High-Mass MALDI-MS Using Ion Conversion Dynode Detectors: Influence of the Conversion Voltage on Sensitivity and Spectral Quality

With the development of special ion conversion dynode (ICD) detectors for high-mass matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS), the mass-to-charge ratio is no longer a limiting factor. Although these detectors have been successfully used in the past, there is lack of understanding of the basic processes in the detector. We present a systematic study to investigate the performance of such an ICD detector and separate the contributions of the MALDI process from the ones of the ion-to-secondary ion and the secondary ion-to-electron conversions. The performance was evaluated as a function of the voltages applied to the conversion dynodes and the sample amount utilized, and we found that the detector reflects the MALDI process correctly: limitations such as sensitivity or deviations from the expected signal intensity ratios originate from the MALDI process itself and not from the detector. Graphical abstract

Relative Oscillation Theory, Weighted Zeros of the Wronskian, and the Spectral Shift Function

We develop an analog of classical oscillation theory for Sturm-Liouville operators which, rather than measuring the spectrum of one single operator, measures the difference between the spectra of two different operators. This is done by replacing zeros of solutions of one operator by weighted zeros of Wronskians of solutions of two different operators. In particular, we show that a Sturm-type comparison theorem still holds in this situation and demonstrate how this can be used to investigate the finiteness of eigenvalues in essential spectral gaps. Furthermore, the connection with Krein's spectral shift function is established.Comment: 26 page

Continuous integral kernels for unbounded Schroedinger semigroups and their spectral projections

By suitably extending a Feynman-Kac formula of Simon [Canadian Math. Soc. Conf. Proc, 28 (2000), 317-321], we study one-parameter semigroups generated by (the negative of) rather general Schroedinger operators, which may be unbounded from below and include a magnetic vector potential. In particular, a common domain of essential self-adjointness for such a semigroup is specified. Moreover, each member of the semigroup is proven to be a maximal Carleman operator with a continuous integral kernel given by a Brownian-bridge expectation. The results are used to show that the spectral projections of the generating Schroedinger operator also act as Carleman operators with continuous integral kernels. Applications to Schroedinger operators with rather general random scalar potentials include a rigorous justification of an integral-kernel representation of their integrated density of states - a relation frequently used in the physics literature on disordered solids.Comment: 41 pages. Final version. Dedicated to Volker Enss on the occasion of his 60th birthda

Perturbation Theory of Schr\"odinger Operators in Infinitely Many Coupling Parameters

In this paper we study the behavior of Hamilton operators and their spectra which depend on infinitely many coupling parameters or, more generally, parameters taking values in some Banach space. One of the physical models which motivate this framework is a quantum particle moving in a more or less disordered medium. One may however also envisage other scenarios where operators are allowed to depend on interaction terms in a manner we are going to discuss below. The central idea is to vary the occurring infinitely many perturbing potentials independently. As a side aspect this then leads naturally to the analysis of a couple of interesting questions of a more or less purely mathematical flavor which belong to the field of infinite dimensional holomorphy or holomorphy in Banach spaces. In this general setting we study in particular the stability of selfadjointness of the operators under discussion and the analyticity of eigenvalues under the condition that the perturbing potentials belong to certain classes.Comment: 25 pages, Late

Mass Discrimination in High-Mass MALDI-MS

In high-mass matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS), the accessible m/z range is limited by the detector used. Therefore, special high-mass detectors based on ion conversion dynodes (ICDs) have been developed. Recently, we have found that mass bias may exist when such ICD detectors are used [Weidmann et al., Anal. Chem. 85(6), 3425-3432 (2013)]. In this contribution, the mass-dependent response of an ICD detector was systematically studied, the response factors for proteins with molecular weights from 35.9 to 129.9kDa were determined, and the reasons for mass bias were identified. Compared with commonly employed microchannel plate detectors, we found that the mass discrimination is less pronounced, although ions with higher masses are weakly favored when using an ICD detector. The relative response was found to depend on the laser power used for MALDI; low-mass ions are discriminated against with higher laser power. The effect of mutual ion suppression in dependence of the proteins used and their molar ratio is shown. Mixtures consisting of protein oligomers that only differ in mass show less mass discrimination than mixtures consisting of different proteins with similar masses. Furthermore, mass discrimination increases for molar ratios far from 1. Finally, we present clear guidelines that help to choose the experimental parameters such that the response measured matches the actual molar fraction as closely as possible. Figure

