Exploring the potential of two-dimensional electronic spectroscopy

Während des letzten Jahrzehntes haben multi-dimensionale ultraschnelle Spektroskopien großes Potential gezeigt, indem sie ein zunehmend breiteres experimentelles Fenster zur Untersuchung der Struktur und der Dynamiken von atomaren und molekularen Systemen auf Femtosekunden- und Pikosekunden-Zeitskalen öffneten. Die Vielseitigkeit und Bedeutung von zwei-dimensionaler elektronischer Spektroskopie beruht auf dem Gewinn an zusätzlicher Information, die man durch Ausweitung der Spektren in zwei Frequenz-Dimensionen erhält. Die vorliegende Dissertation fasst Teile unserer Anstrengungen im Bereich der zwei-dimensionalen elektronischen Spektroskopie zusammen. Der Fortschritt verlief dabei parallel auf zwei Schienen: einerseits führten Verbesserungen in der Instrumentation zu einer breiteren Anwendbarkeit der Methode. Durch die Umsetzung eines kompakten, einfach zu einrichtenden und passiv Phasen-stabilisierten Aufbaus zur Messung von zwei-dimensionalen elektronischen Spektren in drei verschiedenen Phasen-angepassten Geometrien wurde es möglich nicht nur Einzelquanten- sondern auch Doppelquanten-Kohärenzen zu studieren. Auf der anderen Seite wurden die existierenden Methoden angewandt um die elektronischen und vibronischen Dynamiken von molekularen Systemen unterschiedlicher Komplexität zu erforschen. Ein elektronisches Zwei-Level-System, dessen elektronischer Übergang an eine niederfrequente Schwingung gekoppelt ist, diente als Ausgangspunkt in unseren Untersuchungen. Das vibronische Wellenpaket, welches durch die Anregung mit einem Femtosekunden-Laserpuls erzeugt wird, manifestiert sich in oszillierenden Linienformen in zwei-dimensionalen Spektren. In einem nächsten Schritt wurden die Dynamiken der Linienformen eines Monomer-Dimer-Systems im Gleichgewicht untersucht. Es wurde gefunden, dass Exziton-Delokalisations-Effekte im Dimer die Zeitskala der spektralen Diffusion stark beeinflussen. Der Grad an Komplexität erreichte seinen Höhepunkt in der Untersuchung von Pfaden und Zeitskalen des Energietransfers in doppelwandigen zylindrischen J-Aggregaten. Die Dynamiken der Exzitonen in diesen molekularen Nanoröhrchen wurden mittels zeitlicher, energetischer und örtlicher Attribute charakterisiert. Zusätzlich wurde das Zweiexzitonen-Band von C8S3-Aggregaten mittels Doppelquanten-Kohärenz zwei-dimensionaler elektronischer Spektroskopie erforscht, mit dem Ziel ein tieferes Verständnis der elektronischen Struktur und Dynamiken in dieser Klasse von Substanzen zu gewinnen.During the last decade multi-dimensional ultrafast spectroscopies have shown great potential by opening an increasingly broad experimental window into the structure and dynamics of atomic and molecular systems on femtosecond and picosecond timescales. The versatility and significance of two-dimensional electronic spectroscopy relies on the gain of additional information obtained by spreading the spectra into two frequency dimensions. The present work summarizes part of our efforts in the field of two-dimensional electronic spectroscopy. The progress thereby ran parallel on two tracks: on the one hand, improvements in the instrumentation have led to a broader applicability of the method. By implementing a compact, easy to align, and passively phasestabilized setup for recording two-dimensional electronic spectra in three different phase-matching directions, it has become possible to study not only single-quantum but also double-quantum coherences. On the other hand, the existing methods have been applied to study the electronic and vibronic dynamics of molecular systems of varying complexity. An electronic two-level system whose electronic transition is coupled to a low-frequency vibrational mode has served as a starting point in our investigations. The vibronic wave packet that is induced by excitation with a femtosecond laser pulse manifests itself in oscillating line-shapes in the two-dimensional spectra. In a second step, the line-shape dynamics of a monomer-dimer system in equilibrium have been investigated. It was found that exciton delocalization effects in the dimer strongly influence the timescale of spectral diffusion. The degree of complexity reached its maximum in the investigation of pathways and timescales of energy transfer in double-wall cylindrical J-aggregates. Exciton dynamics in these molecular nanotubes have been characterized by temporal, energetic, and spatial properties. In addition, the double-exciton manifold of C8S3 aggregates has been studied by double-quantum two-dimensional electronic spectroscopy with the goal to gain a deeper understanding of the electronic structure and dynamics in this class of systems

