What role does playful behaviour and playful thought take in animal and human development? How does play relate to creativity and, in turn, to innovation? Unravelling the different meanings of ...'play', this book focuses on non-aggressive playful play. The authors emphasise its significance for development and evolution, before examining the importance of playfulness in creativity. This discussion sheds new light on the links between creativity and innovation, distinguishing between the generation of novel behaviour and ideas on the one hand, and the implementation of these novelties on the other. The authors then turn to the role of play in the development of the child and to parallels between play, humour and dreaming, along with the altered states of consciousness generated by some psychoactive drugs. A final chapter looks forward to future research and to what remains to be discovered in this fascinating and important field.
Metastases are the leading cause of mortality in patients with cancer. Metastasis formation requires cancer cells to adapt their cellular phenotype. However, how metabolism supports this adaptation ...of cancer cells is poorly defined. We use 2D versus 3D cultivation to induce a shift in the cellular phenotype of breast cancer cells. We discover that proline catabolism via proline dehydrogenase (Prodh) supports growth of breast cancer cells in 3D culture. Subsequently, we link proline catabolism to in vivo metastasis formation. In particular, we find that PRODH expression and proline catabolism is increased in metastases compared to primary breast cancers of patients and mice. Moreover, inhibiting Prodh is sufficient to impair formation of lung metastases in the orthotopic 4T1 and EMT6.5 mouse models, without adverse effects on healthy tissue and organ function. In conclusion, we discover that Prodh is a potential drug target for inhibiting metastasis formation.
In July 2022, the ongoing monkeypox (MPX) outbreak was declared a public health emergency of international concern. Modified vaccinia Ankara-Bavarian Nordic (MVA-BN, also known as Imvamune, JYNNEOS ...or Imvanex) is a third-generation smallpox vaccine that is authorized and in use as a vaccine against MPX. To date, there are no data showing MPX virus (MPXV)-neutralizing antibodies in vaccinated individuals nor vaccine efficacy against MPX. Here we show that MPXV-neutralizing antibodies can be detected after MPXV infection and after historic smallpox vaccination. However, a two-shot MVA-BN immunization series in non-primed individuals yields relatively low levels of MPXV-neutralizing antibodies. Dose-sparing of an MVA-based influenza vaccine leads to lower MPXV-neutralizing antibody levels, whereas a third vaccination with the same MVA-based vaccine significantly boosts the antibody response. As the role of MPXV-neutralizing antibodies as a correlate of protection against disease and transmissibility is currently unclear, we conclude that cohort studies following vaccinated individuals are necessary to assess vaccine efficacy in at-risk populations.
Science and technologies based on terahertz frequency electromagnetic radiation (100 GHz-30 THz) have developed rapidly over the last 30 years. For most of the 20th Century, terahertz radiation, then ...referred to as sub-millimeter wave or far-infrared radiation, was mainly utilized by astronomers and some spectroscopists. Following the development of laser based terahertz time-domain spectroscopy in the 1980s and 1990s the field of THz science and technology expanded rapidly, to the extent that it now touches many areas from fundamental science to 'real world' applications. For example THz radiation is being used to optimize materials for new solar cells, and may also be a key technology for the next generation of airport security scanners. While the field was emerging it was possible to keep track of all new developments, however now the field has grown so much that it is increasingly difficult to follow the diverse range of new discoveries and applications that are appearing. At this point in time, when the field of THz science and technology is moving from an emerging to a more established and interdisciplinary field, it is apt to present a roadmap to help identify the breadth and future directions of the field. The aim of this roadmap is to present a snapshot of the present state of THz science and technology in 2017, and provide an opinion on the challenges and opportunities that the future holds. To be able to achieve this aim, we have invited a group of international experts to write 18 sections that cover most of the key areas of THz science and technology. We hope that The 2017 Roadmap on THz science and technology will prove to be a useful resource by providing a wide ranging introduction to the capabilities of THz radiation for those outside or just entering the field as well as providing perspective and breadth for those who are well established. We also feel that this review should serve as a useful guide for government and funding agencies.
