Paying for What You Get—Restitution Recovery for Breach of Contract

This article begins with a brief discussion of restitution as a remedy for breach of contract under the Restatement (Second) of Contracts. It then discusses the changes the Restatement of Restitution adopts and the reasons for the changes. Next, it discusses why the changes have not only failed to achieve the goal of clarifying the “prevailing confusion” related to restitution and breach of contract, but have at times created more confusion. It then explains that contract and restitution principles are not only not in tension relative to restitution for breach of contract, but in fact support such a recovery

The Best and Worst of Contracts Decisions: An Anthology

Five hundred years ago, the common law of contract was without substance. It was form-procedure. Plaintiffs picked a form of action, and common law judges made sure someone besides themselves answered all the hard questions; the parties, a jury, or a ritual determined the winner and the remedy. Judges ran a switch on a conflicts-resolution railway. Thomas More, when Chancellor of England (1529-33), urged judges to lay tracks and control the trains. The problem, he said, was that the judges, by the verdict of the jury[,] cast off all quarrels from themselves. The judges soon assumed greater authority, taking responsibility for the law\u27s substance. The consideration requirement was in place by 1539, and judges afterwards imposed doctrine upon doctrine. Over centuries, they created the common law of contract. That law is now mature, more or less, meaning that judges have tools to fix what they want to fix, and feel free to do so. The law they created-the common law of contract-is a remarkable intellectual and political achievement

Guidelines for the use and interpretation of assays for monitoring autophagy (3rd edition)

In 2008 we published the first set of guidelines for standardizing research in autophagy. Since then, research on this topic has continued to accelerate, and many new scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Accordingly, it is important to update these guidelines for monitoring autophagy in different organisms. Various reviews have described the range of assays that have been used for this purpose. Nevertheless, there continues to be confusion regarding acceptable methods to measure autophagy, especially in multicellular eukaryotes. For example, a key point that needs to be emphasized is that there is a difference between measurements that monitor the numbers or volume of autophagic elements (e.g., autophagosomes or autolysosomes) at any stage of the autophagic process versus those that measure fl ux through the autophagy pathway (i.e., the complete process including the amount and rate of cargo sequestered and degraded). In particular, a block in macroautophagy that results in autophagosome accumulation must be differentiated from stimuli that increase autophagic activity, defi ned as increased autophagy induction coupled with increased delivery to, and degradation within, lysosomes (inmost higher eukaryotes and some protists such as Dictyostelium ) or the vacuole (in plants and fungi). In other words, it is especially important that investigators new to the fi eld understand that the appearance of more autophagosomes does not necessarily equate with more autophagy. In fact, in many cases, autophagosomes accumulate because of a block in trafficking to lysosomes without a concomitant change in autophagosome biogenesis, whereas an increase in autolysosomes may reflect a reduction in degradative activity. It is worth emphasizing here that lysosomal digestion is a stage of autophagy and evaluating its competence is a crucial part of the evaluation of autophagic flux, or complete autophagy. Here, we present a set of guidelines for the selection and interpretation of methods for use by investigators who aim to examine macroautophagy and related processes, as well as for reviewers who need to provide realistic and reasonable critiques of papers that are focused on these processes. These guidelines are not meant to be a formulaic set of rules, because the appropriate assays depend in part on the question being asked and the system being used. In addition, we emphasize that no individual assay is guaranteed to be the most appropriate one in every situation, and we strongly recommend the use of multiple assays to monitor autophagy. Along these lines, because of the potential for pleiotropic effects due to blocking autophagy through genetic manipulation it is imperative to delete or knock down more than one autophagy-related gene. In addition, some individual Atg proteins, or groups of proteins, are involved in other cellular pathways so not all Atg proteins can be used as a specific marker for an autophagic process. In these guidelines, we consider these various methods of assessing autophagy and what information can, or cannot, be obtained from them. Finally, by discussing the merits and limits of particular autophagy assays, we hope to encourage technical innovation in the field

