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Recent research indicates that labor market power has contributed to wage inequality and economic stagnation. Although the antitrust laws prohibit firms from restricting competition in labor markets as in product markets, the government does little to address the labor market problem, and private litigation has been rare and mostly unsuccessful. One reason is that the analytic methods for evaluating labor market power in antitrust contexts are far less sophisticated than the legal rules used to judge product market power. To remedy this asymmetry, we propose methods for judging the effects of mergers on labor markets. We also extend our approach to other forms of anticompetitive practices undertaken by employers against workers. We highlight some arguments and evidence indicating that market power may be even more important in labor markets than in product markets.

Recent empirical work on labor markets reveals that they are beset by frictions, including high levels of concentration and frequent collusion, contrary to the traditional view of labor markets as being perfectly competitive. The implications of this work for law and policy have only begun to be explored. The 'University of Chicago Law Review' convened a symposium to bring together scholars from various disciplines and with different subject matter expertise but with a common interest in understanding the regulation of labor markets in light of new empirical results. The papers delivered at the symposium have been published in this symposium issue.

Cancer therapy has traditionally focused on eliminating fast-growing populations of cells. Yet, an increasing body of evidence suggests that small subpopulations of cancer cells can evade strong selective drug pressure by entering a ‘persister’ state of negligible growth. This drug-tolerant state has been hypothesized to be part of an initial strategy towards eventual acquisition of bona fide drug-resistance mechanisms. However, the diversity of drug-resistance mechanisms that can expand from a persister bottleneck is unknown. Here we compare persister-derived, erlotinib-resistant colonies that arose from a single, EGFR-addicted lung cancer cell. We find, using a combination of large-scale drug screening and whole-exome sequencing, that our erlotinib-resistant colonies acquired diverse resistance mechanisms, including the most commonly observed clinical resistance mechanisms. Thus, the drug-tolerant persister state does not limit—and may even provide a latent reservoir of cells for—the emergence of heterogeneous drug-resistance mechanisms. Cancer cells that survive initial drug treatment can persist in the presence of drugs. Here, the authors generate persister cells that are resistant to the EGFR tyrosine kinase inhibitor erlotinib and show by single cell analysis that multiple mechanism give rise to the drug-resistant persister state.

The Mars Science Laboratory spacecraft, containing the Curiosity rover, was launched to Mars on 26 November 2011, and for most of the 253-day, 560-million-kilometer cruise to Mars, the Radiation Assessment Detector made detailed measurements of the energetic particle radiation environment inside the spacecraft. These data provide insights into the radiation hazards that would be associated with a human mission to Mars. We report measurements of the radiation dose, dose equivalent, and linear energy transfer spectra. The dose equivalent for even the shortest round-trip with current propulsion systems and comparable shielding is found to be 0.66 ± 0.12 sievert.

There have long been debates about the nature, scope, and legitimacy of the political question doctrine, the modern version of which originates with the Supreme Court's 1962 decision in 'Baker v Carr'. Despite the differing views, the scholarly commentary has one thing in common: it is focused almost entirely on the Supreme Court. In the sixty years since 'Baker', however, the Court has applied the doctrine as a basis for dismissal in only three majority decisions. By contrast, during this period, the lower courts have applied the doctrine as a basis for dismissal in hundreds of cases. We provide the first empirical account of how the doctrine has operated in the lower courts since 'Baker'. Our account is based on both a quantitative and qualitative analysis of a sample of these decisions. This account reveals a political question doctrine that is substantially different from the one described in most scholarship: It is more vibrant, heavily focused on foreign affairs, often applied in non-constitutional cases, more prudential, and not a permanent disallowance of judicial review. The lower courts use the doctrine to evaluate their own institutional capacity to resolve politically sensitive disputes. It is the lower courts' more limited capacity compared to that of the Supreme Court, combined with their non-discretionary docket, that explains the lower courts' heavier reliance on the doctrine.

