Characterization of Protein-Protein Interactions for Therapeutic Drug Design Utilizing Mass Spectrometry

The number of transferrin based therapeutics progressing to clinical trials remains disappointingly small despite promising capabilities of transporting therapeutic payloads to cancer cells and across the blood brain barrier. This meager success record is largely due to the complexity and heterogeneity of all protein conjugation products that generates difficulties for their analytical characterization. Discussed in this work, transferrin is conjugated to lysozyme as a model therapeutic to deliver this bacteriostatic protein to target central nervous system infections. In this work ESI- and MALDI-MS were used to characterize the modification sites at lysine residues in hopes of characterizing heterogeneity within the conjugate. Identification and quantization of modification sites using MS on tryptic digested samples proved difficult with poor signal to noise ratios and missing peptide fragments. The use of an 18O labeling method that exchanges both C-terminal oxygen atoms with 18O provided more reliable results, but still proved difficult to observe all needed peptide fragments. MALDI-MS allowed for verification of ESI-MS results, but was found unhelpful with full characterization due to abundant overlapping of isotopic labeled peaks. Hoping to create an ideal 1:1 binding ratio between the two proteins, a site-specific modification method using kinetically controlled conditions was used and was confirmed that the method, although capable of producing 1:1 conjugated species, actually created different isomers with separate binding frequencies at each lysine. Online-IEC helped with the identification of isomers and started the initial work of correlating modification sites with bioactivity of the proteins. It was determined that lysozyme has a high chance of being modified at lysine 33 and 116, with a possibility of also being highly modified at lysine 97. More work is needed to complete the characterization, especially with transferrin, but the experimental approaches developed in this work prove to be promising. This work aims at delivering an optimized framework for analytical characterization of protein and antibody conjugates to guide the development of future biopharmaceuticals

Cash Conversion Cycle Management in Small Firms Relationships with Liquidity, Invested Capital, and Firm Performance

This study investigated the relationship between cash conversion cycle and levels of liquidity, invested capital, and performance in small firms over time. In a sample of 879 small U.S. manufacturing firms and 833 small U.S. retail firms, cash conversion cycle was found to be significantly related to all three of these aspects. Firms with more efficient cash conversion cycles were more liquid, required less debt and equity financing, and had higher returns. The results also indicate that small firm owners/managers may be reactive in managing cash conversion cycle. The study highlights the importance of cash conversion cycle as a proactive management tool for small firm owners

SP Equity Case Study

This case involves an entrepreneur who raises a search fund to pursue the acquisition of a software firm. It is intended for the deal structure segment of an entrepreneurial finance course, as it illustrates stages of financing, returns to investors, layering of debt and equity, and valuation, as well as the search/acquisition process. The case is positioned with the entrepreneur having found an “ideal” company to acquire; however, three days prior to closing, he has uncovered some information the seller had been trying to hide. He now needs to decide whether he should continue with the deal

Downsizing and Structural Holes: Their Impact on Layoff Survivors’ Perceptions of Organizational Chaos and Openness to Change

Organizational downsizing places many strains on surviving employees. Despite the implicit relationship between changes to communication networks and employee responses, few studies examine downsizing-induced network changes or the impact of these changes on employees. This longitudinal investigation examined fluctuations in structural holes within a hospitality company\u27s corporate headquarters resulting from the loss and gain of communication contacts. Building on Burt\u27s treatise on structural holes, we tested a measurement of structural holes and its relationship to layoff survivors\u27 perceptions of organizational chaos and their willingness to participate in planned, post downsizing changes. Although the downsizing had a modest impact on surviving employees\u27 structural hole experiences overall, the structural hole index was a significant predictor in longitudinal and within time period comparisons of employees’ perceptions of chaos and openness to change

Quantum logic gates for coupled superconducting phase qubits

Based on a quantum analysis of two capacitively coupled current-biased Josephson junctions, we propose two fundamental two-qubit quantum logic gates. Each of these gates, when supplemented by single-qubit operations, is sufficient for universal quantum computation. Numerical solutions of the time-dependent Schroedinger equation demonstrate that these operations can be performed with good fidelity.Comment: 4 pages, 5 figures, revised for publicatio

Evolution and Diffusion of the Michigan State University Tradition of Organizational Communication Network Research

This article documents the 30-year history of communication network research at Michigan State University (M.S.U.), providing a case study of the evolution and diffusion of an academic innovation. Three past and continuing issues for network scholars are identified: a lack of professional reward for developing user-friendly computer programs, unresolved methodological problems, and a need for better theoretical and conceptual frameworks. The narrative also illustrates the difficulty communication as a discipline has in impacting broader intellectual traditions. The story begins with the first doctoral dissertation (Schwartz, 1968) and the first network analysis software program in 1970 (Richards’ Negopy), continuing to the last dissertation (Susskind, 1996), and ending in 1998 when J. David Johnson left the M.S.U. faculty. Other major players in the M.S.U. network tradition included David K. Berio, Eugene Jacobson, Everett M. Rogers, Vincent Farace, Peter Monge, and Erwin Bettinghaus. Ironically, Schwartz and Susskind met in 1998 while Schwartz was preparing to retire from Cornell University and Susskind was starting as an Assistant Professor in a different department, thus providing closure to the M.S.U. network