Evaluation and Optimization of Mass Spectrometric Settings during Data-dependent Acquisition Mode: Focus on LTQ-Orbitrap Mass Analyzers

Mass-spectrometry-based proteomics has evolved as the preferred method for the analysis of complex proteomes. Undoubtedly, recent advances in mass spectrometry instrumentation have greatly enhanced proteomic analysis. A popular instrument platform in proteomics research is the LTQ-Orbitrap mass analyzer. In this tutorial, we discuss the significance of evaluating and optimizing mass spectrometric settings on the LTQ-Orbitrap during CID data-dependent acquisition (DDA) mode to improve protein and peptide identification rates. We focus on those MS and MS/MS parameters that have been systematically examined and evaluated by several researchers and are commonly used during DDA. More specifically, we discuss the effect of mass resolving power, preview mode for FTMS scan, monoisotopic precursor selection, signal threshold for triggering MS/MS events, number of microscans per MS/MS scan, number of MS/MS events, automatic gain control target value (ion population) for MS and MS/MS, maximum ion injection time for MS/MS, rapid and normal scan rate, and prediction of ion injection time. We furthermore present data from the latest generation LTQ-Orbitrap system, the Orbitrap Elite, along with recommended MS and MS/MS parameters. The Orbitrap Elite outperforms the Orbitrap Classic in terms of scan speed, sensitivity, dynamic range, and resolving power and results in higher identification rates. Several of the optimized MS parameters determined on the LTQ-Orbitrap Classic and XL were easily transferable to the Orbitrap Elite, whereas others needed to be reevaluated. Finally, the Q Exactive and HCD are briefly discussed, as well as sample preparation, LC-optimization, and bioinformatics analysis. We hope this tutorial will serve as guidance for researchers new to the field of proteomics and assist in achieving optimal results

Low-loss multimode interference couplers for terahertz waves

The terahertz (THz) frequency region of the electromagnetic spectrum is located between the traditional microwave spectrum and the optical frequencies, and offers a significant scientific and technological potential in many fields, such as in sensing, in imaging and in spectroscopy. Waveguiding in this intermediate spectral region is a major challenge. Amongst the various THz waveguides suggested, metal-clad plasmonic waveguides and specifically hollow core structures, coated with insulating material are the most promising low-loss waveguides used in both active and passive devices. Optical power splitters are important components in the design of optoelectronic systems and optical communication networks such as Mach-Zehnder Interferometric switches, polarization splitter and polarization scramblers. Several designs for the implementation of the 3dB power splitters have been proposed in the past, such as the directional coupler-based approach, the Y-junction-based devices and the MMI-based approach. In the present paper a novel MMI-based 3dB THz wave splitter is implemented using Gold/polystyrene (PS) coated hollow glass rectangular waveguides. The H-field FEM based full-vector formulation is used here to calculate the complex propagation characteristics of the waveguide structure and the finite element beam propagation method (FE-BPM) and finite difference time domain (FDTD) approach to demonstrate the performance of the proposed 3dB splitter

Low-loss multimode interference couplers for terahertz waves

The terahertz (THz) frequency region of the electromagnetic spectrum is located between the traditional microwave spectrum and the optical frequencies, and offers a significant scientific and technological potential in many fields, such as in sensing, in imaging and in spectroscopy. Waveguiding in this intermediate spectral region is a major challenge. Amongst the various THz waveguides suggested, metal-clad plasmonic waveguides and specifically hollow core structures, coated with insulating material are the most promising low-loss waveguides used in both active and passive devices. Optical power splitters are important components in the design of optoelectronic systems and optical communication networks such as Mach-Zehnder Interferometric switches, polarization splitter and polarization scramblers. Several designs for the implementation of the 3dB power splitters have been proposed in the past, such as the directional coupler-based approach, the Y-junction-based devices and the MMI-based approach. In the present paper a novel MMI-based 3dB THz wave splitter is implemented using Gold/polystyrene (PS) coated hollow glass rectangular waveguides. The H-field FEM based full-vector formulation is used here to calculate the complex propagation characteristics of the waveguide structure and the finite element beam propagation method (FE-BPM) and finite difference time domain (FDTD) approach to demonstrate the performance of the proposed 3dB splitter

The Integrin Receptor in Biologically Relevant Bilayers: Insights from Molecular Dynamics Simulations

Integrins are heterodimeric (αβ) cell surface receptors that are potential therapeutic targets for a number of diseases. Despite the existence of structural data for all parts of integrins, the structure of the complete integrin receptor is still not available. We have used available structural data to construct a model of the complete integrin receptor in complex with talin F2–F3 domain. It has been shown that the interactions of integrins with their lipid environment are crucial for their function but details of the integrin/lipid interactions remain elusive. In this study an integrin/talin complex was inserted in biologically relevant bilayers that resemble the cell plasma membrane containing zwitterionic and charged phospholipids, cholesterol and sphingolipids to study the dynamics of the integrin receptor and its effect on bilayer structure and dynamics. The results of this study demonstrate the dynamic nature of the integrin receptor and suggest that the presence of the integrin receptor alters the lipid organization between the two leaflets of the bilayer. In particular, our results suggest elevated density of cholesterol and of phosphatidylserine lipids around the integrin/talin complex and a slowing down of lipids in an annulus of ~30 Å around the protein due to interactions between the lipids and the integrin/talin F2–F3 complex. This may in part regulate the interactions of integrins with other related proteins or integrin clustering thus facilitating signal transduction across cell membranes

Physical characteristics of localized surface plasmons resulting from nano-scale structured multi-layer thin films deposited on D-shaped optical fiber

