Constructing Alternative Avenues of Jurisdictional Protection: Bypassing Burnham\u27s Roadblock Via § 1404(a)

A plaintiff from Maine sues an insurance company, incorporated in Maine and having its principal place of business in Maine, on a loss incurred in Maine under a contract negotiated, written, and executed in Maine. The plaintiff files the suit in Alabama to take advantage of its liability law, its statute of limitations, its juries, its rules of evidence, and its posture toward plaintiffs. The plaintiff serves a representative of the insurance company traveling in Alabama en route to an industry convention. For all the reasons the plaintiff seeks a forum in Alabama, the defendant wishes to avoid that forum. The importance of forum and the judicial tools available to ensure that the most appropriate forum adjudicates disputes are the subjects of this Note. Prior to Burnham v. Superior Court of California,\u27 a defendant could successfully claim that Alabama\u27s assertion of general jurisdiction should be determined under the constitutional fundamental fairness doctrine developed in the International Shoe Co. v. Washington and Rush v. Savchuk\u27 line of cases. The defendant would explain the regulatory nature of jurisdiction. The defendant would ask the trial court to hold that Alabama\u27s assertion of jurisdiction violates the defendant\u27s due process rights because Alabama lacks a regulatory interest in adjudicating the dispute. The defendant would illustrate Maine\u27s regulatory interests in adjudicating the meaning of contracts, setting policies, and protecting parties whose conduct occurred within its borders. Burnham, with its appeal to tradition and black letter Aristotelian principles, closed this avenue of protection.! It held that a forum\u27s assertion of general jurisdiction based on physical presence unrelated to the cause of action was per se constitutional. Defendants must now seek alternative routes to ensure that the most appropriate forum imposes its regulatory regime on the underlying dispute. In the wake of Burnham, a small handful of scholars predicted that forum non conveniens doctrine and the Federal Transfer Statute, 28 U.S.C. § 1404(a), might become that avenue by allowing trial courts to re- insert fundamental fairness into jurisdiction determinations. This Note illustrates that ? 1404(a) accomplishes this task, although judges and the legal community may not always realize that this is occurring. Part II explains why forum matters. It examines the phenomenon of forum-shopping and the underlying reasons why plaintiffs (and defendants) favor some fora over others. The Part argues that the selection of a forum embodies more than simply choosing a physical location. The selection signifies the imposition of an entire regulatory regime. This Part illustrates how forum, more than anything else, affects the distribution and adjudication of justice in this country. Part III explores the evolution of constitutional jurisdictional principles that came to recognize the importance of forum. By focusing on International Shoe and its progeny, the section traces the development of constitutional fundamental fairness safeguards against a forum\u27s assertion of general jurisdiction. It explains that when the Supreme Court applied the fundamental fairness doctrine, it was really concerned with the imposition of a regulatory regime. The Court made ad hoc value judgments concerning the appropriateness of a forum\u27s regulatory regime. Subsequent developments in jurisdictional jurisprudence appeared to incorporate fundamental fairness into general jurisdiction, thereby ensuring that only those forums with regulatory interests will adjudicate particular disputes. Part IV shows how Burnham v. Superior Court closed this avenue of constitutional protection. It examines how the Supreme Court\u27s decision in Burnham foreclosed further application of the fundamental fairness doctrine developed in the International Shoe line of cases to determinations of the constitutionality of general jurisdiction. This Part addresses the criticism and the black letter basis of the decision. Part V proposes an alternative to Burnham. It traces the development, purpose, and application of the common law doctrine of forum non conveniens. The Part explores the Supreme Court\u27s decision in Gulf Oil Corp. v. Gilbert, in which the Court borrowed heavily from the fundamental fairness standard of International Shoe. Gulf Oil incorporated the notion of forum as regulatory regime into forum non conveniens determinations. Part VI begins the discussion of the Federal Transfer Statute, 28 U.S.C. § 1404. It explains the statute\u27s purpose, legislative history, use, and application in the federal judiciary. The Part illustrates how district courts, in their application of § 1404, have developed numerous factors that go beyond mere convenience to ascertain the appropriateness of transfer. Part VII looks beyond the rhetoric of convenience and concentrates on the many factors that district courts use in deciding § 1404(a) motions. The Part reveals that some trial judges actually conduct a fundamental fairness analysis to impose the proper regulatory regime. It notes that most scholars have expressed disdain at the plethora of factors and have described the entire § 1404(a) jurisprudence as one marked by chaos and inconsistency. These scholars fail to realize that § 1404(a) is accomplishing what the Supreme Court attempted to frustrate in Burnham: the use of ad hoc value judgments under the auspices of fundamental fairness to select the proper forum for a cause of action. Finally, Part VIII examines the obstacles that may prevent § 1404(a) from actually carrying out the goals of fundamental fairness. It questions the Supreme Court\u27s decisions in Van Dusen v. Barrack\u27 and Ferens v. John Deere Co. The Part provides alternatives and exceptions to the rules developed by those cases. It also answers those who argue that the lack of appellate review of § 1404(a) motions pres- ents a major problem. This Part explains that while these concerns are understandable, they are rooted in appeals to black letter rules and undervalue the need for trial judge discretion to make determinations on a case-by-case basis. Finally, it will advise against seduction by black letter rhetoric and support the ad hoc, case-by-case approach used presently, though surreptitiously, by trial judges

