scholarly journals CPExtract, a Software for the Automated Tracer-Based Pathway Specific Screening of Secondary Metabolites in LC-HRMS Data

2021 ◽  
Author(s):  
Bernhard Seidl ◽  
Rainer Schuhmacher ◽  
Christoph Bueschl
Keyword(s):  
Malonic Acid ◽  
Biological Samples ◽  
Software Tool ◽  
Diethyl Ester ◽  
Proof Of Concept ◽  
Commercial Use ◽  
Rule Sets ◽  
Intensity Ratios ◽  
First Time ◽  
Monomethyl Ester

The use of stable isotopically labeled tracers is a long-proven way of specifically detecting and tracking derived metabolites through a metabolic network of interest. While recently developed stable isotope assisted methods and associated, supporting data analysis tools have greatly improved untargeted metabolomics approaches, no software tool is currently available that allows to automatically search LC-HRMS chromatograms for completely free user-definable isotopolog patterns expected for the metabolism of labeled tracer substances. Here we present Custom Pattern Extract (CPExtract), a versatile software tool that allows for the first time the high-throughput search for user-defined isotopolog patterns in LC-HRMS data. The patterns can be specified via a set of rules including the presence or absence of certain isotopologs, their relative intensity ratios as well as chromatographic co-elution. Each isotopolog pattern satisfying the respective rules is verified on a MS-scan level and also in the chromatographic domain. The CPExtract algorithm allows the use of both labeled tracer compounds in non-labeled biological samples as well as a reversed tracer approach, employing non-labeled tracer compounds along with globally labeled biological samples. In a proof of concept study we searched for metabolites specifically arising from the malonate pathway of the filamentous fungi Fusarium graminearum and Trichoderma reesei. 1,2,3- 13 C 3 -malonic acid diethyl ester and native malonic acid monomethyl ester were used as tracers. We were able to reliably detect expected fatty acids and known polyketides. In addition, up to 189 and 270 further, unknown metabolites presumably including novel polyketides were detected in the F. graminearum and T. reesei culture samples respectively, all of which exhibited the user-predicted isotopolog patterns originating from the malonate tracer incorporation. The software can be used for every conceivable tracer approach. Furthermore, the rule sets can be easily adapted or extended if necessary. CPExtract is available free of charge for non-commercial use at https://metabolomics-ifa.boku.ac.at/CPExtract.

scholarly journals Self-Dividing Micelles: A Mechanistic Look with Evolutionary and Clinical Implications

2021 ◽  
pp. 8-20
Keyword(s):  
Fatty Acid ◽  
Amino Acid ◽  
Laboratory Testing ◽  
Prebiotic Chemistry ◽  
Clinical Implications ◽  
Proof Of Concept ◽  
Mass Spec ◽  
First Time ◽  
Division Mechanism ◽  
Viable Treatment

Micellar therapy has become a usefully viable treatment arm in various fields, ranging from oncology to bioimaging. As such, research leading to any improvements or adaptations in administration and techniques can have far-reaching consequences. Potential aspects of prebiotic chemistry may also be explored in such research as well. To that end, proof-of-concept experiments were performed to elucidate a possible mechanism of action for prebiotic protocell division. Representative potentially prebiotically plausible biomolecules, i.e., a fatty acid, amino acid, and nucleotide were mixed and heated in water and subjected to microscopic examination for observation of possible self-division and laboratory testing for the presence of polypeptides and polynucleotides (Biuret, MALDI mass-spec, etc.) with and without the presence of nucleotide. The results are presented for the first time here and a mechanism is proposed that best fits the data obtained. The evolutionary, e.g., prebiotic biomolecular cooperativity, and clinical, e.g., potential antineoplastic micellar/vesicular therapy, ramifications are discussed as well. Keywords: Micelle; Liposome; Protocell; MRNA; Self-division; Mechanism; Solid tumors

scholarly journals Regulostat Inferelator: a novel network biology platform to uncover molecular devices that predetermine cellular response phenotypes

2019 ◽  
Vol 47 (14) ◽  
pp. e82-e82
Author(s):  
Choong Yong Ung ◽  
Mehrab Ghanat Bari ◽  
Cheng Zhang ◽  
Jingjing Liang ◽  
Cristina Correia ◽  
...  
Keyword(s):  
Cellular Response ◽  
Expression Patterns ◽  
Fine Tuning ◽  
Molecular Devices ◽  
Proof Of Concept ◽  
Genetic Circuits ◽  
Continuous Response ◽  
Context Specific ◽  
First Time ◽  
Phenotypic Responses

