Taras Shevchenko National University of Kyiv

Identifying and purchasing new small molecules to test in biological assays are enabling for ligand discovery, but as purchasable chemical space continues to grow into the tens of billions based on inexpensive make-on-demand compounds, simply searching this space becomes a major challenge. We have therefore developed ZINC20, a new version of ZINC with two major new features: billions of new molecules and new methods to search them. As a fully enumerated database, ZINC can be searched precisely using explicit atomic-level graph-based methods, such as SmallWorld for similarity and Arthor for pattern and substructure search, as well as 3D methods such as docking. Analysis of the new make-on-demand compound sets by these and related tools reveals startling features. For instance, over 97% of the core Bemis-Murcko scaffolds in make-on-demand libraries are unavailable from "in-stock" collections. Correspondingly, the number of new Bemis-Murcko scaffolds is rising almost as a linear fraction of the elaborated molecules. Thus, an 88-fold increase in the number of molecules in the make-on-demand versus the in-stock sets is built upon a 16-fold increase in the number of Bemis-Murcko scaffolds. The make-on-demand library is also more structurally diverse than physical libraries, with a massive increase in disc- and sphere-like shaped molecules. The new system is freely available at zinc20.docking.org.

An increasing need of nanotechnology in various industries may cause a huge environment dispersion of nanoparticles in coming years. A concern about nanoparticles interaction with flora and fauna is raised due to a growing load of it in the environment. In recent years, several investigators have shown impact of nanoparticles on plant growth and their accumulation in food source. This review examines the research performed in the last decade to show how metal and metal oxide nanoparticles are influencing the plant metabolism. We addressed here, the impact of nanoparticle on plant in relation to its size, concentration, and exposure methodology. Based on the available reports, we proposed oxidative burst as a general mechanism through which the toxic effects of nanoparticles are spread in plants. This review summarizes the current understanding and the future possibilities of plant-nanoparticle research.

The recently initiated Arecibo Legacy Fast ALFA (ALFALFA) survey aims to map 7000 square degrees of the high galactic latitude sky visible from Arecibo, providing a HI line spectral database covering the redshift range between -1600 km/s and 18,000 km/s with 5 km/s resolution. Exploiting Arecibo's large collecting area and small beam size, ALFALFA is specifically designed to probe the faint end of the HI mass function in the local universe and will provide a census of HI in the surveyed sky area to faint flux limits, making it especially useful in synergy with wide area surveys conducted at other wavelengths. ALFALFA will also provide the basis for studies of the dynamics of galaxies within the Local and nearby superclusters, will allow measurement of the HI diameter function, and enable a first wide-area blind search for local HI tidal features, HI absorbers at z < 0.06 and OH megamasers in the redshift range 0.16 < z < 0.25. Although completion of the survey will require some five years, public access to the ALFALFA data and data products will be provided in a timely manner, thus allowing its application for studies beyond those targeted by the ALFALFA collaboration. ALFALFA adopts a two-pass, minimum intrusion, drift scan observing technique which samples the same region of sky at two separate epochs to aid in the discrimination of cosmic signals from noise and terrestrial interference. Survey simulations, which take into account large scale structure in the mass distribution and incorporate experience with the ALFA system gained from tests conducted during its commissioning phase, suggest that ALFALFA will detect on the order of 20,000 extragalactic HI line sources out to z=0.06, including several hundred with HI masses of less than 10^{7.5} msun.

This paper describes the physics case for a new fixed target facility at CERN SPS. The SHiP (search for hidden particles) experiment is intended to hunt for new physics in the largely unexplored domain of very weakly interacting particles with masses below the Fermi scale, inaccessible to the LHC experiments, and to study tau neutrino physics. The same proton beam setup can be used later to look for decays of tau-leptons with lepton flavour number non-conservation, [Formula: see text] and to search for weakly-interacting sub-GeV dark matter candidates. We discuss the evidence for physics beyond the standard model and describe interactions between new particles and four different portals-scalars, vectors, fermions or axion-like particles. We discuss motivations for different models, manifesting themselves via these interactions, and how they can be probed with the SHiP experiment and present several case studies. The prospects to search for relatively light SUSY and composite particles at SHiP are also discussed. We demonstrate that the SHiP experiment has a unique potential to discover new physics and can directly probe a number of solutions of beyond the standard model puzzles, such as neutrino masses, baryon asymmetry of the Universe, dark matter, and inflation.

