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Monsoon-driven changes in aeolian and fluvial sediment input to the central Red Sea recorded throughout the last 200 000 years
No full textClimatic and associated hydrological changes
controlled the transport processes and composition of the
sediments in the central Red Sea during the last ca. 200 kyr.
Three different source areas for mineral dust are identified.
The dominant source is located in the eastern Sahara (Sudan
and southernmost Egypt). We identify its imprint on Red Sea
sediments by high smectite and Ti contents, low 87Sr / 86Sr,
and high εNd. The availability of deflatable sediments was
controlled by the intensity of tropical rainfall and vegeta-
tion cover over North Africa linked to the African mon-
soon. Intense dust input to the Red Sea occurred during arid
phases, and low input occurred during humid phases. A sec-
ond, less significant source indicated by palygorskite input
is probably located on the eastern Arabian Peninsula and/or
Mesopotamia, while the presence of kaolinite suggests an ad-
ditional minor dust source in northern Egypt. Our grain size
data reflect episodes of fluvial sediment discharge to the cen-
tral Red Sea and document the variable strength in response
to all of the precession-paced insolation maxima during our
study interval including both those that were strong enough
to trigger sapropel formation in the eastern Mediterranean
Sea and those that were not. The African humid period most
strongly expressed in our Red Sea record was the one during
the Eemian last interglacial at ca. 125 ka (when the Baraka
River was far more active than today), followed by those at
198, 108, 84, and 6 ka
Cross-species variability in lobular geometry and cytochrome P450 hepatic zonation: insights into CYP1A2, CYP2D6, CYP2E1 and CYP3A4
No full textThere is a lack of systematic research exploring cross-species variation in liver lobular geometry and zonation patterns of critical drug-metabolizing enzymes, a knowledge gap essential for translational studies. This study investigated the critical interplay between lobular geometry and key cytochrome P450 (CYP) zonation in four species: mouse, rat, pig, and human. We developed an automated pipeline based on whole slide images (WSI) of hematoxylin-eosin-stained liver sections and immunohistochemistry. This pipeline allows accurate quantification of both lobular geometry and zonation patterns of essential CYP proteins. Our analysis of CYP zonal expression shows that all CYP enzymes (besides CYP2D6 with panlobular expression) were observed in the pericentral region in all species, but with distinct differences. Comparison of normalized gradient intensity shows a high similarity between mice and humans, followed by rats. Specifically, CYP1A2 was expressed throughout the pericentral region in mice and humans, whereas it was restricted to a narrow pericentral rim in rats and showed a panlobular pattern in pigs. Similarly, CYP3A4 is present in the pericentral region, but its extent varies considerably in rats and appears panlobular in pigs. CYP2D6 zonal expression consistently shows a panlobular pattern in all species, although the intensity varies. CYP2E1 zonal expression covered the entire pericentral region with extension into the midzone in all four species, suggesting its potential for further cross-species analysis. Analysis of lobular geometry revealed an increase in lobular size with increasing species size, whereas lobular compactness was similar. Based on our results, zonated CYP expression in mice is most similar to humans. Therefore, mice appear to be the most appropriate species for drug metabolism studies unless larger species are required for other purposes, e.g., surgical reasons. CYP selection should be based on species, with CYP2E1 and CYP2D6 being the most preferable to compare four species. CYP1A2 could be considered as an additional CYP for rodent versus human comparisons, and CYP3A4 for mouse/human comparisons. In conclusion, our image analysis pipeline together with suggestions for species and CYP selection can serve to improve future cross-species and translational drug metabolism studies
Tax-Compliance-Management-Systeme (TCMS) – Grundlagen und Implikationen für kleine und mittlere Unternehmen
