144 research outputs found
Plasmon signatures in high harmonic generation
High harmonic generation in polarizable multi-electron systems is
investigated in the framework of multi-configuration time-dependent
Hartree-Fock. The harmonic spectra exhibit two cut offs. The first cut off is
in agreement with the well established, single active electron cut off law. The
second cut off presents a signature of multi-electron dynamics. The strong
laser field excites non-linear plasmon oscillations. Electrons that are ionized
from one of the multi-plasmon states and recombine to the ground state gain
additional energy, thereby creating the second plateau.Comment: Major revision, 12 pages, 5 figures, submitted to J. Phys. B (2005),
accepte
Frank's constant in the hexatic phase
Using video-microscopy data of a two-dimensional colloidal system the
bond-order correlation function G6 is calculated and used to determine the
temperature-dependence of both the orientational correlation length xi6 in the
isotropic liquid phase and the Frank constant F_A in the hexatic phase. F_A
takes the value 72/pi at the hexatic to isotropic liquid phase transition and
diverges at the hexatic to crystal transition as predicted by the KTHNY-theory.
This is a quantitative test of the mechanism of breaking the orientational
symmetry by disclination unbinding
Many-body theory for systems with particle conversion: Extending the multiconfigurational time-dependent Hartree method
We derive a multiconfigurational time-dependent Hartree theory for systems
with particle conversion. In such systems particles of one kind can convert to
another kind and the total number of particles varies in time. The theory thus
extends the scope of the available and successful multiconfigurational
time-dependent Hartree methods -- which were solely formulated for and applied
to systems with a fixed number of particles -- to new physical systems and
problems. As a guiding example we treat explicitly a system where bosonic atoms
can combine to form bosonic molecules and vise versa. In the theory for
particle conversion, the time-dependent many-particle wavefunction is written
as a sum of configurations made of a different number of particles, and
assembled from sets of atomic and molecular orbitals. Both the expansion
coefficients and the orbitals forming the configurations are time-dependent
quantities that are fully determined according to the Dirac-Frenkel
time-dependent variational principle. Particular attention is paid to the
reduced density matrices of the many-particle wavefunction that appear in the
theory and enter the equations of motion. There are two kinds of reduced
density matrices: particle-conserving reduced density matrices which directly
only couple configurations with the same number of atoms and molecules, and
particle non-conserving reduced density matrices which couple configurations
with a different number of atoms and molecules. Closed-form and compact
equations of motion are derived for contact as well as general two-body
interactions, and their properties are analyzed and discussed.Comment: 46 page
Key challenges in designing CHO chassis platforms
Following the success of and the high demand for recombinant protein-based therapeutics during the last 25 years, the pharmaceutical industry has invested significantly in the development of novel treatments based on biologics. Mammalian cells are the major production systems for these complex biopharmaceuticals, with Chinese hamster ovary (CHO) cell lines as the most important players. Over the years, various engineering strategies and modeling approaches have been used to improve microbial production platforms, such as bacteria and yeasts, as well as to create pre-optimized chassis host strains. However, the complexity of mammalian cells curtailed the optimization of these host cells by metabolic engineering. Most of the improvements of titer and productivity were achieved by media optimization and large-scale screening of producer clones. The advances made in recent years now open the door to again consider the potential application of systems biology approaches and metabolic engineering also to CHO. The availability of a reference genome sequence, genome-scale metabolic models and the growing number of various “omics” datasets can help overcome the complexity of CHO cells and support design strategies to boost their production performance. Modular design approaches applied to engineer industrially relevant cell lines have evolved to reduce the time and effort needed for the generation of new producer cells and to allow the achievement of desired product titers and quality. Nevertheless, important steps to enable the design of a chassis platform similar to those in use in the microbial world are still missing. In this review, we highlight the importance of mammalian cellular platforms for the production of biopharmaceuticals and compare them to microbial platforms, with an emphasis on describing novel approaches and discussing still open questions that need to be resolved to reach the objective of designing enhanced modular chassis CHO cell lines.This work has been supported the Federal Ministry for Digital and Economic Affairs (bmwd), the Federal Ministry for Transport, Innovation and Technology (bmvit), the Styrian Business Promotion Agency SFG,
the Standortagentur Tirol, Government of Lower Austria and ZIT - Technology Agency of the City of Vienna through the COMET-Funding Program managed by the Austrian Research Promotion Agency FFG. A.H. has been supported by the Portuguese NORTE-08-5369-FSE-000053 operation. Additional funding came from the PhD program BioToP (Biomolecular Technology of Proteins) of the Austrian Science Fund (FWF Project W1224) and MIT-Portugal PhD program (Bioengineering Systems). The funding agencies had no influence on the conduct of this research. Open Access Funding by the University of Vienna.info:eu-repo/semantics/publishedVersio
Finite elements and the discrete variable representation in nonequilibrium Green's function calculations. Atomic and molecular models
In this contribution, we discuss the finite-element discrete variable
representation (FE-DVR) of the nonequilibrium Green's function and its
implications on the description of strongly inhomogeneous quantum systems. In
detail, we show that the complementary features of FEs and the DVR allows for a
notably more efficient solution of the two-time Schwinger/Keldysh/Kadanoff-Baym
equations compared to a general basis approach. Particularly, the use of the
FE-DVR leads to an essential speedup in computing the self-energies.