Testing of NKA expression by mobile real time PCR is an efficient indicator of smoltification status of farmed Atlantic salmon

Assessment of seawater readiness of freshwater salmon smolts is a crucial husbandry step with economic implications in salmon aquaculture but current methods rely on delayed centralised enzymic activity measurement. The efficiency of a qRT-PCR assay for sodium potassium ATPase (NKA) α1a mRNA was tested in a 3-year study on 19 hatcheries across Scotland incorporating environmental factors such as temperature and metal contamination. The NKA qRT-PCR assay was transferred to a mobile laboratory and on-site testing was carried out at 3 hatchery sites. For the first two years standard enzymatic and gene expression assays had similar success rates in detecting smoltification (NKA activity 60%, qRT-PCR 57%). In the third year, all but one site were determined as sea water ready by qRT-PCR but only at 4 by enzymatic testing. On site testing with mobile qRT-PCR was successfully performed on four farm sites. Altogether, high sensitivity was shown for the in lab (98.9%, SE 0.24) and mobile (93.43%, SE 0.119) assays when tested using a quantitative RNA standard. Some indication for obscured smoltification assay results due to environmental increased heavy metal contamination was observed. Our results prove it is possible to test a smoltification marker on site and provide results on the day of testing during the smolt period allowing for informed decisions on seawater transfer

On the Singular Weyl-Titchmarsh Function of Perturbed Spherical Schroedinger Operators

We investigate the singular Weyl-Titchmarsh m-function of perturbed spherical Schroedinger operators (also known as Bessel operators) under the assumption that the perturbation $q(x)$ satisfies $x q(x) \in L^1(0,1)$. We show existence plus detailed properties of a fundamental system of solutions which are entire with respect to the energy parameter. Based on this we show that the singular m-function belongs to the generalized Nevanlinna class and connect our results with the theory of super singular perturbations.Comment: 35 page

Quantitative analysis of particles, genomes and infectious particles in supernatants of haemorrhagic fever virus cell cultures

Information on the replication of viral haemorrhagic fever viruses is not readily available and has never been analysed in a comparative approach. Here, we compared the cell culture growth characteristics of haemorrhagic fever viruses (HFV), of the Arenaviridae, Filoviridae, Bunyaviridae, and Flavivridae virus families by performing quantitative analysis of cell culture supernatants by (i) electron microscopy for the quantification of virus particles, (ii) quantitative real time PCR for the quantification of genomes, and (iii) determination of focus forming units by coating fluorescent antibodies to infected cell monolayers for the quantification of virus infectivity

Bound States in Mildly Curved Layers

It has been shown recently that a nonrelativistic quantum particle constrained to a hard-wall layer of constant width built over a geodesically complete simply connected noncompact curved surface can have bound states provided the surface is not a plane. In this paper we study the weak-coupling asymptotics of these bound states, i.e. the situation when the surface is a mildly curved plane. Under suitable assumptions about regularity and decay of surface curvatures we derive the leading order in the ground-state eigenvalue expansion. The argument is based on Birman-Schwinger analysis of Schroedinger operators in a planar hard-wall layer.Comment: LaTeX 2e, 23 page

Asymptotic behaviour of the spectrum of a waveguide with distant perturbations

We consider the waveguide modelled by a $n$-dimensional infinite tube. The operator we study is the Dirichlet Laplacian perturbed by two distant perturbations. The perturbations are described by arbitrary abstract operators ''localized'' in a certain sense, and the distance between their ''supports'' tends to infinity. We study the asymptotic behaviour of the discrete spectrum of such system. The main results are a convergence theorem and the asymptotics expansions for the eigenvalues. The asymptotic behaviour of the associated eigenfunctions is described as well. We also provide some particular examples of the distant perturbations. The examples are the potential, second order differential operator, magnetic Schroedinger operator, curved and deformed waveguide, delta interaction, and integral operator