically asked about the status of their disease as well as the sun sensitivity of their skin before and after the use of triple combination treatment. In addition, the patients were assessed by a single trained dermatologist for the presence of any adverse effects arising out of the triple combination treatment in the form of telangiectasia, hypertrichosis, acne, skin atrophy, etc. Results: Majority of patients (51.7% had used the combination treatment well beyond the recommended duration. About one-third (36.7% of the patients rated their melasma as worse at the time of filling the questionnaire as compared with their disease before the use of triple combination treatment. On clinical examination, the evidence of steroid side effects was seen in 26 patients (43.3%. Steroid-induced telangiectasia was the commonest finding, seen

  10. Molecular structure of the collagen triple helix.

    Science.gov (United States)

    Brodsky, Barbara; Persikov, Anton V

    2005-01-01

    The molecular conformation of the collagen triple helix confers strict amino acid sequence constraints, requiring a (Gly-X-Y)(n) repeating pattern and a high content of imino acids. The increasing family of collagens and proteins with collagenous domains shows the collagen triple helix to be a basic motif adaptable to a range of proteins and functions. Its rodlike domain has the potential for various modes of self-association and the capacity to bind receptors, other proteins, GAGs, and nucleic acids. High-resolution crystal structures obtained for collagen model peptides confirm the supercoiled triple helix conformation, and provide new information on hydrogen bonding patterns, hydration, sidechain interactions, and ligand binding. For several peptides, the helix twist was found to be sequence dependent, and such variation in helix twist may serve as recognition features or to orient the triple helix for binding. Mutations in the collagen triple-helix domain lead to a variety of human disorders. The most common mutations are single-base substitutions that lead to the replacement of one Gly residue, breaking the Gly-X-Y repeating pattern. A single Gly substitution destabilizes the triple helix through a local disruption in hydrogen bonding and produces a discontinuity in the register of the helix. Molecular information about the collagen triple helix and the effect of mutations will lead to a better understanding of function and pathology.

  11. Kondo effects in triangular triple quantum dots

    Science.gov (United States)

    Oguri, Akira; Numata, Takahide; Nisikawa, Yunori; Hewson, A. C.

    2009-03-01

    We study the conductance through a triangular triple quantum dot, which is connected to two noninteracting leads, using the numerical renormalization group (NRG). It is found that the system shows a variety of Kondo effects depending on the filling of the triangle. The SU(4) Kondo effect occurs at half-filling, and a sharp conductance dip due to a phase lapse appears in the gate-voltage dependence. Furthermore, when four electrons occupy the three sites on average, a local S=1 moment, which is caused by the Nagaoka mechanism, is induced along the triangle. The temperature dependence of the entropy and spin susceptibility of the triangle shows that this moment is screened by the conduction electrons via two separate stages at different temperatures. The two-terminal and four-terminal conductances show a clear difference at the gate voltages, where the SU(4) or the S=1 Kondo effects occur[1]. We will also discuss effects of deformations of the triangular configuration, caused by the inhomogeneity in the inter-dot couplings and in the gate voltages. [4pt] [1] T.Numata, Y.Nisikawa, A.Oguri, and A.C.Hewson: arXiv:0808.3496.

  12. Reverse triple I method of fuzzy reasoning

    Institute of Scientific and Technical Information of China (English)

    宋士吉; 吴澄

    2002-01-01

    A theory of reverse triple I method with sustention degree is presented by using the implication operator R0 in every step of the fuzzy reasoning. Its computation formulas of supremum for fuzzy modus ponens and infimum for fuzzy modus tollens are given respectively. Moreover, through the generalization of this problem, the corresponding formulas of ?-reverse triple I method with sustention degree are also obtained. In addition, the theory of reverse triple I method with restriction degree is proposed as well by using the operator R0, and the computation formulas of infimum for fuzzy modus ponens and supremum for fuzzy modus tollens are shown.

  13. Trilayered Morphology of an ABC Triple Crystalline Triblock Terpolymer

    KAUST Repository

    Palacios, Jordana K.

    2017-09-07

    Triple crystalline triblock terpolymers are materials with remarkable semicrystalline superstructures. In this work, we report for first time the alternating triple lamellar morphology that self-assembles inside spherulites of a triblock terpolymer composed of poly(ethylene oxide) (PEO), poly(ε-caprolactone) (PCL), and poly(l-lactide) (PLLA). The morphology of the PEO-b-PCL-b-PLLA triblock terpolymer is compared to an analogous PCL-b-PLLA diblock copolymer. Both diblock and triblock form a single phase in the melt. Two crystallization protocols were employed to create particular crystalline morphologies. In both cases, the isothermal crystallization of the PLA block is induced first (at 81 °C, a temperature above the melting points of both PCL and PEO blocks) and PLLA spherulites form a template, whereupon cooling the other two blocks can crystallize within the PLLA interlamellar spaces. WAXS analysis demonstrated the double crystalline and triple crystalline nature of the materials. The lamellar structure was evaluated by AFM observations and SAXS measurements. Moreover, theoretical SAXS curves of one-dimensional structural models were calculated. AFM micrographs of the triblock terpolymer evidenced the three different lamellae of PLLA, PCL and PEO that coexist together within the same spherulite. Three different lamellar thickness were determined, and their dimensions suggested that all blocks crystallized in chain-folded conformations. The evolution of the triple lamellar morphology during heating of tricrystalline samples was followed by in situ synchrotron SAXS measurements. The theoretical analysis of the SAXS curves of the triblock terpolymer allowed us to propose a stacking morphological model, in which a particular trilayer structure exists, where one lamella of PCL or one lamella of PEO is inserted randomly between two adjacent PLLA lamellae.

  14. Triple AIM evaluation and application in advanced node

    Science.gov (United States)

    Wang, Gary C.; Lio, En Chuan; Hung, Yuting; Chen, Charlie; Wang, Sybil; Weng, Tang Chun; Lin, Bill; Yu, Chun Chi

    2016-03-01

    A novel method on advanced node for IBO (Image Based Overlay) data extraction accuracy is demonstrated in this work, and here some special design in triple-AIM (Advanced Imaging Metrology) is able to realize the approach. Since triple AIM design has 3 locations left for patterning layers insertion, a new design with 2 layers locations, location-A (inner) and location-B (middle), are generated by 1st pattering, i.e. once lithography exposure, and the 2 marks grouping are formed on dielectric through lithography and etching process with a predetermined overlay "zero offset" through original mask layout design, as illustrated in Fig. (1). And then, as following top photo resist layer, assumed location-C (outer), lithography patterning process, PR coating, exposure and development complete, full triple-AIM patterns is generated, and 3 sets of overlay data could be obtained, A to B, C to B, C to A. Through re-calculating the overlay raw data of current (2nd patterning layer) to previous (1st patterning layer) layer by averaging [C to B] and [C to A], then theoretically the data extraction of sites would be more accuracy, since the variation of local marks signal, induced by inline process instability, could be minimized through the raw data averaging procedure. Moreover, from raw data [A to B], an extra monitor function for detections of the inline process variation, marks selection and recipe setting optimization could be obtained, since marks in [A] and [BB] locations are both generated in 1st patterning, and with the target "zero". So if the raw data [A to BB] is bigger or smaller than "zero" in some degree, there should be some process issue or marks condition setting error in triple-AIM design.

  15. The triple helix perspective of innovation systems

    NARCIS (Netherlands)

    Leydesdorff, L.; Zawdie, G.

    2010-01-01

    Alongside the neo-institutional model of networked relations among universities, industries, and governments, the triple helix can be provided with a neo-evolutionary interpretation as three selection environments operating upon one another: markets, organisations and technological opportunities. Ho

  16. On triple factorisations of finite groups

    CERN Document Server

    Alavi, S Hassan

    2009-01-01

    This paper introduces and develops a general framework for studying triple factorisations of the form $G=ABA$ of finite groups $G$, with $A$ and $B$ subgroups of $G$. We call such a factorisation nondegenerate if $G\

  17. Triple click reaction strategy for macromolecular diversity.

    Science.gov (United States)

    Tunca, Umit

    2013-01-11

    This Feature Article focuses on the rapidly emerging concept of the "triple click reactions" towards the design and synthesis of macromolecules with well-defined topology and chemical composition, and also precise molecular weight and narrow molecular weight distribution. The term "triple click reaction" used in this feature article is based on the utilization of three chemically and mechanistically different click reactions for polymer-polymer conjugation and post-modification of the polymers. Three sequential click reactions of which two are identical should not be considered to be triple click reactions. The triple click reaction strategy for polymer conjugation and post-modification of polymers is classified in this article based on the resultant architectures: linear and non-linear structures. Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  18. Close Binaries, Triples, and Eclipses

    Science.gov (United States)

    Sanborn, Jason; Zavala, R. T.

    2013-01-01

    Observations of the variable radio source b Per (HR1324) are part of an ongoing survey of close binary systems using the Navy Precision Optical Interferometer. Historical observations of b Per include sparse photometric and spectroscopic observations dating back to 1923, clearly showing this object to be a non-eclipsing, single-lined ellipsoidal variable. This is where the story for b Per stopped until recent inclusion of optical interferometric data which led to the detection of a third, long-period component. As the interferometric observations continue to build up so to is the understanding of this binary system, with the modeled orbital parameters pointing to an edge-on orientation that may allow for the detection of an eclipse by the long-period component. These types of eclipse events are quite rare for long-period binaries due to the nearly edge-on orientation required for their detection, leaving open the opportunity for more traditional methods of observation to add to the body of knowledge concerning this understudied system. Here we present the latest observational data of the b Per system along with an introduction to the best fit orbital parameters governing the eclipsing nature of this complex triple-system.

  19. Triple Pulsar Tests Mass Triplets

    CERN Document Server

    Shao, Lijing

    2016-01-01

    Three conceptually different masses appear in equations of motion for objects under gravity, namely, inertial mass, $m_{\\cal I}$, passive gravitational mass, $m_{\\cal P}$, and active gravitational mass, $m_{\\cal A}$. It is assumed that, for any objects, $m_{\\cal I} = m_{\\cal P} = m_{\\cal A}$ in Newtonian gravity, and $m_{\\cal I} = m_{\\cal P}$ in Einsteinian gravity, oblivious to objects' sophisticated internal structure. Empirical examination of the equivalence probes deep into gravity theories. We propose new tests based on pulsar timing of the stellar triple system, PSR J0337+1715. Various machine-precision three-body simulations are performed, from which, equivalence-violating parameters are extracted with Markov chain Monte Carlo sampling that takes full correlations into account. We show that the difference in masses can be probed to $3\\times10^{-8}$, improving the post-Newtonian constraints of strong equivalence principle by $10^3$--$10^6$. The test of $m_{\\cal P}=m_{\\cal A}$ presents the first test of ...

  20. An analysis of the curative effect of saccharomyces boulardii combined with a standard triple therapy in the treatment of 55 cases of helicobacter pylori-induced peptic ulcer%布拉酵母菌联合标准三联疗法治疗幽门螺杆菌消化性溃疡55例效果分析

    Institute of Scientific and Technical Information of China (English)

    朱路平; 肖飞

    2014-01-01

    目的:分析布拉酵母菌联合标准三联疗法治疗幽门螺杆菌消化性溃疡的临床疗效和安全性。方法随机将109例确诊幽门螺杆菌消化性溃疡进行分组,对照组54例予标准三联疗法治疗,实验组55例予布拉氏酵母菌联合标准三联疗法治疗,观察两组溃疡愈合效果、幽门螺杆菌清除率和不良反应情况。结果实验组溃疡愈合总有效率92.73%明显高于对照组79.63%(P0.05)。结论布拉氏酵母菌联合标准三联疗法能够通过快速恢复幽门螺杆菌消化性溃疡患者肠道菌群的动态平衡、抑制幽门螺杆菌在胃黏膜上皮定值和成长等作用提高幽门螺杆菌清除率。%Objective To analyze the clinical effect and safety of saccharomyces boulardii combined with a standard triple therapy in the treatment of helicobacter pylori-induced peptic ulcer. Methods A total of 109 patients who were diagnosed as helicobacter pylori-induced peptic ulcer were randomly assigned to control group and experimental group. The control group of 54 patients received a standard triple therapy, and the experimental group of 55 patients received saccharomyces boulardii combined with a standard triple therapy. Ulcer recovery, clearance rate of helicobacter pylori and adverse events were observed between the two groups. Results The total effective rate of ulcer recovery in the ex-perimental group was 92.73%, significantly higher than that of 79.63%in the control group(P<0.05); The clearance rate of helicobacter pylori in the experimental group was 90.91%, significantly higher than that of 75.93% in the control group (P<0.05); The incidence of adverse events in the experimental group was 12.73%, and P value was over 0.05 compared to that of 11.11% in the control group. Conclusion The saccharomyces boulardii combined with a standard triple therapy in the treatment of helicobacter pylori-induced peptic ulcer has a significantly effect, and is able to en-hance the

  1. The collagen triple-helix structure.

    Science.gov (United States)

    Brodsky, B; Ramshaw, J A

    1997-03-01

    Recent advances, principally through the study of peptide models, have led to an enhanced understanding of the structure and function of the collagen triple helix. In particular, the first crystal structure has clearly shown the highly ordered hydration network critical for stabilizing both the molecular conformation and the interactions between triple helices. The sequence dependent nature of the conformational features is also under active investigation by NMR and other techniques. The triple-helix motif has now been identified in proteins other than collagens, and it has been established as being important in many specific biological interactions as well as being a structural element. The nature of recognition and the degree of specificity for interactions involving triple helices may differ from globular proteins. Triple-helix binding domains consist of linear sequences along the helix, making them amenable to characterization by simple model peptides. The application of structural techniques to such model peptides can serve to clarify the interactions involved in triple-helix recognition and binding and can help explain the varying impact of different structural alterations found in mutant collagens in diseased states.

  2. HD 181068: A Red Giant in a Triply Eclipsing Compact Hierarchical Triple System

    DEFF Research Database (Denmark)

    Derekas, A.; Kiss, Lazlo L.; Borkovits, T.

    2011-01-01

    by ground-based spectroscopy and interferometry, which show it to be a hierarchical triple with two types of mutual eclipses. The primary is a red giant that is in a 45-day orbit with a pair of red dwarfs in a close 0.9-day orbit. The red giant shows evidence for tidally induced oscillations that are driven...

  3. Building a Distributed Infrastructure for Scalable Triple Stores

    Institute of Scientific and Technical Information of China (English)

    Jing Zhou; Wendy Hall; David De Roure

    2009-01-01

    Built specifically for the Semantic Web, triple stores are required to accommodate a large number of RDF triples and remain primarily centralized. As triple stores grow and evolve with time, there is a demanding need for scalable techniques to remove resource and performance bottlenecks in such systems. To this end, we propose a fully decentralized peer-to-peer architecture for large scale triple stores in which triples are maintained by individual stakeholders, and a semantics-directed search protocol, mediated by topology reorganization, for locating triples of interest. We test our design through simulations and the results show anticipated improvements over existing techniques for distributed triple stores. In addition to engineering future large scale triple stores, our work will in particular benefit the federation of stand-alone triple stores of today to achieve desired scalability.

  4. On Split Lie Triple Systems II

    Indian Academy of Sciences (India)

    Antonio J Calderón Martín; M Forero Piulestán

    2010-04-01

    In [4] it is studied that the structure of split Lie triple systems with a coherent 0-root space, that is, satisfying $[T_0,T_0,T]=0$ and $[T_0,T_,T_0]≠ 0$ for any nonzero root and where $T_0$ denotes the 0-root space and $T_$ the -root space, by showing that any of such triple systems with a symmetric root system is of the form $T=\\mathcal{U}+\\sum_j I_j$ with $\\mathcal{U}$ a subspace of the 0-root space $T_0$ and any $I_j$ a well described ideal of , satisfying $[I_j,T,I_k]=0$ if $j≠ k$. It is also shown in [4] that under certain conditions, a split Lie triple system with a coherent 0-root space is the direct sum of the family of its minimal ideals, each one being a simple split Lie triple system, and the simplicity of is characterized. In the present paper we extend these results to arbitrary split Lie triple systems with no restrictions on their 0-root spaces.

  5. Targeted chemotherapy for triple-negative breast cancers via LHRH receptor.

    Science.gov (United States)

    Föst, Crispin; Duwe, Francesca; Hellriegel, Martin; Schweyer, Stefan; Emons, Günter; Gründker, Carsten

    2011-05-01

    Triple-negative breast cancer does not express estrogen and progesterone receptors and there is no overexpression/amplification of the HER2-neu gene. Therefore, this subtype of breast cancer lacks the benefits of specific therapies which target these receptors. About 60% of all human breast cancers express receptors for luteinizing hormone releasing hormone (LHRH, GnRH), which might be used as a target. The LHRH receptor can be used for targeted chemotherapy with cytotoxic luteinizing hormone releasing hormone agonists such as AEZS-108 (AN-152), in which doxorubicin is linked to [D-Lys6]LHRH. In the present study we have analyzed by in vitro and in vivo experiments whether the cytotoxic LHRH agonist AEZS-108 (AN-152) induces apoptosis in triple-negative human breast cancer cells that express LHRH receptors. LHRH receptor expression in tumor biopsy specimens of triple-negative breast cancers was tested using immunohistochemistry. Cell proliferation was analyzed using alamar blue proliferation assay. Induction of apoptosis was quantified by measurement of loss of mitochondrial membrane potential. In vivo experiments were performed using nude mice bearing xenografted human breast tumors.Thirty-one of 42 triple-negative breast cancers (73.8%) expressed LHRH receptors. We could show that treatment of triple-negative but LHRH-positive MDA-MB-231, HCC1806 and HCC1937 human breast cancer cells with AEZS-108 (AN-152) resulted in apoptotic cell death in vitro via activation of caspase-3. The antitumor effects were confirmed in nude mice. AEZS-108 (AN-152) inhibited the growth of xenotransplants of triple-negative human breast cancers in nude mice completely, without any apparent side effects. The cytotoxic LHRH agonist AEZS-108 (AN-152) seems to be a suitable drug for an efficacious therapy for triple-negative breast cancers with little toxicity.

  6. Triple helix interactions for eco-innovation

    DEFF Research Database (Denmark)

    Hermann, Roberto Rivas; Riisgaard, Henrik; Remmen, Arne

    Authority with insights from consultants, universities and donnor agencies. The proximity of the science park to the canal, has hitherto not yielded with the creation of a “green cluster”, which could be a precedent to promote eco-innovations. These findings suggest that, Triple Helix interactions...... the role of science parks in promoting eco-innovation. This study uses qualitative data gathered in two units of analysis: Panama Canal Authority and City of Knowledge Science Park. The study examines how Triple Helix interactions have built the regional system of eco-innovation at the Panama Canal...... are not institutionalized but take place through adhoc projects. Further, science parks could become mediators in Triple Helix interactions between industry, universities and governments....

  7. Double Fell bundles and Spectral triples

    CERN Document Server

    Martins, Rachel A D

    2007-01-01

    As a natural and canonical extension of Kumjian's Fell bundles over groupoids \\cite{fbg}, we give a definition for a double Fell bundle (a double category) over a double groupoid. We show that finite dimensional double category Fell line bundles tensored with their dual with $S^o$-reality satisfy the finite real spectral triples axioms but not necessarily orientability. This means that these product bundles with noncommutative algebras can be regarded as noncommutative compact manifolds more general than real spectral triples as they are not necessarily orientable. By construction, they unify the noncommutative geometry axioms and hence provide an algebraic enveloping structure for finite spectral triples to give the Dirac operator $D$ new algebraic and geometric structures that are otherwise missing in the transition from Fredholm operator to Dirac operator. The Dirac operator in physical applications as a result becomes less ad hoc. The new noncommutative space we present is a complex line bundle over a dou...

  8. Insulin Aggregation at a Dynamic Solid-Liquid-Air Triple Interface.

    Science.gov (United States)

    Frachon, Thibaut; Bruckert, Franz; Le Masne, Quentin; Monnin, Emmanuel; Weidenhaupt, Marianne

    2016-12-13

    Therapeutic proteins are privileged in drug development because of their exquisite specificity, which is due to their three-dimensional conformation in solution. During their manufacture, storage, and delivery, interactions with material surfaces and air interfaces are known to affect their stability. The growing use of automated devices for handling and injection of therapeutics increases their exposure to protocols involving intermittent wetting, during which the solid-liquid and liquid-air interfaces meet at a triple contact line, which is often dynamic. Using a microfluidic setup, we analyze the effect of a moving triple interface on insulin aggregation in real time over a hydrophobic surface. We combine thioflavin T fluorescence and reflection interference microscopy to concomitantly monitor insulin aggregation and the morphology of the liquid as it dewets the surface. We demonstrate that insulin aggregates in the region of a moving triple interface and not in regions submitted to hydrodynamic shear stress alone, induced by the moving liquid. During dewetting, liquid droplets form on the surface anchored by adsorbed proteins, and the accumulation of amyloid aggregates is observed exclusively as fluorescent rings growing eccentrically around these droplets. The fluorescent rings expand until the entire channel surface sweeped by the triple interface is covered by amyloid fibers. On the basis of our experimental results, we propose a model describing the growth mechanism of insulin amyloid fibers at a moving triple contact line, where proteins adsorbed at a hydrophobic surface are exposed to the liquid-air interface.

  9. Contribution of dipole-dipole interactions to the stability of the collagen triple helix.

    Science.gov (United States)

    Improta, Roberto; Berisio, Rita; Vitagliano, Luigi

    2008-05-01

    Unveiling sequence-stability and structure-stability relationships is a major goal of protein chemistry and structural biology. Despite the enormous efforts devoted, answers to these issues remain elusive. In principle, collagen represents an ideal system for such investigations due to its simplified sequence and regular structure. However, the definition of the molecular basis of collagen triple helix stability has hitherto proved to be a difficult task. Particularly puzzling is the decoding of the mechanism of triple helix stabilization/destabilization induced by imino acids. Although the propensity-based model, which correlates the propensities of the individual imino acids with the structural requirements of the triple helix, is able to explicate most of the experimental data, it is unable to predict the rather high stability of peptides embedding Gly-Hyp-Hyp triplets. Starting from the available X-ray structures of this polypeptide, we carried out an extensive quantum chemistry analysis of the mutual interactions established by hydroxyproline residues located at the X and Y positions of the Gly-X-Y motif. Our data clearly indicate that the opposing rings of these residues establish significant van der Waals and dipole-dipole interactions that play an important role in triple helix stabilization. These findings suggest that triple helix stabilization can be achieved by distinct structural mechanisms. The interplay of these subtle but recurrent effects dictates the overall stability of this widespread structural motif.

  10. The triple point of sulfur hexafluoride

    Science.gov (United States)

    Rourke, P. M. C.

    2016-04-01

    A cryogenic fixed point cell has been filled with high purity (99.999%) sulfur hexafluoride (SF6) and measured in an adiabatic closed-cycle cryostat system. Temperature measurements of the SF6 melting curve were performed using a capsule-type standard platinum resistance thermometer (CSPRT) calibrated over the International Temperature Scale of 1990 (ITS-90) subrange from the triple point of equilibrium hydrogen to the triple point of water. The measured temperatures were corrected by 0.37 mK for the effects of thermometer self-heating, and the liquidus-point temperature estimated by extrapolation to melted fraction F  =  1 of a simple linear regression versus melted fraction F in the range F  =  0.53 to 0.84. Based on this measurement, the temperature of the triple point of sulfur hexafluoride is shown to be 223.555 23(49) K (k  =  1) on the ITS-90. This value is in excellent agreement with the best prior measurements reported in the literature, but with considerably smaller uncertainty. An analysis of the detailed uncertainty budget of this measurement suggests that if the triple point of sulfur hexafluoride were to be included as a defining fixed point of the next revision of the International Temperature Scale, it could do so with a total realization uncertainty of approximately 0.43 mK, slightly larger than the realization uncertainties of the defining fixed points of the ITS-90. Since the combined standard uncertainty of this SF6 triple point temperature determination is dominated by chemical impurity effects, further research exploring gas purification techniques and the influence of specific impurity species on the SF6 triple point temperature may bring the realization uncertainty of SF6 as a fixed point material into the range of the defining fixed points of the ITS-90.

  11. The Effect of Everolimus in an In Vitro Model of Triple Negative Breast Cancer and Osteoclasts

    Science.gov (United States)

    Mercatali, Laura; Spadazzi, Chiara; Miserocchi, Giacomo; Liverani, Chiara; De Vita, Alessandro; Bongiovanni, Alberto; Recine, Federica; Amadori, Dino; Ibrahim, Toni

    2016-01-01

    Metastatic bone disease has a major impact on morbidity of breast cancer (BC) patients. Alterations in mTOR signaling are involved both in cancer progression and in osteoclast differentiation. The purpose of this study was to assess the role of mTOR inhibitor Everolimus (Eve) on osteoclastogenesis induced by triple negative BC cells. To this aim, we developed an in vitro human model of osteoclastogenesis from peripheral blood monocytes co-cultured with the triple negative SCP2 and the hormonal receptor positive MCF7 cell lines. Osteoclastogenesis was evaluated by TRAP staining, evaluation of F actin rings and Calcitonin Receptor expression. Eve significantly reduced differentiation induced by cancer cells and resulted more effective when evaluated in combination with Denosumab and Zoledronic Acid (Zol). Combination with Zol showed a total abrogation of osteoclast differentiation induced by the triple negative cell line, not by MCF7. Finally, we observed that Eve was active in the inhibition of the crosstalk between cancer cells and osteoclasts reproduced by our model, highlighting a new therapeutic choice for the subsetting of triple negative BC patients. We observed a difference in the response to bone-targeted therapy with respect to BC subtypes. Our model may represent a valid platform for preclinical trials on bone-targeted drugs and for the study of the interplay of BC with bone stromal cells. PMID:27809291

  12. The Effect of Everolimus in an In Vitro Model of Triple Negative Breast Cancer and Osteoclasts.

    Science.gov (United States)

    Mercatali, Laura; Spadazzi, Chiara; Miserocchi, Giacomo; Liverani, Chiara; De Vita, Alessandro; Bongiovanni, Alberto; Recine, Federica; Amadori, Dino; Ibrahim, Toni

    2016-11-01

    Metastatic bone disease has a major impact on morbidity of breast cancer (BC) patients. Alterations in mTOR signaling are involved both in cancer progression and in osteoclast differentiation. The purpose of this study was to assess the role of mTOR inhibitor Everolimus (Eve) on osteoclastogenesis induced by triple negative BC cells. To this aim, we developed an in vitro human model of osteoclastogenesis from peripheral blood monocytes co-cultured with the triple negative SCP2 and the hormonal receptor positive MCF7 cell lines. Osteoclastogenesis was evaluated by TRAP staining, evaluation of F actin rings and Calcitonin Receptor expression. Eve significantly reduced differentiation induced by cancer cells and resulted more effective when evaluated in combination with Denosumab and Zoledronic Acid (Zol). Combination with Zol showed a total abrogation of osteoclast differentiation induced by the triple negative cell line, not by MCF7. Finally, we observed that Eve was active in the inhibition of the crosstalk between cancer cells and osteoclasts reproduced by our model, highlighting a new therapeutic choice for the subsetting of triple negative BC patients. We observed a difference in the response to bone-targeted therapy with respect to BC subtypes. Our model may represent a valid platform for preclinical trials on bone-targeted drugs and for the study of the interplay of BC with bone stromal cells.

  13. Triple arthrodesis for adult acquired flatfoot.

    Science.gov (United States)

    Catanzariti, Alan R; Dix, Brian T; Richardson, Phillip E; Mendicino, Robert W

    2014-07-01

    The primary goal of triple arthrodesis for stage III and IV adult acquired flatfoot is to obtain a well-aligned plantigrade foot that will support the ankle in optimal alignment. Ancillary procedures including posterior muscle group lengthening, medial displacement calcaneal osteotomy, medial column stabilization, peroneus brevis tenotomy, or transfer and harvest of regional bone graft are often necessary to achieve adequate realignment. Image intensification is helpful in confirming optimal realignment before fixation. Results of triple arthrodesis are enhanced with adequate preparation of joint surfaces, bone graft/orthobiologics, 2-point fixation of all 3 tritarsal joints, and a vertical heel position.

  14. Triple Bragg diffraction in paratellurite crystal

    Science.gov (United States)

    Kotov, V. M.; Averin, S. V.; Voronko, A. I.; Kotov, E. V.; Tikhomirov, S. A.

    2017-07-01

    Triple Bragg diffraction in a paratellurite crystal has been considered for the case when the plane of diffraction is oblique to the optical axis of the crystal. It has been shown that effective photoelastic constants for isotropic and anisotropic diffraction depend on the inclination of the plane of diffraction insignificantly. Triple Bragg diffraction of 0.63-μm coherent radiation in paratellurite at a 47.3-MHz slow acoustic wave has been experimentally demonstrated. For an optical power of 0.69 W delivered to a piezoconverter, the relative intensities of diffraction orders equal 0.4, 0.4, 0.1, and 0.1, respectively.

  15. $\\kappa$-Deformation and Spectral Triples

    CERN Document Server

    Iochum, B; Schücker, Th; Sitarz, A; 10.5506/APhysPolBSupp.4.305

    2011-01-01

    The aim of the paper is to answer the following question: does $\\kappa$-deformation fit into the framework of noncommutative geometry in the sense of spectral triples? Using a compactification of time, we get a discrete version of $\\kappa$-Minkowski deformation via $C^*$-algebras of groups. The dynamical system of the underlying groups (including some Baumslag--Solitar groups) is used in order to construct \\emph{finitely summable} spectral triples. This allows to bypass an obstruction to finite-summability appearing when using the common regular representation.

  16. TREN (Tris(2-aminoethyl)amine): an effective scaffold for the assembly of triple helical collagen mimetic structures.

    Science.gov (United States)

    Kwak, Juliann; De Capua, Antonia; Locardi, Elsa; Goodman, Murray

    2002-11-27

    A new scaffold, TREN-(suc-OH)(3) where TREN is tris(2-aminoethyl)amine and suc is the succinic acid spacers, was incorporated to assemble triple helices composed of Gly-Nleu-Pro sequences (Nleu denotes N-isobutylglycine). Extensive biophysical studies which include denaturation studies, CD and NMR spectroscopy, and molecular modeling demonstrated that TREN-[suc-(Gly-Nleu-Pro)(n)-NH(2)](3) (n = 5 and 6) form stable triple helical structures in solution. A comparative analysis of TREN-assembled and KTA-assembled collagen mimetics (KTA denotes Kemp triacid, 1,3,5-trimethylcyclohexane-1,3,5-tricarboxylic acid) indicates that the flexibility of the TREN scaffold is superior to the KTA scaffold in inducing triple helicity. This effect most likely arises from the flexibility of the TREN scaffold which allows the three peptide chains to adjust their register for a tighter triple helical packing.

  17. MEIR-KEELER TYPE CONTRACTIONS FOR TRIPLED FIXED POINTS

    Institute of Scientific and Technical Information of China (English)

    Hassen Aydi; Erdal Karapinar; Calogero Vetro

    2012-01-01

    In 2011,Berinde and Borcut [6] introduced the notion of tripled fixed point in partially ordered metric spaces.In our paper,we give some new tripled fixed point theorems by using a generalization of Meir-Keeler contraction.

  18. Revised Reynolds Stress and Triple Product Models

    Science.gov (United States)

    Olsen, Michael E.; Lillard, Randolph P.

    2017-01-01

    Revised versions of Lag methodology Reynolds-stress and triple product models are applied to accepted test cases to assess the improvement, or lack thereof, in the prediction capability of the models. The Bachalo-Johnson bump flow is shown as an example for this abstract submission.

  19. Targeting EGFR in Triple Negative Breast Cancer

    Directory of Open Access Journals (Sweden)

    Naoto T. Ueno, Dongwei Zhang

    2011-01-01

    Full Text Available Our preliminary data show that erlotinib inhibits Triple-negative breast cancer (TNBC in a xenograft model. However, inhibition of metastasis by erlotinib is accompanied by nonspecific effects because erlotinib can inhibit other kinases; thus, more direct targets that regulate TNBC metastasis need to be identified to improve its therapeutic efficacy.

  20. Triple-axis spectrometer DruechaL

    Energy Technology Data Exchange (ETDEWEB)

    Buehrer, W.; Keller, P. [Lab. for Neutron Scattering ETH Zurich, Zurich (Switzerland) and Paul Scherrer Institute, Villigen (Switzerland)

    1996-11-01

    DruechaL is a triple-axis spectrometer located at a cold guide. The characteristics of guide and instrument allow the use of a broad spectral range of neutrons. The resolution in momentum and energy transfer can be tuned to match the experimental requirements by using either collimators or focusing systems (monochromator, antitrumpet, analyser). (author) figs., tabs., refs.

  1. Resolution of a triple axis spectrometer

    DEFF Research Database (Denmark)

    Nielsen, Mourits; Bjerrum Møller, Hans

    1969-01-01

    A new method for obtaining the resolution function for a triple-axis neutron spectrometer is described, involving a combination of direct measurement and analytical calculation. All factors which contribute to the finite resolution of the instrument may be taken into account, and Gaussian...

  2. Triple mode filters with coaxial excitation

    NARCIS (Netherlands)

    Gerini, G.; Bustamante, F.D.; Guglielmi, M.

    2004-01-01

    In this paper we describe triple mode filters in a square waveguide with integrated coaxial input/output excitation. An important feature of the structure proposed is that it is easily amenable to an accurate full wave analysis. In addition to theory, a practical six pole filter with two transmissio

  3. A New Parity Formula: Triple T.

    Science.gov (United States)

    Newton, Richard F.

    Triple T, a graduate project to educate (train) teacher trainers, allows participants to view the schools as a total system and gives educators a means of training people to change that system. It offers an opportunity to develop an alternative means for graduate education. An important element in this program is parity. While parity is more a…

  4. Detecting Triple Systems with Gravitational Wave Observations

    Science.gov (United States)

    Meiron, Yohai; Kocsis, Bence; Loeb, Abraham

    2017-01-01

    The Laser Interferometer Gravitational Wave Observatory (LIGO) has recently discovered gravitational waves (GWs) emitted by merging black hole binaries. We examine whether future GW detections may identify triple companions of merging binaries. Such a triple companion causes variations in the GW signal due to: (1) the varying path length along the line of sight during the orbit around the center of mass; (2) relativistic beaming, Doppler, and gravitational redshift; (3) the variation of the “light”-travel time in the gravitational field of the triple companion; and (4) secular variations of the orbital elements. We find that the prospects for detecting a triple companion are the highest for low-mass compact object binaries which spend the longest time in the LIGO frequency band. In particular, for merging neutron star binaries, LIGO may detect a white dwarf or M-dwarf perturber at a signal-to-noise ratio of 8, if it is within 0.4 {R}ȯ distance from the binary and the system is within a distance of 100 Mpc. Stellar mass (supermassive) black hole perturbers may be detected at a factor 5 × (103×) larger separations. Such pertubers in orbit around a merging binary emit GWs at frequencies above 1 mHz detectable by the Laser Interferometer Space Antenna in coincidence.

  5. Detecting triple systems with gravitational wave observations

    CERN Document Server

    Meiron, Yohai; Loeb, Abraham

    2016-01-01

    The Laser Interferometer Gravitational Wave Observatory (LIGO) has recently discovered gravitational waves (GWs) emitted by merging black hole binaries. We examine whether future GW detections may identify triple companions of merging binaries. Such a triple companion causes variations in the GW signal due to (1) the varying path length along the line of sight during the orbit around the center of mass, (2) relativistic beaming, Doppler, and gravitational redshift, and (3) the variation of the "light"-travel time in the gravitational field of the triple companion, known respectively as Roemer-, Einstein-, and Shapiro-delays in pulsar binaries. We find that the prospects for detecting the triple companion are the highest for low-mass compact object binaries which spend the longest time in the LIGO frequency band with circular orbits. In particular, for merging neutron star binaries, LIGO may detect a white dwarf or M-dwarf perturber at signal to noise ratio of 8, if it is within 0.4 solar radius distance from ...

  6. Discovering Steiner Triple Systems through Problem Solving

    Science.gov (United States)

    Sriraman, Bharath

    2004-01-01

    An attempt to implement problem solving as a teacher of ninth grade algebra is described. The problems selected were not general ones, they involved combinations and represented various situations and were more complex which lead to the discovery of Steiner triple systems.

  7. Significance of nitric oxide synthases: Lessons from triple nitric oxide synthases null mice.

    Science.gov (United States)

    Tsutsui, Masato; Tanimoto, Akihide; Tamura, Masahito; Mukae, Hiroshi; Yanagihara, Nobuyuki; Shimokawa, Hiroaki; Otsuji, Yutaka

    2015-01-01

    Nitric oxide (NO) is synthesized by three distinct NO synthases (neuronal, inducible, and endothelial NOSs), all of which are expressed in almost all tissues and organs in humans. The regulatory roles of NOSs in vivo have been investigated in pharmacological studies with non-selective NOS inhibitors. However, the specificity of the inhibitors continues to be an issue of debate, and the authentic significance of NOSs is still poorly understood. To address this issue, we generated mice in which all three NOS genes are completely disrupted. The triple NOSs null mice exhibited cardiovascular abnormalities, including hypertension, arteriosclerosis, myocardial infarction, cardiac hypertrophy, diastolic heart failure, and reduced EDHF responses, with a shorter survival. The triple NOSs null mice also displayed metabolic abnormalities, including metabolic syndrome and high-fat diet-induced severe dyslipidemia. Furthermore, the triple NOSs null mice showed renal abnormalities (nephrogenic diabetes insipidus and pathological renal remodeling), lung abnormalities (accelerated pulmonary fibrosis), and bone abnormalities (increased bone mineral density and bone turnover). These results provide evidence that NOSs play pivotal roles in the pathogenesis of a wide variety of disorders. This review summarizes the latest knowledge on the significance of NOSs in vivo, based on lessons learned from experiments with our triple mutant model.

  8. Significance of nitric oxide synthases: Lessons from triple nitric oxide synthases null mice

    Directory of Open Access Journals (Sweden)

    Masato Tsutsui

    2015-01-01

    Full Text Available Nitric oxide (NO is synthesized by three distinct NO synthases (neuronal, inducible, and endothelial NOSs, all of which are expressed in almost all tissues and organs in humans. The regulatory roles of NOSs in vivo have been investigated in pharmacological studies with non-selective NOS inhibitors. However, the specificity of the inhibitors continues to be an issue of debate, and the authentic significance of NOSs is still poorly understood. To address this issue, we generated mice in which all three NOS genes are completely disrupted. The triple NOSs null mice exhibited cardiovascular abnormalities, including hypertension, arteriosclerosis, myocardial infarction, cardiac hypertrophy, diastolic heart failure, and reduced EDHF responses, with a shorter survival. The triple NOSs null mice also displayed metabolic abnormalities, including metabolic syndrome and high-fat diet-induced severe dyslipidemia. Furthermore, the triple NOSs null mice showed renal abnormalities (nephrogenic diabetes insipidus and pathological renal remodeling, lung abnormalities (accelerated pulmonary fibrosis, and bone abnormalities (increased bone mineral density and bone turnover. These results provide evidence that NOSs play pivotal roles in the pathogenesis of a wide variety of disorders. This review summarizes the latest knowledge on the significance of NOSs in vivo, based on lessons learned from experiments with our triple mutant model.

  9. Antrodia salmonea induces G2 cell-cycle arrest in human triple-negative breast cancer (MDA-MB-231) cells and suppresses tumor growth in athymic nude mice.

    Science.gov (United States)

    Chang, Chia-Ting; Hseu, You-Cheng; Thiyagarajan, Varadharajan; Huang, Hui-Chi; Hsu, Li-Sung; Huang, Pei-Jane; Liu, Jer-Yuh; Liao, Jiunn-Wang; Yang, Hsin-Ling

    2017-01-20

    Antrodia salmonea (AS), is a well-known folk medicinal mushroom in Taiwan, has been reported to exhibit anti-oxidant, anti-angiogenic, and anti-inflammatory effects. In the present study, we examined the effects of AS on cell-cycle arrest in vitro in MDA-MB-231 cells and on tumor regression in vivo using an athymic nude mice model. AS (0-200μg/mL) treatment significantly induced G2 cell-cycle arrest in MDA-MB-231 cells by reducing the levels of cyclin B1, cyclin A, cyclin E, and CDC2 proteins. In addition, N-acetylcysteine (NAC) pretreatment prevented AS induced G2 cell-cycle arrest, indicating that ROS accumulation and subsequent cell cycle arrest might be a major mechanism of AS-induced cytotoxicity. Further, AS treatment decreased COX-2 expression and induced PARP cleavage was significantly reversed by NAC pretreatment in MDA-MB-231 cells. The in vivo study results revealed that AS treatment was effective in terms of delaying the tumor incidence and reducing the tumor growth in MDA-MB-231-xenografted nude mice. TUNEL assay, immunohistochemical staining and Western blotting confirmed that AS significantly modulated the xenografted tumor progression as demonstrated by induction of apoptosis, autophagy, and cell-cycle arrest. Our data strongly suggest that Antrodia salmonea could be an anti-cancer agent for human breast cancer. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  10. A reconstruction theorem for almost-commutative spectral triples

    CERN Document Server

    Ćaćić, Branimir

    2011-01-01

    We propose an expansion of the definition of almost-commutative spectral triple that accommodates non-trivial fibrations and is stable under inner fluctuation of the metric, and then prove a reconstruction theorem for almost-commutative spectral triples under this definition as a simple consequence of the reconstruction theorem for commutative spectral triples. Along the way, we weaken the orientability hypothesis in Connes's reconstruction theorem for commutative spectral triples, and, following Chakraborty and Mathai, prove a number of results concerning the stability of properties of spectral triples under suitable perturbation of the Dirac operator.

  11. Thermal stability of collagen triple helix.

    Science.gov (United States)

    Xu, Yujia

    2009-01-01

    Chief among the challenges of characterizing the thermal stability of the collagen triple helix are the lack of the reversibility of the thermal transition and the presence of multiple folding-unfolding steps during the thermal transition which rarely follows the simple two-state, all-or-none mechanism. Despite of the difficulties inherited in the quantitative depiction of the thermal transition of collagen, biophysical studies combined with proteolysis and mutagenesis approaches using full-chain collagens, short synthetic peptides, and recombinant collagen fragments have revealed molecular features of the thermal unfolding of the subdomains of collagen and led to a better understanding of the diverse biological functions of this versatile protein. The subdomain of collagen generally refers to a segment of the long, rope-like triple helical molecule that can unfold cooperatively as an independent unit whose properties (their size, location, and thermal stability) are considered essential for the molecular recognition during the self-assembly of collagen and during the interactions of collagen with other macromolecules. While the unfolding of segments of the triple helix at temperatures below the apparent melting temperature of the molecule has been used to interpret much of the features of the thermal unfolding of full-chain collagens, the thermal studies of short, synthetic peptides have firmly established the molecular basis of the subdomains by clearly demonstrating the close dependence of the thermal stability of a triple helix on the constituent amino acid residues at the X and the Y positions of the characteristic Gly-X-Y repeating sequence patterns of the triple helix. Studies using recombinant collagen fragments further revealed that in the context of the long, linear molecule, the stability of a segment of the triple helix is also modulated by long-range impact of the local interactions such as the interchain salt bridges. Together, the combined approaches

  12. Real structures on almost-commutative spectral triples

    CERN Document Server

    Ćaćić, Branimir

    2012-01-01

    We refine the reconstruction theorem for almost-commutative spectral triples to a result for real almost-commutative spectral triples, clarifying, in the process, both concrete and abstract definitions of real commutative and almost-commutative spectral triples. In particular, we find that a real almost-commutative spectral triple algebraically encodes the commutative *-algebra of the base manifold in a canonical way, and that a compact oriented Riemannian manifold admits real (almost-)commutative spectral triples of arbitrary KO-dimension. Moreover, we define a notion of smooth family of real finite spectral triples and of the twisting of a concrete real commutative spectral triple by such a family, with interesting KK-theoretic and gauge-theoretic implications.

  13. A triple quantum dot based nano-electromechanical memory device

    Energy Technology Data Exchange (ETDEWEB)

    Pozner, R.; Lifshitz, E. [Schulich Faculty of Chemistry, Technion-Israel Institute of Technology, Haifa 32000 (Israel); Solid State Institute, Technion-Israel Institute of Technology, Haifa 32000 (Israel); Russell Berrie Nanotechnology Institute, Technion-Israel Institute of Technology, Haifa 32000 (Israel); Peskin, U., E-mail: uri@tx.technion.ac.il [Schulich Faculty of Chemistry, Technion-Israel Institute of Technology, Haifa 32000 (Israel); Russell Berrie Nanotechnology Institute, Technion-Israel Institute of Technology, Haifa 32000 (Israel); Lise Meitner Center for Computational Quantum Chemistry, Technion-Israel Institute of Technology, Haifa 32000 (Israel)

    2015-09-14

    Colloidal quantum dots (CQDs) are free-standing nano-structures with chemically tunable electronic properties. This tunability offers intriguing possibilities for nano-electromechanical devices. In this work, we consider a nano-electromechanical nonvolatile memory (NVM) device incorporating a triple quantum dot (TQD) cluster. The device operation is based on a bias induced motion of a floating quantum dot (FQD) located between two bound quantum dots (BQDs). The mechanical motion is used for switching between two stable states, “ON” and “OFF” states, where ligand-mediated effective interdot forces between the BQDs and the FQD serve to hold the FQD in each stable position under zero bias. Considering realistic microscopic parameters, our quantum-classical theoretical treatment of the TQD reveals the characteristics of the NVM.

  14. Double Planet Meets Triple Star

    Science.gov (United States)

    2002-08-01

    atmosphere, a large campaign involving more than twenty scientists and engineers from the Paris Observatory and associated institutions [1] was organized to observe the July 20, 2002, event involving an occultation of a star of visual magnitude 11 (i.e., about 100 times fainter than what can be perceived with then unaided eye), referred to as "P126" in McDonald and Elliot's catalogue. In May 2002, preparatory observations showed that star to be double, with the brighter component of the system ( "P126 A" ) being likely to be occulted by Pluto, as seen from South America. However, because of the duplicity, the predictions of exactly where the shadow of Pluto would sweep the ground were uncertain by about 0.1 arcsec in the sky, corresponding to more than 2000 km on the ground. The NACO images ESO PR Photo 21b/02 ESO PR Photo 21b/02 [Preview - JPEG: 400 x 469 pix - 47k] [Normal - JPEG: 800 x 937 pix - 208k] ESO PR Photo 21c/02 ESO PR Photo 21c/02 [Preview - JPEG: 400 x 467 pix - 53k] [Normal - JPEG: 800 x 933 pix - 232k] Caption : PR Photo 21b/02 shows one of the images obtained with the NAOS-CONICA (NACO) adaptive optics (AO) camera mounted on the ESO VLT 8.2-m YEPUN telescope at the Paranal Observatory in connection with a stellar occultation by Pluto on July 20, 2002. The star was found to be triple - the three components (A, B and C), as well as Pluto and its moon, Charon, are indicated in PR Photo 21c/02 for easy orientation. The images are based on data available from the NACO data webpage. See the text for details. In the end, the close approach (an "appulse" in astronomical terminology) of Pluto and P126 A was indeed observed from various sites in South America, with several mobile telescopes and also including major facilities at the ESO La Silla and Paranal Observatories. In particular, unique and very sharp images were obtained with the NAOS-CONICA (NACO) adaptive optics (AO) camera mounted on the ESO VLT 8.2-m YEPUN telescope . One of the NACO images is shown in PR

  15. On Spectral Triples in Quantum Gravity I

    DEFF Research Database (Denmark)

    Aastrup, Johannes; M. Grimstrup, Jesper; Nest, Ryszard

    2009-01-01

    This paper establishes a link between Noncommutative Geometry and canonical quantum gravity. A semi-finite spectral triple over a space of connections is presented. The triple involves an algebra of holonomy loops and a Dirac type operator which resembles a global functional derivation operator....... The interaction between the Dirac operator and the algebra reproduces the Poisson structure of General Relativity. Moreover, the associated Hilbert space corresponds, up to a discrete symmetry group, to the Hilbert space of diffeomorphism invariant states known from Loop Quantum Gravity. Correspondingly......, the square of the Dirac operator has, in terms of canonical quantum gravity, the form of a global area-squared operator. Furthermore, the spectral action resembles a partition function of Quantum Gravity. The construction is background independent and is based on an inductive system of triangulations...

  16. Secular Evolution of Hierarchical Triple Star Systems

    CERN Document Server

    Ford, E B; Kozinsky, B

    1999-01-01

    We derive octupole-level secular perturbation equations for hierarchical triple systems, using classical Hamiltonian perturbation techniques. Our equations describe the secular evolution of the orbital eccentricities and inclinations over timescales long compared to the orbital periods. By extending previous work done to leading (quadrupole) order to octupole level (i.e., including terms of order $\\alpha^3$, where $\\alpha\\equiv a_1/a_2<1$ is the ratio of semimajor axes) we obtain expressions that are applicable to a much wider range of parameters. For triple systems containing a close inner binary, we also discuss the possible interaction between the classical Newtonian perturbations and the general relativistic precession of the inner orbit. In some cases we show that this interaction can lead to resonances and a significant increase in the maximum amplitude of eccentricity perturbations. We establish the validity of our analytic expressions by providing detailed comparisons with the results of direct num...

  17. Triple A Syndrome: A Case Report

    Directory of Open Access Journals (Sweden)

    Murat Atmaca

    2014-09-01

    Full Text Available Triple A syndrome is a rarely seen autosomal recessive disease characterized by achalasia, adrenal failure and alacrima. The syndrome is frequently seen in childhood. The appearance of its components are usually ordered as alacrima, achalasia and adrenal failure. The majority of the patients diagnosed in the later stages predominantly present with neurological symptoms. In this study, a 21-year-old male who was referred to our clinic with clinical findings of chronic adrenal failure and was diagnosed WİTH triple A syndrome is presented. This patient had been operated three years ago due to achalasia. The diagnosis and treatment of adrenal failure in this syndrome is the most important determinant and indicator in the prognosis of the disease. Turk Jem 2014; 18: 97-99

  18. On Triple-Cut of Scattering Amplitudes

    CERN Document Server

    Mastrolia, Pierpaolo

    2007-01-01

    It is analysed the triple-cut of one-loop amplitudes in dimensional regularisation within spinor-helicity representation. The triple-cut is defined as a difference of two double-cuts with the same particle content, and a same propagator carrying, respectively, causal and anti-causal prescription in each of the two cuts. That turns out into an effective tool for extracting the coefficients of the three-point functions (and higher-point ones) from one-loop-amplitudes. The phase-space integration is oversimplified by using residues theorem to perform the integration over the spinor variables, via the holomorphic anomaly, and a trivial integration on the Feynman parameter. The results are valid for arbitrary values of dimensions.