Quercetin (Que) and its derivatives are naturally occurring phytochemicals with promising bioactive effects. The antidiabetic, anti-inflammatory, antioxidant, antimicrobial, anti-Alzheimer's, antiarthritic, cardiovascular, and wound-healing effects of Que have been extensively investigated, as well as its anticancer activity against different cancer cell lines has been recently reported. Que and its derivatives are found predominantly in the Western diet, and people might benefit from their protective effect just by taking them via diets or as a food supplement. Bioavailability-related drug-delivery systems of Que have also been markedly exploited, and Que nanoparticles appear as a promising platform to enhance their bioavailability. The present review aims to provide a brief overview of the therapeutic effects, new insights, and upcoming perspectives of Que.

A combination is presented of all inclusive deep
\ninelastic cross sections previously published by the H1 and
\nZEUS collaborations at HERA for neutral and charged current e± p scattering for zero beam polarisation. The datawere
\ntaken at proton beam energies of 920, 820, 575 and 460GeV
\nand an electron beam energy of 27.5GeV. The data correspond
\nto an integrated luminosity of about 1 fb−1 and span
\nsix orders ofmagnitude in negative four-momentum-transfer
\nsquared, Q2, and Bjorken x. The correlations of the systematic
\nuncertainties were evaluated and taken into account for
\nthe combination. The combined cross sections were input
\nto QCD analyses at leading order, next-to-leading order and
\nat next-to-next-to-leading order, providing a new set of parton
\ndistribution functions, called HERAPDF2.0. In addition
\nto the experimental uncertainties, model and parameterisation
\nuncertainties were assessed for these parton distribution
\nfunctions. Variants of HERAPDF2.0 with an alternative
\ngluon parameterisation, HERAPDF2.0AG, and using fixedflavour-
\nnumber schemes, HERAPDF2.0FF, are presented.
\nThe analysiswas extended by includingHERAdata on charm
\nand jet production, resulting in the variant HERAPDF2.0Jets.
\nThe inclusion of jet-production cross sections made a simultaneous
\ndetermination of these parton distributions and the
\nstrong coupling constant possible, resulting in αs (M2Z
\n) =
\n0.1183±0.0009(exp)±0.0005(model/parameterisation)±
\n0.0012(hadronisation)
\n+0.0037
\n−0.0030(scale).An extraction of xFγ Z
\n3
\nand results on electroweak unification and scaling violations
\nare also presented.

The replacement of para-substituted benzenes with saturated bi- and polycyclic bioisosteres - bicyclo[1.1.1]pentane, bicyclo[2.2.2]octane and cubane, - often increases the potency, selectivity and metabolic stability of bioactive compounds. The currently remaining challenge for chemists, however, is to rationally design, synthesize and validate the saturated bioisosteres for ortho- and meta-substituted benzenes.

In the original version of this manuscript, an error was introduced on pp352. '2.7nb:1.6nb' has been corrected to '2.4nb:1.3nb' in the current online and printed version. doi:10.1093/ptep/ptz106.

