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Colorectal cancer (CRC) is the third most common cancer globally. CRC risk is increased by obesity, and by its lifestyle determinants notably physical inactivity and poor nutrition. Obesity results in increased inflammation and oxidative stress which cause genomic damage and contribute to mitochondrial dysregulation and CRC risk. The mitochondrial dysfunction associated with obesity includes abnormal mitochondrial size, morphology and reduced autophagy, mitochondrial biogenesis and expression of key mitochondrial regulators. Although there is strong evidence that increased adiposity increases CRC risk, evidence for the effects of intentional weight loss on CRC risk is much more limited. In model systems, energy depletion leads to enhanced mitochondrial integrity, capacity, function and biogenesis but the effects of obesity and weight loss on mitochondria in the human colon are not known. We are using weight loss following bariatric surgery to investigate the effects of altered adiposity on mitochondrial structure and function in human colonocytes. In summary, there is strong and consistent evidence in model systems and more limited evidence in human subjects that over-feeding and/or obesity result in mitochondrial dysfunction and that weight loss might mitigate or reverse some of these effects.
Existing Solid State Detector systems exhibit limitations in throughput rate and stability when used with intense synchrotron radiation sources. Recent work on a prototype detector system for Fluorescence EXAFS has allowed evaluation of new techniques, made possible by recent improvements in integrated circuit products. The knowledge gained from this investigation is enabling the design of high-count rate detector systems.
Saturn's moon Enceladus has vents emerging from a sub-surface ocean, offering unique probes into the liquid environment. These vents drain into the larger neutral torus in orbit around Saturn. We present a methanol (CH3OH) detection observed with IRAM 30-m from 2008 along the line-of-sight through Saturn's E-ring. Additionally, we also present supporting observations from the Herschel public archive of water (ortho-H2O; 1669.9 GHz) from 2012 at a similar elongation and line-of-sight. The CH3OH 5(1,1)-4(1,1) transition was detected at 5.9σ confidence. The line has 0.43 km s−1 width and is offset by +8.1 km s−1 in the moon's reference frame. Radiative transfer models allow for gas cloud dimensions from 1750 km up to the telescope beam diameter ~73 000 km. Taking into account the CH3OH lifetime against solar photodissociation and the redshifted line velocity, there are two possible explanations for the CH3OH emission: methanol is primarily a secondary product of chemical interactions within the neutral torus that: (1) spreads outward throughout the E-ring or (2) originates from a compact, confined gas cloud lagging Enceladus by several km s−1. We find either scenario to be consistent with significant redshifted H2O emission (4σ) measured from the Herschel public archive. The measured CH3OH:H2O abundance (>0.5%) significantly exceeds the observed abundance in the direct vicinity of the vents (~0.01%), suggesting CH3OH is likely chemically processed within the gas cloud with methane (CH4) as its parent species.
On 1 June 1683, ten proprietors of East Jersey gathered in London for one of their periodic meetings to discuss colonial business. Of the ten, nine were Quakers, including Robert Barclay, Gawen Lawrie, and Edward Byllynge. The tenth, who served as the group’s treasurer, was the London attorney Robert West.’ Unknown to the Friends with whom he met was West’s involvement in the Rye House plotting, the first details of which Sir Leoline Jenkins, secretary of state, learned about eleven days later. On the 19th, the government began its crackdown on the conspirators, in part by issuing an order to search West’s chamber in the Temple. Three days later, West, now in custody, began providing the authorities a detailed account of the conspiracy to murder the king and James duke of York. Among those he implicated were other non-Quaker proprietors of East Jersey, including the barrister Nathaniel Wade and the attorney John Ayloffe, both of whom were involved in the assassination plot. As the authorities pursued the investigation, they learned of plans for a general uprising, at the heart of which were James duke of Monmouth and Lord William Russell.
L’œuvre entreprise il y a cinquante ans par l’ancien Comité Permanent de la Carte du Ciel n’a pas été intégralement accomplie. Si certaines de ses parties peuvent être considérées comme terminées, d’autres ont été perdues de vue ou abandonnées.
