931 resultados para Nature of the science


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The structural and functional organization of the Cct complex was addressed by genetic analyses of subunit interactions and catalytic cooperativity among five of the eight different essential subunits, Cct1p–Cct8p, in the yeast Saccharomyces cerevisiae. The cct1–1, cct2–3, and cct3–1 alleles, containing mutations at the conserved putative ATP-binding motif, GDGTT, are cold-sensitive, whereas single and multiple replacements of the corresponding motif in Cct6p are well tolerated by the cell. We demonstrated herein that cct6–3 (L19S), but not the parolog cct1–5 (R26I), specifically suppresses the cct1–1, cct2–3, and cct3–1 alleles, and that this suppression can be modulated by mutations in a putative phosphorylation motif, RXS, and the putative ATP-binding pocket of Cct6p. Our results suggest that the Cct ring is comprised of a single hetero-oligomer containing eight subunits of differential functional hierarchy, in which catalytic cooperativity of ATP-binding/hydrolysis takes place in a sequential manner different from the concerted cooperativity proposed for GroEL.

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We studied the electronically excited state of the isolated reaction center of photosystem II with high-resolution fluorescence spectroscopy at 5 K and compared the obtained spectral features with those obtained earlier for the primary electron donor. The results show that there is a striking resemblance between the emitting and charge-separating states in the photosystem II reaction center, such as a very similar shape of the phonon wing with characteristic features at 19 and 80 cm−1, almost identical frequencies of a number of vibrational modes, a very similar double-Gaussian shape of the inhomogeneous distribution function, and relatively strong electron-phonon coupling for both states. We suggest that the emission at 5 K originates either from an exciton state delocalized over the inactive branch of the photosystem or from a fraction of the primary electron donor that is long-lived at 5 K. The latter possibility can be explained by a distribution of the free energy difference of the primary charge separation reaction around zero. Both possibilities are in line with the idea that the state that drives primary charge separation in the reaction center of photosystem II is a collective state, with contributions from all chlorophyll molecules in the central part of the complex.

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Acute promyelocytic leukemia (APL) is associated with chromosomal translocations always involving the RARα gene, which variably fuses to one of several distinct loci, including PML or PLZF (X genes) in t(15;17) or t(11;17), respectively. APL in patients harboring t(15;17) responds well to retinoic acid (RA) treatment and chemotherapy, whereas t(11;17) APL responds poorly to both treatments, thus defining a distinct syndrome. Here, we show that RA, As2O3, and RA + As2O3 prolonged survival in either leukemic PML-RARα transgenic mice or nude mice transplanted with PML-RARα leukemic cells. RA + As2O3 prolonged survival compared with treatment with either drug alone. In contrast, neither in PLZF-RARα transgenic mice nor in nude mice transplanted with PLZF-RARα cells did any of the three regimens induce complete disease remission. Unexpectedly, therapeutic doses of RA and RA + As2O3 can induce, both in vivo and in vitro, the degradation of either PML-RARα or PLZF-RARα proteins, suggesting that the maintenance of the leukemic phenotype depends on the continuous presence of the former, but not the latter. Our findings lead to three major conclusions with relevant therapeutic implications: (i) the X-RARα oncoprotein directly determines response to treatment and plays a distinct role in the maintenance of the malignant phenotype; (ii) As2O3 and/or As2O3 + RA combination may be beneficial for the treatment of t(15;17) APL but not for t(11;17) APL; and (iii) therapeutic strategies aimed solely at degrading the X-RARα oncoprotein may not be effective in t(11;17) APL.

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We present a massive equilibrium simulation of the three-dimensional Ising spin glass at low temperatures. The Janus special-purpose computer has allowed us to equilibrate, using parallel tempering, L = 32 lattices down to T ≈ 0.64Tc. We demonstrate the relevance of equilibrium finite-size simulations to understand experimental non-equilibrium spin glasses in the thermodynamical limit by establishing a time-length dictionary. We conclude that non-equilibrium experiments performed on a time scale of one hour can be matched with equilibrium results on L ≈ 110 lattices. A detailed investigation of the probability distribution functions of the spin and link overlap, as well as of their correlation functions, shows that Replica Symmetry Breaking is the appropriate theoretical framework for the physically relevant length scales. Besides, we improve over existing methodologies to ensure equilibration in parallel tempering simulations.

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Aims. Despite their importance to a number of astrophysical fields, the lifecycles of very massive stars are still poorly defined. In order to address this shortcoming, we present a detailed quantitative study of the physical properties of four early-B hypergiants (BHGs) of spectral type B1-4 Ia+; Cyg OB2 #12, ζ1 Sco, HD 190603 and BP Cru. These are combined with an analysis of their long-term spectroscopic and photometric behaviour in order to determine their evolutionary status. Methods. Quantitative analysis of UV–radio photometric and spectroscopic datasets was undertaken with a non-LTE model atmosphere code in order to derive physical parameters for comparison with apparently closely related objects, such as B supergiants (BSGs) and luminous blue variables (LBVs), and theoretical evolutionary predictions. Results. The long-term photospheric and spectroscopic datasets compiled for the early-B HGs revealed that they are remarkably stable over long periods ( ≥ 40 yrs), with the possible exception of ζ1 Sco prior to the 20th century; in contrast to the typical excursions that characterise LBVs. Quantitative analysis of ζ1 Sco, HD 190603 and BP Cru yielded physical properties intermediate between BSGs and LBVs; we therefore suggest that BHGs are the immediate descendants and progenitors (respectively) of such stars, for initial masses in the range ~30−60 M⊙. Comparison of the properties of ζ1 Sco with the stellar population of its host cluster/association NGC 6231/Sco OB1 provides further support for such an evolutionary scenario. In contrast, while the wind properties of Cyg OB2 #12 are consistent with this hypothesis, the combination of extreme luminosity and spectroscopic mass (~110 M⊙) and comparatively low temperature means it cannot be accommodated in such a scheme. Likewise, despite its co-location with several LBVs above the Humphreys-Davidson (HD) limit, the lack of long term variability and its unevolved chemistry apparently excludes such an identification. Since such massive stars are not expected to evolve to such cool temperatures, instead traversing an O4-6Ia → O4-6Ia+ → WN7-9ha pathway, the properties of Cyg OB2 #12 are therefore difficult to understand under current evolutionary paradigms. Finally, we note that as with AG Car in its cool phase, despite exceeding the HD limit, the properties of Cyg OB2 #12 imply that it lies below the Eddington limit – thus we conclude that the HD limit does not define a region of the HR diagram inherently inimical to the presence of massive stars.

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Mutual relations in the area of sports, which in contemporary international contacts often not only reflect the true nature of political relations but sometimes even affect them, can be a valuable contribution to the analysis of this conflict’s nature. Why did the Transnistrian government, despite the use of anti-Moldovan rhetoric, agree to Transnistrian athletes representing Moldova during the Olympics and in other international competitions? Why does it accept the presence of sports teams from both banks of the Dniester playing in the same leagues? Why does Transnistria, despite being much smaller, predominate in many sports? How is it that Sheriff Tiraspol, the flagship football club of the business and political circles controlling Transnistria, managed to win the Moldovan championship ten times in a row and is the main source of players for Moldova’s national team? Does sport really ‘know no borders’ or perhaps the border on the Dniester is different than seems at first sight?