Polarimetry is one of the most promising types of remote sensing for improved characterization of atmospheric aerosol. Indeed, aerosol particles constitute a highly variable atmospheric component characterized by a large number of parameters describing particle sizes, morphologies (including shape and internal structure), absorption and scattering properties, amounts, horizontal and vertical distribution, etc. Reliable monitoring of all these parameters is very challenging, and therefore the aerosol effects on climate and environment are considered to be among the most uncertain factors in climate and environmental research. In this regard, observations that provide both the angular distribution of the scattered atmospheric radiation as well as its polarization state at multiple wavelengths covering the UV–SWIR spectral range carry substantial implicit information on the atmospheric composition. Therefore, high expectations in improving aerosol characterization are associated with detailed passive photopolarimetric observations. The critical need to use space-borne polarimetry for global accurate monitoring of detailed aerosol properties was first articulated in the late 1980s and early 1990s. By now, several orbital instruments have already provided polarization observations from space, and a number of advanced missions are scheduled for launch in the coming years by international and national space agencies. The first and most extensive record of polarimetric imagery was provided by POLDER-I, POLDER-II, and POLDER/PARASOL multi-angle multi-spectral polarization sensors. Polarimetric observations with the POLDER-like design intended for collecting extensive multi-angular multi-spectral measurements will be provided by several instruments, such as the MAI/TG-2, CAPI/TanSat, and DPC/GF-5 sensors recently launched by the Chinese Space Agency. Instruments such as the 3MI/MetOp-SG, MAIA, SpexOne and HARP2 on PACE, POSP, SMAC, PCF, DPC–Lidar, ScanPol and MSIP/Aerosol-UA, MAP/Copernicus CO2 Monitoring, etc. are planned to be launched by different space agencies in the coming decade. The concepts of these future instruments, their technical designs, and the accompanying algorithm development have been tested intensively and analyzed using diverse airborne prototypes. Certain polarimetric capabilities have also been implemented in such satellite sensors as GOME-2/MetOp and SGLI/GCOM-C. A number of aerosol retrieval products have been developed based on the available measurements and successfully used for different scientific applications. However, the completeness and accuracy of aerosol data operationally derived from polarimetry do not yet appear to have reached the accuracy levels implied by theoretical sensitivity studies that analyzed the potential information content of satellite polarimetry. As a result, the dataset provided by MODIS is still most frequently used by the scientific community, yet this sensor has neither polarimetric nor multi-angular capabilities. Admittedly polarimetric multi-angular observations are highly complex and have extra sensitivities to aerosol particle morphology, vertical variability of aerosol properties, polarization of surface reflectance, etc. As such, they necessitate state-of-the-art forward modeling based on first-principles physics which remains rare, and conventional retrieval approaches based on look-up tables turn out to be unsuitable to fully exploit the information implicit in the measurements. Several new-generation retrieval approaches have recently been proposed to address these challenges. These methods use improved forward modeling of atmospheric (polarized) radiances and implement a search in the continuous space of solutions using rigorous statistically optimized inversions. Such techniques provide more accurate retrievals of the main aerosol parameters such as aerosol optical thickness and yield additional parameters such as aerosol absorption. However, the operational implementation of advanced retrieval approaches generally requires a significant extra effort, and the forward-modeling part of such retrievals still needs to be substantially improved. Ground-based passive polarimetric measurements have also been evolving over the past decade. Although polarimetry helps improve aerosol characterization, especially of the fine aerosol mode, the operators of major observational networks such as AERONET remain reluctant to include polarimetric measurements as part of routine retrievals owing to their high complexity and notable increase in effort required to acquire and interpret polarization data. In addition to remote-sensing observations, polarimetric characteristics of aerosol scattering have been measured in situ as well as in the laboratory using polar nephelometers. Such measurements constitute direct observations of single scattering with no contributions from multiple scattering effects and therefore provide unique data for the validation of aerosol optical models and retrieval concepts. This article overviews the above-mentioned polarimetric observations, their history and expected developments, and the state of resulting aerosol products. It also discusses the main achievements and challenges in the exploitation of polarimetry for the improved characterization of atmospheric aerosols.

Phytohormones act as chemical messengers and, under a complex regulation, allow plants to sustain biotic and abiotic stresses. Thus, phytohormones are known for their regulatory role in plant growth and development. Heavy metals (HMs) play an important role in metabolism and have roles in plant growth and development as micronutrients. However, at a level above threshold, these HMs act as contaminants and pose a worldwide environmental threat. Thus, finding eco-friendly and economical deliverables to tackle this problem is a priority. In addition to physicochemical methods, exogenous application of phytohormones, i.e., auxins, cytokinins, and gibberellins, can positively influence the regulation of the ascorbate–glutathione cycle, transpiration rate, cell division, and the activities of nitrogen metabolism and assimilation, which improve plant growth activity. Brassinosteroids, ethylene and salicylic acid have been reported to enhance the level of the anti-oxidant system, decrease levels of ROS, lipid peroxidation and improve photosynthesis in plants, when applied exogenously under a HM effect. There is a crosstalk between phytohormones which is activated upon exogenous application. Research suggests that plants are primed by phytohormones for stress tolerance. Chemical priming has provided good results in plant physiology and stress adaptation, and phytohormone priming is underway. We have reviewed promising phytohormones, which can potentially confer enhanced tolerance when used exogenously. Exogenous application of phytohormones may increase plant performance under HM stress and can be used for agro-ecological benefits under environmental conditions with high HMs level.

Magnonics addresses the physical properties of spin waves and utilizes them for data processing. Scalability down to atomic dimensions, operation in the GHz-to-THz frequency range, utilization of nonlinear and nonreciprocal phenomena, and compatibility with CMOS are just a few of many advantages offered by magnons. Although magnonics is still primarily positioned in the academic domain, the scientific and technological challenges of the field are being extensively investigated, and many proof-of-concept prototypes have already been realized in laboratories. This roadmap is a product of the collective work of many authors, which covers versatile spin-wave computing approaches, conceptual building blocks, and underlying physical phenomena. In particular, the roadmap discusses the computation operations with the Boolean digital data, unconventional approaches, such as neuromorphic computing, and the progress toward magnon-based quantum computing. This article is organized as a collection of sub-sections grouped into seven large thematic sections. Each sub-section is prepared by one or a group of authors and concludes with a brief description of current challenges and the outlook of further development for each research direction.