  19. Triple Negative Breast Cancer and Metabolic Regulation

    Science.gov (United States)

    2015-08-01

    Lactate Dehydrogenase A is an isoform of lactate dehydrogenase, which catalyzes the conversion of pyruvate to lactate . LDHA is expressed in cancer ...AWARD NUMBER: W81XWH-13-1-0167 TITLE: Triple Negative Breast Cancer and Metabolic Regulation PRINCIPAL INVESTIGATOR: Amy S. Yee, Ph.D...Negative Breast Cancer and Metabolic Regulation 5a. CONTRACT NUMBER 5b. GRANT NUMBER W81XWH-13-1-0167 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) Amy S

  20. Triple plasmon resonance of bimetal nanoshell

    Energy Technology Data Exchange (ETDEWEB)

    Shirzaditabar, Farzad [Department of Physics, Razi University, Kermanshah (Iran, Islamic Republic of); Saliminasab, Maryam, E-mail: m.saliminasab@yahoo.com [Young Researchers Club, Kermanshah Branch, Islamic Azad University, Kermanshah (Iran, Islamic Republic of); Arghavani Nia, Borhan [Department of Physics, Kermanshah Branch, Islamic Azad University, Kermanshah (Iran, Islamic Republic of)

    2014-07-15

    In this paper, light absorption spectra properties of a bimetal multilayer nanoshell based on quasi-static approach are investigated. Comparing with silver-dielectric-silver and silver-dielectric-gold nanoshells, gold-dielectric-silver nanoshells have three intense and separated plasmon peaks which are more suitable for multiplex biosensing. Calculations show that relatively small thickness of outer silver shell and large dielectric constant of middle dielectric layer of gold-dielectric-silver nanoshell are suitable to obtain the triple plasmon resonance.

  1. Triple plasmon resonance of bimetal nanoshell

    Science.gov (United States)

    Shirzaditabar, Farzad; Saliminasab, Maryam; Arghavani Nia, Borhan

    2014-07-01

    In this paper, light absorption spectra properties of a bimetal multilayer nanoshell based on quasi-static approach are investigated. Comparing with silver-dielectric-silver and silver-dielectric-gold nanoshells, gold-dielectric-silver nanoshells have three intense and separated plasmon peaks which are more suitable for multiplex biosensing. Calculations show that relatively small thickness of outer silver shell and large dielectric constant of middle dielectric layer of gold-dielectric-silver nanoshell are suitable to obtain the triple plasmon resonance.

  2. Mordell-Weil groups and Zariski triples

    CERN Document Server

    Cogolludo-Agustin, Jose Ignacio

    2011-01-01

    We prove the existence of three irreducible curves $C_{12,m}$ of degree 12 with the same number of cusps and different Alexander polynomials. This exhibits a Zariski triple. Moreover we provide a set of generators for the elliptic threefold with constant $j$-invariant 0 and discriminant curve $C_{12,m}$. Finally we consider general degree $d$ base change of $C_{12d,m}$ and calculate the dimension of the equisingular deformation space.

  3. Triple Teeth: Report of an Unusual Case

    OpenAIRE

    Prashant Babaji; M. A. Prasanth; Gowda, Ajith R.; Soumya Ajith; Henston D'Souza; Ashok, K. P.

    2012-01-01

    Fusion or synodontia is a union of two or more than two developing teeth. Commonly fusion occurs between teeth of the same dentition, mixed dentition, or between normal and supernumerary teeth. Fused primary teeth present with several clinical problems like caries, periodontal problem, arch asymmetry, delayed eruption, ectopic eruption of succedaneous teeth, aesthetic, and other complications. This paper presents a rare and unusual case of triple teeth in mandibular primary dentition.

  4. Triple Teeth: Report of an Unusual Case

    Directory of Open Access Journals (Sweden)

    Prashant Babaji

    2012-01-01

    Full Text Available Fusion or synodontia is a union of two or more than two developing teeth. Commonly fusion occurs between teeth of the same dentition, mixed dentition, or between normal and supernumerary teeth. Fused primary teeth present with several clinical problems like caries, periodontal problem, arch asymmetry, delayed eruption, ectopic eruption of succedaneous teeth, aesthetic, and other complications. This paper presents a rare and unusual case of triple teeth in mandibular primary dentition.

  5. Triple collinear emissions in parton showers

    Energy Technology Data Exchange (ETDEWEB)

    Höche, Stefan [SLAC; Prestel, Stefan [Fermilab

    2017-05-01

    A framework to include triple collinear splitting functions into parton showers is presented, and the implementation of flavor-changing NLO splitting kernels is discussed as a first application. The correspondence between the Monte-Carlo integration and the analytic computation of NLO DGLAP evolution kernels is made explicit for both timelike and spacelike parton evolution. Numerical simulation results are obtained with two independent implementations of the new algorithm, using the two independent event generation frameworks Pythia and Sherpa.

  6. Crystal structure of the collagen triple helix model [(Pro-Pro-Gly)(10)](3).

    Science.gov (United States)

    Berisio, Rita; Vitagliano, Luigi; Mazzarella, Lelio; Zagari, Adriana

    2002-02-01

    The first report of the full-length structure of the collagen-like polypeptide [(Pro-Pro-Gly)(10)](3) is given. This structure was obtained from crystals grown in a microgravity environment, which diffracted up to 1.3 A, using synchrotron radiation. The final model, which was refined to an R(factor) of 0.18, is the highest-resolution description of a collagen triple helix reported to date. This structure provides clues regarding a series of aspects related to collagen triple helix structure and assembly. The strict dependence of proline puckering on the position inside the Pro-Pro-Gly triplets and the correlation between backbone and side chain dihedral angles support the propensity-based mechanism of triple helix stabilization/destabilization induced by hydroxyproline. Furthermore, the analysis of [(Pro-Pro-Gly)(10)](3) packing, which is governed by electrostatic interactions, suggests that charges may act as locking features in the axial organization of triple helices in the collagen fibrils.

  7. Postoperative hypertensive-hypervolaemic-haemodilution (Triple H therapy in the treatment of vasospasm following aneurysmal subarachnoid haemorrhage.

    Directory of Open Access Journals (Sweden)

    Gupta D

    2000-04-01

    Full Text Available Twenty five patients with post operative ischaemic deficits, following clipping of intracranial aneurysms, were studied. Hypertensive-hypervolaemic-haemodilution (triple H therapy was given to all patients using colloids and crystalloids. CVP was used to monitor the fluid therapy. Dopamine was needed in 22 patients to elevate the systemic blood pressure. Vasospasm was confirmed in 20 patients with transcranial doppler studies (TCD. 20 (80% patients survived, 10 (40% with good outcome, 7 (28% with fair, 2 (8% with poor outcome and 1 (4% with vegetative state. There were 5 (20% deaths, 4 of which occurred due to infarct. All these patients had poor Hunt and Hess grade at admission, high Fisher grade haemorrhages in the initial CT scan and/or required prolonged temporary clipping at surgery. One death occurred due to central venous line induced septicaemia. The duration of ′triple H therapy′ amongst the survivors varied from 2-7 days with an average of 4.6 days. The complications of ′triple H therapy′ included hypokalaemia (3 patients, haemorrhagic infarct (1 patient and septicaemia (1 patient. It is concluded that ′triple H therapy′ is useful in treating vasospasm induced ischaemic deficits. It worsens brain oedema in presence of acute infarcts and hence is contraindicated in such patients. A further study involving a larger number of patients with strict haemodynamic and ICP monitoring is suggested to determine the usefulness of individual components of ′triple H therapy′.

  8. Detection of Naja atra Cardiotoxin Using Adenosine-Based Molecular Beacon.

    Science.gov (United States)

    Shi, Yi-Jun; Chen, Ying-Jung; Hu, Wan-Ping; Chang, Long-Sen

    2017-01-07

    This study presents an adenosine (A)-based molecular beacon (MB) for selective detection of Naja atra cardiotoxin (CTX) that functions by utilizing the competitive binding between CTX and the poly(A) stem of MB to coralyne. The 5'- and 3'-end of MB were labeled with a reporter fluorophore and a non-fluorescent quencher, respectively. Coralyne induced formation of the stem-loop MB structure through A₂-coralyne-A₂ coordination, causing fluorescence signal turn-off due to fluorescence resonance energy transfer between the fluorophore and quencher. CTX3 could bind to coralyne. Moreover, CTX3 alone induced the folding of MB structure and quenching of MB fluorescence. Unlike that of snake venom α-neurotoxins, the fluorescence signal of coralyne-MB complexes produced a bell-shaped concentration-dependent curve in the presence of CTX3 and CTX isotoxins; a turn-on fluorescence signal was noted when CTX concentration was ≤80 nM, while a turn-off fluorescence signal was noted with a further increase in toxin concentrations. The fluorescence signal of coralyne-MB complexes yielded a bell-shaped curve in response to varying concentrations of N. atra crude venom but not those of Bungarus multicinctus and Protobothrops mucrosquamatus venoms. Moreover, N. nigricollis venom also functioned as N. atra venom to yield a bell-shaped concentration-dependent curve of MB fluorescence signal, again supporting that the hairpin-shaped MB could detect crude venoms containing CTXs. Taken together, our data validate that a platform composed of coralyne-induced stem-loop MB structure selectively detects CTXs.

  9. Targeting Prolyl Peptidases in Triple-Negative Breast Cancer

    Science.gov (United States)

    2017-02-01

    AWARD NUMBER: W81XWH-16-1-0025 TITLE: Targeting Prolyl Peptidases in Triple-Negative Breast Cancer PRINCIPAL INVESTIGATOR: Carl G. Maki, PhD...SUBTITLE Targeting Prolyl Peptidases in Triple-Negative Breast Cancer 5a. CONTRACT NUMBER 5b. GRANT NUMBER W81XWH-16-1-0025 5c. PROGRAM ELEMENT NUMBER 6...ABSTRACT Triple negative breast cancer (TNBC) is an aggressive sub-type with limited treatment options and poor prognosis. The most life-threatening

  10. Geometrical theory of triple junctions of CSL boundaries.

    Science.gov (United States)

    Gertsman, V Y

    2001-07-01

    When three grain boundaries having misorientations generating coincidence site lattices (CSLs) meet at a triple junction, a common (triple-junction) CSL is formed. A theory is developed as a set of theorems establishing the relationships between the geometrical parameters of the grain-boundary and triple-junction CSLs. Application of the theory is demonstrated in detail for the case of the cubic crystal system. It is also shown how the theory can be extended to an arbitrary crystal lattice.

  11. Triple tooth in primary dentition: A proposed classification

    Directory of Open Access Journals (Sweden)

    Gaddam Shilpa

    2013-01-01

    Full Text Available Triple teeth may result from fusion, gemination or concrescence causing transient esthetic and functional problems in primary dentition and retardation or alteration of development and eruption of permanent successors. We report an unusual case of a boy aged five with fusion among maxillary left primary central incisor, lateral incisor and a supernumerary tooth concomitant with agenesis of permanent lateral incisor. A review of literature on triple tooth was done along with a proposed classification of the triple teeth.

  12. Moduli spaces of Dirac operators for finite spectral triples

    CERN Document Server

    Ćaćić, Branimir

    2009-01-01

    The structure theory of finite real spectral triples developed by Krajewski and by Paschke and Sitarz is generalised to allow for arbitrary KO-dimension and the failure of orientability and Poincare duality, and moduli spaces of Dirac operators for such spectral triples are defined and studied. This theory is then applied to recent work by Chamseddine and Connes towards deriving the finite spectral triple of the noncommutative-geometric Standard Model.

  13. The emerging role of triple helices in RNA biology.

    Science.gov (United States)

    Conrad, Nicholas K

    2014-01-01

    The ability of RNA to form sophisticated secondary and tertiary structures enables it to perform a wide variety of cellular functions. One tertiary structure, the RNA triple helix, was first observed in vitro over 50 years ago, but biological activities for triple helices are only beginning to be appreciated. The recent determination of several RNA structures has implicated triple helices in distinct biological functions. For example, the SAM-II riboswitch forms a triple helix that creates a highly specific binding pocket for S-adenosylmethionine. In addition, a triple helix in the conserved pseudoknot domain of the telomerase-associated RNA TER is essential for telomerase activity. A viral RNA cis-acting RNA element called the ENE contributes to the nuclear stability of a viral noncoding RNA by forming a triple helix with the poly(A) tail. Finally, a cellular noncoding RNA, MALAT1, includes a triple helix at its 3'-end that contributes to RNA stability, but surprisingly also supports translation. These examples highlight the diverse roles that RNA triple helices play in biology. Moreover, the dissection of triple helix mechanisms has the potential to uncover fundamental pathways in cell biology.

  14. Calcaneal "Z" osteotomy effect on hindfoot varus after triple arthrodesis in a cadaver model.

    Science.gov (United States)

    Zanolli, Diego H; Glisson, Richard R; Utturkar, Gangadhar M; Eckel, Tobin T; DeOrio, James K

    2014-12-01

    Triple arthrodesis involves subtalar, talonavicular, and calcaneocuboid joint fusion and is performed to relieve pain and correct deformity. Complications include malunion resulting in equinovarus and lateral column overload, which can lead to painful callosities and stress fractures. This study quantified the effectiveness of a closing-wedge calcaneal "Z" osteotomy for correction of the varus condition and reduction of abnormal loading of the lateral border of the foot. Ten fresh-frozen feet were used. Angle meters were attached to the calcaneus and second cuneiform to measure hindfoot and midfoot varus, and pressure sensors were placed under the first and fifth metatarsal heads to document loading of the borders of the foot. Tensile loads were applied to ten extrinsic tendons and the Achilles tendon while an 1187 N axial foot load was applied. Calcaneus and second cuneiform coronal plane angles and medial and lateral plantar pressures were measured initially, after triple fusion-induced varus, and after "Z" osteotomy. The calcaneal "Z" osteotomy had no significant corrective effect, with hindfoot alignment virtually identical before and after the procedure under the described foot loading conditions. Similarly, second cuneiform inclination, representative of midfoot alignment, showed no change from the osteotomy. Medial and lateral peak plantar pressures after calcaneal "Z" osteotomy did not differ from those measured after varus triple fusion. In this cadaver model of varus malunited triple arthrodesis, the closing-wedge calcaneal "Z" osteotomy was ineffective for correction of bone alignment and lateral forefoot overloading under the tested conditions. The results provide additional information on which to base treatment after triple arthrodesis with varus malunion. © The Author(s) 2014.

  15. Aromatic Interactions Promote Self-association of Collagen Triple-helical Peptides to Higher Order Structures

    Science.gov (United States)

    Kar, Karunakar; Ibrar, Sajjad; Nanda, Vikas; Getz, Todd M.; Kunapuli, Satya P.; Brodsky, Barbara

    2009-01-01

    Aromatic residues are relatively rare within the collagen triple-helix, but they appear to play a specialized role in higher order structure and function. The role of aromatic amino acids in the self-assembly of triple-helical peptides was investigated in terms of the kinetics of self-association, the nature of aggregated species formed, and the ability of these species to activate platelet aggregation. The presence of aromatic residues on both ends of a type IV collagen model peptide is observed to greatly accelerate the kinetics of self-association, decreasing the lag time and leading to insoluble, well defined linear fibrils as well as small soluble aggregates. Both macroscopic visible aggregates and small multi-molecular complexes in solution are capable of inducing platelet aggregation through the glycoprotein VI receptor on platelets. Proline-aromatic CH⋯π interactions are often observed within globular proteins and in protein complexes, and examination of molecular packing in the crystal structure of the integrin binding collagen peptide shows Phe interacts with Pro/Hyp in a neighboring triple-helical molecule. An intermolecular interaction between aromatic amino acids and imino acids within the triple-helix is also supported by the observed inhibitory effect of isolated Phe amino acids on the self-association of (Pro-Hyp-Gly)10. Given the high fraction of Pro and Hyp residues on the surface of collagen molecules, it is likely that imino acid-aromatic CH⋯π interactions are important in formation of higher order structure. It is suggested that the catalysis of type I collagen fibrillogenesis by non-helical telopeptides is due to specific intermolecular CH⋯π interactions between aromatic residues in the telopeptides and Pro/Hyp residues within the triple-helix. PMID:19610672

  16. Secular Evolution of Hierarchical Triple Star Systems

    Science.gov (United States)

    Ford, Eric B.; Kozinsky, Boris; Rasio, Frederic A.

    2000-05-01

    We derive octupole-level secular perturbation equations for hierarchical triple systems, using classical Hamiltonian perturbation techniques. Our equations describe the secular evolution of the orbital eccentricities and inclinations over timescales that are long compared to the orbital periods. By extending previous work done to leading (quadrupole) order to octupole level (i.e., including terms of order α3, where α≡a1/a2quadrupole-level theory of Kozai gives a vanishing result in the limit of zero relative inclination. The classical planetary perturbation theory, while valid to all orders in α, applies only to orbits of low-mass objects orbiting a common central mass, with low eccentricities and low relative inclinations. For triple systems containing a close inner binary, we also discuss the possible interaction between the classical Newtonian perturbations and the general relativistic precession of the inner orbit. In some cases we show that this interaction can lead to resonances and a significant increase in the maximum amplitude of eccentricity perturbations. We establish the validity of our analytic expressions by providing detailed comparisons with the results of direct numerical integrations of the three-body problem obtained for a large number of representative cases. In addition, we show that our expressions reduce correctly to previously published analytic results obtained in various limiting regimes. We also discuss applications of the theory in the context of several observed triple systems of current interest, including the millisecond pulsar PSR B1620-26 in M4, the giant planet in 16 Cygni, and the protostellar binary TMR-1.

  17. Influence and curative effect observation of Bifid Triple Viable Capsules on intestinal mucous membrane barrier function of patients with leukemia chemotherapy induced diarrhea%双歧杆菌三联活菌胶囊对白血病化疗所致腹泻患者肠黏膜屏障功能的影响及疗效观察

    Institute of Scientific and Technical Information of China (English)

    庄贤栩; 裴仁治; 陆滢; 张丕胜; 刘旭辉; 马俊霞; 吴静怡

    2015-01-01

    目的:探讨双歧杆菌三联活菌胶囊对白血病化疗所致腹泻患者肠黏膜屏障功能的影响及疗效观察。方法选取2012年1月~2014年7月在宁波市鄞州人民医院门诊或住院治疗的白血病化疗所致腹泻患者74例。采用随机数字表将其分为观察组(n=37)和对照组(n=37)。两组均采用常规对症支持治疗,包括静脉补液、口服蒙脱石散、静脉营养支持及保持水电解质平衡等。观察组加用双歧杆菌三联活菌胶囊630 mg/次,2次/d,温开水溶解后口服。对照组除不予以双歧杆菌三联活菌胶囊口服外余处理与观察组完全相同。治疗3d后记录两组患者血清内毒素(ET)、降钙素原(PCT)和肿瘤坏死因子-α(TNF-α)水平的变化情况,并对其临床效果及药物不良反应进行比较。结果治疗3 d后,与治疗前比较对照组和观察组患者ET、PCT和TNF-α水平[(0.35±0.09)EU/mL、(7.67±1.25)μg/L、(173.67±36.48)pg/mL,(0.29±0.07)EU/mL、(5.18±0.73)μg/L、(138.34±30.42)pg/mL]较前[(0.42±0.14)EU/mL、(10.19±2.76)μg/L、(215.47±40.23)pg/mL,(0.44±0.11)EU/mL、(9.95±2.97)μg/L、(219.95±38.17)pg/mL]均明显下降(t=2.27、2.42、2.34、2.87、3.42、2.99,P约0.05或P约0.01),且观察组下降值明显大于对照组(t=2.13、2.39、2.17,P约0.05);治疗3 d后,观察组临床总有效率明显较对照组更佳(91.89%比72.97%)(字2=4.57,P约0.05)。两组患者治疗中未发生明显的药物不良反应。结论双歧杆菌三联活菌胶囊能直接补充白血病化疗后腹泻患者的肠道益生菌的数量,纠正肠道微生态平衡失调,重建肠黏膜菌群生物屏障,促进肠黏膜上皮修复,降低肠黏膜的通透性功能,降低血清ET、PCT和TNF-α水平,保护与改善肠黏膜屏障功能。%Objective To discuss influence and curative effect observation of Bifid Triple Viable Capsules on intestinal mucous membrane barrier function of patients with leukemia chemotherapy induced diarrhea

  18. Local index formula and twisted spectral triples

    CERN Document Server

    Moscovici, Henri

    2009-01-01

    We prove a local index formula for a class of twisted spectral triples of type III modeled on the transverse geometry of conformal foliations with locally constant transverse conformal factor. Compared with the earlier proof of the untwisted case, the novel aspect resides in the fact that the twisted analogues of the JLO entire cocycle and of its retraction are no longer cocycles in their respective Connes bicomplexes. We show however that the passage to the infinite temperature limit, respectively the integration along the full temperature range against the Haar measure of the positive half-line, has the remarkable effect of curing in both cases the deviations from the cocycle identity.

  19. Gleason's Theorem for Rectangular JBW-Triples

    Science.gov (United States)

    Edwards, C. Martin; Rüttimann, Gottfried T.

    A JBW*-triple B is said to be rectangular if there exists a W*-algebra A and a pair (p,q) of centrally equivalent elements of the complete orthomodular lattice of projections in A such that B is isomorphic to the JBW*-triple pAq. Any weak*-closed injective operator space provides an example of a rectangular JBW*-triple. The principal order ideal of the complete *-lattice of centrally equivalent pairs of projections in a W*-algebra A, generated by (p,q), forms a complete lattice that is order isomorphic to the complete lattice of weak*-closed inner ideals in B and to the complete lattice of structural projections on B. Although not itself, in general, orthomodular, possesses a complementation that allows for definitions of orthogonality, centre, and central orthogonality to be given. A less familiar notion in lattice theory, that is well-known in the theory of Jordan algebras and Jordan triple systems, is that of rigid collinearity of a pair (e2,f2) and (e2,f2) of elements of . This is defined and characterized in terms of properties of . A W*-algebra A is sometimes thought of as providing a model for a statistical physical system. In this case B, or, equivalently, pAq, may be thought of as providing a model for a fixed sub-system of that represented by A. Therefore, may be considered to represent the set consisting of a particular kind of sub-system of that represented by pAq. Central orthogonality and rigid collinearity of pairs of elements of may be regarded as representing two different types of disjointness, the former, classical disjointness, and the latter, decoherence, of the two sub-systems. It is therefore natural to consider bounded measures m on that are additive on centrally orthogonal and rigidly collinear pairs of elements. Using results of J.D.M. Wright, it is shown that, provided that neither of the two hereditary sub-W*-algebras pAp and qAq of A has a weak*-closed ideal of Type I2, such measures are precisely those that are the restrictions of

  20. Vectorized data acquisition and fast triple-correlation integrals for Fluorescence Triple Correlation Spectroscopy.

    Science.gov (United States)

    Ridgeway, William K; Millar, David P; Williamson, James R

    2013-04-01

    Fluorescence Correlation Spectroscopy (FCS) is widely used to quantitate reaction rates and concentrations of molecules in vitro and in vivo. We recently reported Fluorescence Triple Correlation Spectroscopy (F3CS), which correlates three signals together instead of two. F3CS can analyze the stoichiometries of complex mixtures and detect irreversible processes by identifying time-reversal asymmetries. Here we report the computational developments that were required for the realization of F3CS and present the results as the Triple Correlation Toolbox suite of programs. Triple Correlation Toolbox is a complete data analysis pipeline capable of acquiring, correlating and fitting large data sets. Each segment of the pipeline handles error estimates for accurate error-weighted global fitting. Data acquisition was accelerated with a combination of off-the-shelf counter-timer chips and vectorized operations on 128-bit registers. This allows desktop computers with inexpensive data acquisition cards to acquire hours of multiple-channel data with sub-microsecond time resolution. Off-line correlation integrals were implemented as a two delay time multiple-tau scheme that scales efficiently with multiple processors and provides an unprecedented view of linked dynamics. Global fitting routines are provided to fit FCS and F3CS data to models containing up to ten species. Triple Correlation Toolbox is a complete package that enables F3CS to be performed on existing microscopes.

  1. On The Dynamics Of Dust Grains In A Hierarchical Environment. II Triple Case

    Science.gov (United States)

    de La Fuente Marcos, C.; de La Fuente Marcos, R.

    2002-04-01

    The star formation process usually leads to the formation of protoplanetary disks. Planets are thought to arise from the material of these disks. Amongst the stars in the solar neighbourhood, single systems like our own are a minority. Most stars are found in binaries or in systems of even higher multiplicity. In this paper, we extend the simulations presented in Paper I (de la Fuente Marcos and de la Fuente Marcos, 1998a) to hierarchical triple systems. As in Paper I, we study the stage of planetary formation during which the particulate material is still dispersed as centimetre-to-metre sized primordial aggregates. We investigate the response of the particles, in a protoplanetary disk with radius RD = 100 AU around a solar-like star, to the gravitational field of bound perturbing companions in a moderately wide (300 1600 AU) orbit. As for this problem no analytic description of the orbital evolution of the particles exists, we perform numerical integrations using a Bulirsch Stoer integrator. For this purpose, we have carried out a series of simulations of coplanar hierarchical configurations with three stars using a direct integration code that models gravitational and viscous forces. The massive protoplanetary disk is around one of the components of the triple system. As in Paper I, the evolution in time of the dust sub-disk depends mainly on the nature (prograde or retrograde) of the relative revolution of the stellar companions, and on the temperature and mass of the circumstellar disk. The perturbation of prograde companions induces a trailing spiral structure across the protoplanetary sub-metric dust sub-disk. Metre-sized particles are affected by strong precession. Our results show that the lifetime of particles in a disk in a hierarchical triple system is slightly shorter relative to its valuein Paper I, although the actual value depends on the nature, prograde or retrograde, of the outer companion. The lifetime of particles in a hierarchical triple system

  2. Clinical Efficacy of Capecitabine Combined with Autologous Cytokine-induced Killer Cells Maintenance Therapy in Treatment of Metastatic Triple Negative Breast Cancer%自体CIK细胞联合卡培他滨维持治疗复发转移性三阴性乳腺癌效果观察

    Institute of Scientific and Technical Information of China (English)

    宋树玺; 刘永叶; 丁震宇; 于卉影; 韩雅玲; 谢晓冬

    2015-01-01

    Objective To analyze the clinical efficacy and safety of capecitabine combined with autologous cytokine-induced killer cells ( CIK) maintenance therapy in treatment of metastatic triple negative breast cancer ( MTNBC) . Methods The MTNBC patients undergoing capecitabine-based chemotherapy as first line treatment, whose therapeutic effect was SD or above were selected and divided into treatment group and control group randomly. The treatment group received capecitabine maintenance therapy with autologous CIK after the first line treatment. The control group underwent only capecitabine mainte-nance therapy. Baseline assessment was taken 15 d after the end of the last cycle of chemotherapy. The patients were followed up once every two cycles. The median follow-up time was 11. 2 months. T lymphocyte subpopulation in peripheral blood was measured, the side effects, PFS and OS of both groups were observed. Results CD3+CD8+CTL and CD4+CD25+Treg of treatment group were compared at the time of baseline assessment and 1 month after three cycles of chemotherapy. There was no statistically significant difference (P>0. 05). CD3+T, CD3+CD4+Th, CD3+CD56+CIK showed significant im-provement, compared with that before treatment (P0. 05). Conclusion Maintenance therapy of Capecitabine combined with autologous CIK cells in treatment of MTNBC after first-line treatment improves the immune function to enhance the ability of antitumor by natural immunity, which can prolong PFS, and is safe as well. In short, it can improve the therapeutic effect of maintenance therapy in patients with MTNBC.%目的 探讨自体细胞因子诱导杀伤细胞( CIK)免疫治疗联合卡培他滨治疗复发转移性三阴性乳腺癌( metastatic triple negative breast cancer, MTNBC)的临床效果和安全性. 方法 选取一线应用卡培他滨化疗后效果评价病情稳定( SD)或以上的MTNBC患者,随机分为治疗组和对照组. 两组均应用卡培他滨维持化疗,治疗组在此

  3. Recovery and normalization of triple coincidences in PET

    Energy Technology Data Exchange (ETDEWEB)

    Lage, Eduardo, E-mail: elage@mit.edu; Parot, Vicente; Dave, Shivang R.; Herraiz, Joaquin L. [Madrid-MIT M+Visión Consortium, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139 (United States); Moore, Stephen C.; Sitek, Arkadiusz; Park, Mi-Ae [Division of Nuclear Medicine, Department of Radiology, Harvard Medical School and Brigham and Women’s Hospital, Boston, Massachusetts 02115 (United States); Udías, Jose M. [Grupo de Física Nuclear, Departamento de Física Atómica Molecular y Nuclear, Universidad Complutense de Madrid, CEI Moncloa, Madrid 28040 (Spain); Vaquero, Juan J. [Departamento de Ingeniería Biomédica e Ingeniería Aeroespacial, Universidad Carlos III de Madrid, Leganés 28911 (Spain)

    2015-03-15

    Purpose: Triple coincidences in positron emission tomography (PET) are events in which three γ-rays are detected simultaneously. These events, though potentially useful for enhancing the sensitivity of PET scanners, are discarded or processed without special consideration in current systems, because there is not a clear criterion for assigning them to a unique line-of-response (LOR). Methods proposed for recovering such events usually rely on the use of highly specialized detection systems, hampering general adoption, and/or are based on Compton-scatter kinematics and, consequently, are limited in accuracy by the energy resolution of standard PET detectors. In this work, the authors propose a simple and general solution for recovering triple coincidences, which does not require specialized detectors or additional energy resolution requirements. Methods: To recover triple coincidences, the authors’ method distributes such events among their possible LORs using the relative proportions of double coincidences in these LORs. The authors show analytically that this assignment scheme represents the maximum-likelihood solution for the triple-coincidence distribution problem. The PET component of a preclinical PET/CT scanner was adapted to enable the acquisition and processing of triple coincidences. Since the efficiencies for detecting double and triple events were found to be different throughout the scanner field-of-view, a normalization procedure specific for triple coincidences was also developed. The effect of including triple coincidences using their method was compared against the cases of equally weighting the triples among their possible LORs and discarding all the triple events. The authors used as figures of merit for this comparison sensitivity, noise-equivalent count (NEC) rates and image quality calculated as described in the NEMA NU-4 protocol for the assessment of preclinical PET scanners. Results: The addition of triple-coincidence events with the

  4. VERITAS: Versatile Triple-Axis Spectrometer

    Energy Technology Data Exchange (ETDEWEB)

    Park, Sung Il

    2006-04-15

    Korea Atomic Energy Research Institute is planning to build a cold neutron triple-axis spectrometer at HANARO, the 30 MW research reactor. The spectrometer is expected to be completed in 2008 with the following configuration from the upstream to the downstream. Guide Supermirror m = 2, In-pile Straight Section, {approx} 5 m Curved Guide, {approx} 26 m w/ R 1500 m Straight Guide before the Instrument, {approx} 40 m Filters PG and Be Neutron Velocity Selector (Future) Monochromators Vertically Focusing Monochromators PG(002) and Heusler(111) Doubly Focusing Monochromators (Future) Monochromator-Sample Distance 2 m Collimation C1 Soller Collimators, 20', 40' 80'Beam Height at the Sample Table 1.5 m Sample-Analyzer Distance 1.0 m Collimation C2 Soller Collimators, 20', 40', 80' Radial Collimator Analyzers Horizontally Focusing Analyzers w/ Fixed Vertical Focusing PG(002) and Heusler(111) Analyzer-Detector Distance 0.5 m Detectors 5 cm Tube Detector 25 cm wide Position Sensitive Detector Once completed, the neutron flux at sample is expected to surpass that of SPINS at NCNR, making this instrument one of the most powerful 2nd generation cold neutron triple-axis spectrometers in the world.

  5. Mergers and obliquities in stellar triples

    Energy Technology Data Exchange (ETDEWEB)

    Naoz, Smadar [Harvard Smithsonian Center for Astrophysics, Institute for Theory and Computation, 60 Garden Street, Cambridge, MA 02138 (United States); Fabrycky, Daniel C., E-mail: snaoz@cfa.harvard.edu [Department of Astronomy and Astrophysics, University of Chicago, 5640 South Ellis Avenue, Chicago, IL 60637 (United States)

    2014-10-01

    Many close stellar binaries are accompanied by a faraway star. The 'eccentric Kozai-Lidov' (EKL) mechanism can cause dramatic inclination and eccentricity fluctuations, resulting in tidal tightening of inner binaries of triple stars. We run a large set of Monte Carlo simulations, including the secular evolution of the orbits, general relativistic precession, and tides, and we determine the semimajor axis, eccentricity, inclination, and spin-orbit angle distributions of the final configurations. We find that the efficiency of forming tight binaries (≲ 16 days) when taking the EKL mechanism into account is ∼21%, and about 4% of all simulated systems ended up in a merger event. These merger events can lead to the formation of blue stragglers. Furthermore, we find that the spin-orbit angle distribution of the inner binaries carries a signature of the initial setup of the system; thus, observations can be used to disentangle close binaries' birth configuration. The resulting inner and outer final orbits' period distributions and their estimated fraction suggest that secular dynamics may be a significant channel for the formation of close binaries in triples and even blue stragglers.

  6. Triple Oxygen Isotopes: Fundamental Relationships and Applications

    Science.gov (United States)

    Bao, Huiming; Cao, Xiaobin; Hayles, Justin A.

    2016-06-01

    The element oxygen has three stable isotopes: 16O, 17O, and 18O. For a defined process, a change in 18O/16O scales with the corresponding change in 17O/16O, or the fractionation factors 18α and 17α have a relationship of θ = ln17α/ln18α, in which the triple oxygen isotope exponent θ is relatively fixed but does vary with reaction path, temperature, and species involved. When the small variation is of interest, the distinction of three concepts—θ, S (a slope through data points in δ17O-δ18O space), and C (an arbitrary referencing number for the degree of 17O deviation)—becomes important. Triple oxygen isotope variations can be measured by modern instruments and thus offer an additional line of information on the underlying reaction processes and conditions. Analytical methods and Earth science applications have recently been developed for air oxygen, carbon dioxide, water, silicates, oxides, sulfates, carbonates, and phosphates.

  7. Triple Halo Coil: Development and Comparison with Other TMS Coils

    Science.gov (United States)

    Rastogi, Priyam; Hadimani, Ravi; Jiles, David

    Transcranial Magnetic Stimulation (TMS) is a non-invasive stimulation technique that can be used for the treatment of various neurological disorders such as Parkinson's Disease, PTSD, TBI and anxiety by regulating synaptic activity. TMS is FDA approved for the treatment of major depressive disorder. There is a critical need to develop deep TMS coils that can stimulate deeper regions of the brain without excessively stimulating the cortex in order to provide an alternative to surgical methods. We have developed a novel multi-coil configuration called ``Triple Halo Coil'' (THC) that can stimulate deep brain regions. Investigation of induced electric and magnetic field in these regions have been achieved by computer modelling. Comparison of the results due to THC configuration have been conducted with other TMS coils such as ``Halo Coil'', circular coil and ``Figure of Eight'' coil. There was an improvement of more than 15 times in the strength of magnetic field, induced by THC configuration at 10 cm below the vertex of the head when compared with the ``Figure of Eight'' coil alone. Carver Charitable Trust.

  8. BROWN DWARF BINARIES FROM DISINTEGRATING TRIPLE SYSTEMS

    Energy Technology Data Exchange (ETDEWEB)

    Reipurth, Bo [Institute for Astronomy and NASA Astrobiology Institute University of Hawaii, 640 N. Aohoku Place, Hilo, HI 96720 (United States); Mikkola, Seppo, E-mail: reipurth@ifa.hawaii.edu, E-mail: Seppo.Mikkola@utu.fi [Tuorla Observatory, University of Turku, Väisäläntie 20, Piikkiö (Finland)

    2015-04-15

    Binaries in which both components are brown dwarfs (BDs) are being discovered at an increasing rate, and their properties may hold clues to their origin. We have carried out 200,000 N-body simulations of three identical stellar embryos with masses drawn from a Chabrier IMF and embedded in a molecular core. The bodies are initially non-hierarchical and undergo chaotic motions within the cloud core, while accreting using Bondi–Hoyle accretion. The coupling of dynamics and accretion often leads to one or two dominant bodies controlling the center of the cloud core, while banishing the other(s) to the lower-density outskirts, leading to stunted growth. Eventually each system transforms either to a bound hierarchical configuration or breaks apart into separate single and binary components. The orbital motion is followed for 100 Myr. In order to illustrate 200,000 end-states of such dynamical evolution with accretion, we introduce the “triple diagnostic diagram,” which plots two dimensionless numbers against each other, representing the binary mass ratio and the mass ratio of the third body to the total system mass. Numerous freefloating BD binaries are formed in these simulations, and statistical properties are derived. The separation distribution function is in good correspondence with observations, showing a steep rise at close separations, peaking around 13 AU and declining more gently, reaching zero at separations greater than 200 AU. Unresolved BD triple systems may appear as wider BD binaries. Mass ratios are strongly peaked toward unity, as observed, but this is partially due to the initial assumptions. Eccentricities gradually increase toward higher values, due to the lack of viscous interactions in the simulations, which would both shrink the orbits and decrease their eccentricities. Most newborn triple systems are unstable and while there are 9209 ejected BD binaries at 1 Myr, corresponding to about 4% of the 200,000 simulations, this number has grown to

  9. Fabrication and single-electron-transfer operation of a triple-dot single-electron transistor

    Energy Technology Data Exchange (ETDEWEB)

    Jo, Mingyu, E-mail: mingyujo@eis.hokudai.ac.jp; Uchida, Takafumi; Tsurumaki-Fukuchi, Atsushi; Arita, Masashi; Takahashi, Yasuo [Graduate School of Information Science and Technology, Hokkaido University, Sapporo 060-0814 (Japan); Fujiwara, Akira; Nishiguchi, Katsuhiko [NTT Basic Research Laboratories, NTT Corporation, 3-1 Morinosato Wakamiya, Atsugi 243-0198 (Japan); Ono, Yukinori [Graduate School of Science and Engineering, University of Toyama, 3190 Gofuku, Toyama 930-8555 (Japan); Inokawa, Hiroshi [Research Institute of Electronics, Shizuoka University, 3-5-1, Johoku, Hamamatsu 432-8011 (Japan)

    2015-12-07

    A triple-dot single-electron transistor was fabricated on silicon-on-insulator wafer using pattern-dependent oxidation. A specially designed one-dimensional silicon wire having small constrictions at both ends was converted to a triple-dot single-electron transistor by means of pattern-dependent oxidation. The fabrication of the center dot involved quantum size effects and stress-induced band gap reduction, whereas that of the two side dots involved thickness modulation because of the complex edge structure of two-dimensional silicon. Single-electron turnstile operation was confirmed at 8 K when a 100-mV, 1-MHz square wave was applied. Monte Carlo simulations indicated that such a device with inhomogeneous tunnel and gate capacitances can exhibit single-electron transfer.

  10. Reverse triple I method of restriction for fuzzy reasoning

    Institute of Scientific and Technical Information of China (English)

    2002-01-01

    A theory of reverse triple I method of restriction for implication operator R0 is proposed.And the general computation formulas of infimum for fuzzy modus ponens and supremum for fuzzy modus tollens of a-reverse triple I method of restriction are obtained respectively.

  11. Triple Play Service and IPTV Services Offered within it

    Directory of Open Access Journals (Sweden)

    Dagmar Pajdusakova

    2008-01-01

    Full Text Available This paper deals with Triple Play multimedia service and figures its architecture. Triple Play offers voice, video and data services together in one customer connection. There is offered IPTV (Internet Protocol Television service within this service, where we can include also Video on Demand service and other different additional services. In the paper is described classification of Video on Demand services.

  12. On Twisting Real Spectral Triples by Algebra Automorphisms

    Science.gov (United States)

    Landi, Giovanni; Martinetti, Pierre

    2016-11-01

    We systematically investigate ways to twist a real spectral triple via an algebra automorphism and in particular, we naturally define a twisted partner for any real graded spectral triple. Among other things, we investigate consequences of the twisting on the fluctuations of the metric and possible applications to the spectral approach to the Standard Model of particle physics.

  13. Fibonacci-triple sequences and some fundamental properties

    Directory of Open Access Journals (Sweden)

    Bijendra Singh

    2010-12-01

    Full Text Available Fibonacci sequence stands as a kind of super sequence with fabulous properties. This note presents Fibonacci-Triple sequences that may also be called 3-F sequences. This is the explosive development in the region of Fibonacci sequence. Our purpose of this paper is to demonstrate fundamental properties of Fibonacci-Triple sequence.

  14. The Triple Jump: Assessing Problem Solving in Psychiatry.

    Science.gov (United States)

    O'Gorman, Ethna C.; Trimble, Peter; Smyth, Joe

    1998-01-01

    Describes an attempt to assess a final-year course in psychiatry using the Triple Jump. In this course, students on placement in psychiatric units perfect psychiatry skills that were acquired during the previous year by direct contact with patients. The Triple Jump is used to assess problem-solving skills in management strategy on cases. (PVD)

  15. A canonical trace associated with certain spectral triples

    CERN Document Server

    Paycha, Sylvie

    2010-01-01

    In the abstract pseudodifferential set up of Connes and Moscovici, we prove a general formula for discrepancies of zeta-regularised traces associated with certain spectral triples and we introduce a canonical trace on operators whose order lies outside (minus) the dimension spectrum of the spectral triple.

  16. Construction of Lie Superalgebras from Triple Product Systems

    OpenAIRE

    Okubo, Susumu

    2003-01-01

    Any simple Lie superalgebras over the complex field can be constructed from some triple systems. Examples of Lie superalgebras $D(2,1;\\alpha)$, G(3) and F(4) are given by utilizing a general construction method based upon $(-1,-1)$ balanced Freudenthal-Kantor triple system.

  17. Breakup channels for C-12 triple-alpha continuum states

    NARCIS (Netherlands)

    Diget, C. Aa; Barker, F. C.; Borge, M. J. G.; Boutami, R.; Dendooven, P.; Eronen, T.; Fox, S. P.; Fulton, B. R.; Fynbo, H. O. U.; Huikari, J.; Hyldegaard, S.; Jeppesen, H. B.; Jokinen, A.; Jonson, B.; Kankainen, A.; Moore, I.; Nieminen, A.; Nyman, G.; Penttila, H.; Pucknell, V. F. E.; Riisager, K.; Rinta-Antila, S.; Tengblad, O.; Wang, Y.; Wilhelmsen, K.; Aysto, J.

    The triple-alpha-particle breakup of states in the triple-alpha continuum of C-12 has been investigated by way of coincident detection of all three alpha particles of the breakup. The states have been fed in the beta decay of N-12 and B-12, and the alpha particles measured using a setup that covers

  18. Independent sets in asteroidal triple-free graphs

    NARCIS (Netherlands)

    Broersma, Haitze J.; Kloks, Ton; Kloks, A.J.J.; Kratsch, Dieter; Müller, Haiko

    1997-01-01

    An asteroidal triple is a set of three vertices such that there is a path between any pair of them avoiding the closed neighborhood of the third. A graph is called AT-free if it does not have an asteroidal triple. We show that there is an O(n 2 · (¯m+1)) time algorithm to compute the maximum

  19. "Special Issue": Regional Dimensions of the Triple Helix Model

    Science.gov (United States)

    Todeva, Emanuela; Danson, Mike

    2016-01-01

    This paper introduces the rationale for the special issue and its contributions, which bridge the literature on regional development and the Triple Helix model. The concept of the Triple Helix at the sub-national, and specifically regional, level is established and examined, with special regard to regional economic development founded on…

  20. Regional Dimensions of the Triple Helix Model: Setting the Context

    Science.gov (United States)

    Todeva, Emanuela; Danson, Mike

    2016-01-01

    This paper introduces the rationale for the special issue and its contributions, which bridge the literature on regional development and the Triple Helix model. The concept of the Triple Helix at the sub-national, and specifically regional, level is established and examined, with special regard to regional economic development founded on…

  1. The triple pomeron interaction in the perturbative QCD

    CERN Document Server

    Braun, M

    1995-01-01

    The triple pomeron interaction is studied in the perturbative approach of BFKL-Bartels. At finite momentum transfers \\sqrt{-t} the contribution factorizes in the standard manner with a triple-pomeron vertex proportional to 1/\\sqrt{-t}. At t=0 the contribution is finite, although it grows faster with energy than for finite t and does not factorize.

  2. Government and Governance of Regional Triple Helix Interactions

    Science.gov (United States)

    Danson, Mike; Todeva, Emanuela

    2016-01-01

    This conceptual paper contributes to the discussion of the role of regional government and regional Triple Helix constellations driving economic development and growth within regional boundaries. The impact of regionalism and subsidiarity on regional Triple Helix constellations, and the questions of governmentality, governance and institutional…

  3. Outcome Measures of Triple Board Graduates, 1991-2003

    Science.gov (United States)

    Warren, Marla J.; Dunn, David W.; Rushton, Jerry

    2006-01-01

    Objective: To describe program outcomes for the Combined Training Program in Child and Adolescent Psychiatry, Pediatrics, and Psychiatry (Triple Board Program). Method: All Triple Board Program graduates to date (1991-2003) were asked to participate in a 37-item written survey from February to April 2004. Results: The response rate was 80.7%. Most…

  4. On Twisting Real Spectral Triples by Algebra Automorphisms

    Science.gov (United States)

    Landi, Giovanni; Martinetti, Pierre

    2016-08-01

    We systematically investigate ways to twist a real spectral triple via an algebra automorphism and in particular, we naturally define a twisted partner for any real graded spectral triple. Among other things, we investigate consequences of the twisting on the fluctuations of the metric and possible applications to the spectral approach to the Standard Model of particle physics.

  5. Fibonacci-triple sequences and some fundamental properties

    OpenAIRE

    Bijendra Singh; Omprakash Sikhwal

    2010-01-01

    Fibonacci sequence stands as a kind of super sequence with fabulous properties. This note presents Fibonacci-Triple sequences that may also be called 3-F sequences. This is the explosive development in the region of Fibonacci sequence. Our purpose of this paper is to demonstrate fundamental properties of Fibonacci-Triple sequence.

  6. A Canonical Trace Associated with Certain Spectral Triples

    Science.gov (United States)

    Paycha, Sylvie

    2010-09-01

    In the abstract pseudodifferential setup of Connes and Moscovici, we prove a general formula for the discrepancies of zeta-regularised traces associated with certain spectral triples, and we introduce a canonical trace on operators, whose order lies outside (minus) the dimension spectrum of the spectral triple.

  7. A Canonical Trace Associated with Certain Spectral Triples

    Directory of Open Access Journals (Sweden)

    Sylvie Paycha

    2010-09-01

    Full Text Available In the abstract pseudodifferential setup of Connes and Moscovici, we prove a general formula for the discrepancies of zeta-regularised traces associated with certain spectral triples, and we introduce a canonical trace on operators, whose order lies outside (minus the dimension spectrum of the spectral triple.

  8. Theory of restriction degree of Triple I method with total inference rules of fuzzy reasoning

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    Based on the theory of sustentation degree of Triple I method together with the formulas of a-Triple I modus ponens (MP) and a-Triple I modus tollens( MT), the theory of restriction degree of Triple I method is proposed. Its properties are analyzed, and the general formulas of supremum of a-Triple IMP and infimum of a-Triple I MT are obtained.

  9. Indocyanine green staining for the triple corneal procedure.

    Science.gov (United States)

    Kobayashi, Akira; Segawa, Yoji; Nishimura, Akira; Shirao, Yutaka; Sugiyama, Kazuhisa

    2004-01-01

    In the triple corneal procedure, successful completion of capsulorhexis is of the utmost importance. Another use of indocyanine green dye for better visualization of the anterior lens capsule of mature cataract during the triple corneal procedure is described. Four consecutive patients (mean age, 69.5 years) with both mature cataracts and corneal opacity underwent the triple corneal procedure. After trephination of the recipient cornea, the anterior capsule of the lens was stained with indocyanine green. A continuous curvilinear capsulorhexis (CCC) was performed, after which conventional triple corneal procedures were followed. In all four cases, this technique markedly improved visualization of the lens capsule and resulted in successful and easy manipulation of the CCC and subsequent removal of residual lens cortex. Staining of the anterior capsule of mature cataract in the triple corneal procedure clearly defines the border of the capsule, thus allowing easy and complete execution of CCC.

  10. Control of Collagen Triple Helix Stability by Phosphorylation.

    Science.gov (United States)

    Acevedo-Jake, Amanda M; Ngo, Daniel H; Hartgerink, Jeffrey D

    2017-03-10

    The phosphorylation of the collagen triple helix plays an important role in collagen synthesis, assembly, signaling, and immune response, although no reports detailing the effect this modification has on the structure and stability of the triple helix exist. Here we investigate the changes in stability and structure resulting from the phosphorylation of collagen. Additionally, the formation of pairwise interactions between phosphorylated residues and lysine is examined. In all tested cases, phosphorylation increases helix stability. When charged-pair interactions are possible, stabilization via phosphorylation can play a very large role, resulting inasmuch as a 13.0 °C increase in triple helix stability. Two-dimensional NMR and molecular modeling are used to study the local structure of the triple helix. Our results suggest a mechanism of action for phosphorylation in the regulation of collagen and also expand upon our understanding of pairwise amino acid stabilization of the collagen triple helix.

  11. Can synergy in Triple Helix relations be quantified? A review of the development of the Triple Helix indicator

    NARCIS (Netherlands)

    Leydesdorff, L.; Park, H.W.

    2014-01-01

    Triple Helix arrangements of bi- and trilateral relations can be considered as adaptive ecosystems. During the last decade, we have further developed a Triple Helix indicator of synergy as reduction of uncertainty in niches that can be shaped among three or more sets of relations. Reduction of uncer

  12. Triple-layer smart grid business model

    DEFF Research Database (Denmark)

    Ma, Zheng; Lundgaard, Morten; Jørgensen, Bo Nørregaard

    2016-01-01

    Viewing the smart grid with the theory of business models may open opportunities in understanding and capturing values in new markets. This study tries to discover and map the smart grid ecosystem-based business model framework with two different environments (sub-Saharan Africa and Denmark......), and identifies the parameters for the smart grid solutions to the emerging markets. This study develops a triple-layer business model including the organizational (Niche), environmental (Intermediate), and global (Dominators) factors. The result uncovers an interface of market factors and stakeholders...... in a generic smart grid constellation. The findings contribute the transferability potential of the smart grid solutions between countries, and indicate the potential to export and import smart grid solutions based on the business modeling....

  13. Designing Broadband Access Networks with Triple Redundancy

    DEFF Research Database (Denmark)

    Pedersen, Jens Myrup; Riaz, Muhammad Tahir; Knudsen, Thomas Phillip

    2005-01-01

    An architecture is proposed for designing broadband access networks, which offer triple redundancy to the end users, resulting in networks providing connectivity even in case of any two independent node or line failures. Two physically independent connections are offered by fiber, and the last...... provided by some wireless solution. Based on experience with planning Fiber To The Home, the architecture is designed to meet a number of demands, making it practicable and useful in realworld network planning. The proposed wired topology is planar, and suitable for being fitted onto the road network...... without compromising line independency, and it can be implemented stepwise, the first step being based on a simple ring/tree topology. The double ring is used for the distribution network, ensuring 3-connectivity and making it feasible to use for connecting the base stations of the wireless network...

  14. Polarized triple-axis spectrometer TASP

    Energy Technology Data Exchange (ETDEWEB)

    Boeni, P.; Keller, P. [Lab. for Neutron Scattering ETH Zurich, Zurich (Switzerland) and Paul Scherrer Institute, Villigen (Switzerland)

    1996-11-01

    The polarized triple-axis spectrometer TASP at SINQ has been optimized for measuring magnetic cross sections in condensed matter. The neutrons are polarized or analyzed either by means of benders or Heusler monochromators. The beam divergence, i.e. the intensity, and the spectral range of the neutrons is rather large because of the supermirror coatings of the feeding neutron guide. The intensity can be further increased at the sample position by means of a focussing monochromator and a focussing anti-trumpet. The end position of TASP allows the tailoring of the neutron beam already before the monochromator and to scatter neutrons over very wide ranges of angles. (author) 6 figs., 1 tab., 8 refs.

