Cell division and death can be regulated by the mechanical forces within a tissue. We study the consequences for the stability and roughness of a propagating interface by analyzing a model of ...mechanically regulated tissue growth in the regime of small driving forces. For an interface driven by homeostatic pressure imbalance or leader-cell motility, long and intermediate-wavelength instabilities arise, depending, respectively, on an effective viscosity of cell number change, and on substrate friction. A further mechanism depends on the strength of directed motility forces acting in the bulk. We analyze the fluctuations of a stable interface subjected to cell-level stochasticity, and find that mechanical feedback can help preserve reproducibility at the tissue scale. Our results elucidate mechanisms that could be important for orderly interface motion in developing tissues.
We demonstrate that linear combinations of subregion entropies with canceling boundary terms, commonly used to calculate the topological entanglement entropy, may suffer from spurious nontopological ...contributions even in models with zero correlation length. These spurious contributions are due to a specific kind of long-range string order and persist throughout certain subsystem symmetry-protected phases. We introduce an entropic quantity that measures the presence of such order, and hence should serve as an order parameter for the aforementioned phases.
Climate strongly influences global wildfire activity, and recent wildfire surges may signal fire weather-induced pyrogeographic shifts. Here we use three daily global climate data sets and three fire ...danger indices to develop a simple annual metric of fire weather season length, and map spatio-temporal trends from 1979 to 2013. We show that fire weather seasons have lengthened across 29.6 million km(2) (25.3%) of the Earth's vegetated surface, resulting in an 18.7% increase in global mean fire weather season length. We also show a doubling (108.1% increase) of global burnable area affected by long fire weather seasons (>1.0 σ above the historical mean) and an increased global frequency of long fire weather seasons across 62.4 million km(2) (53.4%) during the second half of the study period. If these fire weather changes are coupled with ignition sources and available fuel, they could markedly impact global ecosystems, societies, economies and climate.
Perceptions of social support availability may be influenced by internal working models, both of how support figures behave in general, and of how specific support figures behave individually. ...Participants were 217 first-year college students in the first semester of their involvement with an athletic team or Greek organization. They reported on the support they perceived to be available from three friends in those organizations at four time-points, over the course of 18 months. Regarding generalized working models, participants who had more supportive high school friends perceived more support available from their new college friends, even after controlling for their actual experiences with the college friends. Regarding friend-specific working models, friends who were perceived as more supportive at the beginning of the study were perceived as increasingly supportive over time, even after controlling for actual experiences with that friend. These findings illustrate the influence of relationship history on perceptions of social support. Feeling supported is not determined only by the responses of an individual’s support figures in times of need. Regular investment in relationships is important both for individuals who wish to feel supported and for support figures who wish to best help others.
Global peatlands store more carbon than is naturally present in the atmosphere
. However, many peatlands are under pressure from drainage-based agriculture, plantation development and fire, with the ...equivalent of around 3 per cent of all anthropogenic greenhouse gases emitted from drained peatland
. Efforts to curb such emissions are intensifying through the conservation of undrained peatlands and re-wetting of drained systems
. Here we report eddy covariance data for carbon dioxide from 16 locations and static chamber measurements for methane from 41 locations in the UK and Ireland. We combine these with published data from sites across all major peatland biomes. We find that the mean annual effective water table depth (WTD
; that is, the average depth of the aerated peat layer) overrides all other ecosystem- and management-related controls on greenhouse gas fluxes. We estimate that every 10 centimetres of reduction in WTD
could reduce the net warming impact of CO
and CH
emissions (100-year global warming potentials) by the equivalent of at least 3 tonnes of CO
per hectare per year, until WTD
is less than 30 centimetres. Raising water levels further would continue to have a net cooling effect until WTD
is within 10 centimetres of the surface. Our results suggest that greenhouse gas emissions from peatlands drained for agriculture could be greatly reduced without necessarily halting their productive use. Halving WTD
in all drained agricultural peatlands, for example, could reduce emissions by the equivalent of over 1 per cent of global anthropogenic emissions.
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•We quantified pelagic microplastic pollution in Lake Hovsgol, Mongolia.•Lake Hovsgol is more polluted with microplastics than Lakes Huron and Superior.•Microplastics came from ...consumer goods; no microbeads/few pellets were observed.•Microplastics were sourced from population centers and distributed by the winds.•Without waste management, even small populations can heavily pollute large lakes.
Despite the large and growing literature on microplastics in the ocean, little information exists on microplastics in freshwater systems. This study is the first to evaluate the abundance, distribution, and composition of pelagic microplastic pollution in a large, remote, mountain lake. We quantified pelagic microplastics and shoreline anthropogenic debris in Lake Hovsgol, Mongolia. With an average microplastic density of 20,264 particles km−2, Lake Hovsgol is more heavily polluted with microplastics than the more developed Lakes Huron and Superior in the Laurentian Great Lakes. Fragments and films were the most abundant microplastic types; no plastic microbeads and few pellets were observed. Household plastics dominated the shoreline debris and were comprised largely of plastic bottles, fishing gear, and bags. Microplastic density decreased with distance from the southwestern shore, the most populated and accessible section of the park, and was distributed by the prevailing winds. These results demonstrate that without proper waste management, low-density populations can heavily pollute freshwater systems with consumer plastics.
