617 research outputs found
Search for Supermassive Black Hole Binaries in the Sloan Digital Sky Survey Spectroscopic Sample
Supermassive black hole (SMBH) binaries are expected in a Lambda CDM
cosmology given that most (if not all) massive galaxies contain a massive black
hole at their center. So far, however, direct evidence for such binaries has
been elusive. We use cross-correlation to search for temporal velocity shifts
in the MgII broad emission lines of 0.36 < z < 2 quasars with multiple
observations in the Sloan Digital Sky Survey. For ~ 10^9 Msun BHs in SMBH
binaries, we are sensitive to velocity drifts for binary separations of ~ 0.1
pc with orbital periods of ~100 years. We find seven candidate sub-pc--scale
binaries with velocity shifts > 3.4 sigma ~ 280 km/s, where sigma is our
systematic error. Comparing the detectability of SMBH binaries with the number
of candidates (N < 7), we can rule out that most 10^9 Msun BHs exist in ~
0.03-0.2 pc scale binaries, in a scenario where binaries stall at sub-pc scales
for a Hubble time. We further constrain that < one-third of quasars host SMBH
binaries after considering gas-assisted sub-pc evolution of SMBH binaries,
although this result is very sensitive to the assumed size of the broad line
region. We estimate the detectability of SMBH binaries with ongoing or
next-generation surveys (e.g., BOSS, Subaru Prime Focus Spectrograph), taking
into account the evolution of the sub-parsec binary in circumbinary gas disks.
These future observations will provide longer time baselines for searches
similar to ours and may in turn constrain the evolutionary scenarios of SMBH
binaries.Comment: Resubmitted to ApJ after referee's comments. 21 pages, 9 figure
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Videos of communication in primary care: a study exploring nurse practitioner and patient consultations in a Walk-in centre
The researcher (an experienced advanced nurse practitioner) examined and interpreted twenty videos of consultations between six nurse practitioners and patients aged between 18 and 65 years. A qualitative visual research method (VS) was used drawing on phenomenology, video elicitation, reflexivity, and narrative hermeneutics. The findings demonstrated shared verbal and visual aspects of conversations. The majority of the videos elicited knowledge-based, rather than predominately emotion or movement-based conversations with both parties both empathic and engaged or task focused. The consultation dynamic in most interviews was harmonious rather than in tension, although there were occasions where the nature of the communication varied during the consultation. Furthermore, each NP demonstrated preferences for one of the three different conversation styles (i.e. knowledge, emotion or movement), as well as different ways of responding to patients who were either active or passively involved in an interaction. This theoretically derived video schema was further developed into a video tool (a process and coding guide along with a coding form). The video tool (VT) provided evidence of good video coding interrater reliability when compared with the results of the VS.
The study recommends that WiC NPs could use the video schema to reflect on their personal consultation styles as there is potential to develop greater awareness of emotion, movement and knowledge in shared conversations, and a facilitative approach that asks open questions and encourages active shared and flexible approaches to consultation communication. Additionally, research using the video tool could further investigate the psychometric properties of the VT and ultimately the effect of the different styles on patient outcomes such as compliance and satisfaction
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Comparative Analysis of Gene Expression in Virulent and Attenuated Strains of Infectious Bronchitis Virus at Subcodon Resolution.
Like all coronaviruses, avian infectious bronchitis virus (IBV) possesses a long, single-stranded, positive-sense RNA genome (∼27 kb) and has a complex replication strategy that includes the production of a nested set of subgenomic mRNAs (sgmRNAs). Here, we used whole-transcriptome sequencing (RNASeq) and ribosome profiling (RiboSeq) to delineate gene expression in the IBV M41-CK and Beau-R strains at subcodon resolution. RNASeq facilitated a comparative analysis of viral RNA synthesis and revealed two novel transcription junction sites in the attenuated Beau-R strain, one of which would generate a sgmRNA encoding a ribosomally occupied open reading frame (dORF) located downstream of the nucleocapsid coding region. RiboSeq permitted quantification of the translational efficiency of virus gene expression and identified, for the first time, sites of ribosomal pausing on the genome. Quantification of reads flanking the programmed ribosomal frameshifting (PRF) signal at the genomic RNA ORF1a/ORF1b junction revealed that PRF in IBV is highly efficient (33 to 40%). Triplet phasing of RiboSeq data allowed precise determination of reading frames and revealed the translation of two ORFs (ORF4b and ORF4c on sgmRNA IR), which are widely conserved across IBV isolates. Analysis of differential gene expression in infected primary chick kidney cells indicated that the host cell response to IBV occurs primarily at the level of transcription, with global upregulation of immune-related mRNA transcripts following infection and comparatively modest changes in the translation efficiencies of host genes. Cellular genes and gene networks differentially expressed during virus infection were also identified, giving insights into the host cell response to IBV infection.IMPORTANCE IBV is a major avian pathogen and presents a substantial economic burden to the poultry industry. Improved vaccination strategies are urgently needed to curb the global spread of this virus, and the development of suitable vaccine candidates will be aided by an improved understanding of IBV molecular biology. Our high-resolution data have enabled a precise study of transcription and translation in cells infected with both pathogenic and attenuated forms of IBV and expand our understanding of gammacoronaviral gene expression. We demonstrate that gene expression shows considerable intraspecies variation, with single nucleotide polymorphisms being associated with altered production of sgmRNA transcripts, and our RiboSeq data sets enabled us to uncover novel ribosomally occupied ORFs in both strains. The numerous cellular genes and gene networks found to be differentially expressed during virus infection provide insights into the host cell response to IBV infection.Wellcome Trust
