National Academy of Sciences of Ukraine

In 2008 we published the first set of guidelines for standardizing research in autophagy. Since then, research on this topic has continued to accelerate, and many new scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Accordingly, it is important to update these guidelines for monitoring autophagy in different organisms. Various reviews have described the range of assays that have been used for this purpose. Nevertheless, there continues to be confusion regarding acceptable methods to measure autophagy, especially in multicellular eukaryotes. For example, a key point that needs to be emphasized is thatthere is a difference between measurements that monitor the numbers or volume of autophagic elements (e.g., autophagosomes or autolysosomes) at any stage of the autophagic process versus those that measure flux through the autophagy pathway (i.e., the completeprocess including the amount and rate of cargo sequestered and degraded). In particular, a block in macroautophagy that results in autophagosome accumulation must be differentiated from stimuli that increase autophagic activity, defined as increasedautophagy induction coupled with increased delivery to, and degradation within, lysosomes (inmost higher eukaryotes and some protists such as Dictyostelium) or the vacuole (in plants and fungi). In other words, it is especially important that investigators new to the field understand that the appearance of more autophagosomes does not necessarily equate with more autophagy. In fact, in manycases, autophagosomes accumulate because of a block in trafficking to lysosomes without a concomitant change in autophagosome biogenesis, whereas an increase in autolysosomes may reflect a reduction in degradative activity. It is worth emphasizing here that lysosomal digestion is a stage of autophagy and evaluating its competence is a crucial part of the evaluation of autophagic flux, or complete autophagy. Here, we present a set of guidelines for the selection and interpretation of methods for use by investigators who aim to examine macroautophagy and related processes, as well as forreviewers who need to provide realistic and reasonable critiques of papers that are focused on these processes. These guidelines are not meant to be a formulaic set of rules, because the appropriate assays depend in part on the question being asked and the system being used. In addition, we emphasize that no individual assay is guaranteed to be the most appropriate one in every situation, and we strongly recommend the use of multipleassays to monitor autophagy. Along these lines, because of the potential for pleiotropic effects due to blocking autophagy through genetic manipulation, it is imperative to target by gene knockout or RNA interference more than one autophagyrelated protein. In addition, some individual Atg proteins, or groups of proteins, are involved in other cellular pathways implying that not all Atg proteins can be used as a specific marker for an autophagic process. In these guidelines, we consider these various methods of assessing autophagy and what information can, or cannot, be obtained from them. Finally, by discussing the merits and limits of particular assays, we hope to encourage technical innovation in the field.

ADVERTISEMENT RETURN TO ISSUEPREVReviewNEXTFluorine in Pharmaceutical Industry: Fluorine-Containing Drugs Introduced to the Market in the Last Decade (2001–2011)Jiang Wang†, María Sánchez-Roselló‡§, José Luis Aceña∥, Carlos del Pozo‡, Alexander E. Sorochinsky∥⊥#, Santos Fustero*‡§, Vadim A. Soloshonok*∥⊥, and Hong Liu*†View Author Information† Key Laboratory of Receptor Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 555 Zu Chong Zhi Road, Shanghai 201203, China‡ Department of Organic Chemistry, Faculty of Pharmacy, University of Valencia, Av. Vicente Andrés Estellés, 46100 Burjassot, Valencia, Spain§ Laboratorio de Moléculas Orgánicas, Centro de Investigación Príncipe Felipe, C/ Eduardo Primo Yúfera 3, 46012 Valencia, Spain∥ Department of Organic Chemistry I, Faculty of Chemistry, University of the Basque Country UPV/EHU, Paseo Manuel Lardizábal 3, 20018 San Sebastian, Spain⊥ IKERBASQUE, Basque Foundation for Science, Alameda Urquijo, 36-5 Plaza Bizkaia, 48011 Bilbao, Spain# Institute of Bioorganic Chemistry and Petrochemistry, National Academy of Sciences of Ukraine, Murmanska Street 1, 02660 Kyiv-94, Ukraine*E-mail: [email protected]*E-mail: [email protected]*E-mail: [email protected]Cite this: Chem. Rev. 2014, 114, 4, 2432–2506Publication Date (Web):December 3, 2013Publication History Received27 May 2013Published online3 December 2013Published inissue 26 February 2014https://pubs.acs.org/doi/10.1021/cr4002879https://doi.org/10.1021/cr4002879review-articleACS PublicationsCopyright © 2013 American Chemical SocietyRequest reuse permissionsArticle Views48704Altmetric-Citations3850LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-Alertsclose SUBJECTS:Anions,Fluorine,Organic compounds,Pharmaceuticals,Reaction products Get e-Alerts

