The distinctive nature of cancer as a disease prompts an exploration of the special characteristics the genes implicated in cancer exhibit. The identification of cancer-associated genes and their ...characteristics is crucial to further our understanding of this disease and enhanced likelihood of therapeutic drug targets success. However, the rate at which cancer genes are being identified experimentally is slow. Applying predictive analysis techniques, through the building of accurate machine learning models, is potentially a useful approach in enhancing the identification rate of these genes and their characteristics. Here, we investigated gene essentiality scores and found that they tend to be higher for cancer-associated genes compared to other protein-coding human genes. We built a dataset of extended gene properties linked to essentiality and used it to train a machine-learning model; this model reached 89% accuracy and > 0.85 for the Area Under Curve (AUC). The model showed that essentiality, evolutionary-related properties, and properties arising from protein-protein interaction networks are particularly effective in predicting cancer-associated genes. We were able to use the model to identify potential candidate genes that have not been previously linked to cancer. Prioritising genes that score highly by our methods could aid scientists in their cancer genes research.
Recent developments in the analysis of amino acid covariation are leading to breakthroughs in protein structure prediction, protein design, and prediction of the interactome. It is assumed that ...observed patterns of covariation are caused by molecular coevolution, where substitutions at one site affect the evolutionary forces acting at neighboring sites. Our theoretical and empirical results cast doubt on this assumption. We demonstrate that the strongest coevolutionary signal is a decrease in evolutionary rate and that unfeasibly long times are required to produce coordinated substitutions. We find that covarying substitutions are mostly found on different branches of the phylogenetic tree, indicating that they are independent events that may or may not be attributable to coevolution. These observations undermine the hypothesis that molecular coevolution is the primary cause of the covariation signal. In contrast, we find that the pairs of residues with the strongest covariation signal tend to have low evolutionary rates, and that it is this low rate that gives rise to the covariation signal. Slowly evolving residue pairs are disproportionately located in the protein's core, which explains covariation methods' ability to detect pairs of residues that are close in three dimensions. These observations lead us to propose the "coevolution paradox": The strength of coevolution required to cause coordinated changes means the evolutionary rate is so low that such changes are highly unlikely to occur. As modern covariation methods may lead to breakthroughs in structural genomics, it is critical to recognize their biases and limitations.
ABSTRACT
JWST is set to transform many areas of astronomy, one of the most exciting is the expansion of the redshift frontier to z > 10. In its first year, alone JWST should discover hundreds of ...galaxies, dwarfing the handful currently known. To prepare for these powerful observational constraints, we use the First Light And Reionization Epoch simulations (flares) to predict the physical and observational properties of the z > 10 population of galaxies accessible to JWST. This is the first time such predictions have been made using a hydrodynamical model validated at low redshift. Our predictions at z = 10 are broadly in agreement with current observational constraints on the far-UV luminosity function and UV continuum slope β, though the observational uncertainties are large. We note tension with recent constraints z ∼ 13 from Harikane et al. (2021) – compared to these constraints, flares predicts objects with the same space density should have an order-of-magnitude lower luminosity, though this is mitigated slightly if dust attenuation is negligible in these systems. Our predictions suggest that in JWST’s first cycle alone, around 600 galaxies should be identified at z > 10, with the first small samples available at z > 13.
Nebular-line emission during the Epoch of Reionization Wilkins, Stephen M; Lovell, Christopher C; Fairhurst, Ciaran ...
Monthly notices of the Royal Astronomical Society,
04/2020, Letnik:
493, Številka:
4
Journal Article
Recenzirano
Odprti dostop
ABSTRACT
Nebular emission lines associated with galactic H ii regions carry information about both physical properties of the ionized gas and the source of ionizing photons as well as providing the ...opportunity of measuring accurate redshifts and thus distances once a cosmological model is assumed. While nebular-line emission has been extensively studied at lower redshift there are currently only few constraints within the epoch of reionization (EoR; z > 6), chiefly due to the lack of sensitive near-IR spectrographs. However, this will soon change with the arrival of the Webb Telescope providing sensitive near-IR spectroscopy covering the rest-frame UV and optical emission of galaxies in the EoR. In anticipation of Webb, we combine the large cosmological hydrodynamical simulation BlueTides with photoionization modelling to predict the nebular emission-line properties of galaxies at z = 8 → 13. We find good agreement with the, albeit limited, existing direct and indirect observational constraints on equivalent widths though poorer agreement with luminosity function constraints.
