The use of the DR CALUX bioassay and indicator polychlorinated biphenyls for screening of elevated levels of dioxins and dioxin-like polychlorinated biphenyls in eel.

The DR CALUX bioassay is a very suitable screening method for dioxins and dioxin-like-PCBs in feed and food. This was, e. g. demonstrated in a survey in the Netherlands to control the dioxin levels in eel. The DR CALUX assay, but also indicator polychlorinated biphenyls (PCB) were evaluated as a screening method. Based on the limit for polychlorinated dibenzo-p-dioxins/dibenzofurans (PCDD/F) [at that time 8 pg toxic equivalents (TEQ)/g eel], and the relation between PCDD/F and dioxin-like-PCB, a decision limit of 30 pg TEQ/g eel was used for screening of 153 field samples. Suspected samples (21) and part of the higher contaminated negative samples (35) were analyzed by GC/MS for dioxins, non-ortho, mono-ortho and indicator PCB, revealing 13 samples exceeding the action limit of 30 pg TEQ/g eel. Only one sample slightly exceeded the dioxin level of 8 pg TEQ/g eel. The relatively low sensitivity for mono-ortho PCB was overcome by the use of reference samples, as shown by the correlation of 0.93 between GC/MS and CALUX determined total TEQ levels. The present data show that the DR CALUX assay can be used for screening of total TEQ levels in eel. The use for dioxins only requires a safe, and therefore relatively low, decision limit. The indicator PCB also showed a good correlation with total TEQ levels, mainly due to the large contribution of the mono-ortho PCB at higher concentrations. The relation with dioxins was very poor and as such indicator PCB seem less suitable than the DR CALUX assay for screening for dioxins only. The present study clearly shows that part of the wild eel samples contains high total TEQ levels and will exceed the future European Union limit of 12 pg TEQ/g eel for dioxins and dioxin-like PCB. Especially at high TEQ levels, dioxin-like PCB contribute most to the total TEQ. In practice, wild eel presents only a minor part of the eel consumed

Instanton Induced Neutrino Majorana Masses in CFT Orientifolds with MSSM-like spectra

Recently it has been shown that string instanton effects may give rise to neutrino Majorana masses in certain classes of semi-realistic string compactifications. In this paper we make a systematic search for supersymmetric MSSM-like Type II Gepner orientifold constructions admitting boundary states associated with instantons giving rise to neutrino Majorana masses and other L- and/or B-violating operators. We analyze the zero mode structure of D-brane instantons on general type II orientifold compactifications, and show that only instantons with O(1) symmetry can have just the two zero modes required to contribute to the 4d superpotential. We however discuss how the addition of fluxes and/or possible non-perturbative extensions of the orientifold compactifications would allow also instantons with $Sp(2)$ and U(1) symmetries to generate such superpotentials. In the context of Gepner orientifolds with MSSM-like spectra, we find no models with O(1) instantons with just the required zero modes to generate a neutrino mass superpotential. On the other hand we find a number of models in one particular orientifold of the Gepner model $(2,4,22,22)$ with $Sp(2)$ instantons with a few extra uncharged non-chiral zero modes which could be easily lifted by the mentioned effects. A few more orientifold examples are also found under less stringent constraints on the zero modes. This class of $Sp(2)$ instantons have the interesting property that R-parity conservation is automatic and the flavour structure of the neutrino Majorana mass matrices has a simple factorized form.Comment: 68 pages, 2 figures; v2. typos corrected, refs adde

Two-dimensional models as testing ground for principles and concepts of local quantum physics

In the past two-dimensional models of QFT have served as theoretical laboratories for testing new concepts under mathematically controllable condition. In more recent times low-dimensional models (e.g. chiral models, factorizing models) often have been treated by special recipes in a way which sometimes led to a loss of unity of QFT. In the present work I try to counteract this apartheid tendency by reviewing past results within the setting of the general principles of QFT. To this I add two new ideas: (1) a modular interpretation of the chiral model Diff(S)-covariance with a close connection to the recently formulated local covariance principle for QFT in curved spacetime and (2) a derivation of the chiral model temperature duality from a suitable operator formulation of the angular Wick rotation (in analogy to the Nelson-Symanzik duality in the Ostertwalder-Schrader setting) for rational chiral theories. The SL(2,Z) modular Verlinde relation is a special case of this thermal duality and (within the family of rational models) the matrix S appearing in the thermal duality relation becomes identified with the statistics character matrix S. The relevant angular Euclideanization'' is done in the setting of the Tomita-Takesaki modular formalism of operator algebras. I find it appropriate to dedicate this work to the memory of J. A. Swieca with whom I shared the interest in two-dimensional models as a testing ground for QFT for more than one decade. This is a significantly extended version of an ``Encyclopedia of Mathematical Physics'' contribution hep-th/0502125.Comment: 55 pages, removal of some typos in section

Challenges Encountered Applying Equilibrium and Non-Equilibrium Binding Free Energy Calculations

Binding free energy calculations have become increasingly valuable to drive decision making in drug discovery projects. However, among other issues, inadequate sampling can reduce accuracy, limiting the value of the technique.In this paper we apply absolute binding free energy calculations to ligands binding to T4 lysozyme L99A and HSP90 using equilibrium and non-equilibrium approaches. We highlight sampling problems encountered in these systems, such as slow side chain rearrangements and slow changes of water placement upon ligand binding. These same types of challenges are likely to show up in other protein-ligand systems as well and we propose some strategies to diagnose and test for such problems in alchemical free energy calculations. We also explore similarities and differences in how the equilibrium and the non-equilibrium approaches handle these problems. Our results show the large amount of work still to be done to make free energy calculations robust and reliable and provide insight for future research in this area. </div

Challenges Encountered Applying Equilibrium and Nonequilibrium Binding Free Energy Calculations

Binding free energy calculations have become increasingly valuable to drive decision making in drug discovery projects. However, among other issues, inadequate sampling can reduce accuracy, limiting the value of the technique. In this paper, we apply absolute binding free energy calculations to ligands binding to T4 lysozyme L99A and HSP90 using equilibrium and nonequilibrium approaches. We highlight sampling problems encountered in these systems, such as slow side chain rearrangements and slow changes of water placement upon ligand binding. These same types of challenges are also likely to show up in other protein-ligand systems, and we propose some strategies to diagnose and test for such problems in alchemical free energy calculations. We also explore similarities and differences in how the equilibrium and the nonequilibrium approaches handle these problems. Our results show the large amount of work still to be done to make free energy calculations robust and reliable and provide insight for future research in this area