A COMPUTATIONAL INVESTIGATION OF THE NEON-LIKE GERMANIUM COLLISIONALLY PUMPED LASER

The complex problem of a collisionally pumped Ne-like geranium laser is examined through several detailed models. The central model is EHYBRID; a 1 1/2D fluid code which self consistently treats the plasma expansion with the atomic physics of the Ne-like ion for 124 excited levels through a collisional radiative treatment. The output of EHYBRID is used as data for ray-tracing and saturation codes which generate experimental observables. A detailed description of the models is given.

A computational model of cellular response to modulated radiation fields

Purpose:
To develop a model to describe the response of cell populations to spatially modulated radiation exposures of relevance to advanced radiotherapies.

Materials and Methods:
A Monte Carlo model of cellular radiation response was developed. This model incorporated damage from both direct radiation and intercellular communication including bystander signaling. The predictions of this model were compared to previously measured survival curves for a normal human fibroblast line (AGO1522) and prostate tumor cells (DU145) exposed to spatially modulated fields.

Results:
The model was found to be able to accurately reproduce cell survival both in populations which were directly exposed to radiation and those which were outside the primary treatment field. The model predicts that the bystander effect makes a significant contribution to cell killing even in uniformly irradiated cells. The bystander effect contribution varies strongly with dose, falling from a high of 80% at low doses to 25% and 50% at 4 Gy for AGO1522 and DU145 cells, respectively. This was verified using the inducible nitric oxide synthase inhibitor aminoguanidine to inhibit the bystander effect in cells exposed to different doses, which showed significantly larger reductions in cell killing at lower doses.

Conclusions:
The model presented in this work accurately reproduces cell survival following modulated radiation exposures, both in and out of the primary treatment field, by incorporating a bystander component. In addition, the model suggests that the bystander effect is responsible for a significant portion of cell killing in uniformly irradiated cells, 50% and 70% at doses of 2 Gy in AGO1522 and DU145 cells, respectively. This description is a significant departure from accepted radiobiological models and may have a significant impact on optimization of treatment planning approaches if proven to be applicable in vivo.

Computational learning of the conditional phase-type (C-Ph) distribution: Learning C-Ph distributions

This paper presents a new algorithm for learning the structure of a special type of Bayesian network. The conditional phase-type (C-Ph) distribution is a Bayesian network that models the probabilistic causal relationships between a skewed continuous variable, modelled by the Coxian phase-type distribution, a special type of Markov model, and a set of interacting discrete variables. The algorithm takes a dataset as input and produces the structure, parameters and graphical representations of the fit of the C-Ph distribution as output.The algorithm, which uses a greedy-search technique and has been implemented in MATLAB, is evaluated using a simulated data set consisting of 20,000 cases. The results show that the original C-Ph distribution is recaptured and the fit of the network to the data is discussed.

Computational identification of self-inhibitory peptides from envelope proteins

Fusion process is known to be the initial step of viral infection and hence targeting the entry process is a promising strategy to design antiviral therapy. The self-inhibitory peptides derived from the enveloped (E) proteins function to inhibit the proteinprotein interactions in the membrane fusion step mediated by the viral E protein. Thus, they have the potential to be developed into effective antiviral therapy. Herein, we have developed a Monte Carlo-based computational method with the aim to identify and optimize potential peptide hits from the E proteins. The stability of the peptides, which indicates their potential to bind in situ to the E proteins, was evaluated by two different scoring functions, dipolar distance-scaled, finite, ideal-gas reference state and residue-specific all-atom probability discriminatory function. The method was applied to a-helical Class I HIV-1 gp41, beta-sheet Class II Dengue virus (DENV) type 2 E proteins, as well as Class III Herpes Simplex virus-1 (HSV-1) glycoprotein, a E protein with a mixture of a-helix and beta-sheet structural fold. The peptide hits identified are in line with the druggable regions where the self-inhibitory peptide inhibitors for the three classes of viral fusion proteins were derived. Several novel peptides were identified from either the hydrophobic regions or the functionally important regions on Class II DENV-2 E protein and Class III HSV-1 gB. They have potential to disrupt the proteinprotein interaction in the fusion process and may serve as starting points for the development of novel inhibitors for viral E proteins. 

