Limits to the spread of an obligate social cheater in the social amoeba Dictyostelium discoideum

Cooperation is widespread across life, but its existence can be threatened by exploitation. Social cheaters can be obligate, incapable of contributing to a necessary function, so that spread of the cheater leads to loss of the function. In the social amoeba Dictyostelium discoideum, obligate social cheaters cannot become dead stalk cells that lift spores up for dispersal, but instead depend on forming chimeras with fully functional altruistic individuals for forming a stalk. Obligate cheaters in D. discoideum are known to pay the cost of being unable to form fruiting bodies on their own. In this study we discovered that there are two additional costs that can apply to obligate cheaters. Even when there are wild-type cells to parasitize, the chimeric fruiting bodies that result have shorter stalks that are disadvantaged in spore dispersal. Furthermore, we found that obligate cheaters were overrepresented among spore cells in chimeras only when they were at low frequencies. Failure to develop into viable fruiting bodies on their own, negative frequency-dependent cheating, and shorter fruiting bodies represent three limits on obligate social cheating so it is not surprising that obligate cheaters have not been found in nature

Some viable models for digital public-interest journalism

The supply of public interest journalism that serves the needs of citizens in a democratic society has always been scarce in the media marketplace when compared with sensationalism, gossip, entertainment, propaganda, and misinformation. This scarce commodity, whose market value lies in its credibility and depends on costly investments of time and money in professional research, has frequently required a subsidy, which for more than a century was provided by advertising. Now that this subsidy has mostly been devoured by technological platforms such as Google and Facebook, the industry and profession are developing new models focused on user needs and wants with a trend toward public service rather than profit. This paper uses deductive and critical methodologies to identify the most promising business models used by media companies to counteract the decline in public-interest journalism. Our proposal is that an appropriate business model can be the best way to revitalize media companies. The research is based on Chesbrough’s business model framework applied to 20 leading digital news publications from 16 countries. In addition, we analyze how Covid-19 has impacted those business models

Adenoviruses in Fecal Samples from Asymptomatic Rhesus Macaques, United States

Isolates contained fiber genes similar to those of adenovirus strains that cause infectious diarrhea in humans

Analysis of Granular Flow in a Pebble-Bed Nuclear Reactor

Pebble-bed nuclear reactor technology, which is currently being revived around the world, raises fundamental questions about dense granular flow in silos. A typical reactor core is composed of graphite fuel pebbles, which drain very slowly in a continuous refueling process. Pebble flow is poorly understood and not easily accessible to experiments, and yet it has a major impact on reactor physics. To address this problem, we perform full-scale, discrete-element simulations in realistic geometries, with up to 440,000 frictional, viscoelastic 6cm-diameter spheres draining in a cylindrical vessel of diameter 3.5m and height 10m with bottom funnels angled at 30 degrees or 60 degrees. We also simulate a bidisperse core with a dynamic central column of smaller graphite moderator pebbles and show that little mixing occurs down to a 1:2 diameter ratio. We analyze the mean velocity, diffusion and mixing, local ordering and porosity (from Voronoi volumes), the residence-time distribution, and the effects of wall friction and discuss implications for reactor design and the basic physics of granular flow.Comment: 18 pages, 21 figure

Cost effectiveness analysis of clinically driven versus routine laboratory monitoring of antiretroviral therapy in Uganda and Zimbabwe.

BACKGROUND: Despite funding constraints for treatment programmes in Africa, the costs and economic consequences of routine laboratory monitoring for efficacy and toxicity of antiretroviral therapy (ART) have rarely been evaluated. METHODS: Cost-effectiveness analysis was conducted in the DART trial (ISRCTN13968779). Adults in Uganda/Zimbabwe starting ART were randomised to clinically-driven monitoring (CDM) or laboratory and clinical monitoring (LCM); individual patient data on healthcare resource utilisation and outcomes were valued with primary economic costs and utilities. Total costs of first/second-line ART, routine 12-weekly CD4 and biochemistry/haematology tests, additional diagnostic investigations, clinic visits, concomitant medications and hospitalisations were considered from the public healthcare sector perspective. A Markov model was used to extrapolate costs and benefits 20 years beyond the trial. RESULTS: 3316 (1660LCM;1656CDM) symptomatic, immunosuppressed ART-naive adults (median (IQR) age 37 (32,42); CD4 86 (31,139) cells/mm(3)) were followed for median 4.9 years. LCM had a mean 0.112 year (41 days) survival benefit at an additional mean cost of $765 [95$7386 [3277,dominated] per life-year gained and $7793 [4442,39179] per quality-adjusted life year gained. Routine toxicity tests were prominent cost-drivers and had no benefit. With 12-weekly CD4 monitoring from year 2 on ART, low-cost second-line ART, but without toxicity monitoring, CD4 test costs need to fall below$3.78 to become cost-effective (<3xper-capita GDP, following WHO benchmarks). CD4 monitoring at current costs as undertaken in DART was not cost-effective in the long-term. CONCLUSIONS: There is no rationale for routine toxicity monitoring, which did not affect outcomes and was costly. Even though beneficial, there is little justification for routine 12-weekly CD4 monitoring of ART at current test costs in low-income African countries. CD4 monitoring, restricted to the second year on ART onwards, could be cost-effective with lower cost second-line therapy and development of a cheaper, ideally point-of-care, CD4 test

