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Optical clocks show unprecedented accuracy, surpassing that of previously available clock systems by more than one order of magnitude. Precise intercomparisons will enable a variety of experiments, including tests of fundamental quantum physics and cosmology and applications in geodesy and navigation. Well-established, satellite-based techniques for microwave dissemination are not adequate to compare optical clocks. Here, we present phase-stabilized distribution of an optical frequency over 920 kilometers of telecommunication fiber. We used two antiparallel fiber links to determine their fractional frequency instability (modified Allan deviation) to 5 × 10⁻¹⁵ in a 1-second integration time, reaching 10⁻¹⁸ in less than 1000 seconds. For long integration times τ, the deviation from the expected frequency value has been constrained to within 4 × 10⁻¹⁹ The link may serve as part of a Europe-wide optical frequency dissemination network.

Background: MicroRNAs are small non-coding RNA molecules, which regulate central mechanisms of tumorigenesis. In colorectal tumours, the combination of gain of 8q and 13q is one of the major factors associated with colorectal adenoma to adenocarcinoma progression. Functional studies on the miR-17-92 cluster localised on 13q31 have shown that its transcription is activated by c-myc, located on 8q, and that it has oncogenic activities. We investigated the contribution of the miR-17-92 cluster during colorectal adenoma to adenocarcinoma progression. Methods: Expression levels of the miR-17-92 cluster were determined in 55 colorectal tumours and in 10 controls by real-time RT–PCR. Messenger RNA c-myc expression was also determined by real-time RT–PCR in 48 tumours with array comparative genomic hybridisation (aCGH) data available. Results: From the six members of the miR-17-92 cluster, all except miR-18a, showed significant increased expression in colorectal tumours with miR-17-92 locus gain compared with tumours without miR-17-92 locus gain. Unsupervised cluster analysis clustered the tumours based on the presence of miR-17-92 locus gain. Significant correlation between the expression of c-myc and the six miRNAs was also found. Conclusion: Increased expression of miR-17-92 cluster during colorectal adenoma to adenocarcinoma progression is associated to DNA copy number gain of miR17-92 locus on 13q31 and c-myc expression.

Objective:This study aimed to identify the oncogenes at 20q involved in colorectal adenoma to carcinoma progression by measuring the effect of 20q gain on mRNA expression of genes in this amplicon.Methods:Segmentation of DNA copy number changes on 20q was performed by array CGH (comparative genomic hybridisation) in 34 non-progressed colorectal adenomas, 41 progressed adenomas (ie, adenomas that present a focus of cancer) and 33 adenocarcinomas. Moreover, a robust analysis of altered expression of genes in these segments was performed by microarray analysis in 37 adenomas and 31 adenocarcinomas. Protein expression was evaluated by immunohistochemistry on tissue microarrays.Results:The genes C20orf24, AURKA, RNPC1, TH1L, ADRM1, C20orf20 and TCFL5, mapping at 20q, were significantly overexpressed in carcinomas compared with adenomas as a consequence of copy number gain of 20q.Conclusion:This approach revealed C20orf24, AURKA, RNPC1, TH1L, ADRM1, C20orf20 and TCFL5 genes to be important in chromosomal instability-related adenoma to carcinoma progression. These genes therefore may serve as highly specific biomarkers for colorectal cancer with potential clinical applications.

Perfluorocarbons (PFCs) are potent greenhouse gases with global warming potentials up to several thousand times greater than CO2 on a 100-year time horizon. The lack of any significant sinks for PFCs means that they have long atmospheric lifetimes of the order of thousands of years. Anthropogenic production is thought to be the only source for most PFCs. Here we report an update on the global atmospheric abundances of the following PFCs, most of which have for the first time been analytically separated according to their isomers: c-octafluorobutane (c-C4F8), n-decafluorobutane (n-C4F10), n-dodecafluoropentane (n-C5F12), n-tetradecafluorohexane (n-C6F14), and n-hexadecafluoroheptane (n-C7F16). Additionally, we report the first data set on the atmospheric mixing ratios of perfluoro-2-methylpentane (i-C6F14). The existence and significance of PFC isomers have not been reported before, due to the analytical challenges of separating them. The time series spans a period from 1978 to the present. Several data sets are used to investigate temporal and spatial trends of these PFCs: time series of air samples collected at Cape Grim, Australia, from 1978 to the start of 2018; a time series of air samples collected between July 2015 and April 2017 at Tacolneston, UK; and intensive campaign-based sampling collections from Taiwan. Although the remote “background” Southern Hemispheric Cape Grim time series indicates that recent growth rates of most of these PFCs are lower than in the 1990s, we continue to see significantly increasing mixing ratios that are between 6 % and 27 % higher by the end of 2017 compared to abundances measured in 2010. Air samples from Tacolneston show a positive offset in PFC mixing ratios compared to the Southern Hemisphere baseline. The highest mixing ratios and variability are seen in air samples from Taiwan, which is therefore likely situated much closer to PFC sources, confirming predominantly Northern Hemispheric emissions for most PFCs. Even though these PFCs occur in the atmosphere at levels of parts per trillion molar or less, their total cumulative global emissions translate into 833 million metric tonnes of CO2 equivalent by the end of 2017, 23 % of which has been emitted since 2010. Almost two-thirds of the CO2 equivalent emissions within the last decade are attributable to c-C4F8, which currently also has the highest emission rates that continue to grow. Sources of all PFCs covered in this work remain poorly constrained and reported emissions in global databases do not account for the abundances found in the atmosphere.

