scholarly journals chroGPS2: differential analysis of epigenome maps in R

2018 ◽  
Author(s):  
Oscar Reina ◽  
Fernando Azorin ◽  
Camille Stephan-Otto Attolini
Keyword(s):  
Case Studies ◽  
De Novo ◽  
Chromatin Domain ◽  
Practical Case ◽  
Differential Analysis ◽  
Starting Point ◽  
Efficient Integration ◽  
Systematic Biases ◽  
Domain Conservation ◽  
Low Dimensional

1Abstract1.1BackgroundsIn the last years we have faced an unprecedented growth in the availability of high-throughput epigenomics data related to the genomic distribution of epigenetic marks, namely transcription factors, histone modifications and other DNA binding proteins. This also pointed out the need for efficient tools for integration, visualization and functional analysis of genomics and epigenomics data. On this subject, we previously developed a computational framework, chroGPS, to integrate and visualize the associations between epigenetic factors and their relation to functional genetic elements in low-dimensional maps. We demonstrated the usefulness of our approach with several practical case studies based on well-defined biological hypothesis.1.2ResultsHere we introduce chroGPS version 2, a major update of our previously developed software with new functionalities for differential analysis of epigenomes. Methods are provided for efficient integration and comparison of data from different conditions or biological backgrounds, accounting and adjusting for systematic biases in order to provide an efficient and statistically robust base for differential analysis. We also include new useful functionalities for general data assessment and quality control prior to comparing maps, such as functions to study chromatin domain conservation between epigenomic backgrounds, to detect gross technical outliers and also to help in the selection of candidate marks for de-novo epigenome mapping. Our software, implemented in R as a Bioconductor package, provides detailed reference and user manuals to allow the final user to reproduce the presented case studies and use them as a starting point for generating and exploring epigenetic maps according to their own experimental needs.1.3ConclusionchroGPS2 extends our previously developed software, providing now a complete, intuitive, efficient and statistically robust framework for generation, visualization, characterization and differential analysis of epigenomic maps, in a way which is easy to adapt to different biological and technical backgrounds allowing exploration and hypothesis testing in multiple biological scenarios.

Matheron's Theory of Regionalised Variables

2019 ◽  
Author(s):  
Georges Matheron
Keyword(s):  
Case Studies ◽  
Physical Meaning ◽  
Practical Case ◽  
Common Structure ◽  
Starting Point ◽  
To Come ◽  
The Many

This book has never been published before, although its contents have provided the basis for hundreds of papers, theses, and books on geostatistics. The chapters are based on the lectures of a summer course given by Georges Matheron in 1970; initially written in French, they were translated into English by Charles Huijbregts. They do not contain mathematical technicalities or practical case studies; instead, they present major topics like estimation variances, kriging systems, mining estimation, and intrinsic theory, all of which are established by simple proofs. The reader is invited to wonder about the physical meaning of the notions Matheron deals with. When Matheron wrote these lectures, he considered the theory of linear geostatistics complete; however, what was an ending for Matheron has been the starting point for most geostatisticians. Many discovered the book’s content indirectly, via the many borrowings one can find in several books; in such a situation, it is always instructive to come back to the original document, where the author's motivations, his physical intuitions, and his thoughts on the meaning of what he does are detailed. The decision to publish this book was motivated by the desire to introduce Matheron’s work to a larger audience. The book has remained faithful to the original notes while introducing a common structure for the chapters and sections, numbering equations sequentially within each chapter, numbering the figures (most of which were redrawn) sequentially, and adding captions. In addition, Matheron’s comments on the exercises, or suggestions for solutions, have been added.

scholarly journals Discovery and Optimization of Selective Inhibitors of Meprin α (Part I)

2021 ◽  
Vol 14 (3) ◽  
pp. 203 ◽  
Author(s):  
Shurong Hou ◽  
Juan Diez ◽  
Chao Wang ◽  
Christoph Becker-Pauly ◽  
Gregg B. Fields ◽  
...  
Keyword(s):  
Inhibitory Activity ◽  
De Novo ◽  
Selective Inhibitors ◽  
Preclinical Development ◽  
Starting Point ◽  
Good Starting Point ◽  
Parallel Screening ◽  
Low Cytotoxicity

Meprin α and β are zinc-dependent proteinases implicated in multiple diseases including cancers, fibrosis, and Alzheimer’s. However, until recently, only a few inhibitors of either meprin were reported and no inhibitors are in preclinical development. Moreover, inhibitors of other metzincins developed in previous years are not effective in inhibiting meprins suggesting the need for de novo discovery effort. To address the paucity of tractable meprin inhibitors we developed ultrahigh-throughput assays and conducted parallel screening of >650,000 compounds against each meprin. As a result of this effort, we identified five selective meprin α hits belonging to three different chemotypes (triazole-hydroxyacetamides, sulfonamide-hydroxypropanamides, and phenoxy-hydroxyacetamides). These hits demonstrated a nanomolar to micromolar inhibitory activity against meprin α with low cytotoxicity and >30-fold selectivity against meprin β and other related metzincincs. These selective inhibitors of meprin α provide a good starting point for further optimization.

