Reflections on a crisis: political disenchantment, moral desolation, and political integrity

Declining levels of political trust and voter turnout, the shift towards populist politics marked by appeals to ‘the people’ and a rejection of ‘politics-as-usual’, are just some of the commonly cited manifestations of our culture of political disaffection. Democratic politics, it is argued, is in crisis. Whilst considerable energy has been expended on the task of lamenting the status of our politics and pondering over recommendations to tackle this perceived crisis, amid this raft of complaints and solutions lurks confusion. This paper seeks to explore the neglected question of what the precise nature of the crisis with which we are confronted involves, and, in so doing, to go some way towards untangling our confusion. Taking my cue from Machiavelli and his value-pluralist heirs, I argue that there is a rift between a morally admirable and a virtuous political life. Failure to appreciate this possibility causes narrations of crisis to misconstrue the moral messiness of politics in ways that lead us to misunderstand how we should respond to disenchantment. Specifically, I suggest that: (i) we think that there is a moral crisis in politics because we have an unsatisfactorily idealistic understanding of political integrity in the first place; and (ii) it is a mistake to imagine that the moral purification of politics is possible or desirable. Put simply, our crisis is not moral per se but primarily philosophical in nature: it relates to the very concepts we employ—the qualities of character and context we presuppose whilst pondering over political integrity

Changing Politics: Towards a New Democracy

In October 2014 the PSA joint-funded a Consultation event ‘Changing Politics – Towards a New Democracy’ with St. George’s House. The Chair of the PSA, Professor Matthew Flinders, chaired the event which brought together participants from a range of fields (including academics, think tankers and practitioners in several policy areas). Today, St. George’s House has published a report which highlights the main themes emerging from the discussion as well as some conclusions and recommendations. It identifies several areas where changes are urgently needed to reinvigorate democracy. The report concludes that to fully succeed in addressing the growth of political apathy and disengagement, parties and leaders must forget their differences and join citizens, academics, charities and others to address this problem with all available energy and resources

Understanding and Challenging Populist Negativity towards Politics: The Perspectives of British Citizens

This article adapts and develops the idea of a cynical or ‘stealth’ understanding of politics to explore how citizens’ estrangement from formal politics is processed cognitively through a populist lens. Earlier work has shown the widespread presence of stealth attitudes in the United States and Finland. We show that stealth attitudes are also well established in Britain, demonstrate their populist character and reveal that age, newspaper readership and concerns about governing practices help predict their adoption by individuals. Yet our survey findings also reveal a larger body of positive attitudes towards the practice of democracy suggesting that there is scope for challenging populist cynicism. We explore these so-called ‘sunshine’ attitudes and connect them to the reform options favoured by British citizens. If we are to challenge populist negativity towards politics, we conclude that improving the operation of representative politics is more important than offering citizens new forms of more deliberative participation

A search for spectral hysteresis and energy-dependent time lags from X-ray and TeV gamma-ray observations of Mrk 421

Blazars are variable emitters across all wavelengths over a wide range of timescales, from months down to minutes. It is therefore essential to observe blazars simultaneously at different wavelengths, especially in the X-ray and gamma-ray bands, where the broadband spectral energy distributions usually peak. In this work, we report on three "target-of-opportunity" (ToO) observations of Mrk 421, one of the brightest TeV blazars, triggered by a strong flaring event at TeV energies in 2014. These observations feature long, continuous, and simultaneous exposures with XMM-Newton (covering X-ray and optical/ultraviolet bands) and VERITAS (covering TeV gamma-ray band), along with contemporaneous observations from other gamma-ray facilities (MAGIC and Fermi-LAT) and a number of radio and optical facilities. Although neither rapid flares nor significant X-ray/TeV correlation are detected, these observations reveal subtle changes in the X-ray spectrum of the source over the course of a few days. We search the simultaneous X-ray and TeV data for spectral hysteresis patterns and time delays, which could provide insight into the emission mechanisms and the source properties (e.g. the radius of the emitting region, the strength of the magnetic field, and related timescales). The observed broadband spectra are consistent with a one-zone synchrotron self-Compton model. We find that the power spectral density distribution at $\gtrsim 4\times 10^{-4}$ Hz from the X-ray data can be described by a power-law model with an index value between 1.2 and 1.8, and do not find evidence for a steepening of the power spectral index (often associated with a characteristic length scale) compared to the previously reported values at lower frequencies.Comment: 45 pages, 15 figure

Multiband variability studies and novel broadband SED modeling of Mrk 501 in 2009

