Scientific publications of the Saarland University
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Comprehensive Qualitative Drug Screening in Emergency Toxicology Using an Automated LC-MSn System:Simultaneous Quantification of Relevant Drugs and Metabolites in Blood Plasma
Get PDFRapid and comprehensive qualitative and quantitative analytical procedures are crucial in 24/7 emergency toxicology (ET) to support diagnosis and treatment of acute intoxications and to monitor their progression and efficacy of detoxification strategies. This study aimed to develop the simultaneous qualitative and quantitative analysis of 62 drugs, as well as seven active metabolites in human blood plasma using an automated liquid chromatography (LC)-linear ion trap mass spectrometry (MS) screening system. Sample preparation was conducted by liquid–liquid extraction, and plasma concentrations were determined using an electronically stored 5-point calibration. Validation was performed according to international guidelines and recommendations for ET including selectivity, carry-over, accuracy, precision, and matrix effects. Finally, applicability was evaluated using case samples and proficiency tests. The method demonstrated selectivity for all analytes, with no significant carry-over or matrix effects. Accuracy and precision recommended for ET could be fulfilled for all tested analytes, except for 10 analytes. Patient plasma samples were analyzed and compared with results obtained by reference LC-tandem MS or gas chromatography-MS methods. Furthermore, the applicability of the method could be demonstrated. It provides a fast, robust, and reliable blood plasma screening for 69 analytes and an additional quantification of 59 analytes relevant in ET. The use of an electronically stored 5-point calibration and a simplified “push and print solution” allows for straightforward assessment of blood plasma levels of the analytes
Einfluss von Tanninsäure und experimenteller Kombinationsspüllösungen auf den oralen Biofilm in-situ
Get PDFDeutsche Zusammenfassung
Ziel: In dieser in-situ-Studie sollen antibakterielle und antiadhärente Effekte der Tanninsäure und deren Kombination mit Natriumfluorid und Pufferlösung auf den oralen Biofilm untersucht werden.
Material und Methode: Vier Probanden haben jeweils drei bovine Schmelzprüfkörper je Quadrant im Oberkiefer für 48 h getragen. Die Probanden sollten nach 3 min und anschließend alle 12 h für 30 s mit je 10 ml einer Spüllösung spülen. Alle Probanden spülten mit Wasser, Chlorhexidin (0,2 %), Tanninsäure (5 %; pH = 2,3), Natriumfluorid (500 ppm F-; pH = 7,9) sowie Tanninsäure und Natriumfluorid (pH = 3,9). In einem zweiten Teil spülten zwei Proban-den zusätzlich mit Phosphatpuffer (150 mM; pH = 7,5) und Tanninsäure plus Phosphatpuffer (pH = 5,5). Nach 48 h wurden die Prüfkörper entnommen und mit LIVE/DEAD BacLight angefärbt und fluoreszenzmikroskopisch untersucht. Weitere Ergebnisse wurden mit dem Rasterelektronen- und Transmissionselektronenmikroskop gewonnen.
Ergebnisse: Die Prüfkörper waren bei der Spülung mit Wasser fast vollständig mit gleichermaßen lebenden und toten Bakterien bedeckt. Mit Chlorhexidin konnte der Biofilm in dieser Studie am stärksten reduziert werden. Die Spülung mit Natriumfluorid zeigte eine geringfügige Reduktion der Bedeckung. Tanninsäure hatte einen guten antibakteriellen Effekt, der Bedeckung und Vitalität signifikant reduzierte. Es zeigten sich jedoch erosive Veränderungen an der Schmelzoberfläche. Die Kombination mit Natriumfluorid konnte nur die Bedeckung noch weiter reduzieren, die Vitalität blieb nahezu unverändert. Die Pufferlösung hatte ähnlich der Negativkontrolle keinen Effekt auf den Biofilm. Die Kombination mit Tanninsäure zeigte, verglichen mit reiner Tanninsäure, eine höhere Bedeckung bei verminderter Vitalität. Es fanden sich keine erosiven Veränderungen.