Pan-Cancer Analysis of lncRNA Regulation Supports Their Targeting of Cancer Genes in Each Tumor Context

Long noncoding RNAs (lncRNAs) are commonly dys-regulated in tumors, but only a handful are known toplay pathophysiological roles in cancer. We inferredlncRNAs that dysregulate cancer pathways, onco-genes, and tumor suppressors (cancer genes) bymodeling their effects on the activity of transcriptionfactors, RNA-binding proteins, and microRNAs in5,185 TCGA tumors and 1,019 ENCODE assays.Our predictions included hundreds of candidateonco- and tumor-suppressor lncRNAs (cancerlncRNAs) whose somatic alterations account for thedysregulation of dozens of cancer genes and path-ways in each of 14 tumor contexts. To demonstrateproof of concept, we showed that perturbations tar-geting OIP5-AS1 (an inferred tumor suppressor) andTUG1 and WT1-AS (inferred onco-lncRNAs) dysre-gulated cancer genes and altered proliferation ofbreast and gynecologic cancer cells. Our analysis in-dicates that, although most lncRNAs are dysregu-lated in a tumor-specific manner, some, includingOIP5-AS1, TUG1, NEAT1, MEG3, and TSIX, synergis-tically dysregulate cancer pathways in multiple tumorcontexts

Pan-cancer Alterations of the MYC Oncogene and Its Proximal Network across the Cancer Genome Atlas

Although theMYConcogene has been implicated incancer, a systematic assessment of alterations ofMYC, related transcription factors, and co-regulatoryproteins, forming the proximal MYC network (PMN),across human cancers is lacking. Using computa-tional approaches, we define genomic and proteo-mic features associated with MYC and the PMNacross the 33 cancers of The Cancer Genome Atlas.Pan-cancer, 28% of all samples had at least one ofthe MYC paralogs amplified. In contrast, the MYCantagonists MGA and MNT were the most frequentlymutated or deleted members, proposing a roleas tumor suppressors.MYCalterations were mutu-ally exclusive withPIK3CA,PTEN,APC,orBRAFalterations, suggesting that MYC is a distinct onco-genic driver. Expression analysis revealed MYC-associated pathways in tumor subtypes, such asimmune response and growth factor signaling; chro-matin, translation, and DNA replication/repair wereconserved pan-cancer. This analysis reveals insightsinto MYC biology and is a reference for biomarkersand therapeutics for cancers with alterations ofMYC or the PMN

Genomic, Pathway Network, and Immunologic Features Distinguishing Squamous Carcinomas

This integrated, multiplatform PanCancer Atlas study co-mapped and identified distinguishing molecular features of squamous cell carcinomas (SCCs) from five sites associated with smokin

Spatial Organization and Molecular Correlation of Tumor-Infiltrating Lymphocytes Using Deep Learning on Pathology Images