No full textDer Arbeitsbericht untersucht, welche Aufgabenbereiche sowie technischen und organisatorischen Optionen kleinen und mittleren Unternehmen (KMU) bei der Einführung eines Tax-Compliance-Management-Systems (TCMS) zur Verfügung stehen. Grundlage bilden eine systematische Litera-turrecherche, Experteninterviews und eine empirische Marktanalyse von 50 Softwareprodukten, deren funktionale Merkmale mithilfe einer PCA-gestützten Clusteranalyse ausgewertet wurden. Die Untersuchung identifiziert vier Aufgabenbereiche als Kernfunktionen eines TCMS: Dokumentation (D), Berichterstattung (B), Kommunikation und Koordination (K) sowie Prozessverwaltung und -automatisierung (P). Die Marktanalyse zeigt, dass bestehende Softwarelösungen diese Aufgaben in unterschiedlicher Tiefe abbilden und sich funktional klar voneinander unterscheiden. Einige Syste-me bündeln Nachweisführung und Compliance-Dokumentation in integrierten Plattformen, wäh-rend andere auf Prozessautomatisierung, Schnittstellenmanagement oder kollaborative Informati-onsarbeit spezialisiert sind. Die Ergebnisse verdeutlichen, dass KMU zwischen unterschiedlichen Lösungsansätzen wählen können – von integrierten Suiten über modulare Cloud-Plattformen bis hin zu offenen und hybriden Architekturen. ERP- oder CRM-Systeme können je nach Branche und Di-gitalisierungsgrad als ergänzende Integrationskomponenten dienen. Der Bericht leistet damit einen Beitrag zur Systematisierung technischer und organisatorischer Gestaltungsoptionen für KMU und zeigt, wie sich regulatorische Anforderungen ressourceneffizient in bestehende IT- und Prozessland-schaften integrieren lassen.:Inhaltsverzeichnis
Inhaltsverzeichnis IV
Abbildungsverzeichnis V
Tabellenverzeichnis V
Abkürzungsverzeichnis VI
Autorenverzeichnis VII
Tax-Compliance-Management-Systeme (TCMS) – Grundlagen und Implikationen für kleine und mittlere Unternehmen 1
1 Tax-Compliance für KMU: Kontext und Problemstellung 1
2 Forschungsmethodik 3
2.1 Strukturierte Literaturanalyse 3
2.1.1 Suchstrategie 3
2.1.2 Screening und Auswahl 3
2.1.3 Herleitung der Aufgabenbereiche 4
2.1.4 Validierung mit Experteninterviews 4
2.2 Analyse der TCMS-Anwendungen 5
3 TCMS aus Sicht der Literatur 6
3.1 Ergebnisse der Literaturanalyse 6
3.2 Grundlage des TCMS 8
3.2.1 Begriff des TCMS 8
3.2.2 Abgrenzung zu anderen Systemen 10
3.3 Aufgabenbereiche eines TCMS 11
3.3.1 Prozessverwaltung und -automatisierung (P) 11
3.3.2 Dokumentation (D) 13
3.3.3 Berichterstattung (B) 14
3.3.4 Kommunikation und Koordination (K) 15
3.3.5 Synthese der Aufgabenbereiche 16
3.4 Wirkungen eines TCMS 18
4 TCMS aus Sicht des Marktes 18
4.1 KMU-spezifische Kriterien und Bewertungskonzept 18
4.2 Datengrundlage und Auswahlverfahren 19
4.3 Ergebnisse der Cluster-Analyse 21
5 Implikationen für KMU 23
5.1 Vorteile einer TCMS-Implementierung für KMU 23
5.2 Herausforderungen einer TCMS-Implementierung für KMU 24
5.3 Strategien für KMU zur Ausgestaltung eines TCMS 25
5.4 Fallbeispiel Finatix: Bestehende Systemlandschaft und explorative Weiterentwicklung im Projekt DigiTax 26
6 Fazit und Aussicht 28
Literaturverzeichnis VIII
Anhang
Anhang 1: Konzeptmatrix SLR
Anhang 2: Ergebnis aus der Marktrecherche zu TCMS-Anwendungen XVI
Anhang 3: Liste relevanter gesetzlicher Vorschriften/Initiativen/Richtlinien in Zusammenhang mit TCMS XIX
Anhang 4: Herleitung der vier Aufgabenbereiche aus Literatur und IDW-Vorschriften XXII
Anhang 5: Beleg für Wirkungen XXVII
Anhang 6: Liste der Anwendungen nach Clustern XXVIII
Anhang 7: Zuordnung der steuerlichen Aufgaben zu den TCMS-Aufgabenbereichen XXI
Simulations of the impact of cloud condensation nuclei and ice-nucleating particles perturbations on the microphysics and radar reflectivity factor of stratiform mixed-phase clouds
No full textIn this research, we delve into the influence of cloud condensation nuclei (CCN) and ice-nucleating particle (INP) concentrations on the morphology and abundance of ice particles in mixed-phase clouds, emphasizing the consequential impact of ice particle shape, number, and size on cloud dynamics and microphysics. Leveraging the synergy of the Advanced Microphysics Prediction System (AMPS) and the Kinematic Driver (KiD) model, we conducted simulations to capture cloud microphysics across diverse CCN and INP concentrations. The Passive and Active Microwave radiative TRAnsfer (PAMTRA) radar forward simulator further augmented our study, offering insights into how the concentrations of CCN and INPs affect radar reflectivities.