Nanoindentation induced deformation anisotropy in WC, β-Si3N4 and ZrB2 crystals

The influence of crystal orientation on elastic and plastic response of WC, β-Si3N4 and ZrB2 ceramic grains is important to understand, model and enhance its composite mechanical properties. In order to investigate this, nanoindentation testing was carried out using Berkovich tip on selected surface areas which were mapped by electron backscatter diffraction (EBSD) prior to the tests. To study the surface morphology after nanoindentation and to characterize the resulted deformation fields around the imprints additional EBSD, atomic force microscopy (AFM) and scanning electron microscopy (SEM) investigations were performed. Considerable elastic and plastic anisotropy was found is WC and β-Si3N4 (Fig. 1a,b) crystals while the orientation dependence of ZrB2 grains exhibited slight influence on hardness and indentation modulus. The measured indentation modulus, as the elastic response, was compared with the model proposed by Vlassak and Nix and our finite element model (FEM) calculations using single crystal elastic constants, as it is shown for β-Si3N4 in Fig. 1c. To explain the obtained hardness anisotropy, as the plastic response, a theoretical model is proposed in which the critical force for slip activation is determined as a function of crystal orientation, based on the possible slip systems of materials. The predictions of the applied models describing both elastic and plastic behaviors are in good agreement with the experimental results, (for β-Si3N4 see in Fig. 1d

Chapter Optical Coherence Tomography – Applications in Non- Destructive Testing and Evaluation

Optimizatio

Self-reported HPV vaccination status and HPV vaccine hesitancy in a nationally representative sample of emerging adults in Croatia

IntroductionThe aim of this study was to determine self-reported human papillomavirus (HPV) vaccination status among emerging adults in Croatia, intention to get the HPV vaccine among unvaccinated individuals and correlates of HPV vaccine hesitancy.MethodsData were collected via a cross-sectional survey based on a probabilistic national sample. The sample included 1,197 individuals aged 18–25 years (50.6% were women) who were recruited from November 2021 to February 2022 as part of the commercial online panel. Analyses included 981 participants who correctly answered two “attention trap” questions using descriptive statistics and multivariate analyses. The data were post-hoc weighted for gender and age and adjusted for clustering effect. To adjust standard errors for the sampling design, multivariate analyses were carried out using the complex samples module in the IBM SPSS 27 statistical software package.ResultsOverall, 18.3% of participants (25.0% of women and 11.7% of men) reported that they were HPV vaccinated, while 21.9% did not know their HPV vaccination status. Of those vaccinated, 65.6% were women. The odds of being HPV-vaccinated were significantly higher among female participants. Among the unvaccinated, 35.4% expressed a willingness to get the vaccine. The odds of vaccination hesitancy were significantly lower among women, participants who reported a higher perceived risk of STIs, those who recognized that HPV could result in cervical cancer, and significantly higher among those who were more religious.ConclusionOur findings suggest a need to increase HPV vaccination uptake in Croatia through raising awareness about HPV vaccine effectiveness and also through the implementation of strategies to make vaccination more available

T cell immune response predicts survival in severely ill COVID-19 patients requiring venovenous extracorporeal membrane oxygenation support

IntroductionThere is a critical gap in understanding which SARS-CoV-2 patients would benefit most from venovenous extracorporeal membrane oxygenation (VV-ECMO) support. The potential role of a dysregulated immune response is still unclear in this patient population.ObjectivesTo assess the potential predictive value of SARS-CoV-2 specific cellular and humoral immune responses for survival in critically ill COVID-19 patients requiring VV-ECMO.MethodsWe conducted a prospective single-center observational study of unvaccinated patients requiring VV-ECMO support treated at the intensive care unit of Semmelweis University Heart and Vascular Center between March and December 2021. Peripheral blood samples were collected to measure the humoral and cellular immune statuses of the patients at the VV-ECMO cannulation. Patients were followed until hospital discharge.ResultsOverall, 35 COVID-19 patients (63% men, median age 37 years) on VV-ECMO support were included in our study. The time from COVID-19 verification to ECMO support was a median (IQR) of 10 (7-14) days. Of the patients, 9 (26%) were discharged alive and 26 (74%) died during their hospital stay. Immune tests confirmed ongoing SARS-CoV-2 infection in all the patients, showing an increased humoral immune response. SARS-CoV-2-specific cellular immune response was significantly higher among survivors compared to the deceased patients. A higher probability of survival was observed in patients with markers indicating a higher T cell response detected by both QuantiFeron (QF) and flow cytometry (Flow) assays. (Flow S1 CD8+ ≥ 0.15%, Flow S1 CD4+ ≥ 0.02%, QF CD4 ≥ 0.07, QF whole genome ≥ 0.59). In univariate Cox proportional hazard regression analysis BMI, right ventricular (RV) failure, QF whole genome T cell level, and Flow S1 CD8+ T cell level were associated with mortality, and we found that an increased T cell response showed a significant negative association with mortality, independent of BMI and RV failure.ConclusionEvaluation of SARS-CoV-2 specific T cell response before the cannulation can aid the risk stratification and evaluation of seriously ill COVID-19 patients undergoing VV-ECMO support by predicting survival, potentially changing our clinical practice in the future

