ARPES insights on the metallic states of YbB6(001): E(k) dispersion, temporal changes and spatial variation

We report high resolution Angle Resolved PhotoElectron Spectroscopy (ARPES) results on the (001) cleavage surface of YbB$_{6}$, a rare-earth compound which has been recently predicted to host surface electronic states with topological character. We observe two types of well-resolved metallic states, whose Fermi contours encircle the time-reversal invariant momenta of the YbB$_{6}$(001) surface Brillouin zone, and whose full (E,$k$)-dispersion relation can be measured wholly unmasked by states from the rest of the electronic structure. Although the two-dimensional character of these metallic states is confirmed by their lack of out-of-plane dispersion, two new aspects are revealed in these experiments. Firstly, these states do not resemble two branches of opposite, linear velocity that cross at a Dirac point, but rather straightforward parabolas which terminate to high binding energy with a clear band bottom. Secondly, these states are sensitive to time-dependent changes of the YbB$_{6}$ surface under ultrahigh vacuum conditions. Adding the fact that these data from cleaved YbB$_{6}$ surfaces also display spatial variations in the electronic structure, it appears there is little in common between the theoretical expectations for an idealized YbB$_{6}$(001) crystal truncation on the one hand, and these ARPES data from real cleavage surfaces on the other.Comment: 8 pages, 4 figures (accepted in Physical Review B

Dirac states with knobs on: interplay of external parameters and the surface electronic properties of 3D topological insulators

Topological insulators are a novel materials platform with high applications potential in fields ranging from spintronics to quantum computation. In the ongoing scientific effort to demonstrate controlled manipulation of their electronic structure by external means, stoichiometric variation and surface decoration are two effective approaches that have been followed. In ARPES experiments, both approaches are seen to lead to electronic band structure changes. Such approaches result in variations of the energy position of bulk and surface-related features and the creation of two-dimensional electron gases.The data presented here demonstrate that a third manipulation handle is accessible by utilizing the amount of illumination a topological insulator surface has been exposed to under typical experimental ARPES conditions. Our results show that this new, third, knob acts on an equal footing with stoichiometry and surface decoration as a modifier of the electronic band structure, and that it is in continuous competition with the latter. The data clearly point towards surface photovoltage and photo-induced desorption as the physical phenomena behind modifications of the electronic band structure under exposure to high-flux photons. We show that the interplay of these phenomena can minimize and even eliminate the adsorbate-related surface band bending on typical binary, ternary and quaternary Bi-based topological insulators. Including the influence of the sample temperature, these data set up a framework for the external control of the electronic band structure in topological insulator compounds in an ARPES setting. Four external knobs are available: bulk stoichiometry, surface decoration, temperature and photon exposure. These knobs can be used in conjunction to tune the band energies near the surface and consequently influence the topological properties of the relevant electronic states.Comment: 16 pages, 8 figure

Variability in lutetium-177 SPECT quantification between different state-of-the-art SPECT/CT systems

Background: Quantitative SPECT imaging in targeted radionuclide therapy with lutetium-177 holds great potential for individualized treatment based on dose assessment. The establishment of dose-effect relations requires a standardized method for SPECT quantification. The purpose of this multi-center study is to evaluate quantitative accuracy and inter-system variations of different SPECT/CT systems with corresponding commercially available quantitative reconstruction algorithms. This is an important step towards a vendor-independent standard for quantitative lutetium-177 SPECT. Methods: Four state-of-the-art SPECT/CT systems were included: Discovery™ NM/CT 670Pro (GE Healthcare), Symbia Intevo™, and two Symbia™ T16 (Siemens Healthineers). Quantitative accuracy and inter-system variations were evaluated by repeatedly scanning a cylindrical phantom with 6 spherical inserts (0.5 – 113 ml). A sphere-to-background activity concentration ratio of 10:1 was used. Acquisition settings were standardized: medium energy collimator, body contour trajectory, photon energy window of 208 keV (± 10%), adjacent 20% lower scatter window, 2 × 64 projections, 128 × 128 matrix size, and 40 s projection time. Reconstructions were performed using GE Evolution with Q.Metrix™, Siemens xSPECT Quant™, Siemens Broad Quantification™ or Siemens Flash3D™ algorithms using vendor recommended settings. In addition, projection data were reconstructed using Hermes SUV SPECT™ with standardized reconstruction settings to obtain a vendor-neutral quantitative reconstruction for all systems. Volumes of interest (VOI) for the spheres were obtained by applying a 50% threshold of the sphere maximum voxel value corrected for background activity. For each sphere, the mean and maximum recovery coefficient (RCmean and RCmax) of three repeated measurements was calculated, defined as the imaged activity concentration divided by the actual activity concentration. Inter-system variations were defined as the range of RC over all systems. Re

