Monster black holes

A combination of ground-based and spacecraft observations has uncovered two black holes of 10 billion solar masses in the nearby Universe. The finding sheds light on how these cosmic monsters co-evolve with galaxies.Comment: 2 pages, 1 figure, LaTeX. Published in Nature "News & Views

Enhanced Protection against Ebola Virus Mediated by an Improved Adenovirus-Based Vaccine

Jason S. Richardson is with the Public Health Agency of Canada, Michel K. Yao is with the Public Health Agency of Canada, Kaylie N. Tran is with the Public Health Agency of Canada and University of Manitoba, Maria A. Croyle is with UT Austin, James E. Strong is with the Public Health Agency of Canada and University of Manitoba, Heinz Feldmann is with the Public Health Agency of Canada and University of Manitoba, Gary P. Kobinger is with the Public Health Agency of Canada and University of Manitoba.Background -- The Ebola virus is transmitted by direct contact with bodily fluids of infected individuals, eliciting death rates as high as 90% among infected humans. Currently, replication defective adenovirus-based Ebola vaccine is being studied in a phase I clinical trial. Another Ebola vaccine, based on an attenuated vesicular stomatitis virus has shown efficacy in post-exposure treatment of nonhuman primates to Ebola infection. In this report, we modified the common recombinant adenovirus serotype 5-based Ebola vaccine expressing the wild-type ZEBOV glycoprotein sequence from a CMV promoter (Ad-CMVZGP). The immune response elicited by this improved expression cassette vector (Ad-CAGoptZGP) and its ability to afford protection against lethal ZEBOV challenge in mice was compared to the standard Ad-CMVZGP vector. Methodology/Principal Findings -- Ad-CMVZGP was previously shown to protect mice, guinea pigs and nonhuman primates from an otherwise lethal challenge of Zaire ebolavirus. The antigenic expression cassette of this vector was improved through codon optimization, inclusion of a consensus Kozak sequence and reconfiguration of a CAG promoter (Ad-CAGoptZGP). Expression of GP from Ad-CAGoptZGP was substantially higher than from Ad-CMVZGP. Ad-CAGoptZGP significantly improved T and B cell responses at doses 10 to 100-fold lower than that needed with Ad-CMVZGP. Additionally, Ad-CAGoptZGP afforded full protections in mice against lethal challenge at a dose 100 times lower than the dose required for Ad-CMVZGP. Finally, Ad-CAGoptZGP induced full protection to mice when given 30 minutes post-challenge. Conclusions/Significance -- We describe an improved adenovirus-based Ebola vaccine capable of affording post-exposure protection against lethal challenge in mice. The molecular modifications of the new improved vaccine also translated in the induction of significantly enhanced immune responses and complete protection at a dose 100 times lower than with the previous generation adenovirus-based Ebola vaccine. Understanding and improving the molecular components of adenovirus-based vaccines can produce potent, optimized product, useful for vaccination and post-exposure therapy.Financial support was received from the following sources: The Public Health Agency of Canada and the Chemical, Biological, Radiological or Nuclear Research and Technology Initiative (grant #CRTI-06-0218RD awarded to GPK). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.Pharmac

Sea ice and pollution-modulated changes in Greenland ice core methanesulfonate and bromine

Reconstruction of past changes in Arctic sea ice extent may be critical for understanding its future evolution. Methanesulfonate (MSA) and bromine concentrations preserved in ice cores have both been proposed as indicators of past sea ice conditions. In this study, two ice cores from central and north-eastern Greenland were analysed at sub-annual resolution for MSA (CH$_3$SO$_3$H) and bromine, covering the time period 1750–2010. We examine correlations between ice core MSA and the HadISST1 ICE sea ice dataset and consult back trajectories to infer the likely source regions. A strong correlation between the low-frequency MSA and bromine records during pre-industrial times indicates that both chemical species are likely linked to processes occurring on or near sea ice in the same source regions. The positive correlation between ice core MSA and bromine persists until the mid-20th century, when the acidity of Greenland ice begins to increase markedly due to increased fossil fuel emissions. After that time, MSA levels decrease as a result of declining sea ice extent but bromine levels increase. We consider several possible explanations and ultimately suggest that increased acidity, specifically nitric acid, of snow on sea ice stimulates the release of reactive Br from sea ice, resulting in increased transport and deposition on the Greenland ice sheet.This research was funded by the National Science Foundation, grant numbers 1023672 and 1204176

