Quinones Facilitate the Self-Assembly of the Phosphorylated Tubulin Binding Region of Tau into Fibrillar Polymers.

The fragment of tau containing the first and third tubulin-binding motifs, involved in self- assembly of tau, was phosphorylated by protein kinase A (PKA). In the presence of hydroxynonenal (HNE) or in the presence of quinones such as juglone, 2,3-dimethoxy-5-methyl-1,4-benzoquinone (coenzyme Q0 or DMM), or menadione, the polymerization of this phosphorylated tau fragment is catalyzed, whereas polymerization of the unmodified fragment takes place in a lesser extent. The quinones coenzyme Q0 and menadione are found in every cell, including neural cells, and may interact with tau protein to facilitate its assembly into filamentous structures. These tau filaments, assembled in the presence of quinones, have a fibrillar morphology very similar to that of paired helical filaments present in the brains of patients with Alzheimer’s disease.pre-print862 K

Graviton emission in Einstein-Hilbert gravity

The five-point amplitude for the scattering of two distinct scalars with the emission of one graviton in the final state is calculated in exact kinematics for Einstein-Hilbert gravity. The result, which satisfies the Steinmann relations, is expressed in Sudakov variables, finding that it corresponds to the sum of two gauge invariant contributions written in terms of a new two scalar - two graviton effective vertex. A similar calculation is carried out in Quantum Chromodynamics (QCD) for the scattering of two distinct quarks with one extra gluon in the final state. The effective vertices which appear in both cases are then evaluated in the multi-Regge limit reproducing the well-known result obtained by Lipatov where the Einstein-Hilbert graviton emission vertex can be written as the product of two QCD gluon emission vertices, up to corrections to preserve the Steinmann relations.Comment: 28 pages, LaTeX, feynmf. v2: typos corrected, reference added. Final version to appear in Journal of High Energy Physic

Black holes and black strings of N=2, d=5 supergravity in the H-FGK formalism

We study general classes and properties of extremal and non-extremal static black-hole solutions of N=2, d=5 supergravity coupled to vector multiplets using the recently proposed H-FGK formalism, which we also extend to static black strings. We explain how to determine the integration constants and physical parameters of the black-hole and black-string solutions. We derive some model-independent statements, including the transformation of non-extremal flow equations to the form of those for the extremal flow. We apply our methods to the construction of example solutions (among others a new extremal string solution of heterotic string theory on K_3 \times S^1). In the cases where we have calculated it explicitly, the product of areas of the inner and outer horizon of a non-extremal solution coincides with the square of the moduli-independent area of the horizon of the extremal solution with the same charges.Comment: 33 pages. Revised version: references added. No other change

Mass and half-life measurements of neutron-deficient iodine isotopes

Neutron-deficient iodine isotopes, 116I and 114I, were produced at relativistic energies by in-flight fragmentation at the Fragment Separator (FRS) at GSI. The FRS Ion Catcher was used to thermalize the ions and to perform highly accurate mass measurements with a Multiple-Reflection Time-of-Flight Mass-Spectrometer (MR-TOF-MS). The masses of both isotopes were measured directly for the first time. The half-life of the 114I was measured by storing the ions in an RF quadrupole for different storage times and counting the remaining nuclei with the MR-TOF-MS. The measured half-life was used to assign the ground state to the measured 114I ions. Predictions on the possible α-decay branch for 114I are presented based on the reduced uncertainties obtained for the Qα-value. Systematic studies of the mass surface were performed with the newly obtained masses, showing better agreement with the expected trend in this mass region.peerReviewe

The QUIJOTE experiment: project status and first scientific results

We present the current status of the QUIJOTE (Q-U-I JOint TEnerife) experiment, a new polarimeter with the aim of characterizing the polarization of the Cosmic Microwave Background, and other galactic or extra-galactic physical processes that emit in microwaves in the frequency range 10–42 GHz, and at large angular scales (around 1 degree resolution). The experiment has been designed to reach the required sensitivity to detect a primordial gravitational wave component in the CMB, provided its tensor-to-scalar ratio is larger than r ∼ 0.05. The project consists of two telescopes and three instruments which will survey a large sky area from the Teide Observatory to provide I, Q and U maps of high sensitivity. The first QUIJOTE instrument, known as Multi-Frequency Instrument (MFI), has been surveying the northern sky in four individual frequencies between 10 and 20 GHz since November 2012, providing data with an average sensitivity of 80 µK beam−1 in Q and U in a region of 20, 000 square-degrees. The second instrument, or Thirty-GHz Instrument (TGI), is currently undergoing the commissioning phase, and the third instrument, or Forty-GHz Instrument (FGI), is in the final fabrication phase. Finally, we describe the first scientific results obtained with the MFI. Some specific regions, mainly along the Galactic plane, have been surveyed to a deeper depth, reaching sensitivities of around 40 µK beam−1. We present new upper limits on the polarization of the anomalous dust emission, resulting from these data, in the Perseus molecular complex and in the W43 molecular complex

The role of therapeutic optimism in recruitment to a clinical trial in a peripartum setting: balancing hope and uncertainty

BACKGROUND: Hope has therapeutic value because it enables people to cope with uncertainty about their future health. Indeed, hope, or therapeutic optimism (TO), is seen as an essential aspect of the provision and experience of medical care. The role of TO in clinical research has been briefly discussed, but the concept, and whether it can be transferred from care to research and from patients to clinicians, has not been fully investigated. The role played by TO in research emerged during interviews with staff involved in a peripartum trial. This paper unpacks the concept of TO in this setting and considers the role it may play in the wider delivery of clinical trials. METHODS: The Got-it trial is a UK-based, randomised placebo-controlled trial that investigates the use of sublingual glyceryl trinitrate (GTN) spray to treat retained placenta. Qualitative data were collected in open-ended interviews with obstetricians, research and clinical midwives (n =27) involved in trial recruitment. Data were analysed using the method of constant comparison. RESULTS: TO influenced staff engagement with Got-it at different points in the trial and in different ways. Prior knowledge of, and familiarity with, GTN meant that from the outset staff perceived the trial as low risk. TO facilitated staff involvement in the trial; staff who already understood GTN's effects were optimistic that it would work, and staff collaborated because they hoped that the trial would address what they identified as an important clinical need. TO could fluctuate over the course of the trial, and was sustained or undermined by unofficial observation of clinical outcomes and speculations about treatment allocation. Thus, TO appeared to be influenced by key situational factors: prior knowledge and experience, clinical need and observed participant outcomes. CONCLUSIONS: Situational TO plays a role in facilitating staff engagement with clinical research. TO may affect trial recruitment by enabling staff to sustain the levels of uncertainty, or individual equipoise, necessary to collaborate with research while also responding to patients' clinical needs. Staff may benefit from training to deal with fluctuations in TO. TRIAL REGISTRATION: ISCRTN88609453 . Registered on 26 March 2014