Rapid Diagnostic Algorithms as a Screening Tool for Tuberculosis: An Assessor Blinded Cross-Sectional Study

Background: A major obstacle to effectively treat and control tuberculosis is the absence of an accurate, rapid, and low-cost diagnostic tool. A new approach for the screening of patients for tuberculosis is the use of rapid diagnostic classification algorithms. Methods: We tested a previously published diagnostic algorithm based on four biomarkers as a screening tool for tuberculosis in a Central European patient population using an assessor-blinded cross-sectional study design. In addition, we developed an improved diagnostic classification algorithm based on a study population at a tertiary hospital in Vienna, Austria, by supervised computational statistics. Results: The diagnostic accuracy of the previously published diagnostic algorithm for our patient population consisting of 206 patients was 54% (CI: 47%–61%). An improved model was constructed using inflammation parameters and clinical information. A diagnostic accuracy of 86% (CI: 80%–90%) was demonstrated by 10-fold cross validation. An alternative model relying solely on clinical parameters exhibited a diagnostic accuracy of 85% (CI: 79%–89%). Conclusion: Here we show that a rapid diagnostic algorithm based on clinical parameters is only slightly improved by inclusion of inflammation markers in our cohort. Our results also emphasize the need for validation of new diagnostic algorithms in different settings and patient populations

The effects of iron fortification on the gut microbiota in African children: a randomized controlled trial in Cote d'Ivoire.

BACKGROUND: Iron is essential for the growth and virulence of many pathogenic enterobacteria, whereas beneficial barrier bacteria, such as lactobacilli, do not require iron. Thus, increasing colonic iron could select gut microbiota for humans that are unfavorable to the host. OBJECTIVE: The objective was to determine the effect of iron fortification on gut microbiota and gut inflammation in African children. DESIGN: In a 6-mo, randomized, double-blind, controlled trial, 6-14-y-old Ivorian children (n = 139) received iron-fortified biscuits, which contained 20 mg Fe/d, 4 times/wk as electrolytic iron or nonfortifoed biscuits. We measured changes in hemoglobin concentrations, inflammation, iron status, helminths, diarrhea, fecal calprotectin concentrations, and microbiota diversity and composition (n = 60) and the prevalence of selected enteropathogens. RESULTS: At baseline, there were greater numbers of fecal enterobacteria than of lactobacilli and bifidobacteria (P < 0.02). Iron fortification was ineffective; there were no differences in iron status, anemia, or hookworm prevalence at 6 mo. The fecal microbiota was modified by iron fortification as shown by a significant increase in profile dissimilarity (P < 0.0001) in the iron group as compared with the control group. There was a significant increase in the number of enterobacteria (P < 0.005) and a decrease in lactobacilli (P < 0.0001) in the iron group after 6 mo. In the iron group, there was an increase in the mean fecal calprotectin concentration (P < 0.01), which is a marker of gut inflammation, that correlated with the increase in fecal enterobacteria (P < 0.05). CONCLUSIONS: Anemic African children carry an unfavorable ratio of fecal enterobacteria to bifidobacteria and lactobacilli, which is increased by iron fortification. Thus, iron fortification in this population produces a potentially more pathogenic gut microbiota profile, and this profile is associated with increased gut inflammation. This trial was registered at controlled-trials.com as ISRCTN21782274

A Novel Immunological Assay for Hepcidin Quantification in Human Serum

Contains fulltext : 81054.pdf (publisher's version ) (Open Access)BACKGROUND: Hepcidin is a 25-aminoacid cysteine-rich iron regulating peptide. Increased hepcidin concentrations lead to iron sequestration in macrophages, contributing to the pathogenesis of anaemia of chronic disease whereas decreased hepcidin is observed in iron deficiency and primary iron overload diseases such as hereditary hemochromatosis. Hepcidin quantification in human blood or urine may provide further insights for the pathogenesis of disorders of iron homeostasis and might prove a valuable tool for clinicians for the differential diagnosis of anaemia. This study describes a specific and non-operator demanding immunoassay for hepcidin quantification in human sera. METHODS AND FINDINGS: An ELISA assay was developed for measuring hepcidin serum concentration using a recombinant hepcidin25-His peptide and a polyclonal antibody against this peptide, which was able to identify native hepcidin. The ELISA assay had a detection range of 10-1500 microg/L and a detection limit of 5.4 microg/L. The intra- and interassay coefficients of variance ranged from 8-15% and 5-16%, respectively. Mean linearity and recovery were 101% and 107%, respectively. Mean hepcidin levels were significantly lower in 7 patients with juvenile hemochromatosis (12.8 microg/L) and 10 patients with iron deficiency anemia (15.7 microg/L) and higher in 7 patients with Hodgkin lymphoma (116.7 microg/L) compared to 32 age-matched healthy controls (42.7 microg/L). CONCLUSIONS: We describe a new simple ELISA assay for measuring hepcidin in human serum with sufficient accuracy and reproducibility