An Over-Massive Black Hole in the Compact Lenticular Galaxy NGC1277

All massive galaxies likely have supermassive black holes at their centers, and the masses of the black holes are known to correlate with properties of the host galaxy bulge component. Several explanations have been proposed for the existence of these locally-established empirical relationships; they include the non-causal, statistical process of galaxy-galaxy merging, direct feedback between the black hole and its host galaxy, or galaxy-galaxy merging and the subsequent violent relaxation and dissipation. The empirical scaling relations are thus important for distinguishing between various theoretical models of galaxy evolution, and they further form the basis for all black hole mass measurements at large distances. In particular, observations have shown that the mass of the black hole is typically 0.1% of the stellar bulge mass of the galaxy. The small galaxy NGC4486B currently has the largest published fraction of its mass in a black hole at 11%. Here we report observations of the stellar kinematics of NGC 1277, which is a compact, disky galaxy with a mass of 1.2 x 10^11 Msun. From the data, we determine that the mass of the central black hole is 1.7 x 10^10 Msun, or 59% its bulge mass. Five other compact galaxies have properties similar to NGC 1277 and therefore may also contain over-sized black holes. It is not yet known if these galaxies represent a tail of a distribution, or if disk-dominated galaxies fail to follow the normal black hole mass scaling relations.Comment: 7 pages. 6 figures. Nature. Animation at http://www.mpia.de/~bosch/blackholes.htm

Long optical plateau in the afterglow of the short GRB 150424A with extended emission

Context. Short-duration gamma-ray bursts (GRBs) with extended emission form a subclass of short GRBs, comprising about 15% of the short-duration sample. Afterglow detections of short GRBs are also rare (about 30%) because of their lower luminosity. Aims. We present a multiband data set of the short burst with extended emission, GRB 150424A, comprising of GROND observations, complemented with data from Swift/UVOT, Swift/XRT, HST, Keck/LRIS, and data points from the literature. The GRB 150424A afterglow shows an extended plateau phase, lasting about 8 h. The analysis of this unique GRB afterglow might shed light on the understanding of afterglow plateau emission, the nature of which is still under debate. Methods. We present a phenomenological analysis made by applying fireball closure relations and interpret the findings in the context of the fireball model. We discuss the plausibility of a magnetar as a central engine, which would be responsible for additional and prolonged energy injection into the fireball. Results. We find convincing evidence for energy injection into the afterglow of GRB 150424A. We find that a magnetar spin-down as the source for a prolonged energy injection requires that at least 4% of the spin-down energy is converted into radiation

2016 Patellofemoral pain consensus statement from the 4th International Patellofemoral Pain Research Retreat, Manchester. Part 1: Terminology, definitions, clinical examination, natural history, patellofemoral osteoarthritis and patient-reported outcome measures

Patellofemoral pain (PFP) typically presents as diffuse anterior knee pain, usually with activities such as squatting, running, stair ascent and descent. It is common in active individuals across the lifespan,1–4 and is a frequent cause for presentation at physiotherapy, general practice, orthopaedic and sports medicine clinics in particular.5 ,6 Its impact is profound, often reducing the ability of those with PFP to perform sporting, physical activity and work-related activities pain-free. Increasing evidence suggests that it is a recalcitrant condition, persisting for many years.7–9 In an attempt to share recent innovations, build on the first three successful biennial retreats and define the ‘state of the art’ for this common, impactful condition; the 4th International Patellofemoral Pain Research Retreat was convened. The 4th International Patellofemoral Research Retreat was held in Manchester, UK, over 3 days (September 2–4th, 2015). After undergoing peer-review for scientific merit and relevance to the retreat, 67 abstracts were accepted for the retreat (50 podium presentations, and 17 short presentations). The podium and short presentations were grouped into five categories; (1) PFP, (2) factors that influence PFP (3) the trunk and lower extremity (4) interventions and (5) systematic analyses. Three keynote speakers were chosen for their scientific contribution in the area of PFP. Professor Andrew Amis spoke on the biomechanics of the patellofemoral joint. Professor David Felson spoke on patellofemoral arthritis,10 and Dr Michael Ratleff's keynote theme was PFP in the adolescent patient.11 As part of the retreat, we held structured, whole-group discussions in order to develop consensus relating to the work presented at the meeting as well as evidence gathered from the literature

Increased Asymmetric and Multi-Daughter Cell Division in Mechanically Confined Microenvironments

