1,722,920 research outputs found
Combinatorial therapy for triple negative breast cancer and the effect of nanoscale surfaces
Full text linkTriple negative breast cancer (TNBC) is a highly aggressive type of breast cancer with urgent clinical need for effective therapies. Resistance to standard clinical therapies with metastatic TNBC pushed the researchers to explore combinatorial therapy regime. A combination of STAT-3 specific inhibitor, reported to act synergistically with metformin in reducing cell growth and inducing apoptosis in TNBCs and agents targeting DNA repair, can produce a new approach to TNBC therapy. Towards this aim, we have generated a combinatorial drug formulation comprising DNA damage repair agents, along with inhibitors for STAT-3 for an optimized effect. The combinatorial formulation includes nifuroxazide, a known STAT-3 inhibitor, and amonafide, an agent known to exert its effect through topoisomerase-II activation pathways. An additional incorporation of pentoxifylline, a methylxanthine derivative known for anti-metastatic effects in breast cancers, could further improve the efficiency. We used drug combination of nifuroxazide, amonafide and pentoxifylline in MDA-MB-231, HCC1806, HCC1143 and BT-549 TNBCs along with normal breast cells, MCF-7 and SkBr3, to find the combinatorial index of the drug cocktail. It was found that combination of pentoxifylline, nifuroxazide and amonafide resulted in a combinatorial index of 0.82 in HCC1806 cells. We also investigated the gene and protein expression effects exerted by combination of drugs responsible to induce synergistic effect and simultaneously suppressing drug resistance through distinct mechanisms of action.
Next, we demonstrate that phenotypically stratified carbon nanoparticle is highly effective in delivering a novel combinatorial triple drug formulation for synergistic regression of TNBC in vitro and in vivo. The combinatorial formulation is comprised of repurposed inhibitors of STAT3 (nifuroxazide), topoisomerase-II-activation-pathway (amonafide) and NFb (pentoxifylline). Synergistic effect of drug combination was established in a panel of TNBC-lines comprising mesenchymal-stem-like, mesenchymal and basal-like cells along with non-TNBC-cells. The delivery of combinatorial drug formulation was achieved using a phenotypically screened carbon nanoparticles for TNBC cell lines. Results indicated a remarkable five-fold improvement (IC50-6.75μM) from the parent drugs with a combinatorial index < 1 in majority of the TNBC cells. Multi-compartmental carbon nanoparticles were then parametrically assessed based on size, charge (positive/negative/neutral) and chemistry (functionalities) to study their likelihood of crossing endocytic barriers from phenotypical standpoint in TNBC lines. Interestingly, a combination of clathrin mediated, energy and dynamin dependent pathways were predominant for sulfonated nanoparticles, whereas pristine and phospholipid particles followed all the investigated endocytic pathways. An exactitude ‘omics’ approach helps to predict that phospholipid encapsulated-particles will predominantly accumulate in TNBC comprising the drug ‘cocktail’. Thus, our efforts might generate a novel triple drug combination as an answer to current TNBC related shortcomings.Submission published under a 24 month embargo labeled 'Closed Access', the embargo will last until 2020-05-01The student, Taylor Kampert, accepted the attached license on 2018-04-25 at 10:13.The student, Taylor Kampert, submitted this Thesis for approval on 2018-04-25 at 10:21.This Thesis was approved for publication on 2018-04-25 at 13:52.DSpace SAF Submission Ingestion Package generated from Vireo submission #12422 on 2018-08-31 at 17:30:16Made available in DSpace on 2018-09-04T20:47:29Z (GMT). No. of bitstreams: 3
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Previous issue date: 2018-04-25Embargo set by: Seth Robbins for item 107452
Lift date: 2020-09-04T20:47:38Z
Reason: Author requested closed access (OA after 2yrs) in Vireo ETD systemEmbargo set by: Seth Robbins for item 107452
Lift date: 2020-09-04T20:50:11Z
Reason: Author requested closed access (OA after 2yrs) in Vireo ETD systemLimited Restriction Lifted for Item 107452 on 2020-09-05T09:15:32Z
Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Elucidating the lack of magnetic order in the heavy-fermion CeCu2Mg
Full text linkMagnetic, transport, and thermal properties of CeCu2Mg are investigated to elucidate the lack of magnetic order in this heavy-fermion compound with a specific heat value, Cmag/T|T→0≈1.2 J/mol K2 and robust effective magnetic moments (μeff≈2.46μB). The lack of magnetic order is attributed to magnetic frustration favored by the hexagonal configuration of the Ce sublattice. In fact, the effect of magnetic field on Cmag/T and residual resistivity ρ0 does not correspond to that of a Fermi liquid (FL) because a broad anomaly appears at Tmax≈1.2 K in Cmag(T)/T, without changing its position up to μ0H=7.5 T. However, the flattening of Cmag/T|T→0 and its magnetic susceptibility χT→0, together with the T2 dependence of ρ(T), reveal a FL behavior for T≤2 K which is also supported by Wilson and Kadowaki-Woods ratios. The unusual coexistence of FL and frustration phenomena can be understood by placing paramagnetic CeCu2Mg in an intermediate section of a frustration-Kondo model. The entropy, Smag, reaches 0.87Rln6 at T≃100 K, with a tendency to approach the expected value Smag=Rln6 of the J=5/2 ground state of Ce3+.Fil: Michor, H.. Technische Universitat Wien; AustriaFil: Sereni, Julian Gustavo Renzo. Comisión Nacional de Energía Atómica. Gerencia del Area de Investigación y Aplicaciones No Nucleares. Gerencia de Física (Centro Atómico Bariloche). División Bajas Temperaturas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Patagonia Norte; ArgentinaFil: Giovannini, M.. CNR-SPIN Corso Perrone, Genova; Italia. Università degli Studi di Genova; ItaliaFil: Kampert, E.. Helmholtz-Zentrum Dresden-Rossendorf; AlemaniaFil: Salamakha, L.. Technische Universitat Wien; AustriaFil: Hilscher, G.. Technische Universitat Wien; AustriaFil: Bauer, E.. Technische Universitat Wien; Austri
Variations on the Author
Full text link“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
Appropriate Similarity Measures for Author Cocitation Analysis
Full text linkWe provide a number of new insights into the methodological discussion about author cocitation analysis. We first argue that the use of the Pearson correlation for measuring the similarity between authors’ cocitation profiles is not very satisfactory. We then discuss what kind of similarity measures may be used as an alternative to the Pearson correlation. We consider three similarity measures in particular. One is the well-known cosine. The other two similarity measures have not been used before in the bibliometric literature. Finally, we show by means of an example that our findings have a high practical relevance.information science;Pearson correlation;cosine;similarity measure;author cocitation analysis
Dispelling the Myths Behind First-author Citation Counts
Full text linkWe conducted a full-scale evaluative citation analysis study of scholars in the XML research field to explore just how different from each other author rankings resulting from different citation counting methods actually are, and to demonstrate the capability of emerging data and tools on the Web in supporting more realistic citation counting methods. Our results contest some common arguments for the continued
use of first-author citation counts in the evaluation of scholars, such as high correlations between author rankings by first-author citation counts and other citation
counting methods, and high costs of using more realistic citation counting methods that are not well-supported by the ISI databases. It is argued that increasingly available digital full text research papers make it possible for citation analysis studies to go beyond what the ISI databases have directly supported and to employ more
sophisticated methods
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