Scientific publications of the Saarland University
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CMV management of patients with leukopenia after CMV high-risk kidney transplantation
Get PDFBackground: For CMV high-risk constellations, guidelines recommend 3–6 months of prophylaxis with valganciclovir (VGCV). Management in preventing CMV primary infection in patients developing VGCV-associated
leukopenia remains challenging.
Methods: We retrospectively analyzed the development of leukopenia during VGCV prophylaxis in 57 seronegative kidney recipients of a CMV-seropositive donor between 2008 and 2021. We analyzed CMV risk and
development of CMV-specific T cells in the first post-transplant year depending on leukopenia during VGCV
prophylaxis and management with CMV-IVIg.
Results: Leukopenia developed in 19/57 patients, with a significant difference in leukocyte counts occurring after
10 weeks of VGCV prophylaxis compared to patients without leukopenia (p = 0.0003). VGCV discontinuation led
to leukocyte reconstitution, which tended to be faster in patients receiving additional prophylaxis with CMV-IVIg
after VGCV discontinuation (n = 11, p = 0.083). In the first post-transplant year, patients with leukopenia had no
higher risk for severe CMV events. Interestingly, patients receiving CMV-IVIg prophylaxis showed a significantly
lower peak CMV-load during primary infection (p = 0.040), with no difference in CMV-specific T-cell levels
compared to patients without leukopenia or patients with additional CMV-IVIg prophylaxis (p = 0.972). Patients
developing adequate CMV-specific T-cell responses less frequently underwent CMV reactivation 50 days
following primary infection.
Conclusion: Leukopenia developed late during VGCV prophylaxis and did not result in an increased risk for CMV
primary infections or severe disease. Leukopenic patients receiving CMV-IVIg tended to have a faster leukocyte
reconstitution and had lower peak DNAemia, which did not adversely affect CMV-specific T-cell induction. CMVIVIg may therefore be considered as an alternative prophylactic strategy in patients with VGCV-associated
leukopenia
Advanced Thermal Imaging Processing and Deep Learning Integration for Enhanced Defect Detection in Carbon Fiber-Reinforced Polymer Laminates
Get PDFCarbon fiber-reinforced polymer (CFRP) laminates are widely used in aerospace,
automotive, and infrastructure industries due to their high strength-to-weight ratio. However, defect detection in CFRP remains challenging, particularly in low signal-to-noise ratio
(SNR) conditions. Conventional segmentation methods often struggle with noise interference and signal variations, leading to reduced detection accuracy. In this study, we evaluate
the impact of thermal image preprocessing on improving defect segmentation in CFRP
laminates inspected via pulsed thermography. Polynomial approximations and first- and
second-order derivatives were applied to refine thermographic signals, enhancing defect
visibility and SNR. The U-Net architecture was used to assess segmentation performance
on datasets with and without preprocessing. The results demonstrated that preprocessing
significantly improved defect detection, achieving an Intersection over Union (IoU) of
95% and an F1-Score of 99%, outperforming approaches without preprocessing. These
findings emphasize the importance of preprocessing in enhancing segmentation accuracy
and reliability, highlighting its potential for advancing non-destructive testing techniques
across various industries
Possibilities and limitations of the sewage-based epidemiology approach in the context of clinical toxicology
No full textThis thesis presents a comprehensive investigation into development, validation, and application of analytical methods used for wastewater (WW)-based epidemiology (WBE). By developing and validating analytical methods for WBE, elucidating the metabolism of five new psychoactive substances and investigating their stability in WW, this thesis aimed to elucidate the possibilities and limitations of WBE in the context of clinical toxicology. For this purpose, two complementary analytical methods for the qualitative and quantitative screening of four drugs of abuse, one cognitive enhancer, and three of their metabolites as biomarkers in WW samples were developed and validated. Furthermore, 24 h composite WW samples and WW gab samples were analyzed, and data then compared to a prior study