Showing papers by "Hungarian Academy of Sciences published in 2019"

Pervasive human-driven decline of life on Earth points to the need for transformative change

Abstract: The human impact on life on Earth has increased sharply since the 1970s, driven by the demands of a growing population with rising average per capita income. Nature is currently supplying more materials than ever before, but this has come at the high cost of unprecedented global declines in the extent and integrity of ecosystems, distinctness of local ecological communities, abundance and number of wild species, and the number of local domesticated varieties. Such changes reduce vital benefits that people receive from nature and threaten the quality of life of future generations. Both the benefits of an expanding economy and the costs of reducing nature's benefits are unequally distributed. The fabric of life on which we all depend-nature and its contributions to people-is unravelling rapidly. Despite the severity of the threats and lack of enough progress in tackling them to date, opportunities exist to change future trajectories through transformative action. Such action must begin immediately, however, and address the root economic, social, and technological causes of nature's deterioration.

The Effect of Minimum Wages on Low-Wage Jobs

Abstract: We estimate the eect of minimum wages on low-wage jobs using 138 prominent state-level minimum wage changes between 1979 and 2016 in the U.S using a dierence-in-dierences approach. We first estimate the eect of the minimum wage increase on employment changes by wage bins throughout the hourly wage distribution. We then focus on the bottom part of the wage distribution and compare the number of excess jobs paying at or slightly above the new minimum wage to the missing jobs paying below it to infer the employment eect. We find that the overall number of low-wage jobs remained essentially unchanged over the five years following the increase. At the same time, the direct eect of the minimum wage on average earnings was amplified by modest wage spillovers at the bottom of the wage distribution. Our estimates by detailed demographic groups show that the lack of job loss is not explained by labor-labor substitution at the bottom of the wage distribution. We also find no evidence of disemployment when we consider higher levels of minimum wages. However, we do find some evidence of reduced employment in tradable sectors. We also show how decomposing the overall employment eect by wage bins allows a transparent way of assessing the plausibility of estimates.

Spontaneous driving forces give rise to protein-RNA condensates with coexisting phases and complex material properties.

Abstract: Phase separation of multivalent protein and RNA molecules underlies the biogenesis of biomolecular condensates such as membraneless organelles. In vivo, these condensates encompass hundreds of distinct types of molecules that typically organize into multilayered structures supporting the differential partitioning of molecules into distinct regions with distinct material properties. The interplay between driven (active) versus spontaneous (passive) processes that are required for enabling the formation of condensates with coexisting layers of distinct material properties remains unclear. Here, we deploy systematic experiments and simulations based on coarse-grained models to show that the collective interactions among the simplest, biologically relevant proteins and archetypal RNA molecules are sufficient for driving the spontaneous emergence of multilayered condensates with distinct material properties. These studies yield a set of rules regarding homotypic and heterotypic interactions that are likely to be relevant for understanding the interplay between active and passive processes that control the formation of functional biomolecular condensates.

The International Pulsar Timing Array: second data release

Abstract: In this paper, we describe the International Pulsar Timing Array second data release, which includes recent pulsar timing data obtained by three regional consortia: the European Pulsar Timing Array, the North American Nanohertz Observatory for Gravitational Waves, and the Parkes Pulsar Timing Array. We analyse and where possible combine high-precision timing data for 65 millisecond pulsars which are regularly observed by these groups. A basic noise analysis, including the processes which are both correlated and uncorrelated in time, provides noise models and timing ephemerides for the pulsars. We find that the timing precisions of pulsars are generally improved compared to the previous data release, mainly due to the addition of new data in the combination. The main purpose of this work is to create the most up-to-date IPTA data release. These data are publicly available for searches for low-frequency gravitational waves and other pulsar science.

Community assessment to advance computational prediction of cancer drug combinations in a pharmacogenomic screen

Abstract: The effectiveness of most cancer targeted therapies is short-lived. Tumors often develop resistance that might be overcome with drug combinations. However, the number of possible combinations is vast, necessitating data-driven approaches to find optimal patient-specific treatments. Here we report AstraZeneca's large drug combination dataset, consisting of 11,576 experiments from 910 combinations across 85 molecularly characterized cancer cell lines, and results of a DREAM Challenge to evaluate computational strategies for predicting synergistic drug pairs and biomarkers. 160 teams participated to provide a comprehensive methodological development and benchmarking. Winning methods incorporate prior knowledge of drug-target interactions. Synergy is predicted with an accuracy matching biological replicates for >60% of combinations. However, 20% of drug combinations are poorly predicted by all methods. Genomic rationale for synergy predictions are identified, including ADAM17 inhibitor antagonism when combined with PIK3CB/D inhibition contrasting to synergy when combined with other PI3K-pathway inhibitors in PIK3CA mutant cells.

