Boussinesq salt-water laboratory experiments of Rayleigh–Taylor instability (RTI) can achieve mixing efficiencies greater than 0.75 when the unstable interface is confined between two stable ...stratifications. This is much greater than that found when RTI occurs between two homogeneous layers when the mixing efficiency has been found to approach 0.5. Here, the mixing efficiency is defined as the ratio of energy used in mixing compared with the energy available for mixing. If the initial and final states are quiescent then the mixing efficiency can be calculated from experiments by comparison of the corresponding density profiles. Varying the functional form of the confining stratifications has a strong effect on the mixing efficiency. We derive a buoyancy-diffusion model for the rate of growth of the turbulent mixing region,
$\def \xmlpi #1{}\def \mathsfbi #1{\boldsymbol {\mathsf {#1}}}\let \le =\leqslant \let \leq =\leqslant \let \ge =\geqslant \let \geq =\geqslant \def \Pr {\mathit {Pr}}\def \Fr {\mathit {Fr}}\def \Rey {\mathit {Re}}\dot{h} = 2 \sqrt{\alpha A g h}$
(where
$A = A(h)$
is the Atwood number across the mixing region when it extends a height
$h$
,
$g$
is acceleration due to gravity and
$\alpha $
is a constant). This model shows good agreement with experiments when the value of the constant
$\alpha $
is set to 0.07, the value found in experiments of RTI between two homogeneous layers (where the height of the turbulent mixing region increases as
$h =\alpha A g t^2$
, an expression which is equivalent to that derived for
$\dot{h}$
).
Research taking place in care homes for older adults has rapidly increased in recent decades, which was seen even more during the COVID-19 pandemic. Challenges in including older adults, particularly ...those living with a level of cognitive decline, have prevented resident voices being at the forefront of research. Furthermore, lack of resources and time pressures within care homes create barriers to accessing staff and care homes. It is important to consider the whole care context within research, alongside resident voices, to consider lived experiences and provide productive and realistic suggestions for change. Co-production is becoming more common in research, and is committed to facilitating inclusion and overcoming individual, social or contextual barriers to communication and inclusivity. The CHAPPI (Care Home Activity Providers Facilitating Public Involvement in Research as a Meaningful Activity for Care Home Residents) project has collaborated with key stakeholders, including care home managers, activity providers and lived experience experts to ensure gaps in knowledge between academia and industry are bridged from project inception. During this ‘Q&A style’ presentation, we (a care home manager and a researcher) will present our experiences of participating in or conducting research, including during the COVID-19 pandemic. We will also highlight lessons learned within the CHAPPI project so far, to discuss how we (as researchers and industry experts) can creatively proceed together, to improve care home research. Finally, we will explore how we can adapt research to fit with care homes to bring an understanding of what is needed to succeed and how we can do better, even during times of extraordinary measures.
The swimming direction of biological or artificial microscale swimmers tends to be randomised over long time-scales by thermal fluctuations. Bacteria use various strategies to bias swimming behaviour ...and achieve directed motion against a flow, maintain alignment with gravity or travel up a chemical gradient. Herein, we explore a purely geometric means of biasing the motion of artificial nanorod swimmers. These artificial swimmers are bimetallic rods, powered by a chemical fuel, which swim on a substrate printed with teardrop-shaped posts. The artificial swimmers are hydrodynamically attracted to the posts, swimming alongside the post perimeter for long times before leaving. The rods experience a higher rate of departure from the higher curvature end of the teardrop shape, thereby introducing a bias into their motion. This bias increases with swimming speed and can be translated into a macroscopic directional motion over long times by using arrays of teardrop-shaped posts aligned along a single direction. This method provides a protocol for concentrating swimmers, sorting swimmers according to different speeds, and could enable artificial swimmers to transport cargo to desired locations.
Age-related change in human haematopoiesis causes reduced regenerative capacity
, cytopenias
, immune dysfunction
and increased risk of blood cancer
, but the reason for such abrupt functional ...decline after 70 years of age remains unclear. Here we sequenced 3,579 genomes from single cell-derived colonies of haematopoietic cells across 10 human subjects from 0 to 81 years of age. Haematopoietic stem cells or multipotent progenitors (HSC/MPPs) accumulated a mean of 17 mutations per year after birth and lost 30 base pairs per year of telomere length. Haematopoiesis in adults less than 65 years of age was massively polyclonal, with high clonal diversity and a stable population of 20,000-200,000 HSC/MPPs contributing evenly to blood production. By contrast, haematopoiesis in individuals aged over 75 showed profoundly decreased clonal diversity. In each of the older subjects, 30-60% of haematopoiesis was accounted for by 12-18 independent clones, each contributing 1-34% of blood production. Most clones had begun their expansion before the subject was 40 years old, but only 22% had known driver mutations. Genome-wide selection analysis estimated that between 1 in 34 and 1 in 12 non-synonymous mutations were drivers, accruing at constant rates throughout life, affecting more genes than identified in blood cancers. Loss of the Y chromosome conferred selective benefits in males. Simulations of haematopoiesis, with constant stem cell population size and constant acquisition of driver mutations conferring moderate fitness benefits, entirely explained the abrupt change in clonal structure in the elderly. Rapidly decreasing clonal diversity is a universal feature of haematopoiesis in aged humans, underpinned by pervasive positive selection acting on many more genes than currently identified.
