390 research outputs found

    Protein function prediction using domain families

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    Here we assessed the use of domain families for predicting the functions of whole proteins. These 'functional families' (FunFams) were derived using a protocol that combines sequence clustering with supervised cluster evaluation, relying on available high-quality Gene Ontology (GO) annotation data in the latter step. In essence, the protocol groups domain sequences belonging to the same superfamily into families based on the GO annotations of their parent proteins. An initial test based on enzyme sequences confirmed that the FunFams resemble enzyme (domain) families much better than do families produced by sequence clustering alone. For the CAFA 2011 experiment, we further associated the FunFams with GO terms probabilistically. All target proteins were first submitted to domain superfamily assignment, followed by FunFam assignment and, eventually, function assignment. The latter included an integration step for multi-domain target proteins. The CAFA results put our domain-based approach among the top ten of 31 competing groups and 56 prediction methods, confirming that it outperforms simple pairwise whole-protein sequence comparisons

    Phase 1 dose escalation study of the allosteric AKT inhibitor BAY 1125976 in advanced solid cancer-Lack of association between activating AKT mutation and AKT inhibition-derived efficacy

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    This open-label, phase I first-in-human study (NCT01915576) of BAY 1125976, a highly specific and potent allosteric inhibitor of AKT1/2, aimed to evaluate the safety, pharmacokinetics, and maximum tolerated dose of BAY 1125976 in patients with advanced solid tumors. Oral dose escalation was investigated with a continuous once daily (QD) treatment (21 days/cycle) and a twice daily (BID) schedule. A dose expansion in 28 patients with hormone receptor-positive metastatic breast cancer, including nine patients harboring th

    First Stellar Abundances in the Dwarf Irregular Galaxy Sextans A

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    We present the abundance analyses of three isolated A-type supergiant stars in the dwarf irregular galaxy Sextans A from high-resolution spectra the UVES spectrograph at the VLT. Detailed model atmosphere analyses have been used to determine the stellar atmospheric parameters and the elemental abundances of the stars. The mean iron group abundance was determined from these three stars to be [(FeII,CrII)/H]=-0.99+/-0.04+/-0.06. This is the first determination of the present-day iron group abundances in Sextans A. These three stars now represent the most metal-poor massive stars for which detailed abundance analyses have been carried out. The mean stellar alpha element abundance was determined from the alpha element magnesium as [alpha(MgI)/H]=-1.09+/-0.02+/-0.19. This is in excellent agreement with the nebular alpha element abundances as determined from oxygen in the H II regions. These results are consistent from star-to-star with no significant spatial variations over a length of 0.8 kpc in Sextans A. This supports the nebular abundance studies of dwarf irregular galaxies, where homogeneous oxygen abundances are found throughout, and argues against in situ enrichment. The alpha/Fe abundance ratio is [alpha(MgI)/FeII,CrII]=-0.11+/-0.02+/-0.10, which is consistent with the solar ratio. This is consistent with the results from A-supergiant analyses in other Local Group dwarf irregular galaxies but in stark contrast with the high [alpha/Fe] results from metal-poor stars in the Galaxy, and is most clearly seen from these three stars in Sextans A because of their lower metallicities. The low [alpha/Fe] ratios are consistent with the slow chemical evolution expected for dwarf galaxies from analyses of their stellar populations.Comment: 40 pages, 8 figures, accepted for publication in A

    A Numerical Study of Transport and Shot Noise at 2D Hopping

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    We have used modern supercomputer facilities to carry out extensive Monte Carlo simulations of 2D hopping (at negligible Coulomb interaction) in conductors with the completely random distribution of localized sites in both space and energy, within a broad range of the applied electric field EE and temperature TT, both within and beyond the variable-range hopping region. The calculated properties include not only dc current and statistics of localized site occupation and hop lengths, but also the current fluctuation spectrum. Within the calculation accuracy, the model does not exhibit 1/f1/f noise, so that the low-frequency noise at low temperatures may be characterized by the Fano factor FF. For sufficiently large samples, FF scales with conductor length LL as (Lc/L)α(L_c/L)^{\alpha}, where α=0.76±0.08<1\alpha=0.76\pm 0.08 < 1, and parameter LcL_c is interpreted as the average percolation cluster length. At relatively low EE, the electric field dependence of parameter LcL_c is compatible with the law LcE0.911L_c\propto E^{-0.911} which follows from directed percolation theory arguments.Comment: 17 pages, 8 figures; Fixed minor typos and updated reference

    Досвід створення та функціонування Державної системи правової інформації Республіки Білорусь

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    Щодо досвіду створення та особливостей функціонування білоруської моделі державної системи правової інформації.Относительно опыта создания и особенностей функционирования белорусской модели государственной системы правовой информации.In relation to the experience of foundation and Рeculiarities of the Belorussia model state system of the legal information functioning

    Localization length and impurity dielectric susceptibility in the critical regime of the metal-insulator transition in homogeneously doped p-type Ge

