scholarly journals “Molecular Anatomy”: a new multi-dimensional hierarchical scaffold analysis tool

2021 ◽  
Vol 13 (1) ◽  
Author(s):  
Candida Manelfi ◽  
Marica Gemei ◽  
Carmine Talarico ◽  
Carmen Cerchia ◽  
Anna Fava ◽  
...  
Keyword(s):  
Graphical Representation ◽  
Biological Activities ◽  
Analysis Tool ◽  
Large Set ◽  
Molecular Scaffold ◽  
Novel Approach ◽  
Molecular Anatomy ◽  
Fragmentation Rules ◽  
Hierarchical Scaffold ◽  
Abstraction Levels

AbstractThe scaffold representation is widely employed to classify bioactive compounds on the basis of common core structures or correlate compound classes with specific biological activities. In this paper, we present a novel approach called “Molecular Anatomy” as a flexible and unbiased molecular scaffold-based metrics to cluster large set of compounds. We introduce a set of nine molecular representations at different abstraction levels, combined with fragmentation rules, to define a multi-dimensional network of hierarchically interconnected molecular frameworks. We demonstrate that the introduction of a flexible scaffold definition and multiple pruning rules is an effective method to identify relevant chemical moieties. This approach allows to cluster together active molecules belonging to different molecular classes, capturing most of the structure activity information, in particular when libraries containing a huge number of singletons are analyzed. We also propose a procedure to derive a network visualization that allows a full graphical representation of compounds dataset, permitting an efficient navigation in the scaffold’s space and significantly contributing to perform high quality SAR analysis. The protocol is freely available as a web interface at https://ma.exscalate.eu.

“Molecular Anatomy”: A New Multi-Dimensional Hierarchical Scaffold Analysis tool 

2021 ◽  
Author(s):  
Candida Manelfi ◽  
Marica Gemei ◽  
Carmine Talarico ◽  
Carmen Cerchia ◽  
Andrea R. Beccari
Keyword(s):  
Graphical Representation ◽  
Biological Activities ◽  
Analysis Tool ◽  
Large Set ◽  
Molecular Scaffold ◽  
Novel Approach ◽  
Molecular Anatomy ◽  
Fragmentation Rules ◽  
Hierarchical Scaffold ◽  
Abstraction Levels

Abstract The scaffold representation is widely employed to classify bioactive compounds on the basis of common core structures or correlate compound classes with specific biological activities. In this paper, we present a novel approach called “Molecular Anatomy” as a flexible and unbiased molecular scaffold-based metrics to cluster large set of compounds. We introduce a set of nine molecular representations at different abstraction levels, combined with fragmentation rules, to define a multi-dimensional network of hierarchically interconnected molecular frameworks. We demonstrate that the introduction of a flexible scaffold definition and multiple pruning rules is an effective method to identify relevant chemical moieties. This approach allows to cluster together different molecular species with similar biological activity, capturing most of the structure activity information, in particular when libraries containing a huge number of singletons are analyzed. We also propose a procedure to derive a network visualization that allows a full graphical representation of compounds dataset, permitting an efficient navigation in the scaffold’s space and significantly contributing to perform high quality SAR analysis.

scholarly journals “Molecular Anatomy”:  A New Multi-Dimensional Hierarchical Scaffold Analysis tool

2021 ◽  
Author(s):  
Candida Manelfi ◽  
Marica Gemei ◽  
Carmine Talarico ◽  
Carmen Cerchia ◽  
Andrea R. Beccari
Keyword(s):  
Graphical Representation ◽  
Analysis Tool ◽  
Large Set ◽  
Molecular Scaffold ◽  
Novel Approach ◽  
Molecular Anatomy ◽  
Fragmentation Rules ◽  
Hierarchical Scaffold ◽  
Abstraction Levels ◽  
Sar Analysis