Novel surface plasmonic optical fiber sensors have been fabricated using multiple coatings deposited on a lapped section of a single mode fiber. UV laser irradiation processing with a phase mask produces a nano-scaled surface relief grating structure resembling nano-wires. The resulting individual corrugations produced by material compaction are approximately 20 μm long with an average width at half maximum of 100 nm and generate localized surface plasmons. Experimental data are presented that show changes in the spectral characteristics after UV processing, coupled with an overall increase in the sensitivity of the devices to surrounding refractive index. Evidence is presented that there is an optimum UV dosage (48 joules) over which no significant additional optical change is observed. The devices are characterized with regards to change in refractive index, where significantly high spectral sensitivities in the aqueous index regime are found, ranging up to 4000 nm/RIU for wavelength and 800 dB/RIU for intensity

Effect of nitrous oxide on cisatracurium infusion demands: a randomized controlled trial

<p>Abstract</p> <p>Background</p> <p>Recent studies have questioned our previous understanding on the effect of nitrous oxide on muscle relaxants, since nitrous oxide has been shown to potentiate the action of bolus doses of mivacurium, rocuronium and vecuronium. This study was aimed to investigate the possible effect of nitrous oxide on the infusion requirements of cisatracurium.</p> <p>Methods</p> <p>70 ASA physical status I-III patients aged 18-75 years were enrolled in this randomized trial. The patients were undergoing elective surgery requiring general anesthesia with a duration of at least 90 minutes. Patients were randomized to receive propofol and remifentanil by target controlled infusion in combination with either a mixture of oxygen and nitrous oxide (Nitrous oxide/TIVA group) or oxygen in air (Air/TIVA group). A 0.1 mg/kg initial bolus of cisatracurium was administered before tracheal intubation, followed by a closed-loop computer controlled infusion of cisatracurium to produce and maintain a 90% neuromuscular block. Cumulative dose requirements of cisatracurium during the 90-min study period after bolus administration were measured and the asymptotic steady state rate of infusion to produce a constant 90% block was determined by applying nonlinear curve fitting to the data on the cumulative dose requirement during the study period.</p> <p>Results</p> <p>Controller performance, i.e. the ability of the controller to maintain neuromuscular block constant at the setpoint and patient characteristics were similar in both groups. The administration of nitrous oxide did not affect cisatracurium infusion requirements. The mean steady-state rates of infusion were 0.072 +/- 0.018 and 0.066 +/- 0.017 mg * kg-1 * h-1 in Air/TIVA and Nitrous oxide/TIVA groups, respectively.</p> <p>Conclusions</p> <p>Nitrous oxide does not affect the infusion requirements of cisatracurium.</p> <p>Trial registration</p> <p>ClinicalTrials.gov NCT01152905; European Clinical Trials Database at <url>http://eudract.emea.eu.int/2006-006037-41</url>.</p

Low-dimensional nano-patterned surface fabricated by direct-write UV-chemically induced geometric inscription technique

We investigate a nano-patterning process which creates reproducible periodic surface topological features that range in size from ∼100 μm to ∼20 μm. Specifically, we have fabricated multi-layered thin films consisting of germanium/silicon strata on a planar substrate, with each layer having nanometers thickness. The material processing exploits focused 244 nm ultra-violet laser light and an opto-mechanical setup typically applied to the inscription of fiber gratings, and is based upon the well-known material compaction interaction of ultra-violet light with germanium oxides. We show this process can be extended to create arrays of metal nano-antennas by adding a metal overlay to the thin film. This results in arrays with dimensions that span nanometer- to centimeter-length scales. Also, each nano-antenna consists of “nano-blocks.” Experimental data are presented that show the UV irradiance dosage used to create these metal nanostructures on D-shaped optical fibers has a direct relationship to their transmission spectral characteristics as plasmonic devices

The role of anthropogenic aerosols in the anomalous cooling from 1960 to 1990 in the CMIP6 Earth System Models

The Earth system models (ESMs) that participated in the sixth Coupled Model Intercomparison Project (CMIP6) tend to simulate excessive cooling in surface air temperature (TAS) between 1960 and 1990. The anomalous cooling is pronounced over the Northern Hemisphere (NH) midlatitudes, coinciding with the rapid growth of anthropogenic sulfur dioxide (SO2) emissions, the primary precursor of atmospheric sulfate aerosols. Structural uncertainties between ESMs have a larger impact on the anomalous cooling than internal variability. Historical simulations with and without anthropogenic aerosol emissions indicate that the anomalous cooling in the ESMs is attributed to the higher aerosol burden in these models. The aerosol forcing sensitivity, estimated as the outgoing shortwave radiation (OSR) response to aerosol concentration changes, cannot well explain the diversity of pothole cooling (PHC) biases in the ESMs. The relative contributions to aerosol forcing sensitivity from aerosol–radiation interactions (ARIs) and aerosol–cloud interactions (ACIs) can be estimated from CMIP6 simulations. We show that even when the aerosol forcing sensitivity is similar between ESMs, the relative contributions of ARI and ACI may be substantially different. The ACI accounts for between 64 % and 87 % of the aerosol forcing sensitivity in the models and is the main source of the aerosol forcing sensitivity differences between the ESMs. The ACI can be further decomposed into a cloud-amount term (which depends linearly on cloud fraction) and a cloud-albedo term (which is independent of cloud fraction, to the first order), with the cloud-amount term accounting for most of the inter-model differences

Research activities arising from the University of Kent

In this paper I describe research activities in the field of optical fiber sensing undertaken by me after leaving the Applied Optics Group at the University of Kent. The main topics covered are long period gratings, neural network based signal processing, plasmonic sensors, and polymer fiber gratings. I also give a summary of my two periods of research at the University of Kent, covering 1985–1988 and 1991–2001