1. |
- Beal, Jacob, et al.
(författare)
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Robust estimation of bacterial cell count from optical density
- 2020
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Ingår i: Communications Biology. - : Springer Science and Business Media LLC. - 2399-3642. ; 3:1
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Tidskriftsartikel (refereegranskat)abstract
- Optical density (OD) is widely used to estimate the density of cells in liquid culture, but cannot be compared between instruments without a standardized calibration protocol and is challenging to relate to actual cell count. We address this with an interlaboratory study comparing three simple, low-cost, and highly accessible OD calibration protocols across 244 laboratories, applied to eight strains of constitutive GFP-expressing E. coli. Based on our results, we recommend calibrating OD to estimated cell count using serial dilution of silica microspheres, which produces highly precise calibration (95.5% of residuals <1.2-fold), is easily assessed for quality control, also assesses instrument effective linear range, and can be combined with fluorescence calibration to obtain units of Molecules of Equivalent Fluorescein (MEFL) per cell, allowing direct comparison and data fusion with flow cytometry measurements: in our study, fluorescence per cell measurements showed only a 1.07-fold mean difference between plate reader and flow cytometry data.
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2. |
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- 2019
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Tidskriftsartikel (refereegranskat)
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3. |
- Ademuyiwa, Adesoji O., et al.
(författare)
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Determinants of morbidity and mortality following emergency abdominal surgery in children in low-income and middle-income countries
- 2016
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Ingår i: BMJ Global Health. - : BMJ Publishing Group Ltd. - 2059-7908. ; 1:4
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Tidskriftsartikel (refereegranskat)abstract
- Background: Child health is a key priority on the global health agenda, yet the provision of essential and emergency surgery in children is patchy in resource-poor regions. This study was aimed to determine the mortality risk for emergency abdominal paediatric surgery in low-income countries globally.Methods: Multicentre, international, prospective, cohort study. Self-selected surgical units performing emergency abdominal surgery submitted prespecified data for consecutive children aged <16 years during a 2-week period between July and December 2014. The United Nation's Human Development Index (HDI) was used to stratify countries. The main outcome measure was 30-day postoperative mortality, analysed by multilevel logistic regression.Results: This study included 1409 patients from 253 centres in 43 countries; 282 children were under 2 years of age. Among them, 265 (18.8%) were from low-HDI, 450 (31.9%) from middle-HDI and 694 (49.3%) from high-HDI countries. The most common operations performed were appendectomy, small bowel resection, pyloromyotomy and correction of intussusception. After adjustment for patient and hospital risk factors, child mortality at 30 days was significantly higher in low-HDI (adjusted OR 7.14 (95% CI 2.52 to 20.23), p<0.001) and middle-HDI (4.42 (1.44 to 13.56), p=0.009) countries compared with high-HDI countries, translating to 40 excess deaths per 1000 procedures performed.Conclusions: Adjusted mortality in children following emergency abdominal surgery may be as high as 7 times greater in low-HDI and middle-HDI countries compared with high-HDI countries. Effective provision of emergency essential surgery should be a key priority for global child health agendas.
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4. |
- Arndt, D. S., et al.
(författare)
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STATE OF THE CLIMATE IN 2017
- 2018
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Ingår i: Bulletin of The American Meteorological Society - (BAMS). - : American Meteorological Society. - 0003-0007 .- 1520-0477. ; 99:8, s. S1-S310
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Forskningsöversikt (refereegranskat)
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5. |
- Arndt, D. S., et al.