Compact radio emission indicates a structured jet was produced by a binary neutron star merger

Abstract: The binary neutron star merger event GW170817 was detected through both electromagnetic radiation and gravitational waves. Its afterglow emission may have been produced by either a narrow relativistic jet or an isotropic outflow. High-spatial-resolution measurements of the source size and displacement can discriminate between these scenarios. We present very-long-baseline interferometry observations, performed 207.4 days after the merger by using a global network of 32 radio telescopes. The apparent source size is constrained to be smaller than 2.5 milli-arc seconds at the 90% confidence level. This excludes the isotropic outflow scenario, which would have produced a larger apparent size, indicating that GW170817 produced a structured relativistic jet. Our rate calculations show that at least 10% of neutron star mergers produce such a jet.

Evaluation of Deep Learning Strategies for Nucleus Segmentation in Fluorescence Images

Abstract: Identifying nuclei is often a critical first step in analyzing microscopy images of cells and classical image processing algorithms are most commonly used for this task Recent developments in deep learning can yield superior accuracy, but typical evaluation metrics for nucleus segmentation do not satisfactorily capture error modes that are relevant in cellular images We present an evaluation framework to measure accuracy, types of errors, and computational efficiency; and use it to compare deep learning strategies and classical approaches We publicly release a set of 23,165 manually annotated nuclei and source code to reproduce experiments and run the proposed evaluation methodology Our evaluation framework shows that deep learning improves accuracy and can reduce the number of biologically relevant errors by half © 2019 The Authors Cytometry Part A published by Wiley Periodicals, Inc on behalf of International Society for Advancement of Cytometry

Gaia Data Release 2. Specific characterisation and validation of all-sky Cepheids and RR Lyrae stars

Abstract: Context. The Gaia second Data Release (DR2) presents a first mapping of full-sky RR Lyrae stars and Cepheids observed by the spacecraft during the initial 22 months of science operations.Aims. The Specific Objects Study (SOS) pipeline, developed to validate and fully characterise Cepheids and RR Lyrae stars (SOS Cep&RRL) observed by Gaia , has been presented in the documentation and papers accompanying the Gaia first Data Release. Here we describe how the SOS pipeline was modified to allow for processing the Gaia multi-band (G , G BP , and G RP ) time-series photometry of all-sky candidate variables and produce specific results for confirmed RR Lyrae stars and Cepheids that are published in the DR2 catalogue.Methods. The SOS Cep&RRL processing uses tools such as the period–amplitude and the period–luminosity relations in the G band. For the analysis of the Gaia DR2 candidates we also used tools based on the G BP and G RP photometry, such as the period–Wesenheit relation in (G , G RP ).Results. Multi-band time-series photometry and characterisation by the SOS Cep&RRL pipeline are published in Gaia DR2 for 150 359 such variables (9575 classified as Cepheids and 140 784 as RR Lyrae stars) distributed throughout the sky. The sample includes variables in 87 globular clusters and 14 dwarf galaxies (the Magellanic Clouds, 5 classical and 7 ultra-faint dwarfs). To the best of our knowledge, as of 25 April 2018, the variability of 50 570 of these sources (350 Cepheids and 50 220 RR Lyrae stars) has not been reported before in the literature, therefore they are likely new discoveries by Gaia . An estimate of the interstellar absorption is published for 54 272 fundamental-mode RR Lyrae stars from a relation based on the G -band amplitude and the pulsation period. Metallicities derived from the Fourier parameters of the light curves are also released for 64 932 RR Lyrae stars and 3738 fundamental-mode classical Cepheids with periods shorter than 6.3 days.