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    We have determined the localization length \xi and the impurity dielectric susceptibility \chi_{\rm imp} as a function of Ga acceptor concentrations (N) in nominally uncompensated ^{70}Ge:Ga just below the critical concentration (N_c) for the metal-insulator transition. Both \xi and \chi_{\rm imp} diverge at N_c according to the functions \xi\propto(1-N/N_c)^{-\nu} and \chi_{\rm imp}\propto(N_c/N-1)^{-\zeta}, respectively, with \nu=1.2\pm0.3 and \zeta=2.3\pm0.6 for 0.99N_c< N< N_c. Outside of this region (N<0.99N_c), the values of the exponents drop to \nu=0.33\pm0.03 and \zeta=0.62\pm0.05. The effect of the small amount of compensating dopants that are present in our nominally uncompensated samples, may be responsible for the change of the critical exponents at N\approx0.99N_c.Comment: RevTeX, 4 pages with 5 embedded figures, final version (minor changes

    Sub-electron Charge Relaxation via 2D Hopping Conductors

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    We have extended Monte Carlo simulations of hopping transport in completely disordered 2D conductors to the process of external charge relaxation. In this situation, a conductor of area L×WL \times W shunts an external capacitor CC with initial charge QiQ_i. At low temperatures, the charge relaxation process stops at some "residual" charge value corresponding to the effective threshold of the Coulomb blockade of hopping. We have calculated the r.m.s.. value QRQ_R of the residual charge for a statistical ensemble of capacitor-shunting conductors with random distribution of localized sites in space and energy and random QiQ_i, as a function of macroscopic parameters of the system. Rather unexpectedly, QRQ_{R} has turned out to depend only on some parameter combination: X0LWν0e2/CX_0 \equiv L W \nu_0 e^2/C for negligible Coulomb interaction and XχLWκ2/C2X_{\chi} \equiv LW \kappa^2/C^{2} for substantial interaction. (Here ν0\nu_0 is the seed density of localized states, while κ\kappa is the dielectric constant.) For sufficiently large conductors, both functions QR/e=F(X)Q_{R}/e =F(X) follow the power law F(X)=DXβF(X)=DX^{-\beta}, but with different exponents: β=0.41±0.01\beta = 0.41 \pm 0.01 for negligible and β=0.28±0.01\beta = 0.28 \pm 0.01 for significant Coulomb interaction. We have been able to derive this law analytically for the former (most practical) case, and also explain the scaling (but not the exact value of the exponent) for the latter case. In conclusion, we discuss possible applications of the sub-electron charge transfer for "grounding" random background charge in single-electron devices.Comment: 12 pages, 5 figures. In addition to fixing minor typos and updating references, the discussion has been changed and expande

    A Numerical Study of Coulomb Interaction Effects on 2D Hopping Transport

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    We have extended our supercomputer-enabled Monte Carlo simulations of hopping transport in completely disordered 2D conductors to the case of substantial electron-electron Coulomb interaction. Such interaction may not only suppress the average value of hopping current, but also affect its fluctuations rather substantially. In particular, the spectral density SI(f)S_I (f) of current fluctuations exhibits, at sufficiently low frequencies, a 1/f1/f-like increase which approximately follows the Hooge scaling, even at vanishing temperature. At higher ff, there is a crossover to a broad range of frequencies in which SI(f)S_I (f) is nearly constant, hence allowing characterization of the current noise by the effective Fano factor F\equiv S_I(f)/2e \left. For sufficiently large conductor samples and low temperatures, the Fano factor is suppressed below the Schottky value (F=1), scaling with the length LL of the conductor as F=(Lc/L)αF = (L_c / L)^{\alpha}. The exponent α\alpha is significantly affected by the Coulomb interaction effects, changing from α=0.76±0.08\alpha = 0.76 \pm 0.08 when such effects are negligible to virtually unity when they are substantial. The scaling parameter LcL_c, interpreted as the average percolation cluster length along the electric field direction, scales as LcE(0.98±0.08)L_c \propto E^{-(0.98 \pm 0.08)} when Coulomb interaction effects are negligible and LcE(1.26±0.15)L_c \propto E^{-(1.26 \pm 0.15)} when such effects are substantial, in good agreement with estimates based on the theory of directed percolation.Comment: 19 pages, 7 figures. Fixed minor typos and updated reference

    Electronic correlation effects and the Coulomb gap at finite temperature

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    We have investigated the effect of the long-range Coulomb interaction on the one-particle excitation spectrum of n-type Germanium, using tunneling spectroscopy on mechanically controllable break junctions. The tunnel conductance was measured as a function of energy and temperature. At low temperatures, the spectra reveal a minimum at zero bias voltage due to the Coulomb gap. In the temperature range above 1 K the Coulomb gap is filled by thermal excitations. This behavior is reflected in the temperature dependence of the variable-range hopping resitivity measured on the same samples: Up to a few degrees Kelvin the Efros-Shkovskii lnRT1/2R \propto T^{-1/2} law is obeyed, whereas at higher temperatures deviations from this law are observed, indicating a cross-over to Mott's lnRT1/4R \propto T^{-1/4} law. The mechanism of this cross-over is different from that considered previously in the literature.Comment: 3 pages, 3 figure
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