Porous molecular materials combine benefits such as convenient processability and the possibility for atom-precise structural fine-tuning which makes them remarkable candidates for specialty ...applications in the areas of gas separation, catalysis, and sensing. In order to realize the full potential of these materials and guide future molecular design, knowledge of the transition from molecular properties into materials behavior is essential. In this work, the class of compounds termed cycloparaphenylenes (CPPs)shape-persistent macrocycles with built-in cavities and radially oriented π-systemswas selected as a conceptually simple class of intrinsically porous nanocarbons to serve as a platform for studying the transition from analyte sorption properties of small aggregates to those of bulk materials. In our detailed investigation, two series of CPPs were probed: previously reported hoop-shaped nCPPs and a novel family of all-phenylene figure-8 shaped (lemniscal) bismacrocycles, termed spiron,nCPPs. A series of nanocarbons with different macrocycle sizes and heteroatom content have been prepared by atom-precise organic synthetic methods, and their structural, photophysical, and electronic attributes were disclosed. Detailed experimental studies (X-ray crystallography, gas sorption, and quartz-crystal microbalance measurements) and quantum chemical calculations provided ample evidence for the importance of the solid-state arrangement on the porosity and analyte uptake ability of intrinsically porous molecular nanocarbons. We demonstrate that this molecular design principle, i.e., incorporation of sterically demanding spiro junctions into the backbone of nanohoops, enables the manipulation of solid-state morphology without significantly changing the nature and size of the macrocyclic cavities. As a result, the novel spiron,nCPPs showed a remarkable performance as high affinity material for vapor analyte sensing.
In this study we further investigate the development of abnormal subauroral ion drifts/polarization streams (ASAID/ASAPS) during the magnetically quiet days of 9–10 October 2003. Our main aim is to ...provide direct observational evidence verifying that the Defense Meteorological Satellite Program F15 detected quiet‐time ASAID/ASAPS features developed due to the formation of a magnetospheric cold plasma ripple‐hot ring current interface. By utilizing multisatellite and multi‐instrument Cluster_C2, Polar, and Defense Meteorological Satellite Program observations, we investigate plasma rippling and Pi2 pulsation events. In good agreement with the associated empirical scenario of plasma sheet rippling, we demonstrate with various C2 and Polar events the following observational results. (1) The rippling of the plasma sheet's inner edge was related to the process of cross‐tail current disruption and its earthward propagation. (2) The Pi2 pulsation of the cross‐tail EY field reversed the local convection flow when EY was dawnward directed and thus caused plasma ripples while (3) energy was provided by the earthward flows' braking/deceleration. (4) The ASAID/ASAPS feature's underlying EY is antisunward (or dawnward) and EZ is inward (or earthward). By tracking the cross‐tail current disruptions' tailward (by Cluster_C2) and earthward (by Polar) propagations, almost simultaneously, our results demonstrate also that the convection flows' local reversal by the dawnward EY is a common feature of both the tailward and the earthward flows. This study demonstrates also, with multiple plasmapause and EY detections made by Polar, the multiple and mixed occurrences of ASAID and SAID in the plasmasphere's rippled outer edge.