C3 glomerulopathy — understanding a rare complement-driven renal disease

Abstract: The C3 glomerulopathies are a group of rare kidney diseases characterized by complement dysregulation occurring in the fluid phase and in the glomerular microenvironment, which results in prominent complement C3 deposition in kidney biopsy samples. The two major subgroups of C3 glomerulopathy - dense deposit disease (DDD) and C3 glomerulonephritis (C3GN) - have overlapping clinical and pathological features suggestive of a disease continuum. Dysregulation of the complement alternative pathway is fundamental to the manifestations of C3 glomerulopathy, although terminal pathway dysregulation is also common. Disease is driven by acquired factors in most patients - namely, autoantibodies that target the C3 or C5 convertases. These autoantibodies drive complement dysregulation by increasing the half-life of these vital but normally short-lived enzymes. Genetic variation in complement-related genes is a less frequent cause. No disease-specific treatments are available, although immunosuppressive agents and terminal complement pathway blockers are helpful in some patients. Unfortunately, no treatment is universally effective or curative. In aggregate, the limited data on renal transplantation point to a high risk of disease recurrence (both DDD and C3GN) in allograft recipients. Clinical trials are underway to test the efficacy of several first-generation drugs that target the alternative complement pathway.

Integrated evolutionary analysis reveals antimicrobial peptides with limited resistance

Abstract: Antimicrobial peptides (AMPs) are promising antimicrobials, however, the potential of bacterial resistance is a major concern. Here we systematically study the evolution of resistance to 14 chemically diverse AMPs and 12 antibiotics in Escherichia coli. Our work indicates that evolution of resistance against certain AMPs, such as tachyplesin II and cecropin P1, is limited. Resistance level provided by point mutations and gene amplification is very low and antibiotic-resistant bacteria display no cross-resistance to these AMPs. Moreover, genomic fragments derived from a wide range of soil bacteria confer no detectable resistance against these AMPs when introduced into native host bacteria on plasmids. We have found that simple physicochemical features dictate bacterial propensity to evolve resistance against AMPs. Our work could serve as a promising source for the development of new AMP-based therapeutics less prone to resistance, a feature necessary to avoid any possible interference with our innate immune system. Antimicrobial peptides (AMPs) are emerging as drug candidates, but the risk of pathogen resistance is not well understood. Here, the authors investigate AMP resistance evolution in E. coli, finding physicochemical features that make AMPs less prone to resistance and no cross- or horizontally-acquired resistance.

Anti-resonance features of destructive quantum interference in single-molecule thiophene junctions achieved by electrochemical gating

Abstract: Controlling the electrical conductance and in particular the occurrence of quantum interference in single-molecule junctions through gating effects has potential for the realization of high-performance functional molecular devices. In this work we used an electrochemically gated, mechanically controllable break junction technique to tune the electronic behaviour of thiophene-based molecular junctions that show destructive quantum interference features. By varying the voltage applied to the electrochemical gate at room temperature, we reached a conductance minimum that provides direct evidence of charge transport controlled by an anti-resonance arising from destructive quantum interference. Our molecular system enables conductance tuning close to two orders of magnitude within the non-faradaic potential region, which is significantly higher than that achieved with molecules not showing destructive quantum interference. Our experimental results, interpreted using quantum transport theory, demonstrate that electrochemical gating is a promising strategy for obtaining improved in situ control over the electrical performance of interference-based molecular devices.

High-fidelity spin and optical control of single silicon-vacancy centres in silicon carbide

Abstract: Scalable quantum networking requires quantum systems with quantum processing capabilities. Solid state spin systems with reliable spin–optical interfaces are a leading hardware in this regard. However, available systems suffer from large electron–phonon interaction or fast spin dephasing. Here, we demonstrate that the negatively charged silicon-vacancy centre in silicon carbide is immune to both drawbacks. Thanks to its 4A2 symmetry in ground and excited states, optical resonances are stable with near-Fourier-transform-limited linewidths, allowing exploitation of the spin selectivity of the optical transitions. In combination with millisecond-long spin coherence times originating from the high-purity crystal, we demonstrate high-fidelity optical initialization and coherent spin control, which we exploit to show coherent coupling to single nuclear spins with ∼1 kHz resolution. The summary of our findings makes this defect a prime candidate for realising memory-assisted quantum network applications using semiconductor-based spin-to-photon interfaces and coherently coupled nuclear spins. Point defects in solids have potential applications in quantum technologies, but the mechanisms underlying different defects’ performance are not fully established. Nagy et al. show how the wavefunction symmetry of silicon vacancies in SiC leads to promising optical and spin coherence properties.

