Masaryk University

ABSTRACT Radiocarbon ( 14 C) ages cannot provide absolutely dated chronologies for archaeological or paleoenvironmental studies directly but must be converted to calendar age equivalents using a calibration curve compensating for fluctuations in atmospheric 14 C concentration. Although calibration curves are constructed from independently dated archives, they invariably require revision as new data become available and our understanding of the Earth system improves. In this volume the international 14 C calibration curves for both the Northern and Southern Hemispheres, as well as for the ocean surface layer, have been updated to include a wealth of new data and extended to 55,000 cal BP. Based on tree rings, IntCal20 now extends as a fully atmospheric record to ca. 13,900 cal BP. For the older part of the timescale, IntCal20 comprises statistically integrated evidence from floating tree-ring chronologies, lacustrine and marine sediments, speleothems, and corals. We utilized improved evaluation of the timescales and location variable 14 C offsets from the atmosphere (reservoir age, dead carbon fraction) for each dataset. New statistical methods have refined the structure of the calibration curves while maintaining a robust treatment of uncertainties in the 14 C ages, the calendar ages and other corrections. The inclusion of modeled marine reservoir ages derived from a three-dimensional ocean circulation model has allowed us to apply more appropriate reservoir corrections to the marine 14 C data rather than the previous use of constant regional offsets from the atmosphere. Here we provide an overview of the new and revised datasets and the associated methods used for the construction of the IntCal20 curve and explore potential regional offsets for tree-ring data. We discuss the main differences with respect to the previous calibration curve, IntCal13, and some of the implications for archaeology and geosciences ranging from the recent past to the time of the extinction of the Neanderthals.

Abstract The Astropy Project supports and fosters the development of open-source and openly developed Python packages that provide commonly needed functionality to the astronomical community. A key element of the Astropy Project is the core package astropy , which serves as the foundation for more specialized projects and packages. In this article, we provide an overview of the organization of the Astropy project and summarize key features in the core package, as of the recent major release, version 2.0. We then describe the project infrastructure designed to facilitate and support development for a broader ecosystem of interoperable packages. We conclude with a future outlook of planned new features and directions for the broader Astropy Project.

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.

Abstract In this article, we review special features of Gwyddion—a modular, multiplatform, open-source software for scanning probe microscopy data processing, which is available at http://gwyddion.net/. We describe its architecture with emphasis on modularity and easy integration of the provided algorithms into other software. Special functionalities, such as data processing from non-rectangular areas, grain and particle analysis, and metrology support are discussed as well. It is shown that on the basis of open-source software development, a fully functional software package can be created that covers the needs of a large part of the scanning probe microscopy user community.

Large corpora are ubiquitous in today’s world and memory quickly becomes the limiting factor in practical applications of the Vector Space Model (VSM). In this paper, we identify a gap in existing implementations of many of the popular algorithms, which is their scalability and ease of use. We describe a Natural Language Processing software framework which is based on the idea of document streaming, i.e. processing corpora document after document, in a memory independent fashion. Within this framework, we implement several popular algorithms for topical inference, including Latent Semantic Analysis and Latent Dirichlet Allocation, in a way that makes them completely independent of the training corpus size. Particular emphasis is placed on straightforward and intuitive framework design, so that modifications and extensions of the methods and/or their application by interested practitioners are effortless. We demonstrate the usefulness of our approach on a real-world scenario of computing document similarities within an existing digital library DML-CZ. 1.

BACKGROUND: Invasive fungal diseases (IFDs) remain important causes of morbidity and mortality. The consensus definitions of the Infectious Diseases Group of the European Organization for Research and Treatment of Cancer and the Mycoses Study Group have been of immense value to researchers who conduct clinical trials of antifungals, assess diagnostic tests, and undertake epidemiologic studies. However, their utility has not extended beyond patients with cancer or recipients of stem cell or solid organ transplants. With newer diagnostic techniques available, it was clear that an update of these definitions was essential. METHODS: To achieve this, 10 working groups looked closely at imaging, laboratory diagnosis, and special populations at risk of IFD. A final version of the manuscript was agreed upon after the groups' findings were presented at a scientific symposium and after a 3-month period for public comment. There were several rounds of discussion before a final version of the manuscript was approved. RESULTS: There is no change in the classifications of "proven," "probable," and "possible" IFD, although the definition of "probable" has been expanded and the scope of the category "possible" has been diminished. The category of proven IFD can apply to any patient, regardless of whether the patient is immunocompromised. The probable and possible categories are proposed for immunocompromised patients only, except for endemic mycoses. CONCLUSIONS: These updated definitions of IFDs should prove applicable in clinical, diagnostic, and epidemiologic research of a broader range of patients at high-risk.

autophagic responses. Here, we critically discuss current methods of assessing autophagy and the information they can, or cannot, provide. Our ultimate goal is to encourage intellectual and technical innovation in the field.

