The molecular basis of frontotemporal dementia

Frontotemporal dementia (FTD) is a clinical syndrome with a heterogeneous molecular basis. Familial FTD has been linked to mutations in several genes, including those encoding the microtubule-associated protein tau (MAPT), progranulin (GRN), valosin-containing protein (VCP) and charged multivescicular body protein 2B (CHMP2B). The associated neuropathology is characterised by selective degeneration of the frontal and temporal lobes (frontotemporal lobar degeneration, FTLD), usually with the presence of abnormal intracellular protein accumulations. The current classification of FTLD neuropathology is based on the identity of the predominant protein abnormality, in the belief that this most closely reflects the underlying pathogenic process. Major subgroups include those characterised by the pathological tau, TDP-43, intermediate filaments and a group with cellular inclusions composed of an unidentified ubiquitinated protein. This review will focus on the current understanding of the molecular basis of each of the major FTLD subtypes. It is anticipated that this knowledge will provide the basis of future advances in the diagnosis and treatment of FT

Bread and butter or bread and circuses?

Does domestic contestation of European Union legitimacy affect the behaviour of the European Commission as an economic and fiscal supervisor? We draw on theories of bureaucratic responsiveness and employ multilevel and topic modelling to examine the extent to which the politicisation of European integration affects the outputs of the European Semester: the Country-Specific Recommendations. We develop two competing sets of hypotheses and test these on an original large-N data set on Commission behaviour with observations covering the period 2011–2017. We detect a twofold effect on the Commission's recommendations: member states that experience greater politicisation receive recommendations that are larger in scope but whose substance is less oriented towards social investment. We argue that this effect is best explained as an outcome of the Commission's institutional risk management strategy of regulatory ‘entrenchment’. The supranational agent issues additional recommendations while simultaneously entrenching on a stronger mandate substantively, which allows it to maintain its regulatory reputation and signal regulatory resolve to observing audiences

The politics of (de-)politicization and venue choice: A scoping review and research agenda on EU financial regulation and economic governance

Scholarly interest in EU financial regulation and economic governance has increased sharply over the last decade, but the literature on their politics remains fragmented. We present a scoping literature review which systematically locates and aggregates academic articles on their politics in ISI-ranked journals between 1999 and 2016. We identify lacunas in this literature by mapping its strands onto the EU political system. We then present a system-level research agenda that focuses on the cycles of depoliticization and politicization that strongly characterize the politics in these areas. Future research must pay careful attention to the conditions, mechanisms and, especially the venues that (dis)allow the linkage of societal politicization to EU-level politics. This approach is deeply rooted in the specifics of the politics of these policy areas, but also draws on the strengths of research in these areas to increase its relevance for broader debates on the future of the EU itself

The State of Self-Organized Criticality of the Sun During the Last 3 Solar Cycles. I. Observations

We analyze the occurrence frequency distributions of peak fluxes $P$, total fluxes $E$, and durations $T$ of solar flares over the last three solar cycles (during 1980--2010) from hard X-ray data of HXRBS/SMM, BATSE/CGRO, and RHESSI. From the synthesized data we find powerlaw slopes with mean values of $\alpha_P=1.72\pm0.08$ for the peak flux, $\alpha_E=1.60\pm0.14$ for the total flux, and $\alpha_T=1.98\pm0.35$ for flare durations. We find a systematic anti-correlation of the powerlaw slope of peak fluxes as a function of the solar cycle, varying with an approximate sinusoidal variation $\alpha_P(t)=\alpha_0+\Delta \alpha \cos{[2\pi (t-t_0)/T_{cycle}]}$, with a mean of $\alpha_0=1.73$, a variation of $\Delta \alpha =0.14$, a solar cycle period $T_{cycle}=12.6$ yrs, and a cycle minimum time $t_0=1984.1$. The powerlaw slope is flattest during the maximum of a solar cycle, which indicates a higher magnetic complexity of the solar corona that leads to an overproportional rate of powerful flares.Comment: subm. to Solar Physic

Solar Stereoscopy with STEREO/EUVI A and B spacecraft from small (6 deg) to large (170 deg) spacecraft separation angles

We performed for the first time stereoscopic triangulation of coronal loops in active regions over the entire range of spacecraft separation angles ($\alpha_{sep}\approx 6^\circ, 43^\circ, 89^\circ, 127^\circ$, and $170^\circ$). The accuracy of stereoscopic correlation depends mostly on the viewing angle with respect to the solar surface for each spacecraft, which affects the stereoscopic correspondence identification of loops in image pairs. From a simple theoretical model we predict an optimum range of $\alpha_{sep} \approx 22^\circ-125^\circ$, which is also experimentally confirmed. The best accuracy is generally obtained when an active region passes the central meridian (viewed from Earth), which yields a symmetric view for both STEREO spacecraft and causes minimum horizontal foreshortening. For the extended angular range of $\alpha_{sep}\approx 6^\circ-127^{\circ}$ we find a mean 3D misalignment angle of $\mu_{PF} \approx 21^\circ-39^\circ$ of stereoscopically triangulated loops with magnetic potential field models, and $\mu_{FFF} \approx 15^\circ-21^\circ$ for a force-free field model, which is partly caused by stereoscopic uncertainties $\mu_{SE} \approx 9^\circ$. We predict optimum conditions for solar stereoscopy during the time intervals of 2012--2014, 2016--2017, and 2021--2023.Comment: Solar Physics, (in press), 22 pages, 9 figure

