562 research outputs found
Social Media, Manipulation, and Violence
This essay addresses an even darker side to social media: its use for manipulation on scales both small and large and its direct and indirect ties to violence. Increasingly, social media is used as a tool to foment violence, particularly in regions of the world where access to the Internet is otherwise limited. Even when a social media site is not itself an instrument to foment violence, it may have the effect of encouraging and validating the extreme views that result in violence. What is the role of social media sites in containing their use for such nefarious purposes, and how should the law govern them? Should such sites be liable for failing to take down misleading or inaccurate content or for allowing hate speech? If not, what are other options for controlling its misuse
Mutasynthesis approaches to the preparation of streptorubin B analogues
Prodiginines are a large family of red-pigmented tripyrrole-based antibiotics.
Their biosynthesis in Streptomyces coelicolor A3(2), by enzymes encoded in the
red gene cluster, involves the condensation of 4-methoxy-2,2′-bipyrrole-5-
carboxaldehyde (MBC) and 2-undecylpyrrole, catalysed by the RedH enzyme to
give undecylprodiginine. This is followed by the mechanistically interesting
oxidative carbocyclisation, catalysed by RedG to give streptorubin B.
In this thesis prodiginine analogues have been generated by a mutasynthetic
approach, in which chemically synthesised analogues of intermediates MBC and
2-undecylpyrrole were fed to mutant strains of S. coelicolor in which one of the
genes required to biosynthesise MBC or 2-undecylpyrrole (redM or redL
respectively) have been deleted. RedH and RedG have been shown to display
relatively broad substrate tolerances and several analogues of both
undecylprodiginine and streptorubin B have been generated by this approach. A
variety of factors which are potentially limiting to substrate tolerances have been
probed, including the steric size, alkyl chain hydrophobicity and introduction of
π-electrons.
The absolute stereochemistry of streptorubin B has been investigated by a
mutasynthetic approach in which 2-undecylpyrrole, stereospecifically labelled
with deuterium, is fed to a mutant strain of S. coelicolor unable to biosynthesise
2-undecylpyrrole. During the course of the investigation streptorubin B was
analysed on a homochiral stationary phase HPLC and evidence of both ent- and
dia-streptorubin B was discovered in the natural product isolated from S.
coelicolor. When the position of the deuterium label from the mutasynthesis
experiment was investigated by 1H-NMR and 2H-NMR the partial epimerization
of the synthetic material became apparent. This made the definitive
determination of the absolute stereochemistry of streptorubin B impossible.
However, a tentative assignment of the absolute stereochemistry was possible.
This was supported by comparison with the related natural products
metacycloprodigiosin, the stereochemistry of which was established here by CD
spectroscopy and chiral HPLC analyses, and roseophilin
Visualizing the recovery of patients in Critical Care Units
The authors would like to take this opportunity to sincerely thank the Patient for providing us with access to her data. The aim is to provide software support for the clinicians in critical care units. Testing software on artificial data is limited. Therefore, having access to real patient data has enabled this project to bridge the chasm between theory and practice. Thank you very much! This work was carried out as a collaboration between the University of Plymouth and University Hospitals Plymouth NHS Trust, Plymouth. The authors are grateful to both organizations for their support to carry out this research.Peer reviewe
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Cyclization of Fungal Nonribosomal Peptides by a Terminal Condensation-Like Domain
Cyclization of linear peptidyl precursors produced by nonribosomal peptide synthetases (NRPSs) is an important step in the biosynthesis of bioactive cyclic peptides. Whereas bacterial NRPSs use thioesterase (TE) domains to perform the cyclization, fungal NRPSs have apparently evolved to use a different enzymatic route. In verified fungal NRPSs that produce macrocyclic peptides, each megasynthetase terminates with a condensation-like (CT) domain that may perform the macrocyclization reaction. To probe the role of such a CT domain, we reconstituted the activities of the Penicillium aethiopicum trimodular NPRS TqaA in Saccharomyces cerevisiae and in vitro. Together with a reconstituted bimodular NRPS AnaPS, we dissected the cyclization steps of TqaA in transforming the linear anthranilate-D-tryptophan-L-alanyl tripeptide into fumiquinazoline F. Extensive biochemical and mutational studies confirmed the essential role of the CT domain in catalyzing cyclization in a thiolation domain-dependent fashion. Our work provided evidence of a likely universal macrocyclization strategy employed by fungal NRPSs
Palaeolithic extinctions and the Taurid Complex
Intersection with the debris of a large (50-100 km) short-period comet during
the Upper Palaeolithic provides a satisfactory explanation for the catastrophe
of celestial origin which has been postulated to have occurred around 12900 BP,
and which presaged a return to ice age conditions of duration ~1300 years. The
Taurid Complex appears to be the debris of this erstwhile comet; it includes at
least 19 of the brightest near-Earth objects. Sub-kilometre bodies in meteor
streams may present the greatest regional impact hazard on timescales of human
