pinecone/core-2020-05-10-deduplication huggingface dataset:
Whole-genome sequencing for prediction of Mycobacterium tuberculosis drug susceptibility and resistance: a retrospective cohort study

SummaryBackgroundDiagnosing drug-resistance remains an obstacle to the elimination of tuberculosis. Phenotypic drug-susceptibility testing is slow and expensive, and commercial genotypic assays screen only common resistance-determining mutations. We used whole-genome sequencing to characterise common and rare mutations predicting drug resistance, or consistency with susceptibility, for all first-line and second-line drugs for tuberculosis.MethodsBetween Sept 1, 2010, and Dec 1, 2013, we sequenced a training set of 2099 Mycobacterium tuberculosis genomes. For 23 candidate genes identified from the drug-resistance scientific literature, we algorithmically characterised genetic mutations as not conferring resistance (benign), resistance determinants, or uncharacterised. We then assessed the ability of these characterisations to predict phenotypic drug-susceptibility testing for an independent validation set of 1552 genomes. We sought mutations under similar selection pressure to those characterised as resistance determinants outside candidate genes to account for residual phenotypic resistance.FindingsWe characterised 120 training-set mutations as resistance determining, and 772 as benign. With these mutations, we could predict 89·2% of the validation-set phenotypes with a mean 92·3% sensitivity (95% CI 90·7–93·7) and 98·4% specificity (98·1–98·7). 10·8% of validation-set phenotypes could not be predicted because uncharacterised mutations were present. With an in-silico comparison, characterised resistance determinants had higher sensitivity than the mutations from three line-probe assays (85·1% vs 81·6%). No additional resistance determinants were identified among mutations under selection pressure in non-candidate genes.InterpretationA broad catalogue of genetic mutations enable data from whole-genome sequencing to be used clinically to predict drug resistance, drug susceptibility, or to identify drug phenotypes that cannot yet be genetically predicted. This approach could be integrated into routine diagnostic workflows, phasing out phenotypic drug-susceptibility testing while reporting drug resistance early.FundingWellcome Trust, National Institute of Health Research, Medical Research Council, and the European Union
Large-N reduction of SU(N) Yang–Mills theory with massive adjoint overlap fermions

AbstractWe study four-dimensional large-N SU(N) Yang–Mills theory coupled to adjoint overlap fermions on a single site lattice. Lattice simulations along with perturbation theory show that the bare quark mass has to be taken to zero as one takes the continuum limit in order to be in the physically relevant center-symmetric phase. But, it seems that it is possible to take the continuum limit with any renormalized quark mass and still be in the center-symmetric physics. We have also conducted a study of the correlations between Polyakov loop operators in different directions and obtained the range for the Wilson mass parameter that enters the overlap Dirac operator
Competition on Fast Track: An Analysis of the First Competitive Market for HSR Services

AbstractThis paper gives an overview of the dual effects of the opening, in Italy, of the new HSR line with a single operator (between 2005-2012) and the effects of a new operator entering the HSR market (2012-onward), on supply, demand and prices, thus inferring the effects of competition in this typically monopolistic market. The analyses are based on source data (laws and regulations, business plans, timetables, prices) as well as ad hoc extensive surveys, such as on-board counts on the HSR and intercity trains, retrospect surveys, and RP/SP interviews. In addition, an integrated modeling system has been developed to forecast the effects of competing timetables/services/prices in terms of different HSR operators, competing modes (air/auto/railways), services (1st class/2nd class, etc.) and newly generated trips
A note on the Harris–Kesten Theorem

AbstractA short proof of the Harris–Kesten result that the critical probability for bond percolation in the planar square lattice is 1/2 was given in [B. Bollobás, O.M. Riordan, A short proof of the Harris–Kesten Theorem, Bull. London Math. Soc. 38 (2006) 470–484], using a sharp-threshold result of Friedgut and Kalai. Here we point out that a key part of this proof may be replaced by an argument of Russo [L. Russo, An approximate zero–one law, Z. Wahrscheinlichkeitstheor. Verwandte Geb. 61 (1982) 129–139] from 1982, using his approximate zero–one law in place of the Friedgut–Kalai result. Russo’s paper gave a new proof of the Harris–Kesten Theorem that seems to have received little attention
An overview of cardiac morphogenesis

