11,051 research outputs found
CRISPR-Cas antimicrobials: Challenges and future prospects
This is the final version. Available from PLoS via the
DOI in this record.Antimicrobial resistance (AMR) poses a serious threat to modern medicine and may render
common infections untreatable. The discovery of new antibiotics has come to a relative standstill during the last decade [1], and developing novel approaches to tackle the spread of AMR
genes will require significant efforts in the coming years [2]. In 2014, several groups independently demonstrated how CRISPR-Cas (clustered regularly interspaced short palindromic
repeats-CRISPR–associated), a bacterial immune system now widely used for genome editing,
can selectively remove AMR genes from bacterial populations. Here, we discuss the current
state of the field of CRISPR-Cas antimicrobials, the challenges ahead, and how they may be
overcome.Biotechnology & Biological Sciences Research Council (BBSRC)Medical Research CouncilNatural Environment Research CouncilWellcome TrustEuropean Research CouncilPeople Programme (Marie Curie Actions) of the European Union’s Horizon 202
11 x 11 Domineering is Solved: The first player wins
We have developed a program called MUDoS (Maastricht University Domineering
Solver) that solves Domineering positions in a very efficient way. This enables
the solution of known positions so far (up to the 10 x 10 board) much quicker
(measured in number of investigated nodes).
More importantly, it enables the solution of the 11 x 11 Domineering board, a
board up till now far out of reach of previous Domineering solvers. The
solution needed the investigation of 259,689,994,008 nodes, using almost half a
year of computation time on a single simple desktop computer. The results show
that under optimal play the first player wins the 11 x 11 Domineering game,
irrespective if Vertical or Horizontal starts the game.
In addition, several other boards hitherto unsolved were solved. Using the
convention that Vertical starts, the 8 x 15, 11 x 9, 12 x 8, 12 x 15, 14 x 8,
and 17 x 6 boards are all won by Vertical, whereas the 6 x 17, 8 x 12, 9 x 11,
and 11 x 10 boards are all won by Horizontal
Forman's Ricci curvature - From networks to hypernetworks
Networks and their higher order generalizations, such as hypernetworks or
multiplex networks are ever more popular models in the applied sciences.
However, methods developed for the study of their structural properties go
little beyond the common name and the heavy reliance of combinatorial tools. We
show that, in fact, a geometric unifying approach is possible, by viewing them
as polyhedral complexes endowed with a simple, yet, the powerful notion of
curvature - the Forman Ricci curvature. We systematically explore some aspects
related to the modeling of weighted and directed hypernetworks and present
expressive and natural choices involved in their definitions. A benefit of this
approach is a simple method of structure-preserving embedding of hypernetworks
in Euclidean N-space. Furthermore, we introduce a simple and efficient manner
of computing the well established Ollivier-Ricci curvature of a hypernetwork.Comment: to appear: Complex Networks '18 (oral presentation
Discovering duplicate tasks in transition systems for the simplification of process models
This work presents a set of methods to improve the understandability of process models. Traditionally, simplification methods trade off quality metrics, such as fitness or precision. Conversely, the methods proposed in this paper produce simplified models while preserving or even increasing fidelity metrics. The first problem addressed in the
paper is the discovery of duplicate tasks. A new method is proposed that avoids overfitting by working on the transition system generated by the log. The method is able to discover duplicate tasks even in the presence of concurrency and choice. The second problem is the structural simplification of the model by identifying optional and repetitive tasks. The tasks are substituted by annotated events that allow the removal of silent tasks and reduce the complexity of the
model. An important feature of the methods proposed in this paper is that they are independent from the actual miner used for process discovery.Peer ReviewedPostprint (author's final draft
Domestic ventilation rates, indoor humidity and dust mite allergens : are our homes causing the asthma pandemic?