Implementing a Registry Federation for Materials Science Data Discovery

As a result of a number of national initiatives, we are seeing rapid growth in the data important to materials science that are available over the web. Consequently, it is becoming increasingly difficult for researchers to learn what data are available and how to access them. To address this problem, the Research Data Alliance (RDA) Working Group for International Materials Science Registries (IMRR) was established to bring together materials science and information technology experts to develop an international federation of registries that can be used for global discovery of data resources for materials science. A resource registry collects high-level metadata descriptions of resources such as data repositories, archives, websites, and services that are useful for data-driven research. By making the collection searchable, it aids scientists in industry, universities, and government laboratories to discover data relevant to their research and work interests. We present the results of our successful piloting of a registry federation for materials science data discovery. In particular, we out a blueprint for creating such a federation that is capable of amassing a global view of all available materials science data, and we enumerate the requirements for the standards that make the registries interoperable within the federation. These standards include a protocol for exchanging resource descriptions and a standard metadata schema for encoding those descriptions. We summarize how we leveraged an existing standard (OAI-PMH) for metadata exchange. Finally, we review the registry software developed to realize the federation and describe the user experience

ACT-Discover: identifying karyotype heterogeneity in pancreatic cancer evolution using ctDNA

Circulating tumour DNA; Pancreatic cancer; Tumour evolutionADN tumoral circulant; Càncer de pàncrees; Evolució tumoralADN tumoral circulante; Cáncer de páncreas; Evolución tumoralBackground Liquid biopsies and the dynamic tracking of somatic mutations within circulating tumour DNA (ctDNA) can provide insight into the dynamics of cancer evolution and the intra-tumour heterogeneity that fuels treatment resistance. However, identifying and tracking dynamic changes in somatic copy number alterations (SCNAs), which have been associated with poor outcome and metastasis, using ctDNA is challenging. Pancreatic adenocarcinoma is a disease which has been considered to harbour early punctuated events in its evolution, leading to an early fitness peak, with minimal further subclonal evolution. Methods To interrogate the role of SCNAs in pancreatic adenocarcinoma cancer evolution, we applied whole-exome sequencing of 55 longitudinal cell-free DNA (cfDNA) samples taken from 24 patients (including 8 from whom a patient-derived xenograft (PDX) was derived) with metastatic disease prospectively recruited into a clinical trial. We developed a method, Aneuploidy in Circulating Tumour DNA (ACT-Discover), that leverages haplotype phasing of paired tumour biopsies or PDXs to identify SCNAs in cfDNA with greater sensitivity. Results SCNAs were observed within 28 of 47 evaluable cfDNA samples. Of these events, 30% could only be identified by harnessing the haplotype-aware approach leveraged in ACT-Discover. The exceptional purity of PDX tumours enabled near-complete phasing of genomic regions in allelic imbalance, highlighting an important auxiliary function of PDXs. Finally, although the classical model of pancreatic cancer evolution emphasises the importance of early, homogenous somatic events as a key requirement for cancer development, ACT-Discover identified substantial heterogeneity of SCNAs, including parallel focal and arm-level events, affecting different parental alleles within individual tumours. Indeed, ongoing acquisition of SCNAs was identified within tumours throughout the disease course, including within an untreated metastatic tumour. Conclusions This work demonstrates the power of haplotype phasing to study genomic variation in cfDNA samples and reveals undiscovered intra-tumour heterogeneity with important scientific and clinical implications. Implementation of ACT-Discover could lead to important insights from existing cohorts or underpin future prospective studies seeking to characterise the landscape of tumour evolution through liquid biopsy.This work was supported by the European Research Council (ERC) no. 670582 (Call: ERC-2014-ADG) to Dr. Hidalgo. R.A.T is supported by the Miguel Servet-II Research Award and the 2021 call for Proyectos de generación de conocimiento by the Institute of Health Carlos III (ISCIII) of the Ministry of Economy [CP17/00199], the Olga Torres Foundation Award to emerging researchers [2017, to R.A.T, 2601], and received research grants from Novartis, Astrazeneca, and Beigene pharmaceuticals, not related to this study. N.M is a Sir Henry Dale Fellow, jointly funded by the Wellcome Trust and the Royal Society (Grant Number 211179/Z/18/Z), and also receives funding from Cancer Research UK Lung Cancer Centre of Excellence, Rosetrees, and the NIHR BRC at University College London Hospitals

