BACKGROUND AND PURPOSE:Idiopathic facial palsy (IFP) accounts for over 60% of peripheral facial palsy (FP) cases. The cause of IFP remains to be determined. Possible etiologies are nerve swelling due to inflammation and/or viral infection. In this study, we applied an integrative mass spectrometry approach to identify possibly altered protein patterns in the cerebrospinal fluid (CSF) of IFP patients.METHODS:We obtained CSF samples from 34 patients with FP. In four patients, varicella-zoster virus was the cause (VZV-FP). Among the 30 patients diagnosed with IFP, 17 had normal CSF parameters, five had slightly elevated CSF cell counts and normal or elevated CSF protein, and eight had normal CSF cell counts but elevated CSF protein. Five patients with primary headache served as controls. All samples were tested for viral pathogens by PCR and subjected to liquid chromatography tandem mass spectrometry and bioinformatics analysis and multiplex cytokine/chemokine arrays.RESULTS:All CSF samples, except those from VZV-FP patients, were negative for all tested pathogens. The protein composition of CSF samples from IFP patients with normal CSF was comparable to controls. IFP patients with elevated CSF protein showed dysregulated proteins involved in inflammatory pathways, findings which were similar to those in VZV-FP patients. Multiplex analysis revealed similarly elevated cytokine levels in the CSF of IFP patients with elevated CSF protein and VZV-FP.CONCLUSIONS:Our study revealed a subgroup of IFP patients with elevated CSF protein that showed upregulated inflammatory pathways, suggesting an inflammatory/infectious cause. However, no evidence for an inflammatory cause was found in IFP patients with normal CSF.

Self-consistent modeling and multi-dimensional simulation of semiconductor nanophotonic devices is an important tool in the development of future integrated light sources and quantum devices. Simulations can guide important technological decisions by revealing performance bottlenecks in new device concepts, contribute to their understanding and help to theoretically explore their optimization potential. The efficient implementation of multi-dimensional numerical simulations for computer-aided design tasks requires sophisticated numerical methods and modeling techniques. We review recent advances in device-scale modeling of quantum dot based single-photon sources and laser diodes by self-consistently coupling the optical Maxwell equations with semi-classical carrier transport models using semi-classical and fully quantum mechanical descriptions of the optically active region, respectively. For the simulation of realistic devices with complex, multi-dimensional geometries, we have developed a novel hp-adaptive finite element approach for the optical Maxwell equations, using mixed meshes adapted to the multi-scale properties of the photonic structures. For electrically driven devices, we introduced novel discretization and parameter-embedding techniques to solve the drift-diffusion system for strongly degenerate semiconductors at cryogenic temperatures. Our methodical advances are demonstrated on various applications, including vertical-cavity surface-emitting lasers, grating couplers and single-photon sources.

The intracellular pathogen Salmonella enterica has evolved an array of traits for propagation and invasion of the intestinal layers. It remains largely elusive how Salmonella adjusts its metabolic states to survive inside immune host cells. In this study, single-cell Raman biotechnology combined with deuterium isotope probing (Raman-DIP) have been applied to reveal metabolic changes of the typhoidal Salmonella Typhi Ty2, the nontyphoidal Salmonella Typhimurium LT2, and a clinical isolate Typhimurium D23580. By initially labeling the Salmonella strains with deuterium, we employed reverse labeling to track their metabolic changes in the time-course infection of THP-1 cell line, human monocyte-derived dendritic cells (MoDCs) and macrophages (Mf). We found that, in comparison with a noninvasive serovar, the invasive Salmonella strains Ty2 and D23580 have downregulated metabolic activity inside human macrophages and dendritic cells and used lipids as alternative carbon source, perhaps a strategy to escape from the host immune response. Proteomic analysis using high sensitivity mass spectrometry validated the findings of Raman-DIP analysis.

