Chemometrics for ion mobility spectrometry data:Recent advances and future prospects

Contains fulltext : 161386.pdf (publisher's version ) (Open Access)Historically, advances in the field of ion mobility spectrometry have been hindered by the variation in measured signals between instruments developed by different research laboratories or manufacturers. This has triggered the development and application of chemometric techniques able to reveal and analyze precious information content of ion mobility spectra. Recent advances in multidimensional coupling of ion mobility spectrometry to chromatography and mass spectrometry has created new, unique challenges for data processing, yielding high-dimensional, megavariate datasets. In this paper, a complete overview of available chemometric techniques used in the analysis of ion mobility spectrometry data is given. We describe the current state-of-the-art of ion mobility spectrometry data analysis comprising datasets with different complexities and two different scopes of data analysis, i.e. targeted and non-targeted analyte analyses. Two main steps of data analysis are considered: data preprocessing and pattern recognition. A detailed description of recent advances in chemometric techniques is provided for these steps, together with a list of interesting applications. We demonstrate that chemometric techniques have a significant contribution to the recent and great expansion of ion mobility spectrometry technology into different application fields. We conclude that well-thought out, comprehensive data analysis strategies are currently emerging, including several chemometric techniques and addressing different data challenges. In our opinion, this trend will continue in the near future, stimulating developments in ion mobility spectrometry instrumentation even further

A multivariate approach to investigate the NMR CPMG pulse sequence for analysing low MW species in polymers

Detection and quantification of low molecular weight components in polymeric samples via nuclear magnetic resonance (NMR) spectroscopy can be difficult due to overlapping signal caused by line broadening characteristics of polymers. A way of overcoming this problem could be the exploitation of the difference in relaxation between small molecules and macromolecular species, such as the application of a T2 filter by using the Carr–Purcell–Meiboom–Gill (CPMG) spin-echo pulse sequence. This technique, largely exploited in metabolomics studies, is applied here to material sciences. A Design of Experiments approach was used for evaluating the effect of different acquisition parameters (relaxation delay, echo time and number of cycles) and sample-related ones (concentration and polymer molecular weight) on selected responses, with a particular interest in performing a reliable quantitative analysis. Polymeric samples containing small molecules were analysed by NMR with and without the application of the filter, and analysis of variance was used to identify the most influential parameters. Results indicated that increasing the polymer concentration, hence sample viscosity, further attenuates polymer signals in CPMG experiments because the T2 of those signals tends to decrease with increasing viscosity. The signal-to-noise ratio measured for small molecules can undergo a minimum loss when specific parameters are chosen in relation to the polymer molecular weight. Furthermore, the difference in dynamics between aliphatic and aromatic nuclei, as well as between mobile and stiff polymers, translates into different results in terms of polymer signal reduction, suggesting that the relaxation filter can also be used for obtaining information on the polymer structure

Use of transabdominal ultrasound-guided transjugular portal vein puncture on radiation dose in transjugular intrahepatic portosystemic shunt formation

PURPOSE:Transjugular intrahepatic portosystemic shunt (TIPS) creation is used to treat portal hypertension complications. Often the most challenging and time-consuming step in the procedure is the portal vein (PV) puncture. TIPS procedures are associated with prolonged fluoroscopy time and high patient radiation exposures. We measured the impact of transabdominal ultrasound guidance for PV puncture on duration of fluoroscopy time and dose.METHODS:We retrospectively analyzed the radiation dose for all TIPS performed over a four-year period with transabdominal ultrasound guidance for PV puncture (n=212, with 210 performed successfully and data available for 206); fluoroscopy time, dose area product (DAP) and skin dose were recorded.RESULTS:Mean fluoroscopy time was 12 min 9 s (SD, ±14 min 38 s), mean DAP was 40.3±73.1 Gy·cm2, and mean skin dose was 404.3±464.8 mGy.CONCLUSION:Our results demonstrate that ultrasound-guided PV puncture results in low fluoroscopy times and radiation doses, which are markedly lower than the only published dose reference levels

Circadian oscillations of cytosolic free calcium regulate the Arabidopsis circadian clock

In the last decade, the view of circadian oscillators has expanded from transcriptional feedback to incorporate post-transcriptional, post-translational, metabolic processes and ionic signalling. In plants and animals, there are circadian oscillations in the concentration of cytosolic-free Ca2+ ([Ca2+]cyt), though their purpose has not been fully characterised. We investigated whether circadian oscillations of [Ca2+] cyt regulate the circadian oscillator of Arabidopsis thaliana. We report that in Arabidopsis, [Ca2+]cyt circadian oscillations can regulate circadian clock function through the Ca2+-dependent action of CALMODULIN-LIKE24 (CML24). Genetic analyses demonstrate a linkage between CML24 and the circadian oscillator, through pathways involving the circadian oscillator gene TIMING OF CAB2 EXPRESSION1 (TOC1).Supported by BBSRC UK research grants BBSRC BB/D010381/1 (A.N.D.), BB/D017904/1 (F.R.) BB/M00113X/1 (H.J.H.) awarded to (A.A.R.W.), Research Studentship (K.H.) and BBSRC Industrial Case (T.H.). A Swiss Science Foundation Award (PBZHP3-123289) and the Isaac Newton Trust Cambridge (M.C.M.R. and S.A.), 678 the National Science Foundation under Grant No. MCB 0817976 (Y-C.T. and J.B.), a Royal Society Grant RG081257 and Corpus Christi College, Cambridge Junior Research Fellowship (M.J.G.), a Cordenadoria de Apoio ao Ensino Superior Brazil 25681 studentship (C.T.H.), IEF Marrie Curie (Project No. 272186) (M.C.M.R.), a Broodbank Fellowship (M.C.M.R.), a Malaysian Government Studentship (N.I.M-H.)