Abstract The European Vegetation Archive ( EVA ) is a centralized database of European vegetation plots developed by the IAVS Working Group European Vegetation Survey. It has been in development since 2012 and first made available for use in research projects in 2014. It stores copies of national and regional vegetation‐ plot databases on a single software platform. Data storage in EVA does not affect on‐going independent development of the contributing databases, which remain the property of the data contributors. EVA uses a prototype of the database management software TURBOVEG 3 developed for joint management of multiple databases that use different species lists. This is facilitated by the SynBioSys Taxon Database, a system of taxon names and concepts used in the individual European databases and their corresponding names on a unified list of European flora. TURBOVEG 3 also includes procedures for handling data requests, selections and provisions according to the approved EVA Data Property and Governance Rules. By 30 June 2015, 61 databases from all European regions have joined EVA , contributing in total 1 027 376 vegetation plots, 82% of them with geographic coordinates, from 57 countries. EVA provides a unique data source for large‐scale analyses of European vegetation diversity both for fundamental research and nature conservation applications. Updated information on EVA is available online at http://euroveg.org/eva-database .

The topic covered in this book is the study of metric and other close characteristics of different spaces and classes of random variables and the application of the entropy method to the investigation of properties of stochastic processes whose values, or increments, belong to given spaces. The following processes appear in detail: pre-Gaussian processes, shot noise processes representable as integrals over processes with independent increments, quadratically Gaussian processes, and, in particular, correlogram-type estimates of the correlation function of a stationary Gaussian process, jointly strictly sub-Gaussian processes, etc. The book consists of eight chapters divided into four parts: The first part deals with classes of random variables and their metric characteristics. The second part presents properties of stochastic processes "imbedded" into a space of random variables discussed in the first part. The third part considers applications of the general theory. The fourth part outlines the necessary auxiliary material. Problems and solutions presented show the intrinsic relation existing between probability methods, analytic methods, and functional methods in the theory of stochastic processes. The concluding sections, "Comments" and "References", gives references to the literature used by the authors in writing the book.

L. and is widely distributed in the Fabaceae family. As an isoflavone, mammalian genistein exerts estrogen-like functions. Several biological effects of genistein have been reported in preclinical studies, such as the antioxidant, anti-inflammatory, antibacterial, and antiviral activities, the effects of angiogenesis and estrogen, and the pharmacological activities on diabetes and lipid metabolism. The purpose of this review is to provide up-to-date evidence of preclinical pharmacological activities with mechanisms of action, bioavailability, and clinical evidence of genistein. The literature was researched using the most important keyword "genistein" from the PubMed, Science, and Google Scholar databases, and the taxonomy was validated using The Plant List. Data were also collected from specialized books and other online resources. The main positive effects of genistein refer to the protection against cardiovascular diseases and to the decrease of the incidence of some types of cancer, especially breast cancer. Although the mechanism of protection against cancer involves several aspects of genistein metabolism, the researchers attribute this effect to the similarity between the structure of soy genistein and that of estrogen. This structural similarity allows genistein to displace estrogen from cellular receptors, thus blocking their hormonal activity. The pharmacological activities resulting from the experimental studies of this review support the traditional uses of genistein, but in the future, further investigations are needed on the efficacy, safety, and use of nanotechnologies to increase bioavailability and therapeutic efficacy.

Curvature impacts physical properties across multiple length scales, ranging from the macroscopic scale, where the shape and size vary drastically with the curvature, to the nanoscale at interfaces and inhomogeneities in materials with structural, chemical, electronic, and magnetic short-range order. In quantum materials, where correlations, entanglement, and topology dominate, the curvature opens the path to novel characteristics and phenomena that have recently emerged and could have a dramatic impact on future fundamental and applied studies of materials. Particularly, magnetic systems hosting non-collinear and topological states and 3D magnetic nanostructures strongly benefit from treating curvature as a new design parameter to explore prospective applications in the magnetic field and stress sensing, microrobotics, and information processing and storage. This Perspective gives an overview of recent progress in synthesis, theory, and characterization studies and discusses future directions, challenges, and application potential of the harnessing curvature for 3D nanomagnetism.

