F-18-FDG uptake is a reliable predictory of functional recovery of akinetic but viable infarct regions as defined by magnetic resonance imaging before and after revascularization

Identification of akinetic but viable myocardium is important for the selection of patients for coronary revascularization. In order to assess predictive values of end-diastolic wall thickness and dobutamine induced wall thickening obtained by magnetic resonance imaging (MRI) and [18F]Fluorodeoxyglucose uptake assessed by positron emission tomography (F-18-FDG-PET), these parameters were compared to recovery of left ventricular function after successful revascularization. Forty patients with chronic myocardial infarction and regional a- or dyskinesia by ventriculography underwent rest- and dobutamine-MRI studies (10 microg dobutamine/kg body weight/min) and F-18-FDG-PET. Viability of the infarct region was considered to be present if; 1) end-diastolic wall thickness was > or =5.5 mm; 2) dobutamine induced wall thickening > or =2 mm could be measured; and 3) normalized F-18-FDG-uptake was > or =50% in > or =50% of akinetic segments. Preserved end-diastolic wall thickness was found in 32/40 patients, functional improvement during dobutamine infusion in 26/40 patients and preserved F-18-FDG-uptake in 29/40 patients. After revascularization regional left ventricular function improved in 25/40 patients. Positive and negative predictive values and diagnostic accuracy were 78%, 100%, and 83% for preserved end-diastolic wall thickness, 92%, 93%, and 93% for dobutamine inducible contraction reserve and 86%, 100%, and 90% for preserved F-18-FDG-uptake. Quantitative assessment of dobutamine induced systolic wall thickening by MRI and F-18-FDG-uptake by PET are highly accurate techniques for the identification of viable myocardium and prediction of functional recovery after successful revascularization. Preserved end-diastolic wall thickness results in an overestimation of viable myocardium compared to functional improvement, but wall thickness <5.5 mm excludes recovery of regional function.     

Dextramabs: A Novel Format of Antibody-Drug Conjugates Featuring a Multivalent Polysaccharide Scaffold

Antibody-drug conjugates (ADCs) are multicomponent biomolecules that have emerged as a powerful tool for targeted tumor therapy. Combining specific binding of an immunoglobulin with toxic properties of a payload, they however often suffer from poor hydrophilicity when loaded with a high amount of toxins. To address these issues simultaneously, we developed dextramabs, a novel class of hybrid antibody-drug conjugates. In these architectures, the therapeutic antibody trastuzumab is equipped with a multivalent dextran polysaccharide that enables efficient loading with a potent toxin in a controllable fashion. Our modular chemoenzymatic approach provides an access to synthetic dextramabs bearing monomethyl auristatin as releasable cytotoxic cargo. They possess high drug-to-antibody ratios, remarkable hydrophilicity, and high toxicity in vitro.     

A variational principle for the scattered wave

A Schwinger-type variational principle is presented for the scattered field in the case of scalar wave scattering with an arbitrary field incident on an object of arbitrary shape with homogeneous Dirichlet boundary conditions. The result is variationally invariant at field points ranging from the surface of the scatterer to the farfield and is an important extension of the usual Schwinger variational principle for the scattering amplitude, which is a farfield quantity. Also, a generic procedure, physically motivated by the general principles of boundary conditions and shadowing, is presented for constructing simple trial functions to approximate the fields. The variational principle and the trial function design are tested for the special case of a spherical scatterer and accurate answers are found over the entire frequency range.     

Simulated caustic patterns for dynamic crack growth in a plate based on a three-dimensional numerical analysis

The rapid growth of a through-the-thickness crack in a nominally elastic plate under Mode I conditions is considered, with emphasis on the three-dimensional aspects of the elastodynamic crack growth process. For points near the crack edge, the assumptions on stress state consistent with plane stress analysis are not valid, and the possibility of an inertial effect associated with rapid lateral contraction must be considered. The steady crack growth process is analyzed here by means of the finite element method, and the degree to which the local fields are described by plane stress analysis is established. In addition, synthetic shadow spot patterns are generated from the numerical three-dimensional solutions. The inferred values of stress intensity factor are compared with the values of the corresponding plane stress dynamic stress intensity factor.     

On the counting function of the lattice profile of periodic sequences

The lattice profile analyzes the intrinsic structure of pseudorandom number sequences with applications in Monte Carlo methods and cryptology. In this paper, using the discrete Fourier transform for periodic sequences and the relation between the lattice profile and the linear complexity, we give general formulas for the expected value, variance, and counting function of the lattice profile of periodic sequences with fixed period. Moreover, we determine in a more explicit form the expected value, variance, and counting function of the lattice profile of periodic sequences for special values of the period.     

Proper actions on cohomology manifolds

Essential results about actions of compact Lie groups on connected manifolds are generalized to proper actions of arbitrary groups on connected cohomology manifolds. Slices are replaced by certain fiber bundle structures on orbit neighborhoods. The group dimension is shown to be effectively finite. The orbits of maximal dimension form a dense open connected subset. If some orbit has codimension at most , then the group is effectively a Lie group.

     

Anomalous dispersion in the Belousov-Zhabotinsky reaction: Experiments and modeling

We report results on dispersion relations and instabilities of traveling waves in excitable systems. Experiments employ solutions of the 1,4-cyclohexanedione Belousov-Zhabotinsky reaction confined to thin capillary tubes which create a pseudo-one-dimensional system. Theoretical analyses focus on a three-variable reaction-diffusion model that is known to reproduce qualitatively many of the experimentally observed dynamics. Using continuation methods, we show that the transition from normal, monotonic to anomalous, single-overshoot dispersion curves is due to an orbit flip bifurcation of the solitary pulse homoclinics. In the case of “wave stacking”, this anomaly induces attractive pulse interaction, slow solitary pulses, and faster wave trains. For “wave merging”, wave trains break up in the wake of the slow solitary pulse due to an instability of wave trains at small wavelength. A third case, “wave tracking” is characterized by the non-existence of solitary waves but existence of periodic wave trains. The corresponding dispersion curve is a closed curve covering a finite band of wavelengths.     

Specht Modules and Simple Modules for Centralizer Algebras of the Symmetric Group

Let Σ_n be the symmetric group on n letters. For l ≤ n identify Σ_l with a subgroup of Σ_n in the natural way. Let k be an algebraically closed field of characteristic p. This article begins to develop a theory for modules over the centralizer algebras kΣ_n^Σ_l that is analogous to James's theory of permutation modules, Specht modules, and simple modules over kΣ_n. We make a conjecture about how to construct all simple kΣ_n^Σ_l-modules, we develop tools to test the conjecture, and we prove that it is correct for all n when l < p.