Abstract The scaffold representation is widely employed to classify bioactive compounds on the basis of common core structures or correlate compound classes with specific biological activities.In this paper, we present a novel approach called “Molecular Anatomy” as a flexible and unbiased molecular scaffold-based metrics to cluster large set of compounds. We introduce a set of nine molecular representations at different abstraction levels, combined with fragmentation rules, to define a multi-dimensional network of hierarchically interconnected molecular frameworks. We demonstrate that the introduction of a flexible scaffold definition and multiple pruning rules is an effective method to identify relevant chemical moieties. This approach allows to cluster together different molecular species with similar biological activity, capturing most of the structure activity information, in particular when libraries containing a huge number of singletons are analyzed. We also propose a procedure to derive a network visualization that allows a full graphical representation of compounds dataset, permitting an efficient navigation in the scaffold’s space and significantly contributing to perform high quality SAR analysis.

scholarly journals Use of Dynamic Analysis to Investigate the Behaviour of Short Neutral Sections in the Overhead Line Electrification

2021 ◽  
Vol 6 (5) ◽  
pp. 62
Author(s):  
John Morris ◽  
Mark Robinson ◽  
Roberto Palacin
Keyword(s):  
Dynamic Analysis ◽  
Dynamic Simulation ◽  
Model Simulation ◽  
Analysis Tool ◽  
Overhead Line ◽  
Element Analysis ◽  
Novel Approach ◽  
Section Model ◽  
The Uk ◽  
Neutral Section

The ‘short’ neutral section is a feature of alternating current (AC) railway overhead line electrification that is often unreliable and a source of train delays. However hardly any dynamic analysis of its behaviour has been undertaken. This paper briefly describes the work undertaken investigating the possibility of modelling the behaviour using a novel approach. The potential for thus improving the performance of short neutral sections is evaluated, with particular reference to the UK situation. The analysis fundamentally used dynamic simulation of the pantograph and overhead contact line (OCL) interface, implemented using a proprietary finite element analysis tool. The neutral section model was constructed using physical characteristics and laboratory tests data, and was included in a validated pantograph/OCL simulation model. Simulation output of the neutral section behaviour has been validated satisfactorily against real line test data. Using this method the sensitivity of the neutral section performance in relation to particular parameters of its construction was examined. A limited number of parameter adjustments were studied, seeking potential improvements. One such improvement identified involved the additional inclusion of a lever arm at the trailing end of the neutral section. A novel application of pantograph/OCL dynamic simulation to modelling neutral section behaviour has been shown to be useful in assessing the modification of neutral section parameters.

scholarly journals Human Defensins: A Novel Approach in the Fight against Skin Colonizing Staphylococcus aureus

Antibiotics ◽  
2020 ◽  
Vol 9 (4) ◽  
pp. 198 ◽  
Author(s):  
Olga Scudiero ◽  
Mariarita Brancaccio ◽  
Cristina Mennitti ◽  
Sonia Laneri ◽  
Barbara Lombardo ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Innate Immunity ◽  
Molecular Mechanisms ◽  
Biological Activities ◽  
Interleukin 1 ◽  
Interleukin 17 ◽  
Skin Infections ◽  
Skin Disorders ◽  
Novel Approach ◽  
Pharmacological Potential

Staphylococcus aureus is a microorganism capable of causing numerous diseases of the human skin. The incidence of S. aureus skin infections reflects the conflict between the host skin′s immune defenses and the S. aureus’ virulence elements. Antimicrobial peptides (AMPs) are small protein molecules involved in numerous biological activities, playing a very important role in the innate immunity. They constitute the defense of the host′s skin, which prevents harmful microorganisms from entering the epithelial barrier, including S. aureus. However, S. aureus uses ambiguous mechanisms against host defenses by promoting colonization and skin infections. Our review aims to provide a reference collection on host-pathogen interactions in skin disorders, including S. aureus infections and its resistance to methicillin (MRSA). In addition to these, we discuss the involvement of defensins and other innate immunity mediators (i.e., toll receptors, interleukin-1, and interleukin-17), involved in the defense of the host against the skin disorders caused by S. aureus, and then focus on the evasion mechanisms developed by the pathogenic microorganism under analysis. This review provides the “state of the art” on molecular mechanisms underlying S. aureus skin infection and the pharmacological potential of AMPs as a new therapeutic strategy, in order to define alternative directions in the fight against cutaneous disease.