Antarctic krill <i>Euphausia superba</i> (hereafter ‘krill’) occur in regions undergoing rapid environmental change, particularly loss of winter sea ice. During recent years, harvesting of krill has increased, possibly enhancing stress on krill and Antarctic ecosystems. Here we review the overall impact of climate change on krill and Antarctic ecosystems, discuss implications for an ecosystem-based fisheries management approach and identify critical knowledge gaps. Sea ice decline, ocean warming and other environmental stressors act in concert to modify the abundance, distribution and life cycle of krill. Although some of these changes can have positive effects on krill, their cumulative impact is most likely negative. Recruitment, driven largely by the winter survival of larval krill, is probably the population parameter most susceptible to climate change. Predicting changes to krill populations is urgent, because they will seriously impact Antarctic ecosystems. Such predictions, however, are complicated by an intense inter-annual variability in recruitment success and krill abundance. To improve the responsiveness of the ecosystem-based management approach adopted by the Commission for the Conservation of Antarctic Marine Living Resources (CCAMLR), critical knowledge gaps need to be filled. In addition to a better understanding of the factors influencing recruitment, management will require a better understanding of the resilience and the genetic plasticity of krill life stages, and a quantitative understanding of under-ice and benthic habitat use. Current precautionary management measures of CCAMLR should be maintained until a better understanding of these processes has been achieved.

Herein, we developed the first ratiometric fluorescent probe for apoptosis detection. This probe incorporates selectively into the outer leaflet of the cell plasma membrane and senses the loss of the plasma membrane asymmetry occurring during the early steps of apoptosis. The high specificity to the plasma membranes was achieved by introduction into the probe of a membrane anchor, composed of a zwitterionic group and a long (dodecyl) hydrophobic tail. The fluorescence reporter of this probe is 4'-(diethylamino)-3-hydroxyflavone, which exhibits excited-state intramolecular proton transfer (ESIPT), resulting in two-band emission highly sensitive to the lipid composition of the biomembranes. Fluorescence spectroscopy, flow cytometry, and microscopy measurements show that the ratio of the two emission bands of the probe changes dramatically in response to apoptosis. This response reflects the changes in the lipid composition of the outer leaflet of the cell plasma membrane because of the exposure of the anionic phospholipids from the inner leaflet at the early steps of apoptosis. Being ratiometric, the response of the new probe can be easily quantified on an absolute scale. This allows monitoring by laser scanning confocal microscopy the degree and spatial distribution of the apoptotic changes at the cell plasma membranes, a feature that can be hardly achieved with the commonly used fluorescently labeled annexin V assay.

Abstract The Laser Interferometer Space Antenna (LISA) has two scientific objectives of cosmological focus: to probe the expansion rate of the universe, and to understand stochastic gravitational-wave backgrounds and their implications for early universe and particle physics, from the MeV to the Planck scale. However, the range of potential cosmological applications of gravitational-wave observations extends well beyond these two objectives. This publication presents a summary of the state of the art in LISA cosmology, theory and methods, and identifies new opportunities to use gravitational-wave observations by LISA to probe the universe.

Excited-state intramolecular proton transfer (ESIPT) in 3-hydroxyflavone dyes allows us to record, in addition to common spectroscopic parameters, the positions of absorption (νabs) and emission (νN*) maxima, two new parameters: the position of the emission maximum of the ESIPT product T* state (νT*) and the intensity ratio of the two emission bands (IN*/IT*). An attempt was made to find a correlation between these parameters and physicochemical characteristics of microenvironment: polarity f(ε), electronic polarizability f(n) and H-bond donor ability. A detailed spectroscopic study of 4′-diethylamino-3-hydroxyflavone in a set of 21 representative solvents demonstrates that the Stokes shift of the N* band (νabs − νN*) correlates strongly with the Lippert function L = f(ε) − f(n), and this correlation does not depend on the effects of intermolecular H-bonding, while the correlation of log(IN*/IT*) with polarity f(ε) can be represented by linear functions that are different for protic and aprotic environments. Cross-correlation analysis of the spectroscopic parameters provides criteria to distinguish specific (H-bonding and other) from universal probe interactions with the environment. We suggest an algorithm, which uses four spectroscopic parameters νabs, νN*, νT* and log(IN*/IT*) to provide a simultaneous estimation of three microenvironment characteristics: f(ε), f(n) and H-bond donor ability. An application of this algorithm in the studies of binary solvent mixtures, reverse micelles and binding sites of proteins demonstrates the power of this approach and suggests a unique possibility to develop a new generation of fluorescence probes and labels in the 3-hydroxyflavone family for studying complex microheterogeneous systems in physical chemistry, colloid chemistry and the biological sciences.

We report on the development of a dilute suspension of ferroelectric particles in a nematic liquid-crystal (LC) host. We found that the submicron particles do not disturb the LC alignment and the suspension macroscopically appears similar to a pure LC with no readily apparent evidence of dissolved particles. The suspension possesses enhanced dielectric anisotropy, and is sensitive to the sign of an applied electric field.