Unilamellar colloids of graphite oxide (GO) were prepared from natural graphite and were grown as monolayer and multilayer thin films on cationic surfaces by electrostatic self-assembly. The multilayer films were grown by alternate adsorption of anionic GO sheets and cationic poly(allylamine hydrochloride) (PAH). The monolayer films consisted of 11−14 Å thick GO sheets, with lateral dimensions between 150 nm and 9 μm. Silicon substrates primed with amine monolayers gave partial GO monolayers, but surfaces primed with Al 13 O 4 (OH) 24 (H 2 O) 12 7+ ions gave densely tiled films that covered approximately 90% of the surface. When alkaline GO colloids were used, the monolayer assembly process selected the largest sheets (from 900 nm to 9 μm) from the suspension. In this case, many of the flexible sheets appeared folded in AFM images. Multilayer (GO/PAH) n films were invariably thicker than expected from the individual thicknesses of the sheets and the polymer monolayers, and this behavior is also attributed to folding of the sheets. Multilayer (GO/PAH) n and (GO/polyaniline) n films grown between indium−tin oxide and Pt electrodes show diodelike behavior, and higher currents are observed with the conductive polyaniline-containing films. The resisitivity of these films is decreased, as expected, by partial reduction of GO to carbon.

Quantitative structure-activity relationship modeling is one of the major computational tools employed in medicinal chemistry. However, throughout its entire history it has drawn both praise and criticism concerning its reliability, limitations, successes, and failures. In this paper, we discuss (i) the development and evolution of QSAR; (ii) the current trends, unsolved problems, and pressing challenges; and (iii) several novel and emerging applications of QSAR modeling. Throughout this discussion, we provide guidelines for QSAR development, validation, and application, which are summarized in best practices for building rigorously validated and externally predictive QSAR models. We hope that this Perspective will help communications between computational and experimental chemists toward collaborative development and use of QSAR models. We also believe that the guidelines presented here will help journal editors and reviewers apply more stringent scientific standards to manuscripts reporting new QSAR studies, as well as encourage the use of high quality, validated QSARs for regulatory decision making.

The LHCb experiment is dedicated to precision measurements of CP violation and rare decays of B hadrons at the Large Hadron Collider (LHC) at CERN (Geneva). The initial configuration and expected performance of the detector and associated systems, as established by test beam measurements and simulation studies, is described.

Deep learning (DL) is a powerful state-of-the-art technique for image processing including remote sensing (RS) images. This letter describes a multilevel DL architecture that targets land cover and crop type classification from multitemporal multisource satellite imagery. The pillars of the architecture are unsupervised neural network (NN) that is used for optical imagery segmentation and missing data restoration due to clouds and shadows, and an ensemble of supervised NNs. As basic supervised NN architecture, we use a traditional fully connected multilayer perceptron (MLP) and the most commonly used approach in RS community random forest, and compare them with convolutional NNs (CNNs). Experiments are carried out for the joint experiment of crop assessment and monitoring test site in Ukraine for classification of crops in a heterogeneous environment using nineteen multitemporal scenes acquired by Landsat-8 and Sentinel-1A RS satellites. The architecture with an ensemble of CNNs outperforms the one with MLPs allowing us to better discriminate certain summer crop types, in particular maize and soybeans, and yielding the target accuracies more than 85% for all major crops (wheat, maize, sunflower, soybeans, and sugar beet).

A complex multidimensional decision hypersurface can be approximated by a set of polynomials in the input signals (properties) which contain information about the hypersurface of interest. The hypersurface is usually described by a number of experimental (vector) points and simple functions of their coordinates. The approach taken in this paper to approximating the decision hypersurface, and hence the input-output relationship of a complex system, is to fit a high-degree multinomial to the input properties using a multilayered perceptronlike network structure. Thresholds are employed at each layer in the network to identify those polynomials which best fit into the desired hypersurface. Only the best combinations of the input properties are allowed to pass to succeeding layers, where more complex combinations are formed. Each element in each layer in the network implements a nonlinear function of two inputs. The coefficients of each element are determined by a regression technique which enables each element to approximate the true outputs with minimum mean-square error. The experimental data base is divided into a training and testing set. The training set is used to obtain the element coefficients, and the testing set is used to determine the utility of a given element in the network and to control overfitting of the experimental data. This latter feature is termed "decision regularization.