Cross-reactive immune responses to SARS-CoV-2 have been observed in pre-pandemic cohorts and proposed to contribute to host protection. Here we assess 52 COVID-19 household contacts to capture immune ...responses at the earliest timepoints after SARS-CoV-2 exposure. Using a dual cytokine FLISpot assay on peripheral blood mononuclear cells, we enumerate the frequency of T cells specific for spike, nucleocapsid, membrane, envelope and ORF1 SARS-CoV-2 epitopes that cross-react with human endemic coronaviruses. We observe higher frequencies of cross-reactive (p = 0.0139), and nucleocapsid-specific (p = 0.0355) IL-2-secreting memory T cells in contacts who remained PCR-negative despite exposure (n = 26), when compared with those who convert to PCR-positive (n = 26); no significant difference in the frequency of responses to spike is observed, hinting at a limited protective function of spike-cross-reactive T cells. Our results are thus consistent with pre-existing non-spike cross-reactive memory T cells protecting SARS-CoV-2-naïve contacts from infection, thereby supporting the inclusion of non-spike antigens in second-generation vaccines.
Biological systems often involve the self-assembly of basic components into complex and functioning structures. Artificial systems that mimic such processes can provide a well-controlled setting to ...explore the principles involved and also synthesize useful micromachines. Our experiments show that immotile, but active, components self-assemble into two types of structure that exhibit the fundamental forms of motility: translation and rotation. Specifically, micron-scale metallic rods are designed to induce extensile surface flows in the presence of a chemical fuel; these rods interact with each other and pair up to form either a swimmer or a rotor. Such pairs can transition reversibly between these two configurations, leading to kinetics reminiscent of bacterial run-and-tumble motion.
Somatic mutations drive the development of cancer and may contribute to ageing and other diseases
. Despite their importance, the difficulty of detecting mutations that are only present in single ...cells or small clones has limited our knowledge of somatic mutagenesis to a minority of tissues. Here, to overcome these limitations, we developed nanorate sequencing (NanoSeq), a duplex sequencing protocol with error rates of less than five errors per billion base pairs in single DNA molecules from cell populations. This rate is two orders of magnitude lower than typical somatic mutation loads, enabling the study of somatic mutations in any tissue independently of clonality. We used this single-molecule sensitivity to study somatic mutations in non-dividing cells across several tissues, comparing stem cells to differentiated cells and studying mutagenesis in the absence of cell division. Differentiated cells in blood and colon displayed remarkably similar mutation loads and signatures to their corresponding stem cells, despite mature blood cells having undergone considerably more divisions. We then characterized the mutational landscape of post-mitotic neurons and polyclonal smooth muscle, confirming that neurons accumulate somatic mutations at a constant rate throughout life without cell division, with similar rates to mitotically active tissues. Together, our results suggest that mutational processes that are independent of cell division are important contributors to somatic mutagenesis. We anticipate that the ability to reliably detect mutations in single DNA molecules could transform our understanding of somatic mutagenesis and enable non-invasive studies on large-scale cohorts.
We analyse the entrainment and energetics of equal and opposite axisymmetric turbulent air plumes in a vertically confined space at a Rayleigh number of
$1.24\times 10^{7}$
using theory and direct ...numerical simulation. On domains of sufficiently large aspect ratio, the steady state consists of turbulent plumes penetrating an interface between two layers of approximately uniform buoyancy. As described by Baines & Turner (
J. Fluid Mech.
, vol. 37(1), 1969, pp. 51–80), upon penetrating the interface the flow in each plume becomes forced and behaves like a constant-momentum jet, due to a reduction in its mean buoyancy relative to the local environment. To observe the behaviour of the plumes we partition the domain into sub-domains corresponding to each plume. Domains of relatively small aspect ratio produce a single primary mean-flow circulation between the sub-domains that is maintained by entrainment into the plumes. At larger aspect ratios the mean flow between the sub-domains bifurcates, indicating the existence of a secondary circulation within each layer associated with entrainment into the jets. The largest aspect ratios studied here exhibit an additional, tertiary, circulation in the vicinity of the interface. Consistency between independent calculations of an effective entrainment coefficient allows us to identify aspect ratios for which the flow can be modelled using plume theory, under the assumption of a two-layer stratification. To study the flow’s energetics we use a local definition of available potential energy (APE). For plumes with Gaussian velocity and buoyancy profiles, the theory we develop suggests that the kinetic energy dissipation is split equally between the jets and the plumes and, collectively, accounts for almost half of the input of APE at the boundaries. In contrast, 1/4 of the APE dissipation and background potential energy (BPE) production occurs in the jets, with the remaining 3/4 occurring in the plumes. These bulk theoretical predictions agree with observations of BPE production from simulations to within 1 % and form the basis of a similarity solution that models the vertical dependence of APE dissipation and BPE production. Unlike results concerning the dissipation of buoyancy variance and the strength of the circulations described above, the model for the flow’s energetics does not involve an entrainment coefficient.
Since their widespread establishment in the 1970s, home support services across Canada have been subject to shifting state logics, policies, and funding models. The impacts and responses of local ...actors differ across historical, socio-cultural, and geographical settings. This paper traces the development and evolution of a small home support society on two rural islands off the coast of British Columbia, Canada. Using historical and current data sources, we demonstrate that local actors have consistently engaged a relational ethic that challenges neo-liberal discourses and practices. Our central thesis is that the islands' distinct social, cultural, and rural features set the context for particular constructions of relational care. We identify three themes central to a relational ethic of home support on two rural islands: the strength of intergenerational connections, community-embedded relationships, and care as compassionate civic engagement. Within each theme, we consider how shifting policy structures inform changes over time in the nature and delivery of home support. To conclude, we elaborate on the conditions that allow for relational care to flourish in a particular rural context, and on the potential relevance to other settings.
•People aging in rural areas have distinct home support needs.•Repeated government cutbacks undermine quality home support for older people.•Clients and workers form meaningful intergenerational connections.•Rural home support challenges personal/professional boundaries.•Rural citizens understand care as a civic duty, but women do most of the work.
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