Universality in the Screening Cloud of Dislocations Surrounding a Disclination

A detailed analytical and numerical analysis for the dislocation cloud surrounding a disclination is presented. The analytical results show that the combined system behaves as a single disclination with an effective fractional charge which can be computed from the properties of the grain boundaries forming the dislocation cloud. Expressions are also given when the crystal is subjected to an external two-dimensional pressure. The analytical results are generalized to a scaling form for the energy which up to core energies is given by the Young modulus of the crystal times a universal function. The accuracy of the universality hypothesis is numerically checked to high accuracy. The numerical approach, based on a generalization from previous work by S. Seung and D.R. Nelson ({\em Phys. Rev A 38:1005 (1988)}), is interesting on its own and allows to compute the energy for an {\em arbitrary} distribution of defects, on an {\em arbitrary geometry} with an arbitrary elastic {\em energy} with very minor additional computational effort. Some implications for recent experimental, computational and theoretical work are also discussed.Comment: 35 pages, 21 eps file

Cartan's spiral staircase in physics and, in particular, in the gauge theory of dislocations

In 1922, Cartan introduced in differential geometry, besides the Riemannian curvature, the new concept of torsion. He visualized a homogeneous and isotropic distribution of torsion in three dimensions (3d) by the "helical staircase", which he constructed by starting from a 3d Euclidean space and by defining a new connection via helical motions. We describe this geometric procedure in detail and define the corresponding connection and the torsion. The interdisciplinary nature of this subject is already evident from Cartan's discussion, since he argued - but never proved - that the helical staircase should correspond to a continuum with constant pressure and constant internal torque. We discuss where in physics the helical staircase is realized: (i) In the continuum mechanics of Cosserat media, (ii) in (fairly speculative) 3d theories of gravity, namely a) in 3d Einstein-Cartan gravity - this is Cartan's case of constant pressure and constant intrinsic torque - and b) in 3d Poincare gauge theory with the Mielke-Baekler Lagrangian, and, eventually, (iii) in the gauge field theory of dislocations of Lazar et al., as we prove for the first time by arranging a suitable distribution of screw dislocations. Our main emphasis is on the discussion of dislocation field theory.Comment: 31 pages, 8 figure

Fermi Large Area Telescope Third Source Catalog

101 pages, 26 figures, accepted for publication in Astrophysical Journal Supplement Series. The ancillary files are PDFs of the full versions of Tables 4 and 8 and a FITS version of Table 11. v3 has corrected Table 6 and minor edits. The 3FGL catalog is available at http://fermi.gsfc.nasa.gov/ssc/data/access/lat/4yr_catalogInternational audienceWe present the third Fermi Large Area Telescope source catalog (3FGL) of sources in the 100 MeV-300 GeV range. Based on the first four years of science data from the Fermi Gamma-ray Space Telescope mission, it is the deepest yet in this energy range. Relative to the 2FGL catalog, the 3FGL catalog incorporates twice as much data as well as a number of analysis improvements, including improved calibrations at the event reconstruction level, an updated model for Galactic diffuse gamma-ray emission, a refined procedure for source detection, and improved methods for associating LAT sources with potential counterparts at other wavelengths. The 3FGL catalog includes 3033 sources above 4 sigma significance, with source location regions, spectral properties, and monthly light curves for each. Of these, 78 are flagged as potentially being due to imperfections in the model for Galactic diffuse emission. Twenty-five sources are modeled explicitly as spatially extended, and overall 232 sources are considered as identified based on angular extent or correlated variability (periodic or otherwise) observed at other wavelengths. For 1009 sources we have not found plausible counterparts at other wavelengths. More than 1100 of the identified or associated sources are active galaxies of the blazar class; several other classes of non-blazar active galaxies are also represented in the 3FGL. Pulsars represent the largest Galactic source class. From source counts of Galactic sources we estimate the contribution of unresolved sources to the Galactic diffuse emission is ~3% at 1 GeV

Cultural constructions of happiness: theory and emprical evidence

In a review of recent cross-cultural evidence on happiness and well-being, the authors identified substantial cultural variations in (1) cultural meanings of happiness, (2) motivations underlying happiness, and (3) predictors of happiness. Specifically, in North American cultural contexts, happiness tends to be defined in terms of personal achievement. Individuals engaging in these cultures are motivated to maximize the experience of positive affect. Moreover, happiness is best predicted by self-esteem. In contrast, in East Asian cultural contexts, happiness tends to be defined in terms of interpersonal connectedness. Individuals engaging in these cultures are motivated to maintain a balance between positive and negative affects. Moreover, happiness is best predicted by perceived embeddedness of the self in a social relationship. Directions for future research are discussed.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/43061/1/10902_2004_Article_5278785.pd