Multiple sclerosis (MS) appears to develop in genetically susceptible individuals as a result of environmental exposures. Epstein-Barr virus (EBV) infection is an almost universal finding among ...individuals with MS. Symptomatic EBV infection as manifested by infectious mononucleosis (IM) has been shown in a previous meta-analysis to be associated with the risk of MS, however a number of much larger studies have since been published.
We performed a Medline search to identify articles published since the original meta-analysis investigating MS risk following IM. A total of 18 articles were included in this study, including 19390 MS patients and 16007 controls. We calculated the relative risk of MS following IM using a generic inverse variance with random effects model. This showed that the risk of MS was strongly associated with IM (relative risk (RR) 2.17; 95% confidence interval 1.97-2.39; p<10(-54)).
Our results establish firmly that a history of infectious mononucleosis significantly increases the risk of multiple sclerosis. Future work should focus on the mechanism of this association and interaction with other risk factors.
A growing recognition of the importance of disruptive innovation has led researchers to examine the question of how disruptive innovation comes about and to what extent it reflects “discovery” versus ...“creation” of opportunities. Earlier research has focused on the organisational preconditions for disruptive innovation to arise. Much less attention has been paid to the role of innovation processes, including their goals and design, in promoting disruptive innovation. In this paper we aim to begin to fill this gap by better understanding how new innovation processes can act as antecedents for disruptive innovation.
We adopt an inductive theory-building methodology using a set of case studies of Chinese firms to develop propositions about how novel R&D and production processes can foster disruptive innovation. We find that in the case of China the adoption of new innovation processes that re-define the focus of innovation and re-engineer traditional R&D processes in ways that allow the novel deployment of Chinese cost advantages can create offerings that incorporate the key elements of disruptive innovation in the sense that they challenge incumbents׳ established business models. Realising disruptive innovation opportunities requires proactive initiatives. We conclude by discussing the managerial implications and possible responses as well as directions for future research.
•We explore how new innovation processes act as antecedents for disruptive innovation.•We use inductive theory-building based on a set of case studies of Chinese firms.•China is a significant source of disruptive innovation.•Novel R&D and production processes can foster disruptive innovation.•Realising disruptive innovation opportunities requires proactive initiatives.
Chronic myeloid leukaemia (CML) arises after transformation of a haemopoietic stem cell (HSC) by the protein-tyrosine kinase BCR-ABL. Direct inhibition of BCR-ABL kinase has revolutionized disease ...management, but fails to eradicate leukaemic stem cells (LSCs), which maintain CML. LSCs are independent of BCR-ABL for survival, providing a rationale for identifying and targeting kinase-independent pathways. Here we show--using proteomics, transcriptomics and network analyses--that in human LSCs, aberrantly expressed proteins, in both imatinib-responder and non-responder patients, are modulated in concert with p53 (also known as TP53) and c-MYC regulation. Perturbation of both p53 and c-MYC, and not BCR-ABL itself, leads to synergistic cell kill, differentiation, and near elimination of transplantable human LSCs in mice, while sparing normal HSCs. This unbiased systems approach targeting connected nodes exemplifies a novel precision medicine strategy providing evidence that LSCs can be eradicated.
In the primary analysis of the Aspirin in Reducing Events in the Elderly (ASPREE) trial, now published in the Journal, we report that the daily use of aspirin did not provide a benefit with regard to ...the primary end point of disability-free survival among older adults. A numerically higher rate of the secondary end point of death from any cause was observed with aspirin than with placebo.
From 2010 through 2014, we enrolled community-dwelling persons in Australia and the United States who were 70 years of age or older (or ≥65 years of age among blacks and Hispanics in the United States) and did not have cardiovascular disease, dementia, or disability. Participants were randomly assigned to receive 100 mg of enteric-coated aspirin or placebo. Deaths were classified according to the underlying cause by adjudicators who were unaware of trial-group assignments. Hazard ratios were calculated to compare mortality between the aspirin group and the placebo group, and post hoc exploratory analyses of specific causes of death were performed.
Of the 19,114 persons who were enrolled, 9525 were assigned to receive aspirin and 9589 to receive placebo. A total of 1052 deaths occurred during a median of 4.7 years of follow-up. The risk of death from any cause was 12.7 events per 1000 person-years in the aspirin group and 11.1 events per 1000 person-years in the placebo group (hazard ratio, 1.14; 95% confidence interval CI, 1.01 to 1.29). Cancer was the major contributor to the higher mortality in the aspirin group, accounting for 1.6 excess deaths per 1000 person-years. Cancer-related death occurred in 3.1% of the participants in the aspirin group and in 2.3% of those in the placebo group (hazard ratio, 1.31; 95% CI, 1.10 to 1.56).
Higher all-cause mortality was observed among apparently healthy older adults who received daily aspirin than among those who received placebo and was attributed primarily to cancer-related death. In the context of previous studies, this result was unexpected and should be interpreted with caution. (Funded by the National Institute on Aging and others; ASPREE ClinicalTrials.gov number, NCT01038583 .).
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