Institution
University of Siena
Education•Siena, Italy•
About: University of Siena is a education organization based out in Siena, Italy. It is known for research contribution in the topics: Population & Cancer. The organization has 12179 authors who have published 33334 publications receiving 1008287 citations. The organization is also known as: Università degli studi di Siena & Universita degli studi di Siena.
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TL;DR: Next generation sequencing and copy number analysis provide insights into the complexity of the CLL coding genome, and reveal an association between NOTCH1 mutational activation and poor prognosis.
Abstract: The pathogenesis of chronic lymphocytic leukemia (CLL), the most common leukemia in adults, is still largely unknown. The full spectrum of genetic lesions that are present in the CLL genome, and therefore the number and identity of dysregulated cellular pathways, have not been identified. By combining next-generation sequencing and copy number analysis, we show here that the typical CLL coding genome contains <20 clonally represented gene alterations/case, including predominantly nonsilent mutations, and fewer copy number aberrations. These analyses led to the discovery of several genes not previously known to be altered in CLL. Although most of these genes were affected at low frequency in an expanded CLL screening cohort, mutational activation of NOTCH1, observed in 8.3% of CLL at diagnosis, was detected at significantly higher frequency during disease progression toward Richter transformation (31.0%), as well as in chemorefractory CLL (20.8%). Consistent with the association of NOTCH1 mutations with clinically aggressive forms of the disease, NOTCH1 activation at CLL diagnosis emerged as an independent predictor of poor survival. These results provide initial data on the complexity of the CLL coding genome and identify a dysregulated pathway of diagnostic and therapeutic relevance.
609 citations
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TL;DR: The MAGIC telescope was used to observe the blazar Markarian 501 (Mrk 501) at energies above 100 GeV from May through July 2005 as mentioned in this paper, and the high sensitivity of the instrument enabled the determination of the flux and spectrum of the source on a night-by-night basis.
Abstract: The blazar Markarian 501 (Mrk 501) was observed at energies above 100 GeV with the MAGIC telescope from May through July 2005. The high sensitivity of the instrument enabled the determination of the flux and spectrum of the source on a night-by-night basis. Throughout our observational campaign, the flux from Mrk 501 was found to vary by an order of magnitude, and to be correlated with spectral changes. Intra-night flux variability with flux-doubling times down to 2 minutes was also observed. The strength of variability increased with the energy of the {gamma}-ray photons. The energy spectra were found to harden significantly with increasing flux, and a spectral peak clearly showed up during very active states. The position of the spectral peak seems to be correlated with the source luminosity.
606 citations
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GNS Science1, Victoria University of Wellington2, Northern Illinois University3, University of Nebraska–Lincoln4, University of Otago5, University of Siena6, Ohio State University7, National Institute of Geophysics and Volcanology8, University of Massachusetts Amherst9, Harvard University10, Pennsylvania State University11, New Mexico Institute of Mining and Technology12, Appalachian State University13, Johns Hopkins University14, University of Milano-Bicocca15, Colorado School of Mines16, Denver Federal Center17, University of Wisconsin–Oshkosh18, University of Parma19, Iowa State University20, Stanford University21, University of Alberta22, Louisiana State University23, Albion College24, Lamont–Doherty Earth Observatory25
TL;DR: A marine glacial record from the upper 600 m of the AND-1B sediment core recovered from beneath the northwest part of the Ross ice shelf is presented and well-dated, ∼40-kyr cyclic variations in ice-sheet extent linked to cycles in insolation influenced by changes in the Earth’s axial tilt (obliquity) during the Pliocene are demonstrated.
Abstract: Thirty years after oxygen isotope records from microfossils deposited in ocean sediments confirmed the hypothesis that variations in the Earth's orbital geometry control the ice ages, fundamental questions remain over the response of the Antarctic ice sheets to orbital cycles. Furthermore, an understanding of the behaviour of the marine-based West Antarctic ice sheet (WAIS) during the 'warmer-than-present' early-Pliocene epoch ( approximately 5-3 Myr ago) is needed to better constrain the possible range of ice-sheet behaviour in the context of future global warming. Here we present a marine glacial record from the upper 600 m of the AND-1B sediment core recovered from beneath the northwest part of the Ross ice shelf by the ANDRILL programme and demonstrate well-dated, approximately 40-kyr cyclic variations in ice-sheet extent linked to cycles in insolation influenced by changes in the Earth's axial tilt (obliquity) during the Pliocene. Our data provide direct evidence for orbitally induced oscillations in the WAIS, which periodically collapsed, resulting in a switch from grounded ice, or ice shelves, to open waters in the Ross embayment when planetary temperatures were up to approximately 3 degrees C warmer than today and atmospheric CO(2) concentration was as high as approximately 400 p.p.m.v. (refs 5, 6). The evidence is consistent with a new ice-sheet/ice-shelf model that simulates fluctuations in Antarctic ice volume of up to +7 m in equivalent sea level associated with the loss of the WAIS and up to +3 m in equivalent sea level from the East Antarctic ice sheet, in response to ocean-induced melting paced by obliquity. During interglacial times, diatomaceous sediments indicate high surface-water productivity, minimal summer sea ice and air temperatures above freezing, suggesting an additional influence of surface melt under conditions of elevated CO(2).