SummaryAccurate knowledge of normal cardiac development is essential for properly understanding the morphogenesis of congenital cardiac malformations that represent the most common congenital anomaly in newborns. The heart is the first organ to function during embryonic development and is fully formed at 8weeks of gestation. Recent studies stemming from molecular genetics have allowed specification of the role of cellular precursors in the field of heart development. In this article we review the different steps of heart development, focusing on the processes of alignment and septation. We also show, as often as possible, the links between abnormalities of cardiac development and the main congenital heart defects. The development of animal models has permitted the unraveling of many mechanisms that potentially lead to cardiac malformations. A next step towards a better knowledge of cardiac development could be multiscale cardiac modelling
Emission of neutron–proton and proton–proton pairs in neutrino scattering

AbstractWe use a recently developed model of relativistic meson-exchange currents to compute the neutron–proton and proton–proton yields in (νμ,μ−) scattering from 12C in the 2p–2h channel. We compute the response functions and cross sections with the relativistic Fermi gas model for different kinematics from intermediate to high momentum transfers. We find a large contribution of neutron–proton configurations in the initial state, as compared to proton–proton pairs. In the case of charge-changing neutrino scattering the 2p–2h cross section of proton–proton emission (i.e., np in the initial state) is much larger than for neutron–proton emission (i.e., two neutrons in the initial state) by a (ω,q)-dependent factor. The different emission probabilities of distinct species of nucleon pairs are produced in our model only by meson-exchange currents, mainly by the Δ isobar current. We also analyze other effects including exchange contributions and the effect of the axial and vector currents
Determination of γ and −2βs from charmless two-body decays of beauty mesons

AbstractUsing the latest LHCb measurements of time-dependent CP violation in the Bs0→K+K− decay, a U-spin relation between the decay amplitudes of Bs0→K+K− and B0→π+π− decay processes allows constraints to be placed on the angle γ of the unitarity triangle and on the Bs0 mixing phase −2βs. Results from an extended approach, which uses additional inputs on B0→π0π0 and B+→π+π0 decays from other experiments and exploits isospin symmetry, are also presented. The dependence of the results on the maximum allowed amount of U-spin breaking is studied. At 68% probability, the value γ=(63.5−6.7+7.2)° modulo 180° is determined. In an alternative analysis, the value −2βs=−0.12−0.16+0.14 rad is found. In both measurements, the uncertainties due to U-spin breaking effects up to 50% are included
Quasifission and difference in formation of evaporation residues in the 16O+184W and 19F+181Ta reactions

AbstractThe role of the entrance channel has been studied to ascertain a cause of the observed difference between the evaporation residue cross sections normalized to the fusion cross sections in the 19F+181Ta and 16O+184W reactions at high excitation energies. The theoretical analysis performed in the framework of the dinuclear system and advanced statistical models showed that the more intense yield of evaporation residues in the 16O+184W reaction in comparison with that in the 19F+181Ta reaction was explained by the large capture and fusion cross sections in the former reaction, which is in agreement with the experimental data. The observed decrease in the evaporation residue cross section normalized to the fusion cross section in the 19F+181Ta reaction, in comparison with one in the 16O+184W reaction at large excitation energies, is caused by the unintentional inclusion of the quasifission and fast fission contributions in the fissionlike fragment yields that were used in reconstructing the experimental fusion cross section in the normalizing procedure. The range of the angular momentum distribution for both systems was similar, but the partial cross sections are different, showing the presence of a difference in the hindrance to complete fusion in both reactions
Pes shape variation in an ornithopod dinosaur trackway (Lower Cretaceous, NW Spain): New evidence of an antalgic gait in the fossil track record

