Game Changers: Rewriting the Playbook A Sports and Entertainment Law Symposium

Attorney Steven Howard Roth participated in the following fireside chat with Akron Law Review Associate Editor Andrew Fleming as part of the Akron Law Review 2023 Symposium at The University of Akron School of Law in April 2023. Some content may be modified and/or abbreviated from its original transcript for purposes of flow and brevity. Attorney Roth is the Founder and a Principal of Roth Firm, LLC, a law firm that represents individuals and domestic and international companies within the middle and upper middle market in business and transactional matters. Attorney Roth’s practice focuses on the areas of mergers and acquisitions, corporate transactions and governance, sports, media and entertainment, intellectual property law, securities, and commercial real estate. Leveraging his unique skill set and experience, Attorney Roth has successfully negotiated and closed over $850 million in transactions for his clients. Since 2020, Attorney Roth has been recognized each year as a Best Lawyers: Ones to Watch and an Ohio Super Lawyers Rising Star. Prior to starting Roth Firm, Attorney Roth worked for several private businesses and organizations, including a regional law firm, as counsel for a private equity company, and as a legal consultant for a multi-billion dollar steel company. Attorney Roth has also worked for multiple professional sports teams, including NFL and NBA franchise teams, governing bodies, and sports agencies. Attorney Roth holds a JD and MBA, with a concentration in banking and finance, from Case Western Reserve University

Characterization of Reactions to Intravenous Immunoglobulin in Neonatal Calves

Intravenous immunoglobulin (IVIG) products improve passive immunity in neonates. Unfortunately, adverse reactions can occur. This study was designed to determine if physiological changes occurring after IVIG administration were the result of rapid infusion of large molecular weight molecules, or from a more complex mechanism resulting in histamine release. The IVIG was concentrated from bovine abattoir blood and contained approximately 35 g IgG/L. A dextran (75,000 MW) solution was prepared as a high molecular weight control that was similar in osmolarity to the IVIG. Holstein bull calves (n=15) under 1 wk of age were assigned to one of three treatment groups: control calves received 500 ml of 0.9% NaCl; dextran calves received 500 ml of dextran; IgG calves received 500 ml of IVIG. Treatments were rapidly administered (less than 5 min) intravenously via jugular catheter. Heart rate, respiration rate, and blood pressure were measured prior to treatment, and at 1, 3, 5, 10, 15, 20, 25, 30, 45, 60, 75, and 90 min after start of infusion. Blood samples were obtained at the same sampling times, centrifuged, and the plasma immediately placed on ice for determination of histamine concentration using an enzyme immunoassay. Mean respiration rates were higher in calves treated with IVIG compared to calves in the other two groups at all time periods measured. Mean heart rates were lower in calves treated with IVIG compared to calves in the other groups through 45 min. Calves treated with dextran had higher mean heart rates than calves on the control treatment from 10 min through 30 min. Mean blood pressure tended to be higher in calves treated with IVIG compared to calves on the control treatment at 1 min, however, there were no differences between groups at any other time period. Mean histamine concentrations were higher in calves treated with IVIG compared to calves on the control treatment at 1 min, but were not different at any other time period. These data indicate that adverse reactions to IVIG in calves are not mediated by high molecular weight molecules or by histamine release

I Used To Call Her Baby

https://digitalcommons.library.umaine.edu/mmb-vp/5292/thumbnail.jp

Q&A: Epistasis

Molecular and Cellular Biolog

What Can You Do About a Wet Basement?

The main solution to the wet basement problem is to provide efficient drainage to remove excess water from the soil around basement walls to relieve the water from the soil around basement walls and to relieve the water pressure that builds up under the basement floor

Has deregulation ruined M1 as a policy guide?

Interest rates ; Money supply ; Monetary policy ; Bank deposits

Improving the process synthesis, potency, and pharmacokinetics of the anticancer compound PAC-1

PAC-1 is an ortho-hydroxy-N-acylhydrazone that induces apoptosis by chelation of antiapoptotic labile zinc, relieving zinc-mediated inhibition of procaspase-3. Favorable results from cell culture and in vivo experiments with PAC-1 and its derivative S-PAC-1 have indicated the potential for translation to the clinic. However, several challenges exist in using PAC-1 in these experiments. This report describes the attempts to improve upon the process synthesis, potency, pharmacokinetics, and safety of PAC-1. The synthetic route to access PAC-1 was successful for the generation of batches of approximately 25 grams, but adaptation to multi-kilogram scale, as would be necessary for a human clinical trial, was not feasible using the existing route. In particular, the route included three chromatographic purification steps, as well as the use of anhydrous hydrazine. Optimization studies indicated that the active pharmaceutical ingredient could be synthesized without purification of any intermediates, and hydrazine monohydrate could be used in place of the anhydrous reagent. A batch of 155 grams of PAC-1 was synthesized using the improved route, and the route was scaled up to produce a batch of greater than 10 kilograms by a contract research organization. The lessons learned through this optimization effort were general and should be applicable if an alternative PAC-1 derivative is identified. In an effort to discover PAC-1 derivatives with improved potency, a combinatorial library of 837 compounds was synthesized. Each of 31 hydrazides was condensed with each of 27 aldehydes. Because standard techniques for isolation and purification of products are impractical for libraries of this size, a solid-phase purification strategy was employed that yielded the library members with an average purity of 91%. Compounds were screened in cell culture, and six potent hits were identified. One of these compounds, B-PAC-1, was studied further in primary isolates from leukemia patients, and animal experiments are currently in progress. An additional challenge is the relatively rapid clearance of PAC-1 from circulation. Many sites of metabolism exist, giving metabolites that arise from oxidative N-dealkylation, olefin oxidation, and arene oxidation. Several derivatives were synthesized containing modifications that prevent the formation of these metabolites. The compounds were evaluated in cell culture, liver microsomes, and mice, and four lead compounds were identified. Pharmacokinetic analysis indicated that each of these four compounds displayed extended elimination half-lives compared to PAC-1 and S-PAC-1, making these compounds viable candidates as next-generation PAC-1 derivatives. One of the most significant challenges in working with PAC-1 in vivo is the neuroexcitation observed upon treatment with elevated doses of compound. Preliminary experiments suggested that the neurotoxicity was not related to the ability of the compound to bind zinc. In order to confirm these results and attempt to determine the portion of the molecule responsible for neurotoxicity, a series of compounds was designed and synthesized containing systematic modifications to PAC-1. Evaluation in cell culture and in vitro further defined the essential nature of the ortho-hydroxy-N-acylhydrazone for activity. Evaluation of the compounds in mice confirmed previous experiments that the neurotoxicity is most likely not a result of metal chelation, but no further conclusions could be drawn from these experiments, and further study will be necessary to fully define the observed neurotoxicity

Volatile mortgage rates - a new fact of life?

Mortgage interest rates now move much more closely with capital market rates than in the past. This important development stems in part from the removal of mortgage usury ceilings. But the main reason for the closer relationship of mortgage rates to capital market rates is growth of the secondary mortgage market.Mortgages ; Secondary markets