It has been widely debated whether transposable elements have a positive or a negative effect on their host cells. This study demonstrated that transposable elements, specifically insertion sequences (ISs), can adopt a defensive role in Escherichia coli. IS1 and IS10 in three different E. coli strains (S17, DH5a and Nissle 1917) rapidly disrupted the I-CeuI gene (encoding I-CeuI endonuclease) on the plasmid pLO11-ICeuI as early as the 1st generation, despite the gene-circuit being under tight control of an arabinose promoter. Proteomics analysis showed that the protein abundance profile of E. coli DH5a with pLO11-ICeuI in 5th generation was nearly opposite to that of control strain (E. coli with pLO11, no I-CeuI). The DNA damage caused by the leaky expression of I-CeuI was enough to trigger a SOS response and alter lipid synthesis, ribosomal activity, RNA/DNA metabolism, central dogma and cell cycle processes in E. coli DH5a. After the ISs disrupted the expression of I-CeuI, cells fully recovered by the 31st generation with a protein abundance profile similar to the control strain. This study showed that ISs readily mutated a harmful gene which subsequently restored host fitness. These observations have implications for the stability of designed gene circuits in synthetic biology.

B. pertussis is the etiological agent of whooping cough, a highly contagious respiratory disease which remains uncontrolled worldwide. Understanding how this pathogen responds to the environmental changes and adapts to different niches found inside the host might contribute to gain insight into bacterial pathogenesis. Comparative analyses of previous transcriptomic and proteomic data suggested that post-transcriptional regulatory mechanisms modulate B. pertussis virulence in response to iron availability. Iron scarcity represents one of the major stresses faced by bacterial pathogens inside the host. In this study, we used gel-free nanoLC-MS/MS-based proteomics to investigate whether Hfq, a highly conserved post-transcriptional regulatory protein, is involved in B. pertussis adaptation to low iron environment. To this end, we compared the protein profiles of wild type B. pertussis and its isogenic hfq deletion mutant strain under iron-replete and iron-depleted conditions. Almost of 33% of the proteins identified under iron starvation was found to be Hfq-dependent. Among them, proteins involved in oxidative stress tolerance and virulence factors that play a key role in the early steps of host colonization and bacterial persistence inside the host cells. Altogether these results suggest that Hfq shapes the infective phenotype of B. pertussis. SIGNIFICANCE: In the last years, it became evident that post-transcriptional regulation of gene expression in ba cteria plays a central role in host-pathogen interactions. Hfq is a bacterial protein that regulates gene expression at post-transcriptional level found pivotal in the establishment of successful infections. In this study, we investigated the role of Hfq in Bordetella pertussis response to iron starvation, one of the main stresses imposed by the host. The data demonstrate that Hfq regulates the abundance of a significant number of B. pertussis proteins in response to iron starvation. Among them, virulence factors and proteins involved in oxidative stress tolerance, key players in host colonization and intracellular bacterial survival. Altogether, our results suggest a relevant role of Hfq in B. pertussis adaptation to the different niches found inside the host eventually granting bacterial pathogenesis.

Bacterial membrane vesicles (MVs) mediate bacterial virulence by enabling secretion and long distance delivery of bacterial effector molecules. Staphylococcus haemolyticus has now been demonstrated to produce membrane vesicles (MVs). The protein content of S. haemolyticus MVs was identified by Mass spectrometry and compared to proteins identified in the total secretome. This information is presented in this data article. Further background and interpretation of the data can be found in the article: Comparative exoproteome profiling of an invasive and a commensal S. haemolyticus isolate (Cavanagh et al., in press). Data are available via Proteome Xchange with identifier PXD010389.

Streptococcus pneumoniae is endowed with a variety of surface-exposed proteins representing putative vaccine candidates. Lipoproteins are covalently anchored to the cell membrane and highly conserved among pneumococcal serotypes. Here, we evaluated these lipoproteins for their immunogenicity and protective potential against pneumococcal colonisation. A multiplex-based immunoproteomics approach revealed the immunogenicity of selected lipoproteins. High antibody titres were measured in sera from mice immunised with the lipoproteins MetQ, PnrA, PsaA, and DacB. An analysis of convalescent patient sera confirmed the immunogenicity of these lipoproteins. Examining the surface localisation and accessibility of the lipoproteins using flow cytometry indicated that PnrA and DacB were highly abundant on the surface of the bacteria. Mice were immunised intranasally with PnrA, DacB, and MetQ using cholera toxin subunit B (CTB) as an adjuvant, followed by an intranasal challenge with S. pneumoniae D39. PnrA protected the mice from pneumococcal colonisation. For the immunisation with DacB and MetQ, a trend in reducing the bacterial load could be observed, although this effect was not statistically significant. The reduction in bacterial colonisation was correlated with the increased production of antigen-specific IL-17A in the nasal cavity. Immunisation induced high systemic IgG levels with a predominance for the IgG1 isotype, except for DacB, where IgG levels were substantially lower compared to MetQ and PnrA. Our results indicate that lipoproteins are interesting targets for future vaccine strategies as they are highly conserved, abundant, and immunogenic.