AIMS: Large randomized trials have shown that beta-blockers reduce mortality and hospital admissions in patients with heart failure. The effects of beta-blockers in elderly patients with a broad range of left ventricular ejection fraction are uncertain. The SENIORS study was performed to assess effects of the beta-blocker, nebivolol, in patients >/=70 years, regardless of ejection fraction. METHODS AND RESULTS: We randomly assigned 2128 patients aged >/=70 years with a history of heart failure (hospital admission for heart failure within the previous year or known ejection fraction </=35%), 1067 to nebivolol (titrated from 1.25 mg once daily to 10 mg once daily), and 1061 to placebo. The primary outcome was a composite of all cause mortality or cardiovascular hospital admission (time to first event). Analysis was by intention to treat. Mean duration of follow-up was 21 months. Mean age was 76 years (SD 4.7), 37% were female, mean ejection fraction was 36% (with 35% having ejection fraction >35%), and 68% had a prior history of coronary heart disease. The mean maintenance dose of nebivolol was 7.7 mg and of placebo 8.5 mg. The primary outcome occurred in 332 patients (31.1%) on nebivolol compared with 375 (35.3%) on placebo [hazard ratio (HR) 0.86, 95% CI 0.74-0.99; P=0.039]. There was no significant influence of age, gender, or ejection fraction on the effect of nebivolol on the primary outcome. Death (all causes) occurred in 169 (15.8%) on nebivolol and 192 (18.1%) on placebo (HR 0.88, 95% CI 0.71-1.08; P=0.21). CONCLUSION: Nebivolol, a beta-blocker with vasodilating properties, is an effective and well-tolerated treatment for heart failure in the elderly.

Abstract Aims Vegetation classification consistent with the Braun‐Blanquet approach is widely used in Europe for applied vegetation science, conservation planning and land management. During the long history of syntaxonomy, many concepts and names of vegetation units have been proposed, but there has been no single classification system integrating these units. Here we (1) present a comprehensive, hierarchical, syntaxonomic system of alliances, orders and classes of Braun‐Blanquet syntaxonomy for vascular plant, bryophyte and lichen, and algal communities of Europe; (2) briefly characterize in ecological and geographic terms accepted syntaxonomic concepts; (3) link available synonyms to these accepted concepts; and (4) provide a list of diagnostic species for all classes. Location European mainland, Greenland, Arctic archipelagos (including Iceland, Svalbard, Novaya Zemlya), Canary Islands, Madeira, Azores, Caucasus, Cyprus. Methods We evaluated approximately 10 000 bibliographic sources to create a comprehensive list of previously proposed syntaxonomic units. These units were evaluated by experts for their floristic and ecological distinctness, clarity of geographic distribution and compliance with the nomenclature code. Accepted units were compiled into three systems of classes, orders and alliances (EuroVegChecklist, EVC ) for communities dominated by vascular plants ( EVC 1), bryophytes and lichens ( EVC 2) and algae ( EVC 3). Results EVC 1 includes 109 classes, 300 orders and 1108 alliances; EVC 2 includes 27 classes, 53 orders and 137 alliances, and EVC 3 includes 13 classes, 24 orders and 53 alliances. In total 13 448 taxa were assigned as indicator species to classes of EVC 1, 2087 to classes of EVC 2 and 368 to classes of EVC 3. Accepted syntaxonomic concepts are summarized in a series of appendices, and detailed information on each is accessible through the software tool EuroVegBrowser. Conclusions This paper features the first comprehensive and critical account of European syntaxa and synthesizes more than 100 yr of classification effort by European phytosociologists. It aims to document and stabilize the concepts and nomenclature of syntaxa for practical uses, such as calibration of habitat classification used by the European Union, standardization of terminology for environmental assessment, management and conservation of nature areas, landscape planning and education. The presented classification systems provide a baseline for future development and revision of European syntaxonomy.

