Microenvironment and tumor cells: two targets for new molecular therapies of hepatocellular carcinoma.

Hepatocellular carcinoma (HCC), is one of the most frequent human cancer and is characterized by a high mortality rate. The aggressiveness appears strictly related to the liver pathological background on which cancer develops. Inflammation and the consequent fibro/cirrhosis, derived from chronic injuries of several origins (viral, toxic and metabolic) and observable in almost all oncological patients, represents the most powerful risk factor for HCC and, at the same time, an important obstacle to the efficacy of systemic therapy. Multiple microenvironmental cues, indeed, play a pivotal role in the pathogenesis, evolution and recurrence of HCC as well as in the resistance to standard therapies observed in most of patients. The identification of altered pathways in cancer cells and of microenvironmental changes, strictly connected in pathogenic feedback loop, may permit to plan new therapeutic approaches targeting tumor cells and their permissive microenvironment, simultaneousl

Study of pretesting effects on electroexplosive devices

Pretesting techniques of suppliers and users and effects on electroexplosive device

La tradizione piccarda di Chrétien de Troyes e il manoscritto BnF fr. 12603 dell'Yvain

Il numero elevato di testimoni piccardi per i romanzi di Chrétien de Troyes dipende certamente dai rapporti che l’autore intrattenne con la contea di Fiandra, dove con ogni probabilità trascorse l’ultima parte della sua vita al servizio di Filippo d’Alsazia, e all’interesse che i successori di quest’ultimo dimostrarono sempre nei confronti suoi e della sua opera, tanto da ritenersi i depositari legittimi dell’ultimo romanzo incompiuto, Perceval, incominciato appunto per incarico di Filippo e continuato, dopo la morte dell’autore, proprio in Fiandra. La prima parte di questo lavoro mira per l’appunto al delineamento dell’ambiente storico-culturale piccardo dove Chrétien operò e dove la sua opera fu letta, copiata ed apprezzata, e dove soprattutto si compì l’appropriazione culturale di un autore champenois da parte della classe dominante. A tale questione si affianca anche l’indagine dell’aspetto linguistico, che è un altro dei problemi posti dall’alto numero di manoscritti nord-orientali. In effetti, il dialetto di Chrétien non era certamente il dialetto piccardo, ma nonostante ciò questo costituisce la principale lingua di trasmissione dei suoi romanzi. La tradizione champenois, scritta in un dialetto se non uguale almeno prossima a quello dell’autore è invece minoritaria. Ciò significa che nella maggior parte dei casi la veste linguistica originaria dei suoi romanzi potrebbe essere stata pesantemente rimaneggiata. Considerando accertato che Chrétien scrivesse in una lingua dai tratti champenois, nella seconda parte di questo lavoro si è conseguentemente tentato di investigare il problema della ricezione linguistica posto dalla tradizione piccarda dell’Yvain, prendendone in considerazione tutti i testimoni ma con attenzione particolare ad uno di essi, il BnF fr. 12603, conosciuto per questo romanzo con la sigla S, di cui si fornisce una descrizione dettagliata

Study of design parameters of explosive initiators with respect to space environments Final report

Environmental hazards to explosives and explosive triggering devices encountered on manned space flight

Multimedia technology as a presentation and archival tool for teaching history/social science

This project was created to provide teachers with a model multimedia project that demonstrates the use of multimedia as both a presentation tool and an archival instrument. It provides teachers with a simple guide to help them teach students how to use multimedia as a productivity tool in the classroom. This outline gives a step by step format that guides teachers and students through the development and presentation process. In addition, an evaluation rubric is provided that offers teachers a concise means to monitor student learning

Is Prophylactic Oxybutynin Safe and Effective in Reducing the Severity of Palmar Hyperhidrosis in Adults?

OBJECTIVE: The objective of this selective EBM review is to determine “Is prophylactic oxybutynin safe and effective in reducing the severity of palmar hyperhidrosis in adults?” STUDY DESIGN: This review is based on two randomized controlled trials (RCTs) and one non-randomized crossover study published in 2008, 2011, and 2012. The studies compared the safety and efficacy of oxybutynin in reducing the severity of palmar hyperhidrosis. DATA SOURCES: All articles used were published in English, in peer-reviewed journals, and found using PubMed, Ebscohost, and Cochrane Review databases. OUTCOMES MEASURED: For all studies, the safety and effectiveness of oxybutynin on palmer hyperhidrosis was evaluated using post-treatment clinical questionnaires. For one study, symptom improvement was quantitatively measured using Transepidermal Water Loss (TEWL) measurements pre- and post-treatment. RESULTS: Van Houte et al. (2008) found no statistical significance (p \u3e 0.05) in effectiveness of sweat inhibition with oxybutynin at doses of 7.5 mg and 15 mg per day. Conversely, the Wolosker et al. studies (2011, 2012) saw statistically significant improvement (\u3e80% of participants) in palmar hyperhidrosis symptoms (sudoresis) with the administration of oxybutynin at doses of 10 mg per day. None of the studies reported worsening symptoms with treatment. Noted side effects primarily included dry mouth, in which moderate to severe cases were reported in 34.8%-48.1% of participants. Despite the prevalence of dry mouth, it was not found to be an impeding factor in the use of oxybutynin for palmar hyperhidrosis. CONCLUSIONS: Results of two of the three studies demonstrate that 10 mg of daily oxybutynin is safe and effective in the prophylactic management of palmar hyperhidrosis in those diagnosed with generalized hyperhidrosis (GH). Further comparative studies are warranted to investigate whether the long-term use of oxybutynin results in continued symptom improvement or tachyphylaxis

