A Global SU(5) F-theory model with Wilson line breaking

We engineer compact SU(5) Grand Unified Theories in F-theory in which GUT-breaking is achieved by a discrete Wilson line. Because the internal gauge field is flat, these models avoid the high scale threshold corrections associated with hypercharge flux. Along the way, we exemplify the `local-to-global' approach in F-theory model building and demonstrate how the Tate divisor formalism can be used to address several challenges of extending local models to global ones. These include in particular the construction of G-fluxes that extend non-inherited bundles and the engineering of U(1) symmetries. We go beyond chirality computations and determine the precise (charged) massless spectrum, finding exactly three families of quarks and leptons but excessive doublet and/or triplet pairs in the Higgs sector (depending on the example) and vector-like exotics descending from the adjoint of SU(5)_{GUT}. Understanding why vector-like pairs persist in the Higgs sector without an obvious symmetry to protect them may shed light on new solutions to the mu problem in F-theory GUTs.Comment: 95 pages (71 pages + 1 Appendix); v2 references added, minor correction

Size and shape constancy in consumer virtual reality

With the increase in popularity of consumer virtual reality headsets, for research and other applications, it is important to understand the accuracy of 3D perception in VR. We investigated the perceptual accuracy of near-field virtual distances using a size and shape constancy task, in two commercially available devices. Participants wore either the HTC Vive or the Oculus Rift and adjusted the size of a virtual stimulus to match the geometric qualities (size and depth) of a physical stimulus they were able to refer to haptically. The judgments participants made allowed for an indirect measure of their perception of the egocentric, virtual distance to the stimuli. The data show under-constancy and are consistent with research from carefully calibrated psychophysical techniques. There was no difference in the degree of constancy found in the two headsets. We conclude that consumer virtual reality headsets provide a sufficiently high degree of accuracy in distance perception, to allow them to be used confidently in future experimental vision science, and other research applications in psychology

Statistical Analysis on the Performance of Molecular Mechanics Poisson-Boltzmann Surface Area versus Absolute Binding Free Energy Calculations: Bromodomains as a Case Study.

Binding free energy calculations that make use of alchemical pathways are becoming increasingly feasible thanks to advances in hardware and algorithms. Although relative binding free energy (RBFE) calculations are starting to find widespread use, absolute binding free energy (ABFE) calculations are still being explored mainly in academic settings due to the high computational requirements and still uncertain predictive value. However, in some drug design scenarios, RBFE calculations are not applicable and ABFE calculations could provide an alternative. Computationally cheaper end-point calculations in implicit solvent, such as molecular mechanics Poisson−Boltzmann surface area (MMPBSA) calculations, could too be used if one is primarily interested in a relative ranking of affinities. Here, we compare MMPBSA calculations to previously performed absolute alchemical free energy calculations in their ability to correlate with experimental binding free energies for three sets of bromodomain−inhibitor pairs. Different MMPBSA approaches have been considered, including a standard single-trajectory protocol, a protocol that includes a binding entropy estimate, and protocols that take into account the ligand hydration shell. Despite the improvements observed with the latter two MMPBSA approaches, ABFE calculations were found to be overall superior in obtaining correlation with experimental affinities for the test cases considered. A difference in weighted average Pearson (rp) and Spearman (rs) correlations of 0.25 and 0.31 was observed when using a standard single-trajectory MMPBSA setup (rp = 0.64 and rs = 0.66 for ABFE; rp = 0.39 and rs = 0.35 for MMPBSA). The best performing MMPBSA protocols returned weighted average Pearson and Spearman correlations that were about 0.1 inferior to ABFE calculations: rp = 0.55 and rs = 0.56 when including an entropy estimate, and rp = 0.53 and rs = 0.55 when including explicit water molecules. Overall, the study suggests that ABFE calculations are indeed the more accurate approach, yet there is also value in MMPBSA calculations considering the lower compute requirements, and if agreement to experimental affinities in absolute terms is not of interest. Moreover, for the specific protein−ligand systems considered in this study, we find that including an explicit ligand hydration shell or a binding entropy estimate in the MMPBSA calculations resulted in significant performance improvements at a negligible computational cost

Massive Abelian Gauge Symmetries and Fluxes in F-theory

F-theory compactified on a Calabi-Yau fourfold naturally describes non-Abelian gauge symmetries through the singularity structure of the elliptic fibration. In contrast Abelian symmetries are more difficult to study because of their inherently global nature. We argue that in general F-theory compactifications there are massive Abelian symmetries, such as the uplift of the Abelian part of the U(N) gauge group on D7-branes, that arise from non-Kahler resolutions of the dual M-theory setup. The four-dimensional F-theory vacuum with vanishing expectation values for the gauge fields corresponds to the Calabi-Yau limit. We propose that fluxes that are turned on along these U(1)s are uplifted to non-harmonic four-form fluxes. We derive the effective four-dimensional gauged supergravity resulting from F-theory compactifications in the presence of the Abelian gauge factors including the effects of possible fluxes on the gauging, tadpoles and matter spectrum.Comment: 49 page

Hyperplasia of lymphoid structures in the hypopharynx: a case report

<p>Abstract</p> <p>Introduction</p> <p>Ectopic tonsillar tissue simulating a benign tumor of the hypopharynx is described in this report.</p> <p>Case presentation</p> <p>We report the case of a 79-year-old Japanese woman with globus sensation. Because clinical observation revealed benign features, tumor tissue was laryngoscopically resected. From the pathological features, for example, existence of germinal center, lymphoid tissue, and crypt involving lymphoepithelial symbiosis, we diagnosed that the lesion was a hyperplasia of ectopic tonsillar tissue.</p> <p>Conclusions</p> <p>Although ectopic tonsillar tissue of the hypopharynx is relatively rare, it should be kept in mind during differential diagnosis.</p