scholarly journals OCAAT: automated analysis of star cluster colour-magnitude diagrams for gauging the local distance scale

2014 ◽  
Vol 10 (S306) ◽  
pp. 298-300
Author(s):  
Gabriel I. Perren ◽  
Ruben A. Vázquez ◽  
Andrés E. Piatti ◽  
André Moitinho
Keyword(s):  
Main Sequence ◽  
Star Clusters ◽  
Automated Analysis ◽  
Star Cluster ◽  
Magellanic Clouds ◽  
Distance Scale ◽  
Analysis Tool ◽  
Large Set ◽  
Uncertainty Estimates ◽  
Local Distance

AbstractStar clusters are among the fundamental astrophysical objects used in setting the local distance scale. Despite its crucial importance, the accurate determination of the distances to the Magellanic Clouds (SMC/LMC) remains a fuzzy step in the cosmological distance ladder. The exquisite astrometry of the recently launched ESA Gaia mission is expected to deliver extremely accurate statistical parallaxes, and thus distances, to the SMC/LMC. However, an independent SMC/LMC distance determination via main sequence fitting of star clusters provides an important validation check point for the Gaia distances. This has been a valuable lesson learnt from the famous Hipparcos Pleiades distance discrepancy problem. Current observations will allow hundreds of LMC/SMC clusters to be analyzed in this light.Today, the most common approach for star cluster main sequence fitting is still by eye. The process is intrinsically subjective and affected by large uncertainties, especially when applied to poorly populated clusters. It is also, clearly, not an efficient route for addressing the analysis of hundreds, or thousands, of star clusters. These concerns, together with a new attitude towards advanced statistical techniques in astronomy and the availability of powerful computers, have led to the emergence of software packages designed for analyzing star cluster photometry. With a few rare exceptions, those packages are not publicly available.Here we present OCAAT (Open Cluster Automated Analysis Tool), a suite of publicly available open source tools that fully automatises cluster isochrone fitting. The code will be applied to a large set of hundreds of open clusters observed in the Washington system, located in the Milky Way and the Magellanic Clouds. This will allow us to generate an objective and homogeneous catalog of distances up to ~ 60 kpc along with its associated reddening, ages and metallicities and uncertainty estimates.

scholarly journals Micro RNA Expression after Ingestion of Fucoidan; A Clinical Study

Marine Drugs ◽  
2020 ◽  
Vol 18 (3) ◽  
pp. 143 ◽  
Author(s):  
Nuri Gueven ◽  
Kevin J. Spring ◽  
Sandra Holmes ◽  
Kiran Ahuja ◽  
Raj Eri ◽  
...  
Keyword(s):  
Single Dose ◽  
Biological Activities ◽  
Micro Rna ◽  
Cell Surface Receptor ◽  
Sulfated Polysaccharides ◽  
Analysis Tool ◽  
Brown Macroalgae ◽  
Double Blind

Fucoidans are a class of fucose-rich sulfated polysaccharides derived from brown macroalgae that exert a range of biological activities in vitro and in vivo. To generate an unbiased assessment of pathways and processes affected by fucoidan, a placebo-controlled double-blind pilot study was performed in healthy volunteers. Blood samples were taken immediately before and 24 h after ingestion of a single dose of 1 g of Undaria pinnatifida fucoidan (UPF) or placebo. Levels of isolated miRNAs were analyzed using Taqman Open Array Human MicroRNA panels. Out of 754 miRNAs screened, UPF affected a total of 53 miRNAs. Pathway analysis using the TALOS data analysis tool predicted 29 different pathways and processes that were largely grouped into cell surface receptor signaling, cancer-related pathways, the majority of which were previously associated with fucoidans. However, this analysis also identified nine pathways and processes that have not been associated with fucoidans before. Overall, this study illustrates that even a single dose of fucoidans has the potential to affect the expression of genes related to fundamental cellular processes. Moreover, it confirms previous data that fucoidans influence immunity, cancer cells, inflammation, and neurological function.

