1,720,966 research outputs found
Going Beyond Counting First Authors in Author Co-citation Analysis
Get PDFThe 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
Get PDF“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
Role of PARP, NF-kB and telomerase in necrosis induced by selective methylation of N3-adenine.
No full textSelective methylation of N3-adenine represents a novel pharmacological strategy for the treatment of mismatch repair-deficient tumors, which are tolerant to O6-methylguanine, the main cytotoxic lesion induced by methylating agents of clinical interest such as temozolomide. However, the biochemical pathways involved in cell death induced by N3-methyladenine have not been clarified, yet. In the present study we show that MeOSO2(CH2)2-lexitropsin (Me-Lex), a compound generating almost exclusively N3-methyladenine, provoked poly(ADP-ribosylation), loss of mitochondrial membrane potential, and increase of ROS production in leukemia cell lines with intact or defective mismatch repair system. These events were followed by a marked reduction of nuclear poly(ADP-ribose) polymerase-1 (PARP-1) expression and Nuclear Factor-kB (NF-kB) activity. Moreover, treatment with Me-Lex induced a profound decrease of telomerase in the cytosol that was accompanied by a transient up-regulation of activity in the nucleus.
PARP-1 inhibition blocked ADP-ribose polymer formation, preserved mitochondrial membrane integrity and counteracted the reduction of NF-kB activity thus preventing the appearance of necrosis. On the other hand, the combination of Me-Lex + PARP-1 inhibitor triggered apoptosis due to disruption of base excision repair process.
In conclusion, the results underline the central and paradoxical role of PARP-1 in cell death induced by N3-methyladenine: effector of necrosis and co-ordinator of methylpurine repair.
Supported by: FIRB 2001, PRIN 2003 and NIH grant RO1 CA29088 projects to GG, LT and BG, respectively
Appropriate Similarity Measures for Author Cocitation Analysis
Get PDFWe 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
Gli inibitori della poli (ADP-ribosio) polimerasi (PARP) per superare la chemioresistenza a metilanti e inibitori di topoisomerasi I
No full textRecentemente abbiamo dimostrato che gli inibitori della poli (ADP-ribosio) polimerasi (PARP) sono in grado di potenziare l’attività antitumorale del metilante temozolomide (TMZ), inibendo il riparo delle N-metilpurine da parte del base excision repair.
In questo studio è stata valutata l’efficacia di nuovi inibitori della PARP nell’aumentare la chemiosensibilità di tumori resistenti alle camptotecine. Infatti, la PARP, favorendo il ricongiungimento dei filamenti di DNA mediato dalla topoisomerasi I, ostacola l’azione citotossica degli inibitori di tale enzima. In particolare, è stata saggiata la capacità di nuovi potenti inibitori della PARP (in grado di attraversare la barriera emato-encefalica e dotati di elevata biodisponibilità orale) di potenziare l’azione antitumorale dell’irinotecano (CPT-11), un farmaco attualmente utilizzato per il trattamento del carcinoma del colon metastatico. Inoltre, è stato valutato se gli inibitori della PARP possano potenziare l’attività antitumorale della combinazione CPT-11/TMZ, attualmente utilizzata per il trattamento di tumori solidi refrattari alla terapia convenzionale.
Gli esperimenti in vitro su colture cellulari di carcinomi del colon umani, caratterizzati da differenti livelli di attività PARP, hanno dimostrato che l’inibitore della PARP GPI 15427 potenzia gli effetti antiproliferativi della 7-etil-10-idrossicamptotecina (SN-38), il metabolita attivo del CPT-11, e della sua associazione con TMZ (indice di combinazione <1) anche in linee tumorali ad alta espressione della PARP.
Gli studi in vivo hanno dimostrato che la somministrazione orale di GPI 15427 riduce notevolmente l’attività PARP dei linfociti di sangue periferico dei topi trattati, analizzati dopo un’ora dal trattamento. Inoltre, gli esperimenti in topi portatori di xenotrapianti di carcinoma del colon, con differenti caratteristiche di aggressività, hanno dimostrato che GPI 15427 (40 mg/kg/per os) in associazione con CPT-11 (10 mg/kg/ip) o con basse dosi di TMZ (10 mg/kg/ip) + CPT-11 (4 mg/kg/ip) inibisce e ritarda significativamente la crescita tumorale rispetto al trattamento con i singoli farmaci o alla combinazione TMZ + CPT-11.
