Petroarchaeological and micropaleontologic classification of Finnish flinty materials: a critical review

The applicability of various geomicroscopic methods on Finnish flinty materials has been tested. Especially microfossil composition, petrographic properties and surface textures provided diagnostic observations. The results show that the prehistoric flinty artefacts of Finland are mainly composed of Carboniferous chert and Cretaceous and Tertiary flint and of jasperoid of unknown geological age

The Science of Pronominal Usage: He and It in Co-Reference to Inanimate Objects in Late Middle English Texts on Alchemy

This is the author's accepted manuscript. The published version can be found at http://dx.doi.org/10.1177/0075424210384225This article explores the variation between he and it in coreference to inanimate entities (such as mercury, sulfur, and salt). Using alchemical texts from the fifteenth century as material, the article demonstrates that there was much more variation in pronominal reference in this period than has previously been shown. Of the possible explanations suggested by previous research, the earlier grammatical gender system and transference from Latin do not seem to play a role, while pronoun clustering and pronominal reanalysis appear to influence the quantitative distribution. The scale of individuation used by Siemund and Stenroos to explain similar usage is shown not to be a straightforward predictor. Other factors such as personification and perceived similarities between animate and inanimate entities may affect the degree of perceived individuation. The choice of he over she seems to be influenced by pronominal reanalysis and straightforward personification in some cases. In other instances, it is speculated that the he usage reflects (stereotypical) gender conceptions in the Middle Ages

VEGF-B-induced vascular growth leads to metabolic reprogramming and ischemia resistance in the heart

Peer reviewe

Subclone eradication analysis identifies targets for enhanced cancer therapy and reveals L1 retrotransposition as a dynamic source of cancer heterogeneity

Treatment-eradicated cancer subclones have been reported in leukemia and have recently been detected in solid tumors. Here we introduce Differential Subclone Eradication and Resistance Analysis (DSER), a method developed to identify molecular targets for improved therapy by direct comparison of genomic features of eradicated and resistant subclones in pre- and post-treatment samples from a patient with BRCA2-deficient metastatic prostate cancer. FANCI and EYA4 were identified as candidate DNA repair-related targets for converting subclones from resistant to eradicable, and RNAi-mediated depletion of FANCI confirmed it as a potential target. The EYA4 alteration was associated with adjacent L1 transposon insertion during cancer evolution upon treatment, raising questions surrounding the role of therapy in L1 activation. Both carboplatin and enzalutamide turned on L1 transposon machinery in LNCaP and VCaP but not in PC-3 and 22Rv1 prostate cancer cell lines. L1 activation in LNCaP and VCaP was inhibited by the antiretroviral drug azidothymidine. L1 activation was also detected post-castration in LuCaP 77 and LuCaP 105 xenograft models and post-chemotherapy in previously published time-series transcriptomic data from SCC25 head and neck cancer cells. In conclusion DSER provides an informative intermediate step toward effective precision cancer medicine and should be tested in future studies, especially those including dramatic but temporary metastatic tumor regression. L1 transposon activation may be a modifiable source of cancer genomic heterogeneity, suggesting the potential of leveraging newly discovered triggers and blockers of L1 activity to overcome therapy resistance

Safety of liver resection and effect on quality of life in patients with benign hepatic disease: Single center experience

<p>Abstract</p> <p>Background</p> <p>Although liver resection has long been established for selected patients with benign hepatic disease, the success of surgical treatment of these patients cannot be evaluated exclusively through postoperative morbidity and mortality. Therefore, the aim of the study was to prove the safety of liver resection in the treatment of benign liver tumors and to evaluate the effect of surgical treatment on the patients' qauality of life.</p> <p>Methods</p> <p>A total of 146 patients who underwent liver resection because of benign liver tumors were included in this study. Postoperative outcome was assessed and patients evaluated their quality of life before surgery and at the present time using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core-30 (QLQ C-30).</p> <p>Results</p> <p>The rate of serious (> grade 2) complications was 4.1% with no postoperative death. The quality of life assessment revealed an overall improvement of general health status after resection (0.7 vs. 0.56, p < 0.001) and additionally a significant reduction of 6 out of 9 symptoms. Furthermore, compelling benefits in the patients' social and emotional coping could be detected after surgery.</p> <p>Conclusions</p> <p>Liver resection for benign liver disease is a safe procedure and leads to a significant improvement of quality of life in selected patients.</p

Discovery and development of ODM-204: A Novel nonsteroidal compound for the treatment of castration-resistant prostate cancer by blocking the androgen receptor and inhibiting CYP17A1

We report the discovery of a novel nonsteroidal dual-action compound, ODM-204, that holds promise for treating patients with castration-resistant prostate cancer (CRPC), an advanced form of prostate cancer characterised by high androgen receptor (AR) expression and persistent activation of the AR signaling axis by residual tissue androgens. For ODM-204, has a dual mechanism of action. The compound is anticipated to efficiently dampen androgenic stimuli in the body by inhibiting CYP17A1, the prerequisite enzyme for the formation of dihydrotestosterone (DHT) and testosterone (T), and by blocking AR with high affinity and specificity. In our study, ODM-204 inhibited the proliferation of androgen-dependent VCaP and LNCaP cells in vitro and reduced significantly tumour growth in a murine VCaP xenograft model in vivo. Intriguingly, after a single oral dose of 10-30 mg/kg, ODM-204 dose-dependently inhibited adrenal and testicular steroid production in sexually mature male cynomolgus monkeys. Similar results were obtained in human chorionic gonadotropin-treated male rats. In rats, leuprolide acetate-mediated (LHRH agonist) suppression of the circulating testosterone levels and decrease in weights of androgen-sensitive organs was significantly and dose-dependently potentiated by the co-administration of ODM-204. ODM-204 was well tolerated in both rodents and primates. Based on our data, ODM-204 could provide an effective therapeutic option for men with CRPC.</p