(författare)
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State of the Climate in 2016
- 2017
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Ingår i: Bulletin of The American Meteorological Society - (BAMS). - 0003-0007 .- 1520-0477. ; 98:8, s. S1-S280
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Tidskriftsartikel (refereegranskat)abstract
- In 2016, the dominant greenhouse gases released into Earth's atmosphere-carbon dioxide, methane, and nitrous oxide-continued to increase and reach new record highs. The 3.5 +/- 0.1 ppm rise in global annual mean carbon dioxide from 2015 to 2016 was the largest annual increase observed in the 58-year measurement record. The annual global average carbon dioxide concentration at Earth's surface surpassed 400 ppm (402.9 +/- 0.1 ppm) for the first time in the modern atmospheric measurement record and in ice core records dating back as far as 800000 years. One of the strongest El Nino events since at least 1950 dissipated in spring, and a weak La Nina evolved later in the year. Owing at least in part to the combination of El Nino conditions early in the year and a long-term upward trend, Earth's surface observed record warmth for a third consecutive year, albeit by a much slimmer margin than by which that record was set in 2015. Above Earth's surface, the annual lower troposphere temperature was record high according to all datasets analyzed, while the lower stratospheric temperature was record low according to most of the in situ and satellite datasets. Several countries, including Mexico and India, reported record high annual temperatures while many others observed near-record highs. A week-long heat wave at the end of April over the northern and eastern Indian peninsula, with temperatures surpassing 44 degrees C, contributed to a water crisis for 330 million people and to 300 fatalities. In the Arctic the 2016 land surface temperature was 2.0 degrees C above the 1981-2010 average, breaking the previous record of 2007, 2011, and 2015 by 0.8 degrees C, representing a 3.5 degrees C increase since the record began in 1900. The increasing temperatures have led to decreasing Arctic sea ice extent and thickness. On 24 March, the sea ice extent at the end of the growth season saw its lowest maximum in the 37-year satellite record, tying with 2015 at 7.2% below the 1981-2010 average. The September 2016 Arctic sea ice minimum extent tied with 2007 for the second lowest value on record, 33% lower than the 1981-2010 average. Arctic sea ice cover remains relatively young and thin, making it vulnerable to continued extensive melt. The mass of the Greenland Ice Sheet, which has the capacity to contribute similar to 7 m to sea level rise, reached a record low value. The onset of its surface melt was the second earliest, after 2012, in the 37-year satellite record. Sea surface temperature was record high at the global scale, surpassing the previous record of 2015 by about 0.01 degrees C. The global sea surface temperature trend for the 21st century-to-date of +0.162 degrees C decade(-1) is much higher than the longer term 1950-2016 trend of +0.100 degrees C decade(-1). Global annual mean sea level also reached a new record high, marking the sixth consecutive year of increase. Global annual ocean heat content saw a slight drop compared to the record high in 2015. Alpine glacier retreat continued around the globe, and preliminary data indicate that 2016 is the 37th consecutive year of negative annual mass balance. Across the Northern Hemisphere, snow cover for each month from February to June was among its four least extensive in the 47-year satellite record. Continuing a pattern below the surface, record high temperatures at 20-m depth were measured at all permafrost observatories on the North Slope of Alaska and at the Canadian observatory on northernmost Ellesmere Island. In the Antarctic, record low monthly surface pressures were broken at many stations, with the southern annular mode setting record high index values in March and June. Monthly high surface pressure records for August and November were set at several stations. During this period, record low daily and monthly sea ice extents were observed, with the November mean sea ice extent more than 5 standard deviations below the 1981-2010 average. These record low sea ice values contrast sharply with the record high values observed during 2012-14. Over the region, springtime Antarctic stratospheric ozone depletion was less severe relative to the 1991-2006 average, but ozone levels were still low compared to pre-1990 levels. Closer to the equator, 93 named tropical storms were observed during 2016, above the 1981-2010 average of 82, but fewer than the 101 storms recorded in 2015. Three basins-the North Atlantic, and eastern and western North Pacific-experienced above-normal activity in 2016. The Australian basin recorded its least active season since the beginning of the satellite era in 1970. Overall, four tropical cyclones reached the Saffir-Simpson category 5 intensity level. The strong El Nino at the beginning of the year that transitioned to a weak La Nina contributed to enhanced precipitation variability around the world. Wet conditions were observed throughout the year across southern South America, causing repeated heavy flooding in Argentina, Paraguay, and Uruguay. Wetter-than-usual conditions were also observed for eastern Europe and central Asia, alleviating the drought conditions of 2014 and 2015 in southern Russia. In the United States, California had its first wetter-than-average year since 2012, after being plagued by drought for several years. Even so, the area covered by drought in 2016 at the global scale was among the largest in the post-1950 record. For each month, at least 12% of land surfaces experienced severe drought conditions or worse, the longest such stretch in the record. In northeastern Brazil, drought conditions were observed for the fifth consecutive year, making this the longest drought on record in the region. Dry conditions were also observed in western Bolivia and Peru; it was Bolivia's worst drought in the past 25 years. In May, with abnormally warm and dry conditions already prevailing over western Canada for about a year, the human-induced Fort McMurray wildfire burned nearly 590000 hectares and became the costliest disaster in Canadian history, with $3 billion (U.S. dollars) in insured losses.
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6. |
- Blunden, Jessica, et al.
