Specificity and reversibility of chemotactic deactivation of human monocytes

The chemotactic deactivation of human monocytes was studied to provide insight into the mechanism of chemotaxis. Deactivation was dependent on the dose of chemoattractant and time of incubation. A concentration in the cell suspension of 10(-8) M N-formylmethionylleucyl phenylalanine (FMLP) for 45 min at 37 degrees C led to 60% suppression of the subsequent specific chemotactic response. Higher concentrations of FMLP led to almost 100% specific suppression. Deactivation was specific under all conditions used. The response to a nonrelated chemoattractant, human serum-derived C5a, was unaffected by incubation in FMLP. Deactivation was also transient. If cells were deactivated at 37 degrees C with FMLP, they recovered within 6 h at 37 degrees C from this deactivation. Both phenomena, deactivation and recovery from deactivation, were temperature dependent. Monocytes could not be deactivated at 0 degrees C, and they did not recover from deactivation when kept at 0 degrees C. Thus, specific deactivation appears to require cellular metabolism, involving loss of receptors or blocking of a step between receptor occupancy and response

Comparing adaptive and fixed bandwidth-based kernel density estimates in spatial cancer epidemiology

Background: Monitoring spatial disease risk (e.g. identifying risk areas) is of great relevance in public health research, especially in cancer epidemiology. A common strategy uses case-control studies and estimates a spatial relative risk function (sRRF) via kernel density estimation (KDE). This study was set up to evaluate the sRRF estimation methods, comparing fixed with adaptive bandwidth-based KDE, and how they were able to detect ‘risk areas’ with case data from a population-based cancer registry. Methods: The sRRF were estimated within a defined area, using locational information on incident cancer cases and on a spatial sample of controls, drawn from a high-resolution population grid recognized as underestimating the resident population in urban centers. The spatial extensions of these areas with underestimated resident population were quantified with population reference data and used in this study as ‘true risk areas’. Sensitivity and specificity analyses were conducted by spatial overlay of the ‘true risk areas’ and the significant (α=.05) p-contour lines obtained from the sRRF. Results: We observed that the fixed bandwidth-based sRRF was distinguished by a conservative behavior in identifying these urban ‘risk areas’, that is, a reduced sensitivity but increased specificity due to oversmoothing as compared to the adaptive risk estimator. In contrast, the latter appeared more competitive through variance stabilization, resulting in a higher sensitivity, while the specificity was equal as compared to the fixed risk estimator. Halving the originally determined bandwidths led to a simultaneous improvement of sensitivity and specificity of the adaptive sRRF, while the specificity was reduced for the fixed estimator. Conclusion: The fixed risk estimator contrasts with an oversmoothing tendency in urban areas, while overestimating the risk in rural areas. The use of an adaptive bandwidth regime attenuated this pattern, but led in general to a higher false positive rate, because, in our study design, the majority of true risk areas were located in urban areas. However, there is a strong need for further optimizing the bandwidth selection methods, especially for the adaptive sRRF.<br

Detecting cancer clusters in a regional population with local cluster tests and Bayesian smoothing methods: a simulation study

Background: There is a rising public and political demand for prospective cancer cluster monitoring. But there is little empirical evidence on the performance of established cluster detection tests under conditions of small and heterogeneous sample sizes and varying spatial scales, such as are the case for most existing population-based cancer registries. Therefore this simulation study aims to evaluate different cluster detection methods, implemented in the open soure environment R, in their ability to identify clusters of lung cancer using real-life data from an epidemiological cancer registry in Germany. Methods: Risk surfaces were constructed with two different spatial cluster types, representing a relative risk of RR = 2.0 or of RR = 4.0, in relation to the overall background incidence of lung cancer, separately for men and women. Lung cancer cases were sampled from this risk surface as geocodes using an inhomogeneous Poisson process. The realisations of the cancer cases were analysed within small spatial (census tracts, N = 1983) and within aggregated large spatial scales (communities, N = 78). Subsequently, they were submitted to the cluster detection methods. The test accuracy for cluster location was determined in terms of detection rates (DR), false-positive (FP) rates and positive predictive values. The Bayesian smoothing models were evaluated using ROC curves. Results: With moderate risk increase (RR = 2.0), local cluster tests showed better DR (for both spatial aggregation scales > 0.90) and lower FP rates (both < 0.05) than the Bayesian smoothing methods. When the cluster RR was raised four-fold, the local cluster tests showed better DR with lower FPs only for the small spatial scale. At a large spatial scale, the Bayesian smoothing methods, especially those implementing a spatial neighbourhood, showed a substantially lower FP rate than the cluster tests. However, the risk increases at this scale were mostly diluted by data aggregation. Conclusion: High resolution spatial scales seem more appropriate as data base for cancer cluster testing and monitoring than the commonly used aggregated scales. We suggest the development of a two-stage approach that combines methods with high detection rates as a first-line screening with methods of higher predictive ability at the second stage.<br

