177,217 research outputs found

    Expression profiling of hepatocellular carcinoma

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    Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related deaths in the world. The molecular mechanism of HCC onset involves a complex interplay of both genetic and epigenetic factors. Hepatic carcinogenesis is characterized by an increase in allelic losses, chromosomal aberrations, gene mutations, epigenetic alterations, changes of gene expression and alterations in molecular cellular pathways. The integration of genetic, epigenetic, genomic, and proteomic data provides insight into the molecular mechanisms underlying hepatocarcinogenesis and is revealing promising clinical approaches. Resulting findings offer the possibility for the identification of relevant biomarkers, useful for the detection, molecular diagnosis, prediction of recurrence and prognosis of HCC as well as for the improved identification of novel therapeutic targets. This will be of utmost importance in the near future as more and more new targeted drugs will become available

    Compositional and Geochemical Signatures for the Sedimentary Evolution of the Middle Triassic–Lower Jurassic Continental Redbeds from Western-Central Mediterranean Alpine Chains

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    Compositional and chemical analyses suggest that Middle Triassic–Lower Liassic continental redbeds (in the internal domains of the Betic, Maghrebian, and Apenninic chains) can be considered a regional lithosome marking the Triassic-Jurassic rift-valley stage of Tethyan rifting, which led to the Pangaea breakup and subsequent development of a mosaic of plates and microplates. Sandstones are quartzose to quartzolithic and represent a provenance of continental block and recycled orogen, made up mainly of Paleozoic metasedimentary rocks similar to those underlying the redbeds. Mudrocks display K enrichments; intense paleoweathering under a hot, episodically humid climate with a prolonged dry season; and sediment recycling. Redbeds experienced temperatures in the range of 100°–160°C and lithostatic/tectonic loading of more than 4 km. These redbeds represent an important stratigraphic signature to reconstruct a continental block (Mesomediterranean Microplate) that separated different realms of the western Tethys from Middle-Late Jurassic to Miocene, when it was completely involved in Alpine orogenesis.This work was funded by the Ministero dell’Universtità e della Ricerca Scientifica–Progetto di Ricerca Nazionale (MIUR-PRIN) 2001–2003 Project (“Age and Sedimentary Characters of the Mesozoic Continental Redbeds [Verrucano] from Northern Apennines to the Betic Cordillera: Implications for Paleogeographic and Tectonic Evolution of the Central-Western Mediterranean Alpine Belts,” S. Critelli, G. Mongelli, V. Perrone), MIUR-ex60% Projects (“Paleogeographic and Paleotectonic Evolution of the Circum-Mediterranean Orogenic Belts, 2001–2005” and “Relationships between Tectonic Accretion, Volcanism, and Clastic Sedimentation within the Circum-Mediterranean Orogenic Belts, 2006,” S. Critelli), the 2006–2008 MIUR-PRIN Project 2006.04.8397 (“The Cenozoic Clastic Sedimentation within the Circum-Mediterranean Orogenic Belts: Implications for Paleogeographic and Paleotectonic Evolution,” S. Critelli, G. Mongelli, V. Perrone), and Research Project CGL2005-03887 MEC (A. Martin-Algarra)

    Appropriate Similarity Measures for Author Cocitation Analysis

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    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