Abstract With the emergence of genome editing technologies and synthetic biology, it is now possible to engineer genetic circuits driving a cell's phenotypic response to a stressor. However, capturing a continuous response, rather than simply a binary ‘on’ or ‘off’ response, remains a bioengineering challenge. No tools currently exist to identify gene candidates responsible for predetermining and fine-tuning cell response phenotypes. To address this gap, we devised a novel Regulostat Inferelator (RSI) algorithm to decipher intrinsic molecular devices or networks that predetermine cellular phenotypic responses. The RSI algorithm is designed to extract gene expression patterns from basal transcriptomic data in order to identify ‘regulostat’ constituent gene pairs, which exhibit rheostat-like mode-of-cooperation capable of fine-tuning cellular response. Our proof-of-concept study provides computational evidence for the existence of regulostats and that these networks predetermine cellular response prior to exposure to a stressor or drug. In addition, our work, for the first time, provides evidence of context-specific, drug–regulostat interactions in predetermining drug response phenotypes in cancer cells. Given RSI-inferred regulostat networks offer insights for prioritizing gene candidates capable of rendering a resistant phenotype sensitive to a given drug, we envision that this tool will be of great value in bioengineering and medicine.

scholarly journals Establishing the concept of aza-[3 + 3] annulations using enones as a key expansion of this unified strategy in alkaloid synthesis

2013 ◽  
Vol 9 ◽  
pp. 1170-1178 ◽  
Author(s):  
Aleksey I Gerasyuto ◽  
Zhi-Xiong Ma ◽  
Grant S Buchanan ◽  
Richard P Hsung
Keyword(s):  
Microwave Irradiation ◽  
Proof Of Concept ◽  
Alkaloid Synthesis ◽  
First Time ◽  
Made In

A successful enone version of an intramolecular aza-[3 + 3] annulation reaction is described here. Use of piperidinium trifluoroacetate salt as the catalyst and toluene as the solvent appears to be critical for a successful annulation. We also demonstrated for the first time that microwave irradiation can accelerate aza-[3 + 3] annulation reactions. An attempt to expand the scope of the enone aza-[3 + 3] annulation was made in the form of propyleine synthesis as a proof of concept. While synthesis of the enone annulation precursor was successfully accomplished, the annulation proved to be challenging and was only modestly successful.

scholarly journals Opening paper 2015- Some comments on Bioglass: Four Eras of Discovery and Development

2015 ◽  
Vol 1 (1) ◽  
Author(s):  
Larry L. Hench
Keyword(s):  
Clinical Application ◽  
Tissue Regeneration ◽  
First Generation ◽  
Scar Tissue ◽  
Interfacial Bonding ◽  
Bioactive Glasses ◽  
Commercial Use ◽  
First Time ◽  
Host Tissues

AbstractHistorically the function of biomaterials was to replace diseased or damaged tissues. First generation biomaterials were selected to be as bio-inert as possible and thereby minimize formation of scar tissue at the interface with host tissues. Bioactive glasseswere discovered in 1969 and provided for the first time an alternative; strong, stable interfacial bonding of an implant with host tissues. In the 1980’s it was discovered that bioactive glasses could be used in particulae form to stimulate osteogenesiswhich thereby led to the concept of regeneration of tissues. This article summarizes the four eras of development of bioactive glasses that have led from concept of bioactivity to widespread clinical and commercial use, with emphasis on the first composition, 45S5 Bioglassr. The four eras are; A) Era of Discovery, B) Era of Clinical Application, C) Era of Tissue Regeneration, and D) Era of Innovation. Key scientific and technological questions answered for the first three eras are presented. Questions still to be answered for the fourth era are included to stimulate innovation in the field.

Identifying the potential of pulsed LED irradiation in synthesis: copper-photocatalysed C–F functionalisation

2018 ◽  
Vol 54 (36) ◽  
pp. 4589-4592 ◽  
Author(s):  
Thomas P. Nicholls ◽  
Johnathon C. Robertson ◽  
Michael G. Gardiner ◽  
Alex C. Bissember
Keyword(s):  
Visible Light ◽  
Product Formation ◽  
Proof Of Concept ◽  
Concept Study ◽  
Catalysed Reaction ◽  
First Time ◽  
Led Irradiation

The results of a proof-of-concept study demonstrate for the first time that pulsed LED irradiation enhances the rate of product formation and the yield of a visible light-mediated photoredox-catalysed reaction.