Schlussfolgerung: Tanninsäure zeigt gute antibakterielle und antiadhärente Ergebnisse. Die Kombination mit Natriumfluorid hatte fast keine Steigerung der antibakteriellen Wirkung zufolge. Nach Kombination mit der Pufferlösung konnten die unerwünschten erosiven Schmelzveränderungen beseitigt werden. Gleichzeitig konnte ein ähnlich guter antibakterieller Effekt erzielt werden wie mit reiner Tanninsäure. Tanninsäure ist auch ohne den sauren Charakter antibakteriell und antiadhärent wirksam. Damit ist sie ein vielversprechendes orales Antiseptikum.Abstract
Objectives: The present in-situ study has the aim to investigate the antibacterial and anti-adherent effects of tannic acid, and its combinations with sodium fluoride and buffer solution, on the oral biofilm.
Materials and methods: Four volunteers each carried three bovine enamel specimens per quadrant with upper jaw splints. Every subject had to rinse with the following agents: water, chlorhexidine (0,2 %), tannic acid (5 %; pH = 2,3), sodium fluoride (500 ppm F-; pH = 7,9) as well as tannic acid and sodium fluoride (pH = 3,9). In a second trial two subjects rinsed additionally with a buffer solution (150 mM; pH = 7,5) and tannic acid plus buffer solution (pH = 5,5). Beginning after 3 min, then every 12 h the subjects rinsed with 10 ml of the agents for 30 s. After 48 h the specimens were removed for analysis. The oral biofilm was stained with LIVE/DEAD BacLight and evaluated with the fluorescence microscope. In addition, scanning electron microscopy and transmission electron microscopy were performed.
Results: The negative control with water showed a nearly fully biofilm covered specimen, featuring equal amounts of dead and live bacteria. Chlorhexidine was able to reduce both parameters surface coverage and biofilm vitality the most in this study. Sodium fluoride showed a low reduction of biofilm coverage. Tannic acid had a good antibacterial effect and reduced coverage as well as vitality significantly. However, the specimens revealed erosive changes of the enamel surface. The combination with sodium fluoride was not able to influence the biofilm vitality, but slightly reduced surface coverage. The buffer solution had no effect on the biofilm and was just as similar as water. Rinsing with buffered tannic acid resulted in a higher coverage, compared with regular tannic acid, with a slightly lower vitality. There were no erosions detected.
Conclusion: Tannic acid provides good antibacterial and anti-adherent effects. Sodium fluoride itself had no significant impact on the biofilm formation and vitality. While the combination of tannic acid and sodium fluoride couldn’t improve the effects by much, the erosive changes were still detected. The buffered tannic acid solution showed similar results as just tannic acid but without any hint of erosion. In conclusion, tannic acid seems to be a promising oral antiseptic despite the lack of biofilm coverage reduction. Furthermore, this study shows that the effects are reproducible without the acidic character of itself
Synthetic Rebalancing of Imbalanced Macro Etch Testing Data for Deep Learning Image Classification
No full textThe adoption of artificial intelligence (AI) in industrial manufacturing lags behind re search progress, partly due to smaller, imbalanced datasets derived from real processes.
In non-destructive aerospace testing, this challenge is amplified by the low defect rates of
high-quality manufacturing. This study evaluates the use of synthetic data, generated via
multiresolution stochastic texture synthesis, to mitigate class imbalance in material defect
classification for the superalloy Inconel 718. Multiple datasets with increasing imbalance
were sampled, and an image classification model was tested under three conditions: native
data, data augmentation, and synthetic data inclusion. Additionally, round robin tests with
experts assessed the realism and quality of synthetic samples. Results show that synthetic
data significantly improved model performance on highly imbalanced datasets. Expert
evaluations provided insights into identifiable artificial properties and class-specific accu racy. Finally, a quality assessment model was implemented to filter low-quality synthetic
samples, further boosting classification performance to near the balanced reference level.
