Stable de Sitter Vacua in 4 Dimensional Supergravity Originating from 5 Dimensions

The five dimensional stable de Sitter ground states in N=2 supergravity obtained by gauging SO(1,1) symmetry of the real symmetric scalar manifold (in particular a generic Jordan family manifold of the vector multiplets) simultaneously with a subgroup R_s of the R-symmetry group descend to four dimensional de Sitter ground states under certain conditions. First, the holomorphic section in four dimensions has to be chosen carefully by using the symplectic freedom in four dimensions; and second, a group contraction is necessary to bring the potential into a desired form. Under these conditions, stable de Sitter vacua can be obtained in dimensionally reduced theories (from 5D to 4D) if the semi-direct product of SO(1,1) with R^(1,1) together with a simultaneous R_s is gauged. We review the stable de Sitter vacua in four dimensions found in earlier literature for N=2 Yang-Mills Einstein supergravity with SO(2,1) x R_s gauge group in a symplectic basis that comes naturally after dimensional reduction. Although this particular gauge group does not descend directly from five dimensions, we show that, its contraction does. Hence, two different theories overlap in certain limits. Examples of stable de Sitter vacua are given for the cases: (i) R_s=U(1)_R, (ii) R_s=SU(2)_R, (iii) N=2 Yang-Mills/Einstein Supergravity theory coupled to a universal hypermultiplet. We conclude with a discussion regarding the extension of our results to supergravity theories with more general homogeneous scalar manifolds.Comment: 54 page

Dynamic Coupling and Allosteric Behavior in a Nonallosteric Protein †

Long-range intraprotein interactions give rise to many important protein behaviors. Understanding how energy is transduced through protein structures to either transmit a signal or elicit conformational changes is therefore a current challenge in structural biology. In an effort to understand such linkages, multiple V→A mutations were made in the small globular protein eglin c. The physical responses, as mapped by NMR spin relaxation, residual dipolar couplings (RDCs), and scalar couplings, illustrate that the interior of this non-allosteric protein forms a dynamic network and that local perturbations are transmitted as dynamic and structural changes to distal sites as far as 16 Å away. Two basic types of propagation responses were observed: contiguous pathways of enhanced (attenuated) dynamics with no change in structure; and dispersed (non-contiguous) changes in methyl rotation rates that appear to result from subtle deformation of backbone structure. In addition, energy transmission is found to be unidirectional. In one mutant, an allosteric conformational change of a side chain is seen in the context of a pathway of propagated changes in ps-ns dynamics. The observation of so many long-range interactions in a small, rigid system lends experimental weight to the idea that all well-folded proteins inherently possess allosteric features [Gunasekaran et al. (2004) Proteins 57, 433−443], and that dynamics are a rich source of information for mapping and gaining mechanistic insight into communication pathways in individual proteins

Waveform detection by deep learning reveals multi-area spindles that are selectively modulated by memory load

Sleep is generally considered to be a state of large-scale synchrony across thalamus and neocortex; however, recent work has challenged this idea by reporting isolated sleep rhythms such as slow oscillations and spindles. What is the spatial scale of sleep rhythms? To answer this question, we adapted deep learning algorithms initially developed for detecting earthquakes and gravitational waves in high-noise settings for analysis of neural recordings in sleep. We then studied sleep spindles in non-human primate electrocorticography (ECoG), human electroencephalogram (EEG), and clinical intracranial electroencephalogram (iEEG) recordings in the human. Within each recording type, we find widespread spindles occur much more frequently than previously reported. We then analyzed the spatiotemporal patterns of these large-scale, multi-area spindles and, in the EEG recordings, how spindle patterns change following a visual memory task. Our results reveal a potential role for widespread, multi-area spindles in consolidation of memories in networks widely distributed across primate cortex

Modeling the impact of the 13-valent pneumococcal conjugate vaccine serotype catch-up program using United States claims data

