332 research outputs found
Experimental and computational analyses reveal that environmental restrictions shape HIV-1 spread in 3D cultures
Here, using an integrative experimental and computational approach, Imle et al. show how cell motility and density affect HIV cell-associated transmission in a three-dimensional tissue-like culture system of CD4+ T cells and collagen, and how different collagen matrices restrict infection by cell-free virions
Computational protein profile similarity screening for quantitative mass spectrometry experiments
Motivation: The qualitative and quantitative characterization of protein abundance profiles over a series of time points or a set of environmental conditions is becoming increasingly important. Using isobaric mass tagging experiments, mass spectrometry-based quantitative proteomics deliver accurate peptide abundance profiles for relative quantitation. Associated data analysis workflows need to provide tailored statistical treatment that (i) takes the correlation structure of the normalized peptide abundance profiles into account and (ii) allows inference of protein-level similarity. We introduce a suitable distance measure for relative abundance profiles, derive a statistical test for equality and propose a protein-level representation of peptide-level measurements. This yields a workflow that delivers a similarity ranking of protein abundance profiles with respect to a defined reference. All procedures have in common that they operate based on the true correlation structure that underlies the measurements. This optimizes power and delivers more intuitive and efficient results than existing methods that do not take these circumstances into account. Results: We use protein profile similarity screening to identify candidate proteins whose abundances are post-transcriptionally controlled by the Anaphase Promoting Complex/Cyclosome (APC/C), a specific E3 ubiquitin ligase that is a master regulator of the cell cycle. Results are compared with an established protein correlation profiling method. The proposed procedure yields a 50.9-fold enrichment of co-regulated protein candidates and a 2.5-fold improvement over the previous method
New Optimization Methods for Converging Perturbative Series with a Field Cutoff
We take advantage of the fact that in lambda phi ^4 problems a large field
cutoff phi_max makes perturbative series converge toward values exponentially
close to the exact values, to make optimal choices of phi_max. For perturbative
series terminated at even order, it is in principle possible to adjust phi_max
in order to obtain the exact result. For perturbative series terminated at odd
order, the error can only be minimized. It is however possible to introduce a
mass shift in order to obtain the exact result. We discuss weak and strong
coupling methods to determine the unknown parameters. The numerical
calculations in this article have been performed with a simple integral with
one variable. We give arguments indicating that the qualitative features
observed should extend to quantum mechanics and quantum field theory. We found
that optimization at even order is more efficient that at odd order. We compare
our methods with the linear delta-expansion (LDE) (combined with the principle
of minimal sensitivity) which provides an upper envelope of for the accuracy
curves of various Pade and Pade-Borel approximants. Our optimization method
performs better than the LDE at strong and intermediate coupling, but not at
weak coupling where it appears less robust and subject to further improvements.
We also show that it is possible to fix the arbitrary parameter appearing in
the LDE using the strong coupling expansion, in order to get accuracies
comparable to ours.Comment: 10 pages, 16 figures, uses revtex; minor typos corrected, refs. adde
Performance of ab initio and density functional methods for conformational equilibria of CnH2n+2 alkane isomers (n=2-8)
Conformational energies of n-butane, n-pentane, and n-hexane have been
calculated at the CCSD(T) level and at or near the basis set limit.
Post-CCSD(T) contribution were considered and found to be unimportant. The data
thus obtained were used to assess the performance of a variety of density
functional methods. Double-hybrid functionals like B2GP-PLYP and B2K-PLYP,
especially with a small Grimme-type empirical dispersion correction, are
capable of rendering conformational energies of CCSD(T) quality. These were
then used as a `secondary standard' for a larger sample of alkanes, including
isopentane and the branched hexanes as well as key isomers of heptane and
octane. Popular DFT functionals like B3LYP, B3PW91, BLYP, PBE, and PBE0 tend to
overestimate conformer energies without dispersion correction, while the M06
family severely underestimates GG interaction energies. Grimme-type dispersion
corrections for these overcorrect and lead to qualitatively wrong conformer
orderings. All of these functionals also exhibit deficiencies in the conformer
geometries, particularly the backbone torsion angles. The PW6B95 and, to a
lesser extent, BMK functionals are relatively free of these deficiencies.
Performance of these methods is further investigated to derive conformer
ensemble corrections to the enthalpy function, , and the Gibbs
energy function, , of these alkanes. While
is only moderately sensitive to the level of theory, exhibits more pronounced sensitivity. Once again, double hybrids
acquit themselves very well.Comment: J. Phys. Chem. A, revised [Walter Thiel festschrift
Tension Dynamics and Linear Viscoelastic Behavior of a Single Semiflexible Polymer Chain
We study the dynamical response of a single semiflexible polymer chain based
on the theory developed by Hallatschek et al. for the wormlike-chain model. The
linear viscoelastic response under oscillatory forces acting at the two chain
ends is derived analytically as a function of the oscillation frequency . We
shall show that the real part of the complex compliance in the low frequency
limit is consistent with the static result of Marko and Siggia whereas the
imaginary part exhibits the power-law dependence +1/2. On the other hand, these
compliances decrease as the power law -7/8 for the high frequency limit. These
are different from those of the Rouse dynamics. A scaling argument is developed
to understand these novel results.Comment: 23 pages, 6 figure
Theoretical study of the electronic spectra of small molecules that incorporate analogues of the copper-cysteine bond
The copper-sulphur bond which binds cysteinate to the metal centre is a key factor in the spectroscopy of blue copper proteins. We present theoretical calculations describing the electronically excited states of small molecules, including CuSH, CuSCH_3, (CH_3)_2SCuSH, (imidazole)-CuSH and (imidazole)_2-CuSH, derived from the active site of blue copper proteins that contain the copper-sulphur bond in order to identify small molecular systems that have electronic structure that is analogous to the active site of the proteins. Both neutral and cationic forms are studied, since these represent the reduced and oxidised forms of the protein, respectively. For CuSH and CuSH^+, excitation energies from time-dependent density functional theory with the B97-1 exchange-correlation functional agree well with the available experimental data and multireference configuration interaction calculations. For the positive ions, the singly occupied molecular orbital is formed from an antibonding combination of a 3d orbital on copper and a 3pπ orbital on sulphur, which is analogous to the protein. This leads several of the molecules to have qualitatively similar electronic spectra to the proteins. For the neutral molecules, changes in the nature of the low lying virtual orbitals leads the predicted electronic spectra to vary substantially between the different molecules. In particular, addition of a ligand bonded directly to copper results in the low-lying excited states observed in CuSH and CuSCH_33 to be absent or shifted to higher energies
Peripheral blood T-cell signatures from high-resolution immune phenotyping of γδ and αβ T-cells in younger and older subjects in the Berlin Aging Study II
Background Aging and latent infection with Cytomegalovirus (CMV) are thought
to be major factors driving the immune system towards immunosenescence,
primarily characterized by reduced amounts of naïve T-cells and increased
memory T-cells, potentially associated with higher morbidity and mortality.