Our experimental framework encompassed CCN concentrations ranging from 10 to 5000 cm−3 and INP concentrations from 0.001 to 10 L−1. Central to our findings is the observation that higher INP concentrations yield smaller ice particles, while an increase in CCN concentrations leads to a subtle growth in their dimensions. Consistent with existing literature, our results spotlight oblate-like crystals as dominant between temperatures of −20 and −16 °C. Notably, high-INP scenarios unveiled a significant prevalence of irregular polycrystals. The aspect ratio (AR) of ice particles exhibited a decline with the rise in both CCN and INP concentrations, highlighting the nuanced interrelation between CCN levels and ice particle shape, especially its ramifications on the riming mechanism.
The forward-simulated radar reflectivities, spanning from −11.83 dBZ (low INP, 0.001 L−1) to 4.65 dBZ (high INP, 10 L−1), elucidate the complex dynamics between CCN and INPs in determining mixed-phase cloud characteristics. Comparable differences in radar reflectivity were also reported from observational studies of stratiform mixed-phase clouds in contrasting aerosol environments. Our meticulous analysis of KiD-AMPS simulation outputs, coupled with insights into aerosol-driven microphysical changes, thus underscores the significance of this study in refining our ability to understand and interpret observations and climate projections
Potential of a Bead-Based Multiplex Assay for SARS-CoV-2 Antibody Detection
No full textSerological assays for SARS-CoV-2 play a pivotal role in the definition of whether patients are infected, the understanding of viral epidemiology, the screening of convalescent sera for therapeutic and prophylactic purposes, and in obtaining a better understanding of the immune response towards the virus. The aim of this study was to investigate the performance of a bead-based multiplex assay. This assay allowed for the simultaneous testing of IgG antibodies against SARS-CoV-2 spike, S1, S2, RBD, and nucleocapsid moieties and S1 of seasonal coronaviruses hCoV-22E, hCoV-HKU1, hCoV-NL63, and hCoV-OC43, as well as MERS and SARS-CoV. We compared the bead-based multiplex assay with commercial ELISA tests. We tested the sera of 27 SARS-CoV-2 PCR-positive individuals who were previously tested with different ELISA assays. Additionally, we investigated the reproducibility of the results by means of multiple testing of the same sera. Finally, the results were correlated with neutralising assays. In summary, the concordance of the qualitative results ranged between 78% and 96% depending on the ELISA assay and the specific antigen. Repeated freezing–thawing cycles resulted in reduced mean fluorescence intensity, while the storage period had no influence in this respect. In our test cohort, we detected up to 36% of sera positive for the development of neutralising antibodies, which is in concordance with the bead-based multiplex and IgG ELISA
Deep-Learning-Based Automatic Sinkhole Recognition: Application to the Eastern Dead Sea