Noroviruses are genetically diverse RNA viruses associated with acute gastroenteritis in mammalian hosts. Phylogenetically, they can be segregated into different genogroups as well as P ...(polymerase)-groups and further into genotypes and P-types based on amino acid diversity of the complete VP1 gene and nucleotide diversity of the RNA-dependent RNA polymerase (RdRp) region of ORF1, respectively. In recent years, several new noroviruses have been reported that warrant an update of the existing classification scheme. Using previously described 2× standard deviation (sd) criteria to group sequences into separate clusters, we expanded the number of genogroups to 10 (GI-GX) and the number of genotypes to 48 (9 GI, 27 GII, 3 GIII, 2 GIV, 2 GV, 2 GVI and 1 genotype each for GVII, GVIII, GIX formerly GII.15 and GX). Viruses for which currently only one sequence is available in public databases were classified into tentative new genogroups (GNA1 and GNA2) and genotypes (GII.NA1, GII.NA2 and GIV.NA1) with their definitive assignment awaiting additional related sequences. Based on nucleotide diversity in the RdRp region, noroviruses can be divided into 60 P-types (14 GI, 37 GII, 2 GIII, 1 GIV, 2 GV, 2 GVI, 1 GVII and 1 GX), 2 tentative P-groups and 14 tentative P-types. Future classification and nomenclature updates will be based on complete genome sequences and will be coordinated and disseminated by the international norovirus classification-working group.
Within four nearby (d < 160 pc) molecular clouds, we statistically evaluated the structure of the interstellar magnetic field, projected on the plane of the sky and integrated along the line of ...sight, as inferred from the polarized thermal emission of Galactic dust observed by Planck at 353 GHz and from the optical and near-infrared polarization of background starlight. We compared the dispersion of the field orientation directly in vicinities with an area equivalent to that subtended by the Planck effective beam at 353 GHz (10′) and using the second-order structure functions of the field orientation angles. We found that the average dispersion of the starlight-inferred field orientations within 10′-diameter vicinities is less than 20°, and that at these scales the mean field orientation is on average within 5° of that inferred from the submillimetre polarization observations in the considered regions. We also found that the dispersion of starlight polarization orientations and the polarization fractions within these vicinities are well reproduced by a Gaussian model of the turbulent structure of the magnetic field, in agreement with the findings reported by the Planck Collaboration at scales ℓ > 10′ and for comparable column densities. At scales ℓ > 10′, we found differences of up to 14.̊7 between the second-order structure functions obtained from starlight and submillimetre polarization observations in the same positions in the plane of the sky, but comparison with a Gaussian model of the turbulent structure of the magnetic field indicates that these differences are small and are consistent with the difference in angular resolution between both techniques. The differences between the second-order structure functions calculated with each technique suggests that the increase in the angular resolution obtained with the starlight polarization observations does not introduce significant corrections to the dispersion of polarization orientations used in the calculation of the molecular-cloud-scale magnetic field strengths reported in previous studies by the Planck Collaboration.
The Balloon-borne Large Aperture Submillimeter Telescope (BLAST) is a suborbital surveying experiment designed to study the evolutionary history and processes of star formation in local galaxies ...(including the Milky Way) and galaxies at cosmological distances. The BLAST continuum camera, which consists of 270 detectors distributed between three arrays, observes simultaneously in broadband (30%) spectral windows at 250, 350, and 500 mum. The optical design is based on a 2 m diameter telescope, providing a diffraction-limited resolution of 30 super(image ) at 250 mum. The gondola pointing system enables raster mapping of arbitrary geometry, with a repeatable positional accuracy of image30 super(image ); postflight pointing reconstruction to image5 super(image ) rms is achieved. The onboard telescope control software permits autonomous execution of a preselected set of maps, with the option of manual override. In this paper we describe the primary characteristics and measured in-flight performance of BLAST. BLAST performed a test flight in 2003 and has since made two scientifically productive long- duration balloon flights: a 100 hr flight from ESRANGE (Kiruna), Sweden to Victoria Island, northern Canada in 2005 June; and a 250 hr, circumpolar flight from McMurdo Station, Antarctica, in 2006 December.