Differential sensing with arrays of de novo designed peptide assemblies

Differential sensing attempts to mimic the mammalian senses of smell and taste to identify analytes and complex mixtures. In place of hundreds of complex, membrane-bound G-protein coupled receptors, differential sensors employ arrays of small molecules. Here we show that arrays of computationally designed de novo peptides provide alternative synthetic receptors for differential sensing. We use self-assembling α-helical barrels (αHBs) with central channels that can be altered predictably to vary their sizes, shapes and chemistries. The channels accommodate environment-sensitive dyes that fluoresce upon binding. Challenging arrays of dye-loaded barrels with analytes causes differential fluorophore displacement. The resulting fluorimetric fingerprints are used to train machine-learning models that relate the patterns to the analytes. We show that this system discriminates between a range of biomolecules, drink, and diagnostically relevant biological samples. As αHBs are robust and chemically diverse, the system has potential to sense many analytes in various settings

"Did the trial kill the intervention?" experiences from the development, implementation and evaluation of a complex intervention

Background: The development, implementation and evaluation of any new health intervention is complex. This paper uses experiences from the design, implementation and evaluation of a rehabilitation programme to shed light on, and prompt discussion around, some of the complexities involved in such an undertaking. Methods: Semi-structured interviews were conducted with 15 trial participants and five members of staff at the conclusion of a trial evaluating a rehabilitation programme aimed at promoting recovery after stem cell transplantation. Results: This study identified a number of challenges relating to the development and evaluation of complex interventions. The difficulty of providing a standardised intervention that was acceptable to patients was highlighted in the participant interviews. Trial participants and some members of staff found the concept of equipoise and randomisation challenging and there was discord between the psychosocial nature of the intervention and the predominant bio-medical culture in which the research took place. Conclusions: A lack of scientific evidence as to the efficacy of an intervention does not preclude staff and patients holding strong views about the benefits of an intervention. The evaluation of complex interventions should, where possible, facilitate not restrict that complexity. Within the local environment where the trial is conducted, acquiescence from those in positions of authority is insufficient; commitment to the trial is required

Markovian evolution of quantum coherence under symmetric dynamics

Both conservation laws and practical restrictions impose symmetry constraints on the dynamics of open quantum systems. In the case of time-translation symmetry, which arises naturally in many physically relevant scenarios, the quantum coherence between energy eigenstates becomes a valuable resource for quantum information processing. In this work we identify the minimum amount of decoherence compatible with this symmetry for a given population dynamics. This yields a generalisation to higher-dimensional systems of the relation T2 2T1 for qubit decoherence and relaxation times. It also enables us to witness and assess the role of non-Markovianity as a resource for coherence preservation and transfer. Moreover, we discuss the relationship between ergodicity and the ability of Markovian dynamics to indenitely sustain a superposition of diferent energy states. Finally, we establish a formal connection between the resource-theoretic and the master equation approaches to thermodynamics, with the former being a non-Markovian generalisation of the latter. Our work thus brings the abstract study of quantum coherence as a resource towards the realm of actual physical applications

Effects of antiplatelet therapy on stroke risk by brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases: subgroup analyses of the RESTART randomised, open-label trial

Background Findings from the RESTART trial suggest that starting antiplatelet therapy might reduce the risk of recurrent symptomatic intracerebral haemorrhage compared with avoiding antiplatelet therapy. Brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases (such as cerebral microbleeds) are associated with greater risks of recurrent intracerebral haemorrhage. We did subgroup analyses of the RESTART trial to explore whether these brain imaging features modify the effects of antiplatelet therapy

PCNA ubiquitylation ensures timely completion of unperturbed DNA replication in fission yeast

PCNA ubiquitylation on lysine 164 is required for DNA damage tolerance. In many organisms PCNA is also ubiquitylated in unchallenged S phase but the significance of this has not been established. Using Schizosaccharomyces pombe, we demonstrate that lysine 164 ubiquitylation of PCNA contributes to efficient DNA replication in the absence of DNA damage. Loss of PCNA ubiquitylation manifests most strongly at late replicating regions and increases the frequency of replication gaps. We show that PCNA ubiquitylation increases the proportion of chromatin associated PCNA and the co-immunoprecipitation of Polymerase δ with PCNA during unperturbed replication and propose that ubiquitylation acts to prolong the chromatin association of these replication proteins to allow the efficient completion of Okazaki fragment synthesis by mediating gap filling