Simulation and modeling using numerical methods is one of the key instruments in any scientific work. In the field of photonics, a wide range of numerical methods are used for studying both fundamental optics and applications such as design, development, and optimization of photonic components. Modeling is key for developing improved photonic devices and reducing development time and cost. Choosing the appropriate computational method for a photonics modeling problem requires a clear understanding of the pros and cons of the available numerical methods. Numerical Methods in Photonics presents six of the most frequently used methods: FDTD, FDFD, 1+1D nonlinear propagation, modal method, Green's function, and FEM. After an introductory chapter outlining the basics of Maxwell's equations, the book includes self-contained chapters that focus on each of the methods. Each method is accompanied by a review of the mathematical principles in which it is based, along with sample scripts, illustrative examples of characteristic problem solving, and exercises. MATLAB® is used throughout the text. This book provides a solid basis to practice writing your own codes. The theoretical formulation is complemented by sets of exercises, which allow you to grasp the essence of the modeling tools.

Staphylococcus aureus can cause bloodstream infections associated with infective endocarditis (IE) and disseminated intravascular coagulopathy (DIC). Both complications involve platelets. In view of an increasing number of antibiotic-resistant strains, new approaches to control systemic S. aureus infection are gaining importance. Using a repertoire of 52 recombinant S. aureus proteins in flow cytometry-based platelet activation and aggregation assays, we identified, in addition to the extracellular adherence protein Eap, three secreted staphylococcal proteins as novel platelet activating proteins. Eap and the chemotaxis inhibitory protein of S. aureus (CHIPS), the formyl peptide receptor-like 1 inhibitory protein (FLIPr) and the major autolysin Atl induced P-selectin expression in washed platelets and platelet-rich plasma. Similarly, AtlA, CHIPS and Eap induced platelet aggregation in whole blood. Fluorescence microscopy illustrated that P-selectin expression is associated with calcium mobilization and re-organization of the platelet actin cytoskeleton. Characterization of the functionally active domains of the major autolysin AtlA and Eap indicates that the amidase domain of Atl and the tandem repeats 3 and 4 of Eap are crucial for platelet activation. These results provide new insights in S. aureus protein interactions with platelets and identify secreted proteins as potential treatment targets in case of antibiotic-resistant S. aureus infection.

Whether mice are an appropriate model for S. aureus infection and vaccination studies is a matter of debate, because they are not considered as natural hosts of S. aureus. We previously identified a mouse-adapted S. aureus strain, which caused infections in laboratory mice. This raised the question whether laboratory mice are commonly colonized with S. aureus and whether this might impact on infection experiments. Publicly available health reports from commercial vendors revealed that S. aureus colonization is rather frequent, with rates as high as 21 % among specific-pathogen-free mice. In animal facilities, S. aureus was readily transmitted from parents to offspring, which became persistently colonized. Among 99 murine S. aureus isolates from Charles River Laboratories half belonged to the lineage CC88 (54.5%), followed by CC15, CC5, CC188 and CC8. A comparison of human and murine S. aureus isolates revealed features of host adaptation. In detail, murine strains lacked hlb-converting phages and superantigen-encoding mobile genetic elements, and were frequently ampicillin-sensitive. Moreover, murine CC88 isolates coagulated mouse plasma faster than human CC88 isolates. Importantly, S. aureus colonization clearly primed the murine immune system, inducing a systemic IgG response specific for numerous S. aureus proteins, including several vaccine candidates. Phospholipase C emerged as a promising test antigen for monitoring S. aureus colonization in laboratory mice. In conclusion, laboratory mice are natural hosts of S. aureus and, therefore, could provide better infection models than previously assumed. Pre-exposure to the bacteria is a possible confounder in S. aureus infection and vaccination studies and should be monitored.