In conclusione, questi dati suggeriscono che la somministrazione orale degli inibitori della PARP potrebbe rappresentare un’efficace strategia terapeutica per superare la resistenza di carcinomi del colon alla chemioterapia.
Finanziamenti: FIRB 2001, PRIN 2003 and PRIN 2004 a GG e LT
Generation of an immortalized human endothelial cell line as a model of neovascular proliferating endothelial cells to assess chemosensitivity to anticancer drugs.
No full textAssessment of chemosensitivity of neovessel endothelium associated to tumor mass is hindered by the limited availability of experimental models of actively proliferating endothelial cells. In fact, primary endothelial cells possess a limited lifespan and replicative senescence represents a major limit to their long-term culture. Moreover, non-dividing senescent cells undergo a gradual loss of phenotypic markers and become unable to respond to mitogenic stimuli. We report the generation of an immortalized human endothelial cell line by transfection of human umbilical vein endothelial cells (HUVEC) with both SV40 large/small T antigens and the catalytic subunit of human telomerase. This cell line (HUV-ST) possesses stabilized telomere length and increased proliferation rate with respect to parental cells or to cells transfected with SV40 T antigens only (HUV-S). Nevertheless. even at PD > 100 it is not tumorigenic and displays all major endothelial phenotypic markers, such as von Willebrand factor, CD31, vascular endothelial growth factor (VEGF) receptors (VEGFRI/Flt-1, VEGR2/KDR) and CD105/endoglin. HUV-ST cells are capable of organizing into tubule-like networks with branching morphology in response to appropriate stimuli and migrate upon exposure to VEGF. Interestingly, HUV-ST cells over-express the tumor endothelial marker-1/endosialin which is regarded as the most differentially expressed molecule in tumor-derived endothelium versus normal-derived endothelium. Analysis of chemosensitivity to the wide spectrum methylating agent temozolomide (TMZ), an anticancer drug more effective against actively dividing cells than against resting or slowing proliferating cells, indicated that HUV-ST cells are more susceptible to the drug with respect to HUVEC or HUV-S cells. Abrogation of poly(ADP-ribose) polymerase activity significantly enhances growth inhibition induced by TMZ. In conclusion, the immortalized human endothelial line HUV-ST represents a suitable model for studying the efficacy of anti-neovascular therapy, mimicking proliferating neovascular endothelial cells associated to the tumor mass
Dispelling the Myths Behind First-author Citation Counts
Get PDFWe 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
N3-methyladenine induces early poly(ADP-ribosylation), reduction of nuclear factor-kappa B DNA binding ability, and nuclear up-regulation of telomerase activity.
No full textMethylation of N3-adenine represents a novel pharmacological strategy for the treatment of resistant tumors. However, little is known about the biochemical pathways involved in cell death induced by N3-methyladenine. In the present study, we show that MeOSO(2) (CH(2))(2)-lexitropsin (Me-Lex), a compound generating almost exclusively N3-methyladenine (>99%), provoked a burst of poly(ADP-ribosylation) and loss of mitochondrial membrane potential in leukemia cells. These events were followed by a marked decrease in nuclear poly(ADP-ribose) polymerase-1 (PARP-1) expression and nuclear factor-kappaB (NF-kappaB) activity. Moreover, DNA damage generated by N3-methyladenine induced a marked decrease in telomerase in the cytosol that was accompanied by a transient up-regulation of activity in the nucleus, as a consequence of nuclear translocation of telomerase in response to genotoxic damage. PARP-1 inhibition blocked ADP-ribose polymer formation, preserved mitochondrial membrane integrity, and counteracted the reduction of NF-kappaB activity, thus preventing the appearance of necrosis. On the other hand, because PARP-1 is a component of the base excision repair (BER), the combination of Me-Lex + PARP-1 inhibitor triggered apoptosis as a result of disruption of BER process. In conclusion, the present study provides new insight into the cellular response to N3-adenine-selective methylating agents that can be exploited for the treatment of tumors unresponsive to classical wide-spectrum methylating agents. Moreover, the results underline the central and paradoxical role of PARP-1 in cell death induced by N3-methyladenine: effector of necrosis and coordinator of methylpurine repair
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