in the same geographical area as well as to a Europe-wide study. Additionally, the in vivo metabolic fate of five deschloroketamine derivatives was elucidated and their microbial biotransformation and WW stability assessed with the aim of finding suitable biomarkers for further WBE studies. Limitations of WBE when used in the context of clinical toxicology were shown, as obtained data is limited to a population size level and cannot be easily transferred to a single patient. Nevertheless, WBE proved to be a useful complementary tool for clinicians.Diese Dissertation präsentiert eine umfassende Untersuchung zur Entwicklung, Validierung und Anwendung analytischer Methoden im Kontext der abwasserbasierten (AW) Epidemiologie (ABE). Durch die Entwicklung und Validierung analytischer Methoden für die ABE, sowie die Aufklärung des Metabolismus von fünf neuen psychoaktiven Substanzen (NPS) und die anschließende Untersuchung ihrer Stabilität im AW, verfolgte diese Arbeit das Ziel, die Möglichkeiten und Limitationen von ABE im Kontext von klinischer Toxikologie (KT) zu untersuchen. Dazu wurden zwei sich ergänzende analytische Methoden für die qualitative und quantitative Analyse von vier Missbrauchsdrogen, einem kognitiven Stimulanz und drei Metaboliten als Biomarker im AW entwickelt und validiert. Weiterhin wurden 24- Stunden AW-Sammelproben und AW-Stichproben analysiert, sowie die erhaltenen Daten anschließend mit einer vorherigen Studie in dieser geographischen Region, sowie Daten aus einer europaweiten Studie verglichen. Des Weiteren wurde der in vivo Metabolismus von fünf Deschloroketamin-Derivaten sowie deren Stabilität im AW untersucht. Die daraus erhaltenen Daten sollten genutzt werden, um potenzielle Biomarker der NPS im AW zu etablieren. Die Grenzen der ABE im Kontext KT zeigten sich dadurch, dass die erhobenen Daten zwar auf einer Populationsebene nutzbar sind, allerdings nicht auf den einzelnen Patienten übertragen werden können. Dennoch erwies sich die ABE als nützliches, ergänzendes Werkzeug für klinische Toxikologen
End-to-end quantum computation of the response function of elastic structures
No full textQuantum computing is at a pivotal stage where hardware advancements are steady, yet most quantum algorithms lack guaranteed advantages in real-world applications. This thesis explores the application of quantum computing to elastic structure problems. In our case, this is related to the broader class of finite element problems. We propose an end-to-end response function calculator for coupled oscillators based on quantum phase estimation, addressing its typical input-output bottlenecks. Specifically, we achieve eigenstate preparation in a single gate, encode a sparse × matrix using at most O (polylog ) gates, and minimize the sampling overhead by reducing the output. These innovations result in an overall runtime that is polynomial in , but outperforms classical alternatives, while reducing memory requirements exponentially compared to classical computation. The core strategy lies in simplifying the problem complexity and focusing on minimalistic outputs while exploiting the full -dimensional Hilbert space only during the intermediate quantum steps. This work demonstrates that quantum computing can not only reduce memory demands, but also achieve meaningful speed-ups when real-world problems are reformulated into humanly manageable subproblems.Quantencomputer entwickeln sich rasant weiter, doch die meisten Quantenalgorithmen verlieren ihren Vorteil bei angewandten Problemen. Diese Arbeit untersucht den Einsatz von Quantencomputern zur Analyse elastischer Strukturen, welcher auf die größere Familie der Finite-Elemente-Probleme übertragbar ist. Wir präsentieren einen vollständigen Algorithmus zur Berechnung von Antwortfunktionen gekoppelter Oszillatoren, der auf der Quantenphasenschätzung basiert und typische Input-Output-Herausforderungen löst. Konkret umfasst dies die Erzeugung von Eigenzuständen in einem einzigen Gatterschritt, die Implementierung einer dünnbesetzten ×-Matrix mit maximal O (polylog ) Gatterschritten sowie die Reduktion des Messaufwands auf das notwendige Minimum. Dies führt zu einer Laufzeit, die polynomiell in ist und klassische Alternativen übertrifft, während der Speicherbedarf im Vergleich zu klassischen Algorithmen exponentiell geringer ist. Der Schlüssel zu diesem Fortschritt liegt in der Vereinfachung der Problemkomplexität und der Fokussierung auf minimale Ausgaben, während der volle -dimensionale Hilbertraum ausschließlich in den quantenmechanischen Zwischenschritten genutzt wird. Diese Arbeit zeigt, dass Quantencomputer nicht nur den Speicherbedarf reduzieren, sondern auch schwer erreichbare Geschwindigkeitsvorteile erzielen können – vorausgesetzt, das Problem kann in handhabbare Teilprobleme umformuliert werden.Bundesministerium für Wirtschaft und Klimaschutz über das quantum computing enhanced service ecosystem for simulation in manufacturing project (QUASIM