  15. Thermal striping in triple jet flow

    Energy Technology Data Exchange (ETDEWEB)

    Durve, A. [Department Of Chemical Engineering, Institute of Chemical Technology, Matunga, Mumbai 400019 (India); Patwardhan, A.W., E-mail: aw.patwardhan@ictmumbai.edu.i [Department Of Chemical Engineering, Institute of Chemical Technology, Matunga, Mumbai 400019 (India); Banarjee, I.; Padmakumar, G.; Vaidyanathan, G. [Experimental Thermal Hydraulics Section, Separation Technology and Hydraulics Division, Fast Reactor Technology Group, Indira Gandhi Centre for Atomic Research, Kalpakkam 603102 (India)

    2010-10-15

    A quantitative analysis of temperature fluctuations is necessary for understanding the implications of thermal striping phenomenon occurring in the core outlet region of the fast breeder reactor (FBR). In the present study, the applicability of the temperature variance model and associated modeling for the triple jet flow has been evaluated. A system of three non-isothermal parallel jets, experimented by and has been used to simulate the flow occurring at the core outlet region of the FBR. The velocity fields of the flow have been predicted using the Reynolds stress model. The performance of the temperature variance model was tested using different turbulent Prandtl numbers and different algebraic models for scalar dissipation rate. The predictions were validated with the experimental results of the respective authors. The predicted values of mean temperature were found to be sensitive to turbulent Prandtl number. In this study turbulent Prandtl number was found to vary along the flow field as a function of turbulent Reynolds number.

  16. Acupoints Combination Characteristics of Jin's Triple Acupuncture

    Institute of Scientific and Technical Information of China (English)

    YUAN Qing; XIAO Yuan-chun

    2007-01-01

    @@ JIN Rui is a leading professor of Guangzhou University of Traditional Chinese Medicine, famous acupuncturist, the initiator of "Jin's Triple Acupuncture", supervisor of doctorial candidates, the first Director of the Department of Acupuncture of Guangzhou College of Traditional Chinese Medicine,head of Acupuncture Institute, a member of the second and third Appraisal Group of the Degree Committee of the State Council, a member of China's International Acupunctural Examination Commission,the permanent member of the second session of China's Acupuncture Society, vice-president of literature association of China's Acupuncture Society,vice-chairman of Guangdong Provincial Acupuncture Society, chairman of Guangzhou Acupuncture Association, a tutor appointed by Personnel Ministry,Public Health Ministry and State Administration of Traditional Chinese Medicine.

  17. Mathematical modelling of triple arterial stenoses.

    Science.gov (United States)

    Ang, K C; Mazumdar, J

    1995-06-01

    This paper examines the effects of triple stenoses (ie. three stenoses in series) in a reasonably large artery. The model developed is axi-symmetric and blood is assumed to be a Newtonian fluid. The governing equations are the Navier-Stokes equations and the continuity equation. These equations are solved using the Finite Element Method and the FIDAP computational fluid dynamics (C.F.D.) package. Various combinations of differing degrees of stenosis in the triplet are considered. Pressure drop profiles and streamline plots of the solutions to these models show that the effects of milder stenoses are diminished in the presence of more severe ones. Also, a pressure recovery is observed whenever a mild stenosis follows a more severe stenosis in multiply stenosed arteries.

  18. [Triple fracture of the shoulder suspensory complex].

    Science.gov (United States)

    Tamimi Mariño, I; Martin Rodríguez, I; Mora Villadeamigo, J

    2013-01-01

    The superior suspensory complex of the shoulder (SSCS) is a ring shaped structure composed of bones and soft tissues that play a fundamental role in the stability of the shoulder joint. Isolated injuries of the SSCS are relatively common, but injuries that affect 3 components are extremely unusual. We present a triple injury of the SSCS in a 26 year old patient with a Neer type ii clavicular fracture, a Kuhn type iii acromion fracture and an Ogawa type i coracoid fracture. An open reduction and stabilization of the clavicle was performed with 2 Kirschner nails. The acromial fracture was synthesized with 2 cannulated screws, and the coracoid fracture was treated conservatively. After 24 months of follow up the patient had an excellent functional outcome according to the Constat-Murley shoulder score and QuickDASH scoring system, and all the fractures healed correctly. Copyright © 2013 SECOT. Published by Elsevier Espana. All rights reserved.

  19. The Triple Helix Perspective of Innovation Systems

    CERN Document Server

    Leydesdorff, Loet

    2010-01-01

    Alongside the neo-institutional model of networked relations among universities, industries, and governments, the Triple Helix can be provided with a neo-evolutionary interpretation as three selection environments operating upon one another: markets, organizations, and technological opportunities. How are technological innovation systems different from national ones? The three selection environments fulfill social functions: wealth creation, organization control, and organized knowledge production. The main carriers of this system-industry, government, and academia-provide the variation both recursively and by interacting among them under the pressure of competition. Empirical case studies enable us to understand how these evolutionary mechanisms can be expected to operate in historical instance. The model is needed for distinguishing, for example, between trajectories and regimes.

  20. [Triple therapy in chronic obstructive pulmonary disease].

    Science.gov (United States)

    Baloira, Adolfo

    2010-01-01

    Chronic obstructive pulmonary disease (COPD) is one of the most important respiratory diseases, characterized by its multicomponent complexity, with chronic inflammation, increased airway resistance and exacerbations. Several drugs are currently available for its treatment, which act on distinct targets. Bronchodilators, especially prolonged-action bronchodilators, are the most potent and there are two groups: beta-2 mimetics and anticholinergics. Inhaled corticosteroids are the main anti-inflammatory drugs but have modest efficacy and their use is reserved for patients with severe disease and frequent exacerbations and/or asthma traits. Associating these three drugs can improve symptom control, improve quality of life and reduce the number of exacerbations. The present article reviews the evidence supporting this triple combination, as well as published studies.

  1. The Triple Helix of the Organizational Knowledge

    Directory of Open Access Journals (Sweden)

    Contantin BRĂTIANU

    2013-09-01

    Full Text Available The purpose of this paper is to present the inner triple helix dynamics of the organizationalknowledge. This is a new perspective of the classical view of tacit knowledge– explicit knowledge dyad of the organizational knowledge promoted by Nonaka and hisco-workers. The new perspective is based on the metaphor that organizational knowledge isa "eld rather than a stock, or stocks and flows. It is a complex metaphor using the thermodynamicsprinciples. The organizational knowledge is composed of three different "elds: cognitiveknowledge, emotional knowledge and spiritual knowledge. These "elds are nonuniform,nonhomogeneous and they interact in a dynamic way. Cognitive "eld contains knowledgeabout what is, emotional "eld contains knowledge about how we feel, and the spiritual "eldcontains knowledge about people’s aspirations and life values. This new perspective opens anew opportunity in understanding the challenges for the 21st century management.

  2. Clinicopathological Features of Triple Negative Breast Carcinoma

    Science.gov (United States)

    Reddy, Gowry Maram; Pai, Radha R.

    2017-01-01

    Introduction Breast carcinoma is one of the most common malignancies affecting women in developing countries. Molecular studies of breast carcinoma have classified the tumour based on the immunohistochemical staining into 4 subtypes, such as Luminal A, Luminal B, HER2/neu Positive and Triple Negative Breast Carcinoma (TNBC). TNBCs are reported to have an aggressive behaviour and wide metastasis, leading to selective treatment outcomes. Aim The aim was to study the clinicopathological features such as age, site, tumour size, histopathological type, histologic grade, lymph node status, stage and treatment outcomes of triple negative breast carcinoma. Materials and Methods A retrospective study was conducted on 108 cases of breast carcinoma received during the period of 2 years. The tumour was classified based on immunohistochemical staining into four subtypes. The clinicopathological details, histomorphological and immunohistochemical features of TNBC were studied. Results Of the 108 patients, 34 patients were diagnosed as TNBC. The average age at presentation was 48 years. Most of the cases showed Nottingham Modification of Scarff Bloom-Richardson (NMBR) grade 3 (55.9%) and stage II (67.6%). Ly-mph node metastasis was seen in 50% of cases. Infiltrating ductal carcinoma (not otherwise specified) type (91.2%) was the most common histological type. Among the other subtypes, Luminal A carcinoma was the most common (36.1%), followed by TNBC (31.5%) and HER2/neu positive carcinomas (28.7%). Compared to the other types of tumours, TNBC showed the most frequent distant lymph node metastasis (50%) when compared to luminal A (38.5%), luminal B (25%), HER2/neu positive (48.4%). Unlike the other types of tumours, TNBC were mostly high-grade. Conclusion TNBC have an aggressive behaviour compared to other subtypes with higher NMBR grade, nuclear pleomorphism, high mitotic rate and lymph node metastasis. PMID:28273970

  3. Triple negative breast cancer: an Indian perspective

    Directory of Open Access Journals (Sweden)

    Akhtar M

    2015-08-01

    Full Text Available Murtaza Akhtar, Subhrajit Dasgupta, Murtuza Rangwala Department of Surgery, NKP Salve Institute of Medical Sciences and Research Centre, Nagpur, Maharashtra, India Introduction: Breast cancer is the most common female cancer in the world. Triple negative breast cancer (TNBC is a recently identified biological variant with aggressive tumor behavior and poor prognosis. Data of hormonal status from the Indian population is scarce due to financial constraints in performing immunohistochemistry evaluation. The present study aims to prospectively analyze receptor status of all breast cancer patients and identify TNBC and compare their clinical profile and short term survival with other non-TNBC group. Materials and methods: All cytologically and histopathologically confirmed cases of carcinoma breast were prospectively enrolled. In a longitudinal study at tertiary care hospital in central India based on the hormonal status, they were further divided into TNBC and other groups. Comparison of risk factors, clinical profile and short-term survival was carried out. Results: A total 85 patients were enrolled and of them 37 (43.7% were TNBC. On comparing risk factors ie, age, age at menarche, total reproductive age, age at first child birth, and menopausal status – no statistical significance was observed between the TNBC and non-TNBC groups. But on comparison of clinical profile TNBC tumors were significantly large with majority of patients presenting as locally advanced breast cancer (83%. No statistical difference was observed in axillary lymph node status between two groups. TNBC tumors were histologically more aggressive (grade 3 compared to other groups. No statistically significant difference was observed in short term overall survival but all three deaths were observed in the TNBC group only and two local recurrences after surgery were observed in the TNBC group. Conclusion: TNBC forms a large proportion of carcinoma breast patients in a central

  4. Fractura triple del complejo suspensorio del hombro

    Directory of Open Access Journals (Sweden)

    Eraclio Delgado Rifá

    2015-06-01

    Full Text Available El complejo suspensorio del hombro es una estructura sumamente importante, compuesta por un anillo de huesos y tejidos blandos. Las lesiones aisladas de este complejo anatómico son frecuentes y no afectan su estabilidad. La interrupción doble conduce a la inestabilidad de esta estructura y usualmente requiere tratamiento quirúrgico. La triple interrupción, por su parte, es sumamente rara y es encontrada en casos de trauma de alta energía a menudo en asociación con otras lesiones. Se presenta una triple lesión del complejo suspensorio del hombro en un paciente de 46 años de edad, con una fractura de la glenoides, del acromion tipo III de Kuhn y de la coracoides tipo II de Ogawa. En este caso, la fractura del acromion fue tratada con fijación percutánea con alambres de Kirschner, por tener asociado lesiones de partes blandas que contraindicaron la reducción abierta. La fractura de la glenoides y de la apófisis coracoides fueron tratadas conservadoramente. Después de 6 meses de evolución, el paciente tuvo un resultado funcional aceptable, con una abducción de 90 grados, los 30 grados de rotación externa y 70 de rotación interna, además asintomático y consolidación de todas las fracturas. A pesar de ser catalogada de una lesión grave del cinturón escapular y estar asociada a otras lesiones se obtuvo un resultado satisfactorio al final del tratamiento.

  5. Comparison of Triple Therapy plus Probiotic Yogurt vs. Standard Triple Therapy on Helicobacter Pylori Eradication

    Directory of Open Access Journals (Sweden)

    Vahid Mirzaee

    2013-04-01

    Full Text Available Background: Treatment of Helicobacter pylori as a major cause of gastric diseases is of utmost concern. We aimed to assess efficacy of triple therapy (amoxicillin, clarithromycin and pantoprazole plus probiotic yogurt (PY on eradication of H. pylori. Materials and Methods: Total 102 H. pylori positive patients were divided to 3 groups equally and randomly. For treatment of each group amoxicillin, clarithromycin and pantoprazole were used. Group A had additional PY and Group B ordinary low fat yogurt in their regimen as well. These groups were compared regarding treatment success.Results: Total number of 88 patients finished the treatment course. The most common experienced side effects were dysgeusia in groups A and B (25.8% and 32.3%, respectively, and dysgeusia with diarrhea and abdominal pain (30.8% in group C. Eradication rate was, respectively, 61.3%, 64.5% and 71.3% in group A, B and C of which difference was not statistically significant. However, the difference between 3 groups in regard to education level was statistically significant (p=0.005.Conclusion: PY enriched triple therapy has decreased side effects of antibiotics consumption; however, this has no impact on eradication of H. pylori. PY and triple therapy can be used concomitantly to increase the patient tolerance.

  6. Relative Stability of the Scleroglucan Triple-Helix and Single Strand: an Insight from Computational and Experimental Techniques

    Science.gov (United States)

    Bocchinfuso, Gianfranco; Mazzuca, Claudia; Conflitti, Paolo; Cori, Davide; Coviello, Tommasina; Palleschi, Antonio

    2016-09-01

    Scleroglucan (Sclg) is a polysaccharide that exhibits a triple helix conformation (triplex), both in aqueous solution and in the solid state, which is lost in DMSO solution, at high temperature and at high pH values. The triplex conformation is characterized by a high rigidity, responsible of Sclg peculiar properties. Although the relative stability of triplex and single strand has already been investigated, different structural details are still missing. In the present study, we analyse the structural properties and the factors stabilizing the single chain and the triple helix of Sclg in different conditions. To this end, we simulated both systems in water and in DMSO. The triple helix has been also simulated in the presence of chemical damages on one of the three strands (to reproduce in silico the effect of sonication) or by inducing a partial unfolding of the triplex structure. The computational results have been compared with experimental evidences in which the triplex denaturation, at alkaline pH values, has been followed by monitoring the UV and CD spectra of Congo red, used as a probe molecule. Our results indicate that sonication breaks the Sclg chains without appreciably changing the stability of the other tracts of triple helix. The simulated perturbed or partially unfolded triplexes show a clear tendency to form less ordered aggregates. Finally, our simulations put in evidence an important role of the hydrophobic interactions both in the triplex stability and in the aggregation processes observed after induced denaturation.

  7. Triple therapy for the management of COPD: a review.

    Science.gov (United States)

    Gaebel, Kathryn; McIvor, R Andrew; Xie, Feng; Blackhouse, Gord; Robertson, Diana; Assasi, Nazila; Hernandez, Paul; Goeree, Ron

    2011-06-01

    Triple therapy for COPD consists of a long-acting anti-cholinergic bronchodilator, a long-acting beta-agonist bronchodilator, and an inhaled corticosteroid. Guidelines from the Canadian Thoracic Society advocate triple therapy for some patients with moderate-to-severe COPD. The objective of this review was to evaluate the evidence based clinical efficacy of triple therapy compared to dual bronchodilator therapy (long-acting anti-cholinergic bronchodilator + beta-agonist bronchodilator) or long-acting anti-cholinergic bronchodilator monotherapy for managing COPD. A systematic literature search was conducted to identify relevant clinical evaluations of triple therapy in the management of moderate to severe COPD. Databases searched included: Medline; EMBASE; CINAHL and PubMed (non-Medline records only). Of 2,314 publications, 4 articles evaluated triple therapy for the management of COPD. Hospitalization rates for COPD exacerbations, reported in 2 trials, were significantly reduced with triple therapy compared to long-acting anti-cholinergic bronchodilator monotherapy, with reported relative risks of 0.53 (95% CI: 0.33, 0.86, p = 0.01) and 0.35 (95% CI: 0.16-0.78, p = 0.011). Exacerbation data is inconsistent between the two trials reporting this outcome. Lung function, dyspnea and quality of life data show statistical significant changes with triple therapy compared to long-acting anti-cholinergic bronchodilator monotherapy but the changes do not reach clinical importance. Triple therapy does decrease the number of hospitalizations for severe/acute COPD exacerbations compared with long-acting anti-cholinergic bronchodilator monotherapy. There is insufficient evidence to determine if triple therapy is superior to dual bronchodilator therapy.

  8. Triple Bioluminescence Imaging for In Vivo Monitoring of Cellular Processes

    Directory of Open Access Journals (Sweden)

    Casey A Maguire

    2013-01-01

    Full Text Available Bioluminescence imaging (BLI has shown to be crucial for monitoring in vivo biological processes. So far, only dual bioluminescence imaging using firefly (Fluc and Renilla or Gaussia (Gluc luciferase has been achieved due to the lack of availability of other efficiently expressed luciferases using different substrates. Here, we characterized a codon-optimized luciferase from Vargula hilgendorfii (Vluc as a reporter for mammalian gene expression. We showed that Vluc can be multiplexed with Gluc and Fluc for sequential imaging of three distinct cellular phenomena in the same biological system using vargulin, coelenterazine, and D-luciferin substrates, respectively. We applied this triple imaging system to monitor the effect of soluble tumor necrosis factor-related apoptosis-inducing ligand (sTRAIL delivered using an adeno-associated viral vector (AAV on brain tumors in mice. Vluc imaging showed efficient sTRAIL gene delivery to the brain, while Fluc imaging revealed a robust antiglioma therapy. Further, nuclear factor-κB (NF-κB activation in response to sTRAIL binding to glioma cells death receptors was monitored by Gluc imaging. This work is the first demonstration of trimodal in vivo bioluminescence imaging and will have a broad applicability in many different fields including immunology, oncology, virology, and neuroscience.

  9. Vectorized data acquisition and fast triple-correlation integrals for Fluorescence Triple Correlation Spectroscopy

    Science.gov (United States)

    Ridgeway, William K.; Millar, David P.; Williamson, James R.

    2013-04-01

    Fluorescence Correlation Spectroscopy (FCS) is widely used to quantify reaction rates and concentrations of molecules in vitro and in vivo. We recently reported Fluorescence Triple Correlation Spectroscopy (F3CS), which correlates three signals together instead of two. F3CS can analyze the stoichiometries of complex mixtures and detect irreversible processes by identifying time-reversal asymmetries. Here we report the computational developments that were required for the realization of F3CS and present the results as the Triple Correlation Toolbox suite of programs. Triple Correlation Toolbox is a complete data analysis pipeline capable of acquiring, correlating and fitting large data sets. Each segment of the pipeline handles error estimates for accurate error-weighted global fitting. Data acquisition was accelerated with a combination of off-the-shelf counter-timer chips and vectorized operations on 128-bit registers. This allows desktop computers with inexpensive data acquisition cards to acquire hours of multiple-channel data with sub-microsecond time resolution. Off-line correlation integrals were implemented as a two delay time multiple-tau scheme that scales efficiently with multiple processors and provides an unprecedented view of linked dynamics. Global fitting routines are provided to fit FCS and F3CS data to models containing up to ten species. Triple Correlation Toolbox is a complete package that enables F3CS to be performed on existing microscopes. Catalogue identifier: AEOP_v1_0 Program summary URL:http://cpc.cs.qub.ac.uk/summaries/AEOP_v1_0.html Program obtainable from: CPC Program Library, Queen’s University, Belfast, N. Ireland Licensing provisions: Standard CPC licence, http://cpc.cs.qub.ac.uk/licence/licence.html No. of lines in distributed program, including test data, etc.: 50189 No. of bytes in distributed program, including test data, etc.: 6135283 Distribution format: tar.gz Programming language: C/Assembly. Computer: Any with GCC and

  10. Ternary Weakly Amenable C*-algebras and JB*-triples

    CERN Document Server

    Ho, Tony; Russo, Bernard

    2012-01-01

    A well known result of Haagerup from 1983 states that every C*-algebra A is weakly amenable, that is, every (associative) derivation from A into its dual is inner. A Banach algebra B is said to be ternary weakly amenable if every continuous Jordan triple derivation from B into its dual is inner. We show that commutative C*-algebras are ternary weakly amenable, but that B(H) and K(H) are not, unless H is finite dimensional. More generally, we inaugurate the study of weak amenability for Jordan Banach triples, focussing on commutative JB*-triples and some Cartan factors.

  11. On Integrable Roots in Split Lie Triple Systems

    Institute of Scientific and Technical Information of China (English)

    A.J.CALDER(O)N MART(I)N

    2009-01-01

    We focus on the notion of an integrable root in the framework of split Lie triple systems T with a coherent 0-root space. As a main result, it is shown that if T has all its nonzero roots integrable, then its standard embedding is a split Lie algebra having all its nonzero roots integrable. As a consequence, a local finiteness theorem for split Lie triple systems, saying that whenever all nonzero roots of T are integrable then T is locally finite, is stated. Finally, a classification theorem for split simple Lie triple systems having all its nonzero roots integrable is given.

  12. Extended superconformal symmetry, Freudenthal triple systems and gauged WZW models

    CERN Document Server

    Günaydin, M

    1995-01-01

    We review the construction of extended ( N=2 and N=4 ) superconformal algebras over triple systems and the gauged WZW models invariant under them. The N=2 superconformal algebras (SCA) realized over Freudenthal triple systems (FTS) admit extension to ``maximal'' N=4 SCA's with SU(2)XSU(2)XU(1) symmetry. A detailed study of the construction and classification of N=2 and N=4 SCA's over Freudenthal triple systems is given. We conclude with a study and classification of gauged WZW models with N=4 superconformal symmetry.

  13. Spectroscopic properties of the triple bond carotenoid alloxanthin

    Science.gov (United States)

    West, Robert; Keşan, Gürkan; Trsková, Eliška; Sobotka, Roman; Kaňa, Radek; Fuciman, Marcel; Polívka, Tomáš

    2016-06-01

    Alloxanthin, which has two triple bonds within its backbone, was studied by steady-state and femtosecond transient absorption spectroscopies. Alloxanthin demonstrates an S2 energy comparable to its non-triple bond homolog, zeaxanthin, while the S1 lifetime of 19 ps is markedly longer than that of zeaxanthin (9 ps). Along with corroborating quantum chemistry calculations, the results show that the long-lived S1 state of alloxanthin, which typically corresponds to the dynamic of a shorter carotenoid backbone, implies the triple bond isolates the conjugation of the backbone, increasing the S1 state energy and diminishing the S1-S2 energy gap.

  14. On Pythagoras Theorem for Products of Spectral Triples

    Science.gov (United States)

    D'Andrea, Francesco; Martinetti, Pierre

    2013-05-01

    We discuss a version of Pythagoras theorem in noncommutative geometry. Usual Pythagoras theorem can be formulated in terms of Connes' distance, between pure states, in the product of commutative spectral triples. We investigate the generalization to both non-pure states and arbitrary spectral triples. We show that Pythagoras theorem is replaced by some Pythagoras inequalities, that we prove for the product of arbitrary (i.e. non-necessarily commutative) spectral triples, assuming only some unitality condition. We show that these inequalities are optimal, and we provide non-unital counter-examples inspired by K-homology.

  15. Superconformal M2-branes and generalized Jordan triple systems

    CERN Document Server

    Nilsson, Bengt E W

    2008-01-01

    Three-dimensional conformal theories with six supersymmetries and SU(4) R-symmetry describing stacks of M2-branes are here proposed to be related to generalized Jordan triple systems. Writing the four-index structure constants in an appropriate form, the Chern-Simons part of the action immediately suggests a connection to such triple systems. In this note we show that the whole theory with six manifest supersymmetries can be naturally expressed in terms of structure constants of generalized Jordan triple systems. We comment on the associated graded Lie algebra, which corresponds to an extension of the gauge group.

  16. Examples of infinite direct sums of spectral triples

    Science.gov (United States)

    Falk, Kevin

    2017-02-01

    We study two ways of summing an infinite family of noncommutative spectral triples. First, we propose a definition of the integration of spectral triples and give an example using algebras of Toeplitz operators acting on weighted Bergman spaces over the unit ball of Cn. Secondly, we construct a spectral triple associated to a general polygonal self-similar set in C using algebras of Toeplitz operators on Hardy spaces. In this case, we show that we can recover the Hausdorff dimension of the fractal set.

  17. Modulation of the BRCA1 Protein and Induction of Apoptosis in Triple Negative Breast Cancer Cell Lines by the Polyphenolic Compound Curcumin

    Directory of Open Access Journals (Sweden)

    Danica L. Rowe

    2009-09-01

    Full Text Available In the current study, we sought to examine the effects of curcumin in a specific type of breast cancer called triple negative breast cancer. These cancers lack expression of the estrogen and progesterone receptors and do not over-express HER2. Current treatment for triple negative breast cancers is limited to cytotoxic chemotherapy, and upon relapse, there are not any therapies currently available. We demonstrate here that the bioactive food compound curcumin induces DNA damage in triple negative breast cancer cells in association with phosphorylation, increased expression, and cytoplasmic retention of the BRCA1 protein. In addition, curcumin promotes apoptosis and prevents anchorage-independent growth and migration of triple negative breast cancer cells. Apoptosis and BRCA1 modulation were not observed in non-transformed mammary epithelial cells, suggesting curcumin may have limited non-specific toxicity. This study suggests that curcumin and potentially curcumin analogues should be tested further in the context of triple negative breast cancer. These results are novel, having never been previously reported, and suggest that curcumin could provide a novel, non-toxic therapy, which could lead to improved survival for patients with triple negative breast cancer. Curcumin should be studied further in this subset of breast cancer patients, for whom treatment options are severely limited.

  18. ERCC1 Expression in Metastatic Triple Negative Breast Cancer Patients Treated with Platinum-Based Chemotherapy

    Science.gov (United States)

    EL Baiomy, Mohamed Ali; El Kashef, Wagdi F

    2017-02-01

    Background: Possible targeted therapies for metastatic triple negative breast cancer (TNBC) include cytotoxic chemotherapy that causes interstrand breaks (platinum-based drugs). The excision repair cross-complementation 1 (ERCC1) enzyme plays an essential role in the nucleotide excision repair pathway, removing platinum-induced DNA adducts and contributing to cisplatin resistance. Detecting ERCC1 overexpression is important in considering treatment options for metastatic TNBC, including individualized approaches to therapy, and may facilitate improved responses or reduction of unnecessary toxicity. We hypothesized that assigning cisplatin based on pretreatment ERCC1 expression would improve response and survival. This study was conducted to assess the impact of ERCC1 expression on PFS, OS and response rates in metastatic triple negative breast cancer patients treated with platinum-based chemotherapy. Methods: From June 2012 to November 2013, 52 metastatic triple negative breast cancer patients were enrolled. ERCC1 protein expression was detected from pretreatment biopsies by Immunohistochemistry. All patients received cisplatin plus paclitaxel. The primary end point was the impact of ERCC1 expression on PFS and OS. Results: 34 patients (65.4%) showed positive ERCC1 expression while 18 (34.6%) proved negative. Positive ERCC1 expression was associated with short PFS (median, 5 months vs. 7 months; P = 0.043), short OS (median, 9 months vs. 11 months; P = 0.033) and poor response to cisplatin based chemotherapy (P = 0.046). Conclusions: This prospective study further validated ERCC1 as a reliable biomarker for customized chemotherapy in metastatic triple negative breast cancer patients. High expression of ERCC1 was thereby fond to be significantly associated with poor outcome in patients treated with platinum based chemotherapy.

  19. Encoding physico-chemical cues in synthetic hydrogels by triple helix assembly of collagen mimetic peptides

    Science.gov (United States)

    Stahl, Patrick

    The ECM is a complex natural system evolved to promote proliferation and differentiation of cells during tissue development. In order to create synthetic biomaterials for studying cell-scaffold interactions and ultimately for engineering tissues, scientists strive to recapitulate many characteristics of ECM by developing hydrogels that contain mechanical cues and biochemical signals such as adhesion moieties and cell growth factors. While synthetic hydrogels bypass limitations of naturally-derived materials (e.g. transfer of pathogens), nature provides inspiration to enhance the functionality of synthetic hydrogels through biomimetic approaches. The collagen triple helix is the basis for the supramolecular structure of collagen in the ECM, and its adaptation in collagen mimetic peptides (CMPs) has provided hybridization mechanisms that can be employed in the formation and functionalization of synthetic hydrogels. The aim of this dissertation is to develop novel poly(ethylene glycol) (PEG)-based hydrogels that employ CMP triple helix assembly as a non-covalent yet target-specific tool to encode physical and chemical cues into the hydrogel with spatial control. We demonstrate that multi-arm PEG functionalized with CMPs form hydrogels supported by physical crosslinks mediated by CMP triple helix. Particle tracking microrheology shows that these physical crosslinks are sensitive to temperature as well as addition of exogenous CMPs that can disrupt crosslinks by competing for triple helix formation. This physical crosslink disruption enables the modulation of bulk hydrogel elasticity and the introduction of local stiffness gradients in PEG-CMP hydrogels. We also present photopolymerized PEG diacrylate (PEGDA) hydrogels displaying CMPs that can be further conjugated to CMPs with bioactive moieties via triple helix hybridization. Encoding these hydrogels with cell-adhesive CMPs induces cell spreading and proliferation. We further demonstrate generation of gradients and

  20. A Study of Neoadjuvant Paclitaxel in Combination With Bavituximab in Early- Stage Triple- Negative Breast Cancer

    Science.gov (United States)

    2017-03-08

    Breast Cancer; Triple Negative Breast Neoplasms; Triple-Negative Breast Neoplasm; Triple-Negative Breast Cancer; Triple Negative Breast Cancer; ER-Negative PR-Negative HER2-Negative Breast Neoplasms; ER-Negative PR-Negative HER2-Negative Breast Cancer

  1. Homotopes of JB*-triples and a Russo—Dye Theorem

    OpenAIRE

    Mackey, Michael

    2009-01-01

    In this note, we look at homotopes of Jordan triple structures and show that, following a renorming, an isotope of a JB*-triple is also a JB*-triple. We also provide a proof of the Russo—Dye theorem for JBW*-triples.

  2. Triple Isotope Water Analyzer for Extraplanetary Studies Project

    Data.gov (United States)

    National Aeronautics and Space Administration — In this Small Business Innovative Research (SBIR) effort, Los Gatos Research (LGR) proposes to develop a miniature, high-resolution, low power, triple-isotope water...

  3. The universal enveloping TRO of a JB*-triple system

    CERN Document Server

    Bohle, Dennis

    2010-01-01

    We associate to every JB*-triple system a so-called universal enveloping TRO and show some functorial properties of this correspondence. We compute the universal enveloping TROs of the finite dimensional Cartan factors.

  4. Tripled Fixed Point in Ordered Multiplicative Metric Spaces

    Directory of Open Access Journals (Sweden)

    Laishram Shanjit

    2017-06-01

    Full Text Available In this paper, we present some triple fixed point theorems in partially ordered multiplicative metric spaces depended on another function. Our results generalise the results of [6] and [5].

  5. The spectrum for overlarge sets of directed triple systems

    Institute of Scientific and Technical Information of China (English)

    Zi-hong; TIAN; Li-jun; Ji

    2007-01-01

    A directed triple system of order v, denoted by DTS(v, λ), is a pair (X,B) where X is a v-set and B is a collection of transitive triples on X such that every ordered pair of X belongs to λ triples of B. An overlarge set of disjoint DTS(v, λ), denoted by OLDTS(v, λ), is a collection {(Y\\{y}, Ai)}i,such that Y is a (v + 1)-set, each (Y\\{y}, Ai) is a DTS(v, λ) and all Ai's form a partition of all transitive triples of Y. In this paper, we shall discuss the existence problem of OLDTS(v, λ) and give the following conclusion: there exists an OLDTS(v, λ) if and only if either λ = 1 and v = 0, 1 (mod 3), or λ = 3 and v≠2.

  6. Triple negative breast cancer: adjuvant chemotherapy effect on survival

    National Research Council Canada - National Science Library

    Steponaviciene, L; Lachej-Mikeroviene, N; Smailyte, G; Aleknavicius, E; Meskauskas, R; Didziapetriene, J

    2011-01-01

    Purpose: The purpose of this study was to evaluate the overall survival of patients with triple negative breast cancer and the impact of different adjuvant chemotherapy regimens on survival.Material/Methods...

  7. The QCD triple Pomeron coupling from string amplitudes

    CERN Document Server

    Bialas, A; Peschanski, R

    1998-01-01

    Using the recent solution of the triple Pomeron coupling in the QCD dipole picture as a closed string amplitude with six legs, its analytical form in terms of hypergeometric functions and numerical value are derived.

  8. Structural alignment of RNA with triple helix structure.

    Science.gov (United States)

    Wong, Thomas K F; Yiu, S M

    2012-04-01

    Structural alignment is useful in identifying members of ncRNAs. Existing tools are all based on the secondary structures of the molecules. There is evidence showing that tertiary interactions (the interaction between a single-stranded nucleotide and a base-pair) in triple helix structures are critical in some functions of ncRNAs. In this article, we address the problem of structural alignment of RNAs with the triple helix. We provide a formal definition to capture a simplified model of a triple helix structure, then develop an algorithm of O(mn(3)) time to align a query sequence (of length m) with known triple helix structure with a target sequence (of length n) with an unknown structure. The resulting algorithm is shown to be useful in identifying ncRNA members in a simulated genome.

  9. Triple Isotope Water Analyzer for Extraplanetary Studies Project

    Data.gov (United States)

    National Aeronautics and Space Administration — Los Gatos Research (LGR) proposes to employ Off-Axis ICOS to develop triple-isotope water analyzers for lunar and other extraplanetary exploration. This instrument...

  10. Rehabilitation of a triple amputee including a hip disarticulation.

    Science.gov (United States)

    Shin, J C; Park, C I; Kim, Y C; Jang, S H; Bang, I K; Shin, J S

    1998-12-01

    A multiple amputee more severe than a triple amputee is uncommon. There have been no reports on the rehabilitation outcome of a triple amputee, including hip disarticulation and transtibial amputation. The authors report the rehabilitation of a patient with left hip disarticulation, right trans-tibial amputation, and left trans-humeral amputation due to a train accident. He has successfully completed the rehabilitation programme and has become independent in prosthetic ambulation, activities of daily living, and driving.

  11. Targeting Histone Abnormality in Triple Negative Breast Cancer

    Science.gov (United States)

    2015-08-01

    respiration by 17β-estradiol through lactate dehydrogenase in MCF7 breast cancer cells. AACR Metabolism and Cancer , Baltimore, October 16-19, 2011. 20...1 AWARD NUMBER: W81XWH-14-1-0237 TITLE: Targeting Histone Abnormality in Triple-Negative Breast Cancer PRINCIPAL INVESTIGATOR: Yi...TITLE AND SUBTITLE 5a. CONTRACT NUMBER Targeting Histone Abnormality in Triple-Negative Breast Cancer 5b. GRANT NUMBER W81XWH-14-1-0237 5c

  12. Triple pelvic osteotomy in the treatment of hip dysplasia.

    Science.gov (United States)

    Vukasinović, Zoran; Spasovski, Dusko; Zivković, Zorica; Slavković, Nemanja; Cerović, Sofija

    2009-01-01

    Insufficient femoral head coverage is found in a variety of diseases, with acetabular dysplasia as the most frequent disorder and triple pelvic osteotomy as the most recently introduced surgical treatment. This study analyses pre- and postoperative pathoanatomic characteristics of triple in comparison to Salter and Chiari osteotomies, with a logistic regression analysis of outcome predictor and effect explanator factors in relation to the chosen type of operation. The study involved 136 adolescents treated with Salter and Chiari osteotomies or a triple pelvic osteotomy at the Institute of Orthopaedic Surgery "Banjica" in Belgrade. The patients were between 10-20 years old at the time of operation. We collected and analyzed data from all the patients: illness history, operative parameters, preoperative and postoperative pathoanatomic data. The data was statistically processed using the statistical software SPSS, defining standard descriptive values, and by using the appropriate tests of analytic statistics: t-test for dependent and independent variables, chi2-test, Fisher's exact test, Wilcoxon's test, parameter correlation, one-way ANOVA, multi-factorial ANOVA and logistic regression, according to the type of the analyzed data and the conditions under which the statistical methods were applied. The average CE angle after triple pelvic osteotomy was 43.5 degrees, more improved than after the Salter osteotomy (33.0 degrees) and Chiari osteotomy (31.4 degrees) (F = 16.822; p triple osteotomy than after the other two types of operations, and with a high significance. Preoperative painful discomfort was found to be a valid predictor of indications for the triple osteotomy over both Chiari and Salter osteotomies. The valid explanators of effect for the triple osteotomy are: postoperative joint congruence (compared to the Chiari osteotomy) and increase in joint coverage (compared to Salter osteotomy). Triple pelvic osteotomy is the method of choice in the management of

  13. TEDI: the TripleSpec Exoplanet Discovery Instrument

    CERN Document Server

    Edelstein, Jerry; Erskine, David J; Feuerstein, W Michael; Marckwordt, Mario; Wishnow, Ed; Lloyd, James P; Herter, Terry; Muirhead, Phillip; Gull, George E; Henderson, Charles; Parshley, Stephen C

    2007-01-01

    The TEDI (TripleSpec - Exoplanet Discovery Instrument) will be the first instrument fielded specifically for finding low-mass stellar companions. The instrument is a near infra-red interferometric spectrometer used as a radial velocimeter. TEDI joins Externally Dispersed Interferometery (EDI) with an efficient, medium-resolution, near IR (0.9 - 2.4 micron) echelle spectrometer, TripleSpec, at the Palomar 200" telescope. We describe the instrument and its radial velocimetry demonstration program to observe cool stars.

  14. Epigenetic Subtypes of Triple-Negative Breast Cancer

    Science.gov (United States)

    2015-10-01

    1 AD______________ AWARD NUMBER: W81XWH-14-1-0213 TITLE: Epigenetic Subtypes of Triple-Negative Breast Cancer PRINCIPAL INVESTIGATOR...SUBTITLE Epigenetic Subtypes of Triple-Negative Breast Cancer 5a. CONTRACT NUMBER W81XWH-14-1-0213 5b. GRANT NUMBER 5c. PROGRAM ELEMENT NUMBER 6...generally dominant. Based on the analysis of a limited number of TNBC cell lines we found that the epigenetic profiles of TNBCs are highly heterogeneous

  15. A statistically derived parameterization for the collagen triple-helix.

    Science.gov (United States)

    Rainey, Jan K; Goh, M Cynthia

    2002-11-01

    The triple-helix is a unique secondary structural motif found primarily within the collagens. In collagen, it is a homo- or hetero-tripeptide with a repeating primary sequence of (Gly-X-Y)(n), displaying characteristic peptide backbone dihedral angles. Studies of bulk collagen fibrils indicate that the triple-helix must be a highly repetitive secondary structure, with very specific constraints. Primary sequence analysis shows that most collagen molecules are primarily triple-helical; however, no high-resolution structure of any entire protein is yet available. Given the drastic morphological differences in self-assembled collagen structures with subtle changes in assembly conditions, a detailed knowledge of the relative locations of charged and sterically bulky residues in collagen is desirable. Its repetitive primary sequence and highly conserved secondary structure make collagen, and the triple-helix in general, an ideal candidate for a general parameterization for prediction of residue locations and for the use of a helical wheel in the prediction of residue orientation. Herein, a statistical analysis of the currently available high-resolution X-ray crystal structures of model triple-helical peptides is performed to produce an experimentally based parameter set for predicting peptide backbone and C(beta) atom locations for the triple-helix. Unlike existing homology models, this allows easy prediction of an entire triple-helix structure based on all existing high-resolution triple-helix structures, rather than only on a single structure or on idealized parameters. Furthermore, regional differences based on the helical propensity of residues may be readily incorporated. The parameter set is validated in terms of the predicted bond lengths, backbone dihedral angles, and interchain hydrogen bonding.

  16. The Triple Helix of University-Industry-Government Relations

    OpenAIRE

    Leydesdorff, Loet

    2012-01-01

    Etzkowitz & Leydesdorff (2000) further elaborated the Triple Helix of University-Industry-Government Relations (cf. Etzkowitz & Leydesdorff, 1995; Lowe, 1982) into a model for studying knowledge-based economies. A series of workshops, conferences, and special issues of journals have developed under this title since 1996. In various countries, the Triple Helix concept has also been used as an operational strategy for regional development and to further the knowledge-based economy. This short r...

  17. KIC 2856960: the impossible triple star

    CERN Document Server

    Marsh, T R; Carter, P J

    2014-01-01

    KIC 2856960 is a star in the Kepler field which was observed by Kepler for 4 years. It shows the primary and secondary eclipses of a close binary of 0.258d as well as complex dipping events that last for about 1.5d at a time and recur on a 204d period. The dips are thought to result when the close binary passes across the face of a third star. In this paper we present an attempt to model the dips. Despite the apparent simplicity of the system and strenuous efforts to find a solution, we find that we cannot match the dips with a triple star while satisfying Kepler's laws. The problem is that to match the dips the separation of the close binary has to be larger than possible relative to the outer orbit given the orbital periods. Quadruple star models can get round this problem but require the addition of a so-far undetected intermediate period of order 5 -- 20d that has be a near-perfect integer divisor of the outer 204d period. Although we have no good explanation for KIC 2856960, using the full set of Kepler ...

  18. Triple Hybrid Energy Harvesting Interface Electronics

    Science.gov (United States)

    Uluşan, H.; Chamanian, S.; Pathirana, W. M. P. R.; Zorlu, Ö.; Muhtaroğlu, A.; Külah, H.

    2016-11-01

    This study presents a novel triple hybrid system that combines simultaneously generated power from thermoelectric (TE), vibration-based electromagnetic (EM) and piezoelectric (PZT) harvesters for a relatively high power supply capability. In the proposed solution each harvesting source utilizes a distinct power management circuit that generates a DC voltage suitable for combining the three parallel supplies. The circuits are designed and implemented in 180 nm standard CMOS technology, and are terminated with a schottky diode to avoid reverse current flow. The harvested AC signal from the EM harvester is rectified with a self-powered AC-DC doubler, which utilizes active diode structures to minimize the forward- bias voltage drop. The PZT interface electronics utilizes a negative voltage converter as the first stage, followed by synchronous power extraction and DC-to-DC conversion through internal switches, and an external inductor. The ultra-low voltage DC power harvested by the TE generator is stepped up through a charge-pump driven by an LC oscillator with fully- integrated center-tapped differential inductors. Test results indicate that hybrid energy harvesting circuit provides more than 1 V output for load resistances higher than 100 kΩ (10 μW) where the stand-alone harvesting circuits are not able to reach 1 V output. This is the first hybrid harvester circuit that simultaneously extracts energy from three independent sources, and delivers a single DC output.

  19. Spectroscopically resolving the Algol triple system

    CERN Document Server

    Kolbas, V; Southworth, J; Lee, C -U; Lee, D -J; Lee, J W; Kim, S -L; Kim, H -I; Smalley, B; Tkachenko, A

    2015-01-01

    Algol ($\\beta$ Persei) is the prototypical semi-detached eclipsing binary and a hierarchical triple system. From 2006 to 2010 we obtained 121 high-resolution and high-S/N \\'{e}chelle spectra of this object. Spectral disentangling yields the individual spectra of all three stars, and greatly improved elements both the inner and outer orbits. We find masses of $M_{\\rm A} = 3.39\\pm0.06$ M$_\\odot$, $M_{\\rm B} = 0.770\\pm0.009$ M$_\\odot$ and $M_{\\rm C} = 1.58\\pm0.09$ M$_\\odot$. The disentangled spectra also give the light ratios between the components in the $B$ and $V$ bands. Atmospheric parameters for the three stars are determined, including detailed elemental abundances for Algol A and Algol C. We find the following effective temperatures: $T_{\\rm A} = 12\\,550\\pm120$ K, $T_{\\rm B} = 4900\\pm300$ K and $T_{\\rm C} = 7550\\pm250$ K. The projected rotational velocities are $v_{\\rm A} \\sin i_{\\rm A} = 50.8\\pm0.8$ km/s, $v_{\\rm B} \\sin i_{\\rm B} = 62\\pm2$ km/s and $v_{\\rm C} \\sin i_{\\rm C} = 12.4\\pm0.6$ km/s. This is t...

  20. Applications of tripled chaotic maps in cryptography

    Energy Technology Data Exchange (ETDEWEB)

    Behnia, S. [Department of Physics, IAU, Urmia (Iran, Islamic Republic of)], E-mail: s.behnia@iaurmia.ac.ir; Akhshani, A. [School of Physics, Universiti Sains Malaysia, 11800 USM, Penang (Malaysia); Akhavan, A. [School of Computer Science, Universiti Sains Malaysia, 11800 USM, Penang (Malaysia); Mahmodi, H. [School of Physics, Universiti Sains Malaysia, 11800 USM, Penang (Malaysia)

    2009-04-15

    Security of information has become a major issue during the last decades. New algorithms based on chaotic maps were suggested for protection of different types of multimedia data, especially digital images and videos in this period. However, many of them fundamentally were flawed by a lack of robustness and security. For getting higher security and higher complexity, in the current paper, we introduce a new kind of symmetric key block cipher algorithm that is based on tripled chaotic maps. In this algorithm, the utilization of two coupling parameters, as well as the increased complexity of the cryptosystem, make a contribution to the development of cryptosystem with higher security. In order to increase the security of the proposed algorithm, the size of key space and the computational complexity of the coupling parameters should be increased as well. Both the theoretical and experimental results state that the proposed algorithm has many capabilities such as acceptable speed and complexity in the algorithm due to the existence of two coupling parameters and high security. Note that the ciphertext has a flat distribution and has the same size as the plaintext. Therefore, it is suitable for practical use in secure communications.

  1. Brown Dwarf Binaries from Disintegrating Triple Systems

    CERN Document Server

    Reipurth, Bo

    2015-01-01

    We have carried out 200,000 N-body simulations of three identical stellar embryos with masses from a Chabrier IMF and embedded in a molecular core. The bodies are initially non-hierarchical and undergo chaotic motions, while accreting using Bondi-Hoyle accretion. The coupling of dynamics and accretion often leads to one or two dominant bodies controlling the center of the cloud core, while banishing the other(s) to the lower-density outskirts, leading to stunted growth. Eventually each system transforms either to a bound hierarchical configuration or breaks apart into separate single and binary components. The orbital motion is followed for 100 Myr. To illustrate the simulations we introduce the 'triple diagnostic diagram', which plots two dimensionless numbers against each other, representing the binary mass ratio and the mass ratio of the third body to the total system mass. Numerous freefloating BD binaries are formed in these simulations. The separation distribution function is in good correspondence with...

  2. Triple jump examinations for dental student assessment.

    Science.gov (United States)

    Navazesh, Mahvash; Rich, Sandra K; Chopiuk, Nasrin Bahari; Keim, Robert G

    2013-10-01

    The triple jump examination (TJE) attempts to assess a higher level of learning with demand for analysis, critical thinking, and resolution of problems presented by written scenarios based on patient care situations. The purpose of this study was to examine the internal consistency, scale reliability, and interrater reliability of the TJE used at the Ostrow School of Dentistry, University of Southern California. On the sample of 2,227 examinations administered by seventy-seven raters across a three-year time period, the Cronbach's coefficient alpha for internal consistency of the overall TJE was found to be good (a=0.869). The internal consistency of the three subscales was found to be acceptable (a=0.731), good (a=0.820), and good (a=0.820). Average and single measures intraclass correlation coefficients (ICC) for scale reliability were significant at p<0.001, indicating strong interrater reliability. There were no statistically significant differences (p≤0.05) in the mean scores assigned on the TJE between rater groups defined by rater experience level with the TJE. A very high level of agreement among rater pairs was also observed. Across the entire three-year study period, with over 19,152 ratings, the seventy-seven raters were in general agreement 99.5 percent of the time and in exact agreement 77.2 percent of the time.

  3. Transformation rules for decomposing heterogeneous data into triples

    Directory of Open Access Journals (Sweden)

    Mrityunjay Singh

    2015-04-01

    Full Text Available In order to fulfill the vision of a dataspace system, it requires a flexible, powerful and versatile data model that is able to represent a highly heterogeneous mix of data such as databases, web pages, XML, deep web, and files. In literature, the triple model was found a suitable candidate for a dataspace system, and able to represent structured, semi-structured and unstructured data into a single model. A triple model is based on the decomposition theory, and represents variety of data into a collection of triples. In this paper, we have proposed a decomposition algorithm for expressing various heterogeneous data models into the triple model. This algorithm is based on the decomposition theory of the triple model. By applying the decomposition algorithm, we have proposed a set of transformation rules for the existing data models. The transformation rules have been categorized for structured, semi-structured, and unstructured data models. These rules are able to decompose most of the existing data models into the triple model. We have empirically verified the algorithm as well as the transformation rules on different data sets having different data models.

  4. A directional nucleation-zipping mechanism for triple helix formation.

    Science.gov (United States)

    Alberti, Patrizia; Arimondo, Paola B; Mergny, Jean-Louis; Garestier, Thérèse; Hélène, Claude; Sun, Jian-Sheng

    2002-12-15

    A detailed kinetic study of triple helix formation was performed by surface plasmon resonance. Three systems were investigated involving 15mer pyrimidine oligonucleotides as third strands. Rate constants and activation energies were validated by comparison with thermodynamic values calculated from UV-melting analysis. Replacement of a T.A base pair by a C.G pair at either the 5' or the 3' end of the target sequence allowed us to assess mismatch effects and to delineate the mechanism of triple helix formation. Our data show that the association rate constant is governed by the sequence of base triplets on the 5' side of the triplex (referred to as the 5' side of the target oligopurine strand) and provides evidence that the reaction pathway for triple helix formation in the pyrimidine motif proceeds from the 5' end to the 3' end of the triplex according to the nucleation-zipping model. It seems that this is a general feature for all triple helices formation, probably due to the right-handedness of the DNA double helix that provides a stronger base stacking at the 5' than at the 3' duplex-triplex junction. Understanding the mechanism of triple helix formation is not only of fundamental interest, but may also help in designing better triple helix-forming oligonucleotides for gene targeting and control of gene expression.

  5. Critical Curves and Caustics of Triple-lens Models

    CERN Document Server

    Danek, Kamil

    2015-01-01

    Among the 25 planetary systems detected up to now by gravitational microlensing, there are two cases of a star with two planets, and two cases of a binary star with a planet. Other, yet undetected types of triple lenses include triple stars or stars with a planet with a moon. The analysis and interpretation of such events is hindered by the lack of understanding of essential characteristics of triple lenses, such as their critical curves and caustics. We present here analytical and numerical methods for mapping the critical-curve topology and caustic cusp number in the parameter space of $n$-point-mass lenses. We apply the methods to the analysis of four symmetric triple-lens models, and obtain altogether 9 different critical-curve topologies and 32 caustic structures. While these results include various generic types, they represent just a subset of all possible triple-lens critical curves and caustics. Using the analyzed models, we demonstrate interesting features of triple lenses that do not occur in two-p...

