Primary malignant giant cell tumor of the sternum

Primary malignant giant cell tumor (PMGCT) is a diagnosis based on the presence of a high-grade sarcomatous component along with a typical benign giant cell tumor (GCT). We report the first case of PMGCT of the sternum in a 28-year-old male with painless swelling over the manubrium sterni. The differential diagnoses of PMGCT and giant cell-rich osteosarcoma were considered. Surgical resection was performed, and the reconstruction was done with a neosternum using polymethyl methacrylate and prolene mesh. At 30 months follow-up, the patient is disease-free

Change Management in Enterprise IT Systems: Process Modeling and Capacity-optimal Scheduling

Abstract—We provide a formal model for the Change Management process for Enterprise IT systems, and develop change scheduling algorithms that seek to attain the “change capacity ” of the system. The change management process handles critical updates in the system that often use overlapping sets of servers, resulting in scheduling conflicts between the corresponding change classes. Furthermore, applications are typically associated with certain permissible downtime windows, which impose constraints on the timing of the change executions. Scheduling of changes for such systems represent a complex dynamic optimization question. In a limiting fluid regime, where changes are assumed nonatomic, we develop a scheduling policy that provably attains the change capacity of the system. We then propose and evaluate an atomic approximation of the optimal fluid scheduling policy, which is well suited for application to a real change management system. Simulation results demonstrate that the expected change execution delay and the capacity attained by the approximate policy is close to the best attainable values, when unavoidable capacity losses due to fragmentation effects are taken into account and is significantly better than a randomized scheduling policy. I

Analysis of Transport Experiments using Pseudo-absorbance Data

The measurement of the concentration distribution of a macromolecule across a solution column by absorption optics usually requires optical transmission profiles of both the sample solution and the buffer, measured under identical conditions, to calculate the absorbance as the logarithm of the ratio of reference to sample intensity. For transport experiments, however, where the changes in the local macromolecule concentration with time are measured, a reference buffer intensity is not necessarily required. We demonstrate that the logarithm of the light transmitted through the sample solution, referred to as pseudo-absorbance, can suffice to determine macromolecular transport parameters of interest, with little loss of precision. Local changes in illumination of the sample column or in the detection efficiency of the transmitted light, as well as temporal fluctuations of the light source intensity can be well-described by consideration of time-invariant and radial-invariant signal components in the pseudo-absorbance data, using the systematic noise decomposition techniques developed recently (Schuck, P., and Demeler, B. (1999) Biophys. J. 76, 2288–2296). The practical use of the method is demonstrated with double-sector and single-sector sedimentation velocity experiments, and with analytical electrophoresis experiments. It is shown that pseudo-absorbance analysis can increase the capacity of a sedimentation velocity experiment in ultracentrifugation, and, in general, can considerably simplify the requirements of optical design

Detection and Identification of the Vibrational Markers for the Quantification of Methionine Oxidation in Therapeutic Proteins

Methionine oxidation is a major degradation pathway in therapeutic proteins which can impact the structure and function of proteins as well as risk to drug product quality. Detecting Met oxidation in proteins by peptide mapping followed by liquid chromatography with mass spectrometry (LC–MS) is the industry standard but is also labor intensive and susceptible to artifacts. In this work, vibrational difference spectroscopy in combination with ¹⁸O isotopic shift enabled us to demonstrate the application of Raman and FTIR techniques for the detection and quantification of Met oxidation in various therapeutic proteins, including mAbs, fusion proteins, and antibody drug conjugate. Vibrational markers of Met oxidation products, such as sulfoxide and sulfone, corresponding to SO and C–SO stretching frequencies were unequivocally identified based ¹⁸O isotoptic shifts. The intensity of the isolated νC–S Raman band at 702 cm^–1 was successfully applied to quantify the average Met oxidation level in multiple proteins. These results are further corroborated by oxidation levels measured by tryptic peptide mapping, and thus the confirmed Met oxidation levels derived from Raman and mass spectrometry are indeed consistent with each other. Thus, we demonstrate the broader application of vibrational spectroscopy to detect the subtle spectral changes associated with various chemical or physical degradation of proteins, including Met oxidation as well as higher order structural changes