European Research Counci
Do bilinguals have different concepts? The case of shape and material in Japanese L2 users of English
An experiment investigated whether Japanese speakers’ categorisation of objects and substances as shape or material is influenced by acquiring English, based on Imai and Gentner (1997). Subjects were presented with an item such as a cork pyramid and asked to choose between two other items that matched it for shape (plastic pyramid) or for material (piece of cork). The hypotheses were that for simple objects the number of shape-based categorisations would increase according to experience of English and that the preference for shape and material-based categorisations of Japanese speakers of English would differ from mono¬lingual speakers of both languages. Subjects were 18 adult Japanese users of English who had lived in English-speaking countries between 6 months and 3 years (short-stay group), and 18 who had lived in English-speaking countries for 3 years or more (long-stay group). Both groups achieved above criterion on an English vocabulary test. Results were: both groups preferred material responses for simple objects and substances but not for complex objects, in line with Japanese mono¬linguals, but the long-stay group showed more shape preference than the short-stay group and also were less different from Americans. These effects of acquiring a second language on categorisation have implications for conceptual representation and methodology
Evolutionary Multi-Objective Design of SARS-CoV-2 Protease Inhibitor Candidates
Computational drug design based on artificial intelligence is an emerging
research area. At the time of writing this paper, the world suffers from an
outbreak of the coronavirus SARS-CoV-2. A promising way to stop the virus
replication is via protease inhibition. We propose an evolutionary
multi-objective algorithm (EMOA) to design potential protease inhibitors for
SARS-CoV-2's main protease. Based on the SELFIES representation the EMOA
maximizes the binding of candidate ligands to the protein using the docking
tool QuickVina 2, while at the same time taking into account further objectives
like drug-likeliness or the fulfillment of filter constraints. The experimental
part analyzes the evolutionary process and discusses the inhibitor candidates.Comment: 15 pages, 7 figures, submitted to PPSN 202
Origins of High-Activity Cage-Catalyzed Michael Addition
Cage catalysis continues to create significant interest, yet catalyst function remains poorly understood. Herein, we report mechanistic insights into coordination-cage-catalyzed Michael addition using kinetic and computational methods. The study has been enabled by the detection of identifiable catalyst intermediates, which allow the evolution of different cage species to be monitored and modeled alongside reactants and products. The investigations show that the overall acceleration results from two distinct effects. First, the cage reaction shows a thousand-fold increase in the rate constant for the turnover-limiting C–C bond-forming step compared to a reference state. Computational modeling and experimental analysis of activation parameters indicate that this stems from a significant reduction in entropy, suggesting substrate coencapsulation. Second, the cage markedly acidifies the bound pronucleophile, shifting this equilibrium by up to 6 orders of magnitude. The combination of these two factors results in accelerations up to 109 relative to bulk-phase reference reactions. We also show that the catalyst can fundamentally alter the reaction mechanism, leading to intermediates and products that are not observable outside of the cage. Collectively, the results show that cage catalysis can proceed with very high activity and unique selectivity by harnessing a series of individually weak noncovalent interactions
The TAOS Project: Upper Bounds on the Population of Small KBOs and Tests of Models of Formation and Evolution of the Outer Solar System
We have analyzed the first 3.75 years of data from TAOS, the Taiwanese
American Occultation Survey. TAOS monitors bright stars to search for
occultations by Kuiper Belt Objects (KBOs). This dataset comprises 5e5
star-hours of multi-telescope photometric data taken at 4 or 5 Hz. No events
consistent with KBO occultations were found in this dataset. We compute the
number of events expected for the Kuiper Belt formation and evolution models of
Pan & Sari (2005), Kenyon & Bromley (2004), Benavidez & Campo Bagatin (2009),
and Fraser (2009). A comparison with the upper limits we derive from our data
constrains the parameter space of these models. This is the first detailed
comparison of models of the KBO size distribution with data from an occultation
survey. Our results suggest that the KBO population is comprised of objects
with low internal strength and that planetary migration played a role in the
shaping of the size distribution.Comment: 18 pages, 16 figures, Aj submitte
A single sub-km Kuiper Belt object from a stellar Occultation in archival data
The Kuiper belt is a remnant of the primordial Solar System. Measurements of
its size distribution constrain its accretion and collisional history, and the
importance of material strength of Kuiper belt objects (KBOs). Small, sub-km
sized, KBOs elude direct detection, but the signature of their occultations of
background stars should be detectable. Observations at both optical and X-ray
wavelengths claim to have detected such occultations, but their implied KBO
abundances are inconsistent with each other and far exceed theoretical
expectations. Here, we report an analysis of archival data that reveals an
occultation by a body with a 500 m radius at a distance of 45 AU. The
probability of this event to occur due to random statistical fluctuations
within our data set is about 2%. Our survey yields a surface density of KBOs
with radii larger than 250 m of 2.1^{+4.8}_{-1.7} x 10^7 deg^{-2}, ruling out
inferred surface densities from previous claimed detections by more than 5
sigma. The fact that we detected only one event, firmly shows a deficit of
sub-km sized KBOs compared to a population extrapolated from objects with r>50
km. This implies that sub-km sized KBOs are undergoing collisional erosion,
just like debris disks observed around other stars.Comment: To appear in Nature on December 17, 2009. Under press embargo until
1800 hours London time on 16 December. 19 pages; 7 figure
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