As atomic and molecular examples we consider the He atom and the linear
version of H in one spatial dimension. For these closed-shell models we,
in Hartree-Fock and second Born approximation, compute the ground-state
properties and compare with the exact findings obtained from the solution of
the few-particle time-dependent Schr\"odinger equation.Comment: 12 pages, 3 figures, submitted as proceedings of conference "PNGF IV
Recon 2.2: from reconstruction to model of human metabolism.
IntroductionThe human genome-scale metabolic reconstruction details all known metabolic reactions occurring in humans, and thereby holds substantial promise for studying complex diseases and phenotypes. Capturing the whole human metabolic reconstruction is an on-going task and since the last community effort generated a consensus reconstruction, several updates have been developed.ObjectivesWe report a new consensus version, Recon 2.2, which integrates various alternative versions with significant additional updates. In addition to re-establishing a consensus reconstruction, further key objectives included providing more comprehensive annotation of metabolites and genes, ensuring full mass and charge balance in all reactions, and developing a model that correctly predicts ATP production on a range of carbon sources.MethodsRecon 2.2 has been developed through a combination of manual curation and automated error checking. Specific and significant manual updates include a respecification of fatty acid metabolism, oxidative phosphorylation and a coupling of the electron transport chain to ATP synthase activity. All metabolites have definitive chemical formulae and charges specified, and these are used to ensure full mass and charge reaction balancing through an automated linear programming approach. Additionally, improved integration with transcriptomics and proteomics data has been facilitated with the updated curation of relationships between genes, proteins and reactions.ResultsRecon 2.2 now represents the most predictive model of human metabolism to date as demonstrated here. Extensive manual curation has increased the reconstruction size to 5324 metabolites, 7785 reactions and 1675 associated genes, which now are mapped to a single standard. The focus upon mass and charge balancing of all reactions, along with better representation of energy generation, has produced a flux model that correctly predicts ATP yield on different carbon sources.ConclusionThrough these updates we have achieved the most complete and best annotated consensus human metabolic reconstruction available, thereby increasing the ability of this resource to provide novel insights into normal and disease states in human. The model is freely available from the Biomodels database (http://identifiers.org/biomodels.db/MODEL1603150001)
Setting and analysis of the multi-configuration time-dependent Hartree-Fock equations
In this paper we motivate, formulate and analyze the Multi-Configuration
Time-Dependent Hartree-Fock (MCTDHF) equations for molecular systems under
Coulomb interaction. They consist in approximating the N-particle Schrodinger
wavefunction by a (time-dependent) linear combination of (time-dependent)
Slater determinants. The equations of motion express as a system of ordinary
differential equations for the expansion coefficients coupled to nonlinear
Schrodinger-type equations for mono-electronic wavefunctions. The invertibility
of the one-body density matrix (full-rank hypothesis) plays a crucial role in
the analysis. Under the full-rank assumption a fiber bundle structure shows up
and produces unitary equivalence between convenient representations of the
equations. We discuss and establish existence and uniqueness of maximal
solutions to the Cauchy problem in the energy space as long as the density
matrix is not singular. A sufficient condition in terms of the energy of the
initial data ensuring the global-in-time invertibility is provided (first
result in this direction). Regularizing the density matrix breaks down energy
conservation, however a global well-posedness for this system in L^2 is
obtained with Strichartz estimates. Eventually solutions to this regularized
system are shown to converge to the original one on the time interval when the
density matrix is invertible.Comment: 48 pages, 1 figur
A multiconfigurational time-dependent Hartree-Fock method for excited electronic states. I. General formalism and application to open-shell states
The solution of the time-dependent Schrodinger equation for systems of interacting electrons is generally a prohibitive task, for which approximate methods are necessary. Popular approaches, such as the time-dependent Hartree-Fock (TDHF) approximation and time-dependent density functional theory (TDDFT), are essentially single-configurational schemes. TDHF is by construction incapable of fully accounting for the excited character of the electronic states involved in many physical processes of interest; TDDFT, although exact in principle, is limited by the currently available exchange-correlation functionals. On the other hand, multiconfigurational methods, such as the multiconfigurational time-dependent Hartree-Fock (MCTDHF) approach, provide an accurate description of the excited states and can be systematically improved. However, the computational cost becomes prohibitive as the number of degrees of freedom increases, and thus, at present, the MCTDHF method is only practical for few-electron systems. In this work, we propose an alternative approach which effectively establishes a compromise between efficiency and accuracy, by retaining the smallest possible number of configurations that catches the essential features of the electronic wavefunction. Based on a time-dependent variational principle, we derive the MCTDHF working equation for a multiconfigurational expansion with fixed coefficients and specialise to the case of general open-shell states, which are relevant for many physical processes of interest. (C) 2011 American Institute of Physics. [doi: 10.1063/1.3600397
RosettaScripts: A Scripting Language Interface to the Rosetta Macromolecular Modeling Suite
Macromolecular modeling and design are increasingly useful in basic research, biotechnology, and teaching. However, the absence of a user-friendly modeling framework that provides access to a wide range of modeling capabilities is hampering the wider adoption of computational methods by non-experts. RosettaScripts is an XML-like language for specifying modeling tasks in the Rosetta framework. RosettaScripts provides access to protocol-level functionalities, such as rigid-body docking and sequence redesign, and allows fast testing and deployment of complex protocols without need for modifying or recompiling the underlying C++ code. We illustrate these capabilities with RosettaScripts protocols for the stabilization of proteins, the generation of computationally constrained libraries for experimental selection of higher-affinity binding proteins, loop remodeling, small-molecule ligand docking, design of ligand-binding proteins, and specificity redesign in DNA-binding proteins
- …