Online in situ prediction of 3-D flame evolution from its history 2-D projections via deep learning

2019 ◽  
Vol 875 ◽  
Author(s):  
Jianqing Huang ◽  
Hecong Liu ◽  
Weiwei Cai
Keyword(s):  
Deep Learning ◽  
Large Scale ◽  
Proof Of Concept ◽  
Time Resolved ◽  
Computational Costs ◽  
Rapid Prediction ◽  
Computational Fluid Dynamics Cfd ◽  
In Situ Prediction ◽  
First Time

Online in situ prediction of 3-D flame evolution has been long desired and is considered to be the Holy Grail for the combustion community. Recent advances in computational power have facilitated the development of computational fluid dynamics (CFD), which can be used to predict flame behaviours. However, the most advanced CFD techniques are still incapable of realizing online in situ prediction of practical flames due to the enormous computational costs involved. In this work, we aim to combine the state-of-the-art experimental technique (that is, time-resolved volumetric tomography) with deep learning algorithms for rapid prediction of 3-D flame evolution. Proof-of-concept experiments conducted suggest that the evolution of both a laminar diffusion flame and a typical non-premixed turbulent swirl-stabilized flame can be predicted faithfully in a time scale on the order of milliseconds, which can be further reduced by simply using a few more GPUs. We believe this is the first time that online in situ prediction of 3-D flame evolution has become feasible, and we expect this method to be extremely useful, as for most application scenarios the online in situ prediction of even the large-scale flame features are already useful for an effective flame control.

scholarly journals Mixed Mode, Sequential and Relaxation Oscillations in the Belousov-Zhabotinsky System

2007 ◽  
Vol 62 (1-2) ◽  
pp. 41-55 ◽  
Author(s):  
Małgorzata Rachwalska
Keyword(s):  
Malonic Acid ◽  
Mixed Mode ◽  
Relaxation Oscillations ◽  
Batch Experiments ◽  
Chemical Mixture ◽  
Mixed Mode Oscillations ◽  
First Time

The behaviour of a system composed of malonic acid (MA), KBrO3, H2SO4, and ferroin was investigated in batch experiments at various concentrations of oxygen above the chemical mixture when changing the concentration of MA. We could observe that at 10% of oxygen or more and for initial concentrations of malonic acid [MA]0 between 0.15 M and 0.6 M the system attains an equilibrium by some of mixed mode oscillations. Such a behaviour of the system could be described by a model used lately. Additionally for [MA]0 = 0.1 M or less at 0 - 20% of oxygen a region of sequential oscillations was discovered (observed for the first time in the system with ferroin) and a trial of understanding of the event is suggested. For rather small [MA]0 ca. 0.025 M no mixed mode oscillations, no sequential ones but the so-called relaxation oscillations were observed.

scholarly journals Design and multicentric Implementation of a generic Software Architecture for Patient Recruitment Systems re-using existing HIS tools and Routine Patient Data

2014 ◽  
Vol 05 (01) ◽  
pp. 264-283 ◽  
Author(s):  
F. Köpcke ◽  
T. Leusch ◽  
R.W. Majeed ◽  
B. Schreiweis ◽  
J. Wenk ◽  
...  
Keyword(s):  
Software Architecture ◽  
Patient Data ◽  
Patient Recruitment ◽  
Proof Of Concept ◽  
University Hospitals ◽  
Feature Sets ◽  
Software Modules ◽  
Recruitment System ◽  
The Given ◽  
First Time

SummaryObjective: (1) To define features and data items of a Patient Recruitment System (PRS); (2) to design a generic software architecture of such a system covering the requirements; (3) to identify implementation options available within different Hospital Information System (HIS) environments; (4) to implement five PRS following the architecture and utilizing the implementation options as proof of concept.Methods: Existing PRS were reviewed and interviews with users and developers conducted. All reported PRS features were collected and prioritized according to their published success and user’s request. Common feature sets were combined into software modules of a generic software architecture. Data items to process and transfer were identified for each of the modules. Each site collected implementation options available within their respective HIS environment for each module, provided a prototypical implementation based on available implementation possibilities and supported the patient recruitment of a clinical trial as a proof of concept.Results: 24 commonly reported and requested features of a PRS were identified, 13 of them prioritized as being mandatory. A UML version 2 based software architecture containing 5 software modules covering these features was developed. 13 data item groups processed by the modules, thus required to be available electronically, have been identified. Several implementation options could be identified for each module, most of them being available at multiple sites. Utilizing available tools, a PRS could be implemented in each of the five participating German university hospitals.Conclusion: A set of required features and data items of a PRS has been described for the first time. The software architecture covers all features in a clear, well-defined way. The variety of implementation options and the prototypes show that it is possible to implement the given architecture in different HIS environments, thus enabling more sites to successfully support patient recruitment in clinical trials.Citation: Trinczek B, Köpcke F, Leusch T, Majeed RW, Schreiweis B, Wenk J, Bergh B, Ohmann C, Röhrig R, Prokosch HU, Dugas M. Design and multicentric implementation of a generic software architecture for patient recruitment systems re-using existing HIS tools and routine patient data. Appl Clin Inf 2014; 5: 264–283 http://dx.doi.org/10.4338/ACI-2013-07-RA-0047

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