69 research outputs found
Spectral binning as an approach to post-acquisition processing of high resolution FIE-MS metabolome fingerprinting data
INTRODUCTION: Flow infusion electrospray high resolution mass spectrometry (FIE-HRMS) fingerprinting produces complex, high dimensional data sets which require specialist in-silico software tools to process the data prior to analysis. OBJECTIVES: Present spectral binning as a pragmatic approach to post-acquisition procession of FIE-HRMS metabolome fingerprinting data. METHODS: A spectral binning approach was developed that included the elimination of single scan m/z events, the binning of spectra and the averaging of spectra across the infusion profile. The modal accurate m/z was then extracted for each bin. This approach was assessed using four different biological matrices and a mix of 31 known chemical standards analysed by FIE-HRMS using an Exactive Orbitrap. Bin purity and centrality metrics were developed to objectively assess the distribution and position of accurate m/z within an individual bin respectively. RESULTS: The optimal spectral binning width was found to be 0.01 amu. 80.8% of the extracted accurate m/z matched to predicted ionisation products of the chemical standards mix were found to have an error of below 3 ppm. The open-source R package binneR was developed as a user friendly implementation of the approach. This was able to process 100 data files using 4 Central Processing Units (CPU) workers in only 55 seconds with a maximum memory usage of 1.36 GB. CONCLUSION: Spectral binning is a fast and robust method for the post-acquisition processing of FIE-HRMS data. The open-source R package binneR allows users to efficiently process data from FIE-HRMS experiments with the resources available on a standard desktop computer. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s11306-022-01923-6
Communicating Processes with Data for Supervisory Coordination
We employ supervisory controllers to safely coordinate high-level
discrete(-event) behavior of distributed components of complex systems.
Supervisory controllers observe discrete-event system behavior, make a decision
on allowed activities, and communicate the control signals to the involved
parties. Models of the supervisory controllers can be automatically synthesized
based on formal models of the system components and a formalization of the safe
coordination (control) requirements. Based on the obtained models, code
generation can be used to implement the supervisory controllers in software, on
a PLC, or an embedded (micro)processor. In this article, we develop a process
theory with data that supports a model-based systems engineering framework for
supervisory coordination. We employ communication to distinguish between the
different flows of information, i.e., observation and supervision, whereas we
employ data to specify the coordination requirements more compactly, and to
increase the expressivity of the framework. To illustrate the framework, we
remodel an industrial case study involving coordination of maintenance
procedures of a printing process of a high-tech Oce printer.Comment: In Proceedings FOCLASA 2012, arXiv:1208.432
If I Had My Way, I'd Have Been a Killer: Songwriting and its Motivations for Leisure and Work
This paper builds on our earlier work (Henderson and Spracklen, 2014) which looked at folk musicians exercising agency in careers that can develop from casual leisure through serious leisure to work. In looking specifically at songwriting, it synthesises theories on the underlying motivations refelecting the view of Born (2010, p.171) who suggests that the ‘theory of cultural production requires reinvention’ citing key themes of ’aesthetics and the cultural object; agency and subjectivity; the place of institutions; history, temporality and change; and problems of value and judgement.’ It examines in a phenomenological way, through songwriter interviews, the cultural production of songs and the motivational factors within the songwriting process. Highlighting that this form of cultural production challenges the hierarchical view of Maslow’s needs and suggests the career arc proposed by Stebbins (1992, p. 68) is not a case of work simply following sequentially from serious and casual leisure
The Effect of Oxidant and the Non-Oxidant Alteration of Cellular Thiol Concentration on the Formation of Protein Mixed-Disulfides in HEK 293 Cells