Superconductivity in the Intercalated Graphite Compound CaC6 and the Roeser–Huber Formalism
No full textThe superconducting transition temperature, Tc, of the graphite intercalation compound,
CaC6, was calculated using the Roeser–Huber (RH) formalism. This method was adapted
to alloys with complex crystal structures by identifying symmetric paths for the supercon ducting charge carriers (Cooper pairs) and incorporating interactions with neighboring
atoms through phonon coupling. The evaluation of the lowest energy levels, ∆(0)
, along all
relevant crystallographic directions reveals a slight anisotropy between the in-plane and
out-of-plane directions, consistent with the experimental observation of the gap anisotropy
by point contact spectroscopy. The Tc values obtained for CaC6, CaC6 with applied high
pressure, and YbC6 show good agreement with experimental data, thereby supporting both
the validity of the RH approach and its predictive capability in describing superconductivity
within complex crystal structures
Acoustically assisted additive manufacturing by laser powder-bed fusion of AlSi10Mg
No full textThe exceptional design freedom offered by additive manufacturing, including the ability to create complex geometries and graded materials, along with its immense lightweight construction potential, are often cited as compelling advantages of the technology. However, these benefits are counterbalanced by challenges such as poor surface quality in the as-built state. Additionally, the formation of porosity, which has yet to be fully mitigated through parameter optimization, significantly diminishes cyclic strength, particularly when pores are located near the surface. Porosity also contributes to the high variability in physical properties, necessitating its reduction or complete elimination to ensure high reliability, consistent process performance, and long-term durability of the manufactured components.
To address these issues, tailored sonication during the build process could offer multiple benefits for both the powder-bed and the emerging component. Initial prototypes and proofs of concept have been developed for Laser Metal Deposition (LMD) systems. However, the integration of an acoustic transducer into a Laser Powder-Bed Fusion (L-PBF) machine remains a challenge, posing numerous interdisciplinary questions in areas such as physical acoustics, mechanical engineering, materials science, and manufacturing technology. This study seeks to develop a functional acoustically assisted additive manufacturing system based on L-PBF. It focuses on designing an effective transducer, understanding the behavior of powder under acoustic excitation, and evaluating the resulting key properties of the manufactured parts
Optimal spatial searches with long-range tunneling
No full textA quantum walk on a lattice is a paradigm of a quantum search in a database. The database qubit strings are
the lattice sites, qubit rotations are tunneling events, and the target site is tagged by an energy shift. For quantum
walks on a continuous time, the walker diffuses across the lattice and the search ends when it localizes at the
target site. The search time T can exhibit Grover’s optimal scaling with the lattice size N, namely, T ∼ √N,
on an all-connected, complete lattice. For finite-range tunneling between sites, instead, Grover’s optimal scaling
is warranted when the lattice is a hypercube of d > 4 dimensions. Here, we show that Grover’s optimum can
be reached in lower dimensions on lattices of long-range interacting particles, when the interaction strength
scales algebraically with the distance r as 1/rα and 0 <α< 3d/2. For α < d the dynamics mimics the one of a
globally connected graph. For d <α< d + 2, the quantum search on the graph can be mapped to a short-range
model on a hypercube with spatial dimension ds = 2d/(α − d), indicating that the search is optimal for ds > 4.