605 citations
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University of Oxford1, Australian National University2, Queen's University Belfast3, University of Maryland, College Park4, University of the Basque Country5, Autonomous University of Madrid6, University of Siena7, Centre national de la recherche scientifique8, University of Tübingen9, University of La Laguna10, University of Cantabria11, University of Trento12, Royal Belgian Institute of Natural Sciences13, University of Massachusetts Amherst14, University of Arizona15, National University of Distance Education16, Weizmann Institute of Science17, Trent University18, University of Genoa19, University of Ferrara20, University of Oviedo21, Université de Montréal22, University College Dublin23, Natural History Museum24
TL;DR: Improved accelerator mass spectrometry 14C techniques are applied to construct robust chronologies from 40 key Mousterian and Neanderthal archaeological sites, showing that there was ample time for the transmission of cultural and symbolic behaviours, as well as possible genetic exchanges, between the two groups.
Abstract: The timing of Neanderthal disappearance and the extent to which they overlapped with the earliest incoming anatomically modern humans (AMHs) in Eurasia are key questions in palaeoanthropology. Determining the spatiotemporal relationship between the two populations is crucial if we are to understand the processes, timing and reasons leading to the disappearance of Neanderthals and the likelihood of cultural and genetic exchange. Serious technical challenges, however, have hindered reliable dating of the period, as the radiocarbon method reaches its limit at ∼50,000 years ago. Here we apply improved accelerator mass spectrometry (14)C techniques to construct robust chronologies from 40 key Mousterian and Neanderthal archaeological sites, ranging from Russia to Spain. Bayesian age modelling was used to generate probability distribution functions to determine the latest appearance date. We show that the Mousterian ended by 41,030-39,260 calibrated years bp (at 95.4% probability) across Europe. We also demonstrate that succeeding 'transitional' archaeological industries, one of which has been linked with Neanderthals (Châtelperronian), end at a similar time. Our data indicate that the disappearance of Neanderthals occurred at different times in different regions. Comparing the data with results obtained from the earliest dated AMH sites in Europe, associated with the Uluzzian technocomplex, allows us to quantify the temporal overlap between the two human groups. The results reveal a significant overlap of 2,600-5,400 years (at 95.4% probability). This has important implications for models seeking to explain the cultural, technological and biological elements involved in the replacement of Neanderthals by AMHs. A mosaic of populations in Europe during the Middle to Upper Palaeolithic transition suggests that there was ample time for the transmission of cultural and symbolic behaviours, as well as possible genetic exchanges, between the two groups.
605 citations
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TL;DR: A peculiar characteristic of the proposed formation control strategy is that the follower position is not rigidly fixed with respect to the leader but varies in proper circle arcs centered in the leader reference frame.
600 citations
Authors
Showing all 12352 results
Name | H-index | Papers | Citations |
---|---|---|---|
Johan Auwerx | 158 | 653 | 95779 |
I. V. Gorelov | 139 | 1916 | 103133 |
Roberto Tenchini | 133 | 1390 | 94541 |
Francesco Fabozzi | 133 | 1561 | 93364 |
M. Davier | 132 | 1449 | 107642 |
Roberto Dell'Orso | 132 | 1412 | 92792 |
Rino Rappuoli | 132 | 816 | 64660 |
Teimuraz Lomtadze | 129 | 893 | 80314 |
Manas Maity | 129 | 1309 | 87465 |
Dezso Horvath | 128 | 1283 | 88111 |
Paolo Azzurri | 126 | 1058 | 81651 |
Vincenzo Di Marzo | 126 | 659 | 60240 |
Igor Katkov | 125 | 972 | 71845 |
Ying Lu | 123 | 708 | 62645 |
Thomas Schwarz | 123 | 701 | 54560 |