Abstract:
A computational model for the mitochondrial respiratory chain that appropriately balances mass, charge, and free energy transduction is introduced and analyzed based on a previously published set of data measured on isolated cardiac mitochondria. The basic components included in the model are the reactions at complexes I, III, and IV of the electron transport system, ATP synthesis at F(1)F(0) ATPase, substrate transporters including adenine nucleotide translocase and the phosphate-hydrogen co-transporter, and cation fluxes across the inner membrane including fluxes through the K/H antiporter and passive H and K permeation. Estimation of 16 adjustable parameter values is based on fitting model simulations to nine independent data curves. The identified model is further validated by comparison to additional datasets measured from mitochondria isolated from rat heart and liver and observed at low oxygen concentration. To obtain reasonable fits to the available data, it is necessary to incorporate inorganic-phosphate-dependent activation of the dehydrogenase activity and the electron transport system. Specifically, it is shown that a model incorporating phosphate-dependent activation of complex III is able to reasonably reproduce the observed data. The resulting validated and verified model provides a foundation for building larger and more complex systems models and investigating complex physiological and pathophysiological interactions in cardiac energetics.

Abstract:
Hepatitis C virus (HCV) is one of the main etiological factors responsible for liver disease worldwide. It has been estimated that there are over 170 million people infected with HCV worldwide. Of these infected individuals, approximately 75% will go on to develop a life long necroinflammatory liver disease, which over decades, can result in serious complications, such as cirrhosis and hepatocellular carcinoma. Currently there is no effective vaccine and whilst antiviral therapies have been improved, they are still only effective in approximately 50% of individuals. HCV infection stands as a major cause of global morbidity and suffering, and places a significant burden on health systems. The second highest cause of liver disease in the western world is alcoholic liver disease. Frequently, HCV infected individuals consume alcohol, and the combined effect of HCV and alcohol consumption is deleterious for both liver disease and response to treatment. This review discusses the impact of alcohol metabolism on HCV replication and the negative impact on interferon (IFN)-α treatment, with a particular focus on how alcohol and HCV act synergistically to increase oxidative stress, ultimately leading to exacerbated liver disease and a reduction in the efficacy of IFN-α treatment. A better understanding of the complicated mechanisms at play in hepatocytes infected with HCV and metabolizing alcohol will hopefully provide better treatment options for chronic hepatitis C individuals that consume alcohol.

Abstract:
Biochemical reaction systems may be viewed as discrete event processes characterized by a number of states and state transitions. These systems may be modeled as state transition systems with transitions representing individual reaction events. Since they often involve a large number of interactions, it can be difficult to construct such a model for a system, and since the resulting state-level model can involve a huge number of states, model analysis can be difficult or impossible. Here, we describe methods for the high-level specification of a system using hypergraphs, for the automated generation of a state-level model from a high-level model, and for the exact reduction of a state-level model using information from the high-level model. Exact reduction is achieved through the automated application of symmetry reduction and invariant manifold reduction techniques to the high-level model, allowing potentially significant reductions without the need to generate a full model. The application of the method to biochemical reaction systems is illustrated by models describing a hypothetical ion-channel at several levels of complexity. The method allows for the reduction of the otherwise intractable example models to a manageable size.

Abstract:
We propose a physically transparent analytic model of astrophysical S-factors as a function of a center-of-mass energy E of colliding nuclei (below and above the Coulomb barrier) for non-resonant fusion reactions. For any given reaction, the S(E)-model contains four parameters [two of which approximate the barrier potential, U(r)]. They are easily interpolated along many reactions involving isotopes of the same elements; they give accurate practical expressions for S(E) with only several input parameters for many reactions. The model reproduces the suppression of S(E) at low energies (of astrophysical importance) due to the shape of the low-r wing of U(r). The model can be used to reconstruct U(r) from computed or measured S(E). For illustration, we parameterize our recent calculations of S(E) (using the Sao Paulo potential and the barrier penetration formalism) for 946 reactions involving stable and unstable isotopes of C, O, Ne, and Mg (with 9 parameters for all reactions involving many isotopes of the same elements, e.g., C+O). In addition, we analyze astrophysically important 12C+12C reaction, compare theoretical models with experimental data, and discuss the problem of interpolating reliably known S(E) values to low energies (E <= 2-3 MeV).