Explaining the PENTA model: a reply to Arvaniti and Ladd

This paper presents an overview of the Parallel Encoding and Target Approximation (PENTA) model of speech prosody, in response to an extensive critique by Arvaniti & Ladd (2009). PENTA is a framework for conceptually and computationally linking communicative meanings to fine-grained prosodic details, based on an articulatory-functional view of speech. Target Approximation simulates the articulatory realisation of underlying pitch targets – the prosodic primitives in the framework. Parallel Encoding provides an operational scheme that enables simultaneous encoding of multiple communicative functions. We also outline how PENTA can be computationally tested with a set of software tools. With the help of one of the tools, we offer a PENTA-based hypothetical account of the Greek intonational patterns reported by Arvaniti & Ladd, showing how it is possible to predict the prosodic shapes of an utterance based on the lexical and postlexical meanings it conveys

The Central Region of Barred Galaxies: Molecular Environment, Starbursts, and Secular Evolution

Despite compelling evidence that stellar bars drive gas into the inner 1--2 kpc or circumnuclear (CN) region of galaxies, there are few large, high resolution studies of the CN molecular gas and star formation (SF). We study a sample of local barred non-starbursts and starbursts with high-resolution CO, optical, Ha, RC, Br-gamma, and HST data, and find the following. (1) The inner kpc of bars differs markedly the outer disk and hosts molecular gas surface densities Sigma-gas-m of 500-3500 Msun pc-2, gas mass fractions of 10--30 %, and epicyclic frequencies of several 100--1000 km s-1 kpc-1.Consequently, gravitational instabilities can only set in at high gas densities and grow on a short timescale (few Myr). This high density, short timescale, `burst' mode may explain why powerful starbursts tend to be in the CN region of galaxies. (2) We suggest that the variety in CO morphologies is due to different stages of bar-driven inflow. At late stages, most of the CN gas is inside the outer inner Lindblad resonance (OILR), and has predominantly circular motions. Across the sample, we find bar pattern speeds with upper limits of 43 to 115 km s-1 kpc-1 and OILR radii of > 500 pc. (3) Barred starbursts and non-starbursts have CN SFRs of 3--11 and 0.1--2 Msun yr-1, despite similar CN gas mass. Sigma-gas-m in the starbursts is larger (1000--3500 Msun pc-2) and close to the Toomre critical density over a large region. (4) Molecular gas makes up 10%--30% of the CN dynamical mass (6--30 x 10^9 Msun).In the starbursts, it fuels CN SFRs of 3--11 Msun yr-1, building young, massive, high V/sigma components. We present evidence for such a pseudo-bulge in NGC 3351. Implications for secular evolution along the Hubble sequence are discussed.Comment: Accepted by the Astrophysical Journal. Paper length reduced to fit within APJ page limits. Version of paper with high resolution figures is at http://www.as.utexas.edu/~sj/papers/ms-hires-sj05a.ps.g

No-go trials can modulate switch cost by interfering with effects of task preparation

It has recently been shown that the cost associated with switching tasks is eliminated following ‘no-go’ trials, in which response selection is not completed, suggesting that the switch cost depends on response selection. However, no-go trials may also affect switch costs by interfering with the effects of task preparation that precede response selection. To test this hypothesis we evaluated switch costs following standard go trials with those following two types of non-response trials: no-go trials, for which a stimulus is presented that indicates no response should be made (Experiment 1); and cue-only trials in which no stimulus is presented following the task cue (Experiment 2). We hypothesized that eliminating no-go stimuli would reveal effects of task preparation on the switch cost in cue-only trials. We found no switch cost following no-go trials (Experiment 1), but a reliable switch cost in cue-only trials (i.e., when no-go stimuli were removed; Experiment 2). We conclude that no-go trials can modulate the switch cost, independent of their effect on response selection, by interfering with task preparation, and that the effects of task preparation on switch cost are more directly assessed by cue-only trials