    PRETREATMENT WITH PEGYLATED INTERFERON PREVENTS EMERGENCE OF LAMIVUDINE MUTANTS IN LAMIVUDINE NAIVE PATIENTS

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    Background: In patients with advanced fibrosis, primary end points of long-term or possibly indefinite antiviral therapy are sustained inhibition of viral replication and avoidance of emergence of resistance. In lamivudine-treated patients, the strongest predictor of emergence of YMDD mutations is baseline hepatitis B virus (HBV) DNA viral load. We aimed to verify whether abatement of viraemia by a short course of pegylated interferon (PEG-IFN-?2a) treatment before lamivudine treatment could prevent the emergence of lamivudine-associated mutations during long-term therapy. Methods: A total of 14 patients with hepatitis B e antigen (HBeAg)-negative infection (3 lamivudine-experienced and 11 lamivudine-naive), with moderate/high viraemia (106 copies/ml) and with Ishak stage 4–6 at liver biopsy were sequentially treated with 180 ?g PEG-IFN-?2a for a period long enough to reach HBV DNA levels ?103 copies/ml or have a decrease of 3 log10 copies/ml from baseline. Lamivudine was then added to PEG-IFN-?2a treatment for 1 month and finally continued as monotherapy for 2 years or until viral breakthrough. Results: Baseline HBV DNA (mean ±se 2.3×107 ±7.2×107 copies/ml) decreased with PEG-IFN-?2a treatment to target value in mean ±se 3.7 ±1.3 months. None of the 11 lamivudine-naive patients developed genotypic resistance and were still HBV-DNA-negative after a mean ±se observation period of 23 ±2 months, whereas the three lamivudine-experienced patients developed YMDD mutations after 6, 9 and 12 months of lamivudine monotherapy (P=0.003, Fisher’s exact test). Conclusions: In lamivudine-naive patients, abatement of HBV DNA103 copies/ml by pretreatment with PEG-IFN-?2a completely prevents the emergence of YMDD mutants after 24 months of lamivudine monotherapy. This sequential schedule can optimize the use of a well tolerated, effective and inexpensive drug, such as lamivudine, in highly viraemic HBV patients

    Sedimentary evolution of the Mesozoic continental redbeds using geochemical and mineralogical tools: the case of Upper Triassic to Lowermost Jurassic Monte di Gioiosa mudstones (Sicily, southern Italy)

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    The continental redbeds from the Internal Domains of the central-western Mediterranean Chains have an important role in the palaeogeographic and palaeotectonic reconstructions of the Alpine circum-Mediterranean orogen evolution since these redbeds mark the Triassic- Jurassic rift-valley stage of Tethyan rifting. The composition and the sedimentary evolution of the Middle Triassic to Lowermost Jurassic continental redbeds of the San Marco d’Alunzio Unit (Peloritani Mountains, Southern Italy), based on mineralogical and chemical analyses, suggests that the studied mudrock sediments share common features with continental redbeds that constitute the Internal Domains of the Alpine Mediterranean Chains. Phyllosilicates are the main components in the mudrocks. The 10 A ° -minerals (illite and micas), the I–S mixed layers, and kaolinite are the most abundant phyllosilicates. The amount of illitic layers in I–S mixed layers coupled with the illite crystallinity values (IC) are typical of high degree of diagenesis, corresponding to a lithostatic/tectonic loading of about 4–5 km. The mineralogical assemblage coupled with the A-CN-K plot suggest post-depositional K-enrichments. Palaeoweathering proxies (PIA and CIW) record intense weathering at the source area. Further, the studied sediments are affected by reworking and recycling processes and, as consequence, it is likely these proxies monitor cumulative effect of weathering. The climate in the early Jurassic favoured recycling and weathering occurred under hot, episodically humid climate with a prolonged dry season. The source-area is the low-grade Paleozoic metasedimentary basement. Mafic supply is minor but not negligible as suggested by provenance proxies

    Electrocardiographic correlates with left ventricular morphology in idiopathic dilated cardiomyopathy