(författare)
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State of the Climate in 2012
- 2013
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Ingår i: Bulletin of The American Meteorological Society - (BAMS). - 0003-0007 .- 1520-0477. ; 94:8, s. S1-S258
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Tidskriftsartikel (refereegranskat)abstract
- For the first time in serveral years, the El Nino-Southern Oscillation did not dominate regional climate conditions around the globe. A weak La Ni a dissipated to ENSOneutral conditions by spring, and while El Nino appeared to be emerging during summer, this phase never fully developed as sea surface temperatures in the eastern conditions. Nevertheless, other large-scale climate patterns and extreme weather events impacted various regions during the year. A negative phase of the Arctic Oscillation from mid-January to early February contributed to frigid conditions in parts of northern Africa, eastern Europe, and western Asia. A lack of rain during the 2012 wet season led to the worst drought in at least the past three decades for northeastern Brazil. Central North America also experienced one of its most severe droughts on record. The Caribbean observed a very wet dry season and it was the Sahel's wettest rainy season in 50 years. Overall, the 2012 average temperature across global land and ocean surfaces ranked among the 10 warmest years on record. The global land surface temperature alone was also among the 10 warmest on record. In the upper atmosphere, the average stratospheric temperature was record or near-record cold, depending on the dataset. After a 30-year warming trend from 1970 to 1999 for global sea surface temperatures, the period 2000-12 had little further trend. This may be linked to the prevalence of La Ni a-like conditions during the 21st century. Heat content in the upper 700 m of the ocean remained near record high levels in 2012. Net increases from 2011 to 2012 were observed at 700-m to 2000-m depth and even in the abyssal ocean below. Following sharp decreases in to the effects of La Ni a, sea levels rebounded to reach records highs in 2012. The increased hydrological cycle seen in recent years continued, with more evaporation in drier locations and more precipitation in rainy areas. In a pattern that has held since 2004, salty areas of the ocean surfaces and subsurfaces were anomalously salty on average, while fresher areas were anomalously fresh. Global tropical cyclone activity during 2012 was near average, with a total of 84 storms compared with the 1981-2010 average of 89. Similar to 2010 and 2011, the North Atlantic was the only hurricane basin that experienced above-normal activity. In this basin, Sandy brought devastation to Cuba and parts of the eastern North American seaboard. All other basins experienced either near-or below-normal tropical cyclone activity. Only three tropical cyclones reached Category 5 intensity-all in Bopha became the only storm in the historical record to produce winds greater than 130 kt south of 7 N. It was also the costliest storm to affect the Philippines and killed more than 1000 residents. Minimum Arctic sea ice extent in September and Northern Hemisphere snow cover extent in June both reached new record lows. June snow cover extent is now declining at a faster rate (-17.6% per decade) than September sea ice extent (-13.0% per decade). Permafrost temperatures reached record high values in northernmost Alaska. A new melt extent record occurred on 11-12 July on the Greenland ice sheet; 97% of the ice sheet showed some form of melt, four times greater than the average melt for this time of year. The climate in Antarctica was relatively stable overall. The largest maximum sea ice extent since records begain in 1978 was observed in September 2012. In the stratosphere, warm air led to the second smallest ozone hole in the past two decades. Even so, the springtime ozone layer above Antarctica likely will not return to its early 1980s state until about 2060. Following a slight decline associated with the global 2 emissions from fossil fuel combustion and cement production reached a record 9.5 +/- 0.5 Pg C in 2011 and a new record of 9.7 +/- 0.5 Pg C is estimated for 2012. Atmospheric CO2 concentrations increased by 2.1 ppm in 2012, to 392.6 ppm. In spring 2012, 2 concentration exceeded 400 ppm at 7 of the 13 Arctic observation sites. Globally, other greenhouse gases including methane and nitrous oxide also continued to rise in concentration and the combined effect now represents a 32% increase in radiative forcing over a 1990 baseline. Concentrations of most ozone depleting substances continued to fall.
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7. |
- Hinkley, Sasha, et al.