We present new observations of trace gases in the stratosphere based on a cost-effective sampling technique that can access much higher altitudes than aircraft. The further development of this method now provides detection of species with abundances in the parts per trillion (ppt) range and below. We obtain mixing ratios for six gases (CFC-11, CFC-12, HCFC-22, H-1211, H-1301, and SF6), all of which are important for understanding stratospheric ozone depletion and circulation. After demonstrating the quality of the data through comparisons with ground-based records and aircraft-based observations, we combine them with the latter to demonstrate its potential. We first compare the data with results from a global model driven by three widely used meteorological reanalyses. Secondly, we focus on CFC-11 as recent evidence has indicated renewed atmospheric emissions of that species relevant on a global scale. Because the stratosphere represents the main sink region for CFC-11, potential changes in stratospheric circulation and troposphere–stratosphere exchange fluxes have been identified as the largest source of uncertainty for the accurate quantification of such emissions. Our observations span over a decade (up until 2018) and therefore cover the period of the slowdown of CFC-11 global mixing ratio decreases measured at the Earth's surface. The spatial and temporal coverage of the observations is insufficient for a global quantitative analysis, but we do find some trends that are in contrast with expectations, indicating that the stratosphere may have contributed to the slower concentration decline in recent years. Further investigating the reanalysis-driven model data, we find that the dynamical changes in the stratosphere required to explain the apparent change in tropospheric CFC-11 emissions after 2013 are possible but with a very high uncertainty range. This is partly caused by the high variability of mass flux from the stratosphere to the troposphere, especially at timescales of a few years, and partly by large differences between runs driven by different reanalysis products, none of which agree with our observations well enough for such a quantitative analysis.

Tides significantly affect polar coastlines by modulating ice shelf melt and modifying shelf water properties through transport and mixing. However, the effect of tides on the marine carbonate chemistry in such regions, especially around Antarctica, remains largely unexplored. We address this topic with two case studies in a coastal polynya in the south-eastern Weddell Sea, neighbouring the Ekström Ice Shelf. The case studies were conducted in January 2015 (PS89) and January 2019 (PS117), capturing semi-diurnal oscillations in the water column. These are pronounced in both physical and biogeochemical variables for PS89. During rising tide, advection of sea ice meltwater from the north-east created a fresher, warmer, and more deeply mixed water column with lower dissolved inorganic carbon (DIC) and total alkalinity (TA) content. During ebbing tide, water from underneath the ice shelf decreased the polynya's temperature, increased the DIC and TA content, and created a more stratified water column. The variability during the PS117 case study was much smaller, as it had less sea ice meltwater input during rising tide and was better mixed with sub-ice shelf water. The contrasts in the variability between the two case studies could be wind and sea ice driven, and they underline the complexity and highly dynamic nature of the system. The variability in the polynya induced by the tides results in an air–sea CO2 flux that can range between a strong sink (−24 mmol m−2 d−1) and a small source (3 mmol m−2 d−1) on a semi-diurnal timescale. If the variability induced by tides is not taken into account, there is a potential risk of overestimating the polynya's CO2 uptake by 67 % or underestimating it by 73 %, compared to the average flux determined over several days. Depending on the timing of limited sampling, the polynya may appear to be a source or a sink of CO2. Given the disproportionate influence of polynyas on heat and carbon exchange in polar oceans, we recommend future studies around the Antarctic and Arctic coastlines to consider the timing of tidal currents in their sampling strategies and analyses. This will help constrain variability in oceanographic measurements and avoid potential biases in our understanding of these highly complex systems.