These findings demonstrate that synthetic data generation, combined with quality control,
is an effective strategy for addressing class imbalance in industrial AI applications
Quality Enhancement of Laser Powder‐Bed Fusion Parts by Acoustically Assisted Additive Manufacturing by Laser Powder‐Bed Fusion and its Application to Lattice Structures
Get PDFAdditive manufacturing technologies such as laser powder-bed fusion (L-PBF) offer great freedom in design, ultralightweight optimization of components, and individualization of products down to a batch size of one. However, parts fabricated from L-PBF suffer from poor quality. Unavoidable porosity, rough surfaces, anisotropic microstructure, and poor geometrical accuracy and their large scatter pose challenges to post-processing, force larger tolerances, or inhibit technical applications. Acoustic assistance during a build job compacts the powder-bed and has an influence on solidification. This is why the technology addresses all the aforementioned drawbacks. It is known that porosity, surface roughness in downskin regions, and microstructural anisotropy decrease without any post-processing if a build job is sonicated. This study focuses on the fabrication of lattice structures by acoustically assisted L-PBF. Even with a parameter set that is not adjusted to thin-walled structures, porosity decreases in the as-built state. Quasistatic compression tests as well as compressive load increase tests are performed. Results show superior mechanical properties of acoustically assisted samples if compared to standard samples
Towards a robust and reproducible evaluation framework for congestion control algorithms
No full textNetwork congestion, the state where systems such as switches or routers receive more data than they can handle, leads to packet losses, increased network delay, and reduced throughput for all data passing through such a congested system. Congestion control remains a key research problem in networking, with both industry and academia proposing solutions to improve network performance. Research on congestion-control algorithms (CCAs) spans about four decades, yet there is still no "one-size fits-all" solution. Due to evolving hardware (programmable switches and NICs), changing traffic patterns, stringent application requirements, etc., new CCAs are being proposed every so often. CCAs for the public Internet or WANs are usually designed by researchers in academia or industry, or by operators of large-scale networked systems. These algorithms must then run in networks where they share network resources with other (existing) CCAs. So, before deployment, designers test if a proposed CCA performs well in its intended environment, without negatively impacting cross-traffic. These evaluations are typically conducted using simulations, modeling, or emulations on lab-based testbeds, or a small or limited set of real-world network paths. Performance insights from such evaluation approaches, however, cannot guarantee that a CCA performs well when it is eventually deployed on complex, real-world network paths. In addition, the evaluation of CCAs is a time-consuming process, compounded by the difficulty of selecting representative network parameters. Furthermore, it is impractical for designers to exhaustively test all possible scenarios in which a CCA might eventually be used. Despite the innovation and research effort that has been invested into designing new CCAs, there is still no consensus within the networking community on how to benchmark their performance. Determining how any CCA falls short compared to the rest, and, most