Ceramic traditions and technological choices revealed by early Iron Age vessels: the case of Vetulonia (southern Tuscany)

Early Iron Age pottery from central Italian regions has so far largely been studied with a particular emphasis on typological and stylistical features. However, an analytical approach to ancient ceramic technology can reveal a wealth of data on the know-how of early Iron Age central Italian craftspeople and their production choices. With this aim we conducted archaeometric analyses of forty vessels from one of the main protohistoric cemeteries of Vetulonia, coupled with geological surveys of the territory around the settlement and the collection of raw materials. The occurrence of a ceramic fabric marked by fragments of metasedimentary rocks, as opposed to a fabric tempered with flint fragments, indicates the existence of separate traditions, characterised by distinct processes and the addition of specific tempers, probably reflecting different technological practices. The significance of our findings is briefly discussed within the historical and social scenario of early Iron Age Vetulonia, at the dawn of urbanisation

Assertiveness in Nursing Students

The problem that this study focused on was that there was minimal evidence on whether or not nursing students become more assertive throughout their academic education. The purpose of this study was to compare the assertiveness scores of sophomore level nursing students and senior level-nursing students. The study was guided by Hildegard Peplau’s theory of interpersonal relations in nursing, which focuses on the therapeutic process between nurses and patients, rather than on internal patient pathology. The descriptive, comparative study used a 15-question survey design and a convenience sample of sophomore and senior level nursing students at a large urban Midwest university. Recruitment, informed consent, and data collection occurred during the sophomore and senior classes. An independent sample T test was used to determine group differences in assertiveness. The results revealed that the sophomore level students were more assertive than the senior level-nursing students

Convergence of Wnt signalling on the HNF4a-driven transcription in controlling liver zonation

BACKGROUND & AIMS: In each hepatocyte, the specific repertoire of gene expression is influenced by its exact location along the portocentrovenular axis of the hepatic lobule and provides a reason for the liver functions compartmentalization defined "metabolic zonation." So far, few molecular players controlling genetic programs of periportal (PP) and perivenular (PV) hepatocytes have been identified; the elucidation of zonation mechanisms remains a challenge for experimental hepatology. Recently, a key role in induction and maintenance of the hepatocyte heterogeneity has been ascribed to Wnt/beta-catenin pathway. We sought to clarify how this wide-ranging stimulus integrates with hepatocyte specificity. METHODS: Reverse transcriptase polymerase chain reaction (RT-PCR) allowed the transcriptional profiling of hepatocytes derived from in vitro differentiation of liver stem cells. The GSK3beta inhibitor 6-bromoindirubin-3'-oxime (BIO) was used for beta-catenin stabilization. Co-immunoprecipitations were used to study biochemical protein interactions while ChIP assays allowed the in vivo inspection of PV and PP genes regulatory regions. RESULTS: We found that spontaneous differentiation of liver stem cells gives rise to PP hepatocytes that, after Wnt pathway activation, switch into PV hepatocytes. Next, we showed that the Wnt downstream player LEF1 interacts with the liver-enriched transcriptional factor HNF4alpha. Finally, we unveiled that the BIO induced activation of PV genes correlates with LEF1 binding to both its own and HNF4alpha consensus, and the repression of PP genes correlates with HNF4alpha displacement from its own consensus. CONCLUSION: Our data show a direct and hitherto unknown convergence of the canonical Wnt signaling on the HNF4alpha-driven transcription providing evidences of a mechanism controlling liver zonated gene expression

'Seeing Shit': Assessing the Visibility of Dung Tempering in Ancient Pottery Using an Experimental Approach

Widespread ethnographic evidence exists for the addition of animal dung to clay during the process of ceramic production. However, conclusive evidence of dung tempering in archaeological ceramics is relatively rare. The aim of this study is to ascertain whether, and under which conditions, dung tempering of pottery is identifiable. To answer these questions, we assessed whether a combination of micro-particle analysis in loose sediment and thin-section petrography can reveal the addition of dung to the clay paste by focusing on faecal spherulites, ash pseudomorphs, phytoliths and coprophilous fungal spores. We analysed several series of experimentally produced ceramic briquettes tempered with different types of dung and dung ash, which were fired at a range of increasing temperatures. Our study shows that the identification of dung tempering represents a challenge, and it depends on a number of different factors, among others the original presence of dung markers in the dung used, the manufacturing process, the firing temperatures and the firing atmosphere. Overall, through a multidisciplinary approach, our work clarifies a variety of issues connected to the identification of dung in ancient pottery, highlighting the role of faecal spherulites as the most promising proxy