Designing a Virtual Enterprise Architecture using Structured System Dynamics

2006 ◽  
Vol 25 (1) ◽  
pp. 13-29
Author(s):  
Nikitas A. Assimakopoulos ◽  
Anastasios N. Riggas
Keyword(s):  
System Dynamics ◽  
Enterprise Architecture ◽  
Business Processes ◽  
Core Competencies ◽  
Virtual Enterprise ◽  
Business Goals ◽  
Starting Point ◽  
Efficient Integration ◽  
Structured System ◽  
The Impact

The starting point for establishing a Virtual Enterprise is a set of existing enterprises which might contribute with some of their functionalities (core competencies) to the formation of the virtual entity. The most important issue, in this formation, is the rapid integration of the business processes of the participating companies. The architecture of the VE must assist companies desiring to enter into a virtual relationship by defining the functions and interfaces of critical business processes, thus allowing for a more rapid and efficient integration of the expertise which will be contributed by each partner in the virtual enterprise. While the integration of computer and communication technologies are no doubt critical issues, the successful attainment of the business goals of the virtual enterprise often depends on its ability to align the business processes and practices of partner enterprises. Focus of this paper, is the presentation of Structured System Dynamics (SSPS) multi-methodology for the design and the evaluation of a Virtual Enterprise Architecture. SSPS uses Systems Thinking and System Dynamics principles as launch pad for its approach. The Systemic Methodologies of Problem Structuring Methodology (PSM) and SAST are also integrated in this new Multi-Methodology. SSPS is a new practical and scientific tool in designing and evaluating a VE architecture providing the ability to determine the impact, reliability, success of the Architectures' models created, refine them and identify potential process improvements. A framework for the rapid and efficient integration of the business processes of the participating companies in the virtual enterprise is provided. For this multi-methodology, a real-life application is also presented for a Virtual Enterprise that constructs Wireless Payment Mechanisms.

scholarly journals Identification of 3,4-Dihydro-2H,6H-pyrimido[1,2-c][1,3]benzothiazin-6-imine Derivatives as Novel Selective Inhibitors of Plasmodium falciparum Dihydroorotate Dehydrogenase

2021 ◽  
Vol 22 (13) ◽  
pp. 7236
Author(s):  
Endah Dwi Hartuti ◽  
Takaya Sakura ◽  
Mohammed S. O. Tagod ◽  
Eri Yoshida ◽  
Xinying Wang ◽  
...  
Keyword(s):  
Drug Target ◽  
De Novo ◽  
Dihydroorotate Dehydrogenase ◽  
Chemical Library ◽  
New Class ◽  
De Novo Biosynthesis ◽  
Starting Point ◽  
Novel Drugs ◽  
Low Toxicity ◽  
Fourth Step

Plasmodium falciparum’s resistance to available antimalarial drugs highlights the need for the development of novel drugs. Pyrimidine de novo biosynthesis is a validated drug target for the prevention and treatment of malaria infection. P. falciparum dihydroorotate dehydrogenase (PfDHODH) catalyzes the oxidation of dihydroorotate to orotate and utilize ubiquinone as an electron acceptor in the fourth step of pyrimidine de novo biosynthesis. PfDHODH is targeted by the inhibitor DSM265, which binds to a hydrophobic pocket located at the N-terminus where ubiquinone binds, which is known to be structurally divergent from the mammalian orthologue. In this study, we screened 40,400 compounds from the Kyoto University chemical library against recombinant PfDHODH. These studies led to the identification of 3,4-dihydro-2H,6H-pyrimido[1,2-c][1,3]benzothiazin-6-imine and its derivatives as a new class of PfDHODH inhibitor. Moreover, the hit compounds identified in this study are selective for PfDHODH without inhibition of the human enzymes. Finally, this new scaffold of PfDHODH inhibitors showed growth inhibition activity against P. falciparum 3D7 with low toxicity to three human cell lines, providing a new starting point for antimalarial drug development.

scholarly journals Computational Analysis of African Swine Fever Virus Protein Space for the Design of an Epitope-Based Vaccine Ensemble

Pathogens ◽  
2020 ◽  
Vol 9 (12) ◽  
pp. 1078 ◽  
Author(s):  
Albert Ros-Lucas ◽  
Florencia Correa-Fiz ◽  
Laia Bosch-Camós ◽  
Fernando Rodriguez ◽  
Julio Alonso-Padilla
Keyword(s):  
T Cell ◽  
Vaccine Development ◽  
De Novo ◽  
African Swine Fever Virus ◽  
African Swine Fever ◽  
Fever Virus ◽  
Economic Losses ◽  
Virus Protein ◽  
Hemorrhagic Disease ◽  
Starting Point