  6. Hypoxia-targeted triple suicide gene therapy radiosensitizes human colorectal cancer cells

    Science.gov (United States)

    HSIAO, HUNG TSUNG; XING, LIGANG; DENG, XUELONG; SUN, XIAORONG; LING, C. CLIFTON; LI, GLORIA C.

    2014-01-01

    The hypoxic microenvironment, an important feature of human solid tumors but absent in normal tissue, may provide an opportunity for cancer-specific gene therapy. The purpose of the present study was to investigate whether hypoxia-driven triple suicide gene TK/CD/UPRT expression enhances cytotoxicity to ganciclovir (GCV) and 5-fluorocytosine (5-FC), and sensitizes human colorectal cancer to radiation in vitro and in vivo. Stable transfectant of human colorectal HCT8 cells was established which expressed hypoxia-inducible vectors (HRE-TK/eGFP and HRE-CD/UPRT/mDsRed). Hypoxia-induced expression/function of TK, CD and UPRT was verified by western blot analysis, flow cytometry, fluorescent microscopy and cytotoxicity assay of GCV and 5-FC. Significant radiosensitization effects were detected after 5-FC and GCV treatments under hypoxic conditions. In the tumor xenografts, the distribution of TK/eGFP and CD/UPRT/mDsRed expression visualized with fluorescence microscopy was co-localized with the hypoxia marker pimonidazole positive staining cells. Furthermore, administration of 5-FC and GCV in mice in combination with local irradiation resulted in tumor regression, as compared with prodrug or radiation treatments alone. Our data suggest that the hypoxia-inducible TK/GCV+CDUPRT/5-FC triple suicide gene therapy may have the ability to specifically target hypoxic cancer cells and significantly improve the tumor control in combination with radiotherapy. PMID:24912473

  7. 冻干重组人三突变型HIF-1α腺病毒生物学效应考察%Characterization of the biological activities of lyophilized recombinant adenovirus expressing the triple mutant of hypoxia inducible factor-lα

    Institute of Scientific and Technical Information of China (English)

    陶宇; 王月刚; 魏旋; 刘城; 陈冬冬; 吴平生

    2011-01-01

    To investigate the influence of lyophilization on the biological activity of recombinant adenovirus-mediated triple mutant of hypoxia inducible factor-la (Ad-HIF-la-564/402/803). Methods Ad-HIF-la-564/ 402/803 was amplified from HEK293A cells and purified by ultracentrifugation in CsCl gradient solutions. The infection efficiency was observed by X-gal staining. The lyophilized adenovirus was prepared under appropriate conditions. Before and after lyophilization, the effect of Ad-HIF-la-564/402/803 on hMVEC proliferation was evaluated by MTS assay. The recombinant adenovirus was confirmed by PCR and DNA sequence analysis before and 1 day, 6 months and 12 months after lyophilization, and hMVECs infected with Ad-HIF-la-564/402/803 at these time points were examined for HIF-la protein expression using Western blotting. Results No significant changes were observed in the effect of lyophilized Ad-HIF-la-564/402/803 on hMVECs proliferation at the optimal multiplicity of infection of 100 pfu/cell (P>0.05). At the 4 time points, the recombinant adenovirus HIF-la showed no structural alterations or significant changes in the expression level of HIF-la protein in the transfected hMVECs (P>0.05). Conclusion Lyophilized Ad-HIF-la-564/402/803 can maintain its biological activities for a long time.%目的 研究冻干对重组人三突变型HIF-1α病毒(Ad-HIF-1α-564/402/803)生物学效应的影响.方法 将前期构建的Ad-HIF-1α-564/402/803在HEK293A细胞中进行扩增,用氯化铯浓度梯度离心法进行腺病毒纯化,X-Gal染色法测定重组腺病毒转染效率,在适宜的条件下制成冻于剂.采用MTS试剂盒观察冻干前后Ad-HIF-1α-564/402/803对hMvECs增殖的影响.分别在冻干前、冻干后1 d、6月、12月四个时间点提取病毒DNA,进行PCR及PCR产物测序鉴定重组人三突变型HIF-1α腺病毒基因;并在4个时间点以Ad-HIF-1α-564/402/803转染hMVECs,提取蛋白进行western blot检测HIF-1α蛋白的表达.结果 X

  8. Collagenolytic Matrix Metalloproteinase Activities toward Peptomeric Triple-Helical Substrates.

    Science.gov (United States)

    Stawikowski, Maciej J; Stawikowska, Roma; Fields, Gregg B

    2015-05-19

    Although collagenolytic matrix metalloproteinases (MMPs) possess common domain organizations, there are subtle differences in their processing of collagenous triple-helical substrates. In this study, we have incorporated peptoid residues into collagen model triple-helical peptides and examined MMP activities toward these peptomeric chimeras. Several different peptoid residues were incorporated into triple-helical substrates at subsites P3, P1, P1', and P10' individually or in combination, and the effects of the peptoid residues were evaluated on the activities of full-length MMP-1, MMP-8, MMP-13, and MMP-14/MT1-MMP. Most peptomers showed little discrimination between MMPs. However, a peptomer containing N-methyl Gly (sarcosine) in the P1' subsite and N-isobutyl Gly (NLeu) in the P10' subsite was hydrolyzed efficiently only by MMP-13 [nomenclature relative to the α1(I)772-786 sequence]. Cleavage site analysis showed hydrolysis at the Gly-Gln bond, indicating a shifted binding of the triple helix compared to the parent sequence. Favorable hydrolysis by MMP-13 was not due to sequence specificity or instability of the substrate triple helix but rather was based on the specific interactions of the P7' peptoid residue with the MMP-13 hemopexin-like domain. A fluorescence resonance energy transfer triple-helical peptomer was constructed and found to be readily processed by MMP-13, not cleaved by MMP-1 and MMP-8, and weakly hydrolyzed by MT1-MMP. The influence of the triple-helical structure containing peptoid residues on the interaction between MMP subsites and individual substrate residues may provide additional information about the mechanism of collagenolysis, the understanding of collagen specificity, and the design of selective MMP probes.

  9. Polyproline and triple helix motifs in host-pathogen recognition.

    Science.gov (United States)

    Berisio, Rita; Vitagliano, Luigi

    2012-12-01

    Secondary structure elements often mediate protein-protein interactions. Despite their low abundance in folded proteins, polyproline II (PPII) and its variant, the triple helix, are frequently involved in protein-protein interactions, likely due to their peculiar propensity to be solvent-exposed. We here review the role of PPII and triple helix in mediating hostpathogen interactions, with a particular emphasis to the structural aspects of these processes. After a brief description of the basic structural features of these elements, examples of host-pathogen interactions involving these motifs are illustrated. Literature data suggest that the role played by PPII motif in these processes is twofold. Indeed, PPII regions may directly mediate interactions between proteins of the host and the pathogen. Alternatively, PPII may act as structural spacers needed for the correct positioning of the elements needed for adhesion and infectivity. Recent investigations have highlighted that collagen triple helix is also a common target for bacterial adhesins. Although structural data on complexes between adhesins and collagen models are rather limited, experimental and theoretical studies have unveiled some interesting clues of the recognition process. Interestingly, very recent data show that not only is the triple helix used by pathogens as a target in the host-pathogen interaction but it may also act as a bait in these processes since bacterial proteins containing triple helix regions have been shown to interact with host proteins. As both PPII and triple helix expose several main chain non-satisfied hydrogen bond acceptors and donors, both elements are highly solvated. The preservation of the solvation state of both PPII and triple helix upon protein-protein interaction is an emerging aspect that will be here thoroughly discussed.

  10. TMEPAI genome editing in triple negative breast cancer cells

    Directory of Open Access Journals (Sweden)

    Bantari W.K. Wardhani

    2017-05-01

    Full Text Available Background: Clustered regularly interspaced short palindromic repeats/CRISPR-associated 9 (CRISPR/Cas9 is a powerful genome editing technique. It consists of RNA-guided DNA endonuclease Cas9 and single guide RNA (gRNA. By combining their expressions, high efficiency cleavage of the target gene can be achieved, leading to the formation of DNA double-strand break (DSB at the genomic locus of interest which will be repaired via NHEJ (non-homologous end joining or HDR (homology-directed repair and mediate DNA alteration. We aimed to apply the CRISPR/Cas9 technique to knock-out the transmembrane prostate androgen-induced protein (TMEPAI gene in the triple negative breast cancer cell line.Methods: Designed gRNA which targets the TMEPAI gene was synthesized, annealed, and cloned into gRNA expression vector. It was co-transfected into the TNBC cell line using polyethylenimine (PEI together with Cas9-GFP and puromycin resistant gene vector. At 24-hours post-transfection, cells were selected by puromycin for 3 days before they were cloned. Selected knock-out clones were subsequently checked on their protein levels by western blotting.Results: CRISPR/Cas9, a genome engineering technique successfully knocked-out TMEPAI in the Hs578T TNBC cell line. Sequencing shows a frameshift mutation in TMEPAI. Western blot shows the absence of TMEPAI band on Hs578T KO cells.Conclusion: TMEPAI gene was deleted in the TNBC cell line using the genomic editing technique CRISPR/Cas9. The deletion was confirmed by genome and protein analysis.

  11. Aromatic interactions promote self-association of collagen triple-helical peptides to higher-order structures.

    Science.gov (United States)

    Kar, Karunakar; Ibrar, Sajjad; Nanda, Vikas; Getz, Todd M; Kunapuli, Satya P; Brodsky, Barbara

    2009-08-25

    Aromatic residues are relatively rare within the collagen triple helix, but they appear to play a specialized role in higher-order structure and function. The role of aromatic amino acids in the self-assembly of triple-helical peptides was investigated in terms of the kinetics of self-association, the nature of aggregated species formed, and the ability of these species to activate platelet aggregation. The presence of aromatic residues on both ends of a type IV collagen model peptide is observed to greatly accelerate the kinetics of self-association, decreasing the lag time and leading to insoluble, well-defined linear fibrils as well as small soluble aggregates. Both macroscopic visible aggregates and small multimolecular complexes in solution are capable of inducing platelet aggregation through the glycoprotein VI receptor on platelets. Proline-aromatic CH...pi interactions are often observed within globular proteins and in protein complexes, and examination of molecular packing in the crystal structure of the integrin binding collagen peptide shows Phe interacts with Pro/Hyp in a neighboring triple-helical molecule. An intermolecular interaction between aromatic amino acids and imino acids within the triple helix is also supported by the observed inhibitory effect of isolated Phe amino acids on the self-association of (Pro-Hyp-Gly)(10). Given the high fraction of Pro and Hyp residues on the surface of collagen molecules, it is likely that imino acid-aromatic CH...pi interactions are important in formation of higher-order structure. We suggest that the catalysis of type I collagen fibrillogenesis by nonhelical telopeptides is due to specific intermolecular CH...pi interactions between aromatic residues in the telopeptides and Pro/Hyp residues within the triple helix.

  12. Ocular Problems in Triple-A Syndrome and Their Management

    Directory of Open Access Journals (Sweden)

    Seydi Okumuş

    2012-12-01

    Full Text Available Triple-A syndrome (Allgrove syndrome, is a rare autosomal recessive syndrome that is characterized by adrenal insufficiency, alacrimia and achalasia. In this report, we present a case of triple-A syndrome and discuss the ocular manifestations of the diseases along with evaluation of the therapeutic options. In addition to the classic triad of triple-A syndrome, our patient had intermittent exotropia. The patient was receiving oral steroids for adrenal insufficiency and artificial tear drops for eye dryness. Surgery was planned for exotropia. Punctum plug insertion was made simultaneously with bilateral lateral rectus recessions. Postoperative follow-up revealed near and distant horizontal deviation at the interval of ±10 PD. The patient’s complaints about eyes regressed significantly as well. Triple-A syndrome is a life threatening and rare disorder that could be fatal when undiagnosed. Punctum plugs are convenient therapy option for the treatment of xerophthalmia encountered in triple-A syndrome. With strabismus surgery including punctum plug insertion, any other surgery can be simultaneously carried out during a single session of general anesthesia. (Turk J Ophthalmol 2012; 42: 492-4

  13. Collagen model peptides: Sequence dependence of triple-helix stability.

    Science.gov (United States)

    Persikov, A V; Ramshaw, J A; Brodsky, B

    2000-01-01

    The triple helix is a specialized protein motif, found in all collagens as well as in noncollagenous proteins involved in host defense. Peptides will adopt a triple-helical conformation if the sequence contains its characteristic features of Gly as every third residue and a high content of Pro and Hyp residues. Such model peptides have proved amenable to structural studies by x-ray crystallography and NMR spectroscopy, suitable for thermodynamic and kinetic analysis, and a valuable tool in characterizing the binding activities of the collagen triple helix. A systematic approach to understanding the amino acid sequence dependence of the collagen triple helix has been initiated, based on a set of host-guest peptides of the form, (Gly-Pro-Hyp)(3)-Gly-X-Y-(Gly-Pro-Hyp)(4). Comparison of their thermal stabilities has led to a propensity scale for the X and Y positions, and the additivity of contributions of individual residues is now under investigation. The local and global stability of the collagen triple helix is normally modulated by the residues in the X and Y positions, with every third position occupied by Gly in fibril-forming collagens. However, in collagen diseases, such as osteogenesis imperfecta, a single Gly may be substituted by another residue. Host-guest studies where the Gly is replaced by various amino acids suggest that the identity of the residue in the Gly position affects the degree of destabilization and the clinical severity of the disease.

  14. Glycine Substitutions in Collagen Heterotrimers Alter Triple Helical Assembly.

    Science.gov (United States)

    Clements, Katherine A; Acevedo-Jake, Amanda M; Walker, Douglas R; Hartgerink, Jeffrey D

    2017-02-13

    Osteogenesis imperfecta typically results from missense mutations in the collagen genome where the required glycine residues are replaced with another amino acid. Many models have attempted to replicate the structure of mutated collagen on the triple helix level. However, composition and register control of the triple helix is complicated and requires extreme precision, especially when these destabilizing mutations are present. Here we present mutations to a composition- and register-controlled AAB helix where one of the requisite glycines in the A chain of the triple helix is changed to serine or alanine. We see a loss of compositional control when the A chain is mutated, resulting in an A'BB composition that minimizes the number of mutations included in the triple helix. However, when both A and B chains are mutated and no nonmutated peptide chains are available, the designed A'A'B' composition is reestablished. Our work shows the ability of the mutations to influence and alter the composition and register of the collagen triple helix.

  15. Longitudinal Neuropsychological Profile in a Patient with Triple A Syndrome

    Directory of Open Access Journals (Sweden)

    Luigi Mazzone

    2013-01-01

    Full Text Available Triple A syndrome is an autosomal recessive disorder characterized by the triad of adrenocorticotropic hormone resistant adrenal insufficiency, achalasia, and alacrima. Our aim was to describe the neuropsychological characteristics and the cooccurring psychopathological and neurological disorders in an Italian male child suffering from Triple A syndrome at the time of admission (T0 and after one year of follow-up (T1. Many difficulties were observed in the motor domain, as well as in manual dexterity and static/dynamic balance domains of the motor task over time. In sharp contrast with previous literature reports on frequent mild cognitive dysfunction in patients with Triple A syndrome, our child did not show any mental retardation. By contrast, he showed an average IQ at T0 with a slight improvement at T1. To our knowledge, this report is the first describing neuropsychological profile and co-occurring psychopathological problems in a child with Triple A syndrome. Considering that the Triple A syndrome is a progressive disorder which can take years to develop the full-blown clinical picture, these patients require periodical medical controls. Moreover, assessment of neuropsychological and psychopathological features should be performed in patients with this disease, in order to underline the variability of this syndrome.

  16. The CALBC RDF Triple Store: retrieval over large literature content

    CERN Document Server

    Croset, Samuel; Li, Chen; Kavaliauskas, Silvestras; Rebholz-Schuhmann, Dietrich

    2010-01-01

    Integration of the scientific literature into a biomedical research infrastructure requires the processing of the literature, identification of the contained named entities (NEs) and concepts, and to represent the content in a standardised way. The CALBC project partners (PPs) have produced a large-scale annotated biomedical corpus with four different semantic groups through the harmonisation of annotations from automatic text mining solutions (Silver Standard Corpus, SSC). The four semantic groups were chemical entities and drugs (CHED), genes and proteins (PRGE), diseases and disorders (DISO) and species (SPE). The content of the SSC has been fully integrated into RDF Triple Store (4,568,678 triples) and has been aligned with content from the GeneAtlas (182,840 triples), UniProtKb (12,552,239 triples for human) and the lexical resource LexEBI (BioLexicon). RDF Triple Store enables querying the scientific literature and bioinformatics resources at the same time for evidence of genetic causes, such as drug ta...

  17. Development of 600 kV triple resonance pulse transformer.

    Science.gov (United States)

    Li, Mingjia; Zhang, Faqiang; Liang, Chuan; Xu, Zhou

    2015-06-01

    In this paper, a triple-resonance pulse transformer based on an air-core transformer is introduced. The voltage across the high-voltage winding of the air-core transformer is significantly less than the output voltage; instead, the full output voltage appears across the tuning inductor. The maximum ratio of peak load voltage to peak transformer voltage is 2.77 in theory. By analyzing pulse transformer's lossless circuit, the analytical expression for the output voltage and the characteristic equation of the triple-resonance circuit are presented. Design method for the triple-resonance pulse transformer (iterated simulation method) is presented, and a triple-resonance pulse transformer is developed based on the existing air-core transformer. The experimental results indicate that the maximum ratio of peak voltage across the load to peak voltage across the high-voltage winding of the air-core transformer is approximately 2.0 and the peak output voltage of the triple-resonance pulse transformer is approximately 600 kV.

  18. Environmental scanning electron microscopy study of the fine structure of the triple line and cassie-wenzel wetting transition for sessile drops deposited on rough polymer substrates.

    Science.gov (United States)

    Bormashenko, Edward; Bormashenko, Yelena; Stein, Tamir; Whyman, Gene; Pogreb, Roman; Barkay, Zahava

    2007-04-10

    The wetting of rough honeycomb micrometrically scaled polymer substrates was studied. A very strong dependence of the apparent contact angle on the drop volume has been established experimentally. The environmental scanning electron microscopy study of the fine structure of the triple line is reported first. The triple line is not smooth and prefers grasping the polymer matrix over air holes. The precursor rim surrounding the drop has been observed. The revealed dependence of the apparent contact angle on the drop volume is explained by the transition between the pure Cassie and combined Wenzel-Cassie wetting regimes, which is induced by capillarity penetration of water into the holes of relief.

  19. AAA-DDD triple hydrogen bond complexes.

    Science.gov (United States)

    Blight, Barry A; Camara-Campos, Amaya; Djurdjevic, Smilja; Kaller, Martin; Leigh, David A; McMillan, Fiona M; McNab, Hamish; Slawin, Alexandra M Z

    2009-10-01

    Experiment and theory both suggest that the AAA-DDD pattern of hydrogen bond acceptors (A) and donors (D) is the arrangement of three contiguous hydrogen bonding centers that results in the strongest association between two species. Murray and Zimmerman prepared the first example of such a system (complex 3*2) and determined the lower limit of its association constant (K(a)) in CDCl(3) to be 10(5) M(-1) by (1)H NMR spectroscopy (Murray, T. J. and Zimmerman, S. C. J. Am. Chem. Soc. 1992, 114, 4010-4011). The first cationic AAA-DDD pair (3*4(+)) was described by Bell and Anslyn (Bell, D. A. and Anslyn, E. A. Tetrahedron 1995, 51, 7161-7172), with a K(a) > 5 x 10(5) M(-1) in CH(2)Cl(2) as determined by UV-vis spectroscopy. We were recently able to quantify the strength of a neutral AAA-DDD arrangement using a more chemically stable AAA-DDD system, 6*2, which has an association constant of 2 x 10(7) M(-1) in CH(2)Cl(2) (Djurdjevic, S., Leigh, D. A., McNab, H., Parsons, S., Teobaldi, G. and Zerbetto, F. J. Am. Chem. Soc. 2007, 129, 476-477). Here we report on further AA(A) and DDD partners, together with the first precise measurement of the association constant of a cationic AAA-DDD species. Complex 6*10(+)[B(3,5-(CF(3))(2)C(6)H(3))(4)(-)] has a K(a) = 3 x 10(10) M(-1) at RT in CH(2)Cl(2), by far the most strongly bound triple hydrogen bonded system measured to date. The X-ray crystal structure of 6*10(+) with a BPh(4)(-) counteranion shows a planar array of three short (NH...N distances 1.95-2.15 A), parallel (but staggered rather than strictly linear; N-H...N angles 165.4-168.8 degrees), primary hydrogen bonds. These are apparently reinforced, as theory predicts, by close electrostatic interactions (NH-*-N distances 2.78-3.29 A) between each proton and the acceptor atoms of the adjacent primary hydrogen bonds.

  20. On the Interface Formation Model for Dynamic Triple Lines

    CERN Document Server

    Bothe, Dieter

    2015-01-01

    This paper revisits the theory of Y. Shikhmurzaev on forming interfaces as a continuum thermodynamical model for dynamic triple lines. We start with the derivation of the balances for mass, momentum, energy and entropy in a three-phase fluid system with full interfacial physics, including a brief review of the relevant transport theorems on interfaces and triple lines. Employing the entropy principle in the form given in [Bothe & Dreyer, Acta Mechanica, doi:10.1007/s00707-014-1275-1] but extended to this more general case, we arrive at the entropy production and perform a linear closure, except for a nonlinear closure for the sorption processes. Specialized to the isothermal case, we obtain a thermodynamically consistent mathematical model for dynamic triple lines and show that the total available energy is a strict Lyapunov function for this system.

  1. Triple inhaled therapy for chronic obstructive pulmonary disease.

    Science.gov (United States)

    Montuschi, Paolo; Malerba, Mario; Macis, Giuseppe; Mores, Nadia; Santini, Giuseppe

    2016-11-01

    Combining individual drugs in a single inhaler is the most convenient way to deliver triple therapy. A long-acting muscarinic receptor antagonist (LAMA) added to an inhaled corticosteroid (ICS)/long-acting β2-adrenoceptor agonist (LABA) fixed-dose combination (FDC) can improve efficacy of pharmacological treatment of patients with chronic obstructive pulmonary disease (COPD). New inhaled ICS/LABA/LAMA FDCs, including fluticasone furoate/vilanterol/umeclidinium, budesonide/formoterol/glycopyrronium and beclometasone/formoterol/glycopyrronium, are in Phase III of clinical development for COPD. Triple inhaled therapy might be particularly useful in patients with severe to very severe COPD, above all in those with peripheral blood or sputum eosinophilia, asthma-COPD overlap syndrome (ACOS) or frequent exacerbators. Future prospective studies should assess efficacy and safety of triple ICS/LABA/LAMA therapy in selected COPD phenotypes.

  2. On universality of scaling law describing roughness of triple line.

    Science.gov (United States)

    Bormashenko, Edward; Musin, Albina; Whyman, Gene; Barkay, Zahava; Zinigrad, Michael

    2015-01-01

    The fine structure of the three-phase (triple) line was studied for different liquids, various topographies of micro-rough substrates and various wetting regimes. Wetting of porous and pillar-based micro-scaled polymer surfaces was investigated. The triple line was visualized with the environmental scanning electron microscope and scanning electron microscope for the "frozen" triple lines. The value of the roughness exponent ζ for water (ice)/rough polymer systems was located within 0.55-0.63. For epoxy glue/rough polymer systems somewhat lower values of the exponent, 0.42 switch of the exponent, when the roughness size approaches to the correlation length of the defects, is also universal.

  3. The Algol triple system spatially resolved at optical wavelengths

    CERN Document Server

    Zavala, R T; Boboltz, D A; Ojha, R; Shaffer, D B; Tycner, C; Richards, M T; Hutter, D J; 10.1088/2041-8205/715/1/L44

    2010-01-01

    Interacting binaries typically have separations in the milli-arcsecond regime and hence it has been challenging to resolve them at any wavelength. However, recent advances in optical interferometry have improved our ability to discern the components in these systems and have now enabled the direct determination of physical parameters. We used the Navy Prototype Optical Interferometer to produce for the first time images resolving all three components in the well-known Algol triple system. Specifically, we have separated the tertiary component from the binary and simultaneously resolved the eclipsing binary pair, which represents the nearest and brightest eclipsing binary in the sky. We present revised orbital elements for the triple system, and we have rectified the 180-degree ambiguity in the position angle of Algol C. Our directly determined magnitude differences and masses for this triple star system are consistent with earlier light curve modeling results.

  4. Pulsed electron-nuclear-electron triple resonance spectroscopy

    Science.gov (United States)

    Thomann, Hans; Bernardo, Marcelino

    1990-05-01

    A new experimental technique, pulsed electron-nuclear-electron triple resonance spectroscopy, is demonstrated. It is based on a modification of the pulse sequence for electron-nuclear double resonance (ENDOR) in which two EPR and one NMR transition are irradiated. The irradiation of one EPR transition is detected via a second EPR transition. The nuclear hyperfine coupling, which separates these EPR transition frequencies, is the irradiated NMR transition. The major advantages of triple resonance spectroscopy include the ability to resolve overlapping nuclear resonances in the ENDOR spectrum and a more direct quantitative assignment of nuclear hyperfine and quadrupole couplings. The triple resonance experiment is an alternative to the recently proposed method of employing rapid magnetic field jumps between microwave pulses for generating hyperfine selective ENDOR spectra.

  5. Optical frequency tripling with improved suppression and sideband selection.

    Science.gov (United States)

    Thakur, Manoj P; Medeiros, Maria C R; Laurêncio, Paula; Mitchell, John E

    2011-12-12

    A novel optical dispersion tolerant millimetre-wave radio-over-fibre system using optical frequency tripling technique with enhanced and selectable sideband suppression is demonstrated. The implementation utilises cascaded optical modulators to achieve either an optical single sideband (OSSB) or double sideband-suppressed carrier (DSB-SC) signal with high sideband suppression. Our analysis and simulation results indicate that the achievable suppression ratio of this configuration is only limited by other system factors such as optical noise and drifting of the operational conditions. The OSSB transmission system performance is assessed experimentally by the transport of 4 WiMax channels modulating a 10 GHz optical upconverted RF carrier as well as for optical frequency doubling and tripling. The 10 GHz and tripled carrier at 30 GHz are dispersion tolerant resulting both in an average relative constellation error (RCE) of -28.7 dB after 40 km of fibre.

  6. The Knowledge-Based Economy and the Triple Helix Model

    CERN Document Server

    Leydesdorff, Loet

    2012-01-01

    1. Introduction - the metaphor of a "knowledge-based economy"; 2. The Triple Helix as a model of the knowledge-based economy; 3. Knowledge as a social coordination mechanism; 4. Neo-evolutionary dynamics in a Triple Helix of coordination mechanism; 5. The operation of the knowledge base; 6. The restructuring of knowledge production in a KBE; 7. The KBE and the systems-of-innovation approach; 8. The KBE and neo-evolutionary theories of innovation; 8.1 The construction of the evolving unit; 8.2 User-producer relations in systems of innovation; 8.3 'Mode-2' and the production of scientific knowledge; 8.4 A Triple Helix model of innovations; 9. Empirical studies and simulations using the TH model; 10. The KBE and the measurement; 10.1 The communication of meaning and information; 10.2 The expectation of social structure; 10.3 Configurations in a knowledge-based economy

  7. Potential of collagen-like triple helical peptides as drug carriers: Their in vivo distribution, metabolism, and excretion profiles in rodents.

    Science.gov (United States)

    Yasui, Hiroyuki; Yamazaki, Chisato M; Nose, Hiroshi; Awada, Chihiro; Takao, Toshifumi; Koide, Takaki

    2013-11-01

    Collagen-model peptides composed of (X-Y-Gly)n sequences were used to study the triple helical structure of collagen. We report the stability of these collagen-like peptides in biological fluids, and their pharmacokinetics including distribution, metabolism, and excretion in animals. A typical collagen-model peptide, H-(Pro-Hyp-Gly)10-OH, was found to be extremely stable in the plasma and distributed mainly in the vascular blood space, and was eliminated through glomerular filtration in the kidneys. Triple helical peptides of (X-Y-Gly)n sequences were quantitatively recovered from the urine of rats after intravenous injection regardless of the differences in peptide net charge between -3 and +6 per triple helix. In contrast, the renal clearance became less efficient when the number of triplet repeats (n) was 12 or more. We also demonstrated the application of a collagen-like triple helical peptide as a novel drug carrier in the blood with a high urinary excretion profile. We further demonstrated that a collagen-like triple helical peptide conjugated to a spin probe, PROXYL, has the potential to evaluate the redox status of oxidative stress-induced animals in vivo.

  8. The evolution of hierarchical triple star-systems

    Science.gov (United States)

    Toonen, Silvia; Hamers, Adrian; Portegies Zwart, Simon

    2016-12-01

    Field stars are frequently formed in pairs, and many of these binaries are part of triples or even higher-order systems. Even though, the principles of single stellar evolution and binary evolution, have been accepted for a long time, the long-term evolution of stellar triples is poorly understood. The presence of a third star in an orbit around a binary system can significantly alter the evolution of those stars and the binary system. The rich dynamical behaviour in three-body systems can give rise to Lidov-Kozai cycles, in which the eccentricity of the inner orbit and the inclination between the inner and outer orbit vary periodically. In turn, this can lead to an enhancement of tidal effects (tidal friction), gravitational-wave emission and stellar interactions such as mass transfer and collisions. The lack of a self-consistent treatment of triple evolution, including both three-body dynamics as well as stellar evolution, hinders the systematic study and general understanding of the long-term evolution of triple systems. In this paper, we aim to address some of these hiatus, by discussing the dominant physical processes of hierarchical triple evolution, and presenting heuristic recipes for these processes. To improve our understanding on hierarchical stellar triples, these descriptions are implemented in a public source code TrES, which combines three-body dynamics (based on the secular approach) with stellar evolution and their mutual influences. Note that modelling through a phase of stable mass transfer in an eccentric orbit is currently not implemented in TrES, but can be implemented with the appropriate methodology at a later stage.

  9. Critical Curves and Caustics of Triple-lens Models

    Science.gov (United States)

    Daněk, Kamil; Heyrovský, David

    2015-06-01

    Among the 25 planetary systems detected up to now by gravitational microlensing, there are two cases of a star with two planets, and two cases of a binary star with a planet. Other, yet undetected types of triple lenses include triple stars or stars with a planet with a moon. The analysis and interpretation of such events is hindered by the lack of understanding of essential characteristics of triple lenses, such as their critical curves and caustics. We present here analytical and numerical methods for mapping the critical-curve topology and caustic cusp number in the parameter space of n-point-mass lenses. We apply the methods to the analysis of four symmetric triple-lens models, and obtain altogether 9 different critical-curve topologies and 32 caustic structures. While these results include various generic types, they represent just a subset of all possible triple-lens critical curves and caustics. Using the analyzed models, we demonstrate interesting features of triple lenses that do not occur in two-point-mass lenses. We show an example of a lens that cannot be described by the Chang-Refsdal model in the wide limit. In the close limit we demonstrate unusual structures of primary and secondary caustic loops, and explain the conditions for their occurrence. In the planetary limit we find that the presence of a planet may lead to a whole sequence of additional caustic metamorphoses. We show that a pair of planets may change the structure of the primary caustic even when placed far from their resonant position at the Einstein radius.

  10. Arctigenin inhibits STAT3 and exhibits anticancer potential in human triple-negative breast cancer therapy.

    Science.gov (United States)

    Feng, Tingting; Cao, Wei; Shen, Wanxiang; Zhang, Liang; Gu, Xinsheng; Guo, Yang; Tsai, Hsiang-I; Liu, Xuewen; Li, Jian; Zhang, Jingxuan; Li, Shan; Wu, Fuyun; Liu, Ying

    2017-01-03

    Triple-negative breast cancers (TNBCs) are the most aggressive and hard-to-treat breast tumors with poor prognosis, and exploration for novel therapeutic drugs is impending. Arctigenin (Atn), a bioactive lignan isolated from seeds of Arctium lappa L, has been reported to inhibit many cancer types; however, the effect of Atn on TNBC remains unclear. In this study, we demonstrated that Atn decreased proliferation, and induced apoptosis in TNBC cells. Furthermore, we explored the underlying mechanism of Atn inhibition on TNBC cells. Computational docking and affinity assay showed that Atn bound to the SH2 domain of STAT3. Atn inhibited STAT3 binding to genomic DNA by disrupting hydrogen bond linking between DNA and STAT3. In addition, Atn augmented Taxotere®-induced TNBC cell cytotoxicity. TNBC xenograft tests also confirmed the antitumor effect of Atn in vivo. These characteristics render Atn as a promising candidate drug for further development and for designing new effective STAT3 inhibitors.

  11. A Remark on Gelfand Duality for Spectral Triples

    CERN Document Server

    Bertozzini, Paolo; Lewkeeratiyutkul, Wicharn

    2008-01-01

    We present a duality between the category of compact Riemannian spin manifolds (equipped with a given spin bundle and charge conjugation) with isometries as morphisms and a suitable "metric" category of spectral triples over commutative pre-C*-algebras. We also construct an embedding of a "quotient" of the category of spectral triples introduced in arXiv:math/0502583v1 into the latter metric category. Finally we discuss a further related duality in the case of orientation and spin-preserving maps between manifolds of fixed dimension.

  12. Non-resonant triple alpha reaction rate at low temperature

    Energy Technology Data Exchange (ETDEWEB)

    Itoh, T.; Tamii, A.; Aoi, N.; Fujita, H.; Hashimoto, T.; Miki, K.; Ogata, K. [Research Center for Nuclear Physics, Osaka University, Ibaraki, Osaka 567-0047 (Japan); Carter, J.; Donaldson, L.; Sideras-Haddad, E. [Schools of Physics, University of Witwatersrand, Johannesburg 2050 (South Africa); Furuno, T.; Kawabata, T. [Departments of Physics, Kyoto University, Sakyo, Kyoto, 606-8502 (Japan); Kamimura, M. [RIKEN Nishina Center, Wako, Saitama, 351-0198 (Japan); Nemulodi, F.; Neveling, R.; Smit, F. D.; Swarts, C. [iThemba Laboratory for Accelerator Based Sciences Somerset, West, 7129 (South Africa)

    2014-05-02

    Our experimental goal is to study the non-resonant triple alpha reaction rate at low temperture (T < 10{sup 8} K). The {sup 13}C(p,d) reaction at 66 MeV has been used to probe the alpha-unbound continuum state in {sup 12}C just below the 2{sup nd} 0{sup +} state at 7.65 MeV. The transition strength to the continuum state is predicted to be sensitive to the non-resonant triple alpha reaction rate. The experiment has been performed at iThemba LABS. We report the present status of the experiment.

  13. Triple pelvic osteotomy in the treatment of hip dysplasia

    Directory of Open Access Journals (Sweden)

    Vukašinović Zoran

    2009-01-01

    Full Text Available Introduction. Insufficient femoral head coverage is found in a variety of diseases, with acetabular dysplasia as the most frequent disorder and triple pelvic osteotomy as the most recently introduced surgical treatment. Objective. This study analyses pre- and postoperative pathoanatomic characteristics of triple in comparison to Salter and Chiari osteotomies, with a logistic regression analysis of outcome predictor and effect explanator factors in relation to the chosen type of operation. Methods. The study involved 136 adolescents treated with Salter and Chiari osteotomies or a triple pelvic osteotomy at the Institute of Orthopaedic Surgery 'Banjica' in Belgrade. The patients were between 10-20 years old at the time of operation. We collected and analyzed data from all the patients: illness history, operative parameters, preoperative and postoperative pathoanatomic data. The data was statistically processed using the statistical software SPSS, defining standard descriptive values, and by using the appropriate tests of analytic statistics: t-test for dependent and independent variables, χ2-test, Fisher's exact test, Wilcoxon's test, parameter correlation, one-way ANOVA, multi-factorial ANOVA and logistic regression, according to the type of the analyzed data and the conditions under which the statistical methods were applied. Results. The average CE angle after triple pelvic osteotomy was 43.5°, more improved than after the Salter osteotomy (33.0° and Chiari osteotomy (31.4° (F=16.822; p<0.01. Postoperative spherical congruence was also more frequent after the triple osteotomy than after the other two types of operations, and with a high significance. Preoperative painful discomfort was found to be a valid predictor of indications for the triple osteotomy over both Chiari and Salter osteotomies. The valid explanators of effect for the triple osteotomy are: postoperative joint congruence (compared to the Chiari osteotomy and increase in joint

  14. On Pythagoras' theorem for products of spectral triples

    CERN Document Server

    D'Andrea, Francesco

    2012-01-01

    We discuss a version of Pythagoras' theorem in noncommutative geometry. Starting from a formulation of the theorem in terms of Connes' distance, between pure states, in the product of commutative spectral triples, we show that for non-pure states it is replaced by some Pythagoras inequalities. We prove the latter in full generality, that is for the product of arbitrary (i.e. non-necessarily commutative) unital spectral triples. Moreover we show that the inequalities are optimal, and provide non-unital counter-examples inspired by K-homology.

  15. Studying the triple - α reaction in hyperspherical harmonic approach

    Science.gov (United States)

    Nguyen, Ngoc; Nunes, Filomena

    2010-11-01

    The triple-α reaction is studied by using hyperspherical harmonic (HH) method [1]. Starting from three body model, we determine the 2^+ state and the 0^+ resonance as well as the quadrupole strength function B(E2). The triple-α reaction rate are calculated. We also carefully consider the contributions of the nonresonant continuum states to the reaction rate at low temperature (T Ogata, M.Kan, M.Kamimura, Prog. Theor. Phys. 122, 1055 (2009).[0pt] [3] R. de Diego, E. Garrido, D.V. Fedorov, A.S. Jensen, arXiv:1005.5647v1.

  16. Triple-mode squeezing with dressed six-wave mixing.

    Science.gov (United States)

    Wen, Feng; Li, Zepei; Zhang, Yiqi; Gao, Hong; Che, Junling; Che, Junling; Abdulkhaleq, Hasan; Zhang, Yanpeng; Wang, Hongxing

    2016-05-12

    The theory of proof-of-principle triple-mode squeezing is proposed via spontaneous parametric six-wave mixing process in an atomic-cavity coupled system. Special attention is focused on the role of dressed state and nonlinear gain on triple-mode squeezing process. Using the dressed state theory, we find that optical squeezing and Autler-Towns splitting of cavity mode can be realized with nonlinear gain, while the efficiency and the location of maximum squeezing point can be effectively shaped by dressed state in atomic ensemble. Our proposal can find applications in multi-channel communication and multi-channel quantum imaging.

  17. Spectral triples and differential calculi related to the Kronecker foliation

    Science.gov (United States)

    Matthes, R.; Richter, O.; Rudolph, G.

    2003-04-01

    Following the ideas of Connes and Moscovici, we describe two spectral triples related to the Kronecker foliation, whose generalized Dirac operators are related to first and second order signature operators. We also consider the corresponding differential calculi Ω D, which are drastically different in the two cases. For the second order signature operator we calculate the Chern character of the spectral triple and the Dixmier trace of certain powers of its Dirac operator. As a side-remark, we give a description of a known calculus on the two-dimensional noncommutative torus in terms of generators and relations.

  18. Fast response of the optical nonlinearity in a GaAs/AlGaAs asymmetric triple quantum well structure

    CERN Document Server

    Ahn, S H; Sawaki, N

    1999-01-01

    The time response of the optical nonlinear behavior in a GaAs/AlGaAs asymmetric triple quantum well structure is estimated by using a picosecond pump-probe method at 77 K. From the results of the transmission of the probe pulse as a function of the delay time at the excitation wavelengths, a rise time of 5 approx 10 ps and a fall time of 8 approx 16 ps are obtained. The nonlinear behavior is attributed to the triple resonance of the electronic states due to the build-up of the internal field induced by the separation of photo-excited electrons and holes. It is found that the rise time is determined by the tunneling transfer time of the electrons in the narrowest well to an adjacent well separated by a thin potential barrier.

  19. Quaternary Evolution of Karliova Triple Junction

    Science.gov (United States)

    Sançar, Taylan; Zabcı, Cengiz; Akyüz, H. Serdar

    2013-04-01

    The arguments to explain Quaternary evolution of Karlıova Triple Junction (KTJ) depends upon two different analogue models. The compressional type of Prandtl Cell Model (PCM) and 60 km wide shear zone with concomitant counter clockwise block rotation used to modelled for west and east of the KTJ respectively. The data for the model of west of the KTJ acquired by extensive field studies, and quantified geomorphic features. Compressional PCM put forward that behavior of slip lines controlled by boundary faults. But the model is not enough to explain slip distribution, age relation of them. At west of the KTJ boundary faults presented by eastern most segments of the North Anatolian Fault Zone (NAFZ) and the East Anatolian Fault Zone (EAFZ). Slip lines, however, presented by Bahçeli and Toklular faults. Both field studies and morphometric analyses undisputedly set forth that there are two different fault types between the NAFZ and EAFZ. The most strain loaded fault type, which are positioned near the NAFZ, start as a strike-slip fault and when it turn to SE its sense of motion change to oblique normal due to changing orientation of principal stress axes. The new orientation of stress axes exposed in the field as a special kind of caprock -cuesta-. The younger slip lines formed very close to junction point and accommodate less slip. Even though slip trajectories started from the boundary faults in compressional PCM, at the west of KTJ, right lateral trajectories more clearly formed close the NAFZ and left lateral trajectories, relatively less strain loaded fault type, are poorly formed close the EAFZ . We think that, this differences between KTJ and compressional PCM result from the distinction of velocity of boundary faults. East of the KTJ governed by completely different mechanism. The region controlled two main fault systems. The Varto Fault Zone (VFZ), the eastern branch of the KTJ, and Murat Fault (MF) delimited the region from north and south respectively. The

  20. Platinum complexes having redox-active PPh2C[triple bond]CFc and/or C[triple bond]CFc as terminal or bridging ligands.

    Science.gov (United States)

    Díez, Alvaro; Lalinde, Elena; Teresa Moreno, M; Sánchez, Sergio

    2009-05-14

    A series of heteronuclear-Pt(ii) complexes containing ferrocenylethynyl units linked directly (Pt-C[triple bond]CFc) or through a phosphorous atom (Pt-PPh(2)C[triple bond]CFc) to the platinum center is reported. The reaction of derivative [cis-Pt(R(F))(2)(PPh(2)C[triple bond]CFc)(2)] (R(F) = C(6)F(5)) with the solvate complex [cis-Pt(R(F))(2)(thf)(2)] leads to the formation of an asymmetrical heteronuclear diplatinum complex [{Pt(R(F))(2)(mu-1kappaP:2eta(2)-PPh(2)C[triple bond]CFc)(2)}Pt(R(F))(2)] having the "cis-Pt(R(F))(2)" fragment coordinated to the triple bonds of both ferrocenylethynylphosphine units, while treatment of [cis-Pt(C[triple bond]CFc)(2)(PPh(2)C[triple bond]CR)(2)] (R = Fc , Ph , tBu ) with the same solvate [cis-Pt(R(F))(2)(thf)(2)], affords double ferrocenylacetylide-bridged diplatinum systems [{Pt(PPh(2)C[triple bond]CR)(2)(mu-eta(1):eta(2)-C[triple bond]CFc)(2)}Pt(R(F))(2)] . The solid-state structures of [cis/trans-Pt(R(F))(2)(PPh(2)C[triple bond]CFc)(2)] /, [cis-Pt(R(F))(2)(PPh(2)C[triple bond]CFc)(tht)] (tht = tetrahydrothiophene), [{Pt(R(F))(2)(mu-1kappaP:2eta(2)-PPh(2)C[triple bond]CFc)(2)}Pt(R(F))(2)] and [{Pt(PPh(2)C[triple bond]CtBu)(2)(mu-eta(1):eta(2)-C[triple bond]CFc)(2)}Pt(R(F))(2)] have been determined by X-ray diffraction methods. The electronic spectra and the electrochemical behaviour of all monoplatinum derivatives are discussed, showing a different extent of interaction between the remote ferrocenyl groups when they belong to PPh(2)C[triple bond]CFc or C[triple bond]CFc ligands. For the diplatinum systems and , containing bridging (kappaP:eta(2)-PPh(2)C[triple bond]CFc ) or (eta(1):eta(2)-C[triple bond, length as m-dash]CFc ) ligands, their electrochemical properties were also compared with the parent precursors.

  1. A Lagrangian framework for deriving triples and quadruples corrections to the CCSD energy

    DEFF Research Database (Denmark)

    Eriksen, Janus Juul; Kristensen, Kasper; Kjærgaard, Thomas;

    2014-01-01

    Using the coupled cluster Lagrangian technique, we have determined perturbative corrections to the coupled cluster singles and doubles (CCSD) energy that converge towards the coupled cluster singles, doubles, and triples (CCSDT) and coupled cluster singles, doubles, triples, and quadruples (CCSDT...

  2. Hoogsteen-position pyrimidines promote the stability and function of the MALAT1 RNA triple helix.

    Science.gov (United States)

    Brown, Jessica A; Kinzig, Charles G; DeGregorio, Suzanne J; Steitz, Joan A

    2016-05-01

    Triple-stranded RNA was first deduced to form in vitro more than 50 years ago and has since been implicated in RNA catalysis, stability, and small molecule binding. Despite the emerging biological significance of RNA triple helices, it remains unclear how their nucleotide composition contributes to their thermodynamic stability and cellular function. To investigate these properties, we used in vitro RNA electrophoretic mobility shift assays (EMSAs) and in vivo intronless β-globin reporter assays to measure the relative contribution of 20 RNA base triples (N•A-U, N•G-C, N•C-G, N•U-A, and N•G-U) to triple-helical stability. These triples replaced a single internal U•A-U within the known structure of the triple-helical RNA stability element of human metastasis-associated lung adenocarcinoma transcript 1 (MALAT1), which contains 10 major-groove base triples. In addition to the canonical C•G-C triple, the noncanonical base triples U•G-C, U•G-U, C•C-G, and U•C-G exhibited at least 30% stability relative to the wild-type U•A-U base triple in both assays. Of these triples, only U•A-U, C•G-C, and U•G-C, when tested as four successive triples, formed stabilizing structures that allowed accumulation of the intronless β-globin reporter. Overall, we find that Hoogsteen-position pyrimidines support triple helix stability and function and that thermodynamic stability, based on EMSA results, is necessary but not sufficient for stabilization activity of the MALAT1 triple helix in cells. These results suggest that additional RNA triple helices containing noncanonical triples likely exist in nature.

  3. Triple-ion interactions for the construction of supramolecular capsules

    NARCIS (Netherlands)

    Oshovsky, G.; Reinhoudt, David; Verboom, Willem

    2006-01-01

    A novel type of [2+4] capsules based on triple-ion interactions was obtained. Four monovalent anions (bromide, nitrate, acetate, and tosylate) bring together two tetrakis(pyridiniummethyl)tetramethyl cavitands by pyridinium−anion−pyridinium interactions. ESI-MS experiments have confirmed the capsule

  4. Ferritin heavy chain in triple negative breast cancer

    DEFF Research Database (Denmark)

    Liu, Ning Qing; De Marchi, Tommaso; Timmermans, Annemieke M

    2014-01-01

    Ferritin heavy chain (FTH1) is a 21-kDa subunit of the ferritin complex, known for its role in iron metabolism, and which has recently been identified as a favorable prognostic protein for triple negative breast cancer (TNBC) patients. Currently, it is not well understood how FTH1 contributes...

  5. Efficacy of Neoadjuvant Cisplatin in Triple-Negative Breast Cancer

    DEFF Research Database (Denmark)

    Szallasi, Zoltan Imre; Eklund, Aron Charles; Li, Qiyuan

    2010-01-01

    PURPOSE Cisplatin is a chemotherapeutic agent not used routinely for breast cancer treatment. As a DNA cross-linking agent, cisplatin may be effective treatment for hereditary BRCA1-mutated breast cancers. Because sporadic triple-negative breast cancer (TNBC) and BRCA1-associated breast cancer...

  6. A triple negative breast cancer: what it is not!

    Directory of Open Access Journals (Sweden)

    Katakkar SB

    2012-02-01

    Full Text Available Suresh B KatakkarRegional Medical Oncology Hematology Leader, Centre for the North, BC Cancer Agency, Prince George, British Columbia, CanadaAbstract: The triple negative cancer is an unusual, and at the same time, a unique entity where the discordance rate is almost 18%. That means 18% of Her2 negative results will transform into a Her2 positive status and will have the affinity to spread to the central nervous system (CNS. With the identification of CD44, CD24, and ALDH1, we may be able to determine which group of triple negative breast cancer patients will have CNS metastasis. This case illustrates the Her2 expressing cells have higher CNS affinity. As the original tumor was Her2 negative, if a genomic assay was then done on this patient, we would have identified the potential of CNS involvement. In conclusion, genomic assays should be routinely done on triple negative cancers.Keywords: triple negative, breast cancer, claudin high or low, genomic microassay

  7. The EU must triple its energy saving policy effect

    NARCIS (Netherlands)

    Wesselink, B.; Eichhammer, W.; Harmsen, R.

    2010-01-01

    The impact of EU energy savings policy must triple to achieve the bloc’s 2020 energy savings goal. But such efforts could get a much better foundation if European leaders set a binding energy consumption target, rather than the current indicative savings target. The evidence for such

  8. Co-innovatie Triple P: integratie van marketingstrategie en personeelsbeleid

    NARCIS (Netherlands)

    Bartels, J.; Hendriks, R.; Ruyter, de P.; Zeelenberg, A.; Engelsman, V.; Eichelsheim, C.; Skoppek, H.; Schmidt, M.

    2008-01-01

    Dit project richt zicht op de integratie van Triple P marketing en personeelsbeleid. Het doel van het project luidt als volgt: “Hoe kun je in de marketing van biologische groenten en fruit effectief gebruik maken van de intrinsieke waarden van duurzame landbouw en maatschappelijk verantwoord onderne

  9. Triple-stack multigap resistive plate chamber with strip readout

    Energy Technology Data Exchange (ETDEWEB)

    Babkin, V., E-mail: vbabkin@cern.ch; Basilev, S.; Buryakov, M.; Golovatyuk, V.; Lobastov, S.; Petrov, V.; Rumyantsev, M.; Schipunov, A.; Shutov, A.; Slepnev, I.; Slepnev, V.

    2016-07-11

    A triple-stack MRPC for the TOF system of the BM@N and the MPD experiments at the future collider NICA was tested. We use three stacks of glass to have symmetrical construction which allows to decrease dispersion and reflections of the signal from the readout strip.

  10. The Triple Helix Model and the Knowledge-Based Economy

    NARCIS (Netherlands)

    Leydesdorff, L.; Meyer, M.

    2010-01-01

    The Triple Helix model of university-industry-government relations can be generalized from a neo-institutional model of networks of relations to a neo-evolutionary model of how three selection environments operate upon one another. Two selection mechanisms operating upon each other can mutually

  11. Peptide tessellation yields micrometre-scale collagen triple helices

    Science.gov (United States)

    Tanrikulu, I. Caglar; Forticaux, Audrey; Jin, Song; Raines, Ronald T.