This paper is concerned with historical changes in domestic ventilation rates, relative humidity and the associated risk of house dust mite colonization. A controlled trial evaluated allergen and water vapour control measures on the level of house dust mite (HDM) Der p1 allergen and indoor humidity, concurrently with changes in lung function in 54 subjects who completed the protocol. Mechanical heat recovery ventilation units significantly reduced moisture content in the active group, while HDM allergen reservoirs in carpets and beds were reduced by circa 96%. Self reported health status confirmed a significant clinical improvement in the active group. The study can form the basis for assessing minimum winter ventilation rates that can suppress RH below the critical ambient equilibrium humidity of 60% and thus inhibit dust mite colonization and activity in temperate and maritime in' uenced climatic regions
First principles modelling of magnesium titanium hydrides
Mixing Mg with Ti leads to a hydride Mg(x)Ti(1-x)H2 with markedly improved
(de)hydrogenation properties for x < 0.8, as compared to MgH2. Optically, thin
films of Mg(x)Ti(1-x)H2 have a black appearance, which is remarkable for a
hydride material. In this paper we study the structure and stability of
Mg(x)Ti(1-x)H2, x= 0-1 by first-principles calculations at the level of density
functional theory. We give evidence for a fluorite to rutile phase transition
at a critical composition x(c)= 0.8-0.9, which correlates with the
experimentally observed sharp decrease in (de)hydrogenation rates at this
composition. The densities of states of Mg(x)Ti(1-x)H2 have a peak at the Fermi
level, composed of Ti d states. Disorder in the positions of the Ti atoms
easily destroys the metallic plasma, however, which suppresses the optical
reflection. Interband transitions result in a featureless optical absorption
over a large energy range, causing the black appearance of Mg(x)Ti(1-x)H2.Comment: 22 pages, 9 figures, 4 table
Constraints on the shapes of galaxy dark matter haloes from weak gravitational lensing
We study the shapes of galaxy dark matter haloes by measuring the anisotropy
of the weak gravitational lensing signal around galaxies in the second
Red-sequence Cluster Survey (RCS2). We determine the average shear anisotropy
within the virial radius for three lens samples: all galaxies with
19<m_r'<21.5, and the `red' and `blue' samples, whose lensing signals are
dominated by massive low-redshift early-type and late-type galaxies,
respectively. To study the environmental dependence of the lensing signal, we
separate each lens sample into an isolated and clustered part and analyse them
separately. We also measure the azimuthal dependence of the distribution of
physically associated galaxies around the lens samples. We find that these
satellites preferentially reside near the major axis of the lenses, and
constrain the angle between the major axis of the lens and the average location
of the satellites to =43.7 deg +/- 0.3 deg for the `all' lenses,
=41.7 deg +/- 0.5 deg for the `red' lenses and =42.0 deg +/- 1.4
deg for the `blue' lenses. For the `all' sample, we find that the anisotropy of
the galaxy-mass cross-correlation function =0.23 +/- 0.12, providing
weak support for the view that the average galaxy is embedded in, and
preferentially aligned with, a triaxial dark matter halo. Assuming an
elliptical Navarro-Frenk-White (NFW) profile, we find that the ratio of the
dark matter halo ellipticity and the galaxy ellipticity
f_h=e_h/e_g=1.50+1.03-1.01, which for a mean lens ellipticity of 0.25
corresponds to a projected halo ellipticity of e_h=0.38+0.26-0.25 if the halo
and the lens are perfectly aligned. For isolated galaxies of the `all' sample,
the average shear anisotropy increases to =0.51+0.26-0.25 and
f_h=4.73+2.17-2.05, whilst for clustered galaxies the signal is consistent with
zero. (abridged)Comment: 28 pages, 23 figues, accepted for publication in A&
CRISPR-Cas immunity leads to a coevolutionary arms race between Streptococcus thermophilus and lytic phage
This is the final version. Available on open access from the Royal Society via the DOI in this recordData accessibility:
The datasets supporting this article have been uploaded as part of the electronic supplementary material, tables.CRISPR-Cas is an adaptive prokaryotic immune system that prevents phage infection. By incorporating phage-derived 'spacer' sequences into CRISPR loci on the host genome, future infections from the same phage genotype can be recognized and the phage genome cleaved. However, the phage can escape CRISPR degradation by mutating the sequence targeted by the spacer, allowing them to re-infect previously CRISPR-immune hosts, and theoretically leading to coevolution. Previous studies have shown that phage can persist over long periods in populations of Streptococcus thermophilus that can acquire CRISPR-Cas immunity, but it has remained less clear whether this coexistence was owing to coevolution, and if so, what type of coevolutionary dynamics were involved. In this study, we performed highly replicated serial transfer experiments over 30 days with S. thermophilus and a lytic phage. Using a combination of phenotypic and genotypic data, we show that CRISPR-mediated resistance and phage infectivity coevolved over time following an arms race dynamic, and that asymmetry between phage infectivity and host resistance within this system eventually causes phage extinction. This work provides further insight into the way CRISPR-Cas systems shape the population and coevolutionary dynamics of bacteria-phage interactions. This article is part of a discussion meeting issue 'The ecology and evolution of prokaryotic CRISPR-Cas adaptive immune systems'.European Union Horizon 202
Minard revisited: exploring augmented reality in information design
This study intends to test and confirm the interest and viability of incorporating augmented reality (AR) technologies in cultural mediation driven by information design, focusing on narrative representation. It is specifically intended to explore semantic relations between reality and virtuality in augmented narratives, ie. expanded narratives through the multimodality enhanced by the use of interactive processes based in augmented reality systems. Departing from Charles Minard’s Figurative Map (1869), three experiments were conducted, in order to reinterpret the program embodied in that artefact, testing several hypotheses in which, through augmented reality, the combination of different modes and media configures different semantic relations between real and virtual. The action-reflection approach undertaken with Figurative Map experiments enabled us to observe and openly systematize different augmented reality functions regarding the physical instance, which can potentially expand traditional forms of information design. Although they are not entirely extrapolatable, the proposal of virtual functions regarding reality were repurposed and adapted from the illustration field, specifically from the semantic relation between text and image. It is acknowledged that this is an open model to be reconsidered and reformulated through several action-reflection iterations and fostered through the narrative study.publishe
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