64 research outputs found
Advanced quantum cascade laser infrared attenuated total reflection spectroscopy
No full textThe overarching topic of this cumulative thesis is the development and application of next-generation quantum cascade laser (QCL) based infrared attenuated total reflection (IR-ATR) infrared spectroscopy.
Cascade lasers (i.e., interband and quantum cascade lasers; ICLs, QCLs) are considered the most advanced mid-infrared light sources, as discussed and exemplified in the introduction section of this dissertation. The characteristic properties of quantum cascade lasers include a broad spectral coverage and tunability in the mid-infrared range (MIR; 3 – 12 µm), well-defined spectral properties, and a high energy density within the emitted spectral band. As a result, spectroscopic information can be obtained based on differentiating molecular signatures. Consequently, the remainder of this cumulative thesis focuses on a variety of analytical applications capitalizing on the unique properties of cascade lasers presented as a series of peer-reviewed research articles.
If laser light sources are combined with appropriate transducers, numerous application opportunities arise in a variety of scenarios ranging from environmental monitoring to bioanalytics. Hence, the development of innovative sensor technologies is an important yet challenging topic. The main purpose of the transducer in optical sensors is to ensure reproducible interaction between the sample and the photons, i.e., herein, light emitted by the laser light source. This is of particular interest if optical sensing technologies aim at taking advantage of inherent molecular specificity without additional chem/bio recognition architectures, as is the case for mid-infrared spectroscopic concepts. While the aforementioned scenarios – environmental vs. life science applications – clearly have their specific needs and requirements, both may capitalize on similar fundamental photonic concepts and building blocks, which are at the core of the present thesis, i.e., mid-infrared laser and mid-infrared waveguide technology.
Analyzing molecular constituents in real-world environmental scenarios requires measurement techniques that may particularly withstand harsh external conditions while providing robust and reliable analytical data. Only a few infrared spectroscopic systems have been developed for harsh environments with most devices in routine practice being deployed in appropriate research facilities providing for a constant measurement environment without the need for portable or mobile devices. Among the most robust sensing concepts in mid-infrared photonics are transducers/sampling interfaces based on single or multiple reflection waveguides facilitating IR-ATR (i.e., evanescent field absorption) spectroscopy, which are readily adaptable to harsh conditions as shown in the present thesis. To this end, conventional multi-reflection ATR concepts were augmented with substrate-integrated hollow waveguide (iHWG) technology pioneered by our research team yielding an exceedingly robust modular transducer platform. This was achieved by developing an iHWG-based invariant light coupling concept for coupling IR photons to an ATR waveguide without the need for any additional optics in a robust and compact arrangement. This innovative assembly was proven useful for conventional broadband IR spectroscopy using Fourier transform infrared spectrometers, as well as QCLs. In the course of this thesis, a robust MIR sensor system was developed for mobile measurement applications at harsh environmental or process analytical conditions. The versatility of the developed sensor technology was demonstrated by coupling to a variety of light sources, the optional use of MIR fiberoptics, and by investigating a series of relevant analytes.
Bioanalytical sensing technologies frequently require addressing exceedingly small sample volumes/quantities or directly addressing live biological specimens or systems. This requires biocompatible and chemically inert transducers when probing samples in life science applications. To this end, diamond is an ideal waveguide material that next to its inertness and biocompatibility provides a broad spectral transmission window that extends well into the MIR regime, which is of particular interest for the present thesis. While conventional diamond ATR crystals with only a few internal reflections readily exist, the present thesis was focused on optimizing frequency-matched thin-film diamond waveguide technology ideally combining with QCL light sources. Using nanocrystalline diamond layers with a thickness of around 20 µm, near single-mode waveguiding behavior has been achieved yielding a homogeneous evanescent field at the waveguide surface rather than hotspots, as encountered via discrete internal reflections using macroscopic ATR waveguides. Thereby, highly miniaturized sensing concepts are facilitated without trading off size against sensitivity. The performance and quantitative analytical capabilities of QCL-based MIR sensors combined with thin-film diamond waveguides were compared to conventional IR-ATR technology for the exemplary analyte caffeine, which is among the most commonly ingested psychoactive substances found in simulating beverages such as tea, coffee, or energy drinks.
The utility of the developed sensing concepts was also shown for the analysis of live biological specimens, i.e., model bacteria, whereby biofilm formation processes were studied in molecular detail using QCLs combined with diamond thin-film waveguide technology for the first time. Different growth phases of bacteria were analyzed and compared with conventional IR spectroscopic data confirming the feasibility of IR laser spectroscopy for complex bioanalytical application scenarios.