    2016-11-01

    Sticky-ended DNA duplexes can associate spontaneously into long double helices; however, such self-assembly is much less developed with proteins. Collagen is the most prevalent component of the extracellular matrix and a common clinical biomaterial. As for natural DNA, the ~103-residue triple helices (~300 nm) of natural collagen are recalcitrant to chemical synthesis. Here we show how the self-assembly of short collagen-mimetic peptides (CMPs) can enable the fabrication of synthetic collagen triple helices that are nearly a micrometre in length. Inspired by the mathematics of tessellations, we derive rules for the design of single CMPs that self-assemble into long triple helices with perfect symmetry. Sticky ends thus created are uniform across the assembly and drive its growth. Enacting this design yields individual triple helices that, in length, match or exceed those in natural collagen and are remarkably thermostable, despite the absence of higher-order association. The symmetric assembly of CMPs provides an enabling platform for the development of advanced materials for medicine and nanotechnology.

  12. Nearby low-mass triple system GJ795

    CERN Document Server

    Malogolovets, E V; Rastegaev, D A; Balega, Yu.Yu.

    2007-01-01

    We report the results of our optical speckle-interferometric observations of the nearby triple system GJ795 performed with the 6-m BTA telescope with diffraction-limited angular resolution. The three components of the system were optically resolved for the first time. Position measurements allowed us to determine the elements of the inner orbit of the triple system. We use the measured magnitude differences to estimate the absolute magnitudes and spectral types of the components of the triple: $M_{V}^{Aa}$=7.31$\\pm$0.08, $M_{V}^{Ab}$=8.66$\\pm$0.10, $M_{V}^{B}$=8.42$\\pm$0.10, $Sp_{Aa}$ $\\approx$K5, $Sp_{Ab}$ $\\approx$K9, $Sp_{B}$ $\\approx$K8. The total mass of the system is equal to $\\Sigma\\mathcal{M}_{AB}$=1.69$\\pm0.27\\mathcal{M}_{\\odot}$. We show GJ795 to be a hierarchical triple system which satisfies the empirical stability criteria.

  13. Subtalar versus triple arthrodesis after intra-articular calcaneal fractures.

    Science.gov (United States)

    Schepers, Tim; Kieboom, Brenda C T; Bessems, Gert H J M; Vogels, Lucas M M; van Lieshout, Esther M M; Patka, Peter

    2010-08-01

    Depending upon initial treatment, between 2 and 30% of patients with a displaced intra-articular calcaneal fracture require a secondary arthrodesis. The aim of this study was to investigate the effect of subtalar versus triple arthrodesis on functional outcome. A total of 33 patients with 37 secondary arthrodeses (17 subtalar and 20 triple) with a median follow-up of 116 months were asked to complete questionnaires regarding disease-specific functional outcome (Maryland Foot Score, MFS), quality of life (SF-36) and overall satisfaction with the treatment (Visual Analogue Scale, VAS). Patient groups were comparable considering median age at fracture, initial treatment (conservative or operative), time to arthrodesis, median follow-up, and post-arthrodesis radiographic angles. The MFS score was similar after subtalar versus triple arthrodesis (59 vs. 56 points; P = 0.79). No statistically significant difference was found for the SF-36 (84 vs. 83 points; P = 0.67) and the VAS (5 vs. 6; P = 0.21). Smoking was statistically significantly associated with a non-union (χ(2) = 6.60, P = 0.017). The current study suggests that there is no significant difference in functional outcome between an in situ subtalar or triple arthrodesis as a salvage technique for symptomatic arthrosis after an intra-articular calcaneal fracture. Smoking is a risk factor for non-union.

  14. Subtalar versus triple arthrodesis after intra-articular calcaneal fractures

    NARCIS (Netherlands)

    T. Schepers (Tim); B.C.T. Kieboom (Brenda); J.H.J.M. Bessems (Gert); L.M.M. Vogels (Lucas); E.M.M. van Lieshout (Esther); P. Patka (Peter)

    2010-01-01

    textabstractDepending upon initial treatment, between 2 and 30% of patients with a displaced intra-articular calcaneal fracture require a secondary arthrodesis. The aim of this study was to investigate the effect of subtalar versus triple arthrodesis on functional outcome. A total of 33 patients

  15. The Triple Helix Model and the Knowledge-Based Economy

    NARCIS (Netherlands)

    Leydesdorff, L.; Meyer, M.

    2010-01-01

    The Triple Helix model of university-industry-government relations can be generalized from a neo-institutional model of networks of relations to a neo-evolutionary model of how three selection environments operate upon one another. Two selection mechanisms operating upon each other can mutually shap

  16. Hydration dynamics of the collagen triple helix by NMR.

    Science.gov (United States)

    Melacini, G; Bonvin, A M; Goodman, M; Boelens, R; Kaptein, R

    2000-07-28

    The hydration of the collagen-like Ac-(Gly-Pro-Hyp)(6)-NH(2) triple-helical peptide in solution was investigated using an integrated set of high-resolution NMR hydration experiments, including different recently developed exchange-network editing methods. This approach was designed to explore the hydration dynamics in the proximity of labile groups, such as the hydroxyproline hydroxyl group, and revealed that the first shell of hydration in collagen-like triple helices is kinetically labile with upper limits for water molecule residence times in the nanosecond to sub-nanosecond range. This result is consistent with a "hopping" hydration model in which solvent molecules are exchanged in and out of solvation sites at a rate that is not directly correlated to the degree of site localization. The hopping model thus reconciles the dynamic view of hydration revealed by NMR with the previously suggested partially ordered semi-clathrate-like cylinder of hydration. In addition, the nanosecond to sub-nanosecond upper limits for water molecule residence times imply that hydration-dehydration events are not likely to be the rate-limiting step for triple helix self-recognition, complementing previous investigations on water dynamics in collagen fibers. This study has also revealed labile proton features expected to facilitate the characterization of the structure and folding of triple helices in collagen peptides.

  17. Triple Bioaffinity Mass Spectrometry Concept for Thyroid Transporter Ligands

    NARCIS (Netherlands)

    Aqai, P.; Fryganas, C.; Mizuguchi, M.; Haasnoot, W.; Nielen, M.W.F.

    2012-01-01

    For the analysis of thyroid transporter ligands, a triple bioaffinity mass spectrometry (BioMS) concept was developed, with the aim at three different analytical objectives: rapid screening of any ligand, confirmation of known ligands in accordance with legislative requirements, and identification o

  18. Organizing product innovation: hierarchy, market or triple-helix networks?

    Science.gov (United States)

    Fitjar, Rune Dahl; Gjelsvik, Martin; Rodríguez-Pose, Andrés

    This paper assesses the extent to which the organization of the innovation effort in firms, as well as the geographical scale at which this effort is pursued, affects the capacity to benefit from product innovations. Three alternative modes of organization are studied: hierarchy, market and triple-helix-type networks. Furthermore, we consider triple-helix networks at three geographical scales: local, national and international. These relationships are tested on a random sample of 763 firms located in five urban regions of Norway which reported having introduced new products or services during the preceding 3 years. The analysis shows that firms exploiting internal hierarchy or triple-helix networks with a wide range of partners managed to derive a significantly higher share of their income from new products, compared to those that mainly relied on outsourcing within the market. In addition, the analysis shows that the geographical scale of cooperation in networks, as well as the type of partner used, matters for the capacity of firms to benefit from product innovation. In particular, firms that collaborate in international triple-helix-type networks involving suppliers, customers and R&D institutions extract a higher share of their income from product innovations, regardless of whether they organize the processes internally or through the network.

  19. On Elliptic Curves Via Heron Triangles and Diophantine Triples

    Directory of Open Access Journals (Sweden)

    F. Izadi

    2014-09-01

    Full Text Available In this article, we construct families of elliptic curves arising from the Heron triangles and Diophantine triples with the Mordell-Weil torsion subgroup of Z/2Z × Z/2Z. These families have ranks at least 2 and 3, respectively, and contain particular examples with rank equal to 7

  20. Quadrupolar, Triple [Delta]-Function Potential in One Dimension

    Science.gov (United States)

    Patil, S. H.

    2009-01-01

    The energy and parity eigenstates for quadrupolar, triple [delta]-function potential are analysed. Using the analytical solutions in specific domains, simple expressions are obtained for even- and odd-parity bound-state energies. The Heisenberg uncertainty product is observed to have a minimum for a specific strength of the potential. The…

  1. Requirements of triple play services towards broadband access networks

    NARCIS (Netherlands)

    Wolfswinkel, R.N. van

    2005-01-01

    In the current broadband market there are many new developments regarding both services and the broadband infrastructures carrying those services. This paper will address what the requirements of services are towards broadband networks. The focus will be on the requirements of triple play related se

  2. Spinal cord atrophy in triple A syndrome associated with a novel compound heterozygous mutation.

    Science.gov (United States)

    Kunte, Hagen; Trendelenburg, George; Matzen, Julia; Ventz, Manfred; Kornak, Uwe; Harms, Lutz

    2010-01-01

    A 38-year-old male patient was admitted with slowly progressive spastic gait disturbance. Imaging revealed general spinal cord atrophy. Because of adrenal insufficiency, alacrima and achalasia, triple A syndrome was suspected. This is a case report of a triple A syndrome patient with a predominance of neurological features and a new heterozygous compound mutation in triple A syndrome gene.

  3. The Novel Selective Reduction of the C-C Triple Bond

    Institute of Scientific and Technical Information of China (English)

    2000-01-01

    A novel reduction system is reported here in which the compounds with terminal C-C triple bond and disubstituted C-C triple bond react with NaBH4/Pd(PPh3)4 in a base condition and only terminal C-C triple bond is reduced.

  4. Behaviors of tribrachial edge flames and their interactions in a triple-port burner

    KAUST Repository

    Yamamoto, Kazuhiro

    2015-05-01

    In a triple-port burner, various non-premixed flames have been observed previously. Especially for the case with two lifted flames, such configuration could be suitable in studying interaction between two tribrachial flames. In the present study, the flame characteristics have been investigated numerically by adopting a reduced kinetic mechanism in the triple-port burner. Four different types of flame configurations, including two attached flames, inner lifted/outer attached flames, inner attached/outer lifted flames, and twin lifted flames, were successfully simulated depending on the flow conditions. The representative edge propagation speed of a single lifted flame or an upstream lifted flame in the case of twin lifted flames increased as the liftoff height became higher. In the twin lifted flames, the inner lifted flame was affected appreciably when the other flame was located further upstream such that the lifted flame located further downstream encountered the axial velocity acceleration induced by the gas expansion from the lifted flame located upstream, while thermal effects were not observed since the temperature of the incoming flow toward the lifted flame was not affected. A unique flip-flop behavior between the inner and outer flames, observed experimentally previously, was successfully captured in the simulation such that the inner lifted flame became attached to the nozzle as the liftoff height of the outer lifted flame grew higher with an increase in the outer air velocity.

  5. HMGA1: a master regulator of tumor progression in triple-negative breast cancer cells.

    Directory of Open Access Journals (Sweden)

    Sandeep N Shah

    Full Text Available Emerging evidence suggests that tumor cells metastasize by co-opting stem cell transcriptional networks, although the molecular underpinnings of this process are poorly understood. Here, we show for the first time that the high mobility group A1 (HMGA1 gene drives metastatic progression in triple negative breast cancer cells (MDA-MB-231, Hs578T by reprogramming cancer cells to a stem-like state. Silencing HMGA1 expression in invasive, aggressive breast cancer cells dramatically halts cell growth and results in striking morphologic changes from mesenchymal-like, spindle-shaped cells to cuboidal, epithelial-like cells. Mesenchymal genes (Vimentin, Snail are repressed, while E-cadherin is induced in the knock-down cells. Silencing HMGA1 also blocks oncogenic properties, including proliferation, migration, invasion, and orthotopic tumorigenesis. Metastatic progression following mammary implantation is almost completely abrogated in the HMGA1 knock-down cells. Moreover, silencing HMGA1 inhibits the stem cell property of three-dimensional mammosphere formation, including primary, secondary, and tertiary spheres. In addition, knock-down of HMGA1 depletes cancer initiator/cancer stem cells and prevents tumorigenesis at limiting dilutions. We also discovered an HMGA1 signature in triple negative breast cancer cells that is highly enriched in embryonic stem cells. Together, these findings indicate that HMGA1 is a master regulator of tumor progression in breast cancer by reprogramming cancer cells through stem cell transcriptional networks. Future studies are needed to determine how to target HMGA1 in therapy.

  6. Chemical modification of the third strand: differential effects on purine and pyrimidine triple helix formation.

    Science.gov (United States)

    Mills, Martin; Arimondo, Paola B; Lacroix, Laurent; Garestier, Thérèse; Klump, Horst; Mergny, Jean-Louis

    2002-01-08

    DNA triple helices offer exciting perspectives toward oligonucleotide-directed control of gene expression. Oligonucleotide analogues are routinely used with modifications in either the backbone or the bases to form more stable triple-helical structures or to prevent their degradation in cells. In this article, different chemical modifications are tested in a model system, which sets up a competition between the purine and pyrimidine motifs. For most modifications, the DeltaH degrees of purine triplex formation is close to zero, implying a nearly temperature-independent affinity constant. In contrast, the pyrimidine triplex is strongly favored at lower temperatures. The stabilization induced by modifications previously known to be favorable to the pyrimidine motif was quantified. Interestingly, modifications favorable to the GT motif (propynyl-U and dU replacing T) were also discovered. In a system where two third strands compete for triplex formation, replacement of the GA or GT strand by a pyrimidine strand may be observed at neutral pH upon lowering the temperature. This purine-to-pyrimidine triplex conversion depends on the chemical nature of the triplex-forming strands and the stability of the corresponding triplexes.

  7. Priming DNA Replication from Triple Helix Oligonucleotides: Possible Threestranded DNA in DNA Polymerases

    Directory of Open Access Journals (Sweden)

    Patrick P. Lestienne

    2011-01-01

    Full Text Available Triplex associate with a duplex DNA presenting the same polypurine or polypyrimidine-rich sequence in an antiparallel orientation. So far, triplex forming oligonucleotides (TFOs are known to inhibit transcription, replication, and to induce mutations. A new property of TFO is reviewed here upon analysis of DNA breakpoint yielding DNA rearrangements; the synthesized sequence of the first direct repeat displays a skewed polypurine- rich sequence. This synthesized sequence can bind the second homologous duplex sequence through the formation of a triple helix, which is able to prime further DNA replication. In these case, the d(G-rich Triple Helix Primers (THP bind the homologous strand in a parallel manner, possibly via a RecA-like mechanism. This novel property is shared by all tested DNA polymerases: phage, retrovirus, bacteria, and human. These features may account for illegitimate initiation of replication upon single-strand breakage and annealing to a homologous sequence where priming may occur. Our experiments suggest that DNA polymerases can bind three instead of two polynucleotide strands in their catalytic centre.

  8. Application of LBIC measurements for characterisation of triple junction solar cells

    Energy Technology Data Exchange (ETDEWEB)

    Kwarikunda, N., E-mail: Nicholas.kwarikunda@live.nmmu.ac.za [Nelson Mandela Metropolitan University, P.O. BOX 77000, Port Elizabeth, 6031 (South Africa); Makerere University, P.O. BOX 7062, Kampala (Uganda); Dyk, E.E. van; Vorster, F.J. [Nelson Mandela Metropolitan University, P.O. BOX 77000, Port Elizabeth, 6031 (South Africa); Okullo, W. [Makerere University, P.O. BOX 7062, Kampala (Uganda); Munji, M.K. [Kenyatta University, P.O. BOX 43844-00100, Nairobi (Kenya)

    2014-04-15

    In this study the Light Beam Induced Current (LBIC) imaging technique was used to characterise InGaP/InGaAs/Ge triple junction solar cells. The study focused on the use of monochromatic and solar light as beam probes to obtain photocurrent response maps from which the presence of any current reducing features on the solar cell were identified. Point illuminated current voltage (I–V) curves were obtained simultaneously while LBIC scanning measurements were being made. Curve fitting using an interval division algorithm based on the single diode model was performed to extract basic point device and performance parameters to give a rough indication of the functioning of the triple junction device. Using red and blue lasers as beam probes, reverse voltage breakdown was observed on the I–V curves which could be attributed to the Ge bottom subcell not being fully activated. The extracted parameters obtained when using monochromatic and solar light beam probes showed a large variation, indicating the dependence of I–V parameters on the spectral content of the beam probe.

  9. Combinatorics of RNA Secondary Structures with Base Triples.

    Science.gov (United States)

    Müller, Robert; Nebel, Markus E

    2015-07-01

    The structure of RNA has been the subject of intense research over the last decades due to its importance for the correct functioning of RNA molecules in biological processes. Hence, a large number of models for RNA folding and corresponding algorithms for structure prediction have been developed. However, previous models often only consider base pairs, although every base is capable of up to three edge-to-edge interactions with other bases. Recently, Höner zu Siederdissen et al. presented an extended model of RNA secondary structure, including base triples together with a folding algorithm-the first thermodynamics-based algorithm that allows the prediction of secondary structures with base triples. In this article, we investigate the search space processed by this new algorithm, that is, the combinatorics of extended RNA secondary structures with base triples. We present generalized definitions for structural motifs like hairpins, stems, bulges, or interior loops occurring in structures with base triples. Furthermore, we prove precise asymptotic results for the number of different structures (size of search space) and expectations for various parameters associated with structural motifs (typical shape of folding). Our analysis shows that the asymptotic number of secondary structures of size n increases exponentially to [Formula: see text] compared to the classic model by Stein and Waterman for which [Formula: see text] structures exist. A comparison with the classic model reveals large deviations in the expected structural appearance, too. The inclusion of base triples constitutes a significant refinement of the combinatorial model of RNA secondary structure, which, by our findings, is quantitatively characterized. Our results are of special theoretical interest, because a closer look at the numbers involved suggests that extended RNA secondary structures constitute a new combinatorial class not bijective with any other combinatorial objects studied so far.

  10. Sums of two-dimensional spectral triples

    DEFF Research Database (Denmark)

    Christensen, Erik; Ivan, Cristina

    2007-01-01

    construct a sum of two dimensional modules which reflects some aspects of the topological dimensions of the compact metric space, but this will only give the metric back approximately. At the end we make an explicit computation of the last module for the unit interval in. The metric is recovered exactly......, the Dixmier trace induces a multiple of the Lebesgue integral but the growth of the number of eigenvalues is different from the one found for the standard differential operator on the unit interval....

  11. mTOR in breast cancer: differential expression in triple-negative and non-triple-negative tumors.

    LENUS (Irish Health Repository)

    Walsh, S

    2012-04-01

    Triple-negative breast cancer (TNBC) is defined by the absence of estrogen receptors (ER), progesterone receptors (PR) and overexpression of HER2. Targeted therapy is currently unavailable for this subgroup of breast cancer patients. mTOR controls cancer cell growth, survival and invasion and is thus a potential target for the treatment of patients with TNBC. Using immunohistochemistry, mTOR and p-mTOR were measured in 89 TNBCs and 99 non-TNBCs. While mTOR expression was confined to tumor cell cytoplasm, p-mTOR staining was located in the nucleus, perinuclear area and in the cytoplasm. Potentially important, was our finding that nuclear p-mTOR was found more frequently in triple-negative than non triple-negative cancers (p < 0.001). These results suggest that mTOR may play a more important role in the progression of TNBC compared to non-TNBC. Based on these findings, we conclude that mTOR may be a new target for the treatment of triple-negative breast cancer.

  12. UV-Induced Triggering of a Biomechanical Initiation Switch Within Collagen Promotes Development of a Melanoma-Permissive Microenvironment in the Skin

    Science.gov (United States)

    2014-11-01

    our studies indicate that the UV-irradiation of triple helical collagen in vitro, in the absence of proteolytic enzymes can induced changes in the...indicate that the UV-irradiation of triple helical collagen in vitro, in the absence of proteolytic enzymes can induced changes in the structure of...HU177 cryptic epitope in collagen type-I may be a result of time and/or temperature dependent refolding of the triple helical confirmation of the

  13. Prevalence of Germline Mutations in Genes Engaged in DNA Damage Repair by Homologous Recombination in Patients with Triple-Negative and Hereditary Non-Triple-Negative Breast Cancers.

    Directory of Open Access Journals (Sweden)

    Pawel Domagala

    Full Text Available This study sought to assess the prevalence of common germline mutations in several genes engaged in the repair of DNA double-strand break by homologous recombination in patients with triple-negative breast cancers and hereditary non-triple-negative breast cancers. Tumors deficient in this type of DNA damage repair are known to be especially sensitive to DNA cross-linking agents (e.g., platinum drugs and to poly(ADP-ribose polymerase (PARP inhibitors.Genetic testing was performed for 36 common germline mutations in genes engaged in the repair of DNA by homologous recombination, i.e., BRCA1, BRCA2, CHEK2, NBN, ATM, PALB2, BARD1, and RAD51D, in 202 consecutive patients with triple-negative breast cancers and hereditary non-triple-negative breast cancers.Thirty five (22.2% of 158 patients in the triple-negative group carried mutations in genes involved in DNA repair by homologous recombination, while 10 (22.7% of the 44 patients in the hereditary non-triple-negative group carried such mutations. Mutations in BRCA1 were most frequent in patients with triple-negative breast cancer (18.4%, and mutations in CHEK2 were most frequent in patients with hereditary non-triple-negative breast cancers (15.9%. In addition, in the triple-negative group, mutations in CHEK2, NBN, and ATM (3.8% combined were found, while mutations in BRCA1, NBN, and PALB2 (6.8% combined were identified in the hereditary non-triple-negative group.Identifying mutations in genes engaged in DNA damage repair by homologous recombination other than BRCA1/2 can substantially increase the proportion of patients with triple-negative breast cancer and hereditary non-triple-negative breast cancer who may be eligible for therapy using PARP inhibitors and platinum drugs.

  14. Dynamical formation & scattering of hierarchical triples: Cross sections, Kozai-Lidov oscillations, and collisions

    CERN Document Server

    Antognini, Joseph M O

    2015-01-01

    Dynamical scattering of binaries and triple systems of stars, planets, and compact objects may produce highly inclined triple systems subject to Kozai-Lidov (KL) oscillations, potentially leading to collisions, mergers, Type Ia supernovae, and other phenomena. We present the results of more than 400 million gravitational scattering experiments of binary-binary, triple-single, and triple-binary scattering. We compute the cross sections for all possible outcomes and explore their dependencies on incoming velocity, mass, semi-major axis, and eccentricity, including analytic fits and discussion of the velocity dependence. For the production of new triple systems by scattering we find that compact triples are preferred, with ratios of outer to inner semi-major axes of ~few--100, flat or quasi-thermal eccentricity distributions, and flat distributions in cosine of the mutual inclination. Dynamically formed triples are thus subject to strong KL oscillations, the "eccentric Kozai mechanism," and non-secular effects. ...

  15. Neoadjuvant Therapy in Operable Breast Cancer: Application to Triple Negative Breast Cancer

    Directory of Open Access Journals (Sweden)

    Foluso O. Ademuyiwa

    2013-01-01

    Full Text Available Systemic treatment for triple negative breast cancer (TNBC: negative for the expression of estrogen receptor and progesterone receptor and HER2 amplification has been limited to chemotherapy options. Neoadjuvant chemotherapy induces tumor shrinkage and improves the surgical outcomes of patients with locally advanced disease and also identifies those at high risk of disease relapse despite today’s standard of care. By using pathologic complete response as a surrogate endpoint, novel treatment strategies can be efficiently assessed. Tissue analysis in the neoadjuvant setting is also an important research tool for the identification of chemotherapy resistance mechanisms and new therapeutic targets. In this paper, we review data on completed and ongoing neoadjuvant clinical trials in patients with TNBC and discuss treatment controversies that face clinicians and researchers when neoadjuvant chemotherapy is employed.

  16. A biomimetic collagen derived peptide exhibits anti-angiogenic activity in triple negative breast cancer.

    Directory of Open Access Journals (Sweden)

    Elena V Rosca

    Full Text Available We investigated the application of a mimetic 20 amino acid peptide derived from type IV collagen for treatment of breast cancer. We showed that the peptide induced a decrease of proliferation, adhesion, and migration of endothelial and tumor cells in vitro. We also observed an inhibition of triple negative MDA-MB-231 xenograft growth by 75% relative to control when administered intraperitoneally for 27 days at 10 mg/kg. We monitored in vivo the changes in vascular properties throughout the treatment using MRI and found that the vascular volume and permeability surface area product decreased significantly. The treatment also resulted in an increase of caspase-3 activity and in a reduction of microvascular density. The multiple mode of action of this peptide, i.e., anti-angiogenic, and anti-tumorigenic, makes it a viable candidate as a therapeutic agent as a monotherapy or in combination with other compounds.

  17. Adenosine Stimulate Proliferation and Migration in Triple Negative Breast Cancer Cells

    Science.gov (United States)

    Fernandez-Gallardo, Miriam; González-Ramírez, Ricardo; Sandoval, Alejandro; Monjaraz, Eduardo

    2016-01-01

    Emerging evidence suggests that the adenosine (Ado) receptors may play crucial roles in tumor progression. Here, we show that Ado increases proliferation and migration in a triple negative breast cancer model, the MDA-MB 231 cell line. The use of specific agonists and antagonists evidenced that these effects depend on the activation of the A2B receptor, which then triggers an intracellular response mediated by the adenylate cyclase/PKA/cAMP signaling pathway. Ado also increases the expression of NaV1.5 channels, a potential biomarker in breast cancer. Together, these data suggest important roles of the A2B receptors and NaV1.5 channels in the Ado-induced increase in proliferation and migration of the MDA-MB 231 cells. PMID:27911956

  18. The first example of erbium triple-stranded helicates displaying SMM behaviour.

    Science.gov (United States)

    Gorczyński, Adam; Kubicki, Maciej; Pinkowicz, Dawid; Pełka, Robert; Patroniak, Violetta; Podgajny, Robert

    2015-10-14

    A series of isostructural C3-symmetrical triple stranded dinuclear lanthanide [Ln2L3](NO3)3 molecules have been synthesized using subcomponent self-assembly of Ln(NO3)3 with 2-(methylhydrazino)benzimidazole and 4-tert-butyl-2,6-diformylphenol, where Ln = Tb (1), Dy (2), Ho (3), Er (4), Tm (5), and Yb (6). The temperature dependent and field dependent magnetic properties of 1-6 were modeled using the van Vleck approximation including the crystal field term HCF, the super-exchange term HSE and the Zeeman term HZE. Ferromagnetic interactions were found in 1, 2, 4 and 6, while antiferromagnetic interactions were found in 3 and 5. The erbium analogue reveals field induced SMM behaviour.

  19. Twisted spectral triple for the Standard Model and spontaneous breaking of the Grand Symmetry

    CERN Document Server

    Devastato, Agostino

    2014-01-01

    Grand symmetry models in noncommutative geometry have been introduced to explain how to generate minimally (i.e. without adding new fermions) an extra scalar field beyond the standard model, which both stabilizes the electroweak vacuum and makes the computation of the mass of the Higgs compatible with its experimental value. In this paper, we use Connes-Moscovici twisted spectral triples to cure a technical problem of the grand symmetry, that is the appearance together with the extra scalar field of unbounded vectorial terms. The twist makes these terms bounded, and also permits to understand the breaking to the standard model as a dynamical process induced by the spectral action. This is a spontaneous breaking from a pre-geometric Pati-Salam model to the almost-commutative geometry of the standard model, with two Higgs-like fields: scalar and vector.

  20. Dicke-Josephson effect in a cross-typed triple-quantum-dot junction

    Science.gov (United States)

    Wang, Xiao-Qi; Yi, Guang-Yu; Gong, Wei-Jiang

    2016-12-01

    We investigate the Dicke-Josephson effect in a superconductor/triple-quantum-dot/superconductor junction in which the central dot is coupled to the superconductors. It is found that the Dicke effect can modulate the Josephson effect in a nontrivial way. In the noninteracting case, the Dicke effect induces a subpeak in the supercurrent spectrum around the energy zero point. When intradot interactions are taken into account, the role of the Dicke effect changes completely. Namely, it tends to suppress the π-phase current near the position of electron-hole symmetry. With the increase of the Coulomb strength, it has an opportunity to reverse the current direction. We thus conclude that the Dicke-Josephson effect is also an important part in describing the Josephson effect in coupled-dot junctions.

  1. Prognostic significance of Bcl-2 in invasive mammary carcinomas: a comparative clinicopathologic study between "triple-negative" and non-"triple-negative" tumors.

    Science.gov (United States)

    Tawfik, Kareem; Kimler, Bruce F; Davis, Marilyn K; Fan, Fang; Tawfik, Ossama

    2012-01-01

    Bcl-2 is a tumorigenic protein that is expressed in 25% to 50% of breast cancers. Although its expression has been widely accepted as a favorable prognostic marker, its protective mechanism of action remains unclear. "Triple-negative" tumors are an aggressive subgroup known to carry a poor prognosis. Studies documenting prognostic significance of Bcl-2 expression in triple-negative in comparison to non-triple-negative breast cancers are limited. Bcl-2 expression was correlated with tumor size, grade, histologic type, lymphovascular invasion, lymph node status, patients' overall survival, estrogen receptor, progesterone receptor, Her-2, p53, and epidermal growth factor receptor in 124 triple-negative and 458 non-triple-negative tumors. There were significant differences between triple-negative and non-triple-negative tumors in their relationship to Bcl-2 expression (81% versus 29%, respectively) and tumor aggression. As previously reported, in non-triple-negative tumors, Bcl-2 positivity correlated with less aggressive tumors (94% of grade I tumors were Bcl-2+ versus 62% of grade III tumors, P < .011) and overall survival (P = .008). However, the opposite was true in patients with triple-negative tumors, where Bcl-2 positivity was associated with poorer survival (P = .64). In triple-negative tumors, Bcl-2 positivity was not associated with any of the aforementioned parameters except for a lower incidence of lymph node metastasis. Moreover, by Cox regression analysis of all variables, in patients with triple-negative tumors, lymphovascular invasion (P = .009) and Bcl-2 expression (P = .028) were predictors of poor survival. In conclusion, there are major clinicopathologic differences between breast cancer phenotypes. Our results establish the value of using Bcl-2 in prognostic stratification of patients and its potential therapeutic implications in selecting patients for treatment.

  2. Photo-active collagen systems with controlled triple helix architecture

    CERN Document Server

    Tronci, Giuseppe; Wood, David J

    2013-01-01

    The design of photo-active collagen systems is presented as a basis for establishing biomimetic materials with varied network architecture and programmable macroscopic properties. Following in-house isolation of type I collagen, reaction with vinyl-bearing compounds of varied backbone rigidity, i.e. 4-vinylbenzyl chloride (4VBC) and glycidyl methacrylate (GMA), was carried out. TNBS colorimetric assay, 1H-NMR and ATR-FTIR confirmed covalent and tunable functionalization of collagen lysines. Depending on the type and extent of functionalization, controlled stability and thermal denaturation of triple helices were observed via circular dichroism (CD), whereby the hydrogen-bonding capability of introduced moieties was shown to play a major role. Full gel formation was observed following photo-activation of functionalized collagen solutions. The presence of a covalent network only slightly affected collagen triple helix conformation (as observed by WAXS and ATR-FTIR), confirming the structural organization of fun...

  3. BIOMONITORING OF ELITE WOMEN TRIPLE-JUMPERS’ ELASTIC FORCE

    Directory of Open Access Journals (Sweden)

    Milan Čoh

    2013-07-01

    Full Text Available The aim of the study was to analyse kinematic and dynamic parameters of elastic force of elite women triple jumpers. The elastic force, in combination with horizontal velocity, is the most important factor of success in a triple jump. To establish the elastic force we conducted a biomechanical analysis, using drop jumps from the heights of 25 and 45 cm. The basic kinematic and dynamic parameters were registered using the Kistler Type 9286 bipedal force platform which had been synchronised with a 3D infra-red kinematic system CCD Smart – 600 E. Based on kinematic and dynamic analysis we can establish that the results in drop jumps are generated by the following variables: jump height, contact time, vertical velocity of takeoff, force impulse and the eccentric phase.

  4. Mosaic triple X syndrome in a female with primary amenorrhea

    Directory of Open Access Journals (Sweden)

    A Venkateshwari

    2012-01-01

    Full Text Available Background: Turner′s syndrome is the most common chromosomal abnormality in females, affecting 1 in 2,500 live female births. It is a result of absence of an X chromosome or the presence of a structurally abnormal X chromosome. Its most consistent clinical features are short stature and ovarian failure. Aim: The aim of the study was to report a rare case of mosaic triple X syndrome in a female with primary amenorrhea. Materials and Methods: The chromosomal analysis using GTG banding was carried out, which revealed a mosaicism with 45,XO/47,XXX chromosomal constitution. Fluorescent in situ hybridization was also carried out to further confirm the observation made in the study. Conclusion: The physical features presented by the female could be due to the 45,XO/47,XXX mosaicism and the karyotype analysis was consistent with the diagnosis and clinical symptoms. Triple X mosaicism was confirmed with conventional and molecular cytogenetic analysis.

  5. Viscous solution of the triple shock reflection problem

    CERN Document Server

    Lau-Chapdelaine, S She-Ming

    2016-01-01

    The reflection of a triple-shock configuration was studied numerically in two dimensions using the Navier-Stokes equations. The flow field was initialized using three shock theory, and the reflection of the triple point on a plane of symmetry was studied. The conditions simulated a stoichiometric methane-oxygen detonation cell at low pressure on time scales preceding ignition, when the gas was assumed to be thermodynamically inert. Viscosity was found to play an important role on some shock reflection mechanisms believed to accelerate reaction rates in detonations where time scales are small. A small wall jet was present in the double Mach reflection and increased in size with Reynolds number, eventually forming a small vortex. Kelvin-Helmholtz instabilities were absent and there was no Mach stem bifurcation at Reynolds numbers corresponding to and exceeding the induction length. Kelvin-Helmholtz instabilities are unlikely to be a source of rapid reactions in detonations at time scales commensurate with the i...

  6. Triple-horizon spherically symmetric spacetime and holographic principle

    CERN Document Server

    Dymnikova, Irina

    2012-01-01

    We present a family of spherically symmetric spacetimes, specified by the density profile of a vacuum dark energy, which have the same global structure as the de Sitter spacetime but the reduced symmetry which leads to a time-evolving and spatially inhomogeneous cosmological term. It connects smoothly two de Sitter vacua with different values of cosmological constant and corresponds to anisotropic vacuum dark fluid defined by symmetry of its stress-energy tensor which is invariant under the radial boosts. This family contains a special class distinguished by dynamics of evaporation of a cosmological horizon which evolves to the triple horizon with the finite entropy, zero temperature, zero curvature, infinite positive specific heat, and infinite scrambling time. Non-zero value of the cosmological constant in the triple-horizon spacetime is tightly fixed by quantum dynamics of evaporation of the cosmological horizon.

  7. Grain boundary and triple junction diffusion in nanocrystalline copper

    Energy Technology Data Exchange (ETDEWEB)

    Wegner, M., E-mail: m.wegner@uni-muenster.de; Leuthold, J.; Peterlechner, M.; Divinski, S. V., E-mail: divin@uni-muenster.de [Institut für Materialphysik, Universität Münster, Wilhelm-Klemm-Straße 10, D-48149, Münster (Germany); Song, X., E-mail: xysong@bjut.edu.cn [College of Materials Science and Engineering, Beijing University of Technology, 100124 Beijing (China); Wilde, G. [Institut für Materialphysik, Universität Münster, Wilhelm-Klemm-Straße 10, D-48149, Münster (Germany); Institute of Nanochemistry and Nanobiology, School of Environmental and Chemical Engineering, Shanghai University, 200444 Shanghai (China)

    2014-09-07

    Grain boundary and triple junction diffusion in nanocrystalline Cu samples with grain sizes, 〈d〉, of ∼35 and ∼44 nm produced by spark plasma sintering were investigated by the radiotracer method using the {sup 63}Ni isotope. The measured diffusivities, D{sub eff}, are comparable with those determined previously for Ni grain boundary diffusion in well-annealed, high purity, coarse grained, polycrystalline copper, substantiating the absence of a grain size effect on the kinetic properties of grain boundaries in a nanocrystalline material at grain sizes d ≥ 35 nm. Simultaneously, the analysis predicts that if triple junction diffusion of Ni in Cu is enhanced with respect to the corresponding grain boundary diffusion rate, it is still less than 500⋅D{sub gb} within the temperature interval from 420 K to 470 K.

  8. Climate variability according to triple saros gravity cycles

    CERN Document Server

    Livingston, William R

    2013-01-01

    I describe a climate model which corresponds directly to eclipse cycles. The theory is based upon a similarity between the 54 year triple saros eclipse period and the periodicity of drought. I argue that eclipse shadows are an indication of gravity cycles, and that variable lunar gravitation is the most significant aspect of the eclipse process. I reinforce the idea that lunar gravitational forcing has a profound effect on the water vapor in Earth's atmosphere, and can affect the density and location of clouds. I explore the possibility that decadal variability of ocean surface levels may be explained by triple saros gravity cycles. I point out that lunar gravitation was excluded from the most significant climate report of 2007, and that climate data contradictions have been overlooked by researchers. I focus on the value of data that has not been aggregated into global averages. I touch upon the history of global warming, and I offer predictions based upon 54 year climate periodicity.

  9. Photodissociation of methyl formate: Conical intersections, roaming and triple fragmentation

    Energy Technology Data Exchange (ETDEWEB)

    Lin, King-Chuen; Tsai, Po-Yu [Department of Chemistry, National Taiwan University, Taipei 106, Taiwan (China); Institute of Atomic and Molecular Sciences, Academia Sinica, Taipei 106, Taiwan (China); Chao, Meng-Hsuan [Department of Chemistry, National Taiwan University, Taipei 106, Taiwan (China); Kasai, Toshio [Department of Chemistry, National Taiwan University, Taipei 106, Taiwan (China); Graduate School of Science, Department of Chemistry, Osaka University, Toyonaka, 560-0043 Osaka (Japan); Lombardi, Andrea [Dipartimento di Chimica, Università di Perugia, 06123 Perugia (Italy); Palazzetti, Federico [Scuola Normale Superiore, 56126 Pisa (Italy); Aquilanti, Vincenzo [Dipartimento di Chimica, Università di Perugia, 06123 Perugia (Italy); Consiglio Nazionale delle Ricerche, Istituto di Struttura della Materia, 00016 Roma (Italy)

    2015-12-31

    The photodissociation channels of methyl formate have been extensively investigated by two different advanced experimental techniques, ion imaging and Fourier-Transform-Infrared emission spectroscopy, combined with quantum chemical calculations and molecular dynamics simulations. Our aim is to characterize the role of alternative routes to the conventional transition-state mediated pathway: the roaming and the triple fragmentation processes. The photolysis experiments, carried out at a range of laser wavelengths in the vicinity of the triple fragmentation threshold, beside the simulation of large bunches of classical trajectories with different initial conditions, have shown that both mechanisms share a common path that involves a conical intersection during the relaxation process from the electronic excited state S{sub 1} to the ground state S{sub 0}.

  10. The Proteomic Landscape of Triple-Negative Breast Cancer

    Directory of Open Access Journals (Sweden)

    Robert T. Lawrence

    2015-04-01

    Full Text Available Triple-negative breast cancer is a heterogeneous disease characterized by poor clinical outcomes and a shortage of targeted treatment options. To discover molecular features of triple-negative breast cancer, we performed quantitative proteomics analysis of twenty human-derived breast cell lines and four primary breast tumors to a depth of more than 12,000 distinct proteins. We used this data to identify breast cancer subtypes at the protein level and demonstrate the precise quantification of biomarkers, signaling proteins, and biological pathways by mass spectrometry. We integrated proteomics data with exome sequence resources to identify genomic aberrations that affect protein expression. We performed a high-throughput drug screen to identify protein markers of drug sensitivity and understand the mechanisms of drug resistance. The genome and proteome provide complementary information that, when combined, yield a powerful engine for therapeutic discovery. This resource is available to the cancer research community to catalyze further analysis and investigation.

  11. Artificial neural network analysis of triple effect absorption refrigeration systems

    Energy Technology Data Exchange (ETDEWEB)

    Hajizadeh Aghdam, A. [Department of Mechanical Engineering, Islamic Azad University (Iran, Islamic Republic of)], email: a.hajizadeh@iaukashan.ac.ir; Nazmara, H.; Farzaneh, B. [Department of Mechanical Engineering, University of Tabriz (Iran, Islamic Republic of)], email: h.nazmara@nioec.org, email: b_farzaneh_ms@yahoo.com

    2011-07-01

    In this study, artificial neural networks are utilized to predict the performance of triple effect series and parallel flow absorption refrigeration systems, with lithium bromide/water as the working fluid. Important parameters such as high generator and evaporator temperatures were varied and their effects on the performance characteristics of the refrigeration unit were observed. Absorption refrigeration systems make energy savings possible because they can use heat energy to produce cooling, in place of the electricity used for conventional vapour compression chillers. In addition, non-conventional sources of energy (such as solar, waste heat, and geothermal) can be utilized as their primary energy input. Moreover, absorption units use environmentally friendly working fluid pairs instead of CFCs and HCFCs, which affect the ozone layer. Triple effect absorption cycles were analysed. Results apply for both series and parallel flow systems. A relative preference for parallel-flow over series-flow is also shown.

  12. EXTREME AO OBSERVATIONS OF TWO TRIPLE ASTEROID SYSTEMS WITH SPHERE

    Energy Technology Data Exchange (ETDEWEB)

    Yang, B.; Wahhaj, Z.; Dumas, C.; Marsset, M. [European Southern Observatory, Santiago (Chile); Beauvalet, L. [National Observatory, Rio de Janeiro (Brazil); Marchis, F.; Nielsen, E. L. [Carl Sagan Center at the SETI Institute, Mountain View, CA (United States); Vachier, F., E-mail: byang@eso.org [Institut de Mécanique Céleste et de Calcul des Éphémérides, Paris (France)

    2016-04-01

    We present the discovery of a new satellite of asteroid (130) Elektra—S/2014 (130) 1—in differential imaging and in integral field spectroscopy data over multiple epochs obtained with Spectro-Polarimetric High-contrast Exoplanet Research/Very Large Telescope. This new (second) moonlet of Elektra is about 2 km across, on an eccentric orbit, and about 500 km away from the primary. For a comparative study, we also observed another triple asteroid system, (93) Minerva. For both systems, component-resolved reflectance spectra of the satellites and primary were obtained simultaneously. No significant spectral difference was observed between the satellites and the primary for either triple system. We find that the moonlets in both systems are more likely to have been created by sub-disruptive impacts as opposed to having been captured.

  13. Mixed Hyperlipidemia Associated with Triple X Syndrome (A Case Report

    Directory of Open Access Journals (Sweden)

    Anton-Pǎduraru Dana-Teodora

    2014-06-01

    Full Text Available Lipid metabolism abnormalities in children may be hereditary or secondary to certain diseases (obesity, type 2 diabetes mellitus. Often elevated triglycerides values are associated with high cholesterol values, playing a major role on atherosclerosis. The triple X syndrome also called “the superfemale syndrome” is not a rare condition, but it is usually undiagnosed or occasionally diagnosed when other investigations are done. The authors present the case of a child admitted in the 3rd Clinic of Pediatrics -“Sf. Maria” Children’s Emergency Hospital, Iaşi -Romania for the continuation of her lipid metabolism investigations, being diagnosed on this occasion with the triple X syndrome. We conclude that the investigation of lipid metabolism, early identification of lipid abnormalities and proper treatment significantly reduce the prevalence of cardiovascular disease in adults. We cannot specify the impact of the presence of the chromosomal anomaly, as it is an accidental association

  14. Triple Helix Formation in a Topologically Controlled DNA Nanosystem.

    Science.gov (United States)

    Yamagata, Yutaro; Emura, Tomoko; Hidaka, Kumi; Sugiyama, Hiroshi; Endo, Masayuki

    2016-04-11

    In the present study, we demonstrate single-molecule imaging of triple helix formation in DNA nanostructures. The binding of the single-molecule third strand to double-stranded DNA in a DNA origami frame was examined using two different types of triplet base pairs. The target DNA strand and the third strand were incorporated into the DNA frame, and the binding of the third strand was controlled by the formation of Watson-Crick base pairing. Triple helix formation was monitored by observing the structural changes in the incorporated DNA strands. It was also examined using a photocaged third strand wherein the binding of the third strand was directly observed using high-speed atomic force microscopy during photoirradiation. We found that the binding of the third strand could be controlled by regulating duplex formation and the uncaging of the photocaged strands in the designed nanospace.

  15. Triple dividends of water consumption charges in South Africa

    Science.gov (United States)

    Letsoalo, Anthony; Blignaut, James; de Wet, Theuns; de Wit, Martin; Hess, Sebastiaan; Tol, Richard S. J.; van Heerden, Jan

    2007-05-01

    The South African government is exploring ways to address water scarcity problems by introducing a water resource management charge on the quantity of water used in sectors such as irrigated agriculture, mining, and forestry. It is expected that a more efficient water allocation, lower use, and a positive impact on poverty can be achieved. This paper reports on the validity of these claims by applying a computable general equilibrium model to analyze the triple dividend of water consumption charges in South Africa: reduced water use, more rapid economic growth, and a more equal income distribution. It is shown that an appropriate budget-neutral combination of water charges, particularly on irrigated agriculture and coal mining, and reduced indirect taxes, particularly on food, would yield triple dividends, that is, less water use, more growth, and less poverty.

  16. Lifestyle Triple P: a parenting intervention for childhood obesity

    Directory of Open Access Journals (Sweden)

    Gerards Sanne MPL

    2012-04-01

    Full Text Available Abstract Background Reversing the obesity epidemic requires the development and evaluation of childhood obesity intervention programs. Lifestyle Triple P is a parent-focused group program that addresses three topics: nutrition, physical activity, and positive parenting. Australian research has established the efficacy of Lifestyle Triple P, which aims to prevent excessive weight gain in overweight and obese children. The aim of the current randomized controlled trial is to assess the effectiveness of the Lifestyle Triple P intervention when applied to Dutch parents of overweight and obese children aged 4–8 years. This effectiveness study is called GO4fit. Methods/Design Parents of overweight and obese children are being randomized to either the intervention or the control group. Those assigned to the intervention condition receive the 14-week Lifestyle Triple P intervention, in which they learn a range of nutritional, physical activity and positive parenting strategies. Parents in the control group receive two brochures, web-based tailored advice, and suggestions for exercises to increase active playing at home. Measurements are taken at baseline, directly after the intervention, and at one year follow-up. Primary outcome measure is the children’s body composition, operationalized as BMI z-score, waist circumference, and fat mass (biceps and triceps skinfolds. Secondary outcome measures are children’s dietary behavior and physical activity level, parenting practices, parental feeding style, parenting style, parental self-efficacy, and body composition of family members (parents and siblings. Discussion Our intervention is characterized by a focus on changing general parenting styles, in addition to focusing on changing specific parenting practices, as obesity interventions typically do. Strengths of the current study are the randomized design, the long-term follow-up, and the broad range of both self-reported and objectively measured

  17. Triple I method and interval valued fuzzy reasoning

    Institute of Scientific and Technical Information of China (English)

    2000-01-01

    The aims of this paper are: (i) to show that the CRI method should be improved and remould into the triple I method, (ii) to propose a new type of fuzzy reasoning with multiple rules of which the premise of each rule is an interval valued fuzzy subset, (iii) to establish the "fire one or leave (FOOL)" principle as pretreatment for solving the fuzzy reasoning problem mentioned in (ii), and (iv) to solve the problem mentioned in (ii).

  18. Triple I method and interval valued fuzzy reasoning

    Institute of Scientific and Technical Information of China (English)

    王国俊

    2000-01-01

    The aims of this paper are.- (i) to show that the CRI method should be improved and remould into the triple I method, (ii) to propose a new type of fuzzy reasoning with multiple rules of which the premise of each rule is an interval valued fuzzy subset, (iii) to establish the "fire one or leave (FOOL)" principle as pretreatment for solving the fuzzy reasoning problem mentioned in (ii), and (iv) to solve the problem mentioned in (ii).

  19. Tulczyjew triples in the constrained dynamics of strings

    Science.gov (United States)

    Grabowski, J.; Grabowska, K.; Urbański, P.

    2016-09-01

    We show that there exists a natural Tulczyjew triple in the dynamics of objects for which the standard (kinematic) configuration space TM is replaced with ∧n TM . In this framework, which is completely covariant, we derive geometrically phase equations, as well as Euler-Lagrange equations, including nonholonomic constraints into the picture. Dynamics of strings and a constrained Plateau problem in statics are particular cases of this framework.

  20. Conformational stability of triazolyl functionalized collagen triple helices.

    Science.gov (United States)

    Erdmann, Roman S; Wennemers, Helma

    2013-06-15

    Functionalized collagen is attractive for the development of synthetic biomaterials. Herein we present the functionalization of azidoproline containing collagen model peptides with various alkynes using click chemistry. The influence on the stability of the collagen triple helix of the stereochemistry of the introduced triazolyl prolines (4R or 4S), the position of their incorporation (Xaa or Yaa) and the substituents attached to them are shown. The results provide a useful guide for the optimal functionalization of collagen using click chemistry.

  1. AND BUSINESS INCUBATORS INTO THE TRIPLE HELIX CONCEPT

    Directory of Open Access Journals (Sweden)

    Sizova, Y.S.

    2016-04-01

    Full Text Available The article’s author endeavors to create a practical model of the Russian economy’s development while integrating such tools of supporting and stimulating entrepreneurship as business incubators and research and technology parks into the Triple Helix concept. The article points out that configurations fusing together the nation-state, business and science/education, possess a greater potential for development.

  2. Period tripling causes rotating spirals in agitated wet granular layers.

    Science.gov (United States)

    Huang, Kai; Rehberg, Ingo

    2011-07-08

    Pattern formation of a thin layer of vertically agitated wet granular matter is investigated experimentally. Rotating spirals with three arms, which correspond to the kinks between regions with different colliding phases, are the dominating pattern. This preferred number of arms corresponds to period tripling of the agitated granular layer, unlike predominantly subharmonic Faraday crispations in dry granular matter. The chirality of the spatiotemporal pattern corresponds to the rotation direction of the spirals.

  3. On the Analysis Method of the Triple Tesh Cross Design

    Institute of Scientific and Technical Information of China (English)

    JinYi

    1995-01-01

    The analysis method of the triple test cross design has been discussed carefully form the two factor experiment design and the genetic models of additive-dominant effect and of epistasis effect-Two points different from the previous reprots have been concluded:(1)both the degrees of freedom of the orthogonal terms C2 and C3 are m;(2) the denominator in the F test to C2 and C3 is the error mean of square between plots.

  4. One-loop triple collinear splitting amplitudes in QCD

    CERN Document Server

    Badger, Simon; Peraro, Tiziano

    2015-01-01

    We study the factorisation properties of one-loop scattering amplitudes in the triple collinear limit and extract the universal splitting amplitudes for processes initiated by a gluon. The splitting amplitudes are derived from the analytic Higgs plus four partons amplitudes. We present compact results for primitive helicity splitting amplitudes making use of super-symmetric decompositions. The universality of the collinear factorisation is checked numerically against the full colour six parton squared matrix elements.