The details of all steps involved in the quantification of biofilm formation in microtiter plates are described. The presented protocol incorporates information on assessment of biofilm production by staphylococci, gained both by direct experience as well as by analysis of methods for assaying biofilm production. The obtained results should simplify quantification of biofilm formation in microtiter plates, and make it more reliable and comparable among different laboratories.

A group of European experts reappraised the guidelines on the therapeutic efficacy of repetitive transcranial magnetic stimulation (rTMS) previously published in 2014 [Lefaucheur et al., Clin Neurophysiol 2014;125:2150-206]. These updated recommendations take into account all rTMS publications, including data prior to 2014, as well as currently reviewed literature until the end of 2018. Level A evidence (definite efficacy) was reached for: high-frequency (HF) rTMS of the primary motor cortex (M1) contralateral to the painful side for neuropathic pain; HF-rTMS of the left dorsolateral prefrontal cortex (DLPFC) using a figure-of-8 or a H1-coil for depression; low-frequency (LF) rTMS of contralesional M1 for hand motor recovery in the post-acute stage of stroke. Level B evidence (probable efficacy) was reached for: HF-rTMS of the left M1 or DLPFC for improving quality of life or pain, respectively, in fibromyalgia; HF-rTMS of bilateral M1 regions or the left DLPFC for improving motor impairment or depression, respectively, in Parkinson's disease; HF-rTMS of ipsilesional M1 for promoting motor recovery at the post-acute stage of stroke; intermittent theta burst stimulation targeted to the leg motor cortex for lower limb spasticity in multiple sclerosis; HF-rTMS of the right DLPFC in posttraumatic stress disorder; LF-rTMS of the right inferior frontal gyrus in chronic post-stroke non-fluent aphasia; LF-rTMS of the right DLPFC in depression; and bihemispheric stimulation of the DLPFC combining right-sided LF-rTMS (or continuous theta burst stimulation) and left-sided HF-rTMS (or intermittent theta burst stimulation) in depression. Level A/B evidence is not reached concerning efficacy of rTMS in any other condition. The current recommendations are based on the differences reached in therapeutic efficacy of real vs. sham rTMS protocols, replicated in a sufficient number of independent studies. This does not mean that the benefit produced by rTMS inevitably reaches a level of clinical relevance.

Plant traits-the morphological, anatomical, physiological, biochemical and phenological characteristics of plants-determine how plants respond to environmental factors, affect other trophic levels, and influence ecosystem properties and their benefits and detriments to people. Plant trait data thus represent the basis for a vast area of research spanning from evolutionary biology, community and functional ecology, to biodiversity conservation, ecosystem and landscape management, restoration, biogeography and earth system modelling. Since its foundation in 2007, the TRY database of plant traits has grown continuously. It now provides unprecedented data coverage under an open access data policy and is the main plant trait database used by the research community worldwide. Increasingly, the TRY database also supports new frontiers of trait-based plant research, including the identification of data gaps and the subsequent mobilization or measurement of new data. To support this development, in this article we evaluate the extent of the trait data compiled in TRY and analyse emerging patterns of data coverage and representativeness. Best species coverage is achieved for categorical traits-almost complete coverage for 'plant growth form'. However, most traits relevant for ecology and vegetation modelling are characterized by continuous intraspecific variation and trait-environmental relationships. These traits have to be measured on individual plants in their respective environment. Despite unprecedented data coverage, we observe a humbling lack of completeness and representativeness of these continuous traits in many aspects. We, therefore, conclude that reducing data gaps and biases in the TRY database remains a key challenge and requires a coordinated approach to data mobilization and trait measurements. This can only be achieved in collaboration with other initiatives.