The composition of both major compartments, γδ as well as αβ T-cells, is
altered by age and CMV, but detailed knowledge of changes to the γδ subset is
currently limited. Results Here, we have surveyed a population of 73 younger
(23–35 years) and 144 older (62–85 years) individuals drawn from the Berlin
Aging Study II, investigating the distribution of detailed differentiation
phenotypes of both γδ and αβ T-cells. Correlation of frequencies and absolute
counts of the identified phenotypes with age and the presence of CMV revealed
a lower abundance of Vδ2-positive and a higher amount of Vδ1-positive cells.
We found higher frequencies of late-differentiated and lower frequencies of
early-differentiated cells in the Vδ1+ and Vδ1-Vδ2-, but not in the Vδ2+
populations in elderly CMV-seropositive individuals confirming the association
of these Vδ2-negative cells with CMV-immunosurveillance. We identified the
highest Vδ1:Vδ2 ratios in the CMV-seropositive elderly. The observed increased
CD4:CD8 ratios in the elderly were significantly lower in CMV-seropositive
individuals, who also possessed a lower naïve and a larger late-differentiated
compartment of CD8+ αβ T-cells, reflecting the consensus in the literature.
Conclusions Our findings illustrate in detail the strong influence of CMV on
the abundance and differentiation pattern of γδ T-cells as well as αβ T-cells
in older and younger people. Mechanisms responsible for the phenotypic
alterations in the γδ T-cell compartment, associated both with the presence of
CMV and with age require further clarification
Prognostic factors in 264 adults with invasive Scedosporium spp. and Lomentospora prolificans infection reported in the literature and FungiScope
Invasive Scedosporium spp. and Lomentospora prolificans infections are an emerging threat in
immunocompromised and occasionally in healthy hosts. Scedosporium spp. is intrinsically resistant
to most, L. prolificans to all the antifungal drugs currently approved, raising concerns about
appropriate treatment decisions. High mortality rates of up to 90% underline the need for comprehensive
diagnostic workup and even more for new, effective antifungal drugs to improve
patient outcome. For a comprehensive analysis, we identified cases of severe Scedosporium spp.
and L. prolificans infections from the literature diagnosed in 2000 or later and the FungiScopeVR
registry. For 208 Scedosporium spp. infections solid organ transplantation (n¼58, 27.9%) and for
56 L. prolificans infection underlying malignancy (n¼28, 50.0%) were the most prevalent risk factors.
L. prolificans infections frequently presented as fungemia (n¼26, 46.4% versus n¼12, 5.8%
for Scedosporium spp.). Malignancy, fungemia, CNS and lung involvement predicted worse outcome
for scedosporiosis and lomentosporiosis. Patients treated with voriconazole had a better
overall outcome in both groups compared to treatment with amphotericin B formulations. This
review discusses the epidemiology, prognostic factors, pathogen susceptibility to approved and
investigational antifungals, and treatment strategies of severe infections caused by Scedosporium
spp. and L. prolificans
An objective comparison of cell-tracking algorithms
We present a combined report on the results of three editions of the Cell Tracking Challenge, an ongoing initiative aimed at promoting the development and objective evaluation of cell segmentation and tracking algorithms. With 21 participating algorithms and a data repository consisting of 13 data sets from various microscopy modalities, the challenge displays today's state-of-the-art methodology in the field. We analyzed the challenge results using performance measures for segmentation and tracking that rank all participating methods. We also analyzed the performance of all of the algorithms in terms of biological measures and practical usability. Although some methods scored high in all technical aspects, none obtained fully correct solutions. We found that methods that either take prior information into account using learning strategies or analyze cells in a global spatiotemporal video context performed better than other methods under the segmentation and tracking scenarios included in the challenge
Exchange energy in the local Airy gas approximation
The Airy gas model of the edge electron gas is used to construct an exchange-energy functional which is an alternative to those obtained in the local density and generalized gradient approximations. Test calculations for rare gas atoms, molecules, solids and surfaces show that the Airy gas functional performs better than the local density approximation in all cases and better than the generalized gradient approximation for solids and surfaces. Typeset using REVTEX 1 Since the pioneering papers on density functional theory (DFT) [1,2] there has been a constant search for exchange-correlation functionals of chemical accuracy. This includes the works on the generalized gradient approximation (GGA) [3–7] which are dedicated efforts to construct local functionals for inhomogeneous systems ranging from atoms to solids based on the uniform electron gas, i.e., the local density approximation (LDA), and density gradient corrections, as well as the development of a number gradien
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