We report that a resonance response with a very high quality factor can be achieved in a planar metamaterial by introducing symmetry breaking in the shape of its structural elements, which enables excitation of trapped modes, i.e., modes that are weakly coupled to free space.

The diffuseness of the ferroelectric phase transition in ${\mathrm{PbMg}}_{1/3}$${\mathrm{Nb}}_{2/3}$${\mathrm{O}}_{3}$ is proposed to be due to quenched random electric fields originating from charged compositional fluctuations. They are responsible for the extreme critical slowing down, the freezing into nanometric ferroelectric domains, and the slow relaxation of the polarization below ${\mathit{T}}_{\mathit{c}}$\ensuremath{\sim}212 K. Barkhausen jumps during poling exclude glassiness, which was conjectured previously. At ${\mathit{T}}_{\mathit{c}}$ a ferroelectric anomaly of the dielectric permittivity appears, if the random fields are overcome by an external electric field.

We sequenced and annotated the genome of the filamentous fungus Fusarium graminearum, a major pathogen of cultivated cereals. Very few repetitive sequences were detected, and the process of repeat-induced point mutation, in which duplicated sequences are subject to extensive mutation, may partially account for the reduced repeat content and apparent low number of paralogous (ancestrally duplicated) genes. A second strain of F. graminearum contained more than 10,000 single-nucleotide polymorphisms, which were frequently located near telomeres and within other discrete chromosomal segments. Many highly polymorphic regions contained sets of genes implicated in plant-fungus interactions and were unusually divergent, with higher rates of recombination. These regions of genome innovation may result from selection due to interactions of F. graminearum with its plant hosts.

Coarse-grained (CG) simulations have become an essential tool to study a large variety of biomolecular processes, exploring temporal and spatial scales inaccessible to traditional models of atomistic resolution. One of the major simplifications of CG models is the representation of the solvent, which is either implicit or modeled explicitly as a van der Waals particle. The effect of polarization, and thus a proper screening of interactions depending on the local environment, is absent. Given the important role of water as a ubiquitous solvent in biological systems, its treatment is crucial to the properties derived from simulation studies. Here, we parameterize a polarizable coarse-grained water model to be used in combination with the CG MARTINI force field. Using a three-bead model to represent four water molecules, we show that the orientational polarizability of real water can be effectively accounted for. This has the consequence that the dielectric screening of bulk water is reproduced. At the same time, we parameterized our new water model such that bulk water density and oil/water partitioning data remain at the same level of accuracy as for the standard MARTINI force field. We apply the new model to two cases for which current CG force fields are inadequate. First, we address the transport of ions across a lipid membrane. The computed potential of mean force shows that the ions now naturally feel the change in dielectric medium when moving from the high dielectric aqueous phase toward the low dielectric membrane interior. In the second application we consider the electroporation process of both an oil slab and a lipid bilayer. The electrostatic field drives the formation of water filled pores in both cases, following a similar mechanism as seen with atomistically detailed models.

Abstract Polythiophenes are one of the most important classes of conjugated polymers, with a wide range of applications, such as conducting films, electrochromics, and field‐effect transistors, which have been the subject of a number of older and more recent reviews. Much less attention has been paid to the light‐emitting properties of this class of materials, although their unique properties present a number of opportunities unavailable from more popular polymeric light emitters such as polyfluorene or poly( p ‐phenylene vinylene). This article reviews achievements to date in applications of thiophene‐based polymers and oligomers as electroluminescent materials. We demonstrate the basic principles of controlling the optical properties of polythiophenes through structural modifications and review the most important light‐emitting materials created from thiophene derivatives. Special attention is paid to consequences of structural variations on the performance of light‐emitting diodes fabricated with these materials.

We report that normal incidence transmission of circularly polarized waves through the lossy anisotropic planar chiral structure is asymmetric in the opposite direction. The new effect is fundamentally distinct from conventional gyrotropy of bulk chiral media and the Faraday effect, where the eigenstates are a pair of counterrotating elliptical states, while the eigenstates of the lossy anisotropic planar chiral structure are two corotating elliptical polarizations.