The Sketch Engine is a leading corpus tool, widely used in lexicography. Now, at 10 years old, it is mature software. The Sketch Engine website offers many ready-to-use corpora, and tools for users to build, upload and install their own corpora. The paper describes the core functions (word sketches, concordancing, thesaurus). It outlines the different kinds of users, and the approach taken to working with many different languages. It then reviews the kinds of corpora available in the Sketch Engine, gives a brief tour of some of the innovations fromthe last few years, and surveys other corpus tools and websites.

ADVERTISEMENT RETURN TO ISSUEPREVReviewNEXTPhotoremovable Protecting Groups in Chemistry and Biology: Reaction Mechanisms and EfficacyPetr Klán*†‡, Tomáš Šolomek†‡, Christian G. Bochet§, Aurélien Blanc∥, Richard Givens⊥, Marina Rubina⊥, Vladimir Popik#, Alexey Kostikov#, and Jakob Wirz∇View Author Information† Department of Chemistry, Faculty of Science, Masaryk University, Kamenice 5, 625 00 Brno, Czech Republic‡ Research Centre for Toxic Compounds in the Environment, Faculty of Science, Masaryk University, Kamenice 3, 625 00 Brno, Czech Republic§ Department of Chemistry, University of Fribourg, Chemin du Musée 9, CH-1700 Fribourg, Switzerland∥ Institut de Chimie, University of Strasbourg, 4 rue Blaise Pascal, 67000 Strasbourg, France⊥ Department of Chemistry, University of Kansas, 1251 Wescoe Hall Drive, 5010 Malott Hall, Lawrence, Kansas 66045, United States# Department of Chemistry, University of Georgia, Athens, Georgia 30602, United States∇ Department of Chemistry, University of Basel, Klingelbergstrasse 80, CH-4056 Basel, Switzerland*E-mail: [email protected]. Phone: +420-54949-4856. Fax: +420-54949-2443.Cite this: Chem. Rev. 2013, 113, 1, 119–191Publication Date (Web):December 21, 2012Publication History Received29 April 2012Published online21 December 2012Published inissue 9 January 2013https://doi.org/10.1021/cr300177kCopyright © 2012 American Chemical SocietyRIGHTS & PERMISSIONSACS AuthorChoiceArticle Views77851Altmetric-Citations1248LEARN 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 InReddit PDF (17 MB) Get e-AlertscloseSUBJECTS:Alcohols,Fluorescence,Irradiation,Organic compounds,Reaction products Get e-Alerts

Bayesian hypothesis testing presents an attractive alternative to p value hypothesis testing. Part I of this series outlined several advantages of Bayesian hypothesis testing, including the ability to quantify evidence and the ability to monitor and update this evidence as data come in, without the need to know the intention with which the data were collected. Despite these and other practical advantages, Bayesian hypothesis tests are still reported relatively rarely. An important impediment to the widespread adoption of Bayesian tests is arguably the lack of user-friendly software for the run-of-the-mill statistical problems that confront psychologists for the analysis of almost every experiment: the t-test, ANOVA, correlation, regression, and contingency tables. In Part II of this series we introduce JASP ( http://www.jasp-stats.org ), an open-source, cross-platform, user-friendly graphical software package that allows users to carry out Bayesian hypothesis tests for standard statistical problems. JASP is based in part on the Bayesian analyses implemented in Morey and Rouder's BayesFactor package for R. Armed with JASP, the practical advantages of Bayesian hypothesis testing are only a mouse click away.

UNLABELLED: Recently, there has been an increasing interest in the development and characterization of patient-derived tumor xenograft (PDX) models for cancer research. PDX models mostly retain the principal histologic and genetic characteristics of their donor tumor and remain stable across passages. These models have been shown to be predictive of clinical outcomes and are being used for preclinical drug evaluation, biomarker identification, biologic studies, and personalized medicine strategies. This article summarizes the current state of the art in this field, including methodologic issues, available collections, practical applications, challenges and shortcomings, and future directions, and introduces a European consortium of PDX models. SIGNIFICANCE: PDX models are increasingly used in translational cancer research. These models are useful for drug screening, biomarker development, and the preclinical evaluation of personalized medicine strategies. This review provides a timely overview of the key characteristics of PDX models and a detailed discussion of future directions in the field.