A Standard Siren Measurement of the Hubble Constant from GW170817 without the Electromagnetic Counterpart

Abstract: We perform a statistical standard siren analysis of GW170817. Our analysis does not utilize knowledge of NGC 4993 as the unique host galaxy of the optical counterpart to GW170817. Instead, we consider each galaxy within the GW170817 localization region as a potential host; combining the redshifts from all of the galaxies with the distance estimate from GW170817 provides an estimate of the Hubble constant, H 0. Considering all galaxies brighter than $0.626{L}_{B}^{\star }$ as equally likely to host a binary neutron star merger, we find ${H}_{0}={77}_{-18}^{+37}$ km s−1 Mpc−1 (maximum a posteriori and 68.3% highest density posterior interval; assuming a flat H 0 prior in the range $\left[10,220\right]$ km s−1 Mpc−1). We explore the dependence of our results on the thresholds by which galaxies are included in our sample, and we show that weighting the host galaxies by stellar mass or star formation rate provides entirely consistent results with potentially tighter constraints. By applying the method to simulated gravitational-wave events and a realistic galaxy catalog we show that, because of the small localization volume, this statistical standard siren analysis of GW170817 provides an unusually informative (top 10%) constraint. Under optimistic assumptions for galaxy completeness and redshift uncertainty, we find that dark binary neutron star measurements of H 0 will converge as $40 \% /\sqrt{(N)}$, where N is the number of sources. While these statistical estimates are inferior to the value from the counterpart standard siren measurement utilizing NGC 4993 as the unique host, ${H}_{0}={76}_{-13}^{+19}$ km s−1 Mpc−1 (determined from the same publicly available data), our analysis is a proof-of-principle demonstration of the statistical approach first proposed by Bernard Schutz over 30 yr ago.

Megaphylogeny resolves global patterns of mushroom evolution

Abstract: Mushroom-forming fungi (Agaricomycetes) have the greatest morphological diversity and complexity of any group of fungi. They have radiated into most niches and fulfil diverse roles in the ecosystem, including wood decomposers, pathogens or mycorrhizal mutualists. Despite the importance of mushroom-forming fungi, large-scale patterns of their evolutionary history are poorly known, in part due to the lack of a comprehensive and dated molecular phylogeny. Here, using multigene and genome-based data, we assemble a 5,284-species phylogenetic tree and infer ages and broad patterns of speciation/extinction and morphological innovation in mushroom-forming fungi. Agaricomycetes started a rapid class-wide radiation in the Jurassic, coinciding with the spread of (sub)tropical coniferous forests and a warming climate. A possible mass extinction, several clade-specific adaptive radiations and morphological diversification of fruiting bodies followed during the Cretaceous and the Paleogene, convergently giving rise to the classic toadstool morphology, with a cap, stalk and gills (pileate-stipitate morphology). This morphology is associated with increased rates of lineage diversification, suggesting it represents a key innovation in the evolution of mushroom-forming fungi. The increase in mushroom diversity started during the Mesozoic-Cenozoic radiation event, an era of humid climate when terrestrial communities dominated by gymnosperms and reptiles were also expanding.

The mesoSPIM initiative: open-source light-sheet microscopes for imaging cleared tissue

Abstract: Light-sheet microscopy is an ideal technique for imaging large cleared samples; however, the community is still lacking instruments capable of producing volumetric images of centimeter-sized cleared samples with near-isotropic resolution within minutes. Here, we introduce the mesoscale selective plane-illumination microscopy initiative, an open-hardware project for building and operating a light-sheet microscope that addresses these challenges and is compatible with any type of cleared or expanded sample ( www.mesospim.org ).

The Generation and Propagation of the Human Alpha Rhythm

Abstract: The alpha rhythm is the longest-studied brain oscillation and has been theorized to play a key role in cognition. Still, its physiology is poorly understood. In this study, we used microelectrodes and macroelectrodes in surgical epilepsy patients to measure the intracortical and thalamic generators of the alpha rhythm during quiet wakefulness. We first found that alpha in both visual and somatosensory cortex propagates from higher-order to lower-order areas. In posterior cortex, alpha propagates from higher-order anterosuperior areas toward the occipital pole, whereas alpha in somatosensory cortex propagates from associative regions toward primary cortex. Several analyses suggest that this cortical alpha leads pulvinar alpha, complicating prevailing theories of a thalamic pacemaker. Finally, alpha is dominated by currents and firing in supragranular cortical layers. Together, these results suggest that the alpha rhythm likely reflects short-range supragranular feedback, which propagates from higher- to lower-order cortex and cortex to thalamus. These physiological insights suggest how alpha could mediate feedback throughout the thalamocortical system.

