Contributors: Gottgens, Berthold, Wilkinson, Adam, Ryan, David, Kucinski, Iwo, Wang, Wei, Yang, Jian, Diamanti, Evangelia, Shaw, Sonia, Tsang, Jason Cheuk-Ho, Wang, Jeuxuan
... Pluripotent stem cell (PSC) differentiation in vitro represents a powerful and tractable model to study mammalian development, and an unlimited source of cells for regenerative medicine. Within hematology, in vitro PSC hematopoiesis affords novel insights into blood formation and represents an exciting potential approach to generate hematopoietic and immune cell types for transplantation and transfusion. Most studies to date have focused on in vitro hematopoiesis from mouse PSCs and human PSCs. However, differences in mouse and human PSC culture protocols have complicated the translation of discoveries between these systems. We recently developed a novel chemical media formulation, Expanded Potential Stem Cell Medium (EPSCM), that maintains mouse PSCs in a unique cellular state that affords extraembryonic differentiation capacity. Herein, we demonstrate that EPSCM can be directly used to stably maintain human PSCs. We further show that human PSCs maintained in EPSCM can spontaneously form embryoid bodies and undergo in vitro hematopoiesis using a simple differentiation protocol, similar to mouse PSC differentiation. EPSCM-maintained human PSCs generated at least two hematopoietic cell populations, which displayed distinct transcriptional profiles by RNA-sequencing analysis. EPSCM also supports gene targeting using homologous recombination, affording generation of a SPI1 (PU.1) reporter PSC line to study and track in vitro hematopoiesis. EPSCM therefore provides a useful tool not only to study pluripotency but also hematopoietic cell specification and developmental-lineage commitment.
Voting Trusts and Antitrust: Rethinking the Role of Shareholder Rights and Private Litigation in Public Regulation, 1880s to 1930s
Contributors: Lamoreaux, N., Philips Sawyer, L.
... Scholars have long recognized that the states’ authority to charter corporations bolstered their antitrust powers in ways that were not available to the federal government. But they have also argued that the growth of large-scale enterprises operating in national and even international markets forced states to stop prosecuting monopolistic combinations out of fear of doing serious damage to their domestic economies. Our paper has revised this conventional view by focusing attention on the lawsuits that minority shareholders brought against their own companies in state courts of law and equity, especially suits that challenged the anticompetitive use of voting trusts. Historically judges had been reluctant to intervene in corporations’ internal affairs and had displayed a particular wariness of shareholders’ private actions. By the end of the nineteenth century, however, they had begun to revise their views and to see shareholders’ private actions as useful checks on economic concentration. Although the balance between judges’ suspicion of and support for shareholders’ activism shifted back and forth over time, the long-run effect was to make devices like voting trusts unsuitable for the purposes of economic concentration.
Contributors: Boulton, Charles, Kirsten, Lamb
Contributors: Lamoreaux, N.
... This essay sets recent expressions of alarm about the monopoly power of technology giants like Google and Amazon in the long history of Americans’ response to big business. It argues that we cannot understand that history unless we realize that Americans have always been concerned about the political and economic dangers of bigness, not just the threat of high prices. The problem policy makers faced after the rise of Standard Oil was how to protect society against those dangers without punishing firms that grew large because they were innovative. The antitrust regime put in place in the early twentieth century managed this balancing act by focusing on large firms’ conduct toward competitors and banning practices that were anticompetitive or exclusionary. Maintaining this balance was difficult, however, and it gave way over time—first to a preoccupation with market power during the post-World War II period, and then to a fixation on consumer welfare in the late twentieth century. Refocusing policy on large firms’ conduct would do much to address current fears about bigness without penalizing firms whose market power comes from innovation.
Contributors: Woroniuk, D., Karam, A., Jamasb, T.
... We apply network theory to analyse the interactions of trading hub prices, and to assess the harmonisation of the European gas market. We construct dynamic networks, where the nodes correspond to the twelve EU trading hubs, and where the edges weight the causality between the variations of the respective gas prices. Network density dynamically calculates the aggregate quantity of causal interactions recorded within the system, which provides information pertaining to the integration of the European gas network. We document a number of spikes in network density, suggesting short periods of improved connectivity of European gas markets. We argue that these results appear to be driven by exogenous factors, such as unseasonal weather patterns, seismic activity and pipeline capacity reductions or outages. The findings elucidate the time varying nature of European gas market dynamics, and the importance of continual monitoring of market evolution.