Exact sampling of self-avoiding paths via discrete Schramm-Loewner evolution

We present an algorithm, based on the iteration of conformal maps, that produces independent samples of self-avoiding paths in the plane. It is a discrete process approximating radial Schramm-Loewner evolution growing to infinity. We focus on the problem of reproducing the parametrization corresponding to that of lattice models, namely self-avoiding walks on the lattice, and we propose a strategy that gives rise to discrete paths where consecutive points lie an approximately constant distance apart from each other. This new method allows us to tackle two non-trivial features of self-avoiding walks that critically depend on the parametrization: the asphericity of a portion of chain and the correction-to-scaling exponent.Comment: 18 pages, 4 figures. Some sections rewritten (including title and abstract), numerical results added, references added. Accepted for publication in J. Stat. Phy

Large and Almost Maximal Neutrino Mixing within the Type II See-Saw Mechanism

Within the type II see-saw mechanism the light neutrino mass matrix is given by a sum of a direct (or triplet) mass term and the conventional (type I) see-saw term. Both versions of the see-saw mechanism explain naturally small neutrino masses, but the type II scenario offers interesting additional possibilities to explain large or almost maximal or vanishing mixings which are discussed in this paper. We first introduce ``type II enhancement'' of neutrino mixing, where moderate cancellations between the two terms can lead to large neutrino mixing even if all individual mass matrices and terms generate small mixing. However, nearly maximal or vanishing mixings are not naturally explained in this way, unless there is a certain initial structure (symmetry) which enforces certain elements of the matrices to be identical or related in a special way. We therefore assume that the leading structure of the neutrino mass matrix is the triplet term and corresponds to zero U_{e3} and maximal theta_{23}. Small but necessary corrections are generated by the conventional see-saw term. Then we assume that one of the two terms corresponds to an extreme mixing scenario, such as bimaximal or tri-bimaximal mixing. Deviations from this scheme are introduced by the second term. One can mimic Quark-Lepton Complementarity in this way. Finally, we note that the neutrino mass matrix for tri-bimaximal mixing can be -- depending on the mass hierarchy -- written as a sum of two terms with simple structure. Their origin could be the two terms of type II see-saw.Comment: 25 pages. Comments and references added, to appear in JHE

General relativistic Sagnac formula revised

The Sagnac effect is a time or phase shift observed between two beams of light traveling in opposite directions in a rotating interferometer. We show that the standard description of this effect within the framework of general relativity misses the effect of deflection of light due to rotational inertial forces. We derive the necessary modification and demonstrate it through a detailed analysis of the square Sagnac interferometer rotating about its symmetry axis in Minkowski space-time. The role of the time shift in a Sagnac interferometer in the synchronization procedure of remote clocks as well as its analogy with the Aharanov-Bohm effect are revised.Comment: 11 pages, 3 figure

Phylogeographical Analysis Reveals the Historic Origin, Emergence, and Evolutionary Dynamics of Methicillin-Resistant Staphylococcus aureus ST228.