(författare)
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The JWST Early Release Science Program for the Direct Imaging and Spectroscopy of Exoplanetary Systems
- 2022
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Ingår i: Publications of the Astronomical Society of the Pacific. - : IOP Publishing. - 0004-6280 .- 1538-3873. ; 134:1039
-
Tidskriftsartikel (refereegranskat)abstract
- The direct characterization of exoplanetary systems with high-contrast imaging is among the highest priorities for the broader exoplanet community. As large space missions will be necessary for detecting and characterizing exo-Earth twins, developing the techniques and technology for direct imaging of exoplanets is a driving focus for the community. For the first time, JWST will directly observe extrasolar planets at mid-infrared wavelengths beyond 5 μm, deliver detailed spectroscopy revealing much more precise chemical abundances and atmospheric conditions, and provide sensitivity to analogs of our solar system ice-giant planets at wide orbital separations, an entirely new class of exoplanet. However, in order to maximize the scientific output over the lifetime of the mission, an exquisite understanding of the instrumental performance of JWST is needed as early in the mission as possible. In this paper, we describe our 55 hr Early Release Science Program that will utilize all four JWST instruments to extend the characterization of planetary-mass companions to ∼15 μm as well as image a circumstellar disk in the mid-infrared with unprecedented sensitivity. Our program will also assess the performance of the observatory in the key modes expected to be commonly used for exoplanet direct imaging and spectroscopy, optimize data calibration and processing, and generate representative data sets that will enable a broad user base to effectively plan for general observing programs in future Cycles.
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8. |
- Hutchinson, David K., et al.
(författare)
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The Eocene-Oligocene transition : a review of marine and terrestrial proxy data, models and model data comparisons
- 2021
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Ingår i: Climate of the Past. - : Copernicus GmbH. - 1814-9324 .- 1814-9332. ; 17:1, s. 269-315
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Forskningsöversikt (refereegranskat)abstract
- The Eocene-Oligocene transition (EOT) was a climate shift from a largely ice-free greenhouse world to an icehouse climate, involving the first major glaciation of Antarctica and global cooling occurring similar to 34 million years ago (Ma) and lasting similar to 790 kyr. The change is marked by a global shift in deep-sea delta O-18 representing a combination of deep-ocean cooling and growth in land ice volume. At the same time, multiple independent proxies for ocean temperature indicate sea surface cooling, and major changes in global fauna and flora record a shift toward more cold-climateadapted species. The two principal suggested explanations of this transition are a decline in atmospheric CO2 and changes to ocean gateways, while orbital forcing likely influenced the precise timing of the glaciation. Here we review and synthesise proxy evidence of palaeogeography, temperature, ice sheets, ocean circulation and CO2 change from the marine and terrestrial realms. Furthermore, we quantitatively compare proxy records of change to an ensemble of climate model simulations of temperature change across the EOT. The simulations compare three forcing mechanisms across the EOT: CO2 decrease, palaeogeographic changes and ice sheet growth. Our model ensemble results demonstrate the need for a global cooling mechanism beyond the imposition of an ice sheet or palaeogeographic changes. We find that CO2 forcing involving a large decrease in CO2 of ca. 40 % (similar to 325 ppm drop) provides the best fit to the available proxy evidence, with ice sheet and palaeogeographic changes playing a secondary role. While this large decrease is consistent with some CO2 proxy records (the extreme endmember of decrease), the positive feedback mechanisms on ice growth are so strong that a modest CO2 decrease beyond a critical threshold for ice sheet initiation is well capable of triggering rapid ice sheet growth. Thus, the amplitude of CO2 decrease signalled by our data-model comparison should be considered an upper estimate and perhaps artificially large, not least because the current generation of climate models do not include dynamic ice sheets and in some cases may be undersensitive to CO2 forcing. The model ensemble also cannot exclude the possibility that palaeogeographic changes could have triggered a reduction in CO2.
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9. |
- Hutchinson, David K., et al.