  5. Prenatal diagnosis and prognosis of triple X syndrome: 47, XXX.

    Science.gov (United States)

    Ben Hamouda, H; Mkacher, N; Elghezal, H; Bannour, H; Kamoun, M; Soua, H; Saad, A; Souissi, M M; Sfar, M T

    2009-11-01

    Triple X syndrome is a relatively common sex chromosomal abnormality occurring in 0,1% of live-born female infants. Most of these infants have a normal phenotype and only a few cases with 47, XXX karyotype have congenital malformations. We report three cases of triple X syndrome that were diagnosed prenatally by genetic amniocentesis for advanced maternal age and have been observed from birth to age of 3 to 12 years. A description of their growth and development is presented. The birth weight was normal in all patients and one of them had facial dysmorphism with right microphtalmia and auricular septal defect. During the first 2 years of life, the neuromotor development of these infants was not distinguishable from chromosomally normal children. By 3 years of age, two patients have a moderate developmental delay in speech and language. One girl 12-year-old had normal schooling. The diagnosis of the triple X syndrome can be never made because clinical demonstrations are not rather important to arouse the demand of a karyotype. Prenatal diagnosis is often made in front of the advanced maternal age. Expectant parents must be counseled as to the significance of this 47, XXX karyotype and prognostic information must be given.

  6. Unraveling high precision stereocontrol in a triple cascade organocatalytic reaction.

    Science.gov (United States)

    Shinisha, C B; Sunoj, Raghavan B

    2008-11-07

    The mechanism and stereoselectivity in an organocatalyzed triple cascade reaction between an aldehyde, electron deficient olefin and an alpha,beta-unsaturated aldehyde are investigated for the first time using density functional theory. The factors responsible for high levels of observed stereoselectivity (Enders et al., Nature, 2006, 441, 861) towards the generation of cyclohexene carbaldehyde with four contiguous stereocentres are unravelled. The triple cascade reaction, comprising a Michael, Michael and aldol sequence as the key elementary reactions, is studied by identifying the corresponding transition states for the stereoselective C-C bond-formation. In the first Michael addition step between the enamine (derived from the chiral catalyst and propanal) and nitrostyrene, energetically the most preferred mode of addition is found to be between the si-face of (E)-anti-enamine on the si-face of nitrostyrene. The addition of the si-face of the nitroalkane anion on the re-face of the iminium ion (formed between the enal and the catalyst) is the lowest energy pathway for the second Michael addition step. The high level of asymmetric induction is rationalized with the help of relative activation barriers associated with the competitive diastereomeric pathways. Interesting weak interactions, along with the steric effects offered by the bulky alpha-substituent on the pyrrolidine ring, are identified as critical to the stereoselectivity in this triple cascade reaction. The predicted stereoselectivities using computed energetics are found to be in perfect harmony with the experimental stereoselectivities.

  7. Unambiguous demonstration of triple-helix-directed gene modification.

    Science.gov (United States)

    Barre, F X; Ait-Si-Ali, S; Giovannangeli, C; Luis, R; Robin, P; Pritchard, L L; Helene, C; Harel-Bellan, A

    2000-03-28

    Triple-helix-forming oligonucleotides (TFOs), which can potentially modify target genes irreversibly, represent promising tools for antiviral therapies. However, their effectiveness on endogenous genes has yet to be unambiguously demonstrated. To monitor endogenous gene modification by TFOs in a yeast model, we inactivated an auxotrophic marker gene by inserting target sequences of interest into its coding region. The genetically engineered yeast cells then were treated with psoralen-linked TFOs followed by UV irradiation, thus generating highly mutagenic covalent crosslinks at the target site whose repair could restore gene function; the number of revertants and spectrum of mutations generated were quantified. Results showed that a phosphoramidate TFO indeed reaches its target sequence, forms crosslinks, and generates mutations at the expected site via a triplex-mediated mechanism: (i) under identical conditions, no mutations were generated by the same TFO at two other loci in the target strain, nor in an isogenic control strain carrying a modified target sequence incapable of supporting triple-helix formation; (ii) for a given target sequence, whether the triplex was formed in vivo on an endogenous gene or in vitro on an exogenous plasmid, the nature of the mutations generated was identical, and consistent with the repair of a psoralen crosslink at the target site. Although the mutation efficiency was probably too low for therapeutic applications, our results confirm the validity of the triple-helix approach and provide a means of evaluating the effectiveness of new chemically modified TFOs and analogs.

  8. Biophysical studies of matrix metalloproteinase/triple-helix complexes.

    Science.gov (United States)

    Fields, Gregg B

    2014-01-01

    Several members of the zinc-dependent matrix metalloproteinase (MMP) family catalyze collagen degradation. The structures of MMPs, in solution and solid state and in the presence and absence of triple-helical collagen models, have been assessed by NMR spectroscopy, small-angle X-ray scattering, and X-ray crystallography. Structures observed in solution exhibit flexibility between the MMP catalytic (CAT) and hemopexin-like (HPX) domains, while solid-state structures are relatively compact. Evaluation of the maximum occurrence (MO) of MMP-1 conformations in solution found that, for all the high MO conformations, the CAT and HPX domains are not in tight contact, and the residues of the HPX domain reported to be responsible for the binding to the collagen triple-helix are solvent exposed. A mechanism for collagenolysis has been developed based on analysis of MMP solution structures. Information obtained from solid-state structures has proven valuable for analyzing specific contacts between MMPs and the collagen triple-helix.

  9. Photo-active collagen systems with controlled triple helix architecture.

    Science.gov (United States)

    Tronci, Giuseppe; Russell, Stephen J; Wood, David J

    2013-08-14

    The design of photo-active collagen systems is presented as a basis for establishing biomimetic materials with varied network architecture and programmable macroscopic properties. Following in-house isolation of type I collagen, reaction with vinyl-bearing compounds of varied backbone rigidity, i.e. 4-vinylbenzyl chloride (4VBC) and glycidyl methacrylate (GMA), was carried out. TNBS colorimetric assay, (1)H-NMR and ATR-FTIR confirmed covalent and tunable functionalization of collagen lysines. Depending on the type and extent of functionalization, controlled stability and thermal denaturation of triple helices were observed via circular dichroism (CD), whereby the hydrogen-bonding capability of introduced moieties was shown to play a major role. Full gel formation was observed following photo-activation of functionalized collagen solutions. The presence of a covalent network only slightly affected collagen triple helix conformation (as observed by WAXS and ATR-FTIR), confirming the structural organization of functionalized collagen precursors. Photo-activated hydrogels demonstrated an increased denaturation temperature (DSC) with respect to native collagen, suggesting that the formation of the covalent network successfully stabilized collagen triple helices. Moreover, biocompatibility and mechanical competence of obtained hydrogels were successfully demonstrated under physiologically-relevant conditions. These results demonstrate that this novel synthetic approach enabled the formation of biocompatible collagen systems with defined network architecture and programmable macroscopic properties, which can only partially be obtained with current synthetic methods.

  10. Assembly of liposomes controlled by triple helix formation.

    Science.gov (United States)

    Jakobsen, Ulla; Vogel, Stefan

    2013-09-18

    Attachment of DNA to the surface of different solid nanoparticles (e.g., gold and silica nanoparticles) is well established, and a number of DNA-modified solid nanoparticle systems have been applied to thermal denaturation analysis of oligonucleotides. We report herein the noncovalent immobilization of oligonucleotides on the surface of soft nanoparticles (i.e., liposomes) and the subsequent controlled assembly by DNA triple helix formation. The noncovalent approach avoids tedious surface chemistry and necessary purification procedures and can simplify and extend the available methodology for the otherwise difficult thermal denaturation analysis of complex triple helical DNA assemblies. The approach is based on lipid modified triplex forming oligonucleotides (TFOs) which control the assembly of liposomes in solution in the presence of single- or double-stranded DNA targets. The thermal denaturation analysis is monitored by ultraviolet spectroscopy at submicromolar concentrations and compared to regular thermal denaturation assays in the absence of liposomes. We report on triplex forming oligonucleotides (TFOs) based on DNA and locked nucleic acid (LNA)/DNA hybrid building blocks and different target sequences (G or C-rich) to explore the applicability of the method for different triple helical assembly modes. We demonstrate advantages and limitations of the approach and show the reversible and reproducible formation of liposome aggregates during thermal denaturation cycles. Nanoparticle tracking analysis (NTA) and dynamic light scattering (DLS) show independently from ultraviolet spectroscopy experiments the formation of liposome aggregates.

  11. Correlation effects in 3D triple-Weyl semimetals

    Science.gov (United States)

    Zhang, Shi-Xin; Jian, Shao-Kai; Yao, Hong

    We study interaction effects, including short-range interactions and long-range Coulomb interactions, in three-dimensional topological triple-Weyl semimetals whose triple-Weyl points are protected by crystalline symmetries. In the low-energy effective field theory of triple-Weyl semimetals, by considering symmetries and utilizing Fierz identity, we find that there are only four independent short-range interaction terms. We then perform Wilsonian renormalization group analysis to determine the effect of short-range interactions at low energy and long distance by finding fixed points as well as stable strong-coupling limits. For those strong-coupling limits due to short-range interactions, spontaneous symmetry-breaking ordering is expected and is analyzed by self-consistent mean-field calculations combined with RG flow. For long-range Coulomb interactions, we find anisotropic screening effect, similar with the one in double-Weyl semimetals, and hence a qualitatively different fixed point from the Gaussian one.

  12. Triple-target microarray experiments: a novel experimental strategy

    Directory of Open Access Journals (Sweden)

    Cooke Howard J

    2004-02-01

    Full Text Available Abstract Background High-throughput, parallel gene expression analysis by means of microarray technology has become a widely used technique in recent years. There are currently two main dye-labelling strategies for microarray studies based on custom-spotted cDNA or oligonucleotides arrays: (I Dye-labelling of a single target sample with a particular dye, followed by subsequent hybridisation to a single microarray slide, (II Dye-labelling of two different target samples with two different dyes, followed by subsequent co-hybridisation to a single microarray slide. The two dyes most frequently used for either method are Cy3 and Cy5. We propose and evaluate a novel experiment set-up utilising three differently labelled targets co-hybridised to one microarray slide. In addition to Cy3 and Cy5, this incorporates Alexa 594 as a third dye-label. We evaluate this approach in line with current data processing and analysis techniques for microarrays, and run separate analyses on Alexa 594 used in single-target, dual-target and the intended triple-target experiment set-ups (a total of 18 microarray slides. We follow this by pointing out practical applications and suitable analysis methods, and conclude that triple-target microarray experiments can add value to microarray research by reducing material costs for arrays and related processes, and by increasing the number of options for pragmatic experiment design. Results The addition of Alexa 594 as a dye-label for an additional – third – target sample works within the framework of more commonplace Cy5/Cy3 labelled target sample combinations. Standard normalisation methods are still applicable, and the resulting data can be expected to allow identification of expression differences in a biological experiment, given sufficient levels of biological replication (as is necessary for most microarray experiments. Conclusion The use of three dye-labelled target samples can be a valuable addition to the standard

  13. Integrating Compassionate, Collaborative Care (the "Triple C") Into Health Professional Education to Advance the Triple Aim of Health Care.

    Science.gov (United States)

    Lown, Beth A; McIntosh, Sharrie; Gaines, Martha E; McGuinn, Kathy; Hatem, David S

    2016-03-01

    Empathy and compassion provide an important foundation for effective collaboration in health care. Compassion (the recognition of and response to the distress and suffering of others) should be consistently offered by health care professionals to patients, families, staff, and one another. However, compassion without collaboration may result in uncoordinated care, while collaboration without compassion may result in technically correct but depersonalized care that fails to meet the unique emotional and psychosocial needs of all involved. Providing compassionate, collaborative care (CCC) is critical to achieving the "triple aim" of improving patients' health and experiences of care while reducing costs. Yet, values and skills related to CCC (or the "Triple C") are not routinely taught, modeled, and assessed across the continuum of learning and practice. To change this paradigm, an interprofessional group of experts recently recommended approaches and a framework for integrating CCC into health professional education and postgraduate training as well as clinical care. In this Perspective, the authors describe how the Triple C framework can be integrated and enhance existing competency standards to advance CCC across the learning and practice continuum. They also discuss strategies for partnering with patients and families to improve health professional education and health care design and delivery through quality improvement projects. They emphasize that compassion and collaboration are important sources of professional, patient, and family satisfaction as well as critical aspects of professionalism and person-centered, relationship-based high-quality care.

  14. Origin of the Degradation of Triple Junction Solar Cells at low Temperature

    Directory of Open Access Journals (Sweden)

    Park Seonyong

    2017-01-01

    Full Text Available The degradation of solar cells under irradiation by high energy particles (electrons, protons is the consequence of the introduction of defects trapping minority carriers, which are then not collected by the junction. However, at low temperature, defects located in the space charge region can also induce a tunneling current that results in an apparent decreases of the maximum power. The degradation produced by this tunneling current can depend on temperature, since the concentration of defects created by an irradiation is usually temperature dependent, and can be larger than the degradation associated with carrier recombination. For instance, as we shall see below, an irradiation with 1 MeV electrons at 120 K with a fluence of 3.0 × 1015 /cm2 induces a decrease of less than 10 % in the short-circuit current (Isc and open-circuit voltage (Voc of triple junction (TJ cells, but a decrease of about 40 % in the maximum power (Pmax, which implies that more than half of the total degradation of Pmax should be assigned to another loss mechanism, tunneling in this case. In this work, we demonstrate that this additional degradation must indeed be ascribed to a tunneling process and we investigate the variation of the tunneling current versus fluence induced by electron irradiation in TJ cells, in order to tentatively ascribe the tunneling components to specific sub-cells.

  15. A reconstruction theorem for Connes-Landi deformations of commutative spectral triples

    CERN Document Server

    Ćaćić, Branimir

    2014-01-01

    We state and prove an extension of Connes's reconstruction theorem for commutative spectral triples to so-called Connes-Landi or isospectral deformations of commutative spectral triples along the action of a compact Abelian Lie group $G$. We do so by proposing an abstract definition for such spectral triples, where noncommutativity is entirely governed by a class in the second group cohomology of the Pontrjagin dual of $G$, and then showing that such spectral triples are well-behaved under further Connes-Landi deformation, thereby allowing for both quantisation from and dequantisation to $G$-equivariant abstract commutative spectral triples. We also construct a discrete analogue of the Connes--Dubois-Violette splitting homomorphism, which then allows us to conclude that sufficiently well-behaved rational Connes--Landi deformations of commutative spectral triples are almost-commutative in the general, topologically non-trivial sense.

  16. Stabilization of collagen-model, triple-helical peptides for in vitro and in vivo applications.

    Science.gov (United States)

    Bhowmick, Manishabrata; Fields, Gregg B

    2013-01-01

    The triple-helical structure of collagen has been accurately reproduced in numerous chemical and recombinant model systems. Triple-helical peptides and proteins have found application for dissecting collagen-stabilizing forces, isolating receptor- and protein-binding sites in collagen, mechanistic examination of collagenolytic proteases, and development of novel biomaterials. Introduction of native-like sequences into triple-helical constructs can reduce the thermal stability of the triple-helix to below that of the physiological environment. In turn, incorporation of nonnative amino acids and/or templates can enhance triple-helix stability. We presently describe approaches by which triple-helical structure can be modulated for use under physiological or near-physiological conditions.

  17. A first-order dynamical model of hierarchical triple stars and its application

    CERN Document Server

    Xu, Xingbo; Fu, Yanning

    2015-01-01

    For most hierarchical triple stars, the classical double two-body model of zeroth-order cannot describe the motions of the components under the current observational accuracy. In this paper, Marchal's first-order analytical solution is implemented and a more efficient simplified version is applied to real triple stars. The results show that, for most triple stars, the proposed first-order model is preferable to the zeroth-order model either in fitting observational data or in predicting component positions.

  18. Outcome of Inhaler Withdrawal in Patients Receiving Triple Therapy for COPD

    OpenAIRE

    Kim, Sae Ahm; Lee, Ji-Hyun; Kim, Eun-Kyung; Kim, Tae-Hyung; Kim, Woo Jin; Lee, Jin Hwa; Yoon, Ho Il; Baek, Seunghee; Lee, Jae Seung; Oh, Yeon-Mok; Lee, Sang-Do

    2015-01-01

    Background The purpose of this study was to document outcomes following withdrawal of a single inhaler (step-down) in chronic obstructive pulmonary disease (COPD) patients on triple therapy (long-acting muscarinic antagonist and a combination of long-acting β2-agonists and inhaled corticosteroid), which a common treatment strategy in clinical practice. Methods Through a retrospective observational study, COPD patients receiving triple therapy over 2 years (triple group; n=109) were compared w...

  19. Deguelin action involves c-Met and EGFR signaling pathways in triple negative breast cancer cells.

    Directory of Open Access Journals (Sweden)

    Rajeshwari Mehta

    Full Text Available BACKGROUND: Treatment of breast cancer patients with antiestrogens and aromatase inhibitor(s or Herceptin have shown significant success in steroid receptor positive or Her-2+ breast cancers respectively. However, choice of treatments for breast cancer patients with negative status for estrogen, progesterone receptors and HER2/neu is limited. As a result, search for appropriate therapy regimen for these triple negative breast cancers (TNBC has become a major focus of investigations for many laboratories. Recently, Deguelin, a natural product isolated from African plant Mundulea sericea (Leguminossae has shown both antiproliferative actions in various cancers including breast as well as chemoprenventive activity against carcinogen induced experimental cancers. In this report we evaluated efficacy and mechanism of action of Deguelin in triple negative breast cancer cell lines. METHODS/FINDINGS: In vitro, Deguelin in a dose and time dependent manner inhibited the growth of MDA-MB-231, MDA-MB-468, BT-549 and BT-20 cells. Deguelin (2 or 4 mg/kg body weight, when injected intraperitoneally, reduced the in vivo tumor growth of MDA-MB-231 cells transplanted subcutaneously in athymic mice. Moreover it was nontoxic as evident from daily observations on mobility, food and water consumption and comparison of bodyweight and other visceral organ weights with those in control animals at the termination of the study. The western blot analyses and immunostaining studies indicated that the deguelin effects may be mediated through EGFR-PAKT/c-Met p-ERK and NF-κB by down regulating their downstream targets such as p-STAT3, c-Myc, Survivin. CONCLUSION/SIGNIFICANCE: These results suggest that Deguelin may have a significant therapeutic value for the treatment of TNBC patients.

  20. The Geometry of Quantum Lens Spaces: Real Spectral Triples and Bundle Structure

    Energy Technology Data Exchange (ETDEWEB)

    Sitarz, Andrzej, E-mail: andrzej.sitarz@uj.edu.pl [Jagiellonian University, Institute of Physics (Poland); Venselaar, Jan Jitse, E-mail: jvensel1@gwdg.de [Georg-August Universität Göttingen, Mathematisches Institut (Germany)

    2015-12-15

    We study almost real spectral triples on quantum lens spaces, as orbit spaces of free actions of cyclic groups on the spectral geometry on the quantum group SU{sub q}(2). These spectral triples are given by weakening some of the conditions of a real spectral triple. We classify the irreducible almost real spectral triples on quantum lens spaces and we study unitary equivalences of such quantum lens spaces. Applying a useful characterization of principal U(1)-fibrations in noncommutative geometry, we show that all such quantum lens spaces are principal U(1)-fibrations over quantum teardrops.

  1. Pembrolizumab and Ruxolitinib Phosphate in Treating Patients With Metastatic Stage IV Triple Negative Breast Cancer

    Science.gov (United States)

    2017-03-15

    Breast Carcinoma Metastatic in the Bone; Estrogen Receptor Negative; HER2/Neu Negative; Progesterone Receptor Negative; Recurrent Breast Carcinoma; Stage IV Breast Cancer; Triple-Negative Breast Carcinoma

  2. Effect of sterically demanding substituents on the conformational stability of the collagen triple helix.

    Science.gov (United States)

    Erdmann, Roman S; Wennemers, Helma

    2012-10-17

    The effect of sterically demanding groups at proline residues on the conformational stability of the collagen triple helix was examined. The thermal stabilities (T(m) and ΔG) of eight different triple helices derived from collagen model peptides with (4R)- or (4S)-configured amidoprolines bearing either methyl or bulkier tert-butyl groups in the Xaa or Yaa position were determined and served as a relative measure for the conformational stability of the corresponding collagen triple helices. The results show that sterically demanding substituents are tolerated in the collagen triple helix when they are attached to (4R)-configured amidoprolines in the Xaa position or to (4S)-configured amidoprolines in the Yaa position. Structural studies in which the preferred conformation of (4R)- or (4S)-configured amidoproline were overlaid with the Pro and Hyp residues within a crystal structure of collagen revealed that the sterically demanding groups point to the outside of these two triple helices and thereby do not interfere with the formation of the triple helix. In all of the other examined collagen derivatives with lower stability of the triple helices, the acetyl or pivaloyl residues point toward the inside of the triple helix and clash with a residue of the neighboring strand. The results also revealed that unfavorable steric dispositions affect the conformational stability of the collagen triple helix more than unfavorable ring puckers of the proline residues. The results are useful for the design of functionalized collagen based materials.

  3. Performance Characteristics of a New Hybrid Triple Quadrupole Time-of-Flight Tandem Mass Spectrometer

    Science.gov (United States)

    Andrews, Genna L.; Simons, Brigitte L.; Young, J. Bryce; Hawkridge, Adam M.; Muddiman, David C.

    2011-01-01

    The TripleTOF 5600 System, a hybrid triple quadrupole time-of-flight mass spectrometer, was evaluated to explore the key figures of merit in generating peptide and protein identifications which included spectral acquisition rates, data quality, proteome coverage, and biological depth. Employing a Saccharomyces cerevisiae tryptic digest, careful consideration of several performance features demonstrated that the speed of the TripleTOF contributed most to the resultant data. The TripleTOF system was operated with 8, 20, and 50 MS/MS events in an effort to compare to other MS technologies and to demonstrate the abilities of the instrument platform. PMID:21619048

  4. Functional outcome after arthroscopic repair of triple shoulder instability

    Directory of Open Access Journals (Sweden)

    Glaydson Gomes Godinho

    Full Text Available ABSTRACT OBJECTIVE: To evaluate the functional outcomes of patients submitted to arthroscopic repair of triple labral lesion. METHODS: This was an analytical retrospective study of patients who underwent arthroscopic treatment of triple labral lesion from March 2005 to December 2014. Patients with at least one year of postoperative follow-up were included. A total of nine patients were evaluated. The mean age was 32.3 years and the dominant side was affected in five patients. Patients were functionally assessed regarding the range of motion (ROM in elevation, external rotation with the arm close to the body the arm in abduction of 90°, and internal rotation, and by the Carter-Rowe score. The degree of satisfaction was assessed at the end of the follow-up period. RESULTS: Three patients had less than five episodes of instability, four patients had between five and ten episodes, and two patients had more than ten episodes. Seven patients had positive O'Brien test for SLAP lesions and positive apprehension test in abduction and external rotation, and only one patient had apprehension in adduction and internal rotation. Three patients persisted with positive O'Brien test and one with apprehension in abduction and external rotation at the end of follow-up. The range of motion was complete in all cases. The median Carter-Rowe score increased from 40 preoperatively to 90 (p = 0.008. CONCLUSION: The arthroscopic repair of triple labral lesions allows for the restoration of the stability of the glenohumeral joint, achieving excellent functional results.

  5. Intraocular Lens Calcifications After (Triple-) Descemet Membrane Endothelial Keratoplasty.

    Science.gov (United States)

    Schrittenlocher, Silvia; Penier, Marius; Schaub, Friederike; Bock, Felix; Cursiefen, Claus; Bachmann, Björn

    2017-07-01

    To identify incidence of and risk factors for calcifications of intraocular lenses (IOLs) after Descemet membrane endothelial keratoplasty (DMEK). Retrospective cohort study. Retrospective review of charts and slit-lamp images of 564 consecutive patients from the prospective Cologne DMEK database who underwent DMEK in pseudophakic eyes or DMEK in combination with cataract surgery (triple-DMEK) between September 3, 2013 and October 30, 2015 at the Department of Ophthalmology, University of Cologne. IOL calcifications after (triple-)DMEK occurred in 14 patients (2.5%). Visual acuities in affected and unaffected eyes were 0.33 ± 0.24 logMAR and 0.16 ± 0.01 logMAR after 3 months (P < .001) as well as 0.28 ± 0.16 logMAR and 0.13 ± 0.08 logMAR (P < .001) after 6 months, respectively. The proportions of triple-DMEK vs DMEK, the use of SF6 gas vs room air for anterior chamber tamponade, and the presence of hydrophilic vs hydrophobic acrylic IOLs were comparable in affected and unaffected eyes. Patients with IOL calcifications had higher rebubbling rates than patients without. Larger pupil diameters at the time of surgery showed a tendency to slightly larger areas of IOL calcifications. IOL calcifications after anterior chamber gas tamponade in DMEK lead to visual impairment and are associated with the number of rebubblings after DMEK. IOL calcifications also occur in hydrophobic acrylic IOLs. Copyright © 2017 Elsevier Inc. All rights reserved.

  6. Clinical significance of morphologic characteristics in triple negative breast cancer.

    Science.gov (United States)

    Ryu, Dong Won; Jung, Min Jung; Choi, Woo Sik; Lee, Chung Han

    2011-05-01

    No clinically useful target molecule has been identified for triple-negative (TN) breast cancer, i.e., estrogen receptor-negative, progesterone receptor-negative, human epidermal growth factor receptor-2-negative phenotype, and its prognosis is poor. The aim of this study is to clarify the clinical and pathologic characteristics of triple negative breast cancer (TNBC). The study subjects, 87 women with TNBC, were a subset of patients operated at Kosin University Gospel Hospital from January 2000 to December 2005. We examined pathologic characteristics such as tumor necrosis, infiltrating border, lymphocytic infiltration, prominent nucleoli in TNBC. And we studied the correlation between TNBC and several factors related to pathologic morphology. Chi-squared tests were used for statistical analysis. Kaplan-Meier estimates are presented for the survival function, and differences in survival were analyzed using the log rank test. Tumor necrosis was found in 51 patients (58.3%) in TNBC. And infiltrating border was found in 71 patients (81.0%). Also continuous lymphocytic distribution and prominent nucleoli was found in 31 patients (35.7%), 52 patients (59.7%), respectively. No association was detected between pathologic characteristics and other biological markers. Patients with tumor necrosis positive for TNBC didn't show shorter disease-free survival (P = 0.4490) or overall survival (P = 0.979) than patients without tumor necrosis. These findings suggest that pathologic characteristics cannot be used to classify triple-negative breast cancer into only two subtypes with differing prognoses. But because our study is small size study, more abundant patients' dates will be needed to evaluate the morphologic characteristics' predictive role.

  7. Triple oxygen isotope systematics of structurally bonded water in gypsum

    Science.gov (United States)

    Herwartz, Daniel; Surma, Jakub; Voigt, Claudia; Assonov, Sergey; Staubwasser, Michael

    2017-07-01

    The triple oxygen isotopic composition of gypsum mother water (gmw) is recorded in structurally bonded water in gypsum (gsbw). Respective fractionation factors have been determined experimentally for 18O/16O and 17O/16O. By taking previous experiments into account we suggest using 18αgsbw-gmw = 1.0037; 17αgsbw-gmw = 1.00195 and θgsbw-gmw = 0.5285 as fractionation factors in triple oxygen isotope space. Recent gypsum was sampled from a series of 10 ponds located in the Salar de Llamara in the Atacama Desert, Chile. Total dissolved solids (TDS) in these ponds show a gradual increase from 23 g/l to 182 g/l that is accompanied by an increase in pond water 18O/16O. Gsbw falls on a parallel curve to the ambient water from the saline ponds. The offset is mainly due to the equilibrium fractionation between gsbw and gmw. However, gsbw represents a time integrated signal biased towards times of strong evaporation, hence the estimated gmw comprises elevated 18O/16O compositions when compared to pond water samples taken on site. Gypsum precipitation is associated with algae mats in the ponds with lower salinity. No evidence for respective vital effects on the triple oxygen isotopic composition of gypsum hydration water is observed, nor are such effects expected. In principle, the array of δ18Ogsbw vs. 17Oexcess can be used to: (1) provide information on the degree of evaporation during gypsum formation; (2) estimate pristine meteoric water compositions; and (3) estimate local relative humidity which is the controlling parameter of the slope of the array for simple hydrological situations. In our case study, local mining activities may have decreased deep groundwater recharge, causing a recent change of the local hydrology.

  8. Nuclear collective flow from gaussian fits to triple differential distributions

    Energy Technology Data Exchange (ETDEWEB)

    Gosset, J.; Demoulins, M.; Babinet, R.; Cavata, C.; Fanet, H.; L' Hote, D.; Lucas, B.; Poitou, J.; Valette, O. (CEA Centre d' Etudes Nucleaires de Saclay, 91 - Gif-sur-Yvette (France). Dept. de Physique Nucleaire); Lemaire, M.C. (Laboratoire National Saturne, Centre d' Etudes Nucleaires de Saclay, 91 - Gif-sur-Yvette (France)); Alard, J.P.; Augerat, J.; Bastid, N.; Charmensat, P.; Dupieux, P.; Fraysse, L.; Marroncle, J.; Montarou, G.; Parizet, M.J.; Qassoud, D.; Rahmani, A. (Clermont-Ferrand-2 Univ., 63 - Aubiere (France). Lab. de Physique Corpusculaire); Brochard, F.; Gorodetzky, P.; Racca, C. (Strasbourg-1 Univ., 67 (France). Centre de Recherches Nucleaires)

    1990-09-13

    In order to study the nuclear collective flow, the triple differential momentum distributions of charged baryons are fitted to a simple anisotropic gaussian distribution, within an acceptance which removes most of the spectator contribution. The adjusted flow angle and aspect ratios are corrected for systematic errors in the determination of the reaction plane. This method has been tested with Monte Carlo simulations and applied to experimental results and intranuclear cascade simulations of argon-nucleus collisions at 400 MeV per nucleon. (orig.).

  9. Management Options in Triple-Negative Breast Cancer

    Science.gov (United States)

    Minami, Christina A.; Chung, Debra U.; Chang, Helena R.

    2011-01-01

    Notorious for its poor prognosis and aggressive nature, triple-negative breast cancer (TNBC) is a heterogeneous disease entity. The nature of its biological specificity, which is similar to basal-like cancers, tumors arising in BRCA1 mutation carriers, and claudin-low cancers, is currently being explored in hopes of finding the targets for novel biologics and chemotherapeutic agents. In this review, we aim to give a broad overview of the disease’s nomenclature and epidemiology, as well as the basic mechanisms of emerging targeted therapies and their performance in clinical trials to date. PMID:21863131

  10. Polygonal triple (Kotz) osteotomy (over 10 years experience)

    OpenAIRE

    Sen, Cengiz; Gunes, Taner; Erdem, Mehmet; Ozger, Harzem; Tozun, I. Remzi

    2006-01-01

    We evaluated the results of polygonal triple (Kotz) osteotomy for the treatment of acetabular dysplasia over 10 years. This study included 31 hips of 27 patients who had the Kotz osteotomy for acetabular dysplasia. The mean age was 21.5 years. We performed the original Kotz osteotomy for the first 22 hips (group I), while the modified Kotz osteotomy through an intra-pelvic approach without damage to the abductor muscle was applied for the last 9 hips (group II). Patients were evaluated by cli...

  11. Current approaches in treatment of triple-negative breast cancer

    Institute of Scientific and Technical Information of China (English)

    Hanan Ahmed Wahba; Hend Ahmed El-Hadaad

    2015-01-01

    Triple-negative breast cancer (TNBC) is diagnosed more frequently in younger and premenopausal women and is highly prevalent in African American women. TNBC is a term derived from tumors that are characterized by the absence of ER, PgR, and HER2. So patients with TNBC do not beneift from hormonal or trastuzumab-based therapies. TNBCs are biologically aggressive, although some reports suggest that they respond to chemotherapy better than other types of breast cancer, prognosis remains poor. hTis is due to:shortened disease-free interval in the adjuvant and neoadjuvant setting and a more aggressive course in the metastatic setting.

  12. Triple Negative Breast Cancer Team Project — EDRN Public Portal

    Science.gov (United States)

    Triple negative breast cancers (TNBC), comprise 15-20% of breast cancers, and are associated with later stage at diagnosis, increased mortality, and occur more frequently in younger women where mammographic screening is less reliable. TNBCs are more likely to be diagnosed by physical exam than by mammographic screening. There is an unmet clinical need for biomarkers for the early detection of TNBC. Here, we are proposing the development of a plasma-based biomarker panel for the routine screening of women over the age of 40 for TNBC that can be used to identify women for further imaging.

  13. Triple-layer Absorptive Structures for Shock Wave Blast Protection

    Institute of Scientific and Technical Information of China (English)

    2000-01-01

    Triple-layer absorptive structure is designed to reinforce a missile silo against shock wave blasts. An energy-absorbing layer and a cushion layer overlay the circular silo cover made of reinforced concrete. The dynamic stress analysis is performed by ABAQUS/Explicit. The mesoscopic structure of the energy absorbing layer is designed as an assembly of ductile tubes containing crushable cellular ceramics. Combined mesoscopic and macroscopic simulations indicate that the structure can enhance the survivability of a missile silo against blast waves.

  14. Long-term stability test of a triple GEM detector

    CERN Document Server

    Adak, R P; Das, S; Ghosal, D; Ghosh, S K; Mondal, A; Nag, D; Nayak, T K; Patra, R N; Prasad, S K; Raha, S; Sahu, P K; Sahu, S; Swain, S

    2016-01-01

    The main aim of the study is to perform the long-term stability test of gain of the single mask triple GEM detector. A simple method is used for this long- term stability test using a radioactive X-ray source with high activity. The test is continued till accumulation of charge per unit area > 12.0 mC/mm2. The details of the chamber fabrication, the test set-up, the method of measurement and the test results are presented in this paper.

  15. Prevention of tooth discoloration associated with triple antibiotics

    Directory of Open Access Journals (Sweden)

    Bona Kim

    2013-05-01

    Full Text Available Regenerative endodontics has a potential to heal a partially necrotic pulp, which can be beneficial for the continued root development and strengthening of immature teeth. For this purpose, triple antibiotic mixture of ciprofloxacin, metronidazole, and minocycline was recommended as intracanal medicament in an attempt to disinfect the root canal system for revascularization of a tooth with a necrotic pulp. However, discoloration of the tooth was reported after applying this. This case shows the idea for preventing the tooth discoloration using a delivery syringe (SW-O-01, Shinwoo dental to avoid the contact between the clinical crown and the antibiotics.

  16. Noncommutative geometry, Grand Symmetry and twisted spectral triple

    CERN Document Server

    Devastato, Agostino

    2015-01-01

    In the noncommutative geometry approach to the standard model we discuss the possibility to derive the extra scalar field sv- initially suggested by particle physicist to stabilize the electroweak vacuum - from a "grand algebra" that contains the usual standard model algebra. We introduce the Connes-Moscovici twisted spectral triples for the Grand Symmetry model, to cure a technical problem, that is the appearance, together with the field sv, of unbounded vectorial terms. The twist makes these terms bounded, and also permits to understand the breaking making the computation of the Higgs mass compatible with the 126 GeV experimental value.

  17. Research on ambiguity resolution aided with triple difference

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    The ambiguity resolution in the field of GPS is investigated in detail. A new algorithm to resolve the ambiguity is proposed. The algorithm first obtains the floating resolution of the ambiguity aided with triple difference measurement. Decorrelation of searching space is done by reducing the ambiguity covariance matrix's dimension to overcome the possible sick factorization of the matrix brought by Z-transformation. In simulation, the proposed algorithm is compared with least-squares ambiguity decorrelation adjustment (LAMBDA). The result shows that the proposed algorithm is better than LAMBDA because of lesser resolving time, which approximately reduces 20% resolving time. Thus, the proposed algorithm adapts to the high dynamic real-time applications.

  18. Fault Tolerant Air Bubble Sensor using Triple Modular Redundancy Method

    Directory of Open Access Journals (Sweden)

    Kuspriyanto Kuspriyanto

    2013-03-01

    Full Text Available Detection of air bubbles in the blood is important for various medical treatments that use Extracorporeal Blood Circuits (ECBC, such as hemodialysis, hemofiltration and cardio-pulmonary bypass. Therefore a reliable air bubble detector is needed. In this study designed a fault tolerant air bubble detector. Triple Modular Redundancy (TMR method is used on the sensor section. A voter circuit of the TMR will choose one of three sensor output to be processed further. Application of TMR will prevent errors in the detection of air bubbles, especially if the sensor fails to work

  19. Characterization of a Deswapped Triple Mutant Bovine Odorant Binding Protein

    Directory of Open Access Journals (Sweden)

    Roberto Favilla

    2011-04-01

    Full Text Available The stability and functionality of GCC-bOBP, a monomeric triple mutant of bovine odorant binding protein, was investigated, in the presence of denaturant and in acidic pH conditions, by both protein and 1-aminoanthracene ligand fluorescence measurements, and compared to that of both bovine and porcine wild type homologues. Complete reversibility of unfolding was observed, though refolding was characterized by hysteresis. Molecular dynamics simulations, performed to detect possible structural changes of the monomeric scaffold related to the presence of the ligand, pointed out the stability of the β-barrel lipocalin scaffold.

  20. Nonlinear triple-point problems on time scales

    Directory of Open Access Journals (Sweden)

    Douglas R. Anderson

    2004-04-01

    Full Text Available We establish the existence of multiple positive solutions to the nonlinear second-order triple-point boundary-value problem on time scales, $$displaylines{ u^{Delta abla}(t+h(tf(t,u(t=0, cr u(a=alpha u(b+delta u^Delta(a,quad eta u(c+gamma u^Delta(c=0 }$$ for $tin[a,c]subsetmathbb{T}$, where $mathbb{T}$ is a time scale, $eta, gamma, deltage 0$ with $Beta+gamma>0$, $0

  1. Recent results on the hierarchical triple system HD 150136

    Science.gov (United States)

    Gosset, E.; Berger, J. P.; Absil, O.; Le Bouquin, J. B.; Sana, H.; Mahy, L.; De Becker, M.

    2013-06-01

    HD 150136 is a hierarchical triple system, non-thermal radio emitter, made of three O stars totalling some 130 solar masses. The 2.67-day inner orbit is rather well-known. Recent works derived a good approximation for the outer orbit with a period of 3000 days. We report here on interferometric observations that allow us to angularly resolve the outer orbit. First evidences for an astrometric displacement are given. The determination of the outer system orbit gives access to the inclinations of the systems and to the masses, including the one of the O3-O3.5 primary star.

  2. Triple Encrypted Holographic Storage and Digital Holographic System

    Institute of Scientific and Technical Information of China (English)

    ZHU Yi-Chao; ZHANG Jia-Sen; GONG Qi-Huang

    2008-01-01

    We propose a triple encrypted holographic memory containing a digital holographic system. The original image is encrypted using double random phase encryption and stored in a LiNbO3:Fe crystal with shift-multiplexing. Both the reference beams of the memory and the digital holographic system are random phase encoded. We theoretically and experimentally demonstrate the encryption and decryption of multiple images and the results show high quality and good fault tolerance. The total key length of this system is larger than 4.7×1033.

  3. The fantasy of the triple threat in academic dentistry.

    Science.gov (United States)

    Koka, Sreenivas

    2009-01-01

    One of the fond hopes of academic administrators is to assemble a faculty with a core of triple threats: individuals who excel in teaching, research, and patient care. This report describes the quest of one faculty member to achieve this T3 status. Gradually it has become clear that excelling in any of these areas is more than a full-time commitment in itself. Although each experience contributes to the skill set of a professional, a realistic view of excellence means concentrating one's efforts.

  4. 王中之王——Triple H

    Institute of Scientific and Technical Information of China (English)

    刘杰

    2009-01-01

    仅拿出一小会,忘记所有的绰号和俗语。纵观所有数不尽的冠军头衔和比赛。无视他是WWE历史上两个最重要组合的领导者,还有他克服被专家视作永远禁赛的伤痛。你只需要用两个字来概括Triple H: The Game(游戏主宰)。

  5. Eccentricity evolution in hierarchical triple systems with eccentric outer binaries

    CERN Document Server

    Georgakarakos, Nikolaos

    2014-01-01

    We develop a technique for estimating the inner eccentricity in hierarchical triple systems, with the inner orbit being initially circular, while the outer one is eccentric. We consider coplanar systems with well separated components and comparable masses. The derivation of short period terms is based on an expansion of the rate of change of the Runge-Lenz vector. Then, the short period terms are combined with secular terms, obtained by means of canonical perturbation theory. The validity of the theoretical equations is tested by numerical integrations of the full equations of motion.

  6. Noncommutative geometry, Grand Symmetry and twisted spectral triple

    Science.gov (United States)

    Devastato, Agostino

    2015-08-01

    In the noncommutative geometry approach to the standard model we discuss the possibility to derive the extra scalar field sv - initially suggested by particle physicist to stabilize the electroweak vacuum - from a “grand algebra” that contains the usual standard model algebra. We introduce the Connes-Moscovici twisted spectral triples for the Grand Symmetry model, to cure a technical problem, that is the appearance, together with the field sv, of unbounded vectorial terms. The twist makes these terms bounded, and also permits to understand the breaking making the computation of the Higgs mass compatible with the 126 GeV experimental value.

  7. Construction of Spectral Triples Starting from Fredholm Modules

    OpenAIRE

    Schrohe, E.; Walze, M.; Warzecha, J. -M.

    1998-01-01

    Let (A,H,F) be a p-summable Fredholm module where the algebra A= C \\Gamma is generated by a discrete group of unitaries in L(H) which is of polynomial growth r. Then we construct a spectral triple (A,H,D) with F= sign D which is q-summable for each q > p+r+1. In case (A,H,F) is (p,\\infty)-summable we obtain (q,\\infty)-summability of (A,H,D) for each q > p+r+1.

  8. Analysis of the Clinicopathologic Features and Prognosis in Triple-Negative Breast Cancer

    Institute of Scientific and Technical Information of China (English)

    Dehong Yang; Hong Liu; Jing Zhao

    2008-01-01

    OBJECTIVE To investigate the clinical and pathological features,as well as prognosis in triple-negative breast cancer patients.METHODS A total of 509 cases of operable breast cancer from January,2002 to June,2002 treated in the Cancer Hospital of Tianjin Medical University were analyzed.The Her-2,ER and PR status was determined using immunohistochemistry.Of the total cases,one group was identified as triple negative breast cancer,ie defined as ER,PR and Her-2 negative.The other group was nontriple-negative breast cancer.Clinicopathologic features of the groups were compared and 5-year disease-free survival (DFS)analyzed by the Kaplan-Meier method.RESULTS Of the total cases,21.4% (109/509) of cases were found to be triple- negative while 78.6% (400/509) were non-triplenegative.The triple negative group had higher incidence rates than the non-triple-negative group of the medullary type and Grade Ⅲ tumors (P < 0.05).There was no other difference in the clinicopathologic features between the 2 groups.From follow-up to June,2007,21.1% (23/109) of the triple-negative group and 12.7%(51/400) of the non-triple negative group had a local recurrence or distant metastasis,resulting in a significant difference (P < 0.05).In the triple-negative group and non-triple-negative group,5-year DFS were 78.9% and 87.3% respectively.There was a statistically significant difference between the 2 groups (P = 0.031).CONCLUSION Compared with non-triple-negative breast cancer,triple-negative breast cancer patients have an increased likehood of a local recurrence or distant metastasis and a poorer prognosis.

  9. Degree of tumor FDG uptake correlates with proliferation index in triple negative breast cancer.

    Science.gov (United States)

    Tchou, Julia; Sonnad, Seema S; Bergey, Meredith R; Basu, Sandip; Tomaszewski, John; Alavi, Abass; Schnall, Mitchell

    2010-12-01

    2-Deoxy-2-[F-18]fluoro-D-glucose (FDG) uptake may be a useful surrogate marker for proliferation index, but the correlation has not always been clear-cut. Previous research by our group suggests that FDG-positron emission tomography (PET) is sensitive in detecting triple negative breast cancer. We therefore performed a pilot study to test if FDG uptake correlated with proliferation index in women with triple negative cancer. To determine whether proliferation index correlates with metabolic uptake of FDG in women with triple negative breast cancer, we performed a retrospective analysis correlating %Ki67 nuclear stain with tumor maximum standardized uptake values (SUVmax) in a group of 41 women, 22 with triple negative and 19 with non-triple negative breast cancer. As expected, [18F]-PET imaging was significantly more sensitive in detecting triple negative breast cancer than non-triple negative breast cancer, 95.5% vs 68.4% (p = 0.036). In general, SUVmax and %Ki67 nuclear stain values rise as histologic grade worsens. Histologic grade of triple negative breast cancer was more often poorly differentiated than non-triple negative cancer (p = 0.001). SUVmax correlated with %Ki67 nuclear staining in our entire cohort (spearman correlation = 0.485, p = 0.002). Moreover, this significant correlation appeared to be driven primarily by a subset of women with triple negative cancer (spearman correlation = 0.497, p = 0.019). Degree of tumor FDG uptake correlated significantly with proliferation index in women with triple negative breast cancer suggesting a potential role of FDG-PET in treatment response monitoring for this group of women. Future studies are necessary to define the role of PET imaging as a non-invasive means to monitor breast cancer treatment response in the neoadjuvant setting.

  10. Viscous solution of the triple-shock reflection problem

    Science.gov (United States)

    Lau-Chapdelaine, S. S.-M.; Radulescu, M. I.

    2016-09-01

    The reflection of a triple-shock configuration was studied numerically in two dimensions using the Navier-Stokes equations. The flow field was initialized using three shock theory, and the reflection of the triple point on a plane of symmetry was studied. The conditions simulated a stoichiometric methane-oxygen detonation cell at low pressure on time scales preceding ignition when the gas was assumed to be inert. Viscosity was found to play an important role on some shock reflection mechanisms believed to accelerate reaction rates in detonations when time scales are small. A small wall jet was present in the double Mach reflection and increased in size with Reynolds number, eventually forming a small vortex. Kelvin-Helmholtz instabilities were absent, and there was no Mach stem bifurcation at Reynolds numbers corresponding to when the Mach stem had travelled distances on the scale of the induction length. Kelvin-Helmholtz instabilities are found to not likely be a source of rapid reactions in detonations at time scales commensurate with the ignition delay behind the Mach stem.

  11. Direct visualization of protease action on collagen triple helical structure.

    Directory of Open Access Journals (Sweden)

    Gabriel Rosenblum

    Full Text Available Enzymatic processing of extracellular matrix (ECM macromolecules by matrix metalloproteases (MMPs is crucial in mediating physiological and pathological cell processes. However, the molecular mechanisms leading to effective physiological enzyme-ECM interactions remain elusive. Only scant information is available on the mode by which matrix proteases degrade ECM substrates. An example is the enzymatic degradation of triple helical collagen II fragments, generated by the collagenase MMP-8 cleavage, during the course of acute inflammatory conditions by gelatinase B/MMP-9. As is the case for many other matrix proteases, it is not clear how MMP-9 recognizes, binds and digests collagen in this important physiological process. We used single molecule imaging to directly visualize this protease during its interaction with collagen fragments. We show that the initial binding is mediated by the diffusion of the protease along the ordered helix on the collagen (3/4 fragment, with preferential binding of the collagen tail. As the reaction progressed and prior to collagen degradation, gelatin-like morphologies resulting from the denaturation of the triple helical collagen were observed. Remarkably, this activity was independent of enzyme proteolysis and was accompanied by significant conformational changes of the working protease. Here we provide the first direct visualization of highly complex mechanisms of macromolecular interactions governing the enzymatic processing of ECM substrates by physiological protease.

  12. Overlay metrology solutions in a triple patterning scheme

    Science.gov (United States)

    Leray, Philippe; Mao, Ming; Baudemprez, Bart; Amir, Nuriel

    2015-03-01

    Overlay metrology tool suppliers are offering today several options to their customers: Different hardware (Image Based Overlay or Diffraction Based Overlay), different target designs (with or without segmentation) or different target sizes (from 5 um to 30 um). All these variations are proposed to resolve issues like robustness of the target towards process variations, be more representative of the design or increase the density of measurements. In the frame of the development of a triple patterning BEOL scheme of 10 nm node layer, we compare IBO targets (standard AIM, AIMid and multilayer AIMid). The metrology tools used for the study are KLA-Tencor's nextgeneration Archer 500 system (scatterometry- and imaging-based measurement technologies on the same tool). The overlay response and fingerprint of these targets will be compared using a very dense sampling (up to 51 pts per field). The benefit of indie measurements compared to the traditional scribes is discussed. The contribution of process effects to overlay values are compared to the contribution of the performance of the target. Different targets are combined in one measurement set to benefit from their different strengths (performance vs size). The results are summarized and possible strategies for a triple patterning schemes are proposed.

  13. Bridging disparate symptoms of schizophrenia: a triple network dysfunction theory.

    Science.gov (United States)

    Nekovarova, Tereza; Fajnerova, Iveta; Horacek, Jiri; Spaniel, Filip

    2014-01-01

    Schizophrenia is a complex neuropsychiatric disorder with variable symptomatology, traditionally divided into positive and negative symptoms, and cognitive deficits. However, the etiology of this disorder has yet to be fully understood. Recent findings suggest that alteration of the basic sense of self-awareness may be an essential distortion of schizophrenia spectrum disorders. In addition, extensive research of social and mentalizing abilities has stressed the role of distortion of social skills in schizophrenia.This article aims to propose and support a concept of a triple brain network model of the dysfunctional switching between default mode and central executive network (CEN) related to the aberrant activity of the salience network. This model could represent a unitary mechanism of a wide array of symptom domains present in schizophrenia including the deficit of self (self-awareness and self-representation) and theory of mind (ToM) dysfunctions along with the traditional positive, negative and cognitive domains. We review previous studies which document the dysfunctions of self and ToM in schizophrenia together with neuroimaging data that support the triple brain network model as a common neuronal substrate of this dysfunction.

  14. The triple-mode pulsating variable V823 Cassiopeiae

    Science.gov (United States)

    Jurcsik, J.; Szeidl, B.; Váradi, M.; Henden, A.; Hurta, Zs.; Lakatos, B.; Posztobányi, K.; Klagyivik, P.; Sódor, Á.

    2006-01-01

    Using extended multicolour CCD photometry of the triple-mode radial pulsator V823 Cas we studied the properties of the coupling frequencies invoked by nonlinear processes. Our results support that a resonance connection affects the mode coupling behaviour. The P1/P0 period ratio of V823 Cas has an “out of range” value if compared with the period ratios of the known double mode pulsators, while the P2/P1 period ratio is normal. The periods and period ratios cannot be consistently interpreted without conflict with pulsation and/or evolution models. We describe this failure with the suggestion that at present, the periods of V823 Cas are in a transient, resonance affected state, thus do not reflect the true parameters of the object. The anomalous period change behaviour of the fundamental and second overtone modes supports this idea. We have also raised the possibility that a f0 +f2 = 2f1 resonance may act in triple mode pulsators.

