1,720,986 research outputs found
In vitro and in vivo reversal of multidrug resistance in a human leukemia-resistant cell line by mdr1 antisense oligodeoxynucleotides.
A major obstacle to successful cancer chemotherapy is the development of multidrug resistance (MDR) by tumor cells. Overexpression of the mdrl gene product P-glycoprotein (P-170) is characteristic of such cells. In this study, in vitro and in vivo reversion of MDR was attempted in a human leukemia cell line resistant to vincristine (HL-60/Vinc) using an 18-mer mdr1 antisense phosphorothioate oligodeoxynucleotide ([S]ODN) in combination with vincristine. As control of sequence specificity, both sense and scrambled [S]ODNs were used. The ability of these [S]ODNs to reverse MDR was studied in vitro and in severe combined immunodeficient (SCID) mice. In vitro treatment with antisense [S]ODNs restored vincristine sensitivity of HL-60/Vinc cells, whereas no changes in drug sensitivity were observed upon treatment with the sense or scrambled sequence. The in vitro effects correlated with inhibition of P-170 expression in HL-60/Vinc cells exposed to the mdr1 antisense [S]ODNs. In vivo reversal of MDR was obtained in SCID mice given injections of HL-60/Vinc cells and systemically treated with [S]ODNs plus vincristine, as indicated by a significantly prolonged survival of SCID mice that received the combination therapy of mdr1 antisense [S]ODNs + vincristine. Treatments with mdr1 antisense or scrambled [S]ODNs, vincristine, or scrambled [S]ODNs + vincristine had no effect on survival. These results suggest that the use of mdr1 antisense ODNs in combination with standard antineoplastic drugs might be useful in reversing MDR in vitro and in vivo
Omicidi mirati a mezzo drone: brevi riflessioni a margine del caso "Lo Porto" tra diritto penale e diritto internazionale
Quale diritto penale in ipotesi di "vittime collaterali" di drone strike? La sempre maggiore rilevanza che il fenomeno degli omicidi mirati a mezzo drone assume nel contesto internazionale pone la necessità di interrogarsi su come, nell'ordinamento interno, le categorie classiche del diritto penale debbano operare rispetto a fattispecie "peculiari", caratterizzate da una distanza fisica e psichica dal target e dall’esistenza di una “catena di comando” coinvolta, a più livelli, nella singola operazione di omicidio mirato. Si cercherà pertanto di capire, partendo dal caso dell'omicidio di un cittadino italiano per mezzo di droni statunitensi in Pakistan, ma fornendo un contributo di portata più generale, quali soggetti della c.d. "catena di comando" sono coinvolti nelle operazioni; successivamente si concentrerà l'attenzione su come gli sviluppi dogmatici e le elaborazioni giurisprudenziali sul tema dell'elemento soggettivo del reato debbano modellarsi rispetto ad omicidi di vittime collaterali commessi tramite drone, negli ultimi anni oggetto di un uso sempre più frequente alla luce della Global War on Terror, di cui gli Stati Uniti d'America si sono resi promotori
Myocardial Tissue Characterization and Aortic Stenosis
In this issue of JASE, Fijalkowski et al.(1) describe an improvement in myocardial reflectivity induced by aortic valve replacement (AVR) in severe aortic stenosis (AS), using integrated backscatter (IBS) analysis, one of the ultrasonic methods for tissue characterization currently available. Furthermore, they found that IBS parameters have a predictive value for left ventricular (LV) reverse remodeling after AVR. The study population consisted of 58 patients with severe AS who were followed up for an average of 18 +/- 5 months after AVR. The authors observed a significant reduction of LV mass index and a significant increase in IBS mean cyclic variation and a decrease in the absolute end-diastole IBS intensity after AVR, showing an improvement of ultrasonic myocardial properties after AVR. They also demonstrated that preoperative analysis of IBS parameters might provide additional information to predict LV reverse remodeling in patients with a mean duration of 1.5 years of follow-up after AVR
Going Beyond Counting First Authors in Author Co-citation Analysis
The 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
Variations on the Author
“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
We 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
We 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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