Our work identifies an exact relation between criticality of long-range and short-range systems, it provides a
quantitative demonstration of the resources that long-range interactions provide for quantum technologies, and
indicates when existing experimental platforms can implement efficient analog quantum search algorithms
Cortical Single-Cell Primers of Abnormal Brain Activity in Parkinson's Disease
No full textAbnormal brain oscillatory activity is a well-established hallmark of bradykinesia and motor impairment
in Parkinson’s disease (PD), yet its molecular underpinnings remain unclear. To address this gap, we
analyzed over 100,000 single-cell RNA transcriptomes from fresh dorsolateral prefrontal cortex tissue
of individuals with PD and non-PD controls, undergoing deep brain stimulation—2 cohorts, which open
up an unprecedent window to the characterization of human cortical brain tissue, aiming to uncover
the molecular mechanisms of abnormal brain oscillatory activity in PD. Fresh brain tissue samples offer
a unique opportunity to precisely elucidate the molecular underpinnings of known, clinically relevant
electrophysiological hallmarks of neurodegeneration, which can be used to inform targeted therapeutic
strategies. We depicted in microglia and astrocytes enrichment of mitochondrial electron transport and
oxidative phosphorylation pathways, which were directly linked to the increase of pathological brain
activity and the decrease of prokinetic brain activity. Additionally, the abnormal phase–amplitude coupling
of beta–gamma brain activity was related to the dysfunction of oligodendrocyte precursor cells and
inflammasome activation mediated by lymphocyte-driven adaptive immunity. We identified a distinct set of
dysregulated genes from the mitogen-activated protein kinase phosphorylation pathways, mitochondrial
electron transport at the intersection of neuroinflammation and neurodegeneration, suggesting pivotal
roles in PD pathology. This unique dataset provides unprecedented insights into the immune and metabolic
dysregulation underlying PD, offering a mechanistic framework for understanding invasive transcriptomic
biomarkers related to prokinetic and pathologic brain activity in PD
Outcomes of Penetrating Keratoplasty Versus Lamellar Endothelial Keratoplasty in Iridocorneal Endothelial Syndrome: A Systematic Review and Meta-Analysis
Get PDFPurpose
To compare surgical outcomes following penetrating keratoplasty (PK), Descemet stripping endothelial keratoplasty (DSEK), and Descemet membrane endothelial keratoplasty (DMEK) in patients with iridocorneal endothelial (ICE) syndrome.
Design
Systematic review and meta-analysis on individual patient data (IPD).
Methods
Pre-registration was performed in the PROSPERO database (registration number: CRD42024539444). Eligible studies from Embase, MEDLINE (via PubMed), and the Cochrane Central Register of Controlled Trials (CENTRAL) were retrieved up to April 24, 2024. Studies were included those reporting clinical outcomes after PK, DSEK, or DMEK- graft survival, best spectacle-corrected visual acuity (BSCVA) and endothelial cell density (ECD) - in people with ICE syndrome. Cochrane Handbook was followed for data extraction/ synthesis, and the Risk of Bias in Non-randomized Studies of Interventions (ROBINS-I) and the Joanna Briggs Institute Critical Appraisal Checklists were used to assess risk of bias. Meta-analyses were conducted using a random-effects model. Heterogeneity between studies was assessed using Q-test and I2 statistics.
Results
Nineteen of the 1963 screened studies were included in the meta-analysis. Multivariate pooled Kaplan-Meier curves with 95% confidence intervals, based on IPD from studies with at least 10 cases indicated that graft survival was better after PK compared to DSEK in patients with ICE syndrome. No significant difference (P = .92) was found in BSCVA improvement between PK [-0.77 (95% CI, -1.45 to -0.09)], DSEK [-0.87 (95% CI, -1.35 to -0.39)] and DMEK [-0.85 (95% CI, -1.07 to -0.62)]. No significant differences in ECD were observed between DSEK and DMEK 6 (P = .88) and 12 months (P = .33) postoperatively. IPD analysis revealed no significant difference in graft survival between patients with and without anytime glaucoma (-0.04 ± 0.50 SEM; P = .940) or cataract surgery (-0.45 ± 0.40 SEM; P = .265).
Conclusions
PK demonstrated better graft survival compared to DSEK in patients with ICE, however, further research and additional evidence are needed to draw more definitive conclusions. Improvements in BSCVA were comparable across PK, DSEK and DMEK. Glaucoma surgery, whether performed before or after keratoplasty, appear to have no significant impact on graft survival
PPIXpress and PPICompare webservers infer condition-specific and differential PPI networks
Get PDFSummary
We present PPIXpress and PPICompare as two webservers that enable analysis of protein–protein interaction networks (PPINs). Given a reference PPIN and user-uploaded expression data from one or multiple samples, PPIXpress constructs context-dependent PPINs based on major transcripts and high-confidence domain interactions data. To derive a differential PPIN that distinguishes two groups of contextualized PPINs, PPICompare identifies statistically significant altered interactions between multiple context-dependent PPINs from PPIXpress. We present a case study where PPIXpress and PPICompare webservers were used in combination to construct the PPINs specific for melanocytic nevi and primary melanoma cells, and to detect the rewired protein interactions between these two sample types.
Availability and implementation
PPIXpress and PPICompare webservers are available at https://service.bioinformatik.uni-saarland.de/ppi-webserver/index_PPIXpress.jsp and https://service.bioinformatik.uni-saarland.de/ppi-webserver/index_PPICompare.jsp, respectively. Alternatively, the webservers and application updates can be found at https://service.bioinformatik.uni-saarland.de/ppi-webserver/