(författare)
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The Eocene-Oligocene transition: a review of marine and terrestrial proxy data, models and model-data comparisons
- 2021
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Ingår i: Climate of the Past. - : European Geosciences Union (EGU). - 1814-9324 .- 1814-9332. ; 17:1, s. 269-315
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Tidskriftsartikel (refereegranskat)abstract
- The Eocene–Oligocene transition (EOT) was a climate shift from a largely ice-free greenhouse world to an icehouse climate, involving the first major glaciation of Antarctica and global cooling occurring ∼ 34 million years ago (Ma) and lasting ∼ 790 kyr. The change is marked by a global shift in deep-sea δ18O representing a combination of deep-ocean cooling and growth in land ice volume. At the same time, multiple independent proxies for ocean tempera- ture indicate sea surface cooling, and major changes in global fauna and flora record a shift toward more cold-climate- adapted species. The two principal suggested explanations of this transition are a decline in atmospheric CO2 and changes to ocean gateways, while orbital forcing likely influenced the precise timing of the glaciation. Here we review and synthesise proxy evidence of palaeogeography, temperature, ice sheets, ocean circulation and CO2 change from the marine and terrestrial realms. Furthermore, we quantitatively com- pare proxy records of change to an ensemble of climate model simulations of temperature change across the EOT. The simulations compare three forcing mechanisms across the EOT: CO2 decrease, palaeogeographic changes and ice sheet growth. Our model ensemble results demonstrate the need for a global cooling mechanism beyond the imposition of an ice sheet or palaeogeographic changes. We find that CO2 forcing involving a large decrease in CO2 of ca. 40 % (∼ 325 ppm drop) provides the best fit to the available proxy evidence, with ice sheet and palaeogeographic changes play- ing a secondary role. While this large decrease is consistent with some CO2 proxy records (the extreme endmember of decrease), the positive feedback mechanisms on ice growth are so strong that a modest CO2 decrease beyond a critical threshold for ice sheet initiation is well capable of triggering rapid ice sheet growth. Thus, the amplitude of CO2 decrease signalled by our data–model comparison should be consid- ered an upper estimate and perhaps artificially large, not least because the current generation of climate models do not in- clude dynamic ice sheets and in some cases may be under- sensitive to CO2 forcing. The model ensemble also cannot exclude the possibility that palaeogeographic changes could have triggered a reduction in CO2.
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10. |
- Campbell, PJ, et al.
(författare)
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Pan-cancer analysis of whole genomes
- 2020
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 578:7793, s. 82-
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Tidskriftsartikel (refereegranskat)abstract
- Cancer is driven by genetic change, and the advent of massively parallel sequencing has enabled systematic documentation of this variation at the whole-genome scale1–3. Here we report the integrative analysis of 2,658 whole-cancer genomes and their matching normal tissues across 38 tumour types from the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium of the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA). We describe the generation of the PCAWG resource, facilitated by international data sharing using compute clouds. On average, cancer genomes contained 4–5 driver mutations when combining coding and non-coding genomic elements; however, in around 5% of cases no drivers were identified, suggesting that cancer driver discovery is not yet complete. Chromothripsis, in which many clustered structural variants arise in a single catastrophic event, is frequently an early event in tumour evolution; in acral melanoma, for example, these events precede most somatic point mutations and affect several cancer-associated genes simultaneously. Cancers with abnormal telomere maintenance often originate from tissues with low replicative activity and show several mechanisms of preventing telomere attrition to critical levels. Common and rare germline variants affect patterns of somatic mutation, including point mutations, structural variants and somatic retrotransposition. A collection of papers from the PCAWG Consortium describes non-coding mutations that drive cancer beyond those in the TERT promoter4; identifies new signatures of mutational processes that cause base substitutions, small insertions and deletions and structural variation5,6; analyses timings and patterns of tumour evolution7; describes the diverse transcriptional consequences of somatic mutation on splicing, expression levels, fusion genes and promoter activity8,9; and evaluates a range of more-specialized features of cancer genomes8,10–18.
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11. |
- Eckert, Sebastian, et al.
(författare)
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Ultrafast Independent N-H and N-C Bond Deformation Investigated with Resonant Inelastic X-Ray Scattering
- 2017
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Ingår i: Angewandte Chemie International Edition. - : Wiley. - 1433-7851 .- 1521-3773. ; 56:22, s. 6088-6092
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Tidskriftsartikel (refereegranskat)abstract
- The femtosecond excited-state dynamics following resonant photoexcitation enable the selective deformation of N-H and N-C chemical bonds in 2-thiopyridone in aqueous solution with optical or X-ray pulses. In combination with multiconfigurational quantum-chemical calculations, the orbital-specific electronic structure and its ultrafast dynamics accessed with resonant inelastic X-ray scattering at the N 1s level using synchrotron radiation and the soft X-ray free-electron laser LCLS provide direct evidence for this controlled photoinduced molecular deformation and its ultrashort time-scale.
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12. |
- Field, Dawn, et al.
(författare)
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The minimum information about a genome sequence (MIGS) specification.
- 2008
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Ingår i: Nature biotechnology. - : Springer Science and Business Media LLC. - 1546-1696 .- 1087-0156. ; 26:5, s. 541-7
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Tidskriftsartikel (refereegranskat)abstract
- With the quantity of genomic data increasing at an exponential rate, it is imperative that these data be captured electronically, in a standard format. Standardization activities must proceed within the auspices of open-access and international working bodies. To tackle the issues surrounding the development of better descriptions of genomic investigations, we have formed the Genomic Standards Consortium (GSC). Here, we introduce the minimum information about a genome sequence (MIGS) specification with the intent of promoting participation in its development and discussing the resources that will be required to develop improved mechanisms of metadata capture and exchange. As part of its wider goals, the GSC also supports improving the 'transparency' of the information contained in existing genomic databases.
