Heart rate variability characteristics of patients with irritable bowel syndrome and associations with symptoms.

Background: Disturbed brain-gut interactions are assumed to be of importance for symptom generation in patients with irritable bowel syndrome (IBS). The autonomic nervous system (ANS) is part of the bidirectional brain-gut communication, but previous studies in IBS show diverging results. We aimed to identify subgroups of IBS patients with distinct ANS characteristics differentiating them from healthy controls (HC), and to study associations between ANS status and symptoms.

A decision theoretical modeling for Phase III investments and drug licensing.

For a new candidate drug to become an approved medicine, several decision points have to be passed. In this article, we focus on two of them: First, based on Phase II data, the commercial sponsor decides to invest (or not) in Phase III. Second, based on the outcome of Phase III, the regulator determines whether the drug should be granted market access.

Travelling wave analysis of a mathematical model of glioblastoma growth.

In this paper we analyse a previously proposed cell-based model of glioblastoma (brain tumour) growth, which is based on the assumption that the cancer cells switch phenotypes between a proliferative and motile state (Gerlee and Nelander, 2012). The dynamics of this model can be described by a system of partial differential equations, which exhibits travelling wave solutions whose wave speed depends crucially on the rates of phenotypic switching. We show that under certain conditions on the model parameters, a closed form expression of the wave speed can be obtained, and using singular perturbation methods we also derive an approximate expression of the wave front shape.

The evolution of carrying capacity in constrained and expanding tumour cell populations.

Cancer cells are known to modify their micro-environment such that it can sustain a larger population, or, in ecological terms, they construct a niche which increases the carrying capacity of the population. It has however been argued that niche construction, which benefits all cells in the tumour, would be selected against since cheaters could reap the benefits without paying the cost. We have investigated the impact of niche specificity on tumour evolution using an individual based model of breast tumour growth, in which the carrying capacity of each cell consists of two components: an intrinsic, subclone-specific part and a contribution from all neighbouring cells.

A decision theoretic approach to optimization of multiple testing procedures.

This paper focuses on the concept of optimizing a multiple testing procedure (MTP) with respect to a predefined utility function. The class of Bonferroni-based closed testing procedures, which includes, for example, (weighted) Holm, fallback, gatekeeping, and recycling/graphical procedures, is used in this context. Numerical algorithms for calculating expected utility for some MTPs in this class are given.

On the choice of doses for phase III clinical trials.

Many potential new medicines fail in phase III clinical trials, because of either insufficient efficacy or intolerability. Such failures may be caused by the absence of an effect and also if a suboptimal dose is being tested. It is thus important to consider how to optimise the choice of dose or doses that continue into the confirmatory phase.

Improved covariance matrix estimators for weighted analysis of microarray data.

Empirical Bayes models have been shown to be powerful tools for identifying differentially expressed genes from gene expression microarray data. An example is the WAME model, where a global covariance matrix accounts for array-to-array correlations as well as differing variances between arrays. However, the existing method for estimating the covariance matrix is very computationally intensive and the estimator is biased when data contains many regulated genes.

Protein adsorption on supported phospholipid bilayers.

Quartz crystal microbalance with dissipation (QCM-D) measurements were used to investigate the adsorption of human fibrinogen, human serum albumin, bovine hemoglobin, horse heart cytochrome c, human immunoglobulin (hIgG), and 10% fetal bovine serum on supported bilayers of egg-phosphatidylcholine (eggPC) lipids. For comparison the adsorption of fibrinogen and hIgG to eggPC bilayers was also studied with surface plasmon resonance (SPR). The supported bilayers were formed in situ by vesicle adhesion and spontaneous fusion onto a SiO(2) surface.

Diffusive transport in networks built of containers and tubes.

We have developed analytical and numerical methods to study the transport of noninteracting particles in large networks consisting of M d -dimensional containers C1,...

An additive edge correction for the influence potential of trees.

The influence potential on a quadrat (IPQ) is an index for measuring the ecological effect that trees have on understory vegetation observed in a quadrat of a plot. IPQ is defined as the sum of the effect of every trees in the plot, where the effect depends on the size of the tree and the distance between the tree and the quadrat. Since only the trees in the plot have been observed and not the trees outside the plot, the true IPQ may be underestimated.

Gravimetric antigen detection utilizing antibody-modified lipid bilayers.

Lipid bilayers containing 5% nitrilotriacetic acid (NTA) lipids supported on SiO2 have been used as a template for immobilization of oligohistidine-tagged single-chained antibody fragments (scFvs) directed against cholera toxin. It was demonstrated that histidine-tagged scFvs could be equally efficiently coupled to an NTA-Ni2+-containing lipid bilayer from a purified sample as from an expression supernatant, thereby providing a coupling method that eliminates time-consuming protein prepurification steps. Irrespective of whether the coupling was made from the unpurified or purified antibody preparation, the template proved to be efficient for antigen (cholera toxin) detection, verified using quartz crystal microbalance with dissipation monitoring.

Interplay between chemical reactions and transport in structured spaces.

The main motivation behind this study is to understand the interplay between the reactions and transport in a geometries that are not compact. Typical examples of compact geometries are a box or a sphere. A network made of containers C(1) , C(2),.