importantly, along what dimensions, remains difficult to answer. Even performing all the pairwise comparisons between the algorithms is hard, because each algorithm behaves differently depending on the underlying network environment. In this thesis, we advocate for a fundamental rethinking of how we approach CCA evaluations. Rather than prescribing a standardized set of tests to be universally applied---an approach that has historically failed to achieve consensus, we emphasize the importance of aligning evaluations with their underlying objectives. By shifting the focus in this way, the burden on designers to subject their CCAs to an exhaustive list of experiments can be avoided, while simultaneously addressing the reproducibility challenges that currently plague this field. To this end, we developed a rigorous and reproducible "recipe" for evaluating CCAs. With this recipe, we were able to uncover fundamental issues in the design of Google's new CCA, BBRv3--work which was recognized with a "Best Paper" award at PAM'24. Furthermore, this research work has helped to highlight the critical network signals one needs to leverage in the design of network-assisted CCAs.Netzüberlastung, d. h. der Zustand, in dem Systeme wie Switches oder Router mehr Daten empfangen, als sie verarbeiten können, führt zu Paketverlusten, erhöhter Netzverzögerung und verringertem Durchsatz für alle Daten, die ein solches überlastetes System durchlaufen. Die Staukontrolle ist nach wie vor ein zentrales Forschungsproblem im Netzbereich, wobei sowohl die Industrie als auch die Wissenschaft Lösungen zur Verbesserung der Netzleistung vorschlagen. Die Forschung zu Algorithmen zur Staukontrolle (CCAs) erstreckt sich über etwa vier Jahrzehnte, doch gibt es noch immer keine "Einheitslösung für alle". Aufgrund der sich weiterentwickelnden Hardware (programmierbare Switches und NICs), sich ändernder Verkehrsmuster, strenger Anwendungsanforderungen usw. werden immer wieder neue CCAs vorgeschlagen. CCAs für das öffentliche Internet oder WANs werden in der Regel von Forschern in Hochschulen oder der Industrie oder von Betreibern großer vernetzter Systeme entwickelt. Diese Algorithmen müssen dann in Netzen laufen, in denen sie sich die Netzressourcen mit anderen (bestehenden) CCAs teilen. Daher testen die Entwickler vor dem Einsatz, ob eine vorgeschlagene CCA in der vorgesehenen Umgebung gut funktioniert, ohne den Querverkehr negativ zu beeinflussen. Diese Bewertungen werden in der Regel mit Hilfe von Simulationen, Modellen oder Emulationen auf laborgestützten Testumgebungen oder einer kleinen oder begrenzten Anzahl von realen Netzwerkpfaden durchgeführt. Die aus solchen Evaluierungsansätzen gewonnenen Leistungserkenntnisse sind jedoch keine Garantie dafür, dass eine CCA auch dann gut funktioniert, wenn sie schließlich auf komplexen, realen Netzpfaden eingesetzt wird. Darüber hinaus ist die Bewertung von CCAs ein zeitaufwändiger Prozess, der durch die Schwierigkeit, repräsentative Netzparameter auszuwählen, noch erschwert wird. Darüber hinaus ist es für die Entwickler unpraktisch, alle möglichen Szenarien, in denen eine CCA letztendlich eingesetzt werden könnte, umfassend zu testen. Trotz des Innovations- und Forschungsaufwands, der in die Entwicklung neuer CCAs investiert wurde, gibt es in der Netzgemeinde noch immer keinen Konsens darüber, wie ihre Leistung zu bewerten ist. Es ist nach wie vor schwierig, festzustellen, inwieweit eine CCA im Vergleich zu den anderen abfällt, und vor allem, in welchen Bereichen. Selbst die Durchführung aller paarweisen Vergleiche zwischen den Algorithmen ist schwierig, da