Antivirals for influenza-Like Illness? A randomised Controlled trial of Clinical and Cost effectiveness in primary CarE (ALIC4 E): the ALIC4 E protocol

INTRODUCTION: Effective management of seasonal and pandemic influenza is a high priority internationally. Guidelines in many countries recommend antiviral treatment for older people and individuals with comorbidity at increased risk of complications. However, antivirals are not often prescribed in primary care in Europe, partly because its clinical and cost effectiveness has been insufficiently demonstrated by non-industry funded and pragmatic studies. METHODS AND ANALYSIS: Antivirals for influenza-Like Illness? An rCt of Clinical and Cost effectiveness in primary CarE is a European multinational, multicentre, open-labelled, non-industry funded, pragmatic, adaptive-platform, randomised controlled trial. Initial trial arms will be best usual primary care and best usual primary care plus treatment with oseltamivir for 5 days. We aim to recruit at least 2500 participants ≥1 year presenting with influenza-like illness (ILI), with symptom duration ≤72 hours in primary care over three consecutive periods of confirmed high influenza incidence. Participant outcomes will be followed up to 28 days by diary and telephone. The primary objective is to determine whether adding antiviral treatment to best usual primary care is effective in reducing time to return to usual daily activity with fever, headache and muscle ache reduced to minor severity or less. Secondary objectives include estimating cost-effectiveness, benefits in subgroups according to age (64 years), severity of symptoms at presentation (low, medium and high), comorbidity (yes/no), duration of symptoms (≤48 hours/>48-72 hours), complications (hospital admission and pneumonia), use of additional prescribed medication including antibiotics, use of over-the-counter medicines and self-management of ILI symptoms. ETHICS AND DISSEMINATION: Research ethics committee (REC) approval was granted by the NRES Committee South Central (Oxford B) and Clinical Trial Authority (CTA) approval by The Medicines and Healthcare products Regulatory Agency. All participating countries gained national REC and CTA approval as required. Dissemination of results will be through peer-reviewed scientific journals and conference presentations

A Novel Substrate-Based HIV-1 Protease Inhibitor Drug Resistance Mechanism

BACKGROUND: HIV protease inhibitor (PI) therapy results in the rapid selection of drug resistant viral variants harbouring one or two substitutions in the viral protease. To combat PI resistance development, two approaches have been developed. The first is to increase the level of PI in the plasma of the patient, and the second is to develop novel PI with high potency against the known PI-resistant HIV protease variants. Both approaches share the requirement for a considerable increase in the number of protease mutations to lead to clinical resistance, thereby increasing the genetic barrier. We investigated whether HIV could yet again find a way to become less susceptible to these novel inhibitors. METHODS AND FINDINGS: We have performed in vitro selection experiments using a novel PI with an increased genetic barrier (RO033-4649) and demonstrated selection of three viruses 4- to 8-fold resistant to all PI compared to wild type. These PI-resistant viruses did not have a single substitution in the viral protease. Full genomic sequencing revealed the presence of NC/p1 cleavage site substitutions in the viral Gag polyprotein (K436E and/or I437T/V) in all three resistant viruses. These changes, when introduced in a reference strain, conferred PI resistance. The mechanism leading to PI resistance is enhancement of the processing efficiency of the altered substrate by wild-type protease. Analysis of genotypic and phenotypic resistance profiles of 28,000 clinical isolates demonstrated the presence of these NC/p1 cleavage site mutations in some clinical samples (codon 431 substitutions in 13%, codon 436 substitutions in 8%, and codon 437 substitutions in 10%). Moreover, these cleavage site substitutions were highly significantly associated with reduced susceptibility to PI in clinical isolates lacking primary protease mutations. Furthermore, we used data from a clinical trial (NARVAL, ANRS 088) to demonstrate that these NC/p1 cleavage site changes are associated with virological failure during PI therapy. CONCLUSIONS: HIV can use an alternative mechanism to become resistant to PI by changing the substrate instead of the protease. Further studies are required to determine to what extent cleavage site mutations may explain virological failure during PI therapy