No full textSinkholes can cause significant damage to infrastructures, agriculture, and endanger lives in active karst regions like the Dead Sea’s eastern shore at Ghor Al-Haditha. The common sinkhole mapping methods often require costly high-resolution data and manual, time-consuming expert analysis. This study introduces an efficient deep learning model designed to improve sinkhole mapping using accessible satellite imagery, which could enhance management practices related to sinkholes and other geohazards in evaporite karst regions. The developed AI system is centered around the U-Net architecture. The model was initially trained on a high-resolution drone dataset (0.1 m GSD, phase I), covering 250 sinkhole instances. Subsequently, it was additionally fine-tuned on a larger dataset from a Pleiades Neo satellite image (0.3 m GSD, phase II) with 1038 instances. The training process involved an automated image-processing workflow and strategic layer freezing and unfreezing to adapt the model to different input scales and resolutions. We show the usefulness of initial layer features learned on drone data, for the coarser, more readily-available satellite inputs. The validation revealed high detection accuracy for sinkholes, with phase I achieving a recall of 96.79% and an F1 score of 97.08%, and phase II reaching a recall of 92.06% and an F1 score of 91.23%. These results confirm the model’s accuracy and its capability to maintain high performance across varying resolutions. Our findings highlight the potential of using RGB visual bands for sinkhole detection across different karst environments. This approach provides a scalable, cost-effective solution for continuous mapping, monitoring, and risk mitigation related to sinkhole hazards. The developed system is not limited only to sinkholes however, and can be naturally extended to other geohazards as well. Moreover, since it currently uses U-Net as a backbone, the system can be extended to incorporate super-resolution techniques, leveraging U-Net based latent diffusion models to address the smaller-scale, ambiguous geo-structures that are often found in geoscientific data
The functional impact of modern human-specific mutations in transcription factors
No full textA key goal in the field of human evolution is clarifying the genetic basis of modern human-specific traits. Identifying genetic derived variants that are present in the majority of people living today, but ancestral in great ape, Neandertal, and Denisovan genomes, provides a starting point for studying the genetic contributions to modern human biology. Genetic variants that can affect gene expression are prime targets for further investigation, since phenotypic differences are often caused by changes in gene expression. Variants that change the function of transcription factors are especially relevant, because transcription factors regulate the expression of multiple genes, allowing for the fine-tuning of biological processes. Here, I identify single nucleotide variants carried by all or almost all present-day humans that result in seven amino acid substitutions distributed across six transcription factors.
I investigate the evolutionary history of these variants on the human lineage. The ancestral forms of notochord homeobox (NOTO), nuclear receptor subfamily 6 group A member 1 (NR6A1), zinc finger protein 292 (ZNF292), and zinc finger protein 816 (ZNF816) exist at low frequencies in people today. In contrast, the ancestral variants of PR/SET domain 10 (PRDM10) and the aryl hydrocarbon receptor (AHR) have not been observed in any modern humans sequenced to date.
