756 research outputs found
Stabilisation and drag reduction of pipe flows by flattening the base profile
Recent experimental observations (Kuehnen et al., 2018) have shown that
flattening a turbulent streamwise velocity profile in pipe flow destabilises
the turbulence so that the flow relaminarises. We show that a similar
phenomenon exists for laminar pipe flow profiles in the sense that the
nonlinear stability of the laminar state is enhanced as the profile becomes
more flattened. Significant drag reduction is also observed for the turbulent
flow when triggered by sufficiently large disturbances. The flattening is
produced by an artificial body force designed to mimick a baffle used in the
experiments of Kuehnen et al. (2018) and the nonlinear stability measured by
the size of the energy of the initial perturbations needed to trigger
transition. In order to make the latter computation more efficient, we examine
how indicative the minimal seed for transition is in measuring transition
thresholds. We first show that the minimal seed is relatively robust to base
profile changes and spectral filtering. We then compare the (unforced)
transition behaviour of the minimal seed with several forms of randomised
initial conditions in the range of Reynolds numbers Re=2400 to 10000 and find
that the energy of the minimal seed after the Orr and oblique phases of its
evolution is close to that of a localised random disturbance. In this sense,
the minimal seed at the end of the oblique phase can be regarded as a good
proxy for typical disturbances (here taken to be the localised random ones) and
is thus used as initial condition in the simulations with the body force. The
enhanced nonlinear stability and drag reduction predicted in the present study
are an encouraging first step in modelling the experiments of Kuehnen et al.
and should motivate future developments to fully exploit the benefits of this
promising direction for flow control
Designing a minimal baffle to destabilise turbulence in pipe flows
Motivated by the results of recent experiments (K\"uhnen et al., Flow Turb.
Combust., vol. 100, 2018, pp. 919-943), we consider the problem of designing a
baffle (an obstacle to the flow) to relaminarise turbulence in pipe flows.
Modelling the baffle as a spatial distribution of linear drag
within the flow ( is the total velocity field and a scalar field), two different optimisation problems are considered to
design at a Reynolds number . In the first, the smallest baffle
defined in terms of a norm of is sought which minimises the
viscous dissipation rate of the flow. In the second, a baffle which minimises
the total energy consumption of the flow is treated. Both problems indicate
that the baffle should be axisymmetric and radially localised near the pipe
wall, but struggle to predict the optimal streamwise extent. A manual search
finds an optimal baffle one radius long which is then used to study how the
amplitude for relaminarisation varies with up to . Large stress
reduction is found at the pipe wall, but at the expense of an increased
pressure drop across the baffle. Estimates are then made of the break even
point downstream of the baffle where the stress reduction at the wall due to
the relaminarised flow compensates for the extra drag produced by the baffle.EPSR
High genetic diversity at the extreme range edge: nucleotide variation at nuclear loci in Scots pine (Pinus sylvestris L.) in Scotland
Nucleotide polymorphism at 12 nuclear loci was studied in Scots pine populations across an environmental gradient in Scotland, to evaluate the impacts of demographic history and selection on genetic diversity. At eight loci, diversity patterns were compared between Scottish and continental European populations. At these loci, a similar level of diversity (θsil=~0.01) was found in Scottish vs mainland European populations, contrary to expectations for recent colonization, however, less rapid decay of linkage disequilibrium was observed in the former (ρ=0.0086±0.0009, ρ=0.0245±0.0022, respectively). Scottish populations also showed a deficit of rare nucleotide variants (multi-locus Tajima's D=0.316 vs D=−0.379) and differed significantly from mainland populations in allelic frequency and/or haplotype structure at several loci. Within Scotland, western populations showed slightly reduced nucleotide diversity (πtot=0.0068) compared with those from the south and east (0.0079 and 0.0083, respectively) and about three times higher recombination to diversity ratio (ρ/θ=0.71 vs 0.15 and 0.18, respectively). By comparison with results from coalescent simulations, the observed allelic frequency spectrum in the western populations was compatible with a relatively recent bottleneck (0.00175 × 4Ne generations) that reduced the population to about 2% of the present size. However, heterogeneity in the allelic frequency distribution among geographical regions in Scotland suggests that subsequent admixture of populations with different demographic histories may also have played a role
The rise of fully turbulent flow
Over a century of research into the origin of turbulence in wallbounded shear
flows has resulted in a puzzling picture in which turbulence appears in a
variety of different states competing with laminar background flow. At slightly
higher speeds the situation changes distinctly and the entire flow is
turbulent. Neither the origin of the different states encountered during
transition, nor their front dynamics, let alone the transformation to full
turbulence could be explained to date. Combining experiments, theory and
computer simulations here we uncover the bifurcation scenario organising the
route to fully turbulent pipe flow and explain the front dynamics of the
different states encountered in the process. Key to resolving this problem is
the interpretation of the flow as a bistable system with nonlinear propagation
(advection) of turbulent fronts. These findings bridge the gap between our
understanding of the onset of turbulence and fully turbulent flows.Comment: 31 pages, 9 figure
5-Phenyl-1,3,4-oxadiazol-2(3H)-ones Are Potent Inhibitors of Notum Carboxylesterase Activity Identified by the Optimization of a Crystallographic Fragment Screening Hit