sich jeder Algorithmus je nach der zugrunde liegenden Netzwerkumgebung anders verhält. In dieser Arbeit plädieren wir für ein grundsätzliches Überdenken der Art und Weise, wie wir an CCA-Bewertungen herangehen. Anstatt eine standardisierte Reihe von Tests vorzuschreiben, die universell angewendet werden sollen - ein Ansatz, der in der Vergangenheit keinen Konsens erzielt hat -, betonen wir, wie wichtig es ist, die Bewertungen an den zugrunde liegenden Zielen auszurichten. Durch diese Verlagerung des Schwerpunkts kann vermieden werden, dass die Konstrukteure ihre CCAs einer erschöpfenden Liste von Experimenten unterziehen müssen, während gleichzeitig die Probleme der Reproduzierbarkeit angegangen werden, die diesen Bereich derzeit plagen. Zu diesem Zweck haben wir ein rigoroses und reproduzierbares "Rezept" für die Bewertung von CCAs entwickelt. Mit diesem Rezept waren wir in der Lage, grundlegende Probleme im Design von Googles neuer CCA, BBRv3, aufzudecken - eine Arbeit, die auf der PAM'24 mit einem "Best Paper"-Award ausgezeichnet wurde. Darüber hinaus hat diese Forschungsarbeit dazu beigetragen, die kritischen Netzwerksignale hervorzuheben, die bei der Entwicklung von netzwerkgestützten CCAs genutzt werden müssen.MPI for Informatics, Max Planck Societ
Influence of thickness on magnetic properties of RF-sputtered amorphous CoNbZr thin films
No full textAmorphous sputtered Co-based thin films are widely used as soft magnetic materials in applications such as
sensors, inductors and magnetic flux concentrators. The magnetic properties of these films can be controlled
by deposition parameters like film thickness, argon pressure, deposition rate and others. In this study, we
present a detailed investigation of the magnetic properties of RF-sputtered Co90Nb8Zr2
films with thicknesses
ranging from 52 nm to 1040 nm. These amorphous films exhibit an average saturation magnetisation of
(1.01 ± 0.04) MA∕m. As the film thickness increases, there is a significant decrease in coercivity, remanent to-saturation magnetisation ratio r∕s
, and maximum permeability. The change in macroscopic magnetic
properties is also reflected by the domain structure. At a thickness of 52 nm, the remanent domain state shows
irregular domains, while films thicknesses above 208 nm exhibit flux-closure domain structures instead. The
thickness-dependent modifications are attributed to the transition between Néel and Bloch type domain walls,
which is expected to occur at approximately 84 nm
Literatur als pacte de générosité : Kollektive Erinnerung in deutsch-französischer Perspektive Abschiedsvorlesung 31. Januar 2024
No full textAbschiedsvorlesung: von 2003 bis 2024 war Patricia Oster-Stierle Inhaberin des Lehrstuhls für Französische Literaturwissenschaft an der Universität des Saarlandes
Eribulin-Induced Peripheral Neuropathy in Locally Advanced or Metastatic Breast Cancer: Final Analysis of the Prospective Cohort IRENE Study
Get PDFEribulin is a preferred treatment for patients with advanced breast cancer (BC)
following anthracyclines and taxanes. The final analysis of the IRENE study assessed the
incidence and resolution of eribulin-induced peripheral neuropathy (EIPN), along with
safety and quality of life (QoL), in patients with advanced/metastatic BC. IRENE was an observational, single-arm, prospective, multicenter cohort study. Patients aged ≥18 years
with locally advanced/metastatic BC that progressed after 1–3 prior chemotherapeutic
regimens received eribulin and were monitored for new-onset or worsening EIPN. Secondary endpoints included time to disease progression, safety, and health-related QoL.