Massive microbial mats covering up to 4-meter-high carbonate buildups prosper at methane seeps in anoxic waters of the northwestern Black Sea shelf. Strong 13C depletions indicate an incorporation of methane carbon into carbonates, bulk biomass, and specific lipids. The mats mainly consist of densely aggregated archaea (phylogenetic ANME-1 cluster) and sulfate-reducing bacteria (Desulfosarcina/Desulfococcus group). If incubated in vitro, these mats perform anaerobic oxidation of methane coupled to sulfate reduction. Obviously, anaerobic microbial consortia can generate both carbonate precipitation and substantial biomass accumulation, which has implications for our understanding of carbon cycling during earlier periods of Earth's history.

Charge and proton transfer reactions in the excited states of organic dyes can be coupled in many different ways. Despite the complementarity of charges, they can occur on different time scales and in different directions of the molecular framework. In certain cases, excited-state equilibrium can be established between the charge-transfer and proton-transfer species. The interplay of these reactions can be modulated and even reversed by variations in dye molecular structures and changes of the surrounding media. With knowledge of the mechanisms of these processes, desired rates and directions can be achieved, and thus the multiple emission spectral features can be harnessed. These features have found versatile applications in a number of cutting-edge technological areas, particularly in fluorescence sensing and imaging.

A combination is presented of the inclusive deep inelastic cross sections measured by the H1 and ZEUS Collaborations in neutral and charged current unpolarised e p scattering at HERA during the period 1994-2000. The data span six orders of magnitude in negative four-momentum-transfer squared, Q 2 , and in Bjorken x. The combination method used takes the correlations of systematic uncertainties into account, resulting in an improved accuracy. The combined data are the sole input in a NLO QCD analysis which determines a new set of parton distributions, HERAPDF1.0, with small experimental uncertainties. This set includes an estimate of the model and parametrisation uncertainties of the fit result.

We have re-evaluated empirical expressions for the abundance determination of N, O, Ne, S, Cl, Ar and Fe taking into account the latest atomic data and constructing an appropriate grid of photoionization models with state-of-the art model atmospheres. Using these expressions we have derived heavy element abundances in the ~310 emission-line galaxies from the Data Release 3 of the Sloan Digital Sky Survey (SDSS) with an observed Hβ flux F(Hβ) > 10-14 erg s-1 cm-2 and for which the [O iii] λ4363 emission line was detected at least at a 2σ level, allowing abundance determination by direct methods. The oxygen abundance 12 + log O/H of the SDSS galaxies lies in the range from ~7.1 (/30) to ~8.5 (0.7 ). The SDSS sample is merged with a sample of 109 blue compact dwarf (BCD) galaxies with high quality spectra, which contains extremely low-metallicity objects. We use the merged sample to study the abundance patterns of low-metallicity emission-line galaxies. We find that extremely metal-poor galaxies (12 + log O/H < 7.6, i.e. Z < /12) are rare in the SDSS sample. The α element-to-oxygen abundance ratios do not show any significant trends with oxygen abundance, in agreement with previous studies, except for a slight increase of Ne/O with increasing metallicity, which we interpret as due to a moderate depletion of O onto grains in the most metal-rich galaxies. The Fe/O abundance ratio is smaller than the solar value, by up to 1 dex at the high metallicity end. We also find that Fe/O increases with decreasing Hβ equivalent width EW(Hβ). We interpret this as a sign of strong depletion onto dust grains, and gradual destruction of those grains on a time scale of a few Myr. All the galaxies are found to have log N/O > –1.6, implying that they have a different nature than the subsample of high-redshift damped Lyα systems with log N/O of ~–2.3 and that their ages are larger than 100–300 Myr. We confirm the apparent increase in N/O with decreasing EW(Hβ), already shown in previous studies, and explain it as the signature of gradual nitrogen ejection by massive stars from the most recent starburst.

This review covers recent experimental and theoretical investigations into cooperative phenomena in crystals containing off-center ions. These phenomena have attracted much attention in recent years because of a general interest in disordered systems, in particular in spin glasses, whose electrical analog is the dipole glass. Specific features of the dipole glass state in alkali halide crystals with off-center ions are discussed and compared with spin glasses. Experimental studies performed in recent years have demonstrated that off-center ions in highly polarizable crystals can at certain concentrations induce ferroelectric domains with regions of macroscopic spontaneous polarization. The physical causes of this phenomenon are examined and some physical properties of crystals exhibiting such an impurity-induced phase transition are analyzed. Primary emphasis is placed on the range of low impurity concentrations, where system properties differ substantially from predictions of mean-field theory.