To study the functional consequences of these human-specific amino acid substitutions, I used CRISPR/Cas genome editing in human stem cells to mutate four of these transcription factors back to their respective ancestral states and analyzed resulting changes in the transcriptome. I find that the variants in PRDM10 and ZNF292 have no effect on the transcriptome. However, for the developmental transcription factor NR6A1, the modern human variant leads to increased repression of NR6A1’s target genes as compared to the ancestral variant. Additionally, for AHR, a ligand-activated transcription factor with a wide range of functions, the modern human variant induces expression of its target genes less efficiently and requires higher doses of some of its ligands, including the environmental carcinogen benzo(a)pyrene, to induce target gene expression. In stem cells these target genes are more highly expressed in chimpanzees than in humans, and I show that this single amino acid difference is responsible for much of the lower AHR target gene expression in modern humans as compared to chimpanzees.:Summary 1
Introduction 1
Aim of the thesis 3
Chapter 1 3
Chapter 2 5
Conclusions and outlook 7
Zusammenfassung 9
Einleitung 9
Zielstellung der Dissertation 11
Kapitel 1 11
Kapitel 2 14
Schlussfolgerung und Ausblick 16
Chapter 1: Evolutionary and functional exploration of transcription factors with modern human-specific amino acid changes 19
Abstract 20
Introduction 21
Results 22
Discussion 34
Methods 38
Acknowledgements 46
Supplementary Tables and Figures 47
Chapter 2: The modern human aryl hydrocarbon receptor is more active when ancestralized by genome editing 67
Abstract 68
Significance statement 69
Introduction 70
Results 72
Discussion 80
Acknowledgements 82
Data availability 82
Supplementary Methods 83
Supplementary Tables and Figures 90
References 97
Acknowledgments 107
Curriculum Vitae 108
Declaration of independence 112
Author contribution statements 11
Environmental struggles and insularity: The right to nature in Mallorca and Tenerife
No full textIslands worldwide experience commodification of land and natural resources that is closely related
to touristic activity and urbanization. Islands represent the epitome of commodified represented
spaces, power, and territorialization, and in this regard, focusing on islands may shed light on how
the production of socio-natures shapes the dynamics of capital accumulation, dispossession, and
resistance. We explore the contestation of urban-tourist development in Mallorca and Tenerife.
Both have experienced an intense expansion of artificial land uses since the touristic boom in the
mid-20th century, which has intensified with neoliberal capitalism and the commodification of
everyday life elements. Environmental struggles in both islands have facilitated greater mobilization
than other claims. An empirical survey of the spatio-temporal evolution of these two islands il-
lustrates and helps to deepen the conceptual development of the right to the island and nature. The
idea of the right to nature consists of the right to influence and rule the processes by which nature–
society relationships are (re)shaped by urbanization and capitalism. The notion of the right to the
island relies on the political action to foster a sustainable island future
The Impact of Obesity on T and NK Cells after LVAD Implantation
No full textInfections are a major problem after left ventricular assist device (LVAD) implantation that affects morbidity, mortality, and the quality of life. Obesity often increases the risk for infection. In the cohort of LVAD patients, it is unknown if obesity affects the immunological parameters involved in viral defense. Therefore, this study investigated whether overweight or obesity affects immunological parameters such as CD8+ T cells and natural killer (NK) cells. Methods: Immune cell subsets of CD8+ T cells and NK cells were compared between normal-weight (BMI 18.5–24.9 kg/m2, n = 17), pre-obese (BMI 25.0–29.9 kg/m2, n = 24), and obese (BMI ≥30 kg/m2, n = 27) patients. Cell subsets and cytokine serum levels were quantified prior to LVAD implantation and at 3, 6, and 12 months after LVAD implantation. Results: At the end of the first postoperative year, obese patients (31.8% ± 2.1%) had a lower proportion of CD8+ T cells than normal-weight patients (42.4% ± 4.1%; p = 0.04), and the percentage of CD8+ T cells was negatively correlated with BMI (p = 0.03; r = −0.329). The proportion of circulating NK cells increased after LVAD implantation patients in normal-weight (p = 0.01) and obese patients (p < 0.01). Patients with pre-obesity showed a delayed increase (p < 0.01) 12 months after LVAD implantation. Further, obese patients showed an increase in the percentage of CD57+ NK cells after 6 and 12 months (p = 0.01) of treatment, higher proportions of CD56bright NK cells (p = 0.01), and lower proportions of CD56dim/neg NK cells (p = 0.03) 3 months after LVAD implantation than normal-weight patients. The proportion of CD56bright NK cells positively correlated with BMI (p < 0.01, r = 0.403) 1 year after LVAD implantation. Conclusions: This study documented that obesity affects CD8+ T cells and subsets of NK cells in patients with LVAD in the first year after LVAD implantation. Lower proportions of CD8+ T cells and CD56dim/neg NK cells and higher proportion of CD56bright NK cells were detected in obese but not in pre-obese and normal-weight LVAD patients during the first year after LVAD implantation. The induced immunological imbalance and phenotypic changes of T and NK cells may influence viral and bacterial immunoreactivity
