Conformational effects on the Circular Dichroism of Human Carbonic Anhydrase II: a multilevel computational study

Circular Dichroism (CD) spectroscopy is a powerful method for investigating conformational changes in proteins and therefore has numerous applications in structural and molecular biology. Here a computational investigation of the CD spectrum of the Human Carbonic Anhydrase II (HCAII), with main focus on the near-UV CD spectra of the wild-type enzyme and it seven tryptophan mutant forms, is presented and compared to experimental studies. Multilevel computational methods (Molecular Dynamics, Semiempirical Quantum Mechanics, Time-Dependent Density Functional Theory) were applied in order to gain insight into the mechanisms of interaction between the aromatic chromophores within the protein environment and understand how the conformational flexibility of the protein influences these mechanisms. The analysis suggests that combining CD semi empirical calculations, crystal structures and molecular dynamics (MD) could help in achieving a better agreement between the computed and experimental protein spectra and provide some unique insight into the dynamic nature of the mechanisms of chromophore interactions

Conserved Mechanisms of Tumorigenesis in the Drosophila Adult Midgut

<div><p>Whereas the series of genetic events leading to colorectal cancer (CRC) have been well established, the precise functions that these alterations play in tumor progression and how they disrupt intestinal homeostasis remain poorly characterized. Activation of the Wnt/Wg signaling pathway by a mutation in the gene APC is the most common trigger for CRC, inducing benign lesions that progress to carcinomas due to the accumulation of other genetic alterations. Among those, Ras mutations drive tumour progression in CRC, as well as in most epithelial cancers. As mammalian and <i>Drosophila</i>'s intestines share many similarities, we decided to explore the alterations induced in the <i>Drosophila</i> midgut by the combined activation of the Wnt signaling pathway with gain of function of Ras signaling in the intestinal stem cells. Here we show that compound Apc-Ras clones, but not clones bearing the individual mutations, expand as aggressive intestinal tumor-like outgrowths. These lesions reproduce many of the human CRC hallmarks such as increased proliferation, blockade of cell differentiation and cell polarity and disrupted organ architecture. This process is followed by expression of tumoral markers present in human lesions. Finally, a metabolic behavioral assay shows that these flies suffer a progressive deterioration in intestinal homeostasis, providing a simple readout that could be used in screens for tumor modifiers or therapeutic compounds. Taken together, our results illustrate the conservation of the mechanisms of CRC tumorigenesis in <i>Drosophila</i>, providing an excellent model system to unravel the events that, upon mutation in Apc and Ras, lead to CRC initiation and progression.</p></div

Orbital stability of periodic waves for the nonlinear Schroedinger equation

The nonlinear Schroedinger equation has several families of quasi-periodic travelling waves, each of which can be parametrized up to symmetries by two real numbers: the period of the modulus of the wave profile, and the variation of its phase over a period (Floquet exponent). In the defocusing case, we show that these travelling waves are orbitally stable within the class of solutions having the same period and the same Floquet exponent. This generalizes a previous work where only small amplitude solutions were considered. A similar result is obtained in the focusing case, under a non-degeneracy condition which can be checked numerically. The proof relies on the general approach to orbital stability as developed by Grillakis, Shatah, and Strauss, and requires a detailed analysis of the Hamiltonian system satisfied by the wave profile.Comment: 34 pages, 7 figure

Light-flavor sea-quark distributions in the nucleon in the SU(3) chiral quark soliton model (I) -- phenomenological predictions --

Theoretical predictions are given for the light-flavor sea-quark distributions including the strange quark ones on the basis of the flavor SU(3) version of the chiral quark soliton model. Careful account is taken here of the SU(3) symmetry breaking effects due to the mass difference between the strange and nonstrange quarks. This effective mass difference $\Delta m_s$ between the strange and nonstrange quarks is the only one parameter necessary for the flavor SU(3) generalization of the model. A particular emphasis of study is put on the {\it light-flavor sea-quark asymmetry} as exemplified by the observables $\bar{d} (x) - \bar{u} (x), \bar{d} (x) / \bar{u} (x), \Delta \bar{u} (x) - \Delta \bar{d} (x)$ as well as on the {\it particle-antiparticle asymmetry} of the strange quark distributions represented by $s (x) - \bar{s} (x), s (x) / \bar{s} (x), \Delta s (x) - \Delta \bar{s} (x)$ etc. As for the unpolarized sea-quark distributions, the predictions of the model seem qualitatively consistent with the available phenomenological information provided by the NMC data for $\bar{d} (x) - \bar{u} (x)$, the E866 data for $\bar{d} (x) / \bar{u} (x)$, the CCFR data and Barone et al.'s fit for $s (x) / \bar{s} (x)$ etc. The model is shown to give several unique predictions also for the spin-dependent sea-quark distribution, such that $\Delta s (x) \ll \Delta \bar{s}(x) \lesssim 0$ and $\Delta \bar{d}(x) < 0 < \Delta \bar{u}(x)$, although the verification of these predictions must await more elaborate experimental investigations in the near future.Comment: 36 pages, 20 EPS figures. The revised version accepted for publication in Phys. Rev. D. The title has been changed, and the body of the paper has been divided into two pieces, i.e.. the present one which discusses the main phenomenological predictions of the model and the other one which describes the detailed formulation of the flavor SU(3) chiral quark soliton model to predict light-flavor quark and antiquark distribution functions in the nucleo

Polynomiality of unpolarized off-forward distribution functions and the D-term in the chiral quark-soliton model

Mellin moments of off-forward distribution functions are even polynomials of the skewedness parameter. This constraint, called polynomiality property, follows from Lorentz- and time-reversal invariance. We prove that the unpolarized off-forward distribution functions in the chiral quark-soliton model satisfy the polynomiality property. The proof is an important contribution to the demonstration that the description of off-forward distribution functions in the model is consistent. As a byproduct of the proof we derive explicit model expressions for moments of the D-term and compute the first coefficient in the Gegenbauer expansion for this term.Comment: 18 pages, no figures. Corrections and improvements in section 6. To appear in Phys.Rev.

