Alkini i aleni

Za kemiju nezasićenih spojeva su karakteristične adicijske reakcije, koje se pojavljuju i kod alkina i alena. Primjeri takvih reakcija su hidratiranje, hidrogeniranje, halogeniranje, hidroboriranje i mnoge slične. Jedna od korisnijih reakcije u izrađivanju ugljikovodičnog skeleta je Diels-Alderova reakcija, a radi se o cikloadiciji alkina ili alkena na 1,3 dialken. Ipak terminalni alkini i aleni mogu, relativno lako, u usporedbi sa alkanima, raditi organometalne spojeve, koji ne nalaze neku praktičnu primjenu, ali mogu služiti kao veoma dobri supstrati u sintezi. Zbog toga se često pojavljuju u njihovoj kemiji i reakcije supstitucije. Postoji nekoliko vrsta reakcija u kojima terminalni alkini i aleni mogu stvoriti nove ugljik-ugljik veze uz dijelomično ili potpuno sačuvanje višestrukih veza. Sinteza alkina se uglavnom provodi eliminaciskim reakcijama iz alkena ili alkana, dok se aleni sintetiziraju izomerizacijom alkina. Obije vrste spojeva pokazuju tendenciju dimerizacije. U slučaju alkina radi se o Glaserovom povezivanju, dok aleni pokazuju manju tendenciju, a povezuju se cikloadicijom. Višestruka veza je uglavnom „meta“ oksidacijskih reagensa. U kemiji alena se susrećemo s aksijalnom kiralnosti, koja za razliku od centralne, nema centar kiralnosti, nego osnu kiralnost. Kao i kod centralne kiralnosti dolazi do zakretanja ravnine svjetlosti, osim ako se radi o racematu

Музично-етнографічні польові дослідження (на прикладі обстеження історичної Хотинщини)

The author of the article researches the approaches of musical-ethnographic work, its methods and goals, as well as the choice of the specific territory and its exploration defined by them. The author comments on his intention to examine the area of Khotyn, which now is a part of Chernivtsy region; explains the methods of examining the territory. Pluses and minuses of the existing song collections dedicated to the given district are under consideration in this article. In conclusion short information about Northern Bessarabia and its population is given

Identification of DUSP4/6 overexpression as a potential rheostat to NRAS-induced hepatocarcinogenesis

Background Upregulation of the mitogen-activated protein kinase (MAPK) cascade is common in hepatocellular carcinoma (HCC). Neuroblastoma RAS viral oncogene homolog (NRAS) is mutated in a small percentage of HCC and is hitherto considered insufficient for hepatocarcinogenesis. We aimed to characterize the process of N-Ras-dependent carcinogenesis in the liver and to identify potential therapeutic vulnerabilities. Methods NRAS V12 plasmid was delivered into the mouse liver via hydrodynamic tail vein injection (HTVI). The resulting tumours, preneoplastic lesions, and normal tissue were characterized by NanoString® gene expression analysis, Western Blot, and Immunohistochemistry (IHC). The results were further confirmed by in vitro analyses of HCC cell lines. Results HTVI with NRAS V12 plasmid resulted in the gradual formation of preneoplastic and neoplastic lesions in the liver three months post-injection. These lesions mostly showed characteristics of HCC, with some exceptions of spindle cell/ cholangiocellular differentiation. Progressive upregulation of the RAS/RAF/MEK/ERK signalling was detectable in the lesions by Western Blot and IHC. NanoString® gene expression analysis of preneoplastic and tumorous tissue revealed a gradual overexpression of the cancer stem cell marker CD133 and Dual Specificity Phosphatases 4 and 6 (DUSP4/6). In vitro, transfection of HCC cell lines with NRAS V12 plasmid resulted in a coherent upregulation of DUSP4 and DUSP6. Paradoxically, this upregulation in PLC/PRF/5 cells was accompanied by a downregulation of phosphorylated extracellular-signal-regulated kinase (pERK), suggesting an overshooting compensation. Silencing of DUSP4 and DUSP6 increased proliferation in HCC cell lines. Conclusions Contrary to prior assumptions, the G12V NRAS mutant form is sufficient to elicit hepatocarcinogenesis in the mouse. Furthermore, the upregulation of the MAPK cascade was paralleled by the overexpression of DUSP4, DUSP6, and CD133 in vivo and in vitro. Therefore, DUSP4 and DUSP6 might fine-tune the excessive MAPK activation, a mechanism that can potentially be harnessed therapeutically