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13. |
- Hudson, Thomas J., et al.
(författare)
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International network of cancer genome projects
- 2010
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 464:7291, s. 993-998
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Tidskriftsartikel (refereegranskat)abstract
- The International Cancer Genome Consortium (ICGC) was launched to coordinate large-scale cancer genome studies in tumours from 50 different cancer types and/or subtypes that are of clinical and societal importance across the globe. Systematic studies of more than 25,000 cancer genomes at the genomic, epigenomic and transcriptomic levels will reveal the repertoire of oncogenic mutations, uncover traces of the mutagenic influences, define clinically relevant subtypes for prognosis and therapeutic management, and enable the development of new cancer therapies.
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14. |
- Kennedy, Matthew, et al.
(författare)
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Amenability, proximality and higher-order syndeticity
- 2022
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Ingår i: Forum of Mathematics, Sigma. - : Cambridge University Press (CUP). - 2050-5094. ; 10
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Tidskriftsartikel (refereegranskat)abstract
- We show that the universal minimal proximal flow and the universal minimal strongly proximal flow of a discrete group can be realized as the Stone spaces of translation-invariant Boolean algebras of subsets of the group satisfying a higher-order notion of syndeticity. We establish algebraic, combinatorial and topological dynamical characterizations of these subsets that we use to obtain new necessary and sufficient conditions for strong amenability and amenability. We also characterize dense orbit sets, answering a question of Glasner, Tsankov, Weiss and Zucker.
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15. |
- Kennedy, Peter G, et al.
(författare)
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Scaling up : examining the macroecology of ectomycorrhizal fungi.
- 2012
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Ingår i: Molecular Ecology. - 0962-1083 .- 1365-294X. ; 21:17, s. 4151-4
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Tidskriftsartikel (refereegranskat)abstract
- Ectomycorrhizal (ECM) fungi play major ecological roles in temperate and tropical ecosystems. Although the richness of ECM fungal communities and the factors controlling their structure have been documented at local spatial scales, how they vary at larger spatial scales remains unclear. In this issue of Molecular Ecology, Tedersoo et al. (2012) present the results of a meta-analysis of ECM fungal community structure that sheds important new light on global-scale patterns. Using data from 69 study systems and 6021 fungal species, the researchers found that ECM fungal richness does not fit the classic latitudinal diversity gradient in which species richness peaks at lower latitudes. Instead, richness of ECM fungal communities has a unimodal relationship with latitude that peaks in temperate zones. Intriguingly, this conclusion suggests the mechanisms driving ECM fungal community richness may differ from those of many other organisms, including their plant hosts. Future research will be key to determine the robustness of this pattern and to examine the processes that generate and maintain global-scale gradients of ECM fungal richness.
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16. |
- Lawrenson, Kate, et al.
(författare)
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Functional mechanisms underlying pleiotropic risk alleles at the 19p13.1 breast-ovarian cancer susceptibility locus
- 2016
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 7
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Tidskriftsartikel (refereegranskat)abstract
- A locus at 19p13 is associated with breast cancer (BC) and ovarian cancer (OC) risk. Here we analyse 438 SNPs in this region in 46,451 BC and 15,438 OC cases, 15,252 BRCA1 mutation carriers and 73,444 controls and identify 13 candidate causal SNPs associated with serous OC (P=9.2 × 10-20), ER-negative BC (P=1.1 × 10-13), BRCA1-associated BC (P=7.7 × 10-16) and triple negative BC (P-diff=2 × 10-5). Genotype-gene expression associations are identified for candidate target genes ANKLE1 (P=2 × 10-3) and ABHD8 (P<2 × 10-3). Chromosome conformation capture identifies interactions between four candidate SNPs and ABHD8, and luciferase assays indicate six risk alleles increased transactivation of the ADHD8 promoter. Targeted deletion of a region containing risk SNP rs56069439 in a putative enhancer induces ANKLE1 downregulation; and mRNA stability assays indicate functional effects for an ANKLE1 3′-UTR SNP. Altogether, these data suggest that multiple SNPs at 19p13 regulate ABHD8 and perhaps ANKLE1 expression, and indicate common mechanisms underlying breast and ovarian cancer risk.
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