Second-order regular variation, convolution and the central limit theorem

AbstractSecond-order regular variation is a refinement of the concept of regular variation which is useful for studying rates of convergence in extreme value theory and asymptotic normality of tail estimators. For a distribution tail 1 − F which possesses second-order regular variation, we discuss how this property is inherited by 1 − F2 and 1 − F∗2. We also discuss the relationship of central limit behavior of tail empirical processes, asymptotic normality of Hill's estimator and second-order regular variation

Transmission of pillar-based photonic crystal waveguides in InP technology

Waveguides based on line defects in pillar photonic crystals have been fabricated in InP/InGaAsP/InP technology. Transmission measurements of different line defects are reported. The results can be explained by comparison with two-dimensional band diagram simulations. The losses increase substantially at mode crossings and in the slow light regime. The agreement with the band diagrams implies a good control on the dimensions of the fabricated features, which is an important step in the actual application of these devices in photonic integrated circuit

The 243 steps of making photonic integrated circuits in InP

The fabrication ofInP-based Photonic Integrated Circuits (PICs) is a complex process. The process used in the COBRA cleanroom in Eindhoven consists of 13 deposition, 10 lithography, 14 dry- and 7 wet-etching steps. Together with the intermediate cleaning, preparation and inspection procedures, the total process flow consists of 243 steps. In this paper we show how we created a robust modular process flow that can be usedfor a large variety of active- and passive circuits. These circuits can be fabricated together in multi-project wafer runs, allowing a drastic reduction of the fabrication costs making even small-volume production economicallyfeasible

The 243 steps of making photonic integrated circuits in InP

The fabrication ofInP-based Photonic Integrated Circuits (PICs) is a complex process. The process used in the COBRA cleanroom in Eindhoven consists of 13 deposition, 10 lithography, 14 dry- and 7 wet-etching steps. Together with the intermediate cleaning, preparation and inspection procedures, the total process flow consists of 243 steps. In this paper we show how we created a robust modular process flow that can be usedfor a large variety of active- and passive circuits. These circuits can be fabricated together in multi-project wafer runs, allowing a drastic reduction of the fabrication costs making even small-volume production economicallyfeasible

Fullerene-assisted electron-beam lithography for pattern improvement and loss reduction in InP membrane waveguide devices

In this Letter, we present a method to prepare a mixed electron-beam resist composed of a positive resist (ZEP520A) and C 60 fullerene. The addition of C 60 to the ZEP resist changes the material properties under electron beam exposure significantly. An improvement in the thermal resistance of the mixed material has been demonstrated by fabricating multimode interference couplers and coupling regions of microring resonators. The fabrication of distributed Bragg reflector structures has shown improvement in terms of pattern definition accuracy with respect to the same structures fabricated with normal ZEP resist. Straight InP membrane waveguides with different lengths have been fabricated using this mixed resist. A decrease of the propagation loss from 6.6 to 3.3¿¿dB/cm has been demonstrated

BCG and adverse events in the context of leprosy

Background: Notwithstanding its beneficial immunoprophylactic outcomes regarding leprosy and childhood TB, BCG vaccination may cause adverse events, particularly of the skin. However, this local hyper-immune reactivity cannot be predicted before vaccination, nor is its association with protection against leprosy known. In this study we investigated the occurrence of adverse events after BCG (re)vaccination in contacts of leprosy patients and analyzed whether the concomitant systemic anti-mycobacterial immunity was associated with these skin manifestations. Methods: Within a randomized controlled BCG vaccination trial in Bangladesh, 14,828 contacts of newly diagnosed leprosy patients received BCG vaccination between 2012 and 2017 and were examined for adverse events 8 to 12 weeks post-vaccination. From a selection of vaccinated contacts, venous blood was obtained at follow-up examination and stimulated with Mycobacterium leprae (M. leprae) antigens in overnight whole-blood assays (WBA). M. leprae phenolic glycolipid-I-specific antibodies and 32 cytokines were determined in WBAs of 13 individuals with and 13 individuals without adverse events after vaccination. Results: Out of the 14,828 contacts who received BCG vaccination, 50 (0.34%) presented with adverse events, mainly (80%) consisting of skin ulcers. Based on the presence of BCG scars, 30 of these contacts (60%) had received BCG in this study as a booster vaccination. Similar to the pathological T-cell immunity observed for tuberculoid leprosy patients, contacts with adverse events at the site of BCG vaccination showed elevated IFN-γ levels in response to M. leprae-specific proteins in WBA. However, decreased levels of sCD40L in serum and GRO (CXCL1) in response to M. leprae simultaneously indicated less T-cell regulation in these individuals, potentially causing uncontrolled T-cell immunity damaging the skin. Conclusion: Skin complications after BCG vaccination present surrogate markers for protective immunity against leprosy, but also indicate a higher risk of developing tuberculoid leprosy

Pathogen-Specific Epitopes as Epidemiological Tools for Defining the Magnitude of Mycobacterium leprae Transmission in Areas Endemic for Leprosy

During recent years, comparative genomic analysis has allowed the identification of Mycobacterium leprae-specific genes with potential application for the diagnosis of leprosy. In a previous study, 58 synthetic peptides derived from these sequences were tested for their ability to induce production of IFN-γ in PBMC from endemic controls (EC) with unknown exposure to M. leprae, household contacts of leprosy patients and patients, indicating the potential of these synthetic peptides for the diagnosis of sub- or preclinical forms of leprosy. In the present study, the patterns of IFN-γ release of the individuals exposed or non-exposed to M. leprae were compared using an Artificial Neural Network algorithm, and the most promising M. leprae peptides for the identification of exposed people were selected. This subset of M. leprae-specific peptides allowed the differentiation of groups of individuals from sites hyperendemic for leprosy versus those from areas with lower level detection rates. A progressive reduction in the IFN-γ levels in response to the peptides was seen when contacts of multibacillary (MB) patients were compared to other less exposed groups, suggesting a down modulation of IFN-γ production with an increase in bacillary load or exposure to M. leprae. The data generated indicate that an IFN-γ assay based on these peptides applied individually or as a pool can be used as a new tool for predicting the magnitude of M. leprae transmission in a given population