In addition to genetic changes, the occurrence of epigenetic alterations is associated with accumulation of both genetic and epigenetic events that promote the development and progression of human cancer. Previously, we reported a set of candidate genes that comprise part of the emerging \"cancer methylome\". In the present study, we first tested 23 candidate genes for promoter methylation in a small number of primary colon tumor tissues and controls. Based on these results, we then examined the methylation frequency of Oncostatin M receptor-beta (OSMR) in a larger number of tissue and stool DNA samples collected from colon cancer patients and controls. We found that OSMR was frequently methylated in primary colon cancer tissues (80%, 80/100), but not in normal tissues (4%, 4/100). Methylation of OSMR was also detected in stool DNA from colorectal cancer patients (38%, 26/69) (cut-off in TaqMan-MSP, 4). Detection of other methylated markers in stool DNA improved sensitivity with little effect on specificity. Promoter methylation mediated silencing of OSMR in cell lines, and CRC cells with low OSMR expression were resistant to growth inhibition by Oncostatin M. Our data provide a biologic rationale for silencing of OSMR in colon cancer progression and highlight a new therapeutic target in this disease. Moreover, detection and quantification of OSMR promoter methylation in fecal DNA is a highly specific diagnostic biomarker for CRC.

Iodine affects the radiative budget and the oxidative capacity of the atmosphere and is consequently involved in important climate feedbacks. A fraction of the iodine emitted by oceans ends up in aerosols, where complex halogen chemistry regulates the recycling of iodine to the gas-phase where it effectively destroys ozone. The iodine speciation and major ion composition of aerosol samples collected during four cruises in the East and West Pacific and Indian Oceans was studied to understand the influences on iodine’s gas-aerosol phase recycling. A significant inverse relationship exists between iodide (I – ) and iodate (IO 3 – ) proportions in both fine and coarse mode aerosols, with a relatively constant soluble organic iodine (SOI) fraction of 19.8% (median) for fine and coarse mode samples of all cruises combined. Consistent with previous work on the Atlantic Ocean, this work further provides observational support that IO 3 – reduction is attributed to aerosol acidity, which is associated to smaller aerosol particles and air masses that have been influenced by anthropogenic emissions. Significant correlations are found between SOI and I – , which supports hypotheses that SOI may be a source for I – . This data contributes to a growing observational dataset on aerosol iodine speciation and provides evidence for relatively constant proportions of iodine species in unpolluted marine aerosols. Future development in our understanding of iodine speciation depends on aerosol pH measurements and unravelling the complex composition of SOI in aerosols.

Leads play an important role in the exchange of heat, gases, vapour, and particles between seawater and the atmosphere in ice-covered polar oceans. In summer, these processes can be modified significantly by the formation of a meltwater layer at the surface, yet we know little about the dynamics of meltwater layer formation and persistence. During the drift campaign of the Multidisciplinary drifting Observatory for the Study of Arctic Climate (MOSAiC), we examined how variation in lead width, re-freezing, and mixing events affected the vertical structure of lead waters during late summer in the central Arctic. At the beginning of the 4-week survey period, a meltwater layer occupied the surface 0.8 m of the lead, and temperature and salinity showed strong vertical gradients. Stable oxygen isotopes indicate that the meltwater consisted mainly of sea ice meltwater rather than snow meltwater. During the first half of the survey period (before freezing), the meltwater layer thickness decreased rapidly as lead width increased and stretched the layer horizontally. During the latter half of the survey period (after freezing of the lead surface), stratification weakened and the meltwater layer became thinner before disappearing completely due to surface ice formation and mixing processes. Removal of meltwater during surface ice formation explained about 43% of the reduction in thickness of the meltwater layer. The remaining approximate 57% could be explained by mixing within the water column initiated by disturbance of the lower boundary of the meltwater layer through wind-induced ice floe drift. These results indicate that rapid, dynamic changes to lead water structure can have potentially significant effects on the exchange of physical and biogeochemical components throughout the atmosphere–lead–underlying seawater system.

Sea-air exchange of carbon dioxide in the Southern Ocean is strongly seasonal, with ocean uptake in summer, which is partly offset by carbon dioxide outgassing in winter. This seasonal balance can shift due to sea ice conditions, inducing interannual variability in the Southern Ocean carbon sink. A decade (2010–2020) of unique, year-round marine carbonate chemistry observations from the Rothera Time Series (West Antarctic Peninsula) reveals that interannual variability in seawater fugacity of carbon dioxide depends on wintertime processes. Sea ice duration controls ocean stratification, which acts as a gateway to the carbon-rich ocean interior. Consequently, years with persistent sea ice cover and high mean winter stratification absorb, on average, 20% more carbon dioxide than years with less sea ice and weaker stratification in winter. Wintertime marine observations are therefore essential to resolve critical processes and reliably quantify interannual variability of the sea-air carbon dioxide flux in seasonally sea ice-covered regions. Interannual variability of ocean uptake of carbon dioxide is governed by winter sea ice cover, according to analysis of carbonate chemistry observations along the West Antarctic Peninsula.