A novel design for high brightness planar technology light-emitting diodes (LEDs) and LED on-wafer arrays on absorbing substrates is proposed. The design integrates features of passive dielectric cavity deposited on top of an oxide– semiconductor distributed Bragg reflector (DBR), the p–n junction with a light emitting region is introduced into the top semiconductor λ/4 DBR period. A multilayer dielectric structure containing a cavity layer and dielectric DBRs is further processed by etching into a micrometer–scale pattern. An oxide–confined aperture is further amended for current and light confinement. We study the impact of the placement of the active region into the maximum or minimum of the optical field intensity and study an impact of the active region positioning on light extraction efficiency. We also study an etching profile composed of symmetric rings in the etched passive cavity over the light emitting area. The bottom semiconductor is an AlGaAs–AlAs multilayer DBR selectively oxidized with the conversion of the AlAs layers into AlOx to increase the stopband width preventing the light from entering the semiconductor substrate. The approach allows to achieve very high light extraction efficiency in a narrow vertical angle keeping the reasonable thermal and current conductivity properties. As an example, a micro-LED structure has been modeled with AlGaAs-AlAs or AlGaAs-AlOx DBRs and an active region based on InGaAlP quantum well(s) emitting in the orange spectral range at ~610 nm. A passive dielectric SiO2 cavity is confined by dielectric Ta2O5/SiO2 and AlGaAs-AlOx DBRs. Cylindrically–symmetric structures with multiple ring patterns are modeled. It is demonstrated that the extraction coefficient of light to the air can be increased from 1.3% up to above 90% in a narrow vertical angle (full width at half maximum (FWHM) below 20°). For very small oxide–confined apertures ~100nm the narrowing of the FWHM for light extraction can be reduced down to 5°. Consequently high efficiency high brightness arrays of micro-LEDs becomes possible. For single emitters the approach is particularly interesting for oscillator strength engineering allowing high speed data transmission and for single photonics applying single quantum dot (QD) emitters and allowing >90% coupling of the emission into single mode fiber. We also note that for longer wavelength (~1300nm) QDs the thickness of the layers and surface patterns significantly increase allowing greatly reduced processing tolerances and applying further simplifications due to the possibility of using high contrast GaAs-AlOx DBRs.

This chapter addresses requirements for vertical-cavity surface-emitting lasers (VCSELs), one of the major devices for data communication to meet the bandwidth demand. Single-mode (SM) operation makes it possible to overcome effects related to significant spectral dispersion of the multimode fiber (MMF) standardized for the 840-860nm wavelength range. The leaky VCSEL concept can allow SM operation without any adjustments in the oxide-confined VCSEL technology and does not require sacrificing the basic VCSEL parameters. The chapter investigates oxide-confined, leaky-design VCSELs and observes the characteristic leakage-effect-induced features in the vertical far-field pattern of the device. This observation confirms the validity of the leaky VCSEL concept, allows for better understanding of the device properties such as possible strain and heat gradients, oxide layer tapering, in-plane light scattering, and absorption. The chapter enables the engineering of advanced devices and photonic-integrated circuits with targeted design of oxide apertures or air gaps through quantitative evaluation of the leaky emission.

Hexagonal sinusoidal nanotextures are well suited to couple light into silicon on glass at normal incidence, as we have shown in an earlier publication [K. Jäger et al., Opt. Express 24, A569 (2016)]. In this manuscript we discuss how these nanotextures perform under oblique incidence illumination. For this numerical study we use a rigorous solver for the Maxwell equations. We discuss nanotextures with periods between 350 nm and 730 nm and an aspect ratio of 0.5.

Optical 3D simulations in many-query and real-time contexts require new solution strategies. We study an adaptive, error controlled reduced basis method for solving parameterized time-harmonic optical scattering problems. Application fields are, among others, design and optimization problems of nano-optical devices as well as inverse problems for parameter reconstructions occurring e. g. in optical metrology. The reduced basis method presented here relies on a finite element modeling of the scattering problem with parameterization of materials, geometries and sources.

Optical chirality has been recently suggested to complement the physically relevant conserved quantities of the well-known Maxwell's equations. This time-even pseudoscalar is expected to provide further insight in polarization phenomena of electrodynamics such as spectroscopy of chiral molecules. Previously, the corresponding continuity equation was stated for homogeneous lossless media only. We extend the underlying theory to arbitrary setups and analyse piecewise-constant material distributions in particular. Our implementation in a Finite Element Method framework is applied to illustrative examples in order to introduce this novel tool for the analysis of time-harmonic simulations of nano-optical devices.