Contributors: Hughes, Josephine, Gilday, Kieran, Scimeca, Luca, Garg, Soham, Iida, Fumiya
... Robotics competitions stimulate the next generation of cutting edge robotics solutions and innovative technologies. The World Robot Summit (WRS) Industrial Assembly challenge posed a key research challenge: how to develop adaptive industrial assembly robots. The overall goal is to develop robots where minimal hardware or software changes are required to manufacture a new or altered product. This will minimize waste and allow the industry to move towards a far more flexible approach to manufacturing; this provide exciting new technologies for the manufacturing industry and support many new business models and approaches. In this paper we present an approach where general purpose grippers and adaptive control approaches have been developed to move towards this research goal. These approaches enables highly flexible and adaptive assembly of a belt drive system. The abilities of this approach were demonstrated by taking part in the World Robot Summit Industrial Assembly Challenge. We achieved second place in the kitting challenge and second place in the adaptive manufacturing challenge and were presented with the Innovation Award.
Vismodegib resistant mutations are not selected in multifocal relapses of locally advanced basal cell carcinoma after vismodegib discontinuation
Contributors: Ighilahriz, M, Benfodda, M, Sharpe, Hayley, Soufir, N, Mourah, S, Dumaz, N, Battistella, M, Savina, A, Bouquet, F, Nikolaev, S
... Hedgehog pathway inhibitors (HPI) inactivating SMO 1, have become first line treatment for patients with locally advanced BCC (laBCC). HPI safety and efficacy have been shown in clinical trials2,3. Nevertheless, common adverse events lead to treatment discontinuation.
A Fluorogenic Probe for Cell Surface Phosphatidylserine Using an Intramolecular Indicator Displacement Sensing Mechanism.
Contributors: Zwicker, Vincent E, Oliveira, Bruno L, Yeo, Jia Hao, Fraser, Stuart T, Bernardes, Goncalo, New, Elizabeth J, Jolliffe, Katrina A
... The detection of externalized phosphatidylserine (PS) on the cell surface is commonly used to distinguish between living, apoptotic and necrotic cells. The tools of choice for many researchers to study apoptosis are Annexin V-fluorophore conjugates. However, the use of this 35 kDa protein is associated with several drawbacks including temperature sensitivity, Ca2+ dependence, and slow binding kinetics. Here, we describe a fluorogenic probe for cell surface PS, PIID, which operates by an intramolecular indicator displacement (IID) mechanism. An intramolecularly bound coumarin indicator is released in the presence of cell surface PS leading to a fluorescence ‘turn-on’ response. P-IID demonstrates superior performance when compared to Annexin V, for both fluorescence imaging and flow cytometry. In particular, P-IID binding to cell surfaces is not reliant on cells being at room temperature or the presence of calcium ions, does not require a wash step, and is significantly faster than that of Annexin V. This allows P-IID to be used in time-lapse imaging of apoptosis using confocal laser scanning microscopy and demonstrates the utility of the IID mechanism in live cells for the first time.
Contributors: Kahn, M. E., Mohaddes, K., Ng, R. N. C., Pesaran, M. H., Raissi, M., Yang, J-C.
... We study the long-term impact of climate change on economic activity across countries, using a stochastic growth model where labour productivity is affected by country-specific climate variables—-defined as deviations of temperature and precipitation from their historical norms. Using a panel data set of 174 countries over the years 1960 to 2014, we find that per-capita real output growth is adversely affected by persistent changes in the temperature above or below its historical norm, but we do not obtain any statistically significant effects for changes in precipitation. Our counterfactual analysis suggests that a persistent increase in average global temperature by 0.04°C per year, in the absence of mitigation policies, reduces world real GDP per capita by 7.22 percent by 2100. On the other hand, abiding by the Paris Agreement, thereby limiting the temperature increase to 0.01°C per annum, reduces the loss substantially to 1.07 percent. These effects vary significantly across countries. We also provide supplementary evidence using data on a sample of 48 U.S. states between 1963 and 2016, and show that climate change has a long-lasting adverse impact on real output in various states and economic sectors, and on labour productivity and employment.
Contributors: Barrow, John, Ganguly, C
... What happens to the most general closed oscillating universes in general relativity? We sketch the development of interest in cyclic universes from the early work of Friedmann and Tolman to modern variations introduced by the presence of a cosmological constant. Then we show what happens in the cyclic evolution of the most general closed anisotropic universes provided by the Mixmaster universe. We show that in the presence of entropy increase its cycles grow in size and age, increasingly approaching flatness. But these cycles also grow increasingly anisotropic at their expansion maxima. If there is a positive cosmological constant, or dark energy, present then these oscillations always end and the last cycle evolves from an anisotropic inflexion point towards a de Sitter future of everlasting expansion.