AbstractTrackways can provide unique insight to animals locomotion through quantitative analysis of variation in track morphology. Long trackways additionally permit the study of trackmaker foot anatomy, providing more insight on limb kinematics. In this paper we have restudied the extensive tracksite at Barranco de La Canal-1 (Lower Cretaceous, La Rioja, NW Spain) focussing on a 25-m-long dinosaur (ornithopod) trackway that was noted by an earlier study (Casanovas et al., 1995; Pérez-Lorente, 2003) to display an irregular pace pattern. This asymmetric gait has been quantified and photogrammetric models undertaken for each track, thus revealing distinct differences between the right and the left tracks, particularly in the relative position of the lateral digits II–IV with respect to the central digit III. Given that the substrate at this site is homogenous, the consistent repetition of the collected morphological data suggests that differences recorded between the right and the left tracks can be linked to the foot anatomy, but more interestingly, to an injury or pathology on left digit II. We suggest that the abnormal condition registered in digit II impression of the left pes can be linked to the statistically significant limping behaviour of the trackmaker. Furthermore, the abnormal condition registered did not affect the dinosaur's speed
Bayesian nonparametric system reliability using sets of priors

AbstractAn imprecise Bayesian nonparametric approach to system reliability with multiple types of components is developed. This allows modelling partial or imperfect prior knowledge on component failure distributions in a flexible way through bounds on the functioning probability. Given component level test data these bounds are propagated to bounds on the posterior predictive distribution for the functioning probability of a new system containing components exchangeable with those used in testing. The method further enables identification of prior–data conflict at the system level based on component level test data. New results on first-order stochastic dominance for the Beta-Binomial distribution make the technique computationally tractable. Our methodological contributions can be immediately used in applications by reliability practitioners as we provide easy to use software tools
Beyond ‘predict and provide’: UK transport, the growth paradigm and climate change

AbstractThirty years ago, Adams (1981) depicted a future UK where everyone was a millionaire lorry driver, simply by extrapolating from contemporary official transport growth assumptions. These assumptions underpinned the ‘predict and provide’ approach which then characterised transport planning. Twenty years later, the New Deal for Transport White Paper (1998) abandoned ‘predict and provide’ as unsustainable. This paper argues that the same growth assumptions that Adams took to their logical (absurd) conclusion have re-emerged to define both transport and the drivers of transport demand. While non-aviation transport is supposed to be carbon-neutral by 2050, the implied reductions in emissions rely on an absolute decoupling of transport demand and its drivers for which there is no evidence in current planning. Targets rely on optimistic, narrowly framed technology forecasts and behaviour change assumptions which appear highly unlikely in the present socio-political climate. Moreover, such is the cost of mitigating these tensions between economic growth and other concerns, it is argued that the targeted outcomes of current policy are as undesirable as they are unlikely. The paper concludes by calling for a transport policy which considers mobility in an integrated, holistic fashion, rather than merely as a dimension of economic growth
Regular singular Sturm–Liouville operators and their zeta-determinants

AbstractWe consider Sturm–Liouville operators on the line segment [0,1] with general regular singular potentials and separated boundary conditions. We establish existence and a formula for the associated zeta-determinant in terms of the Wronski-determinant of a fundamental system of solutions adapted to the boundary conditions. This generalizes the earlier work of the first author, treating general regular singular potentials but only the Dirichlet boundary conditions at the singular end, and the recent results by Kirsten–Loya–Park for general separated boundary conditions but only special regular singular potentials
Antecedent conditions control carbon loss and downstream water quality from shallow, damaged peatlands

