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The early 1980s constituted a watershed in science, mainly concerning the extent and nature of globalization and commercialization of scientific research, and its impact upon the university. Considerable debate has arisen about the sources of this transition, but aside from a few lone voices, the scholarly literature has neglected the concurrent rise of the contract research organization (CRO) and its role in the commercialization of scientific research. The CRO warrants wider attention as a modern paradigm of privatized science in the biopharmaceutical sector. In discussing the CRO's technologies, the purposes they pursue, and the legal and policy initiatives that have fostered their rapid rise, we confront the wider implications of the modern regime of commercialized science for the future conduct of scientific research. We identify five areas of innovation: treatment of human subjects, control of disclosure, subjection of research tools to commercialization, redefinition of authorship, and re-engineering the goals of research.

Introduction IL-13 is the primary upregulated cytokine in atopic dermatitis (AD) skin and is the pathogenic mediator driving AD pathophysiology. Lebrikizumab, tralokinumab and cendakimab are therapeutic monoclonal antibodies (mAb) that target IL-13. Methods We undertook studies to compare in vitro binding affinities and cell-based functional activities of lebrikizumab, tralokinumab and cendakimab. Results Lebrikizumab bound IL-13 with higher affinity (as determined using surface plasma resonance) and slower off-rate. It was more potent in neutralizing IL-13-induced effects in STAT6 reporter and primary dermal fibroblast periostin secretion assays than either tralokinumab or cendakimab. Live imaging confocal microscopy was employed to determine the mAb effects on IL-13 internalization into cells via the decoy receptor IL-13Rα2, using A375 and HaCaT cells. The results showed that only the IL-13/lebrikizumab complex was internalized and co-localized with lysosomes, whereas IL-13/tralokinumab or IL-13/cendakimab complexes did not internalize. Conclusion Lebrikizumab is a potent, neutralizing high-affinity antibody with a slow disassociation rate from IL-13. Additionally, lebrikizumab does not interfere with IL-13 clearance. Lebrikizumab has a different mode of action to both tralokinumab and cendakimab, possibly contributing to the clinical efficacy observed by lebrikizumab in Ph2b/3 AD studies.

The Chicago school of economics has long emphasised the efficiency of decision makers in a competitive economic order in comparison to those in a democratic political order. The purpose of our article is to show that this emphasis emerged from two different re-conceptualisations of liberal democracy by Chicago economists during the post-war period The first was Frank H. Knight's enquiry into whether rational norms for intelligent democratic action provided the means to avoid the failures of liberalism that had become so apparent through the upheavals of the first several decades of the twentieth century. The second came from Aaron Director, who concluded instead that democratic action was inherently irrational and disputatious, and that the efficiency of actions undertaken with the context of the competitive order was to be preferred. Knight argued that an appreciation for competition must be accompanied by recognition of the equally fundamental roles of democratic discussion and ethics, whilst Director asserted the fundamental role of competition in the economic realm and its import for freedom.

None of the existing scholarly literature has explored or appreciated Director’s great respect for Hayek or their relationship. This paper explores the relationship of Hayek and Director, and argues that Director should be viewed as a disciple of Hayek in the immediate post-war period. Newly available archival material in the Director Papers at the University of Chicago as well as material in the Hayek Papers allow for a deeper appreciation of their relationship than was previously possible. The archival record indicates that the central arc of their relationship occurred from 1945 to roughly 1950, when they heavily corresponded, and primarily focuses on this pivotal time period. Through exploring the relationship of Hayek and Director, this paper challenges the frequent claim that Hayek did not influence the post-war Chicago School, and argues that, starting in 1946, Hayek, even though he was not yet at Chicago, influenced the initial intellectual trajectory of the post-war Chicago School through his disciple Director.

Migration of polymorphonuclear neutrophils (PMNL) from the vascular compartment into the pleural space occurs rapidly during the development of parapneumonic effusions. This study investigated the polarized secretion of interleukin (IL)–8 in activated pleural mesothelial cells (PMC) and the migration of PMNL across resting, activated PMC monolayers. Results show that PMC produce IL-8 in a polar manner. When PMC were stimulated with Staphylococcus aureus or IL-1β at the basal or at the apical surface, significantly (P<.05) more IL-8 was released toward the apical surface. This polarized production of IL-8 was confirmed by in situ hybridization. PMNL migration was higher from the basilar to apical than from the apical to basilar surface of PMC. Neutralizing antibodies against IL-8 and intercellular adhesion molecule (ICAM)–1 significantly (P<.001) blocked PMNL migration across activated monolayers. Thus, during pleural inflammation, PMC regulate the influx of PMNL into the pleural space by polar production of IL-8 and expression of ICAM-1