  15. Benign metastasizing leiomyoma in triple location: lungs, parametria and appendix

    Science.gov (United States)

    Raś, Renata; Książek, Mariusz; Skręt-Magierło, Joanna; Kąziołka, Wojciech; Fudali, Ludmiła; Filipowska, Justyna; Skręt, Andrzej

    2016-01-01

    Benign metastasizing leiomyoma (BML) usually are situated in one organ, most often in lungs. BML patients typically have a history of uterine leiomyoma treated with hysterectomy, myomectomy or subtotal hysterectomy. The aim of the study was to present the case of a 53-year-old woman with triple location in the lungs, parametria and appendix. She had undergone a myomectomy 26 years earlier. In 2015, she was admitted to the surgical department because of abdominal pain, whereupon a cholecystectomy was performed. CT scans showed pelvic mass with pulmonary metastasis. Upon discharge the patient was referred to the Gynecology Clinic, where a laparotomy was performed. The intraoperative findings were: 1) uterus with multiple leiomyomas, 2) four tumors in the parametria, 3) tumor connected to the appendix. A subtotal hysterectomy, with a bilateral salpingo-oophorectomy, removal of the tumors from the parametria and appendectomy was performed. Pathology confirmed the diagnosis based on morphology and immunohistochemical staining (strongly positive for estrogen receptors and SMA, while Ki67 was very low, below 1%). Upon postoperative recovery, the patient was referred to the Thoracic Surgery Department. During the thoracotomy, multiple nodes, surrounded by lung parenchyma, were revealed. Wedge resection was performed, for localized pulmonary lesions, and sent for pathological examination. The final pathological diagnosis was benign metastasizing leiomyomatosis. In conclusion, the triple location of BML could possibly be a result of a parallel different metastasizing mechanism, although it is impossible to exclude one mechanism, which may be the cause of the metastases in three locations. PMID:27582687

  16. A new high voltage SOILDMOS with triple RESURF structure

    Institute of Scientific and Technical Information of China (English)

    Hu Xiarong; Zhang Bo; Luo Xiaorong; Yao Guoliang; Chen Xi; Li Zhaoji

    2011-01-01

    A novel triple RESURF (T-resurf) SOILDMOS structure is proposed.This structure has a P-type buried layer.Firstly,the depletion layer can extend on both sides of the P-buried layer,serving as a triple RESURF and leading to a high drift doping and a low on-resistance.Secondly,at a high doping concentration of the drift region,the P-layer can reduce high bulk electric field in the drift region and enhance the vertical electric field at the drain side,which results in uniform bulk electric field distributions and an enhanced BV.The proposed structure is used in SOI devices for the first time.The T-resurf SOILDMOS with BV =315 V is obtained by simulation on a 6 μm-thick SOI layer over a 2 μm-thick buried oxide layer,and its Rsp is reduced from 16.5 to 13.8 mΩ.cm2 in comparison with the double RESURF (D-resurf) SOILDMOS.When the thickness of the SOI layer increases,T-resurf SOILDMOS displays a more obvious effect on the enhancement of BV2/Ron.It reduces Rsp by 25% in 400 V SOILDMOS and by 38% in 550 V SOI LDMOS compared with the D-resurf structure.

  17. Bridging disparate symptoms of schizophrenia: a Triple network dysfunction theory

    Directory of Open Access Journals (Sweden)

    Tereza eNekovarova

    2014-05-01

    Full Text Available Schizophrenia is a complex neuropsychiatric disorder with variable symptomatology, traditionally divided into positive and negative symptoms, and cognitive deficits. Yet, the etiology of this disorder has yet to be fully understood.Recent findings suggest that alteration of the basic sense of self-awareness may be an essential distortion of schizophrenia spectrum disorders. In addition, extensive research of social and mentalizing abilities has stressed the role of distortion of social skills in schizophrenia.This article aims to propose and support a concept of triple brain network model of the dysfunctional switching between default mode and central executive network related to the aberrant activity of salience network. This model could represent a unitary mechanism of a wide array of symptom domains present in schizophrenia including the deficit of SELF (self-awareness and self-representation and theory of mind (ToM dysfunctions along with the traditional positive, negative and cognitive domains. We review previous studies which document the dysfunctions of SELF and ToM in schizophrenia together with neuroimaging data elucidating the triple brain network model as a common neuronal substrate of this dysfunction.

  18. "Triple-bottom-line" assessment of urban stormwater projects.

    Science.gov (United States)

    Taylor, A C; Fletcher, T D

    2006-01-01

    New guidelines have been developed and trialled in Australia to assist urban stormwater managers to assess options for projects that aim to improve urban waterway health. These guidelines help users to examine the financial, ecological and social dimensions of projects (i.e., the so-called "triple-bottom-line"). Features of the assessment process described in the guidelines include use of multi criteria analysis, input from technical experts as well as non-technical stakeholders, and provision of three alternative levels of assessment to suit stormwater managers with differing needs and resources. This paper firstly provides a background to the new guidelines and triple-bottom-line assessment. The assessment methodology promoted in the new guidelines is then briefly summarised. This methodology is compared and contrasted with European guidelines from the "SWARD" project that have been primarily developed for assessing the relative sustainability of options involving urban water supply and sewerage assets. Finally, the paper discusses how assessment methodologies that evaluate the financial, ecological and social dimensions of projects can, under some circumstances, be used to evaluate the relative progress of options for urban water management on a journey towards the widely pursued, but vaguely defined goal of "sustainable development".

  19. Conformational preferences of substituted prolines in the collagen triple helix.

    Science.gov (United States)

    Mooney, Sean D; Kollman, Peter A; Klein, Teri E

    2002-07-05

    Researchers have recently questioned the role hydroxylated prolines play in stabilizing the collagen triple helix. To address these issues, we have developed new molecular mechanics parameters for the simulation of peptides containing 4(R)-fluoroproline (Flp), 4(R)-hydroxyproline (Hyp), and 4(R)-aminoproline (Amp). Simulations of peptides based on these parameters can be used to determine the components that stabilize hydroxyproline over proline in the triple helix. The dihedrals F-C-C-N, O-C-C-N, and N-C-C-N were built using a N-beta-ethyl amide model. One nanosecond simulations were performed on the trimers [(Pro-Pro-Gly)(10)](3), [(Pro-Hyp-Gly)(10)](3), [(Pro-Amp-Gly)(10)](3), [(Pro-Amp(1+)-Gly)(10)](3), and [(Pro-Flp-Gly)(10)](3) in explicit solvent. The results of our simulations suggest that pyrrolidine ring conformation is mediated by the strength of the gauche effect and classical electrostatic interactions.

  20. Bridging disparate symptoms of schizophrenia: a triple network dysfunction theory

    Science.gov (United States)

    Nekovarova, Tereza; Fajnerova, Iveta; Horacek, Jiri; Spaniel, Filip

    2014-01-01

    Schizophrenia is a complex neuropsychiatric disorder with variable symptomatology, traditionally divided into positive and negative symptoms, and cognitive deficits. However, the etiology of this disorder has yet to be fully understood. Recent findings suggest that alteration of the basic sense of self-awareness may be an essential distortion of schizophrenia spectrum disorders. In addition, extensive research of social and mentalizing abilities has stressed the role of distortion of social skills in schizophrenia.This article aims to propose and support a concept of a triple brain network model of the dysfunctional switching between default mode and central executive network (CEN) related to the aberrant activity of the salience network. This model could represent a unitary mechanism of a wide array of symptom domains present in schizophrenia including the deficit of self (self-awareness and self-representation) and theory of mind (ToM) dysfunctions along with the traditional positive, negative and cognitive domains. We review previous studies which document the dysfunctions of self and ToM in schizophrenia together with neuroimaging data that support the triple brain network model as a common neuronal substrate of this dysfunction. PMID:24910597

  1. A millisecond pulsar in a stellar triple system

    CERN Document Server

    Ransom, S M; Archibald, A M; Hessels, J W T; Kaplan, D L; van Kerkwijk, M H; Boyles, J; Deller, A T; Chatterjee, S; Schechtman-Rook, A; Berndsen, A; Lynch, R S; Lorimer, D R; Karako-Argaman, C; Kaspi, V M; Kondratiev, V I; McLaughlin, M A; van Leeuwen, J; Rosen, R; Roberts, M S E; Stovall, K

    2014-01-01

    Gravitationally bound three-body systems have been studied for hundreds of years and are common in our Galaxy. They show complex orbital interactions, which can constrain the compositions, masses, and interior structures of the bodies and test theories of gravity, if sufficiently precise measurements are available. A triple system containing a radio pulsar could provide such measurements, but the only previously known such system, B1620-26 (with a millisecond pulsar, a white dwarf, and a planetary-mass object in an orbit of several decades), shows only weak interactions. Here we report precision timing and multi-wavelength observations of PSR J0337+1715, a millisecond pulsar in a hierarchical triple system with two other stars. Strong gravitational interactions are apparent and provide the masses of the pulsar (1.4378(13) Msun, where Msun is the solar mass and the parentheses contain the uncertainty in the final decimal places) and the two white dwarf companions (0.19751(15) Msun and 0.4101(3) Msun), as well ...

  2. High efficiency triple-junction amorphous solar cells

    Science.gov (United States)

    Ishihara, T.; Terazono, S.; Sasaki, H.; Kawabata, K.; Itagaki, T.

    A fabrication technique for high-efficiency triple-junction a-SiGe:H and a-Si:H pin solar cells is described. The interfacial characteristics of the a-SiGe:H pin cell, which is used for the bottom cell, have been improved by inserting graded bandgap layers at both p/i and n/i interfaces. The photoconductivity of the a-SiGe:H film, prepared by diluting the silane and germane discharge with a large amount of H2 gas, has also been improved. For the a-Si:H pin cell, Vocs as high as 0.99 V have been achieved by optimizing deposition conditions for the microc-Si:H p-layer and a-Si:H i-layer. Thickness of each layer in the triple-junction cell has been adjusted to get maximum output current. A cell with conversion efficiency of 10.6 percent has been obtained for a cell size of 100 sq cm.

  3. The triple-mode pulsating variable V823 Cas

    CERN Document Server

    Jurcsik, J; Varadi, M; Henden, A; Hurta, Z; Lakatos, B; Posztobanyi, K; Klagyivik, P; Sodor, A; Hurta, Zs.

    2005-01-01

    Based on extended multicolour CCD photometry of the triple-mode radial pulsator V823 Cas we studied the properties of the coupling frequencies invoked by nonlinear processes. Our results support that a resonance connection as suggested by Antonello & Aikawa (1998) affects the mode coupling behaviour. The P1/P0 period ratio of V823 Cas has an "out of range" value if compared with the period ratios of the known double mode pulsators, while the P2/P1 period ratio is normal. The periods and period ratios cannot be consistently interpret without conflict with pulsation and/or evolution models. We attempt to interpret this failure by the suggestion that at present, the periods of V823 Cas are in a transient, resonance affected state, thus do not reflect the true parameters of the object. The anomalous period change behaviour of the fundamental and second overtone modes supports this idea. We have also raised the possibility that a f0 + f2 = 2f1 resonance may act in triple mode pulsators.

  4. The Triangle Anomaly in Triple-Regge Limits

    CERN Document Server

    White, Alan R

    2001-01-01

    Reggeized gluon interactions due to a single quark loop are studied in the full triple-regge limit and in closely related helicity-flip helicity-pole limits. Triangle diagram reggeon interactions are generated that include local axial-vector effective vertices. It is shown that the massless quark U(1) anomaly is present as an infra-red divergence in the interactions generated by maximally non-planar Feynman diagrams. A multi-regge asymptotic dispersion relation formalism is developed which provides a systematic counting of anomaly contributions. The 48 triple discontinuities in the dispersion relation are of two kinds. The first kind are to one-particle inclusive cross-sections. The second kind contains the anomaly and the multi-regge theory has some special features, including a signature conservation rule. It is shown that the anomaly is present only in multiple discontinuities obtained from the maximally non-planar diagrams and that in the scattering of elementary quarks or gluons the signature and color p...

  5. Pontryagin invariants and integral formulas for Milnor's triple linking number

    CERN Document Server

    DeTurck, Dennis; Komendarczyk, Rafal; Melvin, Paul; Shonkwiler, Clayton; Vela-Vick, David Shea

    2011-01-01

    To each three-component link in the 3-sphere, we associate a geometrically natural characteristic map from the 3-torus to the 2-sphere, and show that the pairwise linking numbers and Milnor triple linking number that classify the link up to link homotopy correspond to the Pontryagin invariants that classify its characteristic map up to homotopy. This can be viewed as a natural extension of the familiar fact that the linking number of a two-component link in 3-space is the degree of its associated Gauss map from the 2-torus to the 2-sphere. When the pairwise linking numbers are all zero, we give an integral formula for the triple linking number analogous to the Gauss integral for the pairwise linking numbers. The integrand in this formula is geometrically natural in the sense that it is invariant under orientation-preserving rigid motions of the 3-sphere, while the integral itself can be viewed as the helicity of a related vector field on the 3-torus.

  6. TGF-β inhibition enhances chemotherapy action against triple-negative breast cancer.

    Science.gov (United States)

    Bhola, Neil E; Balko, Justin M; Dugger, Teresa C; Kuba, María Gabriela; Sánchez, Violeta; Sanders, Melinda; Stanford, Jamie; Cook, Rebecca S; Arteaga, Carlos L

    2013-03-01

    After an initial response to chemotherapy, many patients with triple-negative breast cancer (TNBC) have recurrence of drug-resistant metastatic disease. Studies with TNBC cells suggest that chemotherapy-resistant populations of cancer stem-like cells (CSCs) with self-renewing and tumor-initiating capacities are responsible for these relapses. TGF-β has been shown to increase stem-like properties in human breast cancer cells. We analyzed RNA expression in matched pairs of primary breast cancer biopsies before and after chemotherapy. Biopsies after chemotherapy displayed increased RNA transcripts of genes associated with CSCs and TGF-β signaling. In TNBC cell lines and mouse xenografts, the chemotherapeutic drug paclitaxel increased autocrine TGF-β signaling and IL-8 expression and enriched for CSCs, as indicated by mammosphere formation and CSC markers. The TGF-β type I receptor kinase inhibitor LY2157299, a neutralizing TGF-β type II receptor antibody, and SMAD4 siRNA all blocked paclitaxel-induced IL8 transcription and CSC expansion. Moreover, treatment of TNBC xenografts with LY2157299 prevented reestablishment of tumors after paclitaxel treatment. These data suggest that chemotherapy-induced TGF-β signaling enhances tumor recurrence through IL-8-dependent expansion of CSCs and that TGF-β pathway inhibitors prevent the development of drug-resistant CSCs. These findings support testing a combination of TGF-β inhibitors and anticancer chemotherapy in patients with TNBC.

  7. WEE1 inhibition targets cell cycle checkpoints for triple negative breast cancers to overcome cisplatin resistance.

    Science.gov (United States)

    Zheng, Hongping; Shao, Fangyuan; Martin, Scots; Xu, Xiaoling; Deng, Chu-Xia

    2017-03-06

    Cisplatin is one of the most commonly used therapeutic drugs for cancer therapy, yet prolonged cisplatin treatment frequently results in drug resistance. To enhance therapeutic effect of cisplatin, we conducted a high throughput screening using a kinase library containing 704 kinases against triple negative breast cancer (TNBC) cells. We demonstrated that cisplatin activates ATR, CHK1 and WEE1, which shut down DNA replication and attenuate cisplatin induced-lethality. WEE1 inhibition sensitizes TNBCs and cisplatin resistant cancer cells to cisplatin-induced lethality, because it not only impairs DNA replication checkpoint more profoundly than inhibition of ATR or CHK1, but also defects G2-M cell cycle checkpoint. Finally, we demonstrated that combined cisplatin treatment and WEE1 inhibition synergistically inhibits xenograft cancer growth accompanied by markedly reduced expression of TNBC signature genes. Thus targeting DNA replication and G2-M cell cycle checkpoint simultaneously by cisplatin and WEE1 inhibition is promising for TNBCs treatment, and for overcoming their cisplatin resistance.

  8. Enhanced cell-specific ablation in zebrafish using a triple mutant of Escherichia coli nitroreductase.

    Science.gov (United States)

    Mathias, Jonathan R; Zhang, Zhanying; Saxena, Meera T; Mumm, Jeff S

    2014-04-01

    Transgenic expression of bacterial nitroreductase (NTR) facilitates chemically-inducible targeted cell ablation. In zebrafish, the NTR system enables studies of cell function and cellular regeneration. Metronidazole (MTZ) has become the most commonly used prodrug substrate for eliciting cell loss in NTR-expressing transgenic zebrafish due to the cell-specific nature of its cytotoxic derivatives. Unfortunately, MTZ treatments required for effective cell ablation border toxic effects, and, thus, likely incur undesirable nonspecific effects. Here, we tested whether a triple mutant variant of NTR, previously shown to display improved activity in bacterial assays, can solve this issue by promoting cell ablation in zebrafish using reduced prodrug treatment regimens. We generated several complementary transgenic zebrafish lines expressing either wild-type or mutant NTR (mutNTR) in specific neural cell types, and assayed prodrug-induced cell ablation kinetics using confocal time series imaging and plate reader-based quantification of fluorescent reporters expressed in targeted cell types. The results show that cell ablation can be achieved in mutNTR expressing transgenic lines with markedly shortened prodrug exposure times and/or at lower prodrug concentrations. The mutNTR variant characterized here can circumvent problematic nonspecific/toxic effects arising from low prodrug conversion efficiency, thus increasing the effectiveness and versatility of this selective cell ablation methodology.

  9. WEE1 inhibition targets cell cycle checkpoints for triple negative breast cancers to overcome cisplatin resistance

    Science.gov (United States)

    Zheng, Hongping; Shao, Fangyuan; Martin, Scots; Xu, Xiaoling; Deng, Chu-Xia

    2017-01-01

    Cisplatin is one of the most commonly used therapeutic drugs for cancer therapy, yet prolonged cisplatin treatment frequently results in drug resistance. To enhance therapeutic effect of cisplatin, we conducted a high throughput screening using a kinase library containing 704 kinases against triple negative breast cancer (TNBC) cells. We demonstrated that cisplatin activates ATR, CHK1 and WEE1, which shut down DNA replication and attenuate cisplatin induced-lethality. WEE1 inhibition sensitizes TNBCs and cisplatin resistant cancer cells to cisplatin-induced lethality, because it not only impairs DNA replication checkpoint more profoundly than inhibition of ATR or CHK1, but also defects G2-M cell cycle checkpoint. Finally, we demonstrated that combined cisplatin treatment and WEE1 inhibition synergistically inhibits xenograft cancer growth accompanied by markedly reduced expression of TNBC signature genes. Thus targeting DNA replication and G2-M cell cycle checkpoint simultaneously by cisplatin and WEE1 inhibition is promising for TNBCs treatment, and for overcoming their cisplatin resistance. PMID:28262781

  10. TGF-β inhibition enhances chemotherapy action against triple-negative breast cancer

    Science.gov (United States)

    Bhola, Neil E.; Balko, Justin M.; Dugger, Teresa C.; Kuba, María Gabriela; Sánchez, Violeta; Sanders, Melinda; Stanford, Jamie; Cook, Rebecca S.; Arteaga, Carlos L.

    2013-01-01

    After an initial response to chemotherapy, many patients with triple-negative breast cancer (TNBC) have recurrence of drug-resistant metastatic disease. Studies with TNBC cells suggest that chemotherapy-resistant populations of cancer stem-like cells (CSCs) with self-renewing and tumor-initiating capacities are responsible for these relapses. TGF-β has been shown to increase stem-like properties in human breast cancer cells. We analyzed RNA expression in matched pairs of primary breast cancer biopsies before and after chemotherapy. Biopsies after chemotherapy displayed increased RNA transcripts of genes associated with CSCs and TGF-β signaling. In TNBC cell lines and mouse xenografts, the chemotherapeutic drug paclitaxel increased autocrine TGF-β signaling and IL-8 expression and enriched for CSCs, as indicated by mammosphere formation and CSC markers. The TGF-β type I receptor kinase inhibitor LY2157299, a neutralizing TGF-β type II receptor antibody, and SMAD4 siRNA all blocked paclitaxel-induced IL8 transcription and CSC expansion. Moreover, treatment of TNBC xenografts with LY2157299 prevented reestablishment of tumors after paclitaxel treatment. These data suggest that chemotherapy-induced TGF-β signaling enhances tumor recurrence through IL-8–dependent expansion of CSCs and that TGF-β pathway inhibitors prevent the development of drug-resistant CSCs. These findings support testing a combination of TGF-β inhibitors and anticancer chemotherapy in patients with TNBC. PMID:23391723

  11. Interaction of collagen triple-helix with carbon nanotubes: Geometric property of rod-like molecules.

    Science.gov (United States)

    Kuboki, Yoshinori; Terada, Michiko; Kitagawa, Yoshimasa; Abe, Shigeaki; Uo, Motohiro; Watari, Fumio

    2009-01-01

    The interactions between carbon nanotubes and important biomolecules, above all collagen molecules, have not been studied in detail. This situation is partly due to the fact that CNT are solid entities, while most of the biomolecules can be prepared in solution. We used turbidity as a means of evaluating the interaction between CNT and collagen molecules. To a stable suspension of CNT (10 ppm in 0.1% Triton), collagen solution was added to obtain a final concentration of 25 ppm. The degree of aggregation was evaluated by measuring the turbidity of the suspension at 660 nm. It was found that native collagen induced distinct aggregation with CNT, while denaturation of this protein at 60 degrees C for 1 hr deprived the molecules of their ability to aggregate with CNT. Also other globular molecules, albumin and lysozyme, did not induce aggregation of CNT. These results indicate that the rigid rod-like structure of the native collagen triple helix is essential for interaction with CNT to cause aggregation. The mechanisms are considered to be dependent upon geometric properties of rod-like collagen molecules. The findings in this paper will open a new avenue to clarify the detailed mechanism of the interaction between collagen molecules and CNT.

  12. Inhibition of triple-negative breast cancer models by combinations of antibodies to EGFR

    Science.gov (United States)

    Ferraro, Daniela A.; Gaborit, Nadège; Maron, Ruth; Cohen-Dvashi, Hadas; Porat, Ziv; Pareja, Fresia; Lavi, Sara; Lindzen, Moshit; Ben-Chetrit, Nir; Sela, Michael; Yarden, Yosef

    2013-01-01

    Breast tumors lacking expression of human epidermal growth factor receptor 2 (HER2) and the estrogen and the progesterone receptors (triple negative; TNBC) are more aggressive than other disease subtypes, and no molecular targeted agents are currently available for their treatment. Because TNBC commonly displays EGF receptor (EGFR) expression, and combinations of monoclonal antibodies to EGFR effectively inhibit other tumor models, we addressed the relevance of this strategy to treatment of TNBC. Unlike a combination of the clinically approved monoclonal antibodies, cetuximab and panitumumab, which displaced each other and displayed no cooperative effects, several other combinations resulted in enhanced inhibition of TNBC’s cell growth both in vitro and in animals. The ability of certain antibody mixtures to remove EGFR from the cell surface and to promote its intracellular degradation correlated with the inhibitory potential. However, unlike EGF-induced sorting of EGFR to lysosomal degradation, the antibody-induced pathway displayed independence from the intrinsic kinase activity and dimer formation ability of EGFR, and it largely avoided the recycling route. In conclusion, although TNBC clinical trials testing EGFR inhibitors reported lack of benefit, our results offer an alternative strategy that combines noncompetitive antibodies to achieve robust degradation of EGFR and tumor inhibition. PMID:23319610

  13. Arctigenin inhibits STAT3 and exhibits anticancer potential in human triple-negative breast cancer therapy

    Science.gov (United States)

    Shen, Wanxiang; Zhang, Liang; Gu, Xinsheng; Guo, Yang; Tsai, Hsiang-i; Liu, Xuewen; Li, Jian; Zhang, Jingxuan; Li, Shan; Wu, Fuyun; Liu, Ying

    2017-01-01

    Triple-negative breast cancers (TNBCs) are the most aggressive and hard-to-treat breast tumors with poor prognosis, and exploration for novel therapeutic drugs is impending. Arctigenin (Atn), a bioactive lignan isolated from seeds of Arctium lappa L, has been reported to inhibit many cancer types; however, the effect of Atn on TNBC remains unclear. In this study, we demonstrated that Atn decreased proliferation, and induced apoptosis in TNBC cells. Furthermore, we explored the underlying mechanism of Atn inhibition on TNBC cells. Computational docking and affinity assay showed that Atn bound to the SH2 domain of STAT3. Atn inhibited STAT3 binding to genomic DNA by disrupting hydrogen bond linking between DNA and STAT3. In addition, Atn augmented Taxotere®-induced TNBC cell cytotoxicity. TNBC xenograft tests also confirmed the antitumor effect of Atn in vivo. These characteristics render Atn as a promising candidate drug for further development and for designing new effective STAT3 inhibitors. PMID:27861147

  14. Amygdalin Regulates Apoptosis and Adhesion in Hs578T Triple-Negative Breast Cancer Cells.

    Science.gov (United States)

    Lee, Hye Min; Moon, Aree

    2016-01-01

    Amygdalin, D-mandelonitrile-β-D-glucoside-6-β-glucoside, belongs to aromatic cyanogenic glycoside group derived from rosaceous plant seed. Mounting evidence has supported the anti-cancer effects of amygdalin. However, whether amygdalin indeed acts as an anti-tumor agent against breast cancer cells is not clear. The present study aimed to investigate the effect of amygdalin on the proliferation of human breast cancer cells. Here, we show that amygdalin exerted cytotoxic activities on estrogen receptors (ER)-positive MCF7 cells, and MDA-MB-231 and Hs578T triple-negative breast cancer (TNBC) cells. Amygdalin induced apoptosis of Hs578T TNBC cells. Amygdalin downregulated B-cell lymphoma 2 (Bcl-2), upregulated Bcl-2-associated X protein (Bax), activated of caspase-3 and cleaved poly ADP-ribose polymerase (PARP). Amygdalin activated a pro-apoptotic signaling molecule p38 mitogen-activated protein kinases (p38 MAPK) in Hs578T cells. Treatment of amygdalin significantly inhibited the adhesion of Hs578T cells, in which integrin α5 may be involved. Taken together, this study demonstrates that amygdalin induces apoptosis and inhibits adhesion of breast cancer cells. The results suggest a potential application of amygdalin as a chemopreventive agent to prevent or alleviate progression of breast cancer, especially TNBC.

  15. Selective, nontoxic CB(2) cannabinoid o-quinone with in vivo activity against triple-negative breast cancer.

    Science.gov (United States)

    Morales, Paula; Blasco-Benito, Sandra; Andradas, Clara; Gómez-Cañas, María; Flores, Juana María; Goya, Pilar; Fernández-Ruiz, Javier; Sánchez, Cristina; Jagerovic, Nadine

    2015-03-12

    Triple-negative breast cancer (TNBC) represents a subtype of breast cancer characterized by high aggressiveness. There is no current targeted therapy for these patients whose prognosis, as a group, is very poor. Here, we report the synthesis and evaluation of a potent antitumor agent in vivo for this type of breast cancer designed as a combination of quinone/cannabinoid pharmacophores. This new compound (10) has been selected from a series of chromenopyrazolediones with full selectivity for the nonpsychotropic CB2 cannabinoid receptor and with efficacy in inducing death of human TNBC cell lines. The dual concept quinone/cannabinoid was supported by the fact that compound 10 exerts antitumor effect by inducing cell apoptosis through activation of CB2 receptors and through oxidative stress. Notably, it did not show either cytotoxicity on noncancerous human mammary epithelial cells nor toxic effects in vivo, suggesting that it may be a new therapeutic tool for the management of TNBC.

  16. Molecular characteristics and metastasis predictor genes of triple-negative breast cancer: a clinical study of triple-negative breast carcinomas.

    Directory of Open Access Journals (Sweden)

    Wen-Hung Kuo

    Full Text Available BACKGROUND: Triple-negative breast cancer is a subtype of breast cancer with aggressive tumor behavior and distinct disease etiology. Due to the lack of an effective targeted medicine, treatment options for triple-negative breast cancer are few and recurrence rates are high. Although various multi-gene prognostic markers have been proposed for the prediction of breast cancer outcome, most of them were proven clinically useful only for estrogen receptor-positive breast cancers. Reliable identification of triple-negative patients with a favorable prognosis is not yet possible. METHODOLOGY/PRINCIPAL FINDINGS: Clinicopathological information and microarray data from 157 invasive breast carcinomas were collected at National Taiwan University Hospital from 1995 to 2008. Gene expression data of 51 triple-negative and 106 luminal breast cancers were generated by oligonucleotide microarrays. Hierarchical clustering analysis revealed that the majority (94% of triple-negative breast cancers were tightly clustered together carrying strong basal-like characteristics. A 45-gene prognostic signature giving 98% predictive accuracy in distant recurrence of our triple-negative patients was determined using the receiver operating characteristic analysis and leave-one-out cross validation. External validation of the prognostic signature in an independent microarray dataset of 59 early-stage triple-negative patients also obtained statistical significance (hazard ratio 2.29, 95% confidence interval (CI 1.04-5.06, Cox P=0.04, outperforming five other published breast cancer prognostic signatures. The 45-gene signature identified in this study revealed that TGF-β signaling of immune/inflammatory regulation may play an important role in distant metastatic invasion of triple-negative breast cancer. CONCLUSIONS/SIGNIFICANCE: Gene expression data and recurrence information of triple-negative breast cancer were collected and analyzed in this study. A novel set of 45-gene

  17. Alternative Polyadenylation in Triple-Negative Breast Tumors Allows NRAS and c-JUN to Bypass PUMILIO Posttranscriptional Regulation.

    Science.gov (United States)

    Miles, Wayne O; Lembo, Antonio; Volorio, Angela; Brachtel, Elena; Tian, Bin; Sgroi, Dennis; Provero, Paolo; Dyson, Nicholas

    2016-12-15

    Alternative polyadenylation (APA) is a process that changes the posttranscriptional regulation and translation potential of mRNAs via addition or deletion of 3' untranslated region (3' UTR) sequences. To identify posttranscriptional-regulatory events affected by APA in breast tumors, tumor datasets were analyzed for recurrent APA events. Motif mapping of the changed 3' UTR regions found that APA-mediated removal of Pumilio regulatory elements (PRE) was unusually common. Breast tumor subtype-specific APA profiling identified triple-negative breast tumors as having the highest levels of APA. To determine the frequency of these events, an independent cohort of triple-negative breast tumors and normal breast tissue was analyzed for APA. APA-mediated shortening of NRAS and c-JUN was seen frequently, and this correlated with changes in the expression of downstream targets. mRNA stability and luciferase assays demonstrated APA-dependent alterations in RNA and protein levels of affected candidate genes. Examination of clinical parameters of these tumors found those with APA of NRAS and c-JUN to be smaller and less proliferative, but more invasive than non-APA tumors. RT-PCR profiling identified elevated levels of polyadenylation factor CSTF3 in tumors with APA. Overexpression of CSTF3 was common in triple-negative breast cancer cell lines, and elevated CSTF3 levels were sufficient to induce APA of NRAS and c-JUN. Our results support the hypothesis that PRE-containing mRNAs are disproportionately affected by APA, primarily due to high sequence similarity in the motifs utilized by polyadenylation machinery and the PUM complex. Cancer Res; 76(24); 7231-41. ©2016 AACR.

  18. Thrombogenic collagen-mimetic peptides: Self-assembly of triple helix-based fibrils driven by hydrophobic interactions.

    Science.gov (United States)

    Cejas, Mabel A; Kinney, William A; Chen, Cailin; Vinter, Jeremy G; Almond, Harold R; Balss, Karin M; Maryanoff, Cynthia A; Schmidt, Ute; Breslav, Michael; Mahan, Andrew; Lacy, Eilyn; Maryanoff, Bruce E

    2008-06-24

    Collagens are integral structural proteins in animal tissues and play key functional roles in cellular modulation. We sought to discover collagen model peptides (CMPs) that would form triple helices and self-assemble into supramolecular fibrils exhibiting collagen-like biological activity without preorganizing the peptide chains by covalent linkages. This challenging objective was accomplished by placing aromatic groups on the ends of a representative 30-mer CMP, (GPO)(10), as with l-phenylalanine and l-pentafluorophenylalanine in 32-mer 1a. Computational studies on homologous 29-mers 1a'-d' (one less GPO), as pairs of triple helices interacting head-to-tail, yielded stabilization energies in the order 1a' > 1b' > 1c' > 1d', supporting the hypothesis that hydrophobic aromatic groups can drive CMP self-assembly. Peptides 1a-d were studied comparatively relative to structural properties and ability to stimulate human platelets. Although each 32-mer formed stable triple helices (CD) spectroscopy, only 1a and 1b self-assembled into micrometer-scale fibrils. Light microscopy images for 1a depicted long collagen-like fibrils, whereas images for 1d did not. Atomic force microscopy topographical images indicated that 1a and 1b self-organize into microfibrillar species, whereas 1c and 1d do not. Peptides 1a and 1b induced the aggregation of human blood platelets with a potency similar to type I collagen, whereas 1c was much less effective, and 1d was inactive (EC(50) potency: 1a/1b > 1c > 1d). Thus, 1a and 1b spontaneously self-assemble into thrombogenic collagen-mimetic materials because of hydrophobic aromatic interactions provided by the special end-groups. These findings have important implications for the design of biofunctional CMPs.

  19. Alternative Polyadenylation in Triple-Negative Breast Tumors Allows NRAS and c-JUN to Bypass PUMILIO Posttranscriptional Regulation

    Science.gov (United States)

    Miles, Wayne O.; Lembo, Antonio; Volorio, Angela; Brachtel, Elena; Tian, Bin; Sgroi, Dennis; Provero, Paolo; Dyson, Nicholas

    2017-01-01

    Alternative polyadenylation (APA) is a process that changes the posttranscriptional regulation and translation potential of mRNAs via addition or deletion of 3′ untranslated region (3′ UTR) sequences. To identify posttranscriptional-regulatory events affected by APA in breast tumors, tumor datasets were analyzed for recurrent APA events. Motif mapping of the changed 3′ UTR regions found that APA-mediated removal of Pumilio regulatory elements (PRE) was unusually common. Breast tumor subtype–specific APA profiling identified triple-negative breast tumors as having the highest levels of APA. To determine the frequency of these events, an independent cohort of triple-negative breast tumors and normal breast tissue was analyzed for APA. APA-mediated shortening of NRAS and c-JUN was seen frequently, and this correlated with changes in the expression of downstream targets. mRNA stability and luciferase assays demonstrated APA-dependent alterations in RNA and protein levels of affected candidate genes. Examination of clinical parameters of these tumors found those with APA of NRAS and c-JUN to be smaller and less proliferative, but more invasive than non-APA tumors. RT-PCR profiling identified elevated levels of polyadenylation factor CSTF3 in tumors with APA. Overexpression of CSTF3 was common in triple-negative breast cancer cell lines, and elevated CSTF3 levels were sufficient to induce APA of NRAS and c-JUN. Our results support the hypothesis that PRE-containing mRNAs are disproportionately affected by APA, primarily due to high sequence similarity in the motifs utilized by polyadenylation machinery and the PUM complex. PMID:27758885

  20. Software-Enabled Project Management Techniques and Their Relationship to the Triple Constraints

    Science.gov (United States)

    Elleh, Festus U.

    2013-01-01

    This study investigated the relationship between software-enabled project management techniques and the triple constraints (time, cost, and scope). There was the dearth of academic literature that focused on the relationship between software-enabled project management techniques and the triple constraints (time, cost, and scope). Based on the gap…

  1. The effectiveness of lifestyle triple P in the Netherlands: A randomized controlled trial

    NARCIS (Netherlands)

    Gerards, S.M.P.L.; Dagnelie, P.C.; Gubbels, J.S.; Buuren, S. van; Hamers, F.J.M.; Jansen, M.W.J.; Goot, O.H.M. van der; Vries, N.K. de; Sanders, M.R.; Kremers, S.P.J.

    2015-01-01

    Introduction Lifestyle Triple P is a general parenting intervention which focuses on preventing further excessive weight gain in overweight and obese children. The objective of the current study was to assess the effectiveness of the Lifestyle Triple P intervention in the Netherlands. Method We used

  2. Risk of regional recurrence in triple-negative breast cancer patients: a Dutch cohort study

    NARCIS (Netherlands)

    Roozendaal, van Lori M.; Smit, Leonie H.M.; Duijsens, Gaston H.N.M.; Vries, de Bart; Siesling, Sabine; Lobbes, Marc B.I.; Boer, de Maaike; Wilt, de Johannes H.W.; Smidt, Marjolein L.

    2016-01-01

    Triple-negative breast cancer is associated with early recurrence and low survival rates. Several trials investigate the safety of a more conservative approach of axillary treatment in clinically T1-2N0 breast cancer. Triple-negative breast cancer comprises only 15 % of newly diagnosed breast cancer

  3. Nanostructured thin films for multiband-gap silicon triple junction solar cells

    NARCIS (Netherlands)

    Schropp, R.E.I.; Li, H. B. T.; Franken, R.H.; Rath, J.K.; van der Werf, C.H.M.; Schuttauf, J.A.; Stolk, R.L.

    2008-01-01

    By implementing nanostructure in multiband-gap proto-Si/proto-SiGe/nc-Si:H triple junction n–i–p solar cells, a considerable improvement in performance has been achieved. The unalloyed active layers in the top and bottom cell of these triple junction cells are deposited by Hot-Wire CVD. A significan

  4. Temperature-insensitive frequency tripling for generating high-average power UV lasers.

    Science.gov (United States)

    Zhong, Haizhe; Yuan, Peng; Wen, Shuangchun; Qian, Liejia

    2014-02-24

    Aimed for generating high-average power ultraviolet (UV) lasers via third-harmonic generation (THG) consisting of frequency doubling and tripling stages, we numerically and experimentally demonstrate a novel frequency tripling scheme capable of supporting temperature-insensitive phase-matching (PM). Two cascaded tripling crystals, with opposite signs of the temperature derivation of phase-mismatch, are proposed and theoretically studied for improving the temperature-acceptance of PM. The proof-of-principle tripling experiment using two crystals of LBO and BBO shows that the temperature acceptance can be ~1.5 times larger than that of using a single tripling crystal. In addition, the phase shift caused by air dispersion, along with its influence on the temperature-insensitive PM, are also discussed. To illustrate the potential applications of proposed two-crystal tripling design in the high-average-power regime, full numerical simulations for the tripling process, are implemented based on the realistic crystals. The demonstrated two-crystal tripling scheme may provide a promising route to high-average-power THG in the UV region.

  5. Added flexibility in triple axis spectrometers: The two RITAs at Risø

    DEFF Research Database (Denmark)

    Lefmann, K.; McMorrow, D.F.; Rønnow, H.M.

    2000-01-01

    The cold-neutron triple-axis spectrometer RITA-I at Rise has been operational for about three years, and in the near future an improved version, RITA-2 will replace the existing triple-axis instrument TAS7. We review the performance of RITA-1 and the operation modes of its flexible secondary...

  6. Effectiveness of the triple P positive parenting program on parenting: A meta-analysis

    NARCIS (Netherlands)

    Graaf, I. de; Speetjens, P.; Smit, F.; Wolff, M. de; Tavecchio, L.

    2008-01-01

    Triple P is a parenting program intended to prevent and to provide treatment for severe behavioral, emotional, and developmental problems in children. The aim of this meta-analysis was to assess the effectiveness of Triple P Level 4 interventions on parenting styles and parental competency. Level 4

  7. Triple Helix Systems: An Analytical Framework for Innovation Policy and Practice in the Knowledge Society

    Science.gov (United States)

    Ranga, Marina; Etzkowitz, Henry

    2013-01-01

    This paper introduces the concept of Triple Helix systems as an analytical construct that synthesizes the key features of university--industry--government (Triple Helix) interactions into an "innovation system" format, defined according to systems theory as a set of components, relationships and functions. Among the components of Triple…

  8. Triple helix conformation-specific blinking of Cy3 in DNA.

    Science.gov (United States)

    Kawai, Kiyohiko; Maruyama, Atsushi

    2015-03-21

    We report that Cy3 undergoes triple helix conformation-specific blinking in DNA. Blinking patterns were affected by the stabilization of the Hoogsteen base-pair, suggesting that not only the presence but also the fluctuating behaviour of the triple helix can be monitored by the changes in the Cy3 blinking patterns.

  9. Procollagen triple helix assembly: an unconventional chaperone-assisted folding paradigm.

    Science.gov (United States)

    Makareeva, Elena; Leikin, Sergey

    2007-10-10

    Fibers composed of type I collagen triple helices form the organic scaffold of bone and many other tissues, yet the energetically preferred conformation of type I collagen at body temperature is a random coil. In fibers, the triple helix is stabilized by neighbors, but how does it fold? The observations reported here reveal surprising features that may represent a new paradigm for folding of marginally stable proteins. We find that human procollagen triple helix spontaneously folds into its native conformation at 30-34 degrees C but not at higher temperatures, even in an environment emulating Endoplasmic Reticulum (ER). ER-like molecular crowding by nonspecific proteins does not affect triple helix folding or aggregation of unfolded chains. Common ER chaperones may prevent aggregation and misfolding of procollagen C-propeptide in their traditional role of binding unfolded polypeptide chains. However, such binding only further destabilizes the triple helix. We argue that folding of the triple helix requires stabilization by preferential binding of chaperones to its folded, native conformation. Based on the triple helix folding temperature measured here and published binding constants, we deduce that HSP47 is likely to do just that. It takes over 20 HSP47 molecules to stabilize a single triple helix at body temperature. The required 50-200 microM concentration of free HSP47 is not unusual for heat-shock chaperones in ER, but it is 100 times higher than used in reported in vitro experiments, which did not reveal such stabilization.

  10. Micro-photoluminescence of GaAs/AlGaAs triple concentric quantum rings.

    Science.gov (United States)

    Abbarchi, Marco; Cavigli, Lucia; Somaschini, Claudio; Bietti, Sergio; Gurioli, Massimo; Vinattieri, Anna; Sanguinetti, Stefano

    2011-10-31

    A systematic optical study, including micro, ensemble and time resolved photoluminescence of GaAs/AlGaAs triple concentric quantum rings, self-assembled via droplet epitaxy, is presented. Clear emission from localized states belonging to the ring structures is reported. The triple rings show a fast decay dynamics, around 40 ps, which is expected to be useful for ultrafast optical switching applications.

  11. The effectiveness of lifestyle triple P in the Netherlands: A randomized controlled trial

    NARCIS (Netherlands)

    Gerards, S.M.P.L.; Dagnelie, P.C.; Gubbels, J.S.; Buuren, S. van; Hamers, F.J.M.; Jansen, M.W.J.; Goot, O.H.M. van der; Vries, N.K. de; Sanders, M.R.; Kremers, S.P.J.

    2015-01-01

    Introduction Lifestyle Triple P is a general parenting intervention which focuses on preventing further excessive weight gain in overweight and obese children. The objective of the current study was to assess the effectiveness of the Lifestyle Triple P intervention in the Netherlands. Method We used

  12. The effects of post coronary stenting triple antiplatelet therapies on platelet functions

    Institute of Scientific and Technical Information of China (English)

    韩雅玲

    2006-01-01

    Objective To explore the effects of triple antiplatelet therapy on platelet aggregation and activation in patients who underwent coronary stenting. Methods 120 inhospital coronary heart disease patients with coronary stenting were randomized into two groups receiving either triple antiplatelet drugs of aspirin and clopidogrel combined with cilostazol or dual antiplatelet drugs of aspirin and clopidogrel. On the first day after stenting cilostazol

  13. Effectiveness of the triple P positive parenting program on parenting: A meta-analysis

    NARCIS (Netherlands)

    Graaf, I. de; Speetjens, P.; Smit, F.; Wolff, M. de; Tavecchio, L.

    2008-01-01

    Triple P is a parenting program intended to prevent and to provide treatment for severe behavioral, emotional, and developmental problems in children. The aim of this meta-analysis was to assess the effectiveness of Triple P Level 4 interventions on parenting styles and parental competency. Level 4

  14. Effectiveness of the Triple P Positive Parenting Program on Parenting: A Meta-Analysis

    Science.gov (United States)

    de Graaf, Ireen; Speetjens, Paula; Smit, Filip; de Wolff, Marianne; Tavecchio, Louis

    2008-01-01

    Triple P is a parenting program intended to prevent and to provide treatment for severe behavioral, emotional, and developmental problems in children. The aim of this meta-analysis was to assess the effectiveness of Triple P Level 4 interventions on parenting styles and parental competency. Level 4 is an intensive training program of 8-10 sessions…

  15. Software-Enabled Project Management Techniques and Their Relationship to the Triple Constraints

    Science.gov (United States)

    Elleh, Festus U.

    2013-01-01

    This study investigated the relationship between software-enabled project management techniques and the triple constraints (time, cost, and scope). There was the dearth of academic literature that focused on the relationship between software-enabled project management techniques and the triple constraints (time, cost, and scope). Based on the gap…

  16. Statistical thermodynamics of the collagen triple-helix/coil transition. Free energies for amino acid substitutions within the triple-helix.

    Science.gov (United States)

    Doig, Andrew J

    2008-11-27

    Collagen sequences frequently deviate from the most thermally stable (Gly-Pro-Hyp)(n) pattern, with many mutations causing osteogenesis imperfecta (or "brittle bone disease"). The effects of collagen mutations have been studied in short peptides. The analysis of this work is problematic, however, as triple-helices fray from their ends, making the coil/triple-helix equilibrium non-two-state. Here, I develop a statistical thermodynamic model to handle this equilibrium that is applicable to peptides that follow the (G-X-Y)(n) pattern, where Gly is present at every third position and where all three chains are identical. Parameters for substitutions at each position are included, as well as a penalty for initiating triple-helix formation. The model is applied to equilibrium experimental data at 37 degrees C to show that the extension of a triple-helix by a three residue unit stabilizes the triple-helix by 0.76 kcal/mol for Gly-Pro-Hyp and 0.33 kcal/mol for Gly-Pro-Pro. The replacement of Hyp by Arg, Asp, or Trp destabilizes the triple-helix by 1.5, 2.4, and 2.9 kcal/mol, respectively, where the substitution is present once in each chain. The model can thus be used to quantitatively interpret data on collagen peptides, giving free energies that can help rationalize mutations that affect collagen stability, and to design new collagen sequences.

  17. Von Neumann Regularity and Quadratic Conorms in JB*-triples and C*-algebras

    Institute of Scientific and Technical Information of China (English)

    Mar(I)a BURGOS; El Amin KAIDI; Antonio Morales CAMPOY; Antonio M. PERALTA; Maribel RAM(I)REZ

    2008-01-01

    We revise the notion of von Neumann regularity in JB*-triples by finding a new character-isationin terms of the range of the quadratic operator Q(a). We introduce the quadratic conorm of anelement a in a JB*-triple as the minimum reduced modulus of the mapping Q(a). It is shown that thequadratic conorm of a coincides with the infimum of the squares of the points in the triple spectrumof a. It is established that a contractive bijection between JBW*-triples is a triple isomorphism if, andonly if, it preserves quadratic conorms. The continuity of the quadratic conorm and the generalizedinverse are discussed. Some applications to C*-algebras and von Neumann algebras are also studied.

  18. Use and Outcomes of Triple Therapy Among Older Patients With Acute Myocardial Infarction and Atrial Fibrillation

    DEFF Research Database (Denmark)

    Hess, Connie N; Peterson, Eric D; Peng, S Andrew

    2015-01-01

    events (MACE) comprising death, readmission for MI, or stroke; the primary safety outcome was bleeding readmission. Outcomes with dual antiplatelet therapy (DAPT) or triple therapy (DAPT plus warfarin) were compared using Cox proportional hazard modeling with inverse probability-weighted propensity...... adjustment. RESULTS: Among 4,959 patients, 27.6% (n = 1,370) were discharged on triple therapy. Relative to DAPT, patients on triple therapy had a similar risk of MACE (adjusted hazard ratio [HR]: 0.99 [95% confidence interval (CI): 0.86 to 1.16]) but significantly greater risk of bleeding requiring...... analyses comparing triple therapy versus DAPT in patients persistently on warfarin versus those not discharged on warfarin who had not filled a warfarin prescription were similar to our primary findings. CONCLUSIONS: Approximately 1 in 4 older AF patients undergoing PCI for MI were discharged on triple...

  19. Increased sensitivity of BRCA defective triple negative breast tumors to plumbagin through induction of DNA Double Strand Breaks (DSB).

    Science.gov (United States)

    Nair, Rakesh Sathish; Kumar, Jerald Mahesh; Jose, Jedy; Somasundaram, Veena; Hemalatha, Sreelatha K; Sengodan, Satheesh Kumar; Nadhan, Revathy; Anilkumar, Thapasimuthu V; Srinivas, Priya

    2016-05-25

    We have earlier shown that Plumbagin (PB) can induce selective cytotoxicity to BRCA1 defective ovarian cancer cells; however, the effect of this molecule in BRCA1 mutated breast cancers has not been analyzed yet. Here, we report that reactive oxygen species (ROS) induced by PB resulted in DNA DSB and activates downstream signaling by ATR/ATM kinases and subsequent apoptosis. PB reduces DNA- dependent protein kinase (DNA-PK) expression and inhibits NHEJ (Non Homologous End Joining) activity in BRCA1 defective breast cancer cells. Also, PB induces apoptosis in two different BRCA1 conditional knock out murine models: MMTV-Cre; BRCA1(Co/Co) and WAP-Cre; BRCA1(Co/Co), at 2 mg/kg body weight, but 32 mg/kg of carboplatin (CN) was needed to induce apoptosis in them. This is the first study where two different tissue specific promoter driven transgenic mice models with BRCA1 exon 11 deletions are used for preclinical drug testing. The apoptosis induced by PB in HR (Homologous Recombination) defective triple negative BRCA1 mutant cell lines and in mouse models occur by inducing ROS mediated DNA DSB. The toxicity profile as compared with CN in transgenic mice provides evidence for PB's safer disposition as a therapeutic lead in breast cancer drug development.

  20. The triple helix frame for Small and Medium-sized Enterprises for innovation and development of offshore wind energy

    DEFF Research Database (Denmark)

    Brink, Tove; Madsen, Svend Ole

    2016-01-01

    from integrating SMEs in a triple helix context. The triple helix approach with government, university and industry participants typically include larger organisations. The research indicates that SMEs could join the triple helix and both contribute and receive benefit from their presence. The findings...

  1. Insights into the enhanced Ce[triple bond, length as m-dash]N triple bond in the HCe[triple bond, length as m-dash]N molecule.

    Science.gov (United States)

    Pu, Zhen; Yu, Wenjie; Roy, Soumendra K; Li, Chaoyang; Ao, Bingyun; Liu, Tianwei; Shuai, Maobing; Wang, Xuefeng

    2017-03-22

    Herein, an experimental study of the vibrational spectra of HCeN was carried out in solid argon, followed by theoretical investigations of molecular structures and the nature of Ce[triple bond, length as m-dash]N bond. The absorption band at 937.7 cm(-1) with the 1.0311 (14)N/(15)N isotopic shift ratio is characteristic of Ce[triple bond, length as m-dash]N stretching band for HCeN, showing a 94 cm(-1) higher shift relative to that of the diatomic CeN molecule. This large frequency shift indicates a much stronger Ce[triple bond, length as m-dash]N bond in HCeN, which is confirmed by DFT calculations. Qualitative orbital interaction and orbital composition analyses suggest that the addition of the H ligand to the Ce center will activate the 4f valence shell and strengthen the covalent bond between Ce and N, which may contribute to enhance the Ce[triple bond, length as m-dash]N triple bond in the HCeN molecule.