AbstractLosses of dissolved organic carbon (DOC) from drained peatlands are of concern, due to the effects this has on the delivery of ecosystem services, and especially on the long-term store of carbon and the provision of drinking water. Most studies have looked at the effect of drainage in deep peat; comparatively, little is known about the behaviour of shallow, climatically marginal peatlands. This study examines water quality (DOC, Abs400, pH, E4/E6 and C/C) during rainfall events from such environments in the south west UK, in order to both quantify DOC losses, and understand their potential for restoration. Water samples were taken over a 19month period from a range of drains within two different experimental catchments in Exmoor National Park; data were analysed on an event basis. DOC concentrations ranging between 4 and 21mgL−1 are substantially lower than measurements in deep peat, but remain problematic for the water treatment process. Dryness plays a critical role in controlling DOC concentrations and water quality, as observed through spatial and seasonal differences. Long-term changes in depth to water table (30days before the event) are likely to impact on DOC production, whereas discharge becomes the main control over DOC transport at the time scale of the rainfall/runoff event. The role of temperature during events is attributed to an increase in the diffusion of DOC, and therefore its transport. Humification ratios (E4/E6) consistently below 5 indicate a predominance of complex humic acids, but increased decomposition during warmer summer months leads to a comparatively higher losses of fulvic acids. This work represents a significant contribution to the scientific understanding of the behaviour and functioning of shallow damaged peatlands in climatically marginal locations. The findings also provide a sound baseline knowledge to support research into the effects of landscape restoration in the future
Measurements of scintillation efficiency and pulse shape for low energy recoils in liquid xenon

AbstractResults of observations of low energy nuclear and electron recoil events in liquid xenon scintillator detectors are given. The relative scintillation efficiency for nuclear recoils is 0.22±0.01 in the recoil energy range 40–70 keV. Under the assumption of a single dominant decay component to the scintillation pulse shape the log-normal mean parameter T0 of the maximum likelihood estimator of the decay time constant for 6 keV <Eee<30 keV nuclear recoil events is equal to 21.0±0.5 ns. It is observed that for electron recoils T0 rises slowly with energy, having a value ∼30 ns at Eee∼15 keV. Electron and nuclear recoil pulse shapes are found to be well fitted by single exponential functions although some evidence is found for a double exponential form for the nuclear recoil pulse shape
The SPAIR method: Isolating incident and reflected directional wave spectra in multidirectional wave basins

AbstractWave tank tests aiming to reproduce realistic or site specific conditions will commonly involve using directionally spread, short-crested sea states. The measurement of these directional characteristics is required for the purposes of calibrating and validating the modelled sea state. Commonly used methods of directional spectrum reconstruction, based on directional spreading functions, have an inherent level of uncertainty associated with them. In this paper we aim to reduce the uncertainty in directional spectrum validation by introducing the SPAIR (Single-summation PTPD Approach with In-line Reflections) method, in combination with a directional wave gauge array. A variety of wave conditions were generated in the FloWave Ocean Energy Research Facility, Edinburgh, UK, to obtain a range of sea state and reflection scenarios. The presented approach is found to provide improved estimates of directional spectra over standard methods, reducing the mean apparent directional deviation down to below 6% over the range of sea states. Additionally, the method isolates incident and reflected spectra in both the frequency and time domain, and can separate these wave systems over 360°. The accuracy of the method is shown to be only slightly sensitive to the level of in-line reflection present, but at present cannot deal with oblique reflections. The SPAIR method, as presented or with slight modification, will allow complex directional sea states to be validated more effectively, enabling multidirectional wave basins to simulate realistic wave scenarios with increased confidence
Sufficient conditions for Hamiltonicity in multiswapped networks

AbstractOTIS networks are interconnection networks amenable to deployment as hybrid networks containing both electronic and optical links. Deficiencies as regards symmetry led to the subsequent formulation of biswapped networks which were later generalized to multiswapped networks so as to still enable optoelectronic implementation (as it happens, multiswapped networks also generalize previously studied hierarchical crossed cubes). Multiswapped networks of the form Msw(H;G) are known to possess good (graph-theoretic) properties as regards their use as (optoelectronic) interconnection networks (in distributed-memory multiprocessors) and in relation to those of the component networks G and H. Combinatorially, they provide a hierarchical mechanism to define new networks from existing networks (so that the properties of the new network can be controlled in terms of the constituent networks). In this paper, we prove that if G and H are Hamiltonian networks then the multiswapped network Msw(H;G) is also Hamiltonian. At the core of our proof is finding specially designed Hamiltonian cycles in 2-dimensional and heavily pruned 3-dimensional tori, irrespective of the actual networks G and H we happen to be working with. This lends credence to the role of tori as fundamental networks within the study of interconnection networks
Coleman–Weinberg inflation in light of Planck