Methicillin-resistant Staphylococcus aureus (MRSA) is a common healthcare-associated pathogen that remains a major public health concern. Sequence type 228 (ST228) was first described in Germany and spread to become a successful MRSA clone in several European countries. In 2000, ST228 emerged in Lausanne and has subsequently caused several large outbreaks. Here, we describe the evolutionary history of this clone and identify the genetic changes underlying its expansion in Switzerland. We aimed to understand the phylogeographic and demographic dynamics of MRSA ST228/ST111 by sequencing 530 representative isolates of this clone that were collected from 14 European countries between 1997 and 2012. The phylogenetic analysis revealed distinct lineages of ST228 isolates associated with specific geographic origins. In contrast, isolates of ST111, which is a single locus variant of ST228 sharing the same spa type t041, formed a monophyletic cluster associated with multiple countries. The evidence points to a German origin of the sampled population, with the basal German lineage being characterized by spa type t001. The highly successful Swiss ST228 lineage diverged from this progenitor clone through the loss of the aminoglycoside-streptothricin resistance gene cluster and the gain of mupirocin resistance. This lineage was introduced first in Geneva and was subsequently introduced into Lausanne. Our results reveal the radiation of distinct lineages of MRSA ST228 from a German progenitor, as the clone spread into different European countries. In Switzerland, ST228 was introduced first in Geneva and was subsequently introduced into Lausanne

Imaging magnonic frequency multiplication in nanostructured antidot lattices

Frequency multiplication is an essential part of electronics and optics which led to numerous indispensable applications. In this paper, we utilize a combination of scanning transmission x ray microscopy and micromagnetic simulations to directly image magnonic frequency multiplication by means of dynamic real space magnetization measurements. We experimentally demonstrate frequency multiplication up to the seventh order, which enables the generation of nanoscale spin waves at 6GHz with excitation frequencies of less than 1GHz. Good agreement between the experiment and micromagnetic simulations allows us to build a micromagnetic model capable of predicting conversion efficiencies and multiplexing capabilities of the system. Furthermore, simulations reveal that more than two rows of antidots do not increase the conversion efficiency substantially. By enabling magnonic multiplexing with low input frequencies while not exceeding the size of a few microns, the device will lead to numerous applications, further advancing the capabilities of magnonic data transmissio

Dehydroabietylamine-Based Cellulose Nanofibril Films: A New Class of Sustainable Biomaterials for Highly Efficient, Broad-Spectrum Antimicrobial Effects

The design of antimicrobial surfaces as integral parts of advanced biomaterials is nowadays a high research priority, as the accumulation of microorganisms on surfaces inflicts substantial costs on the health and industry sectors. At present, there is a growing interest in designing functional materials from polymers abundant in nature, such as cellulose, that combine sustainability with outstanding mechanical properties and economic production. There is also the need to find suitable replacements for antimicrobial silver-based agents due to environmental toxicity and spread of resistance to metal antimicrobials. Herein we report the unprecedented decoration of cellulose nanofibril (CNF) films with dehydroabietylamine 1 (CNF-CMC-1), to give an innovative contact-active surface active against Gram-positive and Gram-negative bacteria including the methicillin-resistant S. aureus MRSA14TK301, with low potential to spread resistance and good biocompatibility, all achieved with low surface coverage. CNF-CMC-1 was particularly effective against S. aureus ATCC12528, causing virtually complete reduction of the total cells from 10 5 colony forming units (CFU)/mL bacterial suspensions, after 24 h of contact. This gentle chemical modification of the surface of CNF fully retained the beneficial properties of the original film, including moisture buffering and strength, relevant in many potential applications. Our originally designed surface represents a new class of ecofriendly biomaterials that optimizes the performance of CNF by adding antimicrobial properties without the need for environmentally toxic silver. © Copyright 2019 American Chemical Society

Quantum Theory in Accelerated Frames of Reference

The observational basis of quantum theory in accelerated systems is studied. The extension of Lorentz invariance to accelerated systems via the hypothesis of locality is discussed and the limitations of this hypothesis are pointed out. The nonlocal theory of accelerated observers is briefly described. Moreover, the main observational aspects of Dirac's equation in noninertial frames of reference are presented. The Galilean invariance of nonrelativistic quantum mechanics and the mass superselection rule are examined in the light of the invariance of physical laws under inhomogeneous Lorentz transformations.Comment: 25 pages, no figures, contribution to Springer Lecture Notes in Physics (Proc. SR 2005, Potsdam, Germany, February 13 - 18, 2005