Fire in Australian savannas: From leaf to landscape

© 2014 The Authors. Global Change Biology Published by John Wiley & Sons Ltd. Savanna ecosystems comprise 22% of the global terrestrial surface and 25% of Australia (almost 1.9 million km2) and provide significant ecosystem services through carbon and water cycles and the maintenance of biodiversity. The current structure, composition and distribution of Australian savannas have coevolved with fire, yet remain driven by the dynamic constraints of their bioclimatic niche. Fire in Australian savannas influences both the biophysical and biogeochemical processes at multiple scales from leaf to landscape. Here, we present the latest emission estimates from Australian savanna biomass burning and their contribution to global greenhouse gas budgets. We then review our understanding of the impacts of fire on ecosystem function and local surface water and heat balances, which in turn influence regional climate. We show how savanna fires are coupled to the global climate through the carbon cycle and fire regimes. We present new research that climate change is likely to alter the structure and function of savannas through shifts in moisture availability and increases in atmospheric carbon dioxide, in turn altering fire regimes with further feedbacks to climate. We explore opportunities to reduce net greenhouse gas emissions from savanna ecosystems through changes in savanna fire management

Impact of Positive Lymph Nodes and Resection Margin Status on the Overall Survival of Patients with Resected Perihilar Cholangiocarcinoma: The ENSCCA Registry

Background: Lymph node metastasis and positive resection margins have been reported to be major determinants of overall survival (OS) and poor recurrence-free survival (RFS) for patients who underwent resection for perihilar cholangiocarcinoma (pCCA). However, the prognostic value of positive lymph nodes independently from resection margin status on OS has not been evaluated. Methods: From the European Cholangiocarcinoma (ENSCCA) registry, patients who underwent resection for pCCA between 1994 and 2021 were included in this retrospective cohort study. The primary outcome was OS stratified for resection margin and lymph node status. The secondary outcome was recurrence-free survival. Results: A total of 325 patients from 11 different centers and six European countries were included. Of these, 194 (59.7%) patients had negative resection margins. In 113 (34.8%) patients, positive lymph nodes were found. Lymph node status, histological grade, and ECOG performance status were independent prognostic factors for survival. The median OS for N0R0, N0R1, N+R0, and N+R1 was 38, 30, 18, and 12 months, respectively (p < 0.001). Conclusion: These data indicate that in the presence of positive regional lymph nodes, resection margin status does not determine OS or RFS in patients with pCCA. Achieving negative margins in patients with positive nodes should not come at the expense of more extensive surgery and associated higher mortality.The ENSCCA Registry is completely funded by the European Association for the Study of the Liver (EASL; Registry grant awards 2016 and 2019 to J.M.B.), Incyte Bioscience International Sàrl (grant award 2020 to J.M.B.) and European Union’s Horizon 2020 Research and Innovation Program (grant number 825510, ESCALON: to J.M.B. and A.L.)

Comparing Survival of Perihilar Cholangiocarcinoma After R1 Resection Versus Palliative Chemotherapy for Unresected Localized Disease

Background: Resection of perihilar cholangiocarcinoma (pCCA) is a complex procedure with a high risk of postoperative mortality and early disease recurrence. The objective of this study was to compare patient characteristics and overall survival (OS) between pCCA patients who underwent an R1 resection and patients with localized pCCA who received palliative systemic chemotherapy. Methods: Patients with a diagnosis of pCCA between 1997–2021 were identified from the European Network for the Study of Cholangiocarcinoma (ENS-CCA) registry. pCCA patients who underwent an R1 resection were compared with patients with localized pCCA (i.e., nonmetastatic) who were ineligible for surgical resection and received palliative systemic chemotherapy. The primary outcome was OS.Results:Overall, 146 patients in the R1 resection group and 92 patients in the palliative chemotherapy group were included. The palliative chemotherapy group more often underwent biliary drainage (95% vs. 66%, p &lt; 0.001) and had more vascular encasement on imaging (70% vs. 49%, p = 0.012) and CA 19.9 was more frequently &gt;200 IU/L (64 vs. 45%, p = 0.046). Median OS was comparable between both groups (17.1 vs. 16 months, p = 0.06). Overall survival at 5 years after diagnosis was 20.0% with R1 resection and 2.2% with chemotherapy. Type of treatment (i.e., R1 resection or palliative chemotherapy) was not an independent predictor of OS (hazard ratio 0.76, 95% confidence interval 0.55–1.07). Conclusions: Palliative systemic chemotherapy should be considered instead of resection in patients with a high risk of both R1 resection and postoperative mortality.</p