High-resolution, multiplexed experiments are a staple in cellular imaging. Analogous experiments in animals are challenging, however, due to substantial scattering and autofluorescence in tissue at ...visible (350-700 nm) and near-infrared (700-1,000 nm) wavelengths. Here, we enable real-time, non-invasive multicolour imaging experiments in animals through the design of optical contrast agents for the shortwave infrared (SWIR, 1,000-2,000 nm) region and complementary advances in imaging technologies. We developed tunable, SWIR-emissive flavylium polymethine dyes and established relationships between structure and photophysical properties for this class of bright SWIR contrast agents. In parallel, we designed an imaging system with variable near-infrared/SWIR excitation and single-channel detection, facilitating video-rate multicolour SWIR imaging for optically guided surgery and imaging of awake and moving mice with multiplexed detection. Optimized dyes matched to 980 nm and 1,064 nm lasers, combined with the clinically approved indocyanine green, enabled real-time, three-colour imaging with high temporal and spatial resolutions.
We analyze the physical parameters of interstellar filaments that we describe by an idealized model of isothermal self-gravitating infinite cylinder in pressure equilibrium with the ambient medium. ...Their gravitational state is characterized by the ratio fcyl of their mass line density to the maximum possible value for a cylinder in a vacuum. Equilibrium solutions exist only for fcyl < 1. This ratio is used in providing analytical expressions for the central density, the radius, the profile of the column density, the column density through the cloud centre, and the FWHM. The dependence of the physical properties on external pressure and temperature is discussed and directly compared to the case of pressure-confined isothermal self-gravitating spheres. Comparison with recent observations of the FWHM and the central column density NH(0) show good agreement and suggest a filament temperature of ~10 K and an external pressure in the range 1.5 × 104 K cm-3 to 5 × 104 K cm-3. Stability considerations indicate that interstellar filaments become increasingly gravitationally unstable with mass line ratio fcyl approaching unity. For intermediate fcyl > 0.5 the instabilities should promote core formation through compression, with a separation of about five times the FWHM. We discuss the nature of filaments with high mass line densities and their relevance to gravitational fragmentation and star formation.
Forests play a crucial role in the global carbon (C) cycle by storing and sequestering a substantial amount of C in the terrestrial biosphere. Due to temporal dynamics in climate and vegetation ...activity, there are significant regional variations in carbon dioxide (CO2) fluxes between the biosphere and atmosphere in forests that are affecting the global C cycle. Current forest CO2 flux dynamics are controlled by instantaneous climate, soil, and vegetation conditions, which carry legacy effects from disturbances and extreme climate events. Our level of understanding from the legacies of these processes on net CO2 fluxes is still limited due to their complexities and their long-term effects. Here, we combined remote sensing, climate, and eddy-covariance flux data to study net ecosystem CO2 exchange (NEE) at 185 forest sites globally. Instead of commonly used non-dynamic statistical methods, we employed a type of recurrent neural network (RNN), called Long Short-Term Memory network (LSTM) that captures information from the vegetation and climate's temporal dynamics. The resulting data-driven model integrates interannual and seasonal variations of climate and vegetation by using Landsat and climate data at each site. The presented LSTM algorithm was able to effectively describe the overall seasonal variability (Nash-Sutcliffe efficiency, NSE = 0.66) and across-site (NSE = 0.42) variations in NEE, while it had less success in predicting specific seasonal and interannual anomalies (NSE = 0.07). This analysis demonstrated that an LSTM approach with embedded climate and vegetation memory effects outperformed a non-dynamic statistical model (i.e. Random Forest) for estimating NEE. Additionally, it is shown that the vegetation mean seasonal cycle embeds most of the information content to realistically explain the spatial and seasonal variations in NEE. These findings show the relevance of capturing memory effects from both climate and vegetation in quantifying spatio-temporal variations in forest NEE.
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