Tracing the ancestry of modern bread wheats

Abstract: For more than 10,000 years, the selection of plant and animal traits that are better tailored for human use has shaped the development of civilizations. During this period, bread wheat (Triticum aestivum) emerged as one of the world’s most important crops. We use exome sequencing of a worldwide panel of almost 500 genotypes selected from across the geographical range of the wheat species complex to explore how 10,000 years of hybridization, selection, adaptation and plant breeding has shaped the genetic makeup of modern bread wheats. We observe considerable genetic variation at the genic, chromosomal and subgenomic levels, and use this information to decipher the likely origins of modern day wheats, the consequences of range expansion and the allelic variants selected since its domestication. Our data support a reconciled model of wheat evolution and provide novel avenues for future breeding improvement. Exome sequencing of a worldwide panel of 487 wheat genotypes, including landraces, cultivars and modern varieties, sheds light on wheat genomic diversity and the evolution of modern bread wheat.

First Measurement of the Hubble Constant from a Dark Standard Siren using the Dark Energy Survey Galaxies and the LIGO/Virgo Binary-Black-hole Merger GW170814

Abstract: We present a multi-messenger measurement of the Hubble constant H 0 using the binary–black-hole merger GW170814 as a standard siren, combined with a photometric redshift catalog from the Dark Energy Survey (DES). The luminosity distance is obtained from the gravitational wave signal detected by the Laser Interferometer Gravitational-Wave Observatory (LIGO)/Virgo Collaboration (LVC) on 2017 August 14, and the redshift information is provided by the DES Year 3 data. Black hole mergers such as GW170814 are expected to lack bright electromagnetic emission to uniquely identify their host galaxies and build an object-by-object Hubble diagram. However, they are suitable for a statistical measurement, provided that a galaxy catalog of adequate depth and redshift completion is available. Here we present the first Hubble parameter measurement using a black hole merger. Our analysis results in ${H}_{0}={75}_{-32}^{+40}\,\mathrm{km}\,{{\rm{s}}}^{-1}\,{\mathrm{Mpc}}^{-1}$, which is consistent with both SN Ia and cosmic microwave background measurements of the Hubble constant. The quoted 68% credible region comprises 60% of the uniform prior range [20, 140] km s−1 Mpc−1, and it depends on the assumed prior range. If we take a broader prior of [10, 220] km s−1 Mpc−1, we find ${H}_{0}={78}_{-24}^{+96}\,\mathrm{km}\,{{\rm{s}}}^{-1}\,{\mathrm{Mpc}}^{-1}$ (57% of the prior range). Although a weak constraint on the Hubble constant from a single event is expected using the dark siren method, a multifold increase in the LVC event rate is anticipated in the coming years and combinations of many sirens will lead to improved constraints on H 0.

Paradigms of Dynamic Control of Thyroid Hormone Signaling.

Abstract: Thyroid hormone (TH) molecules enter cells via membrane transporters and, depending on the cell type, can be activated (i.e., T4 to T3 conversion) or inactivated (i.e., T3 to 3,3'-diiodo-l-thyronine or T4 to reverse T3 conversion). These reactions are catalyzed by the deiodinases. The biologically active hormone, T3, eventually binds to intracellular TH receptors (TRs), TRα and TRβ, and initiate TH signaling, that is, regulation of target genes and other metabolic pathways. At least three families of transmembrane transporters, MCT, OATP, and LAT, facilitate the entry of TH into cells, which follow the gradient of free hormone between the extracellular fluid and the cytoplasm. Inactivation or marked downregulation of TH transporters can dampen TH signaling. At the same time, dynamic modifications in the expression or activity of TRs and transcriptional coregulators can affect positively or negatively the intensity of TH signaling. However, the deiodinases are the element that provides greatest amplitude in dynamic control of TH signaling. Cells that express the activating deiodinase DIO2 can rapidly enhance TH signaling due to intracellular buildup of T3. In contrast, TH signaling is dampened in cells that express the inactivating deiodinase DIO3. This explains how THs can regulate pathways in development, metabolism, and growth, despite rather stable levels in the circulation. As a consequence, TH signaling is unique for each cell (tissue or organ), depending on circulating TH levels and on the exclusive blend of transporters, deiodinases, and TRs present in each cell. In this review we explore the key mechanisms underlying customization of TH signaling during development, in health and in disease states.