Dielectric and calorimetric studies of hydrated purple membrane.

Purple membranes (PM) from halobacteria were hydrated to approximately 0.4 and approximately 0.2 g H(2)O/g of PM and studied by dielectric spectroscopy and differential scanning calorimetry between 120 and 300 K.

van der Waals interaction of simple, parallel polymers.

We study the mutual interactions of simple parallel polymers within the framework of density-functional theory (DFT). As the conventional implementations of DFT do not treat the long-range dispersion [van der Waals (vdW)] interactions, we develop a systematic correction scheme for the nonlocal energy contribution of the polymer interaction at the intermediate to the asymptotic separations. We primarily focus on the three polymers, polyethylene, isotactic polypropylene, and isotactic polyvinylchloride, but the scheme presented applies also more generally to other simple polymers.

van der Waals interactions of polycyclic aromatic hydrocarbon dimers.

Density functional theory is in principle exact and includes also long-range interactions, such as the van der Waals interactions. These are, however, part of the exchange-correlation energy functional that needs to be approximated, and are absent in the local and semilocal standard implementations. Recently a density functional which includes van der Waals interactions for planar systems has been developed, which we show can be extended to provide a treatment of planar molecules.

Two-dimensional hydration shells of alkali metal ions at a hydrophobic surface.

We study the hydration shell formation of alkali metal ions at a graphite surface. Two-dimensional shell structures are found in the initial stage of hydration, in contrast to the three-dimensional structures in bulk water and clusters. Comparison of vibrational spectra with experiments identifies the shell structures and the thermally induced transition from the first to the second shell.

Cooperation driven by mutations in multi-person Prisoner's Dilemma.

The n-person Prisoner's Dilemma is a widely used model for populations where individuals interact in groups. The evolutionary stability of populations has been analysed in the literature for the case where mutations in the population may be considered as isolated events. For this case, and assuming simple trigger strategies and many iterations per game, we analyse the rate of convergence to the evolutionarily stable populations.

Nanopipettes for metal transport.

Here we demonstrate, for the first time experimentally, a nanopipette action for metals using multiwalled carbon nanotubes. The process relies on electromigration forces, created at high electron current densities, enabling the transport of material inside the hollow core of carbon nanotubes. In this way nanoparticles of iron were transported to and from electrically conducting substrates.

Infrared spectroscopy of oxygen adsorbed on hydrogen covered Pt(111).

Using infrared reflection absorption spectroscopy we have investigated how preadsorbed hydrogen affects the adsorption of O(2) on the Pt(111) surface at temperatures below the onset of the water formation reaction. On the fully hydrogen covered surface, Theta(H)=1, O(2) physisorbs at temperatures below 45 K, the weakly dipole active internal stretch vibration is observed at 1548 cm(-1). Unlike on the clean Pt(111) surface, this adsorption state does not act as a precursor for O(2) chemisorption.

Optical manipulation in combination with multiphoton microscopy for single-cell studies.

We demonstrate how optical tweezers can be incorporated into a multiphoton microscope to achieve three-dimensional imaging of trapped cells. The optical tweezers, formed by a cw 1064 nm Nd:YVO4 laser, were used to trap live yeast cells in suspension while the 4',6-diamidino-2-phenylindole-stained nucleus was imaged in three dimensions by use of a pulsed femtosecond laser. The trapped cell was moved in the axial direction by changing the position of an external lens, which was used to control the divergence of the trapping laser beam.

Bivalent cholesterol-based coupling of oligonucletides to lipid membrane assemblies.

By mimicking Nature's way of utilizing multivalent interactions, we introduce in the present work a novel method to improve the strength of cholesterol-based DNA coupling to lipid membranes. The bivalent coupling of DNA was accomplished by hybridization between a 15-mer DNA and a 30-mer DNA, being modified with cholesterol in the 3' and 5' end, respectively. Compared with DNA modified with one cholesterol moiety only, the binding strength to lipid membranes appears to be significantly stronger and even irreversible over the time scale investigated ( approximately 1 hr).

Infrared spectroscopy of physisorbed and chemisorbed O2 on Pt(111).

The adsorption of O2 on the Pt(111) surface, with particular emphasis on the influence of substrate temperature, has been studied by infrared reflection absorption spectroscopy (IRAS). In the temperature range 30-90 K the IRAS spectra reveal three different molecular adsorption states. A physisorbed state appears below 40 K while chemisorbed peroxo- and superoxo-like states are observed in the whole temperature range, the characteristic vibrational frequencies are at full coverages of 16O2, 1543 cm(-1) and around 700 cm(-1) and 870 cm(-1), respectively.

Potential--energy surfaces for excited states in extended systems.

With a simple and physically intuitive method, first-principles calculations of potential-energy surfaces are performed for excited states in a number of illustrative systems, including dimers (H(2) and NaCl) and gas-surface systems [Cl-Na(100) and Cl(2)-Na(100)]. It is based on density-functional theory and is a generalization of the Delta self-consistent field (DeltaSCF) method, where electron-hole pairs are introduced in order to model excited states, corresponding to internal electron transfers in the considered system. The desired excitations are identified by analysis of calculated electron orbitals, local densities of states, and charge densities.