Carboxylesterase Notum is a negative regulator of the Wnt signaling pathway. There is an emerging understanding of the role Notum plays in disease, supporting the need to discover new small-molecule inhibitors. A crystallographic X-ray fragment screen was performed, which identified fragment hit 1,2,3-triazole 7 as an attractive starting point for a structure-based drug design hit-to-lead program. Optimization of 7 identified oxadiazol-2-one 23dd as a preferred example with properties consistent with drug-like chemical space. Screening 23dd in a cell-based TCF/LEF reporter gene assay restored the activation of Wnt signaling in the presence of Notum. Mouse pharmacokinetic studies with oral administration of 23dd demonstrated good plasma exposure and partial blood–brain barrier penetration. Significant progress was made in developing fragment hit 7 into lead 23dd (>600-fold increase in activity), making it suitable as a new chemical tool for exploring the role of Notum-mediated regulation of Wnt signaling
Screening of a Custom-Designed Acid Fragment Library Identifies 1-Phenylpyrroles and 1-Phenylpyrrolidines as Inhibitors of Notum Carboxylesterase Activity
The Wnt family of proteins are secreted signaling proteins that play key roles in regulating cellular functions. Recently, carboxylesterase Notum was shown to act as a negative regulator of Wnt signaling by mediating the removal of an essential palmitoleate. Here we disclose two new chemical scaffolds that inhibit Notum enzymatic activity. Our approach was to create a fragment library of 250 acids for screening against Notum in a biochemical assay followed by structure determination by X-ray crystallography. Twenty fragments were identified as hits for Notum inhibition, and 14 of these fragments were shown to bind in the palmitoleate pocket of Notum. Optimization of 1-phenylpyrrole 20, guided by structure-based drug design, identified 20z as the most potent compound from this series. Similarly, the optimization of 1-phenylpyrrolidine 8 gave acid 26. This work demonstrates that inhibition of Notum activity can be achieved by small, drug-like molecules possessing favorable in vitro ADME profiles
Treatment decisions and employment of breast cancer patients: Results of a population‐based survey
Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/142258/1/cncr30959.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/142258/2/cncr30959_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/142258/3/cncr30959-sup-0001-suppinfo1.pd
How do you say ‘hello’? Personality impressions from brief novel voices
On hearing a novel voice, listeners readily form personality impressions of that speaker. Accurate or not, these impressions are known to affect subsequent interactions; yet the underlying psychological and acoustical bases remain poorly understood. Furthermore, hitherto studies have focussed on extended speech as opposed to analysing the instantaneous impressions we obtain from first experience. In this paper, through a mass online rating experiment, 320 participants rated 64 sub-second vocal utterances of the word ‘hello’ on one of 10 personality traits. We show that: (1) personality judgements of brief utterances from unfamiliar speakers are consistent across listeners; (2) a two-dimensional ‘social voice space’ with axes mapping Valence (Trust, Likeability) and Dominance, each driven by differing combinations of vocal acoustics, adequately summarises ratings in both male and female voices; and (3) a positive combination of Valence and Dominance results in increased perceived male vocal Attractiveness, whereas perceived female vocal Attractiveness is largely controlled by increasing Valence. Results are discussed in relation to the rapid evaluation of personality and, in turn, the intent of others, as being driven by survival mechanisms via approach or avoidance behaviours. These findings provide empirical bases for predicting personality impressions from acoustical analyses of short utterances and for generating desired personality impressions in artificial voices
Order-of-magnitude speedup for steady states and traveling waves via Stokes preconditioning in Channelflow and Openpipeflow
Steady states and traveling waves play a fundamental role in understanding
hydrodynamic problems. Even when unstable, these states provide the
bifurcation-theoretic explanation for the origin of the observed states. In
turbulent wall-bounded shear flows, these states have been hypothesized to be
saddle points organizing the trajectories within a chaotic attractor. These
states must be computed with Newton's method or one of its generalizations,
since time-integration cannot converge to unstable equilibria. The bottleneck
is the solution of linear systems involving the Jacobian of the Navier-Stokes
or Boussinesq equations. Originally such computations were carried out by
constructing and directly inverting the Jacobian, but this is unfeasible for
the matrices arising from three-dimensional hydrodynamic configurations in
large domains. A popular method is to seek states that are invariant under
numerical time integration. Surprisingly, equilibria may also be found by
seeking flows that are invariant under a single very large Backwards-Euler
Forwards-Euler timestep. We show that this method, called Stokes
preconditioning, is 10 to 50 times faster at computing steady states in plane
Couette flow and traveling waves in pipe flow. Moreover, it can be carried out
using Channelflow (by Gibson) and Openpipeflow (by Willis) without any changes
to these popular spectral codes. We explain the convergence rate as a function
of the integration period and Reynolds number by computing the full spectra of
the operators corresponding to the Jacobians of both methods.Comment: in Computational Modelling of Bifurcations and Instabilities in Fluid
Dynamics, ed. Alexander Gelfgat (Springer, 2018
Neuronal circuitry for pain processing in the dorsal horn
Neurons in the spinal dorsal horn process sensory information, which is then transmitted to several brain regions, including those responsible for pain perception. The dorsal horn provides numerous potential targets for the development of novel analgesics and is thought to undergo changes that contribute to the exaggerated pain felt after nerve injury and inflammation. Despite its obvious importance, we still know little about the neuronal circuits that process sensory information, mainly because of the heterogeneity of the various neuronal components that make up these circuits. Recent studies have begun to shed light on the neuronal organization and circuitry of this complex region
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