Cellular molecules possess various mechanisms in responding to oxidant stress. In terms of protein responses, protein S-glutathionylation is a unique post-translational modification of protein reactive cysteines forming disulfides with glutathione molecules. This modification has been proposed to play roles in antioxidant, regulatory and signaling in cells under oxidant stress. Recently, the increased level of protein S-glutathionylation has been linked with the development of diseases. In this report, specific S-glutathionylated proteins were demonstrated in human embryonic kidney 293 cells treated with two different oxidative reagents: diamide and hydrogen peroxide. Diamide is a chemical oxidizing agent whereas hydrogen peroxide is a physiological oxidant. Under the experimental conditions, these two oxidants decreased glutathione concentration without toxicity. S-glutathionylated proteins were detected by immunoblotting and glutathione concentrations were determined by high performance liquid chromatography. We further show the effect of alteration of the cellular thiol pool on the amount of protein S-glutathionylation in oxidant-treated cells. Cellular thiol concentrations were altered either by a specific way using buthionine sulfoximine, a specific inhibitor of glutathione biosynthesis or by a non-specific way, incubating cells in cystine-methionine deficient media. Cells only treated with either buthionine sulfoximine or cystine-methionine deficient media did not induce protein S-glutathionylation, even though both conditions decreased 65% of cellular glutathione. Moreover, the amount of protein S-glutathionylation under both conditions in the presence of oxidants was not altered when compared to the amount observed in regular media with oxidants present. Protein S-glutathionylation is a dynamic reaction which depends on the rate of adding and removing glutathione. Phenylarsine oxide, which specifically forms a covalent adduct with vicinal thiols, was used to determine the possible role of vicinal thiols in the amount of glutathionylation. Our data shows phenylarsine oxide did not change glutathione concentrations, but it did enhance the amount of glutathionylation in oxidant-treated cells
L’usage de la poésie haïku en psycho-oncologie
International audienceAbstract Aim: Our study aims to describe the discourseeffects of specific and structured protocol focused on severalhaiku poems about one patient, who have experienced cancer.Procedure: The protocol consists of 4 steps: a preliminaryexploratory interview, fifteen haiku proposed without a partof the poem (a creative writing filled in by the patient), a freeform haiku composed by the patient, and finally, a finalinterview.Clinical case: A man, D., aged 25, had tumor.Result: Using this protocol, we showed discourse variationson the illness before and after the experience of poetrywriting, by Tropes V8.4 software.Conclusion: Haiku poetry can be a useful tool in the contextof supportive interventions or as preparatory work for engagementin psychotherapeutic intervention. We believe thatthe formal structure of haikus can create conditions for aspecific poetic work composed of: poetic evocation, synthesis,and mapping of the most intimate experiences in oncologyenvironment.Résumé Objectif : Cette étude qualitative et exploratoirevise à décrire les effets d’un protocole poétique centré surles haïkus en psycho-oncologie sur l’approche de la maladiechez un patient atteint de cancer.Matériel et méthodes : Il s’agit d’un protocole d’écriturepoétique composé de quatre étapes : un entretien préliminaire,la proposition de 15 haïkus (sans le vers du milieu)tirés de grands auteurs japonais, la réalisation d’un poèmecomposé librement par deux patients atteints de cancer, unentretien final sur l’expérience de l’écriture poétique.Cas clinique : Un homme, M. D., âgé de 25 ans, qui est entraitement pour un cancer.Résultats : Nous montrons les variations discursives utiliséesavant et après l’expérience de l’écriture poétique, à travers lelogiciel Tropes V8.4.Conclusion : Le travail poétique avec le haïku peut être unoutil utile, dans un contexte de support clinique en institutionou comme préparation à un travail de psychothérapie. Nouspensons que la structure formelle des haïkus peut inviter à untravail poétique spécifique : évocation poétique, synthèse etschématisation des vécus plus intimes en milieu oncologique
A Process Algebra for Supervisory Coordination
A supervisory controller controls and coordinates the behavior of different
components of a complex machine by observing their discrete behaviour.
