Integrated Bioluminescent Immunoassays for High-Throughput Sampling and Continuous Monitoring of Cytokines

Immunoassays show great potential for the detection of low levels of cytokines, due to their high sensitivity and excellent specificity. There is a particular demand for biosensors that enable both high-throughput screening and continuous monitoring of clinically relevant cytokines such as interleukin-6 (IL-6) and tumor necrosis factor-α (TNFα). To this end, we here introduce a novel bioluminescent immunoassay based on the ratiometric plug-and-play immunodiagnostics (RAPPID) platform, with an improved intrinsic signal-to-background and an &gt;80-fold increase in the luminescent signal. The new dRAPPID assay, comprising a dimeric protein G adapter connected via a semiflexible linker, was applied to detect the secretion of IL-6 by breast carcinoma cells upon TNFα stimulation and the production of low concentrations of IL-6 (∼18 pM) in an endotoxin-stimulated human 3D muscle tissue model. Moreover, we integrated the dRAPPID assay in a newly developed microfluidic device for the simultaneous and continuous monitoring of changes in IL-6 and TNFα in the low-nanomolar range. The luminescence-based read-out and the homogeneous nature of the dRAPPID platform allowed for detection with a simple measurement setup, consisting of a digital camera and a light-sealed box. This permits the usage of the continuous dRAPPID monitoring chip at the point of need, without the requirement for complex or expensive detection techniques.</p

Use of Two-Part Regression Calibration Model to Correct for Measurement Error in Episodically Consumed Foods in a Single-Replicate Study Design: EPIC Case Study

In epidemiologic studies, measurement error in dietary variables often attenuates association between dietary intake and disease occurrence. To adjust for the attenuation caused by error in dietary intake, regression calibration is commonly used. To apply regression calibration, unbiased reference measurements are required. Short-term reference measurements for foods that are not consumed daily contain excess zeroes that pose challenges in the calibration model. We adapted two-part regression calibration model, initially developed for multiple replicates of reference measurements per individual to a single-replicate setting. We showed how to handle excess zero reference measurements by two-step modeling approach, how to explore heteroscedasticity in the consumed amount with variance-mean graph, how to explore nonlinearity with the generalized additive modeling (GAM) and the empirical logit approaches, and how to select covariates in the calibration model. The performance of two-part calibration model was compared with the one-part counterpart. We used vegetable intake and mortality data from European Prospective Investigation on Cancer and Nutrition (EPIC) study. In the EPIC, reference measurements were taken with 24-hour recalls. For each of the three vegetable subgroups assessed separately, correcting for error with an appropriately specified two-part calibration model resulted in about three fold increase in the strength of association with all-cause mortality, as measured by the log hazard ratio. Further found is that the standard way of including covariates in the calibration model can lead to over fitting the two-part calibration model. Moreover, the extent of adjusting for error is influenced by the number and forms of covariates in the calibration model. For episodically consumed foods, we advise researchers to pay special attention to response distribution, nonlinearity, and covariate inclusion in specifying the calibration model

A combination of a connector for glass elements and such glass elements

A combination of a connector for glass elements and such glass elements to provide a loadbearing glass construc- tion that comprises at least one glass post and at least one glass beam that are arranged adjacent to each other, wherein the connector is arranged to provide a rotationally fixed connection between the post and the beam.Architectural Engineering +TechnologyArchitecture and The Built Environmen

Diffusie in het systeem Cu-Si

Technische MateriaalwetenschappenApplied Science

Plate of composite construction material, column of a laminated glazing construction material, and method for the manufacture of such a column

A plate of composite material comprising elements of glass and a thermoplastic polymer adhering to the glass. The glass is toughened and the plate is assembled from adjacent and at least partly overlapping and cemented together elements which are each assembled of at least the toughened glass, and the thermoplastic polymer adhered to the glass. The glass is toughened to at least double the strength of non-toughened glass and to at most 50 % of the maximum strength of toughened glass.Architectur

The effect of shear lips, loading transitions and test frequency on constant deltaK and constant load amplitude fatigue tests

Mechanical Maritime and Materials Engineerin

Glass-aluminium bonded joints ; testing, comparing and designing for the ATP

This article presents the research to the bonded joints of the All Transparent Pavilion (ATP), an experimental project built in November 2004 at the faculty of Architecture in Delft. The pavilion is designed to use structural glass elements, bonded with Delo Photobond GB 368, a photo-catalytic transparent adhesive. To avoid bonding on-site and to allow disassembly, the joints were designed as aluminium pieces, bonded to the glass. Some joints of the ATP failed during construction. The tolerances for assembling the two aluminium parts were too small, and joints had to be forced together. The Delo Company suggested an alternative adhesive: The GB 350, a rubber modified version and supposedly tougher version of the GB 368. The research consisted of two parts: First, the mechanical behaviour of GB 368 and GB 350 were compared, and secondly designing an improved solution for the glass-aluminium bonded joint between the main beam and purlin. This article focuses on the mechanical behaviour of GB 368 and GB 350. Three types of tests were performed: tensile tests, low cycle fatigue tests and fracture toughness tests. Results show that both adhesives have low damage tolerance and are therefore sensitive to damage during assembly. Although the GB 350 was recommended by the Delo company because it was designed to resist impact loads, results show the improvement is not enough. The GB 350 is better in static tests, but the fatigue tests show great scatter and the fracture tests show peeling of the adhesive from the adherent surface. Given this, the GB 350 should be more susceptible to corrosion

Improving the engineering strength of heat strengthened glass

Although glass is increasingly used as a structural material, glass is not produced to strength standards, like steel and concrete. Of the three types of glass: annealed, heat strengthened and fully tempered, only heat strengthened glass has the properties to function as a safe structural material. These properties are strength, resistance to stress corrosion cracking, and controlled fragmentation. In this paper the factors controlling the strength of heat strengthened glass are assessed. The dominant influence is the spread in compressive pre-strength. Opportunities for quality control of the compressive pre-strength are analysed using experimental results. The consequences for the predictability of the strength and the requirements for quality controlled are discussed.Structural Design & Mechanic

The strength of glass, hidden damage

The strength of float glass is a necessary engineering parameter. Determining this strength is a complex problem. Earlier results have shown that statistically bending test results are not a homogeneous group. To explain this, a theoiy of "hidden damage" is proposed. The essence of this theory is that the different sides of float glass are unequal, not only because of the differences between the Tin and nitrogen sides, but because of the difference between the side scored under the sheet glass cutting and the side which has the crack propagation ftom the scored side in breaking. Extensive tests on rolled glass suggest that the rolling process damages the glass in a special way, causing "invisible" damage - statistically not a homogeneous distribution of micro-cracks on the edge surface of glass element. These micro-cracks are different on the scored and broken sides of glass. They are the fracture source under the loading and influence negatively on glass element strength and statistics of strength data.This "invisible" damage explains most if not all of the non-homogenous distribution of the test results. It is shown that removal of this damage on the edges of glass elements increases the engineering strength of float glass significantly.Building TechnologyArchitectur