DisProt: intrinsic protein disorder annotation in 2020.

Abstract: The Database of Protein Disorder (DisProt, URL: https://disprot.org) provides manually curated annotations of intrinsically disordered proteins from the literature. Here we report recent developments with DisProt (version 8), including the doubling of protein entries, a new disorder ontology, improvements of the annotation format and a completely new website. The website includes a redesigned graphical interface, a better search engine, a clearer API for programmatic access and a new annotation interface that integrates text mining technologies. The new entry format provides a greater flexibility, simplifies maintenance and allows the capture of more information from the literature. The new disorder ontology has been formalized and made interoperable by adopting the OWL format, as well as its structure and term definitions have been improved. The new annotation interface has made the curation process faster and more effective. We recently showed that new DisProt annotations can be effectively used to train and validate disorder predictors. We believe the growth of DisProt will accelerate, contributing to the improvement of function and disorder predictors and therefore to illuminate the 'dark' proteome.

Microglial cell loss after ischemic stroke favors brain neutrophil accumulation.

Abstract: Stroke attracts neutrophils to the injured brain tissue where they can damage the integrity of the blood–brain barrier and exacerbate the lesion. However, the mechanisms involved in neutrophil transmigration, location and accumulation in the ischemic brain are not fully elucidated. Neutrophils can reach the perivascular spaces of brain vessels after crossing the endothelial cell layer and endothelial basal lamina of post-capillary venules, or migrating from the leptomeninges following pial vessel extravasation and/or a suggested translocation from the skull bone marrow. Based on previous observations of microglia phagocytosing neutrophils recruited to the ischemic brain lesion, we hypothesized that microglial cells might control neutrophil accumulation in the injured brain. We studied a model of permanent occlusion of the middle cerebral artery in mice, including microglia- and neutrophil-reporter mice. Using various in vitro and in vivo strategies to impair microglial function or to eliminate microglia by targeting colony stimulating factor 1 receptor (CSF1R), this study demonstrates that microglial phagocytosis of neutrophils has fundamental consequences for the ischemic tissue. We found that reactive microglia engulf neutrophils at the periphery of the ischemic lesion, whereas local microglial cell loss and dystrophy occurring in the ischemic core are associated with the accumulation of neutrophils first in perivascular spaces and later in the parenchyma. Accordingly, microglia depletion by long-term treatment with a CSF1R inhibitor increased the numbers of neutrophils and enlarged the ischemic lesion. Hence, microglial phagocytic function sets a critical line of defense against the vascular and tissue damaging capacity of neutrophils in brain ischemia.

Overview of first Wendelstein 7-X high-performance operation

Abstract: The optimized superconducting stellarator device Wendelstein 7-X (with major radius $R=5.5\,\mathrm{m}$, minor radius $a=0.5\,\mathrm{m}$, and $30\,\mathrm{m}^3$ plasma volume) restarted operation after the assembly of a graphite heat shield and 10 inertially cooled island divertor modules. This paper reports on the results from the first high-performance plasma operation. Glow discharge conditioning and ECRH conditioning discharges in helium turned out to be important for density and edge radiation control. Plasma densities of $1-4.5\cdot 10^{19}\,\mathrm{m}^{-3}$ with central electron temperatures $5-10\,\mathrm{keV}$ were routinely achieved with hydrogen gas fueling, frequently terminated by a radiative collapse. Plasma densities up to $1.4\cdot 10^{20}\,\mathrm{m}^{-3}$were reached with hydrogen pellet injection and helium gas fueling. Here, the ions are indirectly heated, and at a central density of $8\cdot 10^{19}\,\mathrm{m}^{-3}$ a temperature of $3.4\,\mathrm{keV}$ with $T_e/T_i=1$ was accomplished, which corresponds to $nT_i(0)\tau_E=6.4\cdot 10^{19}\,\mathrm{keVs}/\mathrm{m}^3$ with a peak diamagnetic energy of $1.1\,\mathrm{MJ}$. The discharge behaviour has further improved with boronization of the wall. After boronization, the oxygen impurity content was reduced by a factor of 10, the carbon impurity content by a factor of 5. The reduced (edge) plasma radiation level gives routinely access to higher densities without radiation collapse, e.g. well above $1\cdot 10^{20}\,\mathrm{m}^{-2}$ line integrated density and $T_e=T_i=2\,\mathrm{keV}$ central temperatures at moderate ECRH power. Both X2 and O2 mode ECRH schemes were successfully applied. Core turbulence was measured with a phase contrast imaging diagnostic and suppression of turbulence during pellet injection was observed.