Background: Analysis of US claims data from April 2010 to June 2011 estimated that 39% of the 13-valent pneumococcal conjugate vaccine (PCV13) catch-up eligible cohort would ever receive the catch-up vaccination; a previous analysis assumed 87%. Methods: This updated figure was applied to a previously published 10-year Markov model while holding all other inputs constant. Results: Our model estimated that the catch-up program as currently implemented is estimated to prevent an additional 1.7 million cases of disease in children aged ≤59 months over a 10-year period, compared with routine PCV13 vaccination with no catch-up program. Conclusions: Because 39% catch-up uptake is less than the level of completion of the 4-dose primary PCV13 series, vaccine-preventable cases of pneumococcal disease and related deaths could be decreased further with additional uptake of catch-up vaccination in the catch-up eligible cohort

The LSST Camera Overview

The LSST camera is a wide-field optical (0.35-1um) imager designed to provide a 3.5 degree FOV with better than 0.2 arcsecond sampling. The detector format will be a circular mosaic providing approximately 3.2 Gigapixels per image. The camera includes a filter mechanism and, shuttering capability. It is positioned in the middle of the telescope where cross-sectional area is constrained by optical vignetting and heat dissipation must be controlled to limit thermal gradients in the optical beam. The fast, f/1.2 beam will require tight tolerances on the focal plane mechanical assembly. The focal plane array operates at a temperature of approximately -100 C to achieve desired detector performance. The focal plane array is contained within an evacuated cryostat, which incorporates detector front-end electronics and thermal control. The cryostat lens serves as an entrance window and vacuum seal for the cryostat. Similarly, the camera body lens serves as an entrance window and gas seal for the camera housing, which is filled with a suitable gas to provide the operating environment for the shutter and filter change mechanisms. The filter carousel can accommodate 5 filters, each 75 cm in diameter, for rapid exchange without external intervention

Comparative Genomics of Vancomycin-Resistant Staphylococcus aureus Strains and Their Positions within the Clade Most Commonly Associated with Methicillin-Resistant S. aureus Hospital-Acquired Infection in the United States

Methicillin-resistant Staphylococcus aureus (MRSA) strains are leading causes of hospital-acquired infections in the United States, and clonal cluster 5 (CC5) is the predominant lineage responsible for these infections. Since 2002, there have been 12 cases of vancomycin-resistant S. aureus (VRSA) infection in the United States—all CC5 strains. To understand this genetic background and what distinguishes it from other lineages, we generated and analyzed high-quality draft genome sequences for all available VRSA strains. Sequence comparisons show unambiguously that each strain independently acquired Tn1546 and that all VRSA strains last shared a common ancestor over 50 years ago, well before the occurrence of vancomycin resistance in this species. In contrast to existing hypotheses on what predisposes this lineage to acquire Tn1546, the barrier posed by restriction systems appears to be intact in most VRSA strains. However, VRSA (and other CC5) strains were found to possess a constellation of traits that appears to be optimized for proliferation in precisely the types of polymicrobic infection where transfer could occur. They lack a bacteriocin operon that would be predicted to limit the occurrence of non-CC5 strains in mixed infection and harbor a cluster of unique superantigens and lipoproteins to confound host immunity. A frameshift in dprA, which in other microbes influences uptake of foreign DNA, may also make this lineage conducive to foreign DNA acquisition

Cytoplasmic p53 couples oncogene-driven glucose metabolism to apoptosis and is a therapeutic target in glioblastoma.

Cross-talk among oncogenic signaling and metabolic pathways may create opportunities for new therapeutic strategies in cancer. Here we show that although acute inhibition of EGFR-driven glucose metabolism induces only minimal cell death, it lowers the apoptotic threshold in a subset of patient-derived glioblastoma (GBM) cells. Mechanistic studies revealed that after attenuated glucose consumption, Bcl-xL blocks cytoplasmic p53 from triggering intrinsic apoptosis. Consequently, targeting of EGFR-driven glucose metabolism in combination with pharmacological stabilization of p53 with the brain-penetrant small molecule idasanutlin resulted in synthetic lethality in orthotopic glioblastoma xenograft models. Notably, neither the degree of EGFR-signaling inhibition nor genetic analysis of EGFR was sufficient to predict sensitivity to this therapeutic combination. However, detection of rapid inhibitory effects on [18F]fluorodeoxyglucose uptake, assessed through noninvasive positron emission tomography, was an effective predictive biomarker of response in vivo. Together, these studies identify a crucial link among oncogene signaling, glucose metabolism, and cytoplasmic p53, which may potentially be exploited for combination therapy in GBM and possibly other malignancies