Beyond sample curation and basic pathologic characterization, the digitized H&E-stained images of TCGA samples remain underutilized. To highlight this resource, we present mappings of tumorinfiltrating lymphocytes (TILs) based on H&E images from 13 TCGA tumor types. These TIL maps are derived through computational staining using a convolutional neural network trained to classify patches of images. Affinity propagation revealed local spatial structure in TIL patterns and correlation with overall survival. TIL map structural patterns were grouped using standard histopathological parameters. These patterns are enriched in particular T cell subpopulations derived from molecular measures. TIL densities and spatial structure were differentially enriched among tumor types, immune subtypes, and tumor molecular subtypes, implying that spatial infiltrate state could reflect particular tumor cell aberration states. Obtaining spatial lymphocytic patterns linked to the rich genomic characterization of TCGA samples demonstrates one use for the TCGA image archives with insights into the tumor-immune microenvironment

Software for the frontiers of quantum chemistry:An overview of developments in the Q-Chem 5 package

This article summarizes technical advances contained in the fifth major release of the Q-Chem quantum chemistry program package, covering developments since 2015. A comprehensive library of exchange–correlation functionals, along with a suite of correlated many-body methods, continues to be a hallmark of the Q-Chem software. The many-body methods include novel variants of both coupled-cluster and configuration-interaction approaches along with methods based on the algebraic diagrammatic construction and variational reduced density-matrix methods. Methods highlighted in Q-Chem 5 include a suite of tools for modeling core-level spectroscopy, methods for describing metastable resonances, methods for computing vibronic spectra, the nuclear–electronic orbital method, and several different energy decomposition analysis techniques. High-performance capabilities including multithreaded parallelism and support for calculations on graphics processing units are described. Q-Chem boasts a community of well over 100 active academic developers, and the continuing evolution of the software is supported by an “open teamware” model and an increasingly modular design

Integrated Genomic Analysis of the Ubiquitin Pathway across Cancer Types

Protein ubiquitination is a dynamic and reversibleprocess of adding single ubiquitin molecules orvarious ubiquitin chains to target proteins. Here,using multidimensional omic data of 9,125 tumorsamples across 33 cancer types from The CancerGenome Atlas, we perform comprehensive molecu-lar characterization of 929 ubiquitin-related genesand 95 deubiquitinase genes. Among them, we sys-tematically identify top somatic driver candidates,including mutatedFBXW7with cancer-type-specificpatterns and amplifiedMDM2showing a mutuallyexclusive pattern withBRAFmutations. Ubiquitinpathway genes tend to be upregulated in cancermediated by diverse mechanisms. By integratingpan-cancer multiomic data, we identify a group oftumor samples that exhibit worse prognosis. Thesesamples are consistently associated with the upre-gulation of cell-cycle and DNA repair pathways, char-acterized by mutatedTP53,MYC/TERTamplifica-tion, andAPC/PTENdeletion. Our analysishighlights the importance of the ubiquitin pathwayin cancer development and lays a foundation fordeveloping relevant therapeutic strategies

Molecular characterization and clinical relevance of metabolic expression subtypes in human cancers.

Metabolic reprogramming provides critical information for clinical oncology. Using molecular data of 9,125 patient samples from The Cancer Genome Atlas, we identified tumor subtypes in 33 cancer types based on mRNA expression patterns of seven major metabolic processes and assessed their clinical relevance. Our metabolic expression subtypes correlated extensively with clinical outcome: subtypes with upregulated carbohydrate, nucleotide, and vitamin/cofactor metabolism most consistently correlated with worse prognosis, whereas subtypes with upregulated lipid metabolism showed the opposite. Metabolic subtypes correlated with diverse somatic drivers but exhibited effects convergent on cancer hallmark pathways and were modulated by highly recurrent master regulators across cancer types. As a proof-of-concept example, we demonstrated that knockdown of SNAI1 or RUNX1—master regulators of carbohydrate metabolic subtypes-modulates metabolic activity and drug sensitivity. Our study provides a system-level view of metabolic heterogeneity within and across cancer types and identifies pathway cross-talk, suggesting related prognostic, therapeutic, and predictive utility