The WERA cancer center matrix: strategic management of patient access to precision oncology in a large and mostly rural area of Germany

Purpose Providing Patient Access to Precision Oncology (PO) is a major challenge of clinical oncologists. Here, we provide an easily transferable model from strategic management science to assess the outreach of a cancer center. Methods As members of the German WERA alliance, the cancer centers in Würzburg, Erlangen, Regensburg and Augsburg merged care data regarding their geographical impact. Specifically, we examined the provenance of patients from WERA´s molecular tumor boards (MTBs) between 2020 and 2022 (n = 2,243). As second dimension, we added the provenance of patients receiving general cancer care by WERA. Clustering our catchment area along these two dimensions set up a four-quadrant matrix consisting of postal code areas with referrals towards WERA. These areas were re-identified on a map of the Federal State of Bavaria. Results The WERA Matrix overlooked an active screening area of 821 postal code areas – representing about 50% of Bavaria´s spatial expansion and more than six million inhabitants. The WERA Matrix identified regions successfully connected to our outreach structures in terms of subsidiarity – with general cancer care mainly performed locally but PO performed in collaboration with WERA. We also detected postal code areas with a potential PO backlog – characterized by high levels of cancer care performed by WERA and low levels or no MTB representation. Conclusions The WERA Matrix provided a transparent portfolio of postal code areas, which helped assessing the geographical impact of our PO program. We believe that its intuitive principle can easily be transferred to other cancer centers

Learning from multimedia and hypermedia

Computer-based multimedia and hypermedia resources (e.g., the world wide web) have become one of the primary sources of academic information for a majority of pupils and students. In line with this expansion in the field of education, the scientific study of learning from multimedia and hypermedia has become a very active field of research. In this chapter we provide a short overview with regard to research on learning with multimedia and hypermedia. In two review sections, we describe the educational benefits of multiple representations and of learner control, as these are the two defining characteristics of hypermedia. In a third review section we describe recent scientific trends in the field of multimedia/hypermedia learning. In all three review sections we will point to relevant European work on multimedia/hypermedia carried out within the last 5 years, and often carried out within the Kaleidoscope Network of Excellence. According to the interdisciplinary nature of the field this work might come not only from psychology, but also from technology or pedagogy. Comparing the different research activities on multimedia and hypermedia that have dominated the international scientific discourse in the last decade reveals some important differences. Most important, a gap seems to exist between researchers mainly interested in a “serious” educational use of multimedia/ hypermedia and researchers mainly interested in “serious” experimental research on learning with multimedia/hypermedia. Recent discussions about the pros and cons of “design-based research” or “use-inspired basic research” can be seen as a direct consequence of an increasing awareness of the tensions within these two different cultures of research on education

Predicting species dominance shifts across elevation gradients in mountain forests in Greece under a warmer and drier climate

The Mediterranean Basin is expected to face warmer and drier conditions in the future, following projected increases in temperature and declines in precipitation. The aim of this study is to explore how forests dominated by Abies borisii-regis, Abies cephalonica, Fagus sylvatica, Pinus nigra and Quercus frainetto will respond under such conditions. We combined an individual-based model (GREFOS), with a novel tree ring data set in order to constrain tree diameter growth and to account for inter- and intraspecific growth variability. We used wood density data to infer tree longevity, taking into account inter- and intraspecific variability. The model was applied at three 500-m-wide elevation gradients at Taygetos in Peloponnese, at Agrafa on Southern Pindos and at Valia Kalda on Northern Pindos in Greece. Simulations adequately represented species distribution and abundance across the elevation gradients under current climate. We subsequently used the model to estimate species and functional trait shifts under warmer and drier future conditions based on the IPCC A1B scenario. In all three sites, a retreat of less drought-tolerant species and an upward shift of more drought-tolerant species were simulated. These shifts were also associated with changes in two key functional traits, in particular maximum radial growth rate and wood density. Drought-tolerant species presented an increase in their average maximal growth and decrease in their average wood density, in contrast to less drought-tolerant species