Ab initio theory of the nitrogen-vacancy center in diamond

Abstract: Abstract The nitrogen-vacancy (NV) center in diamond is a solid-state defect qubit with favorable coherence time up to room temperature, which could be harnessed in several quantum-enhanced sensor and quantum communication applications, and has a potential in quantum simulation and computing. The quantum control largely depends on the intricate details about the electronic structure and states of the NV center, the radiative and nonradiative rates between these states, and the coupling of these states to external spins, electric, magnetic, and strain fields, and temperature. This review shows how first-principles calculations contributed to understanding the properties of the NV center and briefly discusses the issues to be solved toward the full ab initio description of solid-state defect qubits.

HPV vaccination in a context of public mistrust and uncertainty: a systematic literature review of determinants of HPV vaccine hesitancy in Europe

Abstract: Europe is increasingly described as the region in the world with the least confidence in vaccination, and particularly in the safety of vaccines. The aim of this systematic literature review was to gather and summarise all peer-reviewed and grey literature published about determinants of Human Papillomavirus (HPV) vaccine hesitancy in Europe. Ten thematic categories were identified across the 103 articles which were included in the review. Participants from European studies most commonly reported issues with the quantity and quality of information available about HPV vaccination; followed by concerns about potential side effects of the vaccine; and mistrust of health authorities, healthcare workers, and new vaccines. Comparative analyses indicated that confidence determinants differed by country and population groups. This evidence supports the need to develop context-specific interventions to improve confidence in HPV vaccination and design community engagement strategies aiming to build public trust.

ROCplot.org: Validating predictive biomarkers of chemotherapy/hormonal therapy/anti-HER2 therapy using transcriptomic data of 3,104 breast cancer patients.

Abstract: Systemic therapy of breast cancer can include chemotherapy, hormonal therapy and targeted therapy. Prognostic biomarkers are able to predict survival and predictive biomarkers are able to predict therapy response. In this report, we describe the initial release of the first available online tool able to identify gene expression-based predictive biomarkers using transcriptomic data of a large set of breast cancer patients. Published gene expression data of 36 publicly available datasets were integrated with treatment data into a unified database. Response to therapy was determined using either author-reported pathological complete response data (n = 1,775) or relapse-free survival status at 5 years (n = 1,329). Treatment data includes chemotherapy (n = 2,108), endocrine therapy (n = 971) and anti-human epidermal growth factor receptor 2 (HER2) therapy (n = 267). The transcriptomic database includes 20,089 unique genes and 54,675 probe sets. Gene expression and therapy response are compared using receiver operating characteristics and Mann-Whitney tests. We demonstrate the utility of the pipeline by cross-validating 23 paclitaxel resistance-associated genes in different molecular subtypes of breast cancer. An additional set of established biomarkers including TP53 for chemotherapy in Luminal breast cancer (p = 1.01E-19, AUC = 0.769), HER2 for trastuzumab therapy (p = 8.4E-04, AUC = 0.629) and PGR for hormonal therapy (p = 8.6E-05, AUC = 0.7), are also endorsed. The tool is designed to validate and rank new predictive biomarker candidates in real time. By analyzing the selected genes in a large set of independent patients, one can select the most robust candidates and quickly eliminate those that are most likely to fail in a clinical setting. The analysis tool is accessible at www.rocplot.org.

TESS Discovery of an Ultra-short-period Planet around the Nearby M Dwarf LHS 3844

Abstract: Data from the newly commissioned Transiting Exoplanet Survey Satellite has revealed a "hot Earth" around LHS 3844, an M dwarf located 15 pc away. The planet has a radius of 1.303 ± 0.022 R⊕ and orbits the star every 11 hr. Although the existence of an atmosphere around such a strongly irradiated planet is questionable, the star is bright enough (I = 11.9, K = 9.1) for this possibility to be investigated with transit and occultation spectroscopy. The star's brightness and the planet's short period will also facilitate the measurement of the planet's mass through Doppler spectroscopy.