In total, 108 (32.2%) out of 335 patients experienced EIPN; 18 (5.4%) experienced grade
≥3 EIPN. Median time to EIPN resolution (EIPN ended or returned to baseline) was 78.7
weeks (95% CI 77.1—not estimable). Median time to disease progression was 4.5 months
(95% CI 3.9–5.5). Treatment-emergent adverse events (TEAEs) occurred in 322 (96.1%)
patients; serious TEAEs occurred in 185 (55.2%) patients. Incidence and resolution rates of
EIPN were comparable with existing evidence from previous trials. TEAEs were consistent
with the established eribulin safety profile, with no new safety signals. Eribulin treatment
did not appear to affect QoL, as measured by EQ-5D-3L and EQ-VAS, or patient-reported
neuropathy symptoms, as measured by the PNQ
Perioperative treatment with cilostazol reverses steatosis and improves liver regeneration after major hepatectomy in a steatotic rat model
Get PDFCilostazol has previously been shown to reduce liver steatosis and enhance hepatic perfusion. We
investigated the effects of cilostazol after major hepatectomy in a steatotic rat model. Six weeks prior
to surgery, Sprague–Dawley rats were fed with a high-fructose diet. The treatment group received
daily 5 mg/kg cilostazol. Seven days following the cilostazol treatment, all animals underwent 70%
liver resection (PHX). Analysis of hepatic blood flow and microcirculation and immunohistochemical
examinations were conducted 30 min after PHX (postoperative day [POD] 0) as well as on POD 1,
POD 3 and POD 7. The weight of cilostazol-treated animals was significantly reduced compared to
untreated controls after completion of the 6-week high-FRC diet. Furthermore, 41% macrovesicular
steatosis was found in the control group compared to 8% in the cilostazol group. Hepatic arterial
and portal venous perfusion were increased in the cilostazol group on POD 7. Lower liver enzyme
release was found postoperatively in cilostazol-treated animals. Moreover, apoptosis and neutrophil
infiltration were reduced after cilostazol treatment. Proliferation of hepatocytes and liver regeneration
after PHX were significantly increased in the cilostazol group. Consequently, cilostazol should be
evaluated as a novel strategy to reduce the rate of liver failure after PHX in steatotic liver
Collagen turnover biomarkers to predict outcome of patients with biliary cancer
Get PDFBackground The collagen-rich tumor stroma plays a crucial role in biliary tract cancer (BTC). Collagen biomarkers
of type I collagen (reC1M), type III collagen (PRO-C3), type IV collagen (C4G), type VIII collagen (PRO-C8), type XI collagen (PRO-C11), type XVII collagen (PRO-C17) and type VIII collagen (TUM) may be used as potential non-invasive
biomarkers.
Methods We measured the seven biomarkers of collagen turnover in sera of 72 patients with BTC at baseline
and after frst and second chemotherapy cycle (CTX). Markers were also assessed in sera of 50 healthy controls
and compared to levels of patients at baseline. The diagnostic and prognostic value of the markers was evaluated
for overall survival (OS) and progression-free survival (PFS).
Results Patients had a median age of 65 years (IQR 57–70), while healthy controls were younger, with a median age
of 46 years (IQR 38–54). The majority of patients (62%) were diagnosed with intrahepatic bile duct adenocarcinoma.
Except C4G, all collagen turnover markers were signifcantly (p<0.001) increased in serum from patients with BTC
compared to healthy controls. PRO-C3 was the best marker to discriminate between patients with BTC and controls,
reaching an area under a receiver operating characteristic (AUROC) of 0.98 (95% CI 0.95; 0.99) with a sensitivity (92%)
and specifcity (94%) balanced cutof of 77.3 ng/ml. Patients with high levels (cohort separated by median split)
of PRO-C8 (HR 2.85, 95% CI 1.42; 5.73) followed by C3M (HR 2.33, 95% CI 1.2; 4.5), PRO-C3 (HR 3.09, 95% CI 1.5; 6.36)
and CA 19–9 (HR 2.52, 95% CI 1.37; 4.64) as reference biomarker had a shorter OS. Notably, only the novel marker
PRO-C8 was also predictive of PFS (HR 3.26, 95% CI 1.53; 6.95). Associations with survival outcomes remained signifcant after adjusting for relevant risk factors (CA 19–9 and CEA at baseline, age, presence of metastases, weight, height
and gender).
Conclusion The collagen turnover markers PRO-C8, C3M, PRO-C3 and the established biomarker CA 19–9 were prognostic for OS in patients with BTC while only PRO-C8 was also predictive for PFS. PRO-C3 showed the best diagnostic
performance to discriminate between patients with BTC and controls. Trial registration Trial registration number and date of registration
NCT00661830 (NCT number)
15 April 2008
Trial registry
The complete registry can found under:
https://clinicaltrials.gov/study/NCT00661830?tab=table#administrative-information (last accessed 01/2025)
Principal investigator and study sponsor
Markus Moehler, MD
Johannes Gutenberg University Main