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    The purpose of the present study was to verify whether the electrocardiographic pattern of patients with idiopathic dilated cardiomyopathy (IDC) might be useful in predicting measurements of left ventricular (LV) morphology. A total of 12 electrocardiographic criteria for LV enlargement were evaluated in 67 patients with IDC, aged 14 to 68 years (mean 48), and were correlated to LV wall thickness, volume and mass, as assessed at angiography (all patients) and echocardiography (50 patients). Linear regression analysis showed weak correlations between multiple electrocardiographic criteria and LV wall thickness, volume and mass. Multiple logistic regression analysis showed that total 12-lead QRS amplitude, voltage criteria of Sokolow and Lyon, overshoot and U-wave inversion were the variables significantly related to LV wall thickness, as assessed by angiography (r = 0.55, p less than 0.005) and echocardiography (r = 0.43, p less than 0.025). The sum of T/R-wave ratios, the RV6/RV5 ratio and the Romhilt-Estes score were predictors of LV end-diastolic volume, as determined by angiography (r = 0.83, p less than 0.001) and echocardiography (r = 0.77, p less than 0.005). Total 12-lead QRS amplitude and the sum of T/R-wave ratios were the only independent predictors of LV mass, either angiographically (r = 0.81, p less than 0.001) or echocardiographically measured (r = 0.71, p less than 0.025). It is concluded that a single electrocardiographic criterion for prediction of LV morphology in patients with IDC is barely effective. Multiple electrocardiographic criteria should be utilized to better predict LV mass and distinguish reliably between LV wall thickening and dilatation

    "Closing the R&D Gap, Evaluating the Sources of R&D Spending"

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    Both spending and tax policies have been implemented in the United States with the goal of stimulating private sector research and development (R&D). Karier questions whether current R&D policy, especially the research and experimentation tax credit, can contribute to closing the gap between nondefense expenditures on R&D in the United States and such expenditures in other countries, such as Japan and Germany. He also explores possible changes to our current R&D policy to make it more effective.

    Sedimentary and thermal evolution of the Eocene-Oligocene mudrocks from the southwestern Thrace Basin (NE Greece)

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    Paleothermal indicators based on clay mineral and organic matter analyses, were integrated with mudrock geochemistry and stratigraphic data to define the sedimentary evolution of the southwestern Thrace Basin during the Eocene to Oligocene. This multi-method approach allowed us to reconstruct the burial evolution of the basin in Eocene and Oligocene times and to study the mudrock composition and relate this to their provenance and source area weathering. The studied mudrocks show similar chemical variations. The distribution of some major and trace elements for the studied samples reflect heterogeneous source areas containing both felsic to mafic rocks. In particular, the Light Rare Earth Elements/Transition elements (LREEs/TEs) ratios are very high for the Avdira and Organi samples (on the average between 1.5 and 2.2 for (La + Ce)/Cr and 3.5-8 for (La + Ce)/Ni), suggesting a felsic source(s), and very low for the Samothraki, Limnos, Paterma and Iasmos samples (on the average between 0.4 and 0.6 for (La + Ce)/Cr and 0.6-1 for (La + Ce)/Ni), suggesting a mainly basic source(s). The mineralogical composition coupled with the A-CN-K and A-N-K plots suggest a complex evolution. The clay mineral data (illite percentage in I/S and the stacking order R and the Kübler Index) coupled to vitrinite reflectance analysis indicate a high to intermediate diagenetic grade for the Middle to Upper Eocene samples (from Iasmos, Gratini, Organi, Paterma, Esimi and Samotraki sections) and a low diagenetic grade for the Upper Eocene to Oligocene samples (from Limnos and Avdira sections). These data helped in interpreting the geodynamic evolution of the studied basins where the magmatic activity plays an important role. In particular, Middle to Upper Eocene sediments show high to intermediate diagenetic grade since they are located in a portion of the basin dominated by Eocene to Oligocene magmatic activity and intrusion of granitoids, whereas, the Upper Eocene to Oligocene sediments are not involved in important magmatic activity and intrusion of granitoids and, thus, show low diagenetic grade. Furthermore, Middle to Upper Eocene sediments experienced deeper burial processes caused by lithostatic load, rather than the uppermost Eocene and Oligocene sediments, in relation of their position along the stratigraphic succession. These data suggest a burial depth of at least 3-4 km with a tectonic exhumation mainly related to the extensional phases of the Miocene age

    Going Beyond Counting First Authors in Author Co-citation Analysis

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    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
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