Background: In addition to its essential role in ribonucleotide reduction, ribonucleotide reductase (RNR) small subunit, RRM2, has been known to play a critical role in determining tumor malignancy. Overexpression of RRM2 significantly enhances the invasive and metastatic potential of tumor. Angiogenesis is critical to tumor malignancy; it plays an essential role in tumor growth and metastasis. It is important to investigate whether the angiogenic potential of tumor is affected by RRM2.

The Russian and Norwegian Arctic are gaining notoriety as an alternative maritime route connecting the Atlantic and Pacific Oceans and as sources of natural resources. The renewed interest in the Northeast Passage or the Northern Sea Route is fueled by a recession of Arctic sea ice coupled with the discovery of new natural resources at a time when emerging and global markets are in growing demand for them. Driven by the expectation of potential future economic importance of the region, political interest and governance has been rapidly developing, mostly within the Arctic Council. However, this paper argues that optimism regarding the potential of Arctic routes as an alternative to the Suez Canal is overstated. The route involves many challenges: jurisdictional disputes create political uncertainties; shallow waters limit ship size; lack of modern deepwater ports and search and rescue (SAR) capabilities requires ships to have higher standards of autonomy and safety; harsh weather conditions and free-floating ice make navigation more difficult and schedules more variable; and more expensive ship construction and operation costs lessen the economic viability of the route. Technological advances and infrastructure investments may ameliorate navigational challenges, enabling increased shipping of natural resources from the Arctic to global markets.

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One of the defining features of both recent and historical cases of global climate change is Arctic amplification (AA). This is the more rapid change in the surface air temperature (SAT) in the Arctic compared to some wider reference region, such as the Northern Hemisphere (NH) mean. Many different metrics have been developed to quantify the degree of AA based on SAT anomalies, trends and variability. The use of different metrics, as well as the choice of data set to use, can affect conclusions about the magnitude and temporal variability of AA. Here we review the established metrics of AA to see how well they agree upon the temporal signature of AA, such as the multi-decadal variability, and assess the consistency in these metrics across different commonly used data sets which cover both the early and late 20th century warming in the Arctic. We find the NOAA 20th century reanalysis most closely matches the observations when using metrics based upon SAT trends (A 2 ), variability (A 3 ) and regression (A 4 ) of the SAT anomalies, and the ERA 20th century reanalysis is closest to the observations in the SAT anomalies (A 1 ) and variability of SAT anomalies (A 3 ). However, there are large seasonal differences in the consistency between data sets. Moreover, the largest differences between the century-long reanalysis products and observations are during the early warming period, likely due to the sparseness of the observations in the Arctic at that time. In the modern warming period, the high density of observations strongly constrains all the reanalysis products, whether they include satellite observations or only surface observations. Thus, all the reanalysis and observation products produce very similar magnitudes and temporal variability in the degree of AA during the recent warming period.

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Ribonucleotide reductase (RNR) plays a critical role in catalyzing the biosynthesis and maintaining the intracellular concentration of 4 deoxyribonucleoside triphosphates (dNTPs). Unbalanced or deficient dNTP pools cause serious genotoxic consequences. Autophagy is the process by which cytoplasmic constituents are degraded in lysosomes to maintain cellular homeostasis and bioenergetics. However, the role of autophagy in regulating dNTP pools is not well understood. Herein, we reported that starvation- or rapamycin-induced autophagy was accompanied by a decrease in RNR activity and dNTP pools in human cancer cells. Furthermore, downregulation of the small subunit of RNR (RRM2) by siRNA or treatment with the RNR inhibitor hydroxyurea substantially induced autophagy. Conversely, cancer cells with abundant endogenous intracellular dNTPs or treated with dNTP precursors were less responsive to autophagy induction by rapamycin, suggesting that autophagy and dNTP pool levels are regulated through a negative feedback loop. Lastly, treatment with si-RRM2 caused an increase in MAP1LC3B, ATG5, BECN1, and ATG12 transcript abundance in xenografted Tu212 tumors in vivo. Together, our results revealed a previously unrecognized reciprocal regulation between dNTP pools and autophagy in cancer cells.

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We investigate factors influencing European winter (DJFM) air temperatures for the period 1979-2015 with the focus on changes during the recent period of rapid Arctic warming (1998)(1999)(2000)(2001)(2002)(2003)(2004)(2005)(2006)(2007)(2008)(2009)(2010)(2011)(2012)(2013)(2014)(2015). We employ meteorological reanalyses analysed with a combination of correlation analysis, two pattern clustering techniques, and backtrajectory airmass identification. In all five selected European regions, severe cold winter events lasting at least 4 days are significantly correlated with warm Arctic episodes. Relationships during opposite conditions of warm Europe/cold Arctic are also significant. Correlations have become consistently stronger since 1998. Large-