Tumour dendritic cells (DCs) internalise antigen and upregulate CCR7, which directs their migration to tumour-draining lymph nodes (dLN). CCR7 expression is coupled to an activation programme enriched in regulatory molecule expression, including PD-L1. However, the spatio-temporal dynamics of CCR7 + DCs in anti-tumour immune responses remain unclear. Here, we use photoconvertible mice to precisely track DC migration. We report that CCR7 + DCs are the dominant DC population that migrate to the dLN, but a subset remains tumour-resident despite CCR7 expression. These tumour-retained CCR7 + DCs are phenotypically and transcriptionally distinct from their dLN counterparts and heterogeneous. Moreover, they progressively downregulate the expression of antigen presentation and pro-inflammatory transcripts with more prolonged tumour dwell-time. Tumour-residing CCR7 + DCs co-localise with PD-1 + CD8 + T cells in human and murine solid tumours, and following anti-PD-L1 treatment, upregulate stimulatory molecules including OX40L, thereby augmenting anti-tumour cytolytic activity. Altogether, these data uncover previously unappreciated heterogeneity in CCR7 + DCs that may underpin a variable capacity to support intratumoural cytotoxic T cells. Recognition of tumour antigen induces dendritic cell activation and migration to the lymph node. Here, the authors use photoconvertible mice to demonstrate that some activated dendritic cells are retained in tumours and gradually lose function, but their ability to support local anti-tumour responses can be augmented by anti-PD-L1 blockade.

Drugs that mirror the cellular effects of starvation mimics are considered promising therapeutics for common metabolic disorders, such as obesity, liver steatosis, and for ageing. Starvation, or caloric restriction, is known to activate the transcription factor EB (TFEB), a master regulator of lipid metabolism and lysosomal biogenesis and function. Here, we report a nanotechnology-enabled high-throughput screen to identify small-molecule agonists of TFEB and discover three novel compounds that promote autophagolysosomal activity. The three lead compounds include the clinically approved drug, digoxin; the marine-derived natural product, ikarugamycin; and the synthetic compound, alexidine dihydrochloride, which is known to act on a mitochondrial target. Mode of action studies reveal that these compounds activate TFEB via three distinct Ca 2+ -dependent mechanisms. Formulation of these compounds in liver-tropic biodegradable, biocompatible nanoparticles confers hepatoprotection against diet-induced steatosis in murine models and extends lifespan of Caenorhabditis elegans . These results support the therapeutic potential of small-molecule TFEB activators for the treatment of metabolic and age-related disorders. Activation of autophagy, via the transcription factor TFEB, is a promising strategy to treat metabolic diseases. Here, the authors report three novel classes of small molecules that promote TFEB nuclear translocation, and provide evidence for the therapeutic efficacy of these compounds in mice and worms.

Horizontal collusion among employers to suppress wages has received almost no attention in the academic literature, in contrast with its more familiar cousin, product-market collusion. The similar economic analysis of labor and product markets might suggest that antitrust should regulate labor and product markets in the same way. But product markets and labor markets do not operate identically: people behave differently as employees and as consumers. Unlike consumers who can switch products relatively easily, employees face significant frictions in changing jobs. Other labor market frictions are created by the pay equity norm and downward nominal wage rigidity. These and related factors stabilize collusive arrangements and facilitate tacit coordination in labor markets. The implications for antitrust law are explored.

Judicial self-restraint, once a rallying cry for judges and law professors, has fallen on evil days. It is rarely invoked or advocated. This Essay traces the rise and fall of its best-known variant—restraint in invalidating legislative action as unconstitutional—as advocated by the \"School of Thayer,\" consisting of James Bradley Thayer and the influential judges and law professors who claimed to be his followers. The Essay argues, among other things, that both the strength and the weakness of the School was an acknowledged absence of a theory of how to decide a constitutional case. The rise of constitutional theory created an unbearable tension between Thayer's claim that judges should uphold a statute unless its invalidity was clear beyond doubt (as it would very rarely be), and constitutional theories that claimed to dispel doubt and yield certifiably right answers in all cases.

This work analyzes the appearance of wide-spread deka-MeV solar energetic proton (SEP) events, in particular the arrival of the first protons within ≈ 4.5 – 45 MeV measured at Earth–Sun L1, and their relationship with their relative solar source longitude. The definition of “wide-spread SEP event” for this study refers to events that are observed as a 25 MeV proton intensity increase at near 1 AU locations that are separated by at least 130 ∘ in solar longitude. Many of these events are seen at all three of the spacecraft, STEREO (Solar-Terrestrial Relations Observatory) A, STEREO B, and SOHO (Solar and Heliospheric Observatory), and may therefore extend far beyond 130 ∘ in longitude around the Sun. A large subset of these events have already been part of a study by Richardson et al. ( Solar Phys ., 289 , 3059, 2014). The event source region identifications draw from this study; more recent events have also been added. Our focus is on answering two specific questions: (1) What is the maximum longitude over which SEP protons show energy dispersion, i.e., a clear sign of arrival of higher-energy protons before those of lower energy? (2) What implications can be drawn from the ensemble of events observed regarding either direct magnetic connectivity to shocks and/or cross-field transport from the site of the eruption in the onset phase of the event?