  2. Polygonal triple (Kotz) osteotomy (over 10 years experience).

    Science.gov (United States)

    Sen, Cengiz; Gunes, Taner; Erdem, Mehmet; Ozger, Harzem; Tozun, I Remzi

    2007-06-01

    We evaluated the results of polygonal triple (Kotz) osteotomy for the treatment of acetabular dysplasia over 10 years. This study included 31 hips of 27 patients who had the Kotz osteotomy for acetabular dysplasia. The mean age was 21.5 years. We performed the original Kotz osteotomy for the first 22 hips (group I), while the modified Kotz osteotomy through an intra-pelvic approach without damage to the abductor muscle was applied for the last 9 hips (group II). Patients were evaluated by clinically and radiologically. The average follow-up was 106 months in group I, and 18 months in group II. The Trendelenburg gait was unchanged for four patients in group I and for one patient in group II. The Harris Hip Score improved in all patients postoperatively. Radiographic assesment showed improvement in both groups in terms of the angle of CE, VCE, and Sharp postoperatively(PTrendelenburg gait compared to the original Kotz osteotomy.

  3. Tetraphenylporphyrin as a protein label for triple detection analytical systems

    Directory of Open Access Journals (Sweden)

    Kamila Konopińska

    2015-12-01

    Full Text Available Porphyrins and metalloporphyrins are promising new protein labels that can be detected using multiple techniques; improving the reliability of the analysis and broadening the range of the linear response. Here, we investigate the potential of 5,10,15,20-tetraphenyl-21H,23H-porphyrin (Tpp as a hybrid protein label. The electrochemical and optical properties of porphyrin conjugated with bovine serum albumin (BSA, chicken egg albumin (CEA and immunoglobulin G (IgG were determined and optimal conditions for Tpp-protein conjugation established. Model conjugates of carboxylated Tpp with BSA and short peptides were characterized using differential pulse voltammetry, UV–Vis spectrophotometry and spectrofluorimetry. These results reveal that Tpp is a promising molecule to be used in a triple detection protein labelling system.

  4. Triple-stimulation technique in multifocal neuropathy with conduction block.

    Science.gov (United States)

    Deroide, Nicolas; Uzenot, David; Verschueren, Annie; Azulay, Jean-Philippe; Pouget, Jean; Attarian, Shahram

    2007-05-01

    In patients with multifocal neuropathy with conduction block (CB), CBs located between the root and Erb's point are not detected in nerve conduction studies. We therefore examined whether the triple-stimulation technique (TST) might provide a useful means of detecting CB proximal to Erb's point. Clinical assessments, extensive nerve conduction studies (NCS), conventional transcranial magnetic stimulation, and TST were performed on 10 patients with multifocal motor neuropathy with CB (MMNCB) and 6 patients with Lewis-Sumner syndrome. Conduction blocks located proximal to Erb's point were detected in 9 patients. Of the CBs, 58% were associated with muscle weakness. The use of TST to detect proximal CB improved the sensitivity of the American Association of Neuromuscular and Electrodiagnostic Medicine criteria for definite or probable MMNCB from 60% to 90%. Thus, the TST is a useful means for detection of proximal CB and gives NCS considerable additional diagnostic power.

  5. An overview of triple negative breast cancer for surgical oncologists.

    Science.gov (United States)

    Sharma, Shiva; Barry, Mitchel; Gallagher, David J; Kell, Malcolm; Sacchini, Virgilio

    2015-09-01

    Triple negative breast cancers (TNBCs) represent a distinct subgroup of breast cancers with an immunohistochemical phenotype that is negative for oestrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER-2). The aim of this article is to provide a broad overview of recent developments in the diagnosis and management of TNBC for surgical oncologists. This overview discusses the subtypes of TNBC and the relationship between this type of breast cancer and the BRCA1 gene. In addition, the article explores recent advances in the treatment of TNBC from a surgical, radiation, and medical oncology point of view. Lastly, evolving therapeutic strategies that have potential to enhance outcomes for patients with TNBC are also discussed.

  6. Structure-property-function relationships in triple helical collagen hydrogels

    CERN Document Server

    Tronci, Giuseppe; Russell, Stephen J; Wood, David J

    2012-01-01

    In order to establish defined biomimetic systems, type I collagen was functionalised with 1,3-Phenylenediacetic acid (Ph) as aromatic, bifunctional segment. Following investigation on molecular organization and macroscopic properties, material functionalities, i.e. degradability and bioactivity, were addressed, aiming at elucidating the potential of this collagen system as mineralization template. Functionalised collagen hydrogels demonstrated a preserved triple helix conformation. Decreased swelling ratio and increased thermo-mechanical properties were observed in comparison to state-of-the-art carbodiimide (EDC)-crosslinked collagen controls. Ph-crosslinked samples displayed no optical damage and only a slight mass decrease (~ 4 wt.-%) following 1-week incubation in simulated body fluid (SBF), while nearly 50 wt.-% degradation was observed in EDC-crosslinked collagen. SEM/EDS revealed amorphous mineral deposition, whereby increased calcium phosphate ratio was suggested in hydrogels with increased Ph content...

  7. Recovery by triple junction motion in heavily deformed metals

    DEFF Research Database (Denmark)

    Yu, Tianbo; Hansen, Niels; Huang, Xiaoxu

    2015-01-01

    A number of processes may occur during recovery, which reduce the stored energy and coarsen the structure, paving the way for the nucleation of recrystallization. In this review, recovery is discussed based on the initial deformed structure. Recovery in samples deformed to low-to-medium strains...... is briefly considered, whereas recovery in samples deformed to much higher strains is discussed in more detail. An example is Al, where a new and important recovery mechanism is triple junction motion, which can remove thin lamellae and consequently increase the thickness of neighbouring lamellae....... This recovery mechanism therefore coarsens the structure and causes a gradual transition from a lamellar to a near equiaxed structure preceding recrystallization. This mechanism is discussed in conjunction with structural pinning, which stabilizes the coarsening microstructure, thereby balancing the forces...

  8. Triple inverter pierce oscillator circuit suitable for CMOS

    Science.gov (United States)

    Wessendorf; Kurt O.

    2007-02-27

    An oscillator circuit is disclosed which can be formed using discrete field-effect transistors (FETs), or as a complementary metal-oxide-semiconductor (CMOS) integrated circuit. The oscillator circuit utilizes a Pierce oscillator design with three inverter stages connected in series. A feedback resistor provided in a feedback loop about a second inverter stage provides an almost ideal inverting transconductance thereby allowing high-Q operation at the resonator-controlled frequency while suppressing a parasitic oscillation frequency that is inherent in a Pierce configuration using a "standard" triple inverter for the sustaining amplifier. The oscillator circuit, which operates in a range of 10 50 MHz, has applications for use as a clock in a microprocessor and can also be used for sensor applications.

  9. Distinct microbiological signatures associated with triple negative breast cancer.

    Science.gov (United States)

    Banerjee, Sagarika; Wei, Zhi; Tan, Fei; Peck, Kristen N; Shih, Natalie; Feldman, Michael; Rebbeck, Timothy R; Alwine, James C; Robertson, Erle S

    2015-10-15

    Infectious agents are the third highest human cancer risk factor and may have a greater role in the origin and/or progression of cancers, and related pathogenesis. Thus, knowing the specific viruses and microbial agents associated with a cancer type may provide insights into cause, diagnosis and treatment. We utilized a pan-pathogen array technology to identify the microbial signatures associated with triple negative breast cancer (TNBC). This technology detects low copy number and fragmented genomes extracted from formalin-fixed paraffin embedded archival tissues. The results, validated by PCR and sequencing, define a microbial signature present in TNBC tissue which was underrepresented in normal tissue. Hierarchical clustering analysis displayed two broad microbial signatures, one prevalent in bacteria and parasites and one prevalent in viruses. These signatures demonstrate a new paradigm in our understanding of the link between microorganisms and cancer, as causative or commensal in the tumor microenvironment and provide new diagnostic potential.

  10. Prisoners of War of the Triple Alliance within Kazakhstan

    Directory of Open Access Journals (Sweden)

    Gulzhaukhar K. Kokebayeva

    2015-03-01

    Full Text Available The work studies the problem of the detention of prisoners of war of the Triple Alliance in the camps, located within Kazakhstan. During the first months of war, the Russian authorities treated the prisoners of war in accordance with ‘Convention on the Treatment of the Prisoners of War’, approved by the Emperor of Russia. The content of this document corresponded to the Hague Convention with Respect to the Laws and Customs of War on Land. The major areas of the detention of prisoners of war were Turkestan and Omsk Military Okrug, combining all military institutions of the Steppe Governorate General, including the ones of North-Eastern and Central Kazakhstan. The source base of the research is the materials of Kazakhstan and German archives, the recollections of the former prisoners of war and the published collections of documents and materials.

  11. Triple-Vessel Percutaneous Coronary Revascularization In Situs Inversus Dextrocardia

    Directory of Open Access Journals (Sweden)

    Nikolaos Kakouros

    2010-01-01

    Full Text Available Dextrocardia with situs inversus occurs in approximately one in 10,000 individuals of whom 20% have primary ciliary dyskinesia inherited as an autosomal recessive trait. These patients have a high incidence of congenital cardiac disease but their risk of coronary artery disease is similar to that of the general population. We report what is, to our knowledge, the first case of total triple-vessel coronary revascularization by percutaneous stent implantation in a 79-year-old woman with situs inversus dextrocardia. We describe the successful use of standard diagnostic and interventional guide catheters with counter rotation and transversely inversed image acquisition techniques. The case also highlights that the right precordial pain may represent cardiac ischemia in this population.

  12. Triple F - A Comet Nucleus Sample Return Mission

    Science.gov (United States)

    Kueppers, Michael; Keller, H. U.; Kuehrt, E.; A'Hearn, M. F.; Altwegg, K.; Bertrand, R.; Busemann, H.; Capria, M. T.; Colangeli, L.; Davidsson, B.; hide

    2008-01-01

    The Triple F (Fresh From the Fridge) mission, a Comet Nucleus Sample Return, has been proposed to ESA's Cosmic Vision program. A sample return from a comet enables us to reach the ultimate goal of cometary research. Since comets are the least processed bodies in the solar system, the proposal goes far beyond cometary science topics (like the explanation of cometary activity) and delivers invaluable information about the formation of the solar system and the interstellar molecular cloud from which it formed. The proposed mission would extract three sample cores of the upper 50 cm from three locations on a cometary nucleus and return them cooled to Earth for analysis in the laboratory. The simple mission concept with a touch-andgo sampling by a single spacecraft was proposed as an M-class mission in collaboration with the Russian space agency ROSCOSMOS.

  13. Hybrid Steepest-Descent Methods for Triple Hierarchical Variational Inequalities

    Directory of Open Access Journals (Sweden)

    L. C. Ceng

    2015-01-01

    Full Text Available We introduce and analyze a relaxed iterative algorithm by combining Korpelevich’s extragradient method, hybrid steepest-descent method, and Mann’s iteration method. We prove that, under appropriate assumptions, the proposed algorithm converges strongly to a common element of the fixed point set of infinitely many nonexpansive mappings, the solution set of finitely many generalized mixed equilibrium problems (GMEPs, the solution set of finitely many variational inclusions, and the solution set of general system of variational inequalities (GSVI, which is just a unique solution of a triple hierarchical variational inequality (THVI in a real Hilbert space. In addition, we also consider the application of the proposed algorithm for solving a hierarchical variational inequality problem with constraints of finitely many GMEPs, finitely many variational inclusions, and the GSVI. The results obtained in this paper improve and extend the corresponding results announced by many others.

  14. Triple differential cross sections of magnesium in doubly symmetric geometry

    Science.gov (United States)

    S, Y. Sun; X, Y. Miao; Xiang-Fu, Jia

    2016-01-01

    A dynamically screened three-Coulomb-wave (DS3C) method is applied to study the single ionization of magnesium by electron impact. Triple differential cross sections (TDCS) are calculated in doubly symmetric geometry at incident energies of 13.65, 17.65, 22.65, 27.65, 37.65, 47.65, 57.65, and 67.65 eV. Comparisons are made with experimental data and theoretical predictions from a three-Coulomb-wave function (3C) approach and distorted-wave Born approximation (DWBA). The overall agreement between the predictions of the DS3C model and the DWBA approach with the experimental data is satisfactory. Project supported by the National Natural Science Foundation of China (Grant No. 11274215).

  15. A Study of Secondary Ion Triple Bond Analogues.

    Science.gov (United States)

    1980-08-20

    into the formation of cluster ions have measured secondary energy spectra (35-42] and the effects of surface adsorbed gases on secondary yields [43,44...GeCI’ Cl:Ge 0.13 GaTe Te:GaP 0.1 SnAs a Sn:GaAs 0.08 SiBr+ Br:Si < 0.02 Sicl+ CI:Si < 0.01 SiSb- Sb:Si c GeAs As :Ge d Gap Ge: GaP e InSe - Se:InPh f... GaSe Se:GaAs f GeBr Br:Ge f GeSb Sb :Ge f SiAS Si: GaAs 9 a Not a triple bond analogue b ’to Ge detected, (signal < "cps) c Large SiSb- signal, implant

  16. Application of triple potential step amperometry method for quantitative electroanalysis

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    A novel quantitative electroanalysis method, triple potential step amperometry (TPSA), was developed and explained with an example of nitrobenzene analyzing in water. The selectivity of TPSA was improved by controlling the potential step within a narrow interval and using enzyme-modified electrode, the narrow potential step makes the method avoid most interferents, and enzyme-modified electrode can enhance the response of target substance selectively. The peak area was investigated for quantitative calibration, such as nitrobenzene concentration showing a linear relation with the peak area, with the correlation coefficients being 0.9995. The t-test and F-test were applied to evaluating the reliability of TPSA, the results showed that there was no evidence of systematic error for TPSA, and the method was of no significant difference from CV. The merit of fast detecting and few potential changing times make the TPSA suitably applicable to low-cost automatic monitoring equipments.

  17. Single-, Dual- and Triple-band Frequency Reconfigurable Antenna

    Directory of Open Access Journals (Sweden)

    I. H. Idris

    2014-09-01

    Full Text Available The paper presents a frequency reconfigurable slot dipole antenna. The antenna is capable of being switched between single-band, dual-band or triple-band operation. The antenna incorporates three pairs of pin-diodes which are located within the dipole arms. The antenna was designed to operate at 2.4 GHz, 3.5 GHz and 5.2 GHz using the aid of CST Microwave Studio. The average measured gains are 1.54, 2.92 and 1.89 dBi for low, mid and high band respectively. A prototype was then constructed in order to verify the performance of the device. A good level of agreement was observed between simulation and measurement.

  18. DEINDUSTRIALISASI SEBUAH ANCAMAN KEGAGALAN TRIPLE TRACK STRATEGY PEMBANGUNAN DI INDONESIA

    Directory of Open Access Journals (Sweden)

    P. Eko Prasetyo

    2015-12-01

    Full Text Available SBY government work effort through the triple-track strategy namely pro-growth, pro jobs and pro-poor developments will be doomed to fail because of a deindustrialization inIndonesia. The phenomenon of deindustrialization is characterized by the continued decline of industrial contribution mainly manufacture industrial sektor to the value added, employment, exports and contribution to GDP growth, would obviously be a serious threat to the government in its efforts to achieve economic growth to reduce unemployment and poverty. Industrial sektor at this time was no longer regarded as a leading sektor in the national and regional development, so that if eagerly handled will have a negative impact more and could threaten the stability of the economic development of Indonesia.

  19. Towards the characterization of an in vitro triple co-culture intestine cell model for permeability studies.

    Science.gov (United States)

    Araújo, Francisca; Sarmento, Bruno

    2013-12-15

    Caco-2 based cell models have been the gold standard in vitro method to study intestinal drug permeability, despite the absence of many important features with major influence in the drug absorption mechanism. In the present work, a triple co-culture comprising Caco-2, HT29-MTX and Raji B cells was established to mimic in a closely way the human intestinal epithelium, presenting the main components in the process of drug absorption, namely the absorptive cells that resemble enterocytes, mucus producers cells and cells able to induce M-cell phenotype on Caco-2 cells. All the three cell lines maintained their function when cultured together with each other being, thus, an asset to new orally administrated drugs development. The seeding ratio of 90:10 between Caco-2 and HT29-MTX showed to be the best to achieve physiological proportions after cells maturation and differentiation in culture. The formation of M-cells phenotype from enterocytes was identified for the first time in a co-culture system comprising Caco-2 and HT29-MTX cells through immunocytochemical techniques. Thus, the triple co-culture model presented in the herein work is a good and reliable alternative to the in vitro methods already existents for the study of drugs permeability. Copyright © 2013 Elsevier B.V. All rights reserved.

  20. Secular chaotic dynamics in hierarchical quadruple systems, with applications to hot Jupiters in stellar binaries and triples

    Science.gov (United States)

    Hamers, Adrian S.; Lai, Dong

    2017-09-01

    Hierarchical quadruple systems arise naturally in stellar binaries and triples that harbour planets. Examples are hot Jupiters (HJs) in stellar triple systems, and planetary companions to HJs in stellar binaries. The secular dynamical evolution of these systems is generally complex, with secular chaotic motion possible in certain parameter regimes. The latter can lead to extremely high eccentricities and, therefore, strong interactions such as efficient tidal evolution. These interactions are believed to play an important role in the formation of HJs through high-eccentricity migration. Nevertheless, a deeper understanding of the secular dynamics of these systems is still lacking. Here, we study in detail the secular dynamics of a special case of hierarchical quadruple systems in either the '2+2' or '3+1' configurations. We show how the equations of motion can be cast in a form representing a perturbed hierarchical three-body system, in which the outer orbital angular-momentum vector is precessing steadily around a fixed axis. In this case, we show that eccentricity excitation can be significantly enhanced when the precession period is comparable to the Lidov-Kozai oscillation time-scale of the inner orbit. This arises from an induced large mutual inclination between the inner and outer orbits driven by the precession of the outer orbit, even if the initial mutual inclination is small. We present a simplified semi-analytic model that describes the latter phenomenon.

  1. Triple helix-forming oligonucleotides conjugated to indolocarbazole poisons direct topoisomerase I-mediated DNA cleavage to a specific site.

    Science.gov (United States)

    Arimondo, P B; Bailly, C; Boutorine, A S; Moreau, P; Prudhomme, M; Sun, J S; Garestier, T; Hélène, C

    2001-01-01

    Topoisomerase I is an ubiquitous DNA-cleaving enzyme and an important therapeutic target in cancer chemotherapy for camptothecins as well as for indolocarbazole antibiotics such as rebeccamycin. To achieve a sequence-specific cleavage of DNA by topoisomerase I, a triple helix-forming oligonucleotide was covalently linked to indolocarbazole-type topoisomerase I poisons. The three indolocarbazole-oligonucleotide conjugates investigated were able to direct topoisomerase I cleavage at a specific site based upon sequence recognition by triplex formation. The efficacy of topoisomerase I-mediated DNA cleavage depends markedly on the intrinsic potency of the drug. We show that DNA cleavage depends also upon the length of the linker arm between the triplex-forming oligonucleotide and the drug. Based on a known structure of the DNA-topoisomerase I complex, a molecular model of the oligonucleotide conjugates bound to the DNA-topoisomerase I complex was elaborated to facilitate the design of a potent topoisomerase I inhibitor-oligonucleotide conjugate with an optimized linker between the two moieties. The resulting oligonucleotide-indolocarbazole conjugate at 10 nM induced cleavage at the triple helix site 2-fold more efficiently than 5 microM of free indolocarbazole, while the other drug-sensitive sites were not cleaved. The rational design of drug-oligonucleotide conjugates carrying a DNA topoisomerase poison may be exploited to improve the efficacy and selectivity of chemotherapeutic cancer treatments by targeting specific genes and reducing drug toxicity.

  2. Triple negative breast cancer therapy with CDK1 siRNA delivered by cationic lipid assisted PEG-PLA nanoparticles.

    Science.gov (United States)

    Liu, Yang; Zhu, Yan-Hua; Mao, Cheng-Qiong; Dou, Shuang; Shen, Song; Tan, Zi-Bin; Wang, Jun

    2014-10-28

    There is no effective clinical therapy yet for triple-negative breast cancer (TNBC) without particular human epidermal growth factor receptor-2, estrogen and progesterone receptor expression. In this study, we report a molecularly targeted and synthetic lethality-based siRNA therapy for TNBC treatment, using cationic lipid assisted poly(ethylene glycol)-b-poly(d,l-lactide) (PEG-PLA) nanoparticles as the siRNA carrier. It is demonstrated that only in c-Myc overexpressed TNBC cells, while not in normal mammary epithelial cells, delivery of siRNA targeting cyclin-dependent kinase 1 (CDK1) with the nanoparticle carrier (NPsiCDK1) induces cell viability decreasing and cell apoptosis through RNAi-mediated CDK1 expression inhibition, indicating the synthetic lethality between c-Myc with CDK1 in TNBC cells. Moreover, systemic delivery of NPsiCDK1 is able to suppress tumor growth in mice bearing SUM149 and BT549 xenograft and cause no systemic toxicity or activate the innate immune response, suggesting the therapeutic promise with such nanoparticles carrying siCDK1 for c-Myc overexpressed triple negative breast cancer.

  3. Triple-negative breast cancer: treatment challenges and solutions

    Directory of Open Access Journals (Sweden)

    Collignon J

    2016-05-01

    Full Text Available Joëlle Collignon,1 Laurence Lousberg,1 Hélène Schroeder,1 Guy Jerusalem,1,21Medical Oncology Department, CHU Sart Tilman Liege, Domaine Universitaire du Sart Tilman, Liege, Belgium; 2University of Liege, Liege, Belgium Abstract: Triple-negative breast cancers (TNBCs are defined by the absence of estrogen and progesterone receptors and the absence of HER2 overexpression. These cancers represent a heterogeneous breast cancer subtype with a poor prognosis. Few systemic treatment options exist besides the use of chemotherapy (CT. The heterogeneity of the disease has limited the successful development of targeted therapy in unselected patient populations. Currently, there are no approved targeted therapies for TNBC. However, intense research is ongoing to identify specific targets and develop additional and better systemic treatment options. Standard adjuvant and neoadjuvant regimens include anthracyclines, cyclophosphamide, and taxanes. Platinum-based CT has been proposed as another CT option of interest in TNBC. We review the role of this therapy in general, and particularly in patients carrying BRCA germ-line mutations. Available data concerning the role of platinum-based CT in TNBC were acquired primarily in the neoadjuvant setting. The routine use of platinum-based CT is not yet recommended by available guidelines. Many studies have reported the molecular characterization of TNBCs. Several actionable targets have been identified. Novel therapeutic strategies are currently being tested in clinical trials based on promising results observed in preclinical studies. These targets include androgen receptor, EGFR, PARP, FGFR, and the angiogenic pathway. We review the recent data on experimental drugs in this field. We also discuss the recent data concerning immunologic checkpoint inhibitors. Keywords: triple-negative breast cancer, molecular subtype, platinum-based chemotherapy, targeted therapy, androgen receptor, BRCA1/2 mutation

  4. Vascular characterisation of triple negative breast carcinomas using dynamic MRI

    Energy Technology Data Exchange (ETDEWEB)

    Li, Sonia P.; Beresford, Mark J.; Ah-See, Mei-Lin W.; Makris, Andreas [Mount Vernon Cancer Centre, Academic Oncology Unit, Northwood, Middlesex (United Kingdom); Padhani, Anwar R.; Taylor, N.J.; Stirling, J.J. [Mount Vernon Hospital, Paul Strickland Scanner Centre, Northwood, Middlesex (United Kingdom); D' Arcy, James A.; Collins, David J. [Royal Marsden NHS Foundation Trust and Institute of Cancer Research, CR UK and EPSRC Cancer Imaging Centre, Sutton, Surrey (United Kingdom)

    2011-07-15

    Triple-negative (ER-/PR-/HER2-) breast carcinomas (TNBC) are aggressive tumours with underexplored imaging features. This study investigates whether their vascular characteristics as assessed by dynamic contrast-enhanced (DCE) and dynamic susceptibility contrast-enhanced (DSC) MRI are distinct from the prognostically more favourable ER+/PR+/HER2- cancers. Patients with primary breast cancer underwent MRI before neoadjuvant chemotherapy and were identified as ER-/PR-/HER2- or ER+/PR+/HER2- from core biopsy specimens. MRI parameters reflecting tissue perfusion, permeability, and extracellular leakage space were measured. Values for inflow transfer constant (K{sup trans}), outflow rate constant (k{sub ep}), leakage space (v{sub e}), area under the gadolinium curve (IAUGC{sub 60}), relative blood volume (rBV) and flow (rBF), and Mean Transit Time (MTT) were compared across receptor status and with known prognostic variables. Thirty seven patients were assessable in total (16 ER-/PR-/HER2-, 21 ER+/PR+/HER2-). Lower v{sub e} (p = 0.001), shorter MTT (p = 0.007) and higher k{sub ep} values (p = 0.044) were observed in TNBC. v{sub e} was lower across all T stages, node-negative (p = 0.004) and low-grade TNBC (p = 0.037). v{sub e} was the best predictor of triple negativity (ROC AUC 0.80). TNBC possess characteristic features on imaging, with lower extracellular space (higher cell density) and higher contrast agent wash-out rate (higher vascular permeability) suggesting a distinctive phenotype detectable by MRI. (orig.)

  5. Triple-negative breast cancer: new perspectives for targeted therapies

    Directory of Open Access Journals (Sweden)

    Tomao F

    2015-01-01

    Full Text Available Federica Tomao,1 Anselmo Papa,2 Eleonora Zaccarelli,2 Luigi Rossi,2 Davide Caruso,2 Marina Minozzi,2 Patrizia Vici,3 Luigi Frati,4 Silverio Tomao21Department of Gynecology and Obstetrics, “Sapienza” University of Rome, Policlinico “Umberto I”, Rome, 2Department of Medico-Surgical Sciences and Biotechnologies, “Sapienza” University of Rome, Oncology Unit, Istituto Chirurgico Ortopedico Traumatologico, Latina, 3Division of Medical Oncology B, Regina Elena National Cancer Institute, Rome, Italy; 4Department of Molecular Medicine, “Sapienza” University of Rome, Policlinico “Umberto I”, Rome, ItalyAbstract: Breast cancer is a heterogeneous disease, encompassing a large number of entities showing different morphological features and having clinical behaviors. It has became apparent that this diversity may be justified by distinct patterns of genetic, epigenetic, and transcriptomic aberrations. The identification of gene-expression microarray-based characteristics has led to the identification of at least five breast cancer subgroups: luminal A, luminal B, normal breast-like, human epidermal growth factor receptor 2, and basal-like. Triple-negative breast cancer is a complex disease diagnosed by immunohistochemistry, and it is characterized by malignant cells not expressing estrogen receptors or progesterone receptors at all, and human epidermal growth factor receptor 2. Along with this knowledge, recent data show that triple-negative breast cancer has specific molecular features that could be possible targets for new biological targeted drugs. The aim of this article is to explore the use of new drugs in this particular setting, which is still associated with poor prognosis and high risk of distant recurrence and death.Keywords: basal-like breast cancer, estrogen–progesterone receptors, gene-expression microarray, human epidermal growth factor receptor 2, chemotherapy, target therapy

  6. Multilayer Antireflection Coating for Triple Junction Solar Cells

    Institute of Scientific and Technical Information of China (English)

    ZHAN Feng; WANG Hai-Li; HE Ji-Fang; WANG Juan; HUANG She-Song; NI Hai-Qiao; NIU Zhi-Chuan

    2011-01-01

    @@ According to the theory of optical films, we simulate the reflectivity of antireflection coatings(ARCS)for solar cells of Gao.51no.5P/GaAs/Ge based on an optical transfer matrix.In order to provide sufficient consideration of the refractive index dispersion effect of multilayer ARCS, we use multi-dimensional matrix data for reliable simulation.After the reflection curves are obtained, the effective average reflectance Re is introduced to optimize the film system by minimizing Re.Optimization of single layer(A1203), double layer(MgF2/ZnS)and triple layer(MgF2/A12O3/ZnS)ARCS is realized by using this method for space and terrestrial applications.Effects of these ARCS are compared after optimization.These theoretical parameters can be used to guide experiments.%According to the theory of optical films, we simulate the reflectivity of antireflection coatings (ARCs) for solar cells of Ga0.5In0.5P/GaAs/Ge based on an optical transfer matrix. In order to provide sufficient consideration of the refractive index dispersion effect of multilayer ARCs, we use multi-dimensional matrix data for reliable simulation. After the reflection curves are obtained, the effective average reflectance Re is introduced to optimize the film system by minimizing Re. Optimization of single layer (Al2O3), double layer (MgF2/ZnS) and triple layer (MgF2/Al2O3/ZnS) ARCs is realized by using this method for space and terrestrial applications. Effects of these ARCs are compared after optimization. These theoretical parameters can be used to guide experiments.

  7. Persistent, triple-virus co-infections in mosquito cells

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    Malasit Prida

    2010-01-01

    Full Text Available Abstract Background It is known that insects and crustaceans can carry simultaneous, active infections of two or more viruses without showing signs of disease, but it was not clear whether co-infecting viruses occupied the same cells or different cells in common target tissues. Our previous work showed that successive challenge of mosquito cell cultures followed by serial, split-passage resulted in stabilized cultures with 100% of the cells co-infected with Dengue virus (DEN and an insect parvovirus (densovirus (DNV. By addition of Japanese encephalitis virus (JE, we tested our hypothesis that stable, persistent, triple-virus co-infections could be obtained by the same process. Results Using immunocytochemistry by confocal microscopy, we found that JE super-challenge of cells dually infected with DEN and DNV resulted in stable cultures without signs of cytopathology, and with 99% of the cells producing antigens of the 3 viruses. Location of antigens for all 3 viruses in the triple co-infections was dominant in the cell nuclei. Except for DNV, this differed from the distribution in cells persistently infected with the individual viruses or co-infected with DNV and DEN. The dependence of viral antigen distribution on single infection or co-infection status suggested that host cells underwent an adaptive process to accommodate 2 or more viruses. Conclusions Individual mosquito cells can accommodate at least 3 viruses simultaneously in an adaptive manner. The phenomenon provides an opportunity for genetic exchange between diverse viruses and it may have important medical and veterinary implications for arboviruses.

  8. Triple negative breast cancer: adjuvant chemotherapy effect on survival.

    Science.gov (United States)

    Steponaviciene, L; Lachej-Mikeroviene, N; Smailyte, G; Aleknavicius, E; Meskauskas, R; Didziapetriene, J

    2011-01-01

    The purpose of this study was to evaluate the overall survival of patients with triple negative breast cancer and the impact of different adjuvant chemotherapy regimens on survival. The study group consisted of 99 breast cancer patients with immunohistochemically confirmed triple negative breast cancer. The impact of various factors as well as the impact of different chemotherapy regimens on survival was evaluated. The overall survival of breast cancer patients was 97.0% (95% CI 90.9-99.0), 84.9% (95% CI 76.1-90.6) and 66.5% (95% CI 55.5-75.3) 10, 30 and 60 months after diagnosis, respectively. Univariate analysis demonstrated that the following were significant risk factors for breast cancer patients survival: patient's age, stage of disease, tumour size, lymph node status, type of surgery and chemotherapy. Better survival was related to younger patients' age, smaller tumour size, lower stage of disease, no lymph nodes involvement. Survival rates were higher among patients who received adjuvant chemotherapy and underwent quadrantectomy. In the multivariate statistical analysis the significant independent prognostic variables influencing survival were lymph node status and adjuvant chemotherapy. Survival rates of the patients, who received adjuvant anthracycline containing chemotherapy were higher, than those in non-anthracycline containing treatment group, but the difference was not statistically significant. Patients who had lymph node status N2-3 and those who did not receive adjuvant chemotherapy showed worse prognosis and survival than other patients. The impact of chemotherapy type (anthracycline containing or non-anthracycline containing) on patients survival was not statistically significant.

  9. Amor: Investigating The Triple Asteroid System 2001 SN263

    Science.gov (United States)

    Jones, T.; Bellerose, Julie; Lee, P.; Prettyman, T.; Lawrence, D.; Smith, P.; Gaffey, M.; Nolan, M.; Goldsten, J.; Thomas, P.; Veverka, J.; Farquhar, R.; Heldmann, J.; Reddy, V.; Williams, B.; Chartres, J.; DeRosee, R.; Dunham, D.

    2010-10-01

    The Amor mission will rendezvous and land at the triple Near-Earth Asteroid system (153591) 2001 SN263 and execute detailed, in-situ science investigations. The spacecraft reaches 2001 SN263 by using a two-year ΔVEGA (ΔV-Earth Gravity Assist) trajectory with a relatively low launch C3 of 33.5 km2/s2. Rendezvous will enable reconnaissance activities including global and regional imaging, shape modeling, system dynamics, and compositional mapping. After landing, Amor will conduct in-situ imaging (panoramic to microscopic scale) and compositional measurements to include elemental abundance. The main objectives are to 1) establish in-situ the long-hypothesized link between C-type asteroids and the primitive carbonaceous chondrite (CC) meteorites, 2) investigate the nature, origin and evolution of C-type asteroids, and 3) investigate the origin and evolution of a multiple asteroid system. The mission also addresses the distribution of volatiles and organic materials, impact hazards, and resources for future exploration. Amor is managed by NASA Ames Research Center in partnership with Orbital Sciences, KinetX, MDA, and Draper with heritage instruments provided by Ball Aerospace, JHU/APL, and Firestar Engineering. The science team brings experience from NEAR, Hayabusa, Deep Impact, Dawn, LCROSS, Kepler, and Mars missions. In this paper, we describe the science, mission design, and main operational challenges of performing in-situ science at this triple asteroid system. Challenges include landing on the asteroid components, thermal environment, short day-night cycles, and the operation of deployed instruments in a low gravity (10^-5 g) environment.

  10. Initiation of triple therapy maintenance treatment among patients with COPD in the US

    Directory of Open Access Journals (Sweden)

    Simeone JC

    2016-12-01

    Full Text Available Jason C Simeone,1 Rakesh Luthra,2 Shuchita Kaila,2 Xiaoyun Pan,1 Tarun D Bhagnani,1 Jieruo Liu,1 Teresa K Wilcox1 1Real-World Evidence, Evidera, Waltham, MA, 2HEOR Value Demonstration Team, Boehringer Ingelheim Pharmaceuticals, Inc., Ridgefield, CT, USA Background: The Global Initiative for Chronic Obstructive Lung Disease (GOLD recommends triple therapy (long-acting muscarinic receptor antagonists, long-acting beta-2 agonists, and inhaled corticosteroids for patients with only the most severe COPD. Data on the proportion of COPD patients on triple therapy and their characteristics are sparse and dated. Objective 1 of this study was to estimate the proportion of all, and all treated, COPD patients receiving triple therapy. Objective 2 was to characterize those on triple therapy and assess the concordance of triple therapy use with GOLD guidelines. Patients and methods: This retrospective study used claims from the IMS PharMetrics Plus database from 2009 to 2013. Cohort 1 was selected to assess Objective 1 only; descriptive analyses were conducted in Cohort 2 to answer Objective 2. A validated claims-based algorithm and severity and frequency of exacerbations were used as proxies for COPD severity. Results: Of all 199,678 patients with COPD in Cohort 1, 7.5% received triple therapy after diagnosis, and 25.5% of all treated patients received triple therapy. In Cohort 2, 30,493 COPD patients (mean age =64.7 years who initiated triple therapy were identified. Using the claims-based algorithm, 34.5% of Cohort 2 patients were classified as having mild disease (GOLD 1, 40.8% moderate (GOLD 2, 22.5% severe (GOLD 3, and 2.3% very severe (GOLD 4. Using exacerbation severity and frequency, 60.6% of patients were classified as GOLD 1/2 and 39.4% as GOLD 3/4. Conclusion: In this large US claims database study, one-quarter of all treated COPD patients received triple therapy. Although triple therapy is recommended for the most severe COPD patients

  11. Jadomycins inhibit type II topoisomerases and promote DNA damage and apoptosis in multidrug resistant triple negative breast cancer cells.

    Science.gov (United States)

    Hall, Steven R; Toulany, Jay; Bennett, Leah G; Martinez-Farina, Camilo F; Robertson, Andrew W; Jakeman, David L; Goralski, Kerry B

    2017-09-13

    Jadomycins are natural products that kill drug-sensitive and multidrug resistant (MDR) breast cancer cells. To date the cytotoxic activity of jadomycins has never been tested in MDR breast cancer cells that are also triple-negative. Additionally, there is only a rudimentary understanding of how jadomycins cause cancer cell death, which includes the induction of intracellular reactive oxygen species (ROS). We first created a paclitaxel-resistant, triple-negative breast cancer cell line (231-TXL) from drug-sensitive MDA-MB-231 cells (231-CON). Using MTT cell viability measuring assays, jadomycins B, S, and F were found to be equipotent in drug-sensitive 231-CON and MDR 231-TXL cells, and using ROS-detecting assays these jadomycins were determined to increase ROS activity in both cell lines by up to 7.3-fold. Jadomycins caused DNA double strand breaks in 231-CON and 231-TXL cells as measured by γH2AX western blotting. Co-incubation with the antioxidant N-acetyl cysteine (NAC) or pro-oxidant auranofin did not affect jadomycin-mediated DNA damage. Jadomycins induced apoptosis in 231-CON and 231-TXL cells as measured by annexin V affinity assays, a process which was retained when ROS were inhibited. This indicated that jadomycins are capable of inducing MDA-MB-231 apoptotic cell death independently of ROS activity. Using qPCR, western blotting, and direct topoisomerase inhibition assays, it was determined that jadomycins inhibit type II topoisomerases and that jadomycins B and F selectively poison topoisomerase IIβ. We therefore propose novel mechanisms through which jadomycins induce breast cancer cell death independently of ROS-activity, through inhibition or poisoning of type II topoisomerases, and induction of DNA damage and apoptosis. The American Society for Pharmacology and Experimental Therapeutics.

  12. Combining the Sterile Insect Technique with the Incompatible Insect Technique: III-Robust Mating Competitiveness of Irradiated Triple Wolbachia-Infected Aedes albopictus Males under Semi-Field Conditions

    Science.gov (United States)

    Zhang, Dongjing; Lees, Rosemary Susan; Xi, Zhiyong; Bourtzis, Kostas; Gilles, Jeremie R. L.

    2016-01-01

    Combination of the sterile insect technique with the incompatible insect technique is considered to be a safe approach to control Aedes albopictus populations in the absence of an accurate and scalable sex separation system or genetic sexing strain. Our previous study has shown that the triple Wolbachia-infected Ae. albopictus strain (wAlbA, wAlbB and wPip) was suitable for mass rearing and females could be completely sterilized as pupae with a radiation dose of at least 28 Gy. However, whether this radiation dose can influence the mating competitiveness of the triple infected males was still unknown. In this study we aimed to evaluate the effects of irradiation on the male mating competitiveness of the triple infected strain under laboratory and semi-field conditions. The results herein indicate that irradiation with a lower, female-sterilizing dose has no negative impact on the longevity of triple infected males while a reduced lifespan was observed in the wild type males (wAlbA and wAlbB) irradiated with a higher male-sterilizing dose, in small cages. At different sterile: fertile release ratios in small cages, triple-infected males induced 39.8, 81.6 and 87.8% sterility in a wild type female population at 1:1, 5:1 and 10:1 release ratios, respectively, relative to a fertile control population. Similarly, irradiated triple infected males induced 31.3, 70.5 and 89.3% sterility at 1:1, 5:1 and 10:1 release ratios, respectively, again relative to the fertile control. Under semi-field conditions at a 5:1 release ratio, relative to wild type males, the mean male mating competitiveness index of 28 Gy irradiated triple-infected males was significantly higher than 35 Gy irradiated wild type males, while triple infected males showed no difference in mean mating competitiveness to either irradiated triple-infected or irradiated wild type males. An unexpected difference was also observed in the relative male mating competitiveness of the triple infected strain after

  13. A peptide study of the relationship between the collagen triple-helix and amyloid.

    Science.gov (United States)

    Parmar, Avanish S; Nunes, Ana Monica; Baum, Jean; Brodsky, Barbara

    2012-10-01

    Type XXV collagen, or collagen-like amyloidogenic component, is a component of amyloid plaques, and recent studies suggest this collagen affects amyloid fibril elongation and has a genetic association with Alzheimer's disease. The relationship between the collagen triple helix and amyloid fibrils was investigated by studying peptide models, including a very stable triple helical peptide (Pro-Hyp-Gly)₁₀ , an amyloidogenic peptide GNNQQNY, and a hybrid peptide where the GNNQQNY sequence was incorporated between (GPO)(n) domains. Circular dichroism and nuclear magnetic resonance (NMR) spectroscopy showed the GNNQQNY peptide formed a random coil structure, whereas the hybrid peptide contained a central disordered GNNQQNY region transitioning to triple-helical ends. Light scattering confirmed the GNNQQNY peptide had a high propensity to form amyloid fibrils, whereas amyloidogenesis was delayed in the hybrid peptide. NMR data suggested the triple-helix constraints on the GNNQQNY sequence within the hybrid peptide may disfavor the conformational change necessary for aggregation. Independent addition of a triple-helical peptide to the GNNQQNY peptide under aggregating conditions delayed nucleation and amyloid fibril growth. The inhibition of amyloid nucleation depended on the Gly-Xaa-Yaa sequence and required the triple-helix conformation. The inhibitory effect of the collagen triple-helix on an amyloidogenic sequence, when in the same molecule or when added separately, suggests Type XXV collagen, and possibly other collagens, may play a role in regulating amyloid fibril formation.

  14. Triple-layered PLGA/nanoapatite/lauric acid graded composite membrane for periodontal guided bone regeneration.

    Science.gov (United States)

    Jamuna-Thevi, Kalitheertha; Saarani, Nur Najiha; Abdul Kadir, Mohamed Rafiq; Hermawan, Hendra

    2014-10-01

    This paper discusses the successful fabrication of a novel triple-layered poly(lactic-co-glycolic acid) (PLGA)-based composite membrane using only a single step that combines the techniques of solvent casting and thermally induced phase separation/solvent leaching. The resulting graded membrane consists of a small pore size layer-1 containing 10 wt% non-stoichiometric nanoapatite (NAp)+1-3 wt% lauric acid (LA) for fibroblastic cell and bacterial inhibition, an intermediate layer-2 with 20-50 wt% NAp+1 wt% LA, and a large pore size layer-3 containing 30-100 wt% NAp without LA to allow bone cell growth. The synergic effects of 10-30 wt% NAp and 1 wt% LA in the membrane demonstrated higher tensile strength (0.61 MPa) and a more elastic behavior (16.1% elongation at break) in 3 wt% LA added membrane compared with the pure PLGA (0.49 MPa, 9.1%). The addition of LA resulted in a remarkable plasticizing effect on PLGA at 3 wt% due to weak intermolecular interactions in PLGA. The pure and composite PLGA membranes had good cell viability toward human skin fibroblast, regardless of LA and NAp contents.

  15. Irreversible electroporation inhibits pro-cancer inflammatory signaling in triple negative breast cancer cells.

    Science.gov (United States)

    Goswami, Ishan; Coutermarsh-Ott, Sheryl; Morrison, Ryan G; Allen, Irving C; Davalos, Rafael V; Verbridge, Scott S; Bickford, Lissett R

    2017-02-01

    Low-level electric fields have been demonstrated to induce spatial re-distribution of cell membrane receptors when applied for minutes or hours. However, there is limited literature on the influence on cell signaling with short transient high-amplitude pulses typically used in irreversible electroporation (IRE) for cancer treatment. Moreover, literature on signaling pertaining to immune cell trafficking after IRE is conflicting. We hypothesized that pulse parameters (field strength and exposure time) influence cell signaling and subsequently impact immune-cell trafficking. This hypothesis was tested in-vitro on triple negative breast cancer cells treated with IRE, where the effects of pulse parameters on key cell signaling factors were investigated. Importantly, real time PCR mRNA measurements and ELISA protein analyses revealed that thymic stromal lymphopoietin (TSLP) signaling was down regulated by electric field strengths above a critical threshold, irrespective of exposure times spanning those typically used clinically. Comparison with other treatments (thermal shock, chemical poration, kinase inhibitors) revealed that IRE has a unique effect on TSLP. Because TSLP signaling has been demonstrated to drive pro-cancerous immune cell phenotypes in breast and pancreatic cancers, our finding motivates further investigation into the potential use of IRE for induction of an anti-tumor immune response in vivo.

  16. Mihail Sebastian - A Danubian Romanian or the Writer’s Triple Identity

    Directory of Open Access Journals (Sweden)

    Alina Beatrice Chesca

    2012-08-01

    Full Text Available Mihail Sebastian – the Romanian writer of Jewish origin - lived in one of the mosttumultuous and frustrating periods of history, the two world wars, marked by deep social and politicalchanges, and, last but not least, by psychological ones. He was part of a generation who experiencedan age of profound changes, when instability, insecurity and alienation were the factors that led toanalyzing the inner world. Mihail Sebastian was destined to be “the child of suffering”, according to awrong mentality induced against the Semitic community along the time; and thus, his life took theshape of his destiny. Undoubtedly, Joseph Hechter’s (his real name childhood was frustrating, thewriter often evoking it as a troubled childhood, which was to mark him for the rest of his life; MihailSebastian recognized the enormous inferiority complex that the “lost” child had because of hisHebrew identity. That is why, Sebastian aspired to re-create a painful reality through art; his worktried a solution, a version of an autobiography marked by the awareness of loss. As far as his birthplace is concerned (the city of Braila, on the Danube river, for Sebastian it represented a “mythicgeography”. “Jewish, Romanian and Danubian” is how the writer named himself or “the mostRomanian Jewish”. Therefore, we can talk about Sebastian’s triple identity: Romanian, Jewish andwriter of the Danube.

  17. 2-Hydroxychalcone and xanthohumol inhibit invasion of triple negative breast cancer cells.

    Science.gov (United States)

    Kim, Sun Young; Lee, Ik-Soo; Moon, Aree

    2013-05-25

    Breast cancer is estimated as one of the most common causes of cancer death among women. In particular, triple negative breast cancers (TNBCs), which do not express the genes for estrogen/progesterone receptors (ER/PR) and human epidermal growth factor receptor 2 (HER2), have been associated with poor prognosis and metastasis. Chalcones, the biosynthetic precursors of flavonoids present in edible plants, exert cytotoxic and chemopreventive activities. Although mounting evidence suggests the anticancer properties of chalcones, limited information is available regarding the inhibitory effects of chalcones on the aggressiveness of breast cancer cells. The present study aimed to investigate the effects of chalcone and its derivatives on the growth and the invasiveness of TNBC cells. Here, we showed that treatment with chalcone, 2-hydroxychalcone, and xanthohumol for 24h inhibited the growth of MDA-MB-231 cells with IC50 values of 18.1, 4.6, and 6.7 μM, respectively. Similarly, Chalcone, 2-hydroxychalcone, and xanthohumol also exerted cytotoxicity in another TNBC cell line, Hs578T. Neohesperidin dihydrochalcone, 4-methoxychalcone, and hesperidin methylchalcone did not show the cytotoxicity on the MDA-MB-231 cells. Xanthohumol and 2-hydroxychalcone induced apoptosis by Bcl-2 downregulation. Importantly, 2-hydroxychalcone and xanthohumol exerted more potent inhibitory effects on the proliferation, MMP-9 expression and invasive phenotype of MDA-MB-231 than chalcone. These results suggest a potential application of these chalcones as anticancer agents that can alleviate malignant progression of TNBC.

  18. Combined Phosphoproteomics and Bioinformatics Strategy in Deciphering Drug Resistant Related Pathways in Triple Negative Breast Cancer

    Directory of Open Access Journals (Sweden)

    Xinyu Deng

    2014-01-01

    Full Text Available Because of the absence of a clear therapeutic target for triple negative breast cancer (TNBC, conventional chemotherapy is the only available systemic treatment option for these patients. Despite chemotherapy treatment, TNBC patients still have worse prognosis when compared with other breast cancer patients. The study is to investigate unique phosphorylated proteins expressed in chemoresistant TNBC cell lines. In the current study, twelve TNBC cell lines were subjected to drug sensitivity assays against chemotherapy drugs docetaxel, doxorubicin, gemcitabine, and cisplatin. Based on their half maximal inhibitory concentrations, four resistant and two sensitive cell lines were selected for further analysis. The phosphopeptides from these cells were enriched with TiO2 beads and fractionated using strong cation exchange. 1,645 phosphoprotein groups and 9,585 unique phosphopeptides were identified by a high throughput LC-MS/MS system LTQ-Orbitrap. The phosphopeptides were further filtered with Ascore system and 1,340 phosphoprotein groups, 2,760 unique phosphopeptides, and 4,549 unique phosphosites were identified. Our study suggested that differentially phosphorylated Cdk5, PML, AP-1, and HSF-1 might work together to promote vimentin induced epithelial to mesenchymal transition (EMT in the drug resistant cells. EGFR and HGF were also shown to be involved in this process.

  19. The Correlation Between PARP1 and BRCA1 in AR Positive Triple-negative Breast Cancer.

    Science.gov (United States)

    Luo, Jiayan; Jin, Juan; Yang, Fang; Sun, Zijia; Zhang, Wenwen; Shi, Yaqin; Xu, Jing; Guan, Xiaoxiang

    2016-01-01

    Triple-negative breast cancer (TNBC) lacks estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER-2) expression and thus cannot benefit from conventional hormonal or anti-HER2 targeted therapies. Anti-androgen therapy has shown a certain effect on androgen receptor (AR) positive TNBC. The emerging researches have proved that poly (ADP-ribose) polymerase (PARP) inhibitor is effective in BRCA1-deficient breast cancers. We demonstrated that combination of AR antagonist (bicalutamide) and PARP inhibitor (ABT-888) could inhibit cell viability and induce cell apoptosis significantly whatever in vitro or in vivo setting in AR-positive TNBC. Previous studies have proved that both BRCA1 and PARP1 have close connections with AR in prostate cancer. We explored the correlation among AR, PARP1 and BRCA1 in TNBC for the first time. After BRCA1 overexpression, the expression of AR and PARP1 were decreased in mRNA and protein levels. Additionally, AR positively regulated PARP1 while PARP1 also up-regulated AR expression in vitro. We also confirmed BRCA1 expression was negatively correlated with AR and PARP1 in TNBC patients using a tissue microarray with TNBC patient samples. These results suggest that the combination of bicalutamide and PARP inhibitor may be a potential strategy for TNBC patients and merits further evaluation.

  20. The Dimension Six Triple Gluon Operator in Higgs+Jet Observables

    CERN Document Server

    Ghosh, Diptimoy

    2014-01-01

    Recently a lot of progress has been made towards a full classification of new physics effects in Higgs observables by means of effective dimension six operators. Specifically, Higgs production in association with a high transverse momentum jet has been suggested as a way to discriminate between operators that modify the Higgs-top coupling and operators that induce an effective Higgs-gluon coupling---a distinction that is hard to achieve with signal strength measurements alone. With this article we would like to draw attention to another source of new physics in Higgs+jet observables: the triple gluon operator $O_{3g}$ (consisting of three factors of the gluon field strength tensor). We compute the distortions of kinematic distributions in Higgs+jet production at a 14 TeV LHC due to $O_{3g}$ and compare them with the distortions due to dimension six operators involving the Higgs doublet. We find that the transverse momentum, the jet rapidity and the difference between the Higgs and jet rapidity are well suited...