scholarly journals Learning to Transfer Relational Representations through Analogy

2019 ◽  
Vol 33 ◽  
pp. 10015-10016
Author(s):  
Gaetano Rossiello ◽  
Alfio Gliozzo ◽  
Michael Glass
Keyword(s):  
State Of The Art ◽  
Relation Extraction ◽  
Knowledge Bases ◽  
The State ◽  
Large Set ◽  
Relational Information ◽  
Siamese Network ◽  
Distant Supervision ◽  
Novel Approach ◽  
Art Methods

We propose a novel approach to learn representations of relations expressed by their textual mentions. In our assumption, if two pairs of entities belong to the same relation, then those two pairs are analogous. We collect a large set of analogous pairs by matching triples in knowledge bases with web-scale corpora through distant supervision. This dataset is adopted to train a hierarchical siamese network in order to learn entity-entity embeddings which encode relational information through the different linguistic paraphrasing expressing the same relation. The model can be used to generate pre-trained embeddings which provide a valuable signal when integrated into an existing neural-based model by outperforming the state-of-the-art methods on a relation extraction task.

Design Automation of Modular Industrial Robots

2009 ◽  
Author(s):  
Mehdi Tarkian ◽  
Johan O¨lvander ◽  
Xiaolong Feng ◽  
Marcus Petterson
Keyword(s):  
Design Automation ◽  
Parametric Design ◽  
Industrial Robot ◽  
Industrial Robots ◽  
Modular Robots ◽  
Integrated Analysis ◽  
Analysis Tool ◽  
Modeling Methodology ◽  
Novel Approach ◽  
Main Components

This paper presents a novel approach for designing modular robots. There are two main components in this approach namely the modeling methodology of the robot and a framework for simulation of the models and execution of an optimization process. To illustrate the presented methodology an integrated analysis tool for an industrial robot is developed combining dynamic and geometric models in a parametric design approach. An optimization case is conducted to visualize the automation capabilities of the proposed framework, and enhance the design for modular industrial robots.

scholarly journals Pseudopterosin Inhibits Proliferation and 3D Invasion in Triple Negative Breast Cancer by Agonizing Glucocorticoid Receptor Alpha

2018 ◽  
Author(s):  
Julia Sperlich ◽  
Nicole Teusch
Keyword(s):  
Breast Cancer ◽  
Glucocorticoid Receptor ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Mononuclear Cells ◽  
Biological Activities ◽  
Tumor Spheroids ◽  
Peripheral Blood Mononuclear ◽  
Surrounding Matrix ◽  
Novel Approach

Pseudopterosin, produced by the sea whip of the genus Antillogorgia, possesses a variety of promising biological activities including potent anti-inflammatory effects. However, few studies examined pseudopterosin in the treatment of cancer cells and, to our knowledge, the ability to inhibit triple negative breast cancer (TNBC) proliferation or invasion has not been explored. Thus, we evaluated the as yet unknown mechanism of action of pseudopterosin: Pseudopterosin was able to inhibit proliferation of TNBC. Interestingly, analyzing breast cancer cell proliferation after knocking down glucocorticoid receptor α (GRα) revealed that anti-proliferative effects of pseudopterosin were significantly inhibited when GRα expression was reduced. Furthermore, pseudopterosin inhibited invasion of MDA-MB-231 3D tumor spheroids embedded in an extracellular-like matrix. Remarkably, the knockdown of GRα in 3D tumor spheroids revealed increased ability of cells to invade the surrounding matrix. In a co-culture, encompassing peripheral blood mononuclear cells (PBMC) and MDA-MB-231 cells, production of interleukin 6 (IL-6) and interleukin 8 (IL-8) significantly increased compared to monoculture. Notably, pseudopterosin proved to block cytokine elevation, representing key players in tumor progression, in the co-culture. Thus, our results reveal pseudopterosin treatment as a potential novel approach in TNBC therapy.

Sign in / Sign up

Export Citation Format

Share Document