African swine fever virus is the etiological agent of African swine fever, a transmissible severe hemorrhagic disease that affects pigs, causing massive economic losses. There is neither a treatment nor a vaccine available, and the only method to control its spread is by extensive culling of pigs. So far, classical vaccine development approaches have not yielded sufficiently good results in terms of concomitant safety and efficacy. Nowadays, thanks to advances in genomic and proteomic techniques, a reverse vaccinology strategy can be explored to design alternative vaccine formulations. In this study, ASFV protein sequences were analyzed using an in-house pipeline based on publicly available immunoinformatic tools to identify epitopes of interest for a prospective vaccine ensemble. These included experimentally validated sequences from the Immune Epitope Database, as well as de novo predicted sequences. Experimentally validated and predicted epitopes were prioritized following a series of criteria that included evolutionary conservation, presence in the virulent and currently circulating variant Georgia 2007/1, and lack of identity to either the pig proteome or putative proteins from pig gut microbiota. Following this strategy, 29 B-cell, 14 CD4+ T-cell and 6 CD8+ T-cell epitopes were selected, which represent a starting point to investigating the protective capacity of ASFV epitope-based vaccines.

On Others’ Emotions, and Ours: a Reflection on Narratives, Categories, and Heuristic Devices

Relations ◽  
2013 ◽  
pp. 9-22
Author(s):  
Sabrina Tonutti
Keyword(s):  
Case Studies ◽  
Social Relations ◽  
Cultural Anthropology ◽  
Collective Phenomena ◽  
Individual Level ◽  
Starting Point ◽  
Heuristic Devices

This article reflects on some epistemological and methodological tenets of cultural anthropology such as the informants’ role in ethnographical research, the relation between collective phenomena and individuals, and that between case studies (individual level) and abstraction (generalization). These tenets will be addressed focusing on the lack of recognition of animals’ individuality and agency in social relations, and on the related humans/animals opposition. With the topic of the emotional lives of animals as a starting point, the essay sets out to reflect on how the narratives we use to interpret and describe them inform our enquiry within an anthropocentric and essentialist view, consequently biasing our understanding of diversity.

scholarly journals Informação, Publicidade, Propaganda: Correspondentes estrangeiros, agências noticiosas e a “Grande Guerra de palavras” da primeira metade do século XX

2021 ◽  
Vol 45 ◽  
pp. 11-31
Author(s):  
Fernando Clara
Keyword(s):  
World War Ii ◽  
Public Space ◽  
Case Studies ◽  
Public Discourse ◽  
Foreign Correspondents ◽  
Decisive Importance ◽  
Starting Point ◽  
News Agencies ◽  
The Great War ◽  
Political Scene

The essay takes as a starting point Goebbels’ speech delivered at the closing session of the Continental Advertising Congress, held in Vienna in June 1938, and explores the transformations that the communicational public space of the first half of the twentieth century underwent following the two world conflicts that erupted then. In the first part, the essay addresses the progressive hybridisation of public discourse at the time, the increasing blurring of information, advertising and propaganda, and the rapid acceleration of the international circulation of communication during the period. In this context, special attention is paid to actors who, though not new to the international political scene – such as foreign correspondents and news agencies –, gained a new and decisive importance throughout the period in question. The second part analyses two case studies involving these actors and their power on the international political scene during World War II. Geographically, the two case studies are centred around an axis that is usually considered peripheral to the war – neutral Portugal – but which appears central and, in a way, paradigmatic to the “Great War of Words” that was also being fought in the international public space.

scholarly journals Over de referentiële waarde van Juffrouw Lina (1888) van M. Emants, van Chateaubriand (1908) van E. Masoin en van de gevalsstudies van J.M. Charcot

1970 ◽  
Vol 62 ◽  
pp. 273-288
Author(s):  
Elke Van Nieuwenhuyze
Keyword(s):  
Case Studies ◽  
The Other ◽  
The Novel ◽  
Other Hand ◽  
French Writer ◽  
Starting Point ◽  
The One ◽  
Jean Martin Charcot

The aim of this article is to trace the referential value of juffrouw Lina (1888)as part of its narrative organisation by means of the narrativist historical theoryof Frank Ankersmit. This starting point demands a confrontation of thisnaturalist novel by Marcellus Emants with the contemporary medical biographyof the French writer and politician Chateaubriand by the Belgian physicianErnest Masoin on the one hand and with some case studies of hystericsby the famous French docter Jean-Martin Charcot on the other hand. lt willbe argued that the narrativity of the novel plays a key-role in the constructionof its referential value on various levels.

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