Urinary metabolic profile of phenylketonuria in patients receiving total parenteral nutrition and medication

Nutrition and drugs are main environmental factors that affect metabolism. We performed metabolomics of urine from an 8‐year‐old patient (case 1) with epilepsy and an 11‐year‐old patient (case 2) with malignant lymphoma who was being treated with methotrexate. Both patients were receiving total parenteral nutrition (TPN). We used our diagnostic procedure consisting of urease pretreatment, partial adoption of stable isotope dilution, gas chromatography/mass spectrometry (GC/MS) measurement and target analysis for 200 analytes including organic acids and amino acids. Surprisingly, their metabolic profiles were identical to that of phenylketonuria. The neopterin level was markedly above normal in case 1, and both neopterin and biopterin were significantly above normal in case 2. Mutation analysis of genomic DNA from case 1 showed neither homozygosity nor heterozygosity for phenylalanine hydroxylase deficiency. The metabolic profiles of both cases were normal when they were not receiving TPN. TPN is presently prohibited for individuals who have inherited disorders that affect amino acid metabolism. Although the Phe content of the TPN was not the sole cause of the PKU profile, its effect, combined with other factors, e.g. specific medication or possibly underlying diseases, led to this metabolic abnormality. The present study suggests that GC/MS‐based metabolomics by target analysis could be important for assuring the safety of the treatments for patients receiving both TPN and methotrexate. Metabolomic profiling, both before and during TPN, is useful for determining the optimal nutritional formula not only for neonates, but also for young children who are known heterozygotes for metabolic disorders or whose status is unknown. Copyright © 2009 John Wiley & Sons, Ltd.     

Comments on worldsheet description of the Omega background

Nekrasov?s partition function is defined on a flat bundle of R⁴ over S¹ called the Omega background. When the fibration is self-dual, the partition function is known to be equal to the topological string partition function, which computes scattering amplitudes of self-dual gravitons and graviphotons in type II superstring compactified on a Calabi-Yau manifold. We propose a generalization of this correspondence when the fibration is not necessarily self-dual.     

Wall Crossing as Seen by Matrix Models

The number of BPS bound states of D-branes on a Calabi-Yau manifold depends on two sets of data, the BPS charges and the stability conditions. For D0 and D2-branes bound to a single D6-brane wrapping a Calabi-Yau 3-fold X, both are naturally related to the Kähler moduli space \({{\mathcal M}(X)}\) . We construct unitary one-matrix models which count such BPS states for a class of toric Calabi-Yau manifolds at infinite ’t Hooft coupling. The matrix model for the BPS counting on X turns out to give the topological string partition function for another Calabi-Yau manifold Y, whose Kähler moduli space \({{\mathcal M}(Y)}\) contains two copies of \({{\mathcal M}(X)}\) , one related to the BPS charges and another to the stability conditions. The two sets of data are unified in \({{\mathcal M}(Y)}\) . The matrix models have a number of other interesting features. They compute spectral curves and mirror maps relevant to the remodeling conjecture. For finite ’t Hooft coupling they give rise to yet more general geometry \({\widetilde{Y}}\) containing Y.     

Nondecoupling of maximal supergravity from the superstring

We consider the conditions necessary for obtaining perturbative maximal supergravity in d dimensions as a decoupling limit of type II superstring theory compactified on a (10-d) torus. For dimensions d=2 and d=3, it is possible to define a limit in which the only finite-mass states are the 256 massless states of maximal supergravity. However, in dimensions d>or=4, there are infinite towers of additional massless and finite-mass states. These correspond to Kaluza-Klein charges, wound strings, Kaluza-Klein monopoles, or branes wrapping around cycles of the toroidal extra dimensions. We conclude that perturbative supergravity cannot be decoupled from string theory in dimensions>or=4. In particular, we conjecture that pure N=8 supergravity in four dimensions is in the Swampland.     

Modular Constraints on Calabi-Yau Compactifications

We derive global constraints on the non-BPS sector of supersymmetric 2d sigma-models whose target space is a Calabi-Yau manifold. When the total Hodge number of the Calabi-Yau threefold is sufficiently large, we show that there must be non-BPS primary states whose total conformal weights are less than 0.656. Moreover, the number of such primary states grows at least linearly in the total Hodge number. We discuss implications of these results for Calabi-Yau geometry.