Radiative Electroweak Symmetry Breaking in a Little Higgs Model

We present a new Little Higgs model, motivated by the deconstruction of a five-dimensional gauge-Higgs model. The approximate global symmetry is $SO(5)_0\times SO(5)_1$, breaking to $SO(5)$, with a gauged subgroup of $[SU(2)_{0L}\times U(1)_{0R}]\times O(4)_1$, breaking to $SU(2)_L \times U(1)_Y$. Radiative corrections produce an additional small vacuum misalignment, breaking the electroweak symmetry down to $U(1)_{EM}$. Novel features of this model are: the only un-eaten pseudo-Goldstone boson in the effective theory is the Higgs boson; the model contains a custodial symmetry, which ensures that $\hat{T}=0$ at tree-level; and the potential for the Higgs boson is generated entirely through one-loop radiative corrections. A small negative mass-squared in the Higgs potential is obtained by a cancellation between the contribution of two heavy partners of the top quark, which is readily achieved over much of the parameter space. We can then obtain both a vacuum expectation value of $v=246$ GeV and a light Higgs boson mass, which is strongly correlated with the masses of the two heavy top quark partners. For a scale of the global symmetry breaking of $f=1$ TeV and using a single cutoff for the fermion loops, the Higgs boson mass satisfies 120 GeV $\lesssim M_H\lesssim150$ GeV over much of the range of parameter space. For $f$ raised to 10 TeV, these values increase by about 40 GeV. Effects at the ultraviolet cutoff scale may also raise the predicted values of the Higgs boson mass, but the model still favors $M_H\lesssim 200$ GeV.Comment: 32 pages, 10 figures, JHEP style. Version accepted for publication in JHEP. Includes additional discussion of sensitivity to UV effects and fine-tuning, revised Fig. 9, added appendix and additional references

The impact of secondary forest regeneration on ground-dwelling ant communities in the Tropical Andes

Natural regeneration of abandoned farmland provides an important opportunity to contribute to global reforestation targets, including the Bonn Challenge. Of particular importance are the montane tropics, where a long history of farming, frequently on marginal soils, has rendered many ecosystems highly degraded and hotspots of extinction risk. Ants play crucial roles in ecosystem functioning, and a key question is how time since abandonment and elevation (and inherent temperature gradients therein) affect patterns of ant recovery within secondary forest systems. Focusing on the Colombian Andes across a 1300 m altitudinal gradient and secondary forest (2–30 years) recovering on abandoned cattle pastures, we find that over time ant community composition and species richness recovered towards that of primary forest. However, these relationships are strongly dependent on elevation with the more open and warmer pasturelands supporting more ants than either primary or secondary forest at a particular elevation. The loss of species richness and change in species composition with elevation is less severe in pasture than forests, suggesting that conditions within pasture and its remaining scattered trees, hedgerows and forest fragments, are more favourable for some species, which are likely in or near thermal debt. Promoting and protecting natural regenerating forests over the long term in the montane tropics will likely offer significant potential for returning ant communities towards primary forest levels

Composition of UHECR and the Pierre Auger Observatory Spectrum

We fit the recently published Pierre Auger ultra-high energy cosmic ray spectrum assuming that either nucleons or nuclei are emitted at the sources. We consider the simplified cases of pure proton, or pure oxygen, or pure iron injection. We perform an exhaustive scan in the source evolution factor, the spectral index, the maximum energy of the source spectrum Z E_{max}, and the minimum distance to the sources. We show that the Pierre Auger spectrum agrees with any of the source compositions we assumed. For iron, in particular, there are two distinct solutions with high and low E_{max} (e.g. 6.4 10^{20} eV and 2 10^{19} eV) respectively which could be distinguished by either a large fraction or the near absence of proton primaries at the highest energies. We raise the possibility that an iron dominated injected flux may be in line with the latest composition measurement from the Pierre Auger Observatory where a hint of heavy element dominance is seen.Comment: 19 pages, 6 figures (33 panels)- Uses iopart.cls and iopart12.clo- In version 2: addition of a few sentences and two reference