Solution Structure of Polymerase μ's BRCT Domain Reveals an Element Essential for Its Role in Nonhomologous End Joining †

The solution structure and dynamics of the BRCT domain from human DNA polymerase μ, implicated in repair of chromosome breaks by nonhomologous end joining (NHEJ), has been determined using NMR methods. BRCT domains are typically involved in protein—protein interactions between factors required for the cellular response to DNA damage. The pol μ BRCT domain is atypical in that, unlike other reported BRCT structures, the pol μ BRCT is neither part of a tandem grouping, nor does it appear to form stable homodimers. Although the sequence of the pol μ BRCT domain has some unique characteristics, particularly the presence of > 10% proline residues, it forms the characteristic αβα sandwich, in which three alpha helices are arrayed around a central four-stranded β-sheet. The structure of helix α1 is characterized by two solvent-exposed hydrophobic residues, F46 and L50, suggesting that this element may play a role in mediating interactions of pol μ with other proteins. Consistent with this argument, mutation of these residues, as well as the proximal, conserved residue R43, specifically blocked the ability of pol μ to efficiently work together with NHEJ factors Ku and XRCC4-ligase IV to join noncomplementary ends together in vitro. The structural, dynamic, and biochemical evidence reported here identifies a functional surface in the pol μ BRCT domain critical for promoting assembly and activity of the NHEJ machinery. Further, the similarity between the interaction regions of the BRCT domains of pol μ and TdT support the conclusion that they participate in NHEJ as alternate polymerases

The Seventh Data Release of the Sloan Digital Sky Survey

This paper describes the Seventh Data Release of the Sloan Digital Sky Survey (SDSS), marking the completion of the original goals of the SDSS and the end of the phase known as SDSS-II. It includes 11663 deg^2 of imaging data, with most of the roughly 2000 deg^2 increment over the previous data release lying in regions of low Galactic latitude. The catalog contains five-band photometry for 357 million distinct objects. The survey also includes repeat photometry over 250 deg^2 along the Celestial Equator in the Southern Galactic Cap. A coaddition of these data goes roughly two magnitudes fainter than the main survey. The spectroscopy is now complete over a contiguous area of 7500 deg^2 in the Northern Galactic Cap, closing the gap that was present in previous data releases. There are over 1.6 million spectra in total, including 930,000 galaxies, 120,000 quasars, and 460,000 stars. The data release includes improved stellar photometry at low Galactic latitude. The astrometry has all been recalibrated with the second version of the USNO CCD Astrograph Catalog (UCAC-2), reducing the rms statistical errors at the bright end to 45 milli-arcseconds per coordinate. A systematic error in bright galaxy photometr is less severe than previously reported for the majority of galaxies. Finally, we describe a series of improvements to the spectroscopic reductions, including better flat-fielding and improved wavelength calibration at the blue end, better processing of objects with extremely strong narrow emission lines, and an improved determination of stellar metallicities. (Abridged)Comment: 20 pages, 10 embedded figures. Accepted to ApJS after minor correction

The Eighth Data Release of the Sloan Digital Sky Survey: First Data from SDSS-III

The Sloan Digital Sky Survey (SDSS) started a new phase in August 2008, with new instrumentation and new surveys focused on Galactic structure and chemical evolution, measurements of the baryon oscillation feature in the clustering of galaxies and the quasar Ly alpha forest, and a radial velocity search for planets around ~8000 stars. This paper describes the first data release of SDSS-III (and the eighth counting from the beginning of the SDSS). The release includes five-band imaging of roughly 5200 deg^2 in the Southern Galactic Cap, bringing the total footprint of the SDSS imaging to 14,555 deg^2, or over a third of the Celestial Sphere. All the imaging data have been reprocessed with an improved sky-subtraction algorithm and a final, self-consistent photometric recalibration and flat-field determination. This release also includes all data from the second phase of the Sloan Extension for Galactic Understanding and Evolution (SEGUE-2), consisting of spectroscopy of approximately 118,000 stars at both high and low Galactic latitudes. All the more than half a million stellar spectra obtained with the SDSS spectrograph have been reprocessed through an improved stellar parameters pipeline, which has better determination of metallicity for high metallicity stars.Comment: Astrophysical Journal Supplements, in press (minor updates from submitted version