Supervisory control theory studies automated synthesis of controller models,
known as supervisors, based on formal models of the machine components and a
formalization of the requirements. Subsequently, code generation can be used to
implement this supervisor in software, on a PLC, or embedded microprocessor. In
this article, we take a closer look at the control loop that couples the
supervisory controller and the machine. We model both event-based and
state-based observations using process algebra and bisimulation-based
semantics. The main application area of supervisory control that we consider is
coordination, referred to as supervisory coordination, and we give an academic
and an industrial example, discussing the process-theoretic concepts employed.Comment: In Proceedings PACO 2011, arXiv:1108.145
Genetic Variation and Reproductive Timing: African American Women from the Population Architecture Using Genomics and Epidemiology (PAGE) Study
Age at menarche (AM) and age at natural menopause (ANM) define the boundaries of the reproductive lifespan in women. Their timing is associated with various diseases, including cancer and cardiovascular disease. Genome-wide association studies have identified several genetic variants associated with either AM or ANM in populations of largely European or Asian descent women. The extent to which these associations generalize to diverse populations remains unknown. Therefore, we sought to replicate previously reported AM and ANM findings and to identify novel AM and ANM variants using the Metabochip (n = 161,098 SNPs) in 4,159 and 1,860 African American women, respectively, in the Women's Health Initiative (WHI) and Atherosclerosis Risk in Communities (ARIC) studies, as part of the Population Architecture using Genomics and Epidemiology (PAGE) Study. We replicated or generalized one previously identified variant for AM, rs1361108/CENPW, and two variants for ANM, rs897798/BRSK1 and rs769450/APOE, to our African American cohort. Overall, generalization of the majority of previously-identified variants for AM and ANM, including LIN28B and MCM8, was not observed in this African American sample. We identified three novel loci associated with ANM that reached significance after multiple testing correction (LDLR rs189596789, p = 5×10-08; KCNQ1 rs79972789, p = 1.9×10-07; COL4A3BP rs181686584, p = 2.9×10-07). Our most significant AM association was upstream of RSF1, a gene implicated in ovarian and breast cancers (rs11604207, p = 1.6×10-06). While most associations were identified in either AM or ANM, we did identify genes suggestively associated with both: PHACTR1 and ARHGAP42. The lack of generalization coupled with the potentially novel associations identified here emphasize the need for additional genetic discovery efforts for AM and ANM in diverse populations. © 2013 Spencer et al
Voicing passion: The emotional economy of songwriting
This article examines articulations of the role of passion in accounts of the life and work of the songwriter. It draws upon a range of interviews with successful artists captured in the Sodajerker On Songwriting podcast. It is suggested that these interviews capture the ‘voicing’ of the conventions of creativity in popular music, exploring a context in which passionate motivation, expression and understanding of the (potentially) affective responses to songs are paramount to the labour of the songwriter. The article explores how the core of this labour deals in emotion, attempting to articulate feelings in recognisable, tradable form. This is a process that is both instrumentally rationalised but often felt to be a deeply authentic process, understood (and believed) to spring from the individual’s emotional experience, so conferring identity in a generic field. In light of current debates about the nature of creative work and emotional labour, the accounts drawn upon here can be seen to epitomise many of the qualities of what constitutes ‘good work’ through a mode of self-actualisation
Identifying New Therapeutic Targets via Modulation of Protein Corona Formation by Engineered Nanoparticles
We introduce a promising methodology to identify new therapeutic targets in cancer. Proteins bind to nanoparticles to form a protein corona. We modulate this corona by using surface-engineered nanoparticles, and identify protein composition to provide insight into disease development.Using a family of structurally homologous nanoparticles we have investigated the changes in the protein corona around surface-functionalized gold nanoparticles (AuNPs) from normal and malignant ovarian cell lysates. Proteomics analysis using mass spectrometry identified hepatoma-derived growth factor (HDGF) that is found exclusively on positively charged AuNPs ((+)AuNPs) after incubation with the lysates. We confirmed expression of HDGF in various ovarian cancer cells and validated binding selectivity to (+)AuNPs by Western blot analysis. Silencing of HDGF by siRNA resulted s inhibition in proliferation of ovarian cancer cells.We investigated the modulation of protein corona around surface-functionalized gold nanoparticles as a promising approach to identify new therapeutic targets. The potential of our method for identifying therapeutic targets was demonstrated through silencing of HDGF by siRNA, which inhibited proliferation of ovarian cancer cells. This integrated proteomics, bioinformatics, and nanotechnology strategy demonstrates that protein corona identification can be used to discover novel therapeutic targets in cancer
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