Instability of the hedgehog shape for the octet baryon in the chiral quark soliton model

In this paper the stability of the hedgehog shape of the chiral soliton is studied for the octet baryon with the SU(3) chiral quark soliton model. The strangeness degrees of freedom are treated by a simplified bound-state approach, which omits the locality of the kaon wave function. The mean field approximation for the flavor rotation is applied to the model. The classical soliton changes shape according to the strangeness. The baryon appears as a rotational band of the combined system of the deformed soliton and the kaon.Comment: 24 pages, LaTeX, 8 eps file

Baryon Structure and the Chiral Symmetry of QCD

Beyond the spontaneous chiral symmetry breaking scale light and strange baryons should be considered as systems of three constituent quarks with an effective confining interaction and a chiral interaction that is mediated by the octet of Goldstone bosons (pseudoscalar mesons) between the constituent quarks.Comment: Lecture given at the 35. Universit\"atswochen f\"ur Kern- und Teilchenphysik, Schladming, Austria, March 1996 (Perturbative and Nonperturbative Aspects of Quantum Field Theory, ed. by H. Latal and W. Schweiger, Springer 1996). Paper (23 pages) with 2 figures and the required macro lamuphy

Real and Virtual Compton Scattering off the Nucleon

A review is given of the very recent developments in the fields of real and virtual Compton scattering off the nucleon. Both real and virtual Compton scattering reactions are discussed at low outgoing photon energy where one accesses polarizabilities of the nucleon. The real Compton scattering at large momentum transfer is discussed which is asymptotically a tool to obtain information on the valence quark wave function of the nucleon. The rapid developments in deeply virtual Compton scattering and associated meson electroproduction reactions at high energy, high photon virtuality and small momentum transfer to the nucleon are discussed. A unified theoretical description of those processes has emerged over the last few years, which gives access to new, generalized parton distributions. The experimental status and perspectives in these fields are also discussed.Comment: 25 pages, 17 figure

Transversity distributions in the nucleon in the large-N_c limit

We compute the quark and antiquark transversity distributions in the nucleon at a low normalization point of 600 MeV in the large-$N_c$ limit, where the nucleon can be described as a soliton of an effective chiral theory (chiral quark-soliton model). The flavor-nonsinglet distributions, $\delta u(x) - \delta d(x)$ and $\delta\bar u(x) - \delta\bar d(x)$, appear in leading order of the $1/N_c$-expansion, while the flavor-singlet distributions, $\delta u(x) + \delta d(x)$ and $\delta\bar u(x) + \delta\bar d(x)$, are non-zero only in next-to-leading order. The transversity quark and antiquark distributions are found to be significantly different from the longitudinally polarized distributions $\Delta u (x) \pm \Delta d (x)$ and $\Delta\bar u (x) \pm \Delta\bar d (x)$, respectively, in contrast to the prediction of the naive non-relativistic quark model. We show that this affects the predictions for the spin asymmetries in Drell-Yan pair production in transversely polarized pp and ppbar collisions.Comment: 45 pages, 16 figure

Numerical study of chemical reaction effects in magnetohydrodynamic Oldroyd B oblique stagnation flow with a non-Fourier heat flux model

Reactive magnetohydrodynamic (MHD) flows arise in many areas of nuclear reactor transport. Working fluids in such systems may be either Newtonian or non-Newtonian. Motivated by these applications, in the current study, a mathematical model is developed for electrically-conducting viscoelastic oblique flow impinging on stretching wall under transverse magnetic field. A non-Fourier Cattaneo-Christov model is employed to simulate thermal relaxation effects which cannot be simulated with the classical Fourier heat conduction approach. The Oldroyd-B non-Newtonian model is employed which allows relaxation and retardation effects to be included. A convective boundary condition is imposed at the wall invoking Biot number effects. The fluid is assumed to be chemically reactive and both homogeneous-heterogeneous reactions are studied. The conservation equations for mass, momentum, energy and species (concentration) are altered with applicable similarity variables and the emerging strongly coupled, nonlinear non-dimensional boundary value problem is solved with robust well-tested Runge-Kutta-Fehlberg numerical quadrature and a shooting technique with tolerance level of 10−4. Validation with the Adomian decomposition method (ADM) is included. The influence of selected thermal (Biot number, Prandtl number), viscoelastic hydrodynamic (Deborah relaxation number), Schmidt number, magnetic parameter and chemical reaction parameters, on velocity, temperature and concentration distributions are plotted for fixed values of geometric (stretching rate, obliqueness) and thermal relaxation parameter. Wall heat transfer rate (local heat flux) and wall species transfer rate (local mass flux) are also computed and it is observed that local mass flux increases with strength of heterogeneous reactions whereas it decreases with strength of homogeneous reactions. The results provide interesting insights into certain nuclear reactor transport phenomena and furthermore a benchmark for more general CFD simulations