PRI: Re-Analysis of a Public Mass Cytometry Dataset Reveals Patterns of Effective Tumor Treatments

Recently, mass cytometry has enabled quantification of up to 50 parameters for millions of cells per sample. It remains a challenge to analyze such high-dimensional data to exploit the richness of the inherent information, even though many valuable new analysis tools have already been developed. We propose a novel algorithm “pattern recognition of immune cells (PRI)” to tackle these high-dimensional protein combinations in the data. PRI is a tool for the analysis and visualization of cytometry data based on a three or more-parametric binning approach, feature engineering of bin properties of multivariate cell data, and a pseudo-multiparametric visualization. Using a publicly available mass cytometry dataset, we proved that reproducible feature engineering and intuitive understanding of the generated bin plots are helpful hallmarks for re-analysis with PRI. In the CD4 + T cell population analyzed, PRI revealed two bin-plot patterns (CD90/CD44/CD86 and CD90/CD44/CD27) and 20 bin plot features for threshold-independent classification of mice concerning ineffective and effective tumor treatment. In addition, PRI mapped cell subsets regarding co-expression of the proliferation marker Ki67 with two major transcription factors and further delineated a specific Th1 cell subset. All these results demonstrate the added insights that can be obtained using the non-cluster-based tool PRI for re-analyses of high-dimensional cytometric data

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

Stereospecificity of the Siderophore Pyochelin Outer Membrane Transporters in Fluorescent Pseudomonads*

Pyochelin (Pch) and enantio-pyochelin (EPch) are enantiomer siderophores that are produced by Pseudomonas aeruginosa and Pseudomonas fluorescens, respectively, under iron limitation. Pch promotes growth of P. aeruginosa when iron is scarce, and EPch carries out the same biological function in P. fluorescens. However, the two siderophores are unable to promote growth in the heterologous species, indicating that siderophore-mediated iron uptake is highly stereospecific. In the present work, using binding and iron uptake assays, we found that FptA, the Fe-Pch outer membrane transporter of P. aeruginosa, recognized (Kd = 2.5 ± 1.1 nm) and transported Fe-Pch but did not interact with Fe-EPch. Likewise, FetA, the Fe-EPch receptor of P. fluorescens, was specific for Fe-EPch (Kd = 3.7 ± 2.1 nm) but did not bind and transport Fe-Pch. Growth promotion experiments performed under iron-limiting conditions confirmed that FptA and FetA are highly specific for Pch and EPch, respectively. When fptA and fetA along with adjacent transport genes involved in siderophore uptake were swapped between the two bacterial species, P. aeruginosa became able to utilize Fe-EPch as an iron source, and P. fluorescens was able to grow with Fe-Pch. Docking experiments using the FptA structure and binding assays showed that the stereospecificity of Pch recognition by FptA was mostly due to the configuration of the siderophore chiral centers C4″ and C2″ and was only weakly dependent on the configuration of the C4′ carbon atom. Together, these findings increase our understanding of the stereospecific interaction between Pch and its outer membrane receptor FptA

Esential cases on natural causation

Bibliografija išnašose ; Rodyklė: p. 619-627This volume of the „Digest of European Tort Law" is the first product of a most ambitious research project: a collection of court decisions from almost all European jurisdictions on the most fundamental aspects of tort law. These cases are not only accumulated, but also structured, analysed and commented both from a national as well as a comparative perspective. Historical aspects are also considered, as are future trends, as outlined by current projects on the harmonisation of European tort laws. This complex comparative study shall thereby not only offer guidance for researching cross-border cases, but also allow a discussion of such harmonisation projects on the basis of real-life case settings. This first volume covers one key aspect of tortious liability – natural causation. The conditio sine qua non rule is examined and tested throughout all jurisdictions, in particular with an eye on whether and to what extent courts are willing to deviate from the strict concept of this formulaMykolo Romerio universiteta

Essential cases on damage

Bibliogr. išnašoseThe increasing Europeanisation of the law of delict/torts has produced textbooks, casebooks, monographs, and also sets of model rules of a genuinely European character. A major gap still existing today relates to the experiences gathered in the national legal systems over the past decades. The present work attempts to fill this gap for one key element of tort law: the notion of damage. It thus does what the previous volume in the ‘Digest of European Tort Law’ series did for another key element, ie natural causation. Once again, the publication contains a selection of the most important cases decided in 26 states across Europe as well as by the European Court of Justice. For each case the facts and the relevant court decision are presented, and the decision is analysed within the wider context of the development of the respective legal system. In addition, the editors provide comparative analyses of the case law reported in this volume concerning all the specific problems raised under the heading of damage. The publication also looks into how key cases would be resolved under the European model rules drafted in the field of tort law; and it also highlights cases from earlier periods of legal history. The editors believe that the material gathered here may provide guidance for an organic convergence of the national legal systems in Europe. It constitutes the basis of an acquis commun that is infinitely richer (though also much more complex) than the rather bland and abstract concepts contained in national codifications, European legislation, and the modern model rulesMykolo Romerio universitetasPrivatinės teisės katedraVytauto Didžiojo universiteta

Essential cases on misconduct

Bibliografija išnašoseThe various national European legal systems offer a broad range of responses to the question of what can be regarded as wrongful behaviour or fault. The present work systematically examines these two important prerequisites for tortious liability under the combined heading of ‘misconduct’. Unlike current textbooks, national casebooks and monographs, it builds on the experiences gathered in the national legal systems over the past decades and thereby fills a major gap which still exists today. It thus does what the previous volumes in the ‘Digest of European Tort Law’ series did for other key elements of tort law, namely natural causation and damage. Once again, the publication contains a selection of the most important cases from 28 states across Europe as well as cases handed down by European Union courts; it also highlights cases from earlier periods of legal history. For each case, the facts and the relevant court decision are presented and these are then accompanied by an analytical commentary. In addition, the editors provide comparative analyses of the cases reported and a special report is dedicated to how key decisions would be resolved under model European rules on tort law. The editors believe that the material gathered here may provide guidance for an organic convergence of the national legal systems in Europe. It constitutes the basis of an acquis commun that is infinitely richer (though also much more complex) than the rather bland and abstract concepts contained in national codifications, European legislation and modern model rulesMykolo Romerio universitetasPrivatinės teisės katedraVytauto Didžiojo universiteta