Bayesian parameter estimation and Bayesian hypothesis testing present attractive alternatives to classical inference using confidence intervals and p values. In part I of this series we outline ten prominent advantages of the Bayesian approach. Many of these advantages translate to concrete opportunities for pragmatic researchers. For instance, Bayesian hypothesis testing allows researchers to quantify evidence and monitor its progression as data come in, without needing to know the intention with which the data were collected. We end by countering several objections to Bayesian hypothesis testing. Part II of this series discusses JASP, a free and open source software program that makes it easy to conduct Bayesian estimation and testing for a range of popular statistical scenarios (Wagenmakers et al. this issue).

ADVERTISEMENT RETURN TO ISSUEPREVViewpointNEXTAre Agricultural Soils Dumps for Microplastics of Urban Origin?Luca Nizzetto*†‡, Martyn Futter§, and Sindre Langaas†View Author Information† Norwegian Institute for Water Research, NO-0349, Oslo, Norway‡ Research Centre for Toxic Compounds in the Environment, Masaryk University, 62500, Brno, Czech Republic§ Department of Aquatic Sciences and Assessment, Swedish University of Agricultural Sciences, Uppsala, Sweden*E-mail: [email protected]Cite this: Environ. Sci. Technol. 2016, 50, 20, 10777–10779Publication Date (Web):September 29, 2016Publication History Received16 August 2016Published online29 September 2016Published inissue 18 October 2016https://pubs.acs.org/doi/10.1021/acs.est.6b04140https://doi.org/10.1021/acs.est.6b04140newsACS PublicationsCopyright © 2016 American Chemical Society. This publication is available under these Terms of Use. Request reuse permissions This publication is free to access through this site. Learn MoreArticle Views36706Altmetric-Citations1019LEARN 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 PDF (2 MB) Get e-AlertscloseSUBJECTS:Plastics,Sludges,Soils,Sustainability,Water treatment Get e-Alerts

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.

The Bronze Age of Eurasia (around 3000–1000 BC) was a period of major cultural changes. However, there is debate about whether these changes resulted from the circulation of ideas or from human migrations, potentially also facilitating the spread of languages and certain phenotypic traits. We investigated this by using new, improved methods to sequence low-coverage genomes from 101 ancient humans from across Eurasia. We show that the Bronze Age was a highly dynamic period involving large-scale population migrations and replacements, responsible for shaping major parts of present-day demographic structure in both Europe and Asia. Our findings are consistent with the hypothesized spread of Indo-European languages during the Early Bronze Age. We also demonstrate that light skin pigmentation in Europeans was already present at high frequency in the Bronze Age, but not lactose tolerance, indicating a more recent onset of positive selection on lactose tolerance than previously thought. An analysis of 101 ancient human genomes from the Bronze Age (3000–1000 bc) reveals large-scale population migrations in Eurasia consistent with the spread of Indo-European languages; individuals frequently had light skin pigmentation but were not lactose tolerant. Was the Bronze Age of a period of major cultural changes because of circulation of ideas or because of large-scale migrations? The authors sequence and analyse low-coverage genomes from 101 ancient humans from across Eurasia to reveal large-scale population migrations and replacements during this time. Analyses indicate that light skin pigmentation was already frequent among Europeans in the Bronze Age but not lactose tolerance, indicating a more recent onset of positive selection on the latter trait than previously believed. The reported findings are also consistent with the spread of Indo-European languages during the Early Bronze Age reported on page 207 of this issue.

The therapeutic landscape of chronic myeloid leukemia (CML) has profoundly changed over the past 7 years. Most patients with chronic phase (CP) now have a normal life expectancy. Another goal is achieving a stable deep molecular response (DMR) and discontinuing medication for treatment-free remission (TFR). The European LeukemiaNet convened an expert panel to critically evaluate and update the evidence to achieve these goals since its previous recommendations. First-line treatment is a tyrosine kinase inhibitor (TKI; imatinib brand or generic, dasatinib, nilotinib, and bosutinib are available first-line). Generic imatinib is the cost-effective initial treatment in CP. Various contraindications and side-effects of all TKIs should be considered. Patient risk status at diagnosis should be assessed with the new EUTOS long-term survival (ELTS)-score. Monitoring of response should be done by quantitative polymerase chain reaction whenever possible. A change of treatment is recommended when intolerance cannot be ameliorated or when molecular milestones are not reached. Greater than 10% BCR-ABL1 at 3 months indicates treatment failure when confirmed. Allogeneic transplantation continues to be a therapeutic option particularly for advanced phase CML. TKI treatment should be withheld during pregnancy. Treatment discontinuation may be considered in patients with durable DMR with the goal of achieving TFR.

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.