Finally, even though QCLs combined with diamond thin-film waveguide technology gave rise to adequately sensitive measurement concepts, there are analytical scenarios where even more sensitivity is required. Hence, it was shown that the strategy of surface-enhanced infrared absorption (SEIRA) spectroscopy may be readily adapted for harnessing the MIR sensing technologies developed in this thesis, especially by using graphene for amplifying selected infrared signatures.
In summary, the results of this cumulative thesis were published within ten peer-reviewed contributions in leading international journals, including seven of them as a first author. A review contribution introduces the fundamentals of cascade lasers and their applications providing selected highlight examples published as a book chapter. The obtained research results address two main areas – environmental/process analytical scenarios and bioanalytics – demonstrating the versatility of waveguide-based laser spectroscopy in the mid-infrared contributing three publications each to robust IR-ATR concepts suitable for harsh environments, and to advanced thin-film diamond waveguide technology for bioanalytical scenarios
Predicting Early and Sustained Virological Responses in Prior Nonresponders to Pegylated Interferon alpha-2b Plus Ribavirin Retreated With Peginterferon alpha-2a Plus Ribavirin and The Benefit-Risk Ratio of Retreatment t
No full textGOALS:
To evaluate the predictive value of complete early virological response (cEVR) on sustained virological response (SVR) following retreatment with peginterferon alpha-2a (40 kDa) plus ribavirin in previous nonresponders to peginterferon alpha-2b (12 kDa).
BACKGROUND:
In the randomized multinational retreatment with Pegasys in patients not responding to PegIntron therapy study, a 72-week regimen of peginterferon alpha-2a (40 kDa) plus ribavirin improved SVR rates over a standard 48-week regimen in previous nonresponders to peginterferon alpha-2b (12 kDa). cEVR, defined as hepatitis C virus RNA <50 IU/mL at treatment week 12, was an important predictor of SVR.
STUDY:
We conducted an exploratory analysis of the retreatment with Pegasys in patients not responding to PegIntron therapy study data to better define the predictive value of cEVR for SVR in this patient population.
RESULTS:
In total, 157 of the 942 patients achieved a cEVR (16.7%). SVR rates were higher with 72 versus 48 weeks of retreatment in patients with a cEVR (57% vs. 35%), whereas SVR rates were <5% in patients without cEVR in both groups. The relative adverse event (AE) burden was lower with 72 weeks of treatment (8.1 vs. 10.1 AEs/y of treatment) as was the estimated number of AEs per SVR achieved (55 vs. 100). Cumulative treatment duration required to achieve 1 SVR was lower with 72 weeks of treatment (6.7 vs. 10.0 y/SVR) and lower still assuming that treatment was stopped at week 12 for non-cEVR patients (3.6 vs. 7.1 y/SVR).
CONCLUSIONS:
cEVR is a reliable predictor of SVR in patients retreated with peginterferon alpha-2a (40 kDa) plus ribavirin. Seventy-two-week retreatment has a more favorable benefit-risk ratio than 48 weeks, especially when cEVR is used to identify patients most likely to be cured
Salvation: Into the Cosmos: Board Game Project Blending 4X and Eurogame Styles
No full textThis project is an attempt at creating a shorter and simpler 4X strategy game. To do this, the author takes elements of the Eurogame genre and combines aspects of The Settlers of Catan by Klaus Teuber and Shattered Plans by Jagex while following the requirements of the German board game award, the Spiel de Jahres. After following the traditional game design process of conceptualization, prototyping, and repeated testing, analysis, and revision, the author succeeded in creating a core foundation for such a game that also had marketing potential on its own
Action and Drama: American Film Titles in Japanese
No full textJapanese titles of foreign films come in many varieties, from direct translation to phonetic representation to something completely different from the original title. This study looks at trends among the Japanese titles of over 6000 American action films and drama films over the past 100 years. The author created a spreadsheet of titles from an online film database and examined katakana usage in each genre decade by decade from the 1920s to present day. The author found that these genres differ greatly from each other in the percentage of katakana-only titles, and in how likely those titles are to be phonetic representations of the original English titles. Finally, the author discovered katakana and Japanese words that occur disproportionately in Japanese titles when compared to their English equivalent in the original titles
An Analysis of the Nonce-Words of Dr. Seuss
No full textThe books of children’s author Dr. Seuss are filled with nonce-words—novel word formations that can only be understood within the context of the books. This paper is an attempt to analyze a subset of these nonce-words and their phonological and orthographical structure. A database of 377 words from 33 books was created and the words were analyzed in terms of their internal structure as well as in their context in the books. The author found that a significant amount of these neologisms were likely influenced by the poetic constructs of rhyme and alliteration. In addition, certain characteristics of the nonce-words were examined, and possible reasons are given to explain their use. These characteristics include unusual word-final double consonants, and the extensive use of the letter z.departmental bulletin pape