Aims. We present an extensive study of the BL Lac object Mrk 501 based on a data set collected during the multi-instrument campaign spanning from 2009 March 15 to 2009 August 1, which includes, among other instruments, MAGIC, VERITAS, Whipple 10 m, and Fermi-LAT to cover the gamma-ray range from 0.1 GeV to 20 TeV; RXTE and Swift to cover wavelengths from UV to hard X-rays; and GASP-WEBT, which provides coverage of radio and optical wavelengths. Optical polarization measurements were provided for a fraction of the campaign by the Steward and St. Petersburg observatories. We evaluate the variability of the source and interband correlations, the gamma-ray flaring activity occurring in May 2009, and interpret the results within two synchrotron self-Compton (SSC) scenarios.Methods. The multiband variability observed during the full campaign is addressed in terms of the fractional variability, and the possible correlations are studied by calculating the discrete correlation function for each pair of energy bands where the significance was evaluated with dedicated Monte Carlo simulations. The space of SSC model parameters is probed following a dedicated grid-scan strategy, allowing for a wide range of models to be tested and offering a study of the degeneracy of model-to-data agreement in the individual model parameters, hence providing a less biased interpretation than the "single-curve SSC model adjustment" typically reported in the literature.Results. We find an increase in the fractional variability with energy, while no significant interband correlations of flux changes are found on the basis of the acquired data set. The SSC model grid-scan shows that the flaring activity around May 22 cannot be modeled adequately with a one-zone SSC scenario (using an electron energy distribution with two breaks), while it can be suitably described within a two (independent) zone SSC scenario. Here, one zone is responsible for the quiescent emission from the averaged 4.5-month observing period, while the other one, which is spatially separated from the first, dominates the flaring emission occurring at X-rays and very-high-energy (> 100 GeV, VHE) gamma-rays. The flaring activity from May 1, which coincides with a rotation of the electric vector polarization angle (EVPA), cannot be satisfactorily reproduced by either a one-zone or a two-independent-zone SSC model, yet this is partially affected by the lack of strictly simultaneous observations and the presence of large flux changes on sub-hour timescales (detected at VHE gamma rays).Conclusions. The higher variability in the VHE emission and lack of correlation with the X-ray emission indicate that, at least during the 4.5-month observing campaign in 2009, the highest energy (and most variable) electrons that are responsible for the VHE gamma rays do not make a dominant contribution to the similar to 1 keV emission. Alternatively, there could be a very variable component contributing to the VHE gamma-ray emission in addition to that coming from the SSC scenario. The studies with our dedicated SSC grid-scan show that there is some degeneracy in both the one-zone and the two-zone SSC scenarios probed, with several combinations of model parameters yielding a similar model-to-data agreement, and some parameters better constrained than others. The observed gamma-ray flaring activity, with the EVPA rotation coincident with the first gamma-ray flare, resembles those reported previously for low frequency peaked blazars, hence suggesting that there are many similarities in the flaring mechanisms of blazars with different jet properties

Multi-omic Analysis of B-Cell Lymphoma Reveals Novel Mechanisms of Chemotherapeutic Drug Resistance

The genetic origins of chemotherapy resistance are well established, however the role of the epigenome and post-transcriptional regulation in drug resistance is less well understood. To investigate mechanisms of drug resistance we performed a systematic genetic, epigenetic, transcriptomic and proteomic analysis of a mafosfamide sensitive and resistant murine lymphoma cell line, along with a series of resistant lines derived by drug dose escalation. Our data suggest that acquired resistance could not be explained by genetic alterations. By integrating our transcriptional profiles with transcription factor binding data we hypothesize that the resistance was associated with changes in the activity of the polycomb repressive complex (Prc2) as well as the transcription factor E2a. We verified that the resistant cells had distinct H3K27me3 and DNA methylation profiles, compared to the parental lines, and differentially expressed genes were enriched for targets of E2a. In addition, the resistant lines appear to de-differentiate to a less mature state along the B cell maturation axis. Overall, we propose that resistant lines are transformed by an E2a and Pcr2 driven cellular program that leads to a less mature B cell state in which the apoptotic cascade induced by mafosfamide treatment is attenuated. Furthermore, combined transcriptomic and proteomic data analysis elucidated mechanisms of resistance involving the ubiquitination activating enzyme Uba1 which were not revealed by analysis of either transcriptomic or proteomic data alone

Anti-Politics, Depoliticization, and Governance

There is a mounting body of evidence pointing towards rising levels of public dissatisfaction with the formal political process. Depoliticization refers to a more discrete range of contemporary strategies that add to this growing trend towards anti-politics by either removing or displacing the potential for choice, collective agency, and deliberation.This book examines the relationship between these two trends as understood within the broader shift towards governance. It brings together a number of contributions from scholars who have a varied range of concerns but who nevertheless share a common interest in developing the concept of depoliticization through their engagement with a set of theoretical, conceptual, methodological, and empirical questions. This volume explores these questions from a variety of different perspectives and uses a number of different empirical examples and case studies from both within the nation state as well as from other regional, global, and multi-level arenas.In this context, this volume examines the potential and limits of depoliticization as a concept and its position and contribution in the nexus between the larger and more established literatures on governance and anti-politics. (Publisher's abstract

Predictive Modeling of Drug Response in Non-Hodgkin's Lymphoma.

We combine mathematical modeling with experiments in living mice to quantify the relative roles of intrinsic cellular vs. tissue-scale physiological contributors to chemotherapy drug resistance, which are difficult to understand solely through experimentation. Experiments in cell culture and in mice with drug-sensitive (Eµ-myc/Arf-/-) and drug-resistant (Eµ-myc/p53-/-) lymphoma cell lines were conducted to calibrate and validate a mechanistic mathematical model. Inputs to inform the model include tumor drug transport characteristics, such as blood volume fraction, average geometric mean blood vessel radius, drug diffusion penetration distance, and drug response in cell culture. Model results show that the drug response in mice, represented by the fraction of dead tumor volume, can be reliably predicted from these inputs. Hence, a proof-of-principle for predictive quantification of lymphoma drug therapy was established based on both cellular and tissue-scale physiological contributions. We further demonstrate that, if the in vitro cytotoxic response of a specific cancer cell line under chemotherapy is known, the model is then able to predict the treatment efficacy in vivo. Lastly, tissue blood volume fraction was determined to be the most sensitive model parameter and a primary contributor to drug resistance