The repair of an injured bronchial epithelial cell (BEC) monolayer requires proliferation and migration of BECs into the injured area. We hypothesized that BEC monolayer injury results in monocyte chemoattractant protein-1 (MCP-1) production, which initiates the repair process. BECs (BEAS-2B from ATCC) were utilized in this study. MCP-1 interacts with CCR2B receptor (CCR2B), resulting in cell proliferation, haptotaxis, and healing of the monolayer. Reverse transcriptase-polymerase chain reaction (RT-PCR) was employed to verify the presence of CCR2B. CCR2B was not merely present but also inducible by interleukin-2 (IL-2) and lipopolysaccharide (LPS). We demonstrated by immunohistochemistry that BECs express MCP-1 after injury and that receptor expression can be regulated by exposure to IL-2 and LPS. Haptotactic migration of cells was enhanced in the presence of MCP-1 and reduced in the presence of CCR2B antibody. This enhanced or depressed ability of the BECs to perform haptotactic migration was shown to be statistically significant (P < 0.05) when compared to controls. Finally, BECs proliferate in response to MCP-1 as proven by electric cell-substrate impedance sensing (ECIS) technology. MCP-1-specific antibodies were shown to neutralize the MCP-1-mediated BEC proliferation. This cascade of events following injury to the bronchial epithelium may provide insight into the mechanism of the repair process.

Asthma is characterized by infiltration and shedding of the bronchial epithelium. The Th2 cytokines IL-4 and IL-13 are involved in the cellular recruitment and infiltration seen in asthma. The effects of IL-4 and IL-13 on cell-matrix interactions and epithelial shedding are unknown. We hypothesize that bronchial airway epithelial cells (BAEC) express paxillin, a structural focal adhesion protein, and downregulation of paxillin by Th2 cytokines lead to BAEC hyperpermeability. We showed by confocal microscopy the presence of paxillin in BAEC. We demonstrated by Western blot analysis that IL-4 and IL-13 stimulation results in downregulation of paxillin production. IL-4 and IL-13 stimulation decreased epithelial cell-matrix attachment as measured by electrical cell-substrate impedance sensing system (ECIS). Our results suggest that Th2 cytokines IL-4 and IL-13 downregulate paxillin production by BAEC, thereby disrupting the cell-matrix interactions. This may help explain the epithelial shedding and epithelial membrane hyperpermeability that occurs in asthma.

In this article, the authors examine two ways that they use music (i.e., popular song lyrics) as an active learning technique in an undergraduate history of economic thought course. First, they use music to help students grasp the ideas of the great thinkers in economics and see their relevance today. Second, because they require students to read original texts and write thesis-driven essays, they use music to teach essential skills related to such assignments. While the article focuses on how they use music as a pedagogical device to teach the history of economic thought, the use of music to teach essential skills could be applied to any economics course in which students engage in higher-level reading and writing.

Sialomucin complex (SMC) is a heterodimeric glycoprotein, and is found on the surfaces of the mesothelia of the pleura, pericardium, and peritoneum. Sialomucins play a significant role in adhesion as well as in defense. In this study, we hypothesized that pleural mesothelial cells (PMCs) express SMC and thus prevent the adherence of ovarian cancer cells (HTB-77) to the pleura. PMCs were plated, and the adherence of HTB-77 cells was observed using a cytofluor. The PMC monolayer was pretreated with sialidase, and HTB-77 adherence was observed using cytofluor. In another set of HTB-77 cells, adherence was observed when the PMC monolayer was pretreated with supernatants of HTB-77 cells. Last, supernatants of HTB-77 cells were assayed for sialidase activity. The removal of SMC by sialidase greatly increased the adherence of HTB-77 cells to the PMC monolayer, which was statistically significant (p < 0.05). Similar results were obtained when the PMC monolayer was pretreated with the supernatants of HTB-77 cells. Supernatants of HTB-77 cells showed the presence of sialidase. The presence of SMC on the PMC acts as a defense layer, and its removal by sialidase increases the susceptibility of the PMC layer to the adherence of malignant cells and to increased metastasis. HTB-77 cells also express sialidase, which by its action on the monolayer aids in the adherence of tumor cells to the pleural surface.

In bacterial empyema, the recruited polymorphonuclear leukocytes (PMN) represent important phagocytic cells involved in antibacterial defense. In this study we demonstrate that pleural fluids (PF) obtained from patients with empyema (EMP) contains significantly higher levels of granulocyte colony stimulating factor (GM-CSF), and PMN incubated in empyema (EMP) pleural fluid (PF) showed significantly less apoptosis than congestive heart failure (CHF) PF. Staphylococcus aureus-stimulated PMC released significantly (P < 0.001) higher levels of GM-CSF than resting PMC. Staphylococcus aureus-stimulated PMC (SPMC)-CM significantly (P < 0.001) inhibited PMN apoptosis. In SPMC-CM-incubated PMN the antiapoptotic gene Bcl-xL mRNA and protein expression was up-regulated; Bak mRNA and protein expression was down-regulated compared to control PMN. The active caspases activity significantly decreased. When SPMC-CM and EMP PF were immunodepleted with GM-CSF antibody, PMN apoptosis was significantly higher. The delay in apoptosis of PMN is in part attributable to the release of cytokine GM-CSF by activated PMC. These findings suggest that S. aureus-activated PMC extend PMN life span by modulating Bcl-xL and Bak gene expression and active caspases activity during acute inflammation and empyema.