As the microenvironment of a cell changes, associated mechanical cues may lead to changes in biochemical signaling and inherently mechanical processes such as mitosis. Here we explore the effects of confined mechanical environments on cellular responses during mitosis. Previously, effects of mechanical confinement have been difficult to optically observe in three-dimensional and in vivo systems. To address this challenge, we present a novel microfluidic perfusion culture system that allows controllable variation in the level of confinement in a single axis allowing observation of cell growth and division at the single-cell level. The device is capable of creating precise confinement conditions in the vertical direction varying from high (3 µm) to low (7 µm) confinement while also varying the substrate stiffness (E = 130 kPa and 1 MPa). The Human cervical carcinoma (HeLa) model with a known 3N+ karyotype was used for this study. For this cell line, we observe that mechanically confined cell cycles resulted in stressed cell divisions: (i) delayed mitosis, (ii) multi- daughter mitosis events (from 3 up to 5 daughter cells), (iii) unevenly sized daughter cells, and (iv) induction of cell death. In the highest confined conditions, the frequency of divisions producing more than two progeny was increased an astounding 50-fold from unconfined environments, representing about one half of all successful mitotic events. Notably, the majority of daughter cells resulting from multipolar divisions were viable after cytokinesis and, perhaps suggesting another regulatory checkpoint in the cell cycle, were in some cases observed to re-fuse with neighboring cells post-cytokinesis. The higher instances of abnormal mitosis that we report in confined mechanically stiff spaces, may lead to increased rates of abnormal, viable, cells in the population. This work provides support to a hypothesis that environmental mechanical cues influences structural mechanisms of mitosis such as geometric orientation of the mitotic plane or planes

Vertical Distribution of Epibenthic Freshwater Cyanobacterial Synechococcus spp. Strains Depends on Their Ability for Photoprotection

Epibenthic cyanobacteria often grow in environments where the fluctuation of light intensity and quality is extreme and frequent. Different strategies have been developed to cope with this problem depending on the distribution of cyanobacteria in the water column. and either constant or enhanced levels of carotenoids were assayed in phycocyanin-rich strains collected from 1.0 and 0.5 m water depths. Protein analysis revealed that while the amount of biliproteins remained constant in all strains during light stress and recovery, the amount of D1 protein from photosystem II reaction centre was strongly reduced under light stress conditions in strains from 7.0 m and 1.0 m water depth, but not in strains collected from 0.5 m depth. spp. strains, depending on their genetically fixed mechanisms for photoprotection

Measurement of the Bottom-Strange Meson Mixing Phase in the Full CDF Data Set

We report a measurement of the bottom-strange meson mixing phase \beta_s using the time evolution of B0_s -> J/\psi (->\mu+\mu-) \phi (-> K+ K-) decays in which the quark-flavor content of the bottom-strange meson is identified at production. This measurement uses the full data set of proton-antiproton collisions at sqrt(s)= 1.96 TeV collected by the Collider Detector experiment at the Fermilab Tevatron, corresponding to 9.6 fb-1 of integrated luminosity. We report confidence regions in the two-dimensional space of \beta_s and the B0_s decay-width difference \Delta\Gamma_s, and measure \beta_s in [-\pi/2, -1.51] U [-0.06, 0.30] U [1.26, \pi/2] at the 68% confidence level, in agreement with the standard model expectation. Assuming the standard model value of \beta_s, we also determine \Delta\Gamma_s = 0.068 +- 0.026 (stat) +- 0.009 (syst) ps-1 and the mean B0_s lifetime, \tau_s = 1.528 +- 0.019 (stat) +- 0.009 (syst) ps, which are consistent and competitive with determinations by other experiments.Comment: 8 pages, 2 figures, Phys. Rev. Lett 109, 171802 (2012

HIV Antigen Incorporation within Adenovirus Hexon Hypervariable 2 for a Novel HIV Vaccine Approach

Adenoviral (Ad) vectors have been used for a variety of vaccine applications including cancer and infectious diseases. Traditionally, Ad-based vaccines are designed to express antigens through transgene expression of a given antigen. However, in some cases these conventional Ad-based vaccines have had sub-optimal clinical results. These sub-optimal results are attributed in part to pre-existing Ad serotype 5 (Ad5) immunity. In order to circumvent the need for antigen expression via transgene incorporation, the “antigen capsid-incorporation” strategy has been developed and used for Ad-based vaccine development in the context of a few diseases. This strategy embodies the incorporation of antigenic peptides within the capsid structure of viral vectors. The major capsid protein hexon has been utilized for these capsid incorporation strategies due to hexon's natural role in the generation of anti-Ad immune response and its numerical representation within the Ad virion. Using this strategy, we have developed the means to incorporate heterologous peptide epitopes specifically within the major surface-exposed domains of the Ad capsid protein hexon. Our study herein focuses on generation of multivalent vaccine vectors presenting HIV antigens within the Ad capsid protein hexon, as well as expressing an HIV antigen as a transgene. These novel vectors utilize HVR2 as an incorporation site for a twenty-four amino acid region of the HIV membrane proximal ectodomain region (MPER), derived from HIV glycoprotein gp41 (gp41). Our study herein illustrates that our multivalent anti-HIV vectors elicit a cellular anti-HIV response. Furthermore, vaccinations with these vectors, which present HIV antigens at HVR2, elicit a HIV epitope-specific humoral immune response