Key Points
Fluctuating magnetospheric cross‐tail EY rippled the plasma sheet's inner edge when ASAID/ASAPS appeared
Cross‐tail EY fluctuated in the Pi2 frequency range leading to ASAID/ASAPS development
Energy for plasma sheet rippling was provided by braking/decelerating earthward convection flows
We present powderday (available at https://github.com/dnarayanan/powderday), a flexible, fast, open-source dust radiative transfer package designed to interface with both idealized and cosmological ...galaxy formation simulations. powderday builds on fsps stellar population synthesis models, and hyperion dust radiative transfer, and employs yt to interface between different software packages. We include our stellar population synthesis modeling on the fly, allowing significant flexibility in the assumed stellar physics and nebular line emission. The dust content follows either simple observationally motivated prescriptions (i.e., constant dust-to-metals ratios, or dust-to-gas ratios that vary with metallicity), direct modeling from galaxy formation simulations that include dust physics, as well as a novel approach that includes the dust content via learning-based algorithms from the simba cosmological galaxy formation simulation. Active galactic nuclei (AGNs) can additionally be included via a range of prescriptions. The output of these models are broadband (912 -1 mm) spectral energy distributions (SEDs), as well as filter-convolved monochromatic images. powderday is designed to eliminate last-mile efforts by researchers that employ different hydrodynamic galaxy formation models and seamlessly interfaces with gizmo, arepo, gasoline, changa, and enzo. We demonstrate the capabilities of the code via three applications: a model for the star formation rate-infrared luminosity relation in galaxies (including the impact of AGNs), the impact of circumstellar dust around AGB stars on the mid-infrared emission from galaxy SEDs, and the impact of galaxy inclination angle on dust attenuation laws.
Fluorophores are powerful tools for interrogating biological systems. Carbon nanotubes (CNTs) have long been attractive materials for biological imaging due to their near-infrared excitation and ...bright, tunable optical properties. The difficulty in synthesizing and functionalizing these materials with precision, however, has hampered progress in this area. Carbon nanohoops, which are macrocyclic CNT substructures, are carbon nanostructures that possess ideal photophysical characteristics of nanomaterials, while maintaining the precise synthesis of small molecules. However, much work remains to advance the nanohoop class of fluorophores as biological imaging agents. Herein, we report an intracellular targeted nanohoop. This fluorescent nanostructure is noncytotoxic at concentrations up to 50 μM, and cellular uptake investigations indicate internalization through endocytic pathways. Additionally, we employ this nanohoop for two-photon fluorescence imaging, demonstrating a high two-photon absorption cross-section (65 GM) and photostability comparable to a commercial probe. This work further motivates continued investigations into carbon nanohoop photophysics and their biological imaging applications.
Abstract
We present results on the morphological and structural evolution of a total of 3956 galaxies observed with JWST at 1.5 <
z
< 6.5 in the JWST CEERS observations that overlap with the CANDELS ...EGS field. This is the biggest visually classified sample observed with JWST yet, ∼20 times larger than previous studies, and allows us to examine in detail how galaxy structure has changed over this critical epoch. All sources were classified by six individual classifiers using a simple classification scheme aimed at producing disk/spheroid/peculiar classifications, whereby we determine how the relative number of these morphologies has evolved since the Universe’s first billion years. Additionally, we explore structural and quantitative morphology measurements using
Morfometryka
, and show that galaxies with
M
*
> 10
9
M
⊙
at
z
> 3 are not dominated by irregular and peculiar structures, either visually or quantitatively, as previously thought. We find a strong dominance of morphologically selected disk galaxies up to
z
= 6 in this mass range. We also find that the stellar mass and star formation rate densities are dominated by disk galaxies up to
z
∼ 6, demonstrating that most stars in the Universe were likely formed in a disk galaxy. We compare our results to theory to show that the fraction of types we find is predicted by cosmological simulations, and that the Hubble Sequence was already in place as early as one billion years after the Big Bang. Additionally, we make our visual classifications public for the community.
With global efforts to mitigate climate change lagging behind what is necessary to achieve Paris Agreement global warming targets, global mean temperatures are increasing, and weather extremes are ...becoming more frequent and more severe. When mitigation falters, adaptation to current and anticipated future climate conditions becomes increasingly urgent. This study provides a novel collection of adaptive capacity and adaptation readiness indicators, which it aggregates into a composite adaptation index to assess the relative adaptation performance of nations. Adaptation performance is assessed using two complementary techniques, a distance to frontier analysis and a dominance analysis. Developed countries perform relatively well and developing countries perform relatively poorly in both exercises. Adaptation performance is found to be closely and positively related to both national income per capita and greenhouse gas emissions per capita, highlighting the inequities of global adaptation performance. These adaptation inequities are consistent with the IPCC assessment that nations most affected by climate change are those that are least able to adapt and contribute least to the problem, creating a need for assistance from developed countries.
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