VHE γ\gamma-ray observations of Markarian 501

Markarian 501, a nearby (z=0.033) X-ray selected BL Lacertae object, is a well established source of Very High Energy (VHE, E>=300 GeV) gamma rays. Dramatic variability in its gamma-ray emission on time-scales from years to as short as two hours has been detected. Multiwavelength observations have also revealed evidence that the VHE gamma-ray and hard X-ray fluxes may be correlated. Here we present results of observations made with the Whipple Collaboration's 10 m Atmospheric Cerenkov Imaging Telescope during 1999 and discuss them in the context of observations made on Markarian 501 during the period from 1996-1998

Large-scale analysis of water stability in bromodomain binding pockets with grand canonical Monte Carlo

Conserved water molecules are of interest in drug design, as displacement of such waters can lead to higher affinity ligands, and in some cases, contribute towards selectivity. Bromodomains, small protein domains involved in the epigenetic regulation of gene transcription, display a network of four conserved water molecules in their binding pockets and have recently been the focus of intense medicinal chemistry efforts. Understanding why certain bromodomains have displaceable water molecules and others do not is extremely challenging, and it remains unclear which water molecules in a given bromodomain can be targeted for displacement. Here we estimate the stability of the conserved water molecules in 35 bromodomains via binding free energy calculations using all-atom grand canonical Monte Carlo simulations. Encouraging quantitative agreement to the available experimental evidence is found. We thus discuss the expected ease of water displacement in different bromodomains and the implications for ligand selectivity

Carbon sequestration in the deep Atlantic enhanced by Saharan dust

Enhanced atmospheric input of dust-borne nutrients and minerals to the remote surface ocean can potentially increase carbon uptake and sequestration at depth. Nutrients can enhance primary productivity, and mineral particles act as ballast, increasing sinking rates of particulate organic matter. Here we present a two-year time series of sediment trap observations of particulate organic carbon flux to 3,000 m depth, measured directly in two locations: the dust-rich central North Atlantic gyre and the dust-poor South Atlantic gyre. We find that carbon fluxes are twice as high and a higher proportion of primary production is exported to depth in the dust-rich North Atlantic gyre. Low stable nitrogen isotope ratios suggest that high fluxes result from the stimulation of nitrogen fixation and productivity following the deposition of dust-borne nutrients. Sediment traps in the northern gyre also collected intact colonies of nitrogen-fixing Trichodesmium species. Whereas ballast in the southern gyre is predominantly biogenic, dust-derived mineral particles constitute the dominant ballast element during the enhanced carbon fluxes in the northern gyre. We conclude that dust deposition increases carbon sequestration in the North Atlantic gyre through the fertilization of the nitrogen-fixing community in surface waters and mineral ballasting of sinking particles

Recent Results from the VERITAS Collaboration

A decade after the discovery of TeV gamma-rays from the blazar Mrk 421 (Punch et al. 1992), the list of TeV blazars has increased to five BL Lac objects: Mrk 421 (Punch et al. 1992; Petry et al. 1996; Piron et al. 2001), Mrk 501 (Quinn et al. 1996; Aharonian et al. 1999; Djannati-Atai et al. 1999), 1ES2344+514 (Catanese et al. 1998), H1426+428 (Horan et al. 2000, 2002; Aharonian et al. 2002; Djannati-Atai et al. 2002) and 1ES1959+650 (Nishiyama et al. 1999; Konopelko et al. 2002; Holder et al. 2002). In this paper we report results from recent observations of Mrk 421, H1426+428 and 1ES1959+650 using the Whipple Observatory 10 m telescope

Exploring recruitment barriers and facilitators in early cancer detection trials: the use of pre-trial focus groups

Background Recruiting to randomized controlled trials is fraught with challenges; with less than one third recruiting to their original target. In preparation for a trial evaluating the effectiveness of a blood test to screen for lung cancer (the ECLS trial), we conducted a qualitative study to explore the potential barriers and facilitators that would impact recruitment. Methods Thirty two people recruited from community settings took part in four focus groups in Glasgow and Dundee (UK). Thematic analysis was used to code the data and develop themes. Results Three sub-themes were developed under the larger theme of recruitment strategies. The first of these themes, recruitment options, considered that participants largely felt that the invitation to participate letter should come from GPs, with postal reminders and face-to-face reminders during primary care contacts. The second theme dealt with understanding randomization and issues related to the control group (where bloods were taken but not tested). Some participants struggled with the concept or need for randomization, or for the need for a control group. Some reported that they would not consider taking part if allocated to the control group, but others were motivated to take part even if allocated to the control group by altruism. The final theme considered perceived barriers to participation and included practical barriers (such as flexible appointments and reimbursement of travel expenses) and psychosocial barriers (such as feeling stigmatized because of their smoking status and worries about being coerced into stopping smoking). Conclusions Focus groups provided useful information which resulted in numerous changes to proposed trial documentation and processes. This was in order to address participants information needs, improve comprehension of the trial documentation, enhance facilitators and remove barriers to participation. The modifications made in light of these findings may enhance trial recruitment and future trials may wish to consider use of pretrial focus groups