An Analysis of the Nonce-Words of Dr. Seuss
No full textThe books of children’s author Dr. Seuss are filled with nonce-words—novel word formations that can only be understood within the context of the books. This paper is an attempt to analyze a subset of these nonce-words and their phonological and orthographical structure. A database of 377 words from 33 books was created and the words were analyzed in terms of their internal structure as well as in their context in the books. The author found that a significant amount of these neologisms were likely influenced by the poetic constructs of rhyme and alliteration. In addition, certain characteristics of the nonce-words were examined, and possible reasons are given to explain their use. These characteristics include unusual word-final double consonants, and the extensive use of the letter z
Retreatment with interferon-alpha and ribavirin in primary interferon-alpha non-responders with chronic hepatitis C
No full textBackground/Aims: Combination therapy with interferon-alpha (IFN-alpha) plus ribavirin is more efficacious than IFN-alpha monotherapy in previously untreated patients with chronic hepatitis C and patients with IFN-alpha relapse. Only limited data are available in IFN-alpha non-responders. In a multicenter trial we therefore evaluated the efficacy of combination therapy in IFN-alpha-resistant chronic hepatitis C. Methods: Eighty-two patients (mean age 46.8 years, 54 males, 28 females) with chronic hepatitis C were treated with IFN-alpha-2a (3 x 6 MIU/week) and ribavirin (14 mg/kg daily) for 12 weeks. Thereafter, treatment was continued only in virological responders (undetectable serum HCV RNA at week 12) with an IFN-alpha dose of 3 x 3 MIU/week and without ribavirin for a further 9 months. The primary study endpoint was an undetectable HCV RNA by RT-PCR at the end of the 24-week follow-up period. Results: After 12 weeks of combination therapy, an initial virological response was observed in 29 of 82 (35.4%) patients. Due to a high breakthrough rate after IFN-a dose reduction and ribavirin discontinuation, an end-of-treatment response was only achieved in 12 of 82 (14.6%) patients. After the follow-up period, a sustained virological response was observed in 8 of 82 (9.8%) patients. Infection with HCV genotype 3 was the only pretreatment parameter, which could predict a sustained response (HCV-1, 5%; HCV-3, 57.1%; p < 0.001). Conclusions: Despite a high initial response rate of 35.4%, sustained viral clearance was achieved only in 9.8% of the retreated primary IFN-alpha non-responders. Higher IFN-alpha induction and maintenance dose, as well as prolonged ribavirin treatment may possibly increase the virological response rates in non-responders, particularly in those infected by HCV-1
Comparative feasibility study of a 30 MW disruptive floater solution with a 15 MW PivotBuoy and a benchmark 15 MW semi-submersible floater in the Bay of Biscay
No full textThis paper investigates the technical, life cycle, and economic feasibility of a 30 MW upscaled downwind turbine, comparing it to a 15 MW X1 Wind PivotBuoy downwind turbine and a benchmark 15 MW IEA Umaine VolturnUS-S upwind turbine in the 450 MW Sud de la Bretagne I wind farm site. The study is significant due to the rising energy demand, the potential for decreasing the levelized cost of energy with increased turbine size, and the optimized use of space. The size limit of current upwind turbine designs could be addressed using a downwind turbine solution.The research is conducted by modelling the global dynamic response of the structure using OpenFAST and computing the natural frequencies and stresses using a finite element model. A lifecycle analysis is performed to identify potential pitfalls and bottlenecks by analysing the individual lifecycle phases. The economic feasibility is assessed by simulating the annual energy production using TOPFARM and utilizing structural analysis and lifecycle assessment to quantify capital, operational, and abandonment expenditures. Based on the annual energy production and the performance indicators the levelized cost of energy is calculated.The findings indicate that while the global stability is within boundaries, the stress in members is too high with a simple scale-up of the proposed design. Bottlenecks are found in lifting operations and supply chain readiness. The levelized cost of energy and capital expenditure increased due to substructure self-weight, rendering the proposed 30 MW scale-up currently unfeasible when compared to the other two wind farms.These findings are important as they demonstrate that the 15 MW X1 Wind PivotBuoy is not scalable without design changes. The levelized cost of energy does not decrease with an increased floater solution. The 15 MW X1 Wind PivotBuoy downwind turbine seems more economically viable, making it a more interesting option for future development.Civil Engineerin
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