390 research outputs found
Protein function prediction using domain families
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
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
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
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 and
temperature , 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 noise, so
that the low-frequency noise at low temperatures may be characterized by the
Fano factor . For sufficiently large samples, scales with conductor
length as , where , and
parameter is interpreted as the average percolation cluster length. At
relatively low , the electric field dependence of parameter is
compatible with the law 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
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
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
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 shunts an external capacitor
with initial charge . 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
of the residual charge for a statistical ensemble of capacitor-shunting
conductors with random distribution of localized sites in space and energy and
random , as a function of macroscopic parameters of the system. Rather
unexpectedly, has turned out to depend only on some parameter
combination: for negligible Coulomb interaction
and for substantial interaction. (Here
is the seed density of localized states, while is the
dielectric constant.) For sufficiently large conductors, both functions
follow the power law , but with different
exponents: for negligible and
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
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 of current
fluctuations exhibits, at sufficiently low frequencies, a -like increase
which approximately follows the Hooge scaling, even at vanishing temperature.
At higher , there is a crossover to a broad range of frequencies in which
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 of the
conductor as . The exponent is significantly
affected by the Coulomb interaction effects, changing from when such effects are negligible to virtually unity when they are
substantial. The scaling parameter , interpreted as the average
percolation cluster length along the electric field direction, scales as when Coulomb interaction effects are negligible
and 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
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 ln law is obeyed,
whereas at higher temperatures deviations from this law are observed,
indicating a cross-over to Mott's ln law. The mechanism of
this cross-over is different from that considered previously in the literature.Comment: 3 pages, 3 figure
- …