Abstract:
We consider the astrophysical reaction rates for radiative neutron capture reactions ($n,\gamma$) in the crust of a neutron star. The presence of degenerate neutrons at high densities (mainly in the inner crust) can drastically affect the reaction rates. Standard rates assuming a Maxwell-Boltzmann distribution for neutrons can underestimate the rates by several orders of magnitude. We derive simple analytical expressions for reaction rates at a variety of conditions with account for neutron degeneracy. We also discuss the plasma effects on the outgoing radiative transition channel in neutron radiative capture reactions and show that these effects can also increase the reaction rates by a few orders of magnitude. In addition, using detailed balance, we analyze the effects of neutron degeneracy and plasma physics on reverse ($\gamma,n$) photodisintegration. We discuss the dependence of the reaction rates on temperature and neutron chemical potential and outline the efficiency of these reactions in the neutron star crust.

Abstract:
Model fit was mostly excellent, especially for American Crows, for which our models explained between 26% and 81% of the observed variance. The impact of WNV on bird populations was quantitatively evaluated by contrasting hypothetical count trajectories (omission of WNV) with observed counts. Populations of American crows were most consistently affected with a substantial cumulative impact in six of ten states. The largest negative impact, almost 60%, was found in Illinois. A regionally substantial decline was also seen for American Robins and House Sparrows, while the other species appeared unaffected.Our results confirm findings from previous studies that single out American Crows as the species most vulnerable to WNV infection. We discuss strengths and limitations of this and other methods for quantifying the impact of WNV on bird populations.In 1998, unusual mortality in Domestic Geese (Anser anser) and White Storks (Ciconia ciconia) in Israel was attributed to WNV infection [1,2]. These were the first reports of lethal WNV infection in birds outside the laboratory. The following year, widespread mortality in wild and exotic birds became the key signature of WNV emergence in North America [3]. The WNV variant in North America was closely related to the virus that had been identified in the epizootic in Israel [4]. American Crows (Corvus brachyrhynchos), as well as other members of the crow family (Corvidae), such as Blue Jays, suffered high mortality [5-10]. Crow mortality was proposed as a reliable indicator of WNV activity [11-17]. Like their old-world relatives [18], American Crows invariably succumbed to experimental WNV infection [19,20]. Directly monitored populations of these birds suffered catastrophic mortality due to WNV infection [21,22]. These observations spawned concerns about the threat WNV might pose to the North American avifauna. While only individual monitoring can offer direct insight into the impact of WNV on bird populations, this approach

Abstract:
We construct an efficient cluster algorithm for ferromagnetic SU(N)-symmetric quantum spin systems. Such systems provide a new regularization for CP(N-1) models in the framework of D-theory, which is an alternative non-perturbative approach to quantum field theory formulated in terms of discrete quantum variables instead of classical fields. Despite several attempts, no efficient cluster algorithm has been constructed for CP(N-1) models in the standard formulation of lattice field theory. In fact, there is even a no-go theorem that prevents the construction of an efficient Wolff-type embedding algorithm. We present various simulations for different correlation lengths, couplings and lattice sizes. We have simulated correlation lengths up to 250 lattice spacings on lattices as large as 640x640 and we detect no evidence for critical slowing down.

Abstract:
Despite several attempts, no efficient cluster algorithm has been constructed for CP(N-1) models in the standard Wilson formulation of lattice field theory. In fact, there is a no-go theorem that prevents the construction of an efficient Wolff-type embedding algorithm. In this paper, we construct an efficient cluster algorithm for ferromagnetic SU(N)-symmetric quantum spin systems. Such systems provide a regularization for CP(N-1) models in the framework of D-theory. We present detailed studies of the autocorrelations and find a dynamical critical exponent that is consistent with z = 0.

Abstract:
D-theory provides an alternative lattice regularization of the (1+1)-d CP(N-1) quantum field theory. In this formulation the continuous classical CP(N-1) fields emerge from the dimensional reduction of discrete SU(N) quantum spins. In analogy to Haldane's conjecture, ladders consisting of an even number of transversely coupled spin chains lead to a CP(N-1) model with vacuum angle \theta = 0, while an odd number of chains yields \theta = \pi. In contrast to Wilson's formulation of lattice field theory, in D-theory no sign problem arises at \theta = \pi, and an efficient cluster algorithm is used to investigate the \theta-vacuum effects. At \theta = \pi there is a first order phase transition with spontaneous breaking of charge conjugation symmetry for CP(N-1) models with N>2.

Abstract:
We present numerical results for 2-d CP(N-1) models at \theta=0 and \pi obtained in the D-theory formulation. In this formulation we construct an efficient cluster algorithm and we show numerical evidence for a first order transition for CP(N-1\geq 2) models at \theta = \pi. By a finite size scaling analysis, we also discuss the equivalence in the continuum limit of the D-theory formulation of the 2-d CP(N-1) models and the usual lattice definition.