Adaptive changes in the neuronal proteome: mitochondrial energy production, endoplasmic reticulum stress, and ribosomal dysfunction in the cellular response to metabolic stress

Impaired energy metabolism in neurons is integral to a range of neurodegenerative diseases, from Alzheimer’s disease to stroke. To investigate the complex molecular changes underpinning cellular adaptation to metabolic stress, we have defined the proteomic response of the SH-SY5Y human neuroblastoma cell line after exposure to a metabolic challenge of oxygen glucose deprivation (OGD) in vitro. A total of 958 proteins across multiple subcellular compartments were detected and quantified by label-free liquid chromatography mass spectrometry. The levels of 130 proteins were significantly increased (P<0.01) after OGD and the levels of 63 proteins were significantly decreased (P<0.01) while expression of the majority of proteins (765) was not altered. Network analysis identified novel protein–protein interactomes involved with mitochondrial energy production, protein folding, and protein degradation, indicative of coherent and integrated proteomic responses to the metabolic challenge. Approximately one third (61) of the differentially expressed proteins was associated with the endoplasmic reticulum and mitochondria. Electron microscopic analysis of these subcellular structures showed morphologic changes consistent with the identified proteomic alterations. Our investigation of the global cellular response to a metabolic challenge clearly shows the considerable adaptive capacity of the proteome to a slowly evolving metabolic challenge

A Quiet Revolution in Diplomacy: Quebec–UK Relations Since 1960

Quebec’s modern international outlook and its current paradiplomacy can be dated largely from the Quiet Revolution of the 1960s. Since then, the provincial government in Quebec City and the federal government in Ottawa have had to tread a fine line in accommodating each other’s constitutional rights in the field of international relations—a line that has occasionally been breached, especially in the years following the Quiet Revolution and in critical periods such as those prior to the 1980 and 1995 referenda. Foreign governments have also had to engage in careful diplomacy in order to avoid upsetting either Ottawa or Quebec City—and this has been especially true in the case of the countries historically most involved with Canada and Quebec—France, the United States, and Britain. But whereas there has been some academic writing on Quebec’s relationships with France and the United States, very little attention has been devoted to Quebec–UK relations since the Quiet Revolution. This article seeks to fill that gap and argues that the Quebec–UK relationship since the 1960s can itself best be characterized as a “quiet revolution” in diplomacy that has largely avoided the controversies that have sometimes dogged Quebec’s relations with France and the United States

The Roosevelt image on trial: FDR, the radio, and the Supreme Court battle of 1937

Presidential Image has become an integral part of the campaign, presidency and legacy of Modern American presidents. Across the 20th century to the age of Trump, presidential image has dominated media coverage and public consciousness, winning elections, gaining support for their leadership in office and shaping their reputation in history. Is the creation of the presidential image part of a carefully conceived public relations strategy or result of the president's critics and opponents? Can the way the media interpret a presidents' actions and words alter their image? And how much influence do cultural outputs contribute to the construction of a presidential image? Using ten presidential case studies. this edited collection features contributions from scholars and political journalists from the UK and America, to analyse aspects of Presidential Image that shaped their perceived effectiveness as America's leader, and to explore this complex, controversial, and continuous element of modern presidential politics

Stochastic Hosting Capacity in LV Distribution Networks

Hosting capacity is defined as the level of penetration that a particular technology can connect to a distribution network without causing power quality problems. In this work, we study the impact of solar photovoltaics (PV) on voltage rise. In most cases, the locations and sizes of the PV are not known in advance, so hosting capacity must be considered as a random variable. Most hosting capacity methods study the problem considering a large number of scenarios, many of which provide little additional information. We overcome this problem by studying only cases where voltage constraints are active, with results illustrating a reduction in the number of scenarios required by an order of magnitude. A linear power flow model is utilised for this task, showing excellent performance. The hosting capacity is finally studied as a function of the number of generators connected, demonstrating that assumptions about the penetration level will have a large impact on the conclusions drawn for a given network

Two decades of pulsar timing of Vela

Pulsar timing at the Mt Pleasant observatory has focused on Vela, which can be tracked for 18 hours of the day. These nearly continuous timing records extend over 24 years allowing a greater insight into details of timing noise, micro glitches and other more exotic effects. In particular we report the glitch parameters of the 2004 event, along with the reconfirmation that the spin up for the Vela pulsar occurs instantaneously to the accuracy of the data. This places a lower limit of about 30 seconds for the acceleration of the pulsar to the new rotational frequency. We also confirm of the low braking index for Vela, and the continued fall in the DM for this pulsar.Comment: Isolated Neutron Stars conference, London, April 24-28 200

Particle number conservation in quantum many-body simulations with matrix product operators

Incorporating conservation laws explicitly into matrix product states (MPS) has proven to make numerical simulations of quantum many-body systems much less resources consuming. We will discuss here, to what extent this concept can be used in simulation where the dynamically evolving entities are matrix product operators (MPO). Quite counter-intuitively the expectation of gaining in speed by sacrificing information about all but a single symmetry sector is not in all cases fulfilled. It turns out that in this case often the entanglement imposed by the global constraint of fixed particle number is the limiting factor.Comment: minor changes, 18 pages, 5 figure