AbstractWe revisit a single field inflationary model based on Coleman–Weinberg potentials. We show that in small field Coleman–Weinberg inflation, the observed amplitude of perturbations needs an extremely small quartic coupling of the inflaton, which might be a signature of radiative origin. However, the spectral index obtained in a standard cosmological scenario turns out to be outside the 2σ region of the Planck data. When a non-standard cosmological framework is invoked, such as brane-world cosmology in the Randall–Sundrum model, the spectral index can be made consistent with Planck data within 1σ, courtesy of the modification in the evolution of the Hubble parameter in such a scheme. We also show that the required inflaton quartic coupling as well as a phenomenologically viable B−L symmetry breaking together with a natural electroweak symmetry breaking can arise dynamically in a generalized B−L extension of the Standard Model where the full potential is assumed to vanish at a high scale
The anomalous dimension of the gluon-ghost mass operator in Yang–Mills theory

AbstractThe local composite gluon-ghost operator (12AaμAμa+αc̄aca) is analysed in the framework of the algebraic renormalization in SU(N) Yang–Mills theories in the Landau, Curci–Ferrari and maximal abelian gauges. We show, to all orders of perturbation theory, that this operator is multiplicatively renormalizable. Furthermore, its anomalous dimension is not an independent parameter of the theory, being given by a general expression valid in all these gauges. We also verify the relations we obtain for the operator anomalous dimensions by explicit 3-loop calculations in the MS scheme for the Curci–Ferrari gauge
Functional Identification of Tumor-Suppressor Genes through an In Vivo RNA Interference Screen in a Mouse Lymphoma Model

SummaryShort hairpin RNAs (shRNAs) capable of stably suppressing gene function by RNA interference (RNAi) can mimic tumor-suppressor-gene loss in mice. By selecting for shRNAs capable of accelerating lymphomagenesis in a well-characterized mouse lymphoma model, we identified over ten candidate tumor suppressors, including Sfrp1, Numb, Mek1, and Angiopoietin 2. Several components of the DNA damage response machinery were also identified, including Rad17, which acts as a haploinsufficient tumor suppressor that responds to oncogenic stress and whose loss is associated with poor prognosis in human patients. Our results emphasize the utility of in vivo RNAi screens, identify and validate a diverse set of tumor suppressors, and have therapeutic implications
Growing Surface Tension of Amorphous-Amorphous Interfaces on Approaching
  the Colloidal Glass Transition

There is mounting evidence indicating that relaxation dynamics in liquids
approaching their glass transition not only becomes increasingly cooperative
(1,2) but the relaxing regions also become more compact in shape(3-7). While
the surface tension of the interface separating neighboring relaxing regions is
thought to play a crucial role in deciding both their size and
morphology(8-10), owing to the amorphous nature of these regions, even
identifying these interfaces has not been possible in bulk liquids. Here, by
devising a scheme to identify self-induced disorder sites in bulk colloidal
liquids, we directly quantified the dynamics of interfaces delineating regions
of high and low configurational overlap. This procedure also helped unveil a
non-monotonicity in dynamical correlations that has never been observed in bulk
supercooled liquids. Using the capillary fluctuation method (11,12), we
measured the surface tension of amorphous-amorphous interfaces with
supercooling and find that it increases rapidly across the mode-coupling area
fraction. Remarkably, a similar growth in the surface tension is also seen in
the presence of a pinned amorphous wall. Our observations help prune theories
of glass formation and opens up new research avenues aimed at tuning the
properties of amorphous-amorphous interfaces, and hence the glass itself, in a
manner analogous to grain boundary engineering in polycrystals (13)