The Computational Complexity of Dominance and Consistency in CP-Nets

We investigate the computational complexity of testing dominance and consistency in CP-nets. Previously, the complexity of dominance has been determined for restricted classes in which the dependency graph of the CP-net is acyclic. However, there are preferences of interest that define cyclic dependency graphs; these are modeled with general CP-nets. In our main results, we show here that both dominance and consistency for general CP-nets are PSPACE-complete. We then consider the concept of strong dominance, dominance equivalence and dominance incomparability, and several notions of optimality, and identify the complexity of the corresponding decision problems. The reductions used in the proofs are from STRIPS planning, and thus reinforce the earlier established connections between both areas.

Computational techniques for a simple theory of conditional preferences

A simple logic of conditional preferences is defined, with a language that allows the compact representation of certain kinds of conditional preference statements, a semantics and a proof theory. CP-nets and TCP-nets can be mapped into this logic, and the semantics and proof theory generalise those of CP-nets and TCP-nets. The system can also express preferences of a lexicographic kind. The paper derives various sufficient conditions for a set of conditional preferences to be consistent, along with algorithmic techniques for checking such conditions and hence confirming consistency. These techniques can also be used for totally ordering outcomes in a way that is consistent with the set of preferences, and they are further developed to give an approach to the problem of constrained optimisation for conditional preferences.

A computational study of the mechanism of CO oxidation by a ceria supported surface rhodium oxide layer

A mechanism of CO oxidation by a thin surface oxide of Rh supported on ceria is proposed: CO is oxidized by the Rh-oxide film, which is subsequently reoxidized by a ceria surface O atom. The proposed mechanism is supported by in situ Raman spectroscopic investigations.

Deployment on GPUs of an application in computational atomic physics

This paper describes the deployment on GPUs of PROP, a program of the 2DRMP suite which models electron collisions with H-like atoms and ions. Because performance on GPUs is better in single precision than in double precision, the numerical stability of the PROP program in single precision has been studied. The numerical quality of PROP results computed in single precision and their impact on the next program of the 2DRMP suite has been analyzed. Successive versions of the PROP program on GPUs have been developed in order to improve its performance. Particular attention has been paid to the optimization of data transfers and of linear algebra operations. Performance obtained on several architectures (including NVIDIA Fermi) are presented.

Comparison of dynamics of wildtype and V94M human UDP-galactose 4-epimerase-A computational perspective on severe epimerase-deficiency galactosemia

UDP-galactose 4'-epimerase (GALE) catalyzes the interconversion of UDP-galactose and UDP-glucose, an important step in galactose catabolism. Type III galactosemia, an inherited metabolic disease, is associated with mutations in human GALE. The V94M mutation has been associated with a very severe form of type III galactosemia. While a variety of structural and biochemical studies have been reported that elucidate differences between the wildtype and this mutant form of human GALE, little is known about the dynamics of the protein and how mutations influence structure and function. We performed molecular dynamics simulations on the wildtype and V94M enzyme in different states of substrate and cofactor binding. In the mutant, the average distance between the substrate and both a key catalytic residue (Tyr157) and the enzyme-bound NAD(+) cofactor and the active site dynamics are altered making substrate binding slightly less stable. However, overall stability or dynamics of the protein is not altered. This is consistent with experimental findings that the impact is largely on the turnover number (kcat), with less substantial effects on Km. Active site fluctuations were found to be correlated in enzyme with substrate bound to just one of the subunits in the homodimer suggesting inter-subunit communication. Greater active site loop mobility in human GALE compared to the equivalent loop in Escherichia coli GALE explains why the former can catalyze the interconversion of UDP-N-acetylgalactosamine and UDP-N-acetylglucosamine while the bacterial enzyme cannot. This work illuminates molecular mechanisms of disease and may inform the design of small molecule therapies for type III galactosemia.