Rethinking Moral Obligation as a Basis for Contract Recovery

Contractual arrangements are private and consensual—the result of bargains made between parties—bargains that satisfy the consideration requirement for enforcement. While the consideration requirement has its detractors, as does the consensual nature of contract, the bargained-for consideration requirement remains a staple of contract law. Yet traditional consideration analysis seems to sometimes leave deserving claimants without a remedy. Thus, a limited group of exceptions has been developed to correct this perceived failing of the doctrine. For some situations, however, the deficiency is more perceived than real, and the solution adds confusion rather than clarity to the law. This is true for the “moral obligation” exception to the doctrine of consideration to allow a contract recovery under what admittedly may be compelling circumstances. There is much to be said for preserving as far as possible the underlying principles of contract law, and resisting the temptation to stretch contract law to provide redress for situations in which other doctrines work even better. The exception, by essentially dispensing with the consideration requirement, unnecessarily departs from the bargain requirement, and brings into the public arena the rather individual and personal decision of just what are the dictates of morality. In the moral obligation cases, the temptation to use a contractual remedy arises largely from a concern that restitution may not work, leaving no other remedy available. Yet restitution often provides adequate remedies, and is actually more satisfactory than contract. As stated by Fuller and Perdue in their well-known article The Reliance Interest in Contract Damages: “We are still all too willing to embrace the conceit that it is possible to manipulate legal concepts without the orientation which comes from the simple inquiry: toward what end is this activity directed?” In these cases, the activity is directed toward compensating for unjust enrichment, and the contract, if there is one, is an agreement to settle the restitution claim. Courts create confusion and unpredictability in the law when they fail to properly state the basis of the claim. As a result, some legitimate claims go unsatisfied, and there is needless litigation over claims that have no real legal basis

Testamentary Designations of Attorneys and Other Employees

This article sets forth a clear, principled analysis by which many of the problems in will construction can be alleviated. Such an analysis requires appropriate consideration of the testator\u27s intent, his freedom to create conditions in the will, and the relationship between the two. Under this type of analysis, the result is not dictated by the nature of the employment. However, the type of employment has some influence on the result, since it has some bearing on the testator\u27s intent. As is so often the case concerning written legal documents, the problems can be virtually eliminated by drafting with an awareness of the pitfalls and clearly stating the testator\u27s intent as to how those pitfalls are to be avoided

The Best and Worst of Contracts Decisions: An Anthology

Five hundred years ago, the common law of contract was without substance. It was form-procedure. Plaintiffs picked a form of action, and common law judges made sure someone besides themselves answered all the hard questions; the parties, a jury, or a ritual determined the winner and the remedy. Judges ran a switch on a conflicts-resolution railway. Thomas More, when Chancellor of England (1529-33), urged judges to lay tracks and control the trains. The problem, he said, was that the judges, by the verdict of the jury[,] cast off all quarrels from themselves. The judges soon assumed greater authority, taking responsibility for the law\u27s substance. The consideration requirement was in place by 1539, and judges afterwards imposed doctrine upon doctrine. Over centuries, they created the common law of contract. That law is now mature, more or less, meaning that judges have tools to fix what they want to fix, and feel free to do so. The law they created-the common law of contract-is a remarkable intellectual and political achievement

MUC1 and HIF-1alpha Signaling Crosstalk Induces Anabolic Glucose Metabolism to Impart Gemcitabine Resistance to Pancreatic Cancer.

Poor response to cancer therapy due to resistance remains a clinical challenge. The present study establishes a widely prevalent mechanism of resistance to gemcitabine in pancreatic cancer, whereby increased glycolytic flux leads to glucose addiction in cancer cells and a corresponding increase in pyrimidine biosynthesis to enhance the intrinsic levels of deoxycytidine triphosphate (dCTP). Increased levels of dCTP diminish the effective levels of gemcitabine through molecular competition. We also demonstrate that MUC1-regulated stabilization of hypoxia inducible factor-1α (HIF-1α) mediates such metabolic reprogramming. Targeting HIF-1α or de novo pyrimidine biosynthesis, in combination with gemcitabine, strongly diminishes tumor burden. Finally, reduced expression of TKT and CTPS, which regulate flux into pyrimidine biosynthesis, correlates with better prognosis in pancreatic cancer patients on fluoropyrimidine analogs