La tâche de la Commission de la Carte du Ciel doit être maintenant d’examiner, à la lueur de cinquante années de progrès scientifiques, et en tenant compte du travail déjà fait, quelles sont celles des anciennes recommandations du Comité Permanent dont il y a lieu de poursuivre l’exécution.
Interaction with an opposing current amplifies wave modulation and accelerates nonlinear wave focusing in regular wavepackets. This results in large-amplitude waves, usually known as rogue waves, even if the wave conditions are less prone to extremes. Laboratory experiments in three independent facilities are presented here to assess the role of opposing currents in changing the statistical properties of unidirectional and directional mechanically generated random wavefields. The results demonstrate in a consistent and robust manner that opposing currents induce a sharp and rapid transition from weakly to strongly non-Gaussian properties. This is associated with a substantial increase in the probability of occurrence of rogue waves for unidirectional and directional sea states, for which the occurrence of extreme and rogue waves is normally the least expected.
The prevailing view of Quakers in the Restoration era depicts them as a defeated movement no longer on the attack but henceforth under siege. They institutionalized, in the words of Richard Bauman, a strategy “of disengagement from the world's affairs” and embraced “a social policy founded on quietism.” Defeated politically, they were forced, according to this view, to relinquish their efforts to advance the cause of liberty “by militant, political means.” Thus the adoption of the peace principle as a hallmark of the Society of Friends emerged, according to Barry Reay, as a response to political defeat and as a stratagem for survival. This interpretation of Restoration Quakerism is similar in many respects to the stereotypical depiction of the Friends in terms of withdrawal and quiescence. I would like to suggest some modifications in this view by reexamining Quaker expectations at the Restoration, the Friends' involvement in political and legal matters, and the emergence and enforcement of the peace principle. The dominant characteristics of Restoration Quakerism are not withdrawal and quiescence but engagement and vigor.
In the mid-1980s Stuart historians began a major re-evaluation of the restoration era. Among the principal themes are the period's unsettledness, the continuing impact of the radical tenets that had been manifested so forcefully in the mid-century upheavals, the significance of religion and ideology, and renewed debate over the origin of political parties. As I have suggested elsewhere, the period is most accurately conceived as a time of recurring crises of varying magnitude and duration. The first extended from Oliver Cromwell's death in September 1658 to the passage of the Conventicle Act in 1664, the second from 1667 to the enactment of the Test Act in 1673, the third from the revelation of the spurious Popish Plot in 1678 to the repression of the Rye House schemers and the Monmouth/Russell/Essex cabal in 1683, the fourth the rebellions of the earl of Argyll and the duke of Monmouth in 1685, and the fifth the crisis that entailed the collapse of James II's regime and the constitutional settlement of 1689.
Bunyan lived through the first four periods of crisis and died amid the final one. It is appropriate to ask how this reinterpretation of the restoration period affects our interpretation of Bunyan. Elsewhere I have offered some suggestions, particularly with respect to the crisis of 1678–83 and our understanding of The Holy War, Of Antichrist and His Ruine, and Seasonable Counsel: or, Advice to Sufferers. This essay will focus on the crisis of 1667–73, the principal interpreter of which is Gary De Krey. For him this controversy at root entailed a crucial debate about liberty of conscience—a revival of the debate that in his judgment was central to the mid-century revolution. De Krey makes a compelling case for the significance of the debate in the period 1667–73 because it challenged many of the assumptions on which the restoration settlement was founded, including the limits of political authority, the relationship between church and Crown, and the rights and obligations of subjects. In their various assertions of the right of conscience, nonconformists rejected the restoration settlement by insisting on God's ultimate sovereignty in the spiritual realm and “the autonomy of the conscience as God's vicegerent in that sphere.” For them the issue was not parliamentary versus royal sovereignty—not least because the policy of persecution was parliamentary—but the sovereignty of the conscience against any persecutorial authority.