"Free Entry and Exit" from the Market: Simplifying or Substantive Assumption?

Economic theory, of necessity, presents an abstraction to the reader. Abstraction is required to achieve the perspective that allows for theory, that is to say, understanding and interpretation, to occur. If the abstraction is done well only inessential details are set aside -- details that would otherwise divert the theorist from grasping the essential or fundamental elements of the process under examination. For example a study of the mechanisms that cause a moving automobile to stop can reasonably abstract from the vehicle's color scheme. For this process to be valid it is critical that the theorist distinguish between "simplifying" and "substantive" assumptions. The former clears away the inessential. The latter elevates or prioritizes the inessential -- thereby contributing to a distorted understanding. The difficulty is that distinguishing between simplifying and substantial assumptions remains, and will always remain, something of an art. Fifty years ago the siren of "Positive Economics" proposed that this critical distinction could be reliably made by adhering to a set of clear and simple rules. While some economists and empirical psychologists maintain a nostalgic commitment to that eclipsed understanding of science, today most thinking practitioners are aware that such an epistemological stance, with its triumphant dismissal of the need for defensible assumptions, was naive -- even misguided. Out of this epistemological vacuum economists have retreated to several crude "fixes" to guide their selection of abstractions. Occasional assertions to the contrary, these methods are conventions. Innocent of any knowledge of these issues, many economists instinctively deploy the abstractions used by their graduate advisor, or rely on those that most frequently appear in what are held to be the profession's premier journals. Economics, perhaps more than ever, is now defined by what economists do. Ideally, the distinction between substantive and simplifying assumptions could be grounded in something more meaningful. Such a ground does exist -- it is called judgment. Unfortunately judgment, like "beauty" or "goodness," is difficult to define without invoking specific cases. The reason is that good judgment requires a sense of context. Context is most readily gained through direct experience, a study of history, or the comparative method. Once acquired, this knowledge enables the researcher to "compare and contrast" one situation with another, to learn from previous efforts to interpret the subject at hand, or to benefit from multiple approaches to a single question. In short, judgment requires the kind of broad-ranging knowledge that is largely absent, even disdained, in the training of the economists of our era ("training" is the appropriate term in this context -- to be contrasted with "education"). To appreciate the implications and importance of the distinction between "simplifying" and "substantive" assumptions, consider the conventional assumption of "Free Entry and Exit."

Fine tuning of the E. coli NusB:NusE complex affinity to BoxA RNA is required for processive antitermination

Phage λ propagation in Escherichia coli host cells requires transcription antitermination on the λ chromosome mediated by λN protein and four host Nus factors, NusA, B, E (ribosomal S10) and G. Interaction of E. coli NusB:NusE heterodimer with the single stranded BoxA motif of λnutL or λnutR RNA is crucial for this reaction. Similarly, binding of NusB:NusE to a BoxA motif is essential to suppress transcription termination in the ribosomal RNA (rrn) operons. We used fluorescence anisotropy to measure the binding properties of NusB and of NusB:NusE heterodimer to BoxA-containing RNAs differing in length and sequence. Our results demonstrate that BoxA is necessary and sufficient for binding. We also studied the gain-of-function D118N NusB mutant that allows λ growth in nusA1 or nusE71 mutants. In vivo λ burst-size determinations, CD thermal unfolding measurements and X-ray crystallography of this as well as various other NusB D118 mutants showed the importance of size and polarity of amino acid 118 for RNA binding and other interactions. Our work suggests that the affinity of the NusB:NusE complex to BoxA RNA is precisely tuned to maximize control of transcription termination

RNA-binding specificity of E. coli NusA

The RNA sequences boxA, boxB and boxC constitute the nut regions of phage λ. They nucleate the formation of a termination-resistant RNA polymerase complex on the λ chromosome. The complex includes E. coli proteins NusA, NusB, NusG and NusE, and the λ N protein. A complex that includes the Nus proteins and other factors forms at the rrn leader. Whereas RNA-binding by NusB and NusE has been described in quantitative terms, the interaction of NusA with these RNA sequences is less defined. Isotropic as well as anisotropic fluorescence equilibrium titrations show that NusA binds only the nut spacer sequence between boxA and boxB. Thus, nutR boxA5-spacer, nutR boxA16-spacer and nutR boxA69-spacer retain NusA binding, whereas a spacer mutation eliminates complex formation. The affinity of NusA for nutL is 50% higher than for nutR. In contrast, rrn boxA, which includes an additional U residue, binds NusA in the absence of spacer. The Kd values obtained for rrn boxA and rrn boxA-spacer are 19-fold and 8-fold lower, respectively, than those for nutR boxA-spacer. These differences may explain why λ requires an additional protein, λ N, to suppress termination. Knowledge of the different affinities now describes the assembly of the anti-termination complex in quantitative terms

AHR2 Mutant Reveals Functional Diversity of Aryl Hydrocarbon Receptors in Zebrafish

The aryl hydrocarbon receptor (AHR) is well known for mediating the toxic effects of TCDD and has been a subject of intense research for over 30 years. Current investigations continue to uncover its endogenous and regulatory roles in a wide variety of cellular and molecular signaling processes. A zebrafish line with a mutation in ahr2 (ahr2hu3335), encoding the AHR paralogue responsible for mediating TCDD toxicity in zebrafish, was developed via Targeting Induced Local Lesions IN Genomes (TILLING) and predicted to express a non-functional AHR2 protein. We characterized AHR activity in the mutant line using TCDD and leflunomide as toxicological probes to investigate function, ligand binding and CYP1A induction patterns of paralogues AHR2, AHR1A and AHR1B. By evaluating TCDD-induced developmental toxicity, mRNA expression changes and CYP1A protein in the AHR2 mutant line, we determined that ahr2hu3335 zebrafish are functionally null. In silico modeling predicted differential binding of TCDD and leflunomide to the AHR paralogues. AHR1A is considered a non-functional pseudogene as it does not bind TCCD or mediate in vivo TCDD toxicity. Homology modeling, however, predicted a ligand binding conformation of AHR1A with leflunomide. AHR1A-dependent CYP1A immunohistochemical expression in the liver provided in vivo confirmation of the in silico docking studies. The ahr2hu3335 functional knockout line expands the experimental power of zebrafish to unravel the role of the AHR during development, as well as highlights potential activity of the other AHR paralogues in ligand-specific toxicological responses

The Social Cost of Labor and Its Importance for Labor Economics

The starting point and core notion of neoclassical or mainstream economics is a reductionist vision of the exchange of commodities. Missing is the historical, social, and legal environments within which exchanges occur. A parallel and equally problematic notion is that labor exists as something of a “found object.” By contrast, the classical school of economists understood that laborers must earn a wage equal to or greater than “subsistence” if society was to be an ongoing enterprise. Laborers must be fed, sheltered, socialized, and educated before they arrive in the labor market. This, in a phrase, is the Social Cost of Labor. If the society in question is at all “advanced” or “complex” the expenses associated with what was once termed the “civic minimum” will also be greater. These considerations, which were a commonplace of economic discourse and policy-making a hundred years ago, have disappeared from contemporary discussions. This presentation will demonstrate that presupposing a “social cost of labor” substantially modifies both the analytics and ethics of labor economics