concern.Comment: 7 pages, 3 figures; accepted for Monthly Notices of the Royal
Astronomical Society (definitive version will be available at
www.blackwell-synergy.com
Automatic Classification of National Health Service Feedback
Text datasets come in an abundance of shapes, sizes and styles. However, determining what factors limit classification accuracy remains a difficult task which is still the subject of intensive research. Using a challenging UK National Health Service (NHS) dataset, which contains many characteristics known to increase the complexity of classification, we propose an innovative classification pipeline. This pipeline switches between different text pre-processing, scoring and classification techniques during execution. Using this flexible pipeline, a high level of accuracy has been achieved in the classification of a range of datasets, attaining a micro-averaged F1 score of 93.30% on the Reuters-21578 “ApteMod” corpus. An evaluation of this flexible pipeline was carried out using a variety of complex datasets compared against an unsupervised clustering approach. The paper describes how classification accuracy is impacted by an unbalanced category distribution, the rare use of generic terms and the subjective nature of manual human classification.</jats:p
Visualizing the recovery of patients in Critical Care Units
This paper presents a detailed case study of the application of techniques from Information Visualization to data collected in Critical Care Units (CCUs). This data is heterogeneous and sometimes incomplete due to the pressures on staff in the environment. Thus, it can be difficult to use conventional means to visualize it meaningfully. The paper presents the software tool called CCViews. It was developed to support visualization of CCU data. It enables clinicians to view the trajectory of patient recovery and track the effectiveness of different interventions such as physiotherapy. Note that this work is underpinned by the world-famous information seeking mantra, which emphasizes the need to provide users with views of their data at differing levels of granularity. </jats:p
Discovery of Large-Scale Gravitational Infall in a Massive Protostellar Cluster
We report Mopra (ATNF), Anglo-Australian Telescope, and Atacama Submillimeter
Telescope Experiment observations of a molecular clump in Carina, BYF73 =
G286.21+0.17, which give evidence of large-scale gravitational infall in the
dense gas. From the millimetre and far-infrared data, the clump has mass ~ 2 x
10^4 Msun, luminosity ~ 2-3 x 10^4 Lsun, and diameter ~ 0.9 pc. From radiative
transfer modelling, we derive a mass infall rate ~ 3.4 x 10^-2 Msun yr-1. If
confirmed, this rate for gravitational infall in a molecular core or clump may
be the highest yet seen. The near-infrared K-band imaging shows an adjacent
compact HII region and IR cluster surrounded by a shell-like photodissociation
region showing H2 emission. At the molecular infall peak, the K imaging also
reveals a deeply embedded group of stars with associated H2 emission. The
combination of these features is very unusual and we suggest they indicate the
ongoing formation of a massive star cluster. We discuss the implications of
these data for competing theories of massive star formation.Comment: v1: 23 pages single-column, 6 figures (some multipart) at end v2: 14
pages 2-column, 6 figures interspersed v3: edited to referee's comments with
new sections and new figures; accepted to MNRAS, 20 pages 2-column, 8 figures
(some multipart) intersperse
CARMA Survey Toward Infrared-bright Nearby Galaxies (STING): Molecular Gas Star Formation Law in NGC4254
This study explores the effects of different assumptions and systematics on
the determination of the local, spatially resolved star formation law. Using
four star formation rate (SFR) tracers (H\alpha with azimuthally averaged
extinction correction, mid-infrared 24 micron, combined H\alpha and
mid-infrared 24 micron, and combined far-ultraviolet and mid-infrared 24
micron), several fitting procedures, and different sampling strategies we probe
the relation between SFR and molecular gas at various spatial resolutions and
surface densities within the central 6.5 kpc in the disk of NGC4254. We find
that in the high surface brightness regions of NGC4254 the form of the
molecular gas star formation law is robustly determined and approximately
linear and independent of the assumed fraction of diffuse emission and the SFR
tracer employed. When the low surface brightness regions are included, the
slope of the star formation law depends primarily on the assumed fraction of
diffuse emission. In such case, results range from linear when the fraction of
diffuse emission in the SFR tracer is ~30% or less (or when diffuse emission is
removed in both the star formation and the molecular gas tracer), to
super-linear when the diffuse fraction is ~50% and above. We find that the
tightness of the correlation between gas and star formation varies with the
choice of star formation tracer. The 24 micron SFR tracer by itself shows the
tightest correlation with the molecular gas surface density, whereas the
H\alpha corrected for extinction using an azimuthally-averaged correction shows
the highest dispersion. We find that for R<0.5R_25 the local star formation
efficiency is constant and similar to that observed in other large spirals,
with a molecular gas depletion time ~2 Gyr.Comment: accepted for publication in ApJ, vol 729, March 10 2011 issue; 30
pages; 14 figures; revised version includes referee's comments; results
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