The Long-Baseline Neutrino Experiment: Exploring Fundamental Symmetries of the Universe

The preponderance of matter over antimatter in the early Universe, the dynamics of the supernova bursts that produced the heavy elements necessary for life and whether protons eventually decay --- these mysteries at the forefront of particle physics and astrophysics are key to understanding the early evolution of our Universe, its current state and its eventual fate. The Long-Baseline Neutrino Experiment (LBNE) represents an extensively developed plan for a world-class experiment dedicated to addressing these questions. LBNE is conceived around three central components: (1) a new, high-intensity neutrino source generated from a megawatt-class proton accelerator at Fermi National Accelerator Laboratory, (2) a near neutrino detector just downstream of the source, and (3) a massive liquid argon time-projection chamber deployed as a far detector deep underground at the Sanford Underground Research Facility. This facility, located at the site of the former Homestake Mine in Lead, South Dakota, is approximately 1,300 km from the neutrino source at Fermilab -- a distance (baseline) that delivers optimal sensitivity to neutrino charge-parity symmetry violation and mass ordering effects. This ambitious yet cost-effective design incorporates scalability and flexibility and can accommodate a variety of upgrades and contributions. With its exceptional combination of experimental configuration, technical capabilities, and potential for transformative discoveries, LBNE promises to be a vital facility for the field of particle physics worldwide, providing physicists from around the globe with opportunities to collaborate in a twenty to thirty year program of exciting science. In this document we provide a comprehensive overview of LBNE's scientific objectives, its place in the landscape of neutrino physics worldwide, the technologies it will incorporate and the capabilities it will possess.Comment: Major update of previous version. This is the reference document for LBNE science program and current status. Chapters 1, 3, and 9 provide a comprehensive overview of LBNE's scientific objectives, its place in the landscape of neutrino physics worldwide, the technologies it will incorporate and the capabilities it will possess. 288 pages, 116 figure

Admixture Mapping Scans Identify a Locus Affecting Retinal Vascular Caliber in Hypertensive African Americans: the Atherosclerosis Risk in Communities (ARIC) Study

Retinal vascular caliber provides information about the structure and health of the microvascular system and is associated with cardiovascular and cerebrovascular diseases. Compared to European Americans, African Americans tend to have wider retinal arteriolar and venular caliber, even after controlling for cardiovascular risk factors. This has suggested the hypothesis that differences in genetic background may contribute to racial/ethnic differences in retinal vascular caliber. Using 1,365 ancestry-informative SNPs, we estimated the percentage of African ancestry (PAA) and conducted genome-wide admixture mapping scans in 1,737 African Americans from the Atherosclerosis Risk in Communities (ARIC) study. Central retinal artery equivalent (CRAE) and central retinal vein equivalent (CRVE) representing summary measures of retinal arteriolar and venular caliber, respectively, were measured from retinal photographs. PAA was significantly correlated with CRVE (ρ = 0.071, P = 0.003), but not CRAE (ρ = 0.032, P = 0.182). Using admixture mapping, we did not detect significant admixture association with either CRAE (genome-wide score = −0.73) or CRVE (genome-wide score = −0.69). An a priori subgroup analysis among hypertensive individuals detected a genome-wide significant association of CRVE with greater African ancestry at chromosome 6p21.1 (genome-wide score = 2.31, locus-specific LOD = 5.47). Each additional copy of an African ancestral allele at the 6p21.1 peak was associated with an average increase in CRVE of 6.14 µm in the hypertensives, but had no significant effects in the non-hypertensives (P for heterogeneity <0.001). Further mapping in the 6p21.1 region may uncover novel genetic variants affecting retinal vascular caliber and further insights into the interaction between genetic effects of the microvascular system and hypertension