Statement of Diane M. Orlowski Before the Commission on the Future of Worker-Management Relations

Testimony_Orlowski_121593.pdf: 167 downloads, before Oct. 1, 2020

Cathosis: Cathepsins in Particle-induced Inflammatory Cell Death: A Dissertation

Sterile particles underlie the pathogenesis of numerous inflammatory diseases. These diseases can often become chronic and debilitating. Moreover, they are common, and include silicosis (silica), asbestosis (asbestos), gout (monosodium urate), atherosclerosis (cholesterol crystals), and Alzeihmer’s disease (amyloid Aβ). Central to the pathology of these diseases is a repeating cycle of particle-induced cell death and inflammation. Macrophages are the key cellular mediators thought to drive this process, as they are especially sensitive to particle-induced cell death and they are also the dominant producers of the cytokine responsible for much of this inflammation, IL-1β. In response to cytokines or microbial cues, IL-1β is synthesized in an inactive form (pro-IL-1β) and requires an additional signal to be secreted as an active cytokine. Although a multimolecular complex, called the NLRP3 inflammasome, controls the activation/secretion of IL-1β (and has been thought to also control cell death) in response to particles in vitro, the in vivo inflammatory response to particles occurs independently of inflammasomes. Therefore, I sought to better understand the mechanisms governing IL-1β production and cell death in response to particles, focusing specifically on the role of lysosomal cathepsin proteases. Inhibitor studies have suggested that one of these proteases, cathepsin B, plays a role in promoting inflammasome activation subsequent to particle-induced lysosomal damage, however genetic models of cathepsin B deficiency have argued otherwise. Through the use of inhibitors, state-of-the-art biochemical tools, and multi-cathepsin-deficient genetic models, I found that multiple redundant cathepsins promote pro-IL-1β synthesis as well as particle-induced NLRP3 activation and cell death. Importantly, I also found that particle-induced cell death does not depend on inflammasomes, suggesting that this may be why inflammasomes do not contribute to particle-induced inflammation in vivo. Therefore, my observations suggest that cathepsins may be multifaceted therapeutic targets involved in the two key pathological aspects of particle-induced inflammatory disease, IL-1β production and cell death

Evaluation of input-intensive soybean management systems and the effect of lactofen application on soybean physiology

In an effort to maximize yields, many soybean growers have begun moving to intensive, input-based soybean management systems. However, limited reliable information exists about the effect of these inputs on soybean yield. The purpose of this study was to evaluate the effect of individual inputs and combinations of inputs as part of high-yield management systems on soybean seed yield and to determine the effect of one of these inputs, lactofen, on soybean physiology. Small plot studies were established in nine states across the Midwest. A number of commercially available soybean inputs were evaluated individually and in combination to determine their effect on soybean yield and quality. Lactofen and comparison treatments were applied to soybeans at multiple growth stages and yield and yield components were determined. When examined across environments, input-intensive combination treatments increased soybean yields from 3.9 to 8.1 %. However, break-even economic analysis indicated that the combination (SOYA) treatments evaluated had 0% probability of breaking across a wide range of yield levels and soybean prices, due to the high input costs. The foliar insecticide showed the highest probability of breaking even across a range of yield levels and crop prices (40% to 99%). Yield increases and breakeven probabilities were generally greatest in the northern states (Minnesota, Wisconsin, Michigan) and similar in the central and southern states. Lactofen application did not kill the apical meristem and had minimal effect on yield components compared to untreated soybeans at any growth stage. Meristem removal increased node m-2 in some environments, but did not increase pods m-2 and seeds m-2 or seed yield

Price support at any price? Costs and benefits of alternative agricultural policies for Poland

The author argues that Poland must choose an agricultural policy that promotes efficiency, structural change, and adjustment to the new market environment and eventual membership in the European Union. That policy must take into account both the needs of, and the financial constraints on, Polish agriculture. Results of simulation experiments performed with the use of the computable general equilibrium model of the Polish economy suggest that Common Agricultural Policy-type price supports are not the most efficient agricultural policy for Poland. The author discusses alternative policies and scenarios. Rather than discuss whether the relationship between farmers'incomes and average Polish wages is fair, the author analyzes whether medium- and long-term development trends in the Polish economy may cause this relationship to deteriorate, and what policies will counteract those trends. Rapid growth in the nonagricultural sectors combined with real appreciation of domestic currency (caused either through good current account performance or significant capital inflows) may jeopardize farmers'relative income position. And such developments are probable if positive projections for economic development and membership in the European Union are realized. The agricultural sector can defend its relative income only by becoming more efficient. Price supports improve farmers'relative income but at a high cost to taxpayers and consumers and to macroeconomic efficiency. To meet these costs, Poland must put in place firm quantity controls. But the author thinks that the best strategy would be to avoid price supports until the moment of joining the European Union's Common Agricultural Policy. In the interim, policies aimed at reducing farm employment seem most appropriate. The author discusses two such policies: encouraging older farmers to retire and promoting jobs in rural areas. He also proposes two feasible scenarios for integrating Polish agriculture with that of the European Union by 2005-10.Markets and Market Access,Economic Theory&Research,Environmental Economics&Policies,Labor Policies,Agricultural Knowledge&Information Systems,Economic Theory&Research,Environmental Economics&Policies,Agricultural Knowledge&Information Systems,Markets and Market Access,Access to Markets

Effects of sunrise/sunset lighting on corticosterone levels in Coturnix quail (Coturnix coturnix)

Both genetics and environment play important roles in the growth, performance, and overall welfare of poultry species. Current commercial production practices typically do not mimic the natural environmental conditions of ancestral poultry species, specifically lighting. The current study aimed to evaluate the impact of genetics and the effect of sunrise/sunset lighting on the stress response of 4 genetic lines of Coturnix quail. The 4 lines utilized in this study included high stress (H), low stress (L), stress control (R), and Arkansas randombred (A) quail lines. Day old chicks from these lines were placed in one of two environmentally controlled rooms. All conditions were kept similar between the rooms until week 4. At week 4, half of the quail in each room were relocated to the other room and the experimental conditions began. One room was subjected to sudden on/off lighting while the other room was subjected to a 1-hour long sunrise/sunset treatment. At 8 weeks of age, blood was collected from one bird in each line of quail at 5 time points: before lights on, 3 points during sunrise lighting, and after lights were on at full intensity. The subsequent plasma samples were evaluated for their corticosterone concentrations. Quail housed in the sunrise/sunset lighting room had numerically lower corticosterone concentrations overall and transferred quail had numerically elevated corticosterone concentrations. In conclusion, sunrise/sunset lighting has the potential to improve overall production, regardless of genetic line

The importance of high performing team members in complex team work: results from quasi-experiments in professional team sports

This paper empirically assesses peer effects of high performing team members in reciprocally interdependent team production. Using data from the National Basketball Association (NBA), we identify peer effects by exploiting unforeseen in-game injuries of high performing players. Results indicate that without a high performing player, other team members maintain efficiency and the division of tasks among each other. However, they slightly increase risk taking and decrease their individual output, resulting in an inferior overall outcome. These effects depend on whether a high performing player has a team-oriented or a self-oriented role in the team. Additionally, we observe that relatively skilled players try to step in for the absent high performing player

Spin-dependent transport in p+-CdBxF2-x - n-CdF2 planar structures

The CV measurements and tunneling spectroscopy are used to study the ballistic transport of the spin-polarized holes by varying the value of the Rashba spin-orbit interaction (SOI) in the p-type quantum well prepared on the surface of the n-CdF2 bulk crystal. The findings of the hole conductance oscillations in the plane of the p-type quantum well that are due to the variations of the Rashba SOI are shown to be evidence of the spin transistor effect, with the amplitude of the oscillations close to e2/h.Comment: 5 pages, 6 figure

The role of the ubiquitination-proteasome pathway in breast cancer: Applying drugs that affect the ubiquitin-proteasome pathway to the therapy of breast cancer

The ubiquitin-proteasome pathway is responsible for most eukaryotic intracellular protein degradation. This pathway has been validated as a target for antineoplastic therapy using both in vitro and preclinical models of human malignancies, and is influenced as part of the mechanism of action of certain chemotherapeutic agents. Drugs whose primary action involves modulation of ubiquitin-proteasome activity, most notably the proteasome inhibitor PS-341, are currently being evaluated in clinical trials, and have already been found to have significant antitumor efficacy. On the basis of the known mechanisms by which these agents work, and the available clinical data, they would seem to be well suited for the treatment of breast neoplasms. Such drugs, alone and especially in combination with current chemotherapeutics, may well represent important advances in the therapy of patients with breast cancer