Libby Weber

Presenilin-1 immunoreactivity is localized intracellularly in Alzheimer's disease brain, but not detected in amyloid plaques

The identification of the cellular and subcellular regions of the Alzheimers disease brain to which the presenilin-1 (PS-1) protein localizes is expected to contribute to an understanding of its pathophysiological role. Toward this end, we have derived an affinity-purified antibody to a synthetic PS-1 peptide. In this report, we demonstrate that this antibody, called SW2, specifically recognizes full-length, 47-kDa PS-1 protein from rat primary cortical neurons, from a human neuronal cell line, and from human brain extracts on Western immunoblots. Immunohistochemical analysis of postmortem brain tissue from control and Alzheimers disease patients using this SW2 antibody indicates an intracellular localization of PS-1 immunoreactivity with prominent perinuclear characteristics in neurons, with staining also detected in neuritic processes. Despite various treatments of the tissue sections, no PS-1 immunoreactivity was observed in neuritic plaques, the hallmark pathological lesions of Alzheimers disease. In addition, confocal microscopic analysis of immunostained cultured primary neurons revealed a prominent perinuclear pattern of PS-1 immunoreactivity consistent with vesicular localization, as well as punctate staining in neuritic processes.

The future of interfirm contract research: Opportunities based on prior research and nontraditional tools

The goal of interfirm contract research is to examine how formal contracts impact transaction success, firm relationships, and ultimately individual and collaborative firm performance when two or more firms interact. Most contract literature uses an economic lens to examine contracts: the property rights perspective, agency theory, and TCE. Property rights-based contract research (Coase, 1960; Demsetz, 1967; Alchian & Demsetz, 1973; Cheung, 1969) examines how efficient property rights assignment mitigates ex ante hazards. Similarly, agency theory-based contract research (e.g., Ross, 1973; Jensen & Meckling, 1976; Harris & Raviv, 1979) investigates how incentive alignment between the principal and agent leads to the mitigation of ex ante hazards. In contrast, TCE-based research (Williamson, 1975, 1985) examines contractual safeguards to mitigate both ex ante and ex post hazards (e.g., Joskow, 1985, 1987, 1990; Crocker & Reynolds, 1993). Because the three economic perspectives dominate, most research addresses how contracts are used to mitigate ex ante or ex post hazards. Therefore, many topics still need to be investigated to enhance our understanding of interfirm contracting.

An Experimental Investigation of the Effect of Contract Frames on Trust in Repeated Exchanges

Scholars continue to debate whether contracts and trust are complements or substitutes. Evidence on both sides is largely based on research that infers trust development from the number of pages or clauses contracts contain rather than measuring trust directly. Prior work also does not consider that contracts can be framed in different ways by including prevention or promotion language. Based on regulatory focus theory and studies of contracts in repeated exchanges, we hypothesize that prevention and promotion-framed safeguards (operationalized as penalties and bonuses, respectively) are differently likely to elicit trust under different conditions. We then report two experiments that use a behavioral measure of trust to examine the relationship between contracts and trust as a function of prevention or promotion frame. Supporting our predictions, Study 1 found greater initial cooperation under prevention than promotion contracts. After repeated exchanges, however, trust was higher under promotion than pr...

The Right Frame of Mind for M&A: The Impact of Merger Characteristics on M&A Deal Frames

According to agency theory, including performance-based consideration (earnout clauses) in the merger contract should align parent and retained target management incentives, leading to better merger performance. Yet, earnouts are frequently not paid out because retained target management fail to reach the performance milestones specified in the contingent provision. So, why does incentive alignment fail? The decision-making literature offers a possible explanation for the inconsistency. Prospect theory suggests that the performance contingent consideration in an earnout clause may be framed as a potential loss or gain, leading retained target management to display risk-seeking or risk-averse behavior. Risk-seeking or risk-averse behavior may positively or negatively impact merger outcomes, depending on the merger characteristics. In this paper, I examine whether specific merger characteristics, including parent’s customer strategy and characteristics of the target’s technology, impact if